Intrapulmonic Cavity or Necrosis on Baseline CT Scan Serves as an Efficacy Predictor of Anti-PD-(L)1 Inhibitor in Advanced Lung Squamous Cell Carcinoma

Tao Lu; Longfeng Zhang; Mingqiu Chen; Xiaobin Zheng; Kan Jiang; Xinlong Zheng; Chao Li; Weijin Xiao; Qian Miao; Shanshan Yang; Gen Lin

doi:10.2147/CMAR.S319480

Intrapulmonic Cavity or Necrosis on Baseline CT Scan Serves as an Efficacy Predictor of Anti-PD-(L)1 Inhibitor in Advanced Lung Squamous Cell Carcinoma

Cancer Manag Res. 2021 Jul 30:13:5931-5939. doi: 10.2147/CMAR.S319480. eCollection 2021.

Authors

Tao Lu^#¹, Longfeng Zhang^#², Mingqiu Chen³, Xiaobin Zheng², Kan Jiang², Xinlong Zheng², Chao Li⁴, Weijin Xiao⁴, Qian Miao², Shanshan Yang², Gen Lin²

Affiliations

¹ Department of Radiology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, People's Republic of China.
² Department of Thoracic Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, People's Republic of China.
³ Department of Thoracic Radiation Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, People's Republic of China.
⁴ Department of Pathology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, People's Republic of China.

^# Contributed equally.

Abstract

Background: Predictive markers for guidance and monitoring of immunotherapy in lung squamous cell carcinoma (LSCC) are an interesting topic but have yet to be fully explored. A primary characteristic of LSCC is tumor necrosis that results in extensive immune suppression in patients. We sought to assess whether tumor necrosis or cavity on baseline CT could effectively predict the efficacy of immune checkpoint inhibitors (ICIs) in advanced LSCC.

Methods: Advanced LSCC cases undergoing pre-treatment chest CT imaging and receiving ICIs were retrospectively collected. All CT images were reviewed by an independent chest radiologist blinded to any previous diagnosis to confirm morphological alterations in necrosis or cavity. We performed Logistic regression and developed Cox proportional hazards models to assess the predictive performance of baseline necrosis or cavity characteristics in advanced LSCC. Survival estimates were observed using Kaplan-Meier curves.

Results: Ninety-three patients were eligible for analysis, predominantly consisting of patients with ECOG performance status of 0 or 1 (97.8%), male patients (95.7%), and heavy smokers (92.5%). Intrapulmonic necrosis or cavity on CT scan was present in 52.7% of all patients. Generally, the objective response rate (ORR) in patients with necrosis or cavity to ICI treatment was significantly worse versus those without (30.6% vs 54.5%, p = 0.020), with the subgroup ORRs as follows: ICI monotherapy (necrosis vs non-necrosis: 10.0% vs 36.8%, p =0.047) and ICI combination therapy (44.8% vs 68.0%, p =0.088). Multivariable analysis identified intrapulmonic necrosis or cavity at baseline as a major risk factor for advanced LSCC (HR 4.042, 95% CI1.149-10.908, p = 0.006). Multivariate Cox analysis showed that baseline necrosis or cavity and ICI monotherapy were unfavorable factors for progression-free survival (HR 1.729; 95% CI1.203-2.484, p =0.003).

Conclusion: LSCC patients with intrapulmonic cavity or necrosis on baseline CT scan may respond poorly to anti-PD-(L)1-treatment, monotherapy and combination therapy alike.

Keywords: cavity; immune-checkpoint inhibitor; lung squamous cell carcinoma; necrosis; predictive marker.

Grants and funding

The funding agencies had no role in the study design, data collection and analysis, decision to publish, or manuscript preparation. This work was supported by the National Natural Science Foundation of China (grant 82072565), the Fujian Provincial Health Systemic Innovation Project (grant 2020CXA010), the Fujian Provincial Health Commission (Grant number 2020QNA014), Beijing Xisike Clinical Oncology Research Foundation (grant Y-2019AZMS-0434), Fujian Provincial Natural Science Foundation (grant 2020J011119).