Journal of Thoracic Oncology最新文献

Introduction: Clinical guidelines recommend upfront osimertinib monotherapy for asymptomatic brain metastases (BM) in epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC), despite a lack of randomised trial evidence. We conducted two randomised phase II trials, OUTRUN and LUOSICNS, to evaluate the efficacy and safety of upfront stereotactic radiosurgery (SRS) plus osimertinib versus osimertinib in this patient population.

Methods: Participants with up to ten BM amenable to SRS were randomised 1:1 to SRS followed by osimertinib (80mg daily) or osimertinib monotherapy. SRS was delivered as a single or multi-fraction regimen. The primary endpoint was 12-month intracranial progression-free survival (ic-PFS). Key secondary endpoints include overall survival (OS), patterns of intracranial progression, and safety. Data from both trials were prospectively pooled for a joint analysis.

Results: Overall, 79 participants were randomised. At a median follow-up of 39.0 months, 12-month ic-PFS was not significantly different between SRS plus osimertinib (n = 39) over osimertinib monotherapy (n = 40) (11%, 95% CI, -10% to 32%, P=.31; median ic-PFS 21.9 versus 17.2 months). Median OS was 46.1 versus 29.1 months. Among those with intracranial progression, 35% in the SRS plus osimertinib group and 57% in the osimertinib monotherapy group underwent SRS at progression. Grade 3/4 radionecrosis occurred in 5% of participants treated with SRS plus osimertinib.

Conclusions: Adding upfront SRS to osimertinib did not significantly improve 12-month ic-PFS in EGFR mutant NSCLC with BM. This represents the first randomised evidence supporting the use of osimertinib monotherapy as upfront therapy in minimally symptomatic patients with low burden BM.

Introduction: The cardiovascular toxicity of radiation therapy (RT) remains incompletely understood in patients with non-small cell lung cancer (NSCLC). Our objective was to define changes in echocardiographic parameters of structure and function with RT and their associations with cardiac dose-volume metrics.

Methods: This multi-center, longitudinal prospective cohort study included participants with NSCLC who received standard, curative-intent thoracic RT. Dose-volume metrics were extracted from centrally contoured cardiac substructures. Echocardiograms at baseline, end of RT, six months post-RT, and 12 months post-RT were core lab-quantified. Repeated-measures multivariable linear regression via generalized estimating equations estimated changes in echocardiographic measures and associations with dose-volume metrics.

Results: Across 125 participants, there was a modest worsening in left ventricular ejection fraction (LVEF) (p=0.019), global longitudinal strain (p<0.001), circumferential strain (p<0.001), and Ea/Ees (p=0.011) post-RT that largely recovered by 12 months. Cardiac dysfunction, defined as LVEF declines of ≥10% to <50%, occurred in 7.2% of participants at a median of 1.7 months after RT initiation. Mean heart dose (MHD) was associated with LVEF declines (-1.1%, 95% confidence interval (CI) [-2.2,0.0] per interquartile range (IQR) increase, p=0.044), as was whole heart V30 (-1.4%, 95%CI[-2.5,-0.3] per IQR increase, p=0.015); with multiple comparisons adjustment, whole heart V30 remained significant (p=0.030).

Conclusions: On average, there were modest changes in cardiac function immediately after RT in patients with NSCLC, with a subset experiencing clinically relevant cardiac dysfunction. While whole heart V30 was associated with LVEF declines, suggesting its relevance in RT planning, there is also a need for newer dose-volume measures.

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