2024
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 eventsProofreading 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.Peer-Reviewed Original ResearchState-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.Peer-Reviewed Original ResearchInconsistencies 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.Peer-Reviewed Original ResearchFRailty 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 heterogeneityCombining chemotherapy, trastuzumab, and immune-checkpoint inhibitors in HER2-positive gastro-oesophageal cancer
Smyth E, Sundar R. Combining chemotherapy, trastuzumab, and immune-checkpoint inhibitors in HER2-positive gastro-oesophageal cancer. The Lancet 2023, 402: 2168-2170. PMID: 37871605, DOI: 10.1016/s0140-6736(23)02296-1.Peer-Reviewed Original ResearchCOVID-19 Severity and Waning Immunity After up to 4 mRNA Vaccine Doses in 73 608 Patients With Cancer and 621 475 Matched Controls in Singapore
Tan W, Tan J, Lim J, Tan R, Bin Lee A, Leong F, Lee S, Chai L, Tan T, Bin Abdul Malek M, Ong B, Lye D, Chiew C, Chng W, Lim S, Bharwani L, Tan I, Sundar R, Tan K. COVID-19 Severity and Waning Immunity After up to 4 mRNA Vaccine Doses in 73 608 Patients With Cancer and 621 475 Matched Controls in Singapore. JAMA Oncology 2023, 9: 1221-1229. PMID: 37440245, PMCID: PMC10346511, DOI: 10.1001/jamaoncol.2023.2271.Peer-Reviewed Original ResearchConceptsIncidence rate ratiosCancer survivorsVaccine doseSevere diseaseCohort studyTreated patientsProspective multicenter observational cohort studyCompeting-risk regression analysisMulticenter observational cohort studyMatched controlsVaccine efficacyVaccine effectivenessRisk of poor outcomesWaning of vaccine effectivenessSevere COVID-19 disease outcomesMRNA vaccine doseRisk of deathObservational cohort studyMRNA-based vaccinesSocioeconomic statusSARS-CoV-2 DeltaRate ratiosCOVID-19 hospitalizationIncidence rateOmicron waveEvidence on Effectiveness of Immune Checkpoint Inhibitors in Patients With Advanced Esophageal Squamous Cell Carcinoma—Reply
Zhao J, Pietrantonio F, Sundar R. Evidence on Effectiveness of Immune Checkpoint Inhibitors in Patients With Advanced Esophageal Squamous Cell Carcinoma—Reply. JAMA Oncology 2023, 9: 1005-1006. PMID: 37166787, DOI: 10.1001/jamaoncol.2023.0975.Peer-Reviewed Original ResearchEffects of prior therapies on outcomes with trifluridine/tipiracil in patients with metastatic gastric/gastroesophageal junction cancer in a randomized phase III trial (TAGS)
Shitara K, George B, Taieb J, Sundar R, Fakih M, Makris L, Benhadji K, Ghidini M. Effects of prior therapies on outcomes with trifluridine/tipiracil in patients with metastatic gastric/gastroesophageal junction cancer in a randomized phase III trial (TAGS). Journal Of Cancer Research And Clinical Oncology 2023, 149: 9361-9374. PMID: 37213030, PMCID: PMC10374776, DOI: 10.1007/s00432-023-04813-z.Peer-Reviewed Original ResearchConceptsProgression-free survivalGastric/gastroesophageal junction cancerJunction cancerSurvival benefitSafety profileEastern Cooperative Oncology Group performance statusRandomized phase III trialAssociated with survival benefitMedian overall survivalPhase III trialsPost hoc exploratory analysisLater-lineTrifluridine/tipiracil treatmentHematologic toxicityPrior therapyMedian overallOverall survivalIII trialsPlacebo armPerformance statusResultsBaseline characteristicsMedian timeRamucirumabTherapy patternsClinical trialsArtificial Intelligence in Clinical Oncology: From Data to Digital Pathology and Treatment.
Senthil Kumar K, Miskovic V, Blasiak A, Sundar R, Pedrocchi A, Pearson A, Prelaj A, Ho D. Artificial Intelligence in Clinical Oncology: From Data to Digital Pathology and Treatment. American Society Of Clinical Oncology Educational Book 2023, 43: e390084. PMID: 37235822, DOI: 10.1200/edbk_390084.Peer-Reviewed Original ResearchConceptsDigital pathologyClinical oncology communityArtificial intelligence (AI)-based applicationsClinical oncologyDeployment of AIDomain of digital pathologyTreatment selectionOncology communityBiomarker developmentArtificial intelligenceImprove patient outcomesAI innovationRegimen optimizationModulating dosesStandard histologyPatient outcomesA Phase I, First-in-Human Study of PRL3-zumab in Advanced, Refractory Solid Tumors and Hematological Malignancies
Chee C, Ooi M, Lee S, Sundar R, Heong V, Yong W, Ng C, Wong A, Lim J, Tan D, Soo R, Tan J, Yang S, Thura M, Al-Aidaroos A, Chng W, Zeng Q, Goh B. A Phase I, First-in-Human Study of PRL3-zumab in Advanced, Refractory Solid Tumors and Hematological Malignancies. Targeted Oncology 2023, 18: 391-402. PMID: 37060431, PMCID: PMC10192144, DOI: 10.1007/s11523-023-00962-w.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaAdvanced solid tumorsFirst-in-human studyEuropean Leukemia NetworkSolid tumorsHematologic malignanciesTreatment-emergent adverse eventsHuman antibodiesDose-escalation cohortsDose-limiting toxicityGrade 2 vomitingPRL-3Refractory solid tumorsResponse Evaluation CriteriaSolid tumor patientsDose-expansion cohortReduced tumor growthFirst-in-humanPhase IStable diseaseStoma outputEvaluation CriteriaMyeloid leukemiaPharmacodynamic relationshipsAdverse eventsControversies in upper GI oncology: first-line checkpoint inhibitor use in metastatic GEA: guided by PD-L1 CPS or not?
Petrillo A, Maron S, Sundar R. Controversies in upper GI oncology: first-line checkpoint inhibitor use in metastatic GEA: guided by PD-L1 CPS or not? ESMO Open 2023, 8: 101211. PMID: 37054477, PMCID: PMC10123152, DOI: 10.1016/j.esmoop.2023.101211.Peer-Reviewed Original ResearchComprehensive molecular phenotyping of ARID1A-deficient gastric cancer reveals pervasive epigenomic reprogramming and therapeutic opportunities
Xu C, Huang K, Law J, Chua J, Sheng T, Flores N, Pizzi M, Okabe A, Tan A, Zhu F, Kumar V, Lu X, Benitez A, Lian B, Ma H, Ho S, Ramnarayanan K, Anene-Nzelu C, Razavi-Mohseni M, Ghani S, Tay S, Ong X, Lee M, Guo Y, Ashktorab H, Smoot D, Li S, Skanderup A, Beer M, Foo R, Wong J, Sanghvi K, Yong W, Sundar R, Kaneda A, Prabhakar S, Mazur P, Ajani J, Yeoh K, So J, Tan P. Comprehensive molecular phenotyping of ARID1A-deficient gastric cancer reveals pervasive epigenomic reprogramming and therapeutic opportunities. Gut 2023, 72: 1651-1663. PMID: 36918265, DOI: 10.1136/gutjnl-2022-328332.Peer-Reviewed Original ResearchConceptsGastric cancerMolecular subtypesPromoter activityMutational signaturesProinflammatory tumor microenvironmentTumor microenvironmental changesMutated driver genesSingle-cell transcriptome profilingCTCF occupancyGC molecular subtypesChromatin profilingDistal enhancerRegulatory networksEpigenetic landscapeBRD4 bindingEpigenomic reprogrammingEpigenomic levelsTumor-intrinsicTumor inflammationTumor microenvironmentTherapeutic vulnerabilitiesTranscriptome profilingDriver genesNFkB inhibitorGene expressionClinical outcome and prognostic factors for Asian patients in Phase I clinical trials
Loh J, Wu J, Chieng J, Chan A, Yong W, Sundar R, Lee S, Wong A, Lim J, Tan D, Soo R, Goh B, Tai B, Chee C. Clinical outcome and prognostic factors for Asian patients in Phase I clinical trials. British Journal Of Cancer 2023, 128: 1514-1520. PMID: 36797357, PMCID: PMC10070409, DOI: 10.1038/s41416-023-02193-2.Peer-Reviewed Original ResearchConceptsNeutrophil-lymphocyte ratioRoyal Marsden HospitalPhase I studyPhase I clinical trialPoor ECOG statusPre-treated patientsPrimary tumor sitePhase I populationLonger-term survivalECOG statusPrognostic factorsPrognostic scoreRetrospective reviewTumor siteAsian patientsSolid tumorsClinical outcomesPoor prognosisBackgroundPatient selectionPrognostic abilityPrognostic modelPatientsPrognosisIncreased scoresScoresClinical relevance of PD-1 positive CD8 T-cells in gastric cancer
Choo J, Kua L, Soe M, Asuncion B, Tan B, Teo C, Tay R, So J, Shabbir A, Guowei K, Tan H, Chan G, Ma H, Ramachandran G, Lum J, Chee C, Sridharan S, Tan P, Sundar R, Yong W. Clinical relevance of PD-1 positive CD8 T-cells in gastric cancer. Gastric Cancer 2023, 26: 393-404. PMID: 36781556, PMCID: PMC10115710, DOI: 10.1007/s10120-023-01364-7.Peer-Reviewed Original ResearchConceptsCD8 T cellsPD-1+CD8+ T cellsT cellsTumor microenvironmentPD-1Overall survivalGastric cancerMultiplex immunohistochemistryT cell-inflamed tumor microenvironmentAssociated with improved OSIncreased PD-1 expressionClinical relevanceGranzyme-B expressionInflamed tumor microenvironmentPD-1 expressionInfluence overall survivalNK cell proportionTreated with immunotherapyPhase 2 trialAssociated with chemotherapyCox proportional hazards modelsProportional hazards modelImproved OSImmunotherapy sensitivityNK cellsImmune checkpoint inhibitor combinations—current and emerging strategies
Walsh R, Sundar R, Lim J. Immune checkpoint inhibitor combinations—current and emerging strategies. British Journal Of Cancer 2023, 128: 1415-1417. PMID: 36747017, PMCID: PMC10070427, DOI: 10.1038/s41416-023-02181-6.Peer-Reviewed Original Research