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 Research
2023
Relative 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 process
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 adenocarcinomaMutational 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
Can 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 standardYale Cancer Center Precision Medicine Tumor Board: molecular findings alter a diagnosis and treatment plan
Gibson JA, Finberg KE, Nalbantoglu I, Cecchini M, Ganzak A, Walther Z, Sklar JL, Eder JP, Goldberg SB. Yale Cancer Center Precision Medicine Tumor Board: molecular findings alter a diagnosis and treatment plan. The Lancet Oncology 2021, 22: 306-307. PMID: 33662283, DOI: 10.1016/s1470-2045(20)30683-5.Peer-Reviewed Case Reports and Technical Notes
2020
A phase 1b expansion study of TAS‐102 with oxaliplatin for refractory metastatic colorectal cancer
Cecchini M, Kortmansky JS, Cui C, Wei W, Thumar JR, Uboha NV, Hafez N, Lacy J, Fischbach NA, Sabbath KD, Gomez CM, Sporn JR, Stein S, Hochster HS. A phase 1b expansion study of TAS‐102 with oxaliplatin for refractory metastatic colorectal cancer. Cancer 2020, 127: 1417-1424. PMID: 33351187, PMCID: PMC8085021, DOI: 10.1002/cncr.33379.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsColorectal NeoplasmsDrug Administration ScheduleDrug CombinationsDrug Resistance, NeoplasmFemaleFluorouracilHumansIrinotecanLeucovorinMaleMiddle AgedOrganoplatinum CompoundsOxaliplatinProgression-Free SurvivalPyrrolidinesResponse Evaluation Criteria in Solid TumorsThymineTrifluridineConceptsMetastatic colorectal cancerOverall response rateRefractory metastatic colorectal cancerProgression-free survivalTAS-102Colorectal cancerDay 1Primary endpointOverall survivalDose escalationDay 5Median progression-free survivalPhase 1b studyMedian overall survivalResponse Evaluation CriteriaTreat populationDose expansionPartial responseStandard dosesUnexpected side effectsStudy treatmentTumor shrinkageUnexpected toxicitiesSide effectsNovel antimetaboliteTargeted Therapies in Advanced Gastric Cancer
Patel TH, Cecchini M. Targeted Therapies in Advanced Gastric Cancer. Current Treatment Options In Oncology 2020, 21: 70. PMID: 32725377, DOI: 10.1007/s11864-020-00774-4.Peer-Reviewed Original ResearchConceptsGastric cancerMetastatic diseaseClinical trialsVascular endothelial growth factor receptor inhibitorDeath ligand 1 (PD-L1) statusEndothelial growth factor receptor inhibitorImmune checkpoint inhibitor pembrolizumabHuman epidermal growth factor 2Epidermal growth factor 2Growth factor receptor inhibitorsBackbone of therapyCheckpoint inhibitor pembrolizumabCombination immune therapyThird-line settingFirst-line settingSecond-line settingAddition of trastuzumabPD-L1 statusAdvanced gastric cancerMetastatic gastric cancerHER2-positive tumorsSquamous cell carcinomaFuture clinical trialsNumerous clinical trialsStandard of careA Single-Institution Experience of Induction 5-Fluorouracil, Leucovorin, Irinotecan, and Oxaliplatin Followed by Surgery Versus Consolidative Radiation for Borderline and Locally Advanced Unresectable Pancreatic Cancer.
Cecchini M, Miccio JA, Pahade J, Lacy J, Salem RR, Johnson SB, Blakaj A, Stein S, Kortmansky JS, Johung KL. A Single-Institution Experience of Induction 5-Fluorouracil, Leucovorin, Irinotecan, and Oxaliplatin Followed by Surgery Versus Consolidative Radiation for Borderline and Locally Advanced Unresectable Pancreatic Cancer. Pancreas 2020, 49: 904-911. PMID: 32658074, DOI: 10.1097/mpa.0000000000001592.Peer-Reviewed Original ResearchConceptsPancreatic ductal adenocarcinomaLA PDACUnresectable pancreatic ductal adenocarcinomaInduction FOLFIRINOXConsolidative radiotherapyOverall survivalAdvanced unresectable pancreatic ductal adenocarcinomaSingle-center retrospective reviewMeaningful survival benefitMedian overall survivalUnresectable pancreatic cancerR0 resection rateKaplan-Meier methodSingle institution experienceBenefits of surgeryLog-rank testConsolidative radiationDefinitive radiationLA patientsPreoperative radiationResection rateSurgery patientsSurvival benefitSurvival impactImproved survival
2019
Challenges with Novel Clinical Trial Designs: Master Protocols
Cecchini M, Rubin EH, Blumenthal GM, Ayalew K, Burris HA, Russell-Einhorn M, Dillon H, Lyerly HK, Reaman GH, Boerner S, LoRusso PM. Challenges with Novel Clinical Trial Designs: Master Protocols. Clinical Cancer Research 2019, 25: 2049-2057. PMID: 30696689, DOI: 10.1158/1078-0432.ccr-18-3544.Peer-Reviewed Original ResearchConceptsClinical trial designPlatform trialsMaster protocolsUmbrella trialsTrial designBasket trialsNovel clinical trial designsPanel of expertsMultiple investigational agentsInnovative clinical trial designsNovel clinical trialsInstitutional review boardDifferent tumor typesExpansion cohortInvestigational agentsSame histologyClinical trialsTumor typesBasket studyPatientsReview boardTrialsDrug development processDrug assessmentHistology
2018
Introduction to the Yale Precision Medicine Tumor Board
Cecchini M, Walther Z, Sklar JL, Bindra RS, Petrylak DP, Eder JP, Goldberg SB. Introduction to the Yale Precision Medicine Tumor Board. The Lancet Oncology 2018, 19: 19-20. PMID: 29304351, DOI: 10.1016/s1470-2045(17)30919-1.Commentaries, Editorials and LettersYale Cancer Center Precision Medicine Tumor Board: two patients, one targeted therapy, different outcomes
Cecchini M, Walther Z, Sklar JL, Bindra RS, Petrylak DP, Eder JP, Goldberg SB. Yale Cancer Center Precision Medicine Tumor Board: two patients, one targeted therapy, different outcomes. The Lancet Oncology 2018, 19: 23-24. PMID: 29304353, DOI: 10.1016/s1470-2045(17)30916-6.Peer-Reviewed Case Reports and Technical Notes
2017
EGFR Exon 19 Deletion in Pancreatic Adenocarcinoma Responds to Erlotinib, Followed by T790M-Mediated Resistance.
Cecchini M, Sklar J, Lacy J. EGFR Exon 19 Deletion in Pancreatic Adenocarcinoma Responds to Erlotinib, Followed by T790M-Mediated Resistance. Journal Of The National Comprehensive Cancer Network 2017, 15: 1085-1089. PMID: 28874593, DOI: 10.6004/jnccn.2017.0151.Peer-Reviewed Original ResearchConceptsPancreatic ductal adenocarcinomaTyrosine kinase inhibitorsMetastatic pancreatic ductal adenocarcinomaEGFR Exon 19 DeletionEGFR tyrosine kinase inhibitorsImmune checkpoint inhibitorsMetastatic pancreatic cancerExon 19 deletionsEpidermal growth factor receptorGrowth factor receptorAdvanced diseaseCheckpoint inhibitorsMultidrug chemotherapyPancreatic cancerDisease progressionDuctal adenocarcinomaPancreatic adenocarcinomaActionable mutationsTumor typesKinase inhibitorsExon 19Factor receptorAdenocarcinomaPatientsErlotinibOlaratumab for the treatment of soft tissue sarcoma.
Deshpande HA, Cecchini M, Ni Choileain S, Jones R. Olaratumab for the treatment of soft tissue sarcoma. Drugs Of Today 2017, 53: 247-255. PMID: 28492292, DOI: 10.1358/dot.2017.53.4.2560077.Peer-Reviewed Original ResearchConceptsSoft tissue sarcomasPhase II studyTissue sarcomasII studyMetastatic diseaseOverall survivalOngoing phase III studiesRandomized phase II studyPlatelet-derived growth factor receptor alphaProgression-free survivalPhase III studyStandard chemotherapy regimensGrowth factor receptor alphaUnited States FoodMechanism of actionChemotherapy regimensIII studyOngoing trialsSolid malignanciesReceptor alphaPhase IbDrug AdministrationSignificant improvementFDA approvalOlaratumab
2016
Electronic Intervention to Improve Structured Cancer Stage Data Capture
Cecchini M, Framski K, Lazette P, Vega T, Strait M, Adelson K. Electronic Intervention to Improve Structured Cancer Stage Data Capture. JCO Oncology Practice 2016, 12: e949-e956. PMID: 27650837, DOI: 10.1200/jop.2016.013540.Peer-Reviewed Original ResearchConceptsStaging rateElectronic health recordsCancer stageClinical trial eligibilityElectronic decision supportTrial eligibilityMonths postinterventionCancer stagingPhysician useClinical notesBPA implementationProblem listHealth recordsElectronic interventionMonthsTreatment planningCancerStagingPhysiciansAct methodologyInterventionUnstructured free textHard stopBPAPatients