Abstract

Diem Vuong¹, Marta Bogowicz¹, Leonard Wee², Oliver Riesterer³, Eugenia Vlaskou Badra¹, Louisa Abigail D'Cruz⁴, Panagiotis Balermpas¹, Janna E. van Timmeren¹, Simon Burgermeister¹, André Dekker², Dirk de Ruysscher², Jan Unkelbach¹, Sandra Thierstein⁵, Eric Innocents Eboulet⁵, Solange Peters⁶, Miklos Pless⁷, Matthias Guckenberger¹, Stephanie Tanadini-Lang¹

¹University Hospital Zurich and University of Zurich, Department of Radiation Oncology, Zurich, Switzerland; ²GROW School for Oncology and Developmental Biology, Maastricht University Medical Centre+, Department of Radiation Oncology (MAASTRO), Maastricht, The Netherlands; ³Kantonsspital Aarau KSA, Radioonkologie-Radiotherapy, Aarau, Switzerland; ⁴Universitätsklinikum Frankfurt, Strahlentherapie und Onkologie, Frankfurt, Germany; ⁵Swiss Group for Clinical Cancer Research (SAKK), Coordinating Center, Bern, Switzerland; ⁶Centre Hospitalier Universitaire Vaudois (CHUV), Department of Oncology, Lausanne, Switzerland; ⁷Kantonsspital Winterthur, Department of Medical Oncology, Winterthur, Switzerland

The anatomical location and extent of the primary lung tumor (PT) has shown prognostic value for outcome prediction; however, its manual assessment is prone to interobserver variability. This study aims to evaluate the feasibility to predict overall survival (OS) using the PT distance to anatomical regions based on cumulative status maps for locally advanced non-small cell lung cancer (NSCLC) patients.

Five stage IIIA/IIIB NSCLC patient cohorts were retrospectively collected, treated either with radiochemotherapy (RCT): RCT1* (n=107), RCT2 (n=85), RCT3 (n=32) or surgery: S1* (n=134), S2 (n=37). Pre-treatment CT scans were registered to a reference patient using an ipsilateral lung contour-only based deformable image registration and the ipsilateral main bronchus as an anatomical landmark (MIM Vista, 6.9.2.). An in-house software was developed to transfer each PT to the reference patient while maintaining the original PT shape. A frequency-weighted cumulative status (fwCS) map was created for both exploratory cohorts (indicated with asterisk), where PT location was uni-labeled with 2 years OS patient status (Fig.1).

Fig.1: Identification of decreased survival areas and extraction of the primary tumor closest distance. Based on the frequency weighted cumulative status (fwCS) map, a permutation test was performed to identify areas with significantly worse OS, from which the closest distance of a primary tumor (blue) was calculated.

To identify regions with significantly worse OS, a permutation test (500 repetitions with resampling) was performed by randomly assignment of survival/death to PT of exploratory cohorts. A voxel was considered significant if its test statistic (mean/standard deviation) was larger than 95% of the test statistics based on the permutation test (referred to as decreased survival areas (DSA)). The closest PT-DSA Euclidean distance was extracted (negative distance was assigned in case of overlap). To account for the PT extent, the distance was scaled with the radius of the volume-equivalent sphere.

Fig.2: Axial slice of the frequency weighted cumulative status (fwCS) map of the S1 cohort (left) and decreased survival areas (right).

In both surgery and RCT cohorts, DSA could be identified which were located proximal to the mediastinum (Fig.2). For the surgery cohort the anatomical high-risk regions were located at right the main bronchus whereas for RCT cohort they further extended in CC direction. In the validation cohorts, the model based on distance to DSA achieved performance: AUC_RCT2[95%CI]=0.67[0.55-0.78] and AUC_RCT3=0.59[0.39-0.79] for RCT patients, but showed worse performance for surgery cohort (AUC_S2=0.52[0.30-0.74]). Closer distance to DSA was associated with worse outcome.

This explanatory analysis quantifies the value of PT location for OS prediction based on cumulative status maps. Closer distance of PT to a high-risk region at the right proximal bronchi was associated with worse prognosis in the RCT cohort.