Quality of Life Outcomes in a Phase 3 Randomized Trial of Optimization of Treatment of Advanced Non–small Cell Lung Cancer Using Radiation Therapy and Chemotherapy: IAEA Multicentric Randomized Phase 3 Study (NCT00864331)

Abstract

Advanced nonsmall cell lung cancer (NSCLC) patients suffer significant intrathoracic morbidity. The purpose of this study was to evaluate whether addition of thoracic radiation to palliative chemotherapy in advanced NSCLC reduces symptoms and improve HRQOL. In this International Atomic Energy Agency (IAEA) sponsored multicentric, randomized phase III trial, advanced NSCLC patients [wet IIIB and IV – AJCC 6th edition] were randomized (1:1) to chemotherapy alone (CT)– (standard arm -3 cycles of platinum based doublet) versus radiation followed by chemotherapy (RT+CT) study arm (16 Gy/2Fr/1wk or 10 Gy/1Fr followed by CT). Quality of life was assessed longitudinally at baseline, 2 -6 weeks, 3 - 4 - 6 and 12 months using validated instrument EORTC HRQOL questionnaire (QLQ C30) and lung specific module (LC 13). Mean scores of individual domains at every time point were compared using the t test and change in scores over time was evaluated by repeated measurement analysis of variance. Linear mixed model included the main effect of the treatment group and an interaction effect of the treatment group with time. In this study, participating 108-advanced NSCLC patients were randomized to CT (n = 58) vs RT+CT (n = 50), from August 2008 to April 2012. Demographic, tumor factors and baseline QOL characteristics were comparable in two groups. Sixty-three (58%) patients had excellent (100%) and 36 (34%) had moderate (<100%) compliance to QOL. Persistent improvement in global QOL was noted and maintained over pretreatment level. Dyspnea, pain, fatigue, cough, and hemoptysis showed gradual improvement with treatment. Global QOL showed statistically and clinically significant improvement (P = 0.02) with RT+CT at 2 weeks. Social, role and emotional functioning were significantly (P<0.05) better with RT+CT at various time points. Despite worse baseline dyspnea scores in RT+CT group, clinically and statistically significant (P = 0.04) improvement was noted in this group at 6 weeks and 3 months, however CT alone group showed no improvement. Pain, constipation, nausea and vomiting and Lung cancer specific symptoms (Dyspnea, hemoptysis, cough, chest/arm pain) showed significant (P<0.05) improvement with RT+CT over CT alone at various intervals. None of the QOL domains were worsened by RT+CT over CT alone. Linear mixed model showed Global HRQOL (P = 0.01), Role (P<0.001) and social functioning (P<0.001) were significantly better with RT+CT over CT alone. Pain (P = 0.009), dyspnea (P = 0.001), nausea/ vomiting (P = 0.04) and lung specific symptoms (dyspnea, cough, pain in chest / other body parts) were significantly (P<0.05) better with RT+CT over CT alone. Short course local thoracic radiation prior to systemic chemotherapy rapidly improves global HRQOL, dyspnea and various other domains by reducing thoracic symptom burden and it also helps in sustained maintenance of HRQOL.