PURPOSE To provide evidence-based recommendations to practicing clinicians on management of patients with stage III non–small-cell lung cancer (NSCLC). METHODS An Expert Panel of medical oncology, thoracic surgery, radiation oncology, pulmonary oncology, community oncology, research methodology, and advocacy experts was convened to conduct a literature search, which included systematic reviews, meta-analyses, and randomized controlled trials published from 1990 through 2021. Outcomes of interest included survival, disease-free or recurrence-free survival, and quality of life. Expert Panel members used available evidence and informal consensus to develop evidence-based guideline recommendations. RESULTS The literature search identified 127 relevant studies to inform the evidence base for this guideline. RECOMMENDATIONS Evidence-based recommendations were developed to address evaluation and staging workup of patients with suspected stage III NSCLC, surgical management, neoadjuvant and adjuvant approaches, and management of patients with unresectable stage III NSCLC. Additional information is available at www.asco.org/thoracic-cancer-guidelines .

Cardiac radiotherapy (RT) may be effective in treating heart failure (HF) patients with refractory ventricular tachycardia (VT). The previously proposed mechanism of radiation-induced fibrosis does not explain the rapidity and magnitude with which VT reduction occurs clinically. Here, we demonstrate in hearts from RT patients that radiation does not achieve transmural fibrosis within the timeframe of VT reduction. Electrophysiologic assessment of irradiated murine hearts reveals a persistent supraphysiologic electrical phenotype, mediated by increases in NaV1.5 and Cx43. By sequencing and transgenic approaches, we identify Notch signaling as a mechanistic contributor to NaV1.5 upregulation after RT. Clinically, RT was associated with increased NaV1.5 expression in 1 of 1 explanted heart. On electrocardiogram (ECG), post-RT QRS durations were shortened in 13 of 19 patients and lengthened in 5 patients. Collectively, this study provides evidence for radiation-induced reprogramming of cardiac conduction as a potential treatment strategy for arrhythmia management in VT patients.

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concurrent chemoradiotherapy for locally advanced non-small cell lung cancer (NSCLC). We performed a prospective trial examining dose-painted intensity-modulated radiotherapy (IMRT) as a strategy to improve the efficacy and safety of chemoradiotherapy for NSCLC. Materials/Methods: Patients with inoperable stage IIB-III NSCLC and ECOG performance status 0-2 who underwent staging PET were eligible for this single-arm study. All patients were treated with a 25-fraction course of dose-painted IMRT. Tumors or lymph nodes with MTV exceeding 25 cc were deemed "high risk" and received 65 Gy. Lesions smaller than 25 cc were considered "low risk" and treated with 57 Gy until November 2014, when the study was amended to reduce the prescription dose for such lesions to 52.5 Gy. All patients received concurrent weekly carboplatin (AUC 2) and paclitaxel (45 mg/m 2) during radiotherapy, and consolidation chemotherapy with the same agents was optional. Patients underwent post-treatment PET 12-16 weeks after completion of IMRT. The primary study endpoint was the absence of high residual metabolic activity (maximum SUV > 6) in the lungs and regional lymph nodes on post-treatment PET. Results: Thirty-five enrolled subjects with 116 hypermetabolic tumors and lymph nodes were eligible for analysis. The primary endpoint was met for 24/30 patients (80%) who underwent post-treatment PET, satisfying our pre-specified efficacy objective. Median follow-up duration for living patients is 17.0 months. Median survival time has not been reached. One and two-year actuarial rates of overall survival are 71% and 51%, respectively. Twenty-three patients (66%) have developed disease progression. Progression in a tumor or lymph node targeted with radiotherapy was observed in five patients at the time of first disease progression. Treating progression in other sites and death without progression as competing risks, the two-year cumulative incidence rate of local disease progression in 25 high-risk lesions is 9%. The two-year cumulative incidence rate of local disease progression in the 91 low-risk lesions that were treated with a low radiotherapy dose is 3%. Conclusion: Dose-painted IMRT based on pre-treatment PET metrics with concurrent chemotherapy for locally advanced NSCLC yields high rates of metabolic response, local disease control, and overall survival. This strategy should be pursued to maximize the therapeutic ratio of radiotherapy in this setting.

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