Treatment outcomes of patients with adenocarcinoma of the uterine cervix after definitive radiotherapy and the prognostic impact of tumor-infiltrating CD8+ lymphocytes in pre-treatment biopsy specimens: a multi-institutional retrospective study

Author:

Miyasaka Yuhei1,Yoshimoto Yuya12,Murata Kazutoshi1,Noda Shin-ei3,Ando Ken4,Ebara Takeshi45,Okonogi Noriyuki6,Kaminuma Takuya1,Yamada Seiji78,Ikota Hayato9,Yokoo Hideaki7,Ohno Tatsuya1,Nakano Takashi16

Affiliation:

1. Depatment of Radiation Oncology, Gunma University Graduate School of Medicine, 3-39-15, Showa-machi, Maebashi, Gunma 371-8511, Japan

2. Department of Radiation Oncology, Fukushima Medical University, 1, Hikarigaoka, Fukushima, Fukushima 960-1247, Japan

3. Department of Radiation Oncology, Saitama Medical University International Medical Center, 1397-1, Yamane, Hidaka, Saitama 350-1241, Japan

4. Department of Radiation Oncology, Gunma Prefectural Cancer Center, 617-1, Takahayashinishi-cho, Ota, Gunma 373-8550, Japan

5. Department of Radiation Oncology, Kyorin University, 6-20-2, Shinkawa, Mitaka, Tokyo 181-8611, Japan

6. National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan

7. Department of Human Pathology, Gunma University Graduate School of Medicine, 3-39-15, Showa-machi, Maebashi, Gunma 371-8511, Japan

8. Department of Diagnostic Pathology, Fujita Health University, 1-98, Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan

9. Department of Diagnostic Pathology, Gunma University Hospital, 3-39-15, Showa-machi, Maebashi, Gunma 371-8511, Japan

Abstract

Abstract The current study aimed to evaluate the outcomes of patients with adenocarcinoma (AC) of the uterine cervix after definitive radiotherapy (RT) and to evaluate prognostic factors, including immunity-related molecules. A total of 71 patients with AC of the uterine cervix from multiple Japanese institutions were retrospectively analysed. Histological subtypes were diagnosed according to the 2014 World Health Organization classification. All patients underwent definitive RT comprising external beam RT and intracavitary brachytherapy with or without concurrent chemotherapy. Immunohistochemical studies were performed to detect the expression of programmed cell death-ligand 1(PD-L1) and CD8. The 5-year locoregional control (LC), overall survival (OS) and progression-free survival (PFS) rates for all patients were 61.8, 49.7 and 36.1%, respectively. The LC, OS and PFS rates were not significantly different among the histological subtypes. Membranous PD-L1 expression was not significantly associated with prognosis. Patients with CD8-positive tumor-infiltrating lymphocytes (CD8+TILs) in the tumor nests had significantly better OS than patients without CD8+TILs in the tumor nests (5-year OS: 53.8 vs 23.8%, P = 0.038). As expected, the International Federation of Gynecology and Obstetrics (FIGO) stage (2008) III–IVA and maximum tumor diameter > 40 mm were significantly associated with worse prognosis. In summary, the presence of CD8+TILs in the tumor nests has the potential to be an independent favorable prognostic factor for patients with AC of the uterine cervix after definitive RT.

Funder

Japan Society for the Promotion of Science

Ministry of Education, Culture, Sports, Science and Technology

Cultivating Global Leaders in Heavy Ion Therapeutics and Engineering

Publisher

Oxford University Press (OUP)

Subject

Health, Toxicology and Mutagenesis,Radiology Nuclear Medicine and imaging,Radiation

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