Search

Background: Low‐risk papillary thyroid carcinoma (LR‐PTC) can be managed by immediate surgery (IS) or active surveillance (AS). We compare the psychological impact of these treatments on patients with LR‐PTC. Methods: Psychological data were collected over 1 year, with assessments at the time of treatment decision (T1), at 6 months (T2) and 12 months (T3) follow‐up. Assessments included 13 validated psychological tools. Results: Of 27 enrolled patients, 20 chose AS and 7 chose IS. The average times to T2 and T3 were 5.7 and 11.3 months, respectively. For both groups, Impact of Events Scale scores significantly decreased (p = 0.001) at T2, and depressive/anxiety symptoms remained low. Conclusions: This study demonstrates the feasibility of assessing psychological outcomes among patients treated for LR‐PTC. Further studies are needed to evaluate the impact of AS versus IS on quality of life and changes that patients experience over longer time periods following their treatment decision. [ABSTRACT FROM AUTHOR]

Aims: We aimed to study the clinicopathological and molecular features of high-grade non-anaplastic thyroid carcinomas (HGTCs), a carcinoma with a prognosis intermediate between those of well-differentiated carcinoma and anaplastic carcinoma. Methods and results: This study included 364 HGTC patients: 200 patients (54.9%) were diagnosed with poorly differentiated thyroid carcinoma (PDTC), based on the Turin consensus (HGTC-PDTC), and 164 were diagnosed with high-grade features that did not meet the Turin criteria (HGTC-nonPDTC). HGTCs are aggressive: the 3-year, 5-year, 10-year and 20-year diseasespecific survival (DSS) rates were 89%, 76%, 60%, and 35%, respectively. Although DSS was similar between HGTC-PDTC and HGTC-nonPDTC patients, HGTC-PDTC was associated with higher rate of radioactive iodine avidity, a higher frequency of RAS mutations, a lower frequency of BRAF V600E mutations and a higher propensity for distant metastasis (DM) than HGTCnonPDTC. Independent clinicopathological markers of worse outcome were: older age, male sex, extensive necrosis and lack of encapsulation for DSS; older age, male sex and vascular invasion for DM-free survival; and older age, necrosis, positive margins and lymph node metastasis for locoregional recurrence-free survival. The frequencies of BRAF, RAS, TERT, TP53 and PTEN alterations were 28%, 40%, 55%, 11%, and 10%, respectively. TP53, PTEN and TERT were independent molecular markers associated with an unfavourable outcome, independently of clinicopathological parameters. The coexistence of BRAF V600E and TERT promoter mutation increased the risk of DM. Conclusions: The above data support the classification of HGTC as a single group with two distinct subtypes based on tumour differentiation: HGTC-PDTC and HGTC-nonPDTC. [ABSTRACT FROM AUTHOR]

Aims: We aimed to study the clinicopathological and molecular features of high‐grade non‐anaplastic thyroid carcinomas (HGTCs), a carcinoma with a prognosis intermediate between those of well‐differentiated carcinoma and anaplastic carcinoma. Methods and results: This study included 364 HGTC patients: 200 patients (54.9%) were diagnosed with poorly differentiated thyroid carcinoma (PDTC), based on the Turin consensus (HGTC‐PDTC), and 164 were diagnosed with high‐grade features that did not meet the Turin criteria (HGTC‐nonPDTC). HGTCs are aggressive: the 3‐year, 5‐year, 10‐year and 20‐year disease‐specific survival (DSS) rates were 89%, 76%, 60%, and 35%, respectively. Although DSS was similar between HGTC‐PDTC and HGTC‐nonPDTC patients, HGTC‐PDTC was associated with higher rate of radioactive iodine avidity, a higher frequency of RAS mutations, a lower frequency of BRAF V600E mutations and a higher propensity for distant metastasis (DM) than HGTC‐nonPDTC. Independent clinicopathological markers of worse outcome were: older age, male sex, extensive necrosis and lack of encapsulation for DSS; older age, male sex and vascular invasion for DM‐free survival; and older age, necrosis, positive margins and lymph node metastasis for locoregional recurrence‐free survival. The frequencies of BRAF, RAS, TERT, TP53 and PTEN alterations were 28%, 40%, 55%, 11%, and 10%, respectively. TP53, PTEN and TERT were independent molecular markers associated with an unfavourable outcome, independently of clinicopathological parameters. The coexistence of BRAF V600E and TERT promoter mutation increased the risk of DM. Conclusions: The above data support the classification of HGTC as a single group with two distinct subtypes based on tumour differentiation: HGTC‐PDTC and HGTC‐nonPDTC. [ABSTRACT FROM AUTHOR]

Background: Several multitargeted tyrosine kinase inhibitors (TKIs) have demonstrated activity in patients with thyroid cancer that is refractory to radioactive iodine (RAI). The antitumor effect is attributed at least in part to the ability of these TKIs to inhibit angiogenesis in these vascular tumors. Vascular endothelial growth factor (VEGF) Trap (VT) is a recombinantly produced fusion protein consisting solely of human sequences for VEGF receptors 1 and 2 extracellular domains and human immunoglobulin 1. Evaluating VT in patients with thyroid cancer is reasonable considering the activity observed with TKIs targeting VEGF.Methods: The current study was a single-institution, phase 2, Simon 2-stage design (21 to >41 patients) study based on the objective response rate and/or 6-month progression-free survival as the primary endpoints. Eligible patients were required to have progressive, RAI-refractory and/or [18 F]fludeoxyglucose-avid, recurrent and/or metastatic, nonmedullary, nonanaplastic thyroid cancer; disease that was measurable using Response Evaluation Criteria In Solid Tumors (RECIST) criteria; and adequate organ and bone marrow function. VT at a dose of 4 mg/kg intravenously was administered every 14 days.Results: A total of 40 patients were included in the analysis. Of these patients, 24 had papillary thyroid cancer, 2 had follicular thyroid cancer, and 11 had Hurthle cell thyroid cancer. The final 3 tumors were classified as poorly differentiated. There were no complete and/or partial responses noted; 34 patients achieved stable disease and 6 patients experienced disease progression as their best response. Of the 34 patients with stable disease, 16 remained on the study for >6 months and 6 patients remained on the study for >12 months. The median duration on treatment was 4.1 months (range, 0.6-30.8 months).Conclusions: Unlike TKIs, which have shown responses in this setting, to the authors' knowledge there have been no responses observed with the use of single-agent VT to date. It does not appear to be a promising drug for the treatment of patients with thyroid cancer. [ABSTRACT FROM AUTHOR]

Summary: Purpose: To assess molecular targeted therapy (MTT)'s ability to affect tumour volume doubling time (TVDT) and disease‐specific survival (DSS) in patients presenting with lung metastasis from radioactive iodine refractory progressive thyroid cancer. Methods: In this retrospective study, we examined the clinical characteristics, average tumour volume doubling times of lung metastasis and disease‐specific survival of patients with lung metastasis from differentiated thyroid cancer who were treated with MTT. Results: The 5‐year DSS from the distant metastasis (DM) diagnosis was 72% with median survival of 8 years (95% CI: 6.6‐9.5). The median survival was 2.9 years after MTT start (95% CI: 2.1‐3.6). On MTT, lung average tumour volume doubling time (midDT) was prolonged to midDT ≥3 years in 75% of patients with baseline midDT ≤1 year and 100% of patients with midDT 1‐3 years. In patients with rapidly progressive thyroid cancer (midDT ≤1 year at baseline), the median survival was 4.5 years in those with MTT‐achieved midDT ≥3 years (95% CI: 2.9‐6.2), as opposed to 2.3 years (95% CI: 0.3‐4.3) and 0.7 years (95% CI: 0.2‐1.3) in those with MTT‐achieved midDT of 1‐3 years and MTT‐achieved midDT ≤1 year, respectively (log rank P < 0.001). Conclusion: Lung midDT is a useful and important clinical marker of disease‐specific survival for patients with progressive radioactive iodine refractory (RAIR) metastatic thyroid cancer. In patients with rapidly progressive metastatic RAIR thyroid cancer, molecular targeted therapy prolongs lung tumour volume doubling time and is associated with improved disease‐specific survival. [ABSTRACT FROM AUTHOR]

Background Following total thyroidectomy ( TT) for papillary thyroid cancer ( PTC), pathological assessment can occasionally reveal incidental perithyroidal lymph nodes ( LNs) with occult metastases. These cN0pN1a patients often receive radioactive iodine ( RAI) therapy for this indication alone . The aim of this study was to determine the central compartment nodal recurrence-free survival in patients treated without RAI compared to those who received RAI treatment. Methods An institutional database of 3664 previously untreated patients with differentiated thyroid cancer operated between 1986 and 2010 was reviewed. A total of 232 pT1-3 patients managed with TT and no neck dissection were subsequently found to have incidental level 6 LNs on pathology. Patients with other indications for RAI, such as extrathyroidal extension and close or positive margins, were excluded. One hundred and four patients remained for analysis. Kaplan-Meier method was used to determine central neck LN recurrence-free survival ( RFS). Results The median age of the cohort was 40 years (range 17-83). The median follow-up was 53 months (range 1-211). The median number of positive LNs removed and maximum LN diameter were 1 (range 1-8) and 5 mm (range 1-16 mm), respectively. A total of 67 (64%) patients had adjuvant RAI and 37 (36%) did not. Patients with vascular invasion ( P = 0·01), LNs >2 mm ( P = 0·07) and >2 positive nodes ( P = 0·06) were more likely to be selected for adjuvant RAI therapy. Patients without RAI therapy had similar 5-year central neck LN RFS compared to those treated with RAI: 96·2% vs 94·6%, respectively ( P = 0·92). Conclusion There is no difference in the 5-year central compartment nodal recurrence-free survival in patients treated without RAI compared to those who received RAI treatment. [ABSTRACT FROM AUTHOR]

Objective Staging systems applied to medullary thyroid cancer (MTC) rely on initial clinical and pathological features and do not consider the response to treatment. To determine whether MTC staging can be improved by incorporating the first postoperative calcitonin measurement. Patients and measurements Eighty-five patients being monitored for MTC (median follow-up 5 years) were retrospectively classified according to both the American Joint Committee on Cancer (AJCC) and the proposed combined risk stratification system (low, intermediate and high risk), which incorporates the first postoperative calcitonin measurement, using the outcomes no evidence of disease (NED), biochemical evidence of disease, structurally identifiable disease and death. Results Ninety per cent of AJCC I patients were classified as NED at final follow-up. When we added a postoperative calcitonin measurement, 95% low-risk patients were classified as NED at final follow-up. AJCC stages I and IV were associated, respectively, with no occurrence and a high rate (63%) of structurally identifiable disease. Stages II and III yielded similar predictions of structurally identifiable disease, 13% and 14%, respectively. When we included the postoperative calcitonin level, the patients with structural evidence of disease included none from the low-risk group, 10% from the intermediate group and 63% from the high-risk group. The proportion of variance explained analysis (PVE) was better for the combined risk stratification system (54%) than for the AJCC system alone (32%). Conclusion Including the first postoperative calcitonin measurement with the anatomical staging system can better predict the clinical outcome of patients with MTC and refine the follow-up of these patients. [ABSTRACT FROM AUTHOR]

The microbiome can significantly impact host phenotypes and serve as an additional source of heritable genetic variation. While patterns across eukaryotes are consistent with a role for symbiotic microbes in host macroevolution, few studies have examined symbiont-driven host evolution or the ecological implications of a dynamic microbiome across temporal, spatial or ecological scales. The pea aphid, Acyrthosiphon pisum, and its eight heritable bacterial endosymbionts have served as a model for studies on symbiosis and its potential contributions to host ecology and evolution. But we know little about the natural dynamics or ecological impacts of the heritable microbiome of this cosmopolitan insect pest. Here we report seasonal shifts in the frequencies of heritable defensive bacteria from natural pea aphid populations across two host races and geographic regions. Microbiome dynamics were consistent with symbiont responses to host-level selection and findings from one population suggested symbiont-driven adaptation to seasonally changing parasitoid pressures. Conversely, symbiont levels were negatively correlated with enemy-driven mortality when measured across host races, suggesting important ecological impacts of host race microbiome divergence. Rapid drops in symbiont frequencies following seasonal peaks suggest microbiome instability in several populations, with potentially large costs of 'superinfection' under certain environmental conditions. In summary, the realization of several laboratory-derived, a priori expectations suggests important natural impacts of defensive symbionts in host-enemy eco-evolutionary feedbacks. Yet negative findings and unanticipated correlations suggest complexities within this system may limit or obscure symbiont-driven contemporary evolution, a finding of broad significance given the widespread nature of defensive microbes across plants and animals. [ABSTRACT FROM AUTHOR]