JNCI Cancer Spectrum最新文献

Background: Cardiometabolic risk factors (CMRF) and cardiovascular disease (CVD) incidence in racially and ethnically underrepresented women with breast cancer (BC) are not well characterized.

Methods: The Pathways Heart Study is a prospective cohort of 14,942 women diagnosed with invasive BC from 2005-2013 at Kaiser Permanente Northern California. Incidence of CMRF and CVD outcomes was determined from electronic records and calculated with competing risk framework for non-CVD death. Fine-Gray proportional hazards regression estimated sub-distribution hazard ratios by race and ethnicity compared with non-Hispanic White (NHW) women, with additional Asian subgroup analysis.

Results: Participants were on average 61 years old at diagnosis and 65% NHW, 7.5% Black, 14.4% Asian, 11.9% Hispanic, 0.4% Pacific Islander, and 0.8% American Indian/Alaska Native. Black and Asian women had 1.2-1.3-times higher incident hypertension risk; Black, Asian, Hispanic, and Pacific Islander women had 1.5-3-times higher incident diabetes risk; Asian women had 1.2-times higher incident dyslipidemia risk.Black women had 1.3-1.4-times higher risk of incident ischemic heart disease (IHD), heart failure (HF) and overall CVD. Filipino women had 1.6-times higher risk of stroke. South Asian women had 2.5-2.6-times higher IHD and HF risk.

Conclusions: Compared with NHW women, racially and ethnically diverse women with BC experienced higher risk of incident diabetes, hypertension, and dyslipidemia. Black and Asian women, particularly Filipino and South Asian, had higher risk of incident CVD. Better characterization of health disparities in cardio-oncology is critical to inform future CVD prevention and treatment.

Background: Physical activity (PA) is associated with improved overall survival (OS) among colorectal cancer (CRC) patients, but research on PA changes after diagnosis remains limited. This study examines associations between OS and changes in PA from CRC diagnosis onward, across stage- and treatment-related subgroups.

Methods: Data were analyzed from patients in two large CRC cohorts (PLCRC and COLON) enrolled between August 2010 and December 2022 (follow-up until February 1st, 2024). This included 3,395 stage I-IIA patients who underwent surgery only, 2,406 stage IIB/C-III patients who received (neo-)adjuvant therapy, and 669 metastatic CRC (mCRC) patients. PA was assessed via the validated SQUASH questionnaire at diagnosis (T0), and at 6, 12, and 24 months post-diagnosis (T6 to T24). Moderate-to-vigorous-intensity recreational activity was quantified by calculating Metabolic Equivalent of Task (MET) hours per week. Associations with OS were examined for change (active [tertile 2 and 3] vs inactive [tertile 1]) between timepoints using multivariable Cox proportional hazards models.

Results: Among surgery-only patients, change from inactivity to activity between T0 and T6 was significantly associated with OS (HR 0.58 [95% CI 0.35-0.96]). For (neo-)adjuvantly treated patients, significant associations were observed between T6 and T12 (0.53 [0.31-0.90]). Among mCRC patients, a significant association was observed between T6 and T12 (0.53 [0.29-0.99]).

Conclusion: Changing from inactivity to activity is significantly associated with prolonged survival during the early months post-diagnosis for surgery-only CRC patients, and later for those undergoing (neo-)adjuvant therapy or with metastatic disease. Validation is warranted in interventional studies.

Background: Patients with metastatic cancer are living longer due to treatment advances. We explored oncologists' perceptions about curability in metastatic cancer.

Methods: We invited medical oncologists to complete a 21-item, online survey. We conducted descriptive analyses, and thematically analyzed free-text responses.

Results: 126 respondents completed the survey. Median age was 39 years (range 27-75). Most respondents worked in Australian (64%), metropolitan (88%), public practices (56%). The most frequently treated cancer types were breast (55%), lung (52%), and colorectal (50%). 82% reported thinking that patients with metastatic cancer can be cured. Cancer types with the highest perceived chance of cure (median percentage) were testicular (81%), melanoma (32%), and colorectal (16%). At the time of diagnosis of metastatic cancer, 51% reported they would ever tell a patient cure was possible. After treatment, 29% reported telling some patients they had been cured, while 74% reported telling some patients that they may have been cured. A higher proportion thought cure was a realistic possibility with immunotherapy (83%) rather than chemotherapy (40%), but only 44% and 27% respectively reported they would tell this to patients. 46% reported discussing the possibility of cure more frequently with immunotherapy, 5% more frequently with chemotherapy, 7% as frequently with both, and 42% not discussing with either. Respondents identified oligometastatic disease, actionable mutations, and durable responses to immunotherapy as factors associated with cure.

Conclusions: Most respondents reported thinking that metastatic cancer is curable, but were reluctant to tell individual patients with metastatic cancer they had been cured.

Background: Deficient mismatch repair (dMMR) and microsatellite instability-high (MSI-H) tumors constitute approximately 15% of localized colorectal cancers (CRC). 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 (CSS). 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. 54 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 (HR = 0.39; 95% CI: 0.17-0.89) and DFS (HR = 0.45; 95% CI: 0.29-0.71). BRAF and KRAS mutations were seen in 52% and 34% of patients, respectively, and were associated with poorer OS (HR = 1.43; 95% CI: 1.13-1.80 and HR = 1.30; 95% CI: 1.09-1.54, 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: Socioeconomic position (SEP) is a fundamental social determinant of health (SDOH) contributing to observed disparities in cancer and cardiovascular (CV) care among individuals with prostate cancer (PC). Understanding the influence of SEP on CV health is essential for addressing outcome inequities within this population.

Methods: We conducted a retrospective study utilizing SEER-Medicare to evaluate CV outcomes in patients ≥65 years with PC from 2012 to 2017. We studied the impact of SEP on Cardiovascular events (CVEs), cardiovascular mortality (CVm), PC-specific mortality (PCsm) and all-cause mortality. CVE, CVm, PCsm were analyzed using competing risk models and all-cause mortality with Cox proportional hazards models. A subgroup analysis was performed in Non-Hispanic Black and Non-Hispanic White individuals.

Results: We included 141,242 patients of whom 76,844 were in high SEP areas (45.6%) and 64,398 in low SEP ones (54.4%). Both groups had a mean age of 72 years; patients in low SEP areas were 67.5% Non-Hispanic White, 34.4% having diabetes, 73.3% hypertension, and 67.7% dyslipidemia versus high SEP group with 85.6% Non-Hispanic White, 30.4% diabetes, 69.9% hypertension, and 70.7% dyslipidemia. Patients in low SEP areas had higher risks of CVm (subdistribution hazard ratio [sHR] 1.18, 95% CI 1.12-1.25), PCsm (sHR: 1.12, 95% CI 1.06-1.17), CVE (sHR 1.07, 95% CI 1.04-1.09), and all-cause mortality (HR 1.16, 95% CI 1.13-1.20). Accentuated results were shown in the Non-Hispanic Black subgroup.

Conclusion: Adverse SEP plays a significant role in shaping outcomes among older patients with PC, contributing to elevated risks of adverse CV and survival outcomes.

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. None have examined pre-diagnosis body size and physical activity across the adult life-course with PDAC survival.

Methods: We evaluated survival by pre-diagnosis self-reported diabetes, and adult life-course body mass index (BMI, kg/m2) and leisure-time physical activity (LTPA) from late adolescence to older age. We determined trajectories for BMI and LTPA using latent-class modeling. We included 2,522 participants diagnosed with PDAC in the National Institutes of Health (NIH)-AARP cohort between 1996 and 2018. Vital status was followed through December 31, 2019. We calculated hazard ratios (HRs) and 95% confidence intervals (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, 1.59) with similar associations by sex. BMI and LTPA and their trajectories were not associated with PDAC survival. Among patients with unknown cancer stage (n = 1385), compared to low-normal BMI (≥18.5-<22.5), obesity at age 18 (HR = 1.56; 95% CI: 1.09, 2.22) and high normal, overweight, and obese BMI at ages 51-70 (HRs=1.33-1.56) were associated with reduced PDAC survival.

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

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.

Introduction: Health-related quality of life (HRQoL) is not routine in early phase clinical trials (EP-CTs), which focus on dose-limiting toxicities and safety. However, for clinicians, understanding the impact of such trials on HRQoL is fundamental to consent patients, especially when the benefits on tumor response may be unknown.

Aims and methods: The PEARLER (Patient diversity And experience in eaRLy phase cancEr clinical tRials) study was conducted with a key aim of focusing on assessing HRQoL in participants undergoing EP-CTs using a multi-center prospective cohort setting. All participants completed a baseline demographic survey on Cycle 1 Day 1 with EORTC-QLQ-C30 on Day 1 of Cycles 1 through 6 or end of treatment (EoT).

Results: Overall, 122 participants were recruited with median age 62. Median baseline Global Health Status (GHS) was 67 and remained unchanged throughout EP-CT (P = .188). GHS deterioration occurred in 29/122 (24%) while improvement occurred in 16/122 (13%). Median baseline Physical Function Score (PFS) was 87. PFS deterioration occurred in 30/122 (25%) while improvement occurred in 6/122 (5%). Baseline median CFS was 84. Cognitive Function Score (CFS) deterioration occurred in 25/122 (20%) while improvement occurred in 20/122 (16%). Baseline median Emotional Function Score (EFS) was 77. EFS deterioration occurred in 14/122 (11%) while improvement occurred in 14/122 (11%). Presence of liver metastases was a negative predictive marker for GHS, CFS, and EFS over time (P = .01, P < .01, and P < .01).

Conclusion: PEARLER is the first prospective cohort study investigating change in HRQoL over time in patients undergoing EP-CTs. Reassuringly, almost three-quarters of participants who undertake EP-CTs either sustain or improve their GHS or PFS. Presence of liver metastases appears to be a negative predictive marker of HRQoL.

Background: The 2024 American Urological Association, American Society for Radiation Oncology, and Society of Urologic Oncology practice guidelines recommend early salvage radiation therapy (RT) for biochemical recurrence after radical prostatectomy and androgen deprivation therapy for high-risk features. Increasingly, men with high-risk disease are undergoing radical prostatectomy. We therefore characterized contemporary RT and androgen deprivation therapy practices within the Michigan Radiation Oncology Quality Consortium and Michigan Urological Surgery Improvement Collaborative.

Methods: Patients receiving postprostatectomy RT from June 9, 2020, to June 9, 2024, were eligible. Prospectively collected data included surgical pathology, RT, and androgen deprivation therapy details. RT was adjuvant (pre-RT prostate-specific antigen [PSA] <0.1 ng/mL), consolidative (persistent PSA ≥0.1), or salvage (all others). Multivariable analyses evaluated associations between clinicopathologic features and androgen deprivation therapy use.

Results: Among 345 patients across 26 centers, 56% had at least 1 high-risk feature: pT3b/T4 (24%), pN1 (6%), grade group 4/5 (30%), pre-RT PSA greater than 0.5 ng/mL (27%). RT was adjuvant (10%), consolidative (28%), or salvage (62%), initiated at median PSA of 0.07 ng/mL (interquartile range [IQR] = 0.03-0.09 ng/mL), 0.5 ng/mL (IQR = 0.3-1.5 ng/mL), and 0.3 ng/mL (IQR = 0.2-0.5 ng/mL), respectively. Median time to RT was 8, 6, and 29 months. A minority were recommended 24 months of androgen deprivation therapy (17%), and very few were recommended intensification with AR-pathway inhibitors (5%). On multivariate analysis, androgen deprivation therapy was associated with pT3b/T4 (odds ratio [OR] = 2.77, 95% confidence interval [CI] = 1.34 to 5.93), pN1 (OR = 6.22, 95% CI = 1.35 to 47.57), grade group 4/5 (OR = 2.87, 95% CI = 1.51 to 5.56), and pre-RT PSA more than 0.5 (OR = 2.11, 95% CI = 1.17 to 3.91).

Conclusions: Within the Michigan Radiation Oncology Quality Consortium, more than half who received postprostatectomy RT had high-risk features; nearly 30% required consolidation for persistently positive PSA. Androgen deprivation therapy was associated with high-risk features, but few received androgen deprivation therapy prolongation or intensification. Studies are needed to personalize androgen deprivation therapy, especially for those with persistent PSA, who are frequently treated yet underrepresented in trials.

Background: We examined late effects clustering among adolescent and young adult (AYA; age 15-39 years at diagnosis) Hodgkin lymphoma (HL) survivors and identified characteristics associated with each cluster.

Methods: We included AYAs with HL in 2006-2018 from the California and Utah Cancer Registries linked to statewide hospitalization, emergency department, and ambulatory surgery visit data. We identified severe late effects >2 years after cancer diagnosis in 9 late effects categories. Latent class analysis (LCA) was used to identify late effects clusters. Multinomial logistic regression models estimated adjusted associations of demographic and treatment characteristics with LCA late effect group.

Results: We identified 4635 AYA HL survivors with median follow-up of 8.2 years and 4 late effects groups: 77.1% had a low probability of any late effect (Low Morbidity), 12.8% had high probability of Thyroid disorders, 8.0% had high probability of Cardiovascular Disease (CVD), and 2.1% had high probability of Multiple Conditions (CVD, diabetes/pancreatic, thyroid, and renal diseases). Publicly insured AYAs were more likely than those with private insurance to be in the CVD (OR = 1.53, 95% CI = 1.18 to 1.98) and Multiple Conditions (OR = 2.17, 95% CI = 1.29 to 3.66) than the Low Morbidity group. AYAs with radiation were more likely to be in the Multiple Conditions (OR = 2.31, 95% CI = 1.41 to 3.78) and Thyroid (OR = 2.81, 95% CI = 2.20 to 3.58) groups. Hematopoietic cell transplantation was associated with Multiple Conditions (OR = 9.50, 95% CI = 5.82 to 15.50), CVD (OR = 3.82, 95% CI = 2.96 to 4.93), and Thyroid (OR = 2.86, 95% CI = 2.12 to 3.85) groups.

Conclusions: While most AYA HL survivors were in the Low Morbidity group, those with public insurance or intense treatment may be at higher risk for multiple conditions.