Distant metastases from thyroid cancer of follicular origin are uncommon. Treatment includes levothyroxine administration, focal treatment modalities with surgery, external radiation therapy and ...thermal ablation, and radioiodine in patients with uptake of 131I in their metastases. Two-thirds of distant metastases become refractory to radioiodine at some point, and when there is a significant tumor burden and documented progression on imaging, a treatment with a kinase inhibitor may provide benefits.
Background:
Radioiodine remnant ablation (RRA) has traditionally been one of the cornerstones of differentiated thyroid cancer (DTC) treatment. The decision to use RRA in low-risk (LR) and ...intermediate-risk (IR) patients is controversial. The aim of this review is to examine the evidence of RRA benefit in the staging, follow-up, and recurrence prevention in LR and IR DTC patients.
Methods:
From a PubMed search, we selected original papers (OPs) using the following inclusion criteria: 1) DTC; 2) LR and IR patients; 3) non-RRA-treated patients or RRA-treated vs non-RRA-treated groups; 4) a report of the outcome of cancer recurrence; and 5) publication since 2008.
Results:
Neck ultrasonography is superior to whole-body scan for disease detection in the neck. A rising or declining serum thyroglobulin level over time provides an excellent positive or negative predictive value, respectively, even in non-RRA-treated patients. No OP demonstrating RRA benefit on recurrence in LR patients was found; two OPs found no evidence of benefit. We found 11 OPs that observed some benefit in reducing recurrence rates with RRA in IR patients and 13 OPs that failed to show benefit from RRA in this group.
Conclusions:
Neck ultrasonography and serum thyroglobulin measurement are equivalent or superior in detecting and localizing residual disease compared to post-therapy whole-body scan. There is no evidence of RRA benefit in recurrence prevention for LR patients. There are conflicting data on IR patients and only a few studies with homogenous and properly stratified populations. A careful evaluation of tumor pathological features and patient characteristics and preferences should guide RRA decision making.
IMPORTANCE: Detection of asymptomatic thyroid nodules has increased. Consensus is lacking regarding the optimal follow-up of cytologically proven benign lesions and sonographically nonsuspicious ...nodules. Current guidelines recommend serial ultrasound examinations and reassessment of cytology if significant growth is observed. OBJECTIVE: To determine the frequency, magnitude, and factors associated with changes in thyroid nodule size. DESIGN, SETTING, AND PARTICIPANTS: Prospective, multicenter, observational study involving 992 consecutive patients with 1 to 4 asymptomatic, sonographically or cytologically benign thyroid nodules. Patients were recruited from 8 hospital-based thyroid-disease referral centers in Italy between 2006 and 2008. Data collected during the first 5 years of follow-up, through January 2013, were analyzed. MAIN OUTCOMES AND MEASURES: Baseline nodule growth (primary end point) was assessed with yearly thyroid ultrasound examinations. Size changes were considered significant for growth if an increase of 20% or more was recorded in at least 2 nodule diameters, with a minimum increase of 2 mm. Baseline factors associated with growth were identified. Secondary end points were the sonographic detection of new nodules and the diagnosis of thyroid cancer during follow-up. RESULTS: Nodule growth occurred in 153 patients (15.4% 95% CI, 14.3%-16.5%). One hundred seventy-four of the 1567 original nodules (11.1% 95% CI, 10.3%-11.9%) increased in size, with a mean 5-year largest diameter increase of 4.9 mm (95% CI, 4.2-5.5 mm), from 13.2 mm (95% CI, 12.1-14.2 mm) to 18.1 mm (95% CI, 16.7-19.4 mm). Nodule growth was associated with presence of multiple nodules (OR, 2.2 95% CI 1.4-3.4 for 2 nodules; OR, 3.2 95% CI, 1.8-5.6 for 3 nodules; and OR, 8.9 95% CI, 4.4-18.0 for 4 nodules), main nodule volumes larger than 0.2 mL (OR, 2.9 95% CI, 1.7-4.9 for volumes >0.2 to <1 mL and OR, 3.0 95% CI, 1.8-5.1 for volumes ≥1 mL), and male sex (OR, 1.7 95% CI, 1.1-2.6), whereas an age of 60 years or older was associated with a lower risk of growth than age younger than 45 years (OR, 0.5 95% CI 0.3-0.9). In 184 individuals (18.5% 95% CI, 16.4%-20.9%), nodules shrank spontaneously. Thyroid cancer was diagnosed in 5 original nodules (0.3% 95% CI, 0.0%-0.6%). Only 2 had grown. An incidental cancer was found at thyroidectomy in a nonvisualized nodule. New nodules developed in 93 patients (9.3% 95% CI, 7.5%-11.1%), with detection of one cancer. CONCLUSIONS AND RELEVANCE: Among patients with asymptomatic, sonographically or cytologically benign thyroid nodules, the majority of nodules exhibited no significant size increase during 5 years of follow-up and thyroid cancer was rare. These findings support consideration of revision of current guideline recommendations for follow-up of asymptomatic thyroid nodules.
Ultrasonography is the best available tool for the initial work-up of thyroid nodules. Substantial interobserver variability has been documented in the recognition and reporting of some of the lesion ...characteristics. A number of classification systems have been developed to estimate the likelihood of malignancy: several of them have been endorsed by scientific societies, but their reproducibility is yet to be assessed. We evaluated the interobserver variability of the AACE/ACE/AME, ACR, ATA, EU-TIRADS and K-TIRADS classification systems and the interobserver concordance in the indication to FNA biopsy. Two raters independently evaluated 1055 ultrasound images of thyroid nodules identified in 265 patients at multiple time points, in two separate sets (501 and 554 images). After the first set of nodules, a joint reading was performed to reach a consensus in the feature definitions. The interobserver agreement (Krippendorff alpha) in the first set of nodules was 0.47, 0.49, 0.49, 0.61 and 0.53, for AACE/ACE/AME, ACR, ATA, EU-TIRADS and K-TIRADS systems, respectively. The agreement for the indication to biopsy was substantial to near-perfect, being 0.73, 0.61, 0.75, 0.68 and 0.82, respectively (Cohen’s kappa). For all systems, agreement on the nodules of the second set increased. Despite the wide variability in the description of single ultrasonographic features, the classification systems may improve the interobserver agreement that further ameliorates after a specific training. When selecting nodules to be submitted to FNA biopsy, that is main purpose of these classifications, the interobserver agreement is substantial to almost perfect.
The main clinical challenge in the management of thyroid cancer is to avoid over-treatment and over-diagnosis in patients with lower-risk disease while promptly identifying those patients with more ...advanced or high-risk disease requiring aggressive treatment. In recent years, novel clinical and molecular data have emerged, allowing the development of new staging systems, predictive and prognostic tools, and treatment approaches. There has been a notable shift toward more conservative management of low- and intermediate-risk patients, characterized by less extensive surgery, more selective use of radioisotopes (for both diagnostic and therapeutic purposes), and less intensive follow-up. Furthermore, the histologic classification; tumor, node, and metastasis (TNM) staging; and American Thyroid Association risk stratification systems have been refined, and this has increased the number of patients in the low- and intermediate-risk categories. There is now a need for new, prospective data to clarify how these changing practices will impact long-term outcomes of patients with thyroid cancer, and new follow-up strategies and biomarkers are still under investigation. On the other hand, patients with more advanced or high-risk disease have a broader portfolio of options in terms of treatments and therapeutic agents, including multitarget tyrosine kinase inhibitors, more selective BRAF or MEK inhibitors, combination therapies, and immunotherapy.
Background
A preoperative neck ultrasound (US) is recommended for all patients with suspected thyroid cancer, to identify features potentially changing surgical extent. The extrathyroidal extension ...(ETE) is considered an indication for total thyroidectomy, but there is limited consensus on its US definition, and the interobserver reliability is low. This study aimed to evaluate the predictive value of neck US for ETE before surgery and to estimate the diagnostic performance of different US findings, evaluated during real-time examinations.
Methods
Patients referred to surgery between November 1, 2015, and May 31, 2019, for a suspicious thyroid cancer underwent a preoperative neck US, with systematic assessment for ETE. Three definitions were tested: very restrictive (capsular disruption with suspicious images of surrounding tissues invasion), restrictive (including also capsular abutment with evidence of capsular disruption), and nonrestrictive (capsular abutment is sufficient). Histopathology report of ETE involving at least soft tissues was considered positive. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated.
Results
The study cohort included 128 patients, with 102 (79.7%) confirmed malignancies, and 44 (43.1%) histological ETE. The nonrestrictive definition had good sensitivity (86.4%) but low specificity (29.8%), with an NPV of 80.6%; the restrictive definition had higher specificity (81%), while the very restrictive had specificity and PPV of 100%.
Conclusions
A more extensive surgical approach should not be based on US suspicion of ETE alone, with the possible exception of gross invasion appearance. The absence of any sign of ETE, on the other hand, has a substantial negative predictive value.
Anaplastic thyroid carcinoma (ATC) is a rare and undifferentiated form of thyroid cancer. Its prognosis is poor: the median overall survival (OS) of patients varies from 4 to 10 months after ...diagnosis. However, a doubling of the OS time may be possible owing to a more systematic use of molecular tests for targeted therapies and integration of fast-track dedicated care pathways for these patients in tertiary centers. The diagnostic confirmation, if needed, requires an urgent biopsy reread by an expert pathologist with additional immunohistochemical and molecular analyses. Therapeutic management, defined in multidisciplinary meetings, respecting the patient's choice, must start within days following diagnosis. For localized disease diagnosed after primary surgical treatment, adjuvant chemo-radiotherapy is recommended. In the event of locally advanced or metastatic disease, the prognosis is very poor. Treatment should then involve chemotherapy or targeted therapy and decompressive cervical radiotherapy. Here we will review current knowledge on ATC and provide perspectives to improve the management of this deadly disease.
Objective
Localization of the vagus nerve is required during intraoperative neuromonitoring (IONM) for thyroid surgery in order to electromyographically verify the functional integrity of inferior ...laryngeal nerve and aim to reduce the risk of postoperative vocal fold paralysis. Classically, the vagus nerve courses within the carotid sheath between the common carotid artery and internal jugular vein, but anatomic variations have been described. Our aim was to compare preoperative ultrasound (US) and intraoperative localization of vagus nerve and to document anatomic variations.
Patients and methods
Retrospective study of patients undergoing thyroidectomy. The vagus nerve was identified 2 cm below the inferior border of the cricoid cartilage, on US performed 6 weeks prior to surgery; then, vagus nerve was identified surgically.
Results
For 82 patients, on preoperative US, the right vagus nerve was in between, superficial, or deep to the vessels in 94%, 2.4%, and 3.6%, and on the left in 72%, 24.4%, and 3.6%. Intraoperatively, the right vagus was in between, superficial, or deep in 90%, 4%, and 6%, and on the left in 67%, 27%, and 6%. US correlated with surgery on the right in 79/82 (96%) and on the left in 78/82 (95%).
Conclusions
To our knowledge, this is the first study directly comparing US and intraoperative findings. The US and surgical findings were identical in 95% on the left and 96% on the right The vagus nerve was superficial in 27% of cases on the left and 4% on the right. Identifying this anatomic variation preoperatively may facilitate IONM.
Key Points
• Localization of the vagus nerve is necessary during thyroid surgery when using neuromonitoring for electromyographic testing of the inferior laryngeal nerve to reduce the risk of postoperative vocal fold paralysis.
• The vagus nerve in the neck can be routinely visualized using ultrasound, and is generally in between the common carotid artery and the internal jugular vein. Its location on ultrasound corresponds very closely to that observed in vivo during surgery (95%).
• At the level of the thyroid lobe, there is an anatomic variant with the vagus nerve superficial to the common carotid artery which is seen more often on the left than on the right.
Purpose
Bone metastases (BM) from differentiated thyroid carcinoma (DTC) impact negatively the quality of life and the life expectancy of patients. The aim of the study was (a) to evaluate the ...overall survival (OS) and prognostic factors of OS and (b) to assess predictive factors of complete BM response (C-BM-R) using radioiodine treatment (RAI) either alone or in association with focal treatment modalities.
Methods
A total of 178 consecutive DTC patients harbouring BM, treated between 1989 and 2015, were enrolled in this retrospective study conducted in two tertiary referral centers. OS analysis was performed for the whole cohort, and only the 145 considered non-RAI refractory patients at BM diagnosis were evaluated for C-BM-R following RAI.
Results
The median OS from BM diagnosis was 57 months (IQR: 24–93). In multivariate analysis, OS was significantly reduced in the case of T4 stage,
18
FDG uptake by the BM and RAI refractory status. Among the 145 DTC considered non-RAI refractory patients at BM diagnosis, 46 patients (31.7%) achieved a C-BM-R following RAI treatment, either alone in 32 (18%) patients or in association with focal BM treatment modalities in 14. The absence of extra-skeletal distant metastasis and of
18
FDG uptake in BM were predictive for C-BM-R.
Conclusions
In nearly one-third of DTC patients with RAI avid BM, RAI alone or in combination with BM focal treatment can induce C-BM-R. The presence of
18
FDG uptake in BM is associated with an absence of C-BM-R and with a poor OS.
18
FDG PET-CT should be performed when BM is suspected.
Purpose
Presence of venous vascular invasion is a criterion of intermediate risk of recurrence in papillary thyroid carcinoma (PTC). However, the presence and type of vascular invasion (lymphatic or ...venous) is often underreported and its impact on PTCs without other risk features remains unknown. The aim of this study was to evaluate the impact of both lymphatic and venous invasion on the risk of recurrence/persistence on otherwise low-risk PTCs.
Methods
Retrospective study including patients with otherwise low-risk PTCs but with vascular invasion, diagnosed between 2013 and 2019. The persistence/recurrence during the follow-up was evaluated. Pathology was reviewed to confirm the presence of lymphovascular invasion and determine the type of invasion.
Results
A total of 141 patients were included. Lymphovascular invasion was confirmed in 20.6%. After surgery, 48.9% (
N
= 69) of the patients received radioactive iodine (RAI). The median follow-up time was 4 3–6 years. Overall, 6 (4.2%) patients experienced persistent/recurrent disease in the neck, including 3 with lymphovascular invasion, confirmed as “only lymphatic”. Overall, patients with tumors harboring lymphovascular invasion had sensibly more persistent/recurrence disease compared with those without lymphovascular invasion (10.3% vs 2.7%,
p
= 0.1), especially in the subgroup of patients not treated with RAI (20% vs 1.6%,
p
= 0.049) OR 15.25, 95% CI 1.24-187.85,
p
= 0.033.
Conclusion
Lymphovascular invasion, including lymphatic invasion only, is associated with a sensibly higher risk of persistent/recurrent disease in otherwise low-risk PTCs, namely in patients not treated with RAI. Lymphatic invasion could have a role in risk-stratification systems for decision making.
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