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Alectinib shows promise in crizotinib-refractory ALK-rearranged NSCLC
Alectinib, an oral, small-molecule, ATP-competitive tyrosine kinase inhibitor of ALK, demonstrated good clinical activity in crizotinib-refractory patients with advanced non–small-cell lung cancer (NSCLC) harboring ALK rearrangements.
The overall response rate (ORR) for all 122 evaluable patients was 49%: 44% for the 96 patients who had received prior chemotherapy, and 69% for the 26 chemotherapy-naive patients. The median duration of response (DOR) for the 61 patients with a partial response was 11.2 months.
“The clinically meaningful ORR and DOR in patients with crizotinib-resistant disease and the sustained CNS response reported from this study, as well as the good tolerability profile, support the additional development of this promising new ALK inhibitor,” wrote Dr. Sai-Hong Ignatius Ou, clinical professor at the University of California, Irvine, and colleagues (J Clin Oncol. 2015 Nov. 23. doi:10.1200/JCO.2015.63.9443).
The observed clinical activity of alectinib in the CNS was consistent with preclinical data showing high CNS tissue penetration and earlier phase I/II results. Among 35 patients with baseline measurable CNS lesions, the ORR was 57%, including seven complete responses. CNS complete responses were observed in 10 of 23 patients (43%) who had no prior brain radiation.
The cumulative incidence rates of CNS progression were lower than were those of non-CNS progression, “which seems to suggest that alectinib can prevent or delay the emergence of CNS metastases,” the authors wrote. At 12 months, 33 patients had a CNS progression and 43 had a non-CNS progression.
Alectinib showed an acceptable safety profile. The most common adverse events were myalgia, fatigue, and gastrointestinal events, usually grade 1 or 2. Grade 3 or 4 adverse events occurred at a rate less than 5%. Most patients maintained therapeutic levels of alectinib throughout the study, indicated by a mean dose intensity of 97%.
The phase II study evaluated 122 patients who had locally advanced or metastatic NSCLC harboring an ALK rearrangement and who had progressed on crizotinib treatment.
Multiple oral doses at 600 mg twice daily produced an overall flat PK profile, supporting sustained alectinib exposure throughout the dosing interval. In contrast to results from the U.S. phase I/II study that reported differences in alectinib exposures between white and Asian patients, this study showed no marked differences between white (n = 6) and Asian (n = 20) patients evaluated.
F. Hoffmann-La Roche supported the study. Dr. Ou disclosed ties with Pfizer, F. Hoffmann-La Roche, Boehringer Ingelheim, ARIAD, AstraZeneca, Clovis Oncology, Astellas Pharma, Ignyta, and Daichi Sankyo. Several of his coauthors reported ties to industry.
Alectinib, an oral, small-molecule, ATP-competitive tyrosine kinase inhibitor of ALK, demonstrated good clinical activity in crizotinib-refractory patients with advanced non–small-cell lung cancer (NSCLC) harboring ALK rearrangements.
The overall response rate (ORR) for all 122 evaluable patients was 49%: 44% for the 96 patients who had received prior chemotherapy, and 69% for the 26 chemotherapy-naive patients. The median duration of response (DOR) for the 61 patients with a partial response was 11.2 months.
“The clinically meaningful ORR and DOR in patients with crizotinib-resistant disease and the sustained CNS response reported from this study, as well as the good tolerability profile, support the additional development of this promising new ALK inhibitor,” wrote Dr. Sai-Hong Ignatius Ou, clinical professor at the University of California, Irvine, and colleagues (J Clin Oncol. 2015 Nov. 23. doi:10.1200/JCO.2015.63.9443).
The observed clinical activity of alectinib in the CNS was consistent with preclinical data showing high CNS tissue penetration and earlier phase I/II results. Among 35 patients with baseline measurable CNS lesions, the ORR was 57%, including seven complete responses. CNS complete responses were observed in 10 of 23 patients (43%) who had no prior brain radiation.
The cumulative incidence rates of CNS progression were lower than were those of non-CNS progression, “which seems to suggest that alectinib can prevent or delay the emergence of CNS metastases,” the authors wrote. At 12 months, 33 patients had a CNS progression and 43 had a non-CNS progression.
Alectinib showed an acceptable safety profile. The most common adverse events were myalgia, fatigue, and gastrointestinal events, usually grade 1 or 2. Grade 3 or 4 adverse events occurred at a rate less than 5%. Most patients maintained therapeutic levels of alectinib throughout the study, indicated by a mean dose intensity of 97%.
The phase II study evaluated 122 patients who had locally advanced or metastatic NSCLC harboring an ALK rearrangement and who had progressed on crizotinib treatment.
Multiple oral doses at 600 mg twice daily produced an overall flat PK profile, supporting sustained alectinib exposure throughout the dosing interval. In contrast to results from the U.S. phase I/II study that reported differences in alectinib exposures between white and Asian patients, this study showed no marked differences between white (n = 6) and Asian (n = 20) patients evaluated.
F. Hoffmann-La Roche supported the study. Dr. Ou disclosed ties with Pfizer, F. Hoffmann-La Roche, Boehringer Ingelheim, ARIAD, AstraZeneca, Clovis Oncology, Astellas Pharma, Ignyta, and Daichi Sankyo. Several of his coauthors reported ties to industry.
Alectinib, an oral, small-molecule, ATP-competitive tyrosine kinase inhibitor of ALK, demonstrated good clinical activity in crizotinib-refractory patients with advanced non–small-cell lung cancer (NSCLC) harboring ALK rearrangements.
The overall response rate (ORR) for all 122 evaluable patients was 49%: 44% for the 96 patients who had received prior chemotherapy, and 69% for the 26 chemotherapy-naive patients. The median duration of response (DOR) for the 61 patients with a partial response was 11.2 months.
“The clinically meaningful ORR and DOR in patients with crizotinib-resistant disease and the sustained CNS response reported from this study, as well as the good tolerability profile, support the additional development of this promising new ALK inhibitor,” wrote Dr. Sai-Hong Ignatius Ou, clinical professor at the University of California, Irvine, and colleagues (J Clin Oncol. 2015 Nov. 23. doi:10.1200/JCO.2015.63.9443).
The observed clinical activity of alectinib in the CNS was consistent with preclinical data showing high CNS tissue penetration and earlier phase I/II results. Among 35 patients with baseline measurable CNS lesions, the ORR was 57%, including seven complete responses. CNS complete responses were observed in 10 of 23 patients (43%) who had no prior brain radiation.
The cumulative incidence rates of CNS progression were lower than were those of non-CNS progression, “which seems to suggest that alectinib can prevent or delay the emergence of CNS metastases,” the authors wrote. At 12 months, 33 patients had a CNS progression and 43 had a non-CNS progression.
Alectinib showed an acceptable safety profile. The most common adverse events were myalgia, fatigue, and gastrointestinal events, usually grade 1 or 2. Grade 3 or 4 adverse events occurred at a rate less than 5%. Most patients maintained therapeutic levels of alectinib throughout the study, indicated by a mean dose intensity of 97%.
The phase II study evaluated 122 patients who had locally advanced or metastatic NSCLC harboring an ALK rearrangement and who had progressed on crizotinib treatment.
Multiple oral doses at 600 mg twice daily produced an overall flat PK profile, supporting sustained alectinib exposure throughout the dosing interval. In contrast to results from the U.S. phase I/II study that reported differences in alectinib exposures between white and Asian patients, this study showed no marked differences between white (n = 6) and Asian (n = 20) patients evaluated.
F. Hoffmann-La Roche supported the study. Dr. Ou disclosed ties with Pfizer, F. Hoffmann-La Roche, Boehringer Ingelheim, ARIAD, AstraZeneca, Clovis Oncology, Astellas Pharma, Ignyta, and Daichi Sankyo. Several of his coauthors reported ties to industry.
FROM JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: Alectinib, an oral, small molecule inhibitor of ALK, showed promising clinical activity in crizotinib-refractory patients with non–small-cell lung cancer (NSCLC).
Major finding: The overall response rate was 49% for all evaluable patients, 44% for those who had received prior chemotherapy, and 69% for chemotherapy-naive patients.
Data source: The phase II study evaluated 122 patients with locally advanced or metastatic NSCLC harboring an ALK rearrangement and who had progressed on crizotinib treatment.
Disclosures: F. Hoffmann-La Roche supported the study. Dr. Ou disclosed ties with Pfizer, F. Hoffmann-La Roche, Boehringer Ingelheim, ARIAD, AstraZeneca, Clovis Oncology, Astellas Pharma, Ignyta, and Daichi Sankyo. Several of his coauthors reported ties to industry.
No benefit from dual anti-HER2 blockade in early breast cancer
A dual anti-HER2 blockade with lapatinib and trastuzumab resulted in modest, nonsignificant disease-free survival improvements over adjuvant trastuzumab alone for patients with early human epidermal growth factor 2 (HER2)-positive breast cancer, according to results of the phase III ALTTO trial.
Disease-free survival (DFS) improved slightly with lapatinib and trastuzumab over trastuzumab alone (555 DFS events; hazard ratio, 0.84; 97.5% CI, 0.70-1.02; P = .048). The 4-year overall survival was 95% for lapatinib and trastuzumab and 94% for trastuzumab alone (HR, 0.80; 95% CI, 0.62-1.03; P = .078) (J Clin Oncol. 2015 Nov 23. [doi: 10.1200/JCO.2015.62.1797]).
The marginal benefit observed in lapatinib arms was offset by additional toxicity. The incidence of diarrhea, mostly grade 1 or 2, was higher in the lapatinib arms and was responsible for treatment discontinuation at a rate from 4% to 9% depending on the lapatinib arm. Slightly more than half of the patients in lapatinib arms experienced rash, compared with about 20% in the trastuzumab arm. Primary or secondary cardiac events were rare in any treatment arm.
Previous studies showed benefit from the dual blockade for heavily pretreated patients with advanced disease, particularly in the hormone receptor–negative population.
“We did not expect to observe the degree of toxicity (especially diarrhea), which ultimately reduced the level of enthusiasm for lapatinib in the adjuvant setting,” wrote Dr. Martine J. Piccart-Gebhart, professor of oncology at Université Libre de Bruxelles and director of the medicine department at the Jules Bordet Institute in Brussels, and her colleagues.
The phase III ALTTO (Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization) trial evaluated 8,381 patients with completely excised invasive nonmetastatic HER2-positive breast cancer from 945 sites in 44 countries.
The 4-year overall survival rates of approximately 95% illustrate the steady improvement in clinical outcomes of early breast cancer. The addition of adjuvant lapatinib to trastuzumab produced a modest treatment effect with additional toxicity, and is not clinically meaningful, according to investigators. The standard of care remains trastuzumab for one year.
Research was supported by GlaxoSmithKline and by the National Cancer Institute of the National Institutes of Health. Dr. Piccart-Gebhart reported consulting or advisory roles with Amgen, Astellas, AstraZeneca, Bayer, Eli Lilly, Invivis, Merck Sharp & Dohme, Novartis, Pfizer, Roche/Genentech, Sanofi, Symphogen, Synthon, and Verastem. Several of her coauthors reported ties to industry.
A dual anti-HER2 blockade with lapatinib and trastuzumab resulted in modest, nonsignificant disease-free survival improvements over adjuvant trastuzumab alone for patients with early human epidermal growth factor 2 (HER2)-positive breast cancer, according to results of the phase III ALTTO trial.
Disease-free survival (DFS) improved slightly with lapatinib and trastuzumab over trastuzumab alone (555 DFS events; hazard ratio, 0.84; 97.5% CI, 0.70-1.02; P = .048). The 4-year overall survival was 95% for lapatinib and trastuzumab and 94% for trastuzumab alone (HR, 0.80; 95% CI, 0.62-1.03; P = .078) (J Clin Oncol. 2015 Nov 23. [doi: 10.1200/JCO.2015.62.1797]).
The marginal benefit observed in lapatinib arms was offset by additional toxicity. The incidence of diarrhea, mostly grade 1 or 2, was higher in the lapatinib arms and was responsible for treatment discontinuation at a rate from 4% to 9% depending on the lapatinib arm. Slightly more than half of the patients in lapatinib arms experienced rash, compared with about 20% in the trastuzumab arm. Primary or secondary cardiac events were rare in any treatment arm.
Previous studies showed benefit from the dual blockade for heavily pretreated patients with advanced disease, particularly in the hormone receptor–negative population.
“We did not expect to observe the degree of toxicity (especially diarrhea), which ultimately reduced the level of enthusiasm for lapatinib in the adjuvant setting,” wrote Dr. Martine J. Piccart-Gebhart, professor of oncology at Université Libre de Bruxelles and director of the medicine department at the Jules Bordet Institute in Brussels, and her colleagues.
The phase III ALTTO (Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization) trial evaluated 8,381 patients with completely excised invasive nonmetastatic HER2-positive breast cancer from 945 sites in 44 countries.
The 4-year overall survival rates of approximately 95% illustrate the steady improvement in clinical outcomes of early breast cancer. The addition of adjuvant lapatinib to trastuzumab produced a modest treatment effect with additional toxicity, and is not clinically meaningful, according to investigators. The standard of care remains trastuzumab for one year.
Research was supported by GlaxoSmithKline and by the National Cancer Institute of the National Institutes of Health. Dr. Piccart-Gebhart reported consulting or advisory roles with Amgen, Astellas, AstraZeneca, Bayer, Eli Lilly, Invivis, Merck Sharp & Dohme, Novartis, Pfizer, Roche/Genentech, Sanofi, Symphogen, Synthon, and Verastem. Several of her coauthors reported ties to industry.
A dual anti-HER2 blockade with lapatinib and trastuzumab resulted in modest, nonsignificant disease-free survival improvements over adjuvant trastuzumab alone for patients with early human epidermal growth factor 2 (HER2)-positive breast cancer, according to results of the phase III ALTTO trial.
Disease-free survival (DFS) improved slightly with lapatinib and trastuzumab over trastuzumab alone (555 DFS events; hazard ratio, 0.84; 97.5% CI, 0.70-1.02; P = .048). The 4-year overall survival was 95% for lapatinib and trastuzumab and 94% for trastuzumab alone (HR, 0.80; 95% CI, 0.62-1.03; P = .078) (J Clin Oncol. 2015 Nov 23. [doi: 10.1200/JCO.2015.62.1797]).
The marginal benefit observed in lapatinib arms was offset by additional toxicity. The incidence of diarrhea, mostly grade 1 or 2, was higher in the lapatinib arms and was responsible for treatment discontinuation at a rate from 4% to 9% depending on the lapatinib arm. Slightly more than half of the patients in lapatinib arms experienced rash, compared with about 20% in the trastuzumab arm. Primary or secondary cardiac events were rare in any treatment arm.
Previous studies showed benefit from the dual blockade for heavily pretreated patients with advanced disease, particularly in the hormone receptor–negative population.
“We did not expect to observe the degree of toxicity (especially diarrhea), which ultimately reduced the level of enthusiasm for lapatinib in the adjuvant setting,” wrote Dr. Martine J. Piccart-Gebhart, professor of oncology at Université Libre de Bruxelles and director of the medicine department at the Jules Bordet Institute in Brussels, and her colleagues.
The phase III ALTTO (Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization) trial evaluated 8,381 patients with completely excised invasive nonmetastatic HER2-positive breast cancer from 945 sites in 44 countries.
The 4-year overall survival rates of approximately 95% illustrate the steady improvement in clinical outcomes of early breast cancer. The addition of adjuvant lapatinib to trastuzumab produced a modest treatment effect with additional toxicity, and is not clinically meaningful, according to investigators. The standard of care remains trastuzumab for one year.
Research was supported by GlaxoSmithKline and by the National Cancer Institute of the National Institutes of Health. Dr. Piccart-Gebhart reported consulting or advisory roles with Amgen, Astellas, AstraZeneca, Bayer, Eli Lilly, Invivis, Merck Sharp & Dohme, Novartis, Pfizer, Roche/Genentech, Sanofi, Symphogen, Synthon, and Verastem. Several of her coauthors reported ties to industry.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: Adjuvant lapatinib and trastuzumab resulted in similar disease-free survival, compared with trastuzumab alone in early HER2-positive breast cancer.
Major finding: Disease-free survival improved slightly with lapatinib and trastuzumab over trastuzumab alone (555 DFS events; hazard rate 0.84; 97.5% CI, 0.70-1.02; P = .048).
Data source: The phase III Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization (ALTTO) trial evaluated 8,381 patients with completely excised invasive nonmetastatic HER2-positive breast cancer.
Disclosures: Research was supported by GlaxoSmithKline and by the National Cancer Institute of the National Institutes of Health. Dr. Piccart-Gebhart reported consulting or advisory roles with Amgen, Astellas, AstraZeneca, Bayer, Eli Lilly, Invivis, Merck Sharp & Dohme, Novartis, Pfizer, Roche/Genentech, Sanofi, Symphogen, Synthon, and Verastem. Several of her coauthors reported ties to industry.
Childhood, young adult cancer survivors face high risk of long-term morbidity
Survivors of cancer diagnosed at early ages, compared with healthy controls, face higher risk of chronic medical problems, according to two independent studies.
Survivors of adolescent and young adult (AYA) cancer had an overall 38% increased risk of hospitalization, which persisted throughout life, according to a Danish Cancer Registry study. The St. Jude Lifetime Study found that long-term survivors of childhood osteosarcoma had significant neurocognitive deficits in attention, memory, processing speed, executive function, and academics. “The morbidity pattern … underscores the need for further implementation of strict evidence-based sex,-, age-, and cancer-specific follow-up plans for survivors, thereby increasing the likelihood for early detection and ultimately prevention of treatment-induced morbidities,” wrote Kathrine Rugbjerg, Ph.D., of the Danish Cancer Society Research Center, Copenhagen, and colleagues (JAMA Onc. 2015 Nov. 19 doi: 10.1001/jamaoncol.2015.4393).
Analysis of the Danish Cancer Registry from 1943 to 2009 included 33,555 5-year survivors of cancer diagnosed between age 15 and 39 years, and 228,447 matched population comparisons. During the median 14-year follow up, cancer survivors had 53,032 hospital admissions, with 38,423 expected, for a standardized hospitalization rate ratio of 1.38 (95% CI, 1.37-1.39). The absolute excess risk (difference between observed and expected hospitalization rates per 100,000 person years of follow-up) remained relatively stable, ranging from 2 to 4 disease-specific hospitalizations per 100 survivors for each year of follow-up.
Categories that carried the highest relative risk of hospitalization for cancer survivors were diseases of blood and blood-forming organs (RR men, 2.36; women, 1.85), infectious and parasitic diseases (men, 1.81; women, 1.62), and malignant neoplasms (men, 1.80; women, 1.52). Treatments for these cancers tend to be intensive and lengthy, the researchers noted.
The AYA cancers that had the highest risk of subsequent hospitalization among survivors included leukemia (RR, 2.21), brain cancer (RR, 1.93), and Hodgkin lymphoma (RR, 1.87).
The large size of the study made possible the calculation of relative risks for hospitalization according to disease category and AYA cancer type. Survivors of brain cancer had high risk of endocrine, nervous system, and sense organ diseases (RR, 5.5); leukemia survivors had high risks of diseases of blood and blood-forming organs, respiratory system diseases, and infectious and parasitic diseases (RRs, 6.3, 4.9, and 6.3, respectively): Hodgkin lymphoma survivors had high risk of malignant neoplasms (RR, 3.7).
On average, AYA survivors spent 50% more days in hospitals than did the comparison cohort.
A separate study compared neurocognitive performance of long-term survivors of childhood osteosarcoma with community controls and found lower reading scores (P = .01), more variability in sustained attention (P = .002), poorer short-term memory (P = .01), slower motor processing speed (P less than .001), and poorer cognitive fluency (P = .006), reported Michelle N. Edelmann, Ph.D., of St Jude Children’s Research Hospital, Memphis, Tenn., and colleagues (JAMA Onc. 2015 Nov. 19. doi: 10.1001/jamaoncol.2015.4398).
The St. Jude Lifetime Cohort Study evaluated 80 survivors of childhood osteosarcoma at a mean 24.7 years after diagnosis, and compared their neurocognitive function results with 39 community controls.
All osteosarcoma survivors had undergone treatment with high-dose methotrexate, but neurocognitive outcomes were not related to cumulative dose or pharmacokinetic indices of methotrexate exposure.
Chronic health conditions can affect neurocognitive functions in survivors of childhood cancers, and the study found that osteosarcoma survivors with grade 3 or 4 adverse chronic health conditions showed poorer memory and processing speeds.
Because adolescents and young adults have a unique pattern of cancer development, as well as different psychosocial stressors compared with younger or older patients, the late-effects burden of AYA cancers may be distinct from survivors of childhood or adult cancers. Studies involving this age group will help guide screening and treatment for AYA survivors.
The analysis by Rugbjerg et al. describes malignant neoplasms that occur frequently in AYA survivors, and these results differ from previous observations. Particularly surprising is the low prevalence of breast and thyroid cancers, two of the most common subsequent malignant neoplasms previously reported in AYA cancer survivors.
While the hospitalization rate ratios offer some insight on the risks faced by AYA survivors, early detection and intervention strategies require a comprehensive view of the cancer treatment–related sequelae, and this must come from both inpatient and outpatient information.
In examining late effects of childhood cancer, a particular area of interest is neurocognitive development, due to its far-reaching affects on education, employment, and quality of life.
The results from Edelmann and colleagues suggested that the risk of neurocognitive impairment in long-term survivors of pediatric osteosarcoma is linked to chronic health conditions and not high-dose methotrexate. However, only a longitudinal study can determine if neurocognitive deficits were present prior to the development of chronic health conditions and linked to chemotherapy exposure.
Furthermore, a genetic predisposition may increase sensitivity to chemotherapy and neurocognitive outcomes.
Given the impact of neurocognitive functioning on the lives of cancer survivors, development of interventions to improve long-term outcomes is imperative.
Dr. Karen Effinger is a pediatric oncologist and instructor in the division of pediatric hematology-oncology, department of pediatrics, Stanford (Calif.) University. Dr. Michael Link is professor and pediatric oncologist in the division of pediatric hematology-oncology, department of pediatrics, Stanford (Calif.) University. These remarks were part of an editorial accompanying the reports (JAMA Oncol. 2015 Nov. 19. doi: 10.1001/jamaoncol.2015.4392). Dr. Effinger and Dr. Link reported having no disclosures.
Because adolescents and young adults have a unique pattern of cancer development, as well as different psychosocial stressors compared with younger or older patients, the late-effects burden of AYA cancers may be distinct from survivors of childhood or adult cancers. Studies involving this age group will help guide screening and treatment for AYA survivors.
The analysis by Rugbjerg et al. describes malignant neoplasms that occur frequently in AYA survivors, and these results differ from previous observations. Particularly surprising is the low prevalence of breast and thyroid cancers, two of the most common subsequent malignant neoplasms previously reported in AYA cancer survivors.
While the hospitalization rate ratios offer some insight on the risks faced by AYA survivors, early detection and intervention strategies require a comprehensive view of the cancer treatment–related sequelae, and this must come from both inpatient and outpatient information.
In examining late effects of childhood cancer, a particular area of interest is neurocognitive development, due to its far-reaching affects on education, employment, and quality of life.
The results from Edelmann and colleagues suggested that the risk of neurocognitive impairment in long-term survivors of pediatric osteosarcoma is linked to chronic health conditions and not high-dose methotrexate. However, only a longitudinal study can determine if neurocognitive deficits were present prior to the development of chronic health conditions and linked to chemotherapy exposure.
Furthermore, a genetic predisposition may increase sensitivity to chemotherapy and neurocognitive outcomes.
Given the impact of neurocognitive functioning on the lives of cancer survivors, development of interventions to improve long-term outcomes is imperative.
Dr. Karen Effinger is a pediatric oncologist and instructor in the division of pediatric hematology-oncology, department of pediatrics, Stanford (Calif.) University. Dr. Michael Link is professor and pediatric oncologist in the division of pediatric hematology-oncology, department of pediatrics, Stanford (Calif.) University. These remarks were part of an editorial accompanying the reports (JAMA Oncol. 2015 Nov. 19. doi: 10.1001/jamaoncol.2015.4392). Dr. Effinger and Dr. Link reported having no disclosures.
Because adolescents and young adults have a unique pattern of cancer development, as well as different psychosocial stressors compared with younger or older patients, the late-effects burden of AYA cancers may be distinct from survivors of childhood or adult cancers. Studies involving this age group will help guide screening and treatment for AYA survivors.
The analysis by Rugbjerg et al. describes malignant neoplasms that occur frequently in AYA survivors, and these results differ from previous observations. Particularly surprising is the low prevalence of breast and thyroid cancers, two of the most common subsequent malignant neoplasms previously reported in AYA cancer survivors.
While the hospitalization rate ratios offer some insight on the risks faced by AYA survivors, early detection and intervention strategies require a comprehensive view of the cancer treatment–related sequelae, and this must come from both inpatient and outpatient information.
In examining late effects of childhood cancer, a particular area of interest is neurocognitive development, due to its far-reaching affects on education, employment, and quality of life.
The results from Edelmann and colleagues suggested that the risk of neurocognitive impairment in long-term survivors of pediatric osteosarcoma is linked to chronic health conditions and not high-dose methotrexate. However, only a longitudinal study can determine if neurocognitive deficits were present prior to the development of chronic health conditions and linked to chemotherapy exposure.
Furthermore, a genetic predisposition may increase sensitivity to chemotherapy and neurocognitive outcomes.
Given the impact of neurocognitive functioning on the lives of cancer survivors, development of interventions to improve long-term outcomes is imperative.
Dr. Karen Effinger is a pediatric oncologist and instructor in the division of pediatric hematology-oncology, department of pediatrics, Stanford (Calif.) University. Dr. Michael Link is professor and pediatric oncologist in the division of pediatric hematology-oncology, department of pediatrics, Stanford (Calif.) University. These remarks were part of an editorial accompanying the reports (JAMA Oncol. 2015 Nov. 19. doi: 10.1001/jamaoncol.2015.4392). Dr. Effinger and Dr. Link reported having no disclosures.
Survivors of cancer diagnosed at early ages, compared with healthy controls, face higher risk of chronic medical problems, according to two independent studies.
Survivors of adolescent and young adult (AYA) cancer had an overall 38% increased risk of hospitalization, which persisted throughout life, according to a Danish Cancer Registry study. The St. Jude Lifetime Study found that long-term survivors of childhood osteosarcoma had significant neurocognitive deficits in attention, memory, processing speed, executive function, and academics. “The morbidity pattern … underscores the need for further implementation of strict evidence-based sex,-, age-, and cancer-specific follow-up plans for survivors, thereby increasing the likelihood for early detection and ultimately prevention of treatment-induced morbidities,” wrote Kathrine Rugbjerg, Ph.D., of the Danish Cancer Society Research Center, Copenhagen, and colleagues (JAMA Onc. 2015 Nov. 19 doi: 10.1001/jamaoncol.2015.4393).
Analysis of the Danish Cancer Registry from 1943 to 2009 included 33,555 5-year survivors of cancer diagnosed between age 15 and 39 years, and 228,447 matched population comparisons. During the median 14-year follow up, cancer survivors had 53,032 hospital admissions, with 38,423 expected, for a standardized hospitalization rate ratio of 1.38 (95% CI, 1.37-1.39). The absolute excess risk (difference between observed and expected hospitalization rates per 100,000 person years of follow-up) remained relatively stable, ranging from 2 to 4 disease-specific hospitalizations per 100 survivors for each year of follow-up.
Categories that carried the highest relative risk of hospitalization for cancer survivors were diseases of blood and blood-forming organs (RR men, 2.36; women, 1.85), infectious and parasitic diseases (men, 1.81; women, 1.62), and malignant neoplasms (men, 1.80; women, 1.52). Treatments for these cancers tend to be intensive and lengthy, the researchers noted.
The AYA cancers that had the highest risk of subsequent hospitalization among survivors included leukemia (RR, 2.21), brain cancer (RR, 1.93), and Hodgkin lymphoma (RR, 1.87).
The large size of the study made possible the calculation of relative risks for hospitalization according to disease category and AYA cancer type. Survivors of brain cancer had high risk of endocrine, nervous system, and sense organ diseases (RR, 5.5); leukemia survivors had high risks of diseases of blood and blood-forming organs, respiratory system diseases, and infectious and parasitic diseases (RRs, 6.3, 4.9, and 6.3, respectively): Hodgkin lymphoma survivors had high risk of malignant neoplasms (RR, 3.7).
On average, AYA survivors spent 50% more days in hospitals than did the comparison cohort.
A separate study compared neurocognitive performance of long-term survivors of childhood osteosarcoma with community controls and found lower reading scores (P = .01), more variability in sustained attention (P = .002), poorer short-term memory (P = .01), slower motor processing speed (P less than .001), and poorer cognitive fluency (P = .006), reported Michelle N. Edelmann, Ph.D., of St Jude Children’s Research Hospital, Memphis, Tenn., and colleagues (JAMA Onc. 2015 Nov. 19. doi: 10.1001/jamaoncol.2015.4398).
The St. Jude Lifetime Cohort Study evaluated 80 survivors of childhood osteosarcoma at a mean 24.7 years after diagnosis, and compared their neurocognitive function results with 39 community controls.
All osteosarcoma survivors had undergone treatment with high-dose methotrexate, but neurocognitive outcomes were not related to cumulative dose or pharmacokinetic indices of methotrexate exposure.
Chronic health conditions can affect neurocognitive functions in survivors of childhood cancers, and the study found that osteosarcoma survivors with grade 3 or 4 adverse chronic health conditions showed poorer memory and processing speeds.
Survivors of cancer diagnosed at early ages, compared with healthy controls, face higher risk of chronic medical problems, according to two independent studies.
Survivors of adolescent and young adult (AYA) cancer had an overall 38% increased risk of hospitalization, which persisted throughout life, according to a Danish Cancer Registry study. The St. Jude Lifetime Study found that long-term survivors of childhood osteosarcoma had significant neurocognitive deficits in attention, memory, processing speed, executive function, and academics. “The morbidity pattern … underscores the need for further implementation of strict evidence-based sex,-, age-, and cancer-specific follow-up plans for survivors, thereby increasing the likelihood for early detection and ultimately prevention of treatment-induced morbidities,” wrote Kathrine Rugbjerg, Ph.D., of the Danish Cancer Society Research Center, Copenhagen, and colleagues (JAMA Onc. 2015 Nov. 19 doi: 10.1001/jamaoncol.2015.4393).
Analysis of the Danish Cancer Registry from 1943 to 2009 included 33,555 5-year survivors of cancer diagnosed between age 15 and 39 years, and 228,447 matched population comparisons. During the median 14-year follow up, cancer survivors had 53,032 hospital admissions, with 38,423 expected, for a standardized hospitalization rate ratio of 1.38 (95% CI, 1.37-1.39). The absolute excess risk (difference between observed and expected hospitalization rates per 100,000 person years of follow-up) remained relatively stable, ranging from 2 to 4 disease-specific hospitalizations per 100 survivors for each year of follow-up.
Categories that carried the highest relative risk of hospitalization for cancer survivors were diseases of blood and blood-forming organs (RR men, 2.36; women, 1.85), infectious and parasitic diseases (men, 1.81; women, 1.62), and malignant neoplasms (men, 1.80; women, 1.52). Treatments for these cancers tend to be intensive and lengthy, the researchers noted.
The AYA cancers that had the highest risk of subsequent hospitalization among survivors included leukemia (RR, 2.21), brain cancer (RR, 1.93), and Hodgkin lymphoma (RR, 1.87).
The large size of the study made possible the calculation of relative risks for hospitalization according to disease category and AYA cancer type. Survivors of brain cancer had high risk of endocrine, nervous system, and sense organ diseases (RR, 5.5); leukemia survivors had high risks of diseases of blood and blood-forming organs, respiratory system diseases, and infectious and parasitic diseases (RRs, 6.3, 4.9, and 6.3, respectively): Hodgkin lymphoma survivors had high risk of malignant neoplasms (RR, 3.7).
On average, AYA survivors spent 50% more days in hospitals than did the comparison cohort.
A separate study compared neurocognitive performance of long-term survivors of childhood osteosarcoma with community controls and found lower reading scores (P = .01), more variability in sustained attention (P = .002), poorer short-term memory (P = .01), slower motor processing speed (P less than .001), and poorer cognitive fluency (P = .006), reported Michelle N. Edelmann, Ph.D., of St Jude Children’s Research Hospital, Memphis, Tenn., and colleagues (JAMA Onc. 2015 Nov. 19. doi: 10.1001/jamaoncol.2015.4398).
The St. Jude Lifetime Cohort Study evaluated 80 survivors of childhood osteosarcoma at a mean 24.7 years after diagnosis, and compared their neurocognitive function results with 39 community controls.
All osteosarcoma survivors had undergone treatment with high-dose methotrexate, but neurocognitive outcomes were not related to cumulative dose or pharmacokinetic indices of methotrexate exposure.
Chronic health conditions can affect neurocognitive functions in survivors of childhood cancers, and the study found that osteosarcoma survivors with grade 3 or 4 adverse chronic health conditions showed poorer memory and processing speeds.
FROM JAMA ONCOLOGY
Key clinical point: Two separate studies demonstrated that survivors of childhood, adolescent, and young adult cancers face high risk of long-term morbidity.
Major finding: The standardized hospitalization rate ratio for survivors of adolescent and young adult cancers compared with healthy controls was 1.38 (95% CI, 1.37-1.39); long-term survivors of childhood osteosarcoma showed significant neurocognitive deficits in attention, memory, processing speed, executive function, and academics.
Data sources: Analysis of the Danish Cancer Registry from 1943 to 2009 included 33,555 5-year survivors of adolescent or young adult cancer; the St. Jude Lifetime Cohort Study evaluated 80 survivors of childhood osteosarcoma treated with high-dose methotrexate.
Disclosures: Dr. Rugbjerg and coauthors reported having no disclosures. Dr. Edelmann and coauthors reported having no disclosures.
Study: Pediatric cancer patients have high rate of germline mutations in predisposition genes
Children and adolescents with cancer were found to have a significantly higher rate of germline mutations in cancer predisposing genes compared with individuals with no known cancer; however, family history of cancer did not predict the presence of a predisposition syndrome for most patients.
Of the 1,120 children with cancer, 8.5% had mutations in predisposition genes, compared with 1.1% in the control group. Mutations in TP53 were most common (50 patients), followed by APC (6), BRCA2 (6), NF1 (4), PMS2 (4), RB1 (3), and RUNX1 (3). Germline TP53 mutations were present in 27 of 39 patients (69%) with adrenocortical tumors, 9 of 47 (19%) with hypodiploid acute lymphoblastic leukemia, and 1 of 4 (25%) with choroid plexus carcinoma (N Engl J Med. 2015 Nov. 18. doi: 10.1056/NEJMoa1508054).
Only 40% of the pediatric patients with pathogenic germline mutations had a family history of cancer, and in just half of those cases the history was consistent with a known cancer-predisposition syndrome. Among patients without predisposition germline mutations, a similar proportion (42%) had a family history of cancer.
“On the basis of these observations, family history cannot be the sole indication used to guide the provision of genetic testing,” wrote Jinghui Zhang, Ph.D., of the department of computational biology, St. Jude’s Research Hospital, Memphis, Tennessee, and her colleagues.
Unexpected germline mutations were found in several cases. Six patients with Ewing’s sarcoma had unexpected pathogenic germline mutations (TP53 in four patients, PMS2 in one and RET in one). Eight patents had heterozygous mutations in BRCA1, BRCA2, or PALB2, supporting the notion that mutations in these genes may play a role in pediatric as well as adult cancer. Other new associations included germline APC and SDHB mutations with neuroblastoma, and APC, VHL, CDH1, PTCH1, and SDHA germline mutations with leukemia.
The St. Jude–Washington University Pediatric Cancer Genome Project (PCGP) included 1,120 patients representing the major types of pediatric cancer, including 53% with leukemia, 22% with CNS tumors, and 26% with non-CNS tumors. Whole genomes were sequenced from 595 patients, whole exomes (coding regions only) from 456 patients, and both whole genomes and exomes from 69 patients. Whole exomes were sequenced from two control cohorts of individuals with no known cancer: 966 from the 1,000 Genome project and 723 from the National Database for Autism Research (cancer predisposition genes known to be associated with autism, NF1 and PTEN, were excluded from analysis with this control set).
The study sequenced whole genomes and exomes, but focused most of the analysis on 60 autosomal dominant cancer predisposition genes. Tumor types with the highest prevalence of germline mutations in these genes were non-CNS solid tumors (48 of 287 patients, 17%) and CNS tumors (21 of 245, 9%). Among patients with adrenocortical tumors, 69% had germline mutations. Despite inclusion of hypodiploid acute lymphoblastic leukemia, the lowest germline mutation prevalence was found in leukemia (26 of 588, 4%).
Dr. Zhang reported having no disclosures. One coauthor reported financial ties to an industry source.
The sequencing study by Zhang et al. found that 8.5% of 1,120 participants with pediatric cancer had pathogenic mutations in an autosomal dominant cancer-predisposition gene, and four of the mutations were mosaic (i.e., present in only a subset of normal cells, probably indicating the defect was not inherited). The four mosaic mutations probably would not be detected by standard genetic testing strategies.
Not surprisingly, more than 50% of the mutations were in the tumor suppressor gene TP53. A long list of other genes identified as potentially disease causing each occurred at a prevalence of less than 6%.
Although the study’s inclusion of certain high-risk childhood cancers could bias the results toward overestimating the proportion of germline cancer predisposition mutations, more likely the results are an underestimate. By evaluating mutations in only a small subset of candidate autosomal dominant genes, the findings to not reflect a thorough assessment of most genes in the genome. In addition, focusing only on the exome ignores DNA mutations in noncoding regions, especially in tissue-specific enhancers, which may have a role in cancer susceptibility. So-called epimutations may affect cancer susceptibility in a nonmendelian fashion. Finally, the ability to study the interaction of several of these events may contribute to our understanding of tumor initiation.
The study raises several important questions. Are children with mutations in APC, BRCA1, or BRCA2 at risk for childhood cancers? How does germline mosaicism influence disease penetrance, and how many of the mosaic mutations were inherited? How do the mutations identified interact with less well known gene mutations elsewhere in the genome to influence malignant transformation? How can the findings translate to the clinic?
The study highlights the fact that family history is insufficient to assess the likelihood of a cancer-predisposition syndrome in any patient with a newly diagnosed cancer.
Dr. John Maris is a pediatric oncologist in the division of oncology and Center for Childhood Cancer Research, Children’s Hospital of Philadelphia, and in the department of pediatrics at the Perelman School of Medicine, University of Pennsylvania. These remarks were part of an editorial accompanying the report (N Engl J Med. 2015 Nov. 18 doi: 10.1056/NEJMoa1508054). Dr. Maris reported having no disclosures.
The sequencing study by Zhang et al. found that 8.5% of 1,120 participants with pediatric cancer had pathogenic mutations in an autosomal dominant cancer-predisposition gene, and four of the mutations were mosaic (i.e., present in only a subset of normal cells, probably indicating the defect was not inherited). The four mosaic mutations probably would not be detected by standard genetic testing strategies.
Not surprisingly, more than 50% of the mutations were in the tumor suppressor gene TP53. A long list of other genes identified as potentially disease causing each occurred at a prevalence of less than 6%.
Although the study’s inclusion of certain high-risk childhood cancers could bias the results toward overestimating the proportion of germline cancer predisposition mutations, more likely the results are an underestimate. By evaluating mutations in only a small subset of candidate autosomal dominant genes, the findings to not reflect a thorough assessment of most genes in the genome. In addition, focusing only on the exome ignores DNA mutations in noncoding regions, especially in tissue-specific enhancers, which may have a role in cancer susceptibility. So-called epimutations may affect cancer susceptibility in a nonmendelian fashion. Finally, the ability to study the interaction of several of these events may contribute to our understanding of tumor initiation.
The study raises several important questions. Are children with mutations in APC, BRCA1, or BRCA2 at risk for childhood cancers? How does germline mosaicism influence disease penetrance, and how many of the mosaic mutations were inherited? How do the mutations identified interact with less well known gene mutations elsewhere in the genome to influence malignant transformation? How can the findings translate to the clinic?
The study highlights the fact that family history is insufficient to assess the likelihood of a cancer-predisposition syndrome in any patient with a newly diagnosed cancer.
Dr. John Maris is a pediatric oncologist in the division of oncology and Center for Childhood Cancer Research, Children’s Hospital of Philadelphia, and in the department of pediatrics at the Perelman School of Medicine, University of Pennsylvania. These remarks were part of an editorial accompanying the report (N Engl J Med. 2015 Nov. 18 doi: 10.1056/NEJMoa1508054). Dr. Maris reported having no disclosures.
The sequencing study by Zhang et al. found that 8.5% of 1,120 participants with pediatric cancer had pathogenic mutations in an autosomal dominant cancer-predisposition gene, and four of the mutations were mosaic (i.e., present in only a subset of normal cells, probably indicating the defect was not inherited). The four mosaic mutations probably would not be detected by standard genetic testing strategies.
Not surprisingly, more than 50% of the mutations were in the tumor suppressor gene TP53. A long list of other genes identified as potentially disease causing each occurred at a prevalence of less than 6%.
Although the study’s inclusion of certain high-risk childhood cancers could bias the results toward overestimating the proportion of germline cancer predisposition mutations, more likely the results are an underestimate. By evaluating mutations in only a small subset of candidate autosomal dominant genes, the findings to not reflect a thorough assessment of most genes in the genome. In addition, focusing only on the exome ignores DNA mutations in noncoding regions, especially in tissue-specific enhancers, which may have a role in cancer susceptibility. So-called epimutations may affect cancer susceptibility in a nonmendelian fashion. Finally, the ability to study the interaction of several of these events may contribute to our understanding of tumor initiation.
The study raises several important questions. Are children with mutations in APC, BRCA1, or BRCA2 at risk for childhood cancers? How does germline mosaicism influence disease penetrance, and how many of the mosaic mutations were inherited? How do the mutations identified interact with less well known gene mutations elsewhere in the genome to influence malignant transformation? How can the findings translate to the clinic?
The study highlights the fact that family history is insufficient to assess the likelihood of a cancer-predisposition syndrome in any patient with a newly diagnosed cancer.
Dr. John Maris is a pediatric oncologist in the division of oncology and Center for Childhood Cancer Research, Children’s Hospital of Philadelphia, and in the department of pediatrics at the Perelman School of Medicine, University of Pennsylvania. These remarks were part of an editorial accompanying the report (N Engl J Med. 2015 Nov. 18 doi: 10.1056/NEJMoa1508054). Dr. Maris reported having no disclosures.
Children and adolescents with cancer were found to have a significantly higher rate of germline mutations in cancer predisposing genes compared with individuals with no known cancer; however, family history of cancer did not predict the presence of a predisposition syndrome for most patients.
Of the 1,120 children with cancer, 8.5% had mutations in predisposition genes, compared with 1.1% in the control group. Mutations in TP53 were most common (50 patients), followed by APC (6), BRCA2 (6), NF1 (4), PMS2 (4), RB1 (3), and RUNX1 (3). Germline TP53 mutations were present in 27 of 39 patients (69%) with adrenocortical tumors, 9 of 47 (19%) with hypodiploid acute lymphoblastic leukemia, and 1 of 4 (25%) with choroid plexus carcinoma (N Engl J Med. 2015 Nov. 18. doi: 10.1056/NEJMoa1508054).
Only 40% of the pediatric patients with pathogenic germline mutations had a family history of cancer, and in just half of those cases the history was consistent with a known cancer-predisposition syndrome. Among patients without predisposition germline mutations, a similar proportion (42%) had a family history of cancer.
“On the basis of these observations, family history cannot be the sole indication used to guide the provision of genetic testing,” wrote Jinghui Zhang, Ph.D., of the department of computational biology, St. Jude’s Research Hospital, Memphis, Tennessee, and her colleagues.
Unexpected germline mutations were found in several cases. Six patients with Ewing’s sarcoma had unexpected pathogenic germline mutations (TP53 in four patients, PMS2 in one and RET in one). Eight patents had heterozygous mutations in BRCA1, BRCA2, or PALB2, supporting the notion that mutations in these genes may play a role in pediatric as well as adult cancer. Other new associations included germline APC and SDHB mutations with neuroblastoma, and APC, VHL, CDH1, PTCH1, and SDHA germline mutations with leukemia.
The St. Jude–Washington University Pediatric Cancer Genome Project (PCGP) included 1,120 patients representing the major types of pediatric cancer, including 53% with leukemia, 22% with CNS tumors, and 26% with non-CNS tumors. Whole genomes were sequenced from 595 patients, whole exomes (coding regions only) from 456 patients, and both whole genomes and exomes from 69 patients. Whole exomes were sequenced from two control cohorts of individuals with no known cancer: 966 from the 1,000 Genome project and 723 from the National Database for Autism Research (cancer predisposition genes known to be associated with autism, NF1 and PTEN, were excluded from analysis with this control set).
The study sequenced whole genomes and exomes, but focused most of the analysis on 60 autosomal dominant cancer predisposition genes. Tumor types with the highest prevalence of germline mutations in these genes were non-CNS solid tumors (48 of 287 patients, 17%) and CNS tumors (21 of 245, 9%). Among patients with adrenocortical tumors, 69% had germline mutations. Despite inclusion of hypodiploid acute lymphoblastic leukemia, the lowest germline mutation prevalence was found in leukemia (26 of 588, 4%).
Dr. Zhang reported having no disclosures. One coauthor reported financial ties to an industry source.
Children and adolescents with cancer were found to have a significantly higher rate of germline mutations in cancer predisposing genes compared with individuals with no known cancer; however, family history of cancer did not predict the presence of a predisposition syndrome for most patients.
Of the 1,120 children with cancer, 8.5% had mutations in predisposition genes, compared with 1.1% in the control group. Mutations in TP53 were most common (50 patients), followed by APC (6), BRCA2 (6), NF1 (4), PMS2 (4), RB1 (3), and RUNX1 (3). Germline TP53 mutations were present in 27 of 39 patients (69%) with adrenocortical tumors, 9 of 47 (19%) with hypodiploid acute lymphoblastic leukemia, and 1 of 4 (25%) with choroid plexus carcinoma (N Engl J Med. 2015 Nov. 18. doi: 10.1056/NEJMoa1508054).
Only 40% of the pediatric patients with pathogenic germline mutations had a family history of cancer, and in just half of those cases the history was consistent with a known cancer-predisposition syndrome. Among patients without predisposition germline mutations, a similar proportion (42%) had a family history of cancer.
“On the basis of these observations, family history cannot be the sole indication used to guide the provision of genetic testing,” wrote Jinghui Zhang, Ph.D., of the department of computational biology, St. Jude’s Research Hospital, Memphis, Tennessee, and her colleagues.
Unexpected germline mutations were found in several cases. Six patients with Ewing’s sarcoma had unexpected pathogenic germline mutations (TP53 in four patients, PMS2 in one and RET in one). Eight patents had heterozygous mutations in BRCA1, BRCA2, or PALB2, supporting the notion that mutations in these genes may play a role in pediatric as well as adult cancer. Other new associations included germline APC and SDHB mutations with neuroblastoma, and APC, VHL, CDH1, PTCH1, and SDHA germline mutations with leukemia.
The St. Jude–Washington University Pediatric Cancer Genome Project (PCGP) included 1,120 patients representing the major types of pediatric cancer, including 53% with leukemia, 22% with CNS tumors, and 26% with non-CNS tumors. Whole genomes were sequenced from 595 patients, whole exomes (coding regions only) from 456 patients, and both whole genomes and exomes from 69 patients. Whole exomes were sequenced from two control cohorts of individuals with no known cancer: 966 from the 1,000 Genome project and 723 from the National Database for Autism Research (cancer predisposition genes known to be associated with autism, NF1 and PTEN, were excluded from analysis with this control set).
The study sequenced whole genomes and exomes, but focused most of the analysis on 60 autosomal dominant cancer predisposition genes. Tumor types with the highest prevalence of germline mutations in these genes were non-CNS solid tumors (48 of 287 patients, 17%) and CNS tumors (21 of 245, 9%). Among patients with adrenocortical tumors, 69% had germline mutations. Despite inclusion of hypodiploid acute lymphoblastic leukemia, the lowest germline mutation prevalence was found in leukemia (26 of 588, 4%).
Dr. Zhang reported having no disclosures. One coauthor reported financial ties to an industry source.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: Children and adolescents with cancer have a significantly higher rate of germline mutations in cancer predisposition genes compared with individuals with no known cancer.
Major finding: Of the 1,120 children with cancer, 8.5% had mutations in predisposition genes, compared with 1.1% in the control group.
Data source: The St. Jude–Washington University Pediatric Cancer Genome Project (PCGP) sequenced whole genomes of 595 patients, whole exomes of 456 patients, and both whole genomes and exomes of 69 patients; whole exomes were sequenced from two control cohorts of 966 and 723 individuals.
Disclosures: Dr. Zhang reported having no disclosures. One coauthor reported financial ties to an industry source.
Suicide Rate High in Patients With Head and Neck Cancer
Patients with head and neck cancer had a threefold higher risk of suicide, compared with the general population, with higher rates among male patients and those with later-stage disease, according to an analysis of SEER data.
Patients with cancers of the hypopharynx had the highest rates (standardized mortality ratio, compared with the general population, 13.91), followed by cancer of the larynx (5.48) and cancer of the oral cavity and oropharynx (5.23).
“Routine screening for suicide risk may not be needed in every patient,” said David Kam, a medical student at Rutgers New Jersey Medical School, Newark, and his colleagues, “but we have identified a certain subset of patients often seen by otolaryngologists as being at increased risk (those who are older, male, with cancers of the hypopharynx, or with history of radiation therapy)” (JAMA Otolaryngol Head Neck Surg. 2015 Nov 12. doi: 10.1001/jamaoto.2015.2480).
Patients who underwent radiation therapy without surgery had about twice the suicide risk as those who underwent surgery alone (5.12 vs. 2.57). The researchers noted a potential selection bias among those treated with radiation alone, as patients with unresectable disease or significant comorbidities may undergo radiation instead of surgery.
Radiation therapy is integral to treating many head and neck cancers but is associated with a lower quality of life because of related morbidity. Despite improvements in quality of life measures associated with intensity-modulated radiation therapy (IMRT), the analysis showed no improvement in suicide rates after 2005, when IMRT was widely commercially available and a large fraction of patients would presumably have received the newer treatment.
An analysis of SEER (Surveillance, Epidemiology, and End Results) data from 1973 to 2011 showed 857 suicides among 350,413 individuals with head and neck cancer. Among all patients, the greatest increase in suicide rates occurred in the first 5 years after diagnosis.
Because of the significantly increased suicide risk among patients with head and neck cancers, research on survival outcomes should expand to include the psychological toll that the cancer, treatments, and resulting morbidity have on patients, the researchers said.
Patients with head and neck cancer had a threefold higher risk of suicide, compared with the general population, with higher rates among male patients and those with later-stage disease, according to an analysis of SEER data.
Patients with cancers of the hypopharynx had the highest rates (standardized mortality ratio, compared with the general population, 13.91), followed by cancer of the larynx (5.48) and cancer of the oral cavity and oropharynx (5.23).
“Routine screening for suicide risk may not be needed in every patient,” said David Kam, a medical student at Rutgers New Jersey Medical School, Newark, and his colleagues, “but we have identified a certain subset of patients often seen by otolaryngologists as being at increased risk (those who are older, male, with cancers of the hypopharynx, or with history of radiation therapy)” (JAMA Otolaryngol Head Neck Surg. 2015 Nov 12. doi: 10.1001/jamaoto.2015.2480).
Patients who underwent radiation therapy without surgery had about twice the suicide risk as those who underwent surgery alone (5.12 vs. 2.57). The researchers noted a potential selection bias among those treated with radiation alone, as patients with unresectable disease or significant comorbidities may undergo radiation instead of surgery.
Radiation therapy is integral to treating many head and neck cancers but is associated with a lower quality of life because of related morbidity. Despite improvements in quality of life measures associated with intensity-modulated radiation therapy (IMRT), the analysis showed no improvement in suicide rates after 2005, when IMRT was widely commercially available and a large fraction of patients would presumably have received the newer treatment.
An analysis of SEER (Surveillance, Epidemiology, and End Results) data from 1973 to 2011 showed 857 suicides among 350,413 individuals with head and neck cancer. Among all patients, the greatest increase in suicide rates occurred in the first 5 years after diagnosis.
Because of the significantly increased suicide risk among patients with head and neck cancers, research on survival outcomes should expand to include the psychological toll that the cancer, treatments, and resulting morbidity have on patients, the researchers said.
Patients with head and neck cancer had a threefold higher risk of suicide, compared with the general population, with higher rates among male patients and those with later-stage disease, according to an analysis of SEER data.
Patients with cancers of the hypopharynx had the highest rates (standardized mortality ratio, compared with the general population, 13.91), followed by cancer of the larynx (5.48) and cancer of the oral cavity and oropharynx (5.23).
“Routine screening for suicide risk may not be needed in every patient,” said David Kam, a medical student at Rutgers New Jersey Medical School, Newark, and his colleagues, “but we have identified a certain subset of patients often seen by otolaryngologists as being at increased risk (those who are older, male, with cancers of the hypopharynx, or with history of radiation therapy)” (JAMA Otolaryngol Head Neck Surg. 2015 Nov 12. doi: 10.1001/jamaoto.2015.2480).
Patients who underwent radiation therapy without surgery had about twice the suicide risk as those who underwent surgery alone (5.12 vs. 2.57). The researchers noted a potential selection bias among those treated with radiation alone, as patients with unresectable disease or significant comorbidities may undergo radiation instead of surgery.
Radiation therapy is integral to treating many head and neck cancers but is associated with a lower quality of life because of related morbidity. Despite improvements in quality of life measures associated with intensity-modulated radiation therapy (IMRT), the analysis showed no improvement in suicide rates after 2005, when IMRT was widely commercially available and a large fraction of patients would presumably have received the newer treatment.
An analysis of SEER (Surveillance, Epidemiology, and End Results) data from 1973 to 2011 showed 857 suicides among 350,413 individuals with head and neck cancer. Among all patients, the greatest increase in suicide rates occurred in the first 5 years after diagnosis.
Because of the significantly increased suicide risk among patients with head and neck cancers, research on survival outcomes should expand to include the psychological toll that the cancer, treatments, and resulting morbidity have on patients, the researchers said.
Suicide rate high in patients with head and neck cancer
Patients with head and neck cancer had a threefold higher risk of suicide, compared with the general population, with higher rates among male patients and those with later-stage disease, according to an analysis of SEER data.
Patients with cancers of the hypopharynx had the highest rates (standardized mortality ratio, compared with the general population, 13.91), followed by cancer of the larynx (5.48) and cancer of the oral cavity and oropharynx (5.23).
“Routine screening for suicide risk may not be needed in every patient,” said David Kam, a medical student at Rutgers New Jersey Medical School, Newark, and his colleagues, “but we have identified a certain subset of patients often seen by otolaryngologists as being at increased risk (those who are older, male, with cancers of the hypopharynx, or with history of radiation therapy)” (JAMA Otolaryngol Head Neck Surg. 2015 Nov 12. doi: 10.1001/jamaoto.2015.2480).
Patients who underwent radiation therapy without surgery had about twice the suicide risk as those who underwent surgery alone (5.12 vs. 2.57). The researchers noted a potential selection bias among those treated with radiation alone, as patients with unresectable disease or significant comorbidities may undergo radiation instead of surgery.
Radiation therapy is integral to treating many head and neck cancers but is associated with a lower quality of life because of related morbidity. Despite improvements in quality of life measures associated with intensity-modulated radiation therapy (IMRT), the analysis showed no improvement in suicide rates after 2005, when IMRT was widely commercially available and a large fraction of patients would presumably have received the newer treatment.
An analysis of SEER (Surveillance, Epidemiology, and End Results) data from 1973 to 2011 showed 857 suicides among 350,413 individuals with head and neck cancer. Among all patients, the greatest increase in suicide rates occurred in the first 5 years after diagnosis.
Because of the significantly increased suicide risk among patients with head and neck cancers, research on survival outcomes should expand to include the psychological toll that the cancer, treatments, and resulting morbidity have on patients, the researchers said.
Patients with head and neck cancer had a threefold higher risk of suicide, compared with the general population, with higher rates among male patients and those with later-stage disease, according to an analysis of SEER data.
Patients with cancers of the hypopharynx had the highest rates (standardized mortality ratio, compared with the general population, 13.91), followed by cancer of the larynx (5.48) and cancer of the oral cavity and oropharynx (5.23).
“Routine screening for suicide risk may not be needed in every patient,” said David Kam, a medical student at Rutgers New Jersey Medical School, Newark, and his colleagues, “but we have identified a certain subset of patients often seen by otolaryngologists as being at increased risk (those who are older, male, with cancers of the hypopharynx, or with history of radiation therapy)” (JAMA Otolaryngol Head Neck Surg. 2015 Nov 12. doi: 10.1001/jamaoto.2015.2480).
Patients who underwent radiation therapy without surgery had about twice the suicide risk as those who underwent surgery alone (5.12 vs. 2.57). The researchers noted a potential selection bias among those treated with radiation alone, as patients with unresectable disease or significant comorbidities may undergo radiation instead of surgery.
Radiation therapy is integral to treating many head and neck cancers but is associated with a lower quality of life because of related morbidity. Despite improvements in quality of life measures associated with intensity-modulated radiation therapy (IMRT), the analysis showed no improvement in suicide rates after 2005, when IMRT was widely commercially available and a large fraction of patients would presumably have received the newer treatment.
An analysis of SEER (Surveillance, Epidemiology, and End Results) data from 1973 to 2011 showed 857 suicides among 350,413 individuals with head and neck cancer. Among all patients, the greatest increase in suicide rates occurred in the first 5 years after diagnosis.
Because of the significantly increased suicide risk among patients with head and neck cancers, research on survival outcomes should expand to include the psychological toll that the cancer, treatments, and resulting morbidity have on patients, the researchers said.
Patients with head and neck cancer had a threefold higher risk of suicide, compared with the general population, with higher rates among male patients and those with later-stage disease, according to an analysis of SEER data.
Patients with cancers of the hypopharynx had the highest rates (standardized mortality ratio, compared with the general population, 13.91), followed by cancer of the larynx (5.48) and cancer of the oral cavity and oropharynx (5.23).
“Routine screening for suicide risk may not be needed in every patient,” said David Kam, a medical student at Rutgers New Jersey Medical School, Newark, and his colleagues, “but we have identified a certain subset of patients often seen by otolaryngologists as being at increased risk (those who are older, male, with cancers of the hypopharynx, or with history of radiation therapy)” (JAMA Otolaryngol Head Neck Surg. 2015 Nov 12. doi: 10.1001/jamaoto.2015.2480).
Patients who underwent radiation therapy without surgery had about twice the suicide risk as those who underwent surgery alone (5.12 vs. 2.57). The researchers noted a potential selection bias among those treated with radiation alone, as patients with unresectable disease or significant comorbidities may undergo radiation instead of surgery.
Radiation therapy is integral to treating many head and neck cancers but is associated with a lower quality of life because of related morbidity. Despite improvements in quality of life measures associated with intensity-modulated radiation therapy (IMRT), the analysis showed no improvement in suicide rates after 2005, when IMRT was widely commercially available and a large fraction of patients would presumably have received the newer treatment.
An analysis of SEER (Surveillance, Epidemiology, and End Results) data from 1973 to 2011 showed 857 suicides among 350,413 individuals with head and neck cancer. Among all patients, the greatest increase in suicide rates occurred in the first 5 years after diagnosis.
Because of the significantly increased suicide risk among patients with head and neck cancers, research on survival outcomes should expand to include the psychological toll that the cancer, treatments, and resulting morbidity have on patients, the researchers said.
Key clinical point: Patients with head and neck cancer have a significantly higher suicide rate than the general population.
Major finding: The standardized suicide ratio for patients with head and neck cancer, compared with the general population, was 3.21.
Data source: An analysis of SEER data from 1973 to 2011 showed 857 suicides among 350,413 individuals with head and neck cancer.
Disclosures: David Kam and his coauthors reported having no relevant financial disclosures.
Survivors of childhood cancers at increased risk for autoimmune diseases
Analysis of cancer registry data from Denmark, Iceland, and Sweden over more than 60 years found that survivors of childhood cancer had a 1.4-fold higher risk of autoimmune disease compared with matched controls.
Results showed significantly increased rates of hospital visits for 11 of 33 autoimmune diseases investigated. The most prominent excesses were for insulin-dependent diabetes mellitus, Addison’s disease, and Hashimoto’s thyroiditis, accounting for more than half the total number of excess autoimmune cases (Ann Rheum Dis 2015 Nov 6. doi: 10.1136/annrheumdis-2015-207659). The investigators could not rule out the influence of surveillance bias, given that hospitalization rate ratios were highest in the first 5 years after cancer diagnosis, potentially a consequence of closer surveillance during that period. For most autoimmune diseases, however, the excess risk persisted through the second and third decades after cancer diagnosis.
The Nordic childhood cancer survivor cohort comprised 25,635 individuals diagnosed with cancer before the age of 20 years, from the 1940s-1950s (start of cancer registries in Denmark, Iceland, and Sweden) to 2008. Expected autoimmune disease rates were based on rates of hospital visits for the comparison cohort, which included 128,023 individuals matched for age, sex, and country of the corresponding survivor. The standardized hospitalization rate ratio is the observed number of autoimmune diseases among survivors divided by the expected rate. Childhood malignancies with the most pronounced risk increases were leukemia (standardized hospitalization rate ratio, 1.6), Hodgkin lymphoma (1.6), renal tumors (1.6), and central nervous system neoplasms (1.4).
“Cure is no longer a sufficient goal in childhood cancer care. As the vast majority of these patients survive, attention must be to paid to their long-term quality of life and health challenges,” wrote Dr. Anna Salifors Holmqvist of the department of clinical sciences, pediatric oncology and hematology, Skane University Hospital, Lund University, Sweden.
Increased risks were noted for a wide range of relatively rare autoimmune diseases after treatment for several types of childhood malignancies, and underlying mechanisms should be addressed in future studies, noted Dr. Holmqvist and her colleagues.
Analysis of cancer registry data from Denmark, Iceland, and Sweden over more than 60 years found that survivors of childhood cancer had a 1.4-fold higher risk of autoimmune disease compared with matched controls.
Results showed significantly increased rates of hospital visits for 11 of 33 autoimmune diseases investigated. The most prominent excesses were for insulin-dependent diabetes mellitus, Addison’s disease, and Hashimoto’s thyroiditis, accounting for more than half the total number of excess autoimmune cases (Ann Rheum Dis 2015 Nov 6. doi: 10.1136/annrheumdis-2015-207659). The investigators could not rule out the influence of surveillance bias, given that hospitalization rate ratios were highest in the first 5 years after cancer diagnosis, potentially a consequence of closer surveillance during that period. For most autoimmune diseases, however, the excess risk persisted through the second and third decades after cancer diagnosis.
The Nordic childhood cancer survivor cohort comprised 25,635 individuals diagnosed with cancer before the age of 20 years, from the 1940s-1950s (start of cancer registries in Denmark, Iceland, and Sweden) to 2008. Expected autoimmune disease rates were based on rates of hospital visits for the comparison cohort, which included 128,023 individuals matched for age, sex, and country of the corresponding survivor. The standardized hospitalization rate ratio is the observed number of autoimmune diseases among survivors divided by the expected rate. Childhood malignancies with the most pronounced risk increases were leukemia (standardized hospitalization rate ratio, 1.6), Hodgkin lymphoma (1.6), renal tumors (1.6), and central nervous system neoplasms (1.4).
“Cure is no longer a sufficient goal in childhood cancer care. As the vast majority of these patients survive, attention must be to paid to their long-term quality of life and health challenges,” wrote Dr. Anna Salifors Holmqvist of the department of clinical sciences, pediatric oncology and hematology, Skane University Hospital, Lund University, Sweden.
Increased risks were noted for a wide range of relatively rare autoimmune diseases after treatment for several types of childhood malignancies, and underlying mechanisms should be addressed in future studies, noted Dr. Holmqvist and her colleagues.
Analysis of cancer registry data from Denmark, Iceland, and Sweden over more than 60 years found that survivors of childhood cancer had a 1.4-fold higher risk of autoimmune disease compared with matched controls.
Results showed significantly increased rates of hospital visits for 11 of 33 autoimmune diseases investigated. The most prominent excesses were for insulin-dependent diabetes mellitus, Addison’s disease, and Hashimoto’s thyroiditis, accounting for more than half the total number of excess autoimmune cases (Ann Rheum Dis 2015 Nov 6. doi: 10.1136/annrheumdis-2015-207659). The investigators could not rule out the influence of surveillance bias, given that hospitalization rate ratios were highest in the first 5 years after cancer diagnosis, potentially a consequence of closer surveillance during that period. For most autoimmune diseases, however, the excess risk persisted through the second and third decades after cancer diagnosis.
The Nordic childhood cancer survivor cohort comprised 25,635 individuals diagnosed with cancer before the age of 20 years, from the 1940s-1950s (start of cancer registries in Denmark, Iceland, and Sweden) to 2008. Expected autoimmune disease rates were based on rates of hospital visits for the comparison cohort, which included 128,023 individuals matched for age, sex, and country of the corresponding survivor. The standardized hospitalization rate ratio is the observed number of autoimmune diseases among survivors divided by the expected rate. Childhood malignancies with the most pronounced risk increases were leukemia (standardized hospitalization rate ratio, 1.6), Hodgkin lymphoma (1.6), renal tumors (1.6), and central nervous system neoplasms (1.4).
“Cure is no longer a sufficient goal in childhood cancer care. As the vast majority of these patients survive, attention must be to paid to their long-term quality of life and health challenges,” wrote Dr. Anna Salifors Holmqvist of the department of clinical sciences, pediatric oncology and hematology, Skane University Hospital, Lund University, Sweden.
Increased risks were noted for a wide range of relatively rare autoimmune diseases after treatment for several types of childhood malignancies, and underlying mechanisms should be addressed in future studies, noted Dr. Holmqvist and her colleagues.
FROM ANNALS OF RHEUMATIC DISEASES
Key clinical point: Survivors of childhood cancers, especially leukemia, Hodgkin lymphoma, and renal tumors, had a significantly increased risk of autoimmune disease.
Major finding: Compared with matched controls, survivors had a 1.4-fold increased risk for hospital contact concerning an autoimmune disease.
Data source: The Nordic childhood cancer survivor cohort comprised 25,635 individuals diagnosed with cancer before age 20 years, from the 1940s-1950s (start of cancer registries in Denmark, Iceland, and Sweden) to 2008.
Disclosures: Dr. Holmqvist and coauthors reported having no disclosures.
Higher Risk for Basal Cell Carcinoma Linked to Menopausal Hormone Therapy
Late age of natural menopause and use of menopausal hormone therapy were associated with significantly increased risk of basal cell carcinoma (BCC), according to results of a large, nationwide cohort study.
Women who experienced menopause at age 55 years or later, compared with age 50-54 years, had higher BCC risk (hazard ratio, 1.50; 95% confidence interval, 1.04-2.17; P for trend = .017). Among all women, those who had used menopausal hormone therapy had a higher risk (HR, 1.16; 95% confidence interval, 1.03-1.30) (J Clin Oncol. 2015 Nov 2. doi: 10.1200/JCO.2015.62.0625).
The findings are consistent with the hypothesis that exposure to endogenous and exogenous estrogens is photocarcinogenic, according to Dr. Elizabeth Cahoon, research fellow in the Radiation Epidemiology Branch of the National Cancer Institute, Bethesda, Md., and colleagues. Women with the highest observed BCC risk were those who experienced natural menopause and used menopausal hormone therapy for 10 or more years (HR, 1.97; 95% CI, 1.35-2.87; P for trend less than .001).
“In contrast to surgical menopause, which is associated with an immediate and dramatic drop in estrogen levels, women undergoing natural menopause may be exposed to a nontrivial amount of total and unopposed estrogen during the menopausal transition,” they wrote. “In this group, the combination of endogenous and exogenous estrogens may have increased the cumulative estrogen exposure (and, thus, the cumulative phototoxic effects).
The prospective study included 46,100 female, white participants of the US Radiologic Technologists Study, an occupational cohort composed of radiologic technologists. All participants were cancer free at baseline, and 4% had an incident BCC during the approximately 10-year follow-up.
Results showed no association between oral contraceptives and BCC, which may be due a to lower susceptibility in young adults to photosensitizing medications or to the lower doses typical of oral contraceptives. The ethinyl estradiol level in oral contraceptives typically ranges from 20 to 50 mcg, compared with a typical equine estrogen dose in menopausal therapy of 625 mcg.
Most reproductive factors evaluated, including age at menarche, number of live births, and age at first birth, showed no association with BCC.
Dr. Cahoon and coauthors reported having no disclosures.
Late age of natural menopause and use of menopausal hormone therapy were associated with significantly increased risk of basal cell carcinoma (BCC), according to results of a large, nationwide cohort study.
Women who experienced menopause at age 55 years or later, compared with age 50-54 years, had higher BCC risk (hazard ratio, 1.50; 95% confidence interval, 1.04-2.17; P for trend = .017). Among all women, those who had used menopausal hormone therapy had a higher risk (HR, 1.16; 95% confidence interval, 1.03-1.30) (J Clin Oncol. 2015 Nov 2. doi: 10.1200/JCO.2015.62.0625).
The findings are consistent with the hypothesis that exposure to endogenous and exogenous estrogens is photocarcinogenic, according to Dr. Elizabeth Cahoon, research fellow in the Radiation Epidemiology Branch of the National Cancer Institute, Bethesda, Md., and colleagues. Women with the highest observed BCC risk were those who experienced natural menopause and used menopausal hormone therapy for 10 or more years (HR, 1.97; 95% CI, 1.35-2.87; P for trend less than .001).
“In contrast to surgical menopause, which is associated with an immediate and dramatic drop in estrogen levels, women undergoing natural menopause may be exposed to a nontrivial amount of total and unopposed estrogen during the menopausal transition,” they wrote. “In this group, the combination of endogenous and exogenous estrogens may have increased the cumulative estrogen exposure (and, thus, the cumulative phototoxic effects).
The prospective study included 46,100 female, white participants of the US Radiologic Technologists Study, an occupational cohort composed of radiologic technologists. All participants were cancer free at baseline, and 4% had an incident BCC during the approximately 10-year follow-up.
Results showed no association between oral contraceptives and BCC, which may be due a to lower susceptibility in young adults to photosensitizing medications or to the lower doses typical of oral contraceptives. The ethinyl estradiol level in oral contraceptives typically ranges from 20 to 50 mcg, compared with a typical equine estrogen dose in menopausal therapy of 625 mcg.
Most reproductive factors evaluated, including age at menarche, number of live births, and age at first birth, showed no association with BCC.
Dr. Cahoon and coauthors reported having no disclosures.
Late age of natural menopause and use of menopausal hormone therapy were associated with significantly increased risk of basal cell carcinoma (BCC), according to results of a large, nationwide cohort study.
Women who experienced menopause at age 55 years or later, compared with age 50-54 years, had higher BCC risk (hazard ratio, 1.50; 95% confidence interval, 1.04-2.17; P for trend = .017). Among all women, those who had used menopausal hormone therapy had a higher risk (HR, 1.16; 95% confidence interval, 1.03-1.30) (J Clin Oncol. 2015 Nov 2. doi: 10.1200/JCO.2015.62.0625).
The findings are consistent with the hypothesis that exposure to endogenous and exogenous estrogens is photocarcinogenic, according to Dr. Elizabeth Cahoon, research fellow in the Radiation Epidemiology Branch of the National Cancer Institute, Bethesda, Md., and colleagues. Women with the highest observed BCC risk were those who experienced natural menopause and used menopausal hormone therapy for 10 or more years (HR, 1.97; 95% CI, 1.35-2.87; P for trend less than .001).
“In contrast to surgical menopause, which is associated with an immediate and dramatic drop in estrogen levels, women undergoing natural menopause may be exposed to a nontrivial amount of total and unopposed estrogen during the menopausal transition,” they wrote. “In this group, the combination of endogenous and exogenous estrogens may have increased the cumulative estrogen exposure (and, thus, the cumulative phototoxic effects).
The prospective study included 46,100 female, white participants of the US Radiologic Technologists Study, an occupational cohort composed of radiologic technologists. All participants were cancer free at baseline, and 4% had an incident BCC during the approximately 10-year follow-up.
Results showed no association between oral contraceptives and BCC, which may be due a to lower susceptibility in young adults to photosensitizing medications or to the lower doses typical of oral contraceptives. The ethinyl estradiol level in oral contraceptives typically ranges from 20 to 50 mcg, compared with a typical equine estrogen dose in menopausal therapy of 625 mcg.
Most reproductive factors evaluated, including age at menarche, number of live births, and age at first birth, showed no association with BCC.
Dr. Cahoon and coauthors reported having no disclosures.
Adjuvant imatinib for 3 years better than 1 year in high-risk GIST
After surgery for high-risk gastrointestinal stromal tumor (GIST), patients who received adjuvant imatinib for 3 years achieved longer relapse-free survival (RFS) and overall survival (OS) compared with those treated for 1 year, according to a study published online in Journal of Clinical Oncology.
With a median follow up of 7.5 years, the 5-year survival rates of greater than 90% represent the highest reported to date in high-risk GIST.
“We speculate that, other than adjuvant imatinib, two procedures were crucially important for achieving the high overall survival rates: longitudinal monitoring of the abdomen with CT to detect GIST recurrence early when the tumor bulk was still small and restarting of imatinib after recurrence was detected,” wrote Dr. Heikki Joensuu of the Comprehensive Cancer Center Helsinki and University of Helsinki, Finland, and colleagues.
Five-year RFS rates for 3- and 1-year treatment durations were 71.1% and 52.3%, respectively (hazard ratio, 0.60; 95% CI, 0.44-0.81; P less than .001); 5-year OS rates were 91.9% and 85.3%, respectively (HR, 0.60; 95% CI, 0.37-0.97; P = .036), the investigators reported (J Clin Oncol. 2015 Nov. 2. doi: 10.1200/JCO.2015.62.9170).
After a median follow up of 90 months, the second planned analysis of the open-label Scandinavian Sarcoma Group XVIII/AIO study evaluated outcomes of 358 patients, 181 in the 12-month group and 177 in the 36-month group. Earlier results from the SSGXVIII/AIO trial (after a 4.5-year follow up) showed significantly longer survival in patients who received imatinib for 3 years versus 1 year, and these results have informed treatment guidelines.
However, two other large randomized trials evaluated adjuvant imatinib for durations less than 3 years in patients with lower-risk GIST, and neither study found a survival benefit. The investigators point out that because low- or intermediate-risk GIST is cured with surgery alone in the great majority of patients, most do not benefit from adjuvant imatinib.
“Hypothetically, these results suggest that obtaining overall survival benefit may require durable administrations of imatinib and that the patients at high risk for recurrence are the optimal target population,” they wrote.
All but two patients reported at least one adverse event, but most events were mild. Previous reports have suggested cardiac toxicity of imatinib, but only one patient had cardiac failure, perhaps due to the low 400 mg adjuvant daily dosage.
Dr. Joensuu reported consulting or advisory roles with Blueprint Medicines, ARIAD Pharmaceuticals, and Orion Pharma. Several of his coauthors reported ties to industry sources.
After surgery for high-risk gastrointestinal stromal tumor (GIST), patients who received adjuvant imatinib for 3 years achieved longer relapse-free survival (RFS) and overall survival (OS) compared with those treated for 1 year, according to a study published online in Journal of Clinical Oncology.
With a median follow up of 7.5 years, the 5-year survival rates of greater than 90% represent the highest reported to date in high-risk GIST.
“We speculate that, other than adjuvant imatinib, two procedures were crucially important for achieving the high overall survival rates: longitudinal monitoring of the abdomen with CT to detect GIST recurrence early when the tumor bulk was still small and restarting of imatinib after recurrence was detected,” wrote Dr. Heikki Joensuu of the Comprehensive Cancer Center Helsinki and University of Helsinki, Finland, and colleagues.
Five-year RFS rates for 3- and 1-year treatment durations were 71.1% and 52.3%, respectively (hazard ratio, 0.60; 95% CI, 0.44-0.81; P less than .001); 5-year OS rates were 91.9% and 85.3%, respectively (HR, 0.60; 95% CI, 0.37-0.97; P = .036), the investigators reported (J Clin Oncol. 2015 Nov. 2. doi: 10.1200/JCO.2015.62.9170).
After a median follow up of 90 months, the second planned analysis of the open-label Scandinavian Sarcoma Group XVIII/AIO study evaluated outcomes of 358 patients, 181 in the 12-month group and 177 in the 36-month group. Earlier results from the SSGXVIII/AIO trial (after a 4.5-year follow up) showed significantly longer survival in patients who received imatinib for 3 years versus 1 year, and these results have informed treatment guidelines.
However, two other large randomized trials evaluated adjuvant imatinib for durations less than 3 years in patients with lower-risk GIST, and neither study found a survival benefit. The investigators point out that because low- or intermediate-risk GIST is cured with surgery alone in the great majority of patients, most do not benefit from adjuvant imatinib.
“Hypothetically, these results suggest that obtaining overall survival benefit may require durable administrations of imatinib and that the patients at high risk for recurrence are the optimal target population,” they wrote.
All but two patients reported at least one adverse event, but most events were mild. Previous reports have suggested cardiac toxicity of imatinib, but only one patient had cardiac failure, perhaps due to the low 400 mg adjuvant daily dosage.
Dr. Joensuu reported consulting or advisory roles with Blueprint Medicines, ARIAD Pharmaceuticals, and Orion Pharma. Several of his coauthors reported ties to industry sources.
After surgery for high-risk gastrointestinal stromal tumor (GIST), patients who received adjuvant imatinib for 3 years achieved longer relapse-free survival (RFS) and overall survival (OS) compared with those treated for 1 year, according to a study published online in Journal of Clinical Oncology.
With a median follow up of 7.5 years, the 5-year survival rates of greater than 90% represent the highest reported to date in high-risk GIST.
“We speculate that, other than adjuvant imatinib, two procedures were crucially important for achieving the high overall survival rates: longitudinal monitoring of the abdomen with CT to detect GIST recurrence early when the tumor bulk was still small and restarting of imatinib after recurrence was detected,” wrote Dr. Heikki Joensuu of the Comprehensive Cancer Center Helsinki and University of Helsinki, Finland, and colleagues.
Five-year RFS rates for 3- and 1-year treatment durations were 71.1% and 52.3%, respectively (hazard ratio, 0.60; 95% CI, 0.44-0.81; P less than .001); 5-year OS rates were 91.9% and 85.3%, respectively (HR, 0.60; 95% CI, 0.37-0.97; P = .036), the investigators reported (J Clin Oncol. 2015 Nov. 2. doi: 10.1200/JCO.2015.62.9170).
After a median follow up of 90 months, the second planned analysis of the open-label Scandinavian Sarcoma Group XVIII/AIO study evaluated outcomes of 358 patients, 181 in the 12-month group and 177 in the 36-month group. Earlier results from the SSGXVIII/AIO trial (after a 4.5-year follow up) showed significantly longer survival in patients who received imatinib for 3 years versus 1 year, and these results have informed treatment guidelines.
However, two other large randomized trials evaluated adjuvant imatinib for durations less than 3 years in patients with lower-risk GIST, and neither study found a survival benefit. The investigators point out that because low- or intermediate-risk GIST is cured with surgery alone in the great majority of patients, most do not benefit from adjuvant imatinib.
“Hypothetically, these results suggest that obtaining overall survival benefit may require durable administrations of imatinib and that the patients at high risk for recurrence are the optimal target population,” they wrote.
All but two patients reported at least one adverse event, but most events were mild. Previous reports have suggested cardiac toxicity of imatinib, but only one patient had cardiac failure, perhaps due to the low 400 mg adjuvant daily dosage.
Dr. Joensuu reported consulting or advisory roles with Blueprint Medicines, ARIAD Pharmaceuticals, and Orion Pharma. Several of his coauthors reported ties to industry sources.
Key clinical point: Patients with high-risk GIST treated with adjuvant imatinib for 3 years had longer relapse-free survival (RFS) and overall survival (OS) than did those treated for 1 year.
Major finding: Five-year RFS rates for 3- and 1-year treatment durations were 71.1% and 52.3%, respectively (hazard ratio, 0.60; 95% CI, 0.44-0.81; P less than .001); 5-year OS rates were 91.9% and 85.3%, respectively (HR, 0.60; 95% CI, 0.37-0.97; P = .036).
Data source: After a median follow up of 90 months, a second planned analysis of the open-label SSGXVIII/AIO study evaluated outcomes of 358 patients, 181 in the 12-month group and 177 in the 36-month group.
Disclosures: Dr. Joensuu reported consulting or advisory roles with Blueprint Medicines, ARIAD Pharmaceuticals, and Orion Pharma. Several of his coauthors reported ties to industry sources.
Adjuvant lapatinib added no benefit against head and neck squamous cell carcinoma
Lapatinib in combination with platinum-based chemoradiotherapy and as long-term maintenance therapy showed no benefit in patients with surgically treated high-risk squamous cell carcinoma of the head and neck (SCCHN).
No difference was observed between treatment arms in the primary endpoint of disease-free survival (DFS) or the secondary endpoints of investigator-assessed DFS and overall survival.
“Certainly, these findings should serve as a note of caution on the risks of initiating large phase III studies (of this and other drugs) with insufficient evidence of single-agent activity,” wrote Dr. Kevin Harrington of the division of radiotherapy and imaging at the Institute of Cancer Research and Royal Marsden Hospital, London, and his colleagues (Journ Clin Onc. 2015 Nov. 2. doi: 10.1200/JCO.2015.61.4370).
The placebo-controlled phase III trial from 84 sites in 21 countries randomized 688 patients with resected SCCHN to receive placebo or lapatinib. The study was halted early because of the apparent plateauing of DFS events at the median follow-up time of 35.3 months, the investigators reported.
DFS events (disease recurrence or death) occurred in 32% of patients who received placebo versus 35% of patients who received lapatinib (HR, 1.10; 95% CI, 0.85-1.43; P = .45). No significant differences in DFS were observed between treatment arms by human papillomavirus or EGFR status.
Lapatinib is a small-molecule inhibitor of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) and was postulated to be active in squamous cell carcinoma of the head and neck tumors because many overexpress EGFR. Lapatinib has shown efficacy in HER2-positive metastatic breast cancer, but not in other EGFR-driven cancers.
Compliance was high in both placebo and lapatinib arms, with 83% and 76%, respectively, achieving greater than 80% compliance. Adverse events of grade 3 or higher were observed in 67% of the placebo arm and 75% of the lapatinib arm. The most common grade 3 or 4 adverse events were lymphopenia and mucosal inflammation.
Lapatinib in combination with platinum-based chemoradiotherapy and as long-term maintenance therapy showed no benefit in patients with surgically treated high-risk squamous cell carcinoma of the head and neck (SCCHN).
No difference was observed between treatment arms in the primary endpoint of disease-free survival (DFS) or the secondary endpoints of investigator-assessed DFS and overall survival.
“Certainly, these findings should serve as a note of caution on the risks of initiating large phase III studies (of this and other drugs) with insufficient evidence of single-agent activity,” wrote Dr. Kevin Harrington of the division of radiotherapy and imaging at the Institute of Cancer Research and Royal Marsden Hospital, London, and his colleagues (Journ Clin Onc. 2015 Nov. 2. doi: 10.1200/JCO.2015.61.4370).
The placebo-controlled phase III trial from 84 sites in 21 countries randomized 688 patients with resected SCCHN to receive placebo or lapatinib. The study was halted early because of the apparent plateauing of DFS events at the median follow-up time of 35.3 months, the investigators reported.
DFS events (disease recurrence or death) occurred in 32% of patients who received placebo versus 35% of patients who received lapatinib (HR, 1.10; 95% CI, 0.85-1.43; P = .45). No significant differences in DFS were observed between treatment arms by human papillomavirus or EGFR status.
Lapatinib is a small-molecule inhibitor of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) and was postulated to be active in squamous cell carcinoma of the head and neck tumors because many overexpress EGFR. Lapatinib has shown efficacy in HER2-positive metastatic breast cancer, but not in other EGFR-driven cancers.
Compliance was high in both placebo and lapatinib arms, with 83% and 76%, respectively, achieving greater than 80% compliance. Adverse events of grade 3 or higher were observed in 67% of the placebo arm and 75% of the lapatinib arm. The most common grade 3 or 4 adverse events were lymphopenia and mucosal inflammation.
Lapatinib in combination with platinum-based chemoradiotherapy and as long-term maintenance therapy showed no benefit in patients with surgically treated high-risk squamous cell carcinoma of the head and neck (SCCHN).
No difference was observed between treatment arms in the primary endpoint of disease-free survival (DFS) or the secondary endpoints of investigator-assessed DFS and overall survival.
“Certainly, these findings should serve as a note of caution on the risks of initiating large phase III studies (of this and other drugs) with insufficient evidence of single-agent activity,” wrote Dr. Kevin Harrington of the division of radiotherapy and imaging at the Institute of Cancer Research and Royal Marsden Hospital, London, and his colleagues (Journ Clin Onc. 2015 Nov. 2. doi: 10.1200/JCO.2015.61.4370).
The placebo-controlled phase III trial from 84 sites in 21 countries randomized 688 patients with resected SCCHN to receive placebo or lapatinib. The study was halted early because of the apparent plateauing of DFS events at the median follow-up time of 35.3 months, the investigators reported.
DFS events (disease recurrence or death) occurred in 32% of patients who received placebo versus 35% of patients who received lapatinib (HR, 1.10; 95% CI, 0.85-1.43; P = .45). No significant differences in DFS were observed between treatment arms by human papillomavirus or EGFR status.
Lapatinib is a small-molecule inhibitor of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) and was postulated to be active in squamous cell carcinoma of the head and neck tumors because many overexpress EGFR. Lapatinib has shown efficacy in HER2-positive metastatic breast cancer, but not in other EGFR-driven cancers.
Compliance was high in both placebo and lapatinib arms, with 83% and 76%, respectively, achieving greater than 80% compliance. Adverse events of grade 3 or higher were observed in 67% of the placebo arm and 75% of the lapatinib arm. The most common grade 3 or 4 adverse events were lymphopenia and mucosal inflammation.
Key clinical point: After surgery for high-risk squamous cell carcinoma of the head and neck, the addition of lapatinib to chemoradiotherapy and as long-term maintenance therapy offered no benefit.
Major finding: Disease-free survival events occurred in 32% of patients who received placebo versus 35% of patients who received lapatinib (HR, 1.10; 95% CI, 0.85-1.43; P = .45).
Data source: A phase III trial from 84 sites in 21 countries randomizing 688 patients with resected SCCHN to receive placebo or lapatinib.
Disclosures: Dr. Harrington reported financial ties to Merck Sharp & Dohme, Oncos Therapeutics, Cellgene, Viralytics, Lytix, Oncolytics Biotech, Genelux, and AstraZeneca. Several of his coauthors reported ties to industry sources.
