International Journal of Cancer最新文献

The effects of cofactors on the impact of body mass index (BMI) change on breast and endometrial cancer are rarely investigated. This cohort study included cancer-free women who underwent national health examinations in 2010-2014 (Cohort 1) and 2009-2013 (Cohort 2), with follow-up through 2021 and 2017, respectively. BMI at baseline and follow-up was combined and categorized into 25 BMI change patterns. Cohort 1 (2.24 million) had 30,323 breast and 5465 uterine corpus cancers, while Cohort 2 (1.46 million) had 8580 breast and 1170 uterine corpus cancers. In Cohort 1, persistent low BMI was associated with a reduced risk of both cancers, particularly in postmenopausal women and never-smokers. However, persistent overweight, obesity I/II, and BMI fluctuation (loss or gain) were linked to an increased risk of both cancers, particularly in postmenopausal women and ever-smokers. Among premenopausal women, substantial BMI loss was associated with increased breast cancer risk. In postmenopausal women, a transition from overweight to underweight (adjusted hazard ratio [aHR]: 4.63, 95% confidence interval [CI]: 1.15-18.59) and from overweight to obesity class II (aHR: 4.06, 95% CI: 1.01-16.30) significantly increased uterine cancer risk. Among smokers, most BMI changes did not show significant association, except for persistent obesity I (aHR: 1.57, 95% CI: 1.01-2.43) and progression from obesity class I to II (aHR: 4.03, 95% CI: 1.97-8.26). Cohort 2 findings were largely consistent with those from Cohort 1. In conclusion, persistent high BMI and further BMI gain were associated with increased risk of both cancers, particularly in postmenopausal women and never-smokers.

In the phase 3 KEYNOTE-042 China study of participants enrolled in China in the global KEYNOTE-042 (NCT02220894) and China extension (NCT03850444) studies, pembrolizumab improved overall survival (OS) versus chemotherapy in locally advanced or metastatic non-small-cell lung cancer (NSCLC) with programmed cell death ligand 1 (PD-L1) tumor proportion score (TPS) ≥50% (hazard ratio [HR], 0.63; 95% CI, 0.43-0.94), ≥20% (0.66; 0.47-0.92), and ≥1% (0.67; 0.50-0.89). We present outcomes from this study after 5 years of follow-up. Chinese participants with previously untreated locally advanced or metastatic NSCLC with PD-L1 TPS ≥1% without EGFR or ALK alterations were eligible. Participants were randomized 1:1 to pembrolizumab 200 mg every 3 weeks for up to 35 cycles or carboplatin plus paclitaxel or pemetrexed with optional pemetrexed maintenance (nonsquamous only). Primary endpoints were OS in the PD-L1 TPS ≥50%, ≥20%, and ≥1% subgroups. Median follow-up was 63.7 (range, 56.3-72.6) months among 262 participants (pembrolizumab, n = 128; chemotherapy, n = 134) included in this study. Pembrolizumab prolonged OS versus chemotherapy in participants with PD-L1 TPS ≥50% (HR, 0.65; 95% CI, 0.45-0.93), ≥20% (0.67; 0.49-0.91), and ≥1% (0.66; 0.51-0.87). Grade 3 to 5 treatment-related AEs occurred in 19.5% and 68.8% of participants in the pembrolizumab and chemotherapy groups, respectively. In conclusion, after 5 years of follow-up, pembrolizumab continued to demonstrate improved OS versus chemotherapy with manageable safety in Chinese participants with previously untreated locally advanced or metastatic NSCLC that expressed PD-L1. These data further support pembrolizumab monotherapy as a standard of care for these patients.

Evaluating trends in HPV-related cancer rates by race is essential for identifying high-risk populations and improving prevention efforts. Using 2011-2022 South African National Cancer Registry data, we analyzed age-standardized incidence rates by race and sex across three periods (2011-2014, 2015-2018, 2019-2022) using linear regression. Significant increases were observed for oropharyngeal squamous cell carcinoma (SCC) among White females (p < .01), vulvar SCC among Asian (p < .01) and Black (p = .02) females, and anal SCC among Colored females and Black males (p < .01). Cervical carcinoma rates remained stable for most racial groups, except for the annual trends showing a 1.9% increase per year (95% CI = 1.0, 2.7) among White females. These findings suggest rising incidence rates for some HPV-related cancers across racial groups in South Africa. Further research is needed to explore the constellation of risk factors contributing to these trends and to guide targeted interventions.

Analyzing T-cell subsets in and between primary colorectal cancer (pCRC) and adjacent non-tumor mucosa (NM) may reveal distinct prognostic value in stage IV versus stages I-III patients. Specimens of pCRC and NM were collected retrospectively from stage IV patients (n = 55) with synchronous liver metastases (LM), and stages I-III patients (n = 44) who developed metachronous LM. CD3⁺, CD8⁺, CD45RO⁺, CD4⁺, and Foxp3⁺ T-cells were quantified in NM and the tumor center (TC) of pCRC using immunohistochemistry. T-cell densities in NM and TC and their ratios (TC/NM) were tested as prognostic variables for overall survival (OS), along with Foxp3⁺/CD8⁺, Foxp3⁺/CD4⁺ and CD4⁺/CD8⁺ ratios. In stages I-III, associations with the time to occurrence of LM were also evaluated. In both groups, NM exhibited greater densities of CD3⁺, CD8⁺, CD45RO⁺, and CD4⁺ cells compared to TC, whereas Foxp3⁺ cells were more abundant in the TC. In stage IV, high densities of Foxp3⁺ cells, high Foxp3⁺/CD4⁺ and Foxp3⁺/CD8⁺ ratios in the NM, and high CD4⁺ cell densities in the TC were associated with longer OS. Stages I-III patients with a high CD4⁺/CD8⁺ ratio in the NM had longer OS, whereas a high Foxp3⁺/CD8⁺ ratio in the TC was associated with a shorter time to LM. We revealed a significant difference in the T-cell landscape between pCRC and adjacent NM with Foxp3⁺ cells predominating in the TC and other subsets in the NM. Assessing T-cells and their ratios in both regions may improve prediction of survival in CRC patients and the time to LM in stages I-III.

Persistent infection with human papillomavirus (HPV) is associated with an increased risk of head and neck cancers (HNC), particularly oropharyngeal cancer. This longitudinal cohort study investigated the prevalence and dynamics of oral HPV infection among healthy adults in South India. A total of 5325 participants were enrolled, and demographic, behavioral, and oral gargle samples were collected. HPV deoxyribonucleic acid (DNA) was detected using nested PCR (PGMY/GP) and genotyped by Sanger sequencing. HPV16 messenger ribonucleic acid (mRNA) expression was analyzed by reverse transcriptase polymerase chain reaction (RT-PCR) and validated using droplet digital polymerase chain reaction (ddPCR). Logistic regression analyses were performed to estimate odds ratios. At baseline, 5011 samples were analyzed; 274 (5.5%) were HPV-positive and 4737 were negative. Among 3792 initially HPV-negative participants followed up, 126 (3.3%) acquired new infections (median 8 months; range, 6-15 months). Of 274 baseline HPV-positive individuals, 241 were followed up: 24 (10%) showed persistence, while 217 (90%) cleared infection after a median of 9 months (range, 6-20 months). Sanger sequencing of 471 samples from prevalent and incident infections yielded 290 (61.6%) high-quality sequences; 284 (98%) were HPV16, with isolated detections of HPV18, HPV66, HPV70, and HPV89. Ten novel variants were identified-nine HPV16 and one HPV89-while remaining sequences aligned with established Indian cervical HPV lineages. None of the 176 HPV16 DNA-positive samples analyzed expressed mRNA by RT-PCR, confirmed in 136 samples using ddPCR. Oral HPV infection among healthy individuals in India appears predominantly transient. Long-term monitoring may elucidate the oncogenic potential of oral HPV in this population.

Chemotherapy is an essential component of cancer treatment, as outlined in the National Comprehensive Cancer Network (NCCN) guidelines for Sub-Saharan Africa (SSA). Lack of access to treatment is a key driver of impaired survival rates. This study assessed patient-perceived barriers to chemotherapy in SSA according to the five dimensions of access to care: availability, accessibility, accommodation, affordability, and acceptability. Telephone interviews were conducted with 553 randomly selected cancer patients (or caretakers), registered between 2018 and 2019 in 11 urban population-based cancer registries across nine countries in SSA. Malignancy types included breast, cervical, prostate, and colorectal cancer; non-Hodgkin lymphoma; and Kaposi sarcoma. Patients rated barriers using a 3-point Likert scale. Barriers to chemotherapy and their associations with patient characteristics were analysed using multivariate ordinal regression analysis. Major barriers included accessibility (cost of transport), affordability (cost of treatment, being absent from home), and acceptability (lack of knowledge/awareness and fear of treatment). Results varied between countries: affordability was especially severe in the Republic of Congo, while in Gabon, fear of treatment prevailed. Knowledge and awareness were particularly concerning in Ethiopia and Zimbabwe. A combined educational level and self-reported wealth variable, and national human development index (HDI) were consistently associated with reported barriers. Overall, 58.6% of participants received chemotherapy, while 13.2% were recommended chemotherapy but did not receive it. A higher HDI correlated with an increased probability of receiving treatment. A complex set of barriers influenced patients' non-receipt of treatment. Regionally adapted strategies, including psychosocial support, financial assistance for vulnerable groups, and education, are essential to improve treatment uptake in SSA.

Pleural mesothelioma (PM) is a lethal cancer primarily caused by asbestos exposure. Not all exposed individuals develop PM, suggesting the involvement of additional factors. This underscores the need for robust predictive models integrating biomarkers from multi-omic domains to improve risk stratification and early detection. We developed and evaluated polygenic risk scores (PRS) and methylation risk scores (MRS) using a retrospective case-control study (749 participants: 387 PM cases, 362 controls) and a nested case-control European Prospective Investigation into Cancer and Nutrition (EPIC)-Meso study (268 participants: 134 preclinical PM cases, 134 matched controls) within the EPIC cohort. Genome-wide association analyses in the retrospective case-control study identified PM-associated variants. The PRS (1123 SNPs with p < 0.001) in the retrospective training subset stratified disease risk in the test set (ORs 3.46-9.54 across top percentiles) and improved model discrimination (AUC = 0.75 vs. 0.71 in baseline model, p = 0.04). In EPIC-Meso, PRS performance was limited (AUC = 0.52). External validation in the UK-Biobank (UKBB) confirmed a modest but consistent association with PM-risk. A Meta-PRS derived from the UKBB-FinnGen meta-analysis replicated this trend in the full retrospective dataset, showing higher OR across top percentiles (2.5-12.3) and improved discrimination (AUC 0.74 vs. 0.72, p = 0.016). MRS, with 68 differentially methylated CpGs (effect-size >|0.10|, FDR p < 0.05) in the retrospective training set, increased the AUC from 0.66 to 0.85 (p < 0.001) in the test set and from 0.51 to 0.62 in EPIC-Meso. PRS was most predictive in low-exposure groups, while MRS remained robust across exposure levels. Combined PRS-MRS models improved discrimination. Integrating multi-omic biomarkers can enhance PM-risk stratification and support earlier, targeted interventions in high-risk asbestos-exposed groups.

Conditional survival provides insights into the evolution of prognosis over time and reveals changing associations of prognostic factors during disease progression. Data on the temporal evolution of prognostic factors in glioblastoma remain scarce. We analyzed 315 patients with IDH-wildtype glioblastoma from a prospectively collected registry (01/2008-06/2017). Our primary outcome was 12-month conditional survival (CS), defined as the probability of surviving the next 12 months given survival for "s" months. This analysis was conducted at five landmarks (s = 0, 6, 12, 18, 24) for baseline prognostic factors, including tumor volume compartments. 12-month conditional survival estimates at s = 0, 6, 12, 18, and 24 months from diagnosis were 0.51 (95% CI 0.45-0.56), 0.46 (95% CI 0.39-0.52), 0.41 (95% CI 0.33-0.49), 0.43 (95% CI 0.33-0.52), and 0.56 (95% CI 0.42-0.67), respectively. At diagnosis (s = 0), 12-month survival estimates varied significantly with age >60 at diagnosis, preoperative tumor rim volume >20 cm³, absence of O⁶-methylguanine-DNA methyltransferase (MGMT) promoter methylation, postoperative KPS ≥70, residual postoperative tumor >1 cm³, or biopsy only. Residual tumor volume mainly influences survival in the initial months following surgery, while MGMT promoter methylation and age remain significant predictors beyond this period. These findings may refine stratification strategies in recurrent glioblastoma trials.

This single-center, open-label, single-arm phase II trial (NCT05165407) aimed to evaluate the efficacy and safety of surufatinib (250 mg orally once daily) combined with sintilimab (200 mg intravenously every 3 weeks) and IBI310 (1 mg/kg intravenously every 6 weeks) in patients with advanced high-grade neuroendocrine neoplasms (HG-NENs). The primary endpoint was the objective response rate (ORR). Secondary endpoints included the disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. As of March 28, 2025, 24 patients with measurable baseline lesions and at least one post-treatment tumor assessment were included in the efficacy-evaluable analysis set. The ORR was 37.5% (95% confidence interval [CI]: 18.8-59.4); DCR, 79.2% (95% CI: 57.8-92.9); and median DoR, 14.8 months. Among 31 treated patients in the full analysis set population, the median PFS was 3.81 months (95% CI: 2.79-4.50), and the median OS was 13.44 months (95% CI: 10.28-not estimable). Subgroup analyses showed improved response in patients with the following characteristics: female sex, age <55 years, ECOG performance status of 1, received ≤1 prior treatment line, without liver metastases, and <2 metastatic sites. Treatment-related adverse events (TRAEs) occurred in 96.8% of patients; 45.2% experienced grade ≥3 TRAEs. Among them, 71.0% experienced TRAEs attributed to sintilimab/IBI310, and 87.1% to surufatinib. Serious adverse events occurred in 45.2% of patients. These findings suggest that surufatinib, IBI310, and sintilimab may offer clinical benefit with manageable toxicity in patients with advanced HG-NENs.

This descriptive analysis evaluates design strategies, regulatory outcomes, and temporal trends in oncology accelerated approvals (AAs) over three decades, comparing solid tumors with hematologic malignancies. We retrospectively reviewed publicly available U.S. Food and Drug Administration (FDA) data on oncology drugs granted AA between December 1992 and January 2025, focusing on those with completed post-approval assessments. Key measures included trial design, endpoints, conversion and withdrawal rates, and time to regulatory resolution. Of 204 AAs representing 204 drug-indication pairs (across 133 drugs), 138 had completed post-approval assessments; 77.5% converted to regular approval, 22.5% were withdrawn. Solid tumors accounted for 63% (87/138) of AAs, and had higher conversion rates to regular approvals compared to hematologic malignancies (82% vs. 71%, respectively). Withdrawals were more frequent in hematologic malignancies compared to solid tumors (29% vs. 18%, respectively). Orphan drug designation and post-approval label modifications were more common in hematologic malignancies than solid tumors (76% vs. 45%, and 18% vs. 11%, respectively). Randomized controlled trials (RCTs) drove most successful conversions (63%). Among 105 AA trials for solid tumors, overall response rate (ORR) was the primary endpoint in 74%, with progression-free survival (PFS) and overall survival (OS) in 13% and 9% AAs, respectively. Hematologic trials favored ORR (33%) and disease-specific endpoints. The most common AA → confirmatory pathway was ORR → PFS (46%). OS as a confirmatory endpoint after surrogate-based AA was linked to higher withdrawal rates, whereas consistent endpoints (e.g., OS → OS) had none. RCTs and aligned endpoints drive successful oncology AA conversions, while surrogate-confirmed OS often precedes withdrawal.