JNCI Journal of the National Cancer Institute最新文献

Introduction: The association of body composition with checkpoint inhibitor outcomes in melanoma is a matter of ongoing debate. In this study, we aim to investigate body mass index (BMI) alongside CT-derived body composition metrics in the largest cohort to date.

Methods: Patients treated with first-line anti-PD1 ± anti-CTLA4 for advanced melanoma were retrospectively identified from 11 melanoma centers in The Netherlands. From baseline CT scans, five body composition metrics were extracted: subcutaneous adipose tissue index, visceral adipose tissue index and skeletal muscle index, density and gauge. These metrics were correlated in uni- and multivariable Cox proportional hazards analysis with progression-free, overall and melanoma-specific survival (PFS, OS and MSS).

Results: A total of 1471 eligible patients were included. Median PFS and OS were 9.1 and 38.1 months, respectively. Worse PFS was observed in underweight patients (multivariable HR = 1.86, 95% CI 1.14-3.06). Furthermore, prolonged OS was observed in patients with higher skeletal muscle density (multivariable HR = 0.88, 95% CI 0.81-0.97) and gauge (multivariable HR = 0.61, 95% CI 0.82-0.998), whereas higher visceral adipose tissue index was associated with worse OS (multivariable HR = 1.12, 95% CI 1.04-1.22). No association with survival outcomes was found for overweight, obesity or subcutaneous adipose tissue.

Discussion: Our findings suggest that underweight BMI is associated with worse PFS, whereas higher skeletal muscle density and lower visceral adipose tissue index were associated with improved OS. These associations were independent of known prognostic factors, including sex, age, performance status and extent of disease. No significant association between higher BMI and survival outcomes was observed.

Introduction: Increases in colon and colorectal cancer incidence among adolescents and young adults (AYAs) have been reported progressively. Most of the increase may be due to an artifact caused by reclassifying appendiceal carcinoids/neuroendocrine tumor (NET) as malignant.

Methods: Age-adjusted incidence and survival data were obtained from the Surveillance, Epidemiology, and End Results (SEER) SEER22 database.

Results: In AYAs during 2000-2020, appendix cancer had an average annual percent change (AAPC) in incidence increase that in males was 3.7 times greater than the next most increasing cancer (AAPC12.8,95%CI: 10.9-14.6 vs AAPC3.4 [kidney] , 95%CI : 2.7-3.5) and correspondingly in females 2.9-fold greater (AAPC14.6,95%CI : 11.9-17.3 vs AAPC4.2 [pancreas], 95%CI : 3.6-4.8). From 2000-2009 to 2015-2020, appendix cancer incidence increased 17-,6.5-and 2.5-fold in children 0-14, AYAs 15-39, and adults 40-49 years of age, respectively. Carcinoid/NET accounted for 95%, 90% and 80% of appendix cancer increase in the three age groups, respectively. In 3,446 AYAs diagnosed during 2010-2020 with 'malignant' appendix NET, the 6-year cancer specific survival was 99.4% (95%CI , 99.0%to99.6%). From 2000-2009 to 2015-2020, colon carcinoma incidence in AYAs increased 61% with the appendix included, and only 11% with the appendix excluded.

Conclusions: Reclassification of appendix NET/carcinoids as malignant has artifactually increased the incidence of colon, colorectum, and all cancer in children and AYAs. Appendix NET/carcinoids are rarely fatal in < 40 year-olds and should not be considered as cancer and included in colorectal cancer analyses. To the extent that the appendix artifact occurs in 40-49 year-olds, recommendations for starting colorectal cancer screening earlier may be affected..

Consensus criteria to diagnose unintentional weight loss, a condition often termed cachexia that affects most patients with advanced cancer, are based on 6-month changes by which time intervention is often ineffective. Leveraging the large and diverse population in Kaiser Permanente Northern California's community oncology practice, we studied 8,338 patients with advanced lung, pancreatic, or colorectal cancers. We calculated weekly weight change measurements from 2-months pre- to 6-months post-diagnosis to identify 4 weight change trajectories (Gain, Stable, Moderate Loss, and Severe Loss) and associated these trajectories with survival. With high agreement, we classified patients into these trajectories after 3 months and found them to be prognostic; those classified in Moderate (HR = 1.55; 95%CI: 1.45-1.67) or Severe Loss (HR = 2.20; 95%CI: 2.01-2.41) at 3 months had significantly increased risk of death compared to the Stable trajectory. Weight loss at 3 months post-diagnosis can accurately classify deleterious weight trajectories, allowing for earlier clinical intervention.

Background: Emerging evidence suggests that bacteria residing in colorectal tissue are plausibly associated with colorectal cancer (CRC). Prior studies investigated the effects of dietary interventions on the fecal microbiome, but few assessed colorectal tissue microbiome endpoints. We investigated the effects of a high-fiber, high-fruit and -vegetable, low-fat dietary intervention on the rectal tissue microbiome in the Polyp Prevention Trial (PPT).

Methods: PPT is a 4-year randomized clinical trial with intervention goals of consuming: 1) ≥ 18 g of fiber per 1,000 kcal/day; 2) ≥3.5 servings of fruits and vegetables per 1,000 kcal/day; and 3) <20% of kcal/day from fat. Using 16S rRNA gene sequencing, we characterized bacteria in rectal biopsies collected at baseline and the end of years 1 and 4 (N = 233 in intervention arm and N = 222 in control arm). We estimated effects of the intervention on alpha/beta diversity and relative abundance of a priori-selected bacteria using repeated-measures linear mixed-effects models.

Results: The intervention did not statistically significantly modify rectal tissue alpha diversity. Compared to the control arm, relative abundance of a priori-selected Porphyromonas (absolute intervention effects [standard errors] at T1 vs T0=-0.24 [0.07] and T4 vs T0=-0.12 [0.07]; P = .004) and Prevotella (absolute intervention effects at T1 vs T0=-0.40 [0.14] and at T4 vs T0=-0.32 [0.15]; P = .01) were more strongly decreased in the intervention arm.

Conclusion: The PPT intervention did not influence rectal tissue microbiome diversity nor the relative abundance of most bacteria, except for two oral-originating bacteria that were previously associated with CRC presence.

Original clinical trial registry number: NCT00339625.

Background: New highly effective, but expensive, immunotherapies have revolutionized the treatment of relapsed pediatric acute lymphoblastic leukemia (ALL) but their long-term clinical and economic impact is unclear. We developed the ALL Policy microsimulation model to estimate long-term clinical and economic outcomes for patients with pediatric ALL aged 0-17 in Ontario, Canada. We also illustrate the model's clinical utility through a cost-effectiveness analysis of blinatumomab in relapsed B-cell ALL.

Methods: The ALL Policy model is informed using health administrative data and chart abstracted data from Ontario, Canada, and published literature. The model estimates lifetime risk of relapse, bone marrow transplant (BMT), conditional life expectancy, quality-adjusted life years (QALY), and total healthcare costs for individuals with pediatric ALL, and can be stratified by relevant clinical characteristics (eg, B-cell or T-cell lineage). Additionally, we subset the model to patients with relapsed B-cell ALL to illustrate use of the model in estimating the cost-effectiveness of blinatumomab vs standard chemotherapy.

Results: Simulated pediatric ALL patients diagnosed from 2002-2012 had a projected conditional life expectancy of 64.90 years. The lifetime risk of BMT was estimated at 12.5%. Lifetime healthcare costs were $244,433 CAD (95% CI $213,314, $303,430). Treatment with blinatumomab compared to standard chemotherapy post-relapse was estimated to result in 1.08 additional QALYs and an additional cost of $59,410 CAD (incremental cost-effectiveness ratio of $54,885/QALY).

Conclusion: The ALL policy model can serve as a modeling foundation for timely economic evaluation. Introduction of blinatumomab in relapsed B-cell ALL may be a cost-effective strategy.

Background: Medicare Advantage (MA) plans may offer more benefits and lower costs relative to Traditional Medicare (TM), but may also provide narrower provider networks and pre-authorization requirements. We explore the impact of a cancer diagnosis on switching between MA and TM after diagnosis.

Methods: We used the 2015-2019 Surveillance, Epidemiology and End Results-Medicare data to examine patterns of switching between MA and TM after cancer relative to those without cancer. We used binomial generalized estimating equations to evaluate the cancer and sociodemographic characteristics of those with higher probabilities of switching.

Results: Among those initially enrolled in MA plans (39.27% of those with vs 40.79% without cancer), 3.76% of individuals with cancer switched to TM compared to 2.23% without cancer. For those initially enrolled in TM, 2.96% of individuals with cancer switched to MA vs 4.35% without cancer. Multivariable analyses demonstrated that, among individuals starting in MA, a cancer diagnosis was associated with a 52.02% increase in switching relative to those without cancer, whereas among those starting in TM, a cancer diagnosis was associated with a 26.90% reduction in switching. Younger individuals, males, dual-eligible, those with more comorbidities, rural-dwellers, and those living in zip codes with higher education and income levels also had higher probabilities of switching from MA to TM.

Conclusions: Prior to diagnosis, MA enrollment is comparable between individuals with and without cancer. However, after diagnosis, individuals with cancer have higher probability of switching from MA to TM and lower probability of switching from TM to MA.