title: Excessive toxicity when treating central tumors in a phase II study of stereotactic body radiation therapy for medically inoperable early-stage lung cancer.
abstract: OBJECTIVE
  Surgical resection is standard therapy in stage I non-small-cell lung cancer (NSCLC); however, many patients are inoperable due to comorbid diseases. Building on a previously reported phase I trial, we carried out a prospective phase II trial using stereotactic body radiation therapy (SBRT) in this population.
  
  
  METHODS
  Eligible patients included clinically staged T1 or T2 (< or = 7 cm), N0, M0, biopsy-confirmed NSCLC. All patients had comorbid medical problems that precluded lobectomy. SBRT treatment dose was 60 to 66 Gy total in three fractions during 1 to 2 weeks.
  
  
  RESULTS
  All 70 patients enrolled completed therapy as planned and median follow-up was 17.5 months. The 3-month major response rate was 60%. Kaplan-Meier local control at 2 years was 95%. Altogether, 28 patients have died as a result of cancer (n = 5), treatment (n = 6), or comorbid illnesses (n = 17). Median overall survival was 32.6 months and 2-year overall survival was 54.7%. Grade 3 to 5 toxicity occurred in a total of 14 patients. Among patients experiencing toxicity, the median time to observation was 10.5 months. Patients treated for tumors in the peripheral lung had 2-year freedom from severe toxicity of 83% compared with only 54% for patients with central tumors.
  
  
  CONCLUSIONS
  High rates of local control are achieved with this SBRT regimen in medically inoperable patients with stage I NSCLC. Both local recurrence and toxicity occur late after this treatment. This regimen should not be used for patients with tumors near the central airways due to excessive toxicity.
authors.affiliation: Department of Radiation Oncology, The University of Texas Southwestern Medical Center, 5801 Forest Park Rd, Dallas, TX 75390-9183, USA. robert.timmerman@utsouthwestern.edu
authors.forename: Robert
authors.initials: R
authors.lastname: Timmerman
authors.forename: Ronald
authors.initials: R
authors.lastname: McGarry
authors.forename: Constantin
authors.initials: C
authors.lastname: Yiannoutsos
authors.forename: Lech
authors.initials: L
authors.lastname: Papiez
authors.forename: Kathy
authors.initials: K
authors.lastname: Tudor
authors.forename: Jill
authors.initials: J
authors.lastname: DeLuca
authors.forename: Marvene
authors.initials: M
authors.lastname: Ewing
authors.forename: Ramzi
authors.initials: R
authors.lastname: Abdulrahman
authors.forename: Colleen
authors.initials: C
authors.lastname: DesRosiers
authors.forename: Mark
authors.initials: M
authors.lastname: Williams
authors.forename: James
authors.initials: J
authors.lastname: Fletcher
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology / Q000532:radiotherapy*; D015897:Comorbidity; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011832:Radiation Injuries; D011878:Radiotherapy / Q000379:methods; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome