Department of Medicine, Division of Hematology and Oncology; Department of Pathology
Cancer Biology | Diseases | Hematology | Immunoprophylaxis and Therapy | Neoplasms | Oncology
BACKGROUND: Extrapulmonary small cell carcinomas (ESCC) are rare but aggressive tumors. Relapses are common despite treatment with chemotherapy and/or radiotherapy. Prospective data for treatment of ESCC are lacking; treatment of these cancers usually incorporates lung small cell carcinoma treatment recommendations. Cancer staging remains the most important prognostic factor. Cancer immunotherapy targeting the PD-1/PD-L1 pathway has shown efficacy in multiple tumor types, and could be an appealing treatment strategy for these rare tumors.
METHODS: We investigated PD-L1 expression by immunochemistry (IHC) in ESCCs diagnosed at University of Massachusetts Medical Center, from 1999 to 2016. 34 cases with sufficient material were selected for PD-L1 IHC analysis using clone E1L3N. PD-L1 expression was evaluated using the combined positive score (CPS). Retrospective chart review was performed. We evaluated the incidence and prognostic value of PD-L1 expression in ESCC at our institution.
RESULTS: Twelve out 34 cases (35%) had PD-L1 CPS scores > /=1. Ten cases had CPS scores ranging 1-5, whereas 2 cases had CPS scores > 80. The overall response rate to the standard chemotherapy with/without radiotherapy in the PD-L1 positive group was 80% versus 67% for the PDL-1 negative group (p-value 0.67). The median overall survival for the PD-L1 positive group, regardless of stage, was 11.5 months versus 7 months for PD-L1 negative group (p-value 0.34). Patients with limited stage disease with positive PD-L1 had a median survival of 53 months compared to 15 months for patients with PD-L1 negative limited stage (p-value 0.80).
CONCLUSIONS: This study showed that at least one third of our ESCC tissue samples expressed PD-L1. There was a trend for higher response rates to the standard chemotherapy with/without radiotherapy and improved survival in PD-L1 positive patients. Further studies are required to understand the implications of immune dysregulation in these aggressive tumors. PD-L1/PD-1 inhibitors should be investigated in this group of patients.
Combined positive score, Extrapulmonary small cell carcinomas, PD-L1 expression and prognostic value
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© The Author(s). 2018. Open Access: This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
DOI of Published Version
J Immunother Cancer. 2018 May 29;6(1):42. doi: 10.1186/s40425-018-0359-1. Link to article on publisher's site
Journal for immunotherapy of cancer
Salhab M, Migdady Y, Donahue M, Xiong Y, Dresser KA, Walsh W, Chen BJ, Liebmann J. (2018). Immunohistochemical expression and prognostic value of PD-L1 in Extrapulmonary small cell carcinoma: a single institution experience. Open Access Publications by UMass Chan Authors. https://doi.org/10.1186/s40425-018-0359-1. Retrieved from https://escholarship.umassmed.edu/oapubs/3465
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This work is licensed under a Creative Commons Attribution 4.0 License.