Management of Desmoplastic Small Round-cell Tumors 

Patients with DSRCT require aggressive multimodal therapy. Current treatment protocols with neoadjuvant chemotherapy, debulking of >90% of the tumor, and radiation therapy have been reported to prolong life but rarely achieve cure. Chemotherapy agents with known activity in DSRCT are very similar to those active in EWS. Both tumors share a EWS fusion protein and may also share molecular mechanisms facilitating proliferation and survival pathways.

Alkylating agents such as cyclophosphamide and ifosfamide are important components of therapy. Currently, a well-recognized treatment schema has been reported by Kushner et al19 who described results in 12 DSRCT patients. This intensive alkylator-based therapy used cyclophosphamide, doxorubicin, vincristine alternating with ifosfamide and etoposide. Its combination with other treatment modalities such as surgery, radiation, autologous stem cell rescue, or the combination of all of the above was used. The median survival time was 19 months. For those achieving complete response, the median followup in this series was 22 months. The toxicity for this regimen can be substantial and often includes hospitalization not only for chemotherapy, but also for fevers associated with myelosuppression and mucositis. An alternative more tolerable outpatient regimen has more recently been used for DSRCT as documented in a case report.20 In this report, neoadjuvant chemotherapy included vincristine, ifosfamide, dexrazoxane/doxorubicin, and etoposide.

Continuous hyperthermic peritoneal perfusion HIPEC with cisplatin was given after extensive cytoreductive surgery. This was followed by irinotecan+temozolomide monthly 2 and then abdominal radiation 30Gy with simultaneous temozolomide. A total of 12 cycles of irinotecan and temozolomide were given and provided a disease-free interval of nearly 2 years. It permitted routine school attendance, and play activities were possible with an excellent quality of life. Aggressive cytoreductive surgery is currently accepted to have a primary role in the achievement of prolonged survival of other malignancies involving the peritoneum.21–23 In DSRCT, La Quaglia and Brennan6 reported that 3-year overall survival was 58% in patients with gross total resection in comparison with 0% in the nonresection cohort. Other therapeutic modalities such as CHPP, also called hyperthermic intrapertitoneal chemotherapy (HIPEC), have been found to improve outcome in carcinoma involving the peritoneum.

23–26 Recently, Hayes-Jordan and colleagues were the ?rst to report on the combined use of cytoreductive surgery and HIPEC in 2 children with DSCRT. Both children received neoadjuvant chemotherapy, followed by cytoreductive surgery and intraoperative HIPEC using cisplatin. At the time of publication, both patients had no evidence of disease 6 and 10 months postoperatively.27 Currently, a phase I trial is ongoing using HIPEC at MD Anderson Cancer Center.8 A more recent series reports a median 3 year survival of 71% with HIPEC and 29% in those receiving chemotherapy and radiotherapy alone.