J Natl Cancer Inst
· 2026 Feb · PMID 41706111
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BACKGROUND: Adverse health events have been reported among US service members who served at Karshi-Khanabad (K2) Air Base, Uzbekistan, but prior studies of cancer risk had key limitations. METHODS: We conducted a nested...BACKGROUND: Adverse health events have been reported among US service members who served at Karshi-Khanabad (K2) Air Base, Uzbekistan, but prior studies of cancer risk had key limitations. METHODS: We conducted a nested case-control study to assess the association between K2 deployment and cancer outcomes among military personnel deployed between 2001-2005. Eight malignant outcomes (brain, colorectal, liver, urinary tract, pancreatic, prostate, leukemia, non-Hodgkin's lymphoma [NHL]) were identified via health records from the Department of Defense and Veterans Administration through 2022. Cases were matched to controls (1:100) on age, sex, and health system usage. Covariate-adjusted conditional logistic regression models estimated outcome likelihood by exposure surrogates without and with lagging. RESULTS: Among 619,403 service members, 15,031 (2.3%) were deployed at least once to K2 (median duration 130 days). We identified cancer cases (count; cumulative incidence per 10,000) for brain (450; 7.3), colorectal (1,542; 25.0), liver (113; 1.8), urinary tract (1,831; 29.7), pancreatic (417; 6.8), prostate (5,165; 83.6), leukemia (707; 11.5), NHL (1,700; 27.5). Across seven of eight outcomes, there were no associations between deployment and case status. In contrast, each additional month of deployment increased the odds of NHL by 13% (95% CI, 4%-23%) and deployment >180 days was associated with higher odds (OR 1.78; 95% CI, 1.08-2.94). When lagging exposure by 12-15 years, these associations strengthened (range: 2.38 [1.17-4.82] to 3.09 [1.73-5.52]). CONCLUSIONS: Long-term K2 deployment was associated with increased likelihood of non-Hodgkin's lymphoma. Careful clinical monitoring and continued follow-up of this cohort for cancer and other outcomes are warranted.
Huang BZ, Chen F, Bogumil D
… +16 more, Han S, Paik A, Wan P, Sheng X, Siegmund KD, Peters U, VoPham T, Wang L, Alderete T, Salhia B, Lenz HJ, Stram DO, Wilkens LR, Le Marchand L, Conti DV, Haiman CA
J Natl Cancer Inst
· 2026 Feb · PMID 41697998
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BACKGROUND: Integrating genetic and lifestyle information has the potential to greatly improve the prediction of colorectal cancer (CRC) risk. However, racial and ethnic minorities are generally underrepresented in gene-...BACKGROUND: Integrating genetic and lifestyle information has the potential to greatly improve the prediction of colorectal cancer (CRC) risk. However, racial and ethnic minorities are generally underrepresented in gene-environment studies of CRC risk. METHODS: We investigated the interplay of genetics and lifestyle on CRC risk in a prospective analysis of 68,397 African American, Japanese American, Latino, Native Hawaiian, and White individuals from the Multiethnic Cohort Study. Genetic predisposition was assessed using a 205-variant polygenic risk score (PRS). Lifestyle was assessed using a lifestyle risk score based on smoking, alcohol consumption, body mass index, physical activity, and diet. The independent and joint associations of the PRS and lifestyle risk score on CRC risk were evaluated using Cox regression. RESULTS: We identified 1,303 incident CRC cases (median 15.1-year follow-up). The highest quintile of the PRS was associated with a 2.4-fold increase in CRC risk compared to the lowest quintile (HRQ5vQ1 2.40, 95% CI 1.99-2.89). The highest quintile of the lifestyle risk score was associated with a 54% increased risk (HRQ5vQ1 1.54, 95% CI 1.26-1.88). This association was stronger among those with high genetic risk (PRS≥50%) (HRQ5vQ1 1.82, 95% CI 1.41-2.35) and non-significant among those with low genetic risk (PRS<50%) (HRQ5vQ1 1.20, 95% CI 0.88-1.64; p-interaction=0.01). Results were similar across race and ethnicity. CONCLUSIONS: Our study suggests that lifestyle modification may offer greater risk reduction among those at higher genetic risk. Future research is warranted to enhance the integration of genetics and lifestyle in CRC risk stratification and screening approaches across populations.
Peacock R, Bedding C, Pacheco B
… +3 more, Hamzeh H, Piccinin C, Gilbert A
J Natl Cancer Inst
· 2026 Jun · PMID 41697992
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BACKGROUND: Patient-reported outcome (PRO) item libraries support flexible PRO assessment in cancer research by facilitating the development of customized item lists. However, little is known about the use of item lists...BACKGROUND: Patient-reported outcome (PRO) item libraries support flexible PRO assessment in cancer research by facilitating the development of customized item lists. However, little is known about the use of item lists in clinical research. This systematic review addresses this by assessing utilization of PRO item libraries and lists in oncology research. METHODS: A systematic review of MEDLINE, Embase, and CINAHL identified cancer studies using PRO item libraries to develop item lists, regardless of study design, published between October 2021 and September 2025. Key features of item library usage were extracted and analyzed descriptively. RESULTS: A total of 78 studies were included (25 trials and feasibility, 53 observational). The Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events system was frequently used (49 of 78), and symptom assessment was the most common application (63 of 78). Item lists were implemented across different settings including novel treatments (19 of 78) and rare cancers (15 of 78). Most item lists were derived from a single PRO item library (72 of 78). In some studies, there was additional customization such as item wording changes (5 of 78) or addition of items adapted from the item library (9 of 78). Item selection methods included literature (32 of 78), patient involvement (8 of 78) and consultation with health-care professionals (11 of 78). Many studies (40 of 78) did not report methods used. CONCLUSIONS: PRO item libraries are increasingly used to create customized item lists in oncology research, primarily for symptom assessment. However, reporting practices for methods used are inconsistent, highlighting the need for standardized guidelines for reporting PRO item lists in clinical trials and routine care to improve transparency, reproducibility, and quality.
Koric A, Bennett DL, Boulos F
… +1 more, Colditz GA
J Natl Cancer Inst
· 2026 Feb · PMID 41697989
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BACKGROUND: The association between histological subtypes of benign breast disease (BBD) and risk of subsequent breast cancer in the post-mammography era of increased BBD detection, requires continued study to inform cli...BACKGROUND: The association between histological subtypes of benign breast disease (BBD) and risk of subsequent breast cancer in the post-mammography era of increased BBD detection, requires continued study to inform clinical management of high-risk women. METHODS: We identified a cohort of 8,915 women diagnosed with histologically-confirmed benign lesions between 2010 and 2023 from the Joanne Knight Breast Health Center in St. Louis. Risk of subsequent breast events after a benign biopsy was assessed with Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (95%CIs). RESULTS: Within a median follow-up of 6.5 years, 363 women developed breast cancer. The cohort was 63.7% White, 32.4% Black, and 3.9% Asian. Breast cancer risk increased across subtypes of BBD, from proliferative disease without hyperplasia (PDWA) to atypical hyperplasia (AH), with AH risk modified by time since biopsy and menopause. Compared with women with nonproliferative disease, age-adjusted risk for breast cancer was 1.69 for PDWA (HR = 95%CI 1.40, 2.30) and 2.78 for AH (HR = 2.78, 95%CI 2.01, 3.85, p trend < 0.0001). Risk estimates attenuated but remained similar in fully adjusted models. Risks associated with BBD subtypes were similar for Black and White women, but Black women with AH had greater risk of breast cancer since recent biopsy (≤4 years) and during the premenopausal period (p het = 0.033). CONCLUSION: Breast cancer risk increases with the degree of epithelial proliferation, highest in AH, amplified by recent biopsy and premenopause, particularly in Black women, consistent with the excess risk seen after ductal carcinoma in situ in this group.
Chhetri R, Modi ND, Menz BD
… +13 more, Cornelisse E, Postma D, Kuderer NM, Lyman GH, Swain SM, Li LX, Abuhelwa AY, McKinnon RA, Vatandoust S, Kichenadasse G, Rowland A, Sorich MJ, Hopkins AM
J Natl Cancer Inst
· 2026 Feb · PMID 41697987
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BACKGROUND: Sex is a recognised modifier of physiology, immunity, and social exposures, yet its independent association with survival and adverse event (AE) prognosis in contemporary anticancer therapy remains poorly def...BACKGROUND: Sex is a recognised modifier of physiology, immunity, and social exposures, yet its independent association with survival and adverse event (AE) prognosis in contemporary anticancer therapy remains poorly defined. The aim of the present study was to assess the association between patient sex and OS, PFS, and grade ≥3 AEs across a pooled individual participant data (IPD) meta-analysis. METHODS: IPD supporting FDA approval of anticancer medicines for solid tumours between 2011 and 2021 were accessed via the Vivli and YODA data sharing platforms. A two-stage random-effects meta-analysis approach was employed, using Cox proportional hazards regression to estimate sex-based prognostic differences in overall survival (OS), progression-free survival (PFS), and grade ≥3 AEs. Analyses were adjusted for key baseline covariates. RESULTS: In a pooled cohort of 20,806 participants from 39 phase II-III trials supporting US FDA approvals of anticancer medicines for advanced solid tumours, across 12 tumour types, female sex was associated with significantly improved OS (HR 0.79, 95% CI 0.73-0.85; P < 0.001) and PFS (HR 0.84, 95% CI 0.79-0.89; P < 0.001). Conversely, females experienced a higher risk of grade ≥3 AEs (HR 1.12, 95% CI 1.07-1.18; P < 0.001). CONCLUSIONS: In the largest analysis of IPD from trials supporting FDA drug approvals, we found that females had a 21% lower risk of death and a 16% lower risk of progression, but a 12% higher risk of severe adverse events. These findings highlight the value of the IPD sharing and the importance of sex-stratified evidence for risk stratification, dose optimisation and patient counselling.
Pocobelli G, Del Vecchio NJ, Cushing-Haugen K
… +12 more, Kamineni A, Corley DA, Rendle KA, Halm EA, Li CI, Oshiro CES, Carroll NM, Silver MI, Greenlee RT, Neslund-Dudas C, Breslau ES, Chubak J
J Natl Cancer Inst
· 2026 Feb · PMID 41697970
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Cancer screening guidelines specify ages at which routine screening should be discontinued and, except for cervical cancer screening, do not require specific screening history criteria be met for discontinuation. We esti...Cancer screening guidelines specify ages at which routine screening should be discontinued and, except for cervical cancer screening, do not require specific screening history criteria be met for discontinuation. We estimated the prevalence of being up to date with average-risk screening guidelines for colorectal, cervical, and lung cancer as of the recommended ages for discontinuation of routine screening. We conducted a descriptive study among several U.S. healthcare systems during 2010-2019. Up-to-date screening prevalence, based on U.S. Preventive Services Task Force guidelines, was ascertained prior to 76th, 66th, and 81st birthdays among persons eligible for colorectal (N = 316,756 persons), cervical (N = 20,282 persons), and lung cancer (N = 1,151 persons) screening, respectively. Up-to-date screening prevalence was 84.4% for colorectal, 58.9% for cervical, and 6.3% for lung cancer screening. Up-to-date screening prevalence at the ages recommended for discontinuing routine colorectal, cervical, and lung cancer screening varied appreciably, and was particularly low for lung cancer screening.
Rutter CM, Maerzluft CE, Matrajt L
… +3 more, Nascimento de Lima P, Issaka RB, Marsh TL
J Natl Cancer Inst
· 2026 Feb · PMID 41697969
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BACKGROUND: Microsimulation models use empirical evidence about cancer epidemiology and screening test performance to predict the long-term effectiveness of screening regimens and are essential for developing cancer scre...BACKGROUND: Microsimulation models use empirical evidence about cancer epidemiology and screening test performance to predict the long-term effectiveness of screening regimens and are essential for developing cancer screening guidelines. Colorectal cancer (CRC) provides a clear example. CRC arises through two pathways, the adenoma-carcinoma pathway and the serrated pathway. Sessile serrated lesions (SSLs) are the primary serrated precursor lesion. SSLs are more difficult to detect and remove than adenomas. METHODS: We describe version 3.0 of the Colorectal Cancer Simulated Population model for Incidence and Natural history (CRC-SPIN), which adds new information about the serrated pathway and CRC risk in adults under 50, then estimate the effectiveness of decennial colonoscopy from 45 to 75 years old. The model was calibrated using a Bayesian approach to estimate 95% credible intervals (CIs) that reflect uncertainty in predictions. RESULTS: The model validated well to studies of the effect of one-time screening and outcomes from surveillance colonoscopy. In the absence of screening, SSLs accounted for 10.6% (95% CI: 3.3-21.6) of CRC, increasing to 23.5% (95% CI: 7.7%-46.0%) with screening due to selective removal of adenomas. Screening was predicted to prevent 93.9% (95% CI: 92.0%-94.3%) of CRC and 95.3% (95% CI: 93.8%-96.5%) of CRC mortality. CONCLUSIONS: Although SSLs are less common than adenomas, they likely make up a large fraction of CRC that arises in people who participate in screening. This points to the importance of improving the ability to detect SSLs, especially large SSLs, at colonoscopy.
Kawashiri T, Yamamoto N, Fujiwara M
… +6 more, Shimizu T, Kobayashi D, Fujita S, Shibata N, Hirota T, Uchida M
J Natl Cancer Inst
· 2026 Feb · PMID 41691455
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BACKGROUND: Hematologic malignancies, including leukemias and lymphomas, remain life‑threatening diseases for which preventive strategies have not yet been established. Recent studies have suggested that sodium-glucose c...BACKGROUND: Hematologic malignancies, including leukemias and lymphomas, remain life‑threatening diseases for which preventive strategies have not yet been established. Recent studies have suggested that sodium-glucose cotransporter 2 (SGLT2) inhibitors have cancer-suppressive properties. This study investigated whether SGLT2 inhibitors are associated with reduced risk of hematologic malignancies in patients with diabetes, using a large-scale medical database. METHODS: Data of patients with diabetes prescribed diabetes medications were extracted from the JMDC Payer database (January 2005 to November 2023). After exclusions, patients were categorized into SGLT2 inhibitor (N = 158,877) and non-SGLT2 inhibitor (N = 118,678) groups. Propensity score matching, accounting for patient characteristics, resulted in 102,478 matched patients per group. The primary endpoint was time to hematologic malignancy; secondary endpoints were time to lymphoma, leukemia, and their subcategories. RESULTS: The incidence of hematologic malignancies was lower in the SGLT2 inhibitor group than in the non-SGLT2 inhibitor group (P<.001, hazard ratio (HR)=0.73[0.62-0.86], risk difference at 5 years (RD)=-0.16%). Lymphoma incidence was also lower in the SGLT2 inhibitor group (P=.003, HR = 0.71[0.57-0.89], RD=-0.12%), whereas no clear evidence of difference was observed for leukemia (P=.06, HR = 0.76[0.57-1.01], RD=-0.02%). Lymphocytic leukemia was associated with lower incidence compared to the non-SGLT2 inhibitor group (P=.04, HR = 0.44[0.19-0.99], RD=-0.02%), whereas no clear evidence of difference was observed for myeloid leukemia (P=.12, HR = 0.76[0.54-1.08], RD=-0.01%). Regarding acute myeloid leukemia (AML), the incidence was low in the SGLT2 inhibitor group (P=.001, HR = 0.34[0.19-0.62], RD=-0.05%). CONCLUSION: SGLT2 inhibitor use may be associated with lower risk of hematologic malignancies in adults with diabetes.
Kerns SL, Dinh PC, Monahan PO
… +10 more, Fung C, Sesso HD, Feldman DR, Hamilton RJ, Pierazio P, Huddart R, Kollmannsberger C, Martin NE, Einhorn LH, Travis LB
J Natl Cancer Inst
· 2026 Feb · PMID 41678227
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Testicular cancer survivors (TCS) experience excess cardiovascular disease (CVD) incidence and mortality. To address the urgent need for new risk prediction tools, we evaluated the AHA's 2024 PREVENT-equation among 1,759...Testicular cancer survivors (TCS) experience excess cardiovascular disease (CVD) incidence and mortality. To address the urgent need for new risk prediction tools, we evaluated the AHA's 2024 PREVENT-equation among 1,759 TC survivors (TCS; median baseline age = 37 years). Baseline median 10- and 30-year CVD risks were 1.3% and 9.1%. Among evaluated survivors with follow-up (N = 737; median age = 45), each 5% increase in 10-year PREVENT risk conferred 2.94-fold odds (95%CI = 1.99-4.35, P < .001) of incident CVD. Those with 10-year PREVENT absolute risk defined as intermediate-high (≥7.5% per AHA) had 12.11-fold higher odds (P < .001). Associations were strongest after four cycles of etoposide/cisplatin (EPX4) (OR = 4.93, P < .001), possibly driven by lower eGFR and slightly older age (P < .001 each), and among TCS without vigorous baseline physical-activity (OR = 4.25, P < .001). EPX4 patients were among those less engaged in activity (P = .005). PREVENT equations, utilizing routine measures, can identify high-risk TCS, highlighting physical-activity as a key modifiable factor for early intervention.
Huber JH, Wang M, Wang R
… +4 more, Schoen MW, Colditz GA, Wang SY, Chang SH
J Natl Cancer Inst
· 2026 Feb · PMID 41652897
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Surveillance, Epidemiology, and End Results (SEER) multiple myeloma (MM) survival statistics (https://seer.cancer.gov/statfacts/html/mulmy.html) that have been used to guide MM management and control have been systematic...Surveillance, Epidemiology, and End Results (SEER) multiple myeloma (MM) survival statistics (https://seer.cancer.gov/statfacts/html/mulmy.html) that have been used to guide MM management and control have been systematically overestimated due to the inclusion of smoldering multiple myeloma (SMM), a premalignant condition of MM. Using the latest SEER release, we estimated the extent of such overestimation in the survival statistics. In 2016, 77.9% out of 5,495 patients reported as overall MM were symptomatic MM and 10.9% were SMM. Median survival was 65.8 months for overall MM versus 56.8 months for symptomatic MM (p < .001). Inclusion of SMM overestimated MM survival by 9 months. Five-year relative survival estimates from 2015-2021 were 61.6% for overall MM, 57.9% for symptomatic MM, and 88.3% for SMM, versus SEER's reported 62.4%. Survival statistics for symptomatic MM and SMM should be reported separately to guide MM management and prevention at the population level.
J Natl Cancer Inst
· 2026 Feb · PMID 41639013
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The National Cancer Policy Forum (NCPF) of the National Academies of Sciences, Engineering, and Medicine was founded in 2006 to serve as a trusted venue for identifying and addressing high-priority policy issues in cance...The National Cancer Policy Forum (NCPF) of the National Academies of Sciences, Engineering, and Medicine was founded in 2006 to serve as a trusted venue for identifying and addressing high-priority policy issues in cancer research and care. NPCF takes a comprehensive, multisectoral, and multidisciplinary approach to strategically consider the entire continuum of cancer research and cancer care. Over the past two decades, the Forum has served a uniquely important role in examining both long-standing and emerging policy issues that are relevant to reducing the burden of cancer, both through prevention and by improving the care and outcomes for those diagnosed with cancer, and exploring solutions from multiple perspectives. The Forum has fostered actionable dialogue among a broad range of participants, including patient advocacy organizations, federal agencies, academia, professional organizations, nonprofits, and industry. NCPF activities inform the cancer community and the general public about a wide range of scientific, clinical, and policy issues through workshops, webinars, and the proceedings published after these convenings. Forum activities have influenced policy through the resulting publications and by providing input to National Academies consensus studies, which provide consensus recommendations. This commentary summarizes the breadth of topics addressed by the Forum over the years and examples of the impact of the Forum activities on policies and procedures, programs and practices, and participants and people around the globe.
Fischer MP, Mayer A, Braun A
… +11 more, Kraft J, Hansen CM, Baumgärtner GL, Asbach P, Padhani AR, Penzkofer T, König F, Awasthi S, Makowski MR, Ripke S, Hamm CA
J Natl Cancer Inst
· 2026 Jun · PMID 41629765
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BACKGROUND: Men with suspected prostate cancer undergo magnetic resonance imaging (MRI) before biopsy. However, approximately 30%-50% of MRIs are negative (Prostate Imaging-Reporting and Data System [PI-RADS] score 1-2),...BACKGROUND: Men with suspected prostate cancer undergo magnetic resonance imaging (MRI) before biopsy. However, approximately 30%-50% of MRIs are negative (Prostate Imaging-Reporting and Data System [PI-RADS] score 1-2), representing a challenge for MRI resource utilization. This study evaluates prostate cancer polygenic risk scores and clinical markers to optimize MRI utilization. METHODS: In this prospective study, 500 cancer-suspected men of Western European descent scheduled for MRI (September 2017-December 2022) were enrolled. Exclusions included prior prostate cancer diagnosis, missing serum prostate-specific antigen (PSA), or PSA levels of at least 25 ng/mL. Patient-specific prostate cancer polygenic risk scores were calculated using genotype data obtained from saliva-derived DNA samples. Participants were grouped as MRI negative and positive (PI-RADS score 3-5). Logistic regression was used to calculate odds ratios (ORs) and to build multivariable risk models, including age, PSA, and polygenic risk scores for MRI positivity. Clinical utility was tested in a holdout test set using decision curve analysis. RESULTS: A total of 386 men (median age = 65 years, interquartile range [IQR] = 53-77 years) were eligible for analysis, which showed statistically significant associations between prostate cancer polygenic risk scores (OR = 1.56, 95% confidence interval [CI] = 1.23 to 1.98; P < .001) with MRI positivity, while PSA alone did not (OR = 1.17, 95% CI = 0.93 to 1.46; P = .18). The highest net benefit was shown using a multivariable age and prostate cancer polygenic risk score model, increasing the proportion of MRI-positive men by 14% compared with PSA alone (60% and 46%, respectively; P = .011). CONCLUSIONS: Genotype-informed risk stratification using prostate cancer polygenic risk scores could increase the proportion of cancer-suspicious findings at MRI, while identifying those who could safely avoid unnecessary MRI.
Ward MC, Kang JJ, Saba NF
… +8 more, Campbell SR, Akhave NS, Chang SS, Spencer SA, Spreafico A, Hanna GJ, Yom SS, Heron DE
J Natl Cancer Inst
· 2026 Feb · PMID 41629764
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Despite decades of progress in the treatment of head and neck cancer, recurrence and second primary cancers continue to occur. The management of non-metastatic, locoregionally recurrent or second primary cancers is a com...Despite decades of progress in the treatment of head and neck cancer, recurrence and second primary cancers continue to occur. The management of non-metastatic, locoregionally recurrent or second primary cancers is a complex multidisciplinary challenge that often occurs without guidance from robust clinical trials. In 2023, the NRG Oncology cooperative group created the Recurrent and Metastatic Working Group with the express directive to investigate how resources could optimally address the key questions for the recurrent and metastatic populations. Here, we present our view of the state of the science and present considerations for future investigations.
Herrera M, Ward M, Hanna GJ
… +3 more, Yom SS, Heron D, Spreafico A
J Natl Cancer Inst
· 2026 Feb · PMID 41627880
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Head and neck cancers represent a diverse group of malignancies with significant heterogeneity in biology and prognosis, for which management of advanced-stage disease remains a formidable challenge. While the incorporat...Head and neck cancers represent a diverse group of malignancies with significant heterogeneity in biology and prognosis, for which management of advanced-stage disease remains a formidable challenge. While the incorporation of immune checkpoint inhibitors has led the way to a new era of treatment possibilities, the current state-of-the-science calls for further innovation and a nuanced approach to clinical trial design to address a number of unmet needs. This white paper from the NRG Oncology Recurrent/Metastatic Head and Neck Working Group aims to critically identify gaps in clinical practice and the scientific literature and to propose actionable recommendations for future research in the framework of recurrent/metastatic squamous cell carcinoma of the head and neck.