Annals of Surgical Oncology 15(9):2500–2505
DOI: 10.1245/s10434-008-0005-0
Treatment Outcomes in Anaplastic Thyroid Carcinoma: Survival Improvement in Young Patients With Localized Disease Treated by Combination of Surgery and Radiotherapy Thomas Yau, MBBS,1 C. Y. Lo, MS,2 R. J. Epstein, MD,1 A. K. Y. Lam, MD, PhD,3 K. Y. Wan, MBBS,4 and Brian H. Lang, MS2
1
Department of Medicine, University of Hong Kong Medical Centre, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong, China 2 Department of Surgery, University of Hong Kong Medical Centre, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong, China 3 Department of Pathology, University of Hong Kong Medical Centre, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong, China 4 Department of Clinical Oncology, University of Hong Kong Medical Centre, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong, China
Background: Anaplastic thyroid carcinoma (ATC) is a notoriously aggressive malignancy associated with a highly lethal clinical course despite therapeutic intervention. Our present study attempts to identify factors that could potentially improve therapeutic strategies by analyzing the clinicopathological features, treatment and outcome of ATC patients managed over the past four decades at our institution. Methods: Fifty patients with biopsy-proven ATC during the period 1966 to 2006 were studied. All patients were managed with surgery, radiotherapy, chemotherapy and/or chemoradiation. Survival was calculated by the Kaplan-Meier method. Potential factors affecting survival were compared by the log rank test. Results: Most patients (88%) presented with a neck mass; 17 patients (34%) also had cervical lymphadenopathy. Distant metastases were clinically present in 9 (18%). Median survival was 97 days, whereas the 1- and 3-year survival was 14% and 8%, respectively. On univariate analysis, patients aged £65 years (P = .04), absence of metastatic disease at presentation (P < .01), surgical resection (P < .01), and postoperative radiotherapy (P < .01) were associated with longer survival. The adoption of cytotoxic chemotherapy was not associated with better survival (P = .4). Moreover, there was no improvement in survival rate over the last four decades despite the adoption of multimodal treatment (P = .5). Conclusion: ATC remains a deadly disease despite technical advances in surgical technique and adoption of multidisciplinary treatment strategies over the last four decades. However, younger patients with localized ATC might benefit from an aggressive multidisciplinary approach. Key Words: Anaplastic thyroid cancer—Young age—Surgery—Radiotherapy.
Anaplastic thyroid carcinoma (ATC) attributes to < 2% of all thyroid carcinoma but accounts for 14% to 39% of all deaths due to thyroid cancer.1,2
Patients with ATC usually have locally advanced or metastatic disease.3–6 It is one of the most aggressive cancers in humans and is associated with death despite therapeutic interventions.7 Its aggressive nature and rarity makes it difficult to design a randomized, controlled trial to assess the effect of different treatments on the outcome. Therefore, the treatment guidelines and strategies relied on a retrospective
Published online June 26, 2008. Address correspondence and reprint requests to: C. Y. Lo, MS; E-mail:
[email protected] Published by Springer Science+Business Media, LLC 2008 The Society of Surgical Oncology, Inc.
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analysis of a large cohort of patients cumulated over a relatively long study period. The treatment for ATC includes surgery, radiotherapy (RT), chemotherapy, and/or combination modalities. However, the treatment strategies are often palliative. Despite an effective palliative modality, extensive surgical resection can be associated with a relatively high morbidity rate.8 On the other hand, RT alone is frequently unable to control and palliate the bulky disease in the neck.9 Some studies suggest that a multidisciplinary approach that combines surgery with postoperative RT and chemotherapy will improve survival in selected patients.10–16 In the present study, we update our experience in management of ATC by enumerating the clinicopathological features, treatment, and outcome of a larger cohort of patients treated over the past four decades. The contribution of adjuvant RT and chemotherapy is also evaluated. Prognostic factors potentially affecting survival are identified, and any potential improvement in the outcome of patients recently treated is evaluated.
METHODS From 1966 to 2006, there were 54 patients identified in our thyroid cancer database to have ATC. They were all confirmed to have ATC after histological review of specimens taken via biopsy or resection by a single pathologist as well as from the autopsy reports. Four patients were excluded from the analysis because of incomplete records. Demographic data, clinical presentation, pathological details, treatment modalities received, and clinical outcome with reference to cancer-specific survival were reviewed and analyzed retrospectively. All patients were followed up until the time of death or last follow-up. In our institution, surgical resection was considered as the primary treatment modality, and chemoirradiation was administered postoperatively in the presence of residual disease after incomplete resection. Chemoirradiation was only considered as the procedure of choice for patients with widely metastatic disease, grossly unresectable disease, and/or poor performance status at the time of presentation with an aim of following surgical resection. Survival was calculated by the Kaplan-Meier method, and potential factors affecting survival were compared with the log rank test. Patients who survived 2 years or more were considered to be potential long-term survivors. Potential prognostic factors such as sex, age (£65 years), presence of metastatic
disease, era of diagnosis (before and after 1996), undergoing surgical resection, anaplastic transformation from recurrent papillary carcinoma, and administration of external RT or chemotherapy were analyzed. The v2 test and Student’s t-test were used to compare the categorical and continuous parameters, respectively, between the long-term survivors and those who were not. RESULTS The demographic data of the 50 ATC patients are summarized in Table 1. There were 16 men and 34 women with a median age of 72 years at the time of presentation (range, 36–104 years). All patients in our cohort were ethnic Chinese. At first presentation, all patients were symptomatic; most patients (88%) had a neck mass. The median duration of symptoms before presentation was 4 months (range, a few hours to >5 years). Moreover, 28 patients (56%) had pressure symptom, and 17 patients (34%) complained of hoarseness of voice. Seventeen patients (34%) had concomitant clinical detectable cervical lymph node metastases; distant metastases were clinically present in nine patients (18%). Three patients had a history of thyrotoxicosis treated with radioactive iodine before presentation. One patient had a history of nasopharyngeal cancer, and one had a history of basal cell carcinoma treated before presentation. Notably, seven patients were initially diagnosed with recurrent papillary thyroid carcinoma and were treated with thyroidectomy followed by radioiodine. The disease transformed into ATC over a median duration of 6 years (range, 2–16 years). Fine-needle aspiration of the thyroid mass was performed for 36 patients (72%) and confirmed the TABLE 1. Demographic data of 50 patients with anaplastic thyroid cancer Characteristic Sex (M:F), n (%) Age (y) Median Range Era of diagnosis (n) 1996 and before After 1996 Clinical presentation, n (%) Neck mass Pressure symptom Hoarseness Cervical lymph node involvement Metastatic disease
Value 16:34 (32:68) 72 36–104 26 24 44 28 17 17
(88) (56) (34) (34)
9 (18)
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diagnosis in 26(52%). Primary surgical treatments were performed for 34 (68%) with curative intent in 16 patients. Of these, 28 patients received total thyroidectomy, 3 patients received subtotal thyroidectomy, 2 patients received lobectomy, and 1 patient had radiofrequency ablation of the tumor. Concomitant neck dissection was performed for 13 patients, including 1 patient with bilateral neck dissections. The median tumor size was 6 cm (range, 1–15 cm). Sixteen (32%) did not receive any surgical resections. Among them, two patients did not receive any surgery because of advanced age and poor performance status. Seven patients had locally extensive disease not amenable to surgery, and two of them required emergency tracheostomy to relieve airway obstruction. The remaining seven patients were diagnosed as having ATC by biopsy without receiving any treatment, or were revealed to have the disease by postmortem examination. These 16 patients were mostly treated with supportive care or occasionally with RT or chemotherapy for palliation. They experienced a rapid deteriorating clinical course, with a median survival of 18 days (range, 4– 50 days) from time of diagnosis. Apart from surgical treatment, RT to the neck was administrated to 23(46%), and 18 patients (36%) received chemotherapy either as part of a chemoirradiation regime or alone for metastatic disease. Figure 1 illustrates the Kaplan-Meier survival of our patient cohort. The overall median survival was 97 days; the 1- and 3-year survivals were 14% and 8%, respectively. Forty-nine patients died over a median of 3 months (range, 4 days to 16 years). Five (10%) were regarded as long-term survivors, and they all had their pathology specimens reviewed. They died over a median of 6 years (range, 3– 16 years). The remaining 45 patients (90%) who were not regarded as long-term survivors died over a median of 3 months (range, 4 days to 22 months). Although the sex distribution was similar among the long-term survivors and those who were not (P = .7), the long-term survivors were statistically significantly younger at diagnosis (60 vs. 73 years, P = .029). No long-term survivors had metastatic disease at presentation when compared with 25% metastatic disease detected in those who were not long-term survivors. However, the difference was not statistically significant (P = .27). Moreover, all longterm survivors had received surgical resection compared with 64% of those who were not (P = .1), and a higher proportion of long-term survivors received postoperative RT (80% vs. 42%, P = .1). There were no statistically significant differences between Ann. Surg. Oncol. Vol. 15, No. 9, 2008
FIG. 1. Kaplan-Meier survival of anaplastic thyroid cancer patients.
the long-term survivors and those who were not receiving chemotherapy (40% vs. 36%, P = .8). At the time of analysis, only one patient still survived 9 years after total thyroidectomy for a 4-cm papillary thyroid cancer with a focus of anaplastic transformation. She received RT and chemotherapy as adjuvant therapy. Interestingly, the patients who developed ATC after transformation from underlying papillary thyroid carcinoma had similar clinical courses and survival as de novo ATC patients. On univariate analysis of those risk factors for survival, patient age £65 years (P = .025), surgical resection (P < .01), external radiation to the neck (P < .01), and no metastatic disease at presentation (P = .02) were highly significantly associated with an improved survival; sex (P = .28), era of diagnosis (before and after 1996) (P = .7), anaplastic transformation of recurrent papillary carcinoma (P = .5), and receipt of chemotherapy (P = .3) did not statistically significantly affect survival (Table 2 and Fig. 2). However, none of these factors was found to be significant in the multivariate analysis.
DISCUSSION Although our study is retrospective in nature, it is one of the biggest series of ATC in the literature. Moreover, it is now recognized that many previously described cases of undifferentiated thyroid cancer are actually cases of thyroid lymphoma or undifferentiated medullary thyroid cancer.17,18 In our present
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TABLE 2. Univariate analyses of potential prognostic factors affecting overall survival Univariate variable
No. of patients
Sex Male 16 Female 34 Age (y) £65 14 >65 36 Metastatic disease Metastases 9 No metastases 41 Era of diagnosis 1996 and before 26 After 1996 24 Anaplastic transformation of papillary thyroid cancer Yes 7 No 43 Surgical resection Yes 34 No 16 External radiotherapy to neck Yes 23 No 27 Chemotherapy Yes 18 No 32
P value .28 .025 .02 .7 .5
