title: Dose escalation of three-dimensional conformal radiotherapy for locally recurrent nasopharyngeal carcinoma: a prospective randomised study.
abstract: OBJECTIVE
  To investigate prospectively the feasibility and efficacy of dose escalation using three-dimensional conformal radiotherapy (3D-CRT) boost technique for locally recurrent nasopharyngeal carcinoma (NPC) in a randomised study.
  
  
  METHODS
  Thirty-six patients with locally recurrent NPC (>6 months interval from previous radical radiotherapy, no cervical lymph-node involvement and no distant metastasis) were enrolled. Treatment included conventional external-beam radiotherapy to 54 Gy, followed by a 3D-CRT boost to the gross tumour region. Patients were randomised to three boost dose levels: 16 Gy, 20 Gy and 24 Gy for groups I, II and III, respectively, with 12 patients in each group. All boost doses were delivered in 4-Gy fractions and 3 fractions per week. Median follow-up was 27 months (range 14-44 months).
  
  
  RESULTS
  Three-year, local-recurrence-free survival rate was significantly higher (72%) for the high-dose group III than for groups I and II (37% and 28%, respectively, P = 0.047). No significant difference was found in the 3-year overall survival rate among the three groups (72%, 59% and 82% for groups I, II and III, respectively). Three-year distant metastases rates were 17%, 0% and 18%, respectively. Skull-base invasion (P = 0.017) and pathology (P = 0.0006) correlated with overall survival. Treatment was well tolerated and no significant difference was observed among the three groups in acute and late toxicities (grade III toxicity is minimal: 17%, 17%, 0% of oral mucositis and 25%, 17%, 17% of nasopharyngeal mucositis in groups I, II, III, respectively, and 8% leukocytopenia only in group II; no grade IV toxicity occurred in any of the groups except for a fatal bleeding in group III).
  
  
  CONCLUSIONS
  Re-irradiation with high-dose 3D-CRT boost technique results in high local control rate and acceptable toxicity in patients with recurrent NPC. Dose escalation to the boost volume to 78 Gy (54 Gy + 24 Gy boost) results in improved recurrence-free survival compared with lower doses.
authors.affiliation: Department of Radiation Oncology, Affiliated Cancer Hospital, Fudan University, Shanghai, People's Republic of China.
authors.forename: J C
authors.initials: JC
authors.lastname: Li
authors.forename: C S
authors.initials: CS
authors.lastname: Hu
authors.forename: G L
authors.initials: GL
authors.lastname: Jiang
authors.forename: N A
authors.initials: NA
authors.lastname: Mayr
authors.forename: J Z
authors.initials: JZ
authors.lastname: Wang
authors.forename: X Y
authors.initials: XY
authors.lastname: He
authors.forename: Y Ru
authors.initials: YR
authors.lastname: Wu
mesh_terms: D000328:Adult; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000532:radiotherapy*; D011446:Prospective Studies; D020266:Radiotherapy, Conformal; D016019:Survival Analysis