Long-term survivor of relapsed MFH on the thigh treated with autologous formalin-fixed tumor vaccine (AFTV) combined with limb-sparing surgery and radiotherapy
© Todoroki et al; licensee BioMed Central Ltd. 2011
Received: 19 July 2010
Accepted: 24 August 2011
Published: 24 August 2011
Malignant fibrous histiocytoma (MFH) is an aggressive spindle cell cancer of soft-tissue sarcoma type in the elderly, mostly affecting the extremities. Lesions > 5 cm, positive margins, and local recurrence are significant poor prognostic indicators. The strongest predictor for distant metastasis was tumor size (> 5 cm), and for overall survival, presence of local recurrence. Limb-sparing extensive tumor resection is preferred to achieve negative surgical margins. However, in some circumstances, amputation is inevitable. Recent studies demonstrated that adjuvant radiotherapy for microscopically positive surgical margins significantly improved local control and disease-free survival rates. Therefore, effective therapeutic strategies against locally relapsed high grade MFH are required to prevent distant metastasis and to achieve long-term disease-free survival. Here, we report local relapse of high grade MFH treated by successive application of autologous formalin-fixed tumor vaccination (AFTV) with limb-sparing surgery and postoperative radiotherapy. The patient is alive and well, disease-free and with no functional impairment, more than five years after treatment.
Malignant fibrous histiocytoma (MFH) is the most common soft-tissue sarcoma. When located in a limb, MFH is currently treated with limb-sparing surgery followed by > 65 Gy external beam radiotherapy [1, 2]. For patients with locally recurrent large tumors (> 5 cm in diameter) on the thigh, limb-sparing surgery with adequate clearance margins is desirable but not always attainable. Additionally, large tumors often result in distant metastasis , for which there is currently no effective chemotherapy . Patients thus face amputation for complete tumor removal; so improved treatment options are urgently required for locally recurrent high-grade MFH. Here, we report application of autologous formalin-fixed tumor vaccination (AFTV) combined with limb-sparing surgery and followed by anticipatory 74 Gy external electron beam radiotherapy in an elderly diabetic patient with locally recurrent MFH after primary limb-sparing surgery. The vaccine was prepared from both the recurrent and the primary tumor after limb-sparing surgery .
Discussion and conclusions
Combining limb-sparing surgery and postoperative radiotherapy with > 65 Gy is standard treatment for patients with high grade large MFH . Treatment of local recurrence of such tumors would also require systemic adjuvant therapy to prevent distant metastasis. However, no effective chemotherapeutic regimen exists. Here, we applied AFTV from the start of postoperative radiotherapy instead of chemotherapy, in consideration of the patient's uncontrolled DM. Details of the AFTV have already been reported . We used a mixture of both paraffin-embedded primary tumor and formalin-fixed secondary tumor as the vaccine. In this way, we aimed to include the original tumor antigens in the primary tumor as well as any possible alterations of the expressed tumor antigens in the progressive metastatic tumor cells. The objective was to eradicate the microscopically observed tumor cells remaining after surgery and irradiation. Hafner et al. reported that decreased immune surveillance might play a role in the development of MFH, based on a significant increase in its incidence in a large series of renal transplant patients (156 per 100,000) . This was another reason to attempt AFTV rather than chemotherapy. Even in the present time, there is no clinically appropriate estimating system of antitumor cellular immune reactivity for the particular patient. Since DTH testing is commonly used to measure specific antitumor cellular immune reactivity we used it to evaluate antitumor cellular immune status in the different timing as just before, complete, and late after AFTV. The reactivity has strengthened from pseudo and true positive during 4 years after AFTV in the reported case. Radiation therapy of 74 Gy by using shrinking field technique has very efficiently controlled locally relapse high grade MFH. As conclusion, results for the case reported here suggest that AFTV in combination with limb-sparing surgery and adjuvant radiotherapy might extend survival of patients with locally advanced high grade MFH of extremities with enhancing specific antitumor immune reactivity.
Written consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
- Delaney TF, Kepka L, Goldberg SI, Hornicek FJ, Gebhardt MC, Yoon SS, Springfield DS, Raskin KA, Harmon DC, Kirsch DG: Radiation therapy for control of soft-tissue sarcomas resected with positive margins. Int J Radiat Oncol Biol Phys. 2007, 67: 1460-1469. 10.1016/j.ijrobp.2006.11.035.View ArticlePubMedGoogle Scholar
- Hohenberger P, Wysocki WM: Neoadjuvant treatment of locally advanced soft tissue sarcoma of the limbs: which treatment to choose?. Oncologist. 2008, 13: 175-186. 10.1634/theoncologist.2007-0165.View ArticlePubMedGoogle Scholar
- Liu SQ, Shiraiwa H, Kawai K, Hayashi H, Akaza H, Kim BS, Oki A, Nishida M, Kubo T, Hashizaki K: Tumor-specific autologous cytotoxic T lymphocytes from tissue sections. Nat Med. 1996, 2: 1283-10.1038/nm1296-1283.View ArticlePubMedGoogle Scholar
- Edge SB, Compton CC: The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 2010, 17: 1471-1474. 10.1245/s10434-010-0985-4.View ArticlePubMedGoogle Scholar
- Ishikawa E, Tsuboi K, Yamamoto T, Muroi A, Takano S, Enomoto T, Matsumura A, Ohno T: Clinical trial of autologous formalin-fixed tumor vaccine for glioblastoma multiforme patients. Cancer Sci. 2007, 98: 1226-1233. 10.1111/j.1349-7006.2007.00518.x.View ArticlePubMedGoogle Scholar
- Hafner J, Kunzi W, Weinreich T: Malignant fibrous histiocytoma and atypical fibroxanthoma in renal transplant recipients. Dermatology. 1999, 198: 29-32. 10.1159/000018060.View ArticlePubMedGoogle Scholar
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