Susan London

Patterns of health care use and costs at the end of life among colorectal cancer (CRC) patients differ considerably between the United States and Canada and offer learning opportunities for both countries, suggests a cross-sectional cohort study.

Total costs were one-fourth higher for U.S. patients, who more often received chemotherapy and imaging in the month leading up to death. Canadian patients in the province of Ontario were more likely to be hospitalized and to die in the hospital.

“Our findings add to the growing body of research describing health care utilization and costs among patients in different systems to inform efforts to improve organization and delivery of care,” write the investigators, led by Karen E. Bremner, BSc, a research associate with the Toronto General Hospital Research Institute, University Health Network, and the Toronto Health Economics and Technology Assessment (THETA) Collaborative. “These findings suggest opportunities for reducing chemotherapy and ICU use in the U.S. and hospitalizations in Ontario.”

The investigators used registries to identify patients who received a diagnosis of CRC of any stage during 2007-2013 and died of any cancer during that period at the age of 66 years or older.

Analyses compared health care use and costs between 16,565 patients from the U.S. Surveillance, Epidemiology, and End Results (SEER) cancer registries linked to Medicare claims and 6,587 patients from the Ontario Cancer Registry linked to administrative health data.

Across months, but especially in the month before death, the SEER-Medicare group was more likely than the Ontario group to receive chemotherapy (15.7% vs. 8.0% in the last month of life) and have imaging tests (39.4% vs. 31.1% in the last month of life), according to results reported in the Journal of Oncology Practice.

Ontario patients more often visited the emergency department (14.7% vs. 6.7%) and were hospitalized (62.5% vs. 51.0%) in the month before death; had longer stays (14.1 vs. 10.9 days); and were more likely to die in the hospital (42.0% vs. 24.3%). But once hospitalized, they were less often admitted to the ICU (17.9% vs. 43.2%).

Mean total costs for all health care resources in the last month of life were 25% higher for the SEER-Medicare group compared with the Ontario group ($17,284 vs. $13,849), with the gap widening by stage at diagnosis. Costs were 12% higher for those with stage 0 to II disease, 27% higher for those with stage III disease, and 32% higher for those with stage IV disease.

The SEER-Medicare group had higher hospitalization costs ($11,180 vs. $9,434) with daily hospital costs that were about twice those of Ontario counterparts ($2,004 vs. $1,067).

“[O]ur descriptive study of health care utilization and costs at the end of life in similar groups of older CRC patients, although not supporting a direct comparison of two health systems, generated hypotheses concerning areas for improvement in service delivery and lower costs in both settings,” Ms. Bremner and coinvestigators maintained.

“In Ontario, improving coordination of end-of-life care and reducing hospitalizations and in-hospital deaths could provide savings,” they noted. “Reducing daily hospital costs and intensity of health care services for SEER-Medicare patients, especially those with stage IV disease at diagnosis, could reduce costs to the Medicare program and decrease the financial burden on patients and families.”

Ms. Bremner disclosed that she had no conflicts of interest. The Ontario arm of the study was funded by the Canadian Centre for Applied Research in Cancer Control, which receives core funding from the Canadian Cancer Society Research Institute.

SOURCE: Bremner KE et al. J Oncol Pract. 2019 Oct 24. doi: 10.1200/JOP.19.00061.

Patterns of health care use and costs at the end of life among colorectal cancer (CRC) patients differ considerably between the United States and Canada and offer learning opportunities for both countries, suggests a cross-sectional cohort study.

Total costs were one-fourth higher for U.S. patients, who more often received chemotherapy and imaging in the month leading up to death. Canadian patients in the province of Ontario were more likely to be hospitalized and to die in the hospital.

“Our findings add to the growing body of research describing health care utilization and costs among patients in different systems to inform efforts to improve organization and delivery of care,” write the investigators, led by Karen E. Bremner, BSc, a research associate with the Toronto General Hospital Research Institute, University Health Network, and the Toronto Health Economics and Technology Assessment (THETA) Collaborative. “These findings suggest opportunities for reducing chemotherapy and ICU use in the U.S. and hospitalizations in Ontario.”

The investigators used registries to identify patients who received a diagnosis of CRC of any stage during 2007-2013 and died of any cancer during that period at the age of 66 years or older.

Analyses compared health care use and costs between 16,565 patients from the U.S. Surveillance, Epidemiology, and End Results (SEER) cancer registries linked to Medicare claims and 6,587 patients from the Ontario Cancer Registry linked to administrative health data.

Across months, but especially in the month before death, the SEER-Medicare group was more likely than the Ontario group to receive chemotherapy (15.7% vs. 8.0% in the last month of life) and have imaging tests (39.4% vs. 31.1% in the last month of life), according to results reported in the Journal of Oncology Practice.

Ontario patients more often visited the emergency department (14.7% vs. 6.7%) and were hospitalized (62.5% vs. 51.0%) in the month before death; had longer stays (14.1 vs. 10.9 days); and were more likely to die in the hospital (42.0% vs. 24.3%). But once hospitalized, they were less often admitted to the ICU (17.9% vs. 43.2%).

Mean total costs for all health care resources in the last month of life were 25% higher for the SEER-Medicare group compared with the Ontario group ($17,284 vs. $13,849), with the gap widening by stage at diagnosis. Costs were 12% higher for those with stage 0 to II disease, 27% higher for those with stage III disease, and 32% higher for those with stage IV disease.

The SEER-Medicare group had higher hospitalization costs ($11,180 vs. $9,434) with daily hospital costs that were about twice those of Ontario counterparts ($2,004 vs. $1,067).

“[O]ur descriptive study of health care utilization and costs at the end of life in similar groups of older CRC patients, although not supporting a direct comparison of two health systems, generated hypotheses concerning areas for improvement in service delivery and lower costs in both settings,” Ms. Bremner and coinvestigators maintained.

“In Ontario, improving coordination of end-of-life care and reducing hospitalizations and in-hospital deaths could provide savings,” they noted. “Reducing daily hospital costs and intensity of health care services for SEER-Medicare patients, especially those with stage IV disease at diagnosis, could reduce costs to the Medicare program and decrease the financial burden on patients and families.”

Ms. Bremner disclosed that she had no conflicts of interest. The Ontario arm of the study was funded by the Canadian Centre for Applied Research in Cancer Control, which receives core funding from the Canadian Cancer Society Research Institute.

SOURCE: Bremner KE et al. J Oncol Pract. 2019 Oct 24. doi: 10.1200/JOP.19.00061.

Patterns of health care use and costs at the end of life among colorectal cancer (CRC) patients differ considerably between the United States and Canada and offer learning opportunities for both countries, suggests a cross-sectional cohort study.

Total costs were one-fourth higher for U.S. patients, who more often received chemotherapy and imaging in the month leading up to death. Canadian patients in the province of Ontario were more likely to be hospitalized and to die in the hospital.

“Our findings add to the growing body of research describing health care utilization and costs among patients in different systems to inform efforts to improve organization and delivery of care,” write the investigators, led by Karen E. Bremner, BSc, a research associate with the Toronto General Hospital Research Institute, University Health Network, and the Toronto Health Economics and Technology Assessment (THETA) Collaborative. “These findings suggest opportunities for reducing chemotherapy and ICU use in the U.S. and hospitalizations in Ontario.”

The investigators used registries to identify patients who received a diagnosis of CRC of any stage during 2007-2013 and died of any cancer during that period at the age of 66 years or older.

Analyses compared health care use and costs between 16,565 patients from the U.S. Surveillance, Epidemiology, and End Results (SEER) cancer registries linked to Medicare claims and 6,587 patients from the Ontario Cancer Registry linked to administrative health data.

Across months, but especially in the month before death, the SEER-Medicare group was more likely than the Ontario group to receive chemotherapy (15.7% vs. 8.0% in the last month of life) and have imaging tests (39.4% vs. 31.1% in the last month of life), according to results reported in the Journal of Oncology Practice.

Ontario patients more often visited the emergency department (14.7% vs. 6.7%) and were hospitalized (62.5% vs. 51.0%) in the month before death; had longer stays (14.1 vs. 10.9 days); and were more likely to die in the hospital (42.0% vs. 24.3%). But once hospitalized, they were less often admitted to the ICU (17.9% vs. 43.2%).

Mean total costs for all health care resources in the last month of life were 25% higher for the SEER-Medicare group compared with the Ontario group ($17,284 vs. $13,849), with the gap widening by stage at diagnosis. Costs were 12% higher for those with stage 0 to II disease, 27% higher for those with stage III disease, and 32% higher for those with stage IV disease.

The SEER-Medicare group had higher hospitalization costs ($11,180 vs. $9,434) with daily hospital costs that were about twice those of Ontario counterparts ($2,004 vs. $1,067).

“[O]ur descriptive study of health care utilization and costs at the end of life in similar groups of older CRC patients, although not supporting a direct comparison of two health systems, generated hypotheses concerning areas for improvement in service delivery and lower costs in both settings,” Ms. Bremner and coinvestigators maintained.

“In Ontario, improving coordination of end-of-life care and reducing hospitalizations and in-hospital deaths could provide savings,” they noted. “Reducing daily hospital costs and intensity of health care services for SEER-Medicare patients, especially those with stage IV disease at diagnosis, could reduce costs to the Medicare program and decrease the financial burden on patients and families.”

Ms. Bremner disclosed that she had no conflicts of interest. The Ontario arm of the study was funded by the Canadian Centre for Applied Research in Cancer Control, which receives core funding from the Canadian Cancer Society Research Institute.

SOURCE: Bremner KE et al. J Oncol Pract. 2019 Oct 24. doi: 10.1200/JOP.19.00061.

First-line sunitinib therapy for metastatic renal cell carcinoma (mRCC) has somewhat differing effectiveness and safety when used in real-world practice, compared with clinical trials, suggests the OSSMAR multicenter retrospective cohort study.

Investigators led by Marwan Ghosn, MD, Hotel-Dieu de France University Hospital and Saint Joseph University, Beirut, Lebanon, analyzed outcomes among 289 patients with mRCC started on sunitinib (Sutent), an oral multitargeted tyrosine kinase inhibitor, between 2006 and 2016 at 10 centers in Africa and the Middle East region.

The patients had a median age at diagnosis of 58.7 years, and 85.8% had clear cell histology. Two-thirds had metastases at diagnosis, and 15.2% and 31.4% had favorable- and poor-risk disease, respectively, according to expanded Memorial Sloan Kettering Cancer Center criteria. Overall, 52.2% had undergone partial or radical nephrectomy, and nearly all were receiving sunitinib as first-line therapy.

Study results, reported in the Journal of Global Oncology, showed that the mean total sunitinib starting dose was 48.1 mg, with most patients (87.6%) started on a dose of 50 mg. On average, the drug was given for 9.6 months.

The overall response rate was 20.8%, and responses lasted for a median of of 8.2 months. With a median follow-up of 7.8 months, patients had a median time to progression of 5.7 months and a median overall survival of 7.8 months. The 12- and 24-month rates of overall survival were 34.3% and 11.4%, respectively.

Although 60.9% of patients experienced adverse events, only 8.0% experienced serious adverse events. The main adverse events were gastrointestinal and hematologic, mirroring those seen previously in trials. About a third of the whole study cohort (28.7%) discontinued sunitinib therapy.

“OSSMAR is the first study in the Middle East involving several Arab countries and evaluating the use of real-time sunitinib in the treatment of mRCC. As a result, this study is of primary importance because it allows for a better assessment of the actual effectiveness and practical adverse events of sunitinib in the population in our region,” Dr. Ghosn and coinvestigators maintained.

Compared with patients in clinical trials, OSSMAR patients had poorer overall survival, possibly due to factors such as a relatively lower nephrectomy rate, real-world influences such as comorbidities, and losses to follow-up, the investigators proposed.

At the same time, the OSSMAR cohort also had a lower rate of adverse events, although this difference likely reflects less rigorous assessment of toxicity in real-world practice, they noted.

Dr. Ghosn disclosed that he has relationships with numerous pharmaceutical companies. The study did not receive any specific funding.

SOURCE: Ghosn M et al. J Glob Oncol. 2019 Oct 5. doi: 10.1200/JGO.18.00238.

First-line sunitinib therapy for metastatic renal cell carcinoma (mRCC) has somewhat differing effectiveness and safety when used in real-world practice, compared with clinical trials, suggests the OSSMAR multicenter retrospective cohort study.

Investigators led by Marwan Ghosn, MD, Hotel-Dieu de France University Hospital and Saint Joseph University, Beirut, Lebanon, analyzed outcomes among 289 patients with mRCC started on sunitinib (Sutent), an oral multitargeted tyrosine kinase inhibitor, between 2006 and 2016 at 10 centers in Africa and the Middle East region.

The patients had a median age at diagnosis of 58.7 years, and 85.8% had clear cell histology. Two-thirds had metastases at diagnosis, and 15.2% and 31.4% had favorable- and poor-risk disease, respectively, according to expanded Memorial Sloan Kettering Cancer Center criteria. Overall, 52.2% had undergone partial or radical nephrectomy, and nearly all were receiving sunitinib as first-line therapy.

Study results, reported in the Journal of Global Oncology, showed that the mean total sunitinib starting dose was 48.1 mg, with most patients (87.6%) started on a dose of 50 mg. On average, the drug was given for 9.6 months.

The overall response rate was 20.8%, and responses lasted for a median of of 8.2 months. With a median follow-up of 7.8 months, patients had a median time to progression of 5.7 months and a median overall survival of 7.8 months. The 12- and 24-month rates of overall survival were 34.3% and 11.4%, respectively.

Although 60.9% of patients experienced adverse events, only 8.0% experienced serious adverse events. The main adverse events were gastrointestinal and hematologic, mirroring those seen previously in trials. About a third of the whole study cohort (28.7%) discontinued sunitinib therapy.

“OSSMAR is the first study in the Middle East involving several Arab countries and evaluating the use of real-time sunitinib in the treatment of mRCC. As a result, this study is of primary importance because it allows for a better assessment of the actual effectiveness and practical adverse events of sunitinib in the population in our region,” Dr. Ghosn and coinvestigators maintained.

Compared with patients in clinical trials, OSSMAR patients had poorer overall survival, possibly due to factors such as a relatively lower nephrectomy rate, real-world influences such as comorbidities, and losses to follow-up, the investigators proposed.

At the same time, the OSSMAR cohort also had a lower rate of adverse events, although this difference likely reflects less rigorous assessment of toxicity in real-world practice, they noted.

Dr. Ghosn disclosed that he has relationships with numerous pharmaceutical companies. The study did not receive any specific funding.

SOURCE: Ghosn M et al. J Glob Oncol. 2019 Oct 5. doi: 10.1200/JGO.18.00238.

First-line sunitinib therapy for metastatic renal cell carcinoma (mRCC) has somewhat differing effectiveness and safety when used in real-world practice, compared with clinical trials, suggests the OSSMAR multicenter retrospective cohort study.

Investigators led by Marwan Ghosn, MD, Hotel-Dieu de France University Hospital and Saint Joseph University, Beirut, Lebanon, analyzed outcomes among 289 patients with mRCC started on sunitinib (Sutent), an oral multitargeted tyrosine kinase inhibitor, between 2006 and 2016 at 10 centers in Africa and the Middle East region.

The patients had a median age at diagnosis of 58.7 years, and 85.8% had clear cell histology. Two-thirds had metastases at diagnosis, and 15.2% and 31.4% had favorable- and poor-risk disease, respectively, according to expanded Memorial Sloan Kettering Cancer Center criteria. Overall, 52.2% had undergone partial or radical nephrectomy, and nearly all were receiving sunitinib as first-line therapy.

Study results, reported in the Journal of Global Oncology, showed that the mean total sunitinib starting dose was 48.1 mg, with most patients (87.6%) started on a dose of 50 mg. On average, the drug was given for 9.6 months.

The overall response rate was 20.8%, and responses lasted for a median of of 8.2 months. With a median follow-up of 7.8 months, patients had a median time to progression of 5.7 months and a median overall survival of 7.8 months. The 12- and 24-month rates of overall survival were 34.3% and 11.4%, respectively.

Although 60.9% of patients experienced adverse events, only 8.0% experienced serious adverse events. The main adverse events were gastrointestinal and hematologic, mirroring those seen previously in trials. About a third of the whole study cohort (28.7%) discontinued sunitinib therapy.

“OSSMAR is the first study in the Middle East involving several Arab countries and evaluating the use of real-time sunitinib in the treatment of mRCC. As a result, this study is of primary importance because it allows for a better assessment of the actual effectiveness and practical adverse events of sunitinib in the population in our region,” Dr. Ghosn and coinvestigators maintained.

Compared with patients in clinical trials, OSSMAR patients had poorer overall survival, possibly due to factors such as a relatively lower nephrectomy rate, real-world influences such as comorbidities, and losses to follow-up, the investigators proposed.

At the same time, the OSSMAR cohort also had a lower rate of adverse events, although this difference likely reflects less rigorous assessment of toxicity in real-world practice, they noted.

Dr. Ghosn disclosed that he has relationships with numerous pharmaceutical companies. The study did not receive any specific funding.

SOURCE: Ghosn M et al. J Glob Oncol. 2019 Oct 5. doi: 10.1200/JGO.18.00238.

Training and alerts increase the likelihood that oncologists will discuss the costs of genomic testing and related treatments with their patients, suggests a nationally representative survey of oncologists.

“Testing can be expensive, and not all tests and related treatments are covered by health insurance,” note the investigators, who were led by K. Robin Yabroff, PhD, an epidemiologist and senior scientific director of the Surveillance and Health Services Research Program at the American Cancer Society in Atlanta.

Using data from the 2017 National Survey of Precision Medicine in Cancer Treatment, the investigators analyzed factors associated with cost discussions among 1,220 oncologists who had discussed genomic testing with their patients in the past year.

Results reported in the Journal of the National Cancer Institute showed that 50.0% of the oncologists often discussed the likely costs of genomic testing and related treatments with patients and 26.3% sometimes did, while 23.7% never or rarely did.

In adjusted analyses, oncologists were more likely to often discuss costs, versus rarely or never, if they had formal training in genomic testing (odds ratio, 1.74). And they were more likely to sometimes or often have these discussions if their practice had electronic medical record alerts for genomic testing (odds ratios, 2.09 and 2.22).

Additional physician factors positively associated with cost discussions were treating only solid cancers or both solid and hematologic cancers versus only hematologic cancers, and using next-generation sequencing gene panel tests. Additional practice factors showing positive associations included seeing a volume of 100 or more patients per month; having 10% or more of patients who were insured by Medicaid or were self-paying or uninsured; and being located in the West as compared with the Northeast.

When the survey was conducted, the cost of available genomic tests to inform treatment was $300 to more than $10,000, and molecularly targeted therapies commonly had a price tag exceeding $100,000 per year, Dr. Yabroff and coinvestigators note. Moreover, insurance coverage of this testing was in limbo.

“With rapid growth in the availability of genomic tests and targeted treatments for cancer and a large pipeline of treatments in development, improving provider discussions about expected out-of-pocket costs will be critical for ensuring informed patient treatment decision making and the opportunity to plan for treatment expenses and help address out-of-pocket costs by linking patients with available resources, and ensuring high-quality cancer care,” they maintain.

“Interventions targeting modifiable oncologist and practice factors, such as training in genomic testing and use of EMR alerts, may help improve cost discussions about genomic testing and related treatments,” the investigators conclude.

Dr. Yabroff did not disclose any relevant conflicts of interest. The study did not receive any specific funding; the survey was funded by the National Institutes of Health.

SOURCE: Yabroff KR et al. J Natl Cancer Inst. 2019 Nov 1. doi: 10.1093/jnci/djz173.

Training and alerts increase the likelihood that oncologists will discuss the costs of genomic testing and related treatments with their patients, suggests a nationally representative survey of oncologists.

“Testing can be expensive, and not all tests and related treatments are covered by health insurance,” note the investigators, who were led by K. Robin Yabroff, PhD, an epidemiologist and senior scientific director of the Surveillance and Health Services Research Program at the American Cancer Society in Atlanta.

Using data from the 2017 National Survey of Precision Medicine in Cancer Treatment, the investigators analyzed factors associated with cost discussions among 1,220 oncologists who had discussed genomic testing with their patients in the past year.

Results reported in the Journal of the National Cancer Institute showed that 50.0% of the oncologists often discussed the likely costs of genomic testing and related treatments with patients and 26.3% sometimes did, while 23.7% never or rarely did.

In adjusted analyses, oncologists were more likely to often discuss costs, versus rarely or never, if they had formal training in genomic testing (odds ratio, 1.74). And they were more likely to sometimes or often have these discussions if their practice had electronic medical record alerts for genomic testing (odds ratios, 2.09 and 2.22).

Additional physician factors positively associated with cost discussions were treating only solid cancers or both solid and hematologic cancers versus only hematologic cancers, and using next-generation sequencing gene panel tests. Additional practice factors showing positive associations included seeing a volume of 100 or more patients per month; having 10% or more of patients who were insured by Medicaid or were self-paying or uninsured; and being located in the West as compared with the Northeast.

When the survey was conducted, the cost of available genomic tests to inform treatment was $300 to more than $10,000, and molecularly targeted therapies commonly had a price tag exceeding $100,000 per year, Dr. Yabroff and coinvestigators note. Moreover, insurance coverage of this testing was in limbo.

“With rapid growth in the availability of genomic tests and targeted treatments for cancer and a large pipeline of treatments in development, improving provider discussions about expected out-of-pocket costs will be critical for ensuring informed patient treatment decision making and the opportunity to plan for treatment expenses and help address out-of-pocket costs by linking patients with available resources, and ensuring high-quality cancer care,” they maintain.

“Interventions targeting modifiable oncologist and practice factors, such as training in genomic testing and use of EMR alerts, may help improve cost discussions about genomic testing and related treatments,” the investigators conclude.

Dr. Yabroff did not disclose any relevant conflicts of interest. The study did not receive any specific funding; the survey was funded by the National Institutes of Health.

SOURCE: Yabroff KR et al. J Natl Cancer Inst. 2019 Nov 1. doi: 10.1093/jnci/djz173.

Training and alerts increase the likelihood that oncologists will discuss the costs of genomic testing and related treatments with their patients, suggests a nationally representative survey of oncologists.

“Testing can be expensive, and not all tests and related treatments are covered by health insurance,” note the investigators, who were led by K. Robin Yabroff, PhD, an epidemiologist and senior scientific director of the Surveillance and Health Services Research Program at the American Cancer Society in Atlanta.

Using data from the 2017 National Survey of Precision Medicine in Cancer Treatment, the investigators analyzed factors associated with cost discussions among 1,220 oncologists who had discussed genomic testing with their patients in the past year.

Results reported in the Journal of the National Cancer Institute showed that 50.0% of the oncologists often discussed the likely costs of genomic testing and related treatments with patients and 26.3% sometimes did, while 23.7% never or rarely did.

In adjusted analyses, oncologists were more likely to often discuss costs, versus rarely or never, if they had formal training in genomic testing (odds ratio, 1.74). And they were more likely to sometimes or often have these discussions if their practice had electronic medical record alerts for genomic testing (odds ratios, 2.09 and 2.22).

Additional physician factors positively associated with cost discussions were treating only solid cancers or both solid and hematologic cancers versus only hematologic cancers, and using next-generation sequencing gene panel tests. Additional practice factors showing positive associations included seeing a volume of 100 or more patients per month; having 10% or more of patients who were insured by Medicaid or were self-paying or uninsured; and being located in the West as compared with the Northeast.

When the survey was conducted, the cost of available genomic tests to inform treatment was $300 to more than $10,000, and molecularly targeted therapies commonly had a price tag exceeding $100,000 per year, Dr. Yabroff and coinvestigators note. Moreover, insurance coverage of this testing was in limbo.

“With rapid growth in the availability of genomic tests and targeted treatments for cancer and a large pipeline of treatments in development, improving provider discussions about expected out-of-pocket costs will be critical for ensuring informed patient treatment decision making and the opportunity to plan for treatment expenses and help address out-of-pocket costs by linking patients with available resources, and ensuring high-quality cancer care,” they maintain.

“Interventions targeting modifiable oncologist and practice factors, such as training in genomic testing and use of EMR alerts, may help improve cost discussions about genomic testing and related treatments,” the investigators conclude.

Dr. Yabroff did not disclose any relevant conflicts of interest. The study did not receive any specific funding; the survey was funded by the National Institutes of Health.

SOURCE: Yabroff KR et al. J Natl Cancer Inst. 2019 Nov 1. doi: 10.1093/jnci/djz173.

Patients whose clear cell renal cell carcinoma (RCC) tumors lack the cytoskeleton linker protein ezrin have a poorer prognosis, finds a single-center retrospective cohort study.

The number of small renal masses discovered incidentally is rising, and some of these tumors can or must be treated less aggressively, according to lead investigator Marcos Vinicius O. Ferrari, MD, urology division, A.C. Camargo Cancer Center, São Paulo, and coinvestigators. “Thus, it is important to identify molecular markers that have prognostic value that can assist physicians in therapeutic strategies.”

The investigators studied 575 consecutive patients who underwent radical or partial nephrectomy for clear cell RCC during 1985-2016. A single pathologist reclassified all cases and determined the most representative tumor areas for tissue immunohistochemistry for ezrin and moesin, proteins that link the actin cytoskeleton to the cell membrane and that play roles in cell adhesion, migration, and growth.

Results reported in Urologic Oncology showed that 18.3% of tumors were negative for ezrin and 2.8% were negative for moesin.

Compared with counterparts who had ezrin-positive tumors, patients with ezrin-negative tumors had higher pathologic T stage (P less than .001); were less likely to have incidentally discovered tumors (P = .007); and were more likely to have clinical stage III or IV disease (P = .012), synchronous metastasis (P less than .001), and an International Society of Urological Pathology histologic grade of 3 or 4 (P = .025).

Similarly, compared with counterparts who had moesin-positive tumors, patients with moesin-negative tumors had higher pathologic T stage (P = .025) and pathologic N stage (P = .007), and were more likely to have clinical stage III or IV disease (P = .027).

The 10-year rate of disease-specific survival was poorer for patients with ezrin-negative vs. ezrin-positive tumors (70% vs. 88%; P less than .001) and for patients with moesin-negative vs. moesin-positive tumors (68% vs. 86%; P = .065). Similarly, the 10-year rate of overall survival was poorer for patients with ezrin-negative vs. ezrin-positive tumors (68% vs. 86%; P = .001) and for patients with moesin-negative vs. moesin-positive tumors (68% vs. 84%; P = .142).

In multivariate analyses, ezrin negativity was associated with a near doubling of the risk of disease-specific survival events (hazard ratio, 1.89; 95% confidence interval, 1.11-3.20) and with a trend toward poorer overall survival. Moesin negativity was not independently associated with either outcome.

“Negative expression of ezrin was associated with major prognostic factors in renal cancer and significantly influenced tumor-related death,” Dr. Ferrari and coinvestigators summarize, noting that this aligns with the pattern seen in bladder and ovarian cancers, but contrasts with the pattern seen in head and neck, colorectal, cervical, and breast cancers.

“The exact mechanism by which negative ezrin expression influences tumor progression and survival rates is unknown,” they conclude. “We encourage further prospective studies to analyze ezrin to determine its value in the prognosis of clear cell RCC.”

Dr. Ferrari disclosed that he had no relevant conflicts of interest. The study did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sector.

SOURCE: Ferrari MVO et al. Urol Oncol. 2019 Oct 22. doi: 10.1016/j.urolonc.2019.09.011.
 

Patients whose clear cell renal cell carcinoma (RCC) tumors lack the cytoskeleton linker protein ezrin have a poorer prognosis, finds a single-center retrospective cohort study.

The number of small renal masses discovered incidentally is rising, and some of these tumors can or must be treated less aggressively, according to lead investigator Marcos Vinicius O. Ferrari, MD, urology division, A.C. Camargo Cancer Center, São Paulo, and coinvestigators. “Thus, it is important to identify molecular markers that have prognostic value that can assist physicians in therapeutic strategies.”

The investigators studied 575 consecutive patients who underwent radical or partial nephrectomy for clear cell RCC during 1985-2016. A single pathologist reclassified all cases and determined the most representative tumor areas for tissue immunohistochemistry for ezrin and moesin, proteins that link the actin cytoskeleton to the cell membrane and that play roles in cell adhesion, migration, and growth.

Results reported in Urologic Oncology showed that 18.3% of tumors were negative for ezrin and 2.8% were negative for moesin.

Compared with counterparts who had ezrin-positive tumors, patients with ezrin-negative tumors had higher pathologic T stage (P less than .001); were less likely to have incidentally discovered tumors (P = .007); and were more likely to have clinical stage III or IV disease (P = .012), synchronous metastasis (P less than .001), and an International Society of Urological Pathology histologic grade of 3 or 4 (P = .025).

Similarly, compared with counterparts who had moesin-positive tumors, patients with moesin-negative tumors had higher pathologic T stage (P = .025) and pathologic N stage (P = .007), and were more likely to have clinical stage III or IV disease (P = .027).

The 10-year rate of disease-specific survival was poorer for patients with ezrin-negative vs. ezrin-positive tumors (70% vs. 88%; P less than .001) and for patients with moesin-negative vs. moesin-positive tumors (68% vs. 86%; P = .065). Similarly, the 10-year rate of overall survival was poorer for patients with ezrin-negative vs. ezrin-positive tumors (68% vs. 86%; P = .001) and for patients with moesin-negative vs. moesin-positive tumors (68% vs. 84%; P = .142).

In multivariate analyses, ezrin negativity was associated with a near doubling of the risk of disease-specific survival events (hazard ratio, 1.89; 95% confidence interval, 1.11-3.20) and with a trend toward poorer overall survival. Moesin negativity was not independently associated with either outcome.

“Negative expression of ezrin was associated with major prognostic factors in renal cancer and significantly influenced tumor-related death,” Dr. Ferrari and coinvestigators summarize, noting that this aligns with the pattern seen in bladder and ovarian cancers, but contrasts with the pattern seen in head and neck, colorectal, cervical, and breast cancers.

“The exact mechanism by which negative ezrin expression influences tumor progression and survival rates is unknown,” they conclude. “We encourage further prospective studies to analyze ezrin to determine its value in the prognosis of clear cell RCC.”

Dr. Ferrari disclosed that he had no relevant conflicts of interest. The study did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sector.

SOURCE: Ferrari MVO et al. Urol Oncol. 2019 Oct 22. doi: 10.1016/j.urolonc.2019.09.011.
 

Patients whose clear cell renal cell carcinoma (RCC) tumors lack the cytoskeleton linker protein ezrin have a poorer prognosis, finds a single-center retrospective cohort study.

The number of small renal masses discovered incidentally is rising, and some of these tumors can or must be treated less aggressively, according to lead investigator Marcos Vinicius O. Ferrari, MD, urology division, A.C. Camargo Cancer Center, São Paulo, and coinvestigators. “Thus, it is important to identify molecular markers that have prognostic value that can assist physicians in therapeutic strategies.”

The investigators studied 575 consecutive patients who underwent radical or partial nephrectomy for clear cell RCC during 1985-2016. A single pathologist reclassified all cases and determined the most representative tumor areas for tissue immunohistochemistry for ezrin and moesin, proteins that link the actin cytoskeleton to the cell membrane and that play roles in cell adhesion, migration, and growth.

Results reported in Urologic Oncology showed that 18.3% of tumors were negative for ezrin and 2.8% were negative for moesin.

Compared with counterparts who had ezrin-positive tumors, patients with ezrin-negative tumors had higher pathologic T stage (P less than .001); were less likely to have incidentally discovered tumors (P = .007); and were more likely to have clinical stage III or IV disease (P = .012), synchronous metastasis (P less than .001), and an International Society of Urological Pathology histologic grade of 3 or 4 (P = .025).

Similarly, compared with counterparts who had moesin-positive tumors, patients with moesin-negative tumors had higher pathologic T stage (P = .025) and pathologic N stage (P = .007), and were more likely to have clinical stage III or IV disease (P = .027).

The 10-year rate of disease-specific survival was poorer for patients with ezrin-negative vs. ezrin-positive tumors (70% vs. 88%; P less than .001) and for patients with moesin-negative vs. moesin-positive tumors (68% vs. 86%; P = .065). Similarly, the 10-year rate of overall survival was poorer for patients with ezrin-negative vs. ezrin-positive tumors (68% vs. 86%; P = .001) and for patients with moesin-negative vs. moesin-positive tumors (68% vs. 84%; P = .142).

In multivariate analyses, ezrin negativity was associated with a near doubling of the risk of disease-specific survival events (hazard ratio, 1.89; 95% confidence interval, 1.11-3.20) and with a trend toward poorer overall survival. Moesin negativity was not independently associated with either outcome.

“Negative expression of ezrin was associated with major prognostic factors in renal cancer and significantly influenced tumor-related death,” Dr. Ferrari and coinvestigators summarize, noting that this aligns with the pattern seen in bladder and ovarian cancers, but contrasts with the pattern seen in head and neck, colorectal, cervical, and breast cancers.

“The exact mechanism by which negative ezrin expression influences tumor progression and survival rates is unknown,” they conclude. “We encourage further prospective studies to analyze ezrin to determine its value in the prognosis of clear cell RCC.”

Dr. Ferrari disclosed that he had no relevant conflicts of interest. The study did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sector.

SOURCE: Ferrari MVO et al. Urol Oncol. 2019 Oct 22. doi: 10.1016/j.urolonc.2019.09.011.
 

Trial success with a stereotactic body radiation therapy (SBRT) regimen for centrally located non–small cell lung cancer (NSCLC) can be largely replicated in real-world practice, suggests a prospective cohort study published in Clinical Oncology.

The Radiation Therapy Oncology Group (RTOG) 0813 trial established the safety and efficacy of 50 Gy or 60 Gy given in five fractions to patients with early-stage central NSCLC (J Clin Oncol. 2019;37:1316-25). But whether similar outcomes can be achieved in routine care and how the degree of tumor centrality affects outcomes remain unclear.

Investigators led by Robert Rulach, MBChB, from the Beatson West of Scotland Cancer Centre, Glasgow, analyzed outcomes for 50 patients treated with the regimen of 50-Gy in five fractions at their institution for T1-2N0M0 stage NSCLC. All had tumors that were moderately central (within 2 cm of the trachea, bronchi, or proximal bronchial tree or having a planning target volume that abutted mediastinal pleura or pericardium); one had an additional tumor that was ultracentral (having a planning target volume that abutted the trachea).

The patients had a median age of 75.1 years. Notably, the majority were medically unfit for surgery (84%) and had an Eastern Cooperative Oncology Group performance status score of 2 or worse (56%). In 60% of patients, the diagnosis was made radiographically using PET/CT imaging; in the rest, the diagnosis was biopsy proven.

Study results showed that all patients completed the radiotherapy regimen of 50 Gy in 5 fractions on alternate days as planned, without treatment delays.

Two patients (4%) died within 90 days of treatment (1 from a chest infection, 1 from an unknown cause). A single patient each experienced early grade 3 esophagitis and grade 3 late dyspnea, for an overall rate of grade 3 toxicity of 4%. None of the patients experienced grade 4 toxicity. The 90-day rate of hospital admission was 20%.

With a median follow-up of 25.2 months, 34 patients died: 18 from causes unrelated to cancer and 16 from cancer recurrence. The cohort had a median overall survival of 27.0 months and a median cancer-specific survival of 39.8 months. The 2-year overall survival rate was 67.6%.

“For patients with early stage moderately central NSCLC, SABR [stereotactic ablative body radiotherapy] using a schedule of 50 Gy/five fractions has acceptable toxicity and overall survival comparable with the published literature, despite treating a majority of patients with a performance status of 2 or worse,” the investigators concluded.

Dr. Rulach disclosed no conflicts of interest. The study did not receive any specific funding.

SOURCE: Rulach R et al. Clin Oncol. 2019 Oct 10. doi: 10.1016/j.clon.2019.09.055.

Trial success with a stereotactic body radiation therapy (SBRT) regimen for centrally located non–small cell lung cancer (NSCLC) can be largely replicated in real-world practice, suggests a prospective cohort study published in Clinical Oncology.

The Radiation Therapy Oncology Group (RTOG) 0813 trial established the safety and efficacy of 50 Gy or 60 Gy given in five fractions to patients with early-stage central NSCLC (J Clin Oncol. 2019;37:1316-25). But whether similar outcomes can be achieved in routine care and how the degree of tumor centrality affects outcomes remain unclear.

Investigators led by Robert Rulach, MBChB, from the Beatson West of Scotland Cancer Centre, Glasgow, analyzed outcomes for 50 patients treated with the regimen of 50-Gy in five fractions at their institution for T1-2N0M0 stage NSCLC. All had tumors that were moderately central (within 2 cm of the trachea, bronchi, or proximal bronchial tree or having a planning target volume that abutted mediastinal pleura or pericardium); one had an additional tumor that was ultracentral (having a planning target volume that abutted the trachea).

The patients had a median age of 75.1 years. Notably, the majority were medically unfit for surgery (84%) and had an Eastern Cooperative Oncology Group performance status score of 2 or worse (56%). In 60% of patients, the diagnosis was made radiographically using PET/CT imaging; in the rest, the diagnosis was biopsy proven.

Study results showed that all patients completed the radiotherapy regimen of 50 Gy in 5 fractions on alternate days as planned, without treatment delays.

Two patients (4%) died within 90 days of treatment (1 from a chest infection, 1 from an unknown cause). A single patient each experienced early grade 3 esophagitis and grade 3 late dyspnea, for an overall rate of grade 3 toxicity of 4%. None of the patients experienced grade 4 toxicity. The 90-day rate of hospital admission was 20%.

With a median follow-up of 25.2 months, 34 patients died: 18 from causes unrelated to cancer and 16 from cancer recurrence. The cohort had a median overall survival of 27.0 months and a median cancer-specific survival of 39.8 months. The 2-year overall survival rate was 67.6%.

“For patients with early stage moderately central NSCLC, SABR [stereotactic ablative body radiotherapy] using a schedule of 50 Gy/five fractions has acceptable toxicity and overall survival comparable with the published literature, despite treating a majority of patients with a performance status of 2 or worse,” the investigators concluded.

Dr. Rulach disclosed no conflicts of interest. The study did not receive any specific funding.

SOURCE: Rulach R et al. Clin Oncol. 2019 Oct 10. doi: 10.1016/j.clon.2019.09.055.

Trial success with a stereotactic body radiation therapy (SBRT) regimen for centrally located non–small cell lung cancer (NSCLC) can be largely replicated in real-world practice, suggests a prospective cohort study published in Clinical Oncology.

The Radiation Therapy Oncology Group (RTOG) 0813 trial established the safety and efficacy of 50 Gy or 60 Gy given in five fractions to patients with early-stage central NSCLC (J Clin Oncol. 2019;37:1316-25). But whether similar outcomes can be achieved in routine care and how the degree of tumor centrality affects outcomes remain unclear.

Investigators led by Robert Rulach, MBChB, from the Beatson West of Scotland Cancer Centre, Glasgow, analyzed outcomes for 50 patients treated with the regimen of 50-Gy in five fractions at their institution for T1-2N0M0 stage NSCLC. All had tumors that were moderately central (within 2 cm of the trachea, bronchi, or proximal bronchial tree or having a planning target volume that abutted mediastinal pleura or pericardium); one had an additional tumor that was ultracentral (having a planning target volume that abutted the trachea).

The patients had a median age of 75.1 years. Notably, the majority were medically unfit for surgery (84%) and had an Eastern Cooperative Oncology Group performance status score of 2 or worse (56%). In 60% of patients, the diagnosis was made radiographically using PET/CT imaging; in the rest, the diagnosis was biopsy proven.

Study results showed that all patients completed the radiotherapy regimen of 50 Gy in 5 fractions on alternate days as planned, without treatment delays.

Two patients (4%) died within 90 days of treatment (1 from a chest infection, 1 from an unknown cause). A single patient each experienced early grade 3 esophagitis and grade 3 late dyspnea, for an overall rate of grade 3 toxicity of 4%. None of the patients experienced grade 4 toxicity. The 90-day rate of hospital admission was 20%.

With a median follow-up of 25.2 months, 34 patients died: 18 from causes unrelated to cancer and 16 from cancer recurrence. The cohort had a median overall survival of 27.0 months and a median cancer-specific survival of 39.8 months. The 2-year overall survival rate was 67.6%.

“For patients with early stage moderately central NSCLC, SABR [stereotactic ablative body radiotherapy] using a schedule of 50 Gy/five fractions has acceptable toxicity and overall survival comparable with the published literature, despite treating a majority of patients with a performance status of 2 or worse,” the investigators concluded.

Dr. Rulach disclosed no conflicts of interest. The study did not receive any specific funding.

SOURCE: Rulach R et al. Clin Oncol. 2019 Oct 10. doi: 10.1016/j.clon.2019.09.055.

Lazertinib, an investigational third-generation oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), has good safety and antitumor activity in patients with EGFR-mutated advanced non–small cell lung cancer (NSCLC), finds a phase 1/2 trial.

Only about one in six patients experienced a grade 3 or 4 adverse event when given the drug at various doses, according to results reported in The Lancet Oncology.

Meanwhile, 54% of patients achieved a response, with a higher rate seen among those whose tumors were positive versus negative for the T790M resistance mutation. Notably, 44% of the subgroup with brain metastases had an intracranial response.

“[O]ur results show that lazertinib is well tolerated, with responses frequently observed in patients with NSCLC harbouring both activating EGFR mutations and EGFR T790M TKI resistance mutations. Intracranial responses were also frequently seen, indicating effective blood-brain barrier penetration,” wrote senior investigator Byoung Chul Cho, MD, PhD, Cancer Center, Yonsei University College of Medicine, Seoul, South Korea, and coinvestigators.

“Lazertinib has a potential therapeutic role in the treatment of NSCLC harbouring EGFR T790M mutations, either alone or in combination with other drugs,” they concluded.

The trial was conducted in Korea among adults having advanced NSCLC with an activating EGFR mutation who experienced progression after treatment with a first- or second-generation EGFR TKI. All were treated on an open-label basis with lazertinib at dose levels from 20 mg to 320 mg once daily, continuously in 21-day cycles.

Dr. Cho and coinvestigators reported results for 127 patients (38 in a dose escalation cohort and 89 in a dose expansion cohort).

Results showed that there were no dose-limiting toxicities and no dose-dependent increases in adverse events. The leading adverse events were grade 1 or 2 rash or acne (30%) and pruritus (27%). Overall, 16% of patients experienced grade 3 or grade 4 adverse events, most commonly grade 3 pneumonia (3%). Only 3% of patients had treatment-related grade 3 or 4 adverse events, while 5% had treatment-related serious adverse events. None experienced adverse events leading to death or treatment-related death.

On independent central review, 54% of patients overall had an objective response (52% had a partial response, 2% had a complete response). The response rate was 57% in patients with T790M-positive tumors compared with 37% in patients with T790M-negative tumors.

The median duration of response was 15.2 months. With a median follow-up of 11.0 months, the median progression-free survival was 9.5 months for the whole study cohort; it was longer in patients whose tumors were positive versus negative for the T790M resistance mutations (9.7 months vs 5.4 months).

Among evaluable patients with brain metastases, the intracranial response rate was 44%, and median intracranial progression-free survival was not reached.

Dr. Cho disclosed relationships with numerous pharmaceutical companies, including Yuhan Corporation, which funded the trial.

SOURCE: Cho BC et al. Lancet Oncol. 2019 Oct 3. doi: 10.1016/S1470-2045(19)30504-2.

Lazertinib, an investigational third-generation oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), has good safety and antitumor activity in patients with EGFR-mutated advanced non–small cell lung cancer (NSCLC), finds a phase 1/2 trial.

Only about one in six patients experienced a grade 3 or 4 adverse event when given the drug at various doses, according to results reported in The Lancet Oncology.

Meanwhile, 54% of patients achieved a response, with a higher rate seen among those whose tumors were positive versus negative for the T790M resistance mutation. Notably, 44% of the subgroup with brain metastases had an intracranial response.

“[O]ur results show that lazertinib is well tolerated, with responses frequently observed in patients with NSCLC harbouring both activating EGFR mutations and EGFR T790M TKI resistance mutations. Intracranial responses were also frequently seen, indicating effective blood-brain barrier penetration,” wrote senior investigator Byoung Chul Cho, MD, PhD, Cancer Center, Yonsei University College of Medicine, Seoul, South Korea, and coinvestigators.

“Lazertinib has a potential therapeutic role in the treatment of NSCLC harbouring EGFR T790M mutations, either alone or in combination with other drugs,” they concluded.

The trial was conducted in Korea among adults having advanced NSCLC with an activating EGFR mutation who experienced progression after treatment with a first- or second-generation EGFR TKI. All were treated on an open-label basis with lazertinib at dose levels from 20 mg to 320 mg once daily, continuously in 21-day cycles.

Dr. Cho and coinvestigators reported results for 127 patients (38 in a dose escalation cohort and 89 in a dose expansion cohort).

Results showed that there were no dose-limiting toxicities and no dose-dependent increases in adverse events. The leading adverse events were grade 1 or 2 rash or acne (30%) and pruritus (27%). Overall, 16% of patients experienced grade 3 or grade 4 adverse events, most commonly grade 3 pneumonia (3%). Only 3% of patients had treatment-related grade 3 or 4 adverse events, while 5% had treatment-related serious adverse events. None experienced adverse events leading to death or treatment-related death.

On independent central review, 54% of patients overall had an objective response (52% had a partial response, 2% had a complete response). The response rate was 57% in patients with T790M-positive tumors compared with 37% in patients with T790M-negative tumors.

The median duration of response was 15.2 months. With a median follow-up of 11.0 months, the median progression-free survival was 9.5 months for the whole study cohort; it was longer in patients whose tumors were positive versus negative for the T790M resistance mutations (9.7 months vs 5.4 months).

Among evaluable patients with brain metastases, the intracranial response rate was 44%, and median intracranial progression-free survival was not reached.

Dr. Cho disclosed relationships with numerous pharmaceutical companies, including Yuhan Corporation, which funded the trial.

SOURCE: Cho BC et al. Lancet Oncol. 2019 Oct 3. doi: 10.1016/S1470-2045(19)30504-2.

Lazertinib, an investigational third-generation oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), has good safety and antitumor activity in patients with EGFR-mutated advanced non–small cell lung cancer (NSCLC), finds a phase 1/2 trial.

Only about one in six patients experienced a grade 3 or 4 adverse event when given the drug at various doses, according to results reported in The Lancet Oncology.

Meanwhile, 54% of patients achieved a response, with a higher rate seen among those whose tumors were positive versus negative for the T790M resistance mutation. Notably, 44% of the subgroup with brain metastases had an intracranial response.

“[O]ur results show that lazertinib is well tolerated, with responses frequently observed in patients with NSCLC harbouring both activating EGFR mutations and EGFR T790M TKI resistance mutations. Intracranial responses were also frequently seen, indicating effective blood-brain barrier penetration,” wrote senior investigator Byoung Chul Cho, MD, PhD, Cancer Center, Yonsei University College of Medicine, Seoul, South Korea, and coinvestigators.

“Lazertinib has a potential therapeutic role in the treatment of NSCLC harbouring EGFR T790M mutations, either alone or in combination with other drugs,” they concluded.

The trial was conducted in Korea among adults having advanced NSCLC with an activating EGFR mutation who experienced progression after treatment with a first- or second-generation EGFR TKI. All were treated on an open-label basis with lazertinib at dose levels from 20 mg to 320 mg once daily, continuously in 21-day cycles.

Dr. Cho and coinvestigators reported results for 127 patients (38 in a dose escalation cohort and 89 in a dose expansion cohort).

Results showed that there were no dose-limiting toxicities and no dose-dependent increases in adverse events. The leading adverse events were grade 1 or 2 rash or acne (30%) and pruritus (27%). Overall, 16% of patients experienced grade 3 or grade 4 adverse events, most commonly grade 3 pneumonia (3%). Only 3% of patients had treatment-related grade 3 or 4 adverse events, while 5% had treatment-related serious adverse events. None experienced adverse events leading to death or treatment-related death.

On independent central review, 54% of patients overall had an objective response (52% had a partial response, 2% had a complete response). The response rate was 57% in patients with T790M-positive tumors compared with 37% in patients with T790M-negative tumors.

The median duration of response was 15.2 months. With a median follow-up of 11.0 months, the median progression-free survival was 9.5 months for the whole study cohort; it was longer in patients whose tumors were positive versus negative for the T790M resistance mutations (9.7 months vs 5.4 months).

Among evaluable patients with brain metastases, the intracranial response rate was 44%, and median intracranial progression-free survival was not reached.

Dr. Cho disclosed relationships with numerous pharmaceutical companies, including Yuhan Corporation, which funded the trial.

SOURCE: Cho BC et al. Lancet Oncol. 2019 Oct 3. doi: 10.1016/S1470-2045(19)30504-2.

Some patients with advanced renal cell carcinoma (RCC) treated with immune checkpoint inhibitors (ICIs) can safely undergo nephrectomy and experience favorable surgical outcomes and pathologic responses, a cohort study suggests.

“The introduction of several novel classes of systemic therapies, including targeted therapies and most recently ICI, has revolutionized the management of metastatic RCC over the last decade,” noted the investigators, who were led by Nirmish Singla, MD, from the department of urology at the University of Texas Southwestern Medical Center, Dallas. “With these new therapies, the role of nephrectomy in the treatment paradigm for advanced RCC has continued to evolve.”

The investigators undertook a single-center retrospective cohort study, assessing outcomes of 11 nephrectomies (10 radical, 1 partial) in 10 patients with advanced RCC who had received ICIs. Half had received nivolumab (Opdivo) alone, while the other half had received nivolumab in combination with ipilimumab (Yervoy); in six patients, these therapies were given first line.

Study results reported in Urologic Oncology showed that, at the time of nephrectomy, the patients had a median age of 64 years, with a range from 41 years to 83 years. Surgery was performed laparoscopically in five cases, and four patients had a concomitant thrombectomy.

The median operative time was 180 minutes, and the median estimated blood loss was 100 mL. None of the patients experienced major intraoperative complications. Four experienced postoperative complications; in three, they were addressed with interventional radiology procedures. The median length of stay was 4 days.

Pathology findings showed that one patient achieved a response to immunotherapy in the primary tumor (pT0), and three of four patients who underwent resection of hepatic, pulmonary, or adrenal metastases had no detectable cancer (pM0). All surgical margins were negative.

During a median postoperative follow-up of 180 days, one patient died of progressive disease more than 3 months after surgery, and another died of pulmonary embolism complicated by sepsis. Six patients did not have any complications or readmissions.

“In our experience, nephrectomy following ICI for RCC is both safe and technically feasible. Surgical and postoperative outcomes are encouraging, and pathologic response to ICI is strikingly favorable in both the primary tumor and metastatic sites,” Dr. Singla and coinvestigators wrote. “Biopsies of lesions responding radiographically to ICIs should be considered prior to surgical excision.”

“As multimodal management in the immunotherapy era continues to evolve, the utility and timing of nephrectomy combined with ICI in selected patients warrants further study,” they conclude.

Dr. Singla disclosed that he had no relevant conflicts of interest. The study did not receive any specific funding.

SOURCE: Singla N et al. Urol Oncol. 2019 Sep 12. doi: 10.1016/j.urolonc.2019.08.012.

Some patients with advanced renal cell carcinoma (RCC) treated with immune checkpoint inhibitors (ICIs) can safely undergo nephrectomy and experience favorable surgical outcomes and pathologic responses, a cohort study suggests.

“The introduction of several novel classes of systemic therapies, including targeted therapies and most recently ICI, has revolutionized the management of metastatic RCC over the last decade,” noted the investigators, who were led by Nirmish Singla, MD, from the department of urology at the University of Texas Southwestern Medical Center, Dallas. “With these new therapies, the role of nephrectomy in the treatment paradigm for advanced RCC has continued to evolve.”

The investigators undertook a single-center retrospective cohort study, assessing outcomes of 11 nephrectomies (10 radical, 1 partial) in 10 patients with advanced RCC who had received ICIs. Half had received nivolumab (Opdivo) alone, while the other half had received nivolumab in combination with ipilimumab (Yervoy); in six patients, these therapies were given first line.

Study results reported in Urologic Oncology showed that, at the time of nephrectomy, the patients had a median age of 64 years, with a range from 41 years to 83 years. Surgery was performed laparoscopically in five cases, and four patients had a concomitant thrombectomy.

The median operative time was 180 minutes, and the median estimated blood loss was 100 mL. None of the patients experienced major intraoperative complications. Four experienced postoperative complications; in three, they were addressed with interventional radiology procedures. The median length of stay was 4 days.

Pathology findings showed that one patient achieved a response to immunotherapy in the primary tumor (pT0), and three of four patients who underwent resection of hepatic, pulmonary, or adrenal metastases had no detectable cancer (pM0). All surgical margins were negative.

During a median postoperative follow-up of 180 days, one patient died of progressive disease more than 3 months after surgery, and another died of pulmonary embolism complicated by sepsis. Six patients did not have any complications or readmissions.

“In our experience, nephrectomy following ICI for RCC is both safe and technically feasible. Surgical and postoperative outcomes are encouraging, and pathologic response to ICI is strikingly favorable in both the primary tumor and metastatic sites,” Dr. Singla and coinvestigators wrote. “Biopsies of lesions responding radiographically to ICIs should be considered prior to surgical excision.”

“As multimodal management in the immunotherapy era continues to evolve, the utility and timing of nephrectomy combined with ICI in selected patients warrants further study,” they conclude.

Dr. Singla disclosed that he had no relevant conflicts of interest. The study did not receive any specific funding.

SOURCE: Singla N et al. Urol Oncol. 2019 Sep 12. doi: 10.1016/j.urolonc.2019.08.012.

Some patients with advanced renal cell carcinoma (RCC) treated with immune checkpoint inhibitors (ICIs) can safely undergo nephrectomy and experience favorable surgical outcomes and pathologic responses, a cohort study suggests.

“The introduction of several novel classes of systemic therapies, including targeted therapies and most recently ICI, has revolutionized the management of metastatic RCC over the last decade,” noted the investigators, who were led by Nirmish Singla, MD, from the department of urology at the University of Texas Southwestern Medical Center, Dallas. “With these new therapies, the role of nephrectomy in the treatment paradigm for advanced RCC has continued to evolve.”

The investigators undertook a single-center retrospective cohort study, assessing outcomes of 11 nephrectomies (10 radical, 1 partial) in 10 patients with advanced RCC who had received ICIs. Half had received nivolumab (Opdivo) alone, while the other half had received nivolumab in combination with ipilimumab (Yervoy); in six patients, these therapies were given first line.

Study results reported in Urologic Oncology showed that, at the time of nephrectomy, the patients had a median age of 64 years, with a range from 41 years to 83 years. Surgery was performed laparoscopically in five cases, and four patients had a concomitant thrombectomy.

The median operative time was 180 minutes, and the median estimated blood loss was 100 mL. None of the patients experienced major intraoperative complications. Four experienced postoperative complications; in three, they were addressed with interventional radiology procedures. The median length of stay was 4 days.

Pathology findings showed that one patient achieved a response to immunotherapy in the primary tumor (pT0), and three of four patients who underwent resection of hepatic, pulmonary, or adrenal metastases had no detectable cancer (pM0). All surgical margins were negative.

During a median postoperative follow-up of 180 days, one patient died of progressive disease more than 3 months after surgery, and another died of pulmonary embolism complicated by sepsis. Six patients did not have any complications or readmissions.

“In our experience, nephrectomy following ICI for RCC is both safe and technically feasible. Surgical and postoperative outcomes are encouraging, and pathologic response to ICI is strikingly favorable in both the primary tumor and metastatic sites,” Dr. Singla and coinvestigators wrote. “Biopsies of lesions responding radiographically to ICIs should be considered prior to surgical excision.”

“As multimodal management in the immunotherapy era continues to evolve, the utility and timing of nephrectomy combined with ICI in selected patients warrants further study,” they conclude.

Dr. Singla disclosed that he had no relevant conflicts of interest. The study did not receive any specific funding.

SOURCE: Singla N et al. Urol Oncol. 2019 Sep 12. doi: 10.1016/j.urolonc.2019.08.012.

Combination therapy with the immune checkpoint inhibitors nivolumab and ipilimumab has durable efficacy in patients with untreated advanced melanoma, with more than half still alive at 5 years and almost three-fourths of them no longer on any treatment, found an update of the CheckMate 067 trial. The combination also had a manageable safety profile and generally maintained health-related quality of life in the long term.

“The apparent plateau with nivolumab plus ipilimumab has continued with longer follow-up … nivolumab plus ipilimumab is … currently the only treatment for metastatic melanoma for which median overall survival has not been reached at 5 years,” noted the investigators, led by James Larkin, FRCP, PhD, a consultant medical oncologist at the Royal Marsden National Health Service Foundation Trust, London. “The current results of the CheckMate 067 trial set a new foundation on which to make improvements in long-term efficacy outcomes with the combination of nivolumab plus ipilimumab.”

The phase 3, randomized, controlled trial pitted nivolumab (Opdivo) plus ipilimumab (Yervoy) combination therapy and nivolumab monotherapy against ipilimumab monotherapy among 945 adults with previously untreated or unresectable metastatic melanoma. Initial results at a median follow-up of about 1 year showed a progression-free survival benefit of the nivolumab regimens (N Engl J Med. 2015;373:23-34), a pattern that has persisted in updates and has been augmented by an overall survival benefit, as seen most recently at a median follow-up of about 4 years (Lancet Oncol. 2018;19:1480-92).

Dr. Larkin and colleagues performed another update, now at a minimum follow-up of 5 years in all patients. This update additionally looked at subsequent therapies and health-related quality of life.

Results reported in the New England Journal of Medicine showed that median overall survival was now 19.9 months with ipilimumab. In comparison, it was not reached with nivolumab-ipilimumab (hazard ratio for death, 0.52) and was 36.9 months with nivolumab alone (HR, 0.63). The 5-year overall survival rate was 26%, compared with 52% and 44%, respectively.

In all groups, complete response rates continued an increase seen since the trial’s initial results were reported. “[T]his indicates that the best response can improve over time with immune checkpoint inhibitors,” Dr. Larkin and coinvestigators maintained.

“The treatment-free interval continued to lengthen in the nivolumab-plus-ipilimumab group, and the percentage of patients who were alive and not receiving treatment continued to increase across the groups,” they further noted. As of the update, the median treatment-free interval was 18.1 months with nivolumab-ipilimumab, 1.8 months with nivolumab, and 1.9 months with ipilimumab. The percentage of those alive who were not receiving any trial treatment or subsequent systemic therapy was 74%, 58%, and 45%, respectively.

Meanwhile, the data did not show any new safety signals. And health-related quality of life, measured with European Quality of Life 5-Dimensions 3-Level questionnaire, was generally sustained during and after treatment, with limited fluctuations outside a 0.08-point clinically meaningful boundary, in the combination-therapy group and the nivolumab group, whereas it deteriorated more often in the ipilimumab group.

Dr. Larkin disclosed grants and personal fees from numerous pharmaceutical companies. The trial was supported by Bristol-Myers Squibb, a grant from the National Cancer Institute, and a grant (to Dr. Larkin) from the National Institute for Health Research Royal Marsden–Institute of Cancer Research Biomedical Research Centre.

SOURCE: Larkin J et al. N Engl J Med. 2019 Sep 28. doi: 10.1056/NEJMoa1910836.

Combination therapy with the immune checkpoint inhibitors nivolumab and ipilimumab has durable efficacy in patients with untreated advanced melanoma, with more than half still alive at 5 years and almost three-fourths of them no longer on any treatment, found an update of the CheckMate 067 trial. The combination also had a manageable safety profile and generally maintained health-related quality of life in the long term.

“The apparent plateau with nivolumab plus ipilimumab has continued with longer follow-up … nivolumab plus ipilimumab is … currently the only treatment for metastatic melanoma for which median overall survival has not been reached at 5 years,” noted the investigators, led by James Larkin, FRCP, PhD, a consultant medical oncologist at the Royal Marsden National Health Service Foundation Trust, London. “The current results of the CheckMate 067 trial set a new foundation on which to make improvements in long-term efficacy outcomes with the combination of nivolumab plus ipilimumab.”

The phase 3, randomized, controlled trial pitted nivolumab (Opdivo) plus ipilimumab (Yervoy) combination therapy and nivolumab monotherapy against ipilimumab monotherapy among 945 adults with previously untreated or unresectable metastatic melanoma. Initial results at a median follow-up of about 1 year showed a progression-free survival benefit of the nivolumab regimens (N Engl J Med. 2015;373:23-34), a pattern that has persisted in updates and has been augmented by an overall survival benefit, as seen most recently at a median follow-up of about 4 years (Lancet Oncol. 2018;19:1480-92).

Dr. Larkin and colleagues performed another update, now at a minimum follow-up of 5 years in all patients. This update additionally looked at subsequent therapies and health-related quality of life.

Results reported in the New England Journal of Medicine showed that median overall survival was now 19.9 months with ipilimumab. In comparison, it was not reached with nivolumab-ipilimumab (hazard ratio for death, 0.52) and was 36.9 months with nivolumab alone (HR, 0.63). The 5-year overall survival rate was 26%, compared with 52% and 44%, respectively.

In all groups, complete response rates continued an increase seen since the trial’s initial results were reported. “[T]his indicates that the best response can improve over time with immune checkpoint inhibitors,” Dr. Larkin and coinvestigators maintained.

“The treatment-free interval continued to lengthen in the nivolumab-plus-ipilimumab group, and the percentage of patients who were alive and not receiving treatment continued to increase across the groups,” they further noted. As of the update, the median treatment-free interval was 18.1 months with nivolumab-ipilimumab, 1.8 months with nivolumab, and 1.9 months with ipilimumab. The percentage of those alive who were not receiving any trial treatment or subsequent systemic therapy was 74%, 58%, and 45%, respectively.

Meanwhile, the data did not show any new safety signals. And health-related quality of life, measured with European Quality of Life 5-Dimensions 3-Level questionnaire, was generally sustained during and after treatment, with limited fluctuations outside a 0.08-point clinically meaningful boundary, in the combination-therapy group and the nivolumab group, whereas it deteriorated more often in the ipilimumab group.

Dr. Larkin disclosed grants and personal fees from numerous pharmaceutical companies. The trial was supported by Bristol-Myers Squibb, a grant from the National Cancer Institute, and a grant (to Dr. Larkin) from the National Institute for Health Research Royal Marsden–Institute of Cancer Research Biomedical Research Centre.

SOURCE: Larkin J et al. N Engl J Med. 2019 Sep 28. doi: 10.1056/NEJMoa1910836.

Combination therapy with the immune checkpoint inhibitors nivolumab and ipilimumab has durable efficacy in patients with untreated advanced melanoma, with more than half still alive at 5 years and almost three-fourths of them no longer on any treatment, found an update of the CheckMate 067 trial. The combination also had a manageable safety profile and generally maintained health-related quality of life in the long term.

“The apparent plateau with nivolumab plus ipilimumab has continued with longer follow-up … nivolumab plus ipilimumab is … currently the only treatment for metastatic melanoma for which median overall survival has not been reached at 5 years,” noted the investigators, led by James Larkin, FRCP, PhD, a consultant medical oncologist at the Royal Marsden National Health Service Foundation Trust, London. “The current results of the CheckMate 067 trial set a new foundation on which to make improvements in long-term efficacy outcomes with the combination of nivolumab plus ipilimumab.”

The phase 3, randomized, controlled trial pitted nivolumab (Opdivo) plus ipilimumab (Yervoy) combination therapy and nivolumab monotherapy against ipilimumab monotherapy among 945 adults with previously untreated or unresectable metastatic melanoma. Initial results at a median follow-up of about 1 year showed a progression-free survival benefit of the nivolumab regimens (N Engl J Med. 2015;373:23-34), a pattern that has persisted in updates and has been augmented by an overall survival benefit, as seen most recently at a median follow-up of about 4 years (Lancet Oncol. 2018;19:1480-92).

Dr. Larkin and colleagues performed another update, now at a minimum follow-up of 5 years in all patients. This update additionally looked at subsequent therapies and health-related quality of life.

Results reported in the New England Journal of Medicine showed that median overall survival was now 19.9 months with ipilimumab. In comparison, it was not reached with nivolumab-ipilimumab (hazard ratio for death, 0.52) and was 36.9 months with nivolumab alone (HR, 0.63). The 5-year overall survival rate was 26%, compared with 52% and 44%, respectively.

In all groups, complete response rates continued an increase seen since the trial’s initial results were reported. “[T]his indicates that the best response can improve over time with immune checkpoint inhibitors,” Dr. Larkin and coinvestigators maintained.

“The treatment-free interval continued to lengthen in the nivolumab-plus-ipilimumab group, and the percentage of patients who were alive and not receiving treatment continued to increase across the groups,” they further noted. As of the update, the median treatment-free interval was 18.1 months with nivolumab-ipilimumab, 1.8 months with nivolumab, and 1.9 months with ipilimumab. The percentage of those alive who were not receiving any trial treatment or subsequent systemic therapy was 74%, 58%, and 45%, respectively.

Meanwhile, the data did not show any new safety signals. And health-related quality of life, measured with European Quality of Life 5-Dimensions 3-Level questionnaire, was generally sustained during and after treatment, with limited fluctuations outside a 0.08-point clinically meaningful boundary, in the combination-therapy group and the nivolumab group, whereas it deteriorated more often in the ipilimumab group.

Dr. Larkin disclosed grants and personal fees from numerous pharmaceutical companies. The trial was supported by Bristol-Myers Squibb, a grant from the National Cancer Institute, and a grant (to Dr. Larkin) from the National Institute for Health Research Royal Marsden–Institute of Cancer Research Biomedical Research Centre.

SOURCE: Larkin J et al. N Engl J Med. 2019 Sep 28. doi: 10.1056/NEJMoa1910836.

A new analysis of 40 years of U.S. cancer data underscores the importance of looking at multiple metrics to discern the complex interplay of factors influencing cancer burden in the population. Findings showed that the epidemiologic signature – a composite of two or three key metrics – differed across cancer types and was favorable in some cases and unfavorable in others.

“Epidemiologic signatures that illustrate trends in population-based data on cancer burden provide insight into true cancer occurrence, overdiagnosis, and treatment advances,” explain the analysts, led by H. Gilbert Welch, MD, MPH, Center for Surgery and Public Health, Brigham and Women’s Hospital, Boston. “They are important indicators of the potential contribution of environmental exposures, primary preventive interventions, new treatments, and changing diagnostic and screening practices.”

Dr. Welch and colleagues analyzed data for the years 1975 through 2015, assessing juxtaposed trends in incidence, mortality, and, when available, metastatic incidence (cancer already metastatic at diagnosis) for 11 cancers individually and for all cancers combined. Incidence data combining invasive and in situ cancers were obtained from the original nine Surveillance, Epidemiology, and End Results (SEER) registries, and mortality data were obtained from the National Vital Statistics System.

The analysts then explored implications of the epidemiologic signatures as they pertain to true cancer occurrence (the underlying incidence of clinically meaningful cancer), overdiagnosis (detection of cancers that will not cause symptoms or death), and treatment advances.
 

Individual cancers

Findings of the analysis, published in a special report in the New England Journal of Medicine, revealed three broad categories of epidemiologic signatures having different implications for the public health and oncology fields.

Desirable signatures showed, for example, declining mortality against a backdrop of stable incidence over the 40-year period, signaling improved treatment, as seen for chronic myeloid leukemia following introduction of imatinib (Gleevec), according to the analysts. Lung cancer incidence and mortality rose and fell in tandem, reflecting an increase in smoking followed by a decrease in response to prevention efforts. Stomach, cervical, and colorectal cancers had both falling incidence – likely reflecting a true decline in occurrence related to prevention and/or screening detection and subsequent treatment of precancerous lesions – and falling mortality.

Undesirable signatures showed a rising incidence juxtaposed with stable mortality and stable or rising metastatic incidence, signaling likely overdiagnosis, Dr. Welch and colleagues proposed. Three cancers—thyroid cancer, kidney cancer, and melanoma—fell into this category; for thyroid cancer and melanoma, fairly recent upticks in metastatic incidence may reflect upstaging.

Finally, some signatures showed mixed signals, with rising incidence and falling mortality. Breast cancer incidence rose and stabilized, coinciding with introduction of screening mammography, and possibly reflecting an increase in true cancer occurrence or overdiagnosis (with stable metastatic incidence favoring the latter), the analysts speculate. Declining mortality since the 1990s may be due to improved treatment or screening, or both. Prostate cancer incidence rose sharply with introduction of prostate-specific antigen screening but then fell to initial levels, suggesting sensitivity of this cancer to diagnostic scrutiny. Falling metastatic incidence indicates screening leads to earlier diagnosis in some cases, while declining mortality starting in the 1990s may again reflect improved treatment or screening, or both.
 

All cancers

The epidemiologic signature for all cancers combined differed somewhat by sex. Women had a rising incidence during the 1980s that was mainly driven by lung and breast cancers, according to Dr. Welch and colleagues; a continued rise since the mid-1990s was largely driven by melanoma, kidney cancer, and thyroid cancer. Declining mortality since 1990 has been primarily due to reductions in deaths from breast and colorectal cancers, and, more recently, lung cancer.

Men had a “volatile pattern” in the incidence of all cancers combined that was attributable to prostate cancer trends; drops in lung and colorectal cancer incidences were offset by rises in melanoma and kidney cancer incidences, the analysts proposed. Declining mortality since 1990 was more marked than that among women and reflects a longer period of decline in lung cancer mortality, plus reductions in deaths from prostate cancer and colorectal cancer.

“Falling mortality means that there has been real progress against cancer in the past 40 years – largely reflecting improved treatment and the decline of a uniquely powerful causal factor: cigarette smoking,” Dr. Welch and colleagues noted. “The lack of an accompanying fall in incidence is an unfortunate side effect of early cancer-detection efforts.”

Dr. Welch reported that he had no relevant disclosures. The analysis did not receive any specific funding.

SOURCE: Welch HG et al. N Engl J Med. 2019;381:1378-86. doi: 10.1056/NEJMsr1905447.

A new analysis of 40 years of U.S. cancer data underscores the importance of looking at multiple metrics to discern the complex interplay of factors influencing cancer burden in the population. Findings showed that the epidemiologic signature – a composite of two or three key metrics – differed across cancer types and was favorable in some cases and unfavorable in others.

“Epidemiologic signatures that illustrate trends in population-based data on cancer burden provide insight into true cancer occurrence, overdiagnosis, and treatment advances,” explain the analysts, led by H. Gilbert Welch, MD, MPH, Center for Surgery and Public Health, Brigham and Women’s Hospital, Boston. “They are important indicators of the potential contribution of environmental exposures, primary preventive interventions, new treatments, and changing diagnostic and screening practices.”

Dr. Welch and colleagues analyzed data for the years 1975 through 2015, assessing juxtaposed trends in incidence, mortality, and, when available, metastatic incidence (cancer already metastatic at diagnosis) for 11 cancers individually and for all cancers combined. Incidence data combining invasive and in situ cancers were obtained from the original nine Surveillance, Epidemiology, and End Results (SEER) registries, and mortality data were obtained from the National Vital Statistics System.

The analysts then explored implications of the epidemiologic signatures as they pertain to true cancer occurrence (the underlying incidence of clinically meaningful cancer), overdiagnosis (detection of cancers that will not cause symptoms or death), and treatment advances.
 

Individual cancers

Findings of the analysis, published in a special report in the New England Journal of Medicine, revealed three broad categories of epidemiologic signatures having different implications for the public health and oncology fields.

Desirable signatures showed, for example, declining mortality against a backdrop of stable incidence over the 40-year period, signaling improved treatment, as seen for chronic myeloid leukemia following introduction of imatinib (Gleevec), according to the analysts. Lung cancer incidence and mortality rose and fell in tandem, reflecting an increase in smoking followed by a decrease in response to prevention efforts. Stomach, cervical, and colorectal cancers had both falling incidence – likely reflecting a true decline in occurrence related to prevention and/or screening detection and subsequent treatment of precancerous lesions – and falling mortality.

Undesirable signatures showed a rising incidence juxtaposed with stable mortality and stable or rising metastatic incidence, signaling likely overdiagnosis, Dr. Welch and colleagues proposed. Three cancers—thyroid cancer, kidney cancer, and melanoma—fell into this category; for thyroid cancer and melanoma, fairly recent upticks in metastatic incidence may reflect upstaging.

Finally, some signatures showed mixed signals, with rising incidence and falling mortality. Breast cancer incidence rose and stabilized, coinciding with introduction of screening mammography, and possibly reflecting an increase in true cancer occurrence or overdiagnosis (with stable metastatic incidence favoring the latter), the analysts speculate. Declining mortality since the 1990s may be due to improved treatment or screening, or both. Prostate cancer incidence rose sharply with introduction of prostate-specific antigen screening but then fell to initial levels, suggesting sensitivity of this cancer to diagnostic scrutiny. Falling metastatic incidence indicates screening leads to earlier diagnosis in some cases, while declining mortality starting in the 1990s may again reflect improved treatment or screening, or both.
 

All cancers

The epidemiologic signature for all cancers combined differed somewhat by sex. Women had a rising incidence during the 1980s that was mainly driven by lung and breast cancers, according to Dr. Welch and colleagues; a continued rise since the mid-1990s was largely driven by melanoma, kidney cancer, and thyroid cancer. Declining mortality since 1990 has been primarily due to reductions in deaths from breast and colorectal cancers, and, more recently, lung cancer.

Men had a “volatile pattern” in the incidence of all cancers combined that was attributable to prostate cancer trends; drops in lung and colorectal cancer incidences were offset by rises in melanoma and kidney cancer incidences, the analysts proposed. Declining mortality since 1990 was more marked than that among women and reflects a longer period of decline in lung cancer mortality, plus reductions in deaths from prostate cancer and colorectal cancer.

“Falling mortality means that there has been real progress against cancer in the past 40 years – largely reflecting improved treatment and the decline of a uniquely powerful causal factor: cigarette smoking,” Dr. Welch and colleagues noted. “The lack of an accompanying fall in incidence is an unfortunate side effect of early cancer-detection efforts.”

Dr. Welch reported that he had no relevant disclosures. The analysis did not receive any specific funding.

SOURCE: Welch HG et al. N Engl J Med. 2019;381:1378-86. doi: 10.1056/NEJMsr1905447.

A new analysis of 40 years of U.S. cancer data underscores the importance of looking at multiple metrics to discern the complex interplay of factors influencing cancer burden in the population. Findings showed that the epidemiologic signature – a composite of two or three key metrics – differed across cancer types and was favorable in some cases and unfavorable in others.

“Epidemiologic signatures that illustrate trends in population-based data on cancer burden provide insight into true cancer occurrence, overdiagnosis, and treatment advances,” explain the analysts, led by H. Gilbert Welch, MD, MPH, Center for Surgery and Public Health, Brigham and Women’s Hospital, Boston. “They are important indicators of the potential contribution of environmental exposures, primary preventive interventions, new treatments, and changing diagnostic and screening practices.”

Dr. Welch and colleagues analyzed data for the years 1975 through 2015, assessing juxtaposed trends in incidence, mortality, and, when available, metastatic incidence (cancer already metastatic at diagnosis) for 11 cancers individually and for all cancers combined. Incidence data combining invasive and in situ cancers were obtained from the original nine Surveillance, Epidemiology, and End Results (SEER) registries, and mortality data were obtained from the National Vital Statistics System.

The analysts then explored implications of the epidemiologic signatures as they pertain to true cancer occurrence (the underlying incidence of clinically meaningful cancer), overdiagnosis (detection of cancers that will not cause symptoms or death), and treatment advances.
 

Individual cancers

Findings of the analysis, published in a special report in the New England Journal of Medicine, revealed three broad categories of epidemiologic signatures having different implications for the public health and oncology fields.

Desirable signatures showed, for example, declining mortality against a backdrop of stable incidence over the 40-year period, signaling improved treatment, as seen for chronic myeloid leukemia following introduction of imatinib (Gleevec), according to the analysts. Lung cancer incidence and mortality rose and fell in tandem, reflecting an increase in smoking followed by a decrease in response to prevention efforts. Stomach, cervical, and colorectal cancers had both falling incidence – likely reflecting a true decline in occurrence related to prevention and/or screening detection and subsequent treatment of precancerous lesions – and falling mortality.

Undesirable signatures showed a rising incidence juxtaposed with stable mortality and stable or rising metastatic incidence, signaling likely overdiagnosis, Dr. Welch and colleagues proposed. Three cancers—thyroid cancer, kidney cancer, and melanoma—fell into this category; for thyroid cancer and melanoma, fairly recent upticks in metastatic incidence may reflect upstaging.

Finally, some signatures showed mixed signals, with rising incidence and falling mortality. Breast cancer incidence rose and stabilized, coinciding with introduction of screening mammography, and possibly reflecting an increase in true cancer occurrence or overdiagnosis (with stable metastatic incidence favoring the latter), the analysts speculate. Declining mortality since the 1990s may be due to improved treatment or screening, or both. Prostate cancer incidence rose sharply with introduction of prostate-specific antigen screening but then fell to initial levels, suggesting sensitivity of this cancer to diagnostic scrutiny. Falling metastatic incidence indicates screening leads to earlier diagnosis in some cases, while declining mortality starting in the 1990s may again reflect improved treatment or screening, or both.
 

All cancers

The epidemiologic signature for all cancers combined differed somewhat by sex. Women had a rising incidence during the 1980s that was mainly driven by lung and breast cancers, according to Dr. Welch and colleagues; a continued rise since the mid-1990s was largely driven by melanoma, kidney cancer, and thyroid cancer. Declining mortality since 1990 has been primarily due to reductions in deaths from breast and colorectal cancers, and, more recently, lung cancer.

Men had a “volatile pattern” in the incidence of all cancers combined that was attributable to prostate cancer trends; drops in lung and colorectal cancer incidences were offset by rises in melanoma and kidney cancer incidences, the analysts proposed. Declining mortality since 1990 was more marked than that among women and reflects a longer period of decline in lung cancer mortality, plus reductions in deaths from prostate cancer and colorectal cancer.

“Falling mortality means that there has been real progress against cancer in the past 40 years – largely reflecting improved treatment and the decline of a uniquely powerful causal factor: cigarette smoking,” Dr. Welch and colleagues noted. “The lack of an accompanying fall in incidence is an unfortunate side effect of early cancer-detection efforts.”

Dr. Welch reported that he had no relevant disclosures. The analysis did not receive any specific funding.

SOURCE: Welch HG et al. N Engl J Med. 2019;381:1378-86. doi: 10.1056/NEJMsr1905447.

Women with early-stage breast cancer are at elevated risk for atrial fibrillation (AF) short term and, to a lesser extent, long term, finds a large Canadian cohort study. Risk was higher for those who had received chemotherapy but not tied to specific cardiotoxic drugs or drug classes.

“Cardiovascular disease is a particularly pertinent clinical concern for women diagnosed with early-stage breast cancer,” note the investigators, led by Husam Abdel-Qadir, MD, PhD, FRCPC, Cardiology Clinic, Women’s College Hospital, Toronto. “Many early-stage breast cancer survivors are older than 65 years and have hypertension, diabetes, or left ventricular dysfunction. Accordingly, a diagnosis of AF would translate to a clinically relevant stroke risk for many early-stage breast cancer survivors.”

The investigators undertook a population-based retrospective cohort study of women in the province of Ontario with stage I-III breast cancer diagnosed between April 2007 and December 2016, matching them 1:3 to cancer-free control women on birth year and receipt of breast imaging.

An initial analysis, based on 95,539 breast cancer patients and 217,456 cancer-free controls, showed that the former and latter groups did not differ significantly on the prevalence of preexisting AF (5.3% vs. 5.2%; P = .21), according to results reported in JAMA Network Open.

Main analyses excluded women with preexisting AF, leaving 68,113 breast cancer patients and 204,330 cancer-free controls having a mean follow-up of 5.7 years. Both groups had a mean age of 60 years at baseline, and prevalences of cardiovascular comorbidities were similar. Within the breast cancer group, 50.4% had left-sided disease; overall, 53.2% received chemotherapy and 71.7% received radiation therapy.

At 10 years after diagnosis, breast cancer patients had a small but significant increase in AF incidence relative to control peers (7.4% vs. 6.8%; P less than .001). When the investigators looked at specific time periods, survivors had a significantly elevated AF risk in year 1 postdiagnosis (hazard ratio, 2.16) and after year 5 postdiagnosis (hazard ratio, 1.20), but not during years 2 through 5.

Analyses beginning 1 year after diagnosis showed a slightly smaller but still significant elevation of AF incidence for the breast cancer group at 9 years of follow-up (10 years after diagnosis) (7.0% vs. 6.5%; P less than .001).

Among breast cancer patients, those who received chemotherapy had a higher risk of AF than those who did not (adjusted hazard ratio, 1.23); however, this elevation of risk was not specifically tied to receipt of anthracyclines or trastuzumab (Herceptin) versus other chemotherapy. Risk was not elevated for those who received radiation therapy.

“Our study findings suggest that a diagnosis of early-stage breast cancer may be associated with a small increase in the risk of AF compared with that for cancer-free women,” Dr. Abdel-Qadir and coinvestigators noted. “Since the absolute risk is small, this finding does not warrant routine surveillance but rather should prompt consideration of AF in the differential diagnosis for women with compatible symptoms.

“The early and late periods of increased AF risk in early-stage breast cancer survivors warrant focused research to better understand the underlying causes and subsequent implications,” they concluded.

Dr. Abdel-Qadir reported receiving grants from the Canadian Cardiovascular Society during the conduct of the study, speaker fees from Amgen, and an honorarium for clinical events adjudication committee membership from the Canadian Vigour Centre for a study funded by AstraZeneca. The study was funded by the Canadian Cardiovascular Society Atrial Fibrillation Research Award.

SOURCE: Abdel-Qadir H et al. JAMA Netw Open. 2019 Sep 4;2(9):e1911838.

Women with early-stage breast cancer are at elevated risk for atrial fibrillation (AF) short term and, to a lesser extent, long term, finds a large Canadian cohort study. Risk was higher for those who had received chemotherapy but not tied to specific cardiotoxic drugs or drug classes.

“Cardiovascular disease is a particularly pertinent clinical concern for women diagnosed with early-stage breast cancer,” note the investigators, led by Husam Abdel-Qadir, MD, PhD, FRCPC, Cardiology Clinic, Women’s College Hospital, Toronto. “Many early-stage breast cancer survivors are older than 65 years and have hypertension, diabetes, or left ventricular dysfunction. Accordingly, a diagnosis of AF would translate to a clinically relevant stroke risk for many early-stage breast cancer survivors.”

The investigators undertook a population-based retrospective cohort study of women in the province of Ontario with stage I-III breast cancer diagnosed between April 2007 and December 2016, matching them 1:3 to cancer-free control women on birth year and receipt of breast imaging.

An initial analysis, based on 95,539 breast cancer patients and 217,456 cancer-free controls, showed that the former and latter groups did not differ significantly on the prevalence of preexisting AF (5.3% vs. 5.2%; P = .21), according to results reported in JAMA Network Open.

Main analyses excluded women with preexisting AF, leaving 68,113 breast cancer patients and 204,330 cancer-free controls having a mean follow-up of 5.7 years. Both groups had a mean age of 60 years at baseline, and prevalences of cardiovascular comorbidities were similar. Within the breast cancer group, 50.4% had left-sided disease; overall, 53.2% received chemotherapy and 71.7% received radiation therapy.

At 10 years after diagnosis, breast cancer patients had a small but significant increase in AF incidence relative to control peers (7.4% vs. 6.8%; P less than .001). When the investigators looked at specific time periods, survivors had a significantly elevated AF risk in year 1 postdiagnosis (hazard ratio, 2.16) and after year 5 postdiagnosis (hazard ratio, 1.20), but not during years 2 through 5.

Analyses beginning 1 year after diagnosis showed a slightly smaller but still significant elevation of AF incidence for the breast cancer group at 9 years of follow-up (10 years after diagnosis) (7.0% vs. 6.5%; P less than .001).

Among breast cancer patients, those who received chemotherapy had a higher risk of AF than those who did not (adjusted hazard ratio, 1.23); however, this elevation of risk was not specifically tied to receipt of anthracyclines or trastuzumab (Herceptin) versus other chemotherapy. Risk was not elevated for those who received radiation therapy.

“Our study findings suggest that a diagnosis of early-stage breast cancer may be associated with a small increase in the risk of AF compared with that for cancer-free women,” Dr. Abdel-Qadir and coinvestigators noted. “Since the absolute risk is small, this finding does not warrant routine surveillance but rather should prompt consideration of AF in the differential diagnosis for women with compatible symptoms.

“The early and late periods of increased AF risk in early-stage breast cancer survivors warrant focused research to better understand the underlying causes and subsequent implications,” they concluded.

Dr. Abdel-Qadir reported receiving grants from the Canadian Cardiovascular Society during the conduct of the study, speaker fees from Amgen, and an honorarium for clinical events adjudication committee membership from the Canadian Vigour Centre for a study funded by AstraZeneca. The study was funded by the Canadian Cardiovascular Society Atrial Fibrillation Research Award.

SOURCE: Abdel-Qadir H et al. JAMA Netw Open. 2019 Sep 4;2(9):e1911838.

Women with early-stage breast cancer are at elevated risk for atrial fibrillation (AF) short term and, to a lesser extent, long term, finds a large Canadian cohort study. Risk was higher for those who had received chemotherapy but not tied to specific cardiotoxic drugs or drug classes.

“Cardiovascular disease is a particularly pertinent clinical concern for women diagnosed with early-stage breast cancer,” note the investigators, led by Husam Abdel-Qadir, MD, PhD, FRCPC, Cardiology Clinic, Women’s College Hospital, Toronto. “Many early-stage breast cancer survivors are older than 65 years and have hypertension, diabetes, or left ventricular dysfunction. Accordingly, a diagnosis of AF would translate to a clinically relevant stroke risk for many early-stage breast cancer survivors.”

The investigators undertook a population-based retrospective cohort study of women in the province of Ontario with stage I-III breast cancer diagnosed between April 2007 and December 2016, matching them 1:3 to cancer-free control women on birth year and receipt of breast imaging.

An initial analysis, based on 95,539 breast cancer patients and 217,456 cancer-free controls, showed that the former and latter groups did not differ significantly on the prevalence of preexisting AF (5.3% vs. 5.2%; P = .21), according to results reported in JAMA Network Open.

Main analyses excluded women with preexisting AF, leaving 68,113 breast cancer patients and 204,330 cancer-free controls having a mean follow-up of 5.7 years. Both groups had a mean age of 60 years at baseline, and prevalences of cardiovascular comorbidities were similar. Within the breast cancer group, 50.4% had left-sided disease; overall, 53.2% received chemotherapy and 71.7% received radiation therapy.

At 10 years after diagnosis, breast cancer patients had a small but significant increase in AF incidence relative to control peers (7.4% vs. 6.8%; P less than .001). When the investigators looked at specific time periods, survivors had a significantly elevated AF risk in year 1 postdiagnosis (hazard ratio, 2.16) and after year 5 postdiagnosis (hazard ratio, 1.20), but not during years 2 through 5.

Analyses beginning 1 year after diagnosis showed a slightly smaller but still significant elevation of AF incidence for the breast cancer group at 9 years of follow-up (10 years after diagnosis) (7.0% vs. 6.5%; P less than .001).

Among breast cancer patients, those who received chemotherapy had a higher risk of AF than those who did not (adjusted hazard ratio, 1.23); however, this elevation of risk was not specifically tied to receipt of anthracyclines or trastuzumab (Herceptin) versus other chemotherapy. Risk was not elevated for those who received radiation therapy.

“Our study findings suggest that a diagnosis of early-stage breast cancer may be associated with a small increase in the risk of AF compared with that for cancer-free women,” Dr. Abdel-Qadir and coinvestigators noted. “Since the absolute risk is small, this finding does not warrant routine surveillance but rather should prompt consideration of AF in the differential diagnosis for women with compatible symptoms.

“The early and late periods of increased AF risk in early-stage breast cancer survivors warrant focused research to better understand the underlying causes and subsequent implications,” they concluded.

Dr. Abdel-Qadir reported receiving grants from the Canadian Cardiovascular Society during the conduct of the study, speaker fees from Amgen, and an honorarium for clinical events adjudication committee membership from the Canadian Vigour Centre for a study funded by AstraZeneca. The study was funded by the Canadian Cardiovascular Society Atrial Fibrillation Research Award.

SOURCE: Abdel-Qadir H et al. JAMA Netw Open. 2019 Sep 4;2(9):e1911838.