Radiation-Induced Soft-Tissue Fibrosarcoma: Surgical Therapy and Salvage

Radiation-Induced Soft-Tissue Fibrosarcoma: Surgical Therapy and Salvage M. B. O Neil, Jr., M.D., William Cocke, M.D., Duncan Mason, M.D., and Edward J. Hurley, M.D. ABSTRACT Soft-tissue fibrosarcomas of the chest wall that occur after radiation for breast carcinoma are rare and usually lethal. The histories of the previously reported patients emphasize the dismal prognosis for untreated patients and suggest that surgical intervention offers the only hope of reasonable palliation. We report another patient, now alive and free from disease 3% years after radical resection. The cases of these patients are reviewed, with emphasis on the clinical presentation, the difficulty of making the diagnosis, and the significant palliation that may be achieved with radical chest wall resection. Soft-tissue fibrosarcomas of the chest wall occurring after radiation for carcinoma of the breast are rare and usually are lethal. The previously published reports on patients emphasize the dismal prognosis for untreated patients, with few 1-year survivors. Surgical intervention offers the only hope of reasonable palliation [l-81. Among the 4 patients reported in the English-language literature who did not receive operative, there was only a single 1-year survivor, while among the 6 treated surgically, all survived at least a year. We present the eleventh case of this disorder. The patient is now alive and free from disease, 3% years after radical resection of a radiationinduced soft-tissue fibrosarcoma of the chest wall. The salient features of these cases are discussed and the clinical presentation, the difficulty of reaching the diagnosis, and the significant relief that may be achieved with radical chest wall resection are emphasized. From the Divisions of Thoracic and Plastic Surgery, University of California, Davis, Medical Center, Sacramento, CA. Accepted for publication June 15, 1981. Address reprint requests to Dr. Hurley, Division of Thorlcic Surgery, University Medical Center, 4301 X Street, Room 213, Sacramento, CA 95817. A 39-year-old woman was admitted to the University of California, Davis, Medical Center on August 18, 1977, with a biopsy-proved fibrosarcoma of the chest wall in a previously irradiated radical mastectomy site. In September, 1966, years prior to admission, she had undergone a standard left radical mastectomy for a carcinoma of the breast that was metastatic to eight of fifteen axillary lymph nodes. One week following mastectomy, she underwent a prophylactic bilateral oophorectomy. Postoperatively, she received irradiation to the left anterior chest wall and axillary, supraclavicular, and parasternal areas. Three superficial skin doses of 4,005,1,016, and 1,016 rads were delivered with a 0-kv source to the skin of the upper anterior chest, left axilla, and sternum, respectively. In addition, she received cobalt 60 irradiation consisting of 4,005 rads to the internal mammary and supraclavicular areas and 3,996 rads to the left anterior chest wall. In May, 1977, she complained of constant, dull sternal pain that had lasted 3 months. A bone scan showed a lesion in the sternum at the sternomanubrial junction. An incisional biopsy of a soft-tissue mass overlying this area showed benign fibrosis, consistent with previous irradiation. Physical examination revealed a well-healed mastectomy scar with postirradiation changes of the skin. There was a healed biopsy incision 2 cm long over the area of the sternomanubrial joint. She had a poorly circumscribed, painful subcutaneous mass, measuring 9 X 6 cm, over the right border of the sternum. Laboratory data included a white blood cell count of 6,900 per mm3, a hemoglobin of.9 gm per 0 ml, and an alkaline phosphatase of 80 U per liter (range, 25 to 90). Chest roentgenograms showed clear lung fields and a discrete lesion of the manubrium, thought to be the callus of a healing fracture. There was a notable soft-tissue density located 1 to 2 cm below 624 0003-497518260624-05$01.25 @ 1981 by The Society of Thoracic Surgeons

625 Case Report: ONeil et al: Radiation-induced Fibrosarcoma Fig 1. The specimen consisting of the sternum, overlying skin, and soft tissue, the heads of both clavicles, and rib tips of ribs one through seven just prior to removal. The patient's head is to the right. Fig 3. Closure of the defect with a full-thickness skin flap created from the patient's right breast and right lateral chest wall tissues. Fig 2. The resulting 18 X 18 cm defect with underlying lungs and mediastinum visible. Patient's head is to the right. the sternomanubrial junction, without underlying sternal changes. These changes were not present in the chest roentgenogram made in January, 1975. A bone scan revealed increased uptake in the sternum, manubrium, and anterior first rib ends bilaterally. The lower sternal uptake had increased compared with the scan in March, 1977. In June, 1977, repeat biopsy of the soft tissue mass revealed a fibrosarcoma. Tomograms of the lung revealed no metastatic pulmonary lesions. In August, 1977, the patient underwent a radical anterior chest wall resection, including the entire sternum, overlying skin, and soft tissue, the heads of both clavicles with sternoclavicular joints, the costal cartilages, and rib tips of ribs one through seven (Fig 1). The resulting chest wall defect (Fig 2), measuring 18 x 18 cm, was closed with Marlex mesh, and covered with a full-thickness skin flap created from the right breast and right lateral chest wall tissues. The flap donor site was covered with a split-thickness skin graft. The patient required mechanical ventilation for five days; thereafter, her convalescence was rapid and she was discharged. Three and one-half years after the operation, she remains clinically free from disease, with normal chest roentgenograms, bone scans, and liver function tests (Fig 3). Pathological Findings Slides of the original breast tumor removed in 1966 were reviewed, and they revealed an infiltrating ductal carcinoma with apparent lymphatic and venous invasion. Eight of fifteen nodes showed metastatic tumor.

626 The Annals of Thoracic Surgery Vol 33 6 June 1982 The operative specimen from the resection of the chest wall fibrosarcoma consisted of skin, subcutaneous tissue, the entire sternum with attached medial portion of eight ribs, and the clavicular heads. The diameter of the overall specimen was 17 cm. There was a 6.5 cm discshaped mass located centrally over the sternum, with a second 1 cm nodule to the left of the sternum. On section, this large, central subcutaneous nodule seemed to consist of a large, solid, irregular but well-circumscribed mass that was fixed to the overlying skin and that replaced all the underlying tissue down to the parietal pleura. The mass appeared to extend grossly through the underlying third rib. The tumor itself extended from the deep dermis through the subcutaneous tissue and underlying sternum to within 1 mm of the serosal surface of the anterior chest wall. The mass had a variable microscopic appearance, ranging from a dense, acellular central collagenous portion to peripheral areas composed of an infiltrating, malignant spindle-cell tumor. The tumor had the appearance of a poorly differentiated fibrosarcoma with sheets of large, haphazardly arranged spindle cells with dense fusiform, sometimes grotesque nuclei and prominent occasional nucleoli. The cytoplasm was indistinct and eosinophilic, in general. Mitotic activity in most cellular areas ranged from 3 to 6 per high-power field. In other areas the tumor cells were smaller, more uniform, and separated by more collagen, and appeared to be arranged in bundles or a herringbone pattern. Mitotic activity was less frequent in these areas. The tumor extended to the right and left internal mammary vessels but did not appear to invade them. A single internal mammary node was free from malignancy. neoplastic elements were seen at the margins of the excision. Comment Radiation-induced malignancies have been known since the reports of Frieben [l] in 1902 and Perthes [2] in 1904. Epidermoid carcinoma is the most common. It was not until 1922 that Beck [l] described a radiation-induced sarcoma. Since then, more than 200 reports of radiation-induced sarcoma have been published, with cases of osteogenic sarcoma pre- dominating. In 1968, Schwartz and Rothstein [51 reported the case of a patient with a softtissue fibrosarcoma occurring after postoperative chest wall irradiation for carcinoma of the breast. Since then, 9 others have been reported in the English-language literature. Data on these patients are summarized in the Table. The appearance of a new tumor mass at the site of a previously resected malignancy suggests recurrence and may delay the diagnosis of radiation-induced tumor. Valuable time is lost while the patient undergoes further radiation to control the "local" recurrence. In addition, biopsy of the lesion may further delay initiation of treatment, since radiation-induced changes may lead to an erroneous diagnosis of radiation-induced fibrosis. This was the initial impression in our patient as well as the patient of Oberman and Oneal [4]. Clinically suspicious lesions mandate repeated biopsies despite benign pathological diagnosis. Multiple recurrent excisions were necessary to make the diagnosis in 5 of the patients whose cases have been reported. The criteria for the diagnosis of radiationinduced malignancy are specific and consist of three elements. First, the lesion must be localized in a previously irradiated area. Second, there must be a clear histological difference between the treated lesion and the current lesion. Third, there must be a latent interval between the radiation and the appearance of the lesion. These criteria were met by our patient and by the previously reported patients. The latency interval was years in our patient, and ranged from 3 to 19 years in the other patients. The clinical course of untreated lesions is short. Four of the patients previously reported did not have operative either because the patient declined or the lesion was considered unresectable. Three died within a year of local invasion and metastatic spread of the fibrosarcoma. One patient survived 4 years with a necrotic scapular lesion involving the upper chest wall and arm. In contrast, of the 6 patients treated operatively, there is no follow-up on 1, 1 is alive after 2 years with disease, 3 survived for 1 to 2 years before dying of widespread metastatic fibrosarcoma, and

627 Case Report: ONeil et al: Radiation-induced Fibrosarcoma Pertinent Data on Patients with Radiation-induced Soft-Tissue Fibrosarcoma Latency Patient Period Delay in Radical Treatment. Author Clinical Course (years) Diagnosis Surgery Course Outcome 1 2 3 4 5 6 7 8 9 Schwartz and Rothstein [51 Gane et a1 [21 Oberman and Oneal [41 Senyszyn et al [6] Senyszyn et al [6] Hatfield and Schulz [3] Hatfield and Schulz [31 Adam and Rief [l] Friedman et a1 [7] Iwasaki et al [8] ONeil et al [present report] 1952 Breast carcinoma; radiation 2/67 Fibrosarcoma of chest wall Breast carcinoma; radiation 2/59 Breast carcinoma; radiation 4/63 Excisional biopsy of chest wall nodulenegative 9/63 Reexcision of recurrent chest wall lesionfibrosarcoma 1/58 Breast carcinoma; radiation /64 Fibrosarcoma of chest wall 2/44 Breast carcinoma; radiation 1963 Scapular lytic lesions 9/67 Biopsy: soft-tissue undifferentiated sarcoma 1945 Breast carcinoma; radiation 1955 Biopsy: fibrosarcoma adjacent to scapula 1958 Breast carcinoma; radiation 1968 Fibrosarcoma 5/61 Breast carcinoma; radiation 2/72 Lump chest wall 4/73 Shoulder metastasis 1964 Breast carcinoma; radiation 12/71 Mass in surgical scar 6/68 Breast carcinoma; radiation 4/72, 8/73 Three local excisions of fibrosarcoma 9/66 Breast carcinoma; radiation 6/77 Biopsy: Fibrosarcoma of parasternal mass 15 14 4 6 19 7 3 Interscapular thoracic amputation Pulmonary metastasis 6/65 Radical chest-wall excision 9/67 Palliative radiation 1968 Forequarter amputation 1970 Recurrent disease in stump 4/73 Interscapular thoracic amputation Multiple local wide excisions 6/73 Radical excision attempted of fibrosarcoma; dead in 6 months 8/77 Radical chest wall resection t reported 4-Month survival; 1-Year survival; (61'35) 2-Month survival; (65) 4-Year survival; (2/68) 8-Month survival; alive with disease (5175) 5-Year survival; no evidence of disease 3Y-Year survival; no evidence of disease (5/81)

628 The Annals of Thoracic Surgery Vol 33 6 June 1982 there is a 5-year survivor without evidence of disease. ne of the 6 patients survived less than a year. Our patient is alive without evidence of disease at 3% years. Clearly, operative prolongs life in these patients. Aggressive radical resection of the lesions appears to offer the best palliation and potential for cure. In the patient of Oberman and Oneal [4], local excision and biopsy were followed by recurrence in 8 months that required wide local excision, which in turn was followed by recurrence in 6 months, which was treated with wide chest wall resection. The patient died 19 months later of widespread metastatic fibrosarcoma. A similar course of events occurred in the patient of Friedman and colleagues [7] who underwent three local excisions before a radical resection was tried. It is tempting to speculate on the possible outcome in these patients had radical chest wall excision been performed at the first sign of disease. While the cases of these patients suggest the apparent ineffectiveness of limited resections, it should be noted that the single 5-year survivor without evidence of recurrent disease had multiple local wide excisions. It is interesting that none of the patients reported, including ours, had evidence of recurrent breast carcinoma. In these apparent cures of the breast carcinoma, an aggressive attack on a new primary tumor is indicated. Numerous reports in the surgical literature that demonstrate successful reconstruction of chest wall defects make it unnecessary for surgeons to be reluctant about the size of the defect created in wide radical excision. Our patient had excellent palliation of pain and functioned normally after wide excision of the anterior chest wall. Our patient and the patients previously reported demonstrate the salient features of radiation-induced soft-tissue sarcoma following postoperative radiation for breast carcinoma. All clinicians dealing with chest wall lesions or breast carcinoma must be aware of these lesions. Adequate palliation and the potential for cure depend on awareness of the lesion, early diagnosis, persistent repeat biopsies in suspicious cases, early aggressive radical excision without fear of the resultant defect, and adequate reconstruction. References 1. Adam YG, Rief R: Radiation-induced fibrosarcoma following treatment for breast cancer. Surgery 81:421, 1977 2. Gane NFC, Lindup R, Strickland P, Bennett MH: Radiation-induced fibrosarcoma. Br J Cancer 24:705, 1970 3. Hatfield PM, Schulz MD: Postirradiation sarcoma. Radiology 96:593, 1970 4. Oberman HA, Oneal RM: Fibrosarcoma of the chest wall following resection and irradiation of carcinoma of the breast. Am J Clin Pathol53:407, 1970 5. Schwartz EE, Rothstein JD: Fibrosarcoma following radiation. JAMA 203:134, 1968 6. Senyszyn JJ, Johnston AD, Jacox HW, Chu FCH: Radiation-induced sarcoma after treatment of breast cancer. Cancer 26:394, 1970 7. Friedman IH, Mori K, Kabakow B: Radiation-induced extraskeletal fibrosarcoma. NY State J Med 77: 1932, 1977 8. Iwasaki K, Nagamitsu S, Tsuneyoshi M: Postirradiation fibrosarcoma following radical mastectomy. Jpn J Surg 8:73, 1978