JNCI Journal of the National Cancer Institute最新文献

Purpose: Overlapping genes are involved with rheumatoid arthritis (RA) and DNA repair pathways. Therefore, we hypothesised that patients with a high polygenic risk score (PRS) for RA will have an increased risk of radiotherapy (RT) toxicity given the involvement of DNA repair.

Methods: Primary analysis was performed on 1494 prostate cancer, 483 lung cancer and 1820 breast cancer patients assessed for development of RT toxicity in the REQUITE study. Validation cohorts were available from the Radiogenomics Consortium. All patients had undergone curative-intent radiotherapy and were assessed prospectively for toxicity. Germline genomic data was available for all patients, allowing a PRS to be calculated using 101 RA risk variants. PRS was analysed as a continuous variable and with >90th percentile cut-off. Associations with acute and late standardised total average toxicity (STAT) scores and individual toxicity end-points were analysed in multivariable models with preselected adjustment variables.

Results: Increasing PRS for RA did not increase the risk of acute or late STAT in any cohort. There was an increased risk of late oesophagitis in the lung cancer cohort (coefficient 0.018, p = .01), however this was not validated (p = .79). No individual acute or late toxicity endpoints were significantly associated with PRS for the prostate or breast cohorts. No significant results were found in the validation cohorts in multivariable models.

Conclusions: Patients with a high genetic risk for RA do not show increased levels of toxicity after radiotherapy suggesting treatment planning does not need to be modified for such patients.

Background: Adolescents and young adults (AYA) with germline CDH1 variants are at risk of overtreatment when precancer lesions are detected with endoscopic screening. We characterize diffuse-type gastric cancer prevalence and survival in AYA managed with prophylactic total gastrectomy (PTG) or endoscopic surveillance.

Methods: Prospective cohort study of 188 individuals aged 39 and younger enrolled from January 27, 2017, to May 1, 2023. Clinicopathologic data, prevalence of early gastric signet ring cell (SRC) lesions, advanced gastric cancer diagnoses, and cancer-specific survival were measured.

Results: Among 188 AYA patients, 104 chose surveillance and 67 pursued PTG for management of elevated gastric cancer risk. AYA who enrolled early in the study period and had SRC lesions detected on preoperative endoscopy were more likely to elect for PTG compared to surveillance. SRC were detected on preoperative endoscopy in 48% of patients who subsequently had PTG, yet nearly all (93%, 62/67) had multifocal SRC (pT1aN0) on final pathology. Median age at enrollment (30 vs. 31 years, p = .21), biologic sex (p = .17), and median number of family members with gastric cancer (3 vs. 4, p = .14) were not different between groups. No patients under surveillance developed advanced cancer or developed cancer recurrence after PTG with a median follow-up of 2.5 years (IQR 1.6-4.0) from initial endoscopy.

Conclusions: Cancer-specific outcomes were not different in AYA who harbored SRC and were managed with surveillance or PTG. Lack of cancer-specific deaths and low prevalence of advanced gastric cancer underscore the risk of overtreatment of SRC lesions and suggest that active surveillance is warranted.

Background: Breast cancer is the most prevalent cancer worldwide and the leading cause of cancer mortality in women. Uptake of breast cancer screening and early-detection practices in low- and middle-income countries (LMIC) has not been synthesized. We aimed to systematically quantify uptake of breast cancer screening in LMIC.

Methods: We performed a systematic review and meta-analysis of observational population-based studies that reported the uptake of screening or early-detection practices. We searched the PubMed, Scopus, Embase, and Web of Knowledge databases to January 2024. We pooled data using random-effects meta-analysis and explored heterogeneity using subgroup analyses.

Results: We included 174 population-based studies encompassing more than 78 million women. Pooled prevalence of self-reported uptake of screening mammography was 22.7% (95% confidence interval = 18.6% to 27.2%), of self-reports of having had a clinical breast examination for screening was 23.1% (95% confidence interval = 19.5% to 27.0%), and of self-reported regular breast self-examination (relevant for breast awareness in LMIC) was 14.6% (95% confidence interval = 11.6% to 17.9%). Uptake of breast cancer screening practices was lowest in Africa and low- and lower-middle income countries. Uptake of breast cancer screening practices remained stable over time or decreased slightly. Women who lived in rural area, were single, had lower income levels, had low educational attainment, were unemployed, were uninsured, and had no family history of breast cancer were generally least likely to self-report uptake of breast cancer screening.

Conclusion: This meta-analysis identified concerningly low uptake of breast cancer screening practices in LMIC. Governments should prioritize developing context-appropriate strategies to address this low uptake to support population-level stage shifting of breast cancer in LMIC.