title: Fractionated high-dose-rate brachytherapy in primary carcinoma of the nasopharynx.
abstract: OBJECTIVE
  A growing body of data suggests that local control in nasopharyngeal cancer (NPC) is related to the radiation dose administered. We conducted a single-institution study of high-dose radiotherapy (RT), which incorporated high-dose-rate (HDR) brachytherapy (BT). These results were analyzed together with data obtained from controls who did not receive BT.
  
  
  METHODS
  The BT group comprised 42 consecutive patients of whom 29 patients were staged according to the tumor, node, metastasis system as T1 through 3, 13 patients were T4, and 34 patients were N+ disease. BT was administered on an outpatient basis by means of a specially designed flexible nasopharyngeal applicator, and the dose distributions were optimized. Treatment for T1 through 3 tumors comprised 60 Gy of external-beam radiotherapy (ERT) followed by six fractions of 3 Gy BT (two fractions per day). Patients with parapharyngeal tumor extension and/or T4 tumors received 70 Gy ERT and four fractions of 3 Gy BT. The no-BT group consisted of all patients treated from 1965 to 1991 (n = 109), of whom 82 patients had stages T1 through 3, 27 patients had T4, and 80 patients had N+ disease. Multivariate Cox proportional hazards analyses were performed by using the end points time to local failure (TTLF), time to distant failure (TTDF), disease-free survival (DFS), cause-specific survival (CSS), and the prognostic factors age, tumor stage, node stage, and grade. Because the overall treatment time varied substantially in the no-BT group, the dependence of local failure (LF) on the physical dose as well as the biologic effective dose (BED) corrected for the overall treatment time (OTT) (BEDcor10) was studied.
  
  
  RESULTS
  The BT group had a superior 3-year local relapse-free rate (86% v 60%; univariate analysis, P = .004). Multivariate analysis showed hazards ratios for BT versus no-BT of 0.24 for TTLF (P = .003), 0.35 for TTDF (P = .038), 0.31 for DFS (P < .001), and 0.44 for CSS (P = .01). The best prognostic group consisted of patients with T1 through 3, N0 through 2b tumors treated with BT who attained a 5-year TTLF of 94% and CSS of 91%. In contrast, the worst prognostic group, i.e., 5-year TTLF of 47% and CSS of 24%, was composed of patients with T4 and/or N2c through 3 tumors who did not receive BT.
  
  
  CONCLUSIONS
  High doses of radiation (73 to 95 Gy) can be administered to patients with NPC with minimal morbidity by means of optimized HDR-BT. The use of a BT boost proved to be of significant benefit, particularly in patients with T1 through 3, N0 through 2b disease. The steep dose-effect relationship seen for the physical dose and the BEDcor10 indicates that the results are dose related. The analysis has identified a poor prognostic group in whom treatment intensification with chemotherapy (CHT) is indicated.
authors.affiliation: Department of Radiation Oncology, University Hospital Rotterdam, Daniel den Hoed Cancer Center, The Netherlands. levendag@rtdh.azr.nl
authors.forename: P C
authors.initials: PC
authors.lastname: Levendag
authors.forename: P I
authors.initials: PI
authors.lastname: Schmitz
authors.forename: P P
authors.initials: PP
authors.lastname: Jansen
authors.forename: W M
authors.initials: WM
authors.lastname: Eijkenboom
authors.forename: A G
authors.initials: AG
authors.lastname: Visser
authors.forename: I K
authors.initials: IK
authors.lastname: Kolkman-Deurloo
authors.forename: D
authors.initials: D
authors.lastname: Sipkema
authors.forename: L L
authors.initials: LL
authors.lastname: Visch
authors.forename: S
authors.initials: S
authors.lastname: Senan
mesh_terms: D000328:Adult; D001918:Brachytherapy / Q000295:instrumentation / Q000379:methods*; D002277:Carcinoma / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy*; D015996:Survival Rate; D016896:Treatment Outcome