title: Mature results of a randomized trial comparing two fractionation schedules of high dose rate endoluminal brachytherapy for the treatment of endobronchial tumors.
abstract: OBJECTIVE
  To determine the efficacy of high dose rate endobronchial brachytherapy (HDR-BT) for the treatment of centrally located lung tumors, two different fractionation schedules were compared regarding local tumor response, side effects and survival. Mature retrospective results with longer follow-up and more patients were analyzed. Initial results were published by Huber et al. in 1995.
  
  
  METHODS
  142 patients with advanced, centrally located malignant tumors with preferential endoluminal growth were randomized to receive 4 fractions of 3.8 Gy (time interval: 1 week, n = 60, group I) or 2 fractions of 7.2 Gy (time interval: 3 weeks, n = 82, group II) endobronchial HDR-BT.Age, gender, tumor stage, Karnofsky Performance Score and histology were equally distributed between both groups.
  
  
  RESULTS
  Local tumor response with 2 fractions of 7.2 Gy was significantly higher as compared to 4 fractions of 3.8 Gy (median 12 vs. 6 weeks; p ≤ 0.015). Median survival was similar in both groups (19 weeks in the 4 fractions group vs. 18 weeks in the 2 fractions group). Fatal hemoptysis was less frequent following irradiation with 2 × 7.2 Gy than with 4 × 3.8 Gy, although the difference did not achieve statistical significance (12.2% vs. 18.3%, respectively. p = 0,345). Patients presenting with squamous cell carcinoma were at higher risk of bleeding compared to other histology (21.9% vs. 9%, p = 0,035).Multivariate analysis with regard to overall survival, revealed histology (p = 0.02), Karnofsky Performance Score (p < 0.0001) and response to therapy (p < 0.0001) as significant prognostic factors. For patients showing complete response the median survival was 57 weeks, while for patients with progressive disease median survival time was 8 weeks, p < 0.0001.The KPS at the start of the treatment was significantly correlated with survival. Patients presenting with a KPS ≤ 60 at the start had a significantly (p = 0,032) shorter survival time (10 weeks) than patients with a KPS > 60 (29 weeks).Moreover, the Karnofsky Performance Score of most patients improved during therapy (p = 0,001), suggesting successful palliation of cancer associated symptoms.Multivariate analysis with regard to local tumor control found no significant factors.
  
  
  CONCLUSIONS
  Endobronchial HDR-BT is an effective local treatment for advanced centrally located malignant tumors with endoluminal tumor growth. Local tumor response was significantly higher after HDR-BT with 2 × 7.2 Gy.
authors.affiliation: Department of Radiotherapy and Radiation Oncology, Ludwig-Maximilians University Munich, Marchioninistr, 15, 81377 Munich, Germany. olivier.niemoeller@med.uni-muenchen.de
authors.forename: Olivier M
authors.initials: OM
authors.lastname: Niemoeller
authors.forename: Barbara
authors.initials: B
authors.lastname: Pöllinger
authors.forename: Maximilian
authors.initials: M
authors.lastname: Niyazi
authors.forename: Stefanie
authors.initials: S
authors.lastname: Corradini
authors.forename: Farkhad
authors.initials: F
authors.lastname: Manapov
authors.forename: Claus
authors.initials: C
authors.lastname: Belka
authors.forename: Rudolf M
authors.initials: RM
authors.lastname: Huber
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001918:Brachytherapy; D001984:Bronchial Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D018287:Carcinoma, Large Cell / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D019583:Dose Fractionation, Radiation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate