Fibrosarcoma

We report a case of cardiac fibrosarcoma that was treated with cardiac tumor resection, chemotherapy, cardiac explantation, tumor repeat resection, and autotransplantation followed by external beam irradiation. The patient was able to achieve clinical remission and remained disease free > 2 years after the initial diagnosis. This case report demonstrates that a sustained remission from cardiac sarcoma is possible with an aggressive combined modality approach.

Key words: adjuvant chemotherapy; cardiac autotransplantation. cardiac sarcoma; postoperative local radiotherapy; remission

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Cardiac sarcoma is a rare cancer. There is no standard approach to cardiac sarcomas, although as in other soft-tissue sarcomas it is initially treated with surgical excision. Unfortunately, surgical margins are rarely free of disease, making local recurrence likely. Due to the failure to achieve local control and the subsequent development of metastatic disease, the prognosis of cardiac sarcomas is poor, with a mean survival of 11 months after surgical resection. (1) The role of chemotherapy for regional disease has not been established, although it has been employed for tumors of large size, high grade, or for positive margins. Neoadjuvant chemotherapy has also been tried in order to achieve cytoreduction prior to surgical intervention or to limit the spread of tumor at the time of surgery. (2) The role of adjuvant chemotherapy following surgery to prevent the development of metastatic disease has not been established. Radiation therapy, although used in patients with positive margins after surgical resection, has been limited due to the risk of cardiac toxicity. (3) Another approach has been cardiac transplantation, which has been used in patients with end-stage heart failure and even as an intervention for unresectable metastatic cardiac tumors. (4,5) An alternative approach has included cardiac tumor resection via explantation and autotransplantation with the advantage of eliminating the need for immunosuppression.

We present a case of a young man with cardiac fibrosarcoma. This case discusses the approach to cardiac soft-tissue sarcoma and is remarkable in the sense that by employing multiple therapeutic strategies, a prolonged remission was achieved. The various strategies included chemotherapy, surgical resection, radiation therapy, and cardiac autotransplantation.

CASE REPORT

The patient was a 21-year-old Haitian man with no medical history. He presented to a community hospital with complaints of a dull substernal chest pain accompanied by 3 weeks of progressive shortness of breath. One episode of hemoptysis had occurred. The initial physical examination was unremarkable except for a grade 3/6 systolic murmur at the left sternal border. The hospital admission chest radiograph revealed cardiomegaly and congestion. Two-dimensional echocardiography was done, revealing a 5 x 6-cm left atrial mass that was subsequently confirmed by transesophageal echocardiography.

The patient was subsequently transferred to our hospital for diagnostic resection of the cardiac tumor. Intraoperatively, the tumor was noted to be fixed to the roof of the atrium and to tissue between the left and right pulmonary veins.

The mass prolapsed across the mitral valve, resulting in transmitral flow obstruction. Resection included partial thickness of the left atrial wall including endocardium and resection of a 8 x 4.5 x 4-cm mass; complete resection was not possible due to the proximity of the mass to the pulmonary veins. Frozen section revealed inadequate margins composed of spindle cell tumor consistent with sarcoma. It was positive for actin, lysozyme, vimentin, and [[alpha].sub.1]-antichymotrypsin and negative for CD34, S-100 protein, and muscle-specific actin (HHF35); therefore, an intermediate- to high-grade tumor consistent with myofibroblastic sarcoma was confirmed. Postoperatively, a staging workup was completed that was found to be negative for metastasis. Due to the presence of positive margins, the patient received postoperative infusional chemotherapy. The chemotherapy regimen included adriamycin (20 mg/[m.sup.2]), ifosfamide (2,500 mg/[m.sup.2]), and mesna (approximately 2,500 mg) for four cycles, which was completed 5 months postoperatively. The patient remained disease free and was followed up with serial transesophageal echocardiographs.

Approximately 14 months after initial diagnosis, a small 1- to 2-cm oscillating echodensity was noted in the left atrium consistent with tumor recurrence. The patient underwent restaging workup with CT scans of the brain, chest and abdomen, and pelvis that were negative for metastasis. The patient was then referred for cardiac tumor repeat resection and autotransplantation. At 15 months after the initial diagnosis, the patient underwent excision and explantation of the heart with excision of the left atrial tumor. Frozen section pathology revealed the margins to be close but clear of tumor. The left atrium underwent reconstruction with bovine pericardium followed by autotransplantation of the heart. The patient did well and was discharged home 7 days postoperatively. The final pathology revealed that the recurrent cardiac fibrosarcoma extended to the inked surgical margin of resection.

Postoperatively, an echocardiogram revealed depressed left atrial function, and he was placed on warfarin therapy. Approximately 11 weeks after autotransplantation, the patient underwent external beam irradiation via three-dimensional conformal radiation with 3,960 cGy in 22 fractions at 180 cGy per fraction. A reduced-volume boost of 2,160 cGy was administered for a total dose of 6,120 cGy (Fig 1). Radiation pneumonitis developed, which improved with treatment with steroids. Eleven months following completion of radiation and 29 months after the initial diagnosis, a rapid recurrence of the left atrial mass developed in the field of prior radiation without evidence of systemic metastasis.

[FIGURE 1 OMITTED]

DISCUSSION

Cardiac tumors are a medical interdisciplinary challenge. Such tumors are often incompletely resectable at diagnosis (Fig 2). Radiation is limited due to the concern for cardiotoxicity, and even chemotherapy, in the past, has been an unproven adjunct to surgical resection. The rarity of cardiac sarcomas and its poor prognosis has minimized the number of studies with adjuvant treatment. The use of anthracycline-based chemotherapy is limited due to the possibility of cardiac toxicity. The poor radiation tolerance of cardiac tissue has also limited the amount of radiation that can be safely administered to the heart. (3) Recurrent tumors also pose a surgical challenge, as complete resection is often difficult from the usual left atrial incisional approach. Even the success of orthotopic cardiac transplantation can be minimized by the recurrence of cardiac tumors thought to be related to immunosuppression. (4,5) Cardiac explantation exposing the entire posterior wall and the replacement of a large part of atrial tissue with bovine pericardium can allow for a more radical resection of the cardiac tumor with the aim of removing as much gross tumor as possible. (6) Only six prior cases of cardiac explantation, tumor resection, and autotransplantation have been undertaken with mixed success. Three patients have died of distant metastasis without evidence of local recurrence; three patients, including our patient, are alive and disease free at least 2 years after initial diagnosis.

[FIGURE 2 OMITTED]

Although local recurrence of disease eventually developed in our patient, this case demonstrates that it is technically feasible to irradiate an explanted heart with acceptable toxicity, and that meticulous interdisciplinary collaboration after initial surgical intervention can result in improved disease-free survival. It is possible that early intervention with postoperative chemotherapy may have prevented the development of systemic metastasis in this patient. Further research into developing methodology aimed at preventing local recurrence is warranted.

ACKNOWLEDGMENT: We thank Joseph Lauritano, RTT, for formulating the three-dimensional radiation plan.

REFERENCES

(1) Burke AP, Cowan D, Virmani R. Primary sarcomas of the heart. Cancer 1992; 69:387-395

(2) Goldie JH. Scientific basis for adjuvant and primary (neoadjuvant) chemotherapy. Semin Oncol 1987; 14:1-7

(3) Stewart JR, Fajardo LF. Radiation induced heart disease: an update. Prog Cardiovasc Dis 1984; 27:173-194

(4) Copeland JG. Cardiac transplantation. Curr Probl Surg 1988; 25:607-672

(5) Michler RE, Goldstein DJ. Treatment of cardiac tumors by orthotopic cardiac transplantation. Semin Oncol 1997; 24: 534-539

(6) Reardon MJ, Defelice CA, Sheinbaum R, et al. Cardiac autotransplant for surgical treatment of a malignant neoplasm. Ann Thorac Surg 1999; 67:1793-1795

* From the Division of Oncology and Hematology (Dr. Mery), Department of Radiation-Oncology (Dr. Haas), Division of Cardiology (Dr. Lazar), and Division of Oncology and Hematology (Dr. Hindenburg), Winthrop University Hospital, and the State University of New York at Stony Brook School of Medicine, Mineola, NY; and Division of Cardiovascular and Thoracic Surgery (Dr. Reardon), Methodist Hospital, Baylor College of Medicine, Houston, TX.

Manuscript received June 4, 2002; revision accepted October 18, 2002.

Correspondence to: Giselle M. Mery, MD, Center for Cancer and Blood Disorders, 6420 Rockledge Dr, Suite 4100, Bethesda, MD 20817; e-mail: gnmery@hotmail.com

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