In the European phase III Lung ART trial reported in The Lancet Oncology, Le Pechoux et al found that three-dimensional (3D) conformal postoperative radiotherapy (PORT) did not improve disease-free survival vs no PORT in patients with stage IIIA N2 non–small cell lung cancer (NSCLC) who had undergone a complete resection.
Study Details
The open-label trial included 501 patients with cytologically or histologically proven mediastinal N2 involvement from sites in France, the United Kingdom, Germany, Switzerland, and Belgium. They were randomly assigned between August 2007 and July 2018 to undergo PORT (n = 252) or no PORT (n =249). Use of neoadjuvant and adjuvant chemotherapy was permitted. Patients received PORT at a dose of 54 Gy in 27 or 30 daily fractions on 5 consecutive days per week. 3D conformal radiotherapy was mandatory; intensity-modulated radiotherapy was permitted in centers with expertise. The primary endpoint was disease-free survival, analyzed by intention to treat at 3 years.
Disease Free-Survival
Staging was performed by F-18 fluorodeoxyglucose positron-emission tomography/computed tomography (FDG-PET/CT) in 92% of the PORT group and 90% of the no-PORT group. A total of 96% of patients received preoperative or adjuvant chemotherapy (preoperative therapy exclusively in 13%).
At the cutoff date (May 2019), median follow-up was 4.8 years (interquartile range = 2.9–7.0 years). At 3 years, disease-free survival was 47% (95% confidence interval = 40%–54%) in the PORT group vs 44% (95% CI = 37%–51%) in the no-PORT group. Median disease-free survival was 30.5 months (95% CI = 24–49 months) in the PORT group vs 22.8 months (95% CI = 17–37 months) in the no-PORT group (adjusted hazard ratio [HR] = 0.86, 95% CI = 0.68–1.08, P = .18).
Overall survival at 3 years was 67% (95% CI = 59%–73%) in the PORT group vs 69% (95% CI = 61%–75%) in the no-PORT group (adjusted HR = 0.97, 95% CI = 0.73–1.28).
Toxicity
Safety analysis included 241 patients in the PORT group who received PORT and 246 in the no-PORT group with available follow-up. Early grade 3 or 4 adverse events were reported in 12% of patients in the PORT group vs 8% of the no-PORT group, with the most common being pneumonitis (5% vs < 1%), lymphopenia (4% vs 0%), and fatigue (3% vs < 1%). Late grade 3 or 4 cardiopulmonary toxicity occurred in 11% of the PORT group vs 5% of the control group. Treatment-related death occurred in three patients in the PORT group: two due to pneumonitis considered partly related to radiotherapy and infection, and one due to chemotherapy toxicity (sepsis).
The investigators concluded: “Lung ART evaluated 3D conformal PORT after complete resection in patients who predominantly had been staged using FDG-PET/CT and received neoadjuvant or adjuvant chemotherapy. Three-year disease-free survival was higher than expected in both groups, but PORT was not associated with an increased disease-free survival compared with no PORT. Conformal PORT cannot be recommended as the standard of care in patients with stage IIIA N2 NSCLC.”
Cecile Le Pechoux, MD, of the Department of Radiation Oncology, International Center for Thoracic Cancers, Gustave Roussy, Villejuif, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was supported by the French National Cancer Institute, Cancer Research UK, Swiss Cancer Research Foundation, and others. For full disclosures of the study authors, visit thelancet.com.
