Intra-abdominal desmoplastic small round cell tumor: The European pediatric Soft tissue sarcoma Study Group (EpSSG) experience
Corresponding Author
Pablo Berlanga
Department of Pediatric and Adolescent Oncology, Gustave-Roussy, Université Paris-Saclay, Villejuif, France
Correspondence
Pablo Berlanga, Department of Pediatric and Adolescent Oncology, Gustave-Roussy, Cancer Campus, Université Paris-Saclay, Gustave Roussy, 114 rue Edouard Vaillant, 94805 Villejuif Cedex, France.
Email: [email protected]
Search for more papers by this authorDaniel Orbach
SIREDO Oncology Center, Institut Curie, PSL University, Paris, France
Search for more papers by this authorReineke A. Schoot
Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
Search for more papers by this authorMichela Casanova
Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
Search for more papers by this authorRita Alaggio
Pathology Department, Ospedale Pediatrico Bambino Gesù IRCCS, Università La Sapienza, Rome, Italy
Search for more papers by this authorNadege Corradini
Department of Pediatric Oncology, Institut d'Hematologie et d'Oncologie Pédiatrique,/Centre, Léon Bérard, Lyon, France
Search for more papers by this authorBernadette Brennan
Pediatric Oncology, Royal Manchester Children's Hospital, Manchester, UK
Search for more papers by this authorGema L. Ramirez-Villar
Pediatric Oncology Unit, Hospital Universitario Virgen del Rocío, Sevilla, Spain
Search for more papers by this authorLisa Lyngsie Hjalgrim
Department of Pediatrics and Adolescent Medicine, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
Search for more papers by this authorJulia C. Chisholm
Children and Young People's Unit, The Royal Marsden NHS Foundation Trust and Institute of Cancer Research, Sutton, UK
Search for more papers by this authorGianni Bisogno
Department of Women's and Children's Health, University of Padua, Padua, Italy
Pediatric Hematology Oncology Division, University Hospital of Padua, Padua, Italy
Search for more papers by this authorBeatrice Coppadoro
Department of Women's and Children's Health, University of Padua, Padua, Italy
Search for more papers by this authorAkmal Safwat
Danish Center for Particle Therapy, Aarhus University Hospital, Aarhus, Denmark
Search for more papers by this authorJohannes H. M. Merks
Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
Division of Imaging and Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
Search for more papers by this authorGabriela Guillen Burrieza
Surgical Oncology and Neonatal Surgery, Pediatric Surgery Department, Hospital Infantil Universitari Vall d'Hebron, Barcelona, Spain
Search for more papers by this authorMax M. van Noesel
Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
Division of Imaging and Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
Search for more papers by this authorAndrea Ferrari
Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
Search for more papers by this authorCorresponding Author
Pablo Berlanga
Department of Pediatric and Adolescent Oncology, Gustave-Roussy, Université Paris-Saclay, Villejuif, France
Correspondence
Pablo Berlanga, Department of Pediatric and Adolescent Oncology, Gustave-Roussy, Cancer Campus, Université Paris-Saclay, Gustave Roussy, 114 rue Edouard Vaillant, 94805 Villejuif Cedex, France.
Email: [email protected]
Search for more papers by this authorDaniel Orbach
SIREDO Oncology Center, Institut Curie, PSL University, Paris, France
Search for more papers by this authorReineke A. Schoot
Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
Search for more papers by this authorMichela Casanova
Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
Search for more papers by this authorRita Alaggio
Pathology Department, Ospedale Pediatrico Bambino Gesù IRCCS, Università La Sapienza, Rome, Italy
Search for more papers by this authorNadege Corradini
Department of Pediatric Oncology, Institut d'Hematologie et d'Oncologie Pédiatrique,/Centre, Léon Bérard, Lyon, France
Search for more papers by this authorBernadette Brennan
Pediatric Oncology, Royal Manchester Children's Hospital, Manchester, UK
Search for more papers by this authorGema L. Ramirez-Villar
Pediatric Oncology Unit, Hospital Universitario Virgen del Rocío, Sevilla, Spain
Search for more papers by this authorLisa Lyngsie Hjalgrim
Department of Pediatrics and Adolescent Medicine, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
Search for more papers by this authorJulia C. Chisholm
Children and Young People's Unit, The Royal Marsden NHS Foundation Trust and Institute of Cancer Research, Sutton, UK
Search for more papers by this authorGianni Bisogno
Department of Women's and Children's Health, University of Padua, Padua, Italy
Pediatric Hematology Oncology Division, University Hospital of Padua, Padua, Italy
Search for more papers by this authorBeatrice Coppadoro
Department of Women's and Children's Health, University of Padua, Padua, Italy
Search for more papers by this authorAkmal Safwat
Danish Center for Particle Therapy, Aarhus University Hospital, Aarhus, Denmark
Search for more papers by this authorJohannes H. M. Merks
Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
Division of Imaging and Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
Search for more papers by this authorGabriela Guillen Burrieza
Surgical Oncology and Neonatal Surgery, Pediatric Surgery Department, Hospital Infantil Universitari Vall d'Hebron, Barcelona, Spain
Search for more papers by this authorMax M. van Noesel
Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
Division of Imaging and Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
Search for more papers by this authorAndrea Ferrari
Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
Search for more papers by this authorPablo Berlanga and Daniel Orbach are the co-first authors.
Abstract
Background
This study describes the clinical findings of a consecutive series of pediatric and adolescent patients with a diagnosis of intra-abdominal desmoplastic small round cell tumor (DSRCT) prospectively enrolled in European pediatric Soft tissue sarcoma Study Group (EpSSG) protocols: the BERNIE study, the EpSSG MTS 2008 study, and the EpSSG NRSTS 2005 study.
Methods
Patients aged less than 21 years with a diagnosis of DSRCT arising in the abdomen were included. All trials recommended a multimodal approach including intensive multidrug chemotherapy and loco-regional treatment with surgery and/or radiotherapy whenever possible.
Results
The analysis included 32 cases (median age 13.7 years, male:female ratio 1.5:1). Three patients had localized tumors, seven had regionally disseminated disease, and 22 extraperitoneal metastases. All but one patient received multidrug chemotherapy and 11 had maintenance chemotherapy. Loco-regional treatment consisted of surgery only in seven cases, surgery plus adjuvant radiotherapy in 10, and radiotherapy only in six. Among the 17 cases who had radiotherapy, six had irradiation of the primary site, 10 had whole abdominopelvic radiotherapy plus boost to macroscopic residual disease, and one had irradiation to lung metastases only. With a median follow-up of 76 months (range: 18–124 months), 5-year event-free and overall survivals were 19.7% and 21.0%, respectively. Event-free survival was significantly worse for patients who did not receive loco-regional treatment (p-value .007).
Conclusions
The study confirmed that the outcome of patients with DSRCT remains dismal and did not improve over recent years despite an intensive multimodal treatment approach.
CONFLICT OF INTEREST STATEMENT
The authors have no potential conflicts of interest to declare.
Open Research
DATA AVAILABILITY STATEMENT
The data are available on request from the authors.
REFERENCES
- 1Kushner BH, LaQuaglia MP, Wollner N, et al. Desmoplastic small round-cell tumor: prolonged progression-free survival with aggressive multimodality therapy. J Clin Oncol. 1996; 14: 1526-1531.
- 2Philippe-Chomette P, Kabbara N, Andre N, et al. Desmoplastic small round cell tumors with EWS-WT1 fusion transcript in children and young adults. Pediatr Blood Cancer. 2012; 58(6): 891-897.
- 3Scheer M, Vokuhl C, Blank B, et al. Desmoplastic small round cell tumors: multimodality treatment and new risk factors. Cancer Med. 2019; 8(2): 527-542.
- 4Honoré C, Amroun K, Vilcot L, et al. Abdominal desmoplastic small round cell tumor: multimodal treatment combining chemotherapy, surgery, and radiotherapy is the best option. Ann Surg Oncol. 2015; 22(4): 1073-1079.
- 5Lal DR, Su WT, Wolden SL, et al. Results of multimodal treatment for desmoplastic small round cell tumors. J Pediatr Surg. 2005; 40: 251-255.
- 6Saab R, Khoury JD, Krasin M, et al. Desmoplastic small round cell tumor in childhood: the St Jude Children's Research Hospital experience. Pediatr Blood Cancer. 2007; 49: 274-279.
- 7Xiang T, Zhang SY, Wang SS, Fei RS, Li H. A nationwide analysis of desmoplastic small round cell tumor. Medicine (Baltimore). 2020; 99(30):e21337.
- 8Wong HH, Hatcher HM, Benson C, et al. Desmoplastic small round cell tumour: characteristics and prognostic factors of 41 patients and review of the literature. Clin Sarcoma Res. 2013; 3(1): 14.
- 9Ferrari A, Bergamaschi L, Chiaravalli S, et al. Multiagent chemotherapy including IrIVA regimen and maintenance therapy in the treatment of desmoplastic small round cell tumor. Tumori. 2022; 108(1): 93-97.
- 10Liu KX, Collins NB, Greenzang KA, et al. The use of interval-compressed chemotherapy with the addition of vincristine, irinotecan, and temozolomide for pediatric patients with newly diagnosed desmoplastic small round cell tumor. Pediatr Blood Cancer. 2020; 67:e28559.
- 11Quaglia MPL, Brennan MF. The clinical approach to desmoplastic small round cell tumor. Surg Oncol. 2000; 9(2): 77-81.
- 12Desai NB, Stein NF, LaQuaglia MP, et al. Reduced toxicity with intensity modulated radiation therapy (IMRT) for desmoplastic small round cell tumor (DSRCT): an update on the whole abdominopelvic radiation therapy (WAP-RT) experience. Int J Radiat Oncol Biol Phys. 2013; 85: e67-e72.
- 13Atallah V, Honore C, Orbach D, et al. Role of adjuvant radiation therapy after surgery for abdominal desmoplastic small round cell tumors. Int J Radiat Oncol Biol Phys. 2016; 95(4): 1244-1253.
- 14Pinnix CC, Fontanilla HP, Hayes-Jordan A, et al. Whole abdominopelvic intensity-modulated radiation therapy for desmoplastic small round cell tumor after surgery. Int J Radiat Oncol Biol Phys. 2012; 83(1): 317-326.
- 15Hayes-Jordan A, Green HL, Lin H, et al. Complete cytoreduction and HIPEC improves survival in desmoplastic small round cell tumor. Ann Surg Oncol. 2014; 21: 220-224.
- 16Msika S, Gruden E, Sarnacki S, et al. Cytoreductive surgery associated to hyperthermic intraperitoneal chemoperfusion for desmoplastic round small cell tumor with peritoneal carcinomatosis in young patients. J Pediatr Surg. 2010; 45: 1617-1621.
- 17Honoré C, Atallah V, Mir O, et al. Abdominal desmoplastic small round cell tumor without extraperitoneal metastases: is there a benefit for HIPEC after macroscopically complete cytoreductive surgery? PLoS One. 2017; 12(2):e0171639.
- 18Bisogno G, Ferrari A, Rosolen A, et al. Sequential intensified chemotherapy with stem cell rescue for children and adolescents with desmoplastic small round-cell tumor. Bone Marrow Transplant. 2010; 45: 907-911.
- 19Bertuzzi A, Castagna L, Quagliuolo V, et al. Prospective study of high-dose chemotherapy and autologous peripheral stem cell transplantation in adult patients with advanced desmoplastic small round-cell tumour. Br J Cancer. 2003; 89(7): 1159-1161.
- 20De Sanctis R, Bertuzzi A, Bisogno G, et al. Imaitinib mesylate in desmoplastic small round cell tumors. Future Oncol. 2017; 13(14): 1233-1237.
- 21Italiano A, Kind M, Cioffi A, et al. Clinical activity of sunitinib in patients with advanced desmoplastic round cell tumor: a case series. Target Oncol. 2013; 8: 211-213.
- 22Frezza A, Benson C, Judson I, et al. Pazopanib in advanced desmoplastic small round cell tumours: a multi-institutional experience. Clin Sarcoma Res. 2014; 4: 7.
- 23Chisholm JC, Merks JHM, Casanova M, et al. Open-label, multicentre, randomised, phase II study of the EpSSG and the ITCC evaluating the addition of bevacizumab to chemotherapy in childhood and adolescent patients with metastatic soft tissue sarcoma (the BERNIE study). Eur J Canc. 2017; 83: 177.
- 24Ferrari A, Merks JHM, Chisholm JC, et al. Outcomes of metastatic non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) treated within the BERNIE study: a randomised, phase II study evaluating the addition of bevacizumab to chemotherapy. Eur J Cancer. 2020; 130: 72-80.
- 25Schoot RA, Chisholm JC, Casanova M, et al. Metastatic rhabdomyosarcoma: results of the European paediatric Soft tissue sarcoma Study Group MTS 2008 study and pooled analysis with the concurrent BERNIE study. J Clin Oncol. 2022; 40(32): 3730-3740.
- 26Ferrari A, Orbach D, Casanova M, et al. Metastatic adult-type non-rhabdomyosarcoma soft tissue sarcomas in children and adolescents: a cohort study from the European paediatric Soft tissue sarcoma Study Group. Cancer. 2023. doi:10.1002/cncr.34814
- 27Ferrari A, van Noesel MM, Brennan B, et al. Pediatric non-rhabdomyosarcoma soft tissue sarcomas: the prospective NRSTS 2005 study by the European pediatric Soft tissue sarcoma Study Group (EpSSG). Lancet Child Adolesc Health. 2021; 5(8): 546-558.
- 28Harmer MH. TNM classification of pediatric tumors. UICC International Union Against Cancer; 1982; 23-28.
- 29Maurer HM, Beltangady M, Gehan EA, et al. The Intergroup Rhabdomyosarcoma Study I: a final report. Cancer. 1988; 61: 209-220.
10.1002/1097-0142(19880115)61:2<209::AID-CNCR2820610202>3.0.CO;2-L CAS PubMed Web of Science® Google Scholar
- 30Bisogno G, De Salvo GL, Bergeron C, et al. Vinorelbine and continuous low-dose cyclophosphamide as maintenance chemotherapy in patients with high-risk rhabdomyosarcoma (RMS 2005): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2019; 20(11): 1566-1575.
- 31Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000; 92(3): 205-216.
- 32van Houwelingen HC. Dynamic prediction by landmarking in event history analysis. Scand J Stat. 2007; 34: 70-85.
- 33Cameron A, Elze M, Casanova M, et al. The impact of radiation therapy in children and adolescents with metastatic rhabdomyosarcoma. Int J Radiat Oncol Biol Phys. 2021; 111(4): 968-978.
- 34Hassan I, Shyyan R, Donohue JH, et al. Intraabdominal desmoplastic small round cell tumors. Cancer. 2005; 104(6): 1264-1270.
- 35Stiles ZE, Dickson PV, Glazer ES, et al. Desmoplastic small round cell tumor: a nationwide study of a rare sarcoma. J Surg Oncol. 2018; 117(8): 1759-1767.
- 36Zhang S, Zhang Y, Yu YH, Li J. Results of multimodal treatment for desmoplastic small round cell tumor of the abdomen and pelvis. Int J Clin Exp Med. 2015; 8(6): 9658-9666.
- 37Sugarbaker PH. Peritonectomy procedures. Ann Surg. 1995; 221(1): 29-42.
- 38Subbiah V, Lamhamedi-Cherradi SE, Cuglievan B, et al. Multimodality treatment of desmoplastic small round cell tumor: chemotherapy and complete cytoreductive surgery improve patient survival. Clin Cancer Res. 2018; 24(19): 4865-4873.
- 39Hayes-Jordan A, Coakley BA, Green HL, et al. Desmoplastic small round cell tumor treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: results of a phase 2 trial. Ann Surg Oncol. 2018; 25(4): 872-877.
- 40Honoré C, Delhorme JB, Nassif E, et al. Can we cure patients with abdominal desmoplastic small round cell tumor? Results of a retrospective multicentric study on 100 patients. Surg Oncol. 2019; 29: 107-112.
- 41Ferrari A, Grosso F, Stacchiotti S, et al. Response to vinorelbine and low-dose cyclophosphamide chemotherapy in two patients with desmoplastic small round cell tumor. Ped Blood Cancer. 2007; 49(6): 864-866.
- 42Slotkin EK, Bowman AS, Levine MF, et al. Comprehensive molecular profiling of desmoplastic small round cell tumor. Mol Cancer Res. 2021; 19(7): 1146-1155.
- 43Emambux S, Kind M, le Loarer F, et al. Clinical activity of eribulin in advanced desmoplastic small round-cell tumor. Anticancer Drugs. 2017; 28(9): 1053-1055.
- 44Uboldi S, Craparotta I, Colella G, et al. Mechanism of action of trabectedin in desmoplastic small round cell tumor cells. BMC Cancer. 2017; 17(1): 107.
- 45Ferrari A, Chiaravalli S, Bergamaschi L, et al. Trabectedin-irinotecan, a potentially promising combination in relapsed desmoplastic small round cell tumor: report of two cases. J Chemother. 2023; 35(2): 163-167. doi:10.1080/1120009X.2022.2067706
- 46Shi C, Feng Y, Zhang LC, et al. Effective treatment of apatinib in desmoplastic small round cell tumor: a case report and literature review. BMC Cancer. 2018; 18(1): 338.
- 47Bétrian S, Bergeron C, Blay JY, et al. Antiangiogenic effects in patients with progressive desmoplastic small round cell tumor: data from the French national registry dedicated to the use of off-labeled targeted therapy in sarcoma (OUTC's). Clin Sarcoma Res. 2017; 7(1): 10.
- 48Thijs AMJ, van der Graaf WTA, van Herpen CML. Temsirolimus for metastatic desmoplastic small round cell tumor. Pediatr Blood Cancer. 2010; 55(7): 1431-1432.
- 49Lamhamedi-Cherradi SE, Maitituoheti M, Menegaz BA, et al. The androgen receptor is a therapeutic target in desmoplastic small round cell sarcoma. Nat Commun. 2022; 13(1): 3057.
- 50Espinosa-Cotton M, Cheung N-K. Immunotherapy and radioimmunotherapy for desmoplastic small round cell tumor. Front Oncol. 2021; 11:772862.
- 51Ogura K, Somwar R, Hmeljak J, et al. Therapeutic potential of NTRK3 inhibition in desmoplastic small round cell tumor. Clin Cancer Res. 2021; 27(4): 1184-1194.
- 52Zuco V, Pasquali S, Tortoreto M, et al. Effectiveness of irinotecan plus trabectedin in a patient-derived xenograft of desmoplastic small round cell tumor. Dis Model Mech. 2021:dmm.049649. doi:10.1242/dmm.049649
10.1242/dmm.049649 Google Scholar
- 53Kubicek P, Cesne AL, Lervat C, et al. Management and outcomes of adolescent and young adult sarcoma patients: results from the French nationwide database NETSARC. BMC Cancer. 2023; 23(1): 69.
- 54Olivier-Gougenheim L, Orbach D, Atallah V, et al. Desmoplastic small round cell tumors with EWS-WT1 transcript expression: should we consider children and adult patients differently? J Pediatr Hematol Oncol. 2022; 44(3): e637-e642.
