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 eventsEffectiveness 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-threeProofreading the way: immune checkpoint inhibitors in polymerase ε/polymerase δ (POLE/POLD1)-altered colorectal cancer
Cecchini M, Sundar R. Proofreading the way: immune checkpoint inhibitors in polymerase ε/polymerase δ (POLE/POLD1)-altered colorectal cancer. Annals Of Oncology 2024, 35: 582-584. PMID: 38910015, DOI: 10.1016/j.annonc.2024.04.006.Commentaries, Editorials and LettersState-of-the-Art Advancements in Gastroesophageal Cancer Treatment: Harnessing Biomarkers for Precision Care.
Balmaceda N, Petrillo A, Krishnan M, Zhao J, Kim S, Klute K, Sundar R. State-of-the-Art Advancements in Gastroesophageal Cancer Treatment: Harnessing Biomarkers for Precision Care. American Society Of Clinical Oncology Educational Book 2024, 44: e431060. PMID: 38771996, DOI: 10.1200/edbk_431060.Peer-Reviewed Original ResearchConceptsGastroesophageal cancerIntegration of immune checkpoint inhibitorsChimeric antigen receptor T cellsImmune checkpoint inhibitorsMetastatic gastroesophageal cancerPD-1 inhibitorsAdoptive cell therapyImmunotherapy-based approachesResectable gastroesophageal cancerAntibody-drug conjugatesCheckpoint inhibitorsPD-1Perioperative chemotherapyTargeted therapyT cellsTreatment paradigmFGFR2 inhibitorsCell therapyClinical challengeBispecific antibodiesImprove outcomesCancer treatmentReduced toxicityTherapyInhibitorsPushing the Frontiers of Cancer Research: Highlights from the Frontiers in Cancer Science Conference 2023.
Lee Y, Chen L, Chew V, Chow E, Deng L, Hunziker W, Lee A, Leong G, Ngeow J, Pervaiz S, Sabapathy K, Skanderup A, Sundar R, Tay Y, Virshup D, Wong S, Tergaonkar V, Tam W. Pushing the Frontiers of Cancer Research: Highlights from the Frontiers in Cancer Science Conference 2023. Cancer Research 2024, 84: 1195-1198. PMID: 38616656, DOI: 10.1158/0008-5472.can-24-0721.Commentaries, Editorials and LettersInconsistencies in the predictive value of PD-L1 in metastatic gastroesophageal cancer
Sundar R, Smyth E. Inconsistencies in the predictive value of PD-L1 in metastatic gastroesophageal cancer. The Lancet Gastroenterology & Hepatology 2024, 9: 495-497. PMID: 38492581, DOI: 10.1016/s2468-1253(24)00043-8.Commentaries, Editorials and LettersFRailty in Australian patients admitted to Intensive care unit after eLective CANCER-related SURGery: a retrospective multicentre cohort study (FRAIL-CANCER-SURG study)
Ling R, Ueno R, Alamgeer M, Sundararajan K, Sundar R, Bailey M, Pilcher D, Subramaniam A. FRailty in Australian patients admitted to Intensive care unit after eLective CANCER-related SURGery: a retrospective multicentre cohort study (FRAIL-CANCER-SURG study). British Journal Of Anaesthesia 2024, 132: 695-706. PMID: 38378383, DOI: 10.1016/j.bja.2024.01.020.Peer-Reviewed Original ResearchConceptsElective surgeryCohort studyMulticentre retrospective cohort studyRetrospective multicentre cohort studyPatients admitted to intensive care unitsAssociated with poor outcomesAssociated with similar effectsAssociated with lower survivalCancer-related surgeryMulticentre cohort studyRetrospective cohort studyLong-term outcomesIntensive care unitAssociated with mortalityPoor outcomeFollow-upICU admissionPrimary outcomeCare unitSurgeryPatientsSurvival informationCancerFrailtyICUEfficacy and Safety of Trifluridine/Tipiracil-Containing Combinations in Colorectal Cancer and Other Advanced Solid Tumors: A Systematic Review
Shitara K, Falcone A, Fakih M, George B, Sundar R, Ranjan S, Van Cutsem E. Efficacy and Safety of Trifluridine/Tipiracil-Containing Combinations in Colorectal Cancer and Other Advanced Solid Tumors: A Systematic Review. The Oncologist 2024, 29: e601-e615. PMID: 38366864, PMCID: PMC11067808, DOI: 10.1093/oncolo/oyae007.Peer-Reviewed Original ResearchConceptsMetastatic colorectal cancerRefractory metastatic colorectal cancerAdverse eventsDiscontinuation rate due to adverse eventsColorectal cancerChemorefractory metastatic colorectal cancerSafety outcomesMedian overall survivalSafety of FTD/TPIProgression-free survivalAdvanced solid tumorsAssociated with improved outcomesEarly-phase studiesSystematic reviewOverall survivalFTD/TPIRetrospective studySolid tumorsBevacizumabClinical efficacyTargeted agentsTumor typesAntineoplastic agentsAdvanced cancerImprove outcomes
2023
Frailty and long-term survival among patients in Australian intensive care units with metastatic cancer (FRAIL-CANCER study): a retrospective registry-based cohort study
Alamgeer M, Ling R, Ueno R, Sundararajan K, Sundar R, Pilcher D, Subramaniam A. Frailty and long-term survival among patients in Australian intensive care units with metastatic cancer (FRAIL-CANCER study): a retrospective registry-based cohort study. The Lancet Healthy Longevity 2023, 4: e675-e684. PMID: 38042160, DOI: 10.1016/s2666-7568(23)00209-x.Peer-Reviewed Original ResearchConceptsIntensive care unitRegistry-based cohort studyLong-term survivalAustralian intensive care unitsRetrospective registry-based cohort studyMetastatic cancerAssociated with shorter survival timeEffect of frailtyClinical Frailty ScaleShorter survival timeSurvival timeCohort studyAssociated with poor long-term survivalCare unitPoor long-term survivalIntensive care unit admissionTime-limited trialsCandidacy of patientsCox proportional hazards regression modelsRobust sandwich variance estimatorProportion of patientsProportional hazards regression modelsHazards regression modelsImpact of frailtyOverall survivalSpatiotemporal genomic profiling of intestinal metaplasia reveals clonal dynamics of gastric cancer progression
Huang K, Ma H, Chong R, Uchihara T, Lian B, Zhu F, Sheng T, Srivastava S, Tay S, Sundar R, Tan A, Ong X, Lee M, Ho S, Lesluyes T, Ashktorab H, Smoot D, Van Loo P, Chua J, Ramnarayanan K, Lau L, Gotoda T, Kim H, Ang T, Khor C, Lee J, Tsao S, Yang W, Teh M, Chung H, So J, Yeoh K, Tan P, Consortium S. Spatiotemporal genomic profiling of intestinal metaplasia reveals clonal dynamics of gastric cancer progression. Cancer Cell 2023, 41: 2019-2037.e8. PMID: 37890493, PMCID: PMC10729843, DOI: 10.1016/j.ccell.2023.10.004.Peer-Reviewed Original ResearchConceptsIntestinal metaplasiaProspective 10-year studyPre-malignant conditionChromatin regulationGastric cancer progressionMicrobial communitiesClinical-only modelClinical-genomic modelsCellular compartmentsIntestinal homeostasisMicrobial dysbiosisTranscriptome profilingDriver genesARID1A mutationsDiverse pathwaysIM patientsClonal dynamicsGenomic profilingSingle-cellEarly malignancyGC riskCell typesGastric cancerCancer progressionLineage heterogeneity