Abstract
Purpose
Little is known about prognostic factors and treatment outcomes in young patients with anaplastic thyroid cancer (ATC). The goal of this study is to define the clinical features of this subgroup.
Material and methods
Patients age 55 or younger with either ATC or well-differentiated thyroid cancer (WDTC) with anaplastic changes were identified using electronic medical record at the Cleveland Clinic. The same number of patients older than 55 was randomly selected to serve as control. Progression-free survival (PFS), overall survival time (OST) and cause-specific mortality (CSM) were measured against age, tumor histology, extent of disease, and treatment modalities.
Results
Twelve patients age 55 or younger were identified. The median age was 51 years. Four patients had WDTC with anaplastic components — mixed tumor group (MTG). Their median PFS, OST, and CSM at 24 months were 21.5 months, 51 months, and 25%, respectively. For the other 8 patients who had pure ATC, their median PFS, OST, and CSM were 3.5 months, 6 months, and 100%, respectively. Patients in the MTG had better survival compared to the pure ATC and control group in terms of PFS (p = 0.0047 and p = 0.0053), OST (p = 0.0028 and p = 0.0029) and the CSM at 24 months (p = 0.0339 and p = 0.0096). In the pure ATC group, patients with positive cervical lymph node and distant metastases had similar overall survival outcomes (6 vs. 8 months, p = 0.4995).
Conclusion
Prognostic factors favoring survival in young patients with ATC include ATC arising within WDTC. Once full anaplastic transformation occurs, age was not a significant factor in survival.
1
Introduction
Malignant thyroid cancers account for approximately 1% of all new cancers . Of these, more than 95% of the cancers are derived from the follicular epithelial cells of the thyroid gland and are further divided into subgroups depending on the degree of differentiation. These groups range from WDTC which comprises of > 90% of all thyroid cancer, including papillary and follicular carcinoma, to the rare undifferentiated or ATC which encompasses less than 2%–5% of all thyroid malignancies . Even though ATC accounts for only a small percentage of all thyroid malignancy, it is highly aggressive and is accountable for more than 50% of all thyroid cancer-related deaths in the United States in 2006 . ATC commonly arises in patient population older than age 60 with a peak incidence in the 6th to 7th decade of life . Despite improved understanding of this disease in recent years, treatment options remain limited and largely ineffective due to the aggressive nature of the cancer. Most patients present with nodal involvement or distant metastasis at the time of diagnosis. Majority of patients with ATC eventually die within two years of diagnosis, and long-term survival is exceedingly rare. Furthermore, there are very few reports of ATC in the younger patient population. The literature mainly consists of case reports, and therefore very little is known about prognostic factors and treatment outcomes in this subgroup of patients. The goal of this study is to define the clinical features of this younger ATC subgroup and to identify factors that might influence the long-term survival.
2
Methods
Patient data were retrospectively collected from a computer database at the Head and Neck Institute and the Department of Pathology at the Cleveland Clinic from the period of 1997–2011. The inclusion criteria for subgroup analysis were age 55 years or younger at time of diagnosis showing either ATC or WDTC with anaplastic changes on pathology. Patients with only WDTC or poorly differentiated thyroid cancer without signs of anaplastic change were excluded. The diagnosis was confirmed by dedicated, subspecialty head and neck pathologists through histological analysis of surgical specimens or through cytology in cases where surgery could not be performed. For survival comparison, an equal number of patients older than age of 55 with ATC were randomly selected from the same computer database using the same criteria to serve as the control group. Standard descriptive statistics were used to analyze patient demographic information, surgical, pathological, and nonsurgical treatment and follow-up data. Presenting signs and symptoms were evaluated and included those reported by patients prior to diagnosis ( Table 1 ). Patients in the younger age group were further divided into two separate groups depending on the tumor histology at the time of diagnosis — MTG and pure ATC group. The MTG consists of WDTC with early anaplastic transformation where the anaplastic component was less than 40% of the specimen. On the other hand, the purely ATC group consists of ATC without (or with minor foci of) well differentiated components. The extent of tumor involvement at the time of diagnosis was also evaluated and was divided into 4 groups — focal (intrathyroidal), local (extrathyroidal invasion of the surrounding soft tissue without regional lymph node metastasis), regional nodal involvement, and distant metastasis. The size of tumor was determined from imaging studies including ultrasound, computed tomography, magnetic resonance imaging or positron emission tomography. PFS was determined from the date of diagnosis to the date of documented progression. OST was determined from the date of diagnosis to the date of death or date of last follow-up. The overall CSM rates at 6, 12 and 24 months were also evaluated. PFS, OST, and CSM rates were measured against age, tumor histology, extent of disease at the time of diagnosis, and treatment modality. PFS and OST were analyzed using the Kaplan Meier analysis and survival comparisons were made using the log-rank test. All patients were followed until death, hospice, or up to December of 2011. This protocol was approved by the Cleveland Clinic Institutional Review Board.
| Younger age group (age < 55) | Control group (age > 55) | |
|---|---|---|
| N | 12 | 12 |
| Median age (range) | 51 (38–55) | 75.5 (66–83) |
| Gender | ||
| Male | 8 | 3 |
| Female | 4 | 9 |
| Median tumor size (cm) | 5.9 ± 2.53 | 5.6 ± 2.6 |
| Extend of disease at diagnosis | ||
| Intrathyroidal | 0 | 0 |
| Local | 2 | 3 |
| Nodal | 5 | 2 |
| Metastasis | 5 | 7 |
| Clinical presentation | ||
| Enlarging neck mass | 11 | 5 |
| Hoarseness | 7 | 5 |
| Dysphagia | 4 | 3 |
| Dyspnea | 4 | 0 |
| Respiratory distress | 0 | 3 |
2
Methods
Patient data were retrospectively collected from a computer database at the Head and Neck Institute and the Department of Pathology at the Cleveland Clinic from the period of 1997–2011. The inclusion criteria for subgroup analysis were age 55 years or younger at time of diagnosis showing either ATC or WDTC with anaplastic changes on pathology. Patients with only WDTC or poorly differentiated thyroid cancer without signs of anaplastic change were excluded. The diagnosis was confirmed by dedicated, subspecialty head and neck pathologists through histological analysis of surgical specimens or through cytology in cases where surgery could not be performed. For survival comparison, an equal number of patients older than age of 55 with ATC were randomly selected from the same computer database using the same criteria to serve as the control group. Standard descriptive statistics were used to analyze patient demographic information, surgical, pathological, and nonsurgical treatment and follow-up data. Presenting signs and symptoms were evaluated and included those reported by patients prior to diagnosis ( Table 1 ). Patients in the younger age group were further divided into two separate groups depending on the tumor histology at the time of diagnosis — MTG and pure ATC group. The MTG consists of WDTC with early anaplastic transformation where the anaplastic component was less than 40% of the specimen. On the other hand, the purely ATC group consists of ATC without (or with minor foci of) well differentiated components. The extent of tumor involvement at the time of diagnosis was also evaluated and was divided into 4 groups — focal (intrathyroidal), local (extrathyroidal invasion of the surrounding soft tissue without regional lymph node metastasis), regional nodal involvement, and distant metastasis. The size of tumor was determined from imaging studies including ultrasound, computed tomography, magnetic resonance imaging or positron emission tomography. PFS was determined from the date of diagnosis to the date of documented progression. OST was determined from the date of diagnosis to the date of death or date of last follow-up. The overall CSM rates at 6, 12 and 24 months were also evaluated. PFS, OST, and CSM rates were measured against age, tumor histology, extent of disease at the time of diagnosis, and treatment modality. PFS and OST were analyzed using the Kaplan Meier analysis and survival comparisons were made using the log-rank test. All patients were followed until death, hospice, or up to December of 2011. This protocol was approved by the Cleveland Clinic Institutional Review Board.
| Younger age group (age < 55) | Control group (age > 55) | |
|---|---|---|
| N | 12 | 12 |
| Median age (range) | 51 (38–55) | 75.5 (66–83) |
| Gender | ||
| Male | 8 | 3 |
| Female | 4 | 9 |
| Median tumor size (cm) | 5.9 ± 2.53 | 5.6 ± 2.6 |
| Extend of disease at diagnosis | ||
| Intrathyroidal | 0 | 0 |
| Local | 2 | 3 |
| Nodal | 5 | 2 |
| Metastasis | 5 | 7 |
| Clinical presentation | ||
| Enlarging neck mass | 11 | 5 |
| Hoarseness | 7 | 5 |
| Dysphagia | 4 | 3 |
| Dyspnea | 4 | 0 |
| Respiratory distress | 0 | 3 |
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