2024
Proofreading 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 ResearchA single arm phase 2 clinical trial of YIV-906 with neoadjuvant concurrent chemo-radiation therapy in patients with locally advanced rectal cancer
Verma N, Johung K, Kortmansky J, Zaheer W, Lacy J, Cecchini M, Stein S, Cheng Y, Lam W, Liu S, Reddy V, Hochster H, Higgins S. A single arm phase 2 clinical trial of YIV-906 with neoadjuvant concurrent chemo-radiation therapy in patients with locally advanced rectal cancer. Journal Of Gastrointestinal Oncology 2024, 15: 1050-1059. PMID: 38989411, PMCID: PMC11231844, DOI: 10.21037/jgo-24-23.Peer-Reviewed Original ResearchAuthor Correction: Mutational signature-based identification of DNA repair deficient gastroesophageal adenocarcinomas for therapeutic targeting
Prosz A, Sahgal P, Huffman B, Sztupinszki Z, Morris C, Chen D, Börcsök J, Diossy M, Tisza V, Spisak S, Likasitwatanakul P, Rusz O, Csabai I, Cecchini M, Baca Y, Elliott A, Enzinger P, Singh H, Ubellaker J, Lazaro J, Cleary J, Szallasi Z, Sethi N. Author Correction: Mutational signature-based identification of DNA repair deficient gastroesophageal adenocarcinomas for therapeutic targeting. Npj Precision Oncology 2024, 8: 98. PMID: 38710943, PMCID: PMC11074298, DOI: 10.1038/s41698-024-00587-w.Peer-Reviewed Original ResearchMutational signature-based identification of DNA repair deficient gastroesophageal adenocarcinomas for therapeutic targeting
Prosz A, Sahgal P, Huffman B, Sztupinszki Z, Morris C, Chen D, Börcsök J, Diossy M, Tisza V, Spisak S, Likasitwatanakul P, Rusz O, Csabai I, Cecchini M, Baca Y, Elliott A, Enzinger P, Singh H, Ubellaker J, Lazaro J, Cleary J, Szallasi Z, Sethi N. Mutational signature-based identification of DNA repair deficient gastroesophageal adenocarcinomas for therapeutic targeting. Npj Precision Oncology 2024, 8: 87. PMID: 38589664, PMCID: PMC11001913, DOI: 10.1038/s41698-024-00561-6.Peer-Reviewed Original ResearchNucleotide excision repairGastric cancer cell linesNucleotide excision repair-deficientPlatinum chemotherapyHR deficiencyCancer cell linesPARP inhibitorsHomologous recombinationGenome sequence dataSensitivity to platinum chemotherapySingle-cell RNA sequencingCell linesHR-deficient cancersDNA repair pathwaysSensitivity to cisplatinRad51 foci assaysMutational signature analysisSequence dataGenomic featuresWhole exomeInduce apoptosisRNA sequencingGastroesophageal adenocarcinomaRepair pathwaysHRD score- Michael Cecchini MD, Ronald R. Salem MD, Marie Robert MD, Suzanne Czerniak MD PhD, Ondrej Blaha Phd, Daniel Zelterman PhD, Moein Rajaei PhD, Jeffrey P. Townsend PhD, Guoping Cai MD MS, Sumedha Chowdhury, Deanne Yugawa BS, Robert Tseng BS, Carlos Mejia Arbelaez MD, Jingjing Jiao MD, Kenneth Shroyer MD PhD, Jaykumar Thumar MBBS, Jeremy Kortmansky MD, Wajih Zaheer MD, Neal Fischbach MD, Justin Persico MD, Stacey Stein MD, Sajid A. Khan MD, Charles Cha MD, Kevin G. Billingsley MD MBA, John W. Kunstman MD MHS, Kimberly L. Johung MD MHS, Christina Wiess BA, Mandar D. Muzumdar MD PhD, Erik Spickard PhD, Vasily N. Aushev PhD, George Laliotis MD MHA MPH MBA, Adham Jurdi MD, Minetta C. Liu MD, Luisa Escobar-Hoyos MsC PhD, Jill Lacy MD. The Perioperative Modified FOLFIRINOX Clinical Trial for Resectable Pancreatic Cancer. JAMA Oncology [Accepted 2/2/2024 ].Peer-Reviewed Original Research
2023
NCI10066: a Phase 1/2 study of olaparib in combination with ramucirumab in previously treated metastatic gastric and gastroesophageal junction adenocarcinoma
Cecchini M, Cleary J, Shyr Y, Chao J, Uboha N, Cho M, Shields A, Pant S, Goff L, Spencer K, Kim E, Stein S, Kortmansky J, Canosa S, Sklar J, Swisher E, Radke M, Ivy P, Boerner S, Durecki D, Hsu C, LoRusso P, Lacy J. NCI10066: a Phase 1/2 study of olaparib in combination with ramucirumab in previously treated metastatic gastric and gastroesophageal junction adenocarcinoma. British Journal Of Cancer 2023, 130: 476-482. PMID: 38135713, PMCID: PMC10844282, DOI: 10.1038/s41416-023-02534-1.Peer-Reviewed Original ResearchRelative Burden of Cancer and Noncancer Mortality Among Long-Term Survivors of Breast, Prostate, and Colorectal Cancer in the US
Kc M, Fan J, Hyslop T, Hassan S, Cecchini M, Wang S, Silber A, Leapman M, Leeds I, Wheeler S, Spees L, Gross C, Lustberg M, Greenup R, Justice A, Oeffinger K, Dinan M. Relative Burden of Cancer and Noncancer Mortality Among Long-Term Survivors of Breast, Prostate, and Colorectal Cancer in the US. JAMA Network Open 2023, 6: e2323115. PMID: 37436746, PMCID: PMC10339147, DOI: 10.1001/jamanetworkopen.2023.23115.Peer-Reviewed Original ResearchConceptsLong-term survivorsCancer-specific mortalityColorectal cancerCancer cohortReceptor statusInitial diagnosisGleason scoreProstate cancerBreast cancerLong-term adult survivorsMedian cancer-specific survivalEnd Results cancer registryProstate-specific antigen levelRectal cancer cohortCancer-specific survivalStage III diseaseYear of diagnosisProgesterone receptor statusEstrogen receptor statusProportion of deathsSurvival time ratioEarly-stage cancerNononcologic outcomesIndex cancerLocalized diseaseQuantitative DNA Repair Biomarkers and Immune Profiling for Temozolomide and Olaparib in Metastatic Colorectal Cancer
Cecchini M, Zhang J, Wei W, Sklar J, Lacy J, Zhong M, Kong Y, Zhao H, DiPalermo J, Devine L, Stein S, Kortmansky J, Johung K, Bindra R, LoRusso P, Schalper K. Quantitative DNA Repair Biomarkers and Immune Profiling for Temozolomide and Olaparib in Metastatic Colorectal Cancer. Cancer Research Communications 2023, 3: 1132-1139. PMID: 37387791, PMCID: PMC10305782, DOI: 10.1158/2767-9764.crc-23-0045.Peer-Reviewed Original ResearchConceptsWhole-exome sequencingMGMT protein expressionColorectal cancerStable diseaseQuantitative immunofluorescenceT cellsProtein expressionPromoter hypermethylationLow MGMT protein expressionPARP inhibitorsRadiographic tumor regressionMetastatic colorectal cancerAdvanced colorectal cancerPretreatment tumor biopsiesEffector T cellsTumor-infiltrating lymphocytesMGMT proteinDNA repair biomarkersBaseline CD8Eligible patientsIncreased CD8Methylguanine-DNA methyltransferaseObjective responseProgressive diseaseImmune markersNCI 7977: A Phase I Dose-Escalation Study of Intermittent Oral ABT-888 (Veliparib) Plus Intravenous Irinotecan Administered in Patients with Advanced Solid Tumors
Cecchini M, Walther Z, Wei W, Hafez N, Pilat M, Boerner S, Durecki D, Eder J, Schalper K, Chen A, LoRusso P. NCI 7977: A Phase I Dose-Escalation Study of Intermittent Oral ABT-888 (Veliparib) Plus Intravenous Irinotecan Administered in Patients with Advanced Solid Tumors. Cancer Research Communications 2023, 3: 1113-1117. PMID: 37377610, PMCID: PMC10292219, DOI: 10.1158/2767-9764.crc-22-0485.Peer-Reviewed Original ResearchConceptsDose-limiting toxicityHomologous recombination deficiencyPARP inhibitorsStable diseaseWeekly irinotecanObjective responseDay 1Day 3Solid tumorsPhase I dose-escalation studyTwice daily days 1I dose-escalation studyPhase I clinical trialDaily days 1Dose level 1Doses of veliparibGrade 3 neutropeniaMultiple-dose schedulesProgression-free survivalAdvanced solid tumorsDose-escalation studyEvaluable patientsNonoverlapping toxicitiesDose scheduleSystemic treatmentDeveloping a definition of immune exclusion in cancer: results of a modified Delphi workshop
Clifton G, Rothenberg M, Ascierto P, Begley G, Cecchini M, Eder J, Ghiringhelli F, Italiano A, Kochetkova M, Li R, Mechta-Grigoriou F, Pai S, Provenzano P, Puré E, Ribas A, Schalper K, Fridman W. Developing a definition of immune exclusion in cancer: results of a modified Delphi workshop. Journal For ImmunoTherapy Of Cancer 2023, 11: e006773. PMID: 37290925, PMCID: PMC10254706, DOI: 10.1136/jitc-2023-006773.Peer-Reviewed Original ResearchConceptsImmune exclusionTumor microenvironmentCheckpoint inhibitorsImmune checkpoint inhibitorsMinority of patientsT cell infiltrationPoor clinical outcomeImmune regulatory pathwaysEffective treatment approachDevelopment of treatmentsVariety of cancersLack of responseCheckpoint therapyImmune profileClinical outcomesClinical benefitPatient outcomesCancer expertsCancer histologyT cellsConsensus definitionTreatment approachesCancer typesRound questionnaireDelphi processPre-operative chemoradiotherapy with or without induction chemotherapy for operable locally-advanced esophageal cancer
Peters G, Talcott W, Peters N, Dhanasopan A, Lacy J, Cecchini M, Kortmansky J, Stein S, Lattanzi S, Park H, Boffa D, Johung K, Jethwa K. Pre-operative chemoradiotherapy with or without induction chemotherapy for operable locally-advanced esophageal cancer. Journal Of Gastrointestinal Oncology 2023, 14: 1181-1192. PMID: 37435226, PMCID: PMC10331751, DOI: 10.21037/jgo-22-1005.Peer-Reviewed Original ResearchProgression-free survivalMedian progression-free survivalOverall survivalIC-CRTInduction chemotherapySingle-institution retrospective cohort studyPre-operative chemoradiotherapyAdvanced esophageal cancerAdvanced esophageal carcinomaPathologic complete responseRetrospective cohort studyKaplan-Meier methodSubset of patientsProportional hazards regressionCycles of inductionAdenocarcinoma histologyCRT cohortCohort studyComplete responsePathologic responseTreatment cohortsDistant metastasisHazards regressionEsophageal cancerEsophageal carcinoma
2022
Impact of early detection on cancer curability: A modified Delphi panel study
Schwartzberg L, Broder M, Ailawadhi S, Beltran H, Blakely L, Budd G, Carr L, Cecchini M, Cobb P, Kansal A, Kim A, Monk B, Wong D, Campos C, Yermilov I. Impact of early detection on cancer curability: A modified Delphi panel study. PLOS ONE 2022, 17: e0279227. PMID: 36542647, PMCID: PMC9770338, DOI: 10.1371/journal.pone.0279227.Peer-Reviewed Original ResearchConceptsBlood testsLikelihood of benefitCancer typesEarly detectionEarly cancer detectionSolid tumorsTotal cancer incidenceAmerican Joint CommitteeLow cure rateRAND/UCLAPotential clinical benefitCancer detectionDelphi panel studyLong cancerClinical benefitCure ratePotential benefitsCancer curabilityMost cancer typesCancer incidenceHigh curabilityJoint CommitteeTreat cancersExpert consensusPanel consensusMultiagent Chemotherapy Followed by Stereotactic Body Radiotherapy Versus Conventional Radiotherapy for Resected Pancreas Cancer
Mokhtech M, Miccio JA, Johung K, Cecchini M, Stein S, Narang AK, Herman JM, Kunstman J, Haddock MG, Anker CJ, Jabbour S, Hallemeier CL, Jethwa KR. Multiagent Chemotherapy Followed by Stereotactic Body Radiotherapy Versus Conventional Radiotherapy for Resected Pancreas Cancer. American Journal Of Clinical Oncology 2022, 45: 450-457. PMID: 36318696, DOI: 10.1097/coc.0000000000000947.Peer-Reviewed Original ResearchConceptsPancreatic ductal adenocarcinomaMultiagent chemotherapyPathologic complete responseStereotactic body radiotherapyOverall survivalComplete responseNonmetastatic pancreatic ductal adenocarcinomaNeoadjuvant multiagent chemotherapyMedian overall survivalNational Cancer DatabaseMargin-negative resectionTreatment of choiceDose/fractionSimilar ratesRegional lymphatic diseaseGy/5 fxNeoadjuvant radiotherapyCox analysisSurgical candidacyProspective evaluationPathologic outcomesBody radiotherapyPancreas cancerCancer DatabaseDuctal adenocarcinomaHybrid-control arm construction using historical trial data for an early-phase, randomized controlled trial in metastatic colorectal cancer
Li C, Ferro A, Mhatre SK, Lu D, Lawrance M, Li X, Li S, Allen S, Desai J, Fakih M, Cecchini M, Pedersen KS, Kim TY, Reyes-Rivera I, Segal NH, Lenain C. Hybrid-control arm construction using historical trial data for an early-phase, randomized controlled trial in metastatic colorectal cancer. Communications Medicine 2022, 2: 90. PMID: 35856081, PMCID: PMC9287310, DOI: 10.1038/s43856-022-00155-y.Peer-Reviewed Original ResearchMetastatic colorectal cancerExperimental armColorectal cancerMetastatic colorectal cancer (mCRC) trialsMetastatic colorectal cancer patientsPhase Ib/IITrial dataHistorical trial dataColorectal cancer trialsDisease control rateObjective response ratePhase 3 trialProgression-free survivalColorectal cancer patientsStandardized mortality ratioEarly phase trialsEarly phase clinical developmentLogistic regression modelsMultiple experimental armsPrimary endpointOverall survivalPrior linesEfficacy signalsSafety profileCombination therapyPD-1 Inhibition in First-Line Treatment of Advanced Esophageal Squamous Cell Carcinoma: More to Come on New Paradigm
Jill Lacy and Michael Cecchini. PD-1 Inhibition in First-Line Treatment of Advanced Esophageal Squamous Cell Carcinoma: More to Come on New Paradigm. The ASCO Post. May 25 2022.Commentaries, Editorials and LettersMaking National Cancer Institute–Designated Comprehensive Cancer Center Knowledge Accessible to Community Oncologists via an Online Tumor Board: Longitudinal Observational Study
Kalra M, Henry E, McCann K, Karuturi MS, Bustamante Alvarez JG, Parkes A, Wesolowski R, Wei M, Mougalian SS, Durm G, Qin A, Schonewolf C, Trivedi M, Armaghani AJ, Wilson FH, Iams WT, Turk AA, Vikas P, Cecchini M, Lubner S, Pathak P, Spencer K, Koshkin VS, Labriola MK, Marshall CH, Beckermann KE, , Sharifi MN, Bejjani AC, Hotchandani V, Housri S, Housri N. Making National Cancer Institute–Designated Comprehensive Cancer Center Knowledge Accessible to Community Oncologists via an Online Tumor Board: Longitudinal Observational Study. JMIR Cancer 2022, 8: e33859. PMID: 35588361, PMCID: PMC9164098, DOI: 10.2196/33859.Peer-Reviewed Original ResearchMutational signature profiling classifies subtypes of clinically different mismatch-repair-deficient tumours with a differential immunogenic response potential
Giner-Calabuig M, De Leon S, Wang J, Fehlmann TD, Ukaegbu C, Gibson J, Alustiza-Fernandez M, Pico MD, Alenda C, Herraiz M, Carrillo-Palau M, Salces I, Reyes J, Ortega SP, Obrador-Hevia A, Cecchini M, Syngal S, Stoffel E, Ellis NA, Sweasy J, Jover R, Llor X, Xicola RM. Mutational signature profiling classifies subtypes of clinically different mismatch-repair-deficient tumours with a differential immunogenic response potential. British Journal Of Cancer 2022, 126: 1595-1603. PMID: 35197584, PMCID: PMC9130322, DOI: 10.1038/s41416-022-01754-1.Peer-Reviewed Original ResearchConceptsLynch-like syndromeMMR-deficient tumorsLynch syndromeMicrosatellite instabilityPercent of tumorsMSH2/MSH6 expressionColorectal cancer tumorsPMS2 protein expressionMutational signaturesResultsFifty-three percentClinical managementNeoantigen presentationMSH6 expressionHallmark of tumorsTumor behaviorMMR deficiencyClinical phenotypeDeficient tumorsTumorsSporadic tumorsCancer tumorsMutational profileProtein expressionRepair deficiencySyndrome
2021
Clinical outcomes of first line FOLFIRINOX vs . gemcitabine plus nab-paclitaxel in metastatic pancreatic cancer at the Yale Smilow Hospital System
Patel T, Miccio J, Cecchini M, Srikumar T, Stein S, Kortmanksy J, Johung K, Lacy J. Clinical outcomes of first line FOLFIRINOX vs . gemcitabine plus nab-paclitaxel in metastatic pancreatic cancer at the Yale Smilow Hospital System. Journal Of Gastrointestinal Oncology 2021, 0: 0-0. PMID: 35070386, PMCID: PMC8748034, DOI: 10.21037/jgo-21-202.Peer-Reviewed Original ResearchMetastatic pancreatic cancerFirst-line FOLFIRINOXTreatment discontinuationFFX groupDose modificationOverall survivalNab-paclitaxelPancreatic cancerGN groupComparative effectivenessMedian TTDFirst-line settingMedian overall survivalOutcomes of patientsTreatment-related toxicityFirst-line therapyKaplan-Meier methodRate of hospitalizationElectronic medical record systemAdjuvant gemcitabineChemotherapy toxicityDiscontinuation ratesLine therapyMedical record systemTreatment toxicityCan a simplified CT response criteria for vascular involvement in pancreatic adenocarcinoma after neoadjuvant therapy predict survival in patients who achieved subsequent R0 resection?
Guo Y, Czeyda-Pommersheim F, Miccio JA, Mahalingam S, Cecchini M, Pahade J. Can a simplified CT response criteria for vascular involvement in pancreatic adenocarcinoma after neoadjuvant therapy predict survival in patients who achieved subsequent R0 resection? Abdominal Radiology 2021, 46: 5609-5617. PMID: 34557934, DOI: 10.1007/s00261-021-03284-5.Peer-Reviewed Original ResearchConceptsSubsequent R0 resectionOverall survivalR0 resectionNeoadjuvant therapyPancreatic ductal adenocarcinomaImaging responseMultivariable Cox proportional hazards analysisCox proportional hazards analysisPostoperative CA19-9Median overall survivalImproved diseaseProportional hazards analysisKaplan-Meier analysisSimilar diseasesPatient ageVascular involvementClinical stagingMethodsRetrospective analysisPredict SurvivalClinical parametersPDAC patientsCA 19CA19-9Mean ageCancer patientsPublication Bias in Gastrointestinal Oncology Trials Performed over the Past Decade
Peters GW, Tao W, Wei W, Miccio JA, Jethwa KR, Cecchini M, Johung KL. Publication Bias in Gastrointestinal Oncology Trials Performed over the Past Decade. The Oncologist 2021, 26: 660-667. PMID: 33728733, PMCID: PMC8342580, DOI: 10.1002/onco.13759.Peer-Reviewed Original ResearchConceptsGI oncologyPublication biasImpact of RCTsFuture trial designMultivariable logistic regressionSignificant publication biasPast trialsAccrual completionCancer RCTsEvidence-based practiceGastrointestinal cancerClinical managementTrial completionTrial designOncology trialsClinical practicePublication statusRCTsTrial questionModern RCTsLogistic regressionHalf of trialsTrialsPhase IIIGold standard