title: Dose escalation in non-small-cell lung cancer using three-dimensional conformal radiation therapy: update of a phase I trial.
abstract: OBJECTIVE
  High-dose radiation may improve outcomes in non-small-cell lung cancer (NSCLC). By using three-dimensional conformal radiation therapy and limiting the target volume, we hypothesized that the dose could be safely escalated.
  
  
  METHODS
  A standard phase I design was used. Five bins were created based on the volume of normal lung irradiated, and dose levels within bins were chosen based on the estimated risk of radiation pneumonitis. Starting doses ranged from 63 to 84 Gy given in 2.1-Gy fractions. Target volumes included the primary tumor and any nodes >or= 1 cm on computed tomography. Clinically uninvolved nodal regions were not included purposely. More recently, selected patients received neoadjuvant cisplatin and vinorelbine.
  
  
  RESULTS
  At the time of this writing, 104 patients had been enrolled. Twenty-four had stage I, four had stage II, 43 had stage IIIA, 26 had stage IIIB, and seven had locally recurrent disease. Twenty-five received chemotherapy, and 63 were assessable for escalation. All bins were escalated at least twice. Although grade 2 radiation pneumonitis occurred in five patients, grade 3 radiation pneumonitis occurred in only two. The maximum-tolerated dose was only established for the largest bin, at 65.1 Gy. Dose levels for the four remaining bins were 102.9, 102.9, 84 and 75.6 Gy. The majority of patients failed distantly, though a significant proportion also failed in the target volume. There were no isolated failures in clinically uninvolved nodal regions.
  
  
  CONCLUSIONS
  Dose escalation in NSCLC has been accomplished safely in most patients using three-dimensional conformal radiation therapy, limiting target volumes, and segregating patients by the volume of normal lung irradiated.
authors.affiliation: Department of Radiation Oncology, Division of Hematology/Oncology, University of Michigan Health System, Ann Arbor, MI, USA. hayman@umich.edu
authors.forename: J A
authors.initials: JA
authors.lastname: Hayman
authors.forename: M K
authors.initials: MK
authors.lastname: Martel
authors.forename: R K
authors.initials: RK
authors.lastname: Ten Haken
authors.forename: D P
authors.initials: DP
authors.lastname: Normolle
authors.forename: R F
authors.initials: RF
authors.lastname: Todd
authors.forename: J F
authors.initials: JF
authors.lastname: Littles
authors.forename: M A
authors.initials: MA
authors.lastname: Sullivan
authors.forename: P W
authors.initials: PW
authors.lastname: Possert
authors.forename: A T
authors.initials: AT
authors.lastname: Turrisi
authors.forename: A S
authors.initials: AS
authors.lastname: Lichter
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D018572:Disease-Free Survival; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D011014:Pneumonia / Q000209:etiology; D020266:Radiotherapy, Conformal / Q000009:adverse effects; D015996:Survival Rate; D014481:United States / Q000453:epidemiology