Featured Publications
Phase I PIANO trial—PIPAC-oxaliplatin and systemic nivolumab combination for gastric cancer peritoneal metastases: clinical and translational outcomes
Sundar R, Chia D, Zhao J, Lee A, Kim G, Tan H, Pang A, Shabbir A, Willaert W, Ma H, Huang K, Hagihara T, Tan A, Ong C, Wong J, Seo C, Walsh R, Chan G, Cheo S, Soh C, Callebout E, Geboes K, Ng M, Lum J, Leow W, Selvarajan S, Hoorens A, Ang W, Pang H, Tan P, Yong W, Chia C, Ceelen W, So J. Phase I PIANO trial—PIPAC-oxaliplatin and systemic nivolumab combination for gastric cancer peritoneal metastases: clinical and translational outcomes. ESMO Open 2024, 9: 103681. PMID: 39288528, PMCID: PMC11421236, DOI: 10.1016/j.esmoop.2024.103681.Peer-Reviewed Original ResearchConceptsGastric cancer peritoneal metastasisPeritoneal cancer indexNivolumab combinationPeritoneal metastasisPeritoneal tumorsNaive CD8+ T cellsCD8+ central memoryEnhanced T cell infiltrationTreatment-related adverse eventsCD8+ T cellsGrade 4 vomitingRegression grade 1First-in-human trialImmune checkpoint inhibitionMemory CD4+T cell infiltrationImmunogenic cell deathSystemic immunotherapyCheckpoint inhibitionSystemic therapyCancer indexCD4+Intraperitoneal treatmentT cellsAdverse eventsSpatially resolved niche and tumor microenvironmental alterations in gastric cancer peritoneal metastases
Zhao J, Ong C, Srivastava S, Chia D, Ma H, Huang K, Sheng T, Ramnarayanan K, Ong X, Tay S, Hagihara T, Tan A, Teo M, Tan Q, Ng G, Tan J, Ng M, Gwee Y, Walsh R, Law J, Shabbir A, Kim G, Tay Y, Her Z, Leoncini G, Teh B, Hong J, Tay R, Teo C, Dings M, Bijlsma M, Lum J, Mathur S, Pietrantonio F, Blum S, van Laarhoven H, Klempner S, Yong W, So J, Chen Q, Tan P, Sundar R. Spatially resolved niche and tumor microenvironmental alterations in gastric cancer peritoneal metastases. Gastroenterology 2024 PMID: 39147169, DOI: 10.1053/j.gastro.2024.08.007.Peer-Reviewed Original ResearchPeritoneal metastasisTumor microenvironmentPrimary tumorTranscoelomic metastasisGastric cancerExpression of therapeutic targetsAssociated with poor prognosisGastric cancer peritoneal metastasisAssociated with increased riskHumanized mouse modelTherapeutic targetComprehensive multi-omics analysisTumor microenvironment signaturesTumor microenvironment alterationsDigital spatial profilingInvestigate molecular alterationsWhole-exome sequencingMatched normal tissuesStromal infiltrationComprehensive molecular characterizationLiver metastasesImmune compositionFGFR2b expressionImprove patient outcomesPredictive markerEffectiveness of Immune Checkpoint Inhibitors in Patients With Advanced Esophageal Squamous Cell Carcinoma
Yap D, Leone A, Wong N, Zhao J, Tey J, Sundar R, Pietrantonio F. Effectiveness of Immune Checkpoint Inhibitors in Patients With Advanced Esophageal Squamous Cell Carcinoma. JAMA Oncology 2023, 9: 215-224. PMID: 36480211, PMCID: PMC9857522, DOI: 10.1001/jamaoncol.2022.5816.Peer-Reviewed Original ResearchConceptsAdvanced esophageal squamous cell carcinomaImmune checkpoint inhibitorsEsophageal squamous cell carcinomaSquamous cell carcinomaPD-L1 expressionKaplan-Meier curvesLow PD-L1 expressionFirst-line trialsProgression-free survivalDuration of responsePD-L1Overall survivalCell carcinomaRandomized clinical trialsPooled analysisClinical trialsCheckpoint inhibitorsTumor proportionEffect of immune checkpoint inhibitorsLow programmed death ligand 1Benefit of immune checkpoint inhibitorsHazard ratioSurvival dataFirst-line settingICI-based regimensChoice of PD-L1 immunohistochemistry assay influences clinical eligibility for gastric cancer immunotherapy
Yeong J, Lum H, Teo C, Tan B, Chan Y, Tay R, Choo J, Jeyasekharan A, Miow Q, Loo L, Yong W, Sundar R. Choice of PD-L1 immunohistochemistry assay influences clinical eligibility for gastric cancer immunotherapy. Gastric Cancer 2022, 25: 741-750. PMID: 35661944, PMCID: PMC9226082, DOI: 10.1007/s10120-022-01301-0.Peer-Reviewed Original ResearchConceptsCombined positive scorePD-L1 combined positive scoreTumor proportion scorePD-L1Gastric cancerImmune cellsPD-L1 immunohistochemistry assaysProgrammed death-ligand 1Resection of gastric cancerStandard-of-care treatmentBackgroundImmune checkpoint inhibitorsGastric cancer immunotherapyPD-L1 positivityPD-L1 scoringPD-L1 immunohistochemistryDeath-ligand 1Metastatic gastric cancerPD-L1-positive samplesInter-assay concordanceCheckpoint inhibitorsDako 22C3ICI therapyCross-sectional studyCancer immunotherapyPatient selectionIntegration of Genomic Biology Into Therapeutic Strategies of Gastric Cancer Peritoneal Metastasis
Gwee Y, Chia D, So J, Ceelen W, Yong W, Tan P, Ong C, Sundar R. Integration of Genomic Biology Into Therapeutic Strategies of Gastric Cancer Peritoneal Metastasis. Journal Of Clinical Oncology 2022, 40: 2830. PMID: 35649219, PMCID: PMC9390822, DOI: 10.1200/jco.21.02745.Peer-Reviewed Educational MaterialsConceptsPeritoneal metastasisSystemic therapyClinical trialsGastric cancerTherapeutic strategiesEmergence of novel therapiesSynchronous peritoneal metastasesKnowledge of cancer biologyTraditional systemic therapiesCurrent standard-of-careSite of metastasisGastric cancer peritoneal metastasisAdvanced gastric cancerSurrounding tumor microenvironmentStandard-of-careInternational clinical guidelinesLocoregional therapeutic strategiesDiagnostic laparoscopyDismal prognosisTumor microenvironmentClinical entityNovel therapiesSurgical techniqueDisease stageMolecular profilingEfficacy of covid-19 vaccines in immunocompromised patients: systematic review and meta-analysis
Lee A, Wong S, Chai L, Lee S, Lee M, Muthiah M, Tay S, Teo C, Tan B, Chan Y, Sundar R, Soon Y. Efficacy of covid-19 vaccines in immunocompromised patients: systematic review and meta-analysis. The BMJ 2022, 376: e068632. PMID: 35236664, PMCID: PMC8889026, DOI: 10.1136/bmj-2021-068632.Peer-Reviewed Original ResearchConceptsImmune mediated inflammatory disorderOrgan transplant recipientsEfficacy of COVID-19 vaccinesTransplant recipientsRisk of biasImmunocompromised patientsSolid cancersInflammatory disordersImmunocompetent controlsHaematological cancersSeroconversion ratesMeta-analysisCOVID-19 vaccineMRNA vaccinesVaccine doseSystematic reviewCOVID-19 mRNA vaccinesWHO International Clinical Trials Registry PlatformCentral Register of Controlled TrialsVaccine non-respondersAssociated with seroconversionInternational Clinical Trials Registry PlatformProspective observational studyRegister of Controlled TrialsLow risk of biasSingle-Cell Atlas of Lineage States, Tumor Microenvironment, and Subtype-Specific Expression Programs in Gastric CancerSingle-Cell Atlas of Gastric Cancer Subtypes
Kumar V, Ramnarayanan K, Sundar R, Padmanabhan N, Srivastava S, Koiwa M, Yasuda T, Koh V, Huang K, Tay S, Ho S, Tan A, Ishimoto T, Kim G, Shabbir A, Chen Q, Zhang B, Xu S, Lam K, Lum H, Teh M, Yong W, So J, Tan P. Single-Cell Atlas of Lineage States, Tumor Microenvironment, and Subtype-Specific Expression Programs in Gastric CancerSingle-Cell Atlas of Gastric Cancer Subtypes. Cancer Discovery 2022, 12: 670-691. PMID: 34642171, PMCID: PMC9394383, DOI: 10.1158/2159-8290.cd-21-0683.Peer-Reviewed Original ResearchConceptsPatient-derived organoidsPlasma cell proportionsGastric cancer subtypesLineage statePredictors of poor clinical prognosisCancer subtypesSingle-cell atlasCell proportionCancer-associated fibroblasts' subtypesCell populationsDiffuse-type tumorsPoor clinical prognosisIn vivo modelsComprehensive single-cell atlasPrimary tumorHistological subtypesRNA-sequencing cohortsTumor microenvironmentClinical stageClinical prognosisGastric malignancyTumor ecosystemGastric cancerCancer heterogeneityTumorLow Programmed Death-Ligand 1–Expressing Subgroup Outcomes of First-Line Immune Checkpoint Inhibitors in Gastric or Esophageal Adenocarcinoma
Zhao J, Yap D, Chan Y, Tan B, Teo C, Syn N, Smyth E, Soon Y, Sundar R. Low Programmed Death-Ligand 1–Expressing Subgroup Outcomes of First-Line Immune Checkpoint Inhibitors in Gastric or Esophageal Adenocarcinoma. Journal Of Clinical Oncology 2021, 40: 392-402. PMID: 34860570, DOI: 10.1200/jco.21.01862.Peer-Reviewed Original ResearchConceptsProgrammed death-ligand 1Combined positive scoreImmune checkpoint inhibitorsKEYNOTE-062First-line treatmentCheckMate-649Checkpoint inhibitorsEsophageal adenocarcinomaKaplan-MeierEstimate time-to-event outcomesFirst-line immune checkpoint inhibitorsPD-L1 combined positive scoreProgrammed death ligand 1 subgroupsPatients treated with pembrolizumabPD-L1-expressing tumorsRandomized phase III trialEfficacy of ICIsPD-L1 subgroupsProgression-free survivalDeath-ligand 1Phase III trialsUS Food and Drug AdministrationPrimary manuscriptsFood and Drug AdministrationCPS-1Epigenetic promoter alterations in GI tumour immune-editing and resistance to immune checkpoint inhibition
Sundar R, Huang K, Kumar V, Ramnarayanan K, Demircioglu D, Her Z, Ong X, Bin Adam Isa Z, Xing M, Tan A, Tai D, Choo S, Zhai W, Lim J, Thakur M, Molinero L, Cha E, Fasso M, Niger M, Pietrantonio F, Lee J, Jeyasekharan A, Qamra A, Patnala R, Fabritius A, De Simone M, Yeong J, Ng C, Rha S, Narita Y, Muro K, Guo Y, Skanderup A, So J, Yong W, Chen Q, Göke J, Tan P. Epigenetic promoter alterations in GI tumour immune-editing and resistance to immune checkpoint inhibition. Gut 2021, 71: 1277-1288. PMID: 34433583, PMCID: PMC9185816, DOI: 10.1136/gutjnl-2021-324420.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitionImmune microenvironmentHuman immune systemCheckpoint inhibitionActive human immune systemGastric cancerHuman T-cell infiltrationT cell cytolytic activityResistance to immune checkpoint inhibitionImmune systemProgression-free survivalImmunotherapy-treated patientsT cell infiltrationTumor immune microenvironmentT cell proportionsImmune-editingImmunotherapy resistanceFunctional in vivo studiesTumor kineticsHumanised miceAlternative promoter useTumor microenvironmentTherapeutic responseCytolytic activityImmune depletionMachine-learning model derived gene signature predictive of paclitaxel survival benefit in gastric cancer: results from the randomised phase III SAMIT trial
Sundar R, Kumarakulasinghe N, Chan Y, Yoshida K, Yoshikawa T, Miyagi Y, Rino Y, Masuda M, Guan J, Sakamoto J, Tanaka S, Tan A, Hoppe M, Jeyasekharan A, Ng C, De Simone M, Grabsch H, Lee J, Oshima T, Tsuburaya A, Tan P. Machine-learning model derived gene signature predictive of paclitaxel survival benefit in gastric cancer: results from the randomised phase III SAMIT trial. Gut 2021, 71: 676-685. PMID: 33980610, PMCID: PMC8921574, DOI: 10.1136/gutjnl-2021-324060.Peer-Reviewed Original ResearchConceptsDisease free survivalValidation cohortGastric cancerGene signatureSurvival benefitPac-SensitiveNo survival differenceSelection of patientsGC trialsFree survivalPaclitaxel chemotherapyCurative surgeryMetastatic patientsPredictive biomarkersTraining cohortSurvival differencesIndependent cohortNanoString panelGC patientsPaclitaxelPatientsNanoString profilingCohortGroup trialUFTSpatial profiling of gastric cancer patient-matched primary and locoregional metastases reveals principles of tumour dissemination
Sundar R, Liu D, Hutchins G, Slaney H, Silva A, Oosting J, Hayden J, Hewitt L, Ng C, Mangalvedhekar A, Ng S, Tan I, Tan P, Grabsch H. Spatial profiling of gastric cancer patient-matched primary and locoregional metastases reveals principles of tumour dissemination. Gut 2020, 70: 1823-1832. PMID: 33229445, PMCID: PMC8458060, DOI: 10.1136/gutjnl-2020-320805.Peer-Reviewed Original ResearchConceptsPrimary gastric cancerLymph node metastasisPrimary tumorGastric cancerIntratumour heterogeneityNode metastasisMatched lymph node metastasesRegional lymph node metastasisMultiplex ligation-dependent probe amplificationLigation-dependent probe amplificationPatient-matchedProgressive genomic changesDNA copy number profilesEndoscopic mucosal biopsiesCopy number profilesTherapeutically relevant genesLocoregional metastasesTumor disseminationResected samplesTargeted therapyHistomorphological phenotypesProbe amplificationBiomarker testingClinical trialsNanoString resultsAre we mis-estimating chemotherapy-induced peripheral neuropathy? Analysis of assessment methodologies from a prospective, multinational, longitudinal cohort study of patients receiving neurotoxic chemotherapy
Molassiotis A, Cheng H, Lopez V, Au J, Chan A, Bandla A, Leung K, Li Y, Wong K, Suen L, Chan C, Yorke J, Farrell C, Sundar R. Are we mis-estimating chemotherapy-induced peripheral neuropathy? Analysis of assessment methodologies from a prospective, multinational, longitudinal cohort study of patients receiving neurotoxic chemotherapy. BMC Cancer 2019, 19: 132. PMID: 30736741, PMCID: PMC6368751, DOI: 10.1186/s12885-019-5302-4.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsCohort StudiesDose-Response Relationship, DrugFemaleHumansLongitudinal StudiesMaleMiddle AgedNeoplasm StagingNeoplasmsPatient Reported Outcome MeasuresPeripheral Nervous System DiseasesPrevalenceProspective StudiesQuality of LifeSeverity of Illness IndexConceptsChemotherapy-induced peripheral neuropathyPeripheral neuropathyNeurotoxic chemotherapyPrevalence of sensory neuropathyCohort study of patientsCumulative chemotherapy dosePlatinum-based chemotherapyLongitudinal cohort study of patientsMeasuring chemotherapy-induced peripheral neuropathyStudy of patientsNerve conduction studiesAssessment of chemotherapy-induced peripheral neuropathyCIPN incidencePatient-reported outcome measuresAssociated with onsetLongitudinal cohort studyChemotherapy doseMotor neurotoxicityClinician-based scalesMotor neuropathySensory neuropathyChemotherapyNeuropathyNatural historyPatients
2024
Scalp cooling therapy for chemotherapy-induced hair loss in patients with breast or gynecological cancers—an Asian tertiary institution experience
Lee V, Loh J, Hui F, Sundar R, Tan B, Lee M, Lin H, Ong L, Visvanadan N, Ow S, Wong A, Chan G, Lim S, Lim Y, Tan D, Ang Y, Choo J, Lee M, Ngoi N, Lee S, Paxman R, Parker A, Lee Y, Lim J. Scalp cooling therapy for chemotherapy-induced hair loss in patients with breast or gynecological cancers—an Asian tertiary institution experience. Supportive Care In Cancer 2024, 32: 762. PMID: 39482416, DOI: 10.1007/s00520-024-08940-2.Peer-Reviewed Original ResearchConceptsHair preservationGynaecological cancerChemotherapy-induced alopeciaScalp cooling therapyHair regrowthCooling therapyTaxane-based chemotherapyCycles of chemotherapyAnthracycline based chemotherapyResultsEighty-three patientsGrade (GComfort scoresWeekly paclitaxelPaclitaxel regimenBased chemotherapyComfort levelChemotherapy cyclesTerminology criteriaAdverse eventsHistorical controlsInstitutional experienceChemotherapyChemotherapy-induced hair lossDrug infusionResultsEighty-threeImmune checkpoint inhibitors in advanced gastroesophageal adenocarcinoma: a series of patient-level meta-analyses in different programmed death-ligand 1 subgroups
Leone A, Mai A, Fong K, Yap D, Kato K, Smyth E, Moehler M, Seong J, Sundar R, Zhao J, Pietrantonio F. Immune checkpoint inhibitors in advanced gastroesophageal adenocarcinoma: a series of patient-level meta-analyses in different programmed death-ligand 1 subgroups. ESMO Open 2024, 9: 103962. PMID: 39426081, PMCID: PMC11533044, DOI: 10.1016/j.esmoop.2024.103962.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsCombined positive scoreBenefit of immune checkpoint inhibitorsCheckpoint inhibitorsOS benefitOverall survivalAnti-programmed cell death protein 1Kaplan-Meier (KM) plotsEfficacy of immune checkpoint inhibitorsFirst-line immune checkpoint inhibitorsPD-L1 combined positive scoreProgrammed death ligand 1 subgroupsCell death protein 1Programmed death-ligand 1Patient-level meta-analysesPatient-level meta-analysisDeath-ligand 1Advanced gastroesophageal adenocarcinomaRandomized clinical trialsCheckMate-649KEYNOTE-062Gastroesophageal adenocarcinomaTherapeutic optionsClinical trialsKM plotsMultimodality Treatment for Locally Advanced Gastric Adenocarcinoma
Srikumar T, Sundar R. Multimodality Treatment for Locally Advanced Gastric Adenocarcinoma. Surgical Clinics Of North America 2024 DOI: 10.1016/j.suc.2024.06.007.Peer-Reviewed Educational MaterialsEORTC stomach cancer PD-L1 biomarker European initiative: the ASPIRE study protocol
Petrillo A, Oudijk L, Sundar R, Daumer C, Casas J, D’Haese D, Mauer M, van Grieken N, Smyth E, Moehler M. EORTC stomach cancer PD-L1 biomarker European initiative: the ASPIRE study protocol. ESMO Gastrointestinal Oncology 2024, 5: 100071. DOI: 10.1016/j.esmogo.2024.100071.Peer-Reviewed Original Research229TiP A phase II trial of a neural network-based treatment decision support tool in patients (pts) with refractory solid organ malignancies
Walsh R, Jayagopal A, Tan T, Pitt J, Sundar R, Lee S, Goh B, Rajan V, Tan D, Jeyasekharan A. 229TiP A phase II trial of a neural network-based treatment decision support tool in patients (pts) with refractory solid organ malignancies. Annals Of Oncology 2024, 35: s307-s308. DOI: 10.1016/j.annonc.2024.08.2233.Peer-Reviewed Original Research1418P Tumor microenvironment B-cell abundance and survival in resectable gastric cancer: A translational analysis from the CLASSIC trial
Sachdeva M, Tay R, KIM Y, Kim H, Cheong J, Grabsch H, Sundar R. 1418P Tumor microenvironment B-cell abundance and survival in resectable gastric cancer: A translational analysis from the CLASSIC trial. Annals Of Oncology 2024, 35: s885. DOI: 10.1016/j.annonc.2024.08.1484.Peer-Reviewed Original ResearchPersonalized dose selection for the first Waldenström macroglobulinemia patient on the PRECISE CURATE.AI trial
Blasiak A, Tan L, Chong L, Tadeo X, Truong A, Senthil Kumar K, Sapanel Y, Poon M, Sundar R, de Mel S, Ho D. Personalized dose selection for the first Waldenström macroglobulinemia patient on the PRECISE CURATE.AI trial. Npj Digital Medicine 2024, 7: 223. PMID: 39191913, PMCID: PMC11350179, DOI: 10.1038/s41746-024-01195-5.Peer-Reviewed Original ResearchArtificial intelligenceClinical decision support systemsDecision support systemIntegration of AIAI-enabled toolsWaldenstrom's macroglobulinemiaBruton tyrosine kinase inhibitor ibrutinibRare diseaseEnhance usersWaldenstrom's macroglobulinemia patientsKinase inhibitor ibrutinibSupport systemSecondary outcome measuresDiagnosed WMDigital health solutionsWM patientsInhibitor ibrutinibMacroglobulinemia patientsDosing recommendationsUsersManagement of rare diseasesClinical efficacyDevelopment of digital technologiesDose selectionPersonalized therapyReal-World Study of Systemic Treatment after First-Line Atezolizumab plus Bevacizumab for Hepatocellular Carcinoma in Asia-Pacific Countries
Lee C, Yoo C, Hong J, Park J, Kim J, Tai D, Kim H, Korphaisarn K, Tanasanvimon S, Chen S, Kim J, Kim I, Kim M, Choo J, Oh S, Chen C, Bae W, Kim H, Huh S, Yen C, Park S, Lee D, Chan L, Kang B, Kang M, Sundar R, Choi H, Chan S, Chon H, Lee M. Real-World Study of Systemic Treatment after First-Line Atezolizumab plus Bevacizumab for Hepatocellular Carcinoma in Asia-Pacific Countries. Liver Cancer 2024, 1-15. DOI: 10.1159/000540969.Peer-Reviewed Original ResearchFirst-line atezolizumabProgression-free survivalImmune checkpoint inhibitorsTyrosine kinase inhibitorsSecond-line regimensOverall survivalHepatocellular carcinomaSecond-line progression-free survivalSecond-line tyrosine kinase inhibitorsPatients treated with tyrosine kinase inhibitorsAssociated with improved OSImmune checkpoint inhibitor combinationsImmune checkpoint inhibitor useMedian progression-free survivalLow tumor burdenAdvanced hepatocellular carcinomaFirst-line regimenReal-world studyCheckpoint inhibitorsTumor burdenSystemic treatmentAtezolizumabBevacizumabRetrospective studyLenvatinib