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Role of Radiation Therapy in Retroperitoneal Sarcomas

Role of Radiation Therapy in Retroperitoneal Sarcomas

Soft-tissue sarcomas arising from the retroperitoneum are rare tumors, and their successful treatment is problematic. This group of tumors tends to be large at presentation, and they exist in a body cavity with few fascial planes to contain them. They frequently abut vital organs or major blood vessels, which further complicates their complete removal.

Surgical resection with clear margins is the only curative treatment for retroperitoneal sarcomas. Although complete gross tumor excision can be performed in up to 79% to 96% of patients, as noted in two recent series, clear margins can be obtained in only 63% of patients who have all gross tumor removed.[1,2] Local failure rates are quite high, varying between 50% and 70% at 5-year follow-up.[3] These high local recurrence rates are inclusive of all tumor grades. Furthermore, overall 5-year survival rates in various series range from 20% to 60%. In most series, survival has been correlated with tumor grade and the ability to perform a resection with clear margins

The high local failure rate coupled with the poor overall survival for retroperitoneal sarcomas has led clinicians, over the last 20 years, to search for effective adjuvant treatment regimens. Much has been written about adjuvant therapy for soft-tissue sarcoma of the retroperitoneum, but the literature on this subject is difficult to interpret. This is due primarily to the rarity of the tumor, the difficulty in collecting prospective data, and the inability to account for multiple variables in a particular study.

Most of the studies that have been reported in the literature are small, from single institutions, and are retrospective. The patients receiving adjuvant therapies in these studies are a mixed group, with varying amounts of residual microscopic or macroscopic disease. Some patients had primary tumors, while others had recurrent disease. Many series included patients who were treated with combinations of surgery, external-beam radiation, intraoperative radiation, brachytherapy, and various chemotherapy regimens.

Adjuvant Radiation Therapy

The article by Drs. Clark and Tepper presents a concise overview of the rationale for neoadjuvant radiation therapy in the treatment of retroperitoneal sarcomas. Their basis for advocating combined therapy is derived from the literature on extremity sarcomas. However, extrapolating from extremity sarcomas to retroperitoneal sarcomas may not be valid for several reasons: (1) Sarcomas of the extremity are often more amenable to complete surgical extirpation; and (2) adjuvant radiation doses to the involved extremity (which can exceed 6,000 cGy with shrinking fields) are not limited by the radiation tolerance of the small intestine. To date, no prospective randomized trial has confirmed the benefit of surgery plus radiation therapy over surgery alone in the treatment of retroperitoneal sarcomas.

At this time, the role of radiation therapy in the treatment of soft-tissue sarcoma arising from the retroperitoneum has yet to be defined. There is evidence to suggest that individual patients with less than ideal surgical margins will experience less local recurrence if they are treated with radiation therapy.[4] This effect is thought to be dose-dependent, with the best local control rates reported from institutions that employ intraoperative boost radiation in the form of intraoperative radiation therapy or brachytherapy.[5] However, any benefit afforded by radiation therapy has to be weighed against the potential significant morbidity that can follow a course of radiation to the retroperitoneum, especially if doses more than 5,500 cGy are to be employed, as suggested by Fein et al.[6] Kinsella et al showed a more than 60% incidence of enteritis using external-beam radiation and a similar incidence of peripheral neuropathy using intraoperative radiation therapy.[7]

Strategies to Reduce the Complications of Radiation

In their article, Drs. Clark and Tepper address these potential complications by advocating the use of preoperative radiation in the treatment of retroperitoneal sarcoma. The potential benefits of preoperative therapy, as they correctly indicate, include smaller treatment fields, protection of adjacent organs that are displaced by in-situ tumor acting as a "tissue expander," and, perhaps, a better chance of achieving clear surgical margins due to tumor shrinkage.

Other strategies can be used to prevent postoperative radiation-associated complications. These include the use of tissue expanders to displace bowel out of the radiation field at the time of resection; the use of a new adhesion prevention film (Seprafilm), coupled with careful positioning of patients during radiation therapy; and the use of an absorbable small bowel sling to exclude the intestine from the radiation field. The advantage of postoperative treatment is that it delivers radiation to limited fields, ie, it treats only those areas thought to be at high risk for recurrence. These high-risk areas can be marked with titanium clips at the time of surgery.

Approach to Radiation Therapy at Fox Chase Cancer Center

Realizing the lack of data confirming the efficacy of combined surgery and radiation in the local control of soft-tissue sarcoma, it is our policy at Fox Chase Cancer Center to treat patients with minimal residual gross disease or positive postoperative margins with radiation therapy. In general, this is postoperative management employing some method to exclude the small intestine from the radiation field. Preoperative radiation is utilized in patients with large (more than 15 cm) or marginally resectable tumors. However, it has been our experience that because of the symptoms created by these patients' bulky tumors (poor appetite, partial small bowel obstruction, and so on), it is difficult for them to complete a 4- to 6-week course of preoperative radiation therapy.

References

1. Karakousis CP, Gerstenbluth R, Kontzoglou K, et al: Retroperitoneal sarcomas and their management. Arch Surg 130:1104-1109, 1995.

2. Kilkenny JW, Bland KI, Copeland EM: Retroperitoneal sarcoma: The University of Florida experience. J Am Coll Surg 182:329-339, 1996.

3. Jaques DP, Coit DG, Brennan MF: Soft tissue sarcoma of the retroperitoneum, in Shui MH, Brennan MF: Management of Soft Tissue Sarcoma, pp 157-159. Philadelphia, Lea & Febiger, 1994.

4. Tepper JE, Suit HD, Wood WC, et al: Radiation therapy of retroperitoneal soft tissue sarcomas. Int J Radiat Oncol Biol Phys 10:825-830, 1984.

5. Sindelar WF, Kinsella TJ, Chen PW, et al: Intraoperative radiotherapy in retroperitoneal sarcomas. Arch Surg 128:402-410, 1993.

6. Fein DA, Corn BW, Lanciano RM, et al: Management of retroperitoneal sarcomas: Does dose escalation impact on locoregional control? Int J Radiat Oncol Biol Phys 31:129-134, 1995.

7. Kinsella TJ, Sindelar WF, Lack E, et al: Preliminary results of a randomized study of adjuvant radiation therapy in resectable adult retroperitoneal soft tissue sarcomas. J Clin Oncol 6:18-25, 1988.

 
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