Comprehensive Genomic Profiling of Rare Tumors in China: Routes to Immunotherapy.

Shuhang Wang,Ning Li,Yuan Fang,Xin Yi,Shujun Xing,Rongrong Chen,Zhiqian Zhang,Ning Jiang,Qin Li

doi:10.3389/fimmu.2021.631483

Abstract

Treatment options for rare tumors are limited, and comprehensive genomic profiling may provide useful information for novel treatment strategies and improving outcomes. The aim of this study is to explore the treatment opportunities of patients with rare tumors using immune checkpoint inhibitors (ICIs) that have already been approved for routine treatment of common tumors. We collected immunotherapy-related indicators data from a total of 852 rare tumor patients from across China, including 136 programmed cell death ligand-1 (PD-L1) expression, 821 tumors mutational burden (TMB), 705 microsatellite instability (MSI) and 355 human leukocyte antigen class I (HLA-I) heterozygosity reports. We calculated the positive rates of these indicators and analyzed the consistency relationship between TMB and PD-L1, TMB and MSI, and HLA-I and PD-L1. The prevalence of PD-L1 positive, TMB-H, MSI-, and HLA-I -heterozygous was 47.8%, 15.5%, 7.4%, and 78.9%, respectively. The consistency ratio of TMB and PD-L1, TMB and MSI, and HLA-I and PD-L1 was 54.8% (78/135), 87.3% (598/685), and 47.4% (54/114), respectively. The prevalence of the four indicators varied widely across tumors systems and subtypes. The probability that neuroendocrine tumors (NETs) and biliary tumors may benefit from immunotherapy is high, since the proportion of TMB-H is as high as 50% and 25.4% respectively. The rates of PD-L1 positivity, TMB-H and MSI-H in carcinoma of unknown primary (CUP) were relatively high, while the rates of TMB-H and MSI-H in soft tissue tumors were both relatively low. Our study revealed the distribution of immunotherapeutic indicators in patients with rare tumors in China. Comprehensive genomic profiling may offer novel therapeutic modalities for patients with rare tumors to solve the dilemma of limited treatment options.

Highlights

There exists no consensus definition for the category of “rare tumors,” either worldwide or in China
programmed cell death ligand-1 (PD-L1) expression was assessed in formalin fixed paraffin embedded (FFPE) tumor tissues using the PD-L1 IHC 22C3 pharmDx assay (Dako, Carpinteria, CA, USA) in 94 patients; using the SP263 pharmDx assay (Ventana Automated Systems, Inc., Tucson, AZ, USA) in 21 patients; and using an unknown method in 21 patients (The PD-L1 test results of these patients were obtained from the previous medical records, and the detection method was not described)
We analyzed the prevalence of immunotherapy predictors and prognostic indicators, including PD-L1, tumors mutational burden (TMB), microsatellite instability (MSI), and human leukocyte antigen class I (HLA-I), and their consistency

Summary

Introduction

There exists no consensus definition for the category of “rare tumors,” either worldwide or in China. Based on the definition of rare tumors by Food and Drug Administration (FDA), National Cancer Institute and European Society for Medical Oncology [1, 2], Professor Li Ning’s team from Clinical Trial Canter, National Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, proposed the definition of rare tumors in China first time This definition was based on data from the National Cancer Registration Office of China National Cancer Canter, combined with the incidence rate of cancer, the characteristics of the population in China, classification according to the International Classification of Diseases and the OncoTrees (http://oncotree.mskcc.org/). In the Chinese population, prevalence of targetable genomic alterations within those rare tumors (ALK, BRAF, BRCA2, CDKN2A, EGFR, HER2, KIT, MET, ROS1) was 32.4%, which is more than 3 times that which is found in the general population according to cBioPortal [3]

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