Desmoplastic small round cell tumors: Multimodality treatment and new risk factors

Monika Scheer; Christian Vokuhl; Bernd Blank; Erika Hallmen; Thekla von Kalle; Marc Münter; Rüdiger Wessalowski; Maite Hartwig; Monika Sparber-Sauer; Paul-Gerhardt Schlegel; Christof M Kramm; Udo Kontny; Bernd Spriewald; Thomas Kegel; Sebastian Bauer; Bernarda Kazanowska; Felix Niggli; Ruth Ladenstein; Gustaf Ljungman; Kirsi Jahnukainen; Jörg Fuchs; Stefan S Bielack; Thomas Klingebiel; Ewa Koscielniak; Cooperative Weichteilsarkom Studiengruppe [CWS]

doi:10.1002/cam4.1940

Desmoplastic small round cell tumors: Multimodality treatment and new risk factors

Cancer Med. 2019 Feb;8(2):527-542. doi: 10.1002/cam4.1940. Epub 2019 Jan 16.

Authors

Monika Scheer¹, Christian Vokuhl², Bernd Blank¹, Erika Hallmen¹, Thekla von Kalle³, Marc Münter⁴, Rüdiger Wessalowski⁵, Maite Hartwig⁶, Monika Sparber-Sauer¹, Paul-Gerhardt Schlegel⁷, Christof M Kramm⁸, Udo Kontny⁹, Bernd Spriewald¹⁰, Thomas Kegel¹¹, Sebastian Bauer¹², Bernarda Kazanowska¹³, Felix Niggli¹⁴, Ruth Ladenstein¹⁵, Gustaf Ljungman¹⁶, Kirsi Jahnukainen¹⁷, Jörg Fuchs¹⁸, Stefan S Bielack^{1

19}, Thomas Klingebiel²⁰, Ewa Koscielniak^{1

21}; Cooperative Weichteilsarkom Studiengruppe [CWS]

Affiliations

¹ Pediatrics 5, Olgahospital, Klinikum Stuttgart, Stuttgart, Germany.
² Kiel Peadiatric Tumour Registry, Department of Pediatric Pathology, University Hospital Kiel, Germany.
³ Radiologisches Institut, Olgahospital, Klinikum Stuttgart, Stuttgart, Germany.
⁴ Radiation Oncology, Klinikum Stuttgart, Stuttgart, Germany.
⁵ Pediatric Oncology Clinic, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.
⁶ Pediatric Hematology and Oncology, University Hamburg-Eppendorf, Hamburg, Germany.
⁷ Children's Hospital, Pediatric Oncology, University Würzburg, Würzburg, Germany.
⁸ Pediatric Hematology and Oncology, University Medical Center Göttingen, Göttingen, Germany.
⁹ Pediatric Hematology and Oncology, University Medical Center Aachen, Aachen, Germany.
¹⁰ Internal Medicine 5, University Hospital Erlangen, Erlangen, Germany.
¹¹ Hematology/Oncology, University of Halle, Halle, Germany.
¹² Sarcoma Center, West German Cancer Center, University of Duisburg-Essen, Essen, Germany.
¹³ Department of Pediatric Hematology/Oncology and BMT, University of Wroclaw, Wroclaw, Poland.
¹⁴ Pediatric Oncology, University of Zürich, Zürich, Switzerland.
¹⁵ St. Anna Kinderspital and St. Anna Kinderkrebsforschung e.V., Vienna, Austria.
¹⁶ Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
¹⁷ Pediatrics, Helsinki University Central Hospital, Helsinki, Finland.
¹⁸ Pediatric Surgery, University Hospital Tübingen, Tübingen, Germany.
¹⁹ Pediatric Hematology and Oncology, University Children's Hospital Münster, Münster, Germany.
²⁰ Department for Children and Adolescents, University Hospital, Goethe-University Frankfurt (Main), Frankfurt, Germany.
²¹ Pediatric Hematology and Oncology, University of Tübingen, Tübingen, Germany.

Abstract

Background: To evaluate optimal therapy and potential risk factors.

Methods: Data of DSRCT patients <40 years treated in prospective CWS trials 1997-2015 were analyzed.

Results: Median age of 60 patients was 14.5 years. Male:female ratio was 4:1. Tumors were abdominal/retroperitoneal in 56/60 (93%). 6/60 (10%) presented with a localized mass, 16/60 (27%) regionally disseminated nodes, and 38/60 (63%) with extraperitoneal metastases. At diagnosis, 23/60 (38%) patients had effusions, 4/60 (7%) a thrombosis, and 37/54 (69%) elevated CRP. 40/60 (67%) patients underwent tumor resection, 21/60 (35%) macroscopically complete. 37/60 (62%) received chemotherapy according to CEVAIE (ifosfamide, vincristine, actinomycin D, carboplatin, epirubicin, etoposide), 15/60 (25%) VAIA (ifosfamide, vincristine, adriamycin, actinomycin D) and, 5/60 (8%) P6 (cyclophosphamide, doxorubicin, vincristine, ifosfamide, etoposide). Nine received high-dose chemotherapy, 6 received regional hyperthermia, and 20 received radiotherapy. Among 25 patients achieving complete remission, 18 (72%) received metronomic therapies. Three-year event-free (EFS) and overall survival (OS) were 11% (±8 confidence interval [CI] 95%) and 30% (±12 CI 95%), respectively, for all patients and 26.7% (±18.0 CI 95%) and 56.9% (±20.4 CI 95%) for 25 patients achieving remission. Extra-abdominal site, localized disease, no effusion or ascites only, absence of thrombosis, normal CRP, complete tumor resection, and chemotherapy with VAIA correlated with EFS in univariate analysis. In multivariate analysis, significant factors were no thrombosis and chemotherapy with VAIA. In patients achieving complete remission, metronomic therapy with cyclophosphamide/vinblastine correlated with prolonged time to relapse.

Conclusion: Pleural effusions, venous thrombosis, and CRP elevation were identified as potential risk factors. The VAIA scheme showed best outcome. Maintenance therapy should be investigated further.

Keywords: C-reactive protein; Trousseau’s syndrome; desmoplastic small round cell tumor; maintenance therapy; soft tissue sarcoma.

Publication types

Clinical Trial
Research Support, Non-U.S. Gov't

MeSH terms

Abdominal Neoplasms / pathology
Abdominal Neoplasms / therapy*
Adolescent
Adult
Antineoplastic Agents / therapeutic use
Antineoplastic Combined Chemotherapy Protocols / therapeutic use
C-Reactive Protein / analysis
Child
Combined Modality Therapy
Desmoplastic Small Round Cell Tumor / pathology
Desmoplastic Small Round Cell Tumor / therapy*
Female
Humans
Male
Pleural Effusion / diagnosis
Prognosis
Risk Factors
Stem Cell Transplantation
Venous Thrombosis / diagnosis
Young Adult

Substances

Antineoplastic Agents
C-Reactive Protein