Industry financial ties to the US cancer ecosystem are everywhere. Kim et al.'s systematic review and meta-analysis finds that financial conflicts of interest exceed 50% prevalence across most oncology domains. These relationships are not always benign. A robust body of health services research, including a 2021 systematic review of 36 studies, demonstrates that 83% of analyses identify a positive association between industry payments and prescribing behavior. Even a single industry-sponsored meal costing <$20 has been linked to significantly higher odds of prescribing the promoted drug. As federal National Institute of Health (NIH) funding faces cuts, industry's role in shaping the research agenda will only expand. Current US policy responses such as the disclosure through the Sunshine Act and dollar thresholds for guideline panelists have had minimal effectiveness in curtailing the money flowing to oncologists. This editorial argues for stronger structural reforms, specifically mandatory cooling-off periods for guideline committee members modeled on existing federal ethics statutes. Disclosure alone is insufficient, and some evidence suggests it may paradoxically license conflicted behavior. Meaningful progress requires moving beyond transparency toward policies that prevent conflicts from influencing clinical decision making.
BACKGROUND:Asian Americans (AA), Native Hawaiians, and Pacific Islanders (NHPI), collectively referred to as AANHPI, are heterogeneous populations with varying cancer risks across ethnic groups. Incidence rates and trends are examined for eight AA groups (Asian Indian/Pakistani, Chinese (including Taiwanese), Filipino, Japanese, Kampuchean, Korean, Laotian, and Vietnamese) and three NHPI groups (Native Hawaiian, Guamanian/Chamorro, and Samoan). METHODS:Annual cancer incidence from 21 Surveillance, Epidemiology, End Results (SEER) registries and population denominators from 2000-2022 were used to calculate incidence rates and average annual percentage change (AAPC). RESULTS:Among females, top five cancers included breast, lung, colon and rectum (CRC), uterus, and thyroid. Cancer incidence trends for breast and uterus were stable or increasing in most groups (AAPC: 0.68% to 5.29% for breast across ethnic groups; 2.13% to 3.65% for uterus). CRC trends were stable or decreasing (-4.01% to-1.06%), except among Asian Indians/Pakistanis (AAPC: 0.79%). Lung cancer increased among Asian Indians/Pakistanis (2.30%) but decreased among Chinese (-1.96%). Thyroid trends increased among Japanese (1.92%) and Vietnamese (1.35%).Among males, top five cancers included prostate, lung, CRC, liver, and non-Hodgkin lymphoma (NHL). Lung, CRC, and liver trends were stable or decreasing in most groups. Prostate trends increased in most groups (2.12% to 5.03%) but decreased among Laotians (-11.79%), Guamanians/Chamorros (-4.67%) and Samoans (-6.89%). NHL trends increased among Asian Indians/Pakistanis (0.98%) and Chinese (1.12%). CONCLUSIONS:A nationwide SEER database for evaluating cancer incidence trends through 2022 in disaggregated AANHPI groups is now available from SEER. It highlights ethnically distinct contemporary patterns relevant to research and cancer control initiatives.
INTRODUCTION:Depression and anxiety are common in adults with colorectal cancer (CRC), especially during chemotherapy, yet underlying biosocial mechanisms remain unclear. We examined whether biological age predicts these symptoms and whether neighborhood deprivation amplifies risk. METHODS:This secondary de-identified EHR analysis (2017-2023) included adults (≥18) with stage II-III CRC receiving chemotherapy (N = 958). Biological age was measured using nine blood biomarkers (i.e., Levine Clinical Biological Age). Depression and anxiety were assessed using PHQ-9 and GAD-7 tools. The Area Deprivation Index (ADI) was used to quantify neighborhood deprivation. Multivariable linear regression examined associations between biological aging and psychological symptoms over 6 months, with Benjamini-Hochberg adjustment (q-values) for multiple testing. RESULTS:Mean biological age was 65.9 years at baseline and increased by 3 years during chemotherapy. Participants reported moderate depression and anxiety symptoms at baseline. In adjusted analyses, increases in biological age were associated with worsening depressive symptoms (B = 0.18, q = 0.048), while higher baseline biological age was associated with greater baseline depressive symptom severity (B = 0.31, q = 0.008). Neighborhood deprivation strengthened associations between biological aging and depressive symptoms at baseline and over time, including changes in biological age and age acceleration (all q ≤ 0.049). CONCLUSIONS:Blood biomarker-based biological age may indicate elevated risk of psychological distress in CRC, particularly in socioeconomically deprived neighborhoods. Integrating biological age and geospatial context may improve high-risk patient identification and guide targeted mental health care.
Proton beam radiotherapy (PBRT) offers dosimetric advantages over intensity-modulated radiation therapy (IMRT), but prospective randomized data in the postoperative unilateral head and neck cancer setting remain limited. We conducted a multicenter, randomized phase II trial comparing PBRT and IMRT for patients with resected, well-lateralized head and neck cancers requiring unilateral adjuvant radiotherapy. Adults were randomized 1:1 to receive PBRT or IMRT to 60 Gy (relative biological effectiveness) in 30 fractions, with elective regions treated to 54 Gy. The primary endpoint was clinician-reported acute grade ≥2 oral mucositis through 3 months after radiotherapy. Ninety-eight patients were analyzable (PBRT, n = 54; IMRT, n = 44) with a median follow-up of 27.2 months. Acute grade ≥2 oral mucositis occurred less frequently with PBRT than IMRT (7.4% versus 22.7%, P = 0.03), as did acute grade ≥2 dysgeusia (9.3% versus 31.8%, P = 0.005). Rates of grade ≥3 dermatitis and grade ≥2 dysphagia were similar between groups, and late toxicities were uncommon with no grade 3 events. Patient-reported outcomes mirrored these findings, although confidence intervals were wide. Three-year local control, progression-free survival, and overall survival were high and were no different between arms. These findings indicate that PBRT reduces clinician-graded acute mucosal toxicity compared with IMRT in unilateral postoperative head and neck radiotherapy, in the context of some numerical but not statistically significant differences in patient-reported outcomes. ClinicalTrials.gov: NCT02923570.
INTRODUCTION:While broad genomic profiling is increasingly used in advanced NSCLC (aNSCLC), the impact of test results on subsequent guideline-concordant targeted therapy selection remains incompletely understood. METHODS:Using a merged dataset of two large, nationwide, patient-level databases, we identified patients who were diagnosed with aNSCLC 2017-2023, had potentially actionable genomic profiling findings, and initiated systemic therapy. Patients were categorized into actionability subgroups based on contemporaneous regulatory approvals and NCCN guideline recommendations. Within each subgroup, we assessed receipt of guideline-concordant targeted therapy within 24 months, including potential underuse (non-receipt of recommended treatment) and overuse (receipt of non-recommended treatment). RESULTS:Among 6620 patients (67.4% ≥65 years, 54.6% female, 68.9% White), guideline-concordant targeted therapy use varied substantially by actionability category: 2313 (89.6%) of 2582 patients with available 1st-line on-label options received them (10.4% underuse), while 212 (67.3%) of 315 patients with available later-line on-label options received them after 1st-line (32.7% underuse). Among 441 patients with available guideline-concordant off-label options, only 122 (27.7%) received them (72.3% underuse). Conversely, 238 (8.6%) of 3282 patients received matched but guideline-discordant off-label options, representing overuse of ineffective or unestablished therapies. Smoking history, squamous histology, and high PD-L1 expression were associated with lower targeted therapy receipt. CONCLUSIONS:In this cohort study of aNSCLC care, the guideline concordance of targeted therapy use varied by clinical actionability of molecular testing results. Underuse was more common in patients with later-line and off-label targeted therapy options. Patients with classical smoking-related risk profiles were substantially less likely to receive targeted therapy even when actionable alterations were identified.
BACKGROUND:Patients with rare cancers have consistently been reported to have poorer survival than patients with common cancers. We hypothesized that the excess mortality could be attributable to differences in tumor histology and stage at diagnosis and, explored whether it reflected a broader relationship between cancer incidence and mortality. METHODS:In a nationwide, population-based cohort study, we included adults diagnosed with a first primary solid malignant tumor in Denmark between 2004 and 2023. Cancers were classified according to Tier 2 of the RARECAREnet classification (rare cancer: incidence <6/100.000). Hazard ratios (HRs) of all-cause mortality according to rarity were estimated using Cox regression adjusted for age, sex and calendar period. Additional analyses further adjusted for tumor histology and stage at diagnosis. Tumor entities were also grouped into six incidence categories to examine survival across the incidence continuum. RESULTS:20.6% of cancer patients were diagnosed with a rare cancer. Patients with rare cancers had a 74% higher mortality than those with common cancers (HR: 1.74, 95% CI: 1.72 to 1.76), but mortality did not generally increase with increasing rarity. After adjustment for tumor histology and stage at diagnosis, the HR was close to unity (HR: 0.96, 95% CI: 0.95 to 0.98). CONCLUSION:Patients with rare cancers experienced higher mortality than those with common cancers. The excess mortality was attenuated after adjustment for tumor histology and stage at diagnosis, indicating that these factors largely explain the survival disadvantage in rare cancers. Improving outcomes for patients with rare cancers should focus on earlier diagnosis and tumor-specific management.
BACKGROUND:The 10-Item Frailty Index Based on a Comprehensive Geriatric Assessment (FI-CGA-10) is a content- and construct-validated measure for quantifying frailty from a CGA. For criterion validation, we assessed its predictive validity for overall survival (OS) in older adults with cancer. METHODS:This prospective cohort study included 1,630 patients with cancer who underwent CGA at a geriatric oncology service (median age 80 years). The FI-CGA-10 comprises ten CGA domains; deficits in each domain were scored 0 (no problem), 0.5 (minor problem), or 1.0 (major problem). Domain scores were summed, divided by 10 (range 0-1), and categorized as fit (<0.20), pre-frail (0.20-0.35), or frail (>0.35). Two Cox proportional hazards models estimated hazard ratios (HRs) for OS: a base model (age, sex, cancer type, and stage) and the base model plus FI-CGA-10 as a categorical variable. Model performance was compared using the likelihood-ratio (LR) test and Harrell's c-index. RESULTS:Overall, 22% were fit, 38% pre-frail, and 40% frail; 28% died within one year. Adding FI-CGA-10 to the base model improved prediction (LR χ² = 140.7; P < .001) and increased the c-index from 0.70 to 0.76 (P < .001). Adjusted HRs for pre-frail and frail (vs. fit) were 2.26 (95% CI, 1.61-3.19) and 5.06 (95% CI, 3.64-7.04), respectively. 1-year OS was 87% (fit), 74% (pre-frail), and 55% (frail). Major problems across all ten domains and minor problems in six domains were associated with worse OS in adjusted models. CONCLUSION:This study provides evidence supporting the predictive validity of the FI-CGA-10 for OS.
BACKGROUND:Tissue-based gene expression assays provide prognostic information in prostate cancer, but their influence on decisions regarding immediate treatment versus conservative management, including active surveillance (AS) and watchful waiting (WW), remains uncertain. METHODS:Using a linkage with the Surveillance, Epidemiology, and End Results program, we evaluated the association between a 22-gene genomic classifier (GC) and initial management among patients with low or intermediate clinical-risk prostate cancer diagnosed from 2015 through 2018. Initial management was classified as immediate therapy or AS/WW, and GC scores were grouped as low (<0.45), intermediate (0.45-0.60), or high (>0.60). Multivariable logistic regression assessed associations between GC category and immediate treatment, stratified by clinical-risk group and adjusted for demographic and clinical covariates. RESULTS:Among 2,547 patients, 286 of 1,030 (27.8%) with low- and 1,113 of 1,517 (73.4%) with intermediate clinical-risk prostate cancer received initial treatment. Use of initial treatment increased with higher GC category. Among patients with low and intermediate clinical-risk prostate cancer, respectively, 20.5% and 57.5% with low GC, 28.3% and 75.8% with intermediate GC, and 46.2% and 88.3% with high GC scores received initial treatment. Higher GC category was independently associated with greater odds of immediate treatment versus AS/WW (versus low GC: intermediate GC, odds ratio [OR] 1.98, 95% confidence interval [CI] 1.57-2.49, p < 0.001; high GC, OR 4.42, 95% CI 3.41-5.71, p < 0.001). CONCLUSIONS:Higher GC scores were associated with greater use of immediate treatment and less use of AS/WW, underscoring the need to determine whether GC testing also predicts long-term outcomes among patients managed with AS.
AIM:Inclusivity within head and neck cancer trials remains poorly characterised potentially limiting the applicability and validity of findings to under-represented groups. Using inclusive frameworks that enhance trial design and delivery for under-served groups we conducted a systematic review of Phase 3 UK-sponsored Head and Heck trial protocols over the last decade. METHODS:Head and Neck Phase 3 trial protocols registered between July 2014 to July 2024 were retrieved from the ISRCTN and ClinicalTrials.gov registries. Trial protocols were assessed using PRO-EDI (Patient-Reported Outcomes for Equity, Diversity, and Inclusion) and the NHIR INCLUDE framework, and findings summarized narratively. Participant characteristics collated included age, sex, race/ethnicity, socioeconomic status, education and disability. RESULTS:A total of 2,157 trial protocols were identified (2,029 ISRCTN and 128 Clinicaltrials.gov) and screened. Fourteen trial protocols met inclusion criteria for final analysis. Reporting of inclusion-related characteristics was inconsistent. Most trials (85.7%) imposed no upper age limit. Only 14.3% of trial protocols referenced ethnicity or socioeconomic status, and 28.6% mandated English proficiency without translation support. Only 28.6% trial protocols explicitly mention biological sex. None documented health literacy considerations or planned subgroup analyses. CONCLUSION:Overall, trial protocols demonstrated lack of inclusive considerations, underscoring the continued gap between policy and practice. The recently published NIHR's mandatory inclusion requirements, evolving standards in journal-led inclusive reporting in research trials and emerging initiatives akin to START-EDI, present opportunities to strengthen transparency, accountability and enhance representation in future head and neck cancer trials.
BACKGROUND:Leiomyosarcoma, the commonest subtype of soft tissue sarcoma, affects a wide range of anatomical sites. Few multi-site analyses of leiomyosarcoma have been performed to characterise differences across anatomical sites, and to identify patient or tumour characteristics independently associated with survival. Such information is critical to inform future design of pan-site trials necessary due to the rarity of leiomyosarcoma. METHODS:We analysed a study cohort of 11,751 patients with leiomyosarcoma across a range of anatomical sites. RESULTS:The uterus(36.3%), limbs(16.6%), superficial trunk(10.8%) and retroperitoneum (9.2%) were the most common anatomical sites. Median follow-up time was 8.4 years. Uterine tumours accounted for a greater proportion in black patients(P-adj<0.001), while the skin(P-adj<0.001) and limbs(P-adj<0.001) were more common sites in the white population. Marked differences in age, grade and stage at diagnosis were observed across anatomical sites. Multivariable analysis identified site, grade, race, marital status and household income as independently associated with outcome: individuals of black race, widowed patients, and those with the lowest income demonstrated significantly shorter survival. The uterus, urinary tract and trunk were among the highest risk sites, while the limbs, head and neck, and male reproductive tract were associated with more favourable outcomes after adjustment. ATRX mutations were enriched(P-adj<0.0001) within uterine cases compared to other sites in a pooled analysis of publicly available sequencing. CONCLUSION:Major disparities in outcome are clear across leiomyosarcoma subgroups defined by anatomical site and patient characteristics. Future trials may wish to account for the intrinsic aggressiveness of tumours arising at different anatomical locations.
BACKGROUND:Women with chronic inflammatory disorders such as rheumatoid arthritis (RA) and spondyloarthritis (SpA) are at increased risk for cervical precancer (CIN2+). It is unknown whether their human papillomavirus (HPV) status differs compared with a general screening population. OBJECTIVES:To determine whether cervical screening reliant on HPV16/18 detection would be appropriate also in RA/SpA. METHODS:We included women with (1) RA (n = 53 816) or (2) SpA (n = 25 496) who were naïve to biologic-/targeted synthetic-disease-modifying anti-rheumatic drugs (b/tsDMARD), (3) women with RA (n = 14 033) or (4) SpA (n = 8297) starting a first b/tsDMARD, and matched (1:5) general population comparators, n = 504 290). Incident HPV infection was categorized as positive for HPV16/18, and/or other (non-16/18) HPV types. Relative risks (RRs) were assessed through log-binomial regression. RESULTS:Women with RA, whether exposed to b/tsDMARDs or not, had a higher prevalence of HPV (statistically significant RR of 1.17-1.18 vs comparators). Among women with SpA, risks were elevated in b/tsDMARD-exposed, as were other (non-16/18) HPV types. B/tsDMARD-naïve women with RA (but not those with bionaïve SpA) had higher risk for CIN2+ than comparators (RR = 1.20, 95% CI = 1.07 to 1.34). However, the proportion of women with CIN2+ positive for HPV16/18 or other HPV types did not differ vs comparators, neither in RA nor in SpA and whether b/tsDMARD-exposed or not. CONCLUSION:Although some women with RA or SpA have higher risks for HPV and CIN2+ than the general population, their proportions of HPV16/18 vs other HPV types in CIN2+ do not differ. This is reassuring for cervical screening risk-stratifying women based on HPV16/18 detection.
Optimal indications for adjuvant CDK4/6 inhibitors in hormone receptor-positive/HER2-negative early breast cancer remain debated, partly because monarchE and NATALEE trials used different eligibility criteria. Using pooled individual patient-level data from three randomized trials conducted before adjuvant CDK4/6 inhibitors (N = 4,795), we estimated baseline prognosis in eligibility-defined subgroups. Among patients with 1-3 positive lymph nodes (N1; N = 1,646), monarchE high-risk features (tumor size ≥5 cm and/or grade 3) identified a subgroup of patients (N = 493) with worse disease-free survival (HR 1.56; 95% CI 1.27-1.92) and overall survival (HR 1.78; 95% CI 1.34-2.36). Among patients meeting NATALEE-only eligibility criteria (N = 1,346), nodal status (N1 vs N0) did not meaningfully discriminate 7-year outcomes. In simulating prognosis among women treated in the pre-CDK4/6 inhibitor era and meeting varying monarchE and NATALEE eligibility criteria, these data may inform future trial design and clinical practice and stimulate efforts to refine clinical, pathological and molecular criteria for patient selection.
Tobacco, alcohol, and human papillomavirus (HPV) are major risk factors for oral cavity (OC) and oropharyngeal (OPC) cancers, yet their specific contributions to the tumor molecular landscape remain incompletely understood. We analyzed somatic alterations in 1,086 tumors (606 OC, 480 OPC, including 287 HPV(+)OPC) profiled with a 1,109-gene panel and evaluated their associations with exposures. PIK3CA alterations were widespread but context-specific: HPV(+)OPC featured APOBEC-driven mutations and co-occurrence of FGFR3 mutations in a subset of cases, while HPV(-)OPC and OC were marked by 3q26/28 (PIK3CA/TP63/SOX2) amplifications. TP53 was the most frequently mutated gene in HPV(-) tumors, with strong enrichment among smokers in HPV(-)OPC, whereas TP53 mutation frequencies in OC were consistently high regardless of smoking status. CCND1 amplifications were largely restricted to HPV(-) tumors and were most frequent in individuals reporting combined tobacco/alcohol use. This combined effect was replicated in the TCGA OC-OPC cohort and mirrored at the transcriptomic level, where CCND1 mRNA expression was highest in dual users. Within OC, characterization of one of the largest cohorts of tumors from never smoker-never drinkers to date (N = 100) showed they were more likely to be from female patients and to exhibit enrichment for FAT1 and CASP8 mutations compared to tumors from ever smoker-ever drinkers (N = 353). Together, these findings define distinct, exposure-driven patterns of somatic alterations by subsite and HPV status, and provide a molecular framework that may inform etiologic-based risk stratification in head and neck cancer.
