title: Individualized radical radiotherapy of non-small-cell lung cancer based on normal tissue dose constraints: a feasibility study.
abstract: OBJECTIVE
  Local recurrence is a major problem after (chemo-)radiation for non-small-cell lung cancer. We hypothesized that for each individual patient, the highest therapeutic ratio could be achieved by increasing total tumor dose (TTD) to the limits of normal tissues, delivered within 5 weeks. We report first results of a prospective feasibility trial.
  
  
  METHODS
  Twenty-eight patients with medically inoperable or locally advanced non-small-cell lung cancer, World Health Organization performance score of 0-1, and reasonable lung function (forced expiratory volume in 1 second > 50%) were analyzed. All patients underwent irradiation using an individualized prescribed TTD based on normal tissue dose constraints (mean lung dose, 19 Gy; maximal spinal cord dose, 54 Gy) up to a maximal TTD of 79.2 Gy in 1.8-Gy fractions twice daily. No concurrent chemoradiation was administered. Toxicity was scored using the Common Terminology Criteria for Adverse Events criteria. An (18)F-fluoro-2-deoxy-glucose-positron emission tomography-computed tomography scan was performed to evaluate (metabolic) response 3 months after treatment.
  
  
  RESULTS
  Mean delivered dose was 63.0 +/- 9.8 Gy. The TTD was most often limited by the mean lung dose (32.1%) or spinal cord (28.6%). Acute toxicity generally was mild; only 1 patient experienced Grade 3 cough and 1 patient experienced Grade 3 dysphagia. One patient (3.6%) died of pneumonitis. For late toxicity, 2 patients (7.7%) had Grade 3 cough or dyspnea; none had severe dysphagia. Complete metabolic response was obtained in 44% (11 of 26 patients). With a median follow-up of 13 months, median overall survival was 19.6 months, with a 1-year survival rate of 57.1%.
  
  
  CONCLUSIONS
  Individualized maximal tolerable dose irradiation based on normal tissue dose constraints is feasible, and initial results are promising.
authors.affiliation: Department of Radiation Oncology (MAASTRO), GROW Research Institute, University Hospital Maastricht, Dr. Tanslaan 12, Maastricht, The Netherlands. angela.vanbaardwijk@maastro.nl
authors.forename: Angela
authors.initials: A
authors.lastname: van Baardwijk
authors.forename: Geert
authors.initials: G
authors.lastname: Bosmans
authors.forename: Liesbeth
authors.initials: L
authors.lastname: Boersma
authors.forename: Stofferinus
authors.initials: S
authors.lastname: Wanders
authors.forename: André
authors.initials: A
authors.lastname: Dekker
authors.forename: Anne Marie C
authors.initials: AM
authors.lastname: Dingemans
authors.forename: Gerben
authors.initials: G
authors.lastname: Bootsma
authors.forename: Wiel
authors.initials: W
authors.lastname: Geraedts
authors.forename: Cordula
authors.initials: C
authors.lastname: Pitz
authors.forename: Jean
authors.initials: J
authors.lastname: Simons
authors.forename: Philippe
authors.initials: P
authors.lastname: Lambin
authors.forename: Dirk
authors.initials: D
authors.lastname: De Ruysscher
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000532:radiotherapy*; D005240:Feasibility Studies; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008168:Lung / Q000000981:diagnostic imaging / Q000528:radiation effects; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000532:radiotherapy*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D011446:Prospective Studies; D011832:Radiation Injuries / Q000150:complications; D011877:Radionuclide Imaging; D011879:Radiotherapy Dosage; D012074:Remission Induction; D013116:Spinal Cord / Q000528:radiation effects; D015996:Survival Rate