title: The Effect of Biologically Effective Dose and Radiation Treatment Schedule on Overall Survival in Stage I Non-Small Cell Lung Cancer Patients Treated With Stereotactic Body Radiation Therapy.
abstract: To determine the effect of biologically effective dose (BED10) and radiation treatment schedule on overall survival (OS) in patients with early-stage non-small cell lung cancer (NSCLC) undergoing stereotactic body radiation therapy (SBRT).
  
  
  
  Using data from 65 treatment centers in the United States, we retrospectively reviewed the records of T1-2 N0 NSCLC patients undergoing SBRT alone from 2006 to 2014. Biologically relevant covariates, including dose per fraction, number of fractions, and time between fractions, were used to quantify BED10and radiation treatment schedule. The linear-quadratic equation was used to calculate BED10and to generate a dichotomous dose variable of <105 Gy versus ≥105 Gy BED10. The primary outcome was OS. We used the Kaplan-Meier method, the log-rank test, and Cox proportional hazards regression with propensity score matching to determine whether prescription BED10was associated with OS.
  
  
  
  We identified 747 patients who met inclusion criteria. The median BED10was 132 Gy, and 59 (7.7%) had consecutive-day fractions. Median follow-up was 41 months, and 452 patients (60.5%) had died by the conclusion of the study. The 581 patients receiving ≥105 Gy BED10had a median survival of 28 months, whereas the 166 patients receiving <105 Gy BED10had a median survival of 22 months (log-rank, P=.01). Radiation treatment schedule was not a significant predictor of OS on univariable analysis. After adjusting for T stage, sex, tumor histology, and Eastern Cooperative Oncology Group performance status, BED10≥105 Gy versus <105 Gy remained significantly associated with improved OS (hazard ratio 0.78, 95% confidence interval 0.62-0.98, P=.03). Propensity score matching on imbalanced variables within high- and low-dose cohorts confirmed a survival benefit with higher prescription dose.
  
  
  
  We found that dose escalation to 105 Gy BED10and beyond may improve survival in NSCLC patients treated with SBRT.
authors.affiliation: Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut.
authors.forename: John M
authors.initials: JM
authors.lastname: Stahl
authors.affiliation: 21st Century Oncology, Fort Myers, Florida.
authors.forename: Rudi
authors.initials: R
authors.lastname: Ross
authors.affiliation: Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut.
authors.forename: Eileen M
authors.initials: EM
authors.lastname: Harder
authors.affiliation: Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut.
authors.forename: Brandon R
authors.initials: BR
authors.lastname: Mancini
authors.affiliation: Cancer Outcomes, Public Policy and Effectiveness Research (COPPER) Center, Yale School of Medicine, New Haven, Connecticut.
authors.forename: Pamela R
authors.initials: PR
authors.lastname: Soulos
authors.affiliation: 21st Century Oncology, Fort Myers, Florida.
authors.forename: Steven E
authors.initials: SE
authors.lastname: Finkelstein
authors.affiliation: 21st Century Oncology, Fort Myers, Florida.
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Shafman
authors.affiliation: 21st Century Oncology, Fort Myers, Florida.
authors.forename: Arie P
authors.initials: AP
authors.lastname: Dosoretz
authors.affiliation: Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut.
authors.forename: Suzanne B
authors.initials: SB
authors.lastname: Evans
authors.affiliation: Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut.
authors.forename: Zain A
authors.initials: ZA
authors.lastname: Husain
authors.affiliation: Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut.
authors.forename: James B
authors.initials: JB
authors.lastname: Yu
authors.affiliation: Cancer Outcomes, Public Policy and Effectiveness Research (COPPER) Center, Yale School of Medicine, New Haven, Connecticut.
authors.forename: Cary P
authors.initials: CP
authors.lastname: Gross
authors.affiliation: Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut. Electronic address: roy.decker@yale.edu.
authors.forename: Roy H
authors.initials: RH
authors.lastname: Decker
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D016014:Linear Models; D008175:Lung Neoplasms / Q000401:mortality* / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D057216:Propensity Score; D016016:Proportional Hazards Models; D016634:Radiosurgery / Q000379:methods* / Q000401:mortality*; D011879:Radiotherapy Dosage; D012062:Relative Biological Effectiveness; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D014481:United States