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Successful treatment of locally advanced anaplastic thyroid carcinoma by chemotherapy and hyperfractionated radiotherapy
Auris Nasus Larynx 36 (2009) 729–732 www.elsevier.com/locate/anl
Successful treatment of locally advanced anaplastic thyroid carcinoma by chemotherapy and hyperfractionated radiotherapy Shogo Shinohara a,*, Masahiro Kikuchi a, Yasushi Naito a, Keizo Fujiwara a, Shinya Hori a, Yosuke Tona a, Hiroshi Yamazaki a, Hiromasa Kobayashi b, Takashi Ishihara b a
Department of Otolaryngology, Kobe City Medical Center General Hospital, Minatojimanaka-machi 4-6, Chuo-Ku, Kobe, Hyogo 650-0046, Japan b Department of Medicine, Kobe City Medical Center General Hospital, Minatojimanaka-machi 4-6, Chuo-Ku, Kobe, Hyogo 650-0046, Japan Received 10 October 2008; accepted 1 February 2009 Available online 9 March 2009
Abstract The authors report a case of anaplastic thyroid carcinoma which was treated with chemotherapy and radiotherapy and proved to achieve pathological CR (complete response) after a radical operation. A 53-year-old female presented with a mass of about 4 cm in diameter arising from the left lobe of her thyroid and surrounding her cervical esophagus. Pre-operative aspiration cytology and open biopsy revealed the tumor was a giant cell anaplastic carcinoma. There was no sign of distant metastasis. Two cycles of chemotherapy were very effective in treating the tumor but regrowth appeared to occur during hyperfractionated radiotherapy. A radical operation, including a resection of the larynx, cervical trachea and esophagus, was successfully performed and no living cancer cells, only granulation and necrosis, were observed in the operation specimen. The patient has been alive for over 2 years since without any evidence of recurrence. # 2009 Elsevier Ireland Ltd. All rights reserved. Keywords: Anaplastic thyroid carcinoma; Pathological CR; Multimodal therapy
1. Introduction
2. Case report
Anaplastic thyroid carcinoma (ATC) is one of the most malignant human neoplasms and the prognosis for this disease is extremely poor. ATCs characteristically grow rapidly and invade adjacent organs with distant metastases in the early stages of this disease [1–5]. Surgical approaches are not appropriate in most cases. Several papers have reported that multimodality treatments with operations, radiotherapy and chemotherapy may prolong survival time, and that in very few cases people can survive this disease. In this paper, we experienced a case of ATC that proved to achieve pathological CR through multi-drug chemotherapy and altered fractionated radiotherapy. This is the first report which proved the efficacy of chemotherapy and radiotherapy pathologically from an operative specimen of an ATC patient.
A 53-year-old woman complaining of anterior neck pain since August 2005 was introduced to Kobe City Medical Center General Hospital in September 2005. Ultrasonography and fine needle aspiration cytology had already been done at the previous clinic and those examinations had shown a 3 cm diameter mass in the left lobe having dysplastic giant cells with multiple nuclei (Fig. 1). A reevaluation was undertaken using ultrasonography, computed tomography (CT), magnetic resonance imaging (MRI), and 67-Gallium citrate scintigraphy. The results showed the tumor arising from the inferior part of the left lobe, 4.1 cm in diameter, extending to a pre-vertebral lesion surrounding the cervical esophagus (Fig. 2a). 67-Gallium citrate was highly taken in the tumor, without any other uptake, which indicated distant metastasis had not appeared. The serum level of any cancer marker (thyroglobulin, SCC, CYFRA, CA19-9, CEA, CA125, Pro-GPR, sIL2R), inflammatory marker (C-reacting protein) and white blood cell counts
* Corresponding author. Tel.: +81 78 302 4321; fax: +81 78 302 7537. E-mail address: [email protected] (S. Shinohara).
0385-8146/$ – see front matter # 2009 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.anl.2009.02.001
730
S. Shinohara et al. / Auris Nasus Larynx 36 (2009) 729–732
Fig. 1. Dysplastic giant cells with multiple nuclei were collected with fine needle aspiration cytology (Papanicolou stain 20).
stayed within normal ranges. We also ruled out the existence of a malignancy in the upper digestive tract with a gastrointestinal fiberscope. An open biopsy was performed for the definitive pathological diagnosis on October 26, 2005. The tumor consisted of typical giant cells with clear cytoplasm and multiple nuclei infiltrated by inflammatory cells (Fig. 3). We examined the expressed protein of the specimen by immunohistochemistry and it proved to be stained partially with epithelial markers (CK-mol, CKM821), but neither with lymphoid markers (LCA, UCHL1, L26, and CD30) nor with thyroglobulin. We ruled out the possibility of malignant lymphoma using flow cytometry and chromosome analysis. The possibility of other sarcomas was also eliminated using Masson’s argentaffin stain. As a result, the tumor was diagnosed as thyroid anaplastic carcinoma. The patient received two cycles of chemotherapy which consisted of cisplatin (40 mg/m2, day 1), doxorubicin (60 mg/m2, day 1), etoposide (100 mg/m2, days 1–3) and peplomycin (5 mg/body, days 1–5), with G-CSF support [6] beginning in November 2005 on 30-day intervals. The tumor size was remarkably reduced and the effect of the treatment was judged as PR (Fig. 2a and b). Aiming at CR, accelerated fractionated radiotherapy (concomitant boost) was started in January 2006. This therapy consisted of 1.8 Gy fraction radiotherapy to the wider field for 5 days, followed by
Fig. 3. Microscopic findings of the tumor from open biopsy. Typical giant cells with clear cytoplasm and multiple nuclei infiltrated by inflammatory cells were identified (hematoxylin–eosin stain, 40).
1.2 Gy BID hyperfractionation to the smaller field (up to 69 Gy). Tumor regrowth appeared on an MRI after the radiation therapy (Fig. 2c). A total pharyngo–laryngo–esophagectomy with bilateral neck and upper mediastinum dissection was performed on March 15, 2006. The upper digestive tract was reconstructed using a gastric tube made with HALS (hand-assisted laparoscopic surgery). The patient was discharged on April 19, 2006 without any major complications and is alive with no evidence of disease showing for over 2 years. A histological examination revealed the tumor had been totally replaced by granulation tissue and necrosis and no cancer cells were identified in a serial section of the operation specimen (pathological CR) (Fig. 4).
3. Discussion Anaplastic thyroid carcinoma (ATC) usually presents as a rapidly growing mass invading adjacent organs (e.g. larynx, trachea, and esophagus). This kind of malignant tumor is also characterized by frequent distant metastases in early stages (almost 24–50% at the time of diagnosis [7–9]). The survival rate is dismal, which had been reported as 3–7% (5
Fig. 2. Time course of computed tomography (CT) findings with contrast enhancement ((A) before treatment; (B) after 2 cycles of chemotherapy; (C) after HRT). Before treatment, a heterogeneously enhanced tumor (white arrows) extended to a pre-vertebral lesion and surrounded the cervical esophagus (a black arrow). Two cycles of chemotherapy were very effective in treating the tumor but it’s regrowth appeared to occur after hyperfractionated radiotherapy.
S. Shinohara et al. / Auris Nasus Larynx 36 (2009) 729–732
Fig. 4. Microscopic findings of the tumor removed in the radical operation after chemotherapy and radiotherapy. They consisted of: (a) granulation tissue and (b) necrosis with (c) inflammatory cell infiltration (hematoxylin– eosin stain, 10).
years) with 4–7 months median survival period in the 1970s and 1980s [10,11] and no progress has been reported recently [8,12,13]. In cases with such an extremely low survival rate, multimodal therapy including radical operation is less favorable than best supportive care. However, there must be a few patients who could survive this malignancy by aggressive multimodal therapies; this presents us with a therapeutic dilemma. In 2001, Sugitani et al. [14] proposed a prognostic index (PI) calculated with the numbers of four pre-treatment factors: the presence of acute symptoms, a large tumor (>5 cm), distant metastasis, and leukocytosis (white blood cell count 10,000/mm3). They analyzed the data of 44 ATC patients and concluded that these four factors were independent for predicting death from ATC. Patients with a PI of 1 had a 62% survival rate of 6 months, whereas no patients with a PI of 3 survived longer than 6 months. All patients with a PI of 4 died from their disease within 3 months. Sugitani et al. also recommended using this index as a means of selecting patients for aggressive therapy. When the PI is low, multimodal treatment should be attempted to obtain the best survival results rather than palliative therapy. Meta-analysis with a cohort consisting of 516 patients with ATC was also conducted by Kebebew et al. in 2005 [9]. Using multivariate analysis (MVA), patient ages <60 years, the presence of an intrathyroidal tumor, and the combined use of surgical and external beam radiation therapy were identified as independent predictors of lower cause-specific mortality. In the present case, we did not detect any distant metastases or leukocytosis before therapy. The growth speed was not so high (from 3 cm to 4.1 cm in diameter after 1 month) at the time of diagnosis. Pre-operative clinical findings did not match any of four factors proposed by Sugitani et al. The patient’s age, 53 years old, was also favorable for Kebebew’s index. However, we did not select a radical operation as an initial treatment because the tumor
731
had infiltrated adjacent organs (the trachea and esophagus). Instead, we chose the chemotherapy regimen proposed by the Japan Society of Thyroid Surgery [6], which turned out to be very effective in the present case with an acceptable toxicity. Hyperfractionated radiotherapy (HRT) was selected as a completion therapy for avoiding an operation. HRT was reported to bring favorable local control rates, despite having no greater effect on overall survival [5,15]. Strangely, the HRT’s effect was judged as PD (progressive disease). Therefore, we performed a radical operation including a resection of the larynx, cervical trachea and esophagus, which resulted in no living cancer cells in the operation specimen; pathological CR had been achieved. As a result, an operation might not be needed. However we cannot realize the pathological change of the tumor before surgery; moreover, surgery has been reported to be mandatory for a few survival chances from ATC [4,9,13]. Fortunately, the patient has now been alive for over 2 years without any evidence of recurrence. We concluded that we had better try multimodal therapy, including radical surgery, on patients with ATC if the preoperative factors proposed in the previous reports [9,13,14] are favorable for their survival.
Acknowledgement This study was financially supported by Kasahara Fund for the promotion of cancer research.
References [1] Kim JH, Leeper RD. Treatment of anaplastic giant and spindle cell carcinoma of the thyroid gland with combination adriamycin and radiation therapy. A new approach. Cancer 1983;52:954–7. [2] Kasai N, Sakamoto A, Uchida M. A combined modality for anaplastic large-cell carcinoma of the thyroid. Auris Nasus Larynx 1985;12(Suppl. 2):572–4. [3] Kim JH, Leeper RD. Treatment of locally advanced thyroid carcinoma with combination doxorubicin and radiation therapy. Cancer 1987;60:2372–5. [4] Tallroth E, Wallin G, Lundell G, Lowhagen T, Einhorn J. Multimodality treatment in anaplastic giant cell thyroid carcinoma. Cancer 1987;60:1428–31. [5] Tennvall J, Lundell G, Hallquist A, Wahlberg P, Wallin G, Tibblin S, Combined doxorubicin, hyperfractionated radiotherapy, and surgery in anaplastic thyroid carcinoma. Report on two protocols. The Swedish anaplastic thyroid cancer group. Cancer 1994;74:1348–54. [6] Intensive chemotherapy for anaplastic thyroid carcinoma: combination of cisplatin, doxorubicin, etoposide and peplomycin with granulocyte granulocyte colony-stimulating factor support. Chemotherapy Committee, the Japanese Society of Thyroid Surgery. Japanese Journal of Clinical Oncology 1995;25:203–7. [7] Voutilainen PE, Multanen M, Haapiainen RK, Leppaniemi AK, Sivula AH. Anaplastic thyroid carcinoma survival. World Journal of Surgery 1999;23:975–8 (discussion 978–979). [8] Kim TY, Kim KW, Jung TS, Kim JM, Kim SW, Chung KW, et al. Prognostic factors for Korean patients with anaplastic thyroid carcinoma. Head & Neck 2007;29:765–72.
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S. Shinohara et al. / Auris Nasus Larynx 36 (2009) 729–732
[9] Kebebew E, Greenspan FS, Clark OH, Woeber KA, McMillan A. Anaplastic thyroid carcinoma. Treatment outcome and prognostic factors. Cancer 2005;103:1330–5. [10] Aldinger KA, Samaan NA, Ibanez M, Hill Jr CS. Anaplastic carcinoma of the thyroid: a review of 84 cases of spindle and giant cell carcinoma of the thyroid. Cancer 1978;41:2267–75. [11] Nel CJ, van Heerden JA, Goellner JR, Gharib H, McConahey WM, Taylor WF, et al., Anaplastic carcinoma of the thyroid: a clinicopathologic study of 82 cases. Mayo Clinic Proceedings 1985; 60:51–8. [12] Jiang JY, Tseng FY. Prognostic factors of anaplastic thyroid carcinoma. Journal of Endocrinological Investigation 2006;29:11–7.
[13] Yau T, Lo CY, Epstein RJ, Lam AK, Wan KY, Lang BH. Treatment outcomes in anaplastic thyroid carcinoma: survival improvement in young patients with localized disease treated by combination of surgery and radiotherapy. Annals of Surgical Oncology 2008;15: 2500–5. [14] Sugitani I, Kasai N, Fujimoto Y, Yanagisawa A. Prognostic factors and therapeutic strategy for anaplastic carcinoma of the thyroid. World Journal of Surgery 2001;25:617–22. [15] Kobayashi T, Asakawa H, Umeshita K, Takeda T, Maruyama H, Matsuzuka F, et al. Treatment of 37 patients with anaplastic carcinoma of the thyroid. Head & Neck 1996;18:36–41.
Successful treatment of locally advanced anaplastic thyroid carcinoma by chemotherapy and hyperfractionated radiotherapy Shogo Shinohara a,*, Masahiro Kikuchi a, Yasushi Naito a, Keizo Fujiwara a, Shinya Hori a, Yosuke Tona a, Hiroshi Yamazaki a, Hiromasa Kobayashi b, Takashi Ishihara b a
Department of Otolaryngology, Kobe City Medical Center General Hospital, Minatojimanaka-machi 4-6, Chuo-Ku, Kobe, Hyogo 650-0046, Japan b Department of Medicine, Kobe City Medical Center General Hospital, Minatojimanaka-machi 4-6, Chuo-Ku, Kobe, Hyogo 650-0046, Japan Received 10 October 2008; accepted 1 February 2009 Available online 9 March 2009
Abstract The authors report a case of anaplastic thyroid carcinoma which was treated with chemotherapy and radiotherapy and proved to achieve pathological CR (complete response) after a radical operation. A 53-year-old female presented with a mass of about 4 cm in diameter arising from the left lobe of her thyroid and surrounding her cervical esophagus. Pre-operative aspiration cytology and open biopsy revealed the tumor was a giant cell anaplastic carcinoma. There was no sign of distant metastasis. Two cycles of chemotherapy were very effective in treating the tumor but regrowth appeared to occur during hyperfractionated radiotherapy. A radical operation, including a resection of the larynx, cervical trachea and esophagus, was successfully performed and no living cancer cells, only granulation and necrosis, were observed in the operation specimen. The patient has been alive for over 2 years since without any evidence of recurrence. # 2009 Elsevier Ireland Ltd. All rights reserved. Keywords: Anaplastic thyroid carcinoma; Pathological CR; Multimodal therapy
1. Introduction
2. Case report
Anaplastic thyroid carcinoma (ATC) is one of the most malignant human neoplasms and the prognosis for this disease is extremely poor. ATCs characteristically grow rapidly and invade adjacent organs with distant metastases in the early stages of this disease [1–5]. Surgical approaches are not appropriate in most cases. Several papers have reported that multimodality treatments with operations, radiotherapy and chemotherapy may prolong survival time, and that in very few cases people can survive this disease. In this paper, we experienced a case of ATC that proved to achieve pathological CR through multi-drug chemotherapy and altered fractionated radiotherapy. This is the first report which proved the efficacy of chemotherapy and radiotherapy pathologically from an operative specimen of an ATC patient.
A 53-year-old woman complaining of anterior neck pain since August 2005 was introduced to Kobe City Medical Center General Hospital in September 2005. Ultrasonography and fine needle aspiration cytology had already been done at the previous clinic and those examinations had shown a 3 cm diameter mass in the left lobe having dysplastic giant cells with multiple nuclei (Fig. 1). A reevaluation was undertaken using ultrasonography, computed tomography (CT), magnetic resonance imaging (MRI), and 67-Gallium citrate scintigraphy. The results showed the tumor arising from the inferior part of the left lobe, 4.1 cm in diameter, extending to a pre-vertebral lesion surrounding the cervical esophagus (Fig. 2a). 67-Gallium citrate was highly taken in the tumor, without any other uptake, which indicated distant metastasis had not appeared. The serum level of any cancer marker (thyroglobulin, SCC, CYFRA, CA19-9, CEA, CA125, Pro-GPR, sIL2R), inflammatory marker (C-reacting protein) and white blood cell counts
* Corresponding author. Tel.: +81 78 302 4321; fax: +81 78 302 7537. E-mail address: [email protected] (S. Shinohara).
0385-8146/$ – see front matter # 2009 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.anl.2009.02.001
730
S. Shinohara et al. / Auris Nasus Larynx 36 (2009) 729–732
Fig. 1. Dysplastic giant cells with multiple nuclei were collected with fine needle aspiration cytology (Papanicolou stain 20).
stayed within normal ranges. We also ruled out the existence of a malignancy in the upper digestive tract with a gastrointestinal fiberscope. An open biopsy was performed for the definitive pathological diagnosis on October 26, 2005. The tumor consisted of typical giant cells with clear cytoplasm and multiple nuclei infiltrated by inflammatory cells (Fig. 3). We examined the expressed protein of the specimen by immunohistochemistry and it proved to be stained partially with epithelial markers (CK-mol, CKM821), but neither with lymphoid markers (LCA, UCHL1, L26, and CD30) nor with thyroglobulin. We ruled out the possibility of malignant lymphoma using flow cytometry and chromosome analysis. The possibility of other sarcomas was also eliminated using Masson’s argentaffin stain. As a result, the tumor was diagnosed as thyroid anaplastic carcinoma. The patient received two cycles of chemotherapy which consisted of cisplatin (40 mg/m2, day 1), doxorubicin (60 mg/m2, day 1), etoposide (100 mg/m2, days 1–3) and peplomycin (5 mg/body, days 1–5), with G-CSF support [6] beginning in November 2005 on 30-day intervals. The tumor size was remarkably reduced and the effect of the treatment was judged as PR (Fig. 2a and b). Aiming at CR, accelerated fractionated radiotherapy (concomitant boost) was started in January 2006. This therapy consisted of 1.8 Gy fraction radiotherapy to the wider field for 5 days, followed by
Fig. 3. Microscopic findings of the tumor from open biopsy. Typical giant cells with clear cytoplasm and multiple nuclei infiltrated by inflammatory cells were identified (hematoxylin–eosin stain, 40).
1.2 Gy BID hyperfractionation to the smaller field (up to 69 Gy). Tumor regrowth appeared on an MRI after the radiation therapy (Fig. 2c). A total pharyngo–laryngo–esophagectomy with bilateral neck and upper mediastinum dissection was performed on March 15, 2006. The upper digestive tract was reconstructed using a gastric tube made with HALS (hand-assisted laparoscopic surgery). The patient was discharged on April 19, 2006 without any major complications and is alive with no evidence of disease showing for over 2 years. A histological examination revealed the tumor had been totally replaced by granulation tissue and necrosis and no cancer cells were identified in a serial section of the operation specimen (pathological CR) (Fig. 4).
3. Discussion Anaplastic thyroid carcinoma (ATC) usually presents as a rapidly growing mass invading adjacent organs (e.g. larynx, trachea, and esophagus). This kind of malignant tumor is also characterized by frequent distant metastases in early stages (almost 24–50% at the time of diagnosis [7–9]). The survival rate is dismal, which had been reported as 3–7% (5
Fig. 2. Time course of computed tomography (CT) findings with contrast enhancement ((A) before treatment; (B) after 2 cycles of chemotherapy; (C) after HRT). Before treatment, a heterogeneously enhanced tumor (white arrows) extended to a pre-vertebral lesion and surrounded the cervical esophagus (a black arrow). Two cycles of chemotherapy were very effective in treating the tumor but it’s regrowth appeared to occur after hyperfractionated radiotherapy.
S. Shinohara et al. / Auris Nasus Larynx 36 (2009) 729–732
Fig. 4. Microscopic findings of the tumor removed in the radical operation after chemotherapy and radiotherapy. They consisted of: (a) granulation tissue and (b) necrosis with (c) inflammatory cell infiltration (hematoxylin– eosin stain, 10).
years) with 4–7 months median survival period in the 1970s and 1980s [10,11] and no progress has been reported recently [8,12,13]. In cases with such an extremely low survival rate, multimodal therapy including radical operation is less favorable than best supportive care. However, there must be a few patients who could survive this malignancy by aggressive multimodal therapies; this presents us with a therapeutic dilemma. In 2001, Sugitani et al. [14] proposed a prognostic index (PI) calculated with the numbers of four pre-treatment factors: the presence of acute symptoms, a large tumor (>5 cm), distant metastasis, and leukocytosis (white blood cell count 10,000/mm3). They analyzed the data of 44 ATC patients and concluded that these four factors were independent for predicting death from ATC. Patients with a PI of 1 had a 62% survival rate of 6 months, whereas no patients with a PI of 3 survived longer than 6 months. All patients with a PI of 4 died from their disease within 3 months. Sugitani et al. also recommended using this index as a means of selecting patients for aggressive therapy. When the PI is low, multimodal treatment should be attempted to obtain the best survival results rather than palliative therapy. Meta-analysis with a cohort consisting of 516 patients with ATC was also conducted by Kebebew et al. in 2005 [9]. Using multivariate analysis (MVA), patient ages <60 years, the presence of an intrathyroidal tumor, and the combined use of surgical and external beam radiation therapy were identified as independent predictors of lower cause-specific mortality. In the present case, we did not detect any distant metastases or leukocytosis before therapy. The growth speed was not so high (from 3 cm to 4.1 cm in diameter after 1 month) at the time of diagnosis. Pre-operative clinical findings did not match any of four factors proposed by Sugitani et al. The patient’s age, 53 years old, was also favorable for Kebebew’s index. However, we did not select a radical operation as an initial treatment because the tumor
731
had infiltrated adjacent organs (the trachea and esophagus). Instead, we chose the chemotherapy regimen proposed by the Japan Society of Thyroid Surgery [6], which turned out to be very effective in the present case with an acceptable toxicity. Hyperfractionated radiotherapy (HRT) was selected as a completion therapy for avoiding an operation. HRT was reported to bring favorable local control rates, despite having no greater effect on overall survival [5,15]. Strangely, the HRT’s effect was judged as PD (progressive disease). Therefore, we performed a radical operation including a resection of the larynx, cervical trachea and esophagus, which resulted in no living cancer cells in the operation specimen; pathological CR had been achieved. As a result, an operation might not be needed. However we cannot realize the pathological change of the tumor before surgery; moreover, surgery has been reported to be mandatory for a few survival chances from ATC [4,9,13]. Fortunately, the patient has now been alive for over 2 years without any evidence of recurrence. We concluded that we had better try multimodal therapy, including radical surgery, on patients with ATC if the preoperative factors proposed in the previous reports [9,13,14] are favorable for their survival.
Acknowledgement This study was financially supported by Kasahara Fund for the promotion of cancer research.
References [1] Kim JH, Leeper RD. Treatment of anaplastic giant and spindle cell carcinoma of the thyroid gland with combination adriamycin and radiation therapy. A new approach. Cancer 1983;52:954–7. [2] Kasai N, Sakamoto A, Uchida M. A combined modality for anaplastic large-cell carcinoma of the thyroid. Auris Nasus Larynx 1985;12(Suppl. 2):572–4. [3] Kim JH, Leeper RD. Treatment of locally advanced thyroid carcinoma with combination doxorubicin and radiation therapy. Cancer 1987;60:2372–5. [4] Tallroth E, Wallin G, Lundell G, Lowhagen T, Einhorn J. Multimodality treatment in anaplastic giant cell thyroid carcinoma. Cancer 1987;60:1428–31. [5] Tennvall J, Lundell G, Hallquist A, Wahlberg P, Wallin G, Tibblin S, Combined doxorubicin, hyperfractionated radiotherapy, and surgery in anaplastic thyroid carcinoma. Report on two protocols. The Swedish anaplastic thyroid cancer group. Cancer 1994;74:1348–54. [6] Intensive chemotherapy for anaplastic thyroid carcinoma: combination of cisplatin, doxorubicin, etoposide and peplomycin with granulocyte granulocyte colony-stimulating factor support. Chemotherapy Committee, the Japanese Society of Thyroid Surgery. Japanese Journal of Clinical Oncology 1995;25:203–7. [7] Voutilainen PE, Multanen M, Haapiainen RK, Leppaniemi AK, Sivula AH. Anaplastic thyroid carcinoma survival. World Journal of Surgery 1999;23:975–8 (discussion 978–979). [8] Kim TY, Kim KW, Jung TS, Kim JM, Kim SW, Chung KW, et al. Prognostic factors for Korean patients with anaplastic thyroid carcinoma. Head & Neck 2007;29:765–72.
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S. Shinohara et al. / Auris Nasus Larynx 36 (2009) 729–732
[9] Kebebew E, Greenspan FS, Clark OH, Woeber KA, McMillan A. Anaplastic thyroid carcinoma. Treatment outcome and prognostic factors. Cancer 2005;103:1330–5. [10] Aldinger KA, Samaan NA, Ibanez M, Hill Jr CS. Anaplastic carcinoma of the thyroid: a review of 84 cases of spindle and giant cell carcinoma of the thyroid. Cancer 1978;41:2267–75. [11] Nel CJ, van Heerden JA, Goellner JR, Gharib H, McConahey WM, Taylor WF, et al., Anaplastic carcinoma of the thyroid: a clinicopathologic study of 82 cases. Mayo Clinic Proceedings 1985; 60:51–8. [12] Jiang JY, Tseng FY. Prognostic factors of anaplastic thyroid carcinoma. Journal of Endocrinological Investigation 2006;29:11–7.
[13] Yau T, Lo CY, Epstein RJ, Lam AK, Wan KY, Lang BH. Treatment outcomes in anaplastic thyroid carcinoma: survival improvement in young patients with localized disease treated by combination of surgery and radiotherapy. Annals of Surgical Oncology 2008;15: 2500–5. [14] Sugitani I, Kasai N, Fujimoto Y, Yanagisawa A. Prognostic factors and therapeutic strategy for anaplastic carcinoma of the thyroid. World Journal of Surgery 2001;25:617–22. [15] Kobayashi T, Asakawa H, Umeshita K, Takeda T, Maruyama H, Matsuzuka F, et al. Treatment of 37 patients with anaplastic carcinoma of the thyroid. Head & Neck 1996;18:36–41.