Yong Sheng Jason Chan
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gmsjcys@nus.edu.sg
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Publication Clinical features and survival outcomes of ocular melanoma in a multi-ethnic Asian cohort(Nature Research, 2020) Tan, L.L.Y.; Hong, J.; Goh, W.L.; Chang, E.W.Y.; Yang, V.S.; Poon, E.; Somasundaram, N.; Farid, M.; Chan, A.S.Y.; Chan, J.Y.; DEAN'S OFFICE (DUKE-NUS MEDICAL SCHOOL)Ocular melanomas are uncommon cancers in Southeast Asia unlike in the West. We conducted a retrospective review of patients (n = 44) with histologically-proven ocular melanoma within a multi-ethnic Asian cohort from Singapore. Clinicopathological features and relapse patterns were examined, and survival outcomes of interest included recurrence-free survival (RFS) and overall survival (OS). Survival analysis was performed using the Kaplan–Meier method and multivariable Cox proportional regression. The study cohort included 18 male and 26 female patients, with a median age of 52 years (range 8–78). Median follow-up was 154 months. For uveal melanomas (n = 29), the 5-year RFS and OS was 56.8% and 76.6%, respectively; whilst for conjunctival melanomas (n = 15), the 5-year RFS and OS was 30.1% and 68.8%, respectively. Fifteen patients (38.5%) eventually developed metastasis, following which the median survival was only 17 months. Multivariate analysis demonstrated that higher T stage was a significant independent predictor for both OS (HR 8.69, 95% CI 1.03 to 73.09, p = 0.047) and RFS (HR 11.62, 95% CI 2.45 to 55.00, p = 0.002). Smoking history was independently predictive of better RFS (HR 0.08, 95% CI 0.01 to 0.78, p = 0.030). In conclusion, our study demonstrates the poor ocular melanoma outcomes in Southeast Asians, highlighting the necessity for urgent research in this area of unmet clinical need. © 2020, The Author(s).Publication A Clinico-Genotypic Prognostic Index for De Novo Composite Diffuse Large B-Cell Lymphoma Arising from Follicular Lymphoma in Asian patients treated in the Rituximab Era(Nature Research, 2020-03-09) Lim, R.M.H.; Chan, N.P.X.; Khoo, L.P.; Cheng, C.L.; Tan, L.; Poon, E.Y.L.; Somasundaram, N.; Farid, M.; Tang, T.P.L.; Tao, M.; Lim, S.T.; Chan, J.Y.; DUKE-NUS MEDICAL SCHOOL; PATHOLOGYComposite follicular lymphoma with diffuse large B-cell lymphoma (FL/DLBCL) is uncommonly found on lymph node biopsy and represents a rare haematological malignancy. We aim to examine clinico-pathological features of patients with FL/DLBCL and investigate predictors of survival outcome. We included in our retrospective study patients with histologically-proven FL/DLBCL at diagnosis (n = 106) and who were subsequently treated with rituximab-based chemoimmunotherapy from 2002–2017 at the National Cancer Centre. The cohort consisted of 34 women and 72 men with a median age of 59 years (range, 24–82). In a multivariate model inclusive of known clinico-pathological parameters at diagnosis, advanced stage (p = 0.0136), presence of MYC and/or BCL6 rearrangement (p = 0.0376) and presence of B symptoms (p = 0.0405) were independently prognostic for worse overall survival (OS). The only remaining independent prognostic variables for worse OS after including first-line treatment data in the model were use of chemotherapy regimens other than R-CHOP (p = 0.0360) and lack of complete response to chemotherapy (p < 0.0001) besides the presence of B symptoms (p = 0.0022). We generated a Clinico-Genotypic Index by point-wise addition of all five adverse parameters (score of 0–1, 2, 3, 4–5) which revealed four prognostic risk groups with a predicted 5-year OS of 100%, 62%, 40% and 0% (p < 0.0001) accounting for 50.0%, 24.5%, 18.9% and 6.6% of the cohort respectively. We propose that R-CHOP should be the recommended first-line regimen for composite FL/DLBCL. © 2020, The Author(s).Publication Biological significance and prognostic relevance of peripheral blood neutrophil-to-lymphocyte ratio in soft tissue sarcoma(Nature Publishing Group, 2018) Chan, J.Y; Zhang, Z; Chew, W; Tan, G.F; Lim, C.L; Zhou, L; Goh, W.L; Poon, E; Somasundaram, N; Selvarajan, S; Sittampalam, K; Chin, F; Teh, J; Tan, M.H; Soo, K.C; Teo, M; Farid, M; Quek, R; SURGERY; DEAN'S OFFICE (DUKE-NUS MEDICAL SCHOOL); DUKE-NUS MEDICAL SCHOOLPeripheral blood indices of systemic inflammation such as the neutrophil-lymphocyte ratio (NLR) have been shown to be prognostic in various cancers. We aim to investigate the clinical significance of these indices in patients with soft tissue sarcoma (STS). Seven hundred and twelve patients with available blood counts at diagnosis and/or metastatic relapse were retrospectively examined. An optimal cutoff for NLR-high (>2.5) in predicting overall survival (OS) was determined using receiver operating curve analyses. Survival analyses were performed using the Kaplan-Meier method and multivariate Cox proportional models. Our results show that NLR was significantly higher in patients with distant metastasis at diagnosis (n = 183) compared to those without (n = 529) (median: 4.36 vs 2.85, p < 0.0001). Progression of localized disease at diagnosis to metastatic relapse within the same patients was associated with an interval increase in NLR (median: 3.21 vs 3.74, p = 0.0003). In multivariate analysis, NLR-high was the only consistent factor independently associated with both worse OS (HR 1.53, 95% CI 1.10–2.13, p = 0.0112) and relapse-free survival (HR 1.41, 95% CI 1.08–1.85, p = 0.0125) in localized disease, as well as OS (HR 1.82, 95% CI 1.16–2.85, p = 0.0087) in metastatic/unresectable disease. In conclusion, high NLR is an independent marker of poor prognosis among patients with STS. © 2018, The Author(s).Publication Whole exome sequencing identifies recessive germline mutations in FAM160A1 in familial NK/T cell lymphoma(Nature Publishing Group, 2018) Chan, J.Y; Ng, A.Y.J; Cheng, C.L; Nairismägi, M.-L; Venkatesh, B; Cheah, D.M.Z; Li, S.-T; Chan, S.H; Ngeow, J; Laurensia, Y; Lim, J.Q; Pang, J.W.L; Nagarajan, S; Song, T; Chia, B; Tan, J; Huang, D; Goh, Y.T; Poon, E; Somasundaram, N; Tao, M; Quek, R.H.H; Farid, M; Khor, C.C; Bei, J.-X; Tan, S.Y; Lim, S.T; Ong, C.K; Tang, T; DEAN'S OFFICE (DUKE-NUS MEDICAL SCHOOL); DUKE-NUS MEDICAL SCHOOL; PAEDIATRICS; BIOCHEMISTRY; PATHOLOGY[No abstract available]Publication Clinical implications of systemic and local immune responses in human angiosarcoma(Nature Research, 2021-02-12) Chan, Jason Yongsheng; Tan, Grace Fangmin; Yeong, Joe; Ong, Chee Wee; Ng, Dave Yong Xiang; Lee, Elizabeth; Koh, Joanna; Ng, Cedric Chuan-Young; Lee, Jing Yi; Liu, Wei; Wong, Ru Xin; Ong, Chin-Ann Johnny; Farid, Mohamad; Teh, Bin Tean; Soo, Khee Chee; DEAN'S OFFICE (DUKE-NUS MEDICAL SCHOOL); DUKE-NUS MEDICAL SCHOOLAngiosarcomas are a rare subtype of soft-tissue sarcomas which exhibit aggressive clinical phenotypes with limited treatment options and poor outcomes. In this study, we investigated the clinical relevance of the peripheral blood neutrophil-to-lymphocyte ratio (NLR) as a marker of systemic immune response, as well as its correlation with intra-tumoral immune profiles in a subgroup of cases (n = 35) using the NanoString PanCancer IO360 panel and multiplex immunohistochemistry. In the overall cohort (n = 150), angiosarcomas of the head and neck (AS-HN) comprised most cases (58.7%) and median overall survival (OS) was 1.1 year. NLR, classified as high in 78 of 112 (70%) evaluable patients, was independently correlated with worse OS (HR 1.84, 95%CI 1.18–2.87, p = 0.0073). Peripheral blood NLR was positively correlated with intra-tumoral NLR (tNLR) (Spearman’s rho 0.450, p = 0.0067). Visualization of tumor-infiltrating immune cells confirmed that tNLR scores correlated directly with both neutrophil (CD15+ cells, rho 0.398, p = 0.0198) and macrophage (CD68+ cells, rho 0.515, p = 0.0018) cell counts. Interestingly, tNLR correlated positively with oncogenic pathway scores including angiogenesis, matrix remodeling and metastasis, and cytokine and chemokine signaling, as well as myeloid compartment scores (all p < 0.001). In patients with documented response assessment to first-line chemotherapy, these pathway scores were all significantly higher in non-responders (47%) compared to responders. In conclusion, systemic and local immune responses may inform chemotherapy response and clinical outcomes in angiosarcomas. © 2021, The Author(s).Publication Treatment patterns and outcomes of older patients with mantle cell lymphoma in an Asian population(BioMed Central Ltd, 2021-05-17) Yang, Xinyi; Khoo, Lay Poh; Chang, Esther Wei Yin; Yang, Valerie Shiwen; Poon, Eileen; Somasundaram, Nagavalli; Farid, Mohamad; Tang, Tiffany Pooi Ling; Tao, Miriam; Lim, Soon Thye; Chan, Jason Yongsheng; DEAN'S OFFICE (DUKE-NUS MEDICAL SCHOOL); DUKE-NUS MEDICAL SCHOOLBackground: Significant progress has been made in the treatment outcomes of mantle cell lymphoma (MCL) since the introduction of cytarabine and rituximab in modern regimens. However, older patients may not readily tolerate these agents nor derive benefit. We investigated the impact of age on treatment patterns and clinical outcomes of MCL patients in an Asian population. Methods: A retrospective study was conducted on patients (n = 66) diagnosed with MCL at the National Cancer Centre Singapore between 1998 and 2018. The median follow-up duration was 40 months. Survival analyses were performed using the Kaplan-Meier method and multivariate Cox proportional models. Results: The median age of the cohort was 59 years (range, 26–84), with a male predominance (73%). The majority (86%) had advanced stage 3–4 disease at diagnosis. Compared with younger patients, older patients aged ?60 years (n = 32; 48.5%) presented more frequently with B-symptoms (75% vs 38%, p = 0.0028), anaemia (75% vs 35%, p = 0.0013), and carried higher prognostic risk scores (sMIPI high risk 84% vs 56%, p = 0.016). Non-cytarabine-based induction chemotherapy was more commonly administered in older patients (76% vs 32%, p = 0.0012). The 5-year overall survival (OS) and progression-free survival (PFS) was 68 and 25% respectively. In a multivariable model, older age (HR 3.42, 95%CI 1.48–7.92, p = 0.004) and anemia (HR 2.56, 95%CI 1.10–5.96, p = 0.029) were independently associated with poorer OS while older age (HR 2.24, 95%CI 1.21–4.14, p = 0.010) and hypoalbuminemia (HR 2.20, 95%CI 1.17–4.13, p = 0.014) were independently associated with poorer PFS. In an exploratory analysis, maintenance rituximab following induction chemotherapy improved PFS in younger patients, with median PFS of 131 months and 45 months with or without maintenance therapy respectively (HR 0.39, 95%CI 0.16–0.93, p = 0.035). In contrast, no survival benefit was observed in older patients. Conclusions: We demonstrated in our analysis that older patients with MCL may harbor adverse clinical features and may not derive benefit from maintenance rituximab, highlighting the need for further research in this area of need. © 2021, The Author(s).Publication Successful therapeutic rechallenge after a severe episode of high dose methotrexate-induced choreoathetosis: A case report(Spandidos Publications, 2019) Chong, L.L.; Ting Wong, E.Y.; Santos-Banta, S.L.L.; Cheng, C.L.; Tan, L.; Ling Poon, E.Y.; Somasundaram, N.; Farid, M.; Tang, T.; Tao, M.; Kheng Khoo, J.B.; Shih, V.; Cheah, D.M.Z.; Ong, C.K.; Lim, S.T.; Chan, J.Y.; DEAN'S OFFICE (DUKE-NUS MEDICAL SCHOOL)Methotrexate (MTX) is an essential chemotherapy drug used in the treatment of malignancies, but it is known to cause complications to the central nervous system. We report a case of severe MTX neurotoxicity in an adult presenting with choreoathetosis despite a normal clearance of MTX. High dose-MTX has been successfully rechallenged without any neurological sequelae. We reviewed the relevant literature of similar manifestations and summarized their clinical data, magnetic resonance imaging features and treatment given. None of them has recurrence of neurotoxicity. We concluded that it is safe to persist with MTX even after a previous episode of toxic leukoencephalopathy. © 2019 Molecular and Clinical Oncology. All rights reserved.