Heidi Moseson, Sachiko Ragosta, Anu Manchikanti Gómez, Jae Corman, Jay Zussman, Bori Lesser-Lee, Sydney Reese, India Rose Carter-Bolick, Juno Obedin-Maliver
{"title":"Acceptability of an organ inventory for cancer screening across gender identity and intersex status","authors":"Heidi Moseson, Sachiko Ragosta, Anu Manchikanti Gómez, Jae Corman, Jay Zussman, Bori Lesser-Lee, Sydney Reese, India Rose Carter-Bolick, Juno Obedin-Maliver","doi":"10.1093/jnci/djae336","DOIUrl":"https://doi.org/10.1093/jnci/djae336","url":null,"abstract":"Objectives To evaluate the acceptability and performance of an organ inventory as an alternative to asking about gender and/or sex assigned at birth in cancer screening. Methods We fielded an online, self-administered survey to a convenience sample of English- or Spanish-speaking transgender and gender-diverse (TGD), intersex, and cisgender people (>/=15 years) in the US. The survey contained an organ inventory developed with community input and questions regarding acceptability. The primary outcome was organ inventory acceptability by the four-item Acceptability of Intervention Measure (AIM). Additional outcomes included inter-method screening agreement between the organ inventory, gender, and sex assigned at birth. Results In 2022, 333 eligible individuals completed the survey; 44.4% cisgender, 34.2% TGD, and 14.1% intersex. Overall, participants rated the organ inventory as acceptable (median AIM score = 18/20, IQR: 16-20). Most (73%) found it easy to understand, and comfortable to complete (65%). Cancer screening eligibility varied based on the method used; relying solely on gender or sex data would have missed some eligible participants that the organ inventory identified. Conclusions Using an organ inventory as an alternative to gender or sex-based screening questions was acceptable, and has implications for addressing cancer screening disparities.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"146 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142820868","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}
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
{"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 (< 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
{"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
{"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 < 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.","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
{"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
{"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
{"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
{"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
{"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 > 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.","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
{"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}