Marissa M Shams-White, Audrey A Goldbaum, Tanya Agurs-Collins, Susan Czajkowski, Kirsten A Herrick, Linda Nebeling, Jill Reedy, Gabriela Riscuta, Sharon Ross, Edward R Sauter
Time-restricted eating (TRE) is a type of intermittent fasting (IF). Food can be consumed as desired during the eating period, but not during the remainder of the day. Studies suggest that many of the health benefits of fasting may not simply be the result of weight loss, but also due to the body’s responses to the fasting that lead to improved metabolic functioning. While animal studies are convincing regarding the benefits of time restricted feeding, human (TRE) studies are less consistent and generally short term (< 1 year). In 2020, the National Cancer Institute (NCI) funded five IF studies, four of which focused on TRE, which addressed the question “How does intermittent fasting affect cancer incidence, treatment response, or outcome?” NCI sponsored a webinar in 2023 featuring investigators of the funded studies in which they discussed challenges as well as their thoughts regarding the most important TRE topics that should be addressed going forward. Six areas were identified, which are discussed below as well as in a recently published NOT-CA-24-073: Factors impacting how Time-Restricted Eating (TRE) influences cancer-related outcomes. Moving the science forward will allow the scientific community to better understand TRE’s potential. This potential includes the development of targeted TRE interventions to optimize long-term adherence to the intervention, which is required to better understand fully explore its potential benefits in cancer risk, increased response to cancer treatment, as well as improved quality and quantity of life among cancer survivors.
{"title":"Time-Restricted Eating and Cancer: Lessons Learned and Considerations for a Path Forward","authors":"Marissa M Shams-White, Audrey A Goldbaum, Tanya Agurs-Collins, Susan Czajkowski, Kirsten A Herrick, Linda Nebeling, Jill Reedy, Gabriela Riscuta, Sharon Ross, Edward R Sauter","doi":"10.1093/jnci/djae331","DOIUrl":"https://doi.org/10.1093/jnci/djae331","url":null,"abstract":"Time-restricted eating (TRE) is a type of intermittent fasting (IF). Food can be consumed as desired during the eating period, but not during the remainder of the day. Studies suggest that many of the health benefits of fasting may not simply be the result of weight loss, but also due to the body’s responses to the fasting that lead to improved metabolic functioning. While animal studies are convincing regarding the benefits of time restricted feeding, human (TRE) studies are less consistent and generally short term (&lt; 1 year). In 2020, the National Cancer Institute (NCI) funded five IF studies, four of which focused on TRE, which addressed the question “How does intermittent fasting affect cancer incidence, treatment response, or outcome?” NCI sponsored a webinar in 2023 featuring investigators of the funded studies in which they discussed challenges as well as their thoughts regarding the most important TRE topics that should be addressed going forward. Six areas were identified, which are discussed below as well as in a recently published NOT-CA-24-073: Factors impacting how Time-Restricted Eating (TRE) influences cancer-related outcomes. Moving the science forward will allow the scientific community to better understand TRE’s potential. This potential includes the development of targeted TRE interventions to optimize long-term adherence to the intervention, which is required to better understand fully explore its potential benefits in cancer risk, increased response to cancer treatment, as well as improved quality and quantity of life among cancer survivors.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"235 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142815779","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}
Roy S Herbst, Gideon Blumenthal, Samir N Khleif, Scott M Lippman, Neal J Meropol, Kristen Rosati, Lawrence N Shulman, Heind Smith, Meina Wang, Robert A Winn, Richard L Schilsky
Public-private partnerships (PPPs) in cancer research have emerged as a pivotal model in the development of strategies to rapidly advance therapeutic innovations. The collaboration between public entities, such as government agencies and research institutions, and private entities, including pharmaceutical and biotechnology companies, as well as nonprofit organizations, brings together diverse expertise, resources, and perspectives to address the challenges of efficient drug development and equitable care delivery. This synergy has the potential to accelerate the translation of basic research findings into tangible clinical applications. However, the implementation of PPPs is challenging and fraught with pitfalls that must be overcome if the PPP is to be successful in achieving its goals. To address these issues, in October 2023, the National Cancer Policy Forum and the Forum on Drug Discovery, Development, and Translation held the “Optimizing Public-Private Partnerships for Clinical Cancer Research” Workshop in Washington D.C. The goal of the workshop was to examine opportunities to promote collaboration among these various entities through public-private partnerships (PPP) to facilitate more timely and effective clinical cancer research. Key guiding principles and strategies were highlighted, and the challenges and barriers to implementing a PPP and recommendations to overcome those obstacles are summarized herein.
{"title":"Optimizing public private partnerships to support clinical cancer research","authors":"Roy S Herbst, Gideon Blumenthal, Samir N Khleif, Scott M Lippman, Neal J Meropol, Kristen Rosati, Lawrence N Shulman, Heind Smith, Meina Wang, Robert A Winn, Richard L Schilsky","doi":"10.1093/jnci/djae279","DOIUrl":"https://doi.org/10.1093/jnci/djae279","url":null,"abstract":"Public-private partnerships (PPPs) in cancer research have emerged as a pivotal model in the development of strategies to rapidly advance therapeutic innovations. The collaboration between public entities, such as government agencies and research institutions, and private entities, including pharmaceutical and biotechnology companies, as well as nonprofit organizations, brings together diverse expertise, resources, and perspectives to address the challenges of efficient drug development and equitable care delivery. This synergy has the potential to accelerate the translation of basic research findings into tangible clinical applications. However, the implementation of PPPs is challenging and fraught with pitfalls that must be overcome if the PPP is to be successful in achieving its goals. To address these issues, in October 2023, the National Cancer Policy Forum and the Forum on Drug Discovery, Development, and Translation held the “Optimizing Public-Private Partnerships for Clinical Cancer Research” Workshop in Washington D.C. The goal of the workshop was to examine opportunities to promote collaboration among these various entities through public-private partnerships (PPP) to facilitate more timely and effective clinical cancer research. Key guiding principles and strategies were highlighted, and the challenges and barriers to implementing a PPP and recommendations to overcome those obstacles are summarized herein.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142815780","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}
Carmen Petitjean, Naomi Wilcox, Lorenzo Ficorella, Joe Dennis, Jonathan Tyrer, Michael Lush, Jacques Simard, Douglas Easton, Antonis C Antoniou, Xin Yang
Background The BOADICEA model predicts breast cancer risk using cancer family history, epidemiological and genetic data. We evaluated its validity in a large prospective cohort. Methods We assessed model calibration, discrimination and risk classification ability in 217,885 women (6,838 incident breast cancers) aged 40-70 years old of self-reported White ethnicity with no previous cancer from the UK Biobank. Age-specific risk classification was assessed using relative risk (RR) thresholds equivalent to the absolute lifetime risk categories of < 17%, 17-30% and ≥30%, recommended by the National Institute for Health and Care Excellence guidelines. We predicted 10-year risks using BOADICEA v.6 considering cancer family history, questionnaire-based risk factors, a 313-SNP polygenic score and pathogenic variants. Mammographic density data were not available. Results The PRS was the most discriminative risk factor (AUC=0.65). Discrimination was highest when considering all risk factors (AUC=0.66). The model was well calibrated overall (E/O=0.99, 95%CI=0.97-1.02; calibration slope=0.99, 95%CI:0.99-1.00), and in deciles of predicted risks. Discrimination was similar in women younger and older than 50 years. There was some underprediction in women under age 50 (E/O=0.89, 95%CI=0.84-0.94; calibration slope=0.96, 95%CI:0.94-0.97), which was explained by the higher breast cancer incidence in UK Biobank than the UK population incidence in this age group. The model classified 87.2%, 11.4% and 1.4% of women in RR categories <1.6, 1.6-3.1 and ≥3.1, identifying 25.6% of incident breast cancer cases in category RR ≥ 1.6. Conclusion BOADICEA, implemented in CanRisk (www.canrisk.org), provides valid 10-year breast cancer risk which can facilitate risk-stratified screening and personalized breast cancer risk management.
{"title":"Evaluating the performance of the BOADICEA model in predicting 10-year breast cancer risks in UK Biobank","authors":"Carmen Petitjean, Naomi Wilcox, Lorenzo Ficorella, Joe Dennis, Jonathan Tyrer, Michael Lush, Jacques Simard, Douglas Easton, Antonis C Antoniou, Xin Yang","doi":"10.1093/jnci/djae335","DOIUrl":"https://doi.org/10.1093/jnci/djae335","url":null,"abstract":"Background The BOADICEA model predicts breast cancer risk using cancer family history, epidemiological and genetic data. We evaluated its validity in a large prospective cohort. Methods We assessed model calibration, discrimination and risk classification ability in 217,885 women (6,838 incident breast cancers) aged 40-70 years old of self-reported White ethnicity with no previous cancer from the UK Biobank. Age-specific risk classification was assessed using relative risk (RR) thresholds equivalent to the absolute lifetime risk categories of &lt; 17%, 17-30% and ≥30%, recommended by the National Institute for Health and Care Excellence guidelines. We predicted 10-year risks using BOADICEA v.6 considering cancer family history, questionnaire-based risk factors, a 313-SNP polygenic score and pathogenic variants. Mammographic density data were not available. Results The PRS was the most discriminative risk factor (AUC=0.65). Discrimination was highest when considering all risk factors (AUC=0.66). The model was well calibrated overall (E/O=0.99, 95%CI=0.97-1.02; calibration slope=0.99, 95%CI:0.99-1.00), and in deciles of predicted risks. Discrimination was similar in women younger and older than 50 years. There was some underprediction in women under age 50 (E/O=0.89, 95%CI=0.84-0.94; calibration slope=0.96, 95%CI:0.94-0.97), which was explained by the higher breast cancer incidence in UK Biobank than the UK population incidence in this age group. The model classified 87.2%, 11.4% and 1.4% of women in RR categories &lt;1.6, 1.6-3.1 and ≥3.1, identifying 25.6% of incident breast cancer cases in category RR ≥ 1.6. Conclusion BOADICEA, implemented in CanRisk (www.canrisk.org), provides valid 10-year breast cancer risk which can facilitate risk-stratified screening and personalized breast cancer risk management.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142815702","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}
Kelly D Blake, Richard P Moser, Heather D’Angelo, Anna Gaysynsky, Robin C Vanderpool
The National Cancer Institute’s (NCI) Health Information National Trends Survey® (HINTS®), was conceived in 1997 during a multidisciplinary conference focused on risk communication that included attendees representing the fields of psychology, health behavior, health education, public health, clinical medicine, and health journalism. The key recommendation from the conference was for NCI to develop a premiere communication-specific population survey to track health and cancer communication-related phenomena. This led to NCI developing and launching HINTS in 2003. HINTS is a cross-sectional, nationally representative survey of the U.S. noninstitutionalized adult population (18 and older) that collects data on the public's need for, access to, and use of health- and cancer-related related information and health- and cancer-related knowledge, attitudes, and behaviors. As of 2024, HINTS had been administered 17 times over a 21-year period. The resulting datasets can be utilized for secondary analysis to examine a range of social and behavioral research questions in cancer control and population sciences. The datasets can be examined individually or merged to test for trends over time or to create larger samples for analysis. The evolution of the program has included testing and changing instrument administration modes, oversampling specific populations, and assessing priority constructs, as well as conducting methodological experiments to keep pace with emerging trends in survey research. HINTS has also expanded beyond its cross-sectional format to include data linkages and a longitudinal panel, enabling researchers to address a wider range of research questions. HINTS methods, data products, and impact are discussed.
{"title":"The Evolution of NCI’s Health Information National Trends Survey: Methods, Data, and Future Directions","authors":"Kelly D Blake, Richard P Moser, Heather D’Angelo, Anna Gaysynsky, Robin C Vanderpool","doi":"10.1093/jnci/djae317","DOIUrl":"https://doi.org/10.1093/jnci/djae317","url":null,"abstract":"The National Cancer Institute’s (NCI) Health Information National Trends Survey® (HINTS®), was conceived in 1997 during a multidisciplinary conference focused on risk communication that included attendees representing the fields of psychology, health behavior, health education, public health, clinical medicine, and health journalism. The key recommendation from the conference was for NCI to develop a premiere communication-specific population survey to track health and cancer communication-related phenomena. This led to NCI developing and launching HINTS in 2003. HINTS is a cross-sectional, nationally representative survey of the U.S. noninstitutionalized adult population (18 and older) that collects data on the public's need for, access to, and use of health- and cancer-related related information and health- and cancer-related knowledge, attitudes, and behaviors. As of 2024, HINTS had been administered 17 times over a 21-year period. The resulting datasets can be utilized for secondary analysis to examine a range of social and behavioral research questions in cancer control and population sciences. The datasets can be examined individually or merged to test for trends over time or to create larger samples for analysis. The evolution of the program has included testing and changing instrument administration modes, oversampling specific populations, and assessing priority constructs, as well as conducting methodological experiments to keep pace with emerging trends in survey research. HINTS has also expanded beyond its cross-sectional format to include data linkages and a longitudinal panel, enabling researchers to address a wider range of research questions. HINTS methods, data products, and impact are discussed.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"23 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805371","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}
Allini Mafra, Mathieu Laversanne, Rafael Marcos-Gragera, Humberto V S Chaves, Charlene Mcshane, Freddie Bray, Ariana Znaor
Background Multiple myeloma (MM) is an important haematological malignancy in older adults, with a relatively poor prognosis. We aimed to present the current global patterns of incidence and mortality from MM, and predict new cases and deaths by 2045. Methods Estimated numbers of MM cases and deaths and age-standardized (World) incidence and mortality rates per 100,000 people were obtained from the GLOBOCAN 2022 database covering 185 countries. Based on the incidence and mortality rates for 2022 and UN population estimates up to 2045, cases and deaths were predicted up to 2045. Findings Globally, 188,000 MM cases and 121,000 deaths were estimated in 2022. Eastern Asia and Northern America accounted for one-fifth of all cases each (21% and 19% respectively), followed by South-Central Asia (11%), and Western Europe (9%). The incidence rates were higher in men than in women with similar geographical patterns. While the incidence rates were highest in Northern America and Australia/New Zealand (≥4/100,000 for both sexes combined), the highest mortality rates (1.8/100,000) were found in Australia/New Zealand, Northern Europe, and Southern Africa. In the absence of changing rates, the estimated incidence and mortality of MM will increase by 71% and 79%, respectively by 2045 relative to 2022. Interpretation Our study highlights the substantial burden and variations in MM incidence and mortality reflecting global disparities in diagnosis and treatment. Improved surveillance and better disease control is needed to mitigate the global impact of MM in the presence of population aging and growth.
{"title":"The global multiple myeloma incidence and mortality burden in 2022 and predictions for 2045","authors":"Allini Mafra, Mathieu Laversanne, Rafael Marcos-Gragera, Humberto V S Chaves, Charlene Mcshane, Freddie Bray, Ariana Znaor","doi":"10.1093/jnci/djae321","DOIUrl":"https://doi.org/10.1093/jnci/djae321","url":null,"abstract":"Background Multiple myeloma (MM) is an important haematological malignancy in older adults, with a relatively poor prognosis. We aimed to present the current global patterns of incidence and mortality from MM, and predict new cases and deaths by 2045. Methods Estimated numbers of MM cases and deaths and age-standardized (World) incidence and mortality rates per 100,000 people were obtained from the GLOBOCAN 2022 database covering 185 countries. Based on the incidence and mortality rates for 2022 and UN population estimates up to 2045, cases and deaths were predicted up to 2045. Findings Globally, 188,000 MM cases and 121,000 deaths were estimated in 2022. Eastern Asia and Northern America accounted for one-fifth of all cases each (21% and 19% respectively), followed by South-Central Asia (11%), and Western Europe (9%). The incidence rates were higher in men than in women with similar geographical patterns. While the incidence rates were highest in Northern America and Australia/New Zealand (≥4/100,000 for both sexes combined), the highest mortality rates (1.8/100,000) were found in Australia/New Zealand, Northern Europe, and Southern Africa. In the absence of changing rates, the estimated incidence and mortality of MM will increase by 71% and 79%, respectively by 2045 relative to 2022. Interpretation Our study highlights the substantial burden and variations in MM incidence and mortality reflecting global disparities in diagnosis and treatment. Improved surveillance and better disease control is needed to mitigate the global impact of MM in the presence of population aging and growth.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"228 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805370","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}
Aitziber Buqué, Norma Bloy, Giulia Petroni, Carlos Jiménez-Cortegana, Ai Sato, Cristina Iribarren, Takahiro Yamazaki, Claudia Galassi, Michal Hensler, Bhavneet Bhinder, Andrea Guarracino, Brady Rippon, Manuel Beltran-Visiedo, Ruth Soler-Agesta, Tania Pannellini, Jitka Fucikova, Sandra Demaria, Xi Kathy Zhou, Olivier Elemento, Silvia C Formenti, Lorenzo Galluzzi
Background Hormone receptor (HR)+ breast cancer is poorly responsive to immune checkpoint inhibitors (ICIs). In some settings, radiation therapy (RT) has been shown to mediate immunostimulatory effects and promote ICI sensitivity. Methods We investigated whether hypofractionated RT may be successfully combined with ICIs in a mouse model of multifocal, metachronous HR+ mammary carcinogenesis. We hypothesized that focal RT targeting the first detectable (primary) tumor combined with ICIs may generate effective immunity, hence delaying the development of new lesions. Results Focal RT in various doses and fractionations limited primary tumor growth, with an optimum for a 20 Gy X 2 regimen (ablative in ∼90% of mice). The degree of primary disease control, however, did not necessarily correlate with overall survival (OS) extension, owing to changes in the development of new neoplastic lesions contributing to global tumor burden. Adding a PD-1 blocker to focal RT delivered in a 10 Gy X 3, 20 Gy X 2 or 8 Gy X 6 regimen failed to alter OS extension enabled by RT alone. Similar results were obtained with a CTLA4 blocker, an IL1B inhibitor, and a PD-1 blocker plus recombinant FLT3LG when combined with the 10 Gy X 3 regimen. Conclusions In this model of HR+ mammary carcinogenesis, RT to the primary tumor ameliorates OS (to an extent depending on dose and fractionation). Increasing local control by RT alone or RT plus immunotherapy beyond a hitherto undefined threshold, however, does not necessarily inhibit the development of subsequent non-irradiated neoplasms and hence does not necessarily provide extra OS benefits.
激素受体（HR）阳性乳腺癌对免疫检查点抑制剂（ICIs）反应较差。在某些情况下，放射治疗（RT）已被证明介导免疫刺激效应并促进ICI敏感性。方法在小鼠多灶、异时性HR+乳腺癌模型中，研究低分割RT与ICIs能否成功联合。我们假设针对第一个可检测到的（原发）肿瘤的局灶性RT联合ICIs可能产生有效的免疫，从而延迟新病变的发展。结果不同剂量和分级的局灶性放射治疗限制了原发肿瘤的生长，20 Gy x2治疗方案的效果最佳（约90%的小鼠消融）。然而，原发疾病的控制程度并不一定与总生存期（OS）延长相关，因为新肿瘤病变的发展变化会增加全球肿瘤负担。在10 Gy X 3、20 Gy X 2或8 Gy X 6方案的局灶性放疗中添加PD-1阻滞剂未能改变单独放疗所带来的OS延长。CTLA4阻滞剂、IL1B抑制剂和PD-1阻滞剂加重组FLT3LG与10 Gy x3方案联合使用时也获得了类似的结果。结论：在HR+乳腺癌模型中，原发肿瘤的放疗改善了OS（程度取决于剂量和分割）。然而，通过单独放疗或放疗加免疫治疗增加局部控制，超过一个迄今未定义的阈值，并不一定能抑制后续非放疗肿瘤的发展，因此不一定能提供额外的OS益处。
{"title":"Impact of radiotherapy dose, fractionation and immunotherapeutic partner in a mouse model of HR+ mammary carcinogenesis","authors":"Aitziber Buqué, Norma Bloy, Giulia Petroni, Carlos Jiménez-Cortegana, Ai Sato, Cristina Iribarren, Takahiro Yamazaki, Claudia Galassi, Michal Hensler, Bhavneet Bhinder, Andrea Guarracino, Brady Rippon, Manuel Beltran-Visiedo, Ruth Soler-Agesta, Tania Pannellini, Jitka Fucikova, Sandra Demaria, Xi Kathy Zhou, Olivier Elemento, Silvia C Formenti, Lorenzo Galluzzi","doi":"10.1093/jnci/djae329","DOIUrl":"https://doi.org/10.1093/jnci/djae329","url":null,"abstract":"Background Hormone receptor (HR)+ breast cancer is poorly responsive to immune checkpoint inhibitors (ICIs). In some settings, radiation therapy (RT) has been shown to mediate immunostimulatory effects and promote ICI sensitivity. Methods We investigated whether hypofractionated RT may be successfully combined with ICIs in a mouse model of multifocal, metachronous HR+ mammary carcinogenesis. We hypothesized that focal RT targeting the first detectable (primary) tumor combined with ICIs may generate effective immunity, hence delaying the development of new lesions. Results Focal RT in various doses and fractionations limited primary tumor growth, with an optimum for a 20 Gy X 2 regimen (ablative in ∼90% of mice). The degree of primary disease control, however, did not necessarily correlate with overall survival (OS) extension, owing to changes in the development of new neoplastic lesions contributing to global tumor burden. Adding a PD-1 blocker to focal RT delivered in a 10 Gy X 3, 20 Gy X 2 or 8 Gy X 6 regimen failed to alter OS extension enabled by RT alone. Similar results were obtained with a CTLA4 blocker, an IL1B inhibitor, and a PD-1 blocker plus recombinant FLT3LG when combined with the 10 Gy X 3 regimen. Conclusions In this model of HR+ mammary carcinogenesis, RT to the primary tumor ameliorates OS (to an extent depending on dose and fractionation). Increasing local control by RT alone or RT plus immunotherapy beyond a hitherto undefined threshold, however, does not necessarily inhibit the development of subsequent non-irradiated neoplasms and hence does not necessarily provide extra OS benefits.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"82 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142809632","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}
Christine M Kava, Anil K Chaturvedi, Virginia Senkomago, Jacqueline M Mix, Lauri E Markowitz, Aimée R Kreimer, Elizabeth R Unger, Mona Saraiya
In addition to oropharyngeal cancers, evidence suggests there may be an etiologic role for human papillomavirus (HPV) in some other head and neck cancers arising from the oral cavity and larynx. We estimated the burden of HPV16-attributable cancers of the oral cavity (ICD-O-3 site codes C02.0-C02.3, C02.9, C03.0, C03.1, C03.9, C04.0, C04.1, C04.8, C04.9, C05.0, C05.8, C05.9, C06.0-C06.2, C06.8, C06.9) and larynx (C32.0-C32.3, C32.8, C32.9) in the United States by pooling estimates from published case studies to calculate HPV16-attributable fractions (HPV16-AFs) and applying the HPV16-AFs to 2016-2020 US Cancer Statistics data. During 2016-2020, of an average annual number of 12,612 oral cavity cancers, 3.9% (n = 497) were estimated to be attributable to HPV16. Of an average annual number of 11,170 laryngeal cancers, 2.8% (n = 309) were estimated to be attributable to HPV16. This information can improve surveillance of HPV16-attributable cancers in the US population and inform our understanding of the potential impact of HPV vaccination on cancers at these two sites.
{"title":"The role of HPV16 in oral cavity and laryngeal cancers in the United States","authors":"Christine M Kava, Anil K Chaturvedi, Virginia Senkomago, Jacqueline M Mix, Lauri E Markowitz, Aimée R Kreimer, Elizabeth R Unger, Mona Saraiya","doi":"10.1093/jnci/djae320","DOIUrl":"https://doi.org/10.1093/jnci/djae320","url":null,"abstract":"In addition to oropharyngeal cancers, evidence suggests there may be an etiologic role for human papillomavirus (HPV) in some other head and neck cancers arising from the oral cavity and larynx. We estimated the burden of HPV16-attributable cancers of the oral cavity (ICD-O-3 site codes C02.0-C02.3, C02.9, C03.0, C03.1, C03.9, C04.0, C04.1, C04.8, C04.9, C05.0, C05.8, C05.9, C06.0-C06.2, C06.8, C06.9) and larynx (C32.0-C32.3, C32.8, C32.9) in the United States by pooling estimates from published case studies to calculate HPV16-attributable fractions (HPV16-AFs) and applying the HPV16-AFs to 2016-2020 US Cancer Statistics data. During 2016-2020, of an average annual number of 12,612 oral cavity cancers, 3.9% (n = 497) were estimated to be attributable to HPV16. Of an average annual number of 11,170 laryngeal cancers, 2.8% (n = 309) were estimated to be attributable to HPV16. This information can improve surveillance of HPV16-attributable cancers in the US population and inform our understanding of the potential impact of HPV vaccination on cancers at these two sites.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805369","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}
Jaimie Z Shing, Anna R Giuliano, Nicole L Brenner, Birgitta Michels, Allan Hildesheim, Sudhir Srivastava, Bradley A Sirak, John Schussler, Danping Liu, Wendy Wang, Tim Waterboer, Aimée R Kreimer
Background Human papillomavirus (HPV)16-E6 seropositivity accurately predicts oropharyngeal squamous cell carcinoma (OPSCC) risk decades before diagnosis; but the biomarker’s translational potential is unknown. To inform considerations for OPSCC screening, we described HPV16-E6 seroprevalence, predictors, and kinetics among cancer-free men. Methods In a cohort study in Brazil, Mexico, and United States, we calculated HPV16-E6 seropositivity [median fluorescence intensity (MFI) units > 1,000], measured by multiplex serology, in cancer-free men. HPV16-E6 seropositivity predictors were assessed using logistic regression, adjusting for country, age, sexual orientation, and lifetime number of partners. Among HPV16-E6 seropositive men, we retrieved all available retrospective serum samples and described temporal HPV16-E6 antibody patterns. Results Of 3,997 men, 14 had HPV16-E6 antibodies detected [seroprevalence = 0.35%; 95% confidence interval (95%CI)=0.19%-0.59%] (median MFI = 2,407; interquartile range = 1,325-5,986). Older age was associated with increased odds of HPV16-E6 seropositivity (50-84 years vs 18-29 years odds ratio = 16.61; 95%CI = 2.20-417.03). Serum from 11 of the 14 seropositive men retested positive; six men had MFI > 5,000, of whom two had MFI > 10,000. Seven men had ≥3 years follow-up; all were persistently seropositive for 3 years. One man was seropositive for nine years but seroreverted at his exit visit. Oral HPV16-DNA (prevalence = 1.13%) was associated with HPV16-E6 seropositivity (odds ratio = 16.87; 95%CI = 3.35-69.55). However, oral HPV16-DNA positivity was not persistent over follow-up, even when HPV16-E6 antibodies were persistently detected. Conclusion HPV16-E6 seropositivity is rare but generally stable once detected; thus, HPV16-E6 antibodies may be an informative biomarker of HPV-driven OPSCC. Few men seroreverted following HPV16-E6 seropositivity but remained close to the seropositivity cut-off; thus, cancer risk among these men is less clear.
{"title":"Natural history of HPV16-E6 serology among cancer-free men in a multicenter longitudinal cohort study","authors":"Jaimie Z Shing, Anna R Giuliano, Nicole L Brenner, Birgitta Michels, Allan Hildesheim, Sudhir Srivastava, Bradley A Sirak, John Schussler, Danping Liu, Wendy Wang, Tim Waterboer, Aimée R Kreimer","doi":"10.1093/jnci/djae326","DOIUrl":"https://doi.org/10.1093/jnci/djae326","url":null,"abstract":"Background Human papillomavirus (HPV)16-E6 seropositivity accurately predicts oropharyngeal squamous cell carcinoma (OPSCC) risk decades before diagnosis; but the biomarker’s translational potential is unknown. To inform considerations for OPSCC screening, we described HPV16-E6 seroprevalence, predictors, and kinetics among cancer-free men. Methods In a cohort study in Brazil, Mexico, and United States, we calculated HPV16-E6 seropositivity [median fluorescence intensity (MFI) units &gt; 1,000], measured by multiplex serology, in cancer-free men. HPV16-E6 seropositivity predictors were assessed using logistic regression, adjusting for country, age, sexual orientation, and lifetime number of partners. Among HPV16-E6 seropositive men, we retrieved all available retrospective serum samples and described temporal HPV16-E6 antibody patterns. Results Of 3,997 men, 14 had HPV16-E6 antibodies detected [seroprevalence = 0.35%; 95% confidence interval (95%CI)=0.19%-0.59%] (median MFI = 2,407; interquartile range = 1,325-5,986). Older age was associated with increased odds of HPV16-E6 seropositivity (50-84 years vs 18-29 years odds ratio = 16.61; 95%CI = 2.20-417.03). Serum from 11 of the 14 seropositive men retested positive; six men had MFI &gt; 5,000, of whom two had MFI &gt; 10,000. Seven men had ≥3 years follow-up; all were persistently seropositive for 3 years. One man was seropositive for nine years but seroreverted at his exit visit. Oral HPV16-DNA (prevalence = 1.13%) was associated with HPV16-E6 seropositivity (odds ratio = 16.87; 95%CI = 3.35-69.55). However, oral HPV16-DNA positivity was not persistent over follow-up, even when HPV16-E6 antibodies were persistently detected. Conclusion HPV16-E6 seropositivity is rare but generally stable once detected; thus, HPV16-E6 antibodies may be an informative biomarker of HPV-driven OPSCC. Few men seroreverted following HPV16-E6 seropositivity but remained close to the seropositivity cut-off; thus, cancer risk among these men is less clear.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805368","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}
Troy J Kleber, Alexander D Sherry, Andrew J Arifin, Gabrielle S Kupferman, Ramez Kouzy, Joseph Abi Jaoude, Timothy A Lin, Esther J Beck, Avital M Miller, Adina H Passy, Zachary R Mccaw, Pavlos Msaouel, Ethan B Ludmir
Background Noninferiority (NI) and equivalence trials evaluate whether an experimental therapy’s effect on the primary endpoint (PEP) is contained within an acceptable margin compared to standard-of-care. The reliability and impact of this conclusion, however, is largely dependent on the justification for this design, the choice of margin, and the analysis population used. Methods A meta-epidemiological study was performed of phase 3 randomized NI and equivalence oncologic trials registered at ClinicalTrials.gov. Data was extracted from each trial’s registration page and primary manuscript. Results We identified 65 NI and 10 equivalence trials that collectively enrolled 61,632 patients. Sixty-one trials (81%) demonstrated NI or equivalence. Sixty-five trials (87%) were justified in the use of an NI or equivalence design either because of an inherent advantage (53 trials), a significant quality-of-life improvement (6 trials), or a significant toxicity improvement (6 trials) of the interventional treatment relative to the control arm. Sixty-nine trials (92.0%) reported a prespecified NI or equivalence margin, of which only 23 (33.3%) provided justification for this margin based on prior literature. For trials with time-to-event PEPs, the median NI margin was a hazard ratio of 1.22 (range, 1.08-1.52). Investigators reported a per-protocol (PP) analysis for the PEP in only 28 trials (37%). Conclusions Although most published NI and equivalence trials have clear justification for their design, few provide rationale for the chosen margin or report a PP analysis. These findings underscore the need for rigorous standards in trial design and reporting.
{"title":"Justification, margin values, and analysis populations for oncologic noninferiority and equivalence trials: a meta-epidemiological study","authors":"Troy J Kleber, Alexander D Sherry, Andrew J Arifin, Gabrielle S Kupferman, Ramez Kouzy, Joseph Abi Jaoude, Timothy A Lin, Esther J Beck, Avital M Miller, Adina H Passy, Zachary R Mccaw, Pavlos Msaouel, Ethan B Ludmir","doi":"10.1093/jnci/djae318","DOIUrl":"https://doi.org/10.1093/jnci/djae318","url":null,"abstract":"Background Noninferiority (NI) and equivalence trials evaluate whether an experimental therapy’s effect on the primary endpoint (PEP) is contained within an acceptable margin compared to standard-of-care. The reliability and impact of this conclusion, however, is largely dependent on the justification for this design, the choice of margin, and the analysis population used. Methods A meta-epidemiological study was performed of phase 3 randomized NI and equivalence oncologic trials registered at ClinicalTrials.gov. Data was extracted from each trial’s registration page and primary manuscript. Results We identified 65 NI and 10 equivalence trials that collectively enrolled 61,632 patients. Sixty-one trials (81%) demonstrated NI or equivalence. Sixty-five trials (87%) were justified in the use of an NI or equivalence design either because of an inherent advantage (53 trials), a significant quality-of-life improvement (6 trials), or a significant toxicity improvement (6 trials) of the interventional treatment relative to the control arm. Sixty-nine trials (92.0%) reported a prespecified NI or equivalence margin, of which only 23 (33.3%) provided justification for this margin based on prior literature. For trials with time-to-event PEPs, the median NI margin was a hazard ratio of 1.22 (range, 1.08-1.52). Investigators reported a per-protocol (PP) analysis for the PEP in only 28 trials (37%). Conclusions Although most published NI and equivalence trials have clear justification for their design, few provide rationale for the chosen margin or report a PP analysis. These findings underscore the need for rigorous standards in trial design and reporting.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"37 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805377","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}
Annelie Johansson, Huma Dar, Anna Nordenskjöld, Gizeh Perez-Tenorio, Nicholas P Tobin, Christina Yau, Christopher C Benz, Laura J Esserman, Laura J van ‘t Veer, Bo Nordenskjöld, Olle Stål, Tommy Fornander, Linda S Lindström
Background Estrogen receptor–positive breast cancer patients have a long-term risk of distant metastatic disease, and premenopausal patients have a higher risk. Randomized studies with long-term follow-up are essential to understand treatment benefit. We elucidated the long-term tamoxifen therapy benefit by menopausal status in the Stockholm tamoxifen trials with 20 years complete follow-up. Methods Secondary analysis of 1242 estrogen receptor–positive and HER2-negative patients that were randomly assigned to 2-5 years of 40 mg adjuvant tamoxifen or no endocrine therapy. Distant recurrence-free interval in tamoxifen-treated vs endocrine untreated patients was assessed by Kaplan–Meier, Cox proportional hazards regression, and time-varying analyses. Results In premenopausal patients, a statistically significant tamoxifen benefit was observed for lymph node–negative (adjusted hazard ratio [HR] = 0.46, 95% confidence interval [CI] = 0.24 to 0.87), progesterone receptor–positive (adjusted HR = 0.61, 95% CI = 0.41 to 0.91), and genomic low-risk tumors (adjusted HR = 0.47, 95% CI = 0.26 to 0.85) but only lasted beyond 10 years for genomic low-risk tumors. Postmenopausal patients showed long-term benefit for all good-prognosis markers including low-grade (adjusted HR = 0.55, 95% CI = 0.41 to 0.73), lymph node–negative (adjusted HR = 0.44, 95% CI = 0.30 to 0.64), progesterone receptor–positive (adjusted HR = 0.60, 95% CI = 0.44 to 0.80), Ki-67 low (adjusted HR = 0.51, 95% CI = 0.38 to 0.68), and genomic low-risk tumors (adjusted HR = 0.53, 95% CI = 0.37 to 0.74), and regardless of tumor size (≤20 mm: adjusted HR = 0.55, 95% CI = 0.39 to 0.77; >20 mm: adjusted HR = 0.64, 95% CI = 0.44 to 0.94). Premenopausal patients with no poor-prognosis tumor characteristics (clinical marker score = 0) showed early benefit and postmenopausal long-term benefit. Conclusions Our study suggests differential tamoxifen benefit by menopausal status. Improved long-term endocrine therapy prediction in premenopausal patients is needed and could involve molecular markers because standard tumor characteristics cannot predict benefit beyond 10 years.
背景雌激素受体阳性乳腺癌患者有远处转移疾病的长期风险，绝经前患者风险更高。长期随访的随机研究对于了解治疗效果至关重要。在斯德哥尔摩的他莫昔芬试验中，我们通过20年的完全随访阐明了他莫昔芬治疗对绝经期患者的长期益处。方法对1242例雌激素受体阳性和her2阴性患者进行二次分析，随机分为2 ~ 5年辅助性他莫昔芬治疗40 mg或不进行内分泌治疗。采用Kaplan-Meier、Cox比例风险回归和时变分析评估他莫昔芬治疗与内分泌治疗患者的远端无复发间期。结果在绝经前患者中，他莫昔芬对淋巴结阴性（校正风险比[HR] = 0.46, 95%可信区间[CI] = 0.24 ~ 0.87）、孕激素受体阳性（校正风险比[HR] = 0.61, 95% CI = 0.41 ~ 0.91）和基因组低危肿瘤（校正风险比= 0.47,95% CI = 0.26 ~ 0.85）有显著的统计学意义，但对基因组低危肿瘤仅持续10年以上。绝经后患者显示长期受益所有预后良好标记包括低级(调整HR = 0.55, 95% CI = 0.41 - 0.73),淋巴淋巴结阴性(调整HR = 0.44, 95% CI = 0.30 - 0.64)、孕激素受体阳性(调整HR = 0.60, 95% CI = 0.44 - 0.80), ki - 67低(调整HR = 0.51, 95% CI = 0.38 - 0.68),和基因组低风险肿瘤(调整HR = 0.53, 95% CI = 0.37 - 0.74),和不论肿瘤大小(≤20毫米:调整HR = 0.55, 95% CI = 0.39 - 0.77;20 mm：调整后HR = 0.64, 95% CI = 0.44 ~ 0.94)。绝经前无不良预后肿瘤特征（临床标志物评分= 0）的患者早期获益，绝经后长期获益。结论：我们的研究表明，它莫西芬的疗效因绝经状态而异。需要改进绝经前患者的长期内分泌治疗预测，并且可能涉及分子标记，因为标准肿瘤特征不能预测超过10年的获益。
{"title":"Differential long-term tamoxifen therapy benefit by menopausal status in breast cancer patients: secondary analysis of a controlled randomized clinical trial","authors":"Annelie Johansson, Huma Dar, Anna Nordenskjöld, Gizeh Perez-Tenorio, Nicholas P Tobin, Christina Yau, Christopher C Benz, Laura J Esserman, Laura J van ‘t Veer, Bo Nordenskjöld, Olle Stål, Tommy Fornander, Linda S Lindström","doi":"10.1093/jnci/djae268","DOIUrl":"https://doi.org/10.1093/jnci/djae268","url":null,"abstract":"Background Estrogen receptor–positive breast cancer patients have a long-term risk of distant metastatic disease, and premenopausal patients have a higher risk. Randomized studies with long-term follow-up are essential to understand treatment benefit. We elucidated the long-term tamoxifen therapy benefit by menopausal status in the Stockholm tamoxifen trials with 20 years complete follow-up. Methods Secondary analysis of 1242 estrogen receptor–positive and HER2-negative patients that were randomly assigned to 2-5 years of 40 mg adjuvant tamoxifen or no endocrine therapy. Distant recurrence-free interval in tamoxifen-treated vs endocrine untreated patients was assessed by Kaplan–Meier, Cox proportional hazards regression, and time-varying analyses. Results In premenopausal patients, a statistically significant tamoxifen benefit was observed for lymph node–negative (adjusted hazard ratio [HR] = 0.46, 95% confidence interval [CI] = 0.24 to 0.87), progesterone receptor–positive (adjusted HR = 0.61, 95% CI = 0.41 to 0.91), and genomic low-risk tumors (adjusted HR = 0.47, 95% CI = 0.26 to 0.85) but only lasted beyond 10 years for genomic low-risk tumors. Postmenopausal patients showed long-term benefit for all good-prognosis markers including low-grade (adjusted HR = 0.55, 95% CI = 0.41 to 0.73), lymph node–negative (adjusted HR = 0.44, 95% CI = 0.30 to 0.64), progesterone receptor–positive (adjusted HR = 0.60, 95% CI = 0.44 to 0.80), Ki-67 low (adjusted HR = 0.51, 95% CI = 0.38 to 0.68), and genomic low-risk tumors (adjusted HR = 0.53, 95% CI = 0.37 to 0.74), and regardless of tumor size (≤20 mm: adjusted HR = 0.55, 95% CI = 0.39 to 0.77; &gt;20 mm: adjusted HR = 0.64, 95% CI = 0.44 to 0.94). Premenopausal patients with no poor-prognosis tumor characteristics (clinical marker score = 0) showed early benefit and postmenopausal long-term benefit. Conclusions Our study suggests differential tamoxifen benefit by menopausal status. Improved long-term endocrine therapy prediction in premenopausal patients is needed and could involve molecular markers because standard tumor characteristics cannot predict benefit beyond 10 years.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"81 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805374","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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