2024
Perioperative Modified FOLFIRINOX for Resectable Pancreatic Cancer
Cecchini M, Salem R, Robert M, Czerniak S, Blaha O, Zelterman D, Rajaei M, Townsend J, Cai G, Chowdhury S, Yugawa D, Tseng R, Arbelaez C, Jiao J, Shroyer K, Thumar J, Kortmansky J, Zaheer W, Fischbach N, Persico J, Stein S, Khan S, Cha C, Billingsley K, Kunstman J, Johung K, Wiess C, Muzumdar M, Spickard E, Aushev V, Laliotis G, Jurdi A, Liu M, Escobar-Hoyos L, Lacy J. Perioperative Modified FOLFIRINOX for Resectable Pancreatic Cancer. JAMA Oncology 2024, 10: 1027-1035. PMID: 38900452, PMCID: PMC11190830, DOI: 10.1001/jamaoncol.2024.1575.Peer-Reviewed Original ResearchProgression-free survivalPancreatic ductal adenocarcinomaOverall survivalCtDNA levelsPhase 2 nonrandomized controlled trialAnalysis of circulating tumor DNAMedian progression-free survivalResectable pancreatic ductal adenocarcinomaControlled trialsAssess surgical candidacyBaseline ctDNA levelModified 5-fluorouracilResectable pancreatic cancerPancreatic protocol computed tomographyAssociated with recurrenceTumor molecular featuresAggressive malignant tumorKaplan-Meier estimatesRandomized clinical trialsStandard of careCtDNA-positivePreoperative cyclesNonrandomized controlled trialsUnresectable diseaseModified FOLFIRINOXProofreading 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 ResearchA phase I study of irinotecan combined with BAY1895344 (ATR inhibitor) in advanced solid tumors: Results of ETCTN 10402 dose escalation.
Heumann T, Stockton S, Cecchini M, Aljumaily R, Shyr C, Whisenant J, Starr J, Dayyani F, Baranda J, Trikalinos N, Ivy S, LoRusso P, Das S, Gore S, Beumer J, Berlin J. A phase I study of irinotecan combined with BAY1895344 (ATR inhibitor) in advanced solid tumors: Results of ETCTN 10402 dose escalation. Journal Of Clinical Oncology 2024, 42: 3077-3077. DOI: 10.1200/jco.2024.42.16_suppl.3077.Peer-Reviewed Original ResearchAdvanced solid tumorsMaximum tolerated doseDose escalationSolid tumorsPhase I study of irinotecanRecommended phase 2 doseRefractory advanced solid tumorsPhase 2 dosePhase I studyAnti-tumor activityBiweekly irinotecanInhibitor irinotecanIrinotecan exposureWeekly irinotecanTolerated doseDosing scheduleCancer xenograftsAdult patientsIrinotecanAssess safetyATR inhibitorsElimusertibSecondary objectivesDoseStandard careA phase I study of ATR inhibitor BAY1895344 (elimusertib) plus topotecan (ETCTN 10402): Results of dose escalation.
Stockton S, Shyr C, Cecchini M, Aljumaily R, Halfdanarson T, Sonbol M, Whisenant J, Ivy S, LoRusso P, Das S, Gore S, Berlin J, Beumer J, Heumann T. A phase I study of ATR inhibitor BAY1895344 (elimusertib) plus topotecan (ETCTN 10402): Results of dose escalation. Journal Of Clinical Oncology 2024, 42: 3076-3076. DOI: 10.1200/jco.2024.42.16_suppl.3076.Peer-Reviewed Original ResearchMaximum tolerated doseDose escalationDose levelsMedian progression-free survivalRecommended phase 2 doseRefractory advanced solid tumorsResults of dose escalationTreatment-related adverse eventsSmall cell lung cancerDisease control ratePhase 2 dosePhase Ia studyDose-limiting toxicityProgression-free survivalAdvanced solid tumorsPhase I studyCell lung cancerAnti-tumor activityExpansion cohortPartial responseTolerated doseTopotecan exposureStudy drugCancer xenograftsRespiratory failurePersonalized risk assessment of new onset depression in long-term cancer survivors.
Taylor M, Westvold S, Long J, Hyslop T, Wang S, Cecchini M, Leapman M, Leeds I, Lustberg M, Spees L, Wheeler S, Gross C, Oeffinger K, Dinan M. Personalized risk assessment of new onset depression in long-term cancer survivors. Journal Of Clinical Oncology 2024, 42: e13798-e13798. DOI: 10.1200/jco.2024.42.16_suppl.e13798.Peer-Reviewed Original ResearchHistory of depressionIncidence of depressionCumulative incidence of depressionRisk of developing depressionLong-term survivorsPredictors of depressionCancer survivorsDisease specific factorsCumulative incidenceNon-HispanicHigher risk of developing depressionRectal cancerLong-term cancer survivorsBreast cancer survivorsCensus tract povertyColon cancerEpisodes of bipolar I disorderPrevalence of depressionMean survival time modelsDiagnosis of depressionReceipt of treatmentAssociated with prior historyHormone receptor statusPatients aged <Adjuvant endocrine therapyAuthor 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 scoreThe Perioperative Modified FOLFIRINOX Clinical Trial for Resectable Pancreatic Cancer
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 carcinomaPhase Ia/Ib Study of BAY1895344 Plus Topoisomerase I Inhibitors with a Focus on Poorly Differentiated Neuroendocrine Carcinomas and Pancreatic Adenocarcinoma
Stockton S, Dan A, Cecchini M, Ajumaily R, Whisenant J, Gore S, Ivy P, LoRusso P, Berlin J, Das S. Phase Ia/Ib Study of BAY1895344 Plus Topoisomerase I Inhibitors with a Focus on Poorly Differentiated Neuroendocrine Carcinomas and Pancreatic Adenocarcinoma. Endocrine Abstracts 2023 DOI: 10.1530/endoabs.89.t1.Peer-Reviewed Original Research
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 Letters