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

Purpose Stereotactic body radiation therapy (SBRT) has emerged as an effective treatment for early-stage lung cancer. Histologic subtyping in surgically resected lung adenocarcinomas is recognized as a prognostic factor, with the presence of solid or micropapillary patterns predicting poor outcomes. Herein, we describe outcomes following SBRT for early-stage lung adenocarcinoma by histologic subtype. Materials and Methods We identified 119 consecutive patients (124 lesions) with stage I-IIA lung adenocarcinoma who were treated with definitive SBRT at our institution between August 2008 and August 2015 and had undergone core biopsy. Histologic subtyping was performed according to the 2015 WHO Classification. Thirty-seven tumors (30%) were of high risk subtype, defined as containing a component of solid and/or micropapillary pattern. Cumulative incidences of local, nodal, regional and distant failure were compared between high risk vs. non-high risk adenocarcinoma subtypes with Gray’s test, and multivariable-adjusted hazard ratios were estimated from propensity score-weighted Cox regression models. Results Median follow-up for the entire cohort was 17 months and 21 months for surviving patients. The 1-year cumulative incidence and adjusted hazard ratio (HR) of local, nodal, regional and distant failure, respectively, in high risk versus non-high risk lesions were 7.3% vs 2.7% (HR 16.8; 95% CI 3.5–81.4), 14.8% vs 2.6% (HR 3.8; 95% CI 0.95–15.0), 4.0% vs 1.2% (HR 20.9; 95% CI 2.3–192.3) and 22.7% vs 3.6% (HR 6.9; 95% CI 2.2–21.1). No significant difference was seen with regard to overall survival. Conclusions Outcomes following SBRT for early-stage adenocarcinoma of the lung are highly correlated with histologic subtype, with micropapillary and solid tumors portending significantly higher rates of locoregional and metastatic progression. In this context, histologic subtype based on core biopsies is a prognostic factor and may have important implications for patient selection, adjuvant treatment, biopsy methods and clinical trial design.

Micropapillary and/or Solid Histologic Subtype Based on Pre-Treatment Biopsy Predicts Local Recurrence After Thermal Ablation of Lung Adenocarcinoma

“…Similar results have recently been reported after stereotactic body radiation therapy in the setting of MIP and SOL subtypes. (25) This work may be used to improve patient selection and stratification, to define optimal follow-up strategies after ablation based on risk of recurrence, and potentially to target larger ablation margins for high risk patients. The fact that subtype identification was performed on biopsy specimens also suggests that even surgical and radiation patients may benefit from biopsies to identify high risk patients.…”

Prognostic Factors in Completely Resected Node-Negative Lung Adenocarcinoma of 3 cm or Smaller

“…[25][26][27] In a LACE-BIO study-related report, patients with micropapillary/solid predominant (but not acinar/papillary) adenocarcinomas obtained a diseasefree survival and specific disease-free survival but no overall survival benefit from adjuvant chemotherapy. 25,26 Leeman et al 28 reported that the outcomes after stereotactic body radiation therapy for early-stage (I-IIA) lung adenocarcinoma correlate highly with histological subtype, with micropapillary and solid tumors portending significantly higher rates of locoregional and metastatic progression. Whether adjuvant chemotherapy improves survival in patients with stage I lung cancer remains controversial.…”

Interdisciplinary multimodality management of stage III nonsmall cell lung cancer

“…Whether or not the predominant histologic subtype of pulmonary adenocarcinoma evaluated in biopsy specimens carries the same prognostic and predictive significance as shown for tumour resections has yet to be proven. For stereotactic body radiotherapy of the lung there is some hint that the subtype determined from core biopsies is relevant for treatment response and failure patterns [21]. As even small percentages of micropapillary and solid patterns seem to have prognostic impact [22,23], the detection of any amount of these high-grade patterns in biopsy specimens should have prognostic relevance as well, but sampling error remains a major drawback especially in biopsies with small tumour volumes included [24].…”