title: Toxicity after central versus peripheral lung stereotactic body radiation therapy: a propensity score matched-pair analysis.
abstract: OBJECTIVE
  To compare toxicity after stereotactic body radiation therapy (SBRT) for "central" tumors-within 2 cm of the proximal bronchial tree or with planning tumor volume (PTV) touching mediastinum-versus noncentral ("peripheral") lung tumors.
  
  
  METHODS
  From November 2005 to January 2011, 229 tumors (110 central, 119 peripheral; T1-3N0M0 non-small-cell lung cancer and limited lung metastases) in 196 consecutive patients followed prospectively at a single institution received moderate-dose SBRT (48-60 Gy in 4-5 fractions [biologic effective dose=100-132 Gy, α/β=10]) using 4-dimensional planning, online image-guided radiation therapy, and institutional dose constraints. Clinical adverse events (AEs) were graded prospectively at clinical and radiographic follow-up using Common Terminology Criteria for Adverse Events version 3.0. Pulmonary function test (PFT) decline was graded as 2 (25%-49.9% decline), 3 (50.0%-74.9% decline), or 4 (≥75.0% decline). Central/peripheral location was assessed retrospectively on planning CT scans. Groups were compared after propensity score matching. Characteristics were compared with χ(2) and 2-tailed t tests, adverse events with χ(2) test-for-trend, and cumulative incidence using competing risks analysis (Gray's test).
  
  
  RESULTS
  With 79 central and 79 peripheral tumors matched, no differences in AEs were observed after 17 months median follow-up. Two-year cumulative incidences of grade ≥2 pain, musculoskeletal, pulmonary, and skin AEs were 14%, 5%, 6%, and 10% (central) versus 19%, 10%, 10%, and 3% (peripheral), respectively (P=.31, .38, .70, and .09). Grade ≥2 cardiovascular, gastrointestinal, and central nervous system AEs were rare (<1%). Two-year incidences of grade ≥2 clinical AEs (28% vs 25%, P=.79), grade ≥2 PFT decline (36% vs 34%, P=.94), grade ≥3 clinical AEs (3% vs 7%, P=.48), and grade ≥3 PFT decline (0 vs 10%, P=.11) were similar for central versus peripheral tumors, respectively. Pooled 2-year incidences of grades 4 and 5 AEs were <1% and 0%, respectively, in both the prematched and matched groups.
  
  
  CONCLUSIONS
  Moderate-dose SBRT with these techniques yields a similarly safe toxicity profile for both central and peripheral lung tumors.
authors.affiliation: Department of Radiation Oncology, Beaumont Health System, Royal Oak, Michigan.
authors.forename: Victor S
authors.initials: VS
authors.lastname: Mangona
authors.affiliation: Oakland University William Beaumont School of Medicine, Rochester, Michigan.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Aneese
authors.affiliation: Department of Radiation Oncology, Beaumont Health System, Royal Oak, Michigan.
authors.forename: Ovidiu
authors.initials: O
authors.lastname: Marina
authors.affiliation: Department of Radiation Oncology, Beaumont Health System, Royal Oak, Michigan.
authors.forename: Richard V
authors.initials: RV
authors.lastname: Hymas
authors.affiliation: Department of Radiation Oncology, Beaumont Health System, Royal Oak, Michigan; Oakland University William Beaumont School of Medicine, Rochester, Michigan.
authors.forename: Dan
authors.initials: D
authors.lastname: Ionascu
authors.affiliation: Department of Radiation Oncology, Beaumont Health System, Royal Oak, Michigan; Oakland University William Beaumont School of Medicine, Rochester, Michigan.
authors.forename: John M
authors.initials: JM
authors.lastname: Robertson
authors.affiliation: Oakland University William Beaumont School of Medicine, Rochester, Michigan; Department of Radiology, Beaumont Health System, Royal Oak, Michigan.
authors.forename: Lori J
authors.initials: LJ
authors.lastname: Gallardo
authors.affiliation: Department of Radiation Oncology, Beaumont Health System, Royal Oak, Michigan; Oakland University William Beaumont School of Medicine, Rochester, Michigan. Electronic address: igrills@beaumont.edu.
authors.forename: Inga Siiner
authors.initials: IS
authors.lastname: Grills
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology / Q000601:surgery*; D016009:Chi-Square Distribution; D019583:Dose Fractionation, Radiation; D005260:Female; D006801:Humans; D015994:Incidence; D008175:Lung Neoplasms / Q000473:pathology / Q000601:surgery*; D008297:Male; D008482:Mediastinum / Q000473:pathology; D008875:Middle Aged; D058958:Organs at Risk / Q000528:radiation effects; D010146:Pain / Q000209:etiology; D057216:Propensity Score; D011832:Radiation Injuries / Q000453:epidemiology*; D016634:Radiosurgery / Q000009:adverse effects* / Q000379:methods; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods; D061089:Radiotherapy, Image-Guided / Q000009:adverse effects / Q000379:methods; D012129:Respiratory Function Tests; D012737:Sex Factors; D047368:Tumor Burden; D055815:Young Adult