title: Dose-response relationship in locoregional control for patients with stage II-III esophageal cancer treated with concurrent chemotherapy and radiotherapy.
abstract: OBJECTIVE
  To evaluate the correlation between radiation dose and locoregional control (LRC) for patients with Stage II-III unresectable esophageal cancer treated with concurrent chemotherapy and radiotherapy.
  
  
  METHODS
  The medical records of 69 consecutive patients with clinical Stage II or III esophageal cancer treated with definitive chemoradiotherapy at the University of Texas M. D. Anderson Cancer Center between 1990 and 1998 were retrospectively reviewed. Of the 69 patients, 43 had received < or =51 Gy (lower dose group) and 26 >51 Gy (higher dose group). The median dose in the lower and higher dose groups was 30 Gy (range, 30-51 Gy) and 59.4 Gy (range, 54-64.8 Gy), respectively. Two fractionation schedules were used: rapid fractionation, delivering 30 Gy at 3 Gy/fraction within 2 weeks, and standard fractionation, delivering > or =45 Gy at 1.8-2 Gy/fraction daily. Total doses of <50 Gy were usually given with rapid fractionation. Cisplatin and 5-fluorouracil were administrated to 93% of the patients.
  
  
  RESULTS
  The patient characteristic that differed between the two groups was that patients in the lower dose group were more likely to have had weight loss >5% (46.2% vs. 23.3%). The lower dose group had more N1 tumors, but the tumor classification and stage grouping were similar in the two groups. The median follow-up time for all patients was 22 months (range, 2-56 months). Patients in the higher dose group had a statistically significant better 3-year local control rate (36% vs. 19%, p = 0.011), disease-free survival rate (25% vs. 10%, p = 0.004), and overall survival rate (13% vs. 3%, p = 0.054). A trend toward a better distant-metastasis-free survival rate was noted in the higher dose group (72% vs. 59%, p = 0.12). The complete clinical response rate was significantly greater in the higher dose group (46% vs. 23%, p = 0.048). In both groups, the most common type of first failure was persistence of the primary tumor. Significantly fewer patients in the higher dose group had tumor persistence after treatment (p = 0.02). No statistically significant difference was found between the two groups in the pattern of locoregional or distant failure. The long-term side effects of chemoradiotherapy were similar in the two groups, although it was difficult to assess the side effects accurately in a retrospective fashion. On multivariate analysis, Stage II (vs. III) disease and radiation dose >51 Gy were independent predictors of improved LRC, and locoregional failure was an independent predictor of worse overall survival.
  
  
  CONCLUSIONS
  Our data suggested a positive correlation between radiation dose and LRC in the population studied. A higher radiation dose was associated with increased LRC and survival in the dose range studied. The data also suggested that better LRC was associated with a lower rate of distant metastasis. A threshold of tumor response to radiation dose might be present, as suggested by the flattened slope in the high-dose area on the dose-response curve. A carefully designed dose-escalation study is required to confirm this assumption.
authors.affiliation: Department of Radiation Oncology, Shanghai Fudan University, Shanghai Medical University, Shanghai Cancer Hospital, Shanghai, People's Republic of China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhang
authors.forename: Zhongxing
authors.initials: Z
authors.lastname: Liao
authors.forename: Jing
authors.initials: J
authors.lastname: Jin
authors.forename: Jaffer
authors.initials: J
authors.lastname: Ajani
authors.forename: Joe Y
authors.initials: JY
authors.lastname: Chang
authors.forename: Melenda
authors.initials: M
authors.lastname: Jeter
authors.forename: Thomas
authors.initials: T
authors.lastname: Guerrero
authors.forename: Craig W
authors.initials: CW
authors.lastname: Stevens
authors.forename: Stephen
authors.initials: S
authors.lastname: Swisher
authors.forename: Linus
authors.initials: L
authors.lastname: Ho
authors.forename: James
authors.initials: J
authors.lastname: Yao
authors.forename: Pamela
authors.initials: P
authors.lastname: Allen
authors.forename: James D
authors.initials: JD
authors.lastname: Cox
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Komaki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D004307:Dose-Response Relationship, Radiation; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D018709:Statistics, Nonparametric
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin; D005472:Fluorouracil