Response to Immune Checkpoint Inhibitors in Recurrent or Metastatic Esophageal Squamous Cell Carcinoma May Be Affected by Tumor Sites

Abstract

<b><i>Introduction:</i></b> Heterogeneous tumor response has been reported in cancer patients treated with immune checkpoint inhibitors (ICIs). This study investigated whether the tumor site is associated with the response to ICIs in patients with recurrent or metastatic esophageal squamous cell carcinoma (ESCC). <b><i>Methods:</i></b> Patients with ESCC who had measurable tumors in the liver, lung, or lymph node (LN) according to the response evaluation criteria in solid tumors (RECIST) 1.1 and received ICIs at 2 medical centers in Taiwan were enrolled. In addition to RECIST 1.1, tumor responses were determined per individual organ basis according to organ-specific criteria modified from RECIST 1.1. Fisher test or χ<sup>2</sup> test was used for statistical analysis. <b><i>Results:</i></b> In total, 37 patients were enrolled. The overall response rate per RECIST 1.1 was 13.5%. Measurable tumors in the LN, lung, and liver were observed in 26, 17, and 13 patients, respectively. The organ-specific response rates were 26.9%, 29.4%, and 15.4% for the LN, lung, and liver tumors, respectively (<i>p</i> = 0.05). The organ-specific disease control rates were 69.2%, 52.9%, and 21.1% for the LN, lung, and liver tumors, respectively (<i>p</i> = 0.024). Five (27.8%) among 18 patients harboring at least 2 involved organs had heterogeneous tumor response. <b><i>Conclusion:</i></b> The response and disease control to ICIs may differ in ESCC tumors located at different metastatic sites, with a lesser likelihood of response and disease control in metastatic liver tumors than in tumors located at the LNs and lung.

Different immune contextures underlie tumor site‐specific responses to immune checkpoint blockade in esophageal cancer

“…As ICIs have been used to treat an increasing number of cancer types and patients, a heterogeneous tumor response to ICIs in tumors located in different organs has been observed 4,5 . However, the mechanisms underlying this heterogeneous tumor response or tumor site‐specific differential response have yet to be thoroughly investigated.…”

“…As ICIs have been used to treat an increasing number of cancer types and patients, a heterogeneous tumor response to ICIs in tumors located in different organs has been observed. 4 , 5 However, the mechanisms underlying this heterogeneous tumor response or tumor site‐specific differential response have yet to be thoroughly investigated. Herein, we report a patient with ESCC presenting with heterogeneous responses to ICIs in tumors located at different organ sites, and we explore how the different immune contextures of tumors may contribute to the differential responses (see methods in Appendix S1 ).…”