title: A collaborative analysis of stereotactic lung radiotherapy outcomes for early-stage non-small-cell lung cancer using daily online cone-beam computed tomography image-guided radiotherapy.
abstract: BACKGROUND
  We report lung stereotactic-body radiotherapy (SBRT) outcomes for a large pooled cohort treated using daily online cone-beam computed tomography.
  
  
  METHODS
  Five hundred and five stage I-IIB (T1-3N0M0) non-small-cell lung cancer (NSCLC) cases underwent SBRT using cone-beam computed tomography image guidance at five international institutions from 1998 to 2010. Median age was 74 years (range, 42-92) whereas median forced expiratory volume in 1 second/diffusing lung capacity for carbon monoxide were 1.4 liter (65%) and 10.8 ml/min/mmHg (53%). Of the 505 cases, 64% were biopsy proven and 87% medically inoperable. Staging was: IA 63%, IB 33%, IIA 2%, and recurrent 1%. Median max tumor dimension was 2.6 cm (range, 0.9-8.5). Median heterogeneously calculated volumetric prescription dose (PD) was 54 Gy (range, 20-64 Gy) in three fractions (range, 1-15) over 8 days (range, 1-27). Median biologically equivalent PD biological equivalent doses (BED10) was 132 Gy (range, 60-180).
  
  
  RESULTS
  With a median follow-up of 1.6 years (range, 0.1-7.3), the 2-year Kaplan-Meier local control (LC), regional control, and distant metastasis (DM) rates were 94%, 89%, and 20%, respectively, whereas cause-specific and overall survival were 87% and 60% (78% operable, 58% inoperable, p = 0.01), respectively. Stage, gross-tumor volume size (≥ 2.7 cm) and PD(BED10) predicted local relapse (LR) and DM. LR was 15% for BED10 less than 105 Gy versus 4% for BED10 of 105 Gy or more (p < 0.001); DM was 31% versus 18% for BED10 less than 105 versus 105 Gy or more (p = 0.01). On multivariate analysis, PD(BED10) and elapsed days during radiotherapy predicted LR; gross-tumor volume size predicted DM. Grade 2 or higher pneumonitis, rib fracture, myositis, and dermatitis were 7%, 3%, 1%, and 2%, respectively.
  
  
  CONCLUSIONS
  In the largest early-stage NSCLC SBRT data set to date, a high rate of local control was achieved, which was correlated with a PD(BED10) of 105 Gy or more. Failures were primarily distant, severe toxicities were rare, and overall survival was encouraging in operable patients.
authors: Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan 48073, USA. igrills@beaumont.edu
authors: Inga Siiner
authors: IS
authors: Grills
authors: Andrew J
authors: AJ
authors: Hope
authors: Matthias
authors: M
authors: Guckenberger
authors: Larry L
authors: LL
authors: Kestin
authors: Maria
authors: M
authors: Werner-Wasik
authors: Di
authors: D
authors: Yan
authors: Jan-Jakob
authors: JJ
authors: Sonke
authors: Jean-Pierre
authors: JP
authors: Bissonnette
authors: Juergen
authors: J
authors: Wilbert
authors: Ying
authors: Y
authors: Xiao
authors: Jose
authors: J
authors: Belderbos
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality / Q000532:radiotherapy* / Q000601:surgery; D003131:Combined Modality Therapy; D054893:Cone-Beam Computed Tomography; D005260:Female; D006801:Humans; D007390:International Agencies; D008175:Lung Neoplasms / Q000401:mortality / Q000532:radiotherapy* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016634:Radiosurgery / Q000379:methods*; D061089:Radiotherapy, Image-Guided; D015996:Survival Rate