Clinical Status and Treatment of Liver Metastasis of Differentiated Thyroid Cancer Using Tyrosine Kinase Inhibitors.

BACKGROUND: Treatment of patients with liver metastasis of differentiated thyroid carcinoma (DTC) has not been sufficiently defined, because liver metastasis of DTC has been described mostly as case reports. Additionally, such patients are considered end-of-treatment responders. A relatively new approach using tyrosine kinase inhibitors (TKIs) may provide opportunities to manage systemic metastasis. This study aims to define the clinical features of DTC patients with liver metastasis and evaluate the benefits of TKIs. METHODS: We retrospectively analyzed clinical features of 29 patients (mean age 67.8 years) diagnosed with liver metastasis of DTC at our institution between January 1981 and May 2017. RESULTS: All patients had distant metastasis at other organ sites upon diagnosis of liver metastasis; 41% of them developed new metastasis afterward. Management after diagnosis of liver metastasis comprised palliative care (48%), radioactive iodine therapy (28%), and TKI therapy (24%). The median survival after diagnosis of liver metastasis was only 4.8 months. Survival rates were significantly better in patients with performance statuses between 0 and 2 on the Eastern Cooperative Oncology Group scale at diagnosis of liver metastasis (n = 22, 76%) treated with TKI compared to those who were not (P = 0.017; log-rank test; hazard ratio 0.19). One-year survival rates were 71.4 and 26.7% for patients treated with or without TKI, respectively. CONCLUSIONS: Patients with liver metastasis had poor clinical prognosis. When other distant metastases existed at diagnosis of liver metastasis, TKI therapy was considered an effective therapeutic option for patients with liver metastasis of DTC.

LONG-TERM OUTCOMES AND PROGNOSTIC FACTORS IN PATIENTS WITH DIFFERENTIATED THYROID CANCER AND DISTANT METASTASES.

OBJECTIVE: Distant metastatic spread is the most frequent cause of thyroid cancer-related death. The objective of this study was to evaluate overall and disease-related survival of patients with differentiated thyroid cancer (DTC) and distant metastases (DM) attending a single medical center and to investigate variables predictive of better long-term outcomes. METHODS: The Rabin Medical Center Thyroid Cancer Registry was searched for patients with DM from DTC. RESULTS: The cohort included 138 patients (58.7% female) diagnosed at age 54.7 ± 19.5 years. Mean primary tumor size was 33.9 ± 26 mm. Most patients (57.7%) were stage T3/T4; 48.7% had extrathyroidal extension; 53.5% had lymph node metastases. Histopathology yielded papillary and follicular thyroid carcinoma in 66.7% and 13.8%, respectively, and intermediate/poorly differentiated carcinoma in 19.6%. All but 2 patients underwent total thyroidectomy, and 133/138 (96.4%) received radioactive iodine (RAI) therapy. DM were synchronous in 55.1%. The mean follow-up was 8.2 years from detection of metastases. The common sites of metastases were the lungs (85.6% of patients), bones (39.9%), brain (5.8%) and liver (3.6%). At last follow-up, resolution was documented in 24.6% of patients, improvement/stable disease in 31.6%, and structurally progressive disease in 43.4%. By the end of the study, 40.6% of patients died, 23.2% of DTC. Improved overall survival and disease progression were associated with younger age, lung-only DM, and metastatic RAI avidity. CONCLUSION: Patients with DTC and DM treated by standard-of-care approaches frequently achieve favorable long-term outcomes. Novel therapies might be necessary in only a minority of these patients, and the reported prognostic factors can aid in their identification. ABBREVIATIONS: CR = complete response; DM = distant metastases; DTC = differentiated thyroid cancer; ETE = extra-thyroidal extension; M0 = detected during follow-up; M1 = detected at diagnosis; MSKCC = Memorial Sloan Kettering Cancer Center; NED = no evidence of disease; OS = overall survival; PFS = progression free survival; PTC = papillary thyroid cancer; RAI = radioactive iodine; Tg = thyroglobulin.

Delay to curative surgery greater than 12 weeks is associated with increased mortality in patients with colorectal and breast cancer but not lung or thyroid cancer.

BACKGROUND: Surgery for cancer is often delayed due to variety of patient-, provider-, and health system-related factors. However, impact of delayed surgery is not clear, and may vary among cancer types. We aimed to determine the impact of the delay from cancer diagnosis to potentially curative surgery on survival. METHODS: Cohort study based on representative sample of patients (n = 7,529) with colorectal, breast, lung and thyroid cancer with local or regional disease who underwent potentially curative surgery as their first therapeutic modality within 1 year of cancer diagnosis. They were diagnosed in 2006 and followed for mortality until April 2011, a median follow-up of 4.7 years. RESULTS: For colorectal and breast cancers, the adjusted hazard ratios (95 % confidence intervals) for all-cause mortality comparing a surgical delay beyond 12 weeks to performing surgery within weeks 1-4 after diagnosis were 2.65 (1.50-4.70) and 1.91 (1.06-3.49), respectively. No clear pattern of increased risk was observed with delays between 4 and 12 weeks, or for any delay in lung and thyroid cancers. Concordance between the area of the patient's residence and the hospital performing surgery, and the patient's income status were associated with delayed surgery. CONCLUSIONS: Delays to curative surgery beyond 12 weeks were associated with increased mortality in colorectal and breast cancers, suggesting that health provision services should be organized to avoid unnecessary treatment delays. Health care systems should also aim to reduce socioeconomic and geographic disparities and to guarantee equitable access to high quality cancer care.

Conservative management of well-differentiated thyroid cancer.

BACKGROUND: Controversy exists over the optimal surgical treatment of well-differentiated thyroid cancer. Conservative surgical management reduces the risk of complications and maintains an overall survival rate equivalent to the more extensive approach. METHODS: We conducted a retrospective review of all patients with well-differentiated thyroid cancer greater than 1 cm (180 patients) who underwent surgery between 1982 and 2002 by a single general surgeon at our institution. The prevailing philosophy was to be as conservative as possible, and the predominant resection was lobectomy and isthmusectomy on the affected side. RESULTS: In total, 90% of patients were in a definable low-risk group: 75% had conservative surgery with 4 recurrences and no mortality, 25% had extensive surgery with 3 recurrences and no mortality. The other 10% were in a definable high-risk group: 90% had extensive surgery with 9 recurrences and 4 deaths. Overall, there were 22 sites of recurrence in 16 patients. There was no recurrence in the residual thyroid tissue, with a median follow-up of 10 years. Three recurrences occurred in the resected thyroid bed; each of these patients had undergone extensive surgery. Twelve recurrences were in lymph nodes; 67% of these patients had extensive surgery. All except 1 of 7 distant metastases occurred in the high-risk group, despite the patient having undergone extensive local surgery. Recurrence did not affect survival in the low-risk group. The extensive surgery group had a 3.4% incidence of recurrent laryngeal nerve injury and a 1.1% incidence of permanent hypocalcemia, with none in the conservative surgery group. CONCLUSION: Conservative surgery for low-risk patients with well-differentiated thyroid cancer appears to be sufficient and avoids complications without significantly increased risk for local, regional or distant recurrence.

Incidental papillary microcarcinoma of the thyroid--factors affecting lymph node metastasis.

BACKGROUND AND AIMS: Despite the overall excellent prognosis for patients with thyroid papillary microcarcinoma (PMC), these tumors are associated with lymph node metastasis. The aim of this study is to identify the rate of lymph node metastasis and evaluate the clinical and pathological factors affecting metastasis in thyroid PMC. METHODS: Among 475 patients with papillary thyroid carcinoma treated between 1990 and 2003, 81 patients (17%) were diagnosed as PMC and the records of these patients were evaluated retrospectively. Clinicopathologic features were evaluated by univariate and multivariate analyses. RESULTS: According to age, metastases, extent, and size risk definition, all patients were in low-risk group. Lymph node metastases were determined in 12.3% of patients. Mean follow-up was 7 years (range from 28 to 192 months). Ten-year disease-free and overall survival rates were 97 and 100%, respectively. Both multifocality and thyroid capsular invasion were found to be independent risk factors for lymph node metastasis by multivariate analysis. CONCLUSION: Patients with thyroid PMC in low-risk group with multifocal tumors and with capsule invasion may have increased risk of lymph node metastasis, and must be considered in follow-up of the patients who have these factors.

Pediatric differentiated thyroid carcinoma: trends in practice and outcomes over 40 years at a single tertiary care institution.

BACKGROUND: This study aims to analyze changes in characteristics, practice and outcomes of pediatric differentiated thyroid cancer (DTC) at our tertiary care institution. METHODS: Patients <21 years of age diagnosed between 1973 and 2013 were identified. Clinicopathological data, treatment and outcomes were obtained by a retrospective review. RESULTS: Thirteen males and 68 females were divided into Group A (n=35, diagnosed before July 1993) and Group B (n=46, diagnosed after July 1993). Group B was more likely to undergo neck ultrasound (US) (70% vs. 23%, p<0.0001) and fine-needle aspiration (FNA) biopsy (80% vs. 26%, p<0.0001). Patients in Group B more often underwent total thyroidectomy as a definitive surgical treatment (87% vs. 69%, p=0.04). There was no difference in radioactive iodine use. Recurrence-free survival was similar. CONCLUSIONS: Increased use of US and FNA has affected initial surgical management in the latter part of the study, possibly due to extension of adult DTC guidelines. The effects of the new pediatric DTC guidelines need further study.

Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer.

PURPOSE: To determine the long-term impact of medical and surgical treatment of well differentiated papillary and follicular thyroid cancer. METHODS: Patients with papillary and follicular cancer (n = 1,355) treated either in U.S. Air Force or Ohio State University hospitals over the past 40 years were prospectively followed by questionnaire or personal examination to determine treatment outcomes. Outcomes were analyzed by Kaplan-Meier survival curves and Cox proportional-hazard regression model. RESULTS: Median follow-up was 15.7 years; 42% (568) of the patients were followed for 20 years and 14% (185) for 30 years. After 30 years, the survival rate was 76%, the recurrence rate was 30%, and the cancer death rate was 8%. Recurrences were most frequent at the extremes of age (< 20 and > 59 years). Cancer mortality rates were lowest in patients younger than 40 years and increased with each subsequent decade of life. Thirty-year cancer mortality rates were greatest in follicular cancer patients, who were more likely to have adverse prognostic factors: older age, larger tumors, more mediastinal node involvement, and distant metastases. When patients with distant metastases at diagnosis were excluded, follicular and papillary cancer mortality rates were similar (10% versus 6%, P not significant [NS]). In a Cox regression model that excluded patients who presented with distant metastases, the likelihood of cancer death was (1) increased by age > or = 40 years, tumor size > or = 1.5 cm, local tumor invasion, regional lymph-node metastases, and delay in therapy > or = 12 months; (2) reduced by female sex, surgery more extensive than lobectomy, and 131I plus thyroid hormone therapy; and (3) unaffected by tumor histologic type. Following 131I therapy given only to ablate normal thyroid gland remnants, the recurrence rate was less than one third the rate after thyroid hormone therapy alone (P < 0.001). No patient treated in this way with 131I has died of thyroid cancer. Low 131I doses (29 to 50 mCi) were as effective as high doses (51 to 200 mCi) in controlling tumor recurrence (7% versus 9%, P = NS). Following 131I therapy, whether given for thyroid remnant ablation or cancer therapy, recurrence and the likelihood of cancer death were reduced by at least half, despite the existence of more adverse prognostic factors in patients given 131I. At 30 years, the cumulative cancer mortality rate following 131I therapy, regardless of the reason for its use, was one third that in patients not so treated (P = 0.03). CONCLUSION: Over the long term, for tumors > or = 1.5 cm that are not initially metastatic to distant sites, near-total thyroidectomy followed by 131I plus thyroid hormone therapy confers a distinct outcome advantage. This therapy reduces tumor recurrence and mortality sufficiently to offset the augmented risks incurred by delayed therapy, age > or = 40 at the time of diagnosis, and tumors that are much larger than 1.5 cm, multicentric, locally invasive, or regionally metastatic.

Analysis of risk of death from differentiated thyroid cancer.

The records of 231 patients with differentiated thyroid cancer, treated at the University Hospital of Granada between 1972 and 1986, were reviewed to determine which factors were associated with a favourable response and prolonged survival. Radical surgery was the initial treatment in the large majority of the patients. During the postoperative period, 174 patients received 131I therapy and 12 patients were treated by external irradiation. All of them received hormone replacement therapy. Median follow up was over 5 years. Kaplan-Meier actuarial overall survival (S) and disease-free survival (DSF) at 10 years were used as end points for analysis. Survival and freedom from relapse at this time were 0.93 +/- 0.02 and 0.63 +/- 0.06, respectively. No flattening of the relapse curve was observed during the period of follow-up. Univariate analysis showed that the prognosis was significantly influenced by age, sex (papillary cancer only), histological type of tumour, clinical-pathological stage of disease and cervical lymph node status (entire group and papillary cancer). Using Cox's regression model, two groups of patients with low and moderate risk of death and moderate and high risk of recurrence could be identified.

Follicular variant of papillary thyroid carcinoma: a long-term follow-up.

HYPOTHESIS: The clinical behavior of the follicular variant of papillary thyroid carcinoma (FVPTC) is similar to pure papillary thyroid carcinoma (PPTC) and completely different from follicular thyroid carcinoma (FTC). DESIGN: Retrospective analysis of prospectively documented data. SETTING: Referral center of a university hospital. PATIENTS: Two hundred thirty-seven consecutive patients with follicular cell-derived thyroid carcinomas were operated on in our institution during a 15-year period, from January 1, 1980, to December 31, 1994. Of the 154 PTC patients, 37 (24%) had FVPTC. The mean follow-up was 128.2 months (10.7 years). MAIN OUTCOME MEASURES: Demographic features, tumor characteristics, local and distant spread, persistence or recurrence of disease, and carcinoma-related mortality were compared between the groups with FVPTC, PPTC, and non-Hürthle cell FTC (NHFTC). RESULTS: The frequency of multicentricity was significantly higher in the FVPTC group than in the PPTC group (P =.03) or in the NHFTC group (P =.01) (12 [32%] of 37 patients vs 17 [15%] of 117 patients vs 6 [10%] of 58 patients, respectively). The incidence of cervical lymph node metastases was lower in the FVPTC group than in the PPTC group (P =.30) and higher than in NHFTC group (P =.004) (12 [32%] of 37 patients vs 53 [45%] of 117 patients vs 6 [10%] of 58 patients, respectively). At diagnosis, no patient with FVPTC showed distant metastases, compared with 5 patients (4%) with PPTC (P =.34) and 19 (33%) with NHFTC (P<.001). There was no carcinoma-related death in the FVPTC group. The strikingly poorer prognosis for the NHFTC group was statistically significant (P<.001), whereas the difference in carcinoma-specific survival between the PPTC and the FVPTC groups did show a trend toward better survival in the FVPTC group. CONCLUSION: The clinical behavior of the FVPTC group did not differ significantly from that of the PPTC group, whereas compared with the NHFTC group, the FVPTC group showed statistically significant differences for most of the analyzed variables.

Mice with a mutation in the thyroid hormone receptor beta gene spontaneously develop thyroid carcinoma: a mouse model of thyroid carcinogenesis.

The molecular genetic basis of thyroid carcinogenesis is not well understood. Most of the existing models of thyroid cancer only rarely show metastases, and this has limited progress in the understanding of the molecular events in thyroid cancer invasion and metastasis. We have recently generated a mutant mouse by introducing a dominant negative mutant thyroid hormone nuclear receptor gene, TRbetaPV, into the TRbeta gene locus. In this TRbetaPV mouse, the regulation of the thyroid-pituitary axis is disrupted, leading to a mouse with high levels of circulating thyroid-stimulating hormone and extensive hyperplasia of follicular epithelium within the thyroid. As TRbeta(PV/PV) mice, but not TRbeta(PV/+) mice, aged, metastatic thyroid carcinoma developed. Histologic evaluation of thyroids of 5-14-month-old mice showed capsular invasion (91%), vascular invasion (74%), anaplasia (35%), and metastasis to the lung and heart (30%). Previous models of thyroid cancer have focused on genes that control initial carcinogenesis, but this model provides an unusual opportunity to study the alterations in gene regulation that occur with clinically relevant changes during progression and metastasis in a predictable fashion.

Increasing incidence and characteristics of differentiated thyroid cancer in Huntington, West Virginia.

Since 1985, we have observed an increasing number of differentiated thyroid cancer cases in Huntington, West Virginia. We describe tumor incidence, patient and tumor characteristics, treatment modalities, and tumor recurrence and death. One hundred seventeen patients with differentiated thyroid cancer were identified between 1976 and 1999. Data were collected from patient records in our practice and the tumor registries at the three hospitals serving our community. The annual incidence of differentiated thyroid cancer increased significantly from fewer than 3 cases per 100,000 prior to 1996 to 9.4 cases per 100,000 in 1999. The median age at diagnosis was 49 years (range, 16-80). The median tumor size was 2.5 cm (range, 1.2-10). Forty-seven percent of the patients had bilateral disease, 28% had three or more tumors, 44% had thyroid capsular invasion, and 16% had gross extrathyroid invasion at surgery. Twenty-two percent had cervical lymph node involvement and 9% had distant metastases at diagnosis. During 1-month to 23-year follow-up, 11% had recurrence, and 5% died of thyroid cancer. In summary, differentiated thyroid cancer has increased dramatically in our community. The tumors appear to be aggressive at diagnosis as reflected by the high percentage of tumors with bilateral, multicentric, and locally invasive disease.

Prognostic factors in well-differentiated thyroid carcinoma.

OBJECTIVES: To test the prognostic significance of standard clinicopathologic factors in patients with well-differentiated thyroid carcinoma (WDTC). STUDY DESIGN: A retrospective chart review of the thyroid cancer database at Mount Sinai Hospital (Toronto, Canada 1963-2000) was carried out. METHODS: All patients consecutively treated for WDTC with a follow-up period of at least 5 years were eligible for inclusion. Relevant patient, tumor, treatment, and outcome data were collected. The main outcome measures were recurrence rate, actuarial overall, and disease-specific survival at 20 years. RESULTS: Three hundred and thirty-three patients (F 275, M 58) with a median age of 39.7 (range 9-82.9) years were eligible for inclusion in this study (median follow-up 10.4 years, range 5-34.4 years, minimum 5 years). The recurrence rate was 15.6% (52 /333). The overall and disease-specific survival at 10 years was 97.5% and 98.5%, respectively. Likewise, the overall and disease-specific survival at 20 years was 88.4% and 93.3%, respectively. Clinicopathologic factors significant on multivariate regression for the development of disease recurrence included family history of WDTC, advanced stage, and total thyroidectomy (all P < .05). Similarly, advanced stage on presentation was associated with a worse disease-specific survival on multivariate regression (all P < .05). There was a trend for age 60 or greater to predict disease-specific survival (P = .09). CONCLUSIONS: WDTC is associated with a significant recurrence rate but good disease-specific survival. The most important prognostic factors are family history of WDTC, extent of surgical treatment (i.e., total thyroidectomy), and advanced initial stage of disease, with a trend for age 60 years and older.

Treatment of patients with carcinoma of the thyroid invading the airway.

OBJECTIVE: To determine if complete resection (vs incomplete resection) improved survival of patients with thyroid carcinoma invading the airway. DESIGN: Retrospective, nonrandomized end point study. SETTING: Tertiary care referral centers. PATIENTS: All patients who had invasion of the airway by thyroid carcinoma and underwent some type of surgical resection. INTERVENTIONS: Surgical resection. MAIN OUTCOME MEASURE: Survival. RESULTS: Complete resection showed significantly better survival than incomplete resection (P = .0136). CONCLUSION: Complete resection of thyroid carcinoma invading the airway offers improved survival compared with incomplete resection.

External beam radiotherapy in the management of differentiated thyroid cancer.

AIMS: No randomised trials have addressed the use of external beam radiotherapy (EBRT) in the treatment of differentiated thyroid cancer. The indications for EBRT, the technique and recommended dose all remain controversial. MATERIALS AND METHODS: We included patients treated with EBRT with curative intent from two cancer centres between 1988 and 2001. Data were collected from hospital notes, radiotherapy prescriptions and local cancer registry. RESULTS: The indications for treatment in the 41 identified patients were macroscopic residual disease 23 (56%), microscopic residual disease 10 (25%), Hurthle cell variants 3 (7%), multiple lymph-node involvement 3 (7%) and other 2 (5%). Delivered doses ranged from 37.5-66 Gy over 3-6.5 weeks. Rate of local recurrence and overall survival at 5 years were as follows: papillary 26% and 67%; follicular 43% and 48%; well differentiated 21% and 67%; focus of poor differentiation/Hurthle cell variants 69% and 32%; complete excision 25% and 61%; residual disease 37% and 59%; EBRT total dose < 50 Gy 63% and 42%; 50-54 Gy 15% and 72%; > 54 Gy 18%, and 68%. CONCLUSIONS: The results in this study are consistent with previous retrospective studies of EBRT. The wide range of indications and doses used with radical intent highlights the lack of clinical and radiobiological data on the response of differentiated thyroid cancer to EBRT. Despite the small study size, the 5-year local recurrence results indicate a possible dose response within the dose range used.

Carcinoma of the thyroid in children--a review.

Thyroid cancer is the third most common solid tumor in children and adolescents. A review was made of the data on 540 such patients reported from nine large centers renowned for their experience with thyroid cancer. In respect to the pathogenesis the only factor conclusively known to promote development of thyroid cancer in the pediatric age group is irradiation, as documented by the Chernobyl experience. The evidence indicates that thyroid carcinoma in the pediatric age group is a biologically independent and more aggressive entity than in adults; paradoxically the prognosis is good. In the great majority of cases the only presenting sign was a neck mass. In a high percentage (60-80%) there were also palpable lymph nodes. The findings regarding lung metastases were not clear-cut: in most series they were present in about 10%, with a high of 28% in one group and a low of 5% in another group. Papillary carcinoma or the follicular variant of papillary carcinoma were the dominant histologic types, pure follicular carcinoma being found much less frequently than among adults with thyroid cancer. Despite the relatively advanced stage of the disease upon diagnosis, only 13 patients died of the disease, 12 to 33 years postoperatively. Recurrence rates ranged between 10% to 35%, with involvement of the lateral neck, thyroidal bed or distant sites 3 to 33 years after treatment; most failures responded to further surgery or radioactive iodine. There is almost general agreement that surgical intervention should consist of total or near total thyroidectomy despite the high rates of recurrent laryngeal nerve paralysis and hypocalcemia. In regard to neck metastases less than radical surgery has proved during the years to be sufficiently effective. Radioactive iodine, used by all at some stage of management for treatment purposes, should be used prophylactically only after due consideration in view of possible teratogenicity.

[Surgical treatment of differentiated carcinoma of the thyroid. Follow-up of 99 cases]. / Il trattamento chirurgico del carcinoma differenziato della tiroide. Follow-up su 99 casi.

The surgical treatment of differentiated thyroid carcinoma continues to be a matter of considerable debate in terms of defining the appropriate extent of thyroid or lymph node resection to ensure optimal patient survival. Whereas, at organ level, the majority of surgeons are in favor of total thyroidectomy, both the extent and timing of lymphadenectomy remain controversial issues. In the light of this, the Authors have conducted a retrospective study in 99 consecutive patients with differentiated thyroid carcinoma. As regards the distribution of the cancers in terms of TNM staging, 60 were stage I, 27 stage II, 11 stage III and 1 stage 4. Almost all the patients underwent total thyroidectomy. Lymphadenectomy was performed at the same time as thyroidectomy in papillary cancers when the nodes were clinically palpable and at a later date in those cases where the nodes subsequently became palpable at follow-up. The in-hospital mortality was 3% and was unrelated to the operation. The median follow-up was 95.8 months (7.98 years). Sixty-nine patients are still alive (71.8%), 66 of them disease-free (68.7%) and 3 with lymph node metastases (3.1%). Our results and those of other investigators suggest that total thyroidectomy should be the first therapeutic choice in differentiated cancers of the thyroid, but allow us to draw no firm conclusions regarding the controversial issue as to which type of lymphadenectomy can best ensure patient survival. To solve this problem we believe that multicenter randomized trials will be necessary. However, progress in molecular biology and tumor genetics is likely to enable us to identify new prognostic factors which may prove useful when deciding on the most appropriate therapeutic option.

[Clinical and morphological characteristics and peculiarities of differentiated thyroid gland cancer course]. / Kliniko-morfologicheskaia kharakteristika i osobennosti techeniia differentsirovannykh form raka shchitovidnoi zhelezy.

221 patients were operated for cancer of the thyroid gland during the last 12 years. Adequate preoperative diagnosis including ultrasound examination, and fine needle aspiration biopsy made it possible to operate 88.7% of patients at earlier (I and II) stages of the disease. Long term results of radical surgical treatment have been studied in 197 (89.1%) patients followed up 5 to 16 years, 49.2% of patients being followed up for no less than 10 years. Majority of patients (95.9%) had differentiated forms of tumors, medullar cancer was detected in 4.1% of patients. Clinical and morphological analysis of differentiated thyroid cancer was carried out in 212 patients. Metastases to lymph nodes of the neck occur more frequently in younger patients, and extracapsular spread of the tumor was revealed in aged persons. Risk factors were male sex, old age, follicular cancer and growth of the tumor through the capsule of the gland. The minimal procedure in case of location of the differentiated tumor in a single lobe of thyroid is extrafascial hemithyreoidectomy with resection of the istmus. Prognosis in radically operated patients is relatively favourable, 5-year survival rate made up 97.5%.

Resection margins and prognosis in locally invasive thyroid cancer.

BACKGROUND: Invasive thyroid cancer is rare, and the extent of surgery controversial. The purpose of this study was to present and evaluate therapeutic prognostic factors. METHODS: We conducted a retrospective single-center study of differentiated thyroid carcinoma invading the larynx, trachea, and/or esophagus treated surgically with macroscopic complete resection. RESULTS: Forty-six patients (average age, 57 years; average follow-up, 4 years) were included. Free margins (R0) were obtained for 22 of 46 (49%) and microscopic residual tumor was present after surgery (R1) for 24 (51%). Ten-year actuarial local control was 100% for R0 and 75% for R1 (p = .08). Five-year local control was lower for recurrent tumors versus inaugurally invasive disease (63% vs 87%; log-rank p = .011). Five-year and 10-year actuarial disease-specific survival (DSS) was correlated with preoperative distant metastases (100% and 87%, respectively, for M0 vs 68% and 34% for M1; p = .01). CONCLUSION: A trend toward lower local control was observed for R1 versus R0. The morbidity of surgery should be weighed against the prognosis if metastases are present.

Role of salvage targeted therapy in differentiated thyroid cancer patients who failed first-line sorafenib.

CONTEXT: Sorafenib, a tyrosine kinase inhibitor, is a common first-line therapy for advanced differentiated thyroid cancer (DTC). However, responses are not durable and drug toxicity remains a problem. OBJECTIVE: The objective of the study was to determine the efficacy of salvage therapy after first-line sorafenib failure. DESIGN: This was a retrospective review at M. D. Anderson Cancer Center from January 2005 to May 2013. PATIENTS: The study included patients with metastatic DTC who received salvage therapy after their initial sorafenib failure (group 2). PATIENTS who received first-line sorafenib only (group 1) were evaluated for comparison of overall survival (OS). OUTCOME MEASURES: Progression-free survival, best response, and median OS were measured. RESULTS: Sixty-four patients with metastatic, radioactive iodine refractory DTC were included; 35 were in group 1 and 25 were in group 2, and the groups were well balanced. Median OS of all 64 patients receiving first line sorafenib was 37 months; median OS was significantly longer with salvage therapy compared with sorafenib alone (58 vs 28 months, P = .013). In group 2, 17 patients were evaluable for best response, although two patients had toxicity with sorafenib, which was discontinued before restaging. Best responses with first-line sorafenib were partial response in 2 of 15 (13%), stable disease in 10 of 15 (67%), and progressive disease in 3 of 15 (20%) patients. With salvage therapy, partial responses were seen in 7 of 17 (41%) and stable disease in 10 of 17 (59%) patients. Median progression-free survival was 7.4 months with first-line sorafenib and 11.4 months with salvage therapy. Salvage therapy included sunitinib (n = 4), pazopanib (n = 3), cabozantinib (n = 4), lenvatinib (n = 3), and vemurafenib (n = 3). CONCLUSIONS: Other targeted agents are effective salvage treatments after sorafenib failure, despite similar mechanisms of action, and should be offered to patients who are able to receive salvage therapy.

Comprehensive MicroRNA expression profiling identifies novel markers in follicular variant of papillary thyroid carcinoma.

BACKGROUND: Follicular variant of papillary thyroid carcinoma (FVPTC) shares features of papillary (PTC) and follicular (FTC) thyroid carcinomas on a clinical, morphological, and genetic level. MicroRNA (miRNA) deregulation was extensively studied in PTCs and FTCs. However, very limited information is available for FVPTC. The aim of this study was to assess miRNA expression in FVPTC with the most comprehensive miRNA array panel and to correlate it with the clinicopathological data. METHODS: Forty-four papillary thyroid carcinomas (17 FVPTC, 27 classic PTC) and eight normal thyroid tissue samples were analyzed for expression of 748 miRNAs using Human Microarray Assays on the ABI 7900 platform (Life Technologies, Carlsbad, CA). In addition, an independent set of 61 tumor and normal samples was studied for expression of novel miRNA markers detected in this study. RESULTS: Overall, the miRNA expression profile demonstrated similar trends between FVPTC and classic PTC. Fourteen miRNAs were deregulated in FVPTC with a fold change of more than five (up/down), including miRNAs known to be upregulated in PTC (miR-146b-3p, -146-5p, -221, -222 and miR-222-5p) and novel miRNAs (miR-375, -551b, 181-2-3p, 99b-3p). However, the levels of miRNA expression were different between these tumor types and some miRNAs were uniquely dysregulated in FVPTC allowing separation of these tumors on the unsupervised hierarchical clustering analysis. Upregulation of novel miR-375 was confirmed in a large independent set of follicular cell derived neoplasms and benign nodules and demonstrated specific upregulation for PTC. Two miRNAs (miR-181a-2-3p, miR-99b-3p) were associated with an adverse outcome in FVPTC patients by a Kaplan-Meier (p < 0.05) and multivariate Cox regression analysis (p < 0.05). CONCLUSIONS: Despite high similarity in miRNA expression between FVPTC and classic PTC, several miRNAs were uniquely expressed in each tumor type, supporting their histopathologic differences. Highly upregulated miRNA identified in this study (miR-375) can serve as a novel marker of papillary thyroid carcinoma, and miR-181a-2-3p and miR-99b-3p can predict relapse-free survival in patients with FVPTC thus potentially providing important diagnostic and predictive value.