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© 2002 American Society for Clinical Oncology
Adjuvant Radiation for Stage IIB Soft Tissue Sarcoma of the ExtremityIndiana University School of Medicine, Indianapolis, IN To the Editor:Local control of extremity soft tissue sarcomas, regardless of local stage or grade, can only be achieved if both gross disease and infiltrating microscopic extension are effectively eliminated. Clinicians have known for decades that compartmental resections, although morbid, can effectively eradicate these two components of local disease. Clinicians have also known that marginal resections (simple excisions) are highly prone to local recurrence from failure to remove microscopic tumor infiltration. The historical work of Suit et al1 demonstrated that compartmental (or near compartmental) radiotherapy can substitute for large resections as a treatment for microscopic extension, effectively allowing limb salvage for extremity sarcomas. Still, there must exist a continuum from low risk of local recurrence to high risk depending on the actual length of the microscopically infiltrating tentacles as compared with the margins of resection, at some point eliminating the need for adjuvant radiotherapy or further resection altogether. The dilemma faced by clinicians who evaluate these patients postoperatively relates to quantifying this risk in a particular patient. In the retrospective study by Alektiar et al,2 from Memorial Sloan-Kettering Cancer Center, some of their patients received adjuvant radiotherapy for stage IIB extremity soft tissue sarcomas and some did not. As is typical for retrospective studies, no consistent explanation could be offered as to the basis for deciding who did and did not receive the adjuvant radiotherapy. Furthermore, the basic information about the actual margins of resection around tumor infiltration was not specifically presented. Previous articles from Memorial Sloan-Kettering describing their radiotherapy technique indicate that their extent of radiotherapy treatment volume is considerably less than used at other prominent institutions.3 In their recent article, Alektiar et al2 conclude that if the surgical resection affords at least 1 mm margin in all directions beyond microscopic tumor, then local control is approximately 80% and not enhanced by adjuvant radiotherapy. This conclusion is in direct conflict with the most recent prospective randomized data from the National Cancer Institute where patients treated with surgery alone for high-grade lesions had approximately the same recurrence rate observed in the Memorial Sloan-Kettering experience, while local recurrence was effectively eliminated with the addition of radiotherapy.4 This discrepancy between prospective and retrospective data should prompt consideration of another explanation apart from the conclusions drawn by the Memorial group. Perhaps the lack of benefit seen in the Memorial experience is more related to shortcomings of their particular radiotherapy technique. Indeed, the typically smaller volumes irradiated at Memorial through predominantly brachytherapy techniques have never been prospectively validated as being equivalent to more encompassing external-beam fields used at most institutions for controlling microscopic tumor extension. Local control approaching 100% should be a primary goal in all treatment strategies for localized soft tissue sarcomas. Limb sparing surgery combined with external-beam radiotherapy has been shown to achieve this goal in prospective reports. It is probably true that some patients with stage IIB extremity sarcomas do not benefit from adjuvant radiotherapy. Unfortunately, the article by Alektiar et al2 did not help us clearly identify these potentially over-treated patients, and their recommendations may actually lead to under-treatment in this population. REFERENCES
1. Suit HD, Mankin HJ, Wood WC, et al: Treatment of the patient with stage M0 soft tissue sarcoma. J Clin Oncol 6: 854-862, 1988
2. Alektiar KM, Leung D, Zelefsky MJ, et al: Adjuvant radiation for stage II-B soft tissue sarcoma of the extremity. J Clin Oncol 20: 1643-1650, 2002
3. Brennan MF, Hilaris B, Shiu MH, et al: Local recurrence in adult soft tissue sarcoma: A randomized trial of brachytherapy. Arch Surg 122: 1289-1293, 1987
4. Yang JC, Chang AE, Baker AR, et al: Randomized prospective study of the benefit of adjuvant radiation therapy in the treatment of soft tissue sarcomas of the extremity. J Clin Oncol 16: 197-203, 1998
ResponseMemorial Sloan-Kettering Cancer Center, New York, NY In Reply:We would like to thank Dr Timmerman for his interest in our article. He made some interesting remarks to which we would like to respond. First, the randomized trial by Yang et al1 did show a 100% local control for high-grade sarcomas, something that everyone would like to duplicate. But the fact is that almost all other reports in the literature, especially those addressing patients with stage II-B disease,2,3 have reported similar local control rates to ours.4 More importantly, in the same trial,1 patients with low-grade sarcomas did not have 100% local control and, in a prior trial from the same institution using the same radiation techniques, showed a somewhat lower local control rate for patients with high-grade sarcomas.5 Second, with regard to the influence of brachytherapy on local control, we clearly stated throughout the article the lack of difference in local control and the type of radiation used ie, brachytherapy versus external-beam radiation. Furthermore, the benefit of adjuvant brachytherapy for patients with high-grade sarcomas has been demonstrated in a prospective randomized trial.6 Third, we were able to identify a subset of patients with central location (axilla or groin) who need further improvements in their multimodality treatment. And finally, we stated that the only way to answer the question of whether adjuvant radiation is needed in this subset of patients would be through a prospective randomized trial. We believe, however, that data such as ours is needed first to determine whether such a question could be answered. REFERENCES
1. Yang J, Chang A, Baker A, et al: Randomized prospective study of the benefit of adjuvant radiation therapy in the treatment of soft tissue sarcomas of the extremity. J Clin Oncol 16: 197-203, 1998
2. Fleming J, Berman R, Cheng S, et al: Long-term outcome of patients with American Joint Committee on Cancer stage IIB extremity soft tissue sarcomas. J Clin Oncol 17: 2772-2780, 1999 3. Cheng E, Dusenbery K, Winters M, et al: Soft tissue sarcomas: Preoperative versus postoperative radiotherapy. J Surg Oncol 61: 90-99, 1996[CrossRef][Medline]
4. Alektiar K, Leung D, Zelefsky , et al: Adjuvant radiation for stage II-B soft tissue sarcoma of the extremity. J Clin Oncol 20: 1643-1650, 2002 5. Rosenberg S, Tepper J, Galtstein E, et al: The treatment of soft-tissue sarcoma of the extremities: Prospective randomized evaluations of (1) limb-sparing surgery plus radiation therapy compared with amputation and (2) the role of adjuvant chemotherapy. Ann Surg 196: 305-315, 1982[Medline]
6. Pisters PW, Harrison LB, Leung DH, et al: Long-term results of a prospective randomized trial of adjuvant brachytherapy in soft tissue sarcoma. J Clin Oncol 14: 859-868, 1996
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Copyright © 2002 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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