Purpose: KRAS G12C is the most common KRAS mutation in primary lung adenocarcinoma (LUAD). Phase I clinical trials have demonstrated encouraging clinical activity of KRAS G12C inhibitors in the metastatic setting. We investigated disease-free survival (DFS) and tumor genomic features in patients with surgically resected KRAS G12C -mutant LUAD.

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Background Postoperative atrial fibrillation (AF) may identify patients at risk of subsequent AF, with its greater risk of stroke. We hypothesized that N-acetylcysteine mitigates inflammation and oxidative stress to reduce the incidence of postoperative AF. Methods In this double-blind, placebo-controlled trial, patients at high risk of postoperative AF scheduled to undergo major thoracic surgery were randomized to N-acetylcysteine plus amiodarone or placebo plus amiodarone. On arrival to the postanesthesia care unit, N-acetylcysteine or placebo bolus (intravenous 50 mg/kg then 50 mg/kg/24 h x 48 h) was administered plus amiodarone (intravenous 150 mg then 1 g/24 h x 48 h). The primary outcome was sustained AF >30 s by telemetry (first 72 h) or symptoms requiring intervention and confirmed by ECG within 7 days of surgery. Systemic markers of inflammation (interleukin-6, interleukin-8, tumor necrosis factor–α, C-reactive protein) and oxidative stress (F2-isoprostane prostaglandin PGF2α [8-iso-PGF2α], isofuran) were assessed immediately after surgery and on postoperative day 2. Patients were phoned monthly to assess the occurrence of AF in year 1. Results Among 154 patients included, postoperative AF occurred in 15 of 78 who received N-acetylcysteine (19%) and 13 of 76 who received placebo (17%) (odds ratio, 1.24; 95.1% confidence interval, 0.53-2.88; p=0.615). The trial was stopped at the interim analysis because of futility. Three of the 28 patients with postoperative AF (11%) were discharged in AF. Regardless of treatment at 1 year, 7 of 28 patients with postoperative AF (25%) had recurrent episodes of AF. Inflammatory and oxidative stress markers were similar between groups. Conclusions Dual therapy comprising N-acetylcysteine plus amiodarone did not reduce the incidence of postoperative AF or markers of inflammation and oxidative stress early after major thoracic surgery, compared with amiodarone alone. Recurrent AF episodes are common among patients with postoperative AF within 1 year of major thoracic surgery.

Objective: To compare the efficacy and safety of induction FOLFOX followed by PET-directed nCRT, induction CP followed by PET-directed nCRT, and nCRT with CP alone in patients with EAC. Summary of Background Data: nCRT with CP is a standard treatment for locally advanced EAC. The results of cancer and leukemia group B 80803 support the use of induction chemotherapy followed by PET-directed chemo-radiation therapy. Methods: We retrospectively identified all patients with EAC who underwent the treatments above followed by esophagectomy. We assessed incidences of pathologic complete response (pCR), near-pCR (ypN0 with ≥90% response), and surgical complications between treatment groups using Fisher exact test and logistic regression; disease-free survival (DFS) and overall survival (OS) were estimated by the Kaplan–Meier method and evaluated using the log-rank test and extended Cox regression. Results: In total, 451 patients were included: 309 (69%) received induction chemotherapy before nCRT (FOLFOX, n = 70; CP, n = 239); 142 (31%) received nCRT with CP. Rates of pCR (33% vs. 16%, P = 0.004), near-pCR (57% vs. 33%, P < 0.001), and 2-year DFS (68% vs. 50%, P = 0.01) were higher in the induction FOLFOX group than in the induction CP group. Similarly, the rate of near-pCR (57% vs. 42%, P = 0.04) and 2-year DFS (68% vs. 44%, P < 0.001) were significantly higher in the FOLFOX group than in the no-induction group. Conclusions: Induction FOLFOX followed by PET-directed nCRT may result in better histopathologic response rates and DFS than either induction CP plus PET-directed nCRT or nCRT with CP alone.