JNCI Cancer Spectrum最新文献

Although cancer prevention, care, and survivorship in the United States has dramatically improved over the last decade, inequities in morbidity and mortality among under-resourced populations have grown, mostly attributed to structural, societal, and institutional factors. To address inequities in cancer-related outcomes, community-engaged research (CEnR) and practice remains essential. CEnR is generally supported by Community Outreach and Engagement (COE) units in National Cancer Institute-designated cancer centers. For more than a decade COE remains a requirement for comprehensive designation and is a significant factor in the overall cancer center scoring. Community engagement occurs on a continuum from community-engaged to community-based participatory research. Engaging communities experiencing inequities in cancer incidence, morbidity, and mortality to ameliorate factors contributing to poorer cancer-related outcomes remains a goal albeit a challenging one. This commentary details both novel and successful approaches that researchers throughout the country have used to engage communities to address cancer-related inequities in their catchment areas by leveraging COE infrastructure to facilitate CEnR across research programs. We also highlight and forward recommendations from a recent scientific pre-conference workshop. Cancer center-led CEnR is critical to engaging with key communities, yet there are tremendous opportunities to better articulate and implement approaches to effective engagement. Internal inequities and barriers in COE infrastructures and how researchers, directors and stakeholders can collaborate to optimize cancer health outcome/CEnR are discussed, in addition to potential solutions involving collaboration with upstream policy stakeholders. In this commentary, we emphasize why this work remains an ongoing but critical priority.

Childhood cancer radiotherapy (RT) increases subsequent neoplasm (SN) risk. Radiation dose may modulate DNA damage responses, but the small sample sizes of prior human studies of homologous recombination repair (HRR) hampered dose-specific investigations. We pooled data for 12,180 survivors (Childhood Cancer Survivor Study [CCSS]=8,339; St. Jude Lifetime Cohort [SJLIFE]=3,841) to estimate associations between deleterious HRR variants and RT-related SNs (RT-SNs, most commonly breast cancer, meningioma, thyroid cancer, and sarcoma) using conditional logistic regression with matched controls. 1,253 (10.3%) survivors were HRR variants carriers and 1,301 (10.7%) developed ≥1 RT-SNs. Variants increased risk of out-of-field RT-SNs (cases, 40/190 = 21.1%; controls, 9.7%; OR, 2.5; 95%CI, 1.7 to 3.6; P = 4.80x10-6), with consistent results across cohorts (CCSS: OR, 2.5; 95%CI, 1.6 to 3.7; P = 3.77x10-5; SJLIFE: OR, 2.5; 95%CI, 1.0 to 6.4; P = 3.07x10-2). No association was observed for in/near-field SNs or those without RT. Findings emphasize HRR variant-conferred susceptibility to RT-SNs and dose-dependent DNA damage repair.

Cognitive effects of breast cancer anti-estrogen endocrine therapy are a salient concern for survivors, given the growing evidence that estrogen plays a role in late-life dementia risk. The APOE4 genotype has been linked with risk for cognitive difficulties, studied mainly in younger cancer survivors. We found that women aged 60+ with non-metastatic breast cancer enrolled in the prospective Thinking and Living with Cancer study who underwent endocrine therapy had lower subjective (P=.06) and objective (P=.08) cognitive function than frequency-matched controls across time. At 5-years, however, women with breast cancer exposed to endocrine therapy and APOE4 carriers in particular exhibited lower learning and memory scores than other groups (p<.05). Our results suggest endocrine therapy may have long-term effects on cognitive function in women with breast cancer, particularly APOE4 carriers. Further characterization of genetic risk for long-term cognitive decline will be useful to inform survivorship care of older women.

Background: Cancer surveillance in mainland China is based on household-registered residents and therefore fails to cover migrant populations. This introduces selection bias and leads to a misestimation of the true cancer burden. Estimating lung cancer incidence and mortality among resident populations provides a more accurate epidemiological and public health assessment.

Methods: Using 2016 data from 487 cancer registries and multidimensional covariates, we developed a Bayesian integrated nested Laplace approximation with stochastic partial differential equation (INLA-SPDE) model to estimate lung cancer incidence and mortality among the resident population, with adjustments for inter-provincial migration.

Results: In 2016, the inter-provincial migrant population in mainland China reached 140.96 million, representing 10.1% of the household-registered residents. The results indicate that the INLA-SPDE model outperformed the Bayesian hierarchical linear model in estimation accuracy, effectively captured spatial heterogeneity and achieved a Bayesian credible interval coverage exceeding 94%. Significant disparities in lung cancer incident cases and deaths between resident populations and household-registered residents were observed in Henan (9,159 cases and 7,539 deaths), Guangdong (8,851 cases and 7,235 deaths), and Shanghai (5,406 cases and 4,332 deaths). The largest rate differences occurred in Shanghai (incidence, 20.4/100,000, 23.7%; mortality, 8.7/100,000, 15.1%).

Conclusion: Disparities in incidence and mortality vary with the direction and magnitude of interprovincial migration, indicating that household-registered residency-based registration overestimates lung cancer burden in high-immigration regions and underestimates it in high-emigration regions. We recommend transitioning to resident population-based registration to improve the accuracy of lung cancer burden estimates of cancer surveillance, particularly in regions with substantial migrant populations.

Background: S0221 investigated weekly vs (vs) every 2 weeks (Q2W) dosing of doxorubicin(A)/cyclophosphamide (C) followed by paclitaxel (P) in patients with high-risk early breast cancer. After an interim analysis, randomization to the two AC arms was stopped for futility and the trial was modified to study only the P schedules.

Patients and methods: Between December 2003 and November 2010, 2716 patients were randomized in a 2 x 2 factorial design to: 15 weeks of weekly A and daily C vs 6 cycles of Q2W AC; and weekly P for 12 weeks vs 6 cycles of Q2W P. Between January 2011 and January 2012, an additional 578 patients were assigned to 4 cycles of Q2W AC x 4 and randomized to weekly vs Q2W P. Updated survival was assessed using log-rank tests and Cox regression models. We compared outcomes by breast cancer subtype as well.

Results: At a median follow-up of 12.1 years, there were no significant differences among the four treatment arms in disease free survival [DFS] (p = 0.91) or overall survival [OS] (p = 0.34) in the original protocol. Among the 578 patients assigned AC for 4 cycles and randomized to P weekly vs Q2W P, there were no overall differences in DFS (p = 0.32) or OS (p = 0.42).

Conclusion: As there were no significant outcome differences in DFS or OS between the studied schedules of AC and P with extended follow-up in the original or revised protocol, either paclitaxel schedule may be recommended, with selection based on toxicity, cost, or patient preference.

Molecular profiling has identified three groups of meningiomas, with MenG C tumors exhibiting the vast majority of recurrences. Efforts to find effective treatments for recurrent meningiomas have remained elusive. Higher WHO-grade meningiomas have exhibited greater Programmed Death Ligand 1 (PD-L1) expression through various methods, but the prognostic value of PD-L1 expression has not been described in the context of molecular profiling. Additionally, trials investigating PD-1/PD-L1 targeted immunotherapies have produced disappointing results. Here, we find that PD-L1 positivity, while prevalent in MenG C tumors, does not predict recurrence in the benign MenG A and B tumors. PD-L1 positivity also occurs independently of CDKN2A/B loss, a core component of the WHO grade that is regularly used in clinical trial selection criteria. Our results indicate that future clinical trials for PD-1/PD-L1 centric immunotherapies should select patients after molecularly profiling tumors to confirm aggressive MenG C status.

Background: Exercise has emerged as a potent, non-pharmacological intervention to enhance immune function in patients with cancer. The effects of exercise are likely influenced by patients' oncologic characteristics, such as cancer treatment, and intervention variables, such as exercise intensity, which can lead to heterogeneous outcomes. This scoping review aims to identify patterns, trends, and gaps in the literature regarding the relationship between chronic exercise training intensity and immune cell parameters in the context of treatment status.

Methods: Reports were retrieved from PubMed, MEDLINE, and CINAHL. Eligible reports were controlled clinical trials of an exercise training intervention with more than one exercise session, included an objectively defined exercise intensity, and reported cellular immune outcomes.

Results: 21 articles (15 randomized controlled trials) were included. Results suggest a dose-response effect of intensity, where vigorous-intensity exercise (reported in 6 studies) elicited beneficial immunomodulation, such as enhanced natural killer cell cytotoxicity. Light-to-moderate and moderate-intensity exercise (reported in 8 studies) resulted in no significant immunological changes in 5 studies, particularly for patients undergoing active treatment. Comparisons across studies were difficult due to heterogeneity in patients' clinical characteristics, intervention details, and immune parameters. Few reported cancer clinical outcomes such as disease progression, and none directly examined the relationships between immune and clinical endpoints.

Conclusions: While direct comparisons of exercise intensities are lacking, these results suggest that vigorous exercise training may exert greater immune modulation than low-to-moderate intensity exercise training. Rigorously designed trials are needed to confirm these findings and establish the role of exercise in oncologic care.

Background: Given excellent prostate cancer outcomes, comorbidity management is critical to survivorship. While hormone therapy or androgen deprivation therapy (ADT) is a mainstay of treatment, they can negatively impact quality of life and survivorship through cardiovascular, sexual, and metabolic effects. ADT-induced metabolic syndrome causes impaired glucose tolerance, muscle mass loss, and weight gain. This systematic review examined recent randomized clinical trials (RCTs) investigating the impact of diet and weight management strategies on mitigating ADT-related adverse effects.

Methods: A systematic review of RCTs (2015-2025) was performed using PubMed/Embase following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. To identify how diet and weight management impacts ADT symptoms, search terms included: "prostate cancer," "diet," "nutrition," "glucagon-like peptide-1 receptor agonists" (GLP-1RA), and "ADT." Risk of Bias 2 (ROB2) and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tools evaluated RCT quality.

Results: Of 2799 publications, 16 met inclusion/exclusion criteria (range, 23-96 patients/RCT). No RCTs had a high risk of bias or evaluated GLP-1RA. Outcomes included metabolic labs, body composition, and quality of life. Mediterranean and low-carbohydrate diets with exercise reduced cardiovascular and metabolic risk factors, with variable durability. Creatine trended toward increasing lean muscle mass. Multidisciplinary care and community involvement improved accountability and outcome durability.

Conclusions: This comprehensive review of diet and ADT in prostate cancer identified nutritional interventions that were safe, feasible, and may be recommended as part of prostate cancer treatment and survivorship. Future RCTs should evaluate optimal diet duration, longer follow-up, multidisciplinary patient support, and novel anti-metabolic therapies like GLP-1RA.

Background: Diabetes and excess body weight are established risk factors for pancreatic ductal adenocarcinoma (PDAC); however, few studies have evaluated their association with PDAC survival. No studies have examined prediagnosis body size and physical activity across the adult life course and their impact on PDAC survival.

Methods: We evaluated survival by prediagnosis self-reported diabetes and adult life course body mass index (BMI) and leisure-time physical activity from late adolescence to older age (eg, ≥50 years). We determined trajectories for BMI and leisure-time physical activity using latent class modeling. We included 2522 participants diagnosed with PDAC in the National Institutes of Health-AARP cohort between 1996 and 2018. Vital status was followed through December 31, 2019. We calculated hazard ratios (HRs) and 95% CIs for PDAC survival using multivariable Cox proportional hazard models. Significance tests were 2 sided.

Results: Diabetes (vs without diabetes) was associated with reduced PDAC survival (HR = 1.36, 95% CI = 1.17 to 1.59), with similar associations by sex. Body mass index and leisure-time physical activity and their trajectories were not associated with PDAC survival. Among patients with unknown cancer stage (n = 1385), compared with low to normal BMI (≥18.5 to <22.5), obesity at age 18 years (HR = 1.56, 95% CI = 1.09 to 2.22) and high normal, overweight, and obese BMI at ages 51 to 70 years (HR = 1.33 to 1.56) were associated with reduced PDAC survival.

Conclusions: Prediagnosis diabetes was associated with reduced PDAC survival. Life-course BMI and leisure-time physical activity were not associated with PDAC survival overall. Higher early-adulthood and older-adulthood BMIs were associated with poorer survival among patients with unstaged disease; however, stage is an important determinant of survival that we were unable to control for in this group.

Background: The incidence rates of testicular germ cell tumors (TGCT) are increasing in adolescents and young adults in the United States, especially in Latinos. We investigated the association between TGCT risk and birth levels of phthalates, known endocrine disrupting chemicals, in a diverse population in California.

Methods: Reverse phase chromatography was applied to newborn blood samples of 196 TGCT cases and 190 controls to measure 10 phthalates, 5 of which passed quality control: mono-2-methyl-2-hydroxypropyl phthalate/mono-3-hydroxy butylphthalate (MHiBP/MHBP), mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(oxo-isononyl) phthalate (MOiNP), and mono(2-ethylhexyl) phthalate (MEHP). We conducted single chemical and mixture analyses using weighted quantile sum (WQS) regression, adjusting for birth and sociodemographic characteristics, and hematocrit. We ran repeated holdout analyses splitting data between training and testing sets 100 times.

Results: None of the single phthalates was significantly related to case status. The overall WQS analyses showed a curvilinear mixture effect related to TGCT risk, approximated with linear and quadratic terms, and dominated by MECPP and MEHP mostly in the lower concentration ranges. For Latinos, the curvilinear mixture effect was dominated by MEHP, and the WQS betas were borderline significant (median b1 = 0.37, 95% CI = -0.25 to 1.28; median b1sq = -0.04, 95% CI = -0.15 to 0.03), with a high level of reproducibility for beta estimations in the repeated analyses (87%-89%). For non-Latino whites, the mixture effect was dominated by MECPP and MHiBP/MHBP, although the signal for curvilinearity and repeated analyses were less robust.

Conclusions: Prenatal exposure to phthalate mixtures may increase TGCT risk later in life, with some variation by racial/ethnic group.