title: Adjuvant fractionated high-dose-rate intracavitary brachytherapy after external beam radiotherapy in Tl and T2 nasopharyngeal carcinoma.
abstract: BACKGROUND
  The value of high-dose-rate intracavitary brachytherapy (HDRIB) for persistent or recurrent nasopharyngeal carcinoma has been well described; however, the benefit of routine adjuvant fractionated HDRIB following external beam radiation therapy (EBRT) has not been completely determined. The objective of this analysis was to evaluate the outcome of two fractions of adjuvant HDRIB treatment in Tl and T2 nasopharyngeal carcinoma.
  
  
  METHODS
  Thirty-three consecutive and nonselected patients who had Tl and T2 non-disseminated nasopharyngeal carcinoma were treated according to an IRB approved institutional research protocol between March 1999 and July 2001. By the 1997 AJCC cancer staging classification, 22 patients (67%) had Tl disease and 11 patients (33%) had T2 disease. Seventeen of these patients who had stage I or stage II disease (i.e., NO or Nl) were treated with EBRT followed by two fractions of adjuvant HDRIB (group 1); 16 patients who had stage III or stage IV disease (i.e., N2 or N3) were treated with concurrent cisplatin, EBRT and adjuvant HDRIB and subsequent adjuvant cisplatin and fluorouracil (5-FU) chemotherapy (group 2). EBRT was delivered by daily conventional fractionation to a total dose of 66 Gy to the primary tumor. Nodal disease received 66 Gy if it was less than 3 cm in maximum diameter and 70 Gy if larger or there was palpable residual disease after 66 Gy. A total of 10 Gy of HDRIB in 2 equal fractions of 5 Gy spaced 1 week apart was delivered starting 1 week after the completion of EBRT. All patients were assessed for treatment response, local control, survival, and toxicity.
  
  
  RESULTS
  The median follow up for all 29 surviving patients is 29 months (range: 17-38 months). One patient died 7 months and one died 18 months after radiation therapy from the effects of distant metastases; two died of unrelated causes. At the time of this analysis, one patient (3%) had persistent local disease and one patient (3%) developed pathologically confirmed local recurrence in the nasopharynx. In addition, one patient (3%) developed recurrence only in a neck node followed by distant metastasis, and two patients (6%) developed distant metastasis without locoregional relapse. The 2-year local control rate at the primary site was 93.6%, and the overall survival and disease-free survival rates were 82% and 74% respectively. All patients experienced some degree of acute and/or late toxicity related to radiation therapy. Ten patients (30%) experienced grade 3 acute and/or late toxicity and six patients (18%) developed grade 4 acute and/or late toxicity. No grade 5 toxicity occurred. No unexpected damage of structures within the HDRIB fields was detected.
  
  
  CONCLUSIONS
  EBRT supplemented by two fractions of adjuvant HDRIB produced a 93.6% local control rate for Tl and T2 nasopharyngeal cancer at 2 years of follow up, with acceptable rates of acute and late toxicity. Brief adjuvant HDRIB appears to permit dose escalation safely, even in patients who receive chemotherapy concurrently with conventional radiation therapy. This strategy needs to be optimized and then tested in a prospective randomized phase III trial to learn if it can improve outcome.
authors.affiliation: Department of Radiation Oncology, National University Hospital, 5 Lower Kent Ridge Road, Singapore 119074, Singapore. lujj@nuh.com.sg
authors.forename: Jiade J
authors.initials: JJ
authors.lastname: Lu
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Shakespeare
authors.forename: Luke Kim Siang
authors.initials: LK
authors.lastname: Tan
authors.forename: Boon Cher
authors.initials: BC
authors.lastname: Goh
authors.forename: Jay S
authors.initials: JS
authors.lastname: Cooper
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols; D001918:Brachytherapy / Q000379:methods*; D002277:Carcinoma / Q000401:mortality / Q000473:pathology* / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D019583:Dose Fractionation, Radiation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology* / Q000532:radiotherapy*; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D011879:Radiotherapy Dosage; D018714:Radiotherapy, Adjuvant; D018570:Risk Assessment; D016019:Survival Analysis; D016896:Treatment Outcome