RARE CANCERS ARE ALSO NOT RARE IN ASIA :THE RARE CANCER BURDEN IN EAST ASIA Tomohiro Matsuda 1, Young-Joo Won 2 RuRu Chun-Ju Chiang 3, Kumiko Saika 1, Jiwon Lim 2 and Annalisa Trama 4 1 National Cancer Center, Japan 2 National Cancer Center, Republic of Korea 3 Taiwan Cancer Registry, Taiwan 4 Istituto Nazionale dei Tumori, Italy IACR2019 Vancouver, Canada

COI Disclosure Information I have no financial relationships to disclose. Lead Presenter/Responsible Researcher: Tomohiro Matsuda The project RARECARE on the basis of epidemiological data coming from population based cancer registries and in collboration with experts multidisciplary groups proposed a definition of rare cancers which differ from the one for rare diseases mainly because rare cancers are not chronic diseases. IACR2019 Vancouver, Canada

Rare cancer definition Rare cancers: incidence <6/100,000/year in Tier 2 in EU (Rare diseases: prevalence<50/100,000/year) The project RARECARE on the basis of epidemiological data coming from population based cancer registries and in collboration with experts multidisciplary groups proposed a definition of rare cancers which differ from the one for rare diseases mainly because rare cancers are not chronic diseases. IACR2019 Vancouver, Canada

Multi-layer structure of rare cancer classifiction Tier 3: WHO BB names of individual cancer entities and ICD-O-3 codes. Tier 2 (215): Grouped by using morph and topo. Consistent diagnostic and therapeutic approaches. Tier 1 (68): Includes NOS morph. major cancer entities in a clinical sense Family (19): Focusing on referral of patients Family Tier Tumor Category HEAD & NECK 1 EPITHELIAL TUMOURS OF NASAL CAVITY AND SINUSES 2 Squamous cell carcinoma with variants of nasal cavity and sinuses Lymphoepithelial carcinoma of nasal cavity and sinuses Undifferentiated carcinoma of nasal cavity and sinuses Intestinal type adenocarcinoma of nasal cavity and sinuses The present analyses are based on the updated version (as of January 2019) of the standard list of rare cancers provided by RARECAREnet expert panel and endorsed by major European cancer organizations and several Asian rare cancer experts . The rationale of the rare cancer list is described in Casali and Trama 2019. In brief, the list is organised into three tiers IACR2019 Vancouver, Canada

Background The project of surveillance of rare cancers in Asian countries (RARECAREnet Asia) provides the first standardized population-based incidence in Asia based on the latest list of rare cancers defined by the RARECARE group. There has been an overwhelming need for Asian countries where more than 40% of cancers are diagnosed currently to adopt and implement cancer control actions based on reliable data (1). Interests of using such data are to plan a preventive intervention in a most efficient manner with an evidence-based practice, and to introduce clinical trials for drug development. However, a major problem with quantifying their overall burden on society in the area other than Western countries is lack of reliable population-based data. In East Asia, such as Japan, the Republic of Korea and Taiwan, they are equipped with population-based cancer registries (PBCR), fortunately. This project is a part of a wider framework and collaboration between epidmiologists and oncologists started with ESMO Asia in 2016. IACR2019 Vancouver, Canada

Background: Cancer Registry in East Asia May 3, 2018 Background: Cancer Registry in East Asia Feature of available data Available data items Available data Year of last F/U Data size classification Digit Topo. Morpho. Birth date Date of Dx. Sex, Age at Dx. Staging Tx. Hosp. of Dx. Hosp. of Tx. (type of hosp.) JP 1993-2015 (high quality 2010-2015) 2016 From 2010, around 900,000/year ICD-O-3 Yes (4digits) Yes (6digits) Yes (Y/M/D) SEER summary stage (Cancer Tx. hospital or other hospital/clinic) KR 1999-2015 1999-2015, around 168,000/year Yes (5digits), (Grade: from 2013) summary stage (from 2005) Yes. No TW 1979-2015 1995-2015) 1995-2015, around 37,500-105,000 /year TNM stage major cancers (after 2004) IACR2019 Vancouver, Canada

Methods Common protocol for data analyses Analyses performed by each PBCR with the standardized analysis tool kit including the latest RARECARE list List of data quality indicators and checks 2 meetings and several call conference PBCR data on patients diagnosed from 2011 to 2015 in JP, KR and TW in comparison with the data in EU IACR2019 Vancouver, Canada

Results Data quality in the 3 Asian countries were as high as EU. DCO%: 0.8-4.8% Topography NOS: 0.01-4% Morphology NOS (mean): 7.3-13.1% MV%: 83.7-91.1% Incidence of all rare cancers was 93.9 in JP, 106.1 in KR and 103.5 in TW and 67.8 in EU corresponding to 16.1% (JP), 23.7% (KR), 24.2% (TW) and 22.2% (EU) of all new cancer diagnoses. Newly diagnosed rare cancers annually: 139,497 (JP), 52,071 (KR) and 24,147 (TW). IACR2019 Vancouver, Canada

Results N of Tier 2 entities with crude incidence rate <6/100,000 in Asia (out of 215): 196 in JP, 203 in KR, 200 in TW, 198 in EU. Same rare cancer entities in 3 Asian countries: 194 entities 189 out of 193 were rare in all the 4 areas Same common cancer entities in 3 Asian countries : 2 entities RARE COMMON IACR2019 Vancouver, Canada

Results Among RARE cancer families, Among COMMON cancer families, Epithelial tumours of nasopharynx, oropharynx and oral cavity and lips were not rare in TW. Epithelial tumours of oral cavity and lip was not rare in JP, neither. Epithelial tumours of gallbladder and extra hepatic biliary tract was not rare in JP and KR. Thyroid cancer was not rare in Asia. Among COMMON cancer families, Epithelial tumours of esophagus was not common in KR. Epithelial tumours of corpus uteri was not common in KR and ovary was not common in KR and TW. Epithelial tumours of kidney was not common in TW. Skin melanoma was not common in Asia. IACR2019 Vancouver, Canada

RARE CANCER FAMILIES HEAD & NECK DIGESTIVE RARE ENDOCRINE ORGAN Japan (2011-15) Korea (2011-15) Taiwan (2011-15) EU (2000-07) Tier 1 List Crude rate C/R EPITHELIAL TUMOURS OF NASOPHARYNX 0.54 R 0.77 6.66 C 0.47 EPITHELIAL TUMOURS OF HYPOPHARYNX AND LARYNX 7.00 3.03 7.30 6.33 EPITHELIAL TUMOURS OF OROPHARYNX 2.47 1.31 6.23 3.34 EPITHELIAL TUMOURS OF ORAL CAVITY AND LIP 6.49 1.92 20.19 4.78 DIGESTIVE RARE EPITHELIAL TUMOURS OF GALLBLADDER AND EXTRAHEPATIC BILIARY TRACT (EBT) 18.15 C 11.32 4.09 R 4.44 ENDOCRINE ORGAN CARCINOMAS OF THYROID GLAND 10.79 C 72.83 13.29 5.07 R HEMATOLOGIC RARE MYELODYSPLASTIC SYNDROME AND MYELODYSPLASTIC/MYELOPROLIFERATIVE DISEASES 6.55 C 1.99 R 1.68 2.47 IACR2019 Vancouver, Canada

COMMON CANCER FAMILIES DIGESTIVE COMMON Japan (2011-15) Korea (2011-15) Taiwan (2011-15) EU (2000-07) Tier 1 List Crude rate C/R EPITHELIAL TUMOURS OF OESOPHAGUS 17.33 C 4.62 R 10.42 7.81 FEMALE GENITAL COMMON EPITHELIAL TUMOURS OF CORPUS UTERI 10.18 C 3.95 R 8.25 11.39 EPITHELIAL TUMOURS OF OVARY AND FALLOPPIAN TUBE 8.00 4.38 5.28 9.38 MALE GENITAL & UROGENITAL COMMON EPITHELIAL TUMOURS OF KIDNEY 12.82 C 8.40 5.30 R 12.71 SKIN COMMON MALIGNANT SKIN MELANOMA 1.30 R 1.07 1.15 14.06 C IACR2019 Vancouver, Canada

Comparison of 3 Asian countries (ASR(W)) RARE IACR2019 Vancouver, Canada

Comparison of 3 Asian countries (ASR(W)) COMMON IACR2019 Vancouver, Canada

Discussion EU based RARECARE rarity threshold fits well to cancer incidence in East Asia. Most of rare cancers between three countries are similiar, and most of the continental gaps found in the current study were due to well known risk factors. IACR2019 Vancouver, Canada

Discussion Nasopharynx and oral cavity cancers in Taiwan Betel quid chewing is popular in Asian countries, including Taiwan. Smoking and alcohol drinking. Prevalence of HPV and EBV is a possible risk factor. Different incidence for esophageal cancers Risk factors for squamous cell carcinoma: smoking, alcohol, diet (Food rich in nitrogenous, tea, coffee, mate consumed at high temperature), genetic predisposition. Liver cancer High prevalence of HBV and HCV career in the area has been known as the main risk factor. IACR2019 Vancouver, Canada

Discussion Gallbladder Thyroid cancer Because of an anomalous pancreatobiliary duct junction (APBDJ), a congenital malformation of the biliary tract that is more frequent in Japan, Korea, and possibly China, than in Western countries. Thyroid cancer Ultrasound screening of thyroid in Korea is also well known “artificial” risk factor for high incidence rate in thyroid cancer. Gastroenteropancreatic neuroendocrine tumour (GEP-NET) Rare in all the 4 areas. The notion was proposed in 2010 by the WHO classification which may result in confusion in the clinical setting in Asian countries. IACR2019 Vancouver, Canada

Future collaborations Survival analysis Prevalence estimation Additional countries interested to join? This research was supported by the Health Labour Sciences Research Grant in Japan (Cancer Control-General- 016, 2018 FY) IACR2019 Vancouver, Canada