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Family planning issues loom large for female radiation oncologists
Results from the survey were reported at the American Society for Radiation Oncology Annual Meeting 2020.
“Female radiation oncologists often spend their childbearing years in training and establishing careers,” commented lead investigator Anna Lee, MD, of the University of Texas MD Anderson Cancer Center in Houston.
“Currently, physician fertility and family planning are rarely discussed or taught in medical school or postgraduate training,” Dr. Lee said.
Dr. Lee and colleagues conducted a national anonymous cross-sectional online survey of female oncologists of all types and all career levels (including trainees). The team circulated a 39-item questionnaire exploring attitudes toward and experiences related to family planning and assisted reproductive technology (ART) by email and social media channels.
A total of 351 radiation oncologists participated, representing one-fifth of the specialty’s entire female workforce nationally and making this study the largest to date on family planning among these physicians.
Most respondents were aged 31-40 years (60%) and married (79%), had children (68%), and were in training (26%) or academic practice (48%).
Survey results
Fully 74% of respondents reported that their career plans strongly influenced the timing of when to start a family, and 29% said family planning considerations influenced their decision regarding their choice of academia versus private practice, Dr. Lee reported.
Overall, 24% of respondents indicated that they had difficulty with infertility or required fertility counseling/treatment, 66% said they wished fertility preservation was discussed at some point during their training, and 22% said either that ART would have benefited them if it had been available or that they were planning to or had already used fertility preservation.
On the topic of maternity leave, some respondents reported that their institution either had no formal leave policy during training or provided less than 1 month of leave (23%) and that they felt pressure to take less time off than was policy (15%).
“Of note, 32 women in our survey were not offered non–radiation-exposing assignments during pregnancy, and an additional 57 had to specifically ask for them,” Dr. Lee remarked.
About one-third of respondents each reported that they did not feel supported during training for issues related to fertility and/or pregnancy (33%) and that they experienced discrimination for being pregnant (32%) and taking maternity leave (30%).
“Systemic changes are necessary early in medical education and training to ensure women are supported and able to advance equitably in the field. As less than a third of the current radiation oncology workforce are women, improvement upon these issues will be necessary to draw more women into the field,” Dr. Lee commented. “Education on ART risks, benefits, and success rates can help physicians and those in training in their family planning, while the lack of education and structured policy can exacerbate the emotional, physical, and financial impact of infertility.
“Until recently, there has been a dearth of policy at the programmatic, institutional, and national level allowing time and protection for pregnancy and maternity leave,” she added. “Thankfully, this summer, the American Board of Medical Specialties announced a progressive leave policy for residents and fellows.”
The new policy, which goes into effect July 2021, allows a minimum of 6 weeks away without exhausting time allowed for vacation or sick leave and without requiring an extension in training.
When career and biology collide
“The collision of professional and biological clocks for women in medicine is an important issue highlighted by this study,” Reshma Jagsi, MD, DPhil, of the University of Michigan in Ann Arbor, said in an interview.
“Prior work focused on women in medicine more generally. A deeper dive into the experiences of women in a specific field may be even more compelling to drive change on the part of professional societies and organizations,” Dr. Jagsi added.
The infertility rate observed in the study could have potentially been skewed by the preponderance of younger respondents (resulting in underestimation) or by greater participation of those interested in the subject (resulting in overestimation), she noted. However, it aligns well with the rate in a study Dr. Jagsi and colleagues conducted among female physicians generally using somewhat different methods. That study was published in the Journal of Women’s Health.
Concern about radiation exposure and its potential reproductive health effects should not deter women from choosing radiation oncology as a specialty, according to Dr. Jagsi.
“Radiation exposure is actually very low in radiation oncology, much lower than in specialties like interventional cardiology, where physicians are in the room where fluoroscopy is being used. It is actually an important misconception about this field that merits correction,” she stressed. “Rather, the fertility concerns are related to the expectations of training and demands of work during the prime childbearing years more generally that can lead women to delay pregnancy, which is an issue common to all medical specialties.”
“The investigators’ conclusions are very reasonable,” Dr. Jagsi said. “Although one might quibble whether the exact proportions reflect the experiences of all women in the field perfectly due to the possibility of selection bias, one cannot question whether a substantial number of women are experiencing these challenges and that they merit intervention.”
The study did not receive specific funding. Dr. Lee and Dr. Jagsi disclosed no relevant conflicts of interest.
SOURCE: Lee A et al. ASTRO 2020, Abstract LBA 6.
Results from the survey were reported at the American Society for Radiation Oncology Annual Meeting 2020.
“Female radiation oncologists often spend their childbearing years in training and establishing careers,” commented lead investigator Anna Lee, MD, of the University of Texas MD Anderson Cancer Center in Houston.
“Currently, physician fertility and family planning are rarely discussed or taught in medical school or postgraduate training,” Dr. Lee said.
Dr. Lee and colleagues conducted a national anonymous cross-sectional online survey of female oncologists of all types and all career levels (including trainees). The team circulated a 39-item questionnaire exploring attitudes toward and experiences related to family planning and assisted reproductive technology (ART) by email and social media channels.
A total of 351 radiation oncologists participated, representing one-fifth of the specialty’s entire female workforce nationally and making this study the largest to date on family planning among these physicians.
Most respondents were aged 31-40 years (60%) and married (79%), had children (68%), and were in training (26%) or academic practice (48%).
Survey results
Fully 74% of respondents reported that their career plans strongly influenced the timing of when to start a family, and 29% said family planning considerations influenced their decision regarding their choice of academia versus private practice, Dr. Lee reported.
Overall, 24% of respondents indicated that they had difficulty with infertility or required fertility counseling/treatment, 66% said they wished fertility preservation was discussed at some point during their training, and 22% said either that ART would have benefited them if it had been available or that they were planning to or had already used fertility preservation.
On the topic of maternity leave, some respondents reported that their institution either had no formal leave policy during training or provided less than 1 month of leave (23%) and that they felt pressure to take less time off than was policy (15%).
“Of note, 32 women in our survey were not offered non–radiation-exposing assignments during pregnancy, and an additional 57 had to specifically ask for them,” Dr. Lee remarked.
About one-third of respondents each reported that they did not feel supported during training for issues related to fertility and/or pregnancy (33%) and that they experienced discrimination for being pregnant (32%) and taking maternity leave (30%).
“Systemic changes are necessary early in medical education and training to ensure women are supported and able to advance equitably in the field. As less than a third of the current radiation oncology workforce are women, improvement upon these issues will be necessary to draw more women into the field,” Dr. Lee commented. “Education on ART risks, benefits, and success rates can help physicians and those in training in their family planning, while the lack of education and structured policy can exacerbate the emotional, physical, and financial impact of infertility.
“Until recently, there has been a dearth of policy at the programmatic, institutional, and national level allowing time and protection for pregnancy and maternity leave,” she added. “Thankfully, this summer, the American Board of Medical Specialties announced a progressive leave policy for residents and fellows.”
The new policy, which goes into effect July 2021, allows a minimum of 6 weeks away without exhausting time allowed for vacation or sick leave and without requiring an extension in training.
When career and biology collide
“The collision of professional and biological clocks for women in medicine is an important issue highlighted by this study,” Reshma Jagsi, MD, DPhil, of the University of Michigan in Ann Arbor, said in an interview.
“Prior work focused on women in medicine more generally. A deeper dive into the experiences of women in a specific field may be even more compelling to drive change on the part of professional societies and organizations,” Dr. Jagsi added.
The infertility rate observed in the study could have potentially been skewed by the preponderance of younger respondents (resulting in underestimation) or by greater participation of those interested in the subject (resulting in overestimation), she noted. However, it aligns well with the rate in a study Dr. Jagsi and colleagues conducted among female physicians generally using somewhat different methods. That study was published in the Journal of Women’s Health.
Concern about radiation exposure and its potential reproductive health effects should not deter women from choosing radiation oncology as a specialty, according to Dr. Jagsi.
“Radiation exposure is actually very low in radiation oncology, much lower than in specialties like interventional cardiology, where physicians are in the room where fluoroscopy is being used. It is actually an important misconception about this field that merits correction,” she stressed. “Rather, the fertility concerns are related to the expectations of training and demands of work during the prime childbearing years more generally that can lead women to delay pregnancy, which is an issue common to all medical specialties.”
“The investigators’ conclusions are very reasonable,” Dr. Jagsi said. “Although one might quibble whether the exact proportions reflect the experiences of all women in the field perfectly due to the possibility of selection bias, one cannot question whether a substantial number of women are experiencing these challenges and that they merit intervention.”
The study did not receive specific funding. Dr. Lee and Dr. Jagsi disclosed no relevant conflicts of interest.
SOURCE: Lee A et al. ASTRO 2020, Abstract LBA 6.
Results from the survey were reported at the American Society for Radiation Oncology Annual Meeting 2020.
“Female radiation oncologists often spend their childbearing years in training and establishing careers,” commented lead investigator Anna Lee, MD, of the University of Texas MD Anderson Cancer Center in Houston.
“Currently, physician fertility and family planning are rarely discussed or taught in medical school or postgraduate training,” Dr. Lee said.
Dr. Lee and colleagues conducted a national anonymous cross-sectional online survey of female oncologists of all types and all career levels (including trainees). The team circulated a 39-item questionnaire exploring attitudes toward and experiences related to family planning and assisted reproductive technology (ART) by email and social media channels.
A total of 351 radiation oncologists participated, representing one-fifth of the specialty’s entire female workforce nationally and making this study the largest to date on family planning among these physicians.
Most respondents were aged 31-40 years (60%) and married (79%), had children (68%), and were in training (26%) or academic practice (48%).
Survey results
Fully 74% of respondents reported that their career plans strongly influenced the timing of when to start a family, and 29% said family planning considerations influenced their decision regarding their choice of academia versus private practice, Dr. Lee reported.
Overall, 24% of respondents indicated that they had difficulty with infertility or required fertility counseling/treatment, 66% said they wished fertility preservation was discussed at some point during their training, and 22% said either that ART would have benefited them if it had been available or that they were planning to or had already used fertility preservation.
On the topic of maternity leave, some respondents reported that their institution either had no formal leave policy during training or provided less than 1 month of leave (23%) and that they felt pressure to take less time off than was policy (15%).
“Of note, 32 women in our survey were not offered non–radiation-exposing assignments during pregnancy, and an additional 57 had to specifically ask for them,” Dr. Lee remarked.
About one-third of respondents each reported that they did not feel supported during training for issues related to fertility and/or pregnancy (33%) and that they experienced discrimination for being pregnant (32%) and taking maternity leave (30%).
“Systemic changes are necessary early in medical education and training to ensure women are supported and able to advance equitably in the field. As less than a third of the current radiation oncology workforce are women, improvement upon these issues will be necessary to draw more women into the field,” Dr. Lee commented. “Education on ART risks, benefits, and success rates can help physicians and those in training in their family planning, while the lack of education and structured policy can exacerbate the emotional, physical, and financial impact of infertility.
“Until recently, there has been a dearth of policy at the programmatic, institutional, and national level allowing time and protection for pregnancy and maternity leave,” she added. “Thankfully, this summer, the American Board of Medical Specialties announced a progressive leave policy for residents and fellows.”
The new policy, which goes into effect July 2021, allows a minimum of 6 weeks away without exhausting time allowed for vacation or sick leave and without requiring an extension in training.
When career and biology collide
“The collision of professional and biological clocks for women in medicine is an important issue highlighted by this study,” Reshma Jagsi, MD, DPhil, of the University of Michigan in Ann Arbor, said in an interview.
“Prior work focused on women in medicine more generally. A deeper dive into the experiences of women in a specific field may be even more compelling to drive change on the part of professional societies and organizations,” Dr. Jagsi added.
The infertility rate observed in the study could have potentially been skewed by the preponderance of younger respondents (resulting in underestimation) or by greater participation of those interested in the subject (resulting in overestimation), she noted. However, it aligns well with the rate in a study Dr. Jagsi and colleagues conducted among female physicians generally using somewhat different methods. That study was published in the Journal of Women’s Health.
Concern about radiation exposure and its potential reproductive health effects should not deter women from choosing radiation oncology as a specialty, according to Dr. Jagsi.
“Radiation exposure is actually very low in radiation oncology, much lower than in specialties like interventional cardiology, where physicians are in the room where fluoroscopy is being used. It is actually an important misconception about this field that merits correction,” she stressed. “Rather, the fertility concerns are related to the expectations of training and demands of work during the prime childbearing years more generally that can lead women to delay pregnancy, which is an issue common to all medical specialties.”
“The investigators’ conclusions are very reasonable,” Dr. Jagsi said. “Although one might quibble whether the exact proportions reflect the experiences of all women in the field perfectly due to the possibility of selection bias, one cannot question whether a substantial number of women are experiencing these challenges and that they merit intervention.”
The study did not receive specific funding. Dr. Lee and Dr. Jagsi disclosed no relevant conflicts of interest.
SOURCE: Lee A et al. ASTRO 2020, Abstract LBA 6.
FROM ASTRO 2020
Molecular features of medulloblastoma may help personalize radiotherapy
Results from this analysis were reported at the American Society for Radiation Oncology Annual Meeting 2020.
“Today, molecular diagnostics play a critical role in the classification of tumors, particularly medulloblastoma,” noted lead investigator Jeff M. Michalski, MD, of Washington University St. Louis, Mo.
“It is now recognized that medulloblastoma can be subgrouped into four distinct entities with unique demographics and tumor behaviors,” he said.
Those four groups are the SHH subgroup, the WNT subgroup, group 3, and group 4.
Study rationale and details
The benefits of current multimodality therapy in controlling and curing medulloblastoma come at the cost of toxicity, especially for younger patients, in terms of neurocognitive deficits, secondary cancers, and growth and neuro-endocrine abnormalities.
With this in mind, Dr. Michalski and colleagues conducted a phase 3 trial to test two strategies for reducing radiation in average-risk medulloblastoma without compromising outcomes.
After craniospinal irradiation (CSI), all patients were randomized to a radiation boost to the whole posterior fossa (PFRT) or an involved field volume (IFRT). Patients aged 8-21 years received CSI at the standard dose (23.4 Gy). Patients aged 3-7 years were randomized to standard-dose CSI or low-dose CSI (18 Gy).
There were 464 patients in whom PFRT to IFRT could be compared and 226 patients in whom standard and low-dose CSI could be compared.
Only 362 patients had sufficient tumor tissue to allow for classification into molecular subgroups. Among these patients, 43.1% fell into the group 4 subgroup, 21.0% into the group 3 subgroup, 18.2% into the SHH subgroup, and 17.7% into the WNT subgroup.
Survival results
The trial’s primary outcomes were event-free and overall survival. Events were defined as progression, recurrence, death, or second malignancy.
For the whole cohort, boost volume did not significantly affect outcomes. IFRT and PFRT yielded similar 5-year event-free survival (82.5% vs. 80.5%; P = .44) and overall survival (84.6% vs. 85.2%; P = .44). However, CSI dose did affect outcomes, with the low dose inferior to the standard dose on both 5-year event-free survival (71.4% vs. 82.9%; P = .028) and overall survival (77.5% vs. 85.6%; P = .049).
In analyses stratified by molecular subgroup, event-free survival did not differ significantly by boost volume within subgroups, except for the SHH subgroup, within which PFRT yielded worse outcomes (P = .018). Similarly, event-free survival did not differ significantly by CSI dose within subgroups, except for group 4, within which the low dose yielded a worse outcome (P = .047).
When specific genomic alterations were also considered, patients in the SHH group had worse outcomes if they had chromosome 14q loss, chromosome 10q loss, or p53 mutation. Patients in group 3 had worse outcomes if they had MYC amplification, iso-chromosome 17q, or both of these abnormalities.
No significant correlations were seen for group 4 patients, and there were too few patients in the WNT subgroup to assess correlations.
“Survival rates following reduced radiation boost volumes were comparable to standard treatment volumes for the primary tumor site. Interestingly, the SHH subgroup had worse event-free survival with whole posterior fossa radiation therapy,” Dr. Michalski commented. “Reduced dose of craniospinal axis irradiation was associated with higher event rates and worse survival, and group 4 was the primary subgroup that drove these inferior outcomes.”
“Specific genomic abnormalities are associated with worse outcomes, and future trials should consider subgroup and these genomic abnormalities in their study design,” he recommended.
‘A new era’ of risk stratification
Current evidence “leads us to conclude that certain molecular subgroups and specific genetic abnormalities within the subgroups are primary drivers of outcome and can be associated with far worse outcomes than what the conventional risk definition might suggest,” said invited discussant Stephanie Terezakis, MD, of the University of Minnesota in Minneapolis.
“In fact, differences in outcomes are greater between molecular subgroups and genomic abnormalities in large trial cohorts than between clinical trials when we use conventional risk definitions,” Dr. Terezakis said.
The ACNS0331 trial’s subgroup findings demonstrate that one size of therapy may not fit all, she elaborated. For example, some patients with favorable tumor biology may still be able to receive deintensified therapy and maintain excellent outcomes, whereas other patients with unfavorable tumor biology could potentially be newly classified as high risk and eligible for intensified therapy.
“This is the subject of ongoing discussions today to try to inform this next generation of trials, to see how we risk-stratify patients,” Dr. Terezakis concluded. “This model of conducting a national clinical trial with biologic endpoints has allowed us to usher in a new era where tumor biology may potentially guide our treatment approaches and lead to more personalized cancer care.”
The trial was funded by the National Cancer Institute, The Brain Tumor Charity, and St. Jude Children’s Research Hospital. Dr. Michalski disclosed relationships with ViewRay, Boston Scientific, Merck, and Blue Earth Diagnostics. Dr. Terezakis disclosed scientific grants from the Radiation Oncology Institute and the Sarcoma Foundation of America.
SOURCE: Michalski JM et al. ASTRO 2020, Abstract 1.
Results from this analysis were reported at the American Society for Radiation Oncology Annual Meeting 2020.
“Today, molecular diagnostics play a critical role in the classification of tumors, particularly medulloblastoma,” noted lead investigator Jeff M. Michalski, MD, of Washington University St. Louis, Mo.
“It is now recognized that medulloblastoma can be subgrouped into four distinct entities with unique demographics and tumor behaviors,” he said.
Those four groups are the SHH subgroup, the WNT subgroup, group 3, and group 4.
Study rationale and details
The benefits of current multimodality therapy in controlling and curing medulloblastoma come at the cost of toxicity, especially for younger patients, in terms of neurocognitive deficits, secondary cancers, and growth and neuro-endocrine abnormalities.
With this in mind, Dr. Michalski and colleagues conducted a phase 3 trial to test two strategies for reducing radiation in average-risk medulloblastoma without compromising outcomes.
After craniospinal irradiation (CSI), all patients were randomized to a radiation boost to the whole posterior fossa (PFRT) or an involved field volume (IFRT). Patients aged 8-21 years received CSI at the standard dose (23.4 Gy). Patients aged 3-7 years were randomized to standard-dose CSI or low-dose CSI (18 Gy).
There were 464 patients in whom PFRT to IFRT could be compared and 226 patients in whom standard and low-dose CSI could be compared.
Only 362 patients had sufficient tumor tissue to allow for classification into molecular subgroups. Among these patients, 43.1% fell into the group 4 subgroup, 21.0% into the group 3 subgroup, 18.2% into the SHH subgroup, and 17.7% into the WNT subgroup.
Survival results
The trial’s primary outcomes were event-free and overall survival. Events were defined as progression, recurrence, death, or second malignancy.
For the whole cohort, boost volume did not significantly affect outcomes. IFRT and PFRT yielded similar 5-year event-free survival (82.5% vs. 80.5%; P = .44) and overall survival (84.6% vs. 85.2%; P = .44). However, CSI dose did affect outcomes, with the low dose inferior to the standard dose on both 5-year event-free survival (71.4% vs. 82.9%; P = .028) and overall survival (77.5% vs. 85.6%; P = .049).
In analyses stratified by molecular subgroup, event-free survival did not differ significantly by boost volume within subgroups, except for the SHH subgroup, within which PFRT yielded worse outcomes (P = .018). Similarly, event-free survival did not differ significantly by CSI dose within subgroups, except for group 4, within which the low dose yielded a worse outcome (P = .047).
When specific genomic alterations were also considered, patients in the SHH group had worse outcomes if they had chromosome 14q loss, chromosome 10q loss, or p53 mutation. Patients in group 3 had worse outcomes if they had MYC amplification, iso-chromosome 17q, or both of these abnormalities.
No significant correlations were seen for group 4 patients, and there were too few patients in the WNT subgroup to assess correlations.
“Survival rates following reduced radiation boost volumes were comparable to standard treatment volumes for the primary tumor site. Interestingly, the SHH subgroup had worse event-free survival with whole posterior fossa radiation therapy,” Dr. Michalski commented. “Reduced dose of craniospinal axis irradiation was associated with higher event rates and worse survival, and group 4 was the primary subgroup that drove these inferior outcomes.”
“Specific genomic abnormalities are associated with worse outcomes, and future trials should consider subgroup and these genomic abnormalities in their study design,” he recommended.
‘A new era’ of risk stratification
Current evidence “leads us to conclude that certain molecular subgroups and specific genetic abnormalities within the subgroups are primary drivers of outcome and can be associated with far worse outcomes than what the conventional risk definition might suggest,” said invited discussant Stephanie Terezakis, MD, of the University of Minnesota in Minneapolis.
“In fact, differences in outcomes are greater between molecular subgroups and genomic abnormalities in large trial cohorts than between clinical trials when we use conventional risk definitions,” Dr. Terezakis said.
The ACNS0331 trial’s subgroup findings demonstrate that one size of therapy may not fit all, she elaborated. For example, some patients with favorable tumor biology may still be able to receive deintensified therapy and maintain excellent outcomes, whereas other patients with unfavorable tumor biology could potentially be newly classified as high risk and eligible for intensified therapy.
“This is the subject of ongoing discussions today to try to inform this next generation of trials, to see how we risk-stratify patients,” Dr. Terezakis concluded. “This model of conducting a national clinical trial with biologic endpoints has allowed us to usher in a new era where tumor biology may potentially guide our treatment approaches and lead to more personalized cancer care.”
The trial was funded by the National Cancer Institute, The Brain Tumor Charity, and St. Jude Children’s Research Hospital. Dr. Michalski disclosed relationships with ViewRay, Boston Scientific, Merck, and Blue Earth Diagnostics. Dr. Terezakis disclosed scientific grants from the Radiation Oncology Institute and the Sarcoma Foundation of America.
SOURCE: Michalski JM et al. ASTRO 2020, Abstract 1.
Results from this analysis were reported at the American Society for Radiation Oncology Annual Meeting 2020.
“Today, molecular diagnostics play a critical role in the classification of tumors, particularly medulloblastoma,” noted lead investigator Jeff M. Michalski, MD, of Washington University St. Louis, Mo.
“It is now recognized that medulloblastoma can be subgrouped into four distinct entities with unique demographics and tumor behaviors,” he said.
Those four groups are the SHH subgroup, the WNT subgroup, group 3, and group 4.
Study rationale and details
The benefits of current multimodality therapy in controlling and curing medulloblastoma come at the cost of toxicity, especially for younger patients, in terms of neurocognitive deficits, secondary cancers, and growth and neuro-endocrine abnormalities.
With this in mind, Dr. Michalski and colleagues conducted a phase 3 trial to test two strategies for reducing radiation in average-risk medulloblastoma without compromising outcomes.
After craniospinal irradiation (CSI), all patients were randomized to a radiation boost to the whole posterior fossa (PFRT) or an involved field volume (IFRT). Patients aged 8-21 years received CSI at the standard dose (23.4 Gy). Patients aged 3-7 years were randomized to standard-dose CSI or low-dose CSI (18 Gy).
There were 464 patients in whom PFRT to IFRT could be compared and 226 patients in whom standard and low-dose CSI could be compared.
Only 362 patients had sufficient tumor tissue to allow for classification into molecular subgroups. Among these patients, 43.1% fell into the group 4 subgroup, 21.0% into the group 3 subgroup, 18.2% into the SHH subgroup, and 17.7% into the WNT subgroup.
Survival results
The trial’s primary outcomes were event-free and overall survival. Events were defined as progression, recurrence, death, or second malignancy.
For the whole cohort, boost volume did not significantly affect outcomes. IFRT and PFRT yielded similar 5-year event-free survival (82.5% vs. 80.5%; P = .44) and overall survival (84.6% vs. 85.2%; P = .44). However, CSI dose did affect outcomes, with the low dose inferior to the standard dose on both 5-year event-free survival (71.4% vs. 82.9%; P = .028) and overall survival (77.5% vs. 85.6%; P = .049).
In analyses stratified by molecular subgroup, event-free survival did not differ significantly by boost volume within subgroups, except for the SHH subgroup, within which PFRT yielded worse outcomes (P = .018). Similarly, event-free survival did not differ significantly by CSI dose within subgroups, except for group 4, within which the low dose yielded a worse outcome (P = .047).
When specific genomic alterations were also considered, patients in the SHH group had worse outcomes if they had chromosome 14q loss, chromosome 10q loss, or p53 mutation. Patients in group 3 had worse outcomes if they had MYC amplification, iso-chromosome 17q, or both of these abnormalities.
No significant correlations were seen for group 4 patients, and there were too few patients in the WNT subgroup to assess correlations.
“Survival rates following reduced radiation boost volumes were comparable to standard treatment volumes for the primary tumor site. Interestingly, the SHH subgroup had worse event-free survival with whole posterior fossa radiation therapy,” Dr. Michalski commented. “Reduced dose of craniospinal axis irradiation was associated with higher event rates and worse survival, and group 4 was the primary subgroup that drove these inferior outcomes.”
“Specific genomic abnormalities are associated with worse outcomes, and future trials should consider subgroup and these genomic abnormalities in their study design,” he recommended.
‘A new era’ of risk stratification
Current evidence “leads us to conclude that certain molecular subgroups and specific genetic abnormalities within the subgroups are primary drivers of outcome and can be associated with far worse outcomes than what the conventional risk definition might suggest,” said invited discussant Stephanie Terezakis, MD, of the University of Minnesota in Minneapolis.
“In fact, differences in outcomes are greater between molecular subgroups and genomic abnormalities in large trial cohorts than between clinical trials when we use conventional risk definitions,” Dr. Terezakis said.
The ACNS0331 trial’s subgroup findings demonstrate that one size of therapy may not fit all, she elaborated. For example, some patients with favorable tumor biology may still be able to receive deintensified therapy and maintain excellent outcomes, whereas other patients with unfavorable tumor biology could potentially be newly classified as high risk and eligible for intensified therapy.
“This is the subject of ongoing discussions today to try to inform this next generation of trials, to see how we risk-stratify patients,” Dr. Terezakis concluded. “This model of conducting a national clinical trial with biologic endpoints has allowed us to usher in a new era where tumor biology may potentially guide our treatment approaches and lead to more personalized cancer care.”
The trial was funded by the National Cancer Institute, The Brain Tumor Charity, and St. Jude Children’s Research Hospital. Dr. Michalski disclosed relationships with ViewRay, Boston Scientific, Merck, and Blue Earth Diagnostics. Dr. Terezakis disclosed scientific grants from the Radiation Oncology Institute and the Sarcoma Foundation of America.
SOURCE: Michalski JM et al. ASTRO 2020, Abstract 1.
FROM ASTRO 2020
PET guidance for radiation therapy improves prostate cancer outcomes
The findings were reported in a plenary session at the American Society for Radiation Oncology Annual Meeting 2020.
“Quite frankly, this is an area where we are shooting in the dark with conventional imaging, and that’s where we think molecular imaging has a potential role,” noted coprincipal investigator Ashesh B. Jani, MD, of the Winship Cancer Institute of Emory University, Atlanta.
“We hypothesized that radiotherapy outcomes can be improved upon by PET by excluding patients with extrapelvic disease and also by improving treatment field decisions and target definition,” Dr. Jani added.
Patients with prostate cancer were eligible for EMPIRE-1 if they had undergone prostatectomy and had a detectable prostate-specific antigen (PSA) level but negative findings on conventional imaging (a bone scan plus abdominopelvic CT and/or MRI).
A total of 165 patients were randomized to RT guided by the conventional imaging alone or combined with PET imaging using the radiotracer fluciclovine (18F). Treatment decisions in the latter group were strictly based on where uptake was seen.
Study results
The trial’s primary endpoint was treatment failure, defined as a PSA level exceeding 0.2 ng/mL from nadir followed by another rise, a continued PSA rise despite RT, progression on imaging or digital rectal exam, or initiation of systemic therapy.
“Most imaging studies tend to focus on diagnostic accuracy, pathologic correlation, and decision changes. It’s a very high bar for an imaging study to influence failure rates,” Dr. Jani pointed out.
Adding 18F-PET to conventional imaging altered the treatment decision for 35.4% of patients in that group (P < .001). It also significantly altered a range of volumetric and dosimetric parameters.
At a median follow-up of 2.48 years, the 3-year rate of failure-free survival was 63.0% with conventional imaging alone and 75.5% with the addition of 18F-PET (P = .003). The corresponding 4-year rate was 51.2% and 75.5%, respectively (P < .001).
In multivariate analysis, the conventional imaging group had double the risk of failure events relative to the PET group (hazard ratio, 2.04; P = .033).
Provider-reported data showed no significant difference between imaging groups in maximum acute or late genitourinary toxicity and gastrointestinal toxicity. An analysis of patient-reported toxicity data is pending.
“Randomized trials of imaging tests with a primary cancer control endpoint are important but uncommonly done,” Dr. Jani commented. “This is the first such trial of PET over conventional imaging in the postprostatectomy radiotherapy setting.”
“Inclusion of fluciclovine resulted in a significant improvement in failure rate at 3 years. This warrants further investigation,” he maintained.
To that end, the investigators have launched the EMPIRE-2 trial, which is comparing RT guided by 18F-PET with PET using another radiotracer that is not yet approved by the Food and Drug Administration, gallium-68 prostate-specific membrane antigen.
Findings in context
“There are several remarkable aspects of the EMPIRE-1 trial worth noting,” said invited discussant Neha Vapiwala, MD, of the University of Pennsylvania, Philadelphia.
She commended the trial’s randomization, given a bias that more imaging is better, and the diversity of its participants that better reflects the general population of prostate cancer patients.
“The study procedures appear to be well tolerated despite a net overall increase in the radiation volume treated in the patients who underwent PET, although we do still await patient-reported toxicity,” Dr. Vapiwala noted. “Finally, a high bar was set, with a clinically meaningful primary endpoint for an imaging study.
“This study ultimately demonstrated that, in the PET arm, better selection with PET was able to result in better patient outcomes,” she maintained.
At the same time, Dr. Vapiwala recommended caution when reducing or withholding definitive local therapy based on PET results, as occurred in 14 patients.
“We must always be able to see the forest from the trees, and when evaluating our patients with PET scans, what we see and what we don’t see is just one piece of the puzzle. Existing level 1 evidence and oncologic principles must still apply,” she said. “While PET can help paint a more complete picture, it should not define the picture itself.”
The study was supported by the National Institutes of Health. Dr. Jani disclosed advisory board service for Blue Earth Diagnostics. Dr. Vapiwala disclosed no relevant conflicts of interest.
SOURCE: Jani A et al. ASTRO 2020, Abstract LBA1.
The findings were reported in a plenary session at the American Society for Radiation Oncology Annual Meeting 2020.
“Quite frankly, this is an area where we are shooting in the dark with conventional imaging, and that’s where we think molecular imaging has a potential role,” noted coprincipal investigator Ashesh B. Jani, MD, of the Winship Cancer Institute of Emory University, Atlanta.
“We hypothesized that radiotherapy outcomes can be improved upon by PET by excluding patients with extrapelvic disease and also by improving treatment field decisions and target definition,” Dr. Jani added.
Patients with prostate cancer were eligible for EMPIRE-1 if they had undergone prostatectomy and had a detectable prostate-specific antigen (PSA) level but negative findings on conventional imaging (a bone scan plus abdominopelvic CT and/or MRI).
A total of 165 patients were randomized to RT guided by the conventional imaging alone or combined with PET imaging using the radiotracer fluciclovine (18F). Treatment decisions in the latter group were strictly based on where uptake was seen.
Study results
The trial’s primary endpoint was treatment failure, defined as a PSA level exceeding 0.2 ng/mL from nadir followed by another rise, a continued PSA rise despite RT, progression on imaging or digital rectal exam, or initiation of systemic therapy.
“Most imaging studies tend to focus on diagnostic accuracy, pathologic correlation, and decision changes. It’s a very high bar for an imaging study to influence failure rates,” Dr. Jani pointed out.
Adding 18F-PET to conventional imaging altered the treatment decision for 35.4% of patients in that group (P < .001). It also significantly altered a range of volumetric and dosimetric parameters.
At a median follow-up of 2.48 years, the 3-year rate of failure-free survival was 63.0% with conventional imaging alone and 75.5% with the addition of 18F-PET (P = .003). The corresponding 4-year rate was 51.2% and 75.5%, respectively (P < .001).
In multivariate analysis, the conventional imaging group had double the risk of failure events relative to the PET group (hazard ratio, 2.04; P = .033).
Provider-reported data showed no significant difference between imaging groups in maximum acute or late genitourinary toxicity and gastrointestinal toxicity. An analysis of patient-reported toxicity data is pending.
“Randomized trials of imaging tests with a primary cancer control endpoint are important but uncommonly done,” Dr. Jani commented. “This is the first such trial of PET over conventional imaging in the postprostatectomy radiotherapy setting.”
“Inclusion of fluciclovine resulted in a significant improvement in failure rate at 3 years. This warrants further investigation,” he maintained.
To that end, the investigators have launched the EMPIRE-2 trial, which is comparing RT guided by 18F-PET with PET using another radiotracer that is not yet approved by the Food and Drug Administration, gallium-68 prostate-specific membrane antigen.
Findings in context
“There are several remarkable aspects of the EMPIRE-1 trial worth noting,” said invited discussant Neha Vapiwala, MD, of the University of Pennsylvania, Philadelphia.
She commended the trial’s randomization, given a bias that more imaging is better, and the diversity of its participants that better reflects the general population of prostate cancer patients.
“The study procedures appear to be well tolerated despite a net overall increase in the radiation volume treated in the patients who underwent PET, although we do still await patient-reported toxicity,” Dr. Vapiwala noted. “Finally, a high bar was set, with a clinically meaningful primary endpoint for an imaging study.
“This study ultimately demonstrated that, in the PET arm, better selection with PET was able to result in better patient outcomes,” she maintained.
At the same time, Dr. Vapiwala recommended caution when reducing or withholding definitive local therapy based on PET results, as occurred in 14 patients.
“We must always be able to see the forest from the trees, and when evaluating our patients with PET scans, what we see and what we don’t see is just one piece of the puzzle. Existing level 1 evidence and oncologic principles must still apply,” she said. “While PET can help paint a more complete picture, it should not define the picture itself.”
The study was supported by the National Institutes of Health. Dr. Jani disclosed advisory board service for Blue Earth Diagnostics. Dr. Vapiwala disclosed no relevant conflicts of interest.
SOURCE: Jani A et al. ASTRO 2020, Abstract LBA1.
The findings were reported in a plenary session at the American Society for Radiation Oncology Annual Meeting 2020.
“Quite frankly, this is an area where we are shooting in the dark with conventional imaging, and that’s where we think molecular imaging has a potential role,” noted coprincipal investigator Ashesh B. Jani, MD, of the Winship Cancer Institute of Emory University, Atlanta.
“We hypothesized that radiotherapy outcomes can be improved upon by PET by excluding patients with extrapelvic disease and also by improving treatment field decisions and target definition,” Dr. Jani added.
Patients with prostate cancer were eligible for EMPIRE-1 if they had undergone prostatectomy and had a detectable prostate-specific antigen (PSA) level but negative findings on conventional imaging (a bone scan plus abdominopelvic CT and/or MRI).
A total of 165 patients were randomized to RT guided by the conventional imaging alone or combined with PET imaging using the radiotracer fluciclovine (18F). Treatment decisions in the latter group were strictly based on where uptake was seen.
Study results
The trial’s primary endpoint was treatment failure, defined as a PSA level exceeding 0.2 ng/mL from nadir followed by another rise, a continued PSA rise despite RT, progression on imaging or digital rectal exam, or initiation of systemic therapy.
“Most imaging studies tend to focus on diagnostic accuracy, pathologic correlation, and decision changes. It’s a very high bar for an imaging study to influence failure rates,” Dr. Jani pointed out.
Adding 18F-PET to conventional imaging altered the treatment decision for 35.4% of patients in that group (P < .001). It also significantly altered a range of volumetric and dosimetric parameters.
At a median follow-up of 2.48 years, the 3-year rate of failure-free survival was 63.0% with conventional imaging alone and 75.5% with the addition of 18F-PET (P = .003). The corresponding 4-year rate was 51.2% and 75.5%, respectively (P < .001).
In multivariate analysis, the conventional imaging group had double the risk of failure events relative to the PET group (hazard ratio, 2.04; P = .033).
Provider-reported data showed no significant difference between imaging groups in maximum acute or late genitourinary toxicity and gastrointestinal toxicity. An analysis of patient-reported toxicity data is pending.
“Randomized trials of imaging tests with a primary cancer control endpoint are important but uncommonly done,” Dr. Jani commented. “This is the first such trial of PET over conventional imaging in the postprostatectomy radiotherapy setting.”
“Inclusion of fluciclovine resulted in a significant improvement in failure rate at 3 years. This warrants further investigation,” he maintained.
To that end, the investigators have launched the EMPIRE-2 trial, which is comparing RT guided by 18F-PET with PET using another radiotracer that is not yet approved by the Food and Drug Administration, gallium-68 prostate-specific membrane antigen.
Findings in context
“There are several remarkable aspects of the EMPIRE-1 trial worth noting,” said invited discussant Neha Vapiwala, MD, of the University of Pennsylvania, Philadelphia.
She commended the trial’s randomization, given a bias that more imaging is better, and the diversity of its participants that better reflects the general population of prostate cancer patients.
“The study procedures appear to be well tolerated despite a net overall increase in the radiation volume treated in the patients who underwent PET, although we do still await patient-reported toxicity,” Dr. Vapiwala noted. “Finally, a high bar was set, with a clinically meaningful primary endpoint for an imaging study.
“This study ultimately demonstrated that, in the PET arm, better selection with PET was able to result in better patient outcomes,” she maintained.
At the same time, Dr. Vapiwala recommended caution when reducing or withholding definitive local therapy based on PET results, as occurred in 14 patients.
“We must always be able to see the forest from the trees, and when evaluating our patients with PET scans, what we see and what we don’t see is just one piece of the puzzle. Existing level 1 evidence and oncologic principles must still apply,” she said. “While PET can help paint a more complete picture, it should not define the picture itself.”
The study was supported by the National Institutes of Health. Dr. Jani disclosed advisory board service for Blue Earth Diagnostics. Dr. Vapiwala disclosed no relevant conflicts of interest.
SOURCE: Jani A et al. ASTRO 2020, Abstract LBA1.
FROM ASTRO 2020
Single and multifraction SBRT found comparable for lung metastases
This was among key findings of a randomized, phase 2 trial reported at the American Society for Radiation Oncology Annual Meeting 2020.
“Most patients [with lung metastases] are treated with lifelong anticancer drug therapy only, with little prospect for long-term cancer control,” investigator Shankar Siva, MBBS, PhD, of Peter MacCallum Cancer Centre in Melbourne, said in a news briefing.
“However, some patients may have limited spread to the lungs and may be suitable for either surgery, which is an invasive approach, or SBRT, which is a noninvasive approach, with the aim to prolong long-term cancer control,” he added.
Patients and treatment
Dr. Siva and colleagues enrolled in their phase 2 trial (SAFRON II/TROG 13.01) 90 patients from 13 centers in Australia and New Zealand.
All patients had one to three lung metastases (from nonhematologic malignancies) that measured up to 5 cm in diameter and were located in the periphery.
The most common primaries were colorectal cancer (47%), lung cancer (11%), and kidney cancer (10%). The trial required that all primary and extrathoracic disease had been definitively treated.
The patients were randomized evenly to lung SBRT delivered with a single-fraction regimen (28 Gy in one fraction) or a multifraction regimen (48 Gy in four fractions) that netted the same biological equivalent dose.
Safety and efficacy
The two treatment groups did not differ significantly with respect to any-grade toxicities at 1 year, with the exception of higher rates of esophagitis and radiation dermatitis in the multifraction group, Dr. Siva reported.
The rate of grade 3 or worse toxicity at 1 year – the trial’s primary endpoint – was 5% with the single fraction and 3% with multiple fractions, with overlapping 80% confidence intervals, meeting the prespecified endpoint for acceptable toxicity.
The single-fraction group had two grade 3 events that resolved with intervention and no grade 4-5 events. The multifraction group had a single grade 5 event (fatal pneumonitis in a patient with underlying interstitial lung disease) and no grade 3-4 events.
The single-fraction and multifraction groups were also similar at 1 year on rates of freedom from local failure (93% and 95%, respectively), disease-free survival (59% and 60%, respectively), and overall survival (95% and 93%, respectively), with overlapping 95% CIs for each outcome.
Analyses of quality of life and cost-effectiveness are ongoing.
Applying the results: Useful in a pandemic?
“Single-session SBRT is safe, convenient, and noninvasive, and appears to be effective, to date, for lung secondaries. This approach may be considered as a one-stop, knockout type of approach for patients who have one to three metastases to the lung,” Dr. Siva proposed.
“These findings may have implications for treatment selection in a resource-constrained environment, such as the current global pandemic, when trying to reduce footfall or thoroughfare within a radiotherapy department, and it’s quite a convenient approach for patients,” he added.
“Stereotactic radiation has an obvious advantage over conventional radiation in several ways and may have a special advantage in the midst of the COVID-19 pandemic to reduce exposure to patients and our hospital personnel,” agreed news briefing moderator Sue S. Yom, MD, PhD, of the University of California, San Francisco.
However, use of stereotactic techniques remains controversial because they require technical precision and additional resources for planning and quality assurance, and they are often more expensive than conventional radiation therapy, she noted. Therefore, there must be evidence to justify their use in a palliative or metastatic setting.
The current trial is noteworthy for pushing the SBRT efficiency envelope, according to Dr. Yom.
“These findings are going to be confirmed by the study team with further follow-up at 3 years,” she pointed out. “If the findings of this study are maintained, it shows that patients with up to three metastatic tumors in the lung can have their treatment given in an extremely efficient manner over one session, which saves them time and hospital resources, and could be very significant to patients’ quality of life.”
The trial is sponsored by the Trans-Tasman Radiation Oncology Group and the Australasian Lung Cancer Trials Group. Dr. Siva disclosed relationships with Varian Industries, Merck, AstraZeneca, Bayer Pharmaceuticals, Bristol Meyers Squibb, and Reflexion. Dr. Yom disclosed no relevant conflicts.
SOURCE: Siva S et al. ASTRO 2020, Abstract 5.
This was among key findings of a randomized, phase 2 trial reported at the American Society for Radiation Oncology Annual Meeting 2020.
“Most patients [with lung metastases] are treated with lifelong anticancer drug therapy only, with little prospect for long-term cancer control,” investigator Shankar Siva, MBBS, PhD, of Peter MacCallum Cancer Centre in Melbourne, said in a news briefing.
“However, some patients may have limited spread to the lungs and may be suitable for either surgery, which is an invasive approach, or SBRT, which is a noninvasive approach, with the aim to prolong long-term cancer control,” he added.
Patients and treatment
Dr. Siva and colleagues enrolled in their phase 2 trial (SAFRON II/TROG 13.01) 90 patients from 13 centers in Australia and New Zealand.
All patients had one to three lung metastases (from nonhematologic malignancies) that measured up to 5 cm in diameter and were located in the periphery.
The most common primaries were colorectal cancer (47%), lung cancer (11%), and kidney cancer (10%). The trial required that all primary and extrathoracic disease had been definitively treated.
The patients were randomized evenly to lung SBRT delivered with a single-fraction regimen (28 Gy in one fraction) or a multifraction regimen (48 Gy in four fractions) that netted the same biological equivalent dose.
Safety and efficacy
The two treatment groups did not differ significantly with respect to any-grade toxicities at 1 year, with the exception of higher rates of esophagitis and radiation dermatitis in the multifraction group, Dr. Siva reported.
The rate of grade 3 or worse toxicity at 1 year – the trial’s primary endpoint – was 5% with the single fraction and 3% with multiple fractions, with overlapping 80% confidence intervals, meeting the prespecified endpoint for acceptable toxicity.
The single-fraction group had two grade 3 events that resolved with intervention and no grade 4-5 events. The multifraction group had a single grade 5 event (fatal pneumonitis in a patient with underlying interstitial lung disease) and no grade 3-4 events.
The single-fraction and multifraction groups were also similar at 1 year on rates of freedom from local failure (93% and 95%, respectively), disease-free survival (59% and 60%, respectively), and overall survival (95% and 93%, respectively), with overlapping 95% CIs for each outcome.
Analyses of quality of life and cost-effectiveness are ongoing.
Applying the results: Useful in a pandemic?
“Single-session SBRT is safe, convenient, and noninvasive, and appears to be effective, to date, for lung secondaries. This approach may be considered as a one-stop, knockout type of approach for patients who have one to three metastases to the lung,” Dr. Siva proposed.
“These findings may have implications for treatment selection in a resource-constrained environment, such as the current global pandemic, when trying to reduce footfall or thoroughfare within a radiotherapy department, and it’s quite a convenient approach for patients,” he added.
“Stereotactic radiation has an obvious advantage over conventional radiation in several ways and may have a special advantage in the midst of the COVID-19 pandemic to reduce exposure to patients and our hospital personnel,” agreed news briefing moderator Sue S. Yom, MD, PhD, of the University of California, San Francisco.
However, use of stereotactic techniques remains controversial because they require technical precision and additional resources for planning and quality assurance, and they are often more expensive than conventional radiation therapy, she noted. Therefore, there must be evidence to justify their use in a palliative or metastatic setting.
The current trial is noteworthy for pushing the SBRT efficiency envelope, according to Dr. Yom.
“These findings are going to be confirmed by the study team with further follow-up at 3 years,” she pointed out. “If the findings of this study are maintained, it shows that patients with up to three metastatic tumors in the lung can have their treatment given in an extremely efficient manner over one session, which saves them time and hospital resources, and could be very significant to patients’ quality of life.”
The trial is sponsored by the Trans-Tasman Radiation Oncology Group and the Australasian Lung Cancer Trials Group. Dr. Siva disclosed relationships with Varian Industries, Merck, AstraZeneca, Bayer Pharmaceuticals, Bristol Meyers Squibb, and Reflexion. Dr. Yom disclosed no relevant conflicts.
SOURCE: Siva S et al. ASTRO 2020, Abstract 5.
This was among key findings of a randomized, phase 2 trial reported at the American Society for Radiation Oncology Annual Meeting 2020.
“Most patients [with lung metastases] are treated with lifelong anticancer drug therapy only, with little prospect for long-term cancer control,” investigator Shankar Siva, MBBS, PhD, of Peter MacCallum Cancer Centre in Melbourne, said in a news briefing.
“However, some patients may have limited spread to the lungs and may be suitable for either surgery, which is an invasive approach, or SBRT, which is a noninvasive approach, with the aim to prolong long-term cancer control,” he added.
Patients and treatment
Dr. Siva and colleagues enrolled in their phase 2 trial (SAFRON II/TROG 13.01) 90 patients from 13 centers in Australia and New Zealand.
All patients had one to three lung metastases (from nonhematologic malignancies) that measured up to 5 cm in diameter and were located in the periphery.
The most common primaries were colorectal cancer (47%), lung cancer (11%), and kidney cancer (10%). The trial required that all primary and extrathoracic disease had been definitively treated.
The patients were randomized evenly to lung SBRT delivered with a single-fraction regimen (28 Gy in one fraction) or a multifraction regimen (48 Gy in four fractions) that netted the same biological equivalent dose.
Safety and efficacy
The two treatment groups did not differ significantly with respect to any-grade toxicities at 1 year, with the exception of higher rates of esophagitis and radiation dermatitis in the multifraction group, Dr. Siva reported.
The rate of grade 3 or worse toxicity at 1 year – the trial’s primary endpoint – was 5% with the single fraction and 3% with multiple fractions, with overlapping 80% confidence intervals, meeting the prespecified endpoint for acceptable toxicity.
The single-fraction group had two grade 3 events that resolved with intervention and no grade 4-5 events. The multifraction group had a single grade 5 event (fatal pneumonitis in a patient with underlying interstitial lung disease) and no grade 3-4 events.
The single-fraction and multifraction groups were also similar at 1 year on rates of freedom from local failure (93% and 95%, respectively), disease-free survival (59% and 60%, respectively), and overall survival (95% and 93%, respectively), with overlapping 95% CIs for each outcome.
Analyses of quality of life and cost-effectiveness are ongoing.
Applying the results: Useful in a pandemic?
“Single-session SBRT is safe, convenient, and noninvasive, and appears to be effective, to date, for lung secondaries. This approach may be considered as a one-stop, knockout type of approach for patients who have one to three metastases to the lung,” Dr. Siva proposed.
“These findings may have implications for treatment selection in a resource-constrained environment, such as the current global pandemic, when trying to reduce footfall or thoroughfare within a radiotherapy department, and it’s quite a convenient approach for patients,” he added.
“Stereotactic radiation has an obvious advantage over conventional radiation in several ways and may have a special advantage in the midst of the COVID-19 pandemic to reduce exposure to patients and our hospital personnel,” agreed news briefing moderator Sue S. Yom, MD, PhD, of the University of California, San Francisco.
However, use of stereotactic techniques remains controversial because they require technical precision and additional resources for planning and quality assurance, and they are often more expensive than conventional radiation therapy, she noted. Therefore, there must be evidence to justify their use in a palliative or metastatic setting.
The current trial is noteworthy for pushing the SBRT efficiency envelope, according to Dr. Yom.
“These findings are going to be confirmed by the study team with further follow-up at 3 years,” she pointed out. “If the findings of this study are maintained, it shows that patients with up to three metastatic tumors in the lung can have their treatment given in an extremely efficient manner over one session, which saves them time and hospital resources, and could be very significant to patients’ quality of life.”
The trial is sponsored by the Trans-Tasman Radiation Oncology Group and the Australasian Lung Cancer Trials Group. Dr. Siva disclosed relationships with Varian Industries, Merck, AstraZeneca, Bayer Pharmaceuticals, Bristol Meyers Squibb, and Reflexion. Dr. Yom disclosed no relevant conflicts.
SOURCE: Siva S et al. ASTRO 2020, Abstract 5.
FROM ASTRO 2020
Pathologic CR in HER2+ breast cancer predicts long-term survival
In fact, for the majority of women, pCR appears to be a marker of cure.
The trial was conducted among 455 women with HER2-positive breast cancer tumors measuring at least 2 cm who were randomized to neoadjuvant trastuzumab, lapatinib, or both drugs in combination, each together with paclitaxel, followed by more chemotherapy and more of the same targeted therapy after surgery.
Relative to trastuzumab alone, trastuzumab plus lapatinib improved rates of pCR, as shown by data published in The Lancet in 2012. However, the dual therapy did not significantly prolong event-free or overall survival, according to data published in The Lancet Oncology in 2014. Findings were similar in an update at a median follow-up of 6.7 years, published in the European Journal of Cancer in 2019.
Study investigator Paolo Nuciforo, MD, PhD, of the Vall d’Hebron Institute of Oncology in Barcelona, reported the trial’s final results, now at a median follow-up of 9.7 years, at the 12th European Breast Cancer Conference.
There were no significant differences in 9-year outcomes by specific HER2-targeted therapy. However, in a landmark analysis among women who were event free and still on follow-up 30 weeks after randomization, those achieving pCR with any of the therapies were 52% less likely to experience events and 63% less likely to die. Benefit was greatest in the subset of patients with hormone receptor–negative disease.
“The long-term follow-up confirms that, independent of the treatment regimen that we use – in this case, the dual blockade was with lapatinib, but similar results can be expected with other dual blockade – the pCR is a very robust surrogate biomarker of long-term survival,” Dr. Nuciforo commented in a press conference, noting that dual trastuzumab and pertuzumab has emerged as the standard of care.
“If we really pay attention to the curve, it’s maybe interesting to see that, after year 6, we actually don’t see any events in the pCR population. So this means that these patients are almost cured. We cannot say the word ‘cure’ in cancer, but it’s very reassuring to see the long-term survival analysis support the use of pCR as an endpoint,” he elaborated.
“Our results support the design of future trial concepts in HER2-positive early breast cancer which use pCR as an early efficacy readout of long-term benefit to escalate or deescalate therapy, particularly for hormone receptor–negative tumors,” Dr. Nuciforo concluded.
Support for current practice
“The study lends support for the current practice of risk-stratifying by pCR as well as making treatment decisions regarding T-DM1 [trastuzumab emtansine], and there hasn’t been a big change between 5-year and 9-year outcomes,” Lisa A. Carey, MD, of the University of North Carolina at Chapel Hill Lineberger Comprehensive Cancer Center, commented in an interview.
The lack of late events in the group with pCR technically meets the definition of cure, Dr. Carey said. “I think it speaks to the relatively early relapse risk in HER2-positive breast cancer and the impact of anti-HER2 therapy that carries forward. In general, these are findings similar to long-term findings of other trials and I suspect will be the same for any regimen.”
Although the analysis of dual lapatinib-trastuzumab therapy was underpowered, the trends seen align with favorable results in the adjuvant APHINITY trial (which combined trastuzumab with pertuzumab) and the neoadjuvant CALGB 40601 trial (which combined trastuzumab with lapatinib), according to Dr. Carey. “There has been a trend in every other study [of dual therapy] performed, so this is consistent.”
Study details
NeoALTTO is noteworthy for having the longest follow-up among all neoadjuvant studies of dual HER2 blockade in early breast cancer, Dr. Nuciforo said.
He reported no significant difference in survival between the treatment arms at 9 years.
The 9-year rate of event-free survival was 69% with lapatinib-trastuzumab, 63% with lapatinib alone, and 65% with trastuzumab alone. The corresponding 9-year rates of overall survival were 80%, 77%, and 76%, respectively.
However, there were significant differences in event-free and overall survival among women who achieved pCR and those who did not.
“pCR was achieved for almost twice as many patients treated with dual HER2 blockade, compared with patients in the single-agent arms,” Dr. Nuciforo pointed out. The pCR rate was 51.3% with lapatinib-trastuzumab, 24.7% with lapatinib alone, and 29.5% with trastuzumab alone.
Relative to peers who did not achieve pCR, women who did had better 9-year event-free survival (77% vs. 61%; adjusted hazard ratio, 0.48; P = .0008). The benefit was stronger in hormone receptor–negative disease (HR, 0.43; P = .002) than in hormone receptor–positive disease (HR, 0.60; P = .15).
The pattern was similar for overall survival at 9 years – 88% in those who achieved a pCR and 72% in those who did not (adjusted HR, 0.37; P = .0004). Again, greater benefit was seen in hormone receptor–negative disease (HR, 0.33; P = .002) than in hormone receptor–positive disease (HR, 0.44; P = .09).
“Biomarker-driven approaches may improve selection of those patients who are more likely to respond to anti-HER2 therapies,” Dr. Nuciforo proposed.
From 6 years onward, there were no additional fatal adverse events or nonfatal serious adverse events recorded, and no additional primary cardiac endpoints were recorded.
The study was funded by Novartis. Dr. Nuciforo and Dr. Carey disclosed no conflicts of interest.
SOURCE: Nuciforo P et al. EBCC-12 Virtual Conference, Abstract 23.
In fact, for the majority of women, pCR appears to be a marker of cure.
The trial was conducted among 455 women with HER2-positive breast cancer tumors measuring at least 2 cm who were randomized to neoadjuvant trastuzumab, lapatinib, or both drugs in combination, each together with paclitaxel, followed by more chemotherapy and more of the same targeted therapy after surgery.
Relative to trastuzumab alone, trastuzumab plus lapatinib improved rates of pCR, as shown by data published in The Lancet in 2012. However, the dual therapy did not significantly prolong event-free or overall survival, according to data published in The Lancet Oncology in 2014. Findings were similar in an update at a median follow-up of 6.7 years, published in the European Journal of Cancer in 2019.
Study investigator Paolo Nuciforo, MD, PhD, of the Vall d’Hebron Institute of Oncology in Barcelona, reported the trial’s final results, now at a median follow-up of 9.7 years, at the 12th European Breast Cancer Conference.
There were no significant differences in 9-year outcomes by specific HER2-targeted therapy. However, in a landmark analysis among women who were event free and still on follow-up 30 weeks after randomization, those achieving pCR with any of the therapies were 52% less likely to experience events and 63% less likely to die. Benefit was greatest in the subset of patients with hormone receptor–negative disease.
“The long-term follow-up confirms that, independent of the treatment regimen that we use – in this case, the dual blockade was with lapatinib, but similar results can be expected with other dual blockade – the pCR is a very robust surrogate biomarker of long-term survival,” Dr. Nuciforo commented in a press conference, noting that dual trastuzumab and pertuzumab has emerged as the standard of care.
“If we really pay attention to the curve, it’s maybe interesting to see that, after year 6, we actually don’t see any events in the pCR population. So this means that these patients are almost cured. We cannot say the word ‘cure’ in cancer, but it’s very reassuring to see the long-term survival analysis support the use of pCR as an endpoint,” he elaborated.
“Our results support the design of future trial concepts in HER2-positive early breast cancer which use pCR as an early efficacy readout of long-term benefit to escalate or deescalate therapy, particularly for hormone receptor–negative tumors,” Dr. Nuciforo concluded.
Support for current practice
“The study lends support for the current practice of risk-stratifying by pCR as well as making treatment decisions regarding T-DM1 [trastuzumab emtansine], and there hasn’t been a big change between 5-year and 9-year outcomes,” Lisa A. Carey, MD, of the University of North Carolina at Chapel Hill Lineberger Comprehensive Cancer Center, commented in an interview.
The lack of late events in the group with pCR technically meets the definition of cure, Dr. Carey said. “I think it speaks to the relatively early relapse risk in HER2-positive breast cancer and the impact of anti-HER2 therapy that carries forward. In general, these are findings similar to long-term findings of other trials and I suspect will be the same for any regimen.”
Although the analysis of dual lapatinib-trastuzumab therapy was underpowered, the trends seen align with favorable results in the adjuvant APHINITY trial (which combined trastuzumab with pertuzumab) and the neoadjuvant CALGB 40601 trial (which combined trastuzumab with lapatinib), according to Dr. Carey. “There has been a trend in every other study [of dual therapy] performed, so this is consistent.”
Study details
NeoALTTO is noteworthy for having the longest follow-up among all neoadjuvant studies of dual HER2 blockade in early breast cancer, Dr. Nuciforo said.
He reported no significant difference in survival between the treatment arms at 9 years.
The 9-year rate of event-free survival was 69% with lapatinib-trastuzumab, 63% with lapatinib alone, and 65% with trastuzumab alone. The corresponding 9-year rates of overall survival were 80%, 77%, and 76%, respectively.
However, there were significant differences in event-free and overall survival among women who achieved pCR and those who did not.
“pCR was achieved for almost twice as many patients treated with dual HER2 blockade, compared with patients in the single-agent arms,” Dr. Nuciforo pointed out. The pCR rate was 51.3% with lapatinib-trastuzumab, 24.7% with lapatinib alone, and 29.5% with trastuzumab alone.
Relative to peers who did not achieve pCR, women who did had better 9-year event-free survival (77% vs. 61%; adjusted hazard ratio, 0.48; P = .0008). The benefit was stronger in hormone receptor–negative disease (HR, 0.43; P = .002) than in hormone receptor–positive disease (HR, 0.60; P = .15).
The pattern was similar for overall survival at 9 years – 88% in those who achieved a pCR and 72% in those who did not (adjusted HR, 0.37; P = .0004). Again, greater benefit was seen in hormone receptor–negative disease (HR, 0.33; P = .002) than in hormone receptor–positive disease (HR, 0.44; P = .09).
“Biomarker-driven approaches may improve selection of those patients who are more likely to respond to anti-HER2 therapies,” Dr. Nuciforo proposed.
From 6 years onward, there were no additional fatal adverse events or nonfatal serious adverse events recorded, and no additional primary cardiac endpoints were recorded.
The study was funded by Novartis. Dr. Nuciforo and Dr. Carey disclosed no conflicts of interest.
SOURCE: Nuciforo P et al. EBCC-12 Virtual Conference, Abstract 23.
In fact, for the majority of women, pCR appears to be a marker of cure.
The trial was conducted among 455 women with HER2-positive breast cancer tumors measuring at least 2 cm who were randomized to neoadjuvant trastuzumab, lapatinib, or both drugs in combination, each together with paclitaxel, followed by more chemotherapy and more of the same targeted therapy after surgery.
Relative to trastuzumab alone, trastuzumab plus lapatinib improved rates of pCR, as shown by data published in The Lancet in 2012. However, the dual therapy did not significantly prolong event-free or overall survival, according to data published in The Lancet Oncology in 2014. Findings were similar in an update at a median follow-up of 6.7 years, published in the European Journal of Cancer in 2019.
Study investigator Paolo Nuciforo, MD, PhD, of the Vall d’Hebron Institute of Oncology in Barcelona, reported the trial’s final results, now at a median follow-up of 9.7 years, at the 12th European Breast Cancer Conference.
There were no significant differences in 9-year outcomes by specific HER2-targeted therapy. However, in a landmark analysis among women who were event free and still on follow-up 30 weeks after randomization, those achieving pCR with any of the therapies were 52% less likely to experience events and 63% less likely to die. Benefit was greatest in the subset of patients with hormone receptor–negative disease.
“The long-term follow-up confirms that, independent of the treatment regimen that we use – in this case, the dual blockade was with lapatinib, but similar results can be expected with other dual blockade – the pCR is a very robust surrogate biomarker of long-term survival,” Dr. Nuciforo commented in a press conference, noting that dual trastuzumab and pertuzumab has emerged as the standard of care.
“If we really pay attention to the curve, it’s maybe interesting to see that, after year 6, we actually don’t see any events in the pCR population. So this means that these patients are almost cured. We cannot say the word ‘cure’ in cancer, but it’s very reassuring to see the long-term survival analysis support the use of pCR as an endpoint,” he elaborated.
“Our results support the design of future trial concepts in HER2-positive early breast cancer which use pCR as an early efficacy readout of long-term benefit to escalate or deescalate therapy, particularly for hormone receptor–negative tumors,” Dr. Nuciforo concluded.
Support for current practice
“The study lends support for the current practice of risk-stratifying by pCR as well as making treatment decisions regarding T-DM1 [trastuzumab emtansine], and there hasn’t been a big change between 5-year and 9-year outcomes,” Lisa A. Carey, MD, of the University of North Carolina at Chapel Hill Lineberger Comprehensive Cancer Center, commented in an interview.
The lack of late events in the group with pCR technically meets the definition of cure, Dr. Carey said. “I think it speaks to the relatively early relapse risk in HER2-positive breast cancer and the impact of anti-HER2 therapy that carries forward. In general, these are findings similar to long-term findings of other trials and I suspect will be the same for any regimen.”
Although the analysis of dual lapatinib-trastuzumab therapy was underpowered, the trends seen align with favorable results in the adjuvant APHINITY trial (which combined trastuzumab with pertuzumab) and the neoadjuvant CALGB 40601 trial (which combined trastuzumab with lapatinib), according to Dr. Carey. “There has been a trend in every other study [of dual therapy] performed, so this is consistent.”
Study details
NeoALTTO is noteworthy for having the longest follow-up among all neoadjuvant studies of dual HER2 blockade in early breast cancer, Dr. Nuciforo said.
He reported no significant difference in survival between the treatment arms at 9 years.
The 9-year rate of event-free survival was 69% with lapatinib-trastuzumab, 63% with lapatinib alone, and 65% with trastuzumab alone. The corresponding 9-year rates of overall survival were 80%, 77%, and 76%, respectively.
However, there were significant differences in event-free and overall survival among women who achieved pCR and those who did not.
“pCR was achieved for almost twice as many patients treated with dual HER2 blockade, compared with patients in the single-agent arms,” Dr. Nuciforo pointed out. The pCR rate was 51.3% with lapatinib-trastuzumab, 24.7% with lapatinib alone, and 29.5% with trastuzumab alone.
Relative to peers who did not achieve pCR, women who did had better 9-year event-free survival (77% vs. 61%; adjusted hazard ratio, 0.48; P = .0008). The benefit was stronger in hormone receptor–negative disease (HR, 0.43; P = .002) than in hormone receptor–positive disease (HR, 0.60; P = .15).
The pattern was similar for overall survival at 9 years – 88% in those who achieved a pCR and 72% in those who did not (adjusted HR, 0.37; P = .0004). Again, greater benefit was seen in hormone receptor–negative disease (HR, 0.33; P = .002) than in hormone receptor–positive disease (HR, 0.44; P = .09).
“Biomarker-driven approaches may improve selection of those patients who are more likely to respond to anti-HER2 therapies,” Dr. Nuciforo proposed.
From 6 years onward, there were no additional fatal adverse events or nonfatal serious adverse events recorded, and no additional primary cardiac endpoints were recorded.
The study was funded by Novartis. Dr. Nuciforo and Dr. Carey disclosed no conflicts of interest.
SOURCE: Nuciforo P et al. EBCC-12 Virtual Conference, Abstract 23.
FROM EBCC-12 VIRTUAL CONFERENCE
Combined features of benign breast disease tied to breast cancer risk
“Benign breast disease is a key risk factor for breast cancer risk prediction,” commented presenting investigator Marta Román, PhD, of the Hospital del Mar Medical Research Institute in Barcelona. “Those women who have had a benign breast disease diagnosis have an increased risk that lasts for at least 20 years.”
To assess the combined influence of various attributes of benign breast disease, the investigators studied 629,087 women, aged 50-69 years, in Spain who underwent population-based mammographic breast cancer screening during 1994-2015 and did not have breast cancer at their prevalent (first) screen. The mean follow-up was 7.8 years.
Results showed that breast cancer risk was about three times higher for women with benign breast disease that was proliferative or that was detected on an incident screen, relative to peers with no benign breast disease. When combinations of factors were considered, breast cancer risk was most elevated – more than four times higher – for women with proliferative benign breast disease with atypia detected on an incident screen.
“We believe that these findings should be considered when discussing risk-based personalized screening strategies because these differences between prevalent and incident screens might be important if we want to personalize the screening, whether it’s the first time a woman comes to the screening program or a subsequent screen,” Dr. Román said.
Practice changing?
The study’s large size and population-based design, likely permitting capture of most biopsy results, are strengths, Mark David Pearlman, MD, of the University of Michigan, Ann Arbor, commented in an interview.
But its observational, retrospective nature opens the study up to biases, such as uncertainty as to how many women were symptomatic at the time of their mammogram and the likelihood of heightened monitoring after a biopsy showing hyperplasia, Dr. Pearlman cautioned.
“Moreover, the relative risk in this study for proliferative benign breast disease without atypia is substantially higher than prior observations of this group. This discrepancy was not discussed by the authors,” Dr. Pearlman said.
At present, women’s risk of breast cancer is predicted using well-validated models that include the question of prior breast biopsies, such as the Gail Model, the Tyrer-Cuzick model (IBIS tool), and the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm, Dr. Pearlman noted.
“This study, without further validation within a model, would not change risk assessment,” he said, disagreeing with the investigators’ conclusions. “What I would say is that further study to determine how to use this observation to decide if any change in screening or management should occur would be more appropriate.”
Study details
The 629,087 women studied underwent 2,327,384 screens, Dr. Román reported. In total, screening detected 9,184 cases of benign breast disease and 9,431 breast cancers.
Breast cancer was diagnosed in 2.4% and 3.0% of women with benign breast disease detected on prevalent and incident screens, respectively, compared with 1.5% of women without any benign breast disease detected.
Elevation of breast cancer risk varied across benign breast disease subtype. Relative to peers without any benign disease, risk was significantly elevated for women with nonproliferative disease (adjusted hazard ratio, 1.95), proliferative disease without atypia (aHR, 3.19), and proliferative disease with atypia (aHR, 3.82).
Similarly, elevation of risk varied depending on the screening at which the benign disease was detected. Risk was significantly elevated when the disease was found at prevalent screens (aHR, 1.87) and more so when it was found at incident screens (aHR, 2.67).
There was no significant interaction of these two factors (P = .83). However, when combinations were considered, risk was highest for women with proliferative benign breast disease with atypia detected on incident screens (aHR, 4.35) or prevalent screens (aHR, 3.35), and women with proliferative benign breast disease without atypia detected on incident screens (aHR, 3.83).
This study was supported by grants from Instituto de Salud Carlos III FEDER and by the Research Network on Health Services in Chronic Diseases. Dr. Román and Dr. Pearlman disclosed no conflicts of interest.
SOURCE: Román M et al. EBCC-12 Virtual Conference, Abstract 15.
“Benign breast disease is a key risk factor for breast cancer risk prediction,” commented presenting investigator Marta Román, PhD, of the Hospital del Mar Medical Research Institute in Barcelona. “Those women who have had a benign breast disease diagnosis have an increased risk that lasts for at least 20 years.”
To assess the combined influence of various attributes of benign breast disease, the investigators studied 629,087 women, aged 50-69 years, in Spain who underwent population-based mammographic breast cancer screening during 1994-2015 and did not have breast cancer at their prevalent (first) screen. The mean follow-up was 7.8 years.
Results showed that breast cancer risk was about three times higher for women with benign breast disease that was proliferative or that was detected on an incident screen, relative to peers with no benign breast disease. When combinations of factors were considered, breast cancer risk was most elevated – more than four times higher – for women with proliferative benign breast disease with atypia detected on an incident screen.
“We believe that these findings should be considered when discussing risk-based personalized screening strategies because these differences between prevalent and incident screens might be important if we want to personalize the screening, whether it’s the first time a woman comes to the screening program or a subsequent screen,” Dr. Román said.
Practice changing?
The study’s large size and population-based design, likely permitting capture of most biopsy results, are strengths, Mark David Pearlman, MD, of the University of Michigan, Ann Arbor, commented in an interview.
But its observational, retrospective nature opens the study up to biases, such as uncertainty as to how many women were symptomatic at the time of their mammogram and the likelihood of heightened monitoring after a biopsy showing hyperplasia, Dr. Pearlman cautioned.
“Moreover, the relative risk in this study for proliferative benign breast disease without atypia is substantially higher than prior observations of this group. This discrepancy was not discussed by the authors,” Dr. Pearlman said.
At present, women’s risk of breast cancer is predicted using well-validated models that include the question of prior breast biopsies, such as the Gail Model, the Tyrer-Cuzick model (IBIS tool), and the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm, Dr. Pearlman noted.
“This study, without further validation within a model, would not change risk assessment,” he said, disagreeing with the investigators’ conclusions. “What I would say is that further study to determine how to use this observation to decide if any change in screening or management should occur would be more appropriate.”
Study details
The 629,087 women studied underwent 2,327,384 screens, Dr. Román reported. In total, screening detected 9,184 cases of benign breast disease and 9,431 breast cancers.
Breast cancer was diagnosed in 2.4% and 3.0% of women with benign breast disease detected on prevalent and incident screens, respectively, compared with 1.5% of women without any benign breast disease detected.
Elevation of breast cancer risk varied across benign breast disease subtype. Relative to peers without any benign disease, risk was significantly elevated for women with nonproliferative disease (adjusted hazard ratio, 1.95), proliferative disease without atypia (aHR, 3.19), and proliferative disease with atypia (aHR, 3.82).
Similarly, elevation of risk varied depending on the screening at which the benign disease was detected. Risk was significantly elevated when the disease was found at prevalent screens (aHR, 1.87) and more so when it was found at incident screens (aHR, 2.67).
There was no significant interaction of these two factors (P = .83). However, when combinations were considered, risk was highest for women with proliferative benign breast disease with atypia detected on incident screens (aHR, 4.35) or prevalent screens (aHR, 3.35), and women with proliferative benign breast disease without atypia detected on incident screens (aHR, 3.83).
This study was supported by grants from Instituto de Salud Carlos III FEDER and by the Research Network on Health Services in Chronic Diseases. Dr. Román and Dr. Pearlman disclosed no conflicts of interest.
SOURCE: Román M et al. EBCC-12 Virtual Conference, Abstract 15.
“Benign breast disease is a key risk factor for breast cancer risk prediction,” commented presenting investigator Marta Román, PhD, of the Hospital del Mar Medical Research Institute in Barcelona. “Those women who have had a benign breast disease diagnosis have an increased risk that lasts for at least 20 years.”
To assess the combined influence of various attributes of benign breast disease, the investigators studied 629,087 women, aged 50-69 years, in Spain who underwent population-based mammographic breast cancer screening during 1994-2015 and did not have breast cancer at their prevalent (first) screen. The mean follow-up was 7.8 years.
Results showed that breast cancer risk was about three times higher for women with benign breast disease that was proliferative or that was detected on an incident screen, relative to peers with no benign breast disease. When combinations of factors were considered, breast cancer risk was most elevated – more than four times higher – for women with proliferative benign breast disease with atypia detected on an incident screen.
“We believe that these findings should be considered when discussing risk-based personalized screening strategies because these differences between prevalent and incident screens might be important if we want to personalize the screening, whether it’s the first time a woman comes to the screening program or a subsequent screen,” Dr. Román said.
Practice changing?
The study’s large size and population-based design, likely permitting capture of most biopsy results, are strengths, Mark David Pearlman, MD, of the University of Michigan, Ann Arbor, commented in an interview.
But its observational, retrospective nature opens the study up to biases, such as uncertainty as to how many women were symptomatic at the time of their mammogram and the likelihood of heightened monitoring after a biopsy showing hyperplasia, Dr. Pearlman cautioned.
“Moreover, the relative risk in this study for proliferative benign breast disease without atypia is substantially higher than prior observations of this group. This discrepancy was not discussed by the authors,” Dr. Pearlman said.
At present, women’s risk of breast cancer is predicted using well-validated models that include the question of prior breast biopsies, such as the Gail Model, the Tyrer-Cuzick model (IBIS tool), and the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm, Dr. Pearlman noted.
“This study, without further validation within a model, would not change risk assessment,” he said, disagreeing with the investigators’ conclusions. “What I would say is that further study to determine how to use this observation to decide if any change in screening or management should occur would be more appropriate.”
Study details
The 629,087 women studied underwent 2,327,384 screens, Dr. Román reported. In total, screening detected 9,184 cases of benign breast disease and 9,431 breast cancers.
Breast cancer was diagnosed in 2.4% and 3.0% of women with benign breast disease detected on prevalent and incident screens, respectively, compared with 1.5% of women without any benign breast disease detected.
Elevation of breast cancer risk varied across benign breast disease subtype. Relative to peers without any benign disease, risk was significantly elevated for women with nonproliferative disease (adjusted hazard ratio, 1.95), proliferative disease without atypia (aHR, 3.19), and proliferative disease with atypia (aHR, 3.82).
Similarly, elevation of risk varied depending on the screening at which the benign disease was detected. Risk was significantly elevated when the disease was found at prevalent screens (aHR, 1.87) and more so when it was found at incident screens (aHR, 2.67).
There was no significant interaction of these two factors (P = .83). However, when combinations were considered, risk was highest for women with proliferative benign breast disease with atypia detected on incident screens (aHR, 4.35) or prevalent screens (aHR, 3.35), and women with proliferative benign breast disease without atypia detected on incident screens (aHR, 3.83).
This study was supported by grants from Instituto de Salud Carlos III FEDER and by the Research Network on Health Services in Chronic Diseases. Dr. Román and Dr. Pearlman disclosed no conflicts of interest.
SOURCE: Román M et al. EBCC-12 Virtual Conference, Abstract 15.
FROM EBCC-12 VIRTUAL CONFERENCE
Gene signature found similarly prognostic in ILC and IDC
ILC is enriched with features indicating low proliferative activity, noted investigator Otto Metzger, MD, of the Dana Farber Cancer Institute in Boston.
“Data from retrospective series have indicated no benefit with adjuvant chemotherapy for patients diagnosed with early-stage ILC,” he said. “It’s fair to say that chemotherapy decisions for patients with ILC remain controversial.”
With this in mind, Dr. Metzger and colleagues analyzed data for 5,313 women who underwent surgery for early-stage breast cancer (node-negative or up to three positive lymph nodes) and were risk-stratified to receive or skip adjuvant chemotherapy based on both clinical risk and the MammaPrint score for genomic risk. Fully 44% of women with ILC had discordant clinical and genomic risks.
With a median follow-up of 8.7 years, the 5-year rate of distant metastasis–free survival among all patients classified as genomic high risk was 92.1% in women with IDC and 88.1% in women with ILC, with overlapping 95% confidence intervals. Rates of distant metastasis–free survival for patients with genomic low risk were 96.4% in women with IDC and 96.6% in women with ILC, again with confidence intervals that overlapped.
The pattern was essentially the same for overall survival, and results carried over into 8-year outcomes as well.
“We believe that MammaPrint is a clinically useful test for patients diagnosed with ILC,” Dr. Metzger said. “There are similar survival outcomes for ILC and IDC when matched by genomic risk. This is an important message.”
It should be standard to omit chemotherapy for patients who have ILC classified as high clinical risk but low genomic risk by MammaPrint, Dr. Metzger recommended. “By contrast, MammaPrint should facilitate chemotherapy treatment decisions for patients diagnosed with ILC and high-risk MammaPrint,” he said.
Prognostic, but predictive?
“This is a well-designed prospective multicenter trial and provides the best evidence to date that MammaPrint is an important prognostic tool for ILC,” Todd Tuttle, MD, of University of Minnesota in Minneapolis, said in an interview.
Dr. Tuttle said he mainly uses the MammaPrint test and the OncoType 21-gene recurrence score to estimate prognosis for his patients with ILC.
These new data establish that MammaPrint is prognostic in ILC, but the value of MammaPrint’s genomic high risk result for making the decision about chemotherapy is still unclear, according to Dr. Tuttle.
“I don’t think we know whether MammaPrint can predict the benefit of chemotherapy for patients with stage I or II ILC,” he elaborated. “We need further high-quality studies such as this one to determine the best treatment strategies for ILC, which is a difficult breast cancer.”
Study details
Of the 5,313 patients studied, 487 had ILC (255 classic and 232 variant) and 4,826 had IDC according to central pathology assessment, Dr. Metzger reported.
MammaPrint classified 39% of the IDC group and 16% of the ILC group (10% of those with classic disease and 23% of those with variant disease) as genomically high risk for recurrence. The Adjuvant! Online tool classified 48.3% of ILC and 51.5% of IDC patients as clinically high risk.
Among the 44% of women with ILC having discordant genomic and clinical risk, discordance was usually due to the combination of low genomic risk and high clinical risk, seen in 38%.
The curves for 5-year distant metastasis–free survival stratified by genomic risk essentially overlapped for the IDC and ILC groups. Furthermore, there was no significant interaction of histologic type and genomic risk on this outcome (P = .547).
The 5-year rate of overall survival among women with genomic high risk was 95.6% in the IDC group and 93.5% in the ILC group. Among women with genomic low risk, 5-year overall survival was 98.1% in the IDC group and 97.7% in the ILC group, again with overlapping confidence intervals within each risk category.
The study was funded with support from the Breast Cancer Research Foundation. Dr. Metzger disclosed consulting fees from AbbVie, Genentech, Roche, and Pfizer. Dr. Tuttle disclosed no conflicts of interest.
SOURCE: Metzger O et al. EBCC-12 Virtual Conference. Abstract 6.
ILC is enriched with features indicating low proliferative activity, noted investigator Otto Metzger, MD, of the Dana Farber Cancer Institute in Boston.
“Data from retrospective series have indicated no benefit with adjuvant chemotherapy for patients diagnosed with early-stage ILC,” he said. “It’s fair to say that chemotherapy decisions for patients with ILC remain controversial.”
With this in mind, Dr. Metzger and colleagues analyzed data for 5,313 women who underwent surgery for early-stage breast cancer (node-negative or up to three positive lymph nodes) and were risk-stratified to receive or skip adjuvant chemotherapy based on both clinical risk and the MammaPrint score for genomic risk. Fully 44% of women with ILC had discordant clinical and genomic risks.
With a median follow-up of 8.7 years, the 5-year rate of distant metastasis–free survival among all patients classified as genomic high risk was 92.1% in women with IDC and 88.1% in women with ILC, with overlapping 95% confidence intervals. Rates of distant metastasis–free survival for patients with genomic low risk were 96.4% in women with IDC and 96.6% in women with ILC, again with confidence intervals that overlapped.
The pattern was essentially the same for overall survival, and results carried over into 8-year outcomes as well.
“We believe that MammaPrint is a clinically useful test for patients diagnosed with ILC,” Dr. Metzger said. “There are similar survival outcomes for ILC and IDC when matched by genomic risk. This is an important message.”
It should be standard to omit chemotherapy for patients who have ILC classified as high clinical risk but low genomic risk by MammaPrint, Dr. Metzger recommended. “By contrast, MammaPrint should facilitate chemotherapy treatment decisions for patients diagnosed with ILC and high-risk MammaPrint,” he said.
Prognostic, but predictive?
“This is a well-designed prospective multicenter trial and provides the best evidence to date that MammaPrint is an important prognostic tool for ILC,” Todd Tuttle, MD, of University of Minnesota in Minneapolis, said in an interview.
Dr. Tuttle said he mainly uses the MammaPrint test and the OncoType 21-gene recurrence score to estimate prognosis for his patients with ILC.
These new data establish that MammaPrint is prognostic in ILC, but the value of MammaPrint’s genomic high risk result for making the decision about chemotherapy is still unclear, according to Dr. Tuttle.
“I don’t think we know whether MammaPrint can predict the benefit of chemotherapy for patients with stage I or II ILC,” he elaborated. “We need further high-quality studies such as this one to determine the best treatment strategies for ILC, which is a difficult breast cancer.”
Study details
Of the 5,313 patients studied, 487 had ILC (255 classic and 232 variant) and 4,826 had IDC according to central pathology assessment, Dr. Metzger reported.
MammaPrint classified 39% of the IDC group and 16% of the ILC group (10% of those with classic disease and 23% of those with variant disease) as genomically high risk for recurrence. The Adjuvant! Online tool classified 48.3% of ILC and 51.5% of IDC patients as clinically high risk.
Among the 44% of women with ILC having discordant genomic and clinical risk, discordance was usually due to the combination of low genomic risk and high clinical risk, seen in 38%.
The curves for 5-year distant metastasis–free survival stratified by genomic risk essentially overlapped for the IDC and ILC groups. Furthermore, there was no significant interaction of histologic type and genomic risk on this outcome (P = .547).
The 5-year rate of overall survival among women with genomic high risk was 95.6% in the IDC group and 93.5% in the ILC group. Among women with genomic low risk, 5-year overall survival was 98.1% in the IDC group and 97.7% in the ILC group, again with overlapping confidence intervals within each risk category.
The study was funded with support from the Breast Cancer Research Foundation. Dr. Metzger disclosed consulting fees from AbbVie, Genentech, Roche, and Pfizer. Dr. Tuttle disclosed no conflicts of interest.
SOURCE: Metzger O et al. EBCC-12 Virtual Conference. Abstract 6.
ILC is enriched with features indicating low proliferative activity, noted investigator Otto Metzger, MD, of the Dana Farber Cancer Institute in Boston.
“Data from retrospective series have indicated no benefit with adjuvant chemotherapy for patients diagnosed with early-stage ILC,” he said. “It’s fair to say that chemotherapy decisions for patients with ILC remain controversial.”
With this in mind, Dr. Metzger and colleagues analyzed data for 5,313 women who underwent surgery for early-stage breast cancer (node-negative or up to three positive lymph nodes) and were risk-stratified to receive or skip adjuvant chemotherapy based on both clinical risk and the MammaPrint score for genomic risk. Fully 44% of women with ILC had discordant clinical and genomic risks.
With a median follow-up of 8.7 years, the 5-year rate of distant metastasis–free survival among all patients classified as genomic high risk was 92.1% in women with IDC and 88.1% in women with ILC, with overlapping 95% confidence intervals. Rates of distant metastasis–free survival for patients with genomic low risk were 96.4% in women with IDC and 96.6% in women with ILC, again with confidence intervals that overlapped.
The pattern was essentially the same for overall survival, and results carried over into 8-year outcomes as well.
“We believe that MammaPrint is a clinically useful test for patients diagnosed with ILC,” Dr. Metzger said. “There are similar survival outcomes for ILC and IDC when matched by genomic risk. This is an important message.”
It should be standard to omit chemotherapy for patients who have ILC classified as high clinical risk but low genomic risk by MammaPrint, Dr. Metzger recommended. “By contrast, MammaPrint should facilitate chemotherapy treatment decisions for patients diagnosed with ILC and high-risk MammaPrint,” he said.
Prognostic, but predictive?
“This is a well-designed prospective multicenter trial and provides the best evidence to date that MammaPrint is an important prognostic tool for ILC,” Todd Tuttle, MD, of University of Minnesota in Minneapolis, said in an interview.
Dr. Tuttle said he mainly uses the MammaPrint test and the OncoType 21-gene recurrence score to estimate prognosis for his patients with ILC.
These new data establish that MammaPrint is prognostic in ILC, but the value of MammaPrint’s genomic high risk result for making the decision about chemotherapy is still unclear, according to Dr. Tuttle.
“I don’t think we know whether MammaPrint can predict the benefit of chemotherapy for patients with stage I or II ILC,” he elaborated. “We need further high-quality studies such as this one to determine the best treatment strategies for ILC, which is a difficult breast cancer.”
Study details
Of the 5,313 patients studied, 487 had ILC (255 classic and 232 variant) and 4,826 had IDC according to central pathology assessment, Dr. Metzger reported.
MammaPrint classified 39% of the IDC group and 16% of the ILC group (10% of those with classic disease and 23% of those with variant disease) as genomically high risk for recurrence. The Adjuvant! Online tool classified 48.3% of ILC and 51.5% of IDC patients as clinically high risk.
Among the 44% of women with ILC having discordant genomic and clinical risk, discordance was usually due to the combination of low genomic risk and high clinical risk, seen in 38%.
The curves for 5-year distant metastasis–free survival stratified by genomic risk essentially overlapped for the IDC and ILC groups. Furthermore, there was no significant interaction of histologic type and genomic risk on this outcome (P = .547).
The 5-year rate of overall survival among women with genomic high risk was 95.6% in the IDC group and 93.5% in the ILC group. Among women with genomic low risk, 5-year overall survival was 98.1% in the IDC group and 97.7% in the ILC group, again with overlapping confidence intervals within each risk category.
The study was funded with support from the Breast Cancer Research Foundation. Dr. Metzger disclosed consulting fees from AbbVie, Genentech, Roche, and Pfizer. Dr. Tuttle disclosed no conflicts of interest.
SOURCE: Metzger O et al. EBCC-12 Virtual Conference. Abstract 6.
FROM EBCC-12 VIRTUAL CONFERENCE
Study advances personalized treatment for older breast cancer patients
Findings from the study were reported at the 12th European Breast Cancer Conference.
“Primary endocrine therapy is usually reserved for older, less fit, and frail women. Rates of use vary widely,” noted investigator Lynda Wyld, MBChB, PhD, of the University of Sheffield (England).
“Although there is no set threshold for who is suitable, some women are undoubtedly over- and undertreated for their breast cancer,” she added.
Dr. Wyld and colleagues undertook the Age Gap study among women older than 70 years with breast cancer recruited from 56 U.K. breast units during 2013-2018.
The main goals were to determine which women can be safely offered primary endocrine therapy as nonstandard care and to develop and test a tool to help women in this age group make treatment decisions.
The first component of the study was a multicenter, prospective cohort study of women with ER+ disease who were eligible for surgery. Results showed that breast cancer–specific mortality was greater with primary endocrine therapy than with surgery in the entire cohort. However, breast cancer–specific mortality was lower with primary endocrine therapy than with surgery in a cohort matched with propensity scores to achieve similar age, fitness, and frailty.
The second component of the study was a cluster-randomized controlled trial of women with operable breast cancer, most of whom had ER+ disease. Results showed that a decision support tool increased awareness of treatment options and readiness to decide. The tool also altered treatment choices, prompting a larger share of patients with ER+ disease to choose primary endocrine therapy.
Prospective cohort study
The prospective observational study was conducted in 2,854 women with ER+ disease who were eligible for surgery and treated in usual practice. Most women (n = 2,354) were treated with surgery (followed by antiestrogen therapy), while the rest received primary endocrine therapy (n = 500).
In the entire cohort, patients undergoing surgery were younger, had a lower level of comorbidity, and were less often frail. But these characteristics were generally similar in a propensity-matched cohort of 672 patients.
At a median follow-up of 52 months, overall and breast cancer–specific survival were significantly poorer with primary endocrine therapy versus surgery in the entire cohort but not in the propensity-matched cohort.
In the entire cohort, the breast cancer–specific mortality was 9.5% with primary endocrine therapy and 4.9% with surgery. In the propensity-matched cohort, breast cancer–specific mortality was 3.1% and 6.6%, respectively.
The overall mortality was 41.8% with primary endocrine therapy and 14.6% with surgery in the entire cohort, but the gap narrowed to 34.5% and 25.6%, respectively, in the propensity-matched cohort.
In the latter, “although there is a slight divergence in overall survival and it’s likely that with longer-term follow-up this will become significant, at the moment, it isn’t,” Dr. Wyld commented.
Curves for breast cancer–specific survival basically overlapped until 5 years, when surgery started to show an advantage. The rate of locoregional recurrence or progression was low and not significantly different by treatment.
None of the women in the entire cohort died from surgery. “But it’s worth bearing in mind that these were all women selected for surgery, who were thought to be fit for it by their surgeons. The least fit women in this cohort will have obviously been offered primary endocrine therapy,” Dr. Wyld cautioned.
Although 19% of patients had a surgical complication, only 2.1% had a systemic surgical complication.
Cluster-randomized controlled trial
In the cluster-randomized controlled trial, researchers compared a decision support tool to usual care. The tool was developed using U.K. registry data from almost 30,000 older women and input from women in this age group on their preferred format and method of presentation, according to Dr. Wyld.
The tool consists of an algorithm available to clinicians online (for input of tumor stage and biology, comorbidities, and functional status) plus a booklet and outcome sheets for patients to take home after discussions that can be personalized to their particulars.
Intention-to-treat analyses were based on 1,339 patients with operable breast cancer, 1,161 of whom had ER+ disease. Per-protocol analyses were based on the subset of 449 patients who were offered a choice between surgery and primary endocrine therapy, presumably because they were less fit and frailer.
Results showed that, at 6 months, mean scores for global quality of life on the EORTC questionnaire did not differ between decision support and usual care in the intention-to-treat population (69.0 vs. 68.9; P = .900), but scores were more favorable with decision support in the per-protocol population (70.7 vs. 66.8; P = .044).
The tool also altered treatment choices, with a larger share of ER+ patients choosing primary endocrine therapy (21.0% vs. 15.4%; P = .029) but still having similar disease outcomes.
Although ER+ patients in the decision support group more often selected primary endocrine therapy, at a median follow-up of 36 months, the groups did not differ significantly on overall survival, cause-specific survival, or time to recurrence in either intention-to-treat or per-protocol analyses.
Larger shares of women in the decision support group reported that they had adequate knowledge about the treatment options available to them (94% vs. 74%), were aware of the advantages and disadvantages of each option (91% vs. 76%), knew which option they preferred (96% vs. 91%), and were ready to make a decision (99% vs. 90%).
Applying results to practice
“Most women over the age of 70 are relatively fit, and the aim should be to treat them with surgery,” Dr. Wyld said. “For the less fit, a point is reached where the oncology benefits of surgery disappear and surgery may just cause harm. This threshold appears to be for women in their mid-80s with moderate to poor health.”
“Use of the Age Gap online tool may enhance shared decision-making for these women while increasing knowledge. And whilst it does seem to increase the use of primary endocrine therapy, this does not seem to have an adverse impact on survival at 36 months of follow-up,” she added.
“The study by Dr. Wyld and colleagues adds to the available literature regarding the scenarios in which some treatments may be omitted without impacting overall survival in older women with breast cancer,” Lesly A. Dossett, MD, of Michigan Medicine in Ann Arbor, commented in an interview.
In her own practice, Dr. Dossett emphasizes the generally favorable prognosis for older women with hormone receptor–positive breast cancer, she said. However, tools that help communicate risk and clarify the value of various therapies are welcome.
“The decision support tool appears to be a promising tool in helping to avoid treatments that are unlikely to benefit older women with breast cancer,” Dr. Dossett said. “The results will be widely applicable, as there is growing recognition that this patient population is at risk for overtreatment.”
The study was funded by the U.K. National Institute for Health Research programme grant for applied research. Dr. Wyld and Dr. Dossett said they had no relevant conflicts of interest.
SOURCES: Wyld L et al. EBCC-12 Virtual Congress. Abstract 8A and Abstract 8B.
Findings from the study were reported at the 12th European Breast Cancer Conference.
“Primary endocrine therapy is usually reserved for older, less fit, and frail women. Rates of use vary widely,” noted investigator Lynda Wyld, MBChB, PhD, of the University of Sheffield (England).
“Although there is no set threshold for who is suitable, some women are undoubtedly over- and undertreated for their breast cancer,” she added.
Dr. Wyld and colleagues undertook the Age Gap study among women older than 70 years with breast cancer recruited from 56 U.K. breast units during 2013-2018.
The main goals were to determine which women can be safely offered primary endocrine therapy as nonstandard care and to develop and test a tool to help women in this age group make treatment decisions.
The first component of the study was a multicenter, prospective cohort study of women with ER+ disease who were eligible for surgery. Results showed that breast cancer–specific mortality was greater with primary endocrine therapy than with surgery in the entire cohort. However, breast cancer–specific mortality was lower with primary endocrine therapy than with surgery in a cohort matched with propensity scores to achieve similar age, fitness, and frailty.
The second component of the study was a cluster-randomized controlled trial of women with operable breast cancer, most of whom had ER+ disease. Results showed that a decision support tool increased awareness of treatment options and readiness to decide. The tool also altered treatment choices, prompting a larger share of patients with ER+ disease to choose primary endocrine therapy.
Prospective cohort study
The prospective observational study was conducted in 2,854 women with ER+ disease who were eligible for surgery and treated in usual practice. Most women (n = 2,354) were treated with surgery (followed by antiestrogen therapy), while the rest received primary endocrine therapy (n = 500).
In the entire cohort, patients undergoing surgery were younger, had a lower level of comorbidity, and were less often frail. But these characteristics were generally similar in a propensity-matched cohort of 672 patients.
At a median follow-up of 52 months, overall and breast cancer–specific survival were significantly poorer with primary endocrine therapy versus surgery in the entire cohort but not in the propensity-matched cohort.
In the entire cohort, the breast cancer–specific mortality was 9.5% with primary endocrine therapy and 4.9% with surgery. In the propensity-matched cohort, breast cancer–specific mortality was 3.1% and 6.6%, respectively.
The overall mortality was 41.8% with primary endocrine therapy and 14.6% with surgery in the entire cohort, but the gap narrowed to 34.5% and 25.6%, respectively, in the propensity-matched cohort.
In the latter, “although there is a slight divergence in overall survival and it’s likely that with longer-term follow-up this will become significant, at the moment, it isn’t,” Dr. Wyld commented.
Curves for breast cancer–specific survival basically overlapped until 5 years, when surgery started to show an advantage. The rate of locoregional recurrence or progression was low and not significantly different by treatment.
None of the women in the entire cohort died from surgery. “But it’s worth bearing in mind that these were all women selected for surgery, who were thought to be fit for it by their surgeons. The least fit women in this cohort will have obviously been offered primary endocrine therapy,” Dr. Wyld cautioned.
Although 19% of patients had a surgical complication, only 2.1% had a systemic surgical complication.
Cluster-randomized controlled trial
In the cluster-randomized controlled trial, researchers compared a decision support tool to usual care. The tool was developed using U.K. registry data from almost 30,000 older women and input from women in this age group on their preferred format and method of presentation, according to Dr. Wyld.
The tool consists of an algorithm available to clinicians online (for input of tumor stage and biology, comorbidities, and functional status) plus a booklet and outcome sheets for patients to take home after discussions that can be personalized to their particulars.
Intention-to-treat analyses were based on 1,339 patients with operable breast cancer, 1,161 of whom had ER+ disease. Per-protocol analyses were based on the subset of 449 patients who were offered a choice between surgery and primary endocrine therapy, presumably because they were less fit and frailer.
Results showed that, at 6 months, mean scores for global quality of life on the EORTC questionnaire did not differ between decision support and usual care in the intention-to-treat population (69.0 vs. 68.9; P = .900), but scores were more favorable with decision support in the per-protocol population (70.7 vs. 66.8; P = .044).
The tool also altered treatment choices, with a larger share of ER+ patients choosing primary endocrine therapy (21.0% vs. 15.4%; P = .029) but still having similar disease outcomes.
Although ER+ patients in the decision support group more often selected primary endocrine therapy, at a median follow-up of 36 months, the groups did not differ significantly on overall survival, cause-specific survival, or time to recurrence in either intention-to-treat or per-protocol analyses.
Larger shares of women in the decision support group reported that they had adequate knowledge about the treatment options available to them (94% vs. 74%), were aware of the advantages and disadvantages of each option (91% vs. 76%), knew which option they preferred (96% vs. 91%), and were ready to make a decision (99% vs. 90%).
Applying results to practice
“Most women over the age of 70 are relatively fit, and the aim should be to treat them with surgery,” Dr. Wyld said. “For the less fit, a point is reached where the oncology benefits of surgery disappear and surgery may just cause harm. This threshold appears to be for women in their mid-80s with moderate to poor health.”
“Use of the Age Gap online tool may enhance shared decision-making for these women while increasing knowledge. And whilst it does seem to increase the use of primary endocrine therapy, this does not seem to have an adverse impact on survival at 36 months of follow-up,” she added.
“The study by Dr. Wyld and colleagues adds to the available literature regarding the scenarios in which some treatments may be omitted without impacting overall survival in older women with breast cancer,” Lesly A. Dossett, MD, of Michigan Medicine in Ann Arbor, commented in an interview.
In her own practice, Dr. Dossett emphasizes the generally favorable prognosis for older women with hormone receptor–positive breast cancer, she said. However, tools that help communicate risk and clarify the value of various therapies are welcome.
“The decision support tool appears to be a promising tool in helping to avoid treatments that are unlikely to benefit older women with breast cancer,” Dr. Dossett said. “The results will be widely applicable, as there is growing recognition that this patient population is at risk for overtreatment.”
The study was funded by the U.K. National Institute for Health Research programme grant for applied research. Dr. Wyld and Dr. Dossett said they had no relevant conflicts of interest.
SOURCES: Wyld L et al. EBCC-12 Virtual Congress. Abstract 8A and Abstract 8B.
Findings from the study were reported at the 12th European Breast Cancer Conference.
“Primary endocrine therapy is usually reserved for older, less fit, and frail women. Rates of use vary widely,” noted investigator Lynda Wyld, MBChB, PhD, of the University of Sheffield (England).
“Although there is no set threshold for who is suitable, some women are undoubtedly over- and undertreated for their breast cancer,” she added.
Dr. Wyld and colleagues undertook the Age Gap study among women older than 70 years with breast cancer recruited from 56 U.K. breast units during 2013-2018.
The main goals were to determine which women can be safely offered primary endocrine therapy as nonstandard care and to develop and test a tool to help women in this age group make treatment decisions.
The first component of the study was a multicenter, prospective cohort study of women with ER+ disease who were eligible for surgery. Results showed that breast cancer–specific mortality was greater with primary endocrine therapy than with surgery in the entire cohort. However, breast cancer–specific mortality was lower with primary endocrine therapy than with surgery in a cohort matched with propensity scores to achieve similar age, fitness, and frailty.
The second component of the study was a cluster-randomized controlled trial of women with operable breast cancer, most of whom had ER+ disease. Results showed that a decision support tool increased awareness of treatment options and readiness to decide. The tool also altered treatment choices, prompting a larger share of patients with ER+ disease to choose primary endocrine therapy.
Prospective cohort study
The prospective observational study was conducted in 2,854 women with ER+ disease who were eligible for surgery and treated in usual practice. Most women (n = 2,354) were treated with surgery (followed by antiestrogen therapy), while the rest received primary endocrine therapy (n = 500).
In the entire cohort, patients undergoing surgery were younger, had a lower level of comorbidity, and were less often frail. But these characteristics were generally similar in a propensity-matched cohort of 672 patients.
At a median follow-up of 52 months, overall and breast cancer–specific survival were significantly poorer with primary endocrine therapy versus surgery in the entire cohort but not in the propensity-matched cohort.
In the entire cohort, the breast cancer–specific mortality was 9.5% with primary endocrine therapy and 4.9% with surgery. In the propensity-matched cohort, breast cancer–specific mortality was 3.1% and 6.6%, respectively.
The overall mortality was 41.8% with primary endocrine therapy and 14.6% with surgery in the entire cohort, but the gap narrowed to 34.5% and 25.6%, respectively, in the propensity-matched cohort.
In the latter, “although there is a slight divergence in overall survival and it’s likely that with longer-term follow-up this will become significant, at the moment, it isn’t,” Dr. Wyld commented.
Curves for breast cancer–specific survival basically overlapped until 5 years, when surgery started to show an advantage. The rate of locoregional recurrence or progression was low and not significantly different by treatment.
None of the women in the entire cohort died from surgery. “But it’s worth bearing in mind that these were all women selected for surgery, who were thought to be fit for it by their surgeons. The least fit women in this cohort will have obviously been offered primary endocrine therapy,” Dr. Wyld cautioned.
Although 19% of patients had a surgical complication, only 2.1% had a systemic surgical complication.
Cluster-randomized controlled trial
In the cluster-randomized controlled trial, researchers compared a decision support tool to usual care. The tool was developed using U.K. registry data from almost 30,000 older women and input from women in this age group on their preferred format and method of presentation, according to Dr. Wyld.
The tool consists of an algorithm available to clinicians online (for input of tumor stage and biology, comorbidities, and functional status) plus a booklet and outcome sheets for patients to take home after discussions that can be personalized to their particulars.
Intention-to-treat analyses were based on 1,339 patients with operable breast cancer, 1,161 of whom had ER+ disease. Per-protocol analyses were based on the subset of 449 patients who were offered a choice between surgery and primary endocrine therapy, presumably because they were less fit and frailer.
Results showed that, at 6 months, mean scores for global quality of life on the EORTC questionnaire did not differ between decision support and usual care in the intention-to-treat population (69.0 vs. 68.9; P = .900), but scores were more favorable with decision support in the per-protocol population (70.7 vs. 66.8; P = .044).
The tool also altered treatment choices, with a larger share of ER+ patients choosing primary endocrine therapy (21.0% vs. 15.4%; P = .029) but still having similar disease outcomes.
Although ER+ patients in the decision support group more often selected primary endocrine therapy, at a median follow-up of 36 months, the groups did not differ significantly on overall survival, cause-specific survival, or time to recurrence in either intention-to-treat or per-protocol analyses.
Larger shares of women in the decision support group reported that they had adequate knowledge about the treatment options available to them (94% vs. 74%), were aware of the advantages and disadvantages of each option (91% vs. 76%), knew which option they preferred (96% vs. 91%), and were ready to make a decision (99% vs. 90%).
Applying results to practice
“Most women over the age of 70 are relatively fit, and the aim should be to treat them with surgery,” Dr. Wyld said. “For the less fit, a point is reached where the oncology benefits of surgery disappear and surgery may just cause harm. This threshold appears to be for women in their mid-80s with moderate to poor health.”
“Use of the Age Gap online tool may enhance shared decision-making for these women while increasing knowledge. And whilst it does seem to increase the use of primary endocrine therapy, this does not seem to have an adverse impact on survival at 36 months of follow-up,” she added.
“The study by Dr. Wyld and colleagues adds to the available literature regarding the scenarios in which some treatments may be omitted without impacting overall survival in older women with breast cancer,” Lesly A. Dossett, MD, of Michigan Medicine in Ann Arbor, commented in an interview.
In her own practice, Dr. Dossett emphasizes the generally favorable prognosis for older women with hormone receptor–positive breast cancer, she said. However, tools that help communicate risk and clarify the value of various therapies are welcome.
“The decision support tool appears to be a promising tool in helping to avoid treatments that are unlikely to benefit older women with breast cancer,” Dr. Dossett said. “The results will be widely applicable, as there is growing recognition that this patient population is at risk for overtreatment.”
The study was funded by the U.K. National Institute for Health Research programme grant for applied research. Dr. Wyld and Dr. Dossett said they had no relevant conflicts of interest.
SOURCES: Wyld L et al. EBCC-12 Virtual Congress. Abstract 8A and Abstract 8B.
FROM EBCC-12 VIRTUAL CONFERENCE
Restarting breast cancer screening after disruption not so simple
according to a modeling study reported at the 12th European Breast Cancer Conference.
Fallout of the pandemic has included reductions in cancer screening and diagnosis, said study investigator Lindy M. Kregting, a PhD student in the department of public health at Erasmus Medical Center, University Medical Center Rotterdam (the Netherlands).
In the Netherlands, new breast cancer diagnoses fell dramatically from historical levels starting in February. The number in April was less than half of that expected.
Ms. Kregting and colleagues used modeling to assess the impact of four strategies for restarting breast cancer screening in the Netherlands. The strategies differed regarding the population affected, the duration of the effects, and changes in stopping age. The usual situation, without any disruption, served as the comparator.
Results showed wide variation across strategies with respect to the increase in screening capacity needed during the latter half of this year – from 0% to 100% – and the excess breast cancer mortality occurring during 2020-2030 – from as many as 181 excess breast cancer deaths to as few as 14.
“The effects of the disruption are dependent on the chosen restart strategy,” Ms. Kregting summarized. “It would be preferred to immediately catch up because this minimizes the impact, but it also requires a very high capacity, so it may not always be possible. A proper alternative would be to increase the stopping age, so no screens are omitted, because this requires a rather normal capacity, and it will result in only small effects on incidence and mortality.”
As screening programs restart in some countries, there are still a lot of unknowns that could affect outcomes, including how many women will attend given that some may stay away out of fear, Ms. Kregting cautioned.
“We plan to do further model calculations when we know exactly what has happened. ... For now, we just assumed some reasonable disruption periods, and we assumed that capacity would be back to the original, before COVID-19, but I think we can say this is probably not the case,” she added.
Study details
Ms. Kregting and colleagues used Dutch breast cancer screening program parameters (biennial digital mammography for women aged 50-75 years) and a microsimulation screening analysis model to simulate four strategies for restarting breast cancer screening after a 6-month disruption:
- “Everyone delay,” a strategy in which all screening continues in the order planned with no change in the stopping age of 75 years (so that one in four women ultimately miss a screening during their lifetime)
- “First rounds no delay,” in which there is a delay in screening except for women having their first screening
- “Continue after stopping age,” in which there is a delay in screening but temporary increasing of the stopping age (to 76.5 years) to ensure all women get their final screen
- “Catch-up after stop,” in which capacity is increased to ensure full catch-up, with all delayed screens caught up in a 6-month period (the second half of 2020).
Results showed that 5,872 women would be screened in the latter half of 2020 if screening proceeded as usual without disruption. The necessary capacity was essentially the same with all of the restarting strategies, except for the catch-up-after-stop strategy, which would require a doubling of that number.
The temporal pattern of breast cancer incidence varied according to restart strategy early on, but incidence essentially returned to that expected with undisrupted screening by 2025 for all four strategies, with some small fluctuations thereafter.
The impact on breast cancer mortality differed considerably long term. It increased slightly and transiently above the expected level with the catch-up-after-stop strategy, but there were sizable, long-lasting increases with the other strategies, with excess deaths still seen in 2060 for the everyone-delay strategy.
In absolute terms, the excess number of breast cancer deaths during 2020-2030, compared with undisrupted screening, was 181 with the everyone-delay strategy, 155 with the first-rounds-no-delay strategy, 145 with the continue-after-stopping-age strategy, and just 14 with the catch-up-after-stop strategy. Ms. Kregting declined to provide numbers for other countries, given that the model is based on the Dutch population and screening program.
Results in context
“The unprecedented burden of COVID-19 on health systems worldwide has important implications for cancer care,” said invited discussant Alessandra Gennari, MD, PhD, of the University of Eastern Piedmont and Maggiore della Carità Hospital, both in Novara, Italy.
“There is a delay in diagnosis due to the fact that screening programs and diagnostic programs have been decreased or suspended in many Western countries where this is standard of care. Patients also are more reluctant to present to health care services, delaying their diagnosis,” Dr. Gennari said.
Findings of this new study add to those of similar studies undertaken in Italy (published in In Vivo) and the United Kingdom (published in The Lancet Oncology) showing the likely marked toll of the pandemic on cancer diagnosis and mortality, Dr. Gennari noted. Taken together, the findings underscore the urgent need for policy interventions to mitigate this impact.
“These interventions should focus on increasing routine diagnostic capacity, through which up to 40% of patients with cancer are diagnosed,” Dr. Gennari recommended. “Public health messaging is needed that accurately conveys the risk of severe illness from COVID-19 versus the risks of not seeking health care advice if patients are symptomatic. Finally, there is a need for provision of evidence-based data on which clinicians can adequately base their decision on how to manage the risks of cancer patients and the risks and benefits of procedures during the pandemic.”
The current study did not have any specific funding, and Ms. Kregting disclosed no conflicts of interest. Dr. Gennari disclosed relationships with Roche, Eisai, Lilly, AstraZeneca, Daiichi Sankyo, Merck, Novartis, and Pfizer.
SOURCE: Kregting L et al. EBCC-12 Virtual Conference, Abstract 24.
according to a modeling study reported at the 12th European Breast Cancer Conference.
Fallout of the pandemic has included reductions in cancer screening and diagnosis, said study investigator Lindy M. Kregting, a PhD student in the department of public health at Erasmus Medical Center, University Medical Center Rotterdam (the Netherlands).
In the Netherlands, new breast cancer diagnoses fell dramatically from historical levels starting in February. The number in April was less than half of that expected.
Ms. Kregting and colleagues used modeling to assess the impact of four strategies for restarting breast cancer screening in the Netherlands. The strategies differed regarding the population affected, the duration of the effects, and changes in stopping age. The usual situation, without any disruption, served as the comparator.
Results showed wide variation across strategies with respect to the increase in screening capacity needed during the latter half of this year – from 0% to 100% – and the excess breast cancer mortality occurring during 2020-2030 – from as many as 181 excess breast cancer deaths to as few as 14.
“The effects of the disruption are dependent on the chosen restart strategy,” Ms. Kregting summarized. “It would be preferred to immediately catch up because this minimizes the impact, but it also requires a very high capacity, so it may not always be possible. A proper alternative would be to increase the stopping age, so no screens are omitted, because this requires a rather normal capacity, and it will result in only small effects on incidence and mortality.”
As screening programs restart in some countries, there are still a lot of unknowns that could affect outcomes, including how many women will attend given that some may stay away out of fear, Ms. Kregting cautioned.
“We plan to do further model calculations when we know exactly what has happened. ... For now, we just assumed some reasonable disruption periods, and we assumed that capacity would be back to the original, before COVID-19, but I think we can say this is probably not the case,” she added.
Study details
Ms. Kregting and colleagues used Dutch breast cancer screening program parameters (biennial digital mammography for women aged 50-75 years) and a microsimulation screening analysis model to simulate four strategies for restarting breast cancer screening after a 6-month disruption:
- “Everyone delay,” a strategy in which all screening continues in the order planned with no change in the stopping age of 75 years (so that one in four women ultimately miss a screening during their lifetime)
- “First rounds no delay,” in which there is a delay in screening except for women having their first screening
- “Continue after stopping age,” in which there is a delay in screening but temporary increasing of the stopping age (to 76.5 years) to ensure all women get their final screen
- “Catch-up after stop,” in which capacity is increased to ensure full catch-up, with all delayed screens caught up in a 6-month period (the second half of 2020).
Results showed that 5,872 women would be screened in the latter half of 2020 if screening proceeded as usual without disruption. The necessary capacity was essentially the same with all of the restarting strategies, except for the catch-up-after-stop strategy, which would require a doubling of that number.
The temporal pattern of breast cancer incidence varied according to restart strategy early on, but incidence essentially returned to that expected with undisrupted screening by 2025 for all four strategies, with some small fluctuations thereafter.
The impact on breast cancer mortality differed considerably long term. It increased slightly and transiently above the expected level with the catch-up-after-stop strategy, but there were sizable, long-lasting increases with the other strategies, with excess deaths still seen in 2060 for the everyone-delay strategy.
In absolute terms, the excess number of breast cancer deaths during 2020-2030, compared with undisrupted screening, was 181 with the everyone-delay strategy, 155 with the first-rounds-no-delay strategy, 145 with the continue-after-stopping-age strategy, and just 14 with the catch-up-after-stop strategy. Ms. Kregting declined to provide numbers for other countries, given that the model is based on the Dutch population and screening program.
Results in context
“The unprecedented burden of COVID-19 on health systems worldwide has important implications for cancer care,” said invited discussant Alessandra Gennari, MD, PhD, of the University of Eastern Piedmont and Maggiore della Carità Hospital, both in Novara, Italy.
“There is a delay in diagnosis due to the fact that screening programs and diagnostic programs have been decreased or suspended in many Western countries where this is standard of care. Patients also are more reluctant to present to health care services, delaying their diagnosis,” Dr. Gennari said.
Findings of this new study add to those of similar studies undertaken in Italy (published in In Vivo) and the United Kingdom (published in The Lancet Oncology) showing the likely marked toll of the pandemic on cancer diagnosis and mortality, Dr. Gennari noted. Taken together, the findings underscore the urgent need for policy interventions to mitigate this impact.
“These interventions should focus on increasing routine diagnostic capacity, through which up to 40% of patients with cancer are diagnosed,” Dr. Gennari recommended. “Public health messaging is needed that accurately conveys the risk of severe illness from COVID-19 versus the risks of not seeking health care advice if patients are symptomatic. Finally, there is a need for provision of evidence-based data on which clinicians can adequately base their decision on how to manage the risks of cancer patients and the risks and benefits of procedures during the pandemic.”
The current study did not have any specific funding, and Ms. Kregting disclosed no conflicts of interest. Dr. Gennari disclosed relationships with Roche, Eisai, Lilly, AstraZeneca, Daiichi Sankyo, Merck, Novartis, and Pfizer.
SOURCE: Kregting L et al. EBCC-12 Virtual Conference, Abstract 24.
according to a modeling study reported at the 12th European Breast Cancer Conference.
Fallout of the pandemic has included reductions in cancer screening and diagnosis, said study investigator Lindy M. Kregting, a PhD student in the department of public health at Erasmus Medical Center, University Medical Center Rotterdam (the Netherlands).
In the Netherlands, new breast cancer diagnoses fell dramatically from historical levels starting in February. The number in April was less than half of that expected.
Ms. Kregting and colleagues used modeling to assess the impact of four strategies for restarting breast cancer screening in the Netherlands. The strategies differed regarding the population affected, the duration of the effects, and changes in stopping age. The usual situation, without any disruption, served as the comparator.
Results showed wide variation across strategies with respect to the increase in screening capacity needed during the latter half of this year – from 0% to 100% – and the excess breast cancer mortality occurring during 2020-2030 – from as many as 181 excess breast cancer deaths to as few as 14.
“The effects of the disruption are dependent on the chosen restart strategy,” Ms. Kregting summarized. “It would be preferred to immediately catch up because this minimizes the impact, but it also requires a very high capacity, so it may not always be possible. A proper alternative would be to increase the stopping age, so no screens are omitted, because this requires a rather normal capacity, and it will result in only small effects on incidence and mortality.”
As screening programs restart in some countries, there are still a lot of unknowns that could affect outcomes, including how many women will attend given that some may stay away out of fear, Ms. Kregting cautioned.
“We plan to do further model calculations when we know exactly what has happened. ... For now, we just assumed some reasonable disruption periods, and we assumed that capacity would be back to the original, before COVID-19, but I think we can say this is probably not the case,” she added.
Study details
Ms. Kregting and colleagues used Dutch breast cancer screening program parameters (biennial digital mammography for women aged 50-75 years) and a microsimulation screening analysis model to simulate four strategies for restarting breast cancer screening after a 6-month disruption:
- “Everyone delay,” a strategy in which all screening continues in the order planned with no change in the stopping age of 75 years (so that one in four women ultimately miss a screening during their lifetime)
- “First rounds no delay,” in which there is a delay in screening except for women having their first screening
- “Continue after stopping age,” in which there is a delay in screening but temporary increasing of the stopping age (to 76.5 years) to ensure all women get their final screen
- “Catch-up after stop,” in which capacity is increased to ensure full catch-up, with all delayed screens caught up in a 6-month period (the second half of 2020).
Results showed that 5,872 women would be screened in the latter half of 2020 if screening proceeded as usual without disruption. The necessary capacity was essentially the same with all of the restarting strategies, except for the catch-up-after-stop strategy, which would require a doubling of that number.
The temporal pattern of breast cancer incidence varied according to restart strategy early on, but incidence essentially returned to that expected with undisrupted screening by 2025 for all four strategies, with some small fluctuations thereafter.
The impact on breast cancer mortality differed considerably long term. It increased slightly and transiently above the expected level with the catch-up-after-stop strategy, but there were sizable, long-lasting increases with the other strategies, with excess deaths still seen in 2060 for the everyone-delay strategy.
In absolute terms, the excess number of breast cancer deaths during 2020-2030, compared with undisrupted screening, was 181 with the everyone-delay strategy, 155 with the first-rounds-no-delay strategy, 145 with the continue-after-stopping-age strategy, and just 14 with the catch-up-after-stop strategy. Ms. Kregting declined to provide numbers for other countries, given that the model is based on the Dutch population and screening program.
Results in context
“The unprecedented burden of COVID-19 on health systems worldwide has important implications for cancer care,” said invited discussant Alessandra Gennari, MD, PhD, of the University of Eastern Piedmont and Maggiore della Carità Hospital, both in Novara, Italy.
“There is a delay in diagnosis due to the fact that screening programs and diagnostic programs have been decreased or suspended in many Western countries where this is standard of care. Patients also are more reluctant to present to health care services, delaying their diagnosis,” Dr. Gennari said.
Findings of this new study add to those of similar studies undertaken in Italy (published in In Vivo) and the United Kingdom (published in The Lancet Oncology) showing the likely marked toll of the pandemic on cancer diagnosis and mortality, Dr. Gennari noted. Taken together, the findings underscore the urgent need for policy interventions to mitigate this impact.
“These interventions should focus on increasing routine diagnostic capacity, through which up to 40% of patients with cancer are diagnosed,” Dr. Gennari recommended. “Public health messaging is needed that accurately conveys the risk of severe illness from COVID-19 versus the risks of not seeking health care advice if patients are symptomatic. Finally, there is a need for provision of evidence-based data on which clinicians can adequately base their decision on how to manage the risks of cancer patients and the risks and benefits of procedures during the pandemic.”
The current study did not have any specific funding, and Ms. Kregting disclosed no conflicts of interest. Dr. Gennari disclosed relationships with Roche, Eisai, Lilly, AstraZeneca, Daiichi Sankyo, Merck, Novartis, and Pfizer.
SOURCE: Kregting L et al. EBCC-12 Virtual Conference, Abstract 24.
FROM EBCC-12 VIRTUAL CONFERENCE
Radiotherapy planning scans reveal breast cancer patients’ CVD risk
Radiotherapy planning scans may be a rich untapped source of information for estimating the risk of cardiovascular disease (CVD) in breast cancer patients, a large study suggests.
Researchers found that breast cancer patients with a coronary artery calcifications (CAC) score exceeding 400 had nearly four times the adjusted risk of fatal and nonfatal CVD events when compared with patients who had a CAC score of 0.
Patients with scores exceeding 400 also had more than eight times the risk of coronary heart disease events. The associations were especially strong in the subset of patients who received anthracycline-containing chemotherapy.
Helena Verkooijen, MD, PhD, of University Medical Center Utrecht (the Netherlands) presented these findings at the 12th European Breast Cancer Conference.
Dr. Verkooijen noted that, over the past 50 years, breast cancer has dramatically declined as a cause of death among breast cancer survivors, while CVD has continued to account for about 20% of the total deaths in this population.
CACs are sometimes incidentally seen in radiotherapy planning CT scans. “Right now, this information is not often used for patient stratification or informing patients about their cardiovascular risk, and this is a pity, because we know that it is an independent risk factor, and, often, the presence of calcifications can occur in the absence of other cardiovascular risk factors,” Dr. Verkooijen said.
Study details
Dr. Verkooijen and and colleagues from the Bragataston Study Group retrospectively studied 15,919 breast cancer patients who had radiotherapy planning CT scans during 2004-2016 at three Dutch institutions.
The researchers used an automated deep-learning algorithm (described in Radiology) to detect and quantify coronary calcium in planning CT scans and calculate CAC scores, classifying them into five categories.
The median follow-up was 51.6 months. Most women (70%) did not have any calcium detected in their coronary arteries (CAC score of 0), while 3% fell into the highest category (CAC score of >400).
The incidence of nonfatal and fatal CVD events increased with CAC score:
- 5.1% with a score of 0.
- 8.5% with a score of 1-10.
- 13.5% with a score of 11-100.
- 17.6% with a score of 101-400.
- 28.0% with a score greater than 400.
In analyses adjusted for age, laterality of radiation, and receipt of cardiotoxic agents – anthracyclines and trastuzumab – women with a score exceeding 400 had sharply elevated adjusted risks of CVD events (hazard ratio, 3.7), of coronary heart disease events specifically (HR, 8.2), and of death from any cause (HR, 2.8), when compared with peers who had a CAC score of 0.
On further scrutiny of CVD events, the pattern was similar regardless of whether radiation was left- or right-sided. However, the association was stronger among women who received anthracyclines as compared with counterparts who did not, with a nearly six-fold higher risk for those with highest versus lowest CAC scores.
When the women were surveyed, nearly 90% said they wanted to be informed about their CAC score and associated CVD risk, even in the absence of evidence-based risk reduction strategies.
Applying the results
“We believe that this is the first time that anyone has conducted a study on this topic on a scale like this, and we show that it is possible to relatively easily identify women at a very high risk of CVD,” Dr. Verkooijen said. “But what do we do with this information, because these scans are not made to answer this question. … This is information that we get that we haven’t really requested. I think we should only use this information when we have really shown that we can help patients reduce their risk of cardiovascular disease.”
To that end, Dr. Verkooijen and colleagues are planning additional research that will look at the potential benefit of referring high-risk patients for cardioprevention strategies and at the role of using the CAC score to personalize treatment strategies.
“This is an interesting and novel approach to predicting cardiac events for patients undergoing breast cancer treatment,” Meena S. Moran, MD, of Yale University in New Haven, Conn., commented in an interview.
The approach would likely be feasible in typical practice with widespread availability of the automated algorithm and might even alter treatment planning in real time, she said. “From the standpoint of radiation oncology, it would mean running the software to generate a CAC score, which would allow for modifications in decision-making during treatment planning, such as whether or not to include the internal mammary nodal chain in a patient who may be in the ‘gray zone’ for regional nodal radiation. For example, if a patient has a high CAC score, plus if they have received (or are receiving) cardiotoxic drugs, radiation oncologists can use that information as an additional factor to consider in the decision-making of whether or not to include the internal mammary chain, which inevitably can increase the dose delivered to the heart,” Dr. Moran elaborated.
Dr. Verkooijen’s study was supported by the Dutch Cancer Society, the European Commission, the Dutch Digestive Foundation, the Netherlands Organisation for Scientific Research, and Elekta. Dr. Verkooijen and Dr. Moran disclosed no conflicts of interest.
SOURCE: Gal R et al. EBCC-12 Virtual Congress, Abstract 7.
Radiotherapy planning scans may be a rich untapped source of information for estimating the risk of cardiovascular disease (CVD) in breast cancer patients, a large study suggests.
Researchers found that breast cancer patients with a coronary artery calcifications (CAC) score exceeding 400 had nearly four times the adjusted risk of fatal and nonfatal CVD events when compared with patients who had a CAC score of 0.
Patients with scores exceeding 400 also had more than eight times the risk of coronary heart disease events. The associations were especially strong in the subset of patients who received anthracycline-containing chemotherapy.
Helena Verkooijen, MD, PhD, of University Medical Center Utrecht (the Netherlands) presented these findings at the 12th European Breast Cancer Conference.
Dr. Verkooijen noted that, over the past 50 years, breast cancer has dramatically declined as a cause of death among breast cancer survivors, while CVD has continued to account for about 20% of the total deaths in this population.
CACs are sometimes incidentally seen in radiotherapy planning CT scans. “Right now, this information is not often used for patient stratification or informing patients about their cardiovascular risk, and this is a pity, because we know that it is an independent risk factor, and, often, the presence of calcifications can occur in the absence of other cardiovascular risk factors,” Dr. Verkooijen said.
Study details
Dr. Verkooijen and and colleagues from the Bragataston Study Group retrospectively studied 15,919 breast cancer patients who had radiotherapy planning CT scans during 2004-2016 at three Dutch institutions.
The researchers used an automated deep-learning algorithm (described in Radiology) to detect and quantify coronary calcium in planning CT scans and calculate CAC scores, classifying them into five categories.
The median follow-up was 51.6 months. Most women (70%) did not have any calcium detected in their coronary arteries (CAC score of 0), while 3% fell into the highest category (CAC score of >400).
The incidence of nonfatal and fatal CVD events increased with CAC score:
- 5.1% with a score of 0.
- 8.5% with a score of 1-10.
- 13.5% with a score of 11-100.
- 17.6% with a score of 101-400.
- 28.0% with a score greater than 400.
In analyses adjusted for age, laterality of radiation, and receipt of cardiotoxic agents – anthracyclines and trastuzumab – women with a score exceeding 400 had sharply elevated adjusted risks of CVD events (hazard ratio, 3.7), of coronary heart disease events specifically (HR, 8.2), and of death from any cause (HR, 2.8), when compared with peers who had a CAC score of 0.
On further scrutiny of CVD events, the pattern was similar regardless of whether radiation was left- or right-sided. However, the association was stronger among women who received anthracyclines as compared with counterparts who did not, with a nearly six-fold higher risk for those with highest versus lowest CAC scores.
When the women were surveyed, nearly 90% said they wanted to be informed about their CAC score and associated CVD risk, even in the absence of evidence-based risk reduction strategies.
Applying the results
“We believe that this is the first time that anyone has conducted a study on this topic on a scale like this, and we show that it is possible to relatively easily identify women at a very high risk of CVD,” Dr. Verkooijen said. “But what do we do with this information, because these scans are not made to answer this question. … This is information that we get that we haven’t really requested. I think we should only use this information when we have really shown that we can help patients reduce their risk of cardiovascular disease.”
To that end, Dr. Verkooijen and colleagues are planning additional research that will look at the potential benefit of referring high-risk patients for cardioprevention strategies and at the role of using the CAC score to personalize treatment strategies.
“This is an interesting and novel approach to predicting cardiac events for patients undergoing breast cancer treatment,” Meena S. Moran, MD, of Yale University in New Haven, Conn., commented in an interview.
The approach would likely be feasible in typical practice with widespread availability of the automated algorithm and might even alter treatment planning in real time, she said. “From the standpoint of radiation oncology, it would mean running the software to generate a CAC score, which would allow for modifications in decision-making during treatment planning, such as whether or not to include the internal mammary nodal chain in a patient who may be in the ‘gray zone’ for regional nodal radiation. For example, if a patient has a high CAC score, plus if they have received (or are receiving) cardiotoxic drugs, radiation oncologists can use that information as an additional factor to consider in the decision-making of whether or not to include the internal mammary chain, which inevitably can increase the dose delivered to the heart,” Dr. Moran elaborated.
Dr. Verkooijen’s study was supported by the Dutch Cancer Society, the European Commission, the Dutch Digestive Foundation, the Netherlands Organisation for Scientific Research, and Elekta. Dr. Verkooijen and Dr. Moran disclosed no conflicts of interest.
SOURCE: Gal R et al. EBCC-12 Virtual Congress, Abstract 7.
Radiotherapy planning scans may be a rich untapped source of information for estimating the risk of cardiovascular disease (CVD) in breast cancer patients, a large study suggests.
Researchers found that breast cancer patients with a coronary artery calcifications (CAC) score exceeding 400 had nearly four times the adjusted risk of fatal and nonfatal CVD events when compared with patients who had a CAC score of 0.
Patients with scores exceeding 400 also had more than eight times the risk of coronary heart disease events. The associations were especially strong in the subset of patients who received anthracycline-containing chemotherapy.
Helena Verkooijen, MD, PhD, of University Medical Center Utrecht (the Netherlands) presented these findings at the 12th European Breast Cancer Conference.
Dr. Verkooijen noted that, over the past 50 years, breast cancer has dramatically declined as a cause of death among breast cancer survivors, while CVD has continued to account for about 20% of the total deaths in this population.
CACs are sometimes incidentally seen in radiotherapy planning CT scans. “Right now, this information is not often used for patient stratification or informing patients about their cardiovascular risk, and this is a pity, because we know that it is an independent risk factor, and, often, the presence of calcifications can occur in the absence of other cardiovascular risk factors,” Dr. Verkooijen said.
Study details
Dr. Verkooijen and and colleagues from the Bragataston Study Group retrospectively studied 15,919 breast cancer patients who had radiotherapy planning CT scans during 2004-2016 at three Dutch institutions.
The researchers used an automated deep-learning algorithm (described in Radiology) to detect and quantify coronary calcium in planning CT scans and calculate CAC scores, classifying them into five categories.
The median follow-up was 51.6 months. Most women (70%) did not have any calcium detected in their coronary arteries (CAC score of 0), while 3% fell into the highest category (CAC score of >400).
The incidence of nonfatal and fatal CVD events increased with CAC score:
- 5.1% with a score of 0.
- 8.5% with a score of 1-10.
- 13.5% with a score of 11-100.
- 17.6% with a score of 101-400.
- 28.0% with a score greater than 400.
In analyses adjusted for age, laterality of radiation, and receipt of cardiotoxic agents – anthracyclines and trastuzumab – women with a score exceeding 400 had sharply elevated adjusted risks of CVD events (hazard ratio, 3.7), of coronary heart disease events specifically (HR, 8.2), and of death from any cause (HR, 2.8), when compared with peers who had a CAC score of 0.
On further scrutiny of CVD events, the pattern was similar regardless of whether radiation was left- or right-sided. However, the association was stronger among women who received anthracyclines as compared with counterparts who did not, with a nearly six-fold higher risk for those with highest versus lowest CAC scores.
When the women were surveyed, nearly 90% said they wanted to be informed about their CAC score and associated CVD risk, even in the absence of evidence-based risk reduction strategies.
Applying the results
“We believe that this is the first time that anyone has conducted a study on this topic on a scale like this, and we show that it is possible to relatively easily identify women at a very high risk of CVD,” Dr. Verkooijen said. “But what do we do with this information, because these scans are not made to answer this question. … This is information that we get that we haven’t really requested. I think we should only use this information when we have really shown that we can help patients reduce their risk of cardiovascular disease.”
To that end, Dr. Verkooijen and colleagues are planning additional research that will look at the potential benefit of referring high-risk patients for cardioprevention strategies and at the role of using the CAC score to personalize treatment strategies.
“This is an interesting and novel approach to predicting cardiac events for patients undergoing breast cancer treatment,” Meena S. Moran, MD, of Yale University in New Haven, Conn., commented in an interview.
The approach would likely be feasible in typical practice with widespread availability of the automated algorithm and might even alter treatment planning in real time, she said. “From the standpoint of radiation oncology, it would mean running the software to generate a CAC score, which would allow for modifications in decision-making during treatment planning, such as whether or not to include the internal mammary nodal chain in a patient who may be in the ‘gray zone’ for regional nodal radiation. For example, if a patient has a high CAC score, plus if they have received (or are receiving) cardiotoxic drugs, radiation oncologists can use that information as an additional factor to consider in the decision-making of whether or not to include the internal mammary chain, which inevitably can increase the dose delivered to the heart,” Dr. Moran elaborated.
Dr. Verkooijen’s study was supported by the Dutch Cancer Society, the European Commission, the Dutch Digestive Foundation, the Netherlands Organisation for Scientific Research, and Elekta. Dr. Verkooijen and Dr. Moran disclosed no conflicts of interest.
SOURCE: Gal R et al. EBCC-12 Virtual Congress, Abstract 7.
FROM EBCC-12 VIRTUAL CONFERENCE
