An Asian multi-regional registry study of rare cancers: The MASTER KEY ASIA and MASTER KEY Japan projects.
Authors: Okuma Hitomi Sumiyoshi , Yonemori Kan , Ishioka Chikashi , Baba Eishi , Kinoshita Ichiro , Muto Manabu , Imasa Marcelo Severino Bulauitan , Voon Pei Jye , de Almeida Kathleen Yasmin , Soo Hoo Hwoei Fen , Ichimura Masahiko , Mizoguchi Chiharu , Munakata Wataru , Kohsaka Shinji , Shibata Taro , Yatabe Yasushi , Nakamura Kenichi , Mano Hiroyuki , Yamamoto Noboru 
Published: June 2023

e15052 Background: The importance of biomarker-based treatment and individual therapeutic strategies can be even more substantial in rare cancers, which confront particular difficulties, such as delayed or inaccurate diagnosis, lack of clinical knowledge, and less interest in the development of innovative treatment. However, large-scale studies point to the challenge of drug development disparities between populations, demonstrating the need to better understand the diverse genomic and clinical characteristics. Methods: The present study aimed to characterize rare tumors and recognize the genomic and clinical diversity of Asian and Japanese cohorts. The study included patients with histologically diagnosed rare cancer, defined as those with an annual incidence of < 6/100,000 people. Patients’ clinical data as well as biomarker data were collected. Biomarker analysis included next-generation sequencing (NGS), immunohistochemical staining, fluorescent in situ hybridization (FISH), or single gene testing. Tumor Mutational Burden (TMB) was evaluated through NGS, and was defined as TMB-High (≥10 per Mb) or TMB-Low ( < 10 per Mb). Results: For the Japanese cohort, a total of 2797 solid rare cancer (MKJ solid) and 260 hematological malignancy (MKJ Hem) patients were enrolled in the study between May 2017 and Dec 2022. For the Asian cohort (MKA solid), a total of 226 solid rare cancer patients were enrolled between Nov 2021 to Dec 2022, from countries of Malaysia (n = 175), Philippines (n = 27), Korea (n = 13), and Taiwan (n = 11). From the MKA, 185 patients received a complete diagnosis, of which 92 had genetic biomarker analysis. MKJ solid had 2702 patients diagnosed, among which 1460 were genetically analyzed. The median age for solid rare cancer patients was 55.3 years for MKJ solid, and 50.6 years for MKA solid. Soft tissue sarcomas and CNS/Brain rare cancers were the most frequent types of rare cancers in the recruited patients of MKJ (n = 611 and 395, respectively), but Head and Neck cancers were less common in the Japanese cohort compared to other Asia countries (MKJ = 8%, MKA = 18%). TP53 is a common biomarker in solid cancer alterations, and it was indeed the most recurrent alteration in both solid cancer cohorts, altered in 50% of the MKA solid cohort and in 66% of the MKJ solid cohort. The proportion of TMB-high was 12% and 8% in the MKA solid and MKJ solid cohorts, respectively. Conclusions: The clinical and genomic characteristics of rare cancers from an Asian multi-regional registry study were identified. These cohorts provide a novel way to understand the population-based dimension of rare cancers and, therefore, the need for detailed molecular investigations to enhance clinical oncology practice.