Background Adoptive cell therapy (ACT) is a newly emerging treatment modality for solid tumors with heterogenous outcomes and limited biomarkers to guide patient selection. The relationship between tumor burden and ACT efficacy is poorly understood. We sought to investigate whether CT-based volumetric analysis helps predict treatment outcomes after ACT with the aim of improving patient selection.

Methods This retrospective study included consecutive patients with advanced solid tumor who received ACT on protocol in the Department of Investigational Cancer Therapeutics between August 2017 and June 2023. Manual segmentation of primary and measurable metastatic lesions on pre-treatment CT scans was performed, and tumor volume was calculated from these measurements. Tumor burden was defined as the involvement status, volume, or lesion counts within specific organs (lungs, pleura, lymph nodes, liver, adrenals, bone, and soft tissue) and across the whole body. Tumor response was evaluated by RECIST 1.1. Survival analysis included Kaplan-Meier curves and Cox regressions.

Results We identified 93 consecutive advanced solid tumor patients treated with ACT. The median age at treatment was 61 years, with median follow-up of 39.9 months. Liver tumor burden (LTB) (defined as liver tumor volume/total liver volume by CT) was associated with worse response (p=0.037), OS (HR 1.8, 95%CI 1.1-3; p = 0.02), and PFS (HR 1.9, 95% CI 1.2-3.2; p = 0.007). In multivariate analysis, LTB remained prognostic of PFS (HR 2.11, 95% CI 1.23-3.63; p = 0.007) and OS (HR 2.7, 95% CI 1.53-4.75; p < 0.001) after adjustment for clinicopathological factors, including age, gender, RECIST response, ICANS and tumor measurement metrics (tumor diameter, tumor volume). Conversely, the presence of lung metastases was associated with improved PFS (HR 0.48, 95% CI [0.29, 0.74], p=0.003) and OS (HR 0.56, 95% CI [0.33, 0.95], p=0.03). Tumor measurements of the whole body and other metastatic sites were not predictive of outcomes.

Conclusions To our knowledge, this is the first volumetric analysis of baseline risk factors of clinical outcomes for solid tumor patients treated with ACT, and the first study to suggest differential outcomes by organ involvement in a tumor agnostic fashion. Higher baseline liver tumor burden was associated with increased likelihood of disease progression and worsened survival for solid tumor patients treated with ACT, reinforcing the clinical challenge of treating patients with liver metastases. Meanwhile, lung metastases were associated with improved PFS and OS. These results suggest a recapitulation of observations for immune checkpoint inhibitors in solid tumors.