High proportion of tumor necrosis predicts poor survival in surgically resected high-grade neuroendocrine carcinoma of the lung

Akira Sugimoto; Shigeki Umemura; Tomohiro Miyoshi; Tokiko Nakai; Takashi Kuroe; Kaname Nosaki; Takaya Ikeda; Hibiki Udagawa; Keisuke Kirita; Yoshitaka Zenke; Shingo Matsumoto; Kiyotaka Yoh; Seiji Niho; Masahiro Tsuboi; Koichi Goto; Genichiro Ishii

doi:10.1016/j.lungcan.2021.05.018

High proportion of tumor necrosis predicts poor survival in surgically resected high-grade neuroendocrine carcinoma of the lung

Lung Cancer. 2021 Jul:157:1-8. doi: 10.1016/j.lungcan.2021.05.018. Epub 2021 May 24.

Authors

Affiliations

¹ Department of Pathology and Clinical Laboratories, National Cancer Center Hospital East, Kashiwa, Japan; Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
² Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
³ Department of Thoracic Surgery, National Cancer Center Hospital East, Kashiwa, Japan.
⁴ Department of Pathology and Clinical Laboratories, National Cancer Center Hospital East, Kashiwa, Japan.
⁵ Department of Pathology and Clinical Laboratories, National Cancer Center Hospital East, Kashiwa, Japan; Division of Innovative Pathology and Laboratory Medicine, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Japan. Electronic address: gishii@east.ncc.go.jp.

PMID: 34049251
DOI: 10.1016/j.lungcan.2021.05.018

Abstract

Objectives: Tumor necrosis is a negative prognostic factor in various cancers. High-grade neuroendocrine carcinomas (HGNEC) of the lung, such as small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC), commonly have histopathological features of tumor necrosis. However, the prognostic value of tumor necrosis remains unknown.

Materials and methods: A total of 81 patients with HGNEC (SCLC, n = 42; LCNEC, n = 39) who underwent complete resection were enrolled. The proportion of necrosis in the tumor tissues was quantified using digital image analysis. We analyzed the relationship between the proportion of necrosis, clinicopathological factors, and prognosis. Moreover, we examined the correlation between genomic alterations and proportion of necrosis.

Results: The median proportion of necrosis was 10.6 % (range, 0-62.8 %). The proportion of necrosis was not significantly different between SCLC (median, 5.1 %; range, 0-62.8 %) and LCNEC (median: 14.2 %; range, 0-59.3 %) (p = 0.14). The cumulative incidence of recurrence (CIR) and lung cancer-specific cumulative incidence of death (LC-CID) were significantly higher in patients with 10 % or higher necrosis (necrosis ≥ 10 %) than in those with less than 10 % (necrosis < 10 %) (hazard ratio [HR], 2.94; 95 % confidence interval [CI], 1.30-6.64, and HR, 2.87; 95 % CI, 1.13-7.29, respectively). In the bivariate analysis, necrosis ≥ 10 % was independently associated with higher CIR and tended to be associated with higher LC-CID. The frequency of genomic alterations in the PI3K/AKT/mTOR pathway, MYC family, MAPK/ERK pathway, and major RTK signaling pathways were not different between the necrosis ≥ 10 % and necrosis < 10 % groups for both SCLC and LCNEC.

Conclusion: High proportion of tumor necrosis (≥ 10 %) had a negative prognostic value in surgically resected HGNEC.

Keywords: High-grade neuroendocrine carcinoma; Large cell neuroendocrine carcinoma; Prognosis; Small cell lung cancer; Tumor necrosis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Large Cell*
Carcinoma, Neuroendocrine* / surgery
Humans
Lung
Lung Neoplasms* / surgery
Necrosis
Neoplasm Recurrence, Local
Prognosis