JNCI Cancer Spectrum最新文献

Background: Texas has the largest uninsured population in the country. To cover medical costs of uninsured patients, multiple counties offer Financial Assistance Programs (FAPs). The association of these programs with access to cancer treatment and survival has not been studied.

Methods: Population-based Texas Cancer Registry was used to include uninsured patients aged 18 to 64 years and diagnosed with liver, lung, or pancreatic cancer from 2017 to 2021. County FAP status was ascertained from official county or county hospital websites. Multivariable binary logistic regression analyses were used to determine the adjusted odds of receipt of any cancer treatment (surgery, chemotherapy, or radiation). Subsample analyses were performed for patients with non-metastatic cancer and residents of metropolitan areas. Multivariable Cox Proportional Hazards analyses were used for survival analysis.

Results: Among 5,477 uninsured patients, 47.7% were reported to have received cancer treatment. On multivariable analysis, living in a county that offered (vs. did not offer) FAPs was associated with 1.49 higher odds of receiving cancer treatment (95%CI: 1.28-1.73). Survival analysis indicated that the Hazards of death were 44% to 55% lower for patients who received cancer treatment and lived in FAP counties (vs. did not receive cancer treatment and did not live in FAP Counties).

Relevance: For uninsured patients with cancer, residence in a county that offers financial assistance was associated with significantly increased odds of receiving treatment and significantly lower hazards of death. These findings provide evidence for policy interventions that may improve cancer care and outcomes for uninsured patients.

Background: The addition of immune checkpoint inhibitors (ICIs) to perioperative treatment for resectable gastric or gastroesophageal junction (GEJ) cancers has shown promising results. However, current pivotal trials (KEYNOTE-585 and MATTERHORN) have reported conflicting survival outcomes. To clarify their therapeutic value, we conducted a meta-analysis evaluating the efficacy and safety of adding ICIs to this population.

Methods: PubMed, Embase, and major oncology conference abstracts were systematically searched for randomized controlled trials (RCTs) comparing ICIs plus chemotherapy versus chemotherapy alone in patients with resectable gastric or GEJ adenocarcinoma. Outcomes included pathological complete response (pCR), event-free survival (EFS), overall survival (OS), and treatment-related adverse events (TRAEs). Risk differences (RDs) and hazard ratios (HRs) were pooled using a fixed-effect model meta-analysis.

Results: Seven RCTs involving 2510 patients were included. Compared with chemotherapy alone, chemoimmunotherapy significantly improved pCR (17.6% vs. 6.1%; RD = 0.11, 95% CI = 0.09 to 0.14, P < .001), EFS (HR = 0.76, 95% CI = 0.66 to 0.86, P < .001), and OS (HR = 0.82, 95% CI = 0.71 to 0.94, P = .005). Subgroup analyses showed statistically significant efficacy in PD-L1 positive tumors, whereas no significant benefit was observed in PD-L1 negative patients. Grade ≥3 TRAEs were not significantly increased with chemoimmunotherapy (66.1% vs. 62.7%; RD = 0.04, 95% CI = 0.00 to 0.08, P = .08).

Conclusions: The addition of ICIs to perioperative chemotherapy improves pathological and survival outcomes in resectable gastric or GEJ cancers, particularly in PD-L1 positive populations, without increasing grade ≥3 TRAEs. These findings support chemoimmunotherapy as a promising curative strategy.

Background: Treatment response to immune checkpoint inhibitors (ICIs) varies considerably, a phenomenon known as treatment effect heterogeneity (HTE). While HTE is explored via one-variable-at-a-time subgroup analyses in randomised controlled trials (RCTs), this method has limitations, which the risk-modelling approach seeks to address.

Methods: Applying the risk-modelling approach, individual patient data from ten RCTs (six supporting FDA atezolizumab label: OAK, IMpower130, IMpower150, IMpower133, IMbrave150, IMspire150; four unlabelled indications: IMpower131, and IMpower132, IMmotion151, IMvigor211) were analysed by an extreme gradient-boosting algorithm to predict pre-treatment prognosis for overall survival. The predicted risk scores were evaluated as efficacy modifiers categorically (high, intermediate, low risk groups) and continuously in Cox models with treatment-by-risk-group interaction terms. Sensitivity and exploratory analyses investigated absolute and meta-analysed treatment effect and compared the results with established prognostic tools and treatment effect predictors. Statistical significance tests are two-sided.

Results: Among the ten RCTs (N = 7053), one trial-IMvigor211 - showed significant HTE by pre-treatment prognosis across all evaluations (risk groups, risk scores, sensitivity analyses: p < .001). Amongst other trials, no significant HTE was detected (risk group and risk score analysis interaction test: OAK p = .61, 0.77; IMpower130 p = .13, 0.52; IMpower131: p = .21, 0.02; IMpower150: p = .14, 0.36; IMpower133: p = .38, 0.12; IMbrave150: p = .15, 0.08; IMspire150: p = .24, 0.6; IMpower132: p = .15, 0.81; IMmotion151: p = .48, 0.21).

Conclusion: The risk-modelling approach showed no clear link between pre-treatment prognosis and ICI efficacy in most RCTs, particularly those supporting atezolizumab's FDA label. In IMvigor211, patients with better pre-treatment prognosis were more likely to benefit from atezolizumab treatment for platinum-refractory metastatic urothelial carcinoma.

Background: A growing population of older adult cancer survivors faces competing cancer and non-cancer health risks. There are limited real-world data on recurrence patterns beyond five years post-treatment.

Methods: This was a SEER-Medicare retrospective cohort study of patients aged ≥66 with stage I-III breast, colon, or rectal cancer who received definitive surgery and survived ≥5 years from diagnosis without recurrence or second primary malignancy. Late recurrence (5-10 years post-diagnosis) was identified using a validated algorithm to detect treated recurrence in Medicare claims. Demographic and clinical characteristics collected at cancer diagnosis were assessed as predictors of late treated recurrence using restricted mean survival time (RMST) regression.

Results: The sample included 12,859 breast, 17,329 colon, and 4,427 rectal cancer survivors. The cumulative incidence of late treated recurrence 5-10 years post-diagnosis was 5.0% in breast, 4.4% in colon, and 8.0% in rectal cancer survivors. In all cohorts, stage was associated with shorter RMST. The absolute risk difference between stage I and III was greatest in breast (2.% vs 18.1%), followed by rectal (5.2% vs. 10.3%) and colon (2.7% vs 6.7%) cancer survivors (P < .001 for all cohorts). Though their effect on RMST was modest (<5%), higher grade, node-positive, and ER-positive disease in breast, left-sided tumors in colon, and radiation in rectal cancer were associated with late treated recurrence. Across all cohorts, the incidence of other-cause mortality (24.1%-34.0%) exceeded cancer-specific mortality (2.9%-6.2%).

Conclusions: Late treated recurrence in older long-term survivors is uncommon, but risk remains elevated 5 years post-diagnosis in those with more advanced stage.

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: 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.