Influence of Tumor Cavitation on Assessing the Clinical Benefit of Anti-PD1 or PD-L1 Inhibitors in Advanced Lung Squamous Cell Carcinoma

A significant portion of lung squamous cell cancer (LUSC) shows radiographic signs of cavitation, which is not considered in current RECIST v1.1 or iRECIST guidelines. We reviewed radiologic data of 785 stage IV LUSC patients treated with PD-1/PD-L1 antibodies combined with platinum-based doublet chemotherapy. 131 patients exhibited cavitation lesions pre- or after-treatment. The response was assessed both by RECIST v1.1 and mRECIST. Survival curves for different response categories were prepared using Kaplan-Meier and log-rank tests. Weighted kappa statistics were used to assess interobserver reproducibility. We found that traditional testing methods have underestimated the benefits of immunotherapy in 9.2% of LUSC patients with tumor cavitation. mRECIST assessment resulted in a higher response rate than RECIST v1.1 (66% versus 57%) and better identified patients with PFS and OS benefits due to cavitation. The interobserver reproducibility of mRECIST for tumor cavitation evaluation was acceptable (0.821). mRECIST measurement of target lesions incorporating cavitation assessment provides better size change discrimination than measuring the external diameter alone, offering a feasible and robust method for response evaluation and predicting patient benefits. These results may inform further modifications to RECIST V1.1 to better reflect efficacy with immunotherapy. Purpose: A considerable portion of lung squamous cell cancer (LUSC) displays radiographic signs of cavitation. The cavitation of lesions is not accounted for in the prevailing Evaluation Criteria of Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or iRECIST in lung cancer. We hypothesized that cavitation might alter response assessment in these patients. Patients and Methods: We performed a retrospective radiologic review of 785 patients with stage IV LUSC treated with PD-1/PD-L1 antibody combined with platinum-based doublet chemotherapy. 131 patients exhibited cavitation lesions pre- or after-treatment. Response was assessed by RECIST v1.1 and a modified Evaluation Criteria in Solid Tumors (mRECIST) guidelines in which the longest diameter of any cavity was subtracted from the overall longest diameter of that lesion to measure target lesions. The response rate and PFS and OS between mRECIST and RECIST v1.1 were compared. Survival curves of different response categories in each criterion were prepared using the method of Kaplan-Meier and log-rank tests. Weighted kappa statistics were used to assess interobserver reproducibilities and to compare response rates. The chi-square test confirmed the relationship between PD-L1 expression and posttreatment cavitation. Results: Notable cavitation of pulmonary lesions was seen in 16.7% of 785 patients treated with immunotherapy combined with platinum-based chemotherapy. Using the mRECIST for response assessment resulted in a higher response rate than RECIST v1.1 (66% vs. 57%). mRECIST might better identify patients with PFS and OS benefits who have cavitation. The chi-square test revealed a marginally significant difference between PD-L1 expression and tumor cavitation. Interobserver reproducibility of mRECIST for tumor cavitation evaluation was acceptable (the weighted k coefficients for mRECIST criteria was 0.821). Conclusion: Cavitation lesions at baseline and after checkpoint treatment are common in LUSC patients. mRECIST records a significantly higher response rate than RECIST for these LUSC patients. Response assessment might be improved by incorporating cavitation into volume assessment for target lesions. These results may inform further modifications to RECIST V1.1 to better reflect efficacy with immunotherapy