Long-Term Remission in a Case of Anaplastic Thyroid Carcinoma following Local Irradiation and High-Dose Chemotherapy with Autologous Peripheral Blood Stem Cell Transplantation

Introduction

Anaplastic thyroid carcinoma (ATC) is one of the most aggressive neoplasms with a mean survival of 6 months after diagnosis, and long-term survival is very low (1). Furthermore, because ATC is very rare, it has been difficult to evaluate factors that may influence treatment and survival (2). In some reports, systemic chemotherapy agents have been reported to improve treatment results for ATC (3,4), and aggressive multimodal therapy combining surgery, radiation and chemotherapy may provide some benefits (5–11). However, long-term survivors still have been very rare. We describe herein a long-term survivor of ATC successfully treated with autologous peripheral blood stem cell transplantation (auto-PBSCT).

Case Report

In September 1996, a 37-year-old Japanese female was referred to us presenting with a rapidly growing thyroid mass that has enlarged significantly in the course of only 10 days. She also suffered from anterior cervical pain. On physical examination, a 5 × 4 cm-sized hard, irregular, and tender mass in the right lobe of the thyroid was palpated, and was confirmed by computed tomography (Fig. 1a). Fine-needle aspiration was performed and ATC including components of well-differentiated carcinoma was diagnosed cytologically (Fig. 1b and 1c). There were multiple and bilateral cervical lymph node metastases without distant metastasis. The disease was judged to be at stage IV (T3N1bM0) according to the TNM classification. The patient was treated with a modified PACE regimen consisting of cisplatin, pirarubicin, etoposide (VP-16), and peplomycin as previously described (12). This chemotherapy was repeated twice with a 3-week interval in September and October 1996. Then, the patient was further treated with carboplatin (CBDCA) (300 mg/sqm i.v.) on day 1 and VP-16 (250 mg/sqm i.v.) for 4 days. During the hematological recovery, granulocyte-colony stimulating factor was administered subcutaneously to mobilize peripheral blood stem cells (PBSC), and mononuclear cells were collected. Thereafter, three cycles of a modified PACE regimen were repeated. For the remaining lymph node metastases local radiation therapy of 50 Gy in total was added, and the lymph node metastases disappeared after the radiation therapy. The primary tumor regressed and was confined almost to the right thyroid enough to be surgically operable. Then, the patient underwent right lobectomy in April 1997. However, since viable cells were histologically identified in the tumor resected, one cycle of a modified PACE regimen was added. In an attempt to eradicate the resistant tumor cells, she received high-dose chemotherapy (HDC) as adjuvant therapy supported with auto-PBSCT in August 1997 after informed consent was obtained. She had no complications but hypothyroidism prior to auto-PBSCT. The conditioning regimen consisted of CBDCA 500 mg/sqm once daily i.v. for 4 days (total dose 2000 mg/sqm), mitoxantrone 20 mg/sqm once daily i.v. for 2 days (total dose 40 mg/sqm), VP-16 1000 mg/sqm once daily i.v. for 2 days (total dose 2000 mg/sqm), and cyclophosphamide 2000 mg/sqm once daily i.v. for 2 days (total dose 4000 mg/sqm). After the conditioning, 9.8 × 10 ⁶ frozen-thawed CD34 positive cells/kg were infused on day 0. The granulocyte count exceeded 0.5 × 10 ⁹ /L on day 10 and platelet count did 50 × 10 ⁹ /L on day 13. As for the regimen-related toxicity, gastrointestinal and oral toxicities were grade I according to ECOG criteria. She was discharged without sequelae on day 23. At the time of this writing in September 2007, she has been free of the disease for more than 10 years.

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Figure 1.

Cervical computed tomography revealed huge mass (arrow) in the right lobe of the thyroid (a). Fine-needle aspiration revealed anaplastic thyroid carcinoma including well-differentiated carcinoma (b). Malignant cells were immunohistochemically stained with cytokeratin (c).

Discussion

ATC is extremely aggressive and median survival time of ATC patients is reported as 2 to 12 months (1). In addition, because of the rare incidence of the disease, treatment for ATC has not been established (2). In previous reports, a single chemotherapeutic agent for ATC has appeared to be inadequate due to the rapid progression of the disease and easy development of drug resistance (13,14). However, in some reports, combinations of chemotherapeutic agents have been reported to improve treatment results for ATC, and limited reported experience with combination modalities suggests that aggressive and appropriate combinations of surgery, radiation and chemotherapy may provide some benefits (5–11). Though, long-term survivors have been very rare. In a series of 37 patients with ATC, combination modalities improved the prognosis when compared with palliative treatment (median survival time was 8 months and 2 months, respectively), but there were only 3 long-term survivors for more than 3 years, treated with combination of chemotherapy, radiation and surgery (15). In the same report, one patient with ATC received HDC with autologous bone marrow transplantation, and the primary neck tumor and pulmonary metastases disappeared. However, the patient died of superior vena cava thromboembolism 6 months after diagnosis. In the present case, the complete response was not obtained by the conventional-dose combined chemotherapy. However, as the patient had chemosensitive disease, she underwent HDC to eradicate the resistant malignant cells.

She is alive and well without evidence of disease at 10 years. To the best of our knowledge, this is the first report of ATC that has been followed up for a long-term period after auto-PBSCT. HDC with auto-PBSCT offers a mechanism of overcoming drug resistance. ATC is a lethal tumor, however, this case will suggest that intensive therapeutic approach such as HDC with auto-PBSCT may be useful. Further investigation is warranted and required in the context of clinical trials.