sarcoma european and latin american network (selnet
TRANSCRIPT
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
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].
© 2020 The Authors.The Oncologist published by Wiley Periodicals LLC on behalf of AlphaMed Press.
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.
© 2020 The Authors.The Oncologist published by Wiley Periodicals LLC on behalf of AlphaMed Press.
www.TheOncologist.com
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
© 2020 The Authors.The Oncologist published by Wiley Periodicals LLC on behalf of AlphaMed Press.
SELNET Recommendations in Sarcoma During COVID-194
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
visceralsarcomas:Localized
disease
29.Intram
urallesions<1–2
cmin
thegastrointestinaltract[Stronglyrecommen
ded
,90%
]30.Uterinemasspredominantlyintram
ural,norecenthistory
ofsymptomsorsigns,more
likelyto
be
myofibromas
[Recommen
ded
,87%
]
GISTorother
visceralsarcomas:Advanceddisease
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
)
© 2020 The Authors.The Oncologist published by Wiley Periodicals LLC on behalf of AlphaMed Press.
www.TheOncologist.com
Martin-Broto, Hindi, Aguilar Jr. et al. 5
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
visceralsarcomas:Localized
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
visceralsarcomas:Advanceddisease
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
visceralsarcomas:Localized
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
visceralsarcomas:Advanceddisease
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
)
© 2020 The Authors.The Oncologist published by Wiley Periodicals LLC on behalf of AlphaMed Press.
SELNET Recommendations in Sarcoma During COVID-196
Table
1.(continued
)
Higher
Priority
Lower
Priority
75.Perioperativechem
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
92.Perioperativechem
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
visceralsarcomas:Localized
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
visceralsarcomas:Advanceddisease
k
100.
TKIforfirst,second,andthirdlinein
metastaticdisease
withim
atinib,sunitinib,andregorafenib,
respectively[Stronglyrecommen
ded
,94%
]
GISTan
dother
visceralsarcomas:Localized
disease
101.
Adjuvantim
atinib
with<40%
ofrecurren
cerisk
(heatmaps)[Recommen
ded
,81%
]
GISTan
dother
visceralsarcomas:Advanceddisease
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.
Perioperativeradiationtherapy(preferablypostoperativeduringCOVID-19outbreak)in
>5cm
and
superficialSTSofanygradein
limbs/trunkwall[Recommen
ded
,77%
]106.
Perioperativeradiationtherapy(preferablypostoperativeduringCOVID-19outbreak)in
<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
)
© 2020 The Authors.The Oncologist published by Wiley Periodicals LLC on behalf of AlphaMed Press.
www.TheOncologist.com
Martin-Broto, Hindi, Aguilar Jr. et al. 7
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.
Anysymptomaticmetastaticlesionthat
could
bealleviated
withradiationtherapy,balancingrisk/ben
efit
[Stronglyrecommen
ded
,97%
]
GISTan
dother
visceralsarcomas:Localized
disease
117.
Radiationtherapyforunresectablebreastoruterinesarcoma[Stronglyrecommen
ded
,97%
]
GISTandother
visceralsarcomas:Advanceddisease
118.
Anysymptomaticmetastaticlesionthat
could
bealleviated
withradiationtherapy,balancingrisk/ben
efit
[Stronglyrecommen
ded
,100%]
GISTan
dother
visceralsarcomas:Localized
disease
119.
Postoperativeradiationtherapyin
breastsarcomalarger
than
5cm
orhighgrade[Noconsensus,only
65%agreed
]
GISTandother
visceralsarcomas:Advanceddisease
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]
showslevel3ofrecommen
dationwhen
applyingtheESMO-M
CBSV1�1
:Form
2A.Theben
efitfrom
trabectedin
inL-sarcoma(liposarcomaandleiomyosarcoma)
[47]
showslevel3ofrecommen
dationwhen
applyingtheESMO-M
CBSV1�1
:Form
2B.Theben
efitfrom
trabectedin
intranslocation-related
sarcoma[48]
showslevel4ofrecommen
dationwhen
applyingthe
ESMO-M
CBSV1�1
:Form
2A(ben
efitin
OS).Theben
efitfrom
pazopanib
inpretreatedSTSexcludingliposarcoma[49]
showslevel3ofrecommen
dationwhen
applyingtheESMO-M
CBSV1�1
:Form
2B.
Theben
efitfrom
thecombinationofgemcitabineanddacarbazinein
pretreatedSTS[50]
showslevel4ofrecommen
dationwhen
applyingtheESMO-M
CBSV1�1
:Form
2A(ben
efitin
OS).Theben
efitfrom
© 2020 The Authors.The Oncologist published by Wiley Periodicals LLC on behalf of AlphaMed Press.
SELNET Recommendations in Sarcoma During COVID-198
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]
showslevel4ofrecommen
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]
showslevel3ofrecommen
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.
© 2020 The Authors.The Oncologist published by Wiley Periodicals LLC on behalf of AlphaMed Press.
www.TheOncologist.com
Martin-Broto, Hindi, Aguilar Jr. et al. 9
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
Recommendationno. 105
.008 Recommendationno. 105
.01
Strongly agree 25 64
Agree 38 36 Agree 100 63
Disagree 31 0 Disagree 0 37
Strongly disagree 6 0
Recommendationno. 111
.021 Recommendationno. 111
.002
Strongly agree 41 21
Agree 53 21 Agree 43 94
Disagree 6 58 Disagree 57 6
Strongly disagree 0 0
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.
© 2020 The Authors.The Oncologist published by Wiley Periodicals LLC on behalf of AlphaMed Press.
SELNET Recommendations in Sarcoma During COVID-1910
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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