European Journal of Cancer (2014) 50, 128– 136

A v a i l a b l e a t w w w . s c i e nc e d i r e c t . c o m

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Primary cardiac sarcomas: A retrospective study of theFrench Sarcoma Group q

0959-8049/$ - see front matter � 2013 Published by Elsevier Ltd.

http://dx.doi.org/10.1016/j.ejca.2013.09.012

Granting acknowledgement: IRC & JYB’s work are supported by INCA LYRIC grant INCA_4664, LabexANR-10-LABX-0061, EuroSa278472, NetSArc and RREPs.Presentation: This article was presented at the ASCO 2010 annual meeting.⇑ Corresponding author: Address: Centre G-F Leclerc, 1 rue du Pr Marion, BP77980, 21079 Dijon Cedex, France. Tel.: +33 (0)3 80 73 75

+33 (0)3 80 73 77 12.E-mail address: nisambert@cgfl.fr (N. Isambert).

Nicolas Isambert a,⇑, Isabelle Ray-Coquard b, Antoine Italiano c, Maria Rios d,Pierre Kerbrat e, Melanie Gauthier a, Aurelien Blouet f, Loıc Chaigneau g,Florence Duffaud h, Sophie Piperno-Neumann i, Jean-Emmanuel Kurtz j,Nicolas Girard k, Olivier Collard l, Emmanuelle Bompas m, Nicolas Penel n,Jacques-Olivier Bay o, Cecile Guillemet p, Franc�oise Collin a, Jean-Yves Blay b,Axel Le Cesne q, Juliette Thariat r

a Centre Georges-Franc�ois Leclerc, Dijon, Franceb Centre Leon Berard, Lyon, Francec Institut Bergonie, Bordeaux, Franced Centre Alexis Vautrin, Nancy, Francee Centre Eugene Marquis, Rennes, Francef Institut Claudius Regaud, Toulouse, Franceg CHRU Jean Minjoz, Besanc�on, Franceh Hopital La Timone, Marseille, Francei Institut Curie, Paris, Francej Hopital de Hautepierre, Strasbourg, Francek Hopital Louis Pradel, Lyon, Francel Institut de Cancerologie Lucien Neuwirth, Saint-Priest-en-Jarez, Francem Institut de Cancerologie de l’Ouest Rene Gauducheau, Saint Herblain, Francen Centre Oscar Lambret, Lille, Franceo Hotel-Dieu, Clermont-Ferrand, Francep Centre Henry Becquerel, Rouen, Franceq Institut Gustave Roussy, Villejuif, Francer Centre Antoine Lacassagne, Nice, France

Available online 14 October 2013

rc FP7-

28; fax:

N. Isambert et al. / European Journal of Cancer 50 (2014) 128–136 129

KEYWORDS

SarcomaCardiacSurgeryRadiotherapyChemotherapy

Abstract Introduction: Primary cardiac sarcomas (PCS) are rare tumours of dismal progno-sis.Methods: Data of 124 patients with PCS referred to institutions of the French Sarcoma Group(FSG) from 1977 and 2010 were reviewed.Results: Median age was 48.8 years. PCS were poorly-differentiated sarcomas (N = 45,36.3%), angiosarcomas (N = 40, 32.3%), leiomyosarcomas (N = 16, 12.9%) and others(N = 23, 18.6%). At diagnosis, 100 patients (80.6%) were localised and 24 (19.4%) metastatic.Tumours were located in the right (N = 47, 38.8%), left atrial cavities (N = 45, 37.2%) orencompassed several locations in nine cases (7.4%). Surgery was performed in 81 cases(65.3%). Heart transplant was performed in five patients. Radiotherapy adjuvant (N = 18,14.5%) or alone (N = 6, 4.8%) was performed in non-metastatic patients only (N = 24,19.4%). With a median follow-up of 51.2 months, median overall survival (OS) was17.2 months for the entire cohort, 38.8 months after complete resection versus 18.2 afterincomplete resection and 11.2 months in non-resected patients. Radiotherapy was associatedwith improved progression-free survival (PFS) on multivariate analysis. Chemotherapy wassignificantly associated with better OS only in non-operated patients but not in operatedpatients. In non-metastatic patients, surgery (hazard ratio [HR] = 0.42, p < 0.001), male gen-der (HR = 0.56, p = .032) was associated with better OS and surgery (HR = 0.61; p = .076),radiotherapy (HR = 0.43; p = .004) and chemotherapy (HR = 0.30, p = .003) improved PFS.Conclusion: Only surgical resection is associated with a perspective of prolonged survival.Chemotherapy is associated with a better outcome in non-resected patients.� 2013 Published by Elsevier Ltd.

1. Introduction

The vast majority of adult primary cardiactumours (75%) is benign but the proportions dependon cardiac subsite. Half of the primary tumours ofthe right atrium are malignant while a majority of leftatrium tumours are benign [1,2,3] and mostly consistof myxomas (50–75%) [1,4,5]. Sarcomas represent75–95% of adult primary cardiac tumours [6,7].Metastatic cardiac tumours are 30 times more com-mon than primary neoplasms [9–12]. The prevalenceof primary cardiac cancers varies from 0.001% to0.03% in necropsy series [12]. Based on retrospectivesmall heterogeneous case series, primary cardiacsarcomas (PCS) are aggressive tumours of unfavor-able prognosis with a median survival rate of lessthan 1 year. The level of evidence for the optimalmultimodal management of PCS is low due to diseaserarity. Thus the optimal management of PCS is oftenextrapolated from that of extra-cardiac soft-tissue sar-comas, which however is debatable because cardiacsurgery and irradiation of dose-limiting organs likethe heart are specific to PCS.

The aim of this multi-institutional retrospectiveFrench Sarcoma Group (FSG) study, the largest seriesof PCS reported to our knowledge, was to describe clin-ical, histological and treatment characteristics, and toidentify predictive factors of outcomes in a homogenousgroup of patients with PCS.

2. Patients and methods

2.1. Study design

This FSG review-board-approved study was basedon retrospective PCS patient data identified viaNational encodings and multidisciplinary staff archivesfrom FSG’s institutions between 1977 and 2010.

2.2. Patients and disease

Age at diagnostic, gender, symptoms at diagnosis,time to diagnosis, tumour characteristics (anatomiclocation, size, grade and histological type, stage ofdisease), treatment and outcomes were collected.Systematic review was performed by expert pathologistsof the FSG with histology established according to theWorld Health Organization Classification of Tumours[13] and grade according to the FNCLCC gradingsystem [14]. Patients were treated at the discretion oftheir physician in the absence of guidelines dedicatedto this particular sarcoma site.

2.3. Statistical analysis

Data were described as frequency (percentage) ormean (SD) and median [extreme values]. Differencesbetween groups were evaluated by the Chi square orFisher exact tests for categorical variables and Student

130 N. Isambert et al. / European Journal of Cancer 50 (2014) 128–136

or Mann Whitney tests for continuous variables. Overallsurvival (OS) was defined as the time elapsed from thedate of diagnostic until death (all causes). Survivingpatients were censored at last follow-up date. Progression-free survival (PFS) was defined as the time that elapsedfrom the date of diagnosis until the date of progressionor death, whichever came first. Survival curves weredrawn with the Kaplan–Meier’s method and comparedwith the log-rank test. Univariate and multivariateanalyses (Cox proportional hazard model) were usedto calculate hazard ratios with 95% confidence intervals(95CI).

The role of age, gender, histology, anatomic location,size, grade, metastatic stage, surgery, chemotherapy andradiotherapy were examined in univariate analyses forOS and PFS. All predefined variables were included inmultivariate analyses using backward selection(stopping condition: p < 0.15). Internal validation wasassessed with bootstrap (120 replications). Similaranalyses were then performed in non-metastatic patientsonly. P-values were two-sided and considered significantwhen 60.05. Analyses were performed using the StataV11 software.

Table 1Patient characteristics.

N = 124 %

Age

Mean (sd) 47.1 (16.1)Median [min–max] 48.8 [3.5–82]Missing 1

Sex

Female 70 56.5Male 54 43.5

Tumour size (mm)

Mean (sd) 62.6 (26.7)Median [min–max] 60 [3–160]Missing 47

Histology

Angiosarcoma 40 32.3Leiomyosarcoma 16 12.9Poorly differentiated Sarcoma 45 36.3Other sarcoma 23 18.6

Site

LA 45 37.2RA 47 38.8LV 10 8.3RV 7 5.8Pericardium 3 2.5Extended over several sites 9 7.4Missing 3

Stage

M0 100 80.6M+ 24 19.4

S, sarcoma; LA, left atria; RA, right atria; LV left ventricle; RV, rightventricle; sd, standard deviation.Other sarcomas included: synovialosarcoma (n = 7), rhabdomyosar-coma (n = 7), Ewing sarcoma (n = 4), liposarcoma (n = 3) andchondrosarcoma (n = 2).

3. Results

3.1. Patients and disease characteristics

Patient characteristics are summarised in Table 1.Fifty-four males (43.5%) and 70 females (56.5%) witha median age of 48.8 years (range 3.5–82) were included.Median time between first symptoms and diagnosis was3 months (range 0–53). Symptoms at diagnosis werenon-specific: dyspnoea (48%), thoracic pain (22%), heartfailure (13%) and pericarditis (5%) or others, includingtamponade (22%). Median tumour size at diagnosiswas 60 mm (range 3–160). Histology was obtained per-operatively, by surgical biopsy or CT scan/ultrasound-guided biopsy of primary or biopsy of metastasis in59.7%, 25.0%, 9.7% or 4.8%, respectively (by unknownmeans in 0.8% of patients). A biopsy was morefrequently performed in right PCS (29/58) than leftPCS (13/55) (p = .004). Histological subtypes and dis-ease extent are provided in Table 1. Of 24 patients withmetastases at diagnosis, fourteen (58.3%) and ninepatients had single or multiple metastases, respectively.Sites of metastases were the lung (N = 9, 37.5%), liver(N = 7, 29.2%), bone (N = 7, 29.2%) and/or brain(N = 4, 16.7%). Tumours were mainly located in theatrial cavities (right N = 47, 37.9%; left N = 45,36.3%). Other anatomic locations included the rightventricle (N = 7, 6.6%), left ventricle (N = 10, 8.1%),pericardium (N = 3, 2.4%) and heart not otherwise spec-ified (N = 3, 2.4%). In nine cases (7.2%), the tumourencompassed several cardiac subsites. Histologies variedaccordingly to anatomic location (p < .001), i.e. angio-sarcomas were predominantly right-sided (N = 32,80%) and poorly-differentiated sarcomas (N = 28,62%) and leiomyosarcomas (N = 12, 75%) left-sided.Other histologies grouped were evenly distributed.

3.2. Treatment

Surgical resection was performed in most patientswith localised (N = 75, 75%) and metastatic disease(N = 6; 25%). Complete resection was achieved in 10out of 75 (13.3%) patients with localised disease andnone of the metastatic patients (Table 2). Five patientsunderwent heart transplant after marginal resection forangiosarcoma (N = 1, 1.2%), poorly-differentiated PCS(N = 2, 2.5%) and rhabdomyosarcoma (N = 2, 2.5%).The quality of resection was similar across cardiacsubsites (p = .074). There were four/44 (9.1%) completeresections in right PCS versus six/54 (13.3%) in left PCS,and 26/44 (59.1%) R1/R2 resections in right PCS versus27/54 (60.0%) in left PCS.

Radiotherapy was delivered in 24 non-metastaticcases (24%). None of the metastatic patients underwentirradiation. It was carried out in the postoperativesetting (N = 18, 75%) or as exclusive local therapy

000.

250.

500.

751.

00

OSPFS

Table 2Treatment of patients.

Non-metastatic disease atdiagnostic (N = 100)

% Metastatic disease atdiagnostic (N = 24)

% All patients(N = 124)

%

Treatment surgery 75 75.0 6 25.0 81 65.3R0 resection 10 10.0 0 0.0 10 8.1R1 or R2 resection 51 51.0 5 20.8 56 45.2Unknown 14 14.0 1 4.2 15 12.1Heart transplant 4 4.0 1 4.2 5 4.0

Chemotherapy 90 90.0 21 87.5 111 89.5Monotherapy 19 19.0 8 33.3 27 21.8Combination 70 70.0 13 54.2 83 66.9Unknown 1 1.0 1 0.8

Radiotherapy 24 24.0 0 0.0 24 19.4

Combination of treatment

No treatment 2 2.0 2 8.3 4 3.2Surgery alone 7 7.0 1 4.2 8 6.5Chemotherapy alone 17 17.0 16 66.7 33 26.6Surgery + chemotherapy 50 50.0 5 20.8 55 44.3Surgery + radiotherapy 1 1.0 0 0 1 0.8Chemotherapy + radiotherapy 6 6.0 0 0 6 4.8Surgery + chemotherapy + radiotherapy 17 17.0 0 0 17 13.7

R0, complete resection; R1, microscopically incomplete resection; R2, macroscopically incomplete resection.

N. Isambert et al. / European Journal of Cancer 50 (2014) 128–136 131

(N = 6, 25%). Among the 18 operated patients, 1/18(5.6%), 10/18 (55.6%) and 7/18 (38.9%) had completeresection (R0), microscopically incomplete resection(R1) and macroscopically incomplete resection (R2)resection, respectively. Median dose was 50 Gy (range10–64). It was associated with sequential chemotherapyin 23 (95.8%) patients.

Chemotherapy was performed either in the adjuvant(N = 55, 44.4%) or neoadjuvant setting (N = 11, 8.9%)or for metastatic/unresectable disease (N = 41, 33.1%).For 90% of patients, chemotherapy regimen containedan anthracyclin. Chemotherapy was delivered as mono-therapy (N = 18, 21.7%) or in combination (78.3%)(Table 2). Although not significant, right-heart PCSreceived neoadjuvant chemotherapy more frequentlythan left-heart PCS and left-heart PCS received moreadjuvant chemotherapy (or no chemotherapy at all),than right-heart PCS. Surgery alone, resection incombination with doxorubicin-containing chemother-apy, or sequential radiotherapy and chemotherapy wereapplied in 18 (18%), 43 (43%) and 16 (16%) patients withlocalised disease, respectively.

Among metastatic patients, six of the 24 patientswere operated on, of whom none had complete resec-tion. One patient underwent heart transplant. A major-ity of patients (n = 21, 87.5%) underwent chemotherapy,mostly using a combination chemotherapy regimen(54.2%), and none had radiotherapy (Table 2).

0.

121 48 20 9 7 5 4PFS122 69 34 20 13 8 7OS

N at risk

0 12 24 36 48 60 72

Months

Fig. 1. Overall survival and progression free survival of the entirecohort of patients.

3.3. Survival

Survival data were available for 122 patients (twopatients lost to follow-up after diagnosis). Median

follow-up was 51.2 months (range 0.03–152.9). At thetime of analysis, 85 patients (69.7%) had died, 33 (27%)were alive and 4 (3.3%) were lost to follow-up.

Among initially non-metastatic patients, 43 (43%)became metastatic, in the lung (N = 19, 44.2%) andbrain (N = 9, 20.9%) within a median interval of11 months (range 2–85). Twenty-three patients (23%)also relapsed locally within a median time of 10 months(range 2–54).

3.3.1. Progression-free survival (PFS)

Median progression-free survival was 11 months[95CI 9.2–12.7] (Figs. 1 and 3). On univariate analysis,surgery, chemotherapy and radiotherapy were signifi-cantly associated with improved PFS. On multivariate

Logrank test : p=0.015

0.00

0.25

0.50

0.75

1.00

23 20 12 8 4 4 3Other sarcoma45 24 10 6 5 2 2UPS15 8 4 3 2 0 0Leiomyosarcoma39 17 8 3 2 2 2Angiosarcoma

N at risk

0 12 24 36 48 60 72

Months

Angiosarcoma

Leiomyosarcoma

UPS

Other sarcoma

Histological subtype

Logrank test : p=0.004

0.00

0.25

0.50

0.75

1.00

23 9 1 0 0 0 0M+99 60 33 20 13 8 7M0

N at risk

0 12 24 36 48 60 72

Months

M0

M+

Metastatic stage

Logrank test : p<0.001

0.00

0.25

0.50

0.75

1.00

80 56 31 19 12 8 7Yes 42 13 3 1 1 0 0No

N at risk

0 12 24 36 48 60 72

Months

No

Yes

Surgery

Logrank test : p=0.035

0.00

0.25

0.50

0.75

1.00

24 19 11 6 5 4 3Yes97 49 23 14 8 4 4No

N at risk

0 12 24 36 48 60 72

Months

No

Yes

RadiotherapyC

A

C

B

D

Fig. 2. Overall survival.

132 N. Isambert et al. / European Journal of Cancer 50 (2014) 128–136

analysis, surgery, radiotherapy and chemotherapy wereassociated with improved PFS.

By subgroup univariate analyses in non-metastaticpatients only, chemotherapy and radiotherapy wereassociated with better PFS while surgery was not(p = .076). On multivariate analysis, radiotherapy (haz-ard ratio [HR] = 0.43, [95CI 0.24–0.77], p = .004) andchemotherapy (HR = 0.29, [95CI 0.13–0.65], p = .003)were associated with better survival (Fig. 3).

3.3.2. Overall survival

Median overall survival (OS) was 17.2 months [95CI13.5–22.3] (Fig. 1). On univariate analysis, histology,stage, surgery and radiotherapy were significantly asso-ciated with OS (Table 3, Fig. 2). Four-year OS was 8.4%in angiosarcomas and 28.8% in other sarcomas grouped(p = .015) (Fig. 2). Survival was 38.8 months [95CI 1.9–1] for patients who underwent complete (R0) resectionversus 18.2 months [95CI 12.3–25.3] for those undergo-ing microscopically (R1) or macroscopically incomplete(R2) resection (p = .191). Median OS of the five trans-planted patients was 27.5 months [95CI 13.5–1].

On multivariate analysis, there was a significant inter-action between surgery and chemotherapy. Chemother-apy was significantly associated with better survival innon-resected patients only (Table 4).

Analyses were then performed in the non-metastaticpatient population only. On univariate analysis, surgery(HR = 0.40, [95CI 0.22–0.70], p = .001) was signifi-cantly associated with better OS. On multivariate analy-sis, surgery and male gender were associated with betterOS.

4. Discussion

In this collaborative study of the FSG, left and right-heart sarcomas were evenly distributed and symptoms atdiagnosis were non-specific. A majority of PCS occurredin the atrial cavities. Angiosarcomas were predomi-nantly right-sided and in the right atrial cavity, whilepoorly-differentiated PCS were mostly left-sided andpredominantly located in the left atrial cavity. Leiomyo-sarcomas and other histological subtypes grouped weremostly located in the left atrial cavity. In this series,most frequent histologies were poorly-differentiated sar-comas followed by angiosarcomas and leiomyosarco-mas. Similarly, a 16-cardiac sarcoma-patient seriesrecently reported a predominance of angiosarcomasand undifferentiated sarcomas [8]. In contrast with theliterature, our series neither included osteosarcomas,nor intimal sarcomas and included numerous leiomyo-sarcomas [6]. In this series, dyspnoea and chest painwere the commonest symptoms. Five patients presented

Logrank test : p=0.020

0.00

0.25

0.50

0.75

1.00

79 37 18 9 7 5 4Yes42 11 2 0 0 0 0No

N at risk

0 12 24 36 48 60 72

Months

No

Yes

Surgery

Logrank test : p<0.001

0.00

0.25

0.50

0.75

1.00

109 47 19 8 6 4 3Yes12 1 1 1 1 1 1No

N at risk

0 12 24 36 48 60 72

Months

No

Yes

Chemotherapy

Logrank test : p=0.009

0.00

0.25

0.50

0.75

1.00

24 14 7 5 4 4 3Yes96 33 13 4 3 1 1No

N at risk

0 12 24 36 48 60 72Months

No

Yes

Radiotherapy

A

B

C

Fig. 3. Progression free survival by radiotherapy and chemotherapyand surgery.

N. Isambert et al. / European Journal of Cancer 50 (2014) 128–136 133

with neurological symptoms [15]. Symptoms oflife-threatening intracardiac obstruction are also possi-ble [11]. Four percent, as in this series, to 36% of pri-mary cardiac tumours are detected incidentally [8].Left-heart PCS are more prone to solid obstructivemasses presenting with early heart failure [16]. Right-heart PCS tend to be bulky and infiltrative resulting inlater symptoms.

Given their extreme rarity left-heart PCS are oftenmisdiagnosed [17] for myxomas and the diagnosis mayonly be corrected preoperatively or on pathologicfindings [18]. This may explain the poor completeresection rates in our series. According to the literature,right-sided tumours are more suggestive of malignancy,and should be biopsied.

As previously demonstrated, angiosarcomas are partic-ularly prone to metastases compared to other histologiesand had the worst prognosis in this series. The medianoverall survival of cardiac sarcomas of 11–18 monthsand a five-year survival of 20% in the literature are con-sistent with the present data [19–21]. Patients with PCSthus fare much worse than those observed withsarcomas of the limbs, in whom five-year overall sur-vival is about 65% and also worse than that of visceralsarcomas [22].

Complete resection is hardly achievable in PCS dueto tumour inaccessibility and the vital role of cardiacstructures, often requiring surgery in emergency. In thecurrent series, cardiac surgery was performed in mostpatients, including metastatic patients, but completeresection was scarce. Surgery was a major prognosticfactor for survival, regardless of the quality of resectionand metastatic status. This may indicate a particularparadigm, different from that of soft-tissue sarcomasof the limbs, as even incomplete resection appearsworthwhile for immediate vital reasons and tumour con-trol. Noteworthy however, safe margins yielded bettersurvival. Additionally, heart transplant yielded a bettersurvival rate than that seen in the whole series. It hasalready been suggested that heart transplantation maybe an alternative either for unresectable tumours whenconservative surgery or complete resection is not feasi-ble, including for cardiac metastases [23,24]. The pri-mary aim of surgery in terms of survival in metastaticPCS is probably a more functional short-term outcomethan prolonged survival [25] and should probably beindicated for pauci-metastatic patients only. A furtheralternative reserved to left-heart sarcomas might beautotransplantation, which consists of removing theheart, resecting the tumour with sufficient margins,reconstructing the heart and finally reimplanting theheart. This has been performed successfully in well-trained teams with 1.4% operative mortality [26].

External beam radiation therapy was performed inone fourth of our patients with localised disease andnone of those with metastatic disease. Radiotherapyprovided a benefit on PFS. Radiotherapy [27], with orwithout sequential chemotherapy [8], has been tradition-ally performed in PCS and cardiac metastases. This hasbeen so despite the risk of myocardial injury owing tothe limited tolerance of the normal heart to ionisingradiation, which not only depends on the total dosebut also on the dose per fraction and volume of safeheart irradiated [28]. This may sound surprising in view

Table 3Prognostic factors on overall survival (univariate analysis).

Univariate Cox analysis

Death/total (85/122) HR CI95% p-Value

Age (years) 0.767649 46/61 1>49 39/61 1.07 [0.69–1.64]

Gender 0.366Female 48/68 1Male 37/54 0.81 [0.53–1.26]

Histology 0.019

Angiosarcoma 32/39 1Leiomyosarcoma 11/15 0.23 [0.33–1.31]Poorly differentiated sarcoma 28/45 0.64 [0.39–1.07]Other sarcomas 14/23 0.36 [0.19–0.69]

Site 0.833Left atrium 29/45 1Right atrium 34/45 1.31 [0.79–2.17]Leftventricle 4/10 1.03 [0.36–2.97]Right ventricle 5/7 1.47 [0.57–3.82]Extended over several sites 7/9 1.22 [0.53–2.80]Missing 6/6

Stage 0.005

M0 68/99 1M+ 17/23 2.22 [1.28–3.87]

Surgery <0.001

No 31/42 1Yes 54/80 0.09 [0.23–0.59]

Chemotherapy 0.181No 9/12 1Yes 76/110 0.62 [0.31–1.25]

Radiotherapy 0.038

No 70/97 1Yes 15/24 0.54 [0.31–0.97]Missing 0/1

M0, non-metastatic; M+, metastatic; HR, hazard ratio.

Table 4Prognostic factors on overall survival (multivariate analysis).

Multivariate Cox analysis

Death/total(85/121)

Hazardratio (HR)

CI95% p-Value

Surgery and

chemotherapy

<0.001

Surgery + chemotherapy 4/4 1Surgery alone 5/8 1.14 [0.45–

2.91]Chemotherapy alone 27/38 2.33 [1.42–

3.81]No treatment 49/71 32.51 [9.63–

109.79]

Radiotherapy 0.115No 70/97 1Yes 15/24 0.62 [0.35–

1.12]

134 N. Isambert et al. / European Journal of Cancer 50 (2014) 128–136

of the known low curability of most sarcomas toradiotherapy and the need for high dose irradiation of

sensitive structures like the heart, coronaries and lung[29]. In the series, radiotherapy, performed with a med-ian dose was 50 Gy mostly for patients with incompleteresection or unresectable disease, was associated withbetter overall survival on univariate analysis and betterprogression-free survival on multivariate analysis. Asmost PCS patients died of locoregional progression,the trend for better survival with irradiation might bethrough the improvement of locoregional control.Unexpectedly, and contrary to numerous reports ofthe literature on the use of radiotherapy in metastatictumours of the heart, none of the patients with PCS met-astatic to other organs underwent irradiation in the cur-rent series.

Anthracyclin-based chemotherapy was significantlyassociated with better overall survival, in the overallpopulation and in non-metastatic patients. Mostpatients underwent chemoradiation in the adjuvantsetting for localised disease and also almost all patientswith metastatic disease. However, it seems difficult torecommend systematic adjuvant chemotherapy,

N. Isambert et al. / European Journal of Cancer 50 (2014) 128–136 135

particularly because of potential biases in the analysis.The recently published phase III EORTC 62931 trialsuggests that adjuvant chemotherapy with high-dosedoxorubicin and ifosfamide in resected grade II–IIIsoft-tissue sarcoma yields no benefit in terms ofrelapse-free survival or overall survival in unselectedpatients [30]. Mean tumour size in the current studywas 6.2 cm and most sarcomas were high grade.Right-heart PCS were more likely to receive neoadju-vant chemotherapy while left-heart PCS received moreadjuvant chemotherapy or no chemotherapy. Recentdata suggest than taxanes are more beneficial thananthracyclin-ifosfamide regimens in angiosarcomas.Hitherto, the current study suggests continuing investi-gations on its role in the setting of the different histolog-ical subtypes of PCS. Because of the rarity of such anentity, it is unlikely that any clinical trial will ever beinitiated and thus this series represents a uniqueobservation.

5. Conclusion

Surgery is the mainstay of treatment in PCS. Theremay be an additional advantage of complete resection.Left-heart PCS benefits from upfront surgery. Theliterature also suggests an additional benefit of hearttransplant or autotransplantation for left heart-PCS.Right-heart sarcomas might benefit from neoadjuvantchemotherapy when complete resection does not seempossible upfront. Radiotherapy appears feasible andbeneficial in cases with incomplete resection or no sur-gery. Its role in metastatic PCS could not be evaluatedin the current series. There was a benefit of chemother-apy in non-operated patients in this series. The role ofchemotherapy being similar in our series regardless ofhistology may evolve towards the use of more persona-lised targeted therapies efficient in specific histologicalsubtypes or molecular patterns. The poor prognosis ofPCS warrants extensive multidisciplinary research andcohort studies to promote earlier diagnosis and developmeans to achieve complete resection upfront as well asto improve local and systemic treatments.

6. Authors’ contributions statement

Nicolas Isambert: conception of study, literaturesearch, data collection, data analysis, data interpreta-tion, writing, figures, editing, final review and submis-sion; Isabelle Ray-Coquard: data collection, finalreview; Antoine Italiano: data collection, final review;Maria Rios: data collection, final review; Pierre Kerbrat:data collection, final review; Melanie Gauthier: concep-tion of study, statistics – data analysis and final review;Aurelien Blouet: data collection, final review; LoıcChaigneau: data collection, final review; FlorenceDuffaud: data collection, final review; Sophie Piperno-

Neumann: data collection, final review; Jean-EmmanuelKurtz: data collection, final review; Nicolas Girard: datacollection, final review; Olivier Collard: data collection,final review; Emmanuelle Bompas: data collection, finalreview; Nicolas Penel: data collection, final review;Jacques-OlivierBay: data collection, final review; CecileGuillemet: data collection, final review; Franc�oiseCollin: conception of study, data collection, final review;Jean-Yves Blay: data collection, final review; Axel LeCesne: data collection, final review; Juliette Thariat:literature search, data collection, data interpretation,writing, editing and final review.

Conflict of interest statement

None declared.

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