title: DART-bid (Dose-differentiated accelerated radiation therapy, 1.8 Gy twice daily)--a novel approach for non-resected NSCLC: final results of a prospective study, correlating radiation dose to tumor volume.
abstract: BACKGROUND
  Sequential chemo-radiotherapies with intensive radiation components deliver promising results in non-resected non-small cell lung cancer (NSCLC). In general, radiation doses are determined by dose constraints for normal tissues, not by features relevant for tumor control. DART-bid targets directly the doses required for tumor control, correlating doses to tumor volume in a differentiated mode.
  
  
  METHODS
  Radiation doses to primary tumors were aligned along increasing tumor size within 4 groups (<2.5 cm/2.5-4.5 cm/4.5-6.0 cm/>6.0 cm; mean number of three perpendicular diameters). ICRU-doses of 73.8 Gy/79.2 Gy/84.6 Gy/90.0 Gy, respectively, were applied. Macroscopically involved nodes were treated with a median dose of 59.4 Gy, nodal sites about 6 cm cranial to involved nodes electively with 45 Gy. Fractional doses were 1.8 Gy twice daily (bid).2 cycles chemotherapy were given before radiotherapy.Between 2004 and 2009, 160 not selected patients with 164 histologically/cytologically proven NSCLC were enrolled; Stage I: 38 patients; II: 6 pts.; IIIA: 69 pts.; IIIB: 47 pts. Weight loss >5%/3 months: 38 patients (24%).Primary endpoints are local and regional tumor control rates at 2 years (as >90% of locoregional failures occur within 2 years). Secondary endpoints are survival and toxicity. With a minimum follow-up time of 2 years for patients alive, the final results are presented.
  
  
  RESULTS
  32 local and 10 regional recurrences occurred. The local and regional tumor control rates at 2 years are 77% and 93%, respectively.The median overall survival (OS) time is 28.0 months, the 2- and 5-year OS rates are 57% and 19%, respectively. For stage III patients, median OS amounts to 24.3 months, 2- /5-year OS rates to 51% and 18%, respectively.2 treatment-related deaths (progressive pulmonary fibrosis) occurred in patients with pre-existing pulmonary fibrosis. Further acute and late toxicity was mild.
  
  
  CONCLUSIONS
  This novel approach yields a high level of locoregional tumor control and survival times. In general it is well tolerated. In all outcome parameters it seems to compare favourably with simultaneous chemo-radiotherapies, at present considered 'state of the art'; and is additionally amenable for an unselected patient population.
authors.affiliation: Department of Radiation Oncology and radART-Institute for research and development on Advanced Radiation Technologies, Paracelsus Medical University, Salzburg, Austria. k.wurstbauer@salk.at
authors.forename: Karl
authors.initials: K
authors.lastname: Wurstbauer
authors.forename: Heinz
authors.initials: H
authors.lastname: Deutschmann
authors.forename: Karin
authors.initials: K
authors.lastname: Dagn
authors.forename: Peter
authors.initials: P
authors.lastname: Kopp
authors.forename: Franz
authors.initials: F
authors.lastname: Zehentmayr
authors.forename: Bernd
authors.initials: B
authors.lastname: Lamprecht
authors.forename: Peter
authors.initials: P
authors.lastname: Porsch
authors.forename: Birgit
authors.initials: B
authors.lastname: Wegleitner
authors.forename: Michael
authors.initials: M
authors.lastname: Studnicka
authors.forename: Felix
authors.initials: F
authors.lastname: Sedlmayer
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D059248:Chemoradiotherapy; D002945:Cisplatin / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted; D050397:Radiotherapy, Intensity-Modulated; D015996:Survival Rate
chemical_list: D016190:Carboplatin; D002945:Cisplatin