Miguel Arguello-Tomas MD, Elionor Lynton-Pons MSc, Nil Albiol MD, Anna López-Ferrer MD, PhD, Jorge Sierra MD, PhD, Esther Moga MD, PhD, Carol Moreno MD, PhD
Background
Autoimmune disorders (AIDs) are frequent in patients with chronic lymphocytic leukemia (CLL). There is little information on the clinical characteristics and pathogenesis of nonhematologic AIDs in patients with CLL, although both entities present immunologic alterations in their clinical onset.
Methods
This single-center series included 907 patients with CLL who had a median follow-up of 6.6 years (range, 0.1–36.4 years).
Results
In total, 156 patients developed an AID, including 99 patients (10.9%) with nonhematologic AIDs, 46 (5.1%) with autoimmune cytopenia (AIC), and 11 (1.2%) with both; autoimmune hypothyroidism and psoriasis were the most frequent AIDs. Patients with nonhematologic AIDs had low-risk genetic features and were related to a better time to first treatment than patients with AIC (13.8 vs. 5.5 years; p < .001). Patients with both CLL and psoriasis had the lowest risk of progression. The authors performed a T-cell/natural killer-cell and cytokine assessment among patients who had CLL with and without psoriasis. An unsupervised hierarchical clustering revealed a distinct cluster characterized by an expansion of T-helper 17 cells, T-regulatory cells, interleukin-17F, and interleukin-23.
Conclusions
The current findings suggest that nonhematologic AIDs are prevalent in patients with CLL, and these patients have a better prognosis than patients who have AIC. The expansion of interleukin-17F–producing cells in patients with psoriasis may explain their good prognosis.
{"title":"Clinical and immunologic characteristics of nonhematologic autoimmune disorders in chronic lymphocytic leukemia","authors":"Miguel Arguello-Tomas MD, Elionor Lynton-Pons MSc, Nil Albiol MD, Anna López-Ferrer MD, PhD, Jorge Sierra MD, PhD, Esther Moga MD, PhD, Carol Moreno MD, PhD","doi":"10.1002/cncr.70216","DOIUrl":"10.1002/cncr.70216","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Autoimmune disorders (AIDs) are frequent in patients with chronic lymphocytic leukemia (CLL). There is little information on the clinical characteristics and pathogenesis of nonhematologic AIDs in patients with CLL, although both entities present immunologic alterations in their clinical onset.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This single-center series included 907 patients with CLL who had a median follow-up of 6.6 years (range, 0.1–36.4 years).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In total, 156 patients developed an AID, including 99 patients (10.9%) with nonhematologic AIDs, 46 (5.1%) with autoimmune cytopenia (AIC), and 11 (1.2%) with both; autoimmune hypothyroidism and psoriasis were the most frequent AIDs. Patients with nonhematologic AIDs had low-risk genetic features and were related to a better time to first treatment than patients with AIC (13.8 vs. 5.5 years; <i>p</i> < .001). Patients with both CLL and psoriasis had the lowest risk of progression. The authors performed a T-cell/natural killer-cell and cytokine assessment among patients who had CLL with and without psoriasis. An unsupervised hierarchical clustering revealed a distinct cluster characterized by an expansion of T-helper 17 cells, T-regulatory cells, interleukin-17F, and interleukin-23.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The current findings suggest that nonhematologic AIDs are prevalent in patients with CLL, and these patients have a better prognosis than patients who have AIC. The expansion of interleukin-17F–producing cells in patients with psoriasis may explain their good prognosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 24","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145720231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pooja Karukonda MD, Brian G. Czito MD, Eileen Duffy RN, BSN, Hope E. Uronis MD, Thomas A. D'Amico MD, John H. Strickler MD, Donna Niedzwiecki PhD, Christopher G. Willett MD, Manisha Palta MD
Introduction
Esophagogastric cancers are common and carry a poor prognosis. A standard option for locally advanced disease has been neoadjuvant chemoradiation (CRT) followed by surgical resection. The primary goal of this study was to investigate whether the addition of pembrolizumab to neoadjuvant CRT improves pathologic complete response (pCR) rates, compared to historical controls.
Methods
This is a single-institution, prospective, single-arm phase 2 trial (NCT03064490). Patients received three cycles of pembrolizumab (200 mg every 3 weeks) concurrent with neoadjuvant CRT (45 Gy/25 fractions, concurrent weekly carboplatin and paclitaxel), followed by surgical resection. Patients were eligible to receive three additional cycles of adjuvant pembrolizumab if they did not experience significant toxicity during neoadjuvant treatment. Pathologic response and acute toxicities were evaluated. Survival and recurrence data were tabulated.
Results
A total of 35 patients were enrolled over 5 years, with 30 patients completing prescribed neoadjuvant treatment followed by surgical resection. Eleven of 30 patients (36·7%) experienced a pCR and 15/30 patients (50%) experienced a major pathologic response. Rates of grade 3-4 toxicity were comparable to historical controls, and there were no grade 5 toxicities. Median progression-free and overall survival were numerically higher in patients who experienced a major pathologic response.
Conclusion
The addition of pembrolizumab to neoadjuvant CRT followed by surgical resection was overall well-tolerated and resulted in numerically higher rates of pCR compared to historical controls. Further studies with optimized patient selection are warranted to validate the efficacy of this treatment paradigm.
{"title":"Pembrolizumab, Radiotherapy, and Chemotherapy in Neoadjuvant Treatment of Malignant Esophago-gastric Diseases (PROCEED): A single-arm phase 2 trial","authors":"Pooja Karukonda MD, Brian G. Czito MD, Eileen Duffy RN, BSN, Hope E. Uronis MD, Thomas A. D'Amico MD, John H. Strickler MD, Donna Niedzwiecki PhD, Christopher G. Willett MD, Manisha Palta MD","doi":"10.1002/cncr.70213","DOIUrl":"10.1002/cncr.70213","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Esophagogastric cancers are common and carry a poor prognosis. A standard option for locally advanced disease has been neoadjuvant chemoradiation (CRT) followed by surgical resection. The primary goal of this study was to investigate whether the addition of pembrolizumab to neoadjuvant CRT improves pathologic complete response (pCR) rates, compared to historical controls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This is a single-institution, prospective, single-arm phase 2 trial (NCT03064490). Patients received three cycles of pembrolizumab (200 mg every 3 weeks) concurrent with neoadjuvant CRT (45 Gy/25 fractions, concurrent weekly carboplatin and paclitaxel), followed by surgical resection. Patients were eligible to receive three additional cycles of adjuvant pembrolizumab if they did not experience significant toxicity during neoadjuvant treatment. Pathologic response and acute toxicities were evaluated. Survival and recurrence data were tabulated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 35 patients were enrolled over 5 years, with 30 patients completing prescribed neoadjuvant treatment followed by surgical resection. Eleven of 30 patients (36·7%) experienced a pCR and 15/30 patients (50%) experienced a major pathologic response. Rates of grade 3-4 toxicity were comparable to historical controls, and there were no grade 5 toxicities. Median progression-free and overall survival were numerically higher in patients who experienced a major pathologic response.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The addition of pembrolizumab to neoadjuvant CRT followed by surgical resection was overall well-tolerated and resulted in numerically higher rates of pCR compared to historical controls. Further studies with optimized patient selection are warranted to validate the efficacy of this treatment paradigm.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 24","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145720080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maryse J. Luijendijk MSc, Philippe R. Lee Meeuw Kjoe PhD, Noor Wortelboer MSc, Annemiek van Ommen-Nijhof PhD, A. Elise van Leeuwen-Stok PhD, Joost A. Agelink van Rentergem PhD, Ivar E. Vermeulen PhD, Inge R. Konings MD, PhD, Agnes Jager MD, PhD, Gabe S. Sonke MD, PhD, Elsken van der Wall MD, PhD, Sanne B. Schagen PhD
Background
Endocrine treatment for breast cancer may adversely affect cognition. Given the widespread use of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i), assessing the cognitive effects of this combination is important.
Methods
In the SONIA trial, patients with hormone receptor–positive, HER2-negative (HR+HER2−) advanced breast cancer (ABC) starting first-line treatment with an aromatase inhibitor were randomized to treatment with (arm A) or without (arm B) CDK4/6i. Cognitive function was assessed at baseline and after 9 months with the online Amsterdam Cognition Scan. Standardized z scores at baseline and regression-based change scores at 9 months were computed on the basis of matched cancer-free controls. Rates of clinically meaningful decline were compared with estimated false-positive rates of observing decline by chance.
Results
Altogether, 260 patients (arm A, N = 130; arm B, N = 130) and 130 matched controls participated at baseline; 199 patients (arm A, N = 108; arm B, N = 91) and 120 matched controls completed the follow-up. At baseline, patients performed significantly worse than controls across all cognitive domains. Over the course of 9 months, no group-level decline in cognitive function occurred in either treatment arm, with minimal differences between treatment arms. At the individual level, however, the rate of clinically meaningful decline in patients (arm A, 15.7%; arm B, 14.3%) but not in controls (6.7%) was significantly higher than the false-positive rate (7.5%), which indicates decline in a small subset of patients.
Conclusions
Patients with HR+HER2− ABC showed impaired cognitive function at initial diagnosis compared to cancer-free controls. During first-line endocrine treatment with aromatase inhibitors, cognitive function declined in a small group of patients, regardless of the addition of CDK4/6i.
{"title":"Cognitive function during endocrine treatment with or without cyclin-dependent kinase 4/6 inhibitors for advanced breast cancer","authors":"Maryse J. Luijendijk MSc, Philippe R. Lee Meeuw Kjoe PhD, Noor Wortelboer MSc, Annemiek van Ommen-Nijhof PhD, A. Elise van Leeuwen-Stok PhD, Joost A. Agelink van Rentergem PhD, Ivar E. Vermeulen PhD, Inge R. Konings MD, PhD, Agnes Jager MD, PhD, Gabe S. Sonke MD, PhD, Elsken van der Wall MD, PhD, Sanne B. Schagen PhD","doi":"10.1002/cncr.70212","DOIUrl":"10.1002/cncr.70212","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Endocrine treatment for breast cancer may adversely affect cognition. Given the widespread use of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i), assessing the cognitive effects of this combination is important.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In the SONIA trial, patients with hormone receptor–positive, HER2-negative (HR<sup>+</sup>HER2<sup>−</sup>) advanced breast cancer (ABC) starting first-line treatment with an aromatase inhibitor were randomized to treatment with (arm A) or without (arm B) CDK4/6i. Cognitive function was assessed at baseline and after 9 months with the online Amsterdam Cognition Scan. Standardized <i>z</i> scores at baseline and regression-based change scores at 9 months were computed on the basis of matched cancer-free controls. Rates of clinically meaningful decline were compared with estimated false-positive rates of observing decline by chance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Altogether, 260 patients (arm A, <i>N</i> = 130; arm B, <i>N</i> = 130) and 130 matched controls participated at baseline; 199 patients (arm A, <i>N</i> = 108; arm B, <i>N</i> = 91) and 120 matched controls completed the follow-up. At baseline, patients performed significantly worse than controls across all cognitive domains. Over the course of 9 months, no group-level decline in cognitive function occurred in either treatment arm, with minimal differences between treatment arms. At the individual level, however, the rate of clinically meaningful decline in patients (arm A, 15.7%; arm B, 14.3%) but not in controls (6.7%) was significantly higher than the false-positive rate (7.5%), which indicates decline in a small subset of patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Patients with HR<sup>+</sup>HER2<sup>−</sup> ABC showed impaired cognitive function at initial diagnosis compared to cancer-free controls. During first-line endocrine treatment with aromatase inhibitors, cognitive function declined in a small group of patients, regardless of the addition of CDK4/6i.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 24","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145720210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lingkai Zhang MD, Zhaopei Liu MD, Yawei Ding PhD, Jiaxing Sun PhD, Yuzhen Wu PhD, Xiaohe Su MD, Kaifeng Jin MD, Han Zeng MD, Hailong Liu PhD, Yuan Chang MD, Yu Zhu PhD, Zewei Wang MD, Le Xu PhD, Weijuan Zhang PhD, Jiejie Xu PhD
Background
Sex differences are a hallmark of urothelial carcinoma (UC), and profoundly influence disease progression and therapeutic outcomes. As critical effector immune cells with intrinsic sexual dimorphism, the contributions of natural killer (NK) cells to this clinical discrepancy remain incompletely understood.
Methods
In this multicohort retrospective study of 885 patients with UC (671 males; 214 females), individuals were stratified into NKhigh and NKlow subgroups on the basis of immunohistochemical or transcriptomic evaluation. The association of NK cells with clinical outcomes and the tumor immune microenvironment (TME) was systematically assessed across sexes. Single-cell RNA sequencing and flow cytometry were deployed to decipher the functional state of NK cells.
Results
Although NK cell infiltration levels were comparable between sexes, their clinical impact was markedly divergent: high NK infiltration conferred a significant survival advantage and superior response to both chemotherapy and immunotherapy exclusively in male patients. Further immune profiling revealed that NKhigh male patients exhibited a coordinated antitumor microenvironment, characterized by immunotype A features, tertiary lymphoid structure formation, and abundant infiltration of dendritic cells and effector T cells. Mechanistically, male-derived NK cells maintained robust cytotoxic and inflammatory programs, whereas female-derived NK cells were polarized toward a stressed, dysfunctional state with decidual-like characteristics.
Conclusions
Altogether, this study establishes NK cells as pivotal mediators of sex differences in UC. The stark contrast in NK cell phenotypes underscores a fundamental sexual dimorphism within the TME, which highlights the urgent need for sex-tailored immunotherapy strategies.
{"title":"Natural killer cell infiltration elicits gender-dependent dichotomous clinical outcomes in urothelial carcinoma","authors":"Lingkai Zhang MD, Zhaopei Liu MD, Yawei Ding PhD, Jiaxing Sun PhD, Yuzhen Wu PhD, Xiaohe Su MD, Kaifeng Jin MD, Han Zeng MD, Hailong Liu PhD, Yuan Chang MD, Yu Zhu PhD, Zewei Wang MD, Le Xu PhD, Weijuan Zhang PhD, Jiejie Xu PhD","doi":"10.1002/cncr.70196","DOIUrl":"10.1002/cncr.70196","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Sex differences are a hallmark of urothelial carcinoma (UC), and profoundly influence disease progression and therapeutic outcomes. As critical effector immune cells with intrinsic sexual dimorphism, the contributions of natural killer (NK) cells to this clinical discrepancy remain incompletely understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this multicohort retrospective study of 885 patients with UC (671 males; 214 females), individuals were stratified into NK<sup>high</sup> and NK<sup>low</sup> subgroups on the basis of immunohistochemical or transcriptomic evaluation. The association of NK cells with clinical outcomes and the tumor immune microenvironment (TME) was systematically assessed across sexes. Single-cell RNA sequencing and flow cytometry were deployed to decipher the functional state of NK cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Although NK cell infiltration levels were comparable between sexes, their clinical impact was markedly divergent: high NK infiltration conferred a significant survival advantage and superior response to both chemotherapy and immunotherapy exclusively in male patients. Further immune profiling revealed that NK<sup>high</sup> male patients exhibited a coordinated antitumor microenvironment, characterized by immunotype A features, tertiary lymphoid structure formation, and abundant infiltration of dendritic cells and effector T cells. Mechanistically, male-derived NK cells maintained robust cytotoxic and inflammatory programs, whereas female-derived NK cells were polarized toward a stressed, dysfunctional state with decidual-like characteristics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Altogether, this study establishes NK cells as pivotal mediators of sex differences in UC. The stark contrast in NK cell phenotypes underscores a fundamental sexual dimorphism within the TME, which highlights the urgent need for sex-tailored immunotherapy strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 24","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145712683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Justin C. Brown PhD, Abigail L. Tice PhD, Bret H. Goodpaster PhD, Fanchao Yi PhD, Shengping Yang PhD, Mohamedtaki A. Tejani MD
Background
Older adults who are long-term survivors of cancer are vulnerable to developing mobility disability than noncancer controls; it is unknown if physical activity improves objective measures of lower-extremity physical performance, such as the Short Physical Performance Battery (SPPB) and 400-m walk, that are predictors of mobility disability in this population.
Methods
The Lifestyle Interventions and Independence for Elders (LIFE) study was a multicenter randomized trial that enrolled 1635 adults aged 70−89 years, of whom 371 (22.7%) reported a history of cancer and were included in this secondary analysis. Participants were randomized to health education or physical activity. End points included the SPPB and 400-m walk.
Results
Randomization to physical activity, compared with health education, improved the SPPB score at 6 months (0.45 points [95% confidence interval (CI), 0.05–0.86]; p = .027), 12 months (0.43 points [95% CI, 0.02–0.83]; p = .039), and 24 months (0.45 points [95% CI, 0.04–0.87]; p = .031). Randomization to physical activity, compared with health education, improved the 400-m walk speed at 6 months (0.042 m/s [95% CI, 0.017–0.066]; p < .001) and 12 months (0.036 m/s [95% CI, 0.011–0.060]; p = .004) but not 24 months (0.013 m/s [95% CI, −0.012 to 0.038]; p = .30). Moderate-to-vigorous intensity physical activity volume at 6 months mediated 25.3% (95% CI, 4.1–46.6 [p = .019]) and 30.3% [95% CI, 10.3–50.4 [p = .003]) of the effect of randomization on the SPPB score and 400-m walk speed at 12 months, respectively.
Conclusion
Physical activity may improve lower-extremity physical performance compared to health education in older adults who are long-term survivors of cancer.
背景：癌症长期幸存者的老年人比非癌症对照者更容易发生行动障碍；目前尚不清楚体育活动是否能改善作为该人群行动障碍预测指标的下肢物理性能的客观测量，如短时间物理性能测试（SPPB）和400米步行。方法：生活方式干预和老年人独立性（LIFE）研究是一项多中心随机试验，招募了1635名年龄在70-89岁之间的成年人，其中371名（22.7%）报告有癌症病史，并纳入了该次要分析。参与者被随机分为健康教育组和体育活动组。终点包括SPPB和400米步行。结果：与健康教育组相比，随机运动组提高了6个月时SPPB评分(0.45分[95%可信区间（CI）， 0.05-0.86]；p = 0.027)、12个月（0.43点[95% CI， 0.02-0.83]; p = 0.039）和24个月（0.45点[95% CI， 0.04-0.87]; p = 0.031）。与健康教育相比，随机分配到体育活动组，在6个月时提高了400米步行速度(0.042米/秒[95% CI， 0.017-0.066]； p结论：与健康教育相比，体育活动可以改善老年癌症长期幸存者的下肢运动能力。
{"title":"Effects of physical activity on performance measures in older adult cancer survivors","authors":"Justin C. Brown PhD, Abigail L. Tice PhD, Bret H. Goodpaster PhD, Fanchao Yi PhD, Shengping Yang PhD, Mohamedtaki A. Tejani MD","doi":"10.1002/cncr.70197","DOIUrl":"10.1002/cncr.70197","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Older adults who are long-term survivors of cancer are vulnerable to developing mobility disability than noncancer controls; it is unknown if physical activity improves objective measures of lower-extremity physical performance, such as the Short Physical Performance Battery (SPPB) and 400-m walk, that are predictors of mobility disability in this population.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The Lifestyle Interventions and Independence for Elders (LIFE) study was a multicenter randomized trial that enrolled 1635 adults aged 70−89 years, of whom 371 (22.7%) reported a history of cancer and were included in this secondary analysis. Participants were randomized to health education or physical activity. End points included the SPPB and 400-m walk.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Randomization to physical activity, compared with health education, improved the SPPB score at 6 months (0.45 points [95% confidence interval (CI), 0.05–0.86]; <i>p</i> = .027), 12 months (0.43 points [95% CI, 0.02–0.83]; <i>p</i> = .039), and 24 months (0.45 points [95% CI, 0.04–0.87]; <i>p</i> = .031). Randomization to physical activity, compared with health education, improved the 400-m walk speed at 6 months (0.042 m/s [95% CI, 0.017–0.066]; <i>p</i> < .001) and 12 months (0.036 m/s [95% CI, 0.011–0.060]; <i>p</i> = .004) but not 24 months (0.013 m/s [95% CI, −0.012 to 0.038]; <i>p</i> = .30). Moderate-to-vigorous intensity physical activity volume at 6 months mediated 25.3% (95% CI, 4.1–46.6 [<i>p</i> = .019]) and 30.3% [95% CI, 10.3–50.4 [<i>p</i> = .003]) of the effect of randomization on the SPPB score and 400-m walk speed at 12 months, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Physical activity may improve lower-extremity physical performance compared to health education in older adults who are long-term survivors of cancer.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 24","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12694757/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145720038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. van der Leij MD, Jop C. Teepen PhD, Leontien C. M. Kremer, Heleen J. H. van der Pal MD, PhD, M. M. van den Heuvel-Eibrink, Dorine Bresters MD, PhD, Andrica C. H. de Vries MD, PhD, A. J. Keijzer-Schellekens, Cecile M. Ronckers MD, PhD, Rosella Hermens MD, Marloes Louwerens MD, Sebastian Neggers MD, PhD, Gerlof D. Valk, H. M. van Santen
Purpose
Primary hypothyroidism is common in childhood cancer survivors (CCS). Exposure to radiation and hematopoietic stem cell transplantation (HSCT) are known risk factors; however, the impact of chemotherapy and the role of thyroid peroxidase antibodies (anti-TPO) remain unclear. The prevalence of primary hypothyroidism, anti-TPO, and treatment-related risk factors in a cohort of CCS was assessed.
Methods
In total, 1774 five-year CCS were included. The prevalence of primary hypothyroidism according to treatment strategy was evaluated: radiotherapy involving the thyroid gland (±chemotherapy), chemotherapy only, HSCT, and controls. Multivariable logistic regression was performed to identify risk factors for hypothyroidism.
Results
After a median follow-up time of 25.3 years (range, 14.8–54.7), primary hypothyroidism was present in 8.2%. When evaluating subgroups specifically, the prevalence of primary hypothyroidism increased to 28% in CCS treated with radiotherapy and 30.6% after HSCT. In multivariable analyses, survivors treated with chemotherapy only were not at increased risk of hypothyroidism (odds ratio [OR], 0.74; 95% CI, 0.28–2.00), whereas survivors treated with radiotherapy had an almost 14-fold increased risk (OR, 13.91; 95% CI, 5.34–36.22). In irradiated CCS, the use of platinating agents was associated with an increased risk of hypothyroidism (OR, 3.25; 95% CI, 1.39–7.59). The prevalence of anti-TPO did not differ between the treatment groups (p = .42).
Conclusions
Primary hypothyroidism is prevalent after radiation exposure and HSCT. Chemotherapy only does not increase the risk for primary hypothyroidism. The use of platinating agents combined with radiotherapy may increase its risk. Treatment for childhood cancer does not increase the risk of anti-TPO.
{"title":"Primary hypothyroidism after treatment for childhood cancer in the Dutch Childhood Cancer Survivor Study: Hypothyroidism in childhood cancer survivors","authors":"S. van der Leij MD, Jop C. Teepen PhD, Leontien C. M. Kremer, Heleen J. H. van der Pal MD, PhD, M. M. van den Heuvel-Eibrink, Dorine Bresters MD, PhD, Andrica C. H. de Vries MD, PhD, A. J. Keijzer-Schellekens, Cecile M. Ronckers MD, PhD, Rosella Hermens MD, Marloes Louwerens MD, Sebastian Neggers MD, PhD, Gerlof D. Valk, H. M. van Santen","doi":"10.1002/cncr.70198","DOIUrl":"10.1002/cncr.70198","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>Primary hypothyroidism is common in childhood cancer survivors (CCS). Exposure to radiation and hematopoietic stem cell transplantation (HSCT) are known risk factors; however, the impact of chemotherapy and the role of thyroid peroxidase antibodies (anti-TPO) remain unclear. The prevalence of primary hypothyroidism, anti-TPO, and treatment-related risk factors in a cohort of CCS was assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In total, 1774 five-year CCS were included. The prevalence of primary hypothyroidism according to treatment strategy was evaluated: radiotherapy involving the thyroid gland (±chemotherapy), chemotherapy only, HSCT, and controls. Multivariable logistic regression was performed to identify risk factors for hypothyroidism.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>After a median follow-up time of 25.3 years (range, 14.8–54.7), primary hypothyroidism was present in 8.2%. When evaluating subgroups specifically, the prevalence of primary hypothyroidism increased to 28% in CCS treated with radiotherapy and 30.6% after HSCT. In multivariable analyses, survivors treated with chemotherapy only were not at increased risk of hypothyroidism (odds ratio [OR], 0.74; 95% CI, 0.28–2.00), whereas survivors treated with radiotherapy had an almost 14-fold increased risk (OR, 13.91; 95% CI, 5.34–36.22). In irradiated CCS, the use of platinating agents was associated with an increased risk of hypothyroidism (OR, 3.25; 95% CI, 1.39–7.59). The prevalence of anti-TPO did not differ between the treatment groups (<i>p</i> = .42).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Primary hypothyroidism is prevalent after radiation exposure and HSCT. Chemotherapy only does not increase the risk for primary hypothyroidism. The use of platinating agents combined with radiotherapy may increase its risk. Treatment for childhood cancer does not increase the risk of anti-TPO.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 24","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145720054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Inna Y. Gong MD, PhD, Mark J. Soto MSc, Bahar Rafinejad-Farahani MPH, Joseph M. Unger PhD, Rena M. Conti PhD, Carmen E. Guerra MD, MScE, Amit Oza MD, Meredith Rosenthal PhD, Danielle Rodin MD, MPH
Background
Clinical trials (CTs) are essential for expanding treatment options across hematologic malignancies (HM) and providing access to novel treatments. However, older adults with HM are often underrepresented in CTs, and a national-level evaluation of factors influencing their participation is lacking.
Methods
The authors conducted a retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, identifying patients ≥66 years old diagnosed with HM between 2006 and 2018 (follow-up to December 2019). CT participation was defined by Medicare claims for CT services. Cumulative incidence and Fine-Gray models were used to estimate participation rates and adjusted hazard ratios (aHRs) assessed the association between participation and sociodemographic factors.
Results
The cohort (n = 53,919) was 50% female, median age 78 years old, and 86% White. Cumulative incidence of CT participation was low at 2.7% at 1 year after diagnosis, increasing to 4.3% at 5 years. After adjustment for the competing risk of death, significantly lower CT participation was observed for older age (vs. 66–69 years: aHR for 70–74 years, 0.79 [95% CI, 0.71–0.88]; aHR for 75–79 years, 0.63 [95% CI, 0.56–0.70]; aHR for 80–84 years, 0.41 [95% CI, 0.36–0.46]; aHR for ≥85 years, 0.21 [95% CI, 0.18–0.24]), female sex (aHR, 0.79 [95% CI, 0.73–0.86]), Black race (aHR, 0.73 [95% CI, 0.59–0.90]), certain comorbidities (aHR for pulmonary disease, 0.76 [95% CI, 0.68–0.85]; aHR for renal disease, 0.67 [95% CI, 0.59–0.76]), dual Medicare–Medicaid eligibility (aHR, 0.66 [95% CI, 0.56–0.77]), and distance to National Cancer Institute centers from the patient’s ZIP code (aHR for ≥250 miles, 0.64 [95% CI, 0.48–0.86]).
Conclusions
These results highlight the need for targeted interventions, such as CT navigator programs and decentralized trials, to increase older adult participation in HM CTs.
{"title":"Disparities in clinical trial participation among older adult Medicare beneficiaries with hematologic malignancies from 2006 to 2019: A SEER–Medicare analysis","authors":"Inna Y. Gong MD, PhD, Mark J. Soto MSc, Bahar Rafinejad-Farahani MPH, Joseph M. Unger PhD, Rena M. Conti PhD, Carmen E. Guerra MD, MScE, Amit Oza MD, Meredith Rosenthal PhD, Danielle Rodin MD, MPH","doi":"10.1002/cncr.70204","DOIUrl":"10.1002/cncr.70204","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Clinical trials (CTs) are essential for expanding treatment options across hematologic malignancies (HM) and providing access to novel treatments. However, older adults with HM are often underrepresented in CTs, and a national-level evaluation of factors influencing their participation is lacking.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The authors conducted a retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, identifying patients ≥66 years old diagnosed with HM between 2006 and 2018 (follow-up to December 2019). CT participation was defined by Medicare claims for CT services. Cumulative incidence and Fine-Gray models were used to estimate participation rates and adjusted hazard ratios (aHRs) assessed the association between participation and sociodemographic factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The cohort (<i>n</i> = 53,919) was 50% female, median age 78 years old, and 86% White. Cumulative incidence of CT participation was low at 2.7% at 1 year after diagnosis, increasing to 4.3% at 5 years. After adjustment for the competing risk of death, significantly lower CT participation was observed for older age (vs. 66–69 years: aHR for 70–74 years, 0.79 [95% CI, 0.71–0.88]; aHR for 75–79 years, 0.63 [95% CI, 0.56–0.70]; aHR for 80–84 years, 0.41 [95% CI, 0.36–0.46]; aHR for ≥85 years, 0.21 [95% CI, 0.18–0.24]), female sex (aHR, 0.79 [95% CI, 0.73–0.86]), Black race (aHR, 0.73 [95% CI, 0.59–0.90]), certain comorbidities (aHR for pulmonary disease, 0.76 [95% CI, 0.68–0.85]; aHR for renal disease, 0.67 [95% CI, 0.59–0.76]), dual Medicare–Medicaid eligibility (aHR, 0.66 [95% CI, 0.56–0.77]), and distance to National Cancer Institute centers from the patient’s ZIP code (aHR for ≥250 miles, 0.64 [95% CI, 0.48–0.86]).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These results highlight the need for targeted interventions, such as CT navigator programs and decentralized trials, to increase older adult participation in HM CTs.</p>\u0000 </section>\u0000 </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 24","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12690631/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145712640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhidong Gao MD, Chao Wang MD, Jian Li MD, Peng Zhang MD, Xin Wu MD, Yi Wang MD, Liming Zhang MD, Tao Chen MD, Bo Zhang MD, Ming Wang MD, Haoran Qian MD, Ye Zhou MD, Shijie Li MD, Yan Sun MD, Han Liang MD, Yulong He MD, Yong Li MD, Hui Cao MD, Shukui Qin MD, Lin Shen MD, Yingjiang Ye MD, PhD, Chinese Society of Clinical Oncology (CSCO) Expert Committee on Gastrointestinal Stromal Tumor
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract, with malignant potential ranging from very low risk to high risk. Small GISTs, defined as those with measuring <2 cm in greatest dimension, generally exhibit benign or indolent behavior, although a few exhibit aggressive features. The evidence of epidemiology, biologic behavior, diagnosis, treatment, and surveillance of small GISTs is limited, and the treatment status in clinical practice has no uniform standards. Thus the Chinese Society of Clinical Oncology Expert Committee on Gastrointestinal Stromal Tumor systemically reviewed the latest evidence using the Delphi method and provided recommendations for diagnosing and treating small GISTs.
{"title":"Chinese expert consensus on diagnosis and treatment of small gastrointestinal stromal tumors (2025 edition)","authors":"Zhidong Gao MD, Chao Wang MD, Jian Li MD, Peng Zhang MD, Xin Wu MD, Yi Wang MD, Liming Zhang MD, Tao Chen MD, Bo Zhang MD, Ming Wang MD, Haoran Qian MD, Ye Zhou MD, Shijie Li MD, Yan Sun MD, Han Liang MD, Yulong He MD, Yong Li MD, Hui Cao MD, Shukui Qin MD, Lin Shen MD, Yingjiang Ye MD, PhD, Chinese Society of Clinical Oncology (CSCO) Expert Committee on Gastrointestinal Stromal Tumor","doi":"10.1002/cncr.70152","DOIUrl":"https://doi.org/10.1002/cncr.70152","url":null,"abstract":"<p>Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract, with malignant potential ranging from very low risk to high risk. Small GISTs, defined as those with measuring <2 cm in greatest dimension, generally exhibit benign or indolent behavior, although a few exhibit aggressive features. The evidence of epidemiology, biologic behavior, diagnosis, treatment, and surveillance of small GISTs is limited, and the treatment status in clinical practice has no uniform standards. Thus the Chinese Society of Clinical Oncology Expert Committee on Gastrointestinal Stromal Tumor systemically reviewed the latest evidence using the Delphi method and provided recommendations for diagnosing and treating small GISTs.</p>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 S3","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://acsjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/cncr.70152","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145699084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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