JNCI Journal of the National Cancer Institute最新文献

Background: Despite advances in breast cancer treatment, recurrence remains common and contributes to higher mortality risk. Among the potential mechanisms, inflammation plays a key role in recurrence by promoting tumor progression. Exercise provides a wide array of health benefits and may reduce inflammation, potentially reducing mortality risk. However, the effects of exercise, including mode (ie, resistance training [RT], aerobic training [AT], and combined RT and AT) and program duration, on inflammatory biomarkers in breast cancer survivors remain to be elucidated.

Methods: A systematic search was undertaken in PubMed, CINAHL, Embase, SPORTDiscus, and CENTRAL in August 2024. Randomized controlled trials examining the effects of exercise on interleukin-1 beta (IL-1β), interleukin 6 (IL-6), IL-8, IL-10, tumor necrosis factor alpha (TNF-α), and C-reactive protein (CRP) were included. A random-effects meta-analysis was undertaken to quantify the magnitude of change.

Results: Twenty-two studies were included (n = 968). Exercise induced small to large statistically significant reductions in IL-6 (standardized mean difference [SMD] = -0.85; 95% CI = -1.68 to -0.02; P = .05) and TNF-α (SMD = -0.40; 95% CI = -0.81 to 0.01; P = .05) and a trend for a decrease in CRP. When stratifying by exercise mode, trends toward reduction in IL-6 and TNF-α were observed for combined exercise, while changes were not generally affected by exercise program duration.

Conclusion: Exercise, especially combined RT and AT, can reduce pro-inflammatory biomarkers, and may be a suitable strategy to reduce inflammation in breast cancer survivors. However, further research is needed to investigate the effects of exercise mode and program duration on markers of inflammation in this survivor group.

Background: Recent advancements in cancer treatments have improved survival rates, but rising costs associated with these innovations raise concerns about their financial impact on patients. This study investigates the trade-off between improved survival and the financial toxicity over time in advanced non-small cell lung cancer (NSCLC).

Methods: We conducted a retrospective cohort study using linked data from the Western Washington SEER cancer registry and TransUnion credit records, focusing on adults diagnosed with advanced NSCLC, bladder, uterine, head and neck, and liver cancers between 2013 and 2017. Financial toxicity was assessed through major adverse financial events (AFEs), including collections, charge offs, liens, delinquent payments, foreclosures, repossessions, and bankruptcies. Multivariable multinomial logistic regression evaluated trends in a composite outcome of survival and AFEs for NSCLC patients within 2 years post-diagnosis. A falsification test evaluated a negative control group of advanced cancers lacking new therapies.

Results: Our study included 6548 patients (mean age 69; 42% female; 86% non-Hispanic White). Two-year survival for NSCLC patients increased from 15.2% to 19.2% between 2013 and 2017 (mean change 4.0%pt, 95% CI = 0.7 to 7.3). The proportion of survivors without AFEs increased by 2.2%pt (95% CI = -0.6 to 5.1), while those alive with major AFEs increased by 1.9%pt (95% CI = 0.02 to 3.6). This trend was absent in the negative control group.

Conclusions: The trade-off between survival gains and increased economic hardships linked to treatment innovations underscores the need to expand our focus beyond clinical outcomes and implement protective measures that ensure healthcare advancements promote population health without inducing financial distress.

Li Fraumeni syndrome (LFS) arising from germline TP53 mutation results in defective DNA repair and increased risk of multiple primary cancers beginning in childhood. Curative intent radiotherapy is often used to treat childhood cancer, but its impact on children with LFS has not been reviewed. We undertook a retrospective case-series review of 47 children with a solid cancer diagnosed age less than 16 years to assess time and survival after second cancer diagnosis. After radiotherapy for the first cancer diagnosis, median time to second primary cancer diagnosis was 13.3 years and median survival 9.7 years. Where no radiotherapy was received, median time to second primary cancer diagnosis was 25.1 years (χ2 = 14.8, P < .0001; Hazard Ratio = 7.9 [95% CI = 2.8 to 22.6]), and median survival of 29.2 years (χ2 = 12.5, P = .004, Hazard Ratio = 3.2 [95% CI = 1.5 to 6.6]). Radiotherapy for first cancer in children with LFS is associated with adverse outcomes and ought to be considered only in the absence of other potentially curative options. Where unavoidable, second cancer risks must be minimized.

Background: HIV prevalence in Harare reached a maximum of around 33% of adults in 1995, before falling to 12% in 2019. We examine trends in the incidence of Kaposi sarcoma (KS), non-Hodgkin lymphoma (NHL), Hodgkin lymphoma, and squamous cell conjunctival cancers (SCCCs) in the population of Harare in relation to changes in HIV prevalence, and the increasing availability and use of antiretroviral therapy (ART).

Methods: Data from the population-based cancer registry of Harare are used to calculate incidence rates for the Black (African) population for the years 1990-2019.

Results: Incidence of KS increased to a peak in the late 1990s, after which rates declined, especially at younger ages. Mean age at diagnosis increased by about 8 years in men and 6 years in women. SCCC shows a similar trend to that of KS, with a dramatic 10-fold increase in incidence, followed by an equivalent fall. Although Hodgkin lymphoma showed no change in incidence over the 30-year period, rates of NHL progressively increased. Incidence in younger adults (aged younger than 44) stabilized after about 2001 but continued to increase in older individuals.

Conclusions: The availability of high-quality cancer registry data over a long period has provided a unique opportunity to study the effects of the epidemic of HIV-AIDs and of ART availability on the risk of cancer in an African population. As HIV prevalence fell and ART coverage expanded, incidence of KS and SCCC declined, whereas for NHL the trends suggest that long-term infection with HIV may pose an increased risk, despite ART.

Background: Emerging evidence suggests that bacteria residing in colorectal tissue are plausibly associated with colorectal cancer. Prior studies investigated the effects of dietary interventions on the fecal microbiome, but few assessed colorectal tissue microbiome endpoints. We investigated the effects of a high-fiber, high-fruit, high-vegetable, and low-fat dietary intervention on the rectal tissue microbiome in the Polyp Prevention Trial (PPT).

Methods: PPT is a 4-year randomized clinical trial with intervention goals of consuming (1) at least 18 g of fiber per 1000 kcal/day; (2) at least 3.5 servings of fruits and vegetables per 1000 kcal/day; and (3) no more than 20% of kcal/day from fat. Using 16S ribosomal RNA gene sequencing, we characterized bacteria in rectal biopsies collected at baseline and the end of years 1 and 4 (n = 233 in intervention arm and n = 222 in control arm). We estimated effects of the intervention on alpha and beta diversity and relative abundance of a priori-selected bacteria using repeated-measures linear mixed-effects models.

Results: The intervention did not statistically significantly modify rectal tissue alpha diversity. Compared with the control arm, relative abundance of a priori-selected Porphyromonas (absolute intervention effects [standard errors] at T1 vs T0 = -0.24 [0.07] and T4 vs T0 = -0.12 [0.07]; P = .004) and Prevotella (absolute intervention effects at T1 vs T0 = -0.40 [0.14] and at T4 vs T0 = -0.32 [0.15]; P = .01) were more strongly decreased in the intervention arm.

Conclusion: The PPT intervention did not influence rectal tissue microbiome diversity or the relative abundance of most bacteria, except for 2 oral-originating bacteria that were previously associated with colorectal cancer presence.

Background: General adiposity, assessed by body mass index (BMI), is a well-established cancer risk factor. This study compared waist circumference (WC), a measure of abdominal adiposity, with BMI as a risk factor for obesity-related cancers, and assessed whether WC provides additional information beyond BMI.

Methods: We analyzed data from 339 190 individuals in a pooled Swedish cohort with baseline BMI and WC assessments from 1981 to 2019 (61% objectively measured, mean age 51.4 years). Cancer diagnoses were obtained from the Swedish Cancer Register. Hazard ratios (HRs) for WC and BMI were calculated using multivariable-adjusted Cox regression. To account for WC's greater variability, we corrected HRs using regression dilution ratios. To assess WC's additional contribution beyond BMI, we analyzed WC residuals in multivariable, BMI-adjusted models.

Results: During a median follow-up of 13.9 years (interquartile range: 8.0-22.5), 18 185 IARC-established obesity-related cancers were recorded. In men, a 1-standard deviation (SD) increase in WC was associated with a 25% higher risk of obesity-related cancers (HR1-SD = 1.25, 95% CI = 1.21 to 1.30), compared to a 19% increase for BMI (HR1-SD = 1.19, 95% CI = 1.15 to 1.23, P = 0.014 for heterogeneity). Among women, associations were weaker and similar for both WC (HR1-SD = 1.13, 95% CI = 1.11 to 1.16) and BMI (HR1-SD = 1.13, 95% CI = 1.11 to 1.15, P = 0.357 for heterogeneity). Waist circumference residuals were more strongly associated with obesity-related cancer risk in men (HR1-SD = 1.09, 95% CI = 1.06 to 1.12) than in women (HR1-SD = 1.03, 95% CI = 1.02 to 1.05). Including an additional 6893 potential obesity-related cancers yielded similar patterns of associations.

Conclusion(s): Waist circumference is a stronger risk factor than BMI for obesity-related cancer in men, conveying additional risk information, whereas this is less evident in women.

Nearly 20 million people in the U.S. are living with and beyond a cancer diagnosis, many of whom survive for decades after treatment. As this population continues to grow and age, primary care (PC) plays an increasingly important role in managing long-term and late effects of treatment. However, efforts to improve survivorship care (SC) delivery in PC have only recently gained attention. With more survivors relying on their primary care clinicians (PCCs), there is a clear need to strengthen the implementation of high-quality SC in PC settings. In this commentary, we explore how high-quality SC can be implemented in PC, using the implementation plan outlined in the National Academies of Sciences, Engineering, and Medicine (NASEM) report Implementing High-Quality Primary Care: Rebuilding the Foundation of Health Care. We describe the evidence on PCCs' roles across the cancer care continuum and map the evidence to the NASEM report's five implementation objectives: payment, access, workforce, digital health, and accountability. Through this work, we identify future directions for policy and research to ensure that PC can serve as a "common good" for all cancer survivors.

Background: Uterine cancer incidence and mortality are increasing, with concomitant disparities in outcomes between racial groups. Natural history modeling can evaluate risk factors, predict future trends, and simulate approaches to reducing mortality and disparities.

Methods: We designed a natural history model of uterine cancer using a multistage clonal expansion design. The model is informed by National Health and Nutrition Examination Survey, National Health Examination Survey, age, time period, birth cohort, and birth certificate data on reproductive histories and body mass index (BMI). We fit and calibrated the model to Surveillance, Epidemiology, and End Results data by race and ethnicity as well as histologic subgroup. We projected future incidence and estimated the degree of contribution of BMI, reproductive history, and competing hysterectomy to excess uterine cancer incidence.

Results: The model accurately replicated Surveillance, Epidemiology, and End Results incidence for endometrioid, nonendometrioid, and sarcoma subgroups for non-Hispanic Black and non-Hispanic White patients. For endometrioid, nonendometrioid, and sarcomas, BMI-attributable risks are greater for non-Hispanic White than for non-Hispanic Black patients; reproductive history-attributable risks are greater for non-Hispanic Black patients. Between 2018 and 2050, endometrioid incidence is projected to rise by 64.9% in non-Hispanic Black individuals and17.5% in non-Hispanic White individuals; the projected rise for the nonendometrioid subgroup is 41.4% in non-Hispanic Black individuals and 22.5% in non-Hispanic White individuals; the sarcoma incidence projected increase is 36% in non-Hispanic Black individuals and 29.2% in non-Hispanic White individuals.

Conclusions: Uterine cancer risk is substantially explained by reproductive history and BMI, with differences observed between non-Hispanic Black and non-Hispanic White individuals and future projections indicating perpetuation of disparities. Lower rates of hysterectomy and rising obesity rates will likely contribute to continued increases in uterine cancer incidence.