Treatment Outcomes of External Beam Radiation Therapy for Unresectable Locally Advanced Thyroid Cancer with or without Metastasis: A Retrospective Single-Center Study

We evaluated treatment outcomes of external beam radiation therapy (EBRT) for unresectable locally advanced thyroid cancer (LATC) with or without metastasis. We enrolled 11 LATC patients who underwent EBRT (median age: 76 (45–83) years; six males and five females). Eastern Cooperative Oncology Group performance statuses of 0 (n = 3), 1 (n = 1), 2 (n = 6), and 3 (n = 1) were observed. Histologic types included papillary carcinoma (n = 5), anaplastic carcinoma (n = 3), and squamous cell carcinoma (n = 3). The organs invaded by the tumor that caused it to be deemed unresectable were common carotid artery (n = 5), trachea (n = 4), aorta (n = 1) and larynx (n = 1). The median follow-up time was 6 months. One, seven, two, and one patient showed complete response (CR), partial response (PR), stable disease, and progressive disease, respectively. The rate of local CR+PR was 73%; moreover, 75% of patients achieved a >30% tumor size reduction within 6 months. The median local progression-free survival of patients with local CR+PR was 11.5 (4–68) months. The median overall survival was 6 (1–68) months. Grade 3 acute complications occurred in five (45%) patients. No patients had Grade 4 or 5 complications. In conclusion, EBRT reduced the tumor volume in 75% of LATC patients without inducing severe toxicity. This therapy should be considered as a treatment option for LATC.

The efficacy and safety of anlotinib in neoadjuvant treatment in locally advanced thyroid cancer: A single-arm phase II clinical trial.

6069 Background: Surgery is the primary treatment for locally advanced thyroid cancer (TC). For some locally advanced TC, R0/R1 resection could not be achieved at initial diagnosis and neoadjuvant treatment would be an option. However, there is still little evidence regarding neoadjuvant treatment in locally advanced TC. Methods: This single-arm, phase 2 study investigated the efficacy and safety of Anlotinib (12mg orally daily, for two weeks on/on week off) for 2-6 cycles in patients with locally advanced TC in the neoadjuvant setting. Operable patients received surgery after neoadjuvant treatment. The primary endpoint was objective response rate (ORR). Results: A total of 13 patients were included and received an average of 3.5 cycles (range: 3-6 cycles) of Anlotinib treatment. 12 cases were papillary thyroid cancer, and 1 was follicular thyroid cancer. The ORR of Anlotinib was 76.9% with 10 partial response (PR), 2 stable disease (SD), and 1 progressive disease (PD). 8 PR and 1 SD patients received surgery after neoadjuvant treatment, of whom 8 had R0/1 resections and 1 had R2 resection. 2 PR patients refused to have surgery and the rest 2 patients were not operable. The R0/1 resection rate for intent to treat population was 61.5% and for per-protocol population was 72.7%. The maximum reduction in sum of tumor diameter was an average of 34.8% (range: 30.9%-45.5%) for PR patients. Most adverse events were grade 1 or 2. Common adverse events of all grade were hypertension (76.9%), hypertriglyceridemia (69.2%), proteinuria (53.8%), TSH increase (53.8%), cholesterol elevation (53.8%) and hand-foot syndrome (38.5%). The majority of adverse events discontinued after the neoadjuvant treatment stopped. Conclusions: Anlotinib demonstrated antitumor activity in the neoadjuvant treatment in locally advanced TC and the majority of patients achieved R0/1 resection. Adverse events were consistent with the known Anlotinib adverse event profile. These results suggest that Anlotinib neoadjuvant treatment represents a new option for locally advanced TC. Clinical trial information: NCT04309136.

Aggressive Thyroid Cancer is Associated With Suppressor Circulating Immunophenotype

Introduction: The influence of the immune system on follicular cell-derived thyroid cancer behavior has been suggested by various studies but this information has not been comprehensively translated into a prediction for thyroid cancer prognosis. We aimed to identify circulating immune cell profiles associated with thyroid cancer prognosis. This information would be a significant advance in the field of thyroid cancer management. Methods: We performed a single-center prospective cohort study of 32 follicular-cell derived thyroid cancer patients enrolled at the time of initial or subsequent surgery. We performed peripheral blood multi-parameter flow cytometry and collected relevant clinicopathologic, biochemical and radiologic data. We classified patients based on the AJCC TNM cancer stage, American Thyroid Association (ATA) initial risk of recurrence, and status of disease during follow-up. Results: On initial immunophenotyping, patients with aggressive/advanced thyroid cancer (ATA high risk vs. intermediate/low risk; AJCC stage 3/4 vs. 1/2; recurrence or distant metastases vs. no evidence of disease during follow-up) demonstrated increased circulating monocytes and granulocytes but decreased all lymphocytes, T cells (specifically CD4+ and gamma delta) and natural killer (NK) T-like cells. Further immunophenotyping revealed that aggressive/advanced thyroid cancer had increased circulating CD4+CD45+RO effector memory but decreased CD4+CD45+RA central memory T cells and increased regulatory T cells. Stage 3/4 thyroid cancer patients additionally had increased circulating CD33+HLADR- myeloid-derived suppressor cells (MDSCs) as compared to stage1/2. Conclusions: Aggressive thyroid cancer at presentation (AJCC stage, ATA risk category) or during follow-up (distant metastases) is characterized by a circulating immunophenotype comprising of increased immune suppressor cells (regulatory T cells, MDSCs, effector memory T cells) but decreased immune activator cells (CD4+ T cells, gamma delta T cells, NK T-like cells, central memory T cells) as compared to less aggressive thyroid cancer. This circulating immunophenotype may serve as a biomarker for cancer prognosis and guide the selection and development of novel immunotherapies for advanced thyroid cancer.

Effect of Metabolic Health on Severity of Thyroid Cancer: The Scripps Clinic Thyroid Cancer Cohort Analysis

Introduction: The increasing prevalence of obesity has been linked to increased risk of cancers such as prostate, breast and endometrium, but its role in thyroid cancer is not clearly established. Since prevalence of obesity-related metabolic disturbances (dyslipidemia, dysglycemia) varies among individuals, it has been suggested that poor metabolic health, rather than obesity (defined by BMI), plays a role in thyroid cancer. We performed a retrospective review of our thyroid cancer cohort to evaluate the association between metabolic health and severity of thyroid cancer. Objectives: 1. Association between dyslipidemia and stages of thyroid cancer 2. Association between dysglycemia and stages of thyroid cancer. Methodology: The Scripps Clinic Thyroid Cancer Cohort includes 656 patients diagnosed with thyroid cancer from 2017-2020 in the Scripps Health System. IRB approval for our study was obtained in January 2020. Inclusion criteria: 1. Confirmed thyroid cancer on surgical pathology 2. First available lipid profile at least 6 months prior to diagnosis 3. First available HbA1c at least 6 months prior to diagnosis. A total of 214 patients with an available lipid profile were included in the analysis. Of those, 148 had an available HbA1c. Definitions used: 1. Dyslipidemia - total cholesterol >=200 mg/dl or HDL <40 mg/dl in males, <50 mg/dl in females or triglycerides >=150 mg/dl. 2. Dysglycemia - HbA1c >=5.7%. Thyroid cancer stages were compared in patients with and without dyslipidemia and dysglycemia. Subgroup analysis was performed for patients above age of 55 years (n=103) due to difference in AJCC staging. Results: A larger proportion of dyslipidemic patients (28.4% vs 18.1%) had stage 2-4 thyroid cancer, but the difference was not statistically significant (p 0.07). A larger proportion of dysglycemic patients (36.3% vs 15.6%) had stage 2-4 thyroid cancer, a statistically significant difference (p 0.003). Similar findings were noted on subgroup analysis: a larger proportion of dyslipidemic (15.2% vs 8.2%) patients had Stage 3-4 thyroid cancer without statistical significance (p 0.1), while a statistically significant higher percentage of dysglycemic patients (20% vs 2.7%, p 0.01), had stage 3-4 thyroid cancer. A larger proportion of advanced thyroid cancer cases was noted in patients with both dyslipidemia and dysglycemia as compared to patients with only one abnormality or none. Conclusions: 1. Poor metabolic health, particularly dysglycemia, is associated with advanced stages of thyroid cancer, especially in the >=55 years age group. Dysglycemia with dyslipidemia confers highest probability of advanced thyroid cancer. 2. Mechanisms by which dysglycemia affects thyroid cancer severity requires further rigorous study. 3. Based on our study, we recommend a thorough discussion regarding risk of advanced thyroid cancer in patients with poor metabolic health and thyroid nodules.