JNCI Journal of the National Cancer Institute最新文献

Background: Thyroid hormones influence reproductive and metabolic pathways that may affect ovarian cancer development and progression. However, epidemiological evidence is limited and inconsistent. We examined the association between physician-diagnosed thyroid dysfunction and ovarian cancer risk and survival in a large prospective cohort.

Methods: We included 80,348 women from the E3N cohort who completed at least one biennial questionnaire enquiring about physician-diagnosed thyroid dysfunction (hyperthyroidism or hypothyroidism) between 1992 and 2014. We used Cox regression models with time-varying exposure to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for ovarian cancer incidence through 2018 and, among women diagnosed with ovarian cancer, for overall survival through 2024. Models were adjusted for established ovarian cancer risk or prognostic factors.

Results: During follow-up (up to 2018), 589 ovarian cancer cases were identified. Overall, pre-diagnostic thyroid dysfunction was not associated with ovarian cancer risk. However, hypothyroidism diagnosed ≥5 years earlier was associated with reduced risk (HR = 0.65, 95% CI = 0.45-0.95) and hyperthyroidism diagnosed ≥5 years earlier and not using levothyroxine was associated with increased risk (HR = 1.70, 95%CI = 1.04-2.78). We found no meaningful association between pre-diagnostic thyroid dysfunction and survival following an ovarian cancer diagnosis.

Conclusions: Hypothyroidism may be associated with decreased ovarian cancer risk, and hyperthyroidism with increased ovarian cancer risk. Neither hyperthyroidism nor hypothyroidism appeared to affect survival. Whether these associations are causal or whether levothyroxine use plays a role in the development of cancer should be investigated further.

Background: Sex is a recognised modifier of physiology, immunity, and social exposures, yet its independent association with survival and adverse event (AE) prognosis in contemporary anticancer therapy remains poorly defined. The aim of the present study was to assess the association between patient sex and OS, PFS, and grade ≥3 AEs across a pooled individual participant data (IPD) meta-analysis.

Methods: IPD supporting FDA approval of anticancer medicines for solid tumours between 2011 and 2021 were accessed via the Vivli and YODA data sharing platforms. A two-stage random-effects meta-analysis approach was employed, using Cox proportional hazards regression to estimate sex-based prognostic differences in overall survival (OS), progression-free survival (PFS), and grade ≥3 AEs. Analyses were adjusted for key baseline covariates.

Results: In a pooled cohort of 20,806 participants from 39 phase II-III trials supporting US FDA approvals of anticancer medicines for advanced solid tumours, across 12 tumour types, female sex was associated with significantly improved OS (HR 0.79, 95% CI 0.73-0.85; P < 0.001) and PFS (HR 0.84, 95% CI 0.79-0.89; P < 0.001). Conversely, females experienced a higher risk of grade ≥3 AEs (HR 1.12, 95% CI 1.07-1.18; P < 0.001).

Conclusions: In the largest analysis of IPD from trials supporting FDA drug approvals, we found that females had a 21% lower risk of death and a 16% lower risk of progression, but a 12% higher risk of severe adverse events. These findings highlight the value of the IPD sharing and the importance of sex-stratified evidence for risk stratification, dose optimisation and patient counselling.

Background: Patient reported outcome (PRO) item libraries support flexible PRO assessment in cancer research by facilitating the development of customized item lists. However, little is known about the use of item lists in clinical research. This systematic review addresses this by assessing utilization of PRO item libraries and lists in oncology research.

Methods: Systematic review of MEDLINE, Embase and CINAHL identified cancer studies using PRO item libraries to develop item lists, regardless of study design, published between October 2021-September 2025. Key features of item library usage were extracted and analyzed descriptively.

Results: Seventy-eight studies were included (25 trials/feasibility; 53 observational). The Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events system was frequently used (49/78) and symptom assessment was the most common application (63/78). Item lists were implemented across different settings including novel treatments (19/78) and rare cancers (15/78). Most item lists were derived from a single PRO item library (72/78). In some studies, there was additional customization such as item wording changes (5/78), or addition of items adapted from the item library (9/78). Item selection methods included, literature (32/78), patient involvement (8/33) and consultation with healthcare professionals (11/78). Many studies (40/78) did not report methods used.

Conclusions: PRO item libraries are increasingly used to create customized item lists in oncology research, primarily for symptom assessment. However, reporting practices for methods used are inconsistent, highlighting the need for standardized guidelines for reporting PRO item lists in clinical trials and routine care to improve transparency, reproducibility, and quality.

Background: Integrating genetic and lifestyle information has the potential to greatly improve the prediction of colorectal cancer (CRC) risk. However, racial and ethnic minorities are generally underrepresented in gene-environment studies of CRC risk.

Methods: We investigated the interplay of genetics and lifestyle on CRC risk in a prospective analysis of 68,397 African American, Japanese American, Latino, Native Hawaiian, and White individuals from the Multiethnic Cohort Study. Genetic predisposition was assessed using a 205-variant polygenic risk score (PRS). Lifestyle was assessed using a lifestyle risk score based on smoking, alcohol consumption, body mass index, physical activity, and diet. The independent and joint associations of the PRS and lifestyle risk score on CRC risk were evaluated using Cox regression.

Results: We identified 1,303 incident CRC cases (median 15.1-year follow-up). The highest quintile of the PRS was associated with a 2.4-fold increase in CRC risk compared to the lowest quintile (HRQ5vQ1 2.40, 95% CI 1.99-2.89). The highest quintile of the lifestyle risk score was associated with a 54% increased risk (HRQ5vQ1 1.54, 95% CI 1.26-1.88). This association was stronger among those with high genetic risk (PRS≥50%) (HRQ5vQ1 1.82, 95% CI 1.41-2.35) and non-significant among those with low genetic risk (PRS<50%) (HRQ5vQ1 1.20, 95% CI 0.88-1.64; p-interaction=0.01). Results were similar across race and ethnicity.

Conclusions: Our study suggests that lifestyle modification may offer greater risk reduction among those at higher genetic risk. Future research is warranted to enhance the integration of genetics and lifestyle in CRC risk stratification and screening approaches across populations.

Cancer screening guidelines specify ages at which routine screening should be discontinued and, except for cervical cancer screening, do not require specific screening history criteria be met for discontinuation. We estimated the prevalence of being up to date with average-risk screening guidelines for colorectal, cervical, and lung cancer as of the recommended ages for discontinuation of routine screening. We conducted a descriptive study among several U.S. healthcare systems during 2010-2019. Up-to-date screening prevalence, based on U.S. Preventive Services Task Force guidelines, was ascertained prior to 76th, 66th, and 81st birthdays among persons eligible for colorectal (N = 316,756 persons), cervical (N = 20,282 persons), and lung cancer (N = 1,151 persons) screening, respectively. Up-to-date screening prevalence was 84.4% for colorectal, 58.9% for cervical, and 6.3% for lung cancer screening. Up-to-date screening prevalence at the ages recommended for discontinuing routine colorectal, cervical, and lung cancer screening varied appreciably, and was particularly low for lung cancer screening.

Background: The association between histological subtypes of benign breast disease (BBD) and risk of subsequent breast cancer in the post-mammography era of increased BBD detection, requires continued study to inform clinical management of high-risk women.

Methods: We identified a cohort of 8,915 women diagnosed with histologically-confirmed benign lesions between 2010 and 2023 from the Joanne Knight Breast Health Center in St. Louis. Risk of subsequent breast events after a benign biopsy was assessed with Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (95%CIs).

Results: Within a median follow-up of 6.5 years, 363 women developed breast cancer. The cohort was 63.7% White, 32.4% Black, and 3.9% Asian. Breast cancer risk increased across subtypes of BBD, from proliferative disease without hyperplasia (PDWA) to atypical hyperplasia (AH), with AH risk modified by time since biopsy and menopause. Compared with women with nonproliferative disease, age-adjusted risk for breast cancer was 1.69 for PDWA (HR = 95%CI 1.40, 2.30) and 2.78 for AH (HR = 2.78, 95%CI 2.01, 3.85, p trend < 0.0001). Risk estimates attenuated but remained similar in fully adjusted models. Risks associated with BBD subtypes were similar for Black and White women, but Black women with AH had greater risk of breast cancer since recent biopsy (≤4 years) and during the premenopausal period (p het = 0.033).

Conclusion: Breast cancer risk increases with the degree of epithelial proliferation, highest in AH, amplified by recent biopsy and premenopause, particularly in Black women, consistent with the excess risk seen after ductal carcinoma in situ in this group.

Background: Microsimulation models use empirical evidence about cancer epidemiology and screening test performance to predict the long-term effectiveness of screening regimens and are essential for developing cancer screening guidelines. Colorectal cancer (CRC) provides a clear example. CRC arises through two pathways, the adenoma-carcinoma pathway and the serrated pathway. Sessile serrated lesions (SSLs) are the primary serrated precursor lesion. SSLs are more difficult to detect and remove than adenomas.

Methods: We describe version 3.0 of the Colorectal Cancer Simulated Population model for Incidence and Natural history (CRC-SPIN), which adds new information about the serrated pathway and CRC risk in adults under 50, then estimate the effectiveness of decennial colonoscopy from 45 to 75 years old. The model was calibrated using a Bayesian approach to estimate 95% credible intervals (CIs) that reflect uncertainty in predictions.

Results: The model validated well to studies of the effect of one-time screening and outcomes from surveillance colonoscopy. In the absence of screening, SSLs accounted for 10.6% (95% CI: 3.3-21.6) of CRC, increasing to 23.5% (95% CI: 7.7%-46.0%) with screening due to selective removal of adenomas. Screening was predicted to prevent 93.9% (95% CI: 92.0%-94.3%) of CRC and 95.3% (95% CI: 93.8%-96.5%) of CRC mortality.

Conclusions: Although SSLs are less common than adenomas, they likely make up a large fraction of CRC that arises in people who participate in screening. This points to the importance of improving the ability to detect SSLs, especially large SSLs, at colonoscopy.