Sofia Palmér, Antonis Valachis, Henrik Lindman, Daniel Robert Smith, Åsa Wickberg, Fredrika Killander, Judith Bjöhle, Zakaria Einbeigi, Greger Nilsson, Johan Ahlgren, Kenneth Villman
Background This prospective cohort study aimed to assess whether postoperative radiotherapy could safely be omitted in women ≥ 65 years with low-risk, estrogen receptor (ER)-positive T1N0 breast cancer treated with breast-conserving surgery and adjuvant endocrine therapy. Methods Eligible patients were women ≥ 65 years with unifocal, non-lobular, grade 1 or 2, ER-positive, pT1N0 breast cancer treated with breast-conserving surgery and endocrine therapy for five years. Patients were followed up with mammography at least annually for 10 years. The primary endpoint was local recurrence. Secondary endpoints were contralateral breast cancer, recurrence-free survival, and overall survival. Results The final study cohort included 601 patients with a median age of 71 years (range: 65 to 90 years) and a median tumor size of 11 mm (range: 3 to 20 mm). Median follow-up time was 119 months (interquartile range: 103 to 121 months). The cumulative incidence of local recurrence was 1.5% (95% confidence interval (CI): 0.8 to 2.8%) and 5.5% (95% CI: 3.8 to 7.6%) at 5 and 10 years, respectively. The cumulative incidence of contralateral breast cancer was 1.7% (95% CI: 0.9 to 3.0%) at 5 years and 4.5% (95% CI: 3.0 to 6.6%) at 10 years. The overall survival rate at 10 years was 83.1% (95% CI: 80.8 to 85.4%). In total, three patients (0.5%) died due to breast cancer. Conclusion Our results support the possibility to omit radiotherapy after breast-conserving surgery in a well-defined subgroup of women aged ≥ 65 years with low-risk, ER-positive, pT1N0 breast cancer receiving adjuvant endocrine therapy.
{"title":"Omission of postoperative radiotherapy after breast-conserving surgery in low-risk breast cancer","authors":"Sofia Palmér, Antonis Valachis, Henrik Lindman, Daniel Robert Smith, Åsa Wickberg, Fredrika Killander, Judith Bjöhle, Zakaria Einbeigi, Greger Nilsson, Johan Ahlgren, Kenneth Villman","doi":"10.1093/jnci/djae315","DOIUrl":"https://doi.org/10.1093/jnci/djae315","url":null,"abstract":"Background This prospective cohort study aimed to assess whether postoperative radiotherapy could safely be omitted in women ≥ 65 years with low-risk, estrogen receptor (ER)-positive T1N0 breast cancer treated with breast-conserving surgery and adjuvant endocrine therapy. Methods Eligible patients were women ≥ 65 years with unifocal, non-lobular, grade 1 or 2, ER-positive, pT1N0 breast cancer treated with breast-conserving surgery and endocrine therapy for five years. Patients were followed up with mammography at least annually for 10 years. The primary endpoint was local recurrence. Secondary endpoints were contralateral breast cancer, recurrence-free survival, and overall survival. Results The final study cohort included 601 patients with a median age of 71 years (range: 65 to 90 years) and a median tumor size of 11 mm (range: 3 to 20 mm). Median follow-up time was 119 months (interquartile range: 103 to 121 months). The cumulative incidence of local recurrence was 1.5% (95% confidence interval (CI): 0.8 to 2.8%) and 5.5% (95% CI: 3.8 to 7.6%) at 5 and 10 years, respectively. The cumulative incidence of contralateral breast cancer was 1.7% (95% CI: 0.9 to 3.0%) at 5 years and 4.5% (95% CI: 3.0 to 6.6%) at 10 years. The overall survival rate at 10 years was 83.1% (95% CI: 80.8 to 85.4%). In total, three patients (0.5%) died due to breast cancer. Conclusion Our results support the possibility to omit radiotherapy after breast-conserving surgery in a well-defined subgroup of women aged ≥ 65 years with low-risk, ER-positive, pT1N0 breast cancer receiving adjuvant endocrine therapy.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yara Abdou, William E Barlow, Julie R Gralow, Funda Meric-Bernstam, Kathy S Albain, Daniel F Hayes, Nancy U Lin, Edith A Perez, Lori J Goldstein, Stephen K L Chia, Sukhbinder Dhesy-Thind, Priya Rastogi, Emilio Alba, Suzette Delaloge, Anne F Schott, Steven Shak, Priyanka Sharma, Danika L Lew, Jieling Miao, Joseph M Unger, Debasish Tripathy, Gabriel N Hortobagyi, Lajos Pusztai, Kevin Kalinsky
Background The phase III RxPONDER trial has impacted treatment for node-positive(1-3), hormone receptor-positive, HER2-negative breast cancer with 21-gene recurrence score (RS) ≤ 25. We investigated how these findings apply to different racial and ethnic groups within the trial. Methods The trial randomized women to endocrine therapy (ET) or to chemotherapy plus ET. The primary clinical outcome was invasive disease-free survival (IDFS) with distant relapse-free survival (DRFS) as a secondary outcome. Multivariable Cox models were used to evaluate the association between race/ethnicity and survival outcomes, adjusting for clinicopathologic characteristics, RS, and treatment. Results A total of 4,048 women with self-reported race/ethnicity were included: Hispanic (15.1%), non-Hispanic Black (NHB)(6.1%), Native American/Pacific Islander (0.8%), Asian (8.0%), and non-Hispanic White (NHW)(70%). No differences in RS distribution, tumor size, or number of positive nodes were observed by race/ethnicity. Relative to NHWs, IDFS was worse for NHBs (5-year IDFS 91.6% vs 87.1%, HR = 1.37; 95% CI 1.03-1.81) and better for Asians (91.6% vs 93.9%, HR = 0.64; 95% CI 0.46-0.91). Relative to NHW, DRFS was worse for NHBs (5-year DRFS 95.8% vs 91.0%, HR = 1.65; 95% CI 1.17-2.32) and better for Asians (95.8% vs 96.7%, HR = 0.59; 95% CI 0.37-0.95). Adjusting for clinical characteristics, particularly body mass index, diminished the effect of race on outcomes. Chemotherapy treatment efficacy did not differ by race/ethnicity. Conclusions NHB women had worse clinical outcomes compared to NHWs in the RxPONDER trial despite similar RS and comparable treatment. Our study emphasizes the persistent racial disparities in breast cancer outcomes while highlighting complex interactions among contributing factors. Trial Registration ClinicalTrials.gov: NCT01272037
RxPONDER III期试验对淋巴结阳性（1-3）、激素受体阳性、her2阴性、21基因复发评分(RS)≤25的乳腺癌的治疗有影响。我们在试验中调查了这些发现如何适用于不同的种族和民族群体。方法将女性随机分为内分泌治疗组（ET）和化疗+ ET两组。主要临床结局为侵袭性无病生存期（IDFS），远端无复发生存期（DRFS）为次要结局。多变量Cox模型用于评估种族/民族与生存结果之间的关系，调整临床病理特征、RS和治疗。结果共纳入4,048名自我报告种族/民族的妇女：西班牙裔（15.1%）、非西班牙裔黑人（NHB）（6.1%）、美洲原住民/太平洋岛民（0.8%）、亚洲人（8.0%）和非西班牙裔白人（NHW）（70%）。RS分布、肿瘤大小或阳性淋巴结数量未见种族/民族差异。相对于非健康人群，非健康人群的IDFS更差(5年IDFS 91.6% vs 87.1%, HR = 1.37；95% CI 1.03-1.81)，亚洲人更好(91.6% vs 93.9%, HR = 0.64；95% ci 0.46-0.91)。相对于非健康人群，非健康人群的DRFS更差(5年DRFS 95.8% vs 91.0%, HR = 1.65；95% CI 1.17-2.32)，亚洲人更好(95.8% vs 96.7%, HR = 0.59；95% ci 0.37-0.95)。调整临床特征，特别是身体质量指数，减少了种族对结果的影响。化疗的疗效没有因种族而异。结论：在RxPONDER试验中，尽管RS和治疗方法相似，但与nhw相比，NHB女性的临床结果更差。我们的研究强调了乳腺癌结局中持续存在的种族差异，同时强调了影响因素之间复杂的相互作用。临床试验注册：NCT01272037
{"title":"Race and Clinical Outcomes in Hormone Receptor-Positive, HER2-Negative, Node-Positive Breast Cancer in the Randomized RxPONDER Trial","authors":"Yara Abdou, William E Barlow, Julie R Gralow, Funda Meric-Bernstam, Kathy S Albain, Daniel F Hayes, Nancy U Lin, Edith A Perez, Lori J Goldstein, Stephen K L Chia, Sukhbinder Dhesy-Thind, Priya Rastogi, Emilio Alba, Suzette Delaloge, Anne F Schott, Steven Shak, Priyanka Sharma, Danika L Lew, Jieling Miao, Joseph M Unger, Debasish Tripathy, Gabriel N Hortobagyi, Lajos Pusztai, Kevin Kalinsky","doi":"10.1093/jnci/djae314","DOIUrl":"https://doi.org/10.1093/jnci/djae314","url":null,"abstract":"Background The phase III RxPONDER trial has impacted treatment for node-positive(1-3), hormone receptor-positive, HER2-negative breast cancer with 21-gene recurrence score (RS) ≤ 25. We investigated how these findings apply to different racial and ethnic groups within the trial. Methods The trial randomized women to endocrine therapy (ET) or to chemotherapy plus ET. The primary clinical outcome was invasive disease-free survival (IDFS) with distant relapse-free survival (DRFS) as a secondary outcome. Multivariable Cox models were used to evaluate the association between race/ethnicity and survival outcomes, adjusting for clinicopathologic characteristics, RS, and treatment. Results A total of 4,048 women with self-reported race/ethnicity were included: Hispanic (15.1%), non-Hispanic Black (NHB)(6.1%), Native American/Pacific Islander (0.8%), Asian (8.0%), and non-Hispanic White (NHW)(70%). No differences in RS distribution, tumor size, or number of positive nodes were observed by race/ethnicity. Relative to NHWs, IDFS was worse for NHBs (5-year IDFS 91.6% vs 87.1%, HR = 1.37; 95% CI 1.03-1.81) and better for Asians (91.6% vs 93.9%, HR = 0.64; 95% CI 0.46-0.91). Relative to NHW, DRFS was worse for NHBs (5-year DRFS 95.8% vs 91.0%, HR = 1.65; 95% CI 1.17-2.32) and better for Asians (95.8% vs 96.7%, HR = 0.59; 95% CI 0.37-0.95). Adjusting for clinical characteristics, particularly body mass index, diminished the effect of race on outcomes. Chemotherapy treatment efficacy did not differ by race/ethnicity. Conclusions NHB women had worse clinical outcomes compared to NHWs in the RxPONDER trial despite similar RS and comparable treatment. Our study emphasizes the persistent racial disparities in breast cancer outcomes while highlighting complex interactions among contributing factors. Trial Registration ClinicalTrials.gov: NCT01272037","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nina N Sanford, Qian Shi, David M Hein, William A Hall
Background The National Clinical Trials Network (NCTN) is the largest government sponsored organization in the United States tasked with funding randomized controlled trials (RCTs) in oncology. It is unknown whether there are differences in study design by treatment modality. We evaluated differences in methodology between trials testing radiotherapy versus systemic therapy. Methods The Clinical Trials Support Unit website was used to identify active RCTs of systemic or radiotherapy across NCTN cooperative groups through December 31, 2023. Studies in disease sites with > 5 radiotherapy trials were included. Each trial’s protocol was reviewed to obtain key design information that were descriptively compared: primary endpoint, hypothesis testing type (superiority vs non-inferiority), non-inferiority margin, hypothesized effect size, power, and significance level. Results A total of 186 RCTs (142 systemic therapy, 44 radiotherapy) were examined. Comparing primary endpoints, 59.1% vs 26.8% of radiotherapy vs systemic therapy trials, respectively, had a primary endpoint of overall survival. Nearly 1/3 of radiotherapy trials (31.2%) were non-inferiority vs 6.3% of systemic therapy trials. Among breast cancer trials, 75% of radiotherapy studies were non-inferiority vs 11.1% systemic. Target effect size, power, and significance level were similar by treatment modality within tumor types and disease settings. Conclusion Among NCTN cooperative group RCTs, there were marked differences in study design between radiotherapy vs systemic therapy trials. A higher benchmark for defining success for radiotherapy interventions was observed with greater emphasis on overall survival as primary endpoint. This may reflect differences in therapeutic mechanism by modality and types of study questions posed.
{"title":"Benchmarks of Success in Radiotherapy versus Systemic Therapy National Clinical Trials Network (NCTN) Randomized Controlled Trials Sponsored by the National Cancer Institute (NCI)","authors":"Nina N Sanford, Qian Shi, David M Hein, William A Hall","doi":"10.1093/jnci/djae313","DOIUrl":"https://doi.org/10.1093/jnci/djae313","url":null,"abstract":"Background The National Clinical Trials Network (NCTN) is the largest government sponsored organization in the United States tasked with funding randomized controlled trials (RCTs) in oncology. It is unknown whether there are differences in study design by treatment modality. We evaluated differences in methodology between trials testing radiotherapy versus systemic therapy. Methods The Clinical Trials Support Unit website was used to identify active RCTs of systemic or radiotherapy across NCTN cooperative groups through December 31, 2023. Studies in disease sites with > 5 radiotherapy trials were included. Each trial’s protocol was reviewed to obtain key design information that were descriptively compared: primary endpoint, hypothesis testing type (superiority vs non-inferiority), non-inferiority margin, hypothesized effect size, power, and significance level. Results A total of 186 RCTs (142 systemic therapy, 44 radiotherapy) were examined. Comparing primary endpoints, 59.1% vs 26.8% of radiotherapy vs systemic therapy trials, respectively, had a primary endpoint of overall survival. Nearly 1/3 of radiotherapy trials (31.2%) were non-inferiority vs 6.3% of systemic therapy trials. Among breast cancer trials, 75% of radiotherapy studies were non-inferiority vs 11.1% systemic. Target effect size, power, and significance level were similar by treatment modality within tumor types and disease settings. Conclusion Among NCTN cooperative group RCTs, there were marked differences in study design between radiotherapy vs systemic therapy trials. A higher benchmark for defining success for radiotherapy interventions was observed with greater emphasis on overall survival as primary endpoint. This may reflect differences in therapeutic mechanism by modality and types of study questions posed.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"40 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yibai Zhao, Roman Gulati, Zhenwei Yang, Lisa Newcomb, Yingye Zheng, Kehao Zhu, Menghan Liu, Eveline A M Heijnsdijk, Michael C Haffner, Matthew Cooperberg, Scott E Eggener, Angelo M De Marzo, Adam S Kibel, Dimitris Rizopoulos, Ingrid J Hall, Ruth Etzioni
Background Implications of relabeling grade group (GG) 1 prostate cancer as non-cancer will depend on the recommended active surveillance (AS) strategy. Whether relabeling should prompt de-intensifying, PSA-based active monitoring approaches is unclear. We investigated outcomes of biopsy-based AS strategies vs PSA-based active monitoring for GG1 diagnoses under different patient adherence rates. Methods We analyzed longitudinal PSA levels and time to GG ≥ 2 reclassification among 850 patients diagnosed with GG1 disease from the Canary Prostate Active Surveillance Study (2008-2013). We then simulated 20,000 patients over 12 years, comparing GG ≥ 2 detection under biennial biopsy against three PSA-based strategies:(1) PSA: biopsy for PSA change ≥20%/year, (2) PSA+MRI: MRI for PSA change ≥20%/year and biopsy for PI-RADS ≥3, and (3) Predicted risk: biopsy for predicted upgrading risk ≥10%. Results Under biennial biopsies and 20% dropout to active treatment, 17% of patients had a > 2-year delay in GG ≥ 2 detection. The PSA strategy reduced biopsies by 39% but delayed detection in 32% of patients. The PSA+MRI strategy cut biopsies by 52%, with a 34% delay. The predicted risk strategy reduced biopsies by 31%, with only an 8% delay. These findings are robust to biopsy sensitivity and confirmatory biopsy. Conclusions PSA-based active monitoring could substantially reduce biopsy frequency; however, a precision strategy based on an individual upgrading risk is most likely to minimize delays in disease progression detection. This strategy may be preferred if AS is deintensified under relabeling, provided patient adherence remains unaffected.
{"title":"Projected Outcomes of Reduced-Biopsy Management of Grade Group 1 Prostate Cancer: Implications for Relabeling","authors":"Yibai Zhao, Roman Gulati, Zhenwei Yang, Lisa Newcomb, Yingye Zheng, Kehao Zhu, Menghan Liu, Eveline A M Heijnsdijk, Michael C Haffner, Matthew Cooperberg, Scott E Eggener, Angelo M De Marzo, Adam S Kibel, Dimitris Rizopoulos, Ingrid J Hall, Ruth Etzioni","doi":"10.1093/jnci/djae296","DOIUrl":"https://doi.org/10.1093/jnci/djae296","url":null,"abstract":"Background Implications of relabeling grade group (GG) 1 prostate cancer as non-cancer will depend on the recommended active surveillance (AS) strategy. Whether relabeling should prompt de-intensifying, PSA-based active monitoring approaches is unclear. We investigated outcomes of biopsy-based AS strategies vs PSA-based active monitoring for GG1 diagnoses under different patient adherence rates. Methods We analyzed longitudinal PSA levels and time to GG ≥ 2 reclassification among 850 patients diagnosed with GG1 disease from the Canary Prostate Active Surveillance Study (2008-2013). We then simulated 20,000 patients over 12 years, comparing GG ≥ 2 detection under biennial biopsy against three PSA-based strategies:(1) PSA: biopsy for PSA change ≥20%/year, (2) PSA+MRI: MRI for PSA change ≥20%/year and biopsy for PI-RADS ≥3, and (3) Predicted risk: biopsy for predicted upgrading risk ≥10%. Results Under biennial biopsies and 20% dropout to active treatment, 17% of patients had a > 2-year delay in GG ≥ 2 detection. The PSA strategy reduced biopsies by 39% but delayed detection in 32% of patients. The PSA+MRI strategy cut biopsies by 52%, with a 34% delay. The predicted risk strategy reduced biopsies by 31%, with only an 8% delay. These findings are robust to biopsy sensitivity and confirmatory biopsy. Conclusions PSA-based active monitoring could substantially reduce biopsy frequency; however, a precision strategy based on an individual upgrading risk is most likely to minimize delays in disease progression detection. This strategy may be preferred if AS is deintensified under relabeling, provided patient adherence remains unaffected.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"170 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142678561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Andrea Romanos-Nanclares, Walter C Willett, Bernard Rosner, Daniel G Stover, Sagar D Sardesai, Michelle D Holmes, Wendy Y Chen, Rulla M Tamimi, Fred K Tabung, A Heather Eliassen
Background Dietary patterns promoting chronic inflammation, including the empirical dietary inflammatory pattern (EDIP), have been associated with certain cancers. Investigating whether this dietary pattern is associated with breast cancer—where the role of inflammation is less well-defined—could provide valuable insights and potentially improve strategies for preventing this cancer. Methods We prospectively followed 76,386 women from Nurses’ Health Study (NHS, 1984-2018) and 92,886 women from Nurses’ Health Study II (NHSII, 1991-2019). Diet was assessed by food frequency questionnaires (FFQs) every 4 years, starting at baseline. The inflammatory potential of diet was evaluated using the validated EDIP based on plasma CRP, IL-6, and TNFα-R2. Higher scores indicate higher dietary inflammatory potential. Hazard ratios and 95%CIs of overall and subtypes of breast cancer were estimated using multivariable-adjusted Cox regression models. Results During 4,490,842 person-years of follow-up, we documented 11,026 breast cancer cases. Women in the highest, compared with the lowest, EDIP quintile were at higher breast cancer risk (HRQ5vs.Q1=1.12; 95% CI, 1.05, 1.19; P-trend<0.001). The association was stronger for ER-negative tumors (HRQ5vs.Q1=1.29; 95% CI, 1.09, 1.53; P-trend=0.003). Also, we observed that the association of EDIP with breast cancer risk differed by molecular subtype, with the strongest association observed with basal-like tumors (HRQ5vs.Q1=1.80; 95% CI, 1.20, 2.71; P-trend=0.004). Conclusions Higher EDIP scores were associated with a modestly increased risk of breast cancer, which was more pronounced for ER-negative and basal-like breast tumors. These results support the hypothesis that diet-related inflammation plays a role in breast cancer etiology, particularly tumors lacking hormone receptors.
{"title":"Proinflammatory Dietary Pattern and Risk of Total and Subtypes of Breast Cancer Among U.S. Women","authors":"Andrea Romanos-Nanclares, Walter C Willett, Bernard Rosner, Daniel G Stover, Sagar D Sardesai, Michelle D Holmes, Wendy Y Chen, Rulla M Tamimi, Fred K Tabung, A Heather Eliassen","doi":"10.1093/jnci/djae301","DOIUrl":"https://doi.org/10.1093/jnci/djae301","url":null,"abstract":"Background Dietary patterns promoting chronic inflammation, including the empirical dietary inflammatory pattern (EDIP), have been associated with certain cancers. Investigating whether this dietary pattern is associated with breast cancer—where the role of inflammation is less well-defined—could provide valuable insights and potentially improve strategies for preventing this cancer. Methods We prospectively followed 76,386 women from Nurses’ Health Study (NHS, 1984-2018) and 92,886 women from Nurses’ Health Study II (NHSII, 1991-2019). Diet was assessed by food frequency questionnaires (FFQs) every 4 years, starting at baseline. The inflammatory potential of diet was evaluated using the validated EDIP based on plasma CRP, IL-6, and TNFα-R2. Higher scores indicate higher dietary inflammatory potential. Hazard ratios and 95%CIs of overall and subtypes of breast cancer were estimated using multivariable-adjusted Cox regression models. Results During 4,490,842 person-years of follow-up, we documented 11,026 breast cancer cases. Women in the highest, compared with the lowest, EDIP quintile were at higher breast cancer risk (HRQ5vs.Q1=1.12; 95% CI, 1.05, 1.19; P-trend&lt;0.001). The association was stronger for ER-negative tumors (HRQ5vs.Q1=1.29; 95% CI, 1.09, 1.53; P-trend=0.003). Also, we observed that the association of EDIP with breast cancer risk differed by molecular subtype, with the strongest association observed with basal-like tumors (HRQ5vs.Q1=1.80; 95% CI, 1.20, 2.71; P-trend=0.004). Conclusions Higher EDIP scores were associated with a modestly increased risk of breast cancer, which was more pronounced for ER-negative and basal-like breast tumors. These results support the hypothesis that diet-related inflammation plays a role in breast cancer etiology, particularly tumors lacking hormone receptors.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142678563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Megan Othus, Sandip P Patel, Young Kwang Chae, Eliana Dietrich, Howard Streicher, Elad Sharon, Razelle Kurzrock
Background Associations between immune-related adverse events (irAEs) from checkpoint inhibitor therapy and outcomes have been previously evaluated, with most prior research finding a positive association between toxicity and survival. This prior research has generally reported on more common tumor types. We use a unique data resource of a federally-funded basket trial ((NCT02834013) for patients with rare cancers (N = 684) to evaluate associations between irAEs and overall survival and progression-free survival. Methods Patients were treated with nivolumab and ipilimumab; the trial was opened at > 1000 sites. Landmark Cox regression models were used to assess first cycle irAE associations with progression-free and overall survival. Results We found that grade 1-2 treatment-related irAEs in the first cycle of therapy were associated with longer overall survival (OS) (multivariable hazard ratio, 95% confidence interval, p-value: 0.61, 0.49-0.75, p < .001) compared to no treatment-related irAE, while grade 3-4 irAEs were associated with shorter OS (HR = 1.41, 95% CI = 1.04-1.90, p = .025). Similar, but weaker, associations were observed with progression-free survival (PFS) and grade 1-2 treatment-related irAEs: HR = 0.83, 95% CI = 0.67-1.01, p = .067 and grade 3-4: HR = 1.35, 95% CI = 1.02-1.78, p = .037 compared to no treatment-related irAEs. Grade 1-2 dermatologic toxicity was associated with improved OS compared to other grade 1-2 toxicities (HR = 0.67, 95% CI = 0.52-0.85, p = .002). There was no significant OS difference between patients with Grade 1-2 fatigue, gastrointestinal, metabolic, hepatic, endocrine, and thyroid toxicities vs other Grade 1-2 toxicities. Conclusions In this large cohort of patients with rare tumors receiving checkpoint inhibitor therapy, grade of irAE in the first cycle was predictive for survival.
{"title":"First Cycle Toxicity and Survival in Patients with Rare Cancers Treated with Checkpoint Inhibitors","authors":"Megan Othus, Sandip P Patel, Young Kwang Chae, Eliana Dietrich, Howard Streicher, Elad Sharon, Razelle Kurzrock","doi":"10.1093/jnci/djae297","DOIUrl":"https://doi.org/10.1093/jnci/djae297","url":null,"abstract":"Background Associations between immune-related adverse events (irAEs) from checkpoint inhibitor therapy and outcomes have been previously evaluated, with most prior research finding a positive association between toxicity and survival. This prior research has generally reported on more common tumor types. We use a unique data resource of a federally-funded basket trial ((NCT02834013) for patients with rare cancers (N = 684) to evaluate associations between irAEs and overall survival and progression-free survival. Methods Patients were treated with nivolumab and ipilimumab; the trial was opened at &gt; 1000 sites. Landmark Cox regression models were used to assess first cycle irAE associations with progression-free and overall survival. Results We found that grade 1-2 treatment-related irAEs in the first cycle of therapy were associated with longer overall survival (OS) (multivariable hazard ratio, 95% confidence interval, p-value: 0.61, 0.49-0.75, p &lt; .001) compared to no treatment-related irAE, while grade 3-4 irAEs were associated with shorter OS (HR = 1.41, 95% CI = 1.04-1.90, p = .025). Similar, but weaker, associations were observed with progression-free survival (PFS) and grade 1-2 treatment-related irAEs: HR = 0.83, 95% CI = 0.67-1.01, p = .067 and grade 3-4: HR = 1.35, 95% CI = 1.02-1.78, p = .037 compared to no treatment-related irAEs. Grade 1-2 dermatologic toxicity was associated with improved OS compared to other grade 1-2 toxicities (HR = 0.67, 95% CI = 0.52-0.85, p = .002). There was no significant OS difference between patients with Grade 1-2 fatigue, gastrointestinal, metabolic, hepatic, endocrine, and thyroid toxicities vs other Grade 1-2 toxicities. Conclusions In this large cohort of patients with rare tumors receiving checkpoint inhibitor therapy, grade of irAE in the first cycle was predictive for survival.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"77 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142678558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Noah Hammarlund, Sarah K Holt, Ruth Etzioni, Danté Morehead, Jenney R Lee, Erika M Wolff, Yohali Burrola-Mendez, Liz Sage, John L Gore, Yaw A Nyame
Black individuals are less likely to be treated for prostate cancer even though they are more than twice as likely to die compared to White individuals. The complex causes of these inequities are influenced by social and structural factors, including racism, which contribute to the differential delivery of care. This study investigates how factors related to the location of where individuals live and receive care affect treatment inequities for prostate cancer between Black and White individuals. We hypothesize that both location and race independently influence treatment inequities. We used data from the Surveillance, Epidemiology, and End Results (SEER) cancer registry linked to Medicare claims to estimate the treatment inequity, as defined by differences in radiation or radical prostatectomy. Fixed effects at the physician, hospital, and patient ZIP code levels were incorporated to adjust for all time-invariant factors at these levels. The results indicate that residential location-related factors explain only half of the treatment inequity, while provider- and hospital-level factors do not significantly account for disparities. Even after accounting for all time-invariant factors, significant differences in treatment rates persist. The study highlights the importance of understanding race as a social construct and racism as a systemic and structural phenomenon in addressing treatment inequities. These findings provide a necessary step toward understanding equitable care and designing interventions to solve this inequity.
{"title":"The Association of Where Patients with Prostate Cancer Live and Receive Care on Racial Treatment Inequities","authors":"Noah Hammarlund, Sarah K Holt, Ruth Etzioni, Danté Morehead, Jenney R Lee, Erika M Wolff, Yohali Burrola-Mendez, Liz Sage, John L Gore, Yaw A Nyame","doi":"10.1093/jnci/djae302","DOIUrl":"https://doi.org/10.1093/jnci/djae302","url":null,"abstract":"Black individuals are less likely to be treated for prostate cancer even though they are more than twice as likely to die compared to White individuals. The complex causes of these inequities are influenced by social and structural factors, including racism, which contribute to the differential delivery of care. This study investigates how factors related to the location of where individuals live and receive care affect treatment inequities for prostate cancer between Black and White individuals. We hypothesize that both location and race independently influence treatment inequities. We used data from the Surveillance, Epidemiology, and End Results (SEER) cancer registry linked to Medicare claims to estimate the treatment inequity, as defined by differences in radiation or radical prostatectomy. Fixed effects at the physician, hospital, and patient ZIP code levels were incorporated to adjust for all time-invariant factors at these levels. The results indicate that residential location-related factors explain only half of the treatment inequity, while provider- and hospital-level factors do not significantly account for disparities. Even after accounting for all time-invariant factors, significant differences in treatment rates persist. The study highlights the importance of understanding race as a social construct and racism as a systemic and structural phenomenon in addressing treatment inequities. These findings provide a necessary step toward understanding equitable care and designing interventions to solve this inequity.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"57 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142678560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Scarlett Lin Gomez, Mindy DeRouen, Moon S Chen, Heather Wakelee, Jeffrey B Velotta, Lori C Sakoda, Salma Shariff-Marco, Peggy Reynolds, Iona Cheng
Lung cancer is a leading cause of cancer mortality for most ethnic groups of Asian American females, including Chinese, Korean, Japanese, and Vietnamese Americans, a striking pattern given the exceedingly low prevalence of smoking among Asian American females in the general population. Recent research demonstrates that among Asian American females diagnosed with lung cancer, the vast majority of patients have never smoked, as high as > 80% among Chinese and Asian Indian American females. Despite declining rates in lung cancer overall in the United States, rates among Asian American females who have never smoked appear to be increasing. This Commentary articulates extant knowledge, based on studies in Asia, of a range of risk factors such as a family history of lung cancer, history of lung diseases including tuberculosis and chronic obstructive pulmonary diseases, exposure to cooking fumes and second-hand smoke, and various putative risk factors. Unique mutational profiles at the tumor level, including higher prevalence of EGFR mutations among Asian populations, highlight the importance of tumor genomic testing of newly-diagnosed patients. Additional research is essential, given the high burden of disease among Asian American females who have never smoked, and limited knowledge regarding contributing risk factors specific to Asian American females, as the risk factors identified in Asians living in Asia may not apply.
{"title":"Elevated risk of lung cancer among asian American females who have never smoked: an emerging cancer disparity","authors":"Scarlett Lin Gomez, Mindy DeRouen, Moon S Chen, Heather Wakelee, Jeffrey B Velotta, Lori C Sakoda, Salma Shariff-Marco, Peggy Reynolds, Iona Cheng","doi":"10.1093/jnci/djae299","DOIUrl":"https://doi.org/10.1093/jnci/djae299","url":null,"abstract":"Lung cancer is a leading cause of cancer mortality for most ethnic groups of Asian American females, including Chinese, Korean, Japanese, and Vietnamese Americans, a striking pattern given the exceedingly low prevalence of smoking among Asian American females in the general population. Recent research demonstrates that among Asian American females diagnosed with lung cancer, the vast majority of patients have never smoked, as high as &gt; 80% among Chinese and Asian Indian American females. Despite declining rates in lung cancer overall in the United States, rates among Asian American females who have never smoked appear to be increasing. This Commentary articulates extant knowledge, based on studies in Asia, of a range of risk factors such as a family history of lung cancer, history of lung diseases including tuberculosis and chronic obstructive pulmonary diseases, exposure to cooking fumes and second-hand smoke, and various putative risk factors. Unique mutational profiles at the tumor level, including higher prevalence of EGFR mutations among Asian populations, highlight the importance of tumor genomic testing of newly-diagnosed patients. Additional research is essential, given the high burden of disease among Asian American females who have never smoked, and limited knowledge regarding contributing risk factors specific to Asian American females, as the risk factors identified in Asians living in Asia may not apply.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"23 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142678557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tyler G Erath, Fang Fang Chen, Michael DeSarno, Derek Devine, Adam M Leventhal, Warren K Bickel, Stephen T Higgins
Background Understanding disparities in adolescent cigarette smoking is important for effective prevention. Methods We investigated disparities in adolescent smoking based on cumulative reported psychosocial/health risk among respondents ages 12-17 years in the US National Survey of Drug Use and Health from 2002 to 2019. Multivariable regression estimated associations of cumulative risk, survey years, and their interaction predicting past-month and daily smoking. Eleven psychosocial/health variables associated with youth smoking formed composite measures of cumulative risk, categorizing risk as Low (0-2), Moderate (3-4), or High (5+). The main outcomes were weighted past-month and daily smoking by cumulative risk and time, examining prevalence and proportional change across years. Results Among 244,519 adolescents, greater cumulative risk predicted higher smoking prevalence across all outcomes. Compared to the Low-risk category, past-month smoking odds (adjusted odds ratio, 95%CI) were 9.14 (8.58-9.72) and 46.15 (43.38-49.10) times greater in the Moderate- and High-risk categories. For daily smoking, odds were 14.11 (11.92-16.70) and 97.32 (83.06-114.03) times greater among the Moderate- and High-risk categories. Regarding proportional change, the Low-risk category exhibited the steepest decline in past-month smoking from 2002-2003 to 2018-2019 (-85.1%), followed by the Moderate- (-79.2%) and High-risk (-65.7%) categories. Daily smoking declined more steeply among the Low- (-96.5%) and Moderate- (-90.5%) than High-risk category (-86.4%). Conclusions Cumulative risk is a robust predictor of adolescent smoking. While record-setting reductions in adolescent smoking extend across risk categories, disparities favoring youth with fewer risks are evident throughout. Recognizing cumulative risk can inform the development of more targeted and effective prevention efforts.
{"title":"Cumulative Psychosocial and Health Disparities in US Adolescent Cigarette Smoking, 2002 to 2019","authors":"Tyler G Erath, Fang Fang Chen, Michael DeSarno, Derek Devine, Adam M Leventhal, Warren K Bickel, Stephen T Higgins","doi":"10.1093/jnci/djae286","DOIUrl":"https://doi.org/10.1093/jnci/djae286","url":null,"abstract":"Background Understanding disparities in adolescent cigarette smoking is important for effective prevention. Methods We investigated disparities in adolescent smoking based on cumulative reported psychosocial/health risk among respondents ages 12-17 years in the US National Survey of Drug Use and Health from 2002 to 2019. Multivariable regression estimated associations of cumulative risk, survey years, and their interaction predicting past-month and daily smoking. Eleven psychosocial/health variables associated with youth smoking formed composite measures of cumulative risk, categorizing risk as Low (0-2), Moderate (3-4), or High (5+). The main outcomes were weighted past-month and daily smoking by cumulative risk and time, examining prevalence and proportional change across years. Results Among 244,519 adolescents, greater cumulative risk predicted higher smoking prevalence across all outcomes. Compared to the Low-risk category, past-month smoking odds (adjusted odds ratio, 95%CI) were 9.14 (8.58-9.72) and 46.15 (43.38-49.10) times greater in the Moderate- and High-risk categories. For daily smoking, odds were 14.11 (11.92-16.70) and 97.32 (83.06-114.03) times greater among the Moderate- and High-risk categories. Regarding proportional change, the Low-risk category exhibited the steepest decline in past-month smoking from 2002-2003 to 2018-2019 (-85.1%), followed by the Moderate- (-79.2%) and High-risk (-65.7%) categories. Daily smoking declined more steeply among the Low- (-96.5%) and Moderate- (-90.5%) than High-risk category (-86.4%). Conclusions Cumulative risk is a robust predictor of adolescent smoking. While record-setting reductions in adolescent smoking extend across risk categories, disparities favoring youth with fewer risks are evident throughout. Recognizing cumulative risk can inform the development of more targeted and effective prevention efforts.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"69 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Selin Bicer, Angela Nelson, Katerina Carayannis, Jonathan Kimmelman
Background Phase 2 trials are instrumental for designing definitive efficacy trials or attaining accelerated approval. However, high attrition of drug candidates in phase 2 raises questions about their supporting evidence. Methods We developed a typology of supporting evidence for phase 2 cancer trials. We also devised a scheme for capturing elements that enable an assessment of the strength of such evidence. Using this framework, we content analyzed supporting evidence provided in protocols of 50 randomly sampled phase 2 cancer monotherapy trials starting between January 2014 and January 2019, available on ClinicalTrials.gov. Results Of the 50 protocols in our sample, 52% were industry funded. Most invoked supporting evidence deriving from trials against different cancers (n = 28, 56%) or preclinical studies (n = 48, 96%), but not from clinical studies involving the target drug-indication pairing (n = 23, 46%). When presenting evidence from models, only one protocol (2%) explained their translational relevance. Instead, protocols implied translatability by describing molecular (86%) and pathophysiological (84%) processes shared by model and target systems. Protocols often provided information for assessing the magnitude, precision and risk of bias for supporting trials (n = 43, 93%, 91%, 47%, respectively). However, such information was often unavailable for preclinical studies (n = 49, 53%, 22%, 59%). Conclusion Supporting evidence is key to justifying the commitment of scientific resources and patients to a clinical hypothesis. Protocols often omit elements that would enable critical assessment of supporting evidence for phase 2 monotherapy cancer trials. These gaps suggest the promise of more structured approaches for presenting supporting evidence.
{"title":"Supporting Evidence in Phase 2 Cancer Trial Protocols: A Content Analysis","authors":"Selin Bicer, Angela Nelson, Katerina Carayannis, Jonathan Kimmelman","doi":"10.1093/jnci/djae281","DOIUrl":"https://doi.org/10.1093/jnci/djae281","url":null,"abstract":"Background Phase 2 trials are instrumental for designing definitive efficacy trials or attaining accelerated approval. However, high attrition of drug candidates in phase 2 raises questions about their supporting evidence. Methods We developed a typology of supporting evidence for phase 2 cancer trials. We also devised a scheme for capturing elements that enable an assessment of the strength of such evidence. Using this framework, we content analyzed supporting evidence provided in protocols of 50 randomly sampled phase 2 cancer monotherapy trials starting between January 2014 and January 2019, available on ClinicalTrials.gov. Results Of the 50 protocols in our sample, 52% were industry funded. Most invoked supporting evidence deriving from trials against different cancers (n = 28, 56%) or preclinical studies (n = 48, 96%), but not from clinical studies involving the target drug-indication pairing (n = 23, 46%). When presenting evidence from models, only one protocol (2%) explained their translational relevance. Instead, protocols implied translatability by describing molecular (86%) and pathophysiological (84%) processes shared by model and target systems. Protocols often provided information for assessing the magnitude, precision and risk of bias for supporting trials (n = 43, 93%, 91%, 47%, respectively). However, such information was often unavailable for preclinical studies (n = 49, 53%, 22%, 59%). Conclusion Supporting evidence is key to justifying the commitment of scientific resources and patients to a clinical hypothesis. Protocols often omit elements that would enable critical assessment of supporting evidence for phase 2 monotherapy cancer trials. These gaps suggest the promise of more structured approaches for presenting supporting evidence.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"41 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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