title: A quality-adjusted time without symptoms or toxicity (Q-TWiST) analysis of adjuvant radiation therapy and chemotherapy for resectable rectal cancer.
abstract: 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.
  
  
  OBJECTIVE
  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
  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.
authors.affiliation: Division of Biostatistics, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
authors.forename: R D
authors.initials: RD
authors.lastname: Gelber
authors.forename: A
authors.initials: A
authors.lastname: Goldhirsch
authors.forename: B F
authors.initials: BF
authors.lastname: Cole
authors.forename: H S
authors.initials: HS
authors.lastname: Wieand
authors.forename: G
authors.initials: G
authors.lastname: Schroeder
authors.forename: J E
authors.initials: JE
authors.lastname: Krook
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D017281:Cost of Illness; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D011379:Prognosis; D011788:Quality of Life; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy* / Q000601:surgery; D016896:Treatment Outcome
chemical_list: D005472:Fluorouracil