Chemotherapy effectiveness in the treatment of non-medullary well-differentiated thyroid cancer: A systematic review.
Ana Alberto TamaritEsther MartÃÂnAlberto TorresTeresa GarcÃÂa ManriqueMaria Carmen Álamo de la GalaLuís de la Cruz-MerinoTomás MartÃÂn
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e17058 Background: Nowadays, the use of chemotherapy in the well-differentiated non medullary thyroid cancer, locally advanced stage and/or with radioiodine refractory metastases (Advanced CDT) is considered of scanty value. However, in the last 40 years was not published any phase III study nor a systematic review of its use in clinical setting. Methods: A systematic literature search was performed in databases such as Medline and Embase, among others. Two independent reviewers analyzed the articles selected full text, made a critical reading and extracted results using forms designed specifically. A qualitative synthesis of the results was performed and the accumulated data were calculated. Results: Of 509 references identified by searching the database, sixteen studies with 473 patients published in the last 40 years were included. Four studies included only patients with well-differentiated tumors. The overall response rate was 22.5% (between 0-57%) with a 2.5% complete responses and a clinical benefit (BC) in 51% (19-93 %) of cases. In addition, unlike modern studies a performance status > 2 was described in about 40% of patients. Five studies published individual survival data from 54 patients with advanced CDT: the median survival was estimated at 18 months (95% CI 0 to 37.5), with significant differences between patients treated before 2000 versus patients treated later (7 vs 41 months, P < 0.00) Overall survival time was unable to assess due to lack of data and the heterogeneity of the included studies. However, these data must be interpreted with caution because of the high risk of bias detected. Conclusions: Although it has not been able to find firm evidence on the effectiveness of chemotherapy, the results shown seems to have some efficacy, therefore, it could be necessary to be tested in well-designed studies versus or in combination with new therapies.Keywords:
Medullary Thyroid Cancer
Controversies in familial thyroid cancer 2014Thyroid cancer is the sixth most common cancer in women, and the majority of patients with thyroid cancer has sporadic disease.However, about 25% of patients with medullary thyroid cancer and 5% with papillary thyroid cancer have familial tumors.Currently, there are numerous controversies regarding the mode of inheritance, tumor behavior, extent of surgical resection for optimal results, coexisting thyroid pathology, risk of other cancers, and extent of postoperative treatment of patients with familial thyroid cancer.This review aimed to give insight to surgeons on this interesting topic.
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Patients with thyroid cancer who have extrathyroidal extension (ETE) are considered to have more advanced tumors. However, data on the impact of ETE on patient outcomes remain limited. The purpose of this study was to evaluate the association between ETE and survival in patients with thyroid cancer.The National Cancer Database (1998-2012) was queried for all adult patients with differentiated thyroid cancer and medullary thyroid cancer. Patients were divided into three groups: no ETE (T1 and T2 tumors), minimal ETE (T3 tumors <4 cm), and extensive ETE (T4 tumors <4 cm). Patient demographic, clinical, and pathologic factors were evaluated for all patients. A Cox proportional hazards model was developed for each histology to identify factors associated with survival.In total, 241,118 patients with differentiated thyroid cancer met the inclusion criteria; 86.9% had no ETE, 9.1% minimal ETE, and 4.0% extensive ETE. Compared with patients with no ETE, patients with minimal and extensive ETE were more likely to have larger tumors (1.4 cm vs. 1.8 cm and 2.0 cm, respectively), lymphovascular invasion (8.6% vs. 28.0% and 35.1%, respectively), positive margins after thyroidectomy (6.1% vs. 35.2% and 45.9%, respectively), and regional lymph node metastases (32.5% vs. 67.0% and 74.6%, respectively; all p < 0.01). After adjustment, minimal ETE (hazard ratio [HR] = 1.13; p < 0.01) and extensive ETE (HR = 1.74; p < 0.01) were associated with compromised survival for patients with differentiated thyroid cancer. In total, 3415 patients with medullary thyroid cancer met the inclusion criteria; 87.9% had no ETE, 7.1% minimal ETE, and 5.0% extensive ETE. Compared with patients with no ETE, patients with minimal and extensive ETE were more likely to have larger tumors (1.7 cm vs. 2.2 cm and 2.2 cm, respectively), lymphovascular invasion (19.2% vs. 68.9% and 79.3%, respectively), positive margins after thyroidectomy (5.8% vs. 44.1% and 51.9%, respectively), and regional lymph node metastases (39.0% vs. 90.5% and 94.4%, respectively; all p < 0.01). After adjustment, extensive ETE (HR = 1.63; p = 0.01) was associated with compromised survival for patients with medullary thyroid cancer.In patients with differentiated and medullary thyroid cancers, ETE is associated with compromised survival. Given these findings, ETE should be included in the thyroid cancer treatment guidelines.
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Sorafenib and lenvatinib can be effective for advanced differentiated thyroid cancer, and vandetanib and cabozantinib can be effective options for advanced medullary thyroid cancer. When first-line tyrosine kinase inhibitors fail for patients, evidence supports salvage therapy for differentiated thyroid cancer but is less compelling for medullary thyroid cancer.
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Protein kinase inhibitors (PKIs) have emerged as highly promising therapies in progressive metastatic radioiodine-refractory differentiated thyroid cancer and in medullary thyroid cancer; two were recently approved in the USA for use in medullary thyroid cancer (vandetanib, cabozantinib), and another for use in progressive metastatic radioiodine-refractory differentiated thyroid cancer (sorafenib). Although more than 90% of thyroid cancer patients fare well in response to conventional treatment, PKI therapy has the potential to provide benefit. Nonetheless, PKIs produce numerous side effects, may worsen quality of life, may hasten mortality (by 1–2%), require discerning clinical acumen, are not yet proven to improve thyroid cancer survival and are very costly. This raises questions about who should prescribe PKIs, and about whether their use in thyroid cancer is truly beneficent and ethically justified. Restraint should be exercised in their use in thyroid cancer, with potential risks and benefits carefully weighed and solutions devised to help ameliorate many of the problems associated with their use.
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Purpose of review Thyroid cancer is the most common endocrine cancer in adults with rising incidence. Challenges in imaging thyroid cancer are twofold: distinguishing thyroid cancer from benign thyroid nodules, which occur in 50% of the population over 50 years; and correct staging of thyroid cancer to facilitate appropriate radical surgery in a single session. The clinical management of thyroid cancer patients has been covered in detail by the 2015 guidelines of the American Thyroid Association (ATA). The purpose of this review is to state the principles underlying optimal multimodal imaging of thyroid cancer and aid clinicians in avoiding important pitfalls. Recent findings Recent additions to the literature include assessment of ultrasound-based scoring systems to improve selection of nodules for fine needle biopsy (FNB) and the evaluation of new radioactive tracers for imaging thyroid cancer. Summary The mainstay of diagnosing thyroid cancer is thyroid ultrasound with ultrasound-guided FNB. Contrast-enhanced computed tomography and PET with [ 18 F]-fluorodeoxyglucose (FDG) and MRI are reserved for advanced and/or recurrent cases of differentiated thyroid cancer and anaplastic thyroid cancer, while [ 18 F]FDOPA and [ 68 Ga]DOTATOC are the preferred tracers for medullary thyroid cancer.
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The treatment of thyroid cancer is evolving. The molecular mechanisms of carcinogenesis for many thyroid cancers have been investigated, and have yielded targets for potential therapies. These targets include VEGFR in the treatment of all thyroid cancers, BRAF in the treatment of papillary thyroid cancer, and RET in the treatment of medullary thyroid cancer (MTC). Many promising drugs that target one or more of these proteins are currently being evaluated, including sorafenib and sunitinib, both of which are still under development for the treatment of thyroid cancer but which have been approved for use in other malignancies. In addition, compounds such as vandetanib (AstraZeneca plc) and XL-184 (Bristol-Myers Squibb Co/Exelixis Inc) have demonstrated activity in early-phase clinical trials of MTC and are being tested further in randomized trials.
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