Stephen Chan Hong Kong, China

Stephen L. Chan MD (CUHK), FRCP (Edin., Lond.), FHKCP, FHKAM (Medicine) Stephen Lam CHAN is a Clinical Professor in the Department of Clinical Oncology at the Chinese University of Hong Kong (CUHK). He is renowned for his clinical and translational research on hepatobiliary and pancreatic cancers. Prof. Chan has authored over 270 papers published in peer-reviewed journals. Internationally, he has served on the scientific committees of ASCO and ESMO conferences, and is currently the President of the International Liver Cancer Association (ILCA). Prof. Chan is an associate editor for journals such as the Journal of Hepatology. Locally, he is a board director of the CUHK Medical Centre and the Assistant Dean (Health Systems) of the Faculty of Medicine at CUHK. He also established the Hand in Hand Cancer Foundation, a charity dedicated to serving patients in need.

21 MARCH

Time	Session

13:30 15:00	[Symposium] NET Neuroendocrine Tumors Ching-Chung ChangTaiwan Moderator Shyang-Rong ShihTaiwan Moderator The impact of mutational status on the heterogeneity of MEN1Multiple Endocrine Neoplasia type 1 (MEN1) is a rare syndromic disease primarily characterized by parathyroid adenomas, duodenopancreatic neuroendocrine neoplasms (dpNENs), and pituitary neuroendocrine tumors (pitNETs). Although over 750 germline MEN1 mutations have been identified, there is no definitive genotype-phenotype correlation, and specific mutations cannot reliably predict clinical presentations. However, the overall presence or absence of a germline mutation fundamentally alters the disease trajectory. This presentation investigates the clinical heterogeneity between germline mutation-positive (GP-MEN1) and mutation-negative (GN-MEN1) patients. Approximately 10-30% of patients meeting clinical MEN1 criteria are GN-MEN1, which may represent phenocopies (e.g., MEN4, MEN5) or sporadic co-occurrences. Distinct clinical disparities exist between the two cohorts. GP-MEN1 patients exhibit an earlier median onset (33-35 years), aggressive and multiglandular disease, and a high probability of developing a third cardinal tumor, leading to a poorer prognosis. Conversely, GN-MEN1 patients present significantly later (46-52 years), rarely develop a third cardinal tumor, and experience a more indolent course with a life expectancy comparable to the general population. In a cohort analysis from National Taiwan University Hospital (NTUH), the paradigm of pitNETs in MEN1 has shifted towards non-functioning microadenomas due to modern screening. GP-MEN1 patients with pitNETs were diagnosed at a younger age, showed higher sellar floor involvement, and had a higher prevalence of adrenal tumors and non-functioning GEP-NENs. In contrast, GN-MEN1 patients were older and more frequently presented with insulinomas. In conclusion, germline mutational status is a critical determinant of MEN1 clinical heterogeneity. Genetic testing is essential not only for confirming diagnoses and facilitating targeted therapies but also for exonerating non-carriers. Although current guidelines recommend uniform surveillance for all MEN1 diagnostic categories, the distinctively indolent phenotype of GN-MEN1 suggests that a modified, de-escalated surveillance approach may be more appropriate and warrants further formal investigation. PitNET in Multiple Endocrine Neoplasm Sang Ouk ChinCanada Speaker PitNET in Multiple Endocrine NeoplasmMultiple endocrine neoplasia type 1 (MEN1) is a hereditary autosomal-dominant syndrome involving neoplasms of the parathyroid glands, pituitary gland, and endocrine components of the gastrointestinal system. Pituitary neuroendocrine tumors (PitNETs) develop in roughly 40% of individuals with MEN1 and constitute the initial clinical presentation in approximately 10% of cases. Recent epidemiological data indicate a modest female predominance, with tumors smaller than 1 cm occurring more frequently than larger lesions. Hormone-secreting PitNETs are observed more often than non-functioning tumors, representing nearly 36–48% of cases, and prolactin-secreting adenomas remain the most prevalent subtype. In comparison with sporadic PitNETs, those associated with MEN1 are more likely to exhibit plurihormonal secretion, greater tumor size, and locally aggressive behavior, while age at diagnosis and the relative frequency of functional tumors appear comparable. Patients lacking detectable MEN1 gene mutations often present with larger and more clinically apparent PitNETs at diagnosis. Although rare, pituitary carcinoma has been documented in six patients with MEN1, including one individual without an identifiable MEN1 mutation. Current evidence suggests that management strategies for MEN1-related PitNETs largely parallel those used for sporadic tumors. PitNETs have also been described in multiple endocrine neoplasia type 4 (MEN4), though comprehensive epidemiologic characterization remains limited, and MEN4 should be considered in patients with MEN1-like clinical features and negative MEN1 genetic testing. Oncologist Perspective of NET Management Stephen ChanHong Kong, China Speaker Oncologist Perspective of NET Management The impact of mutational status on the heterogeneity of MEN1 Shyang-Rong ShihTaiwan Speaker The impact of mutational status on the heterogeneity of MEN1Multiple Endocrine Neoplasia type 1 (MEN1) is a rare syndromic disease primarily characterized by parathyroid adenomas, duodenopancreatic neuroendocrine neoplasms (dpNENs), and pituitary neuroendocrine tumors (pitNETs). Although over 750 germline MEN1 mutations have been identified, there is no definitive genotype-phenotype correlation, and specific mutations cannot reliably predict clinical presentations. However, the overall presence or absence of a germline mutation fundamentally alters the disease trajectory. This presentation investigates the clinical heterogeneity between germline mutation-positive (GP-MEN1) and mutation-negative (GN-MEN1) patients. Approximately 10-30% of patients meeting clinical MEN1 criteria are GN-MEN1, which may represent phenocopies (e.g., MEN4, MEN5) or sporadic co-occurrences. Distinct clinical disparities exist between the two cohorts. GP-MEN1 patients exhibit an earlier median onset (33-35 years), aggressive and multiglandular disease, and a high probability of developing a third cardinal tumor, leading to a poorer prognosis. Conversely, GN-MEN1 patients present significantly later (46-52 years), rarely develop a third cardinal tumor, and experience a more indolent course with a life expectancy comparable to the general population. In a cohort analysis from National Taiwan University Hospital (NTUH), the paradigm of pitNETs in MEN1 has shifted towards non-functioning microadenomas due to modern screening. GP-MEN1 patients with pitNETs were diagnosed at a younger age, showed higher sellar floor involvement, and had a higher prevalence of adrenal tumors and non-functioning GEP-NENs. In contrast, GN-MEN1 patients were older and more frequently presented with insulinomas. In conclusion, germline mutational status is a critical determinant of MEN1 clinical heterogeneity. Genetic testing is essential not only for confirming diagnoses and facilitating targeted therapies but also for exonerating non-carriers. Although current guidelines recommend uniform surveillance for all MEN1 diagnostic categories, the distinctively indolent phenotype of GN-MEN1 suggests that a modified, de-escalated surveillance approach may be more appropriate and warrants further formal investigation. 201BC

Time

Session

13:30

15:00

[Symposium] NET

Neuroendocrine Tumors

Ching-Chung ChangTaiwan Moderator

Shyang-Rong ShihTaiwan Moderator The impact of mutational status on the heterogeneity of MEN1Multiple Endocrine Neoplasia type 1 (MEN1) is a rare syndromic disease primarily characterized by parathyroid adenomas, duodenopancreatic neuroendocrine neoplasms (dpNENs), and pituitary neuroendocrine tumors (pitNETs). Although over 750 germline MEN1 mutations have been identified, there is no definitive genotype-phenotype correlation, and specific mutations cannot reliably predict clinical presentations. However, the overall presence or absence of a germline mutation fundamentally alters the disease trajectory. This presentation investigates the clinical heterogeneity between germline mutation-positive (GP-MEN1) and mutation-negative (GN-MEN1) patients. Approximately 10-30% of patients meeting clinical MEN1 criteria are GN-MEN1, which may represent phenocopies (e.g., MEN4, MEN5) or sporadic co-occurrences. Distinct clinical disparities exist between the two cohorts. GP-MEN1 patients exhibit an earlier median onset (33-35 years), aggressive and multiglandular disease, and a high probability of developing a third cardinal tumor, leading to a poorer prognosis. Conversely, GN-MEN1 patients present significantly later (46-52 years), rarely develop a third cardinal tumor, and experience a more indolent course with a life expectancy comparable to the general population. In a cohort analysis from National Taiwan University Hospital (NTUH), the paradigm of pitNETs in MEN1 has shifted towards non-functioning microadenomas due to modern screening. GP-MEN1 patients with pitNETs were diagnosed at a younger age, showed higher sellar floor involvement, and had a higher prevalence of adrenal tumors and non-functioning GEP-NENs. In contrast, GN-MEN1 patients were older and more frequently presented with insulinomas. In conclusion, germline mutational status is a critical determinant of MEN1 clinical heterogeneity. Genetic testing is essential not only for confirming diagnoses and facilitating targeted therapies but also for exonerating non-carriers. Although current guidelines recommend uniform surveillance for all MEN1 diagnostic categories, the distinctively indolent phenotype of GN-MEN1 suggests that a modified, de-escalated surveillance approach may be more appropriate and warrants further formal investigation.

PitNET in Multiple Endocrine Neoplasm

Sang Ouk ChinCanada Speaker PitNET in Multiple Endocrine NeoplasmMultiple endocrine neoplasia type 1 (MEN1) is a hereditary autosomal-dominant syndrome involving neoplasms of the parathyroid glands, pituitary gland, and endocrine components of the gastrointestinal system. Pituitary neuroendocrine tumors (PitNETs) develop in roughly 40% of individuals with MEN1 and constitute the initial clinical presentation in approximately 10% of cases. Recent epidemiological data indicate a modest female predominance, with tumors smaller than 1 cm occurring more frequently than larger lesions. Hormone-secreting PitNETs are observed more often than non-functioning tumors, representing nearly 36–48% of cases, and prolactin-secreting adenomas remain the most prevalent subtype. In comparison with sporadic PitNETs, those associated with MEN1 are more likely to exhibit plurihormonal secretion, greater tumor size, and locally aggressive behavior, while age at diagnosis and the relative frequency of functional tumors appear comparable. Patients lacking detectable MEN1 gene mutations often present with larger and more clinically apparent PitNETs at diagnosis. Although rare, pituitary carcinoma has been documented in six patients with MEN1, including one individual without an identifiable MEN1 mutation. Current evidence suggests that management strategies for MEN1-related PitNETs largely parallel those used for sporadic tumors. PitNETs have also been described in multiple endocrine neoplasia type 4 (MEN4), though comprehensive epidemiologic characterization remains limited, and MEN4 should be considered in patients with MEN1-like clinical features and negative MEN1 genetic testing.
Oncologist Perspective of NET Management

Stephen ChanHong Kong, China Speaker Oncologist Perspective of NET Management
The impact of mutational status on the heterogeneity of MEN1

Shyang-Rong ShihTaiwan Speaker The impact of mutational status on the heterogeneity of MEN1Multiple Endocrine Neoplasia type 1 (MEN1) is a rare syndromic disease primarily characterized by parathyroid adenomas, duodenopancreatic neuroendocrine neoplasms (dpNENs), and pituitary neuroendocrine tumors (pitNETs). Although over 750 germline MEN1 mutations have been identified, there is no definitive genotype-phenotype correlation, and specific mutations cannot reliably predict clinical presentations. However, the overall presence or absence of a germline mutation fundamentally alters the disease trajectory. This presentation investigates the clinical heterogeneity between germline mutation-positive (GP-MEN1) and mutation-negative (GN-MEN1) patients. Approximately 10-30% of patients meeting clinical MEN1 criteria are GN-MEN1, which may represent phenocopies (e.g., MEN4, MEN5) or sporadic co-occurrences. Distinct clinical disparities exist between the two cohorts. GP-MEN1 patients exhibit an earlier median onset (33-35 years), aggressive and multiglandular disease, and a high probability of developing a third cardinal tumor, leading to a poorer prognosis. Conversely, GN-MEN1 patients present significantly later (46-52 years), rarely develop a third cardinal tumor, and experience a more indolent course with a life expectancy comparable to the general population. In a cohort analysis from National Taiwan University Hospital (NTUH), the paradigm of pitNETs in MEN1 has shifted towards non-functioning microadenomas due to modern screening. GP-MEN1 patients with pitNETs were diagnosed at a younger age, showed higher sellar floor involvement, and had a higher prevalence of adrenal tumors and non-functioning GEP-NENs. In contrast, GN-MEN1 patients were older and more frequently presented with insulinomas. In conclusion, germline mutational status is a critical determinant of MEN1 clinical heterogeneity. Genetic testing is essential not only for confirming diagnoses and facilitating targeted therapies but also for exonerating non-carriers. Although current guidelines recommend uniform surveillance for all MEN1 diagnostic categories, the distinctively indolent phenotype of GN-MEN1 suggests that a modified, de-escalated surveillance approach may be more appropriate and warrants further formal investigation.

201BC