Journal of Clinical Oncology最新文献

Purpose: To examine the associations between Medicaid expansion and stage at diagnosis, timely initiation and receipt of guideline-concordant treatment, and 5-year overall survival (OS) among people with non-small cell lung cancer (NSCLC).

Methods: Individuals newly diagnosed with stage I to IV NSCLC at age 18-64 years between January 1, 2004, and December 31, 2023, in 50 states and Washington, DC, were identified from the National Cancer Database. We examined the association of Medicaid expansion and (1) early-stage diagnosis (I and II); (2) timely initiation of guideline-concordant treatment within 30 days after diagnosis; (3) receipt of all first-course guideline-concordant treatment; and (4) 5-year OS. We applied conventional and updated (Sun and Abraham) difference-in-differences (DID) approaches to examine the changes in study outcomes associated with Medicaid expansion using multivariable linear probability models to estimate stage and treatment and multivariable flexible parametric survival models to investigate survival overall and by key factors.

Results: Compared with people in nonexpansion states (n = 164,228), people in expansion states (n = 350,290) were more likely to be female, non-Hispanic White, or living in areas with higher family income or in nonmetropolitan areas. Medicaid expansion was associated with increases in early-stage NSCLC diagnosis (DID: 1.02 percentage points [ppt; 95% CI, 0.52 to 1.52]), timely treatment initiation (2.10 ppt [95% CI, 0.05 to 4.15]), and higher 5-year OS (1.79 ppt [95% CI, 1.32 to 2.26]). In stratified analyses, people living in areas with lower household income were more likely to benefit from Medicaid expansion.

Conclusion: Medicaid expansion was associated with improvements in early detection, timeliness of guideline-concordant treatment, and survival for people with NSCLC. Anticipated Medicaid coverage losses may jeopardize these gains.

Purpose: Predictive biomarkers to guide selection of first-line chemotherapy for advanced pancreatic ductal adenocarcinoma (PDAC) are an unmet clinical need. This study used the Computational Histology Artificial Intelligence (CHAI) platform to develop and validate a histomorphology-based G-chemo versus F-chemo (GvF) biomarker that predicts benefit from first-line fluoropyrimidine-based (F-chemo) versus gemcitabine-based (G-chemo) regimens.

Methods: The CHAI platform extracted quantitative histomorphologic features from whole-slide images of hematoxylin and eosin-stained diagnostic biopsies. In a multi-institutional development cohort, features associated with differential outcomes as measured by time to next treatment or death (TNTD) between F-chemo-treated and G-chemo-treated patients produced continuous biomarker scores, which were dichotomized into G-pref or F-pref results. The biomarker and threshold were locked. An independent validation cohort from the prospective COMPASS and Know Your Tumor studies assessed differential treatment outcomes by TNTD and overall survival (OS).

Results: There were 477 patients (development: 178; validation: 299). In validation, among 173 F-pref patients, those treated with F-chemo had significantly better outcomes than G-chemo for both TNTD (P = .035; median TNTD: F-chemo 8.6 months; G-chemo 7.5 months) and OS (P = .003; median OS: F-chemo 14.4 months; G-chemo 11.7 months). Among 126 G-pref patients, G-chemo had significantly superior TNTD (P = .038; median TNTD: F-chemo 7.2 months; G-chemo 9.6 months), but no difference in OS (P = .5; median OS: F-chemo 12.4 months; G-chemo 14.3 months). In propensity score-weighted analysis, the biomarker predicted treatment effect (biomarker-treatment interaction TNTD P < .001; OS P = .005). RNA subtypes were associated with TNTD and OS but did not predict differential treatment effects (P = .3).

Conclusion: The histomorphology-based GvF biomarker predicted differential treatment benefit of first-line GvF. This biomarker can guide optimal treatment selection for first-line therapy in advanced PDAC.

Clinical trials and real-world evidence have established the benefit of chimeric antigen receptor (CAR) T-cell therapy to reduce progression of hematologic malignancies and, in some settings, increase overall survival. However, recent studies have highlighted that patients in long-term remission remain at risk of morbidity and nonrelapse mortality, primarily because of infections and subsequent myeloid malignancies. In addition, these patients may also be survivors of chemotherapy, radiation, and/or stem-cell transplant, with broad survivorship needs. Here, we provide a roadmap for the care of patients in long-term remission after CAR-T-cell therapies and discuss avenues for future research.

Purpose: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a unique myeloid malignancy with CD123 interleukin-3 receptor-α overexpression and poor prognosis.

Methods: This phase I/II, open-label, multicenter study evaluated pivekimab sunirine (PVEK), a novel CD123 antibody-drug conjugate, 0.045 mg/kg once every 3 weeks, in adults with frontline (no previous systemic therapy and de novo BPDCN or coexisting hematologic malignancy) or relapsed/refractory BPDCN (ClinicalTrials.gov identifier: NCT03386513) The primary end point in the primary analysis population (PAP; frontline de novo) was composite complete response (CCR; CR+ clinical CR) rate.

Results: Of 84 patients, 33 had frontline BPDCN (22 de novo [20 in PAP]; 11 with previous or concomitant malignancy) and 51 had relapsed/refractory disease. The median (range) age was 72 (63-76) years. In the PAP (n = 20), the CCR rate was 75% (95% CI, 51 to 91; n = 15; median duration: 10.6 [95% CI, 3.8 to not reached] months) and the median overall survival (OS) was 16.6 (95% CI, 7.2 to not reached) months. Eight of these 15 (53%) patients proceeded to stem-cell transplant (SCT). The corresponding rate for relapsed/refractory disease was 14% (95% CI, 6 to 26; n = 7; median duration: 9.2 [95% CI, 2.4 to not reached] months), and the median OS was 5.8 (95% CI, 3.9 to 8.4) months. Adverse events (AEs) included peripheral edema (54%), fatigue (26%), and infusion-related reactions (26%). Grade ≥3 events included neutropenia (16%), thrombocytopenia (14%), and peripheral edema (12%). Serious AEs included pneumonia (6%) and febrile neutropenia (5%). Two on-treatment cases of reversible veno-occlusive disease (VOD) occurred. Of the total 19 patients who proceeded to SCT, VOD was reported in five patients (four with relapsed/refractory BPDCN).

Conclusion: PVEK, with convenient dosing, led to high, durable responses, especially in frontline BPDCN, and a manageable safety profile.

A pediatric oncologist's experience of a patient's death through the new lens of motherhood.