Journal of Clinical Oncology最新文献

Purpose: Modern ALL therapy aims to reduce toxicity, while maintaining and improving the current high cure rates. Acute and late sequelae of anthracyclines are of major concern. The AIEOP-BFM ALL 2009 trial aimed to clarify the need for anthracyclines in low-risk patients.

Patients and methods: After 2 weeks of induction therapy, which included two daunorubicin (DNR) doses once weekly (30 mg/m² each) as part of a 4-drug therapy, patients age 1-17 years with newly diagnosed non-high-risk B-ALL either positive for ETV6::RUNX1 or with rapid treatment response, as assessed by induction day-15 evaluation, were randomly assigned to receive either two additional doses of DNR (control arm [CA]) or no further DNR during induction (experimental arm [EA]). Patients treated as randomly assigned were included in the primary analysis on noninferiority in event-free survival (EFS). Adverse reactions of special interest (ARSI) were analyzed in the as-treated population.

Results: Of 6,136 patients enrolled in AIEOP-BFM ALL 2009, 2,514 patients (41.0%) were eligible for this random assignment, with 82.7% actually randomly assigned (EA: n = 1,040 and CA: n = 1,039). The 5-year EFS was 92.5% (SE 0.8%) in CA and 92.2% (SE 0.9%) in EA. Accordingly, cumulative incidence of relapse was 5.8% (SE 0.7%) and 5.7% (SE 0.7%), and overall survival was 97.6% (SE 0.5%) and 97.4% (SE 0.5%) in CA and EA, respectively. Life-threatening and fatal ARSI were similar in the two arms, but there was a three times lower incidence of invasive fungal infections in the EA (0.5% v 1.5%, P = .02).

Conclusion: A reduced DNR dose during induction did not compromise the outcome of patients with favorable prognostic factors but did diminish infectious toxicity indicated by the lower rate of invasive fungal infections.

Purpose: Identifying discrete subgroups associated with treatment response and resistance in localized Ewing sarcoma (EWS) remains a challenge. The primary objective of the Children's Oncology Group (COG) biology study AEWS18B1-Q was to molecularly characterize patients with localized EWS on prospective modern-day trials.

Patients and methods: We analyzed clinical and molecular features from patients with localized EWS enrolled on frontline COG trials. All patients had available formalin-fixed paraffin-embedded (FFPE) tissue, frozen tissue, or whole-genome-amplified material. Sequencing was performed for identification of canonical fusions, recurrent copy number alterations (CNAs), and alterations in TP53 and STAG2. Available tissue was analyzed for loss of STAG2 protein expression. Molecular features were evaluated for their association with cumulative incidence of relapse in univariate and multivariable analyses.

Results: Three hundred fifty-one patients had sufficient tissue, which in most cases was extracted from two FFPE slides. EWS canonical fusions were identified in 282 patients (80.3%). Pathogenic mutations in TP53 and STAG2 were identified in 5.1% and 7.6% of patients, respectively. A total of 63.1% of patients were found to have recurrent CNAs. In univariate analysis, there was an increased cumulative incidence of relapse in patients with TP53 mutation (5-year cumulative incidence of relapse 43%, 95% CI [17% to 67%] v 22%, 95% CI [17% to 27%]; Gray's test P = .039), STAG2 mutation (53%, 95% CI [29% to 73%] v 21%, 95% CI [16% to 26%]; P < .001), and recurrent CNAs (30%, 95% CI [22% to 37%] v 16%, 95% CI [9% to 24%]; P = .005). In a multivariable analysis, STAG2 mutation was the only molecular biomarker that remained prognostic.

Conclusion: This is a prospective validation of the molecular prognostic features of patients with localized EWS receiving standard-of-care therapy on therapeutic clinical trials. Building on previous work, patients with STAG2 mutations were at high risk of relapse.

This is a deeply personal narrative an inpatient oncology doctor reflects on the profound personal and professional impact of losing her young family member to cancer, illuminating the intimate intersection of grief, loss, and healing.