title: Histologic Subtype in Core Lung Biopsies of Early-Stage Lung Adenocarcinoma is a Prognostic Factor for Treatment Response and Failure Patterns After Stereotactic Body Radiation Therapy.
abstract: Stereotactic body radiation therapy (SBRT) has emerged as an effective treatment for early-stage lung cancer. The histologic subtype of surgically resected lung adenocarcinoma is recognized as a prognostic factor, with the presence of solid or micropapillary patterns predicting poor outcomes. We describe the outcomes after SBRT for early-stage lung adenocarcinoma stratified by histologic subtype.
  
  
  
  We identified 119 consecutive patients (124 lesions) with stage I to IIA lung adenocarcinoma who had undergone definitive SBRT at our institution from August 2008 to August 2015 and had undergone core biopsy. Histologic subtyping was performed according to the 2015 World Health Organization classification. Of the 124 tumors, 37 (30%) were a high-risk subtype, defined as containing a component of solid and/or micropapillary pattern. The cumulative incidences of local, nodal, regional, and distant failure were compared between the high-risk and non-high-risk adenocarcinoma subtypes using Gray's test, and multivariable-adjusted hazard ratios (HRs) were estimated from propensity score-weighted Cox regression models.
  
  
  
  The median follow-up for the entire cohort was 17 months and for surviving patients was 21 months. The 1-year cumulative incidence of and adjusted HR for local, nodal, regional, and distant failure in high-risk versus non-high-risk lesions was 7.3% versus 2.7% (HR 16.8; 95% confidence interval [CI] 3.5-81.4), 14.8% versus 2.6% (HR 3.8; 95% CI 0.95-15.0), 4.0% versus 1.2% (HR 20.9; 95% CI 2.3-192.3), and 22.7% versus 3.6% (HR 6.9; 95% CI 2.2-21.1), respectively. No significant difference was seen with regard to overall survival.
  
  
  
  The outcomes after SBRT for early-stage adenocarcinoma of the lung correlate highly with histologic subtype, with micropapillary and solid tumors portending significantly higher rates of locoregional and metastatic progression. In this context, the histologic subtype determined from core biopsies is a prognostic factor and could have important implications for patient selection, adjuvant treatment, biopsy methods, and clinical trial design.
authors.affiliation: Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Leeman
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 Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Joseph
authors.initials: J
authors.lastname: Montecalvo
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Meier
authors.initials: M
authors.lastname: Hsu
authors.affiliation: Department of Epidemiology and 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: Donata
authors.initials: D
authors.lastname: von Reibnitz
authors.affiliation: Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Kelly
authors.initials: K
authors.lastname: Panchoo
authors.affiliation: Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Ellen
authors.initials: E
authors.lastname: Yorke
authors.affiliation: Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Prasad S
authors.initials: PS
authors.lastname: Adusumilli
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: William
authors.initials: W
authors.lastname: Travis
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: D000230:Adenocarcinoma / Q000473:pathology* / Q000532:radiotherapy* / Q000556:secondary; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008168:Lung / Q000473:pathology*; D008175:Lung Neoplasms / Q000473:pathology* / Q000532:radiotherapy*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011379:Prognosis; D057216:Propensity Score; D016016:Proportional Hazards Models; D016634:Radiosurgery; D013997:Time Factors; D016896:Treatment Outcome; D047368:Tumor Burden