Role of Radiation Therapy in Retroperitoneal Sarcomas

Soft-tissue sarcomas arising from the retroperitoneum are raretumors, and their successful treatment is problematic. This groupof tumors tends to be large at presentation, and they exist ina body cavity with few fascial planes to contain them. They frequentlyabut vital organs or major blood vessels, which further complicatestheir complete removal.

Surgical resection with clear margins is the only curative treatmentfor retroperitoneal sarcomas. Although complete gross tumor excisioncan be performed in up to 79% to 96% of patients, as noted intwo recent series, clear margins can be obtained in only 63% ofpatients who have all gross tumor removed.[1,2] Local failurerates 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 rangefrom 20% to 60%. In most series, survival has been correlatedwith tumor grade and the ability to perform a resection with clearmargins

The high local failure rate coupled with the poor overall survivalfor retroperitoneal sarcomas has led clinicians, over the last20 years, to search for effective adjuvant treatment regimens.Much has been written about adjuvant therapy for soft-tissue sarcomaof the retroperitoneum, but the literature on this subject isdifficult to interpret. This is due primarily to the rarity ofthe tumor, the difficulty in collecting prospective data, andthe inability to account for multiple variables in a particularstudy.

Most of the studies that have been reported in the literatureare small, from single institutions, and are retrospective. Thepatients receiving adjuvant therapies in these studies are a mixedgroup, with varying amounts of residual microscopic or macroscopicdisease. Some patients had primary tumors, while others had recurrentdisease. Many series included patients who were treated with combinationsof surgery, external-beam radiation, intraoperative radiation,brachytherapy, and various chemotherapy regimens.

Adjuvant Radiation Therapy

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

At this time, the role of radiation therapy in the treatment ofsoft-tissue sarcoma arising from the retroperitoneum has yet tobe defined. There is evidence to suggest that individual patientswith less than ideal surgical margins will experience less localrecurrence if they are treated with radiation therapy.[4] Thiseffect is thought to be dose-dependent, with the best local controlrates reported from institutions that employ intraoperative boostradiation in the form of intraoperative radiation therapy or brachytherapy.[5]However, any benefit afforded by radiation therapy has to be weighedagainst the potential significant morbidity that can follow acourse of radiation to the retroperitoneum, especially if dosesmore than 5,500 cGy are to be employed, as suggested by Fein etal.[6] Kinsella et al showed a more than 60% incidence of enteritisusing external-beam radiation and a similar incidence of peripheralneuropathy using intraoperative radiation therapy.[7]

Strategies to Reduce the Complications of Radiation

In their article, Drs. Clark and Tepper address these potentialcomplications by advocating the use of preoperative radiationin the treatment of retroperitoneal sarcoma. The potential benefitsof preoperative therapy, as they correctly indicate, include smallertreatment fields, protection of adjacent organs that are displacedby in-situ tumor acting as a "tissue expander," and,perhaps, a better chance of achieving clear surgical margins dueto tumor shrinkage.

Other strategies can be used to prevent postoperative radiation-associatedcomplications. These include the use of tissue expanders to displacebowel out of the radiation field at the time of resection; theuse of a new adhesion prevention film (Seprafilm), coupled withcareful positioning of patients during radiation therapy; andthe use of an absorbable small bowel sling to exclude the intestinefrom the radiation field. The advantage of postoperative treatmentis that it delivers radiation to limited fields, ie, it treatsonly those areas thought to be at high risk for recurrence. Thesehigh-risk areas can be marked with titanium clips at the timeof surgery.

Approach to Radiation Therapy at Fox Chase Cancer Center

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

References:

1. Karakousis CP, Gerstenbluth R, Kontzoglou K, et al: Retroperitonealsarcomas 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 theretroperitoneum, in Shui MH, Brennan MF: Management of Soft TissueSarcoma, pp 157-159. Philadelphia, Lea & Febiger, 1994.

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

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

6. Fein DA, Corn BW, Lanciano RM, et al: Management of retroperitonealsarcomas: 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 resultsof a randomized study of adjuvant radiation therapy in resectableadult retroperitoneal soft tissue sarcomas. J Clin Oncol 6:18-25,1988.