A QUALITY-ADJUSTED TIME WITHOUT SYMPTOMS OR TOXICITY (Q-TWIST) ANALYSIS OF ADJUVANT RADIATION-THERAPY AND CHEMOTHERAPY FOR RESECTABLE RECTAL-CANCER

Background: Combined radiation therapy and chemotherapy after surgery, compared with postsurgical radiation therapy alone, has been shown to improve disease-free survival and overall survival significantly amon g patients with poor-prognosis (i.e., advanced stage disease or metast asis to regional lymph nodes) resectable rectal cancer, However, the c ombined therapy is associated with more toxic effects, raising the que stion of whether the benefits of the treatment justify its quality-of- life costs for the individual patient, Purpose: To assess the trade-of fs between improved survival and increased treatment toxicity, we rean alyzed data from a randomized clinical trial that compared the efficac y of combined adjuvant chemotherapy and radiation therapy with adjuvan t radiation therapy alone in the treatment of patients with poor-progn osis resectable rectal cancer, Methods: The data were from a North Cen tral Cancer Treatment Group trial in which 204 patients with poor-prog nosis rectal cancer were randomly assigned to receive either postopera tive radiation therapy alone or radiation therapy plus fluorouracil-ba sed chemotherapy, A quality-adjusted time without symptoms or toxicity (Q-TWIST) analysis was used to account for freedom from symptomatic d isease and from early and late side effects of treatment, All reported P values are two-sided, Results: As reported previously, the combined therapy reduced the risk of relapse by 34% (95% confidence interval [ CI] = 12%-50%; P =.0016) and reduced the overall death rate by 29% (95 % CI = 7%-45%; P =.025) in comparison with adjuvant radiation therapy alone, In the 5 years following assignment to treatment, patients who received the combined therapy had more time with toxicity (3.1 months; 95% CI = 2.0-4.1 months), shorter survival after relapse (3.6 months less; 95% CI = 0.9-6.3 months less), and more TWiST (6.1 months; 95% C I 0.2-12.0 months) than patients who received adjuvant radiation thera py alone, Despite an increase in the amount of time that individuals s pent with early and late toxic effects, the Q-TWIST analysis indicated that the combined therapy conferred significantly greater benefit for a wide range of patient preferences about living with the toxicity of treatment or the symptoms of overt disease, Conclusions and Implicati ons: Use of combined chemotherapy and radiation therapy as an adjuvant to surgery for patients with poor-prognosis resectable rectal cancer is justified, since the improved outcome in terms of delayed recurrenc e and increased survival balances the time spent with early and late t oxic effects, The Q-TWiST method is an excellent way to compare treatm ent outcomes that include quality-of-life considerations.