title: Hyperfractionated radiotherapy in locally advanced nasopharyngeal cancer. An analysis of 43 consecutive patients.
abstract: BACKGROUND
  Despite numerous randomized trials suggesting a benefit of unconventional fractionation in locally advanced head and neck cancer, the role of this approach in nasopharyngeal carcinoma is debatable. Based on the current clinical experience, the authors introduced hyperfractionated irradiation in the treatment of locally advanced head and neck cancer, including nasopharyngeal tumors. The preliminary results of this treatment approach in nasopharyngeal cancer patients are presented, with special focus on the pattern of failure and toxicity.
  
  
  METHODS
  43 patients with nasopharyngeal cancer (stage II-IV, TNM 1997) underwent hyperfractionated irradiation. In 34 cases, radiotherapy was preceded by a median of three cycles of cisplatin-based induction chemotherapy. Irradiation was delivered using a shrinking-field technique up to a total dose of 74.4 Gy in 62 fractions of 1.2 Gy twice daily (minimum 6-h interval)/5 days/week.
  
  
  RESULTS
  Acute toxicity of hyperfractionated radiotherapy was significant but tolerable. Mucositis proved the most common side effect (grade 3: 24 patients, grade 4: three patients). Severe late toxicity was not observed. 30 of 34 patients (88%) responded to induction chemotherapy. At 6 weeks after completion of radiotherapy, complete response was seen in 35 patients (81%), partial response in five (12%), stable disease in one, and progressive disease in two. After a median follow-up of 32 months, 18 patients (41%) developed progressive disease. Primary tumor progression was observed in three patients, and seven patients each showed regional lymph node progression and distant metastases. In one case both regional lymph node progression and distant metastases were diagnosed. The 2-year progression-free survival and overall survival rates were 58% and 84%, respectively.
  
  
  CONCLUSIONS
  Hyperfractionated radiotherapy seems a feasible and active regimen in locally advanced nasopharyngeal carcinoma. Accompanying acute and late toxicity is acceptable and does not compromise delivery of the planned irradiation dose. This regimen is associated with a high local control rate; relatively high nodal and distant failure, however, call for further treatment modifications, e. g., optimization of irradiation technique and/or dose escalation as well as improved systemic therapies.
authors.affiliation: Department of Radiation Oncology, European Institute of Oncology, Milan, Italy. barbara.fossa@ieo.it
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Jereczek-Fossa
authors.forename: Anna
authors.initials: A
authors.lastname: Morra
authors.forename: Filippo
authors.initials: F
authors.lastname: DeBraud
authors.forename: Daniela
authors.initials: D
authors.lastname: Alterio
authors.forename: Chiara
authors.initials: C
authors.lastname: Mazzetta
authors.forename: Andrea
authors.initials: A
authors.lastname: Rocca
authors.forename: Gianpiero
authors.initials: G
authors.lastname: Catalano
authors.forename: Livia
authors.initials: L
authors.lastname: Bianchi
authors.forename: Marcella
authors.initials: M
authors.lastname: Pasetti
authors.forename: Fausto
authors.initials: F
authors.lastname: Chiesa
authors.forename: Roberto
authors.initials: R
authors.lastname: Bruschini
authors.forename: Roberto
authors.initials: R
authors.lastname: Orecchia
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019583:Dose Fractionation, Radiation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D009367:Neoplasm Staging; D011878:Radiotherapy / Q000009:adverse effects / Q000379:methods*; D012189:Retrospective Studies; D016019:Survival Analysis