International Journal of Cancer最新文献

Modifiable risk factors, such as smoking, alcohol consumption, and excess weight, are associated with cancer incidence but data on their associations with population-based mortality among cancer patients are limited. Pooled data from seven health studies conducted in Finland during 1972-2015 were used to assess the associations of smoking, alcohol consumption, body mass index, physical inactivity, and education on mortality among 224,820 participants, of whom 10,637 were diagnosed with colorectal, lung, pancreatic, prostate or breast cancer. We estimated age-standardized relative survival and relative excess risks of death (RER) using piecewise constant excess hazard models. Current smoking was associated with increased excess mortality in male pancreatic cancer (RER compared with never-smokers 1.54, 95% CI 1.08-2.19) and prostate cancer patients (1.55, CI 1.08-2.23), as well as in female lung cancer patients (1.44, CI 1.07-1.92). Obesity was associated with increased excess mortality in prostate cancer patients (1.56, CI 1.06-2.30) and physical inactivity in colorectal cancer (1.33, CI 1.01-1.76 in men; 1.36, CI 1.06-1.74 in women) and male lung cancer patients (1.15, CI 1.02-1.30). Excess mortality was systematically elevated among patients with low education with statistically significant associations for male lung and female pancreatic cancer. Several lifestyle-related factors were associated with increased excess mortality among cancer patients but not consistently over all cancer sites or in both sexes. It is notable that even in a Nordic welfare state with potentially equal healthcare, marked socioeconomic inequalities persist in mortality among cancer patients.

The association between mycotoxins and esophageal cancer (EC) risk remains poorly understood, highlighting the need for evidence from population-based prospective studies. We conducted a case-cohort study nested within the Taizhou Longitudinal Study to investigate this relationship, analyzing baseline urinary mycotoxins in 866 randomly selected subcohort members and 240 incident EC cases (including seven cases from the subcohort). Using ultra-high performance liquid chromatography-triple quadrupole-tandem mass spectrometry, we measured three mycotoxins: ochratoxin A (OTA), T-2 toxin (T-2), and fumonisin B1 (FB1). While FB1 was detectable in over 88% of urine samples, OTA and T-2 were detected in less than 30% of samples. EC cases showed slightly higher detection rates for all three mycotoxins compared to the subcohort subjects. Weighted Cox proportional hazards regression analyses for case-cohort studies revealed that, after adjusting for potential confounders, the urinary levels of three mycotoxins-OTA (hazard ratio [HR] = 1.07, 95% confidence interval [CI]: 0.73-1.56), T-2 (HR = 1.01, 95% CI: 0.51-2.00), and FB1 (HR = 0.94, 95% CI: 0.53-1.64)-as well as co-exposure to these three mycotoxins (HR = 1.33, 95% CI: 0.34-5.28), showed no significant association with EC risk. These results remained consistent even after excluding the first 2 years of follow-up to minimize the influence of potential reverse causation. Our case-cohort study found no clear associations between urinary mycotoxins-OTA, T-2, or FB1-and EC risk in the studied population.

First-line chemo-immunotherapy has significantly improved survival in extensive-stage small-cell lung cancer (ES-SCLC). However, rapid disease progression still occurs, with a median progression-free survival (PFS) of only 4.5-5.8 months from induction therapy. We initiated two single-arm, phase II studies to assess the first-line maintenance therapy with tislelizumab plus anti-angiogenic drugs following induction therapy in ES-SCLC patients. Previously untreated ES-SCLC patients were enrolled to receive tislelizumab plus platinum-based chemotherapy as induction therapy for 4 cycles, followed by tislelizumab plus sitravatinib (Trial 1) or anlotinib (Trial 2) as maintenance therapy in a 21-day cycle. The primary endpoint was the 1-year PFS rate in the maintenance analysis set (MAS, including patients receiving ≥1 dose of maintenance therapy). Outcomes in MAS were calculated from the start of maintenance therapy. Twenty-one patients were enrolled, and 18 patients entered the maintenance phase in each trial. From the start of the maintenance therapy, the median PFS was 6.4 and 7.8 months (1-year PFS rates of 22.2% and not reached), respectively; the median overall survival (OS) was 18.3 months and not reached. From induction therapy, the corresponding median PFS was 9.1 and 10.8 months, with a median OS of 17.6 months and not reached. In MAS, the most common grade ≥3 treatment-related adverse events (TRAEs) included hypertension (22.2%) in Trial 1 and fatigue (5.6%) in Trial 2. No patients died from TRAEs in either trial. Maintenance therapy with tislelizumab plus sitravatinib or anlotinib yielded clinically meaningful survival results and was generally well tolerated in ES-SCLC, warranting further exploration in larger-scale trials.

In stages II and III hormone receptor positive (HR+) breast cancer, selecting patients for primary surgery (PS) or neoadjuvant therapy remains challenging. This study assessed the occurrence of minimally invasive surgery in the case of PS, neoadjuvant endocrine therapy (NET), and neoadjuvant chemotherapy (NACT). This cohort study included women diagnosed with stages II and III, HR+ breast cancer in 2020-2022 in the Netherlands. Women with positive human epidermal growth factor receptor 2 (HER2+) cancer were excluded. Outcomes focused on surgical techniques and additional treatment. Of the 7809 patients, 4046 (51.8%) underwent PS, 956 (12.2%) received NET and 2807 (35.9%) NACT. NET patients were older (median: 71 years [33-94]), while NACT patients had larger tumors and more lymph node involvement (p < .001). Breast-conserving surgery (BCS) was the first procedure in 2153 (53.2%) PS women, in 694 (72.6%) NET women and 1564 (55.7%) NACT cases. There was no difference regarding free surgical margins in NET versus NACT patients (p = .421). After adjusting for T-stage, BCS occurred significantly more frequently after NET (p < .001). Minimal invasive surgery on the axilla was common after NET (83.9%) and NACT (81.5%). In the PS group, 85% received adjuvant systemic therapy. Optimizing patient selection for neoadjuvant strategies could reduce surgical morbidity. NET was frequently associated with BCS, showed comparable surgical margin outcomes to NACT, and contributed to reduced axillary surgery. These findings suggest that NET is an effective strategy, compared to PS, to facilitate less invasive surgery on the breast and axilla, in HR+/HER2-, stages II and III breast cancer.

Diffuse intrinsic pontine gliomas (DIPG) are highly aggressive brainstem tumors, representing the leading cause of pediatric cancer-related mortality despite their rarity. DIPGs are predominantly characterized by the H3K27M mutation, which drives tumorigenesis through epigenomic reprogramming and dysregulated gene expression. A major barrier to therapeutic advancement has been the scarcity of representative preclinical models, historically limited by the rarity of tumor tissue samples. Recent advancements in biopsy safety and model development have accelerated progress in understanding DIPG biology and developing novel therapies. While current murine models offer valuable insights, they often fail to replicate the tumor's genetic and microenvironmental complexity fully. Non-murine models offer cost-effective platforms but are limited by anatomical and immunological differences that reduce their relevance to human DIPG. This review highlights advances and limitations in DIPG models, emphasizing the need for integrative approaches using multiple systems to validate therapies, as no single model can fully capture the disease's complexity. Addressing these gaps could lead to the development of novel treatments for DIPG.

The gut-liver axis may play an important role in hepatocarcinogenesis. However, limited prospective research has explored associations with liver cancer risk. We conducted a nested case-control study based in 12 prospective cohort studies from across the United States, which included 867 cases of liver cancer and 867 matched controls. We measured bacterial translocation markers, specifically immunoglobulin (Ig) A, IgG, and IgM against lipopolysaccharide and flagellin; soluble CD14 (a co-receptor for lipopolysaccharide); and lipopolysaccharide-binding protein. Multivariable conditional logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI) between bacterial translocation marker concentrations per doubling in concentrations and liver cancer risk. Lipopolysaccharide-binding protein concentrations were most strongly associated with higher liver cancer risk (OR per doubling in concentrations: 1.48, 95% CI: 1.23-1.79). Concentrations of anti-flagellin IgA (1.13, 1.01-1.28) and IgG (1.13, 1.01-1.28), anti-lipopolysaccharide IgG (1.20, 1.01-1.42), and soluble CD14 (1.12, 1.01-1.24) were also associated with liver cancer risk. When analyses were separated into hepatocellular carcinoma (HCC, N = 436 cases) and intrahepatic cholangiocarcinoma (ICC, N = 110 cases), no evidence of heterogeneity was observed except for lipopolysaccharide-binding protein concentrations, which were positively associated with HCC (1.77, 1.34-2.33) but not ICC (0.67, 0.37-1.22; p-heterogeneity = .003). Associations did not differ by time to liver cancer diagnosis or other subgroups. These findings support the role of gut barrier dysfunction in hepatocarcinogenesis, necessitating further research to understand the complex interplay among the mechanisms and risk factors disrupting the gut barrier, microbiota, and liver cancer.

While the association between tobacco consumption and oral cancer is well established, the effect of tobacco cessation, particularly chewing tobacco, is less extensively studied. We aim to explore the effect of tobacco cessation on the risk of buccal mucosa cancer (BMC). A case-control study was conducted across five cancer centres in India. We enrolled 2320 BMC and 2302 frequency-matched controls. Information was collected on smoking and chewing (products, duration and quitting). Unconditional logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (95% CI) of the effect of tobacco cessation compared to current users, after adjusting for potential confounders. For both smoking and chewing, the odds reduced rapidly after 5 years of quitting, so that those who had quit smoking ≥10 years ago had only 0.39 (95% CI 0.28-0.54) the odds of BMC compared to those who continued to smoke, and those who quit chewing ≥10 years ago had 0.58 (95% CI 0.43-0.81) the odds of BMC compared to those who continued to chew. Chewing with areca nut was associated with almost double the risk of chewing without (OR 1.86, 95% CI 1.53-2.26) but the rate of reduction of risk with quitting was similar. These findings show clearly the benefits of quitting and inform policies that emphasize chewing tobacco cessation, given its widespread prevalence in India.

Cervical cancer screening in the Netherlands consists of human papillomavirus (HPV) testing followed by cytological triage at age 30, 35, 40, 50, and 60 years. Women are also invited at age 45, 55 and 65 years if they did not test HPV-negative 5 years earlier (risk-based invitation). With influx of birth cohorts vaccinated against HPV, de-intensification may be needed to maintain a cost-effective program. We used an updated and recalibrated model of type-specific HPV transmission and cervical carcinogenesis to estimate the cost-effectiveness of 16 strategies with reduced screening intensity. Strategies varied by starting age, screening interval, and number of risk-based invitations, possibly stratified for HPV vaccination status. Cost-effectiveness was measured by net monetary benefit (NMB). A positive NMB indicates that a strategy is cost-effective compared to the current policy. Two strategies without stratification for HPV vaccination status had a positive NMB. An NMB of EUR 1.6 million per 100,000 women was obtained when, compared to current screening, the invitation at age 35 was based on the HPV-test result at age 30. An NMB of EUR 1.8 million per 100,000 women was obtained when women were re-invited every 5 years if they were HPV-positive or had not been tested 5 years earlier. If reduced screening was only applied to vaccinated women, the highest NMB was EUR 1.3 million per 100,000 women. Thus, reducing screening in HPV-vaccinated cohorts is cost-effective when re-inviting women after 10 years if they test HPV-negative. Stratification for HPV vaccination status does not improve the cost-effectiveness of screening.

This study aimed to evaluate the efficacy and safety of apatinib, an oral VEGFR2 tyrosine kinase inhibitor, combined with docetaxel and S-1 (DS) as first-line therapy for metastatic gastric cancer (mGC) patients whose median overall survival (mOS) with chemotherapy typically remains below 12 months. In this prospective, multi-center, single-arm phase II trial (NCT03154983), patients received docetaxel (75 mg/m², day 1) and S-1 (body surface area-based dosing, days 1-14) every 3 weeks, plus daily apatinib (500 mg), for up to 6 planned cycles. 45 patients were enrolled, with a median follow-up time of 12.4 months. Median progression-free survival (PFS) and overall survival (OS) were 7.6 months (95% CI: 5.8%-9.4%) and 12.4 months (95% CI: 9.3%-15.5%), respectively in the full analysis set. Patients completing ≥4 cycles achieved a better mOS of 14.5 months (95% CI: 12.0%-17.1%). The objective response rate (ORR) and disease control rate (DCR) were 62.2% (95% CI, 46.5%-76.2%) and 82.2% (95% CI, 67.9%-92.0%), respectively, including one complete response (CR). Grade 3-4 treatment-related adverse events occurred in 48.9% of patients, most commonly oral mucositis and neutropenia. These findings support apatinib plus DS as a promising biomarker-independent first-line treatment strategy for mGC.

We analysed reimbursement differences for prostate (PC), renal cell (RCC), and urothelial (UC) cancers drugs in Canada, France, England, Wales, Scotland, Spain, Italy, and Portugal, assessing substantial clinical benefit (SCB) and pivotal trials characteristics. This is a retrospective analysis of PC, RCC, and UC drug-indication pairs (2005-2024). Approvals were identified via FDA and EMA. Reimbursement recommendations were reviewed. Primary endpoint was reimbursement rate by SCB, tumour type, and country. Trial characteristics, overall survival (OS), and quality of life (QoL) were analysed. SCB was defined by ESMO-MCBS v1.1. Statistical significance set at p < .05. Fifty-five drug-indication pairs for PC (20), RCC (20), and UC (15) were analysed. Most trials were randomized, open-label, phase 3, and in the metastatic settings. Canada (PC: 85%, RCC: 75%, UC: 53%) and France (PC: 85%; RCC: 75%; UC: 33%) had highest reimbursement rates; while Portugal, lowest (PC: 65%; RCC: 50%; UC: 20%). Among SCB indications, PC reimbursement was highest in Canada, France, and Spain (91%), and lowest in England (64%). For RCC, was highest in Canada, France, and Italy (100%), and lowest in Portugal (57%). For UC, was highest in Canada (100%), and lowest in Wales and England (33%). OS was primary endpoint in 47% trials; QoL was assessed in 25%. OS benefit was observed in 53%; QoL in only 9%. This study reveals marked international variation in genitourinary cancer drug reimbursement, particularly in Europe and for UC-even for indications with SCB. Most trials lacked evidence of OS or QoL benefit.