Tumor thickness in mesothelioma predicts differential response to neoadjuvant therapy and survival

The Journal of Thoracic and Cardiovascular Surgery 2022 December 14 [Link]

Nicolas Zhou, Cynthia S Bell, Hope A Feldman, Cara L Haymaker, Wayne L Hofstetter, Anne S Tsao, Reza J Mehran, David C Rice, Boris Sepesi; Mesothelioma Immune Genomic Group


Objective: Neoadjuvant systemic therapy in resectable malignant pleural mesothelioma remains controversial and demonstrates variable responses. We sought to evaluate tumor thickness as a predictor of response to neoadjuvant therapy and as a prognostic marker for overall survival.

Methods: Data from patients who underwent neoadjuvant therapy followed by cytoreductive surgery from 2002 to 2019 were reviewed. Baseline and postneoadjuvant therapy tumor thickness were measured on computed tomography. Radiological tumor response was categorized as progressive disease (≥20% increase), partial response (≥30% decrease), or stable disease (in between). Tumor response outcomes were modeled using logistic regression and multinomial regression models. Overall survival was evaluated based on tumor thickness and tumor response.

Results: Of the 143 patients reviewed, 36 (25%) had progressive disease, 54 (38%) had stable disease, and 56 (39%) had partial response. The baseline tumor thickness of the progressive disease group (36 mm) was lower than in both stable disease and partial response groups (both 63 mm; P < .001). Both logistic regression and multinomial regression analyses demonstrated that thicker baseline tumor thickness was associated with decreased probability of progressive disease and increased probability of partial response. In a multivariable Cox model, thicker postneoadjuvant therapy tumor thickness was associated with worse overall survival (hazard ratio, 1.01, 95% confidence interval, 1.00-1.01, P = .008). The same trend was observed for thicker baseline tumor thickness (hazard ratio, 1.02, 95% confidence interval, 1.01-1.04, P = .008), and the risk was decreased in tumors with partial response (hazard ratio, 0.98, 95% confidence interval, 0.96-0.100, P = .014).

Conclusions: We present the first study demonstrating the relationship between baseline tumor thickness and differential radiographic response to neoadjuvant therapy and survival. Further studies are needed to validate tumor thickness as both a prognostic and predictive biomarker.