Abstract 3789: Mapping lesion specific response and relapse patterns in metastatic colorectal cancer patients

Abstract

Abstract Considerable lesion-specific response heterogeneity exists in metastatic colorectal cancer patients, largely due to organ-specific ecological environments and evolutionary pressures. Metastatic lesions with poor response to therapy often become tumor sanctuary sites, leading to systemic resistance and tumor relapse. To map the lesion-specific response and relapse patterns, we investigated the longitudinal dynamics of individual lesions in metastatic colorectal cancer patients. Tumor longitudinal data in 4,308 colorectal cancer patients with 40,612 individual lesions were collected from eight Phase III trials in Project Data Sphere. First, tumor response dynamics (regression after treatment and progression upon resistance) were characterized using an empirical mathematical model. Next, tumor response time (when the lesion size decreases ≥20% from baseline) and relapse time (when the lesion size increases ≥30% from tumor nadir) were estimated for each individual lesion in patients being treated with bevacizumab, panitumumab, and/or chemotherapy. Random effect cox proportional models were applied to predict lesion-specific response and relapse probabilities and temporal sequence. We then took machine learning algorithm k-means to cluster patients based on their lesion relapse sequence. We found the response probabilities across organs are: Liver > Distal Lymph Nodes (LN) > Abdomen > Spleen > Lung > Regional LN > Adrenal > Muscle/Soft Tissue > Bone > Brain/CNS. Lesion relapse temporal sequence are: Brain/CNS > Liver > Adrenal > Muscle/Soft tissue > Abdomen > Bone > Spleen > Lung > Distal LN > Regional LN. Of note, lesions in the bone, brain, adrenal, and muscle/soft tissues often had low responses and high relapse probabilities, implying the greatest potential as tumor sanctuary sites. Liver, the most common metastatic organ in colorectal cancer, showed highest response rate but high relapse probabilities. Interestingly, the organ-specific response rate and relapse probabilities are respectively in line with drug distribution profiles and organ-specific immune landscape. Organ-specific relapse sequence in each patient is significantly correlated with patient long-term survival (p<0.0001). Patients with relapse lesions occurring in multiple organs had worst survival. Patients whose liver lesions relapsed first had worse survival than those who first relapsed in other organs. In conclusion, our study provides insights into the lesion-specific response and relapse heterogeneity in metastatic colorectal cancer, and yields substantial implications for designing lesion-specific therapeutics. Citation Format: Jiawei Zhou, Quefeng Li, Amber Cipriani, Yanguang Cao. Mapping lesion specific response and relapse patterns in metastatic colorectal cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3789.