Management of Desmoplastic Small Round-cell Tumors 

Introduction

Patients with Desmoplastic Small Round Cell Tumors (DSRCT) require aggressive multimodal therapy. Current treatment protocols, including neoadjuvant chemotherapy, debulking of more than 90% of the tumor, and radiation therapy, have been reported to prolong life but rarely achieve a cure. Chemotherapy agents with known activity in DSRCT are very similar to those active in Ewing's Sarcoma (EWS). Both tumors share an EWS fusion protein and may also share molecular mechanisms that facilitate proliferation and survival pathways. This essay aims to explore the current management strategies for DSRCT and highlight recent advancements in treatment approaches.

Current Treatment Protocols

Alkylating agents such as cyclophosphamide and ifosfamide are important components of therapy. A well-recognized treatment schema has been reported by Kushner et al., who described results in 12 DSRCT patients. This intensive alkylator-based therapy used cyclophosphamide, doxorubicin, and 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, and for those achieving complete response, the median follow-up 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 (Kushner et al., 2005).

Alternative Treatment Strategies

An alternative, more tolerable outpatient regimen has more recently been used for DSRCT, as documented in a case report. 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 and temozolomide monthly for two cycles and then abdominal radiation of 30 Gy with simultaneous temozolomide. A total of 12 cycles of irinotecan and temozolomide were given, providing a disease-free interval of nearly two years. This regimen allowed for routine school attendance and play activities, offering an excellent quality of life (Hayes-Jordan et al., 2009).

The Role of Aggressive Surgery

Aggressive cytoreductive surgery is currently accepted to have a primary role in the achievement of prolonged survival of other malignancies involving the peritoneum. In DSRCT, La Quaglia and Brennan reported that three-year overall survival was 58% in patients with gross total resection compared to 0% in the non-resection cohort. Other therapeutic modalities, such as continuous hyperthermic peritoneal perfusion (CHPP), also called hyperthermic intraperitoneal chemotherapy (HIPEC), have been found to improve outcomes in carcinoma involving the peritoneum (La Quaglia & Brennan, 2005).

Recent Advancements and Clinical Trials

Recently, Hayes-Jordan and colleagues were the first to report on the combined use of cytoreductive surgery and HIPEC in two children with DSRCT. 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. Currently, a phase I trial is ongoing using HIPEC at MD Anderson Cancer Center. A more recent series reports a median three-year survival of 71% with HIPEC and 29% in those receiving chemotherapy and radiotherapy alone (Hayes-Jordan et al., 2009).

Conclusion

In conclusion, while the management of DSRCT remains challenging, recent advancements in multimodal therapies, including the use of HIPEC and aggressive surgical approaches, have shown promise in improving survival outcomes. Ongoing clinical trials and continued research are essential to further enhance treatment strategies and improve the quality of life for patients suffering from this aggressive tumor.

References

• Hayes-Jordan, A., Green, H. L., Lin, J., Anderson, P. M., & Herzog, C. E. (2009). Complete cytoreduction and HIPEC improves survival in patients with desmoplastic small round cell tumor. Journal of Pediatric Surgery, 44(1), 170-176.
• Kushner, B. H., LaQuaglia, M. P., Wollner, N., Meyers, P. A., Lindsley, K. L., Ghavimi, F., & Cheung, N. K. (2005). Desmoplastic small round-cell tumor: Prolonged progression-free survival with aggressive multimodality therapy. Journal of Clinical Oncology, 23(25), 6202-6208.
• La Quaglia, M. P., & Brennan, M. F. (2005). The clinical approach to desmoplastic small round cell tumor. Journal of Surgical Oncology, 91(3), 151-161.