Abstract PS5-42: Change in intra-lesion heterogeneity on CT predicts long-term survival following treatment with CDK4/6 inhibitors in hormone receptor-positive metastatic breast cancer (MBC)
Authors: Braman Nathaniel , Kunte Siddharth , Bera Kaustav , Abraham Jame , Montero Albert , Madabhushi Anant 
Published: February 2021

Abstract
Background: CDK 4/6 inhibitors are currently standard of care for patients CDK 4/6 inhibitors but currently lack validated predictive markers. We evaluated whether changes in intra-lesional heterogeneity, extracted computationally from routine computed tomography (CT) of MBC could predict survival following treatment with CDK 4/6 inhibitors.
Methods: 33 patients with ER+ breast cancer metastasized to the liver who received palbociclib in combination with anti-estrogen therapy were identified from a registry. For each patient, CT exams were acquired prior to treatment and following initiation of treatment (median time between scans of 106 +/- 48.6 days). Liver metastases were manually delineated on all scans with consultation of radiology reports. On each scan, gray level co-occurrence matrix (GLCM) entropy, a computational measure of intra-lesional heterogeneity, was calculated and averaged across all metastatic lesions and its change over treatment was computed. For comparison, response was also assessed via RECIST v1.1: 65% of patients had objective response/stable disease, while 35% had progressive disease on scan following initiation of treatment. Imaging metrics were assessed individually and in a multivariate comparison including clinical features for association with overall survival (OS) via a cox proportional hazards model.
Results: Change in intra-lesion heterogeneity was associated with OS with a hazard ratio [HR] of 2.82 (p=0.019). An increase in entropy between the pre- and treatment scan was associated with poorer viability on treatment including CDK inhibitors, indicating that a favorable response can be distinguished by a decrease in intra-lesion heterogeneity. RECIST response was also associated with OS (HR=0.24, p&lt;0.001). In a multivariable comparison with clinical variables, change in GLCM entropy and response per RECIST criteria both demonstrated multivariate significance. Neither the heterogeneity measure on the pre-treatment scan (HR=0.56, p=0.23) nor the scan acquired during treatment (HR=1.51, p=0.27) treatment scans alone were significantly associated with overall survival.
Conclusions: The change in lesion heterogeneity on clinical imaging following the initiation of treatment was found to offer independent value in distinguishing patients with favorable survival following CDK 4/6 inhibitor treatment.
Multivariate association of imaging features and clinical variables with overall survivalHazard ratio (HR)p-valueChange in Heterogeneity4.670.019RECIST response0.160.003PR status1.010.99HER2 status1.130.92Age1.040.26Pathology0.770.39Line of Treatment1.360.12
Citation Format: Nathaniel Braman, Siddharth Kunte, Kaustav Bera, Jame Abraham, Albert Montero, Anant Madabhushi. Change in intra-lesion heterogeneity on CT predicts long-term survival following treatment with CDK4/6 inhibitors in hormone receptor-positive metastatic breast cancer (MBC) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS5-42.