title: Multi-institutional experience of stereotactic body radiotherapy for large (≥5 centimeters) non-small cell lung tumors.
abstract: BACKGROUND
  Stereotactic body radiotherapy (SBRT) is the standard of care for patients with nonoperative, early-stage non-small cell lung cancer (NSCLC) measuring < 5 cm, but its use among patients with tumors measuring ≥5 cm is considerably less defined, with the existing literature limited to small, single-institution reports. The current multi-institutional study reported outcomes evaluating the largest such population reported to date.
  
  
  METHODS
  Clinical/treatment characteristics, outcomes, toxicities, and patterns of failure were assessed in patients with primary NSCLC measuring ≥5 cm without evidence of distant/lymph node metastasis who underwent SBRT using ≤5 fractions. Statistics included Kaplan-Meier survival analyses and univariate/multivariate Cox proportional hazards models.
  
  
  RESULTS
  A total of 92 patients treated from 2004 through 2016 were analyzed from 12 institutions. The median follow-up was 12 months (15 months in survivors). The median age and tumor size among the patients were 73 years (range, 50-95 years) and 5.4 cm (range, 5.0-7.5 cm), respectively. The median dose/fractionation was 50 Gray/5 fractions. The actuarial local control rates at 1 year and 2 years were 95.7% and 73.2%, respectively. The disease-free survival rate was 72.1% and 53.5%, respectively, at 1 year and 2 years. The 1-year and 2-year disease-specific survival rates were 95.5% and 78.6%, respectively. The median, 1-year, and 2-year overall survival rates were 21.4 months, 76.2%, and 46.4%, respectively. On multivariate analysis, lung cancer history and pre-SBRT positron emission tomography maximum standardized uptake value were found to be associated with overall survival. Posttreatment failures were most commonly distant (33% of all disease recurrences), followed by local (26%) and those occurring elsewhere in the lung (23%). Three patients had isolated local failures. Grade 3 to 4 toxicities included 1 case (1%) and 4 cases (4%) of grade 3 dermatitis and radiation pneumonitis, respectively (toxicities were graded according to the Common Terminology Criteria for Adverse Events [version 4.0]). Grades 2 to 5 radiation pneumonitis occurred in 11% of patients. One patient with a tumor measuring 7.5 cm and a smoking history of 150 pack-years died of radiation pneumonitis.
  
  
  CONCLUSIONS
  The results of the current study, which is the largest study of patients with NSCLC measuring ≥5 cm reported to date, indicate that SBRT is a safe and efficacious option. Cancer 2017;123:688-696. © 2016 American Cancer Society.
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 Kentucky, Lexington, Kentucky.
authors.forename: Sameera S
authors.initials: SS
authors.lastname: Kumar
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, Mayo Clinic, Rochester, Minnesota.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Hallemeier
authors.affiliation: Department of Radiation Oncology, University of California at San Francisco, San Francisco, California.
authors.forename: Steve E
authors.initials: SE
authors.lastname: Braunstein
authors.affiliation: Department of Radiation Medicine, Oregon Health and Science University, Portland, Oregon.
authors.forename: John
authors.initials: J
authors.lastname: Holland
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: S Iskhanian
authors.affiliation: Department of Radiation Oncology, University of Miami Sylvester Comprehensive Cancer Center, Miami, Florida.
authors.forename: Hanmanth J
authors.initials: HJ
authors.lastname: Neboori
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, University of California at Los Angeles, Los Angeles, California.
authors.forename: Percy
authors.initials: P
authors.lastname: Lee
authors.affiliation: Department of Radiation Oncology, Loyola University Stritch School of Medicine, Maywood, Illinois.
authors.forename: Fiori
authors.initials: F
authors.lastname: Alite
authors.affiliation: Department of Radiation Medicine, Oregon Health and Science University, Portland, Oregon.
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Walker
authors.affiliation: Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: John M
authors.initials: JM
authors.lastname: Stahl
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 Radiation Oncology, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Brian S
authors.initials: BS
authors.lastname: Bingham
authors.affiliation: Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, New Jersey.
authors.forename: Christina
authors.initials: C
authors.lastname: Hadzitheodorou
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, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.
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 / Q000453:epidemiology / Q000473:pathology / Q000532:radiotherapy*; D018572:Disease-Free Survival; D019583:Dose Fractionation, Radiation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology / Q000473:pathology / Q000532:radiotherapy*; D016634:Radiosurgery; D016896:Treatment Outcome
keywords: chemotherapy; image-guided radiotherapy; non-small cell lung cancer; stereotactic body radiotherapy; toxicity