2023
Platinum Sensitivity in IDH1/2 Mutated Intrahepatic Cholangiocarcinoma: Not All “BRCAness” Is Created Equal
Doroshow D, Wei W, Mehrotra M, Sia D, Eder J, Bindra R, Houldsworth J, LoRusso P, Walther Z. Platinum Sensitivity in IDH1/2 Mutated Intrahepatic Cholangiocarcinoma: Not All “BRCAness” Is Created Equal. Cancer Investigation 2023, 41: 646-655. PMID: 37505929, DOI: 10.1080/07357907.2023.2242957.Peer-Reviewed Original ResearchConceptsClinical benefit rateIntrahepatic cholangiocarcinomaPlatinum sensitivityUnresectable intrahepatic cholangiocarcinomaObjective response rateMulticenter retrospective studyHomologous recombination repairDefective homologous recombination (HR) repairPrimary endpointPlatinum chemotherapyRetrospective studyPreclinical dataBenefit rateWildtype tumorsResponse rateMT tumorsWT diseasePatientsGene defectsCholangiocarcinomaTumorsNCI 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 treatmentEfficacy of Osimertinib in Patients with Lung Cancer Positive for Uncommon EGFR Exon 19 Deletion Mutations
Grant M, Aredo J, Starrett J, Stockhammer P, van Rosenburgh I, Wurtz A, Piper-Valillo A, Piotrowska Z, Falcon C, Yu H, Aggarwal C, Scholes D, Patil T, Nguyen C, Phadke M, Li F, Neal J, Lemmon M, Walther Z, Politi K, Goldberg S. Efficacy of Osimertinib in Patients with Lung Cancer Positive for Uncommon EGFR Exon 19 Deletion Mutations. Clinical Cancer Research 2023, 29: of1-of8. PMID: 36913537, PMCID: PMC10493186, DOI: 10.1158/1078-0432.ccr-22-3497.Peer-Reviewed Original ResearchConceptsProgression-free survivalNon-small cell lung cancerInferior progression-free survivalMulticenter retrospective cohortEfficacy of osimertinibMulti-institutional cohortCell lung cancerExon 19 deletion mutationUncommon EGFRRetrospective cohortClinical outcomesClinical efficacyLung cancerOsimertinib efficacyEGFR mutationsPreclinical modelsEx19delPatientsAACR Genie databaseLater linesOsimertinibMutant cohortFirst lineCohortEfficacy
2022
Biochemical and structural basis for differential inhibitor sensitivity of EGFR with distinct exon 19 mutations
van Alderwerelt van Rosenburgh I, Lu D, Grant M, Stayrook S, Phadke M, Walther Z, Goldberg S, Politi K, Lemmon M, Ashtekar K, Tsutsui Y. Biochemical and structural basis for differential inhibitor sensitivity of EGFR with distinct exon 19 mutations. Nature Communications 2022, 13: 6791. PMID: 36357385, PMCID: PMC9649653, DOI: 10.1038/s41467-022-34398-z.Peer-Reviewed Original ResearchCirculating Tumor DNA Kinetics Predict Progression-Free and Overall Survival in EGFR TKI–Treated Patients with EGFR-Mutant NSCLC (SWOG S1403)
Mack PC, Miao J, Redman MW, Moon J, Goldberg SB, Herbst RS, Melnick MA, Walther Z, Hirsch FR, Politi K, Kelly K, Gandara DR. Circulating Tumor DNA Kinetics Predict Progression-Free and Overall Survival in EGFR TKI–Treated Patients with EGFR-Mutant NSCLC (SWOG S1403). Clinical Cancer Research 2022, 28: 3752-3760. PMID: 35713632, PMCID: PMC9444942, DOI: 10.1158/1078-0432.ccr-22-0741.Peer-Reviewed Original ResearchConceptsProgression-free survivalOverall survivalEGFR mutationsNon-small cell lung cancerCycle 3 day 1Median progression-free survivalMedian overall survivalRisk of progressionCell lung cancerPresence of brainEGFR-mutant NSCLCBaseline ctDNAM1b stageProgression-FreeRECIST responseSerial plasmaLiver metastasesDecreased riskEGFR-TKILung cancerComplete clearanceLong-term benefitsClinical trialsTreatment outcomesPlasma clearanceComprehensive molecular profiling of pancreatic ductal adenocarcinoma in FNA, biopsy, and resection specimens
Razzano D, Bouza SJ, Hernandez PV, Wang M, Robert ME, Walther Z, Cai G. Comprehensive molecular profiling of pancreatic ductal adenocarcinoma in FNA, biopsy, and resection specimens. Cancer Cytopathology 2022, 130: 726-734. PMID: 35511415, DOI: 10.1002/cncy.22589.Peer-Reviewed Original ResearchConceptsFine-needle aspirationFine-needle biopsyPancreatic ductal adenocarcinomaOncomine Comprehensive AssayResection specimensMolecular alterationsMolecular testingFNB samplesDuctal adenocarcinomaTherapeutic implicationsSuccess rateComprehensive molecular analysisComprehensive molecular testingComprehensive molecular profilingPotential therapeutic implicationsSimilar success ratesResection casesKRAS mutationsFNB specimensFNA materialFNA specimensAmplification analysisMolecular profilingFusion assessmentGene mutationsAn Appraisal of Immunohistochemical Stain Use in Hepatic Metastasis Highlights the Effectiveness of the Individualized, Case-Based Approach: Analysis of Data From a Tertiary Care Medical Center.
Wang JD, Sebastian C, Walther Z, Suresh T, Lacy J, Zhang X, Jain D. An Appraisal of Immunohistochemical Stain Use in Hepatic Metastasis Highlights the Effectiveness of the Individualized, Case-Based Approach: Analysis of Data From a Tertiary Care Medical Center. Archives Of Pathology & Laboratory Medicine 2022, 147: 185-192. PMID: 35512224, DOI: 10.5858/arpa.2021-0457-oa.Peer-Reviewed Original ResearchConceptsLiver biopsyUnknown primaryIHC markersPrimary siteTrue carcinomaTertiary care medical centerAvailable clinicopathologic dataSquamous cell carcinomaClinicopathologic dataHepatic metastasesNonepithelial tumorsCell carcinomaInstitutional databaseClinical managementStain usePractice patternsNeuroendocrine neoplasmsImmunohistochemical markersMedical CenterMorphologic patternsIndividualized approachCarcinomaBiopsyMetastasisTumorsYale Precision Medicine Tumor Board: reawakening the guardian of the genome
Grant MJ, Finberg KE, Walther Z, Stein SM, Lacy J, Eder JP, Goldberg SB. Yale Precision Medicine Tumor Board: reawakening the guardian of the genome. The Lancet Oncology 2022, 23: 337-338. PMID: 35240081, DOI: 10.1016/s1470-2045(22)00037-7.Peer-Reviewed Case Reports and Technical Notes
2021
Pathogenic BRCA2 germline variants in combined hepatocellular‐cholangiocarcinoma
Li H, Zhang X, Finberg KE, Walther Z, Jain D, Gibson J. Pathogenic BRCA2 germline variants in combined hepatocellular‐cholangiocarcinoma. Pathology International 2021, 72: 138-140. PMID: 34808016, DOI: 10.1111/pin.13188.Peer-Reviewed Original ResearchEpidermotropic metastasis of squamous cell carcinoma of the tonsil: A case report with molecular confirmation
Li P, Barbieri A, Walther Z, McNiff J, Panse G. Epidermotropic metastasis of squamous cell carcinoma of the tonsil: A case report with molecular confirmation. Journal Of Cutaneous Pathology 2021, 48: 1514-1519. PMID: 34302376, DOI: 10.1111/cup.14108.Peer-Reviewed Case Reports and Technical NotesConceptsSquamous cell carcinomaOropharyngeal squamous cell carcinomaCell carcinomaDe novo squamous cell carcinomaPrimary oropharyngeal squamous cell carcinomaTonsillar squamous cell carcinomaTargetable genetic aberrationsLesion biopsy specimensSkin biopsy specimenSkin lesion biopsy specimensMetastatic diseaseEpidermal involvementEpidermotropic metastasesMetastatic lesionsPoor prognosisBiopsy specimenCase reportClinical historyBiopsy specimensSecondary diseaseSkin lesionsTumor originMetastatic specimensMetastasisNeck skinYale 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
Yale Cancer Center Precision Medicine Tumor Board: new technology, new drugs, and the value of repeat testing
Hafez N, Walther Z, Eder JP, Sklar JL, Gettinger SN, Finberg KE, Goldberg SB. Yale Cancer Center Precision Medicine Tumor Board: new technology, new drugs, and the value of repeat testing. The Lancet Oncology 2020, 21: 343-344. PMID: 32950226, DOI: 10.1016/s1470-2045(20)30010-3.Peer-Reviewed Case Reports and Technical Notes
2019
The EGFR Exon 19 Mutant L747-A750>P Exhibits Distinct Sensitivity to Tyrosine Kinase Inhibitors in Lung Adenocarcinoma
Truini A, Starrett JH, Stewart T, Ashtekar K, Walther Z, Wurtz A, Lu D, Park JH, DeVeaux M, Song X, Gettinger S, Zelterman D, Lemmon MA, Goldberg SB, Politi K. The EGFR Exon 19 Mutant L747-A750>P Exhibits Distinct Sensitivity to Tyrosine Kinase Inhibitors in Lung Adenocarcinoma. Clinical Cancer Research 2019, 25: 6382-6391. PMID: 31182434, PMCID: PMC6825535, DOI: 10.1158/1078-0432.ccr-19-0780.Peer-Reviewed Original ResearchEndogenous development of Cystoisospora belli in intestinal and biliary epithelium of humans
Dubey JP, Evason KJ, Walther Z. Endogenous development of Cystoisospora belli in intestinal and biliary epithelium of humans. Parasitology 2019, 146: 865-872. PMID: 30859916, DOI: 10.1017/s003118201900012x.Peer-Reviewed Original ResearchConceptsBiliary epitheliumC. belliEpithelial cellsCystoisospora belliSingle parasitophorous vacuoleDuodenal biopsiesBiliary tractDepressed immunityPAS-positive granulesHistopathologic diagnosisHost epithelial cellsBiopsy samplesDigestive disordersSame PVParasitophorous vacuoleParasite multipliesCertain inclusionTransmission cycleEpitheliumCoccidian parasitesAsexual stagesBelliMerozoitesCellsOocysts
2018
Yale 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 NotesIntroduction 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 Letters
2017
Analytical Validation of the Next-Generation Sequencing Assay for a Nationwide Signal-Finding Clinical Trial Molecular Analysis for Therapy Choice Clinical Trial
Lih CJ, Harrington RD, Sims DJ, Harper KN, Bouk CH, Datta V, Yau J, Singh RR, Routbort MJ, Luthra R, Patel KP, Mantha GS, Krishnamurthy S, Ronski K, Walther Z, Finberg KE, Canosa S, Robinson H, Raymond A, Le LP, McShane LM, Polley EC, Conley BA, Doroshow JH, Iafrate AJ, Sklar JL, Hamilton SR, Williams PM. Analytical Validation of the Next-Generation Sequencing Assay for a Nationwide Signal-Finding Clinical Trial Molecular Analysis for Therapy Choice Clinical Trial. Journal Of Molecular Diagnostics 2017, 19: 313-327. PMID: 28188106, PMCID: PMC5397672, DOI: 10.1016/j.jmoldx.2016.10.007.Peer-Reviewed Original ResearchConceptsNext-generation sequencingNational Cancer Institute-Molecular AnalysisMultiple clinical laboratoriesParaffin-embedded clinical specimensTherapy Choice (NCI-MATCH) trialClinical Laboratory Improvement AmendmentsNext-generation sequencing assayPrecision medicine studiesStandard treatmentRefractory cancerClinical trialsBiopsy collectionClinical specimensPanel assayClinical useOverall sensitivityMedicine studiesPairwise concordanceReportable variantsCompliant useNGS assaysTrialsPrecision medicineCell linesClinical laboratoriesCongenital Extrahepatic Portosystemic Shunt (Abernethy Malformation Type Ib) With Associated Hepatocellular Carcinoma
Benedict M, Rodriguez-Davalos M, Emre S, Walther Z, Morotti R. Congenital Extrahepatic Portosystemic Shunt (Abernethy Malformation Type Ib) With Associated Hepatocellular Carcinoma. Pediatric And Developmental Pathology 2017, 20: 354-362. PMID: 28727971, DOI: 10.1177/1093526616686458.Peer-Reviewed Case Reports and Technical NotesConceptsAbernethy malformationCongenital portosystemic shuntsHepatocellular carcinomaPortosystemic shuntPortal veinVena cavaCongenital absenceCongenital extrahepatic portosystemic shuntAssociated Hepatocellular CarcinomaSplanchnic venous systemNodular regenerative hyperplasiaExtrahepatic portosystemic shuntSmall hepatocellular carcinomaFocal nodular hyperplasiaRegenerative hyperplasiaClinical manifestationsImmunohistochemical characteristicsIntrahepatic shuntsLiver adenomasTypical presentationPortal bloodNodular hyperplasiaVenous systemComplete diversionResult of malformation
2014
Acquired Resistance of EGFR-Mutant Lung Adenocarcinomas to Afatinib plus Cetuximab Is Associated with Activation of mTORC1
Pirazzoli V, Nebhan C, Song X, Wurtz A, Walther Z, Cai G, Zhao Z, Jia P, de Stanchina E, Shapiro EM, Gale M, Yin R, Horn L, Carbone DP, Stephens PJ, Miller V, Gettinger S, Pao W, Politi K. Acquired Resistance of EGFR-Mutant Lung Adenocarcinomas to Afatinib plus Cetuximab Is Associated with Activation of mTORC1. Cell Reports 2014, 7: 999-1008. PMID: 24813888, PMCID: PMC4074596, DOI: 10.1016/j.celrep.2014.04.014.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdenocarcinoma of LungAfatinibAnimalsAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsCell Line, TumorCetuximabDrug Resistance, NeoplasmErbB ReceptorsHumansLung NeoplasmsMechanistic Target of Rapamycin Complex 1MiceMice, NudeMice, TransgenicMultiprotein ComplexesMutationQuinazolinesRandom AllocationTOR Serine-Threonine KinasesXenograft Model Antitumor AssaysConceptsTyrosine kinase inhibitorsFirst-generation tyrosine kinase inhibitorEGFR-mutant lung adenocarcinomaLung adenocarcinomaMechanisms of resistanceEGFR antibody cetuximabPotential therapeutic strategyBiopsy specimensAntibody cetuximabDrug combinationsMouse modelTherapeutic strategiesAfatinibAddition of rapamycinCetuximabDual inhibitionAcquired ResistanceKinase inhibitorsGenomic alterationsAdenocarcinomaPatientsActivationGenomic mechanismsDrugsMTORC1 activationReduced NF1 Expression Confers Resistance to EGFR Inhibition in Lung Cancer
de Bruin EC, Cowell C, Warne PH, Jiang M, Saunders RE, Melnick MA, Gettinger S, Walther Z, Wurtz A, Heynen GJ, Heideman DA, Gómez-Román J, García-Castaño A, Gong Y, Ladanyi M, Varmus H, Bernards R, Smit EF, Politi K, Downward J. Reduced NF1 Expression Confers Resistance to EGFR Inhibition in Lung Cancer. Cancer Discovery 2014, 4: 606-619. PMID: 24535670, PMCID: PMC4011693, DOI: 10.1158/2159-8290.cd-13-0741.Peer-Reviewed Original ResearchConceptsLung cancerMAP-ERK kinase (MEK) inhibitorsEGF receptorEGFR-mutant lung adenocarcinomaKinase inhibitorsHuman lung cancer cell linesResistance of lungSubgroup of patientsLung cancer cell linesCancer cell linesClinical responsivenessCombination therapyEGFR-TKIEGFR mutationsErlotinib resistanceLung adenocarcinomaRAS-ERK signalingEGFR inhibitionMEK inhibitorsErlotinibReduced expressionNF1 expressionPatientsCell linesNeurofibromin levels