Raghav Sundar, MD, PhD
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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, 167: 1384-1398.e4. 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 trialUFT
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