JNCI Cancer Spectrum最新文献

Background: Care delivery trials to integrate early palliative care in community oncology practices are needed to enhance guideline-concordant care; however, little is known about how to successfully implement these trials within national research networks.

Methods: A process evaluation was conducted to identify and address practice and patient recruitment challenges within a nationwide cluster randomized trial testing 2 implementation strategies (virtual learning collaborative vs technical assistance) for integrating the Educate, Nurture, Advise, Before Life Ends (ENABLE) early palliative care program in the National Cancer Institute Community Oncology Research Program. To examine implementation barriers, we collected quantitative practice and clinician characteristics via surveys and conducted qualitative interviews with clinicians and staff. Interview data were coded and summarized using content analyses to identify barriers to implementing study procedures and the ENABLE program.

Results: Surveys and interviews were completed by 33 clinicians, 23 ENABLE coaches, and 19 coordinators in 9 practice clusters between April 2021 and June 2022. Although 78% of practice clusters identified availability of some palliative care services, none routinely referred all newly diagnosed advanced cancer patients to these services as recommended by guidelines. Key research and clinical ENABLE implementation barriers included limited staffing during and after COVID-19, low physician buy-in, belief that ENABLE overlapped with existing palliative services, and participant burden. In response, several trial modifications were made to enhance flexibility with study procedures and the clinical ENABLE intervention.

Conclusions: Implementation trials within cancer clinical trial networks must employ pragmatic and iterative study procedures to accommodate clinical practice workflows.

Trial registration: ClinicalTrials.gov Identifier: NCT04062552.

Background: Breast cancer screening is crucial for early detection and improved survival in Alzheimer disease and related dementias (ADRD) patients, but real-world evidence of its effects on survival and prognosis remains insufficient.

Methods: We conducted a retrospective cohort study using Surveillance, Epidemiology, and End Results-Medicare data (1999-2019) to analyze the impact of breast cancer screening on prognosis (ie, cancer stage) and survival in ADRD women with breast cancer diagnosed at ages 67 years and older. Logistic and Cox regression models were employed to assess the relationship between screening and risk of advanced stage at diagnosis and length of survival, adjusted for relevant covariates (eg, marital status, comorbidities, age at screening).

Results: The cohort included 8739 ADRD patients with breast cancer, with 4483 completed at least 1 screening between their ADRD and first breast cancer diagnosis. The cohort completed screening had statistically significant lower rates of advanced-stage diagnosis (22.2% vs 42.6%) and longer survival (65.9 vs 45.7 months) compared with the cohort without any screening history. Unscreened patients had 2.7 times higher odds of advanced-stage diagnosis and 2 times higher hazard of death than patients with at least 1 screening completed before breast cancer diagnosis. Effects of comorbidities, age, and race were statistically significant on diagnosis stage and survival in breast cancer patients.

Conclusion: Our study demonstrated the benefit of screening in early diagnosis and longer survival in ADRD patients with breast cancer, which advocates for an expansion of current breast cancer screening recommendations to more effectively guide cancer care for ADRD patients.

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.

Background: Prior studies suggest positive associations of type 2 diabetes (T2D) with risk of non-Hodgkin lymphoma (NHL) and multiple myeloma (MM), but few studies had sufficient statistical power to evaluate associations for specific histological subtypes.

Methods: We pooled data from the Cancer Prevention Study-II Nutrition Cohort, California Teachers' Study, Health Professionals Follow-up Study, Nurses' Health Study (NHS), and NHSII cohorts and a sample of Kaiser Permanente Southern California members (585,114 total study participants). We confirmed incident diagnoses of NHL and MM using medical records or cancer registries. T2D history was assessed by self-report or clinical diagnosis. We estimated the associations of T2D history (yes/no) and T2D duration with risk of overall NHL, NHL subtypes, or MM using multivariable Cox regression models adjusted for age, sex, cohort, follow-up year, race, education, smoking, and body mass index.

Results: We confirmed 11,478 NHL and 2,783 MM diagnoses over a median follow-up of 20 years. T2D history was not associated with overall NHL risk but was positively associated with risk of diffuse large B-cell lymphoma (DLBCL; hazard ratio [HR] = 1.15, 95% confidence interval [CI] = 1.04 to 1.28) and MM (HR = 1.20, 95% CI = 1.07 to 1.35) and inversely associated with risk of lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (HR = 0.45, 95% CI = 0.27 to 0.75), T-cell NHL (HR = 0.78, 95% CI = 0.62 to 0.97), and mycosis fungoides/Sézary syndrome (HR = 0.67, 95% CI = 0.46 to 0.98). T2D duration was positively associated with risk of DLBCL and MM.

Conclusions: Our findings suggest a role for T2D in DLBCL and MM; thus, T2D prevention may be important in reducing their incidence. Some unexpected inverse associations require further investigation.

Background: Patients with incurable gastroesophageal adenocarcinoma have an impaired health-related quality of life (HRQOL). Exercise combined with nutritional support may improve this outcome. Careful evaluation of this supportive care strategy is needed to avoid burdening patients at this vulnerable stage with interventions that may offer no (meaningful) benefit. Therefore, this study aims to investigate the effects of a combined exercise and nutritional intervention on HRQOL in patients with incurable gastroesophageal adenocarcinoma.

Methods: RADICES (the effect of exeRcise And Diet on quality of life in patients with Incurable Cancer of Esophagus and Stomach) is a multicenter randomized controlled trial aiming to include 196 patients with incurable gastroesophageal adenocarcinoma. Participants are randomly assigned (1:1) to a patient-tailored intervention or a control group. The intervention group is provided with 2 training sessions per week and biweekly nutritional consultations, delivered by trained physiotherapists and dietitians, during 12 weeks. The control group receives usual care supplemented with general physical activity advice. The primary outcome is the difference in HRQOL between the intervention group and the control group at 12 weeks, accounting for baseline HRQOL, measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-30 summary score. HRQOL is assessed at baseline, 6 weeks, 12 weeks, and every 3 months thereafter up to 1 year. Key secondary outcomes include patient-reported outcomes, cardiorespiratory fitness, dietary intake, disease progression, overall survival, and cost-effectiveness. Adherence and safety are monitored throughout the intervention period.

Conclusion: This study will generate evidence on the effectiveness of a patient-tailored combined exercise and nutritional intervention in patients with incurable gastroesophageal adenocarcinoma. If effective for HRQOL, this intervention could be integrated into standard care for patients with incurable gastroesophageal adenocarcinoma.

Trial registration: clinicaltrials.gov NCT06138223. Date of trial registration: November 18, 2023 Date and version study protocol: 28-04-2025 version 3.1 Date start recruitment: 19-01-2024.

Background: Deficient mismatch repair (dMMR) and microsatellite instability-high (MSI-H) tumors constitute ∼15% of localized colorectal cancers (CRCs). Prognostic biomarkers such as tumor-infiltrating lymphocytes (TILs) and BRAF and KRAS mutations may guide personalized treatment for these patients, and this systematic review and meta-analysis aimed to evaluate their impact on survival outcomes.

Methods: Literature searches were conducted across PubMed, Embase, Cochrane Library, and Web of Science, including studies published between 2004 and 2023. The primary outcomes were overall survival (OS), disease-free survival (DFS), and cancer-specific survival. The risk of bias was assessed using the Newcastle-Ottawa Scale, and the certainty of evidence using the GRADE approach.

Results: The literature search yielded 5636 articles. Fifty-four studies were included in the systematic review and 31 studies in the meta-analysis, totaling 4551 patients. High TIL density was significantly associated with improved OS (hazard ratio [HR] = 0.39, 95% CI = 0.17 to 0.89) and DFS (HR = 0.45, 95% CI = 0.29 to 0.71). BRAF and KRAS mutations were seen in 52% and 34% of patients, respectively, and were associated with poorer OS (HR = 1.43, 95% CI = 1.13 to 1.80 and HR = 1.30, 95% CI = 1.09 to 1.54, respectively). Quality of evidence was moderate to high across all exposures and outcomes.

Conclusion: High infiltration of TILs correlated with improved OS and DFS, whereas BRAF and KRAS mutations were associated with worse OS in patients with localized dMMR/MSI-H CRC. These findings highlight the potential utility of biomarkers for improving prognostic assessment and personalizing management in dMMR CRC.

Cognitive effects of breast cancer antiestrogen 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 nonmetastatic 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 diagnosis originating in emergency departments (emergency presentation) contributes to poorer cancer survival and reflects aggressive disease and limited access to routine health care. This study characterized emergency presentations for a range of cancers and subclassified by whether patients were hospitalized after the emergency encounter, with the hypothesis that, compared with those hospitalized, patients not requiring hospitalization more specifically represent barriers to timely and adequate care.

Methods: We analyzed Surveillance, Epidemiology, and End Results-Medicare data for patients aged 66 years and older diagnosed with 14 cancer types (2008-2017; n = 614 885). We described emergency presentation overall and demographic and clinical characteristics across subgroups using linear regression and assessed differences in health-care utilization before the emergency presentation classification window.

Results: In total, 234 606 (38%) patients were classified as emergency presentations, with 187 439 (80%) hospitalized. Emergency presentations were more likely than nonemergency presentations to have prediagnostic emergency care (40%, 95% confidence interval [CI] = 40% to 40%) vs 30% (95% CI = 29% to 30%) and less likely to have nonemergency care for potential cancer symptoms (61%, 95% CI = 61% to 61%, vs 67%, 95% CI = 67% to 67%), with minimal variation between inpatient and outpatient emergency presentations. Compared with inpatient emergency presentations, outpatient emergency presentations were more often younger than 70 years old (24%, 95% CI = 23% to 24%, vs 19%, 95% CI = 19% to 19%), nonmetropolitan residents (25%, 95% CI = 24% to 25%, vs 12%, 95% CI = 12% to 12%), and had localized cancer (25%, 95% CI = 25% to 26%, vs 17%, 95% CI = 17% to 17%).

Conclusions: More than one-third of older adult US cancer patients with these cancer types are diagnosed through emergency presentation, with most requiring hospitalization. Outpatient emergency presentations are more common among patients in rural areas with less advanced cancers, suggesting they may be an informative indicator of avoidable barriers to care less influenced by underlying health status.