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, 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 markerIntegration 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 profiling
2024
Abstract 2759: Transcriptional intra-tumoral heterogeneity of putative therapeutic targets in colorectal cancer peritoneal metastases
Zhao J, Ong J, Chia D, Teo M, Tan Q, Ng G, Tan J, Ma H, Ong X, Tay S, Tan P, Sundar R. Abstract 2759: Transcriptional intra-tumoral heterogeneity of putative therapeutic targets in colorectal cancer peritoneal metastases. Cancer Research 2024, 84: 2759-2759. DOI: 10.1158/1538-7445.am2024-2759.Peer-Reviewed Original ResearchColorectal cancer peritoneal metastasesCRC PMPeritoneal metastasisColorectal cancerIntra-tumor heterogeneitySystemic regimensTherapeutic targetAmerican Association for Cancer Research annual meetingsPrognosis of peritoneal metastasisResistant to systemic chemotherapyPlasma-peritoneal barrierOncological surgical resectionColorectal cancer patientsSystemic chemotherapySurgical resectionPalliative surgerySystemic therapyAntineoplastic therapyPotential therapeutic targetExploratory laparotomyTranscoelomic metastasisPoor prognosisFFPE tissue samplesSynchronous PMPoor responseAbstract 1497: Humanized mouse model unveils niche conditioning in gastric cancer peritoneal metastasis
Zhao J, Chia D, Her Z, Ma H, Ong X, Tay S, So J, Chen Q, Tan P, Sundar R. Abstract 1497: Humanized mouse model unveils niche conditioning in gastric cancer peritoneal metastasis. Cancer Research 2024, 84: 1497-1497. DOI: 10.1158/1538-7445.am2024-1497.Peer-Reviewed Original ResearchHumanized mouse modelPeritoneal metastasisGastric cancer peritoneal metastasisPrimary tumorAdjacent peritoneumMouse modelTranscoelomic metastasisHost immune systemEpithelial mesenchymal transitionOrthotopic modelAmerican Association for Cancer Research annual meetingsGastric cancerNovel humanized mouse modelNSG modelImmune systemExpression of M2 macrophagesFunctional human cellsPeritoneal disseminationT-regsOrthotopic inoculationDendritic cellsNOD-SCIDImmune infiltrationPeritoneal samplesNormal peritoneumOncogenic aberrations in primary gastric cancer tumors to predict metachronous peritoneal metastasis.
Zhao J, Huang K, Chia D, Law J, Tan A, So J, Tan P, Sundar R. Oncogenic aberrations in primary gastric cancer tumors to predict metachronous peritoneal metastasis. Journal Of Clinical Oncology 2024, 42: 392-392. DOI: 10.1200/jco.2024.42.3_suppl.392.Peer-Reviewed Original ResearchPeritoneal metastasisPrimary tumorWhole-exome sequencingARID1A mutationsGastric cancerMedian follow-up durationGS tumorsPrimary tumors of patientsMetachronous peritoneal metastasesAssociated with PMFollow-up durationGastric cancer tumorsPoor survival outcomesPrimary GC tumorsMetachronous PMAdvanced tumorsCDH1 mutationsSurgical resectionOncogenic aberrationsSurvival outcomesClinical outcomesPoor prognosisFollowed-upProspective cohortRHOA mutationsUnveiling the prognostic significance of malignant ascites in advanced gastrointestinal cancers: a marker of peritoneal carcinomatosis burden
Provenzano L, Gwee Y, Conca V, Lonardi S, Bozzarelli S, Tamburini E, Passardi A, Zaniboni A, Tosi F, Aprile G, Nasca V, Boccaccino A, Ambrosini M, Vetere G, Carullo M, Guaglio M, Battaglia L, Zhao J, Chia D, Yong W, Tan P, So J, Kim G, Shabbir A, Ong C, Casella F, Cremolini C, Bencivenga M, Sundar R, Pietrantonio F. Unveiling the prognostic significance of malignant ascites in advanced gastrointestinal cancers: a marker of peritoneal carcinomatosis burden. Therapeutic Advances In Medical Oncology 2024, 16: 17588359241289517. PMID: 39502404, PMCID: PMC11536604, DOI: 10.1177/17588359241289517.Peer-Reviewed Original ResearchMetastatic colorectal cancerMetastatic gastric cancerMetastatic gastric cancer patientsPeritoneal metastasisMalignant ascitesAdvanced gastrointestinal cancerSurvival outcomesMedian peritoneal cancer index scoreGastrointestinal cancerPeritoneal cancer index scoreGastric cancerMetastatic colorectal cancer patientsSubgroup of patientsMedian OSProgression-freeOverall survivalSystemic therapyPrognostic significancePatient survivalAscites groupPoor outcomeRetrospective analysisColorectal cancerRandomized trialsAscites
2023
1550P Evaluating the novel combination of pressurized intraperitoneal aerosol chemotherapy-oxaliplatin (PIPAC-OX) as an immunomodulator in combination with systemic nivolumab for gastric cancer peritoneal metastases
Sundar R, Chia D, Ceelen W, Chia C, Kim G, Shabbir A, Willaert W, Ong J, Wong J, Seo C, Tan H, Callebout E, Geboes K, Ng M, Lum J, Leow W, Selvarajan S, Hoorens A, Yong W, So J. 1550P Evaluating the novel combination of pressurized intraperitoneal aerosol chemotherapy-oxaliplatin (PIPAC-OX) as an immunomodulator in combination with systemic nivolumab for gastric cancer peritoneal metastases. Annals Of Oncology 2023, 34: s869. DOI: 10.1016/j.annonc.2023.09.1462.Peer-Reviewed Original ResearchMalignant ascites as a marker of peritoneal carcinomatosis burden in patients with colorectal and gastroesophageal cancer.
Gwee Y, Chia D, Provenzano L, Lonardi S, Conca V, Cremolini C, Yong W, Tan P, So J, Kim G, Shabbir A, Ong J, Pietrantonio F, Sundar R. Malignant ascites as a marker of peritoneal carcinomatosis burden in patients with colorectal and gastroesophageal cancer. Journal Of Clinical Oncology 2023, 41: 455-455. DOI: 10.1200/jco.2023.41.4_suppl.455.Peer-Reviewed Original ResearchPeritoneal cancer indexPresence of malignant ascitesPeritoneal metastasisMalignant ascitesColorectal cancer patientsGastric cancerColorectal cancerOverall survivalGastrointestinal malignanciesPoor survivalCohort of gastric cancerMedian peritoneal cancer indexPeritoneal cancer index scoreFirst-line systemic treatmentResistant to systemic therapyMetastatic gastrointestinal malignanciesMedian overall survivalStage IV diseaseMetastatic CRC patientsAbsence of ascitesClinico-pathological dataPoor survival outcomesTertiary oncology centerStudy of patientsRandomized clinical trials
2022
Outcomes of a Phase II Study of Intraperitoneal Paclitaxel Plus Systemic Capecitabine and Oxaliplatin (XELOX) for Gastric Cancer with Peritoneal Metastases
Chia D, Sundar R, Kim G, Ang J, Shabbir A, So J, Yong W. Outcomes of a Phase II Study of Intraperitoneal Paclitaxel Plus Systemic Capecitabine and Oxaliplatin (XELOX) for Gastric Cancer with Peritoneal Metastases. Annals Of Surgical Oncology 2022, 30: 1889-1890. PMID: 36564654, DOI: 10.1245/s10434-022-12877-3.Peer-Reviewed Original ResearchASO Visual Abstract: Outcomes of a Phase II Study of Intraperitoneal Paclitaxel Plus Systemic Capecitabine and Oxaliplatin (XELOX) for Gastric Cancer with Peritoneal Metastases
Chia D, Sundar R, Kim G, Ang J, Lum J, Nga M, Goh G, Seet J, Chee C, Tan H, Ho J, Ngoi N, Lee M, Muthu V, Chan G, Pang A, Ang Y, Choo J, Lim J, Teh J, Lwin A, Soon Y, Shabbir A, So J, Yong W. ASO Visual Abstract: Outcomes of a Phase II Study of Intraperitoneal Paclitaxel Plus Systemic Capecitabine and Oxaliplatin (XELOX) for Gastric Cancer with Peritoneal Metastases. Annals Of Surgical Oncology 2022, 29: 8608-8609. DOI: 10.1245/s10434-022-12043-9.Peer-Reviewed Original ResearchASO Author Reflections: Combination Intra-Peritoneal and Systemic Chemotherapy for Gastric Cancer with Peritoneal Metastases
Chia D, Ang J, Sundar R, Kim G, Shabbir A, So J, Yong W. ASO Author Reflections: Combination Intra-Peritoneal and Systemic Chemotherapy for Gastric Cancer with Peritoneal Metastases. Annals Of Surgical Oncology 2022, 29: 8606-8607. PMID: 36192514, DOI: 10.1245/s10434-022-12102-1.Peer-Reviewed Original ResearchOutcomes of a Phase II Study of Intraperitoneal Paclitaxel plus Systemic Capecitabine and Oxaliplatin (XELOX) for Gastric Cancer with Peritoneal Metastases
Chia D, Sundar R, Kim G, Ang J, Lum J, Nga M, Goh G, Seet J, Chee C, Tan H, Ho J, Ngoi N, Lee M, Muthu V, Chan G, Pang A, Ang Y, Choo J, Lim J, Teh J, Lwin A, Soon Y, Shabbir A, So J, Yong W. Outcomes of a Phase II Study of Intraperitoneal Paclitaxel plus Systemic Capecitabine and Oxaliplatin (XELOX) for Gastric Cancer with Peritoneal Metastases. Annals Of Surgical Oncology 2022, 29: 8597-8605. PMID: 36070113, DOI: 10.1245/s10434-022-11998-z.Peer-Reviewed Original ResearchConceptsGastric cancer peritoneal metastasisIP-PTXConversion surgeryIntraperitoneal paclitaxelMedian OSSystemic chemotherapyPeritoneal metastasisSC groupConversion to negative cytologyResultsThe median OSProgression-free survivalPhase II studyMethodsForty-four patientsIntravenous oxaliplatinMedian PFSOral capecitabineSystemic capecitabineExtraperitoneal metastasesNegative cytologyPeritoneal diseaseOverall survivalPerformance statusPrimary endpointSecondary endpointsIP cohortResistance to systemic immune checkpoint inhibition in the peritoneal niche
Chia D, Gwee Y, Sundar R. Resistance to systemic immune checkpoint inhibition in the peritoneal niche. Journal For ImmunoTherapy Of Cancer 2022, 10: e004749. PMID: 35728873, PMCID: PMC9214396, DOI: 10.1136/jitc-2022-004749.Commentaries, Editorials and LettersConceptsImmune checkpoint inhibitionResistance to immune checkpoint inhibitionPeritoneal metastasisCheckpoint inhibitionMetastatic nicheResponse to ICIImmune checkpoint inhibition therapySensitive to immune checkpoint inhibitionIntrinsic tumor factorsPresence of ascitesDeficient mismatch repairPeritoneal microenvironmentTumor factorsMalignant ascitesPrimary resistanceClinical entityTherapeutic optionsMicrosatellite instable tumorsPeritoneal cavityGastrointestinal cancerParacrine factorsAscitesConcurrent ascitesPatientsInstable tumors
2021
Outcomes of a phase II study of intraperitoneal paclitaxel plus systemic capecitabine and oxaliplatin (XELOX) for gastric cancer with peritoneal metastases.
Chia D, Sundar R, Kim G, Ang J, Lum J, Nga M, Cheng Ean C, Tan H, Ho J, Ngoi N, Lee M, Muthu V, Chan G, Pang A, Ang Y, Choo J, Lim J, Shabbir A, Yong W, So J. Outcomes of a phase II study of intraperitoneal paclitaxel plus systemic capecitabine and oxaliplatin (XELOX) for gastric cancer with peritoneal metastases. Journal Of Clinical Oncology 2021, 39: 165-165. DOI: 10.1200/jco.2021.39.3_suppl.165.Peer-Reviewed Original ResearchIP paclitaxelSystemic chemotherapyPeritoneal metastasisConversion surgeryGastric cancerMedian OSSC groupProspective phase 2 trialIP groupProgression-free survivalPhase II studyBaseline performance statusWound-related complicationsStandard-of-careGCPM patientsIntraperitoneal paclitaxelIV oxaliplatinMedian PFSSystemic capecitabineExtraperitoneal metastasesNegative cytologyOverall survivalPerformance statusPrimary endpointSecondary endpoints
2020
Radiological evaluation of malignant pleural mesothelioma - defining distant metastatic disease
Collins D, Sundar R, Constantinidou A, Dolling D, Yap T, Popat S, O’Brien M, Banerji U, de Bono J, Lopez J, Tunariu N, Minchom A. Radiological evaluation of malignant pleural mesothelioma - defining distant metastatic disease. BMC Cancer 2020, 20: 1210. PMID: 33298007, PMCID: PMC7724793, DOI: 10.1186/s12885-020-07662-y.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBone NeoplasmsBrain NeoplasmsClinical Trials, Phase I as TopicCombined Modality TherapyDiagnostic ImagingFemaleHumansKaplan-Meier EstimateLiver NeoplasmsLung NeoplasmsMaleMesothelioma, MalignantMiddle AgedPeritoneal NeoplasmsPleural NeoplasmsProportional Hazards ModelsRetrospective StudiesConceptsDistant metastasisPeritoneal metastasisMPM patientsTreatment paradigmCohort of MPM patientsFrequency of distant metastasesIncidence of bone metastasesPresence of distant metastasesPattern of metastatic spreadDistant metastatic diseaseDistant metastatic disseminationBackgroundMalignant pleural mesotheliomaPresence of symptomsIncidence of boneMetastatic diseaseMetastatic sitesBone metastasesOverall survivalMetastatic spreadContralateral lungPrognostic implicationsMetastatic disseminationRadiological investigationsRetrospective studyPleural mesotheliomaPIPAC-OX: A Phase I Study of Oxaliplatin-Based Pressurized Intraperitoneal Aerosol Chemotherapy in Patients with Peritoneal Metastases
Kim G, Tan L, Sundar R, Lieske B, Chee C, Ho J, Shabbir A, Babak M, Ang W, Goh B, Yong W, Wang L, So J. PIPAC-OX: A Phase I Study of Oxaliplatin-Based Pressurized Intraperitoneal Aerosol Chemotherapy in Patients with Peritoneal Metastases. Clinical Cancer Research 2020, 27: 1875-1881. PMID: 33148667, DOI: 10.1158/1078-0432.ccr-20-2152.Peer-Reviewed Original ResearchConceptsPressurized intraperitoneal aerosol chemotherapyPressurized intraperitoneal aerosolized chemotherapy proceduresPeritoneal cancer indexPeritoneal metastasisAerosol chemotherapyMedian peritoneal cancer indexPeritoneal Regression Grading ScoreRecommended phase II doseGrade 2 pancreatitisHighest-dose cohortPhase II doseDose-limiting toxicityFirst-line chemotherapyDose-escalation designTreat peritoneal metastasisPhase I studyImprove drug distributionII doseStable diseaseCancer indexMedian ageCohort expansionGastrointestinal tumorsPharmacokinetic analysisDose levelsSafety and tolerability of oxaliplatin based pressurized intraperitoneal aerosol chemotherapy (PIPAC) for patients with peritoneal carcinomatosis: A phase I dose-finding study in Asian patients.
Sundar R, Kim G, Tan H, Wang L, Chue K, Tai C, Teo S, Jang C, Chee C, Lieske B, Chee C, Shabbir A, So J, Yong W. Safety and tolerability of oxaliplatin based pressurized intraperitoneal aerosol chemotherapy (PIPAC) for patients with peritoneal carcinomatosis: A phase I dose-finding study in Asian patients. Journal Of Clinical Oncology 2020, 38: 360-360. DOI: 10.1200/jco.2020.38.4_suppl.360.Peer-Reviewed Original ResearchPressurized intraperitoneal aerosol chemotherapyPeritoneal carcinomatosis indexDose-limiting toxicityHyperthermic intraperitoneal chemotherapyPhase 1 studyDose cohortsAsian patientsDose-escalation phase 1 studyPIPAC administrationsGrade 3 adverse eventsMedian peritoneal carcinomatosis indexPeritoneal carcinomatosis index scoreRecommended phase 2 dosePressurized intraperitoneal aerosolized chemotherapy proceduresFailure of standard therapyPhase I dose-finding studyGastrointestinal primary tumorsHighest dose cohortPhase 2 doseDose-escalation studyIntraperitoneal chemotherapyPeritoneal carcinomatosisEscalation studyPeritoneal metastasisOxaliplatin chemotherapy
2018
Extended outcomes of intraperitoneal and systemic chemotherapy for gastric cancer with peritoneal metastases.
Chan D, Syn N, Neogh C, Phua N, . E, Ho J, Sundar R, Tan C, Ngoi N, Chee C, Shabbir A, So J, Yong W. Extended outcomes of intraperitoneal and systemic chemotherapy for gastric cancer with peritoneal metastases. Journal Of Clinical Oncology 2018, 36: 125-125. DOI: 10.1200/jco.2018.36.4_suppl.125.Peer-Reviewed Original ResearchConversion gastrectomyPeritoneal metastasisGastric cancerIP paclitaxelMedian OSPeritoneal cytologyDay 1Positive peritoneal washing cytologyTreated with 8 cyclesSurvival rateNegative peritoneal cytologyPeritoneal washing cytologyRecurrent gastric adenocarcinomaHand-foot syndromeMedian follow-upOverall survival rateWeek of restTime of reportingMedian no.Tumor perforationSystemic chemotherapyFebrile neutropeniaIncreasing drug concentrationPeritoneal diseasePeritoneal dissemination