title: Local control and toxicity in a large cohort of central lung tumors treated with stereotactic body radiation therapy.
abstract: OBJECTIVE
  Stereotactic body radiation therapy (SBRT) in central lung tumors has been associated with higher rates of severe toxicity. We sought to evaluate toxicity and local control in a large cohort and to identify predictive dosimetric parameters.
  
  
  METHODS
  We identified patients who received SBRT for central tumors according to either of 2 definitions. Local failure (LF) was estimated using a competing risks model, and multivariate analysis (MVA) was used to assess factors associated with LF. We reviewed patient toxicity and applied Cox proportional hazard analysis and log-rank tests to assess whether dose-volume metrics of normal structures correlated with pulmonary toxicity.
  
  
  RESULTS
  One hundred twenty-five patients received SBRT for non-small cell lung cancer (n=103) or metastatic lesions (n=22), using intensity modulated radiation therapy. The most common dose was 45 Gy in 5 fractions. Median follow-up was 17.4 months. Incidence of toxicity ≥ grade 3 was 8.0%, including 5.6% pulmonary toxicity. Sixteen patients (12.8%) experienced esophageal toxicity ≥ grade 2, including 50% of patients in whom PTV overlapped the esophagus. There were 2 treatment-related deaths. Among patients receiving biologically effective dose (BED) ≥80 Gy (n=108), 2-year LF was 21%. On MVA, gross tumor volume (GTV) was significantly associated with LF. None of the studied dose-volume metrics of the lungs, heart, proximal bronchial tree (PBT), or 2 cm expansion of the PBT ("no-fly-zone" [NFZ]) correlated with pulmonary toxicity ≥grade 2. There were no differences in pulmonary toxicity between central tumors located inside the NFZ and those outside the NFZ but with planning target volume (PTV) intersecting the mediastinum.
  
  
  CONCLUSIONS
  Using moderate doses, SBRT for central lung tumors achieves acceptable local control with low rates of severe toxicity. Dosimetric analysis showed no significant correlation between dose to the lungs, heart, or NFZ and severe pulmonary toxicity. Esophageal toxicity may be an underappreciated risk, particularly when PTV overlaps the esophagus.
authors.affiliation: Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Ankit
authors.initials: A
authors.lastname: Modh
authors.affiliation: Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Andreas
authors.initials: A
authors.lastname: Rimner
authors.affiliation: Department of Medical Physics Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Eric
authors.initials: E
authors.lastname: Williams
authors.affiliation: Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Amanda
authors.initials: A
authors.lastname: Foster
authors.affiliation: Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Mihir
authors.initials: M
authors.lastname: Shah
authors.affiliation: Department of Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Weiji
authors.initials: W
authors.lastname: Shi
authors.affiliation: Department of Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Daphna Y
authors.initials: DY
authors.lastname: Gelblum
authors.affiliation: Department of Radiation Oncology, Mount Sinai Medical Center, New York, New York.
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Rosenzweig
authors.affiliation: Department of Medical Physics Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Ellen D
authors.initials: ED
authors.lastname: Yorke
authors.affiliation: Department of Medical Physics Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Andrew
authors.initials: A
authors.lastname: Jackson
authors.affiliation: Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York. Electronic address: wua@mskcc.org.
authors.forename: Abraham J
authors.initials: AJ
authors.lastname: Wu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology / Q000601:surgery*; D004947:Esophagus / Q000528:radiation effects*; D005260:Female; D006801:Humans; D008168:Lung / Q000528:radiation effects*; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology / Q000601:surgery*; D058958:Organs at Risk / Q000528:radiation effects*; D016016:Proportional Hazards Models; D011832:Radiation Injuries / Q000473:pathology; D016634:Radiosurgery / Q000009:adverse effects* / Q000379:methods; D011879:Radiotherapy Dosage; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects* / Q000379:methods; D012189:Retrospective Studies; D017211:Treatment Failure