caa a22 4500 397564899 CHVBK 20180308164826.0 cr unu---uuuuu 161202e19960807xx s 000 0 eng 10.1093/jnci/88.15.1039 doi (NATIONALLICENCE)oxford-10.1093/jnci/88.15.1039 A Quality-Adjusted Time Without Symptoms or Toxicity (Q-TWiST) Analysis of Adjuvant Radiation Therapy and Chemotherapy for Resectable Rectal Cancer [Elektronische Daten] [Richard D. Gelber, Aron Goldhirsch, Bernard F. Cole, Harry S. Wieand, Georgene Schroeder, James E. Krook] 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 among patients with poor-prognosis (i.e., advanced stage disease or metastasis to regional lymph nodes) resectable rectal cancer. However, the combined therapy is associated with more toxic effects, raising the question of whether the benefits of the treatment justify its quality-of-life costs for the individual patient. Purpose: To assess the trade-offs between improved survival and increased treatment toxicity, we reanalyzed data from a randomized clinical trial that compared the efficacy of combined adjuvant chemotherapy and radiation therapy with adjuvant radiation therapy alone in the treatment of patients with poor-prognosis resectable rectal cancer. Methods: The data were from a North Central Cancer Treatment Group trial in which 204 patients with poor-prognosis rectal cancer were randomly assigned to receive either postoperative radiation therapy alone or radiation therapy plus fluorouracil-based chemotherapy. A quality-adjusted time without symptoms or toxicity (Q-TWiST) analysis was used to account for freedom from symptomatic disease 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% CI = 0.2-12.0 months) than patients who received adjuvant radiation therapy alone. Despite an increase in the amount of time that individuals spent 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 Implications: 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 recurrence and increased survival balances the time spent with early and late toxic effects. The Q-TWiST method is an excellent way to compare treatment outcomes that include quality-of-life considerations. [J Natl Cancer Inst 1996; 88: 1039-45] © Oxford University Press ARTICLES nationallicence Gelber Richard D. Division of Biostatistics, Dana-Farber Cancer Institute, Department of Pediatrics, Harvard Medical School, and Department of Biostatistics, Harvard School of Public Health Boston, MA aut Goldhirsch Aron International Breast Cancer Study Group Ospedale Civico, Lugano, Switzerland aut Cole Bernard F. Center for Statistical Science, Brown University Providence, RI aut Wieand Harry S. Department of Biostatistics, School of Public Health, University of Pittsburgh PA aut Schroeder Georgene North Central Cancer Treatment Group Statistical Center Rochester, MN aut Krook James E. Department of Hematology and Oncology Duluth Clinic, MN aut JNCI: Journal of the National Cancer Institute Oxford University Press 88/15(1996-08-07), 1039-1045 0027-8874 88:15<1039 1996 88 jnci https://doi.org/10.1093/jnci/88.15.1039 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/jnci/88.15.1039 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Gelber Richard D. Division of Biostatistics, Dana-Farber Cancer Institute, Department of Pediatrics, Harvard Medical School, and Department of Biostatistics, Harvard School of Public Health Boston, MA aut NATIONALLICENCE 700 1- Goldhirsch Aron International Breast Cancer Study Group Ospedale Civico, Lugano, Switzerland aut NATIONALLICENCE 700 1- Cole Bernard F. Center for Statistical Science, Brown University Providence, RI aut NATIONALLICENCE 700 1- Wieand Harry S. Department of Biostatistics, School of Public Health, University of Pittsburgh PA aut NATIONALLICENCE 700 1- Schroeder Georgene North Central Cancer Treatment Group Statistical Center Rochester, MN aut NATIONALLICENCE 700 1- Krook James E. Department of Hematology and Oncology Duluth Clinic, MN aut NATIONALLICENCE 773 0- JNCI: Journal of the National Cancer Institute Oxford University Press 88/15(1996-08-07), 1039-1045 0027-8874 88:15<1039 1996 88 jnci Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford