Progression and Relapse of Pediatric Soft Tissue Sarcoma: Individualized Approach of Treatment – Experience from a Major Pediatric Cancer Center in Europe

Abstract

BackgroundThe outcome of children with refractory or relapsed soft tissue sarcoma (STS) is extremely poor. Whereas larger clinical trials evaluated specific treatment modalities, real-life data on individual multimodal therapeutic strategies, given alone or in combination, are scarce.

Patients and Methods We retrospectively analyzed the clinical course of 18 pediatric patients with progression of or relapsed STS treated between 2008 and 2018 in our institution.

Results A total of 18 patients (median age 12.4 years) suffered from progression or relapse of alveolar (n=7), embryonal (n=5), undifferentiated (n=2) rhabdomyosarcoma or desmoplastic small round cell tumor (n=4). 14 patents had an initial stage IV disease. All but one patient died. Median survival was 12.5 months. Shortest survival was seen in patients with systemic progression of the disease, longest in patients with local relapse. Patients with an Oberlin score<2 at the time of relapse had a significant longer time of survival than those with a score≥2. No significant advantage of a specific therapeutic modality was observed.

Discussion We critically analyzed the clinical course in the real-life setting, in which various treatment options were applied to an individual patient according to the best of available data. We observed that some patients died within a short period of time despite multiple treatment modalities, which underlines the need for better prognostic parameters.

Conclusion In addition to well characterized clinical factors such as local or systemic relapse, the Oberlin score could be helpful in counselling patients and their families for choosing the best strategy of care.

Zusammenfassung

Hintergrund Die Prognose von Kindern mit refraktärem oder rezidiviertem Weichteilsarkom (STS) ist extrem schlecht. Während in prospektiven Studien der Benefit von spezifischen Behandlungsmodalitäten untersucht wurde, finden sich in der Literatur kaum Daten zu individuellen Therapiestrategien, die allein oder in Kombination verabreicht wurden.

Patienten und Methoden Wir analysierten retrospektiv den Verlauf aller pädiatrischen Patienten mit Progress oder Rezidiv eines STS, die zwischen 2008 und 2018 in unserer Klinik behandelt wurden.

Ergebnisse Insgesamt betreuten wir 18 Patienten (medianes Alter 12,4 Jahre) mit einem Progress/Rezidiv eines alveolären (n=7), embryonalen (n=5), oder undifferenzierten (n=2) Rhabdomyosarkoms oder eines desmoplastischen kleinen Rundzelltumors (n=4). 14 Patienten hatten initial ein Stadium IV. Bis auf einen Patienten verstarben alle Kinder, wobei die mediane Überlebenszeit 12,5 Monate betrug. Die kürzeste Überlebenszeit hatten Kinder mit systemischem Progress, die längste Kinder mit Lokalrezidiv. Patienten mit einem Oberlin-Score<2 zum Zeitpunkt des Rezidivs hatten eine signifikant längere Überlebenszeit als Patienten mit einem Score≥2. Kein bestimmtes therapeutisches Vorgehen zeigte einen signifikanten Vorteil.

Diskussion Die kritische Analyse im “real-life setting” zeigt, dass einige Patienten trotz intensivster kombinierter Therapiemethoden innerhalb kurzer Zeit verstarben, was die Notwendigkeit besserer prognostischer Parameter unterstreicht.

Schlussfolgerung Neben bereits gut charakterisierten klinischen Faktoren könnte der Oberlin-Score bei der Beratung von Patienten hinsichtlich der Wahl des besten therapeutischen Vorgehens hilfreich sein.

Key words

soft tissue sarcoma - pediatric - relapse - progression - child - outcome

Schlüsselwörter

Weichteilsarkom - Kinder - Rezidiv - Progress - Prognose

Publication History

Article published online:
11 July 2023

• References

• 1 Sparber-Sauer M, Stegmaier S, Vokuhl C. et al. Rhabdomyosarcoma diagnosed in the first year of life: Localized, metastatic, and relapsed disease. Outcome data from five trials and one registry of the Cooperative Weichteilsarkom Studiengruppe (CWS). Pediatric Blood and Cancer 2019; 66: 1-12
• 2 Heske CM, Chi YY, Venkatramani R. et al. Survival outcomes of patients with localized FOXO1 fusion-positive rhabdomyosarcoma treated on recent clinical trials: A report from the Soft Tissue Sarcoma Committee of the Children’s Oncology Group. Cancer 2021; 127: 946-956
• 3 Sparber-Sauer M, Ferrari A, Kosztyla D. et al. Long-term results from the multicentric European randomized phase 3 trial CWS/RMS-96 for localized high-risk soft tissue sarcoma in children, adolescents, and young adults. Pediatric Blood and Cancer 2022; 1-11
• 4 Sparber-Sauer M, Seitz G, von Kalle T. et al. Alveolar soft-part sarcoma: Primary metastatic disease and metastatic relapse occurring during long-term follow-up: Treatment results of four Cooperative Weichteilsarkom Studiengruppe (CWS) trials and one registry. Pediatric Blood and Cancer 2018; 65: 1-9
• 5 Bernbeck B, Bahci S, Meisel R. et al. Serial intense chemotherapy combining topotecan, etoposide, carboplatin and cyclophosphamide (TECC) followed by autologous hematopoietic stem cell support in patients with high risk soft tissue sarcoma (STS). Klinische Padiatrie 2007; 219: 318-322
• 6 Klingebiel T, Pertl U, Hess CF. et al. Treatment of children with relapsed soft tissue sarcoma: Report of the German CESS/CWS REZ 91 trial. Medical and Pediatric Oncology 1998; 30: 269-275 10.1002/SICI)1096-911X(199805)30:5<269: AID-MPO2>3.0.CO;2-D
• 7 Defachelles AS, Bogart E, Casanova M. et al. Randomized Phase II Trial of Vincristine-Irinotecan With or Without Temozolomide, in Children and Adults With Relapsed or Refractory Rhabdomyosarcoma: A European Paediatric Soft Tissue Sarcoma Study Group and Innovative Therapies for Children With Cancer. Journal of Clinical Oncology 2021; 39: 2979-2990
• 8 Shah NK, Yegya-Raman N, Jones JA. et al. Radiation therapy in metastatic soft tissue sarcoma: From palliation to ablation. Cancers 2021; 13
• 9 Salerno KE, Alektiar KM, Baldini EH. et al. Radiation Therapy for Treatment of Soft Tissue Sarcoma in Adults: Executive Summary of an ASTRO Clinical Practice Guideline. Practical Radiation Oncology 2021; 11: 339-351
• 10 Wakefield DV, Eaton BR, Dove APH. et al. Is there a role for salvage re-irradiation in pediatric patients with locoregional recurrent rhabdomyosarcoma? Clinical outcomes from a multi-institutional cohort. Radiotherapy and Oncology 2018; 129: 513-519
• 11 De Corti F, Bisogno G, Dall’Igna P. et al. Does surgery have a role in the treatment of local relapses of non-metastatic rhabdomyosarcoma?. Pediatric Blood & Cancer 2011; 57: 1261-1265
• 12 Dombrowski ND, Wolter NE, Robson CD. et al. Role of Surgery in Rhabdomyosarcoma of the Head and Neck in Children. Laryngoscope 2021; 131: E984-E992
• 13 Pillozzi S, Bernini A, Palchetti I. et al. Soft tissue sarcoma: An insight on biomarkers at molecular, metabolic and cellular level. Cancers 2021; 13: 1-26
• 14 Yohe ME, Heske CM, Stewart E. et al. Insights into pediatric rhabdomyosarcoma research: Challenges and goals. Pediatric Blood and Cancer 2019; 66: 1-10
• 15 Koscielniak E, Blank B, Vokuhl C. et al. Long-Term Clinical Outcome and Prognostic Factors of Children and Adolescents with Localized Rhabdomyosarcoma Treated on the CWS-2002P Protocol. Cancers 2022; 14
• 16 Oberlin O, Rey A, Lyden E. et al. Prognostic factors in metastatic rhabdomyosarcomas: Results of a pooled analysis from United States and European Cooperative Groups. Journal of Clinical Oncology 2008; 26: 2384-2389
• 17 Vassal G, Couanet D, Stockdale E. et al. Phase II trial of irinotecan in children with relapsed or refractory rhabdomyosarcoma: A joint study of the French Society of Pediatric Oncology and the United Kingdom Children’s Cancer Study Group. Journal of Clinical Oncology 2007; 25: 356-361
• 18 Heske CM, Mascarenhas L. Relapsed rhabdomyosarcoma. Journal of Clinical Medicine 2021; 10: 1-15
• 19 Dantonello TM, Int-Veen C, Schuck A. et al. Survival following disease recurrence of primary localized alveolar rhabdomyosarcoma. Pediatric Blood & Cancer 2013; 60: 1267-1273
• 20 Winter S, Fasola S, Brisse H. et al. Relapse after localized rhabdomyosarcoma: Evaluation of the efficacy of second-line chemotherapy. Pediatric Blood & Cancer 2015; 62: 1935-1941
• 21 Cameron AL, Elze MC, Casanova M. et al. The Impact of Radiation Therapy in Children and Adolescents With Metastatic Rhabdomyosarcoma. International Journal of Radiation Oncology Biology Physics 2021; 111: 968-978
• 22 Réguerre Y, Martelli H, Rey A. et al. Local therapy is critical in localised pelvic rhabdomyosarcoma: Experience of the International Society of Pediatric Oncology Malignant Mesenchymal Tumor (SIOP-MMT) committee. European Journal of Cancer 2012; 48: 2020-2027
• 23 Doyen J, Jazmati D, Geismar D. et al. Outcome and Patterns of Relapse in Childhood Parameningeal Rhabdomyosarcoma Treated With Proton Beam Therapy. International Journal of Radiation Oncology Biology Physics 2019; 105: 1043-1054
• 24 Braschi EL, Kharod SM, Morris CG. et al. Reirradiation in conservative salvage of recurrent soft-Tissue sarcoma an analysis of treatment efficacy and toxicities. American Journal of Clinical Oncology: Cancer Clinical Trials 2021; 44: 624-628
• 25 Heinz AT, Ebinger M, Schönstein A. et al. Cooperative Weichteilsarkom Studiengruppe (CWS). Second-line treatment of pediatric patients with relapsed rhabdomyosarcoma adapted to initial risk stratification: Data of the European Soft Tissue Sarcoma Registry (SoTiSaR). Pediatr Blood Cancer 2023; e30363
• 26 Van Tilburg CM, Pfaff E, Pajtler KW. et al. The pediatric precision oncology inform registry: Clinical outcome and benefit for patients with very high-evidence targets. Cancer Discovery 2021; 11: 2764-2779