Sarcoma European and Latin American Network (SELNET

Sarcoma European and Latin American Network (SELNET)

Recommendations on Prioritization in Sarcoma Care During the

COVID-19 PandemicJAVIER MARTIN-BROTO ,a,b NADIA HINDI,a,b SAMUEL AGUIAR JR,c RONALD BADILLA-GONZÁLEZ,g VICTOR CASTRO-OLIDEN,h MATIAS CHACÓN,j

RAQUEL CORREA-GENEROSO,k ENRIQUE DE �ALAVA,l,m,n DAVIDE MARÍA DONATI,o MIKAEL ERIKSSON,p MARTIN FALLA-JIMENEZ,i GISELA GERMAN,q

MARIA LETICIA GOBO SILVA,d FRANCOIS GOUIN,r ALESSANDRO GRONCHI,s JUAN CARLOS HARO-VARAS,h NATALIA JIMÉNEZ-BRENES,u BERND KASPER,v

CELSO ABDON LOPES DE MELLO,e ROBERT MAKI,w PAULA MARTÍNEZ-DELGADO,a HECTOR MARTÍNEZ-SAID,x JORGE LUIS MARTINEZ-TLAHUEL,y

JOSE MANUEL MORALES-PÉREZ,z FRANCISCO CRISTOBAL MUÑOZ-CASARES,aa SUELY A. NAKAGAWA,f EDUARDO JOSE ORTIZ-CRUZ,bb

EMANUELA PALMERINI,cc SHREYASKUMAR PATEL,dd DAVID S. MOURA,a SILVIA STACCHIOTTI,t MARIE PIERRE SUNYACH,ee CLAUDIA M. VALVERDE,gg

FEDERICO WAISBERG,j JEAN-YVES BLAYffaGroup of Advanced Therapies and Biomarkers in Sarcoma, Institute of Biomedicine of Seville (IBIS, HUVR, CSIC, Universidad de Sevilla),Sevilla, Spain; bDepartment of Medical Oncology, University Hospital Virgen del Rocio, Seville, Spain; Departments of cPelvic Surgery,dRadiation Therapy, eMedical Oncology, and fOrthopedics, A.C. Camargo Cancer Center, S~ao Paulo, Brazil; gDepartment of Medical

Oncology, Rafael �Angel Calderón Guardia Hospital, San José, Costa Rica; Departments of hMedical Oncology and iBreast and SoftTissues Surgery, Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru; jDepartment of Medical Oncology, Alexander FlemingCancer Institute, Buenos Aires, Argentina; kRadiotherapy Department, Virgen de la Victoria University Hospital, Málaga, Spain;lPathology Department, University Hospital Virgen del Rocío, Seville, Spain; mCIBERONC, Madrid, Spain; nDepartment of Normal andPathological Cytology and Histology, School of Medicine, University of Seville, Seville, Spain; oUnit of Orthopedic Pathology andOsteoarticular Tissue Regeneration, Rizzoli Orthopedic Institute, Bologna, Italy; pDepartment of Medical Oncology, Skane UniversityHospital-Lund, Lund, Sweden; qDepartment of Medical Oncology, Hospital Oncológico Provincial, Córdoba, Argentina; rDepartment ofOrthopedic Surgery, Centre León Bérard, Lyon, France; Departments of sSurgery and tMedical Oncology, Fondazione IRCCS IstitutoNazionale dei Tumori and University of Milan, Milan, Italy; uDepartment of Medical Oncology, San Vicente de Paúl Hospital, Heredia,Costa Rica; vDepartment of Medical Oncology, Mannheim University Medical Center, Mannheim, Germany; wDepartment of MedicalOncology, Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA;Departments of xMedical Oncology and ySurgery, Instituto Nacional de Cancerología, Mexico City, Mexico; zRadiology Department andaaDepartment of Surgery, University Hospital Virgen del Rocio, Seville, Spain; bbOrthopedic Surgery and Traumatology Department, LaPaz University Hospital, Madrid, Spain; ccDepartment of Medical Oncology, Rizzoli Orthopedic Institute, Bologna, Italy; ddDepartment ofMelanoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA; Departments of eeRadiationTherapy and ffMedical Oncology, Centre León Bérard, Lyon, France; ggDepartment of Medical Oncology, Vall d’Hebron Hospital,Barcelona, SpainDisclosures of potential conflicts of interest may be found at the end of this article.

Key Words. COVID-19 • Sarcoma • Guidelines • Patient care • Multidisciplinary

ABSTRACT

Background. The COVID-19 outbreak has resulted in collisionbetween patients infected with SARS-CoV-2 and those with can-cer on different fronts. Patients with cancer have been impactedby deferral, modification, and even cessation of therapy. Adaptivemeasures to minimize hospital exposure, following the precau-tionary principle, have been proposed for cancer care during

COVID-19 era. We present here a consensus on prioritizing rec-ommendations across the continuum of sarcoma patient care.Material and Methods. A total of 125 recommendations wereproposed in soft-tissue, bone, and visceral sarcoma care. Recom-mendations were assigned as higher or lower priority if they can-not or can be postponed at least 2–3 months, respectively. The

Correspondence: Javier Martin-Broto, M.D., Ph.D., Department of Medical Oncology, University Hospital Virgen del Rocío, Instituto de Biome-dicina de Sevilla, LAB 214, C/Antonio Maura Montaner s/n, 41013 – Seville, Spain. Telephone: 34 955923113; e-mail: [email protected] Received June 3, 2020; accepted for publication August 14, 2020. http://dx.doi.org/10.1634/theoncologist.2020-0516This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits useand distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adapta-tions are made.

© 2020 The Authors.The Oncologist published by Wiley Periodicals LLC on behalf of AlphaMed Press.

The Oncologist 2020;25:1–12 www.TheOncologist.com

Sarcomas

https://orcid.org/0000-0001-7350-6916

mailto:[email protected]

mailto:[email protected]

http://dx.doi.org/10.1634/theoncologist.2020-0516

http://creativecommons.org/licenses/by-nc-nd/4.0/

consensus level for each recommendation was classified as“strongly recommended” (SR) if more than 90% of expertsagreed, “recommended” (R) if 75%–90% of experts agreed and“no consensus” (NC) if fewer than 75% agreed. Sarcoma expertsfrom 11 countries within the Sarcoma European-Latin AmericanNetwork (SELNET) consortium participated, including countries inthe Americas and Europe. The European Society for MedicalOncology-Magnitude of clinical benefit scale was applied tosystemic-treatment recommendations to support prioritization.Results. There were 80 SRs, 35 Rs, and 10 NCs among the125 recommendations issued and completed by 31 multi-

disciplinary sarcoma experts. The consensus was higheramong the 75 higher-priority recommendations (85%, 12%,and 3% for SR, R, and NC, respectively) than in the 50 lower-priority recommendations (32%, 52%, and 16% for SR, R, andNC, respectively).Conclusion. The consensus on 115 of 125 recommendationsindicates a high-level of convergence among experts. TheSELNET consensus provides a tool for sarcoma multi-disciplinary treatment committees during the COVID-19outbreak. The Oncologist 2020;25:1–12

Implications for Practice: The Sarcoma European-Latin American Network (SELNET) consensus on sarcoma prioritizationcare during the COVID-19 era issued 125 pragmatical recommendations distributed as higher or lower priority to protectcritical decisions on sarcoma care during the COVID-19 pandemic. A multidisciplinary team from 11 countries reached con-sensus on 115 recommendations. The consensus was lower among lower-priority recommendations, which shows reticenceto postpone actions even in indolent tumors. The European Society for Medical Oncology-Magnitude of Clinical Benefit scalewas applied as support for prioritizing systemic treatment. Consensus on 115 of 125 recommendations indicates a high levelof convergence among experts. The SELNET consensus provides a practice tool for guidance in the decisions of sarcoma mul-tidisciplinary treatment committees during the COVID-19 outbreak.

INTRODUCTION

Deferral, modification, and even cessation of therapy arehindrances affecting patients with cancer during the currentCOVID-19 outbreak. The balance between adapting mea-sures to minimize hospital exposure, following the precau-tionary principle, and offering a more relaxed diagnostic ortherapeutic management while preserving the patient’s sur-vival options is not easy.

More than 80 reports, often short reports and letters,have addressed the intersection of cancer and COVID-19care. Although the risk of morbidity and mortality is almostalways higher in patients with cancer than in patientsinfected with COVID-19 (i.e., risk of death for pancreaticcancer is greater than 90%, whereas for COVID-19-infected patients, it is usually lower than 5%) [1], thetruth is that the precautionary principle has prevailedover cancer care continuation in many cases [2]. Electivesurgeries were largely suspended, in some instances,because of shortage of ventilators, and thus the operatingtheaters became extemporaneous intensive care units.Some reports have focused on the real impact (directand indirect) of the COVID-19 outbreak in patients withcancer. In some locales where the admissions for SARS-CoV-2 far exceeded the hospital capacity, it was to beexpected that cancer care would be compromised in avariety of ways.

Patients with cancer constitute a large populationwith a spectrum of risk with respect to immunosuppres-sion. Cancer immunoediting, which represents the inter-play between tumor and immune system, ultimatelyleads to changes in immune cells, immune modulators,cytokines, and molecules expression toward the escapephase and the development of an immunosuppressivetumor microenvironment [3]. Both specific diagnosesand their treatment with chemotherapy, surgical resec-tion, and newer treatments variably compromise immune

function and render some patients with cancer more sus-ceptible to infections [4].

As with other infections, the innate and adaptive armsof the immune system play different key roles in theCOVID-19 infection and evolution. SARS-CoV-2 causes anoverwhelming persistent innate-induced inflammation thatcan lead to a cytokine storm, cytokine-associated lunginjury, and diffuse organ involvement [5]. Alterations of theCD4+ and CD8+ T cells subsets have been observed, withloss of functional diversity in CD4+ T cells and increasedexpression of regulatory molecules in CD8+ T cells [6, 7].Hence, it can be assumed that the systemic immunosup-pressive state of patients with cancer might result in anincreased risk of COVID-19 infection and poorer prognosisfor this group of patients.

Epidemiological statistics of the cases in China sugg-ested that patients with cancer were at greater risk thanthe general population, data which appear to be borne outmore for hematologic malignancies than solid tumors,although there still appears to be greater risk even forpatients with solid tumor for fatal outcomes from SARS-CoV-2[8]. Noteworthy, it has been reported that COVID-19–related deaths were strongly associated with male sex,older age, and deprivation; severe asthma; uncontrolleddiabetes; cancer; and several other previous, clinical condi-tions [9].

Importantly, a recent epidemiological report from theU.K. based on 800 patients with cancer with COVID-19infection observed a mortality rate of 28%, with older age,male gender, and comorbidities, such as cardiovascular dis-ease, significant prognostic factors related to higher mortal-ity. Remarkably, chemotherapy or other systemic therapyadministered within 4 weeks of testing positive for COVID-19 did not have significant effect on mortality from COVID-19 disease [10].


SELNET Recommendations in Sarcoma During COVID-192

Taken together, rapidly evolving data indicate that onco-logic patients, such as patients with sarcoma, constitute ahigh-risk group more likely to suffer higher mortality andmorbidities than in the general population if infected bySARS-CoV-2.

Additionally, during the COVID-19 outbreak, the majorrisk for patients with cancer is the inability to receive neces-sary medical services. Decisions on whether or not to post-pone cancer treatment and clinical trials need to be madeon a patient-by-patient basis and according to the inherenttumor risk in each patient and the prevailing situation,because delays could lead to tumor progression and, ulti-mately, poorer outcomes [11]. An article on patients’ per-spectives reported that up to 30% of oncologic patientshave had changes in their treatment or follow-up care dur-ing the COVID-19 pandemic [12]. Beyond the increasedrisks, including requiring mechanical ventilation and death,that should be prospectively analyzed in oncologic patientswith COVID-19 infection, it is also relevant to take intoaccount the impact of the precautionary principle that isimplemented in our patients [13]. The latter implies thatpatients with cancer have suffered delays or cancellation ofdiagnostic tests, surgeries, radiation therapies, or systemictreatments.

The aim of this article is to build a consensus on prioriti-zation aspects in sarcoma care during the current COVID-19outbreak or future outbreaks, which could appropriatelybalance the precautionary principle while preserving thehighest survival probabilities in sarcoma patients.

This consensus has been developed within the SarcomaEuropean-Latin American Network (SELNET). This is aconsortium granted by the European Commission withinthe Horizon 2020 Call, within the program H2020-SC1-BHC-2018-2020 (better health and care, economic growth, andsustainable health systems). The aim of the SELNET consor-tium is to improve clinical outcome in sarcoma care,through a network of reference centers in sarcoma [14].

These guidelines are intended to add value over andabove other clinical practice guidelines reported for onco-logic patients in the context of COVID-19 outbreak. Thus,our guidance focuses specifically on patients with sarcomaand thoroughly provides precise details on prioritization of125 clinical sarcoma situations, whereas the National Insti-tute for Health and Care Excellence (NICE) offers a generalrecommendation for any oncologic patient [15], and theEuropean Society for Medical Oncology (ESMO) offers amore general recommendation of prioritization for patientswith sarcoma [16].

MATERIALS AND METHODS

The recommendations have been divided into two scenar-ios, higher and lower priority, to make them simple and rep-licable. Higher priority is defined as an undelayableprocedure, because the inherent risk of the tumor, affectingsurvival or morbidity, would likely exceed the risk of COVID-19 infection if this procedure had not been performed. Bycontrast, lower priority is defined as a delayable procedure(at least 2–3 months), because the inherent risk of thetumor, affecting survival or morbidity, would be low enough

that the patient could minimize or avoid hospital frequenta-tion and, consequently, reduce the risk of infection byCOVID-19. A total of 125 recommendations have been pro-posed in soft tissue, bone, and visceral sarcomas to thor-oughly cover details for diagnosis, surgery, radiation therapy,systemic treatments, follow-up, and clinical research.

These recommendations were proposed by the SELNETcoordinator team and shared with the official partners ofSELNET network. Associated partners were not involved inthis consensus. Each point derived from multidisciplinary(MDT) expertise discussion from the SELNET coordinationaimed to be pragmatic, detailed, and patient-oriented foreach recommendation.

Official partners had the competence to give their ownopinion if this was clear enough for them or to give theopinion of their MDT on certain recommendations.

In this consensus, MDT experts participated from ACCamargo Cancer Center (Sao Paulo, Brazil), Instituto AlexanderFleming (Buenos Aires, Argentina), Instituto Nacional deEnfermedades Neoplasicas (Lima, Peru), Instituto Nacional deCancerologia (Mexico DF, Mexico), Hospital Calderon Guardia(San José, Costa Rica), Centre Leon Berard (Lyon, France),Istituto Nazionale dei Tumori (Milan, Italy), IRCCS Istituto Ort-opedico Rizzoli (Bologna, Italy), Abramson Cancer Center(Philadelphia, Pennsylvania), University Hospital Lund (Lund,Sweden), Mannheim University Medical Center (Mannheim,Germany), MD Anderson Cancer Center (Houston, Texas),Spanish group for Research on Sarcomas, and University Hos-pital Virgen del Rocio (Sevilla, Spain). Besides that, a Europeanpatient advocacy group (Sarcoma Patients EuroNet) was alsoinvolved in this consensus, as well as the external scientificand ethics committees of SELNET.

Among 31 participating experts in the consensus, therewere 18 oncologists (15 for adults and 3 for pediatrics),4 orthopedic surgeons, 4 surgical oncologists, 2 radiationoncologists, 1 pathologist, and 1 radiologist. As SELNETmainly focuses on adult-type sarcomas, no exclusive pediat-ric oncologist participated in the consensus. Fourteen LatinAmerican sarcoma experts participated in the consensus:nine oncologists, four surgeons, and one radiation thera-pist. Correlations between Latin American and EuropeanUnion (E.U.)-U.S. expert recommendations were evalu-ated using Pearson’s χ2 test for bivariate options (agree-ment or disagreement) and Mann-Whitney U test formultivariate options (strongly agree, agree, disagree, andstrongly disagree).

For each recommendation, every participant chose fromthe following options: strongly agree, agree, disagree, andstrongly disagree. The neutral option was not offered toavoid ambiguity.

Those recommendations with ≥90% of consensus(at least strongly agree plus agree obtained in ≥90% of par-ticipants) were considered as strongly recommended. Thosewith ≥75% but <90% were considered as recommended,and the remaining recommendations were considered as“no consensus was obtained.” The cutoff of 75% has beenthe median threshold to define consensus in Delphi studies[17], whereas the demanding 90% cut-off was arbitrarilychosen to indicate the highest consensus range if at leastthis percentage was reached.


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Martin-Broto, Hindi, Aguilar Jr. et al. 3

To mitigate the subjectiveness, the ESMO-Magnitude ofClinical Benefit Scale (MCBS) V1.1 was applied to re-commendations involving systemic treatments to supportthis prioritization strategy (supplemental online Appendix 1)[18, 19]. Although MCBS has not been formally evaluated forsarcoma therapies, MCBS methodology was followed for theestimation of the benefit obtained with different sarcomasystemic treatments (supplemental online Appendix 2).

RESULTS

From a total of 31 fulfilled questionnaires analyzed, the rec-ommendations were distributed as strongly recommended(SR) in 80, recommended (R) in 35, and no consensus(NC) in 10. The consensus was higher among the 75 higher-priority recommendations (85%, 12%, and 3% for SR, R,and NC, respectively) than in the 50 lower-priority recom-mendations (32%, 52%, and 16% for SR, R, and NC,respectively).

Table 1 describes the consensus level for each recom-mendation and indicates the MCBS in most contexts of sys-temic treatments. The statistical distribution for eachrecommendation is presented in supplemental onlineAppendix 1.

Of note, statistically significant differences betweenLatin American and E.U.-U.S. expert recommendationswere only detected by Pearson’s χ2 and Mann-WhitneyU test in 3 of 125 recommendations (Table 2). E.U.-U.S.experts proved to be more conservative for the adviceof adjuvant chemotherapy in high grade chondrosarcoma,the advice of adjuvant radiotherapy in low-grade, deepsoft-tissue sarcoma (STS) larger than 5 cm, and for theadvice of adjuvant radiotherapy in superficial STS largerthan 5 cm.

DISCUSSION

Because sarcoma multidisciplinary committees are socritical to patient outcomes [20–27], we emphasize themessage that these meetings should continue, at least intele-committee format, in the COVID-19 era. Tele-committees should be scheduled on a regular basis(e.g., weekly), and the following specialists should partici-pate: pathologists, radiologists, surgeons, radiation oncolo-gists, and medical oncologists.

In this article, a prioritization of diagnostic, care, andfollow-up procedures across different sarcoma contexts hasbeen reached by consensus among sarcoma experts fromdifferent disciplines and from 11 countries among LatinAmerican, North America, and Europe. This consensus hasbeen developed within the SELNET consortium as a guideto protect cancer care in the complex and heterogeneousfield of sarcoma during the COVID-19 outbreak. This con-sensus is intended to offer precise advice on different clini-cal sarcoma scenarios that the oncology community couldface, with the aim of prioritizing or postponing differentclinical decisions in patients with sarcoma. The generaloncology community should network with expert centersfrom sarcoma suspicion, and these guidelines can be usedto determine which actions can and cannot be postponed

in the management of patients with sarcoma in the COVID-19 era.

Several oncology societies and health care providersissued recommendations, most often on their websites,regarding adaptive strategies for emergent standards ofcare in patients with cancer during the COVID-19 pandemic[28]. The Cancer Core Europe, which encompasses sevencancer centers and oncologic institutes in seven Europeancountries, published a general consensus on the adaptivemeasures to minimize the number of hospital visits and toprevent anticancer treatment that could induce complica-tions of COVID-19 infections. The methodology for theserecommendations was not defined, however [29].

The NICE issued prioritization guidelines on the use ofsystemic and radiation treatments for cancer. This guideestablished six prioritization levels, from the first for cura-tive treatments offering more than 50% chance of successand adjuvant or neoadjuvant treatment that adds at least50% chance of cure compared with surgery or radiationtherapy alone, to the last level, which is defined as a non-curative regimen with a 15%–50% chance of palliation ortemporary tumor control and less than 1 year expectedextension of life [30]. Similarly, a radiotherapy prioritizationguide was issued with five levels. The general modificationsare based on postponing or avoiding radiation therapy incases of little added value or changing treatment plans toshorten the number of visits to a health care facility [15].ESMO issued several guidelines, by tumor type, for prioritiz-ing care into three or four categories. In the case of sar-coma, the low-priority profile is typified by a stable patientwho can safely have delays in treatment for the duration ofthe COVID-19 pandemic. The intermediate profile is exem-plified by a patient with a noncritical situation but one inwhich delay beyond 6 weeks could impair clinical outcomes[16]. The Society of Surgical Oncology has joined individualsarcoma expert opinions and has issued six recommenda-tion points based on prioritizing actions considering severalsarcoma contexts [31].

Certainly, this prioritization does not focus only on indi-vidual patient risk but also highlights the community risksand benefit: the reduction of people in transit and the isola-tion of patients in general decreases contagion risk in thecommunity, leaving more resources to treat the impact ofCOVID-19 pandemic. However, there are consequences forother group of patients, such as patients with cancer. In TheNetherlands, a remarkable drop in cancer diagnosis wasnoticed from pandemic initiation according to a nationwidecancer registry [32].

There are three principal approaches to conducting con-sensus methodology research: the consensus developmentpanel, the nominal group process, and the Delphi technique[33]. The latter two require at least two sessions or rounds,being more complex. The consensus development panel isthe most common approach used in health care research.This approach consists of organized meetings of experts ina given field and usually requires experts in different disci-plines to make a multidisciplinary consensus. Usually, thisapproach is supported by the literature evidence, and thereare some face-to-face discussions. In sarcoma oncology,ESMO guidelines follow this consensus development panel



Table

1.Prioritizingrecommen

dationsclassified

byhigher

andlower

priority

withconsensusresultsforeach

recommen

dation(percentage

agreeingwiththerecommen

dation)

Higher

Priority

Lower

Priority

Multidisciplin

arySarcomaTelecommittees

Soft-tissue,

bone,

orvisceralsarcoma:

Localized

andad

vanceddisease

1.Everynew

suspicionofsarcoma(softtissue,bone,orvisceral)diagnosis.Theonlyexceptionsbeingthe

caseslikelyto

bewell-differentiated

liposarcomaorlow-riskgastricGIST[Stronglyrecommen

ded

,97%

]2.

Therapeu

ticplanforpatientspreviouslydiagnosedwithanysarcomawithmetastaticlife-threaten

ing

lesions;Ew

ingsarcoma;high-graderecurren

tresectabletumors;high-risklocalized

sarcoma;

osteo

sarcoma;

rhabdomyosarcoma(embryonal,alveo

lar,andsclerosing)

[Stronglyrecommen

ded

,100%]

3.Therapeu

ticplanforrecurren

torprogressingsarcomas

[Stronglyrecommen

ded

,97%

]

Soft-tissue,

bone,

orvisceralsarcoma:

Localized

andad

vanceddisease

4.Cases

withdiagnosticsuspicionofbonelesionslikelyto

beben

ign;desmoid

tumors;lipomas;TG

CT

[Stronglyrecommen

ded

,97%

].5.

Indolenttumorsforwhichthecommitteediscussioncanbedelayed

,atphysiciandiscretion.(i.e.,those

infollow-upwithlengthintervalsof6moorlonger)[Stronglyrecommen

ded

,94%

]

DiagnosticProcess

Soft-tissuesarcoma:

Localized

disease

6.Deeplesionslarger

than

3cm

oranytumorlarger

than

5cm

inlim

bsortrunkwallw

ithnolipomaaspect

[Stronglyrecommen

ded

,100%]

7.Anylumpthat

even

notfittingwithpoint1had

experiencedarecentfastgrowth

[Strongly

recommen

ded

,97%

]8.

Lesionswithsuspicionoflocalrecurren

ce[Stronglyrecommen

ded

,97%

]9.

Localn

eurofibromaorTG

CTwithsuspicionofmalignanttransform

ation[Stronglyrecommen

ded

,97%

]

Soft-tissuesarcoma:

Advanceddisease

10.Anynew

tumorallesionin

somatictissues

withapparen

tmetastaticspread

[Strongly

recommen

ded

,100%]

11.Anynew

metastaticrecurren

cewithunexpectedbeh

aviorforthetumorcontext

[Strongly

recommen

ded

,94%

]

Soft-tissuesarcoma:

Localized

disease

12.Lesionsnotfittingwiththepoints1or2ofthehigher

priority

[Stronglyrecommen

ded

,97%

]13.Retroperitonealm

asswiththeappearance

ofwell-differentiated

liposarcoma[Noconsensus,only74%

agreed

]14.Lesionswithappearance

ofdesmoid

tumorsoroligosymptomaticlesionswithappearance

ofTG

CT[No

consensus,74%]

Soft-tissuesarcoma:

Advanceddisease

15.Lungmicronodules(<1cm

)[Recommen

ded

,81%

]16.Appearance

ofmetastaticspread

inthecontext

ofindolenttumors(i.e.EMCh,o

rASPS)

[Noconsensus,

only74%agreed

]

Bonesarcoma:

Localized

disease

17.Anynew

tumorallesionwithsuspicionofmalignancy

[Stronglyrecommen

ded

,100%]

18.Bonetumorswithoutsuspicionofmalignancy

butwithrisk

offracture

[Stronglyrecommen

ded

,100%]

19.Osteo

chondromas

orGCTB

withsuspicionofmalignanttransform

ation[Stronglyrecommen

ded

,97%

]20.Anysuspicionoflocalrecurren

ce[Stronglyrecommen

ded

,100%]

Bonesarcoma:

Advanceddisease

21.Anynew

bonetumorwithmetastaticspread

[Stronglyrecommen

ded

,97%

]22.Anynew

metastaticrecurren

cewithunexpectedbeh

aviorforthetumorcontext

[Strongly

recommen

ded

,97%

]

Bonesarcoma:

Localized

disease

23.Bonelesionslikelyto

beben

ignwithoutsymptomsorcomplicationrisks[Recommen

ded

,87%

]

Bonesarcoma:

Advanceddisease

24.Lungmicronodules(<1cm

)[Recommen

ded

,77%

]25.Indolentmetastaticdisease

(i.e.,adam

antinoma,periostealo

steo

sarcoma)

[Recommen

ded

,87%

]

GISTorother

visceralsarcomas:Localized

disease

26.Clinicallyeviden

tintram

uralgastrointestinallesion[Stronglyrecommen

ded

,97%

]27.Clinicalandradiologicalsuspicionofuterineleiomyosarcoma(subserosalm

ass,withrecentsymptoms)

[Stronglyrecommen

ded

,97%

]

GISTorother

visceralsarcomas:Advanceddisease

28.Anyappearance

ofnew

nodulessuspectedofmetastaticspread

(excep

tformicronodulesorindolent).

Biopsy

ofmetastaticnoduleswillnotbenecessary

inthecontext

ofconsisten

tnaturalh

istory

[Recommen

ded

,84%

]

GISTorother


disease

29.Intram

urallesions<1–2

cmin

thegastrointestinaltract[Stronglyrecommen

ded

,90%

]30.Uterinemasspredominantlyintram

ural,norecenthistory

ofsymptomsorsigns,more

likelyto

be

myofibromas

[Recommen

ded

,87%

]

GISTorother


31.Appearance

ofmetastaticspread

inthecontext

ofindolentGIST(PDGFRAmutant,KIT/PD

GFRAwild

type)

[Recommen

ded

,81%

]

Surgery

Soft-tissuesarcoma:

Localized

disease

32.High-risk(≥40%risk

fordeath,assessedbySarculator)localized

STSoflim

bs/trunkwall(afterneo

adjuvant

treatm

entifindicated

)[Stronglyrecommen

ded

,100%]

33.Interm

ediate-riskSTS(20%

–40%

risk

fordeath,assessedbySarculator)[Stronglyrecommen

ded

,97%

]

Soft-tissuesarcoma:

Localized

disease

40.Low-risktumors(<20%risk

fordeath)(w

ell-differentiated

liposarcoma;atypicalliposarcoma;low-riskSFT)

[Recommen

ded

,81%

]41.Localrecurren

ceoflow-risktumor[Recommen

ded

,87%

]

(continued

)




Table

1.(continued

)

Higher

Priority

Lower

Priority

34.Anylocalrecurren

ceofgrade2or3STSoflim

bs/trunkwall[Stronglyrecommen

ded

,100%]

35.LocaltherapyforextraskeletalEwingsarcoma,orrhabdomyosarcoma(embryonal,alveo

lar,and

sclerosing)

[Stronglyrecommen

ded

,97%

]36.Anysurgicalcomplicationen

tailingrisk

forthepatient[Recommen

ded

,87%

]37.Retroperitonealsarcoma(ded

ifferentiated

liposarcoma,leiomyosarcoma,other

high/interm

ediate

grade

sarcomas)[Stronglyrecommen

ded

,100%]

Soft-tissuesarcoma:

Advanceddisease

38.Metastasectomiesin

oligometastaticpatientswithan

adeq

uatetimeintervalwithoutprogression

[Stronglyrecommen

ded

,94%

]39.Anylife-threaten

ingresectablemetastaticspread

inadeq

uateMDTdiscussion[Strongly

recommen

ded

,97%

]

42.Retroperitonealsarcoma(w

ell-differentiated

liposarcoma,low-gradeSFT,desmoid

tumors)

[Recommen

ded

,84%

]

Soft-tissuesarcoma:

Advanceddisease

43.Indicatemetastasectomybutdueto

indolentbeh

aviorofSTS,thiscanbepostponed

(i.e.EMCh,A

SPS)

[Recommen

ded

,87%

]44.SynchronousmetastaticSTSormetachronousmetastaticSTSwithashortrelapse

interval,w

here

system

ictherapycould

betriedfirst[Recommen

ded

,87%

]45.Pu

lmonarymicronoduleswithuncertainmalignantnature

[Recommen

ded

,84%

]

Bonesarcoma:

Localized

disease

46.High-gradeconventionalosteo

sarcomaandskeletalEw

ingsarcomaafterneo

adjuvantchem

otherapy

[Stronglyrecommen

ded

,97%

]47.High-gradeconventionalchondrosarcoma[Stronglyrecommen

ded

,100%]

48.Mesen

chym

alchondrosarcoma(upfrontorafterneo

adjuvantchem

otherapy,followingMDTdecision)

[Stronglyrecommen

ded

,100%]

49.Other

high-gradeprimarybonetumors[Stronglyrecommen

ded

,97%

]50.High-gradeorinterm

ediate

gradein

localrecurren

ce[Stronglyrecommen

ded

,97%

]51.Anysurgicalcomplicationthat

would

besolved

bysurgery[Stronglyrecommen

ded

,100%]

Bonesarcoma:

Advanceddisease

52.Metastasectomiesas

partofmultim

odalitytreatm

entin

osteo

sarcomaorEw

ingsarcoma[Strongly

recommen

ded

,94%

]53.Oligometastaticchondrosarcomawithouteviden

ceoflocalrecurren

ce[Stronglyrecommen

ded

,97%

]54.Oligometastatichigh-gradebonesarcomawithouteviden

ceoflocalrecurren

ce[Strongly

recommen

ded

,97%

]

Bonesarcoma:

Localized

disease

55.Low-gradeosteo

sarcoma(parostealandother

variants)[Recommen

ded

,84%

]56.Low-gradechondrosarcoma[Stronglyrecommen

ded

,90.32%]

57.Adam

antinoma[Recommen

ded

,87%

]58.GCTB

withoutsuspicionofmalignanttransform

ation(consider

inductionwithden

osumab)

[Recommen

ded

,87%

]59.Anyother

low-gradebonesarcoma[Recommen

ded

,84%

]

Bonesarcoma:

Advanceddisease

60.Indicated

metastasectomybutdueto

indolentbeh

avior,thiscanbepostponed

(i.e.,adam

antinoma,low-

gradebonetumors)[Stronglyrecommen

ded

,90%

]61.MetastaticGCTB

(den

osumab

canbeatherapeu

ticoption)[Stronglyrecommen

ded

,90%

]62.Pu

lmonarymicronoduleswithuncertainmalignantnature

[Stronglyrecommen

ded

,90%

]

GISTorother


disease

63.Clinicallyeviden

tGIST(consider

neo

adjuvantim

atinib

forgastroesophagealjunctionorgastricantrum

or

duoden

alorrectalGISToranybulkyGISTto

facilitatesurgery)

[Stronglyrecommen

ded

,100%]

64.SymptomaticGISTnotsuitableforneo

adjuvantim

atinib

(i.e.,im

atinib

intolerantorgenotyperesistantto

imatinib)[Stronglyrecommen

ded

,97%

]65.Anyother

visceralgrade2orgrade3sarcomas

orsymptomaticlow-grade[Stronglyrecommen

ded

,100%]

GISTorother


66.In

thecontext

ofuniqueoroligometastaticrespondingpatientsforwhom

extending3-moim

atinib

could

bedifficult[Stronglyrecommen

ded

,90%

]67.Multicen

tricGISTorwithnodalinvolvem

ent(i.e.K

IT/PDGFRAwild

typeGIST)

[Strongly

recommen

ded

,94%

]68.Metastaticlesioncausingsymptomaticorother

seriouseffect

notam

enablewithim

atinib

[Strongly

recommen

ded

,97%

]

GISTorother


disease

69.Low-riskorvery-low-riskGISTwithoutclinicalcomplications[Recommen

ded

,87%

]70.In

thecontext

ofindolentGISTs

(i.e.,PD

GFRAmutantsorKIT/PD

GFRAwild

type)

consider

postponing

surgerybased

onother

relevantfactors[Stronglyrecommen

ded

,100%]

71.Anylow-gradevisceralsarcomawithoutrelevant

symptomsorother

complications

[Recommen

ded

,87%

]

GISTan

dother


72.Nodulewithin

massas

GISTprogressionthat

could

bepostponed

ormanaged

withradiofreq

uen

cy[Stronglyrecommen

ded

,97%

]73.MetastaticindolentGIST(evenoligometastatic)(i.e.P

DGFRA)that

could

bepostponed

[Strongly

recommen

ded

,97%

]

Med

icalOncology

Soft-tissuesarcoma:

Localized

disease

74.Neo

adjuvantchem

otherapyforextraskeletalEwingsarcomaa

,bandped

iatric-typerhabdomyosarcomac

(embryonal,alveo

lar,andsclerosing)

[Stronglyrecommen

ded

,97%

]

Soft-tissuesarcoma:

Localized

disease

82.Perioperativechem

otherapyin

localized

STSoflim

bs/trunkwalllargerthan

5cm

,grade3,

anddeep

tumorsbutwithrisk

ofdeath

less

than

40%based

onSarculatorwould

bepostponed

ornot

recommen

ded

[Stronglyrecommen

ded

,90%

]

(continued

)



Table

1.(continued

)

Higher

Priority

Lower

Priority


otherapyin

high-riskSTSoflim

bs/trunkwall(>40%

death-riskbased

onSarculator)(3

cycles

ofep

irubicin

+ifosfam

ide)

inselected

patientsd[Stronglyrecommen

ded

,97%

]76.Po

tentiallyresectablelocalized

STS[Noconsensus,only74%agreed

]

Soft-tissuesarcoma:

Advanceddisease

e

77.Overtlydisease

progression[Stronglyrecommen

ded

,94%

]78.New

lydiagnosedmetastaticdisease

(other

than

doubtfulm

icronodules)[Stronglyrecommen

ded

,97%

]79.Symptomaticpatientsin

relationto

theirtumorvolume[Stronglyrecommen

ded

,94%

]80.Patien

tswithalreadyinitiatedchem

otherapy,orother

system

ictreatm

entwithclinicalorradiological

ben

efit[Stronglyrecommen

ded

,100%]

81.Po

tentiallyresectableadvancedSTS[Stronglyrecommen

ded

,90%

]

Soft-tissuesarcoma:

Advanceddisease

83.New

lydiagnosedmetastaticdisease

withmicronodules[Recommen

ded

,84%

]84.IndolentSTSorslowprogressive

STSwithbarelyornosymptomaticim

pact[Strongly

recommen

ded

,90%

]85.Progressive

disease

beyondsecondwithlowprobability

ofclinicalben

efit[Recommen

ded

,84%

]

Bonesarcoma:

Localized

disease

86.Neo

adjuvantchem

otherapyin

osteo

sarcomaf,gorEw

ingskeletalsarcomaa

,b

[Stronglyrecommen

ded

,94%

]87.Neo

adjuvantchem

otherapyin

mesen

chym

alchondrosarcomapotentiallyresectable.

[Recommen

ded

,87%

]

Bonesarcoma:

Advanceddisease

88.Upfrontchem

otherapyin

metastaticosteo

sarcomaorEw

ingsarcomab

[Stronglyrecommen

ded

,100%]

89.Chem

otherapyin

recurren

tadvancedosteo

sarcomanotsuitableforsurgeryh

[Strongly

recommen

ded

,100%]

90.Chem

otherapyin

recurren

tadvancedEw

ingsarcomai[Stronglyrecommen

ded

,100%]

91.Metastaticundifferentiated

high-gradebonesarcoma[Stronglyrecommen

ded

,94%

]

Bonesarcoma:

Localized

disease


otherapyin

high-gradebonesarcoma(i.e.U

ndifferentiated

high-gradepleomorphic

bonesarcoma)

[Noconsensus,only68%agreed

]93.Perioperativechem

otherapyin

high-gradechondrosarcoma[Recommen

ded

,81%

]

Bonesarcoma:

Advanceddisease

94.System

ictreatm

entbeyondsecondlineofmetastaticdisease

inosteo

sarcomaorbeyondthirdlinein

Ewingsarcoma[Recommen

ded

,81%

]95.Anychem

otherapylinein

chondrosarcoma[Recommen

ded

,87%

]96.Im

atinib

inadvanced/recurren

tasym

ptomaticchordoma[Stronglyrecommen

ded

,94%

]

GISTan

dother


disease

j

97.Neo

adjuvantim

atinib

inlocally

advancedGISTwithsensitive

genotype(tofacilitateposteriorsurgery)

[Stronglyrecommen

ded

,94%

]98.Neo

adjuvantim

atinib

ingastro-esophagealjunction,o

rgastricantrum

orrectalGIST(tominim

ize

morbidity)

withsensitive

genotype[Stronglyrecommen

ded

,100%]

99.Adjuvantim

atinib

inpatientswith>40%

ofrecurren

cerisk

(heatmaps)[Stronglyrecommen

ded

,100%]

GISTan

dother


k

100.

TKIforfirst,second,andthirdlinein

metastaticdisease

withim

atinib,sunitinib,andregorafenib,

respectively[Stronglyrecommen

ded

,94%

]

GISTan

dother


disease

101.

Adjuvantim

atinib

with<40%

ofrecurren

cerisk

(heatmaps)[Recommen

ded

,81%

]

GISTan

dother


102.

Metastaticindolentdisease

(i.e.,PD

GFRAmutant)[Recommen

ded

,87%

]103.

Radiologicalp

rogressionwithoutclinicalim

pact[Noconsensus,68%]

Rad

iationOncology

Soft-tissuesarcoma:

Localized

disease

104.

Perioperativeradiationtherapy(preferablypostoperativeduringCOVID-19outbreak)in

grade2–3,>5

cm,anddeepSTSoflim

bs/trunkwall[Stronglyrecommen

ded

,97%

]105.


>5cm

and

superficialSTSofanygradein

limbs/trunkwall[Recommen

ded

,77%

]106.


<5cm

anddeep

STSofanygradein

limbs/trunkwall[Noconsensus,only61%agreed

]107.

Radiationtherapyin

casesofheadandnecksarcomas

[Stronglyrecommen

ded

,90%

]108.

Radiationtherapyin

rhabdomyosarcomas

(embryonal,alveo

lar,andsclerosing)

andextraskeletalEwing

sarcoma[Stronglyrecommen

ded

,100%]

Soft-tissuesarcoma:

Advanceddisease

109.

Anysymptomaticmetastaticlesionthat

could

bealleviated

withradiationtherapy,balancingrisk/ben

efit

[Stronglyrecommen

ded

,97%

]

Soft-tissuesarcoma:

Localized

disease

111.

Postoperativeradiationtherapyin

lowgrade,>5

cm,anddeepSTSoflim

bsortrunkwall[No

consensus,71%]

Soft-tissuesarcoma:

Advanceddisease

112.

Radiationtherapyforlocalcontrolo

fasym

ptomaticprimarytumorin

thecontext

ofmetastaticSTS

[Recommen

ded

,84%

]

(continued

)




Table

1.(continued

)

Higher

Priority

Lower

Priority

110.

Radiationtherapyforsymptomaticprimarytumorin

thecontext

ofmetastasis[Strongly

recommen

ded

,100%]

Bonesarcoma:

Localized

disease

113.

RadiationtherapyisskeletalEw

ingsarcomaaccordingto

CPG

[Stronglyrecommen

ded

,100%]

114.

Unresectableosteo

sarcomaafterinductionchem

otherapy[Stronglyrecommen

ded

,94%

]115.

Defi

nitiveradiationtherapyforgrade3chondrosarcoma[Recommen

ded

,87%

]

Bonesarcoma:

Advanceddisease

116.


could

bealleviated


efit

[Stronglyrecommen

ded

,97%

]

GISTan

dother


disease

117.

Radiationtherapyforunresectablebreastoruterinesarcoma[Stronglyrecommen

ded

,97%

]

GISTandother


118.


could

bealleviated


efit

[Stronglyrecommen

ded

,100%]

GISTan

dother


disease

119.

Postoperativeradiationtherapyin

breastsarcomalarger

than

5cm

orhighgrade[Noconsensus,only

65%agreed

]

GISTandother


120.

Radiationtherapyforunresectablebreastoruterinesarcomawithmetastaticspread

[Noconsensus,

only74%agreed

]

Follo

w-Up

Soft-tissue,

bone,

orvisceralsarcoma:

Localized

andad

vanceddisease

121.

Thefollow-uprecommen

dationforhigh-riskSTS,conventionalosteo

sarcoma,Ew

ingsarcoma,

rhabdomyosarcoma(embryonal,alveo

lar,orsclerosing),h

igh-riskGISTaftercompletionofadjuvant

imatinib

isto

sched

uleCTscansorchestx-ray(insomecases):every3–4moforthefirst3years;every6

moin

fourthorfifthyears;everyyear

afterthefifthyear

[Stronglyrecommen

ded

,97%

]

Soft-tissue,

bone,

orvisceralsarcoma:

Localized

andad

vanceddisease

122.

Thefollow-uprecommen

dationforlow-interm

ediate

risk

ofSTS,low-gradeosteo

sarcoma,high-riskGIST

under

adjuvantim

atinib,interm

ediate-low-riskoflocalized

GISTisto

sched

uleCTscansorchestx-ray(in

somecases):every5–6moforthefirst5years;everyyear

afterthefifthyear

[Strongly

recommen

ded

,97%

]

Consider,intheappropriatecontext,toprolongtheinterval2–3moifthepatientisbeyondthefirst3yearsoffollow-up.

Theobjectiveisto

minim

izepatientcontact

withthehospitalduringtheCOVID-19outbreak.Asmuch

aspossible,teleconsultationsshould

beusedduringfollow-up.

ClinicalTrials

Soft-tissue,

bone,

orvisceralsarcoma:

Localized

andad

vanceddisease

123.

Tonew

enrollm

ent:therapieslikelyto

improve

clinicaloutcome(drugs

withstrongpreclinicalrationale,

drugs

showingpromisingresultsin

previousclinicaltrials,d

rugs

withrobustpredictive

biomarker,

therapytargetingaddictive

signalingpathway

insometumors,therapytargetingrelevantsignalingin

orphan

diseases)[Stronglyrecommen

ded

,97%

]124.

Tomaintain

thetreatm

entunder

trial:patientswithclinicalorradiologicalb

enefi

t,patientsstillnot

assessed

forefficacy

withoutrelevanttoxicity

[Stronglyrecommen

ded

,100%]

Soft-tissue,

bone,

orvisceralsarcoma:

localized

andad

vanceddisease

125.

Tonew

enrollm

ent:therapiesforindolenten

tities

(TGCT,GCTB

,desmoid

tumors)forwhichthe

enrollm

entcanbepostponed

,phaseItrialswithsubstantialnumber

ofprocedures,seriouslogistic

difficultiesdueto

thepandem

icsituation,C

AR-T

cells

based

trials(itcould

requireintensive

care

support),im

munomodulationtherapiesthat

could

exacerbatetheinflam

matory

response

toSA

RS-CoV-2

[Stronglyrecommen

ded

,90%

]

Consider

adaptingproceduresin

agreem

entwiththetrialsponsoras

relaxtheintervalofclinicalvisits,tominim

izeas

much

aspossiblehospitalfreq

uen

tation.

aTheben

efitfrom

alternatingcycles

ofVDC(vincristine,

doxorubicin,cyclophosphamide)

andIE

(ifosfam

ideandetopo

side)

overvincristine,

doxorubicin,cyclophospham

idechem

otherapyin

Ewingsarcoma

[39]

showslevelA

ofrecommen

dationwhen

applyingtheEuropeanSocietyforMed

icalOncology

(ESM

O)-MagnitudeofClinicalBen

efitScale(M

CBS)

V1�1

:Form

1.bTheben

efitfrom

VDC/IEovervincristine,ifosfam

ide,doxorubicin,etoposidechem

otherapyin

Ewingsarcoma[40]

showslevelB

ofrecommen

dationwhen

applying

theESMO-MCBSV1�1

:Form

1.c Theben

efitfrom

ifosfam

ide,

vincristine,

actinomycin

Dwhen

compared

withother

regimen

tswithmore

drugs

(IVA+Carbo

-etopo

side-ep

irubicin

andIVA(ifosfam

ide,

vincristine,

actinomycin

D)+doxorubi-

cin)in

rhabdomyosarcoma[41,

42]showslevelBofrecommen

dationwhen

applyingtheESMO-M

CBSV1�1

:Form

1(IVAistherecommen

ded

optionas

resulted

inless

toxicity

withthesamesurvival

outcome).

dTheben

efitfrom

threecycles

ofep

irubicin

andifosfam

idein

theperioperativesettingin

high-riskpatientswithSTS[43–45]showslevelA

ofrecommen

dationwhenapplyingtheESMO-M

CBSV1�1

:Form

1.(Advanceddisease)

eTheben

efitfrom

eribulin

inliposarcoma[46]

showslevel4ofrecommen

dationwhen

applyingtheESMO-M

CBSV1�1

:Form

2A(ben

efitin

overallsurvival

[OS]).Theben

efitfrom

eribulin

inL-sarcoma(lip-

osarcomaandleiomyosarcoma)

[46]


dationwhen

applyingtheESMO-M

CBSV1�1

:Form

2A.Theben

efitfrom

trabectedin

inL-sarcoma(liposarcomaandleiomyosarcoma)

[47]


dationwhen

applyingtheESMO-M

CBSV1�1

:Form

2B.Theben

efitfrom

trabectedin

intranslocation-related

sarcoma[48]


dationwhen

applyingthe

ESMO-M

CBSV1�1

:Form

2A(ben

efitin

OS).Theben

efitfrom

pazopanib

inpretreatedSTSexcludingliposarcoma[49]


dationwhen

applyingtheESMO-M

CBSV1�1

:Form

2B.

Theben

efitfrom

thecombinationofgemcitabineanddacarbazinein

pretreatedSTS[50]


dationwhen

applyingtheESMO-M

CBSV1�1

:Form

2A(ben

efitin

OS).Theben

efitfrom



approach [25, 27, 34]. The consensus we present herehas two main differences in comparison with the consen-sus development panel. Despite the proposed prioritizingrecommendations based on the published evidence, thereare no comparative studies analyzing, for instance, thedelay of some treatments in patients with sarcoma. Inaddition, no formal face-to-face meeting was organizedbecause of inherent confinement constraints. In contrast,the fact that all expert participants provided their ownopinion on each recommendation ensures more indepen-dence and the quality of the conclusions, avoiding inter-ferences that could arise in a face-to-face discussion.

In contrast, with the aim to minimize the subjectivityin the recommendation process, the ESMO-MCBS was ful-filled, at least for systemic therapies applied in sarcoma.We tried to adopt the grade 3 or higher and grades A orB scores, in the systemic treatment, as the cut-off for pre-serving the use of such treatments in the COVID-19 pan-demic era. The ESMO-MCBS v1.1 is a validated scalemeasuring the magnitude of clinical benefit and addsvalue with just the statistical significance focus [18].Although there is not yet an ESMO-MCBS for sarcoma,our exercise has followed the rules of the scale and is anadditional support for this consensus.

The fact that 80 of 125 recommendations were“strongly recommended” and only 10 were “no consen-sus” indicates a high grade of accord among sarcomaexperts in this consensus on prioritization. The fact thatlower consensus was obtained in the low priority groupmight indicate the reticence of sarcoma experts in post-poning treatment, even in indolent or low-risk cases.

This consensus has been mainly addressed keeping inmind Latin-American communities, and thus it has pur-sued simplicity and concision, taking into considerationthat there are many health care providers in each coun-try. Hence, assigning higher or lower priority to thoseundelayable or delayable treatments, respectively, facili-tates the decision-making process in patients with sar-coma. Additionally, this SELNET consensus issues125 recommendations, which indicates a high level ofthoroughness, covering a substantial spectrum ofsarcoma care.

Follow-up recommendations in the context of sar-coma remains largely unstudied [35] and usually arebased on conventions; thus, in high-risk patients, forexample, the imaging tests are performed every 3–4months for the first 3 years, then every 6 months for the4th and 5th years, and so on, once per year. This strategyis based on the higher risk of recurrence observed in thefirst 3 years after treatment for localized disease and thefact that the asymptomatic recurrence, detected by com-puted tomography scan for instance, could potentiallyhave higher curative options. There are some reportsaddressing the relevance of smaller size as independentprognostic relevance, at the time of metastatic disease,for longer survival [36–38]. Nevertheless, the truth is thatconvincing evidence that determined strategy is relatedwith better survival is lacking, and a lead-time bias canoccur in highly interventionist follow-up.

thecombinationofgemcitabineanddocetaxelinadvancedSTS[51]

andin

advanced

leiomyosarcoma[52]

showslevel1

ofrecommen

dationwhen

applyingtheESMO-M

CBSV1�1

:Form

2C.Theben

efitfrom

high-dose

ifosfam

idein

advancedSTS[53]

showslevel4

ofrecommen

dationwhen

applyingtheESMO-M

CBSV1�1

:Form

3.Theben

efitfrom

doxorubicin

inadvanced

STS[54]

show

slevel4

ofrecommen

da-

tionwhenapplyingtheESMO-M

agnitudeofClinicalBen

efitScale(M

CBS)

V1�1

:Form

3.f Theben

efitfrom

adjuvantchem

otherapyin

resected

conventionalosteo

sarcoma[55,56]showslevelA

ofrecommen

dationwhen

applyingtheESMO-M

CBSV1�1

:Form

1.gTheben

efitfrom

theadditionofMifam

urtideto

adjuvantchem

otherapyin

resected

conventionalosteo

sarcoma[57]

show

slevelA

ofrecommen

dationwhen

applyingtheESMO-M

CBSV1�1

-Form

1.hTheben

efitfrom

cisplatinin

advancedosteo

sarcoma[58]

showslevel4

ofrecommen

dationwhen

applyingtheESMO-M

CBSV1�1

:Form

C.Theben

efitfrom

cisplatin+doxorubicin

+ifosfam

idein

advanced

osteo

sarcoma[59]


dationwhen

applyingtheESMO-M

CBSV1�1

:Form

C.Theben

efitfrom

ifosfam

ide-etoposidein

advancedosteo

sarcoma[60]

show

slevel3ofrecommen

dation

when

applyingtheESMO-M

CBSV1�1

:Form

C.Theben

efitfrom

high-dose

ifosfam

idein

advancedosteo

sarcoma[61]

showslevel4

ofrecommen

dationwhen

applyingtheESMO-M

CBSV1�1

:Form

C.Theben

-efi

tfrom

sorafenib

pluseverolim

us[62]

andregorafenib

[63]

inadvancedosteo

sarcomashowslevel2

ofrecommen

dationwhen

applyingtheESMO-M

CBSV1�1

-Form

C.

i Theben

efitfrom

gemcitabineanddocetaxelinEw

ingsarcoma[64,65]showslevel2

ofrecommen

dationwhen

applyingtheESMO-M

CBSV1�1

:Form

C.Theben

efitfrom

Cyclophospham

ide-topotecancannot

beproperlyassessed

withthecurren

tlyavailableeviden

ce.Theben

efitfrom

high-dose

ifosfam

idein

Ewingsarcoma[66]

showslevel3

ofrecommen

dationwhen

applyingtheESMO-M

CBSV1�1

-Form

C.

j Theben

efitfrom

3yearsofadjuvantim

atinib

inlocalized

GIST[67]

showslevelA

ofrecommen

dationwhen

applyingtheESMO-M

CBSV1�1

-Form

1.k The

ben

efitfrom

imatinib

inadvancedGIST[68]

showslevel4

ofrecommen

dationwhen

applyingtheESMO-M

CBSV1�1

:Form

3.Theben

efitfrom

sunitinib

inadvancedGIST[69,

70]show

slevel4

ofrecom-

men

dationwhen

applyingtheESMO-M

CBSV1�1

:Form

2BandForm

2A,respectively.Theben

efitfrom

regorafenib

inadvanced

GIST[71]


dationwhen

applyingtheESMO-M

CBS

V1�1

:Form

2B.Theben

efitfrom

ripretinib

inadvanced

GIST[72]

show

slevel4

ofrecommen

dationwhen

applyingtheESMO-M

CBSV1�1

:Form

2BandForm

2A,respectively.

Abbreviations:ASPS,alveolar

softpartsarcoma;CAR-T,chim

ericantigenreceptorT-Cell;CT,computedtomography;EM

Chextraskeletalm

yxoid

chond

rosarcoma;GCTB

,giantcelltumorofbone;

GIST,gastro-

intestinal

stromal

tumor;MCBS,

Magnitude

ofClinical

Ben

efitScale;

MDT,

multidisciplinary;

SFT,

solitaryfibroustumor;STS,

soft-tissuesarcoma;

TGCT,

tenosynovialgiantcelltumor;TKI,tyrosinekinase

inhibitor.




CONCLUSION

This SELNET consensus provides a tool for multidisciplinarysarcoma committees during the COVID-19 outbreak. Thedetail of different recommendations and the distinctionbetween the two levels of prioritization enables a practicalapproach for Latin-American health care providers and sar-coma expert centers.

ACKNOWLEDGMENTS

The authors would like to thank the SELNET project. SELNEThas received funding from the European Union’s Horizon2020 research and innovation programme under grantagreement No. 825806.

AUTHOR CONTRIBUTIONSConception/design: Javier Martin-Broto, Nadia HindiProvision of study material or patients: Javier Martin-Broto, Nadia Hindi,Samuel Aguiar Jr., Ronald Badilla-González, Victor Castro-Oliden, MatíasChacón, Raquel Correa-Generoso, Enrique de �Alava, Davide María Donati,Mikael Eriksson, Martín Falla-Jimenez, Gisela German, María Leticia GoboSilva, Francois Gouin, Alessandro Gronchi, Juan Carlos Haro-Varas, NataliaJiménez-Brenes, Bernd Kasper, Celso Abdon Lopes de Mello, Robert Maki,Paula Martínez-Delgado, Héctor Martínez-Said, Jorge Luis Martinez-Tlahuel, José Manuel Morales-Pérez, Francisco Cristóbal Muñoz-Casares,Suely Nakagawa, Eduardo José Ortiz-Cruz, Emanuela Palmerini,Shreyaskumar Patel, David S. Moura, Silvia Stacchiotti, Marie PierreSunyach, Claudia M. Valverde, Federico Waisberg, Jean-Yves Blay

Collection and/or assembly of data: Javier Martin-Broto, Nadia Hindi,Samuel Aguiar Jr., Ronald Badilla-González, Victor Castro-Oliden, MatíasChacón, Raquel Correa-Generoso, Enrique de �Alava, Davide María Donati,Mikael Eriksson, Martín Falla-Jimenez, Gisela German, María Leticia Gobo

Silva, Francois Gouin, Alessandro Gronchi, Juan Carlos Haro-Varas, NataliaJiménez-Brenes, Bernd Kasper, Celso Abdon Lopes de Mello, Robert Maki,Paula Martínez-Delgado, Héctor Martínez-Said, Jorge Luis Martinez-Tlahuel, José Manuel Morales-Pérez, Francisco Cristóbal Muñoz-Casares,Suely Nakagawa, Eduardo José Ortiz-Cruz, Emanuela Palmerini,Shreyaskumar Patel, David S. Moura, Silvia Stacchiotti, Marie Pierre Sun-yach, Claudia M. Valverde, Federico Waisberg, Jean-Yves Blay

Data analysis and interpretation: Javier Martin-Broto, Nadia HindiManuscript writing: Javier Martin-Broto, Nadia Hindi, Samuel Aguiar Jr.,Ronald Badilla-González, Victor Castro-Oliden, Matías Chacón, RaquelCorrea-Generoso, Enrique de �Alava, Davide María Donati, MikaelEriksson, Martín Falla-Jimenez, Gisela German, María Leticia Gobo Silva,Francois Gouin, Alessandro Gronchi, Juan Carlos Haro-Varas, NataliaJiménez-Brenes, Bernd Kasper, Celso Abdon Lopes de Mello, Robert Maki,Paula Martínez-Delgado, Héctor Martínez-Said, Jorge Luis Martinez-Tlahuel, José Manuel Morales-Pérez, Francisco Cristóbal Muñoz-Casares,Suely Nakagawa, Eduardo José Ortiz-Cruz, Emanuela Palmerini,Shreyaskumar Patel, David S. Moura, Silvia Stacchiotti, Marie PierreSunyach, Claudia M. Valverde, Federico Waisberg, Jean-Yves Blay

Final approval of manuscript: Javier Martin-Broto, Nadia Hindi, SamuelAguiar Jr., Ronald Badilla-González, Victor Castro-Oliden, Matías Chacón,Raquel Correa-Generoso, Enrique de �Alava, Davide María Donati, MikaelEriksson, Martín Falla-Jimenez, Gisela German, María Leticia Gobo Silva,Francois Gouin, Alessandro Gronchi, Juan Carlos Haro-Varas, NataliaJiménez-Brenes, Bernd Kasper, Celso Abdon Lopes de Mello, Robert Maki,Paula Martínez-Delgado, Héctor Martínez-Said, Jorge Luis Martinez-Tlahuel, José Manuel Morales-Pérez, Francisco Cristóbal Muñoz-Casares,Suely Nakagawa, Eduardo José Ortiz-Cruz, Emanuela Palmerini,Shreyaskumar Patel, David S. Moura, Silvia Stacchiotti, Marie PierreSunyach, Claudia M. Valverde, Federico Waisberg, Jean-Yves Blay,

DISCLOSURES

Javier Martin-Broto: PharmaMar, Eisai, Immix BioPharma, Novartis(RF), PharmaMar (ET), PharaMar, Eli Lilly & Co, Bayer, Eisai (H-advisory board participation), PharmaMar, Eli Lilly & Co, AROG,Bayer, Eisai, Lixte, Karyopharm, Deciphera, GlaxoSmithKline,Novartis, Blueprint, Nektar, Forma, Amgen, Daiichi Sankyo (RF-

Table 2. Mann-Whitney U and Pearson’s χ2 test for those recommendations with statistical differences between LATAMand E.U.-U.S. experts

Recommendations

Mann-Whitney test

Recommendations

Pearson’s χ2 test

LATAM, % E.U.-U.S., % p value LATAM, % E.U.-U.S., % p value

Recommendationno. 93

.001 Recommendationno. 93

.009

Strongly agree 38 7

Agree 31 64 Agree 57 100

Disagree 31 22 Disagree 43 0

Strongly disagree 0 7



.01

Strongly agree 25 64






.002

Strongly agree 41 21




Recommendation (R) no. 93 collects agreement as a low priority for adjuvant chemotherapy in high-grade localized chondrosarcoma. R no. 105collects agreement as a high priority for perioperative radiation therapy in superficial soft-tissue sarcoma (STS) larger than 5 cm, and R no. 114collects agreement as a lower priority for low-grade, deep STS and larger than 5 cm.Abbreviations: E.U., European Union; LATAM, Latin-American.



institutional); Robert Maki: Bayer, Deciphera Eisai, MorphotekImmune Design Janssen, Pharma Mar, Karyopharm, Eli Lilly & Co,Imclone Presage Springworks (C/A), Bayer, Karyopharm, Lilly, PfizerSpringworks, Regeneron, Presage (RF-institution); Jorge LuisMartinez-Tlahuel: Amgen, Eli Lilly & Co (C/A); EmanuelaPalmerini: Deciphera, Eusa Pharma, Daichi Sankyo (C/A); David

S. Moura: PharmaMar, Eisai, Immix BioPharma, Novartis (RF-institution), PharmaMar, Eisai, Celgene, Bayer, Pfizer (Other). Theother authors indicated no financial relationships.(C/A) Consulting/advisory relationship; (RF) Research funding; (E) Employment; (ET) Expert

testimony; (H) Honoraria received; (OI) Ownership interests; (IP) Intellectual property rights/

inventor/patent holder; (SAB) Scientific advisory board

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