Changing Management in Patients with Papillary Thyroid Cancer

Opinion statement The incidence of thyroid cancer has been increasing over the past 30 years, and it is now the seventh most common cancer in women. Papillary thyroid cancer is the most common subtype of thyroid cancer, occurring in 80% of cases. Its main pattern of spread is to cervical lymph nodes, with distant metastases occurring uncommonly. Initial treatment of papillary thyroid cancer involves resection of the primary tumor, with resection of regional lymph nodes if involved with metastatic disease. Postoperative adjuvant therapy consists of radioactive iodine ablation for most patients, followed by thyroid-stimulating hormone (TSH) suppression with thyroxine. An ongoing controversy in the surgical treatment of papillary thyroid cancer is that of extent of thyroid gland and nodal resection. Consensus guidelines recommend total or near-total thyroidectomy, rather than thyroid lobectomy, as the initial procedure of choice, given its advantages of treating potential multicentric disease, facilitating maximal uptake of adjuvant radioactive iodine, and facilitating the post-treatment follow-up by monitoring serum thyroglobulin (Tg) levels. In the hands of an experienced endocrine surgeon, complication rates are comparable to those for lobectomy. Major changes in the management of patients with papillary thyroid cancer over the last 10 years include the use of preoperative neck ultrasound, which can detect nonpalpable cervical lymph node metastases and potentially change the initial operation. In addition, neck ultrasound and measurement of serum Tg levels have taken the place of routine whole body radioactive iodine scans in the postoperative follow-up of patients with papillary thyroid cancer. Recurrent locoregional cervical lymph node disease should be treated by compartmental lymph node dissection, followed by another treatment dose of radioactive iodine. Chemotherapy is generally ineffective for the treatment of metastatic disease. For those patients whose tumor has become radioactive iodine resistant, emerging therapies include redifferentiation agents, antiangiogenic agents, and multi-tyrosine kinase inhibitors.     

Clinical presentation and clinical outcomes in Chernobyl-related paediatric thyroid cancers: what do we know now? What can we expect in the future?

Over the last 20 years, nearly 5000 cases of differentiated thyroid cancer have been diagnosed and treated in the regions of Russia, Ukraine and Belarus in young people previously exposed to the Chernobyl radioactive fallout during childhood. At diagnosis, 60-70% of the Chernobyl-related paediatric thyroid cancers had clinically evident cervical lymph node metastases (N1) and 10-15% had distant metastases (M1). Despite early reports suggesting that the paediatric thyroid cancer cases that developed after exposure to Chernobyl fallout were particularly aggressive, it now seems that the initial presentation and early clinical course of most of these cases are very similar to both non-radiation-associated paediatric thyroid cancers and thyroid cancers that arise after exposure to external beam irradiation. Over an average clinical follow-up period of about 10 years, the disease-specific mortality rate in these paediatric thyroid cancer cases that developed after the Chernobyl accident is quite low (1% or less). As would be expected in paediatric thyroid cancer, short-term recurrence rates range from 7 to 28% in published reports (mean 17%). However, long-term studies of paediatric thyroid cancer suggest that although the 30 year disease-specific mortality rate should be about 1%, the risk of developing structural disease recurrence is nearly 30% (of which 80% are expected to be locoregional recurrences and 20% are probably new distant metastases). Projected over 30 years of follow-up, a 1% disease-specific mortality in this cohort of 5000 patients would equate to about 50 deaths directly attributable to thyroid cancer. However, a 30% recurrence rate would also mean that about 1500 patients may develop a clinically meaningful recurrence that would need to be diagnosed and treated. It is imperative that we continue to work with our colleagues in Belarus, Ukraine and Russia to ensure that this large volume of patients destined to develop clinically significant recurrences are diagnosed and treated in a timely manner. Ready access to modern disease detection tools (serum thyroglobulin, postoperative neck ultrasonography, cytology/pathology support, and radioactive iodine scanning) and treatments (surgery for recurrent disease, radioactive iodine therapy) in their major academic centres are mandatory if we expect to achieve the excellent clinical outcomes that should be seen when paediatric thyroid cancer recurrence is diagnosed early and treated appropriately.     

Risk of second malignancies among survivors of pediatric thyroid cancer

Background

Thyroid carcinoma is a very rare tumor in the pediatric age group, accounting for only 1.5–3% of childhood carcinomas in the United States and Europe. We aimed to identify the risk of a second malignancy among pediatric thyroid cancer survivors.

Methods

The cohort analysis consisted of pediatric cancer patients aged less than 20 years, diagnosed with a primary thyroid cancer, identified by site code ICD-0-3: C739, and reported to the SEER 9 database between 1973 and 2013. They were followed up until December 31, 2013; the end of the study period, or up to death if earlier.

Results

Out of 1769 patients diagnosed primarily with thyroid carcinoma, 42 patients had a total of 45 incidences of subsequent malignancies. The mean age of patients at the initial diagnosis of thyroid cancer was 16 years. Females (90.5%) had a significantly higher incidence of second malignancies (SM) than males (9.5%). The overall Standardized Incidence Ratio (SIR) of SM in the study patients was higher than expected (SIR?=?1.48). Some specific sites showed significantly higher incidences: the salivary glands (SIR?=?33.95), the gum and other parts of the mouth [excluding the lips, tongue, salivary glands and floor of the mouth] (SIR?=?24.53)*** and the kidneys (SIR?=?5.72). The overall risk of SM in patients who had received radioactive iodine was higher than expected (SIR?=?4.41). The cumulative incidence of SM after treatment of thyroid cancer in children increases steadily over 40 years (11.92%).

Conclusions

Race, gender, histological subtypes, and radioactive iodine are potentially significant prognostic factors for the development of SM among pediatric thyroid cancer survivors. Identification of underlying mechanisms that raise the risk of SM is important for both treatment and follow-up strategies.

     

Clinical management and outcome of papillary and follicular (differentiated) thyroid cancer presenting with distant metastasis at diagnosis

BACKGROUND: Differentiated thyroid cancer has a good prognosis and only rarely presents with distant metastasis at diagnosis. The clinical outcome of this presentation was assessed with respect to survival and factors that may determine prognosis. METHODS: A retrospective review was undertaken of patients with stage M1 differentiated thyroid cancer at presentation (n = 49), referred from 1980-2000 at a single institution. RESULTS: The median age was 68 (range, 17-90), with 69% females. The initial site(s) of metastasis were lung only, 45%, bone only, 39%, other single site, 4%, and multiple sites, 12%. Histology: papillary, 51%, follicular, 49%. Initial treatment(s) included: thyroidectomy, 82%, radioactive iodine (RAI), 88%, excision of metastasis, 29%, radiotherapy, 47%, and chemotherapy, 6%. With a median follow-up time of 3.5 years, 25 patients are alive (51%) and 24 died (49%), with 3-year and 5-year actuarial survivals of 69% and 50%, respectively. Only a minority of patients (4/25, 16%) had no clinical evidence of disease at last follow-up. Most deaths (17/24, 71%) were due to progressive cancer. Prognosis was associated with age, site of metastasis, histology, and iodine avidity of the metastasis. Patients aged 45 years (P = .001). The 3-year survival for lung only versus bone only metastasis was 77% versus 56% (P = .02); for papillary versus follicular carcinoma, 75% versus 62% (P = .006); for iodine-avid disease (n = 29) versus not avid (n = 14), 82% versus 57% (P = .02), respectively. In multivariate analysis after adjusting for age, only histology and iodine avidity remained significant for survival. The hazard ratio for follicular histology was 3.7 (95% confidence interval [CI], 1.1-12.1, P = .03), and for tumors not avid for iodine, 3.4 (95% CI, 1.2-9.2, P = .02). CONCLUSIONS: The data support the aggressive management of patients presenting with stage M1 thyroid cancer, with thyroidectomy and RAI. Complete clinical eradication of disease was rarely seen, and 50% of patients survived for more than 5 years. Young patients with papillary tumors and/or iodine-avid disease have an even better prognosis.     

Standard and Emerging Therapies for Metastatic Differentiated Thyroid Cancer

Differentiated thyroid cancer accounts for >90% of cases of thyroid cancer, with most patients having an excellent prognosis. Distant metastases occur in 10%–15% of patients, decreasing the overall 10-year survival rate in this group to 40%. Radioactive iodine has been the mainstay of treatment for distant metastases, with good results when lesions retain the ability to take up iodine. For patients with metastatic disease resistant to radioactive iodine, treatment options are few and survival is poor. Chemotherapy and external beam radiotherapy have been used in these patients, but with disappointing results. In recent years, our understanding of the molecular pathways involved in thyroid cancer has increased and a number of molecular targets have been identified. These targets include the proto-oncogenes BRAF and RET, known to be common mutations in thyroid cancer; vascular endothelial growth factor receptor and platelet-derived growth factor receptor, associated with angiogenesis; and the sodium-iodide symporter, with the aim of restoring its expression and hence radioactive iodine uptake. There are now multiple trials of tyrosine kinase inhibitors, angiogenesis inhibitors, and other novel agents available to patients with metastatic thyroid cancer. This review discusses both traditional and novel treatments for metastatic differentiated thyroid cancer with a particular focus on emerging treatments for patients with radioactive iodine–refractory disease.     

Papillary thyroid cancer: Surgical management of lymph node metastases

Opinion statement Papillary thyroid cancer (PTC), the most common thyroid malignancy, is associated with cervical lymph node metastases in 30% to 90% of patients. While surgery is the primary treatment modality for PTC, radioactive iodine and thyroid hormone suppression often complement the treatment plan. Although thyroid hormone suppression may decrease the incidence of recurrent disease and radioactive iodine may diagnose and treat metastases, lymph node dissection (LND) is the mainstay treatment for clinically evident cervical lymph node metastases. The surgical treatment options published in the literature include the traditional radical LND, the modified radical LND, the selective LND (compartment-based resection based on documented lymph node metastases), and a ‘berry picking’ resection (in which only the grossly abnormal lymph nodes are excised). At the University of California, San Francisco, we prefer the modified radical LND with preservation of the cervical sensory nerves for the first lymph node dissection with the ‘berry picking’ procedure limited to surgical treatment of recurrent nodal metastases in previously resected lymph node basins. Some centers are evaluating the potential role of sentinel lymph node biopsies for PTC. While the extent of lymphadenectomy is debated, most physicians treating patients with PTC agree that clinical evidence of lymphatic metastases should be surgically exercised and there is no role for prophylactic LND.     

Modern management of differentiated thyroid cancer

The outcome in differentiated thyroid cancer is excellent. Simple prognostic factors, including the age of the patient at diagnosis, the size of the primary cancer, completeness of surgical excision, and the presence of distant metastases, allow the clinician to judge how a patient will do. The preferred treatment is total thyroidectomy and in selected patients radioactive iodine can be used to ablate residual thyroid or functioning metastases in lymph nodes and distant sites. The physician has two excellent methods for following the patient: the whole-body scan with radionuclides of iodine, and measurement of serum thyroglobulin. In patients with elevated thyroglobulin and negative scans with radioactive iodine, there is increasing evidence that positron emission tomography (PET) is helpful in locating the site of thyroglobulin production.     

Differentiated thyroid carcinomas in children and adolescents

An analysis of differentiated thyroid carcinomas in children and adolescents revealed that the incidence was 3.05% of total number of patients with differentiated thyroid cancers in all age groups. There was a female preponderance. The incidence of papillary, follicular and papillary with follicular elements was equal. There were no papillary carcinomas observed in children younger than 10 years. The predominant mode of presentation was a solitary nodule of thyroid and some of them had associated cervical adenopathy. A considerable number presented with only cervical adenopathy. The incidence of nodal metastases was 50% at time of presentation and lung involvement was present in 15% of children at the time of diagnosis. Radioiodine treatment was given in 70% of children. Ablation was achieved in 86% of patients given two doses of radioiodine (200 millicuries). The more resistant cases were those with lung and nodal metastases. There was complete ablation in 100% with only residual thyroid tissue, 83% in those with associated nodal metastases, and 57% in those with lung involvement. Average duration of follow-up was 10.3 years (range, 2 to 19 years). Recurrence rate or relapse was observed in 8.5% and was in the regional nodes. There was no recorded mortality due to the disease.     

Brain metastases of malignant germ cell tumors in children and adolescents

BACKGROUND: Brain metastases of pediatric germ cell tumors are uncommon, and there is limited information regarding their incidence, clinical presentation, response to treatment, and influence on survival. METHODS: The authors reviewed the experience with brain metastases from pediatric germ cell tumors at St. Jude Children's Research Hospital (Memphis, TN) over a 40-year period. RESULTS: Between March 1962 and February 2002, 16 of 206 patients with germ cell tumors (7.8%) had brain metastases at the time of initial presentation (n = 2), later in the course of the illness (n = 12), or at autopsy (n = 2). Twelve of 16 patients (75%) had symptoms referable to the brain (nausea/emesis, headaches, or seizures), and 14 (88%) had pulmonary metastases at the time brain metastases were identified. Patients with brain metastases were more likely to have an extragonadal primary tumor (P = 0.013), advanced-stage disease at initial presentation (P = 0.016), and choriocarcinoma within the primary tumor (P < 0.001). The incidence of brain metastases was significantly lower in the second 2 decades of the study period (5 of 135 patients [3.7%]) than in the first 2 decades (11 of 71 patients [15.5%]; P = 0.005). Two of the 16 patients in the current study are long-term survivors. CONCLUSIONS: Brain metastases are uncommon in childhood germ cell tumors, and their incidence appears to be decreasing. In the current study, most patients with such metastases were symptomatic and had pulmonary metastases at the time brain metastases were identified. Patients with the highest risk of developing brain metastases include those with extragonadal tumors, those with high disease stage at initial presentation, and those with choriocarcinoma as a component of the primary tumor. The probability of survival is poor, although a small proportion of patients may become long-term survivors.     

Papillary thyroid cancer

Opinion statement Papillary thyroid cancer (PTC), the most common thyroid malignancy, is associated with an excellent prognosis. Overall survival is more than 90%. The first-line treatment is surgical excision, and although the debate continues as to whether a total thyroidectomy or thyroid lobectomy should be recommended, most patients at the University of California, San Francisco are treated with a total thyroidectomy. Not only has this been shown to be superior for overall survival in select patient populations, but local recurrence is also significantly lower with this approach. Total thyroidectomy also optimizes the adjuvant treatment options that are unique to “differentiated” thyroid cancer because these malignant cells retain many of the features of the native thyroid follicular cell. These cellular features are used for specialized investigations and treatment options in patients with PTC. For example, PTC cells retain the ability to produce thyroglobulin, to be stimulated by thyroidstimulating hormone (TSH), and to take up iodine. These features are vital and separate differentiated thyroid cancer from other epithelial malignancies because such features can be used in clinical follow-up (monitoring serum thyroglobulin levels, whole body radioactive iodine scans) and in the treatment of patients with PTC (TSH suppression, radioactive iodine ablation of thyroid remnant, local recurrences, and regional or distant metastases). In summary, the wide array of treatment options for patients with PTC includes surgery, radioactive iodine, thyroid hormone suppression of TSH, external beam radiation (less commonly), and rarely, chemotherapy. This continues to be an area of exciting research for emerging therapy, much of which concentrates on enhancing or re-establishing the differentiated features of the thyroid cancer cell, in an effort to optimize the adjuvant treatment options. The treatment options that are chosen depend on patient factors, disease factors, and the decisions of the patient and treatment team.     

Follicular adenoma and carcinoma of the thyroid gland

Follicular neoplasms of the thyroid gland include benign follicular adenoma and follicular carcinoma. Currently, a follicular carcinoma cannot be distinguished from a follicular adenoma based on cytologic, sonographic, or clinical features alone. The pathogenesis of follicular carcinoma may be related to iodine deficiency and various oncogene and/or microRNA activation. Advances in molecular testing for genetic mutations may soon allow for preoperative differentiation of follicular carcinoma from follicular adenoma. Until then, a patient with a follicular neoplasm should undergo a diagnostic thyroid lobectomy and isthmusectomy, which is definitive treatment for a benign follicular adenoma or a minimally invasive follicular cancer. Additional therapy is necessary for invasive follicular carcinoma including completion thyroidectomy, postoperative radioactive iodine ablation, whole body scanning, and thyrotropin suppressive doses of thyroid hormone. Less than 10% of patients with follicular carcinoma will have lymph node metastases, and a compartment-oriented neck dissection is reserved for patients with macroscopic disease. Regular follow-up includes history and physical examination, cervical ultrasound and serum TSH, and thyroglobulin and antithyroglobulin antibody levels. Other imaging studies are reserved for patients with an elevated serum thyroglobulin level and a negative cervical ultrasound. Systemic metastases most commonly involve the lung and bone and less commonly the brain, liver, and skin. Microscopic metastases are treated with high doses of radioactive iodine. Isolated macroscopic metastases can be resected with an improvement in survival. The overall ten-year survival for patients with minimally invasive follicular carcinoma is 98% compared with 80% in patients with invasive follicular carcinoma.     

Clinico-morphological peculiarities of thyroid cancer among children exposed to the Chernobyl disaster radiation

The paper deals with a comparison of clinico-morphological patterns of sporadic thyroid cancer and that in pediatric patients exposed to radiation during the Chernobyl disaster. The latter are highly prone to both local and regional metastatic spread to the lymph nodes (intrathyroid distribution--61%; extension through capsule--42%, and metastases to the neck lymph nodes--66%). However, these data do not differ significantly from those for intact areas. Yet, cancer occurs in exposed cohorts at an earlier stage: its incidence at age 4-6 is 2-3.5 higher and that of relapse such as presentation of latent metastases to the lymph nodes and tumor foci development in residual tumor tissue is 1.6 times the average. Also, morphological patterns have changed: typical papillary cancer incidence has dropped by half while the diffuse follicular variety has grown 1.8-fold.     

Differentiated thyroid cancer in children: diagnosis and management

PURPOSE OF REVIEW: Differentiated thyroid cancer is the most common endocrine malignancy in children. In 2006, the American Thyroid Association Guidelines Taskforce released detailed management recommendations for differentiated thyroid cancer, which primarily addressed the approach for treating adult patients. Children with differentiated thyroid cancer present with more advanced disease and yet have a more favorable outcome than adults. Thus optimal treatment for younger patients with differentiated thyroid cancer may differ from that for adults. RECENT FINDINGS: All available data regarding differentiated thyroid cancer treatment in children are retrospective. In the past year, several large case series have been published that strengthen the argument for total thyroidectomy at the time of diagnosis, followed by administration of radioactive iodine for remnant ablation. There have also been recent advances in understanding the genetic abnormalities associated with pediatric thyroid cancer. SUMMARY: The optimal treatment of differentiated thyroid cancer in pediatric patients continues to be debated. Recent publications from institutions around the world provide useful data regarding current approaches to this unusual disease. Further collaborative studies are needed to further refine the surgical approach, particularly the extent of lymph-node dissection, radioactive iodine dosing, and the role of genetic analysis in diagnosis and clinical approach.     

Follicular thyroid cancer

Patients with differentiated thyroid cancer generally have a good prognosis and high cure rates; however, subgroups of patients exist who develop progressive disease with significant morbidity and mortality. We analyzed the clinical outcome of patients with follicular thyroid cancer and distant metastases to define their presentation, impact of therapy and clinical outcome. A group of 44 patients with follicular thyroid cancer which had metastasized to the lungs or the skeleton was identified. All patients were treated at M.D. Anderson Cancer Center between 1965 and 1994. The group included 26 women and 18 men, with a median age of 56 years (range, 23 to 80 years). The primary tumor was limited to the thyroid in most cases. At the time of writing 13 patients were alive with metastatic disease a median of 43 months (range, 4 to 230 months) after diagnosis, while 27 patients died of thyroid cancer a median of 83 months (range, 4 to 238 months) after diagnosis. Bone pain was the chief complaint in almost all the 24 patients in whom distant metastases were present at diagnosis. In the 20 patients who initially presented with localized disease, distant metastases to the skeleton and/or lungs were detected after a median interval of 53 months (range, 8 to 216 months). Symptomatic spinal cord compression occurred in 13 patients and preceded their death by 4 to 34 months. Radioiodine uptake was seen in most bone metastases but in only about half of metastatic foci in the lungs. Radiotherapy was palliative and useful for bone metastases. We conclude that patients with follicular thyroid cancer and distant metastases have a distinct clinical profile that includes prominent skeletal and pulmonary involvement and substantial morbidity and mortality. Intensive multimodality therapy is required to optimize the clinical outcome.     

Management of well-differentiated thyroid carcinoma presenting within a thyroglossal duct cyst

BACKGROUND AND OBJECTIVE: Well-differentiated thyroid carcinoma (WDTC) is diagnosed in approximately 1.5% of thyroglossal duct cysts (TGDC). No clear consensus exists regarding further management after adequate excision of the cyst, especially the role of total thyroidectomy and postoperative radioactive iodine therapy. The current review was undertaken in an attempt to clarify these issues. METHODS: Demographic, clinical, tumor, treatment, pathology, and outcome data on 57 eligible patients reported in recent literature were pooled together with 5 patients treated at our institution for this analysis. RESULTS: A Sistrunk operation was performed for resection of the thyroglossal duct cyst in the majority (90%) of patients. Histologic examination of the tumor in the cyst revealed that papillary carcinoma was the most frequent (92%) histologic type. A total thyroidectomy was performed consequent to the diagnosis of thyroglossal duct cyst carcinoma in approximately half of the 62 patients. A malignant tumor was reported in 27% of the thyroidectomy specimens. Postoperative radioactive iodine therapy was administered in 16 (26%) patients. With a median follow-up of 71 months (range 1-456 months), the 5- and 10-year Kaplan-Meier overall survival was 100 and 95.6%, respectively. There were no disease-related deaths reported in any of the patients. Univariate analysis revealed that the only significant predictor of overall survival was the extent of primary surgery for the thyroglossal cyst. The addition of total thyroidectomy to Sistrunk operation did not have a significant impact on outcome (P = 0.1). Patients treated with postoperative radioactive iodine (RAI) fared significantly worse than those that did not need RAI, which may be explained by the fact that this modality would generally be used in patients with higher risk tumors. CONCLUSIONS: The Sistrunk operation is adequate for most patients with incidentally diagnosed TGDC carcinoma in the presence of a clinically and radiologically normal thyroid gland. Results of adequate excision using the Sistrunk operation are excellent and the concept of risk-groups should be used to identify patients, who would benefit from more aggressive treatment.     

Survival of patients with pulmonary metastases in differentiated thyroid cancer

To clarify the factors affecting survival of the patients with differentiated thyroid cancer and pulmonary metastases, 46 patients treated at our hospital during the past 23 years were studied using statistical analysis. Nineteen patients died as a result of their thyroid cancer. The follow-up period ranged from 1 to 31 years with a median of 10.5 years. Age at primary surgery, interval between primary surgery and appearance of pulmonary metastases and RI therapy affected survival from primary surgery and age at pulmonary metastases and RI therapy determined survival after pulmonary metastases, as revealed by the Cox proportional hazard model. These results suggest that prognostic factor of patients with differentiated thyroid cancer and pulmonary metastases is the age at initial surgery and at appearance of pulmonary metastases. But RI therapy could change the course of pulmonary metastases of thyroid cancer.     

Prognostic factors in patients with Hürthle cell neoplasms of the thyroid

BACKGROUND: Hürthle cell neoplasms, often considered a variant of follicular thyroid neoplasms, represent 3% of thyroid carcinomas. Only a handful of publications have focused on the biologic behavior, prognostic factors, and treatment outcomes of Hürthle cell carcinoma. The objective of the current study was to identify the clinical and pathologic features of Hürthle cell carcinomas that predict disease progression or death. METHODS: The authors reviewed medical records of patients who were treated for Hürthle cell carcinoma (HCC) and Hürthle cell adenoma (HCA) at The University of Texas M. D. Anderson Cancer Center from March 1944 to February 1995, including follow-up information. The pathologic diagnosis was confirmed by one of the authors. RESULTS: The authors identified 127 patients with Hürthle cell neoplasms, 89 patients with HCC and 38 patients with HCA. Seven patients with HCC had foci of anaplastic thyroid carcinoma. Survival for this subgroup was worse compared with the overall group and was analyzed separately. The HCC group was significantly older (age 51.8 years vs. age 43.1. years) and had larger tumors (4.3 cm vs. 2.9 cm) compared with the HCA group. No differences were seen in gender or previous radiation exposure. Forty percent of patients in the HCC group died of thyroid carcinoma, whereas no patients in the HCA group died of the disease. There has been no improvement in all-cause and disease specific mortality in the past 5 decades for patients with these neoplasms. Conventional staging systems predicted mortality with minor differences. Of the patients with known metastasis, 38% showed radioiodine uptake. Univariate analysis identified older age, higher disease stage, tumor size, extraglandular invasion, multifocality, lymph node disease, distant metastasis, extensive surgery, external beam radiation therapy, and chemotherapy as factors that were associated with decreased survival. Tumor encapsulation was associated with improved survival. Although radioactive iodine treatment had no overall effect on survival, subgroup analysis showed that patients who received radioactive iodine for adjuvant ablation therapy had better outcomes compared either with patients who did not receive radioactive iodine or with patients who received radioactive iodine as treatment for residual disease. Multivariate analysis indicated that older age and larger tumor size predicted worse survival through an association with worse behaving tumors (multifocal, less encapsulated, and with extraglandular invasion). The decreased survival in patients with lymph node metastases may be explained by its association with distant metastases. The association of extensive surgery, external beam radiation therapy, and chemotherapy with worse survival also disappeared once those factors were analyzed together with other prognostic factors, such as distant metastases. CONCLUSIONS: Several clinical and pathologic prognostic factors were identified in patients with HCC and HCA. Older age and larger tumor size predicted reduced survival. Radioactive iodine therapy may confer a survival benefit when it is used for adjuvant ablation therapy, but not when residual disease is present. The authors could not demonstrate a survival benefit for the use of extensive surgery, external beam radiation therapy, or chemotherapy.     

Selective surgery and adjuvant therapy based on risk classifications of well-differentiated thyroid cancer

BACKGROUND: The prognosis of well-differentiated thyroid cancer has been stratified into low- and high-risk groups. These risk groups can be used to predict prognosis and to guide treatment. METHODS: Retrospective study of 962 patients with well-differentiated thyroid cancer treated from 1940 to 1998. Stratification into low- and high-risk groups based on age, metastases, extent, and size (AMES). Effects on survival of surgery, lymph node dissection, and radiation therapy were examined. RESULTS: Seven hundred twenty-eight cases were papillary and 234 were follicular carcinoma. Seven hundred-fifty cases were low risk and 207 high risk. Twenty-year survival was 97.4% in the low-risk patients and 54.0% in high-risk patients (P < 0.001); it was 63.2% in the younger high-risk group and 41.0% in the older high-risk group (P < 0.001). Older high-risk patients had a survival advantage with bilateral thyroidectomy. Extent of surgery did not change survival in either the younger high-risk group or the low-risk group. Lymph node dissection and radioactive iodine ablation did not have an impact on survival. DISCUSSION: Well-differentiated thyroid cancer in low-risk patients has a favorable outcome regardless of treatment. Low-risk patients can be safely treated with unilateral thyroidectomy alone. Risk stratification with a modification of the AMES criteria can be used to guide treatment.     

Distant metastases in papillary thyroid cancer. A review of 91 patients

Of 731 patients with papillary thyroid cancer, 91 had metastases outside regional lymph nodes. The most common site was intrathoracic, occurring in 73 of the 91 patients. Miliary, micronodular pulmonary metastases, with iodine 131 (I-131) uptake and "curable" by I-131 treatment were encountered in seven patients. It has not been established whether this was a transient stage in additional patients. In 38 patients rounded, macronodular pulmonary metastases were found. Another 21 patients had unilateral pulmonary infiltration and mediastinal enlargement. Pulmonary infiltrations may be hematogenic, or may possibly occur via regional, mediastinal lymph nodes. Mortality within 1 year of the diagnosis of distant metastases exceeded 50%. Occurrence of distant metastases showed a slight but highly significant association with male sex, advanced age, and advanced local tumor stage. Better prognostic determinants are, however, required if adequate of the individual patient with papillary thyroid cancer is to be achieved.     

Survival in patients with papillary thyroid cancer is not affected by the use of radioactive isotope

INTRODUCTION: Papillary cancer is the most common neoplasm of the thyroid. The mainstay of treatment is thyroidectomy, but most patients are additionally treated with radioactive iodine (RAI). Its utility is controversial. This study seeks to determine whether RAI use affects patient outcome and to identify specific cohorts of patients that benefit from its use. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database is a large-scale sample of approximately 14% of the US population. It was used to identify patients with papillary carcinoma of the thyroid. Statistical analyses were used to compare prognostic factors such as lymph node status, age, tumor size, and treatment with RAI. RESULTS: A total of 14,545 patients were identified in SEER as having papillary cancer of the thyroid. Multivariate analysis showed significantly worse outcome in patients with age>45 years, tumor size >2 cm, lymph node disease, and distant metastases. Multivariate analysis failed to show RAI significantly affecting mortality. Survival between those not treated with RAI was similar to those whose treatment included it (P = 0.9176). Subgroup analysis identified patients older than 45 years with primary tumors >2 cm and disease in the lymph nodes with distant metastatic disease as the only group positively affected by RAI. CONCLUSIONS: Despite its widespread use in the treatment of well-differentiated papillary cancer of the thyroid, RAI only affects a survival advantage in older patients with large primary tumors involving the lymph nodes and with distant spread. Treating other patient groups is costly and offers no improvement in outcome.