One year follow-up reveals no difference in quality of life between high dose and conventional dose radiation: a quality of life assessment of RTOG 94-05

Abstract Purpose: This study evaluated and compared the quality of life (QOL) outcomes for patients with esophageal cancer receiving combined modality therapy (CMT) with conventional dose radiation (RT) vs. high dose RT as used in RTOG study 94-05. Materials and Methods: Between June 12, 1995 and July 1, 1999, 236 patients with cT1-4NxM0 esophageal cancers were randomized on RTOG 94-05 to conventional dose (CD) CMT: 50.4 Gy RT + concurrent 5-FU and cisplatin administered on weeks 1 and 5 and repeated 4 weeks post RT vs. high dose (HD) CMT: 64.8 Gy RT + the same chemotherapy. QOL was assessed using the Functional Assessment of Cancer Therapy (FACT) - Head & Neck (version 2). This questionnaire was administered to patients pre-treatment, post-treatment, at 8 months from the start of CMT, at 1 year and at 6-month intervals to year 5. Results: Of 209 eligible protocol patients, 169 (81%) participated in the pre-treatment QOL component of RTOG 94-05 (83 in the HD arm and 86 in the CD arm). The principle reason for non-participation was institutional error. The distribution of pre-treatment characteristics by participation in QOL assessment was similar in both treatment arms. African-Americans, patients with ≥ 10% weight loss, and patients with low performance status were significantly less likely to complete QOL forms (p=0.04, p=0.01 and p=0.004 respectively). Baseline QOL parameters were similar in the two treatment arms. Pulmonary symptoms were the most significant pre-treatment dysfunction reported. Female gender and ≥ 10% pre-treatment weight loss correlated with pre-treatment total QOL scores. Women reported lower overall QOL as well as worse physical and emotional well-being in the HD arm as compared to the CD arm (p=0.07, p=0.01 and p=0.03 respectively). Patients with ≥ 10% weight loss reported decreased QOL in nearly all domains in both treatment groups, although more pronounced in the 64.8 Gy arm. Treatment arm assignment, age, performance status, tumor size and histology did not significantly correlate with overall pre-treatment QOL. At treatment completion, 96 patients (46%) completed QOL forms (46 HD, 50 CD); non-participation was due to death in 17, delayed completion in 23 and missing in 33. QOL was worse post-treatment in both arms with total QOL scores significantly lower than baseline in the HD arm (p=0.05). Similarly, women reported lower QOL on the 64.8 Gy arm (overall QOL p=0.06, physical well-being p=0.06, relationship with physician p=0.02 and emotional well-being p=0.02). Among the various QOL domains, pre-treatment weight loss of ≥ 10% only significantly correlated with decreased family well-being on the HD arm (p=0.04). Seventy-three patients (35%) participated in QOL assessment at 8 months post CMT (40 HD, 33 CD); the principle reason for non-participation was patient death. QOL scores were similarly restored to baseline in the two treatment arms, with head and neck symptoms reported as improved. Pre-treatment weight loss remained a significant predictor for overall QOL, as well as for social and family well being. Gender had no significant effect on QOL at 8 months. Fifty-seven patients were available for QOL participation at 1 year (25 HD, 32 CD) with no significant differences in QOL scores between the two treatment arms. Preliminary analysis at 2 years showed no local control or survival benefit for the high dose arm. Conclusion: In this randomized trial of RT dose escalation, functional and symptomatic scores of QOL were decreased after CMT in both treatment arms with total QOL scores significantly poorer than baseline in the high dose group. This early decrease in QOL for the 64.8 Gy arm was restored to baseline after 8 months, and at 1 year there were no significant differences in QOL scores between the two treatment arms. Therefore, for patients treated with CMT for esophageal cancer who remain alive at 1 year, RT dose escalation to 64.8 Gy appears to be as well tolerated as the conventional 50.4 Gy arm from the patient's perspective.