JNCI Cancer Spectrum最新文献

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.

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.

Background: Sepsis is a major cause of death in cancer patients, yet its variation by cancer type and patient characteristics remains underexplored. We analyzed sepsis mortality in a large cancer cohort, focusing on gender and demographic disparities.

Methods: We analyzed 3 577 100 cancer cases from the SEER database (1975-2019) and calculated the standardized mortality ratio (SMR) and absolute excess risk (AER), stratified by gender, cancer type, and demographics. Logistic regression identified factors linked to sepsis mortality odds, while Cox proportional hazards models evaluated their time-dependent effects.

Results: Cancer patients experienced an excess sepsis mortality rate of 1.68 deaths per 10 000 person-years compared to the general population. Among 11 926 cancer patients who died from sepsis (0.39% of 3.07 million cases), males had consistently higher mortality than females. Risk was highest in older adults, Black, unmarried, or widowed males with high-grade cancer. Liver and pancreatic cancers showed the highest SMR and AER, followed by stomach, lung, and hematologic cancers, whereas breast and prostate cancers had lower mortality. Patients diagnosed within the first year of cancer diagnosis faced the greatest risk. Logistic regression identified protective factors including female sex, younger age, localized cancer, marriage, and radiation therapy, while Cox models highlighted the time-dependent protective effects of these factors.

Conclusions: Sepsis mortality varied significantly by gender, cancer type, and demographic characteristics. These findings emphasize the need for gender-specific and personalized management strategies to reduce sepsis mortality in high-risk cancer patients.

Individual-level social determinants of health are associated with pancreatic ductal adenocarcinoma; however, it is currently unknown whether neighborhood-level socioeconomic disadvantage is related to the risk of pancreatic ductal adenocarcinoma diagnosis. Area deprivation index is a validated tool to measure neighborhood-level disadvantage. We conducted a retrospective cohort study of 5 069 429 patients in the Veterans Health Administration between October 1, 2001, and December 31, 2021. Area deprivation index percentiles were grouped using national area deprivation index decile cutoffs. In multivariable analysis, the lowest area deprivation index group, representing the highest neighborhood-level socioeconomic status, was associated with increased hazards for pancreatic ductal adenocarcinoma (adjusted hazard ratio [HR] = 1.13, 95% confidence interval [CI] = 1.06 to 1.21) compared with those with median area deprivation index percentiles. Differences in pancreatic ductal adenocarcinoma hazards were not seen in the other area deprivation index percentiles. These results suggest that within the Veterans Health Administration, a relatively equal access health-care system, there is limited contribution of neighborhood-level socioeconomic deprivation to pancreatic ductal adenocarcinoma, except for patients with the highest neighborhood-level socioeconomic status (lowest area deprivation index).

Background: Accumulating evidence suggests that one-carbon nutrient intake reduces the risk of colorectal cancer (CRC), although folate fortification has been associated with a temporary increase in CRC incidence. We hypothesized that one-carbon nutrients might harbor preventive and protumor effects on CRC according to tumor conditions and investigated whether the effect of one-carbon nutrients on CRC risk differs by TP53 status.

Methods: In this prospective study of 21 708 Japanese participants, we applied a multivariable Cox proportional hazards model and examined the associations of dietary intakes of folate, vitamin B6, vitamin B12, and methionine with TP53-overexpressing (n = 192), TP53-nonoverexpressing (n = 301), TP53-mutated (n = 180), and TP53 wild-type (n = 134) CRC risk defined by TP53 immunohistochemistry and target sequence.

Results: Vitamin B12 and methionine intakes were not associated with any CRC subtypes defined by TP53 status. Meanwhile, folate intake was marginally associated with decreased TP53-mutated CRC risk (hazard ratio [HR] with 95% confidence interval [CI] for the highest folate intake quartile compared with the lowest (HR = 0.82, 95% CI = 0.46 to 1.45) and increased TP53 wild-type CRC risk (HR = 1.50, 95% CI = 0.78 to 2.90). A heterogeneous effect of folate on CRC subtypes was detected (P = .03 for heterogeneity between TP53 mutation statuses). In women, the association between vitamin B6 and CRC also differed by TP53 mutation status (P = .007 for heterogeneity). The hazard ratio of vitamin B6 was 0.71 (95% CI = 0.30 to 1.67) for TP53-mutated CRC and 3.89 (95% CI = 1.79 to 8.49) for TP53 wild-type CRC. However, no heterogeneous effects were observed between TP53 expression statuses.

Conclusion: This study supports the hypothesis that the effect of one-carbon nutrient intake on CRC differs according to tumor conditions.

The TMEM173/STING protein is linked to therapeutic resistance in preclinical models of HNSCC (Head and neck squamous cell carcinoma). To evaluate STING as a biomarker, quantitative immunofluorescence (QIF) was performed on a tissue microarray (TMA) cohort of primary HNSCC (n = 72). Cytokeratin and 4,6-diamidino-2-phenylindole (DAPI) staining were used to differentiate between tumor or stromal compartments, and patient groups were dichotomized based on STING QIF scores. HNSCCs display variable STING protein levels in both tumor cell and stromal compartments. STING QIF score in tumor cells is associated with p16 positivity, with similar nonsignificant trends observed for stromal QIF values. In cohort 1, elevated STING levels in either tumor cells (P = .029) or stroma (P = .023) significantly improved DFS. These findings were validated in a second oropharyngeal HNSCC TMA cohort (n = 92) where borderline or significant differences in DFS were observed for elevated STING in tumor cells (P = .066) or the stroma (P = .028). A more detailed breakdown of failure patterns in cohort 2 revealed that elevated STING in tumor (P = .015) or stroma (P = .054) predicts local-regional control, and a trend for reduced distant failure was also observed for elevated stromal STING (P = .067). Local-regional recurrence was rare in HPV+ tumors and occurred only with low STING expression. In multivariate analysis, p16 was a significant predictor for local control, whereas elevated STING was of borderline significance (P = .051). These results suggest that STING protein levels in the tumor cell are a biomarker for predicting HNSCC local control after radiation therapy, and elevated STING in tumor stroma may be associated with a reduced risk of distant failure.

Background: The purpose of this systematic review and meta-analysis was to (i) evaluate effects of exercise on cancer-related lymphedema (CRL) incidence, and (ii) explore whether effect differed according to patient and exercise intervention characteristics.

Methods: A search of 6 electronic databases was undertaken to identify intervention studies published up to May 2025. Studies included individuals at risk of and with CRL, comparing exercise to no exercise, and reporting lymphedema outcomes. Meta-analyses using random effects models estimated the relative risk (RR) of exercise on CRL. Exploratory subgroup analyses were conducted for upper- vs lower-limb lymphedema, <5 or 5+ lymph nodes dissected, and exercise intervention characteristics including exercise mode and degree of supervision. Overall quality of evidence was assessed using the GRADE approach.

Results: Seventeen studies (published 2002-2024) involving 2739 individuals were included. Most (88%, n = 15) studies focused on upper-limb lymphedema post-breast cancer, and 2 studies investigated risk of lower-limb lymphedema. With low overall certainty, the RR of developing CRL for those in the exercise group compared with the non-exercise group was 0.71 (95% confidence interval [CI] = 0.53 to 0.96). The majority of evidence is derived from studying those at high risk of breast cancer-related lymphedema, but subgroup analyses suggest that the benefit may extend outside the breast cancer setting. Subgroup analyses support participation in any/all exercise modes, even when unsupervised.

Conclusion: These findings underscore the promise of exercise for CRL risk reduction and the urgent need for rigorously designed trials to clarify effects across patient risk profiles, cancer types, and exercise approaches.

Prospero registration number: CRD42020196623.

Introduction: Cancer survivors are at-risk for transportation insecurity given the frequency of medical visits and cost of care. Little is known about how transportation insecurity relates to important social relationship measures adversely impacting cancer survivors (eg, loneliness, lack of emotional support). Thus, we evaluated the association between transportation insecurity and social relationship measures among patients with and without a history of cancer.

Methods: Using data from the 2023 Behavioral Risk Factor Surveillance System, we characterized relationships between transportation insecurity and two social relationship measures: (1) loneliness and (2) emotional support among individuals with and without a history of cancer. We used multivariable logistic regression models to estimate associations between transportation insecurity and adverse social relationships, with sensitivity analyses for at-risk groups. Models were adjusted for sociodemographic and health-related covariates.

Results: We identified 237,180 respondents with 29,579 reporting a history of cancer (12.5%). Transportation insecurity was more common among individuals who were younger, non-White, uninsured or publicly insured, unemployed, unable to work, and not partnered. Transportation insecurity was associated with both social relationship measures (loneliness: aOR = 1.24-3.00, 95% CI; lack of emotional support aOR = 1.31-2.47, 95% CI). Although these associations were consistent across cancer and non-cancer populations, in univariate analyses individuals with a history of cancer reported transportation insecurity more often if they were younger (18 to 49 years), non-White, had Medicaid, or no insurance compared to those without a history of cancer.

Conclusion: These findings highlight intersections between transportation insecurity and unmet social relationship needs among individuals with and without a history of cancer.=.

Background: While care delivery trials to integrate early palliative care in community oncology practices are needed to enhance guideline-concordant care, 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 two 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 (NCORP). 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.