title: Fractionated high-dose-rate and pulsed-dose-rate brachytherapy: first clinical experience in squamous cell carcinoma of the tonsillar fossa and soft palate.
abstract: OBJECTIVE
  Fractionated high-dose-rate (fr.HDR) and pulsed-dose-rate (PDR) brachytherapy (BT) regimens, which simulate classical continuous low-dose-rate (LDR) interstitial radiation therapy (IRT) schedules, have been developed for clinical use. This article reports the initial results using these novel schedules in squamous cell carcinoma (SCC) of the tonsillar fossa (TF) and/or soft palate (SP).
  
  
  METHODS
  Between 1990 and 1994, 38 patients with TF and SP tumors (5 T1, 22 T2, 10 T3, and 1 T4) were treated by fr.HDR or PDR brachytherapy, either alone or in combination with external irradiation (ERT). Half of the patients were treated with fr.HDR, which entailed twice-daily fractions of > or = 3 Gy. The other 19 patients were administered PDR, which consisted of pulses of < or = 2 Gy delivered 4-8 times/day. The median cumulative dose of IRT +/- ERT series was 66 Gy (range 55-73). The results in these patients treated by brachytherapy were compared to 72 patients with similar tumors treated in our institute with curative intent, using ERT alone. The median cumulative dose of ERT-only series was 70 Gy (range 40-77).
  
  
  RESULTS
  Excellent locoregional control was achieved with the use of IRT +/- ERT, with only 13% (5 of 38) developing local failure, and salvage surgery being possible in three of the latter (60%). Neither BT scheme (fr.HDR vs. PDR) nor tumor site (TF vs. SP) significantly influenced local control rates. The type and severity of the side effects observed are comparable to those reported in the literature for LDR-IRT. These results contrast sharply with our ERT-only series, in which 39% of patients (28 of 72) developed local failure, with surgical salvage being possible only in three patients (11%). Taking the data set of 110 patients, in a univariate analysis IRT, T stage, N stage, overall treatment time (OTT), and BEDcor10 (biological effective dose with a correction for the OTT) were significant prognostic factors for local relapse-free survival (LRFS) and overall survival (OS) at 3 years. Using Cox proportional hazard analysis, only T stage and BEDcor10 remained significant for LRFS (p < 0.001 and 0.008, respectively), as well as for OS (p < 0.001 and 0.003, respectively). With regard to the current (IRT) and historical (ERT) series, for the LRFS at 3 years, dose-response relationships were established, significant, however, only for the BEDcor10 (p = 0.03).
  
  
  CONCLUSIONS
  The 3-year LRFS of approximately 90% for TF and SP tumors reported here is comparable with the best results in the literature, particularly given the fact that 30% of the patients (11 of 38) presented with T3/4 tumors. When compared with our historical (ERT-only) controls, the patients treated with IRT had superior local control. A dose-response relationship was established for the BEDcor10.
authors.affiliation: Department of Radiation Oncology, Dr. Daniel den Hoed Cancer Center/University Hospital Rotterdam-Dijkzigt, The Netherlands.
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: S
authors.initials: S
authors.lastname: Senan
authors.forename: W M
authors.initials: WM
authors.lastname: Eijkenboom
authors.forename: D
authors.initials: D
authors.lastname: Sipkema
authors.forename: C A
authors.initials: CA
authors.lastname: Meeuwis
authors.forename: I K
authors.initials: IK
authors.lastname: Kolkman-Deurloo
authors.forename: A G
authors.initials: AG
authors.lastname: Visser
mesh_terms: D001918:Brachytherapy / Q000379:methods*; D002294:Carcinoma, Squamous Cell / Q000532:radiotherapy*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D008297:Male; D010157:Palatal Neoplasms / Q000532:radiotherapy*; D010160:Palate, Soft; D011879:Radiotherapy Dosage; D014067:Tonsillar Neoplasms / Q000532:radiotherapy*