title: Influence of Fractionation Scheme and Tumor Location on Toxicities After Stereotactic Body Radiation Therapy for Large (≥5 cm) Non-Small Cell Lung Cancer: A Multi-institutional Analysis.
abstract: To describe the impact of fractionation scheme and tumor location on toxicities in stereotactic body radiation therapy (SBRT) for ≥5-cm non-small cell lung cancer (NSCLC), as part of a multi-institutional analysis.
  
  
  
  Patients with primary ≥5-cm N0 M0 NSCLC who underwent ≤5-fraction SBRT were examined across multiple high-volume SBRT centers. Collected data included clinical/treatment parameters; toxicities were prospectively assessed at each institution according to the Common Terminology Criteria for Adverse Events. Patients treated daily were compared with those treated every other day (QOD)/other nondaily regimens. Stratification between central and peripheral tumors was also performed.
  
  
  
  Ninety-two patients from 12 institutions were evaluated (2004-2016), with median follow-up of 12 months. In total there were 23 (25%) and 6 (7%) grade ≥2 and grade ≥3 toxicities, respectively. Grades 2 and 3 pulmonary toxicities occurred in 9% and 4%, respectively; 1 patient treated daily experienced grade 5 radiation pneumonitis. Of the entire cohort, 46 patients underwent daily SBRT, and 46 received QOD (n=40)/other nondaily (n=6) regimens. Clinical/treatment parameters were similar between groups; the QOD/other group was more likely to receive 3-/4-fraction schemas. Patients treated QOD/other experienced significantly fewer grade ≥2 toxicities as compared with daily treatment (7% vs 43%, P<.001). Patients treated daily also had higher rates of grade ≥2 pulmonary toxicities (P=.014). Patients with peripheral tumors (n=66) were more likely to receive 3-/4-fraction regimens than those with central tumors (n=26). No significant differences in grade ≥2 toxicities were identified according to tumor location (P>.05).
  
  
  
  From this multi-institutional study, toxicity of SBRT for ≥5-cm lesions is acceptable, and daily treatment was associated with a higher rate of toxicities.
authors.affiliation: Department of Radiation Oncology, University of Nebraska Medical Center, Omaha, Nebraska.
authors.forename: Vivek
authors.initials: V
authors.lastname: Verma
authors.affiliation: Department of Biostatistics, College of Public Health, University of Nebraska Medical Center, Omaha, Nebraska.
authors.forename: Valerie K
authors.initials: VK
authors.lastname: Shostrom
authors.affiliation: Department of Radiation Oncology, University of Nebraska Medical Center, Omaha, Nebraska.
authors.forename: Weining
authors.initials: W
authors.lastname: Zhen
authors.affiliation: Department of Radiation Oncology, University of Nebraska Medical Center, Omaha, Nebraska.
authors.forename: Mutian
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Radiation Oncology, University of California, San Francisco, San Francisco, California.
authors.forename: Steve E
authors.initials: SE
authors.lastname: Braunstein
authors.affiliation: Department of Radiation Medicine, Oregon Health & Science University, Portland, Oregon.
authors.forename: John
authors.initials: J
authors.lastname: Holland
authors.affiliation: Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Hallemeier
authors.affiliation: Department of Radiation Oncology, Loyola University Stritch School of Medicine, Maywood, Illinois.
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Harkenrider
authors.affiliation: Department of Radiation Oncology, University of Miami Sylvester Comprehensive Cancer Center, Miami, Florida.
authors.forename: Adrian
authors.initials: A
authors.lastname: Iskhanian
authors.affiliation: Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, New Jersey.
authors.forename: Salma K
authors.initials: SK
authors.lastname: Jabbour
authors.affiliation: Department of Radiation Oncology, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Albert
authors.initials: A
authors.lastname: Attia
authors.affiliation: Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, California.
authors.forename: Percy
authors.initials: P
authors.lastname: Lee
authors.affiliation: Department of Radiation Oncology, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
authors.forename: Kyle
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Roy H
authors.initials: RH
authors.lastname: Decker
authors.affiliation: Department of Radiation Oncology, University of Kentucky, Lexington, Kentucky.
authors.forename: Ronald C
authors.initials: RC
authors.lastname: McGarry
authors.affiliation: Department of Radiation Oncology, University of Maryland Medical Center, Baltimore, Maryland. Electronic address: charlessimone@umm.edu.
authors.forename: Charles B
authors.initials: CB
authors.lastname: Simone
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality* / Q000473:pathology / Q000532:radiotherapy*; D015897:Comorbidity; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008175:Lung Neoplasms / Q000401:mortality* / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D017564:Radiation Pneumonitis / Q000401:mortality* / Q000473:pathology / Q000517:prevention & control; D016634:Radiosurgery / Q000379:methods / Q000401:mortality*; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology