Treatment Of Well-differentiated Thyroid Cancer Research Articles

Insurance-Based Disparities in Guideline-Concordant Thyroid Cancer Care in the Era of De-escalation

IntroductionPrior studies have demonstrated insurance-based disparities in the treatment of well-differentiated thyroid cancer. However, it remains unclear whether these disparities have persisted in the era of the 2015 American Thyroid Association (ATA) management guidelines. The goal of this study was to assess whether insurance type is associated with the receipt of guideline-concordant and timely thyroid cancer treatment in a modern cohort. MethodsPatients diagnosed with well-differentiated thyroid cancer between 2016 and 2019 were identified from the National Cancer Database. Appropriateness of surgical and radioactive iodine treatment (RAI) was determined based on the 2015 ATA guidelines. Multivariable logistic regression and Cox proportional hazard regression analyses, stratified at age 65, were used to evaluate the associations between insurance type and appropriateness and timeliness of the treatment. Results125,827 patients were included (private = 71%, Medicare = 19%, Medicaid = 10%). Compared to privately insured patients, patients with Medicaid more frequently presented with tumors >4 cm in size (11% versus 8%, P < 0.001) and regional metastases (29% versus 27%, P < 0.001). However, patients with Medicaid were also less likely to undergo appropriate surgical treatment (odds ratio 0.69, P < 0.001), less likely to undergo surgery within 90 d of diagnosis (hazard ratio 0.80, P < 0.001), and more likely to be undertreated with RAI (odds ratio 1.29, P < 0.001). There were no differences in the likelihood of guideline-concordant surgical or medical treatment by insurance type in patients ≥65 y old. ConclusionsIn the era of the 2015 ATA guidelines, patients with Medicaid remain less likely to receive guideline-concordant, timely surgery and more likely to be undertreated with RAI compared to privately insured patients.

Simulated data-driven hospital selection for surgical treatment of well-differentiated thyroid cancer in older adults

BackgroundThyroid surgery at high-quality hospitals is associated with fewer complications. We evaluated the impact of referring older adults with thyroid cancer to higher-performing local hospitals. MethodsWe performed a simulation study of Surveillance, Epidemiology, and End Results–Medicare patients, aged ≥66 years, who underwent a thyroidectomy for well-differentiated thyroid cancer (2013–2017). An 80% sample was used to calculate each hospital’s risk-standardized 30-day serious adverse event rate, dividing hospitals into quartiles by performance. Hospitals located ≤30 miles of the remaining 20% of patients were compared, and 30-day serious adverse event rates and costs were simulated as if patients were treated at higher-quality hospitals using logistic regression with each alternative hospital’s fixed-effect. ResultsWe identified 8,946 patients who underwent thyroid resection at 843 hospitals. Average risk-adjusted serious adverse event rates ranged from 13.9% to 52.9% between quartile 1 and 4 hospitals (P < .001). We identified higher-quality hospitals for 43.7% of patients. Simulating care at the best local hospital reduced predicted serious adverse event rates from 25.6% (95% confidence interval, 24.7–26.4) to 16.2% (95% confidence interval, 15.5–16.8; P < .001), while modestly lowering average costs from $12,883 (95% confidence interval, 12,500–13,267) to $12,679 (95% confidence interval, 12,304–13,056; P = .029). ConclusionSimulated care at higher-performing hospitals decreased serious adverse event rates after thyroid resection. Optimizing hospital selection may reduce postoperative morbidity without compromising preferences for local treatment.

Well-Differentiated Thyroid Cancer: Who Should Get Postoperative Radiation?

The mainstay of treatment of well-differentiated thyroid cancer (WDTC) is surgery followed by adjuvant radioactive iodine therapy. Postoperative radiation therapy (PORT) is rarely used. The aim of our study was to report our experience of patients with WDTC who were selected to receive PORT. After Institutional Review Board approval, patients who received PORT were identified from a departmental database of 6259 patients with WDTC treated with primary surgery from 1986 to 2015. We carried out propensity matching to compare outcomes with a cohort of patients who did not receive PORT. The main outcome of interest was central neck recurrence-free probability (CNRFP), while secondary outcomes were lateral neck recurrence-free probability (LNRFP), disease-specific survival (DSS), and overall survival (OS). From 6259 patients, 32 (0.5%) patients with a median age of 65.2 years received PORT. Tall-cell variant papillary thyroid carcinoma was the most common pathology (45%). Patients who received PORT had no difference in CNRFP compared with patients treated without PORT (10-year CNRFP 88% vs. 73%; p=0.18). Furthermore, patients who received PORT had superior LNRFP (10-year LNRFP 100% vs. 62%; p=0.001) compared with the no-PORT cohort. Despite this, patients who received PORT had similar DSS (71% PORT vs. 75% no-PORT) and OS (65% PORT vs. 58% no-PORT group) as the no-PORT cohort. Our data show that select patients who received PORT had improved locoregional recurrence-free probability; however, this did not translate into improved DSS and OS. At our institution, we recommend the use of PORT only in highly selected patients with locally advanced primary tumors who are deemed to have a high risk of central neck recurrence for which salvage surgery would result in unacceptable risk to the airway.

Pre-Operative Antithyroid Antibodies in Differentiated Thyroid Cancer

ObjectiveTo evaluate the significance of antithyroglobulin and antithyroid peroxidase antibody levels associated with locoregional metastatic disease in patients with well-differentiated thyroid cancer. MethodsPatients underwent initial treatment for well-differentiated thyroid cancer at our institution between 2014 and 2018. The following variables were collected: age, sex, pre-operative thyroid-stimulating hormone, thyroglobulin, antithyroglobulin antibody (TgAb), antithyroid peroxidase antibody (TPOAb), the extent of surgery, T-stage, N-stage, extrathyroidal extension (ETE), extranodal extension (ENE), lymphovascular invasion, and multifocal disease. The relationships between disease status and pre-operative TPOAb, TgAb, thyroglobulin, and thyroid-stimulating hormone were analyzed. ResultsA total of 405 patients (mean age, 52 years) were included in the study, of which 66.4% were women. Elevated TgAb was associated with the presence of lymph node metastases (LNM) in both the central and lateral neck (P < .01), with a stronger correlation to N1b versus N1a disease (P = .03). The presence of ETE was inversely related to the TgAb titer (P = .03). TPOAb was associated with a lower T-stage (P = .04), fewer LNM (P = .04), and a lower likelihood of ETE (P = .02). From multivariable analysis, TgAb ≥40 IU/mL was an independent predictive factor for a higher N-stage (P < .01 for N0 vs N1; P = .01 for N1a vs N1b), and ENE (P < .01). TPOAb ≥60 IU/mL was associated with a lower T-stage (P = .04 for T <3) and absence of ETE (P = .01). ConclusionElevated pre-operative TgAb was an independent predictor of nodal metastases and ENE, while elevated TPOAb was associated with a lower pathologic T- and N-stage. Pre-operative antithyroid antibody titers may be useful to inform the disease extent and features.

Micronuclei Formation upon Radioiodine Therapy for Well-Differentiated Thyroid Cancer: The Influence of DNA Repair Genes Variants.

Radioiodine therapy with 131I remains the mainstay of standard treatment for well-differentiated thyroid cancer (DTC). Prognosis is good but concern exists that 131I-emitted ionizing radiation may induce double-strand breaks in extra-thyroidal tissues, increasing the risk of secondary malignancies. We, therefore, sought to evaluate the induction and 2-year persistence of micronuclei (MN) in lymphocytes from 26 131I-treated DTC patients and the potential impact of nine homologous recombination (HR), non-homologous end-joining (NHEJ), and mismatch repair (MMR) polymorphisms on MN levels. MN frequency was determined by the cytokinesis-blocked micronucleus assay while genotyping was performed through pre-designed TaqMan® Assays or conventional PCR-restriction fragment length polymorphism (RFLP). MN levels increased significantly one month after therapy and remained persistently higher than baseline for 2 years. A marked reduction in lymphocyte proliferation capacity was also apparent 2 years after therapy. MLH1 rs1799977 was associated with MN frequency (absolute or net variation) one month after therapy, in two independent groups. Significant associations were also observed for MSH3 rs26279, MSH4 rs5745325, NBN rs1805794, and tumor histotype. Overall, our results suggest that 131I therapy may pose a long-term challenge to cells other than thyrocytes and that the individual genetic profile may influence 131I sensitivity, hence its risk-benefit ratio. Further studies are warranted to confirm the potential utility of these single nucleotide polymorphisms (SNPs) as radiogenomic biomarkers in the personalization of radioiodine therapy.

Current Status of Theranostics in Jordan.

Exploring the unknown is one of the key factors that lead to great discoveries in mankind history. With the advances in medicine and the development of new approaches towards patient care, like next-generation sequencing and patient-centered care, the need for treatments tailored to patient through personalized medicine has become more compelling. Theranostics has been introduced as a combination of a diagnostic tool and a therapeutic tool on the same vector for a specific disease, to facilitate personalized medicine. Nuclear medicine has shown the capability of providing a strong platform for this new approach through its arms, molecular imaging, and targeted molecular therapies. Though the prototype of theranostics has been practiced in Jordan since decades in the field of diagnosis and treatment of well-differentiated thyroid cancer, recently, the King Hussein Cancer Center (KHCC), a leading and comprehensive cancer center in Jordan and in the Middle East, has leaped forward to introduce the new approaches of theranostics through the nuclear medicine applications. This paper sheds the light on the most important aspects of this new theranostics practice in Jordan such as peptide receptor radionuclide therapy (PRRT) and prostate-specific membrane antigen (PSMA)-based theranostics.

The efficacy of radioactive iodine for the treatment of well-differentiated thyroid cancer with distant metastasis.

ObjectiveRadioactive iodine (131I) has been used as a treatment for high-risk well-differentiated thyroid cancer after thyroidectomy. The aim of this study was to evaluate the long-term follow-up results after using high accumulated doses of 131I (>600 mCi) for the treatment of well-differentiated thyroid cancer.Patients and methodsIn this study, we retrospectively evaluated prospectively enrolled patients with well-differentiated thyroid cancer who were treated and followed up in Chang Gung Memorial Hospital in Linkou and Keelung, Taiwan. All the patients underwent thyroidectomy between 1979 and 2016.ResultsFor our study, 228 patients with papillary and follicular thyroid carcinoma with distant metastases were enrolled. Of the 228 patients, 71 (31.1%) received 131I therapy with an accumulated dose of at least 600 mCi. Forty-four died because of disease-specific mortality (DSM) after a mean follow-up of 10.6±6.3 years. Compared with the patients in the DSM group, which included 27 survival cases, patients who were younger, and those with a multifocal tumor, more extensive thyroidectomy, and papillary thyroid carcinoma showed better prognosis. The DSM group included a higher percentage of patients who developed a secondary primary cancer after receiving a diagnosis of thyroid cancer than the survival group (18.2 vs. 3.7%). However, the difference did not reach statistical significance (P=0.075).Conclusion131I provided an effective therapeutic modality for well-differentiated thyroid cancer patients with distant metastasis. After a mean of follow-up 10 years, more than 60% of cases resulted in DSM when high accumulated 131I doses were administered.

Radioiodine Treatment of Well-Differentiated Thyroid Cancer: Balancing Risks and Benefits.

Radioiodine Treatment of Well-Differentiated Thyroid Cancer: Balancing Risks and Benefits.

Risk of Hematologic Malignancies After Radioiodine Treatment of Well-Differentiated Thyroid Cancer.

Purpose To investigate the risk and outcomes of second hematologic malignancies (SHMs) in a population-based cohort of patients with well-differentiated thyroid cancer (WDTC) treated or not with radioactive iodine (RAI). Methods Patients with WDTC were identified from SEER registries. Competing risk regression analysis was performed to calculate the risks of SHMs that occurred after WDTC treatment and outcomes after SHM development were assessed. Results Of 148,215 patients with WDTC, 53% received surgery alone and 47% received RAI. In total, 783 patients developed an SHM after a median interval of 6.5 years (interquartile range, 3.3 to 11.2 years) from WDTC diagnosis. In multivariable analysis, compared with those undergoing thyroidectomy alone, RAI treatment was associated with an increased early risk of developing acute myeloid leukemia (AML; hazard ratio, 1.79; 95% CI, 1.13 to 2.82; P = .01) and chronic myeloid leukemia (CML; hazard ratio, 3.44; 95% CI, 1.87 to 6.36; P < .001). This increased risk of AML and CML after RAI treatment was seen even in low-risk and intermediate-risk WDTC tumors. Occurrence of AML but not CML in patients with WDTC was associated with shorter median overall survival compared with matched controls (8.0 years v 31.0 years; P = .001). In addition, AML developing after RAI trended toward inferior survival compared with matched controls with de novo AML (median overall survival, 1.2 years v 2.9 years; P = .06). Conclusion Patients with WDTC treated with RAI had an increased early risk of developing AML and CML but no other hematologic malignancies. AML that arises after RAI treatment has a poor prognosis. RAI use in patients with WDTC should be limited to patients with high-risk disease features, and patients with WDTC treated with adjuvant RAI should be monitored for myeloid malignancies as part of cancer surveillance.

Evaluation of Ovarian Reserve with AMH Level in Patients with Well-Differentiated Thyroid Cancer Receiving Radioactive Iodine Ablation Treatment.

Introduction: Radioactive iodine (RAI) ablation treatment is used for patients diagnosed with well-differentiated thyroid cancer in order to reduce the risk of recurrence. RAI ablation treatment can adversely affect gonads in males and females. In this study, we aimed to determine ovary damage and infertility risk due to RAI, using serum anti-Müllerian hormone (AMH) level, in females who received RAI ablation treatment. Materials and Methods: 45 female patients who have not gone through the menopause and had received RAI ablation treatment for well-differentiated thyroid cancer in premenopausal period, and 40 healthy females as control groups were included in this study. The serum AMH, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), thyroid stimulating hormone (TSH) and creatinine levels of the patients included in the study were analyzed and compared to those of the control group with similar demographical characteristics. Results: No differences were found between the patient group and control group in terms of age, height, weight, body mass index, LH, E2 and creatinine. The difference in AMH, FSH and TSH between both groups were found to be significant. There was no statistically significant relation between the age and AMH levels. Similarly, no statistically significant relation between RAI exposure duration and AMH levels was determined. When the patients below and above the age of 35 were compared with regard to AMH (2.95±1.79 and 2.75±1.94, respectively) and FSH (5.45±1.63 and 5.99±3.06, respectively), the difference between them was found to be statistically insignificant. Oligo/anovulation was detected in 7 patients (15.6% of the patient group) after RAI treatment, 8 (17.8%) patients became pregnant after RAI treatment, and none of the patients, who were actively trying to get pregnant, were unable to achieve it. Conclusion: According to these results, it may be concluded that low AMH levels due to RAI treatment can cause damage to the ovaries of patients; nevertheless, considering the AMH levels and the absence of infertility in the patients, the infertility risk was found to be low.

Central Neck Dissection in the Treatment of Well-Differentiated Thyroid Cancer

Therapeutic central compartment neck dissection (CCND) is required for confirmed nodal metastasis in patients with differentiated thyroid cancer. The need for routine prophylactic CCND in patients with papillary thyroid cancer is controversial. This article presents the current evidence to inform the debate against the background of the recommendations of US and British thyroid cancer guidelines. Potential advantages of pCCND include reduced local recurrence, preventing the need for further central compartment surgery and improved staging. Opponents claim that there is no proven patient benefit and that there is increased risk of recurrent laryngeal nerve injury and hypocalcemia.

Risk of hematologic malignancies following radiation treatment for well-differentiated thyroid cancer in the United States over 37 years.

6633 Background: Radiation therapy (XRT) including radioisotopes (RI), radioactive implants (RAI) and external beam radiation (EBRT) are commonly used for treatment of well differentiated thyroid malignancies (WDTMs) – papillary and follicular. We investigated the risk of all secondary hematologic malignancies (SHMs) in a population-based cohort of patients (pts) with WDTMs treated with XRT. Methods: Surveillance, Epidemiology, and End Results (SEER) 17 registries were queried to identify a cohort of 52,121 adult pts with WDTM as the first primary cancer between 1/1973 and 12/2010 who had adequate follow up. To determine the risk of development of SHM at least one year after the diagnosis of WDTM, pts who received XRT were compared to those who did not. SHMs included leukemias, lymphomas and Multiple Myeloma (MM). Fine and Gray competing risk regression analysis was performed with SHM as a time-dependent endpoint and death from any cause, development of non-hematologic malignancy as the competing events. ...

Current status and future perspectives in differentiated thyroid cancer.

Thyroid cancer is increasing all over the world. The exact cause of this increase is still debated and there are conflicting reports. Sophisticated molecular studies suggest that environmental chemicals may have effects of thyroid carcinogenesis. The development of powerful molecular biology techniques has enabled targeted next-generation sequencing for detection of mutations in thyroid cancer, and this technique can make a specific diagnosis of thyroid cancer in cytologically indeterminate cases. The initial treatment of well-differentiated thyroid cancer (DTC) is surgery followed by radioiodine remnant ablation. However, further studies are needed to determine the optimal dosage of radioactive iodine for DTC patients with lateral neck metastasis. DTC is an indolent tumor and may cause death even decades later. Thus, long-term follow-up is mandatory. Recently, dynamic risk stratification (DRS) has begun to use stimulated thyroglobulin level at 1 year after the initial treatment and restratified the risk in accordance with the response to the initial treatment. This DRS strategy accurately predicts disease free survival and can be widely used in daily clinical settings. For the iodine refractory metastatic disease, redifferentiation therapy and targeted therapy are two promising alternative treatments. Sorafenib is the first approved agent for the treatment of progressive iodine refractory advanced thyroid cancer in Korea and may be very helpful for radioactive-refractory locally advanced or metastatic DTC. Selumetinib may be an effective redifferentiating agent and could be used within several years.

A comparative North American experience of robotic thyroidectomy in a thyroid cancer population

This study seeks to explore the efficacy of robotic thyroidectomy in treating a North American population with differentiated thyroid cancer (DTC) as compared with the conventional cervical approach. A retrospective analysis of our prospectively collected thyroid surgery database was performed. We included all consecutive patients that underwent thyroidectomy for the treatment of well-differentiated thyroid cancer, performed by a single surgeon. Twenty-four robotic transaxillary and 35 conventional thyroidectomy procedures were performed. Average size of the tumor was 1.1 ± 0.2 cm in the robotic group and 1.7 ± 0.3 cm in the cervical group (p = 0.16). Average total operative time for the robotic group was 133 ± 65.4 and 119.7 ± 22.5 min in the cervical group (p = 0.34). No robotic cases required conversion. One patient required reoperation for recurrent disease at 24 months follow-up. Both groups had similar blood loss (p = 0.37) and all margins were negative for malignancy on permanent pathology. All patients were discharged home within 24 h. Postoperative stimulated thyroglobulin levels were similar for the two groups (p = 0.82). Our experience with robotic transaxillary thyroidectomy confirms this technique is feasible. It is possible to achieve a safe and effective oncologic result in a select group of North American patients with DTC.

Factors That Influence Radioactive Iodine Use for Thyroid Cancer

There is variation in the use of radioactive iodine (RAI) as treatment for well-differentiated thyroid cancer. The factors involved in physician decision-making for RAI remain unknown. We surveyed physicians involved in postsurgical management of patients with thyroid cancer from 251 hospitals. Respondents were asked to rate the factors important in influencing whether a thyroid cancer patient receives RAI. Multivariable analyses controlling for physician age, gender, specialty, case volume, and whether they personally administer RAI, were performed to determine correlates of importance placed on patients' and physicians' worry about death from cancer and differences between low- versus higher-case-volume physicians. The survey response rate was 63% (534/853). Extent of disease, adequacy of surgical resection, patients' willingness to receive RAI, and patients' age were the factors physicians were most likely to report as quite or very important in influencing recommendations for RAI to patients with thyroid cancer. Interestingly, both physicians' and patients' worry about death from thyroid cancer were also important in determining RAI use. Physicians with less thyroid cancer cases per year were more likely than higher-volume physicians to report patients' (p<0.001) and physicians' worry about death (p=0.016) as quite or very important in decision-making. Other factors more likely to be of greater importance in determining RAI use for physicians with lower thyroid cancer patient volume versus higher include the accepted standard at the affiliated hospital (p=0.020), beliefs about RAI expressed by colleagues comanaging patients (p=0.003), and patient distance from the nearest facility administering RAI (p=0.012). In addition to the extent of disease and adequacy of surgical resection, physicians place importance on physician and patient worry about death from thyroid cancer when deciding whether to treat a patient with RAI. The factors important to physician decision-making differ based on physician thyroid-cancer case-volume, with worry about death being more influential for low-case-volume physicians. As the mortality from thyroid cancer is low, the importance placed on death in decision making may be unwarranted.

Intraoperative Ultrasound-guided Excision of Cervical Lymph Nodes for Recurrent Differentiated Thyroid Cancer

ABSTRACT As a result of sensitive thyroglobulin assays and widespread use of cervical ultrasound, endocrine surgeons are encountering patients with impalpable suspicious or frankly metastatic cervical lymph nodes in the follow-up phase after treatment for welldifferentiated thyroid cancer. The surgical excision of impalpable disease of recurrent or persistent thyroid cancer can represent a significant challenge which may require some means of intraoperative localization to ensure that affected nodes are removed. Surgeon-performed intraoperative ultrasound (IOUS) can be used for guiding excision of suspicious but impalpable cervical nodes. The IOUS-guided excision technique is described. The successful application of IOUS to localize and guide resection of impalpable nodal recurrences of papillary thyroid carcinoma in two patients is reported. The utilization of IOUS to guide resection of impalpable pathological nodes in the context of thyroid carcinoma is a safe and practical technique which avoids the need for additional localization procedures and unnecessary potential morbidity for the patient. How to cite this article Biggar M, Wong C, Law M, Bennett IC. Intraoperative Ultrasound-guided Excision of Cervical Lymph Nodes for Recurrent Differentiated Thyroid Cancer. World J Endoc Surg 2013;5(2):45-49.

Radioiodine treatment of well-differentiated thyroid cancer

Ablation refers to the first administration of radioiodine to a patient with WDTC. Usually, this dose is administered within 4–6 weeks after total thyroidectomy. Because some thyroid tissue is usually present in the neck even after total thyroidectomy, optimal follow-up is achieved following the ablation or destruction of this normal residual thyroid tissue. Other objectives of ablation are discussed below in the “Objectives of radioiodine ablation and treatment” section. The term “Treatment” applies subsequently, when there is evidence of residual and the distinction in the definitions aids in physician to physician communication of the therapeutic interventions. While most endocrinologists use the term “dosage” to apply to the amount of radioiodine administered, the more appropriate term is “activity”. Rather, “dosage,” should be used to express the amount of the radiation absorbed dose in rads or grays administered to the patient.

Prospective Single-Arm Study of Radioprotection by Amifostine in High Dose Radioactive Iodine Therapy for Thyroid Cancer

ABSTRACT Purpose Xerostomia, sialoadenitis, taste dysfunction and nausea are well known toxicities following high dose radioactive iodine (RAI) treatment for well-differentiated thyroid cancer. This prospective study sought to determine the incidence rates for RAI adverse effects and to determine, whether the radioprotector, amifostine could decrease the duration of the adverse effects in single treatment patients. Materials and methods Patients with differentiated thyroid cancer received 150 mCi RAI after total thyroidectomy. All patients were pretreated with 1 mg granisetron and 4 mg dexamethasone. Patients in the amifostine arm (n = 27) were prospectively enrolled and received 500 mg amifostine subcutaneously. Adverse effects were scored based on the CTCAE at 1 month, 6 months, and yearly intervals using a physician administered questionnaire. The results were compared with a retrospective no amifostine cohort (n = 22) for whom data was collected with the identical questionnaire. Results The overall incidence of xerostomia, sialadenitis, taste dysfunction and nausea in the treatment group was 26, 22, 52 and 26% respectively. Only grades 1 and 2 adverse effects were observed. The mean duration (days) of xerostomia (control vs treatment)—37.3 vs 21.9 (F test, p = 0.016), taste dysfunction—45.5 vs 23.5 (F test, p = 0.001), sialadenitis— 16.8 vs 7.5 and nausea—18.7 vs 5.1. Conclusion In patients treated once with high dose RAI, who develop xerostomia, sialoadenitis, taste dysfunction, and/or nausea, the duration of symptoms appears to be reduced by pretreatment with 500 mg of subcutaneous amifostine without significant treatment related adverse effects. How to cite this article Sandhu A, Ioffe V, Karakla D, Wadsworth JT, Mendoza A, Rao N, Dignan K, Mason E, Goffman TE. Prospective Single-Arm Study of Radioprotection by Amifostine in High Dose Radioactive Iodine Therapy for Thyroid Cancer. J Postgrad Med Edu Res 2012;46(2):90-94.

Role of Recombinant Human Thyrotropin (rhTSH) in the Treatment of Well-Differentiated Thyroid Cancer

Since the introduction of radioiodine (RAI) for treatment of well-differentiated thyroid cancer (DTC) more than 50years ago, prolonged periods of hypothyroidism were routinely used as part of the treatment regimen. Recombinant human TSH (rhTSH) was introduced in the 1990s as a tool to elevate the serum TSH without the need for thyroid hormone withdrawal and symptomatic hypothyroidism. After being initially approved as a diagnostic tool for use in RAI scanning and stimulated thyroglobulin testing, rhTSH was approved as an adjunct to RAI remnant ablation in patients without distant metastases in Europe in 2005 and in the US in 2007. Following successful use of rhTSH for diagnostic purposes, it has been extensively studied for use with therapeutic doses of RAI in the setting of RAI remnant ablation and is now an integral part of DCT therapy. The use of rhTSH in clinical practice in the last decade was coupled with the growing interest in an individualized, risk-stratified approach to the management of patients with DCT. While traditional treatment for DTC included surgery and RAI therapy for all patients, many more recent studies demonstrated the value of selective use of RAI only in patients who will probably benefit from treatment. This manuscript reviews the evolving role of rhTSH in the current risk adapted climate of thyroid cancer management with particular emphasis on the use of rhTSH as an aid to RAI therapy.

A Risk-Adapted Approach to the Use of Radioactive Iodine and External Beam Radiation in the Treatment of Well-Differentiated Thyroid Cancer

Both radioactive iodine (RAI) and external beam radiation therapy (EBRT) offer important clinical benefits in properly selected patients with differentiated thyroid cancer. With the increased emphasis on a risk-adapted model for the management of thyroid cancer, it is important to identify which patients are most likely to benefit from radiation therapies given in the adjuvant setting and as treatment of gross residual disease. This review compares the authors' current management practices with the recommendations of published guidelines from both the National Comprehensive Cancer Network and the American Thyroid Association. Because of the lack of prospective randomized studies on either RAI or EBRT in differentiated thyroid cancer, recommendations must be based on retrospective cohort studies that vary in selection criteria, histologies, sample size, inclusion criteria, and follow-up. RAI has an important adjuvant therapy and treatment function in properly selected patients. Likewise, EBRT is associated with increased locoregional control and palliative therapeutic effects in high-risk patients.