2023
Emerging Prognostic and Predictive Significance of Stress Keratin 17 in HPV-Associated and Non HPV-Associated Human Cancers: A Scoping Review
Lozar T, Wang W, Gavrielatou N, Christensen L, Lambert P, Harari P, Rimm D, Burtness B, Kuhar C, Carchman E. Emerging Prognostic and Predictive Significance of Stress Keratin 17 in HPV-Associated and Non HPV-Associated Human Cancers: A Scoping Review. Viruses 2023, 15: 2320. PMID: 38140561, PMCID: PMC10748233, DOI: 10.3390/v15122320.Peer-Reviewed Original ResearchConceptsSquamous cell carcinomaTriple-negative breast cancerCancer typesPredictive significancePrognostic factorsClinical outcomesPrognostic significanceCell carcinomaHuman cancersCervical squamous cell carcinomaNeck squamous cell carcinomaAvailable clinical evidenceCochrane Central RegisterInferior clinical outcomesPositive prognostic factorNegative predictive factorNegative prognostic factorWeb of ScienceCentral RegisterControlled TrialsCervical cancerClinical evidencePredictive factorsPancreatic cancerEligible studiesNoncanonical HPV carcinogenesis drives radiosensitization of head and neck tumors
Schrank T, Kothari A, Weir W, Stepp W, Rehmani H, Liu X, Wang X, Sewell A, Li X, Tasoulas J, Kim S, Yarbrough G, Xie Y, Flamand Y, Marur S, Hayward M, Wu D, Burtness B, Anderson K, Baldwin A, Yarbrough W, Issaeva N. Noncanonical HPV carcinogenesis drives radiosensitization of head and neck tumors. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2216532120. PMID: 37523561, PMCID: PMC10410762, DOI: 10.1073/pnas.2216532120.Peer-Reviewed Original ResearchConceptsNF-κB-related genesEstrogen receptor alpha expressionDeintensification of therapyTreatment-related morbidityTumor-infiltrating CD4Receptor alpha expressionHPV carcinogenesisRadiosensitization of headOncogenic subtypesPIK3CA alterationsHNSCC tumorsPatient outcomesNeck tumorsT cellsTreatment responseHNSCC cellsTherapeutic intensityAtypical featuresIndependent cohortAlpha expressionNF-κBActive tumorTNF receptorTumorsPatient data
2022
Outcomes Stratification of Head and Neck Cancer Using Pre- and Post-treatment DNA Methylation From Peripheral Blood
Qian D, Ulrich B, Peng G, Zhao H, Conneely K, Miller A, Bruner D, Eldridge R, Wommack E, Higgins K, Shin D, Saba N, Smith A, Burtness B, Park H, Stokes W, Beitler J, Xiao C. Outcomes Stratification of Head and Neck Cancer Using Pre- and Post-treatment DNA Methylation From Peripheral Blood. International Journal Of Radiation Oncology • Biology • Physics 2022, 115: 1217-1228. PMID: 36410685, DOI: 10.1016/j.ijrobp.2022.11.009.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkers, TumorCarcinoma, Squamous CellDNA MethylationHead and Neck NeoplasmsHumansPrognosisSquamous Cell Carcinoma of Head and NeckConceptsRecurrence-free survivalWorse recurrence-free survivalOverall survivalMethylation risk scoreRadiation therapyValidation cohortPeripheral bloodDiscovery cohortOutcome stratificationShorter recurrence-free survivalNeck squamous cell carcinomaGastrostomy tube insertionHigher neutrophil countOral cavity cancerAforementioned risk factorsSquamous cell carcinomaPeripheral blood samplesNonmetastatic HNSCCNeutrophil countPrognostic factorsCox regressionPrognostic valueCell carcinomaTube insertionImmune modulationIntegrating Targeted Therapies in the Management of Head and Neck Cancers
Burtness B. Integrating Targeted Therapies in the Management of Head and Neck Cancers. The Cancer Journal 2022, 28: 329-330. PMID: 36165719, DOI: 10.1097/ppo.0000000000000624.Peer-Reviewed Original Research
2021
Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): An update on 107 randomized trials and 19,805 patients, on behalf of MACH-NC Group
Lacas B, Carmel A, Landais C, Wong SJ, Licitra L, Tobias JS, Burtness B, Ghi MG, Cohen EEW, Grau C, Wolf G, Hitt R, Corvò R, Budach V, Kumar S, Laskar SG, Mazeron JJ, Zhong LP, Dobrowsky W, Ghadjar P, Fallai C, Zakotnik B, Sharma A, Bensadoun RJ, Redda M, Racadot S, Fountzilas G, Brizel D, Rovea P, Argiris A, Nagy ZT, Lee JW, Fortpied C, Harris J, Bourhis J, Aupérin A, Blanchard P, Pignon JP, Group M, Adelstein D, Alfonsi M, Belkacemi Y, Bar-Ad V, Bernier J, Bratland Å, Calais G, Campbell B, Caudell J, Chabaud S, Chamorey E, Chaukar D, Choi K, Choussy O, Collette L, Cruz J, Dani C, Dauzier E, Forastiere A, Garaud P, Gregoire V, Hackshaw A, Haddad E, Haffty B, Hansen A, Hayoz S, Horiot J, Jeremic B, Karrison T, Langendijk J, Lapeyre M, Lartigau E, Leong T, Le Q, Lee P, Lewin F, Lin A, Lopes A, Mehta S, Moon J, Moyal E, Occéan B, Olmi P, Orecchia R, O'Sullivan B, Overgaard J, Petit C, Quon H, Sanguineti G, Satar T, Simes J, Simon C, Sire C, Staar S, Stromberger C, Strojan P, Temam S, Thomson D, Timochenko A, Torri V, Tseroni V, Vermorken J, Vokes E, Waldron J, Wernecke K, Widder J, Zackrisson B. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): An update on 107 randomized trials and 19,805 patients, on behalf of MACH-NC Group. Radiotherapy And Oncology 2021, 156: 281-293. PMID: 33515668, PMCID: PMC8386522, DOI: 10.1016/j.radonc.2021.01.013.Peer-Reviewed Original ResearchConceptsLoco-regional treatmentConcomitant CTConcomitant chemotherapyOverall survivalNeck cancerNon-metastatic headPoor performance statusSquamous cell headIndividual patient dataNon-metastatic carcinomasAddition of inductionFixed-effects modelPerformance statusPatient ageDistant metastasisRandomized trialsMain endpointCell headStage IIIMeta-AnalysisPatientsChemotherapyPatient dataTrialsCancer
2019
Pathologic staging changes in oral cavity squamous cell carcinoma: Stage migration and implications for adjuvant treatment
Lee NCJ, Eskander A, Park HS, Mehra S, Burtness BA, Husain Z. Pathologic staging changes in oral cavity squamous cell carcinoma: Stage migration and implications for adjuvant treatment. Cancer 2019, 125: 2975-2983. PMID: 31090934, DOI: 10.1002/cncr.32161.Peer-Reviewed Original ResearchConceptsOral cavity squamous cell carcinomaPathologic extranodal extensionDepth of invasionAJCC Cancer Staging ManualCancer Staging ManualSquamous cell carcinomaOverall survivalPT3N0 patientsStage migrationStaging ManualCell carcinomaStaging systemAJCC-8 staging systemPathologic tumor classificationNational Cancer DatabaseRisk of deathNew staging systemPStage IVBUpstaged tumorsAdjuvant treatmentDefinitive surgeryExtranodal extensionPostoperative radiotherapyPT classificationPT1 tumorsHyperprogression after one dose of nivolumab in sinonasal cancer: A case report
Xiang JJ, Uy NF, Minja FJ, Verter EE, Burtness BA. Hyperprogression after one dose of nivolumab in sinonasal cancer: A case report. The Laryngoscope 2019, 130: 907-910. PMID: 31058321, DOI: 10.1002/lary.28042.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Agents, ImmunologicalCarcinoma, Squamous CellDisease ProgressionFemaleHumansMiddle AgedNivolumabParanasal Sinus NeoplasmsConceptsImmune checkpoint inhibitorsDose of nivolumabSquamous cell carcinomaSinonasal cancerCell carcinomaDisease progressionMaxillary sinus squamous cell carcinomaSinus squamous cell carcinomaNeck squamous cell carcinomaComplete vision lossICI initiationCheckpoint inhibitorsFirst doseLytic metastasesDistal metastasisCase reportIntracranial invasionVision lossImproved outcomesHyperprogressionIndividual riskDoseNivolumabCarcinomaMetastasis
2018
Patterns of failure in high-metastatic node number human papillomavirus-positive oropharyngeal carcinoma
Lee NCJ, Kelly JR, Park HS, An Y, Judson BL, Burtness BA, Husain ZA. Patterns of failure in high-metastatic node number human papillomavirus-positive oropharyngeal carcinoma. Oral Oncology 2018, 85: 35-39. PMID: 30220317, DOI: 10.1016/j.oraloncology.2018.08.001.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overBrachytherapyCarcinoma, Squamous CellCombined Modality TherapyFemaleFollow-Up StudiesHumansLymphatic MetastasisMaleMiddle AgedNeck DissectionNeoplasm MetastasisNeoplasm Recurrence, LocalOropharyngeal NeoplasmsPapillomavirus InfectionsProgression-Free SurvivalProportional Hazards ModelsRadiotherapy, AdjuvantRetrospective StudiesSalvage TherapyConceptsProgression-free survivalInvolved lymph nodesDistant metastasisPatterns of failureLocoregional recurrenceLymph nodesHuman papillomavirus-positive oropharyngeal carcinomaMultivariate analysisEdition American Joint CommitteeRate of DMWorse progression-free survivalHigh DM rateDedicated clinical trialsAmerican Joint CommitteeCancer (AJCC) staging systemProportional hazards regressionExternal beam radiationOropharynx cancerFree survivalNeck dissectionOropharyngeal carcinomaOverall survivalDisease recurrenceIntraoperative brachytherapyOPC patientsNational treatment times in oropharyngeal cancer treated with primary radiation or chemoradiation
Morse E, Judson B, Husain Z, Burtness B, Yarbrough W, Sasaki C, Cheraghlou S, Mehra S. National treatment times in oropharyngeal cancer treated with primary radiation or chemoradiation. Oral Oncology 2018, 82: 122-130. PMID: 29909886, DOI: 10.1016/j.oraloncology.2018.02.010.Peer-Reviewed Original ResearchMeSH KeywordsAgedCarcinoma, Squamous CellChemoradiotherapyFemaleHumansMaleMiddle AgedOropharyngeal NeoplasmsPrognosisRetrospective StudiesSurvival AnalysisTime FactorsConceptsRadiation treatment durationHuman papilloma virus-positive tumorsVirus-positive tumorsOverall survivalOropharyngeal cancerTreatment durationTreatment endMedian durationTreatment initiationTreatment delayHuman papilloma virus-associated tumorsHuman papilloma virus-negative tumorsEnd intervalOropharyngeal squamous cell carcinomaCox proportional hazards regressionNational Cancer DatabaseProportional hazards regressionSquamous cell carcinomaVirus-associated tumorsVirus-negative tumorsMultivariable logisticHazards regressionCell carcinomaHuman papillomaCancer DatabasePostoperative Chemoradiation in High-Risk Cutaneous Squamous Cell Carcinoma of the Head and Neck
Bhatia AK, Burtness BA, Decker RH. Postoperative Chemoradiation in High-Risk Cutaneous Squamous Cell Carcinoma of the Head and Neck. Journal Of Clinical Oncology 2018, 36: jco.2018.77.798. PMID: 29547345, DOI: 10.1200/jco.2018.77.7987.Peer-Reviewed Original ResearchCarcinoma, Squamous CellChemoradiotherapyHead and Neck NeoplasmsHumansPostoperative PeriodSkin Neoplasms
2017
Demethylation Therapy as a Targeted Treatment for Human Papillomavirus–Associated Head and Neck Cancer
Biktasova A, Hajek M, Sewell A, Gary C, Bellinger G, Deshpande HA, Bhatia A, Burtness B, Judson B, Mehra S, Yarbrough WG, Issaeva N. Demethylation Therapy as a Targeted Treatment for Human Papillomavirus–Associated Head and Neck Cancer. Clinical Cancer Research 2017, 23: 7276-7287. PMID: 28916527, DOI: 10.1158/1078-0432.ccr-17-1438.Peer-Reviewed Original ResearchConceptsClinical trialsHNSCC cellsMatrix metalloproteinasesHuman papillomavirus-associated headNeck squamous cell carcinomaSquamous cell carcinomaAbility of HPVClin Cancer ResTumor cell proliferationNeck cancer cellsWindow trialsCell carcinomaEffective therapyPreclinical modelsHPVHPV oncogenesMouse modelMouse blood vesselsDNA demethylating agentHNSCCXenografted tumorsHPV genesIFN responseTherapyTumor samplesDouble‐blind, randomized phase 3 trial of low‐dose 13‐cis retinoic acid in the prevention of second primaries in head and neck cancer: Long‐term follow‐up of a trial of the Eastern Cooperative Oncology Group‐ACRIN Cancer Research Group (C0590)
Bhatia AK, Lee J, Pinto HA, Jacobs CD, Limburg PJ, Rubin P, Arusell RM, Dunphy EP, Khandekar JD, Reiner SA, Baez‐Diaz L, Celano P, Li S, Li Y, Burtness BA, Adams GL, Pandya KJ. Double‐blind, randomized phase 3 trial of low‐dose 13‐cis retinoic acid in the prevention of second primaries in head and neck cancer: Long‐term follow‐up of a trial of the Eastern Cooperative Oncology Group‐ACRIN Cancer Research Group (C0590). Cancer 2017, 123: 4653-4662. PMID: 28786105, PMCID: PMC5693641, DOI: 10.1002/cncr.30920.Peer-Reviewed Original ResearchConceptsSecond primary tumorsOverall survivalFormer smokersDevelopment of SPTsIncidence of SPTsEarly-stage SCCHNFuture prevention trialsImproved overall survivalClinical risk factorsSquamous cell cancerLog-rank testLong-term resultsPotential survival advantageCompeting-risk approachCumulative incidenceIndex tumorCell cancerPrevention trialsPrimary tumorRisk factorsSubset analysisDry skinSurvival advantagePatientsTargeted interventionsComparison of Survival Outcomes Among Human Papillomavirus–Negative cT1-2 N1-2b Patients With Oropharyngeal Squamous Cell Cancer Treated With Upfront Surgery vs Definitive Chemoradiation Therapy: An Observational Study
Kelly JR, Park HS, An Y, Contessa JN, Yarbrough WG, Burtness BA, Decker R, Husain Z. Comparison of Survival Outcomes Among Human Papillomavirus–Negative cT1-2 N1-2b Patients With Oropharyngeal Squamous Cell Cancer Treated With Upfront Surgery vs Definitive Chemoradiation Therapy: An Observational Study. JAMA Oncology 2017, 3: 1107-1111. PMID: 28056116, PMCID: PMC5824218, DOI: 10.1001/jamaoncol.2016.5769.Peer-Reviewed Original ResearchConceptsOropharyngeal squamous cell carcinomaHPV-negative oropharyngeal squamous cell carcinomaNegative oropharyngeal squamous cell carcinomaMultivariable Cox regressionPrimary surgical resectionOverall survivalUpfront surgerySurgical resectionObservational studyChemoradiation therapySurgical patientsAdjuvant CRTSurvival outcomesCox regressionNational Cancer Data BaseOropharyngeal squamous cell cancerDefinitive chemoradiation therapyMost surgical patientsConcurrent chemoradiation therapyHPV-positive diseaseMargin-negative resectionOptimal patient selectionPrimary treatment modalityUpfront surgical resectionKaplan-Meier analysisBiomarkers predict enhanced clinical outcomes with afatinib versus methotrexate in patients with second-line recurrent and/or metastatic head and neck cancer
Cohen EEW, Licitra LF, Burtness B, Fayette J, Gauler T, Clement PM, Grau JJ, del Campo JM, Mailliez A, Haddad RI, Vermorken JB, Tahara M, Guigay J, Geoffrois L, Merlano MC, Dupuis N, Krämer N, Cong XJ, Gibson N, Solca F, Ehrnrooth E, Machiels J. Biomarkers predict enhanced clinical outcomes with afatinib versus methotrexate in patients with second-line recurrent and/or metastatic head and neck cancer. Annals Of Oncology 2017, 28: 2526-2532. PMID: 28961833, PMCID: PMC5834024, DOI: 10.1093/annonc/mdx344.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, IntravenousAdministration, OralAfatinibAntimetabolites, AntineoplasticBiomarkers, TumorBiopsyCarcinoma, Squamous CellDisease-Free SurvivalHead and Neck NeoplasmsHumansMethotrexateNeoplasm MetastasisNeoplasm Recurrence, LocalPredictive Value of TestsQuinazolinesSquamous Cell Carcinoma of Head and NeckConceptsProgression-free survivalMetastatic headEfficacy outcomesMedian progression-free survivalRecurrent/metastatic headNeck squamous cell carcinomaTumor biomarkersNeck 1 trialP16-positive diseaseSecond-line afatinibOverall study populationSubset of patientsP16-negative tumorsSquamous cell carcinomaEnhanced clinical outcomesBiomarker analysisM HNSCCTherapy-naïveBaseline characteristicsStudy entryClinical outcomesHNSCC patientsPlatinum therapyCell carcinomaNeck cancerTreatment guidelines and patterns of care in oral cavity squamous cell carcinoma: Primary surgical resection vs. nonsurgical treatment
Fujiwara RJT, Burtness B, Husain ZA, Judson BL, Bhatia A, Sasaki CT, Yarbrough WG, Mehra S. Treatment guidelines and patterns of care in oral cavity squamous cell carcinoma: Primary surgical resection vs. nonsurgical treatment. Oral Oncology 2017, 71: 129-137. PMID: 28688680, DOI: 10.1016/j.oraloncology.2017.06.013.Peer-Reviewed Original ResearchMeSH KeywordsAgedCarcinoma, Squamous CellFemaleHealth Services AccessibilityHumansMaleMiddle AgedMouth NeoplasmsPractice Guidelines as TopicSurvival AnalysisConceptsOral cavity squamous cell carcinomaNational Cancer Data BaseLate-stage diseasePrimary nonsurgical treatmentOral cavity malignancyNonsurgical treatmentSquamous cell carcinomaOverall survivalSurgical resectionCell carcinomaTreatment modalitiesNational Comprehensive Cancer Network Clinical Practice GuidelinesAcademic/research programMultimodality clinical trialsDefinitive radiation therapyImproved overall survivalDecreased overall survivalPrimary surgical resectionOral cavity cancerNon-randomized natureClinical practice guidelinesPatterns of careNon-white raceProportional hazards modelBinary logistic regressionThe prognostic value of extranodal extension in human papillomavirus‐associated oropharyngeal squamous cell carcinoma
An Y, Park HS, Kelly JR, Stahl JM, Yarbrough WG, Burtness BA, Contessa JN, Decker RH, Koshy M, Husain ZA. The prognostic value of extranodal extension in human papillomavirus‐associated oropharyngeal squamous cell carcinoma. Cancer 2017, 123: 2762-2772. PMID: 28323338, DOI: 10.1002/cncr.30598.Peer-Reviewed Original ResearchMeSH KeywordsCarcinoma, Squamous CellChemoradiotherapy, AdjuvantFemaleHead and Neck NeoplasmsHumansMaleMiddle AgedMultivariate AnalysisNeoplasm InvasivenessNeoplasm StagingOropharyngeal NeoplasmsOtorhinolaryngologic Surgical ProceduresPapillomaviridaePapillomavirus InfectionsPrognosisPropensity ScoreProportional Hazards ModelsRadiotherapy, AdjuvantRetrospective StudiesSquamous Cell Carcinoma of Head and NeckSurvival RateConceptsOropharyngeal squamous cell carcinomaENE-positive patientsHPV-positive oropharyngeal squamous cell carcinomaExtranodal extensionHPV-positive patientsOverall survivalPrimary surgeryPT4 tumorsAdjuvant chemoradiationConcurrent chemoradiotherapyAdjuvant treatmentPositive oropharyngeal squamous cell carcinomaPT3/pT4 tumorsMultivariable Cox regression analysisNational Cancer Data BasePredictors of OSPropensity score-matched comparisonAdjuvant concurrent chemoradiotherapyCharlson-Deyo scoreInvolved lymph nodesAdverse prognostic factorInferior overall survivalLymph node statusCox regression analysisSingle-institution studyTRAF3/CYLD mutations identify a distinct subset of human papillomavirus‐associated head and neck squamous cell carcinoma
Hajek M, Sewell A, Kaech S, Burtness B, Yarbrough WG, Issaeva N. TRAF3/CYLD mutations identify a distinct subset of human papillomavirus‐associated head and neck squamous cell carcinoma. Cancer 2017, 123: 1778-1790. PMID: 28295222, PMCID: PMC5419871, DOI: 10.1002/cncr.30570.Peer-Reviewed Original ResearchConceptsHPV-positive HNSCCNeck squamous cell carcinomaDe-escalation therapyHPV-positive HNSCCsMechanisms of HPVRecurrent metastatic diseaseBetter overall survivalSquamous cell carcinomaNuclear factor-κB signalingFactor-κB signalingNew therapeutic strategiesNuclear factor κBHPV vaccineCancer Genome AtlasCurative optionHPV statusMetastatic diseaseOverall survivalCervical cancerPatient survivalSmoking characteristicsCell carcinomaHuman papillomavirusLifelong morbidityClinical trialsA Comparison of Prognostic Ability of Staging Systems for Human Papillomavirus–Related Oropharyngeal Squamous Cell Carcinoma
Husain ZA, Chen T, Corso CD, Wang Z, Park H, Judson B, Yarbrough W, Deshpande H, Mehra S, Kuo P, Decker RH, Burtness BA. A Comparison of Prognostic Ability of Staging Systems for Human Papillomavirus–Related Oropharyngeal Squamous Cell Carcinoma. JAMA Oncology 2017, 3: 358-365. PMID: 27737449, DOI: 10.1001/jamaoncol.2016.4581.Peer-Reviewed Original ResearchConceptsOropharyngeal squamous cell cancerAJCC/UICC systemStaging systemStage IAStage IBHuman papillomavirusPrognostic abilityUICC systemAJCC/UICC staging systemStage IICurrent American Joint CommitteeOropharyngeal squamous cell carcinomaInternational Cancer Control (UICC) staging systemOropharyngeal cancer NetworkNational Cancer DatabasePrimary radiation therapyOverall survival rateAmerican Joint CommitteeCancer/UnionEdition staging systemKaplan-Meier methodSquamous cell cancerNovel staging systemSquamous cell carcinomaLog-rank testThe risk of level IB nodal involvement in oropharynx cancer: Guidance for submandibular gland sparing irradiation
Lee NCJ, Kelly JR, Park HS, Yarbrough WG, Burtness BA, Husain ZA. The risk of level IB nodal involvement in oropharynx cancer: Guidance for submandibular gland sparing irradiation. Practical Radiation Oncology 2017, 7: e317-e321. PMID: 28356201, DOI: 10.1016/j.prro.2017.02.004.Peer-Reviewed Original ResearchMeSH KeywordsCarcinoma, Squamous CellFemaleHead and Neck NeoplasmsHumansLymph Node ExcisionLymph NodesLymphatic MetastasisMaleMiddle AgedNeoplasm StagingOrgan Sparing TreatmentsOropharyngeal NeoplasmsPapillomaviridaeParotid GlandRadiotherapy, AdjuvantRetrospective StudiesSquamous Cell Carcinoma of Head and NeckSubmandibular GlandXerostomiaConceptsOropharyngeal squamous cell cancerPositive nodesNodal involvementLevel Ib lymph nodesIb lymph nodesPrimary surgical treatmentRetrospective chart reviewCohort of patientsCommon side effectsSquamous cell cancerIpsilateral neckNodal dissectionOropharynx cancerChart reviewNeck irradiationLymph nodesSurgical treatmentCell cancerLevel IbNodal stationsNegative imagingRadiation therapyLower riskSide effectsPatientsHuman Papillomavirus Genotypes Conferring Poor Prognosis in Head and Neck Squamous Cell Carcinoma
Psyrri A, Rampias T, Burtness B. Human Papillomavirus Genotypes Conferring Poor Prognosis in Head and Neck Squamous Cell Carcinoma. JAMA Oncology 2017, 3: 125. PMID: 27607105, DOI: 10.1001/jamaoncol.2016.3409.Peer-Reviewed Original Research