• Non ci sono risultati.

Impact of physician experience and multidisciplinary team on clinical outcome in patients receiving sorafenib

N/A
N/A
Protected

Academic year: 2021

Condividi "Impact of physician experience and multidisciplinary team on clinical outcome in patients receiving sorafenib"

Copied!
3
0
0

Testo completo

(1)

Please cite this article in press as: Gardini AC, et al. Impact of physician experience and multidisci-plinary team on clinical outcome in patients receiving sorafenib. Clin Res Hepatol Gastroenterol (2018), https://doi.org/10.1016/j.clinre.2018.11.005

ARTICLE IN PRESS

+Model

CLINRE-1207; No.ofPages3

ClinicsandResearchinHepatologyandGastroenterology(2018)xxx,xxx.e1—xxx.e3

Availableonlineat

ScienceDirect

www.sciencedirect.com

LETTER

TO

THE

EDITOR

Impact

of

physician

experience

and

multidisciplinary

team

on

clinical

outcome

in

patients

receiving

sorafenib

KEYWORDS Sorafenib; Hepatocellularcarcinoma; TACE; Chemoembolization; Multidisciplinaryteam; Physicianexperience Deareditor,

The experience level of the physician could alter the disease outcome. Tsung-Ming Chen et al [1] have shown that the survival of HCC patients was dependent on the level of experience of the physicians in charge of these patients. Differences in survival wasobserved in patients withBCLCAandBCLCBstages, notin patientswithBCLC C. The study was published before the introduction of sorafenib in clinical practice.In the real world, stillfew patientswithadvancedHCCareproperlymanagedby ded-icated physicians experienced in HCC management, with stillunclearclinical impactonsurvival. In other oncology diseases severalstudieshaveinvestigatedtheimpactof a multidisciplinary team (MDT) framework and/or multidis-ciplinary clinic (i.e. multiple consultations with different membersofanMDTduringasinglepatientvisit)onpatient outcome, assessmentand management.Resultshave gen-erally indicated that MDTs and/or multidisciplinary clinics were associated withchanges in staging/diagnosis, initial managementplans,higherratesoftreatment,shortertime to treatment after diagnosis, better survival, and adher-enceto clinical guidelines.Forthis reason,we evaluated theprognosticeffectsinpatientscaredbyphysicianswith differingexperienceinHCCmanagement.

We enrolledpatients receivingsorafenib for advanced-orintermediate-stageHCChistologicallyconfirmedor diag-nosedaccordingtotheAmericanAssociationfor theStudy

of Liver Diseases (AASLD) 2005 guidelines and refractory toor no longer amenable to locoregional therapies were consideredforthepresentstudy.Inthisstudy,wedefined ‘‘patientsmanagedbyadedicatedphysician’’(DPpatients) thosepatientsmanagedbyanoncologistdedicatedtoHCC patients.Dedicatedphysicianscloselycooperatedwiththe MDT,whichwascomposedofanoncologist,ahepatologist,a surgeon,aradiologist,adermatologist,apathologist,a biol-ogistandapalliativecarephysician.Wedefined‘‘patients notmanagedbyadedicatedphysician’’(nDPpatients)those whoweremanagedbyan oncologistnotdedicatedtoHCC patients.Non-dedicatedphysiciansdidnotcooperatewith the MDT. This retrospective study was conducted on 77 advancedHCCpatients consecutivelytreatedat our insti-tute(IstitutoScientificoRomagnoloperloStudioelaCura deiTumori(IRST),IRCCS,Meldola,Italy)from2011to2015. Amongtheentirecohort,49patients(63.6%)weremanaged byonededicatedoncologist,whiletheremaining28patients (36.4%)weremanagedbythreenon-dedicatedoncologists. Patientcharacteristicswerewellbalancedbetweenthetwo groups.

Patients managed by a dedicated physician (DP) had a median PFS of 4.6months (95% CI 2.8—6.0) compared to2.0months(95% CI 1.2—2.5)for those notmanaged by a dedicatedphysician (nDP) (P<0.0001) (HR0.35, 95% CI 0.21—0.58,P<0.0001)(Fig.1A).DPpatientshadamedian OS of 13.3 months (95% CI 6.8—15.6) compared to 3.1 months (95% CI 2.1—9.7) for nDP patients (P=0.002) (HR 0.44,95%CI0.26—0.75,P=0.003)(Fig.1B).OSwas indepen-dent of second line-treatment.After adjustingfor clinical covariates (BCLC stage, performance status, meld score, basallevelofalphafetoprotein,extraepaticvs.hepatic dis-ease,starting dose of sorafenib),the physiciandedicated remainedindependentprognosticfactorsforPFS(HR=0.26, 95% CI 0.13—0.52, P=0.0001) and OS (HR=0.34, 95% CI 0.16—0.73, P=0.006). nDP patients showed a higher per-centage of progression at the first CT re-evaluation than nDPpatients(79.3%vs.46.9%,respectively)(P=0.008).We alsoobserved that nDP patients showeda lower percent-age of DCR (22.7%) than DP patients (46.2%) at the first CTre-evaluation (P=0.030).Sorafenib wasreduced in the firsttwomonthsof treatmentin DPpatients comparedto nDP patients (51% vs. 85.7%, respectively) (P=0.003). DP https://doi.org/10.1016/j.clinre.2018.11.005

(2)

Please cite this article in press as: Gardini AC, et al. Impact of physician experience and multidisci-plinary team on clinical outcome in patients receiving sorafenib. Clin Res Hepatol Gastroenterol (2018), https://doi.org/10.1016/j.clinre.2018.11.005

ARTICLE IN PRESS

+Model

CLINRE-1207; No.ofPages3

xxx.e2 Lettertotheeditor

Figure1

patientswereseenmorefrequentlyinthefirsttwomonths thannDPpatients[median3consultations(range1—5)vs. 2 (range 1—4), P=0.0002; average 2.98 (standard devia-tion1.05)vs.2.03(standard deviation0.82),P<0.0001].A dermatologist saw 28.5% of nDP patients against 100% of DP patients for dermal toxicity (P=0.001). In our study, we found that DP patients had a better outcome than nDP patients. In our opinion, there are two reasons for thisresult:bettermanagementofsorafenib-relatedadverse events(AEs)andthepresenceofanMDT(19—20).

AEs include hand—foot skin reaction, rash, upper and lowergastrointestinaldistress(i.e.diarrhea), fatigue,and hypertension.TheseAEscommonlyrangefromgrade1to3, accordingtotheCommonTerminologyCriteriaforAdverse Events,andoftenoccurearlyintreatment.ThegoalofAEs management is to prevent, treat, and/or minimize their effect,therebyenabling patients toremain ontreatment andimprovetheirqualityoflife.OurstudyshowedthatPD patientshaveasmallerdose reductionofsorafenibinthe firsttwomonthsoftherapy,thankstoabettercontrolofthe AEsbythededicatedphysician.

Forexample,HSFRlesionsaresharplydemarcated, ery-thematous,edematous,painful,highlytenderblistersthat make walkingdifficulty. HSFR isdose-dependent andvery characteristicallylocalized inareas ofpressureor friction ontheskin,adjacenttothecalluses.Anappropriate mana-gementofskintoxicitybyanexpert dermatologist,would increasepatientcompliancetotreatmentandimprove qual-ityoflife.

Tooptimizecare,thepatientswithHCCshouldbe man-agedbyanMDT[2].TheMDTmustbeperformedby:medical oncologist,hepatologist,hepatobiliarysurgeon,diagnostic radiologistand/oraninterventionalradiologist,pathologist, biologistandpalliativecarephysician[2].

AccordingtotheAmericanAssociation forthe Studyof LiverDiseases PracticeGuidelines for the managementof HCC, the complexity of HCC suggests that it should be managed in a multidisciplinary setting [3]. Unfortunately, multidisciplinarymanagementis notfullyimplemented.A recentsurveyin theUnitedStates found thatonly 44%of physiciansregularlyadopt amultidisciplinary approachto treatHCC[4].

AnMDTcantakeintoconsiderationalltheavailable ther-apies, giving the patients the possibilityto be treated in themostaggressiveandeffectiveway.Inthepresentstudy, patients evaluatedin an MDTreceived significantly more associatedtherapies than nPDpatients witharemarkable outcomeimprovement.

Acloseinteractionbetweenthehepatologist,oncologist, radiologistandsurgeonisnecessarytostrictlymonitorthe underlyingliverdisease,optimizetheclinicaloutcomesand choose the most effective treatment. Among the oncolo-gist’sresponsibilitiesisthemanagementofAEsinducedby systemicdrugs.

AstheMDTpresidesovertheentiremanagementofHCC patients,itistheidealsettingforobservationaland trans-lationalresearch.Forthisreasonthefigureofthebiologist is very important within the MDT. Translational research projects aim to identify novel prognostic predictors and molecular targets, and tofacilitate their implementation intheroutineclinicalmanagementofpatients[5—10].

Our results showed that the survival of patients with advanced HCC was dependent onboth the experience of thephysicianandthemultidisciplinaryapproach.

Disclosure

of

interest

The author hasnot supplied hisdeclaration of competing interest.

References

[1]ChenTM,etal.Managementandpatientsurvivalin hepato-cellularcarcinoma:does thephysician’slevelof experience matter?JGastroenterolHepatol2008;23:179—88.

[2]Sherman M, et al. Multidisciplinary Canadian consensus recommendationsforthemanagementandtreatmentof hep-atocellularcarcinoma.CurrOncol2011;18:228—40.

[3]Bruix J, Sherman M. Management of hepatocellular carci-noma:anupdate.Hepatology2011;53:1020—2.

[4]Abou-Alfa G, Colombo M. Shaping the future management ofhepatocellular carcinoma. Semin Liver Dis2013;33(Suppl 1):S20—3.

(3)

Please cite this article in press as: Gardini AC, et al. Impact of physician experience and multidisci-plinary team on clinical outcome in patients receiving sorafenib. Clin Res Hepatol Gastroenterol (2018), https://doi.org/10.1016/j.clinre.2018.11.005

ARTICLE IN PRESS

+Model

CLINRE-1207; No.ofPages3

Lettertotheeditor xxx.e3

[5]CasadeiGardiniA,etal.eNOSpolymorphismsandclinical out-comeinadvancedHCCatientsreceivingsorafenib:finalresults oftheePHASstudy.Oncotarget2016[epubaheadofprint]. [6]CasadeiGardiniA,etal.Earlyonsetofhypertensionandserum

electrolytechangesas potentialpredictive factors of activ-ityinadvancedHCCpatientstreatedwithsorafenib:results fromaretrospectiveanalysisoftheHCC-AVRgroup.Oncotarget 2016;7:15243—51.

[7]Casadei Gardini A, et al. Metformin and insulin impact on clinicaloutcomeinpatientswithadvancedhepatocellular car-cinoma receiving sorafenib: validation study and biological rationale.EurJCancer2017;86:106—14.

[8]Casadei Gardini A, et al. Efficacy of sorafenib in BRAF-mutated non-small-cell lung cancer (NSCLC) and no response in synchronous BRAF wild type-hepatocellular carcinoma: a case report. BMC Cancer 2016;7(16):429, http://dx.doi.org/10.1186/s12885-016-2463-2.

[9]CasadeiGardiniA,etal.Immuneinflammationindicatorsand implicationforimmunemodulationstrategiesinadvanced hep-atocellularcarcinomapatientsreceivingsorafenib.Oncotarget 2016,http://dx.doi.org/10.18632/oncotarget.1156.

[10] Casadei Gardini A. et al. Multicenter Prospective Study of AngiogenesisPolymorphismValidationinHCCPatientsTreated withSorafenib.AnINNOVATEStudyProtocol.Tumori.2017Dec 1:tj5000704.

AndreaCasadeiGardinia,∗

EmanuelaScarpib

FrancescoGiuseppeFoschic

GiorgiaMarisid

MarcoMaltonie

GiovanniLucaFrassinetia

aDepartmentofMedicalOncology,IstitutoScientifico

RomagnoloperloStudioelaCuradeiTumori(IRST)IRCCS, Meldola,Italy

bUnitofBiostatisticsandClinicalTrials,Istituto

ScientificoRomagnoloperloStudioelaCuradeiTumori (IRST)IRCCS,Meldola,Italy

cDepartmentofInternalMedicine,FaenzaHospital,AUSL

Romagna,Faenza,Italy

dBiosciencesLaboratory,IstitutoScientificoRomagnoloper

loStudioelaCuradeiTumori(IRST)IRCCS,Meldola,Italy

ePalliativeCareUnit,IstitutoScientificoRomagnoloperlo

StudioelaCuradeiTumori(IRST)IRCCS,Meldola,Italy

Correspondingauthor.

E-mailaddress:andrea.casadei@irst.emr.it (A.C.Gardini)

Riferimenti

Documenti correlati

minimo se la regolarizzazione degli errori e delle omissioni avviene entro il termine per la presentazione della dichiarazione relativa all’anno successivo a

In particolare si è concentrata l'attenzione sui livelli collegati all'accessibilità del litorale, ossia la morfologia del litorale, le aree edificate, le

Dynamical heterogeneities 22 are clusters of particles with correlated motion, that are commonly identified via the investigation of the time dependence of the distribution of

La tomba di Muḥammad ibn ‘Alī al-Tirmiḏī sorge non lontano dalle rovine della città vecchia, è un edifi - cio di mattoni di grande bellezza, con un alto portale e una

These simulations employ a realistic description of the electronic wave packet launched by the attosecond pulse and, furthermore, they account for non-adiabatic and nuclear

The computation of the magnetic permeability appears to be harder than the evaluation of the conductivity, but the multi-frequency approach leads to accurate approximations of

Polyphenols are mostly antioxidant and anti-inflammatory compounds, able to modulate abnormal cellular signaling induced by pro-inflammatory stimuli and oxidative stress, as