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Background Financial toxicity (FT), encompassing objective and subjective impacts of cancer care costs, is linked to poorer quality of life, reduced treatment adherence, and higher mortality. While patient‐level risk factors have been examined, a system‐level perspective incorporating socioeconomic context is needed to understand global variation in FT. Methods MEDLINE, CINAHL, Embase, and Web of Science were searched from inception to 06/27/2025 for peer‐reviewed, English‐language studies describing self‐reported FT outcomes among adults with cancer. Reviewers extracted study characteristics, FT prevalence, predictors, and measurement tools. Financial, physical, and social asset measures from the World Bank were merged with FT data by study country and year of data collection. Focusing on studies reporting Comprehensive Score for Financial Toxicity (COST) scores, multilevel random effects meta‐analysis was performed. Univariate and multivariate multilevel meta‐regression evaluated relationships between country‐level assets and COST. Results One hundred thirty‐two studies from 22 countries were included, with FT prevalence ranging from 4.0% to 100.0%. Three‐level meta‐analysis of 75 COST‐based studies (15 countries; 83,623 patients) yielded a pooled mean COST score of 21.2 (95% CI: 19.1–23.3; 95% prediction interval: 13.3–32.4), though substantial heterogeneity (I2 = 99.2%) and a predominance of studies from the US (55%) limited its standalone interpretability. Variance decomposition showed that 46% of heterogeneity was attributable to between‐country differences. Higher log GDP per capita was associated with higher COST (β = 4.44, 95% CI: 2.90–5.98), explaining 43.1% of between‐country variance. Higher out‐of‐pocket health expenditure, population‐level financial hardship, and vulnerable employment were associated with worse FT. GDP associations were robust to sensitivity analyses excluding US‐based studies. Conclusions FT among cancer patients is linked to structural conditions governing access to education, employment, and financial systems, although expanded research in low‐resource settings is needed. These findings highlight the roles of economic development strategies and investment in human capital in helping to safeguard against population‐level FT.

Objective Given growing recognition that social determinants of health influence cancer outcomes and functional status, we sought to examine associations between social vulnerability, measured by CDC's Social Vulnerability Index (SVI), and pretreatment swallowing function, quantified by Modified Barium Swallow Impairment Profiles (MBSImP), in patients with oropharyngeal squamous cell carcinoma (OPSCC). Study Design and Setting Retrospective analysis of patients at Northwestern University with pretreatment MBSImP studies. Methods MBSImP oral total (OT) and pharyngeal total (PT) scores were calculated, and SVI assigned to patient residential address at diagnosis. Associations between overall SVI, SVI subcomponents, clinical variables, and OT and PT scores were assessed using univariable and multivariable linear regression. Results 149 OPSCC patients with median age 63 years; 83.9% were male, 89.9% White, and 91.9% p16+. On univariable analysis, SVI was significantly associated with higher (worse) OT (β = 3.3; 95% CI: 1.8, 4.8; P < .001) and PT scores (β = 3.6; 95% CI: 0.75, 6.4; P = .013). After multivariable adjustment, SVI remained independently associated with increased OT scores (β = 2.3; 95% CI: 0.36, 4.2; P = .020); PT impairment was independently predicted by tumor subsite (tonsil vs. base of tongue: β = −1.8; 95% CI: −3.4, −0.28; P = .021). All four SVI domains were significantly linked to OT in univariable models. Conclusion Social vulnerability independently predicts oral‐phase swallowing impairment in OPSCC patients, while tumor subsite primarily determines pharyngeal swallowing impairment. These findings highlight the need to consider social determinants in pretreatment assessment, as well as further research to clarify how social determinants impact swallowing outcomes to identify effective, targeted interventions for high‐risk groups.

The international Intermediate Clinical Endpoints in Cancer of the Prostate working group has established metastasis-free survival as a surrogate for overall survival in localised prostate cancer based on the findings of 19 predominantly radiotherapy-based trials. We sought to comprehensively assess aggregate trial-level performance of commonly reported intermediate clinical endpoints across all randomised trials in localised prostate cancer. For this meta-analysis, we searched PubMed for all trials in localised or biochemically recurrent prostate cancer published between Jan 1, 1970, and Jan 15, 2020. Eligible trials had to be randomised, therapeutic, reporting overall survival and at least one intermediate clinical endpoint, and with a sample size of at least 70 participants. Trials of metastatic disease were excluded. Intermediate clinical endpoints included biochemical failure, local failure, distant metastases, biochemical failure-free survival, progression-free survival, and metastasis-free survival. Candidacy for surrogacy was assessed using the second condition of the meta-analytical approach (ie, correlation of the treatment effect of the intermediate clinical endpoint and overall survival), using R2 weighted by the inverse variance of the log intermediate clinical endpoint hazard ratio. The intermediate clinical endpoint was deemed to be a surrogate for overall survival if R2 was 0·7 or greater. 75 trials (53 631 patients) were included in our analysis. Median follow-up was 9·1 years (IQR 5·7–10·6). Biochemical failure (R2 0·38 [95% CI 0·11–0·64]), biochemical failure-free survival (R2 0·12 [0·0030–0·33]), biochemical failure and clinical failure (R2 0·28 [0·0045–0·65]), and local failure (R2 0·085 [0·00–0·37]) correlated poorly with overall survival. Progression-free survival (R2 0·46 [95% CI 0·22–0·67]) showed moderate correlation with overall survival, and metastasis-free survival (R2 0·78 [0·59–0·89]) correlated strongly. Intermediate clinical endpoints based on biochemical and local failure did not meet the second condition of the meta-analytical approach and are not surrogate endpoints for overall survival in localised prostate cancer. Our findings validate metastasis-free survival as the only identified surrogate endpoint for overall survival to date. Prostate Cancer Foundation and National Institutes of Health.

Purpose Patients with head/neck squamous cell carcinomas (HNSCC) experience significant tumor- and treatment-related side effects. No efficient summary measure capturing the totality of side effect burden currently exists. We examined associations between a single patient-reported outcome (PRO) item evaluating side effect bother (FACT GP5, “I am bothered by side effects of treatment”) with overall side effects in HNSCC. Methods We performed a retrospective secondary analysis of development of the Functional Assessment of Cancer Therapy (FACT) Head/Neck Symptom Index (FHNSI-10), which included completing FACT-HN (including Head/Neck Cancer Subscale (HNCS) and Trial Outcome Index (TOI)) and the pain intensity numeric rating scale (NRS). We calculated Spearman’s correlations between GP5 and these measures of patient-reported global health, head/neck side effects, and pain intensity NRS. A correlation of > 0.4 was considered sufficient evidence of association. Results Ninety-seven patients completed baseline and 85 completed 3-month follow-up surveys. GP5 was highly correlated with FACT-HN total score (baseline r  = 0.66, 3 months r  = 0.67) and FHNSI-10 (baseline r  = 0.63, 3 months r  = 0.65). GP5 correlated with multiple FACT-HN subscales including FACT-G, physical well-being, functional well-being, HNCS, and TOI (range baseline r  = 0.53–0.77, range 3 months r  = 0.49–0.77). Worsening GP5 score was associated with worsening overall HNCS ( p  = 0.002), worsening FHNSI-10 score ( p  < 0.001), and worsening mean pain intensity ( p  < 0.001). Conclusion GP5 exhibited validity within HNSCC, exhibiting substantial correlations with a number of HNSCC-related PRO measures including FACT-HN and FHNSI-10. Worsening GP5 was associated with worsening HNCS, FHNSI summary score, and pain intensity. GP5 has promise as a summary indicator of symptom and side effect bother in HNSCC.

Abstract Context Adrenocortical carcinoma (ACC) is a rare malignancy with high rates of recurrence and poor prognosis. The role of radiotherapy (RT) in localized ACC has been controversial, and RT is not routinely offered. Objective To evaluate the benefit of adjuvant RT on outcomes in ACC. Design This is a retrospective propensity-matched analysis. Setting All patients were seen through the University of Michigan’s Endocrine Oncology program, and all those who underwent RT were treated at the University of Michigan. Participants Of 424 patients with ACC, 78 were selected; 39 patients underwent adjuvant radiation. Intervention Adjuvant RT to the tumor bed and adjacent lymph nodes. Main Outcomes Measures Time to local failure, distant failure, or death. Results Median follow-up time was 4.21 years (95% CI, 2.79 to 4.94). The median radiation dose was 55 Gy (range, 45 to 60). The 3-year overall survival estimate for patients improved from 48.6% for patients without RT (95% CI, 29.7 to 65.2) to 77.7% (95% CI, 56.3 to 89.5) with RT, with a hazard ratio (HR) of 3.59 (95% CI, 1.60 to 8.09; P = 0.002). RT improved local recurrence-free survival (RFS) from 34.2% (95% CI, 18.8 to 50.3) to 59.5% (95% CI, 39.0 to 75.0), with an HR of 2.67 (95% CI, 1.38 to 5.19; P = 0.0035). RT improved all RFS from 18.3% (95% CI, 6.7 to 34.3) to 46.7% (95% CI, 26.9 to 64.3), with an HR 2.59 (95% CI, 1.40 to 4.79; P = 0.0024). Conclusions In the largest single institution study to date, adjuvant RT after gross resection of ACC improved local RFS, all RFS, and overall survival in this propensity-matched analysis. Adjuvant RT should be considered a part of multidisciplinary management for patients with ACC. It is unknown if adjuvant radiotherapy in patients with ACC improves outcomes. In this retrospective study, adjuvant radiotherapy improved outcomes for patients with ACC.

Introduction Patients with head and neck squamous cell carcinoma (HNSCC) are at risk for long-term side effects and require thorough survivorship care following completion of radiation therapy (RT). We aimed to identify survivorship interest and needs following RT. Methods Patients with HNSCC who completed RT from Jan 2013 to April 2023 completed questions based on the five-domain Cancer Survivorship Framework (physical effects, psychosocial effects, cancer screening, chronic conditions, health promotion) and the Consolidated Framework for Implementation Research (interest, knowledge, barriers). Results Of 1,123 patients, 317 participated (response rate 28%). Patients were 64% ( n  = 203) male with a mean age of 64 years (SD 12), with 66% ( n  = 209) finishing treatment > 2-years prior. 36% ( n  = 115) were interested in, 34% ( n  = 108) prioritized, and 28% ( n  = 88) had information related to survivorship. For survivorship domains, within physical effects, dry mouth (40%, n  = 126) and trouble swallowing (24%, n  = 75) were most bothersome. For psychosocial, 15% ( n  = 46) reported current depression (mean PHQ2 score ≥ 3) and 71% ( n  = 226) felt mental health needs were not addressed during treatment. Forty-two percent felt that diet, exercise, and smoking were not addressed ( n  = 134). Seventy-six percent ( n  = 240) understood the importance of cancer screening. Most patients wished to address survivorship topics in one long visit (45%, n  = 142) and preferred in-person visits (60%, n  = 190). Potential barriers included insurance coverage and scheduling concerns. Conclusion In post-RT HNSCC survivors, survivorship interest and knowledge were limited. There is a need for education on survivorship. Implications These findings provide a foundation for developing robust survivorship care programs that meet the diverse needs of this patient population.

The increased incidence of human papillomavirus (HPV)-related cancers has motivated efforts to optimise treatment for these patients with excellent prognosis. Validation of surrogates for overall survival could expedite the investigation of new therapies. We sought to evaluate candidate intermediate clinical endpoints in trials assessing definitive treatment of p16-positive oropharyngeal cancer with chemotherapy or radiotherapy. We did a retrospective review of five multicentre, randomised trials (NRG/RTOG 9003, 0129, 0234, 0522, and 1016) that tested radiotherapy with or without chemotherapy in patients (aged ≥18 years) with p16-positive localised head or neck squamous-cell carcinomas. Eight intermediate clinical endpoints were considered as potential surrogates for overall survival: freedom from local progression, freedom from regional progression, freedom from distant metastasis, freedom from locoregional progression, freedom from any progression, locoregional progression-free survival, progression-free survival, and distant metastasis-free survival. We used a two-stage meta-analytical framework, which requires high correlation between the intermediate clinical endpoint and overall survival at the patient level (condition 1), and high correlation between the treatment effect on the intermediate clinical endpoint and the treatment effect on overall survival (condition 2). For both, an r2 greater than 0·7 was used as criteria for clinically relevant surrogacy. We analysed 1373 patients with oropharyngeal cancer from May 9, 2020, to Nov 22, 2023. 1231 (90%) of patients were men, 142 (10%) were women, and 1207 (88%) were White, with a median age of 57 years (IQR 51–62). Median follow-up was 4·2 years (3·1–5·1). For the first condition, correlating the intermediate clinical endpoints with overall survival at the individual and trial level, the three composite endpoints of locoregional progression-free survival (Kendall's τ 0·91 and r2 0·72), distant metastasis-free survival (Kendall's τ 0·93 and r2 0·83), and progression-free survival (Kendall's τ 0·88 and r2 0·70) were highly correlated with overall survival at the patient level and at the trial-group level. For the second condition, correlating treatment effects of the intermediate clinical endpoints and overall survival, the composite endpoints of locoregional progression-free survival (r2 0·88), distant metastasis-free survival (r2 0·96), and progression-free survival (r2 0·92) remained strong surrogates. Treatment effects on the remaining intermediate clinical endpoints were less strongly correlated with overall survival. We identified locoregional progression-free survival, distant metastasis-free survival, and progression-free survival as surrogates for overall survival in p16-positive oropharyngeal cancers treated with chemotherapy or radiotherapy, which could serve as clinical trial endpoints. NRG Oncology Operations, NRG Oncology SDMC, the National Cancer Institute, Eli Lilly, Aventis, and the University of Michigan.

PurposeAccrual to clinical trials that challenge well-established treatment paradigms represents a unique challenge. Physician opinions on investigation of a novel approach to breast cancer treatment, in which patients with complete response to neoadjuvant chemotherapy are offered omission of lumpectomy, are unknown. NRG-CC006 sought to describe physician attitudes toward a novel approach to breast cancer treatment.MethodsWe recruited 18 participants in the fields of surgery, medical oncology, and radiation oncology to participate in the semi-structured telephone interviews. Main outcomes are qualitative themes associated with omission of surgery.ResultsOf 18 interview participants, specialty and gender were evenly represented across surgery, medical oncology, and radiation oncology. Qualitative themes included general attitudes toward treatment de-escalation, stakeholder considerations, and trial/protocol considerations. The vast majority of participants expressed interest in investigation of omission of surgery, with all participants endorsing need for further investigation into treatment de-escalation. Stakeholder considerations in opening such a trial emphasized need for multidisciplinary involvement and, particularly, the unique role of surgeons as gatekeepers in breast cancer treatment. Finally, participants endorsed a need for further foundational studies to develop ways to predict complete pathologic response to chemotherapy without surgical intervention.ConclusionsPhysicians expressed interest in investigating a novel approach to breast cancer treatment that would omit surgery in complete responders to neoadjuvant chemotherapy. Multidisciplinary input, and specifically surgeon engagement, will be key to the success of future investigations. Ongoing work to develop approaches to predict pathologic complete response accurately is needed to achieve the promise of this idea.ClinTrials #: BR005: NCT03188393 June 13, 2017