The Use of Radiation Therapy in the Management of Selected Patients with Atypical Lipomas

Background and Objectives. Atypical lipomas are uncommon, slow-growing benign tumors. While surgery has been the primary treatment modality, we have managed some patients with radiation (RT) as a component of the treatment and have reported their outcomes in this study. Methods. A retrospective review of all cases of extremity and trunk atypical lipomas in The Sarcoma Database at the study institution was conducted. Results. Thirteen patients were identified. All patients underwent surgical resection at initial presentation and received pre- or postoperative radiation for subtotal resection (n = 2), local recurrence (n = 8), or progressive disease (n = 3). The median total radiation dose was 50 Gy. Median followup was 65.1 months. All patients treated with RT remained free of disease at the last followup. No grade 3 or higher late toxicity from radiation was observed. No cases of tumor dedifferentiation occurred. Conclusion. For recurrent or residual atypical lipomas, a combination of reexcision and RT can provide long-term local control with acceptable morbidity. For recurrent tumors, pre-op RT of 50 Gy appears to be an effective and well-tolerated management approach.

e role and utility of preoperative or adjuvant radiation in management of these lesions is not well known. We have managed some patients with recurrent or subtotally resected tumors with radiation as a component of the treatment. In this study, we review the outcomes of thirteen patients with atypical lipoma treated with radiation therapy (RT) at the Massachusetts General Hospital during the years of 1995-2010.

Methods
A retrospective review of all cases of atypical lipoma treated with radiation at the Massachusetts General Hospital was conducted. Patients were excluded if RT was completed aer January 2010. irteen consecutively treated patients were identi�ed, initially diagnosed between 1987 and 2007. Median age at diagnosis was 54 (range: 36-76 years).
With the exception of one chest wall lesion, all lesions were located in the upper ( ) or lower ( ) extremity. Of the lower extremity lesions, seven were in the thigh and one was in the calf. Of the upper extremity lesions, two were in the forearm, one in the deltoid, and one in the proximal arm.
Details of each patient and treatment are shown in Table 1. Tumors were diagnosed based on reported histologic features aer pathology review at Massachusetts General Hospital. Toxicity was graded based on Common Terminology Criteria for Adverse Events v4.0 (CTCAE).
Gross total resection (GTR) was de�ned as tumor resected with negative margins. Subtotal resection (STR) was de�ned as gross residual disease. Local recurrence was de�ned as regrowth of tumor aer a gross total resection. Progressive disease was de�ned as growth of residual tumor aer STR.
All the patients underwent surgical resection at initial presentation, either GTR ( ), STR ( ), or extent of resection unknown ( ). Of patients with GTR, local recurrence was identi�ed at a mean of 58.5 months (range, 20.0-133.8 months) following resection. e locally recurrent tumor was treated with either preoperative RT (50 Gy in 2 Gy fractions) and GTR ( ), or resection followed by postoperative RT (50-66 Gy in 2 Gy fractions) ( ). Of the group of four patients with STR, two were monitored clinically and treated aer evidence of disease progression, and the remaining two were treated adjuvantly with radiation for the following reasons. e �rst adjuvantly treated patient had atypical lipoma of the chest wall, and underwent tumor excision at an outside institution with gross residual disease. He presented with limb paresthesias prior to resection. He was recommended radiation followed by reexcision over observation due to his symptoms, and also because it was felt that a local recurrence would be difficult to resect given the tumor location. He received 50 Gy in 2 Gy fractions, followed by gross total excision of residual tumor. A second adjuvantly treated patient had subtotal excision of tumor that was overlying the sciatic nerve. Adjuvant radiation to 60 Gy in 30 fractions was administered due to concern of residual disease le within the region of the sciatic nerve. e remaining two patients, who were monitored clinically aer STR, ultimately required RT with ( ) or without excision ( ) for progressive disease. e �rst patient in this group had a subtotal excision of atypical lipoma arising from the thigh, with postoperative scans revealing slow growth of residual tumor. e patient opted for reresection, 58.1 months aer initial resection. is was followed by adjuvant radiation to 61.2 Gy in 34 fractions. e other patient underwent initial subtotal resection of an anterior compartment tumor of the leg, and surgery was not recommended due to potential functional morbidity (foot drop). He ultimately received radiation to 70 Gy in 2 Gy fractions to residual tumor, measuring 18.2 × 6.5 × 3.4 cm in size. is was delivered with a combination of photons and protons, 46.3 months aer initial resection, due to slow increase in size. Posttreatment scans showed no further tumor growth.
ree patients had surgery with extent of initial resection unknown. One patient received excision, chemotherapy, and reexcision (all delivered in Greece; details of surgical extent and chemotherapy are unknown), followed by local recurrence aer 27.4 months, which was treated with preoperative RT and excision. e second patient underwent two excisions in a span of 12 years, followed by local recurrence 10.3 years aer last resection, also treated with preoperative RT and excision. e third patient underwent three excisions within a span of �ve years, followed by local recurrence 5 years aer last resection, and was managed with excision and brachytherapy with RT delivered �ve days postoperatively with low-dose rate Ir-192 brachytherapy to a dose of 60 Gy prescribed to 5 mm from the plane of the implant.

Results
Median followup from time of last radiation treatment was 65.1 months (range, 3.7-196.0 months; average 73.1 months). Local tumor control was achieved in all 13 patients treated with radiation. ere were no cases of metastatic disease or tumor dedifferentiation on followup. Summary of treatment is shown in Table 2.
One patient, who received preoperative RT (50 Gy in 2 Gy fractions), developed a postoperative wound infection, requiring hospitalization and administration of IV antibiotics two months aer surgery. She recovered fully.
No cases of grade 3 or higher late toxicity from radiation were observed. ere were two patients who developed grade 1 lower extremity edema in the treated limb. is includes the patient with grade 3 infection, as detailed above, and a patient who received resection and postoperative RT aer initial gross total resection. One patient developed grade 1 telangiectasias; this patient had received brachytherapy to 60 Gy. Another patient, who was treated at initial presentation with subtotal excision followed by adjuvant RT (60 Gy in 2 Gy fractions), developed grade 2 sciatic neuropathy, requiring narcotics for pain control. Of note, she had tumor overlying the sciatic nerve at presentation.

Discussion
Atypical lipomas are well-differentiated, slow-growing tumors that typically occur in the trunk and extremities and have a long natural history. Although surgery is the primary treatment modality, the likelihood of local recurrence is considered to be signi�cant. It is di�cult to estimate the true rates of local failure from published series due to the small number of patients and heterogeneity in tumor classi�cation, but reported rates range from 8-52% (Table 3) [1, 3, 5-10, 12, 14, 15]. Rates of tumor dedifferentiation range from 0 to 13% in published reports [3-6, 8-10, 13-15].
No cases of tumor dedifferentiation occurred in this present series. Subclassi�cation of atypical lipomas has been explored by several series in an effort to identify factors associated with local recurrence; however, due to small sample sizes, results have been inconclusive. One report by Kooby et al. [3] reviewed 91 lipomatous tumors and identi�ed sclerosing histology to be associated with higher likelihood of local failure. A positive margin was also identi�ed to be associated with increased failures, suggesting these subsets of patients should receive reexcision and consideration of adjuvant treatment.
Standard management of local recurrence is reexcision. However, RT may have a role in providing long-term local control, particularly in areas where wide margins are challenging to achieve. To our knowledge, to date, there has not been any literature focusing on the use of RT in management of recurrent or incompletely resected atypical lipoma.
In this paper, eleven patients were treated for recurrent disease. All patients initially received surgical resection as primary treatment, with average time to recurrence of 63.2 months. Of this group, ten received a combination of RT and surgery and one received RT alone. At median followup of 48.7 months, all patients remained free of disease, demonstrating that long-term control can be achieved with the addition of RT.
Two patients received adjuvant RT at initial presentation due to gross residual disease. At last followup (of 196.0 and 81.0 months, resp.), the patients remained free of recurrent disease, suggesting that long-term local control can be achieved with RT even in the setting of residual tumor. Sarcoma 5 e potential long-term morbidity of RT and surgery is important to consider when devising a management strategy. One patient, who received 60 Gy of adjuvant radiation following subtotal resection, developed late grade 2 sciatic neuropathy. Preoperative RT is typically delivered to a lower dose, typically 50 Gy, and carries less risk of late �brosis [16] with long-term control equivalent to postoperative RT. Of patients with recurrent atypical lipomas, 6 received preoperative RT followed by gross tumor resection, and 3 underwent surgery followed by adjuvant RT. No grade 3 or higher late toxicity from radiation was observed, and all patients had control of their tumors.
In conclusion, atypical lipomas are slow-growing tumors with a propensity to recur locally; thus, long-term followup is recommended. RT can provide durable local control for patient and is recommended for patients at especially high risk of recurrence, due to multiply recurrent disease or residual gross tumor. For recurrent tumors, our results suggest a combination of reexcision and RT can provide longterm local control with acceptable morbidity. In the setting of gross residual disease, adjuvant RT can be considered to prevent local progression.