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}
Background Establishing whether women with major depressive disorder (MDD) who develop breast cancer (BC) have poor outcomes is key to optimizing care for this population. To address this, we examined associations between MDD and BC recurrence and mortality. Methods Using medical record data from the Veterans Affairs Healthcare System, we established a retrospective cohort of women with local or regional stage invasive BC between 2010 and 2019 and followed through 2022. We used a two-year window to identify women diagnosed with MDD prior to BC diagnosis. We used multivariable Cox-proportional hazards regression to estimate associations between MDD and BC recurrence and mortality while accounting for competing-risks and adjusting for sociodemographic, clinical, lifestyle, and tumor characteristics. Results We identified 6,051 women with BC, of whom 1,754 (29%) had MDD. The mean age at BC diagnosis was 57 years (standard deviation = 11). In multivariable analyses, women with MDD had a 37% (hazard ratio (HR)=1.37; 95% confidence interval (CI): 1.19-1.57) higher risk of recurrence and a 30% (HR = 1.30; 95% CI: 1.02-1.64) higher risk of BC mortality. The association between MDD and recurrence was stronger among women with estrogen receptor-positive BC. In secondary analyses, there were significant interactions between MDD and multiple exposures with respect to recurrence, including current smoking, substance abuse, and non-receipt of screening mammography. Conclusions Women with MDD had inferior BC outcomes compared to women without a history of MDD. Research is needed to investigate underlying mechanisms linking depression to BC progression and evaluate interventions to improve outcomes in this high-risk population.
{"title":"Impact of major depressive disorder on breast cancer outcomes: a national retrospective cohort study","authors":"Maya Aboumrad, Corinne Joshu, Kala Visvanathan","doi":"10.1093/jnci/djae287","DOIUrl":"https://doi.org/10.1093/jnci/djae287","url":null,"abstract":"Background Establishing whether women with major depressive disorder (MDD) who develop breast cancer (BC) have poor outcomes is key to optimizing care for this population. To address this, we examined associations between MDD and BC recurrence and mortality. Methods Using medical record data from the Veterans Affairs Healthcare System, we established a retrospective cohort of women with local or regional stage invasive BC between 2010 and 2019 and followed through 2022. We used a two-year window to identify women diagnosed with MDD prior to BC diagnosis. We used multivariable Cox-proportional hazards regression to estimate associations between MDD and BC recurrence and mortality while accounting for competing-risks and adjusting for sociodemographic, clinical, lifestyle, and tumor characteristics. Results We identified 6,051 women with BC, of whom 1,754 (29%) had MDD. The mean age at BC diagnosis was 57 years (standard deviation = 11). In multivariable analyses, women with MDD had a 37% (hazard ratio (HR)=1.37; 95% confidence interval (CI): 1.19-1.57) higher risk of recurrence and a 30% (HR = 1.30; 95% CI: 1.02-1.64) higher risk of BC mortality. The association between MDD and recurrence was stronger among women with estrogen receptor-positive BC. In secondary analyses, there were significant interactions between MDD and multiple exposures with respect to recurrence, including current smoking, substance abuse, and non-receipt of screening mammography. Conclusions Women with MDD had inferior BC outcomes compared to women without a history of MDD. Research is needed to investigate underlying mechanisms linking depression to BC progression and evaluate interventions to improve outcomes in this high-risk population.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"600 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601146","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}
Arianis Tatiana Ramírez, David Mesher, Armando Baena, Yuli Salgado, Elena Kasamatsu, Carmen Cristaldo, Rodrigo Álvarez, Freddy David Rojas, Katherine Ramírez, Julieta Guyot, Odessa Henríquez, Hans González Palma, Bettsy Flores, Jhaquelin Peñaranda, María José Vero, Isabel Robinson, Mary Luz Rol, Guillermo Rodríguez, Carolina Terán, Annabelle Ferrera, María Alejandra Picconi, Alejandro Calderon, Laura Mendoza, Carolina Wiesner, Maribel Almonte, Rolando Herrero
Background Cervical cytology is recommended by WHO as a triage option in HPV-based cervical cancer screening programmes. We assessed the performance of cytology to detect CIN3+ without and with knowledge of HPV positivity. Methods Women were screened with cytology and HPV across ESTAMPA study centres in Latin America. Screen-positives were referred to colposcopy with biopsy and treatment as needed. Cytology was initially interpreted without knowing HPV results. A subset of cytologies from HPV-positive women were re-interpreted at the same laboratories, with knowledge of HPV status, blinded to previous cytology and histological diagnosis. Performance indicators for cytology to detect CIN3+ without and with knowledge of HPV positivity were estimated. Findings A total of 4,087 women were included, of which 490 had histologically confirmed CIN3 + (455 CIN3 and 35 cancers). Cytology sensitivity without knowledge of HPV positivity for CIN3+ was 47.2% (95% CI: 42.5-51.9), whereas with knowledge of HPV positivity, the sensitivity was higher (58.9%, 95% CI: 54.2-63.5), p < .0001. The specificity without knowledge of HPV was 89.4% (95% CI: 88.2-90.5), while with knowledge of HPV positivity was 78.9% (95% CI: 77.4-80.4), p < .0001. Performance estimates varied by study centre for cytology without knowing the HPV positivity, (range from 32.8% to 61.5% for sensitivity; range 80.7% to 98.6% for specificity). Similarly, performance varied with knowledge of HPV positivity (36.1% to 93.4% for sensitivity; 39.6% to 98.6% for specificity). Conclusion The increase in sensitivity of cytology with HPV knowledge was limited and highly variable, reinforcing the need for alternative triage methods to support cervical cancer elimination goals.
{"title":"Impact of knowledge of HPV positivity on cervical cytology performance in latin america","authors":"Arianis Tatiana Ramírez, David Mesher, Armando Baena, Yuli Salgado, Elena Kasamatsu, Carmen Cristaldo, Rodrigo Álvarez, Freddy David Rojas, Katherine Ramírez, Julieta Guyot, Odessa Henríquez, Hans González Palma, Bettsy Flores, Jhaquelin Peñaranda, María José Vero, Isabel Robinson, Mary Luz Rol, Guillermo Rodríguez, Carolina Terán, Annabelle Ferrera, María Alejandra Picconi, Alejandro Calderon, Laura Mendoza, Carolina Wiesner, Maribel Almonte, Rolando Herrero","doi":"10.1093/jnci/djae283","DOIUrl":"https://doi.org/10.1093/jnci/djae283","url":null,"abstract":"Background Cervical cytology is recommended by WHO as a triage option in HPV-based cervical cancer screening programmes. We assessed the performance of cytology to detect CIN3+ without and with knowledge of HPV positivity. Methods Women were screened with cytology and HPV across ESTAMPA study centres in Latin America. Screen-positives were referred to colposcopy with biopsy and treatment as needed. Cytology was initially interpreted without knowing HPV results. A subset of cytologies from HPV-positive women were re-interpreted at the same laboratories, with knowledge of HPV status, blinded to previous cytology and histological diagnosis. Performance indicators for cytology to detect CIN3+ without and with knowledge of HPV positivity were estimated. Findings A total of 4,087 women were included, of which 490 had histologically confirmed CIN3 + (455 CIN3 and 35 cancers). Cytology sensitivity without knowledge of HPV positivity for CIN3+ was 47.2% (95% CI: 42.5-51.9), whereas with knowledge of HPV positivity, the sensitivity was higher (58.9%, 95% CI: 54.2-63.5), p &lt; .0001. The specificity without knowledge of HPV was 89.4% (95% CI: 88.2-90.5), while with knowledge of HPV positivity was 78.9% (95% CI: 77.4-80.4), p &lt; .0001. Performance estimates varied by study centre for cytology without knowing the HPV positivity, (range from 32.8% to 61.5% for sensitivity; range 80.7% to 98.6% for specificity). Similarly, performance varied with knowledge of HPV positivity (36.1% to 93.4% for sensitivity; 39.6% to 98.6% for specificity). Conclusion The increase in sensitivity of cytology with HPV knowledge was limited and highly variable, reinforcing the need for alternative triage methods to support cervical cancer elimination goals.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"72 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601392","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}
Mattias Hammarström, Marike Gabrielson, Jenny Bergqvist, Cecilia Lundholm, Alessio Crippa, Magnus Bäcklund, Yvonne Wengström, Signe Borgquist, Erik Eliasson, Mikael Eriksson, José Tapia, Kamila Czene, Per Hall
Purpose Monitoring metabolites of tamoxifen, such as endoxifen, has been suggested as a strategy to ascertain therapeutic effect of tamoxifen therapy but clinical guidelines are missing. Herein we aim to investigate the outcome of endoxifen concentrations of low dose tamoxifen, using change in mammographic breast density (MBD) as a proxy for therapy response. Material and Methods In the randomized KARISMA trial, including five doses of tamoxifen, measurements of plasma endoxifen concentrations, determination of CYP2D6 metabolizer status and MBD change over the trial period, were carried out. Association between endoxifen concentrations and relative MBD change after 6 months treatment was analysed using linear regression in a spline model. Results A total of 824 women (335 premenopausal, 489 postmenopausal) were included. In analyses of premenopausal women, a spline model described a MBD decrease, equivalent to the mean (-18.5%) seen in women exposed to 20 mg tamoxifen, at endoxifen concentrations of 2–3 ng/mL. The MBD decrease reached a nadir at endoxifen levels of 3 ng/mL and did not decrease further at higher endoxifen concentrations. Most intermediate and normal tamoxifen-metabolizers (≈ 90% of all participants) reached an endoxifen concentration of > 2 ng/mL at tamoxifen doses of 5 and 10 mg. No MBD decrease was seen in the postmenopausal group. Conclusion We have identified a possible window of effect on MBD at endoxifen concentrations of 2–3 ng/mL in premenopausal women, which corresponds to the doses of 5 and 10 mg tamoxifen. Since MBD change was used as a surrogate marker for therapy response, results should be confirmed using clinically established outcomes measures. Trial Registration ClinicalTrials.gov ID: NCT03346200
{"title":"Influence of endoxifen on mammographic density—results from the KARISMA trial","authors":"Mattias Hammarström, Marike Gabrielson, Jenny Bergqvist, Cecilia Lundholm, Alessio Crippa, Magnus Bäcklund, Yvonne Wengström, Signe Borgquist, Erik Eliasson, Mikael Eriksson, José Tapia, Kamila Czene, Per Hall","doi":"10.1093/jnci/djae280","DOIUrl":"https://doi.org/10.1093/jnci/djae280","url":null,"abstract":"Purpose Monitoring metabolites of tamoxifen, such as endoxifen, has been suggested as a strategy to ascertain therapeutic effect of tamoxifen therapy but clinical guidelines are missing. Herein we aim to investigate the outcome of endoxifen concentrations of low dose tamoxifen, using change in mammographic breast density (MBD) as a proxy for therapy response. Material and Methods In the randomized KARISMA trial, including five doses of tamoxifen, measurements of plasma endoxifen concentrations, determination of CYP2D6 metabolizer status and MBD change over the trial period, were carried out. Association between endoxifen concentrations and relative MBD change after 6 months treatment was analysed using linear regression in a spline model. Results A total of 824 women (335 premenopausal, 489 postmenopausal) were included. In analyses of premenopausal women, a spline model described a MBD decrease, equivalent to the mean (-18.5%) seen in women exposed to 20 mg tamoxifen, at endoxifen concentrations of 2–3 ng/mL. The MBD decrease reached a nadir at endoxifen levels of 3 ng/mL and did not decrease further at higher endoxifen concentrations. Most intermediate and normal tamoxifen-metabolizers (≈ 90% of all participants) reached an endoxifen concentration of &gt; 2 ng/mL at tamoxifen doses of 5 and 10 mg. No MBD decrease was seen in the postmenopausal group. Conclusion We have identified a possible window of effect on MBD at endoxifen concentrations of 2–3 ng/mL in premenopausal women, which corresponds to the doses of 5 and 10 mg tamoxifen. Since MBD change was used as a surrogate marker for therapy response, results should be confirmed using clinically established outcomes measures. Trial Registration ClinicalTrials.gov ID: NCT03346200","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"70 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142597283","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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