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
I 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.
Purpose
To determine efficacy and safety of thermal ablation (TA) for the local treatment of lung metastases of thyroid cancer.
Methods
We retrospectively studied 47 patients from 10 centers treated ...by TA (radiofrequency, microwaves, and cryoablation) over 10 years. The endpoints were overall survival (OS), local efficacy, complications (CTCAE classification), and factors associated with survival. OS curves after first TA were built using the Kaplan–Meier method and compared with the log-rank test.
Results
A total of 107 lung metastases during 75 sessions were treated by radiofrequency (
n
= 56), microwaves (
n
= 9), and cryoablation (
n
= 10). Median follow-up time after TA was 5.2 years (0.2–13.3). OS was 93% at 2 years (95% confidence interval (CI): 86–94) and 79% at 3 years (95% CI: 66–91). On univariate and multivariate analysis with a Cox model, histology was the only significant factor for OS. OS at 3 years was 94% for follicular, oncocytic, or papillary follicular variant carcinomas, compared to 59% for papillary, medullary, insular or anaplastic carcinomas (
P
= 0.0001). The local control rate was 98.1% at 1 year and 94.8% at 2, 3, 4, and 5 years. Morbidity was low with no major complications (grade 4 and 5 CTCAE) and no complications in 29 of 75 sessions (38.7%).
Conclusions
TA is a useful, safe and effective option for local treatment of lung metastases from thyroid carcinoma. Prolonged OS was obtained, especially for lung metastases from follicular, oncocytic, or papillary follicular variant carcinomas. Achieving disease control with TA delays the need for systemic treatment.
Lymph node involvement (LNI) is one of the most important prognostic factors for poor survival in medullary thyroid carcinoma (MTC). At diagnosis, LNI is found in over 50% of sporadic MTCs, and ...especially in large tumours. Cervical lymph node dissection is therefore mandatory during MTC surgery. However, some large tumours (responsible for high preoperative basal calcitonin levels) are found to lack LNI, and can be cured definitely. Preoperative detection of these particular tumours might spare patients from undergoing extensive cervical dissection. The objective of the present retrospective study of a series of large sporadic MTCs was to identify clinical, biological and pathological factors that were predictive of LNI. Consecutive cases of large, sporadic MTCs (measuring at least 1 cm in diameter) were retrieved and reviewed. The levels of several mature microRNAs (miRs) in paraffin-embedded samples were assessed using qPCR. Of the 54 MTCs, 26 had LNI and 28 were pN0. Relative to pN0 patients, patients with LNI had a significant higher preoperative basal calcitonin level (
p
= 0.0074) and a greater prevalence of infiltrative margins (
p
< 0.0001), lymphovascular invasion (
p
= 0.0004), extrathyroidal extension (
p
< 0.0001), a higher pT stage (
p
= 0.0003) and more abundant desmoplastic stroma (
p
= 0.0006). Tumour expression levels of miR-21 (
p
= 0.0008) and miR-183 (
p
= 0.0096) were higher in the LNI group. The abundance of desmoplastic stroma (
p
= 0.007) and the miR-21 expression level (
p
= 0.0026) were independent prognostic factors for LNI. The abundance of desmoplastic stroma and high levels of miR-21 expression were strong indicators of LNI, and may thus help the surgeon to choose the extent of cervical lymph node dissection for large, sporadic MTCs with no preoperatively obvious LNI.
Quality of life is an important issue in endocrine tumors because of the high prevalence of benign tumors and the indolent course of most malignant tumors.
To evaluate the frequency and the intensity ...of pain and anxiety in patients undergoing thyroid nodule fine-needle aspiration cytology (FNAC) and to identify factors associated with pain.
Single center prospective study in the setting of a one-stop outpatient diagnostic clinic for thyroid nodules. Pain was evaluated using a 100-mm visual analogue scale (VAS) immediately following (VAS1) and 30 minutes after (VAS2) FNAC and was considered significant if ≥ 30. Anxiety symptoms were assessed prior to FNAC using a self-report measure questionnaire: the state form of Spielberger State-Trait Anxiety Inventory (STAI, form Y-A). FNAC was performed with a 25-gauge needle and a moderate aspiration and two passes for each nodule.
Two hundred eighteen consecutive patients (163 females, 55 males; mean age 53 years, range 12-84 years) undergoing FNAC of one to three nodules were included. VAS1 was ≥ 30 in 24% of the patients and VAS(2) was ≥ 30 in 13% of the patients. Independent significant factors correlated to a VAS1 of ≥ 30 were age under 25 years and the number of nodules being biopsied. Independent significant factors correlated to a VAS2 of ≥ 30 were VAS1 ≥ 30 and female sex. No correlation was found between pain and nodule size or nodule depth, nor the duration of application of the eutectic mixture of local anesthetics (EMLA) patch prior to FNAC. The mean STAI score for anxiety was 37 ± 12. The average STAI score was significantly higher in women (39) than in men (33; p = 0.01). There was no significant correlation between STAI score and age under 25 years, previous FNAC, number of nodules biopsied, or acetaminophen administration, but the STAI score was significantly correlated to VAS1 and VAS2.
FNAC-related pain is frequent and correlates with the number of nodules biopsied, age under 25 years, female sex, and anxiety.
Neuroendocrine tumors from gastro-pancreatic origin (GEP-NET) can be responsible for liver metastases. Such metastases can be the dominant part of the disease as well due to the tumor burden itself ...or the symptoms related to such liver metastases. Intra-arterial therapies are commonly used in liver only or liver-dominant disease and encompass trans-arterial chemoembolization (TACE), trans-arterial embolization (TAE), and radioembolization (RE). TACE performed with drug emulsified in Lipiodol has been used for the past 20 years with reported overall survival in the range of 3-4 years, with objective response up to 75%. Response to TACE is higher when treatment is used as a first-line therapy and degree of liver involvement is lower. Benefit of TACE over TAE is unproven in randomized study, but reported in retrospective studies namely in pancreatic NETs. RE provides early interesting results that need to be further evaluated in terms of benefit and toxicity. Radiofrequency ablation allows control of small size and numbered liver metastases, with low invasiveness. Ideal metastases to target are one metastasis <5 cm, or three metastases <3 cm, or a sum of diameter of all metastases below 8 cm. Ablation therapies can be applied in the lung or in the bones when needed, and more invasive surgery should be probably saved for large-size metastases. Even if the indication of image-guided therapy in the treatment of GEP-NET liver metastases needs to be refined, such therapies allow for manageable invasive set of treatments able to address oligometastatic patients in liver, lung, and bones. These treatments applied locally will save the benefit and the toxicity of systemic therapy for more advanced stage of the disease.
Metastatic lung carcinoids (MLCs) remain poorly characterized and no prognostic stratification exists.
We conducted a retrospective study including patients with MLCs in two European expert centers. ...The aims were to characterize these cases and to identify prognostic factors of survival and effectiveness of their treatments.
A total of 162 patients with MLC were included: 50% were women, and the median age was 61 years. Half of the patients had synchronous metastases, mainly located in the liver (75%), bone (42%), and lung (25%). According to WHO classification, MLCs were typical (28%), atypical (60%), or unspecified (12%). A functioning syndrome was observed in 43% of cases and an uptake at somatostatin receptor scintigraphy in 76% of cases. The 5-year overall survival rate was 60% and at 10 years this was 25%. In multivariate analysis, Eastern Cooperative Oncology Group performance status of 0-1 (hazard ratio HR: 5.81, 95% confidence interval CI: 2.10–16.11), uptake on SRS (HR: 0.38, 95% CI: 0.22–0.66), low serum chromogranin A (HR: 2.27, 95% CI: 1.36–3.81), and typical carcinoid (HR: 1.87, 95% CI: 1.26–2.78) were associated with better survival. According to Response Evaluation Criteria in Solid Tumors version 1.0, the highest objective response rates were obtained after radiofrequency ablation of metastases (86%), liver embolization (56%), peptide receptor radionuclide therapy (27%), and oxaliplatin-based chemotherapy (18%).
MLCs are characterized by a high frequency of atypical carcinoids, functioning syndrome, and liver/bone metastases. WHO classification, performance status, somatostatin receptor scintigraphy, and chromogranin A were associated with longer survival. Partial response was more frequent with locoregional therapies, peptide receptor radionuclide therapy, or oxaliplatin-based chemotherapy.
Persistent/recurrent disease in the neck is frequent in patients with differentiated thyroid cancer (DTC).
Assess efficacy, safety, and prognostic factors of first neck reoperation in DTC.
...Retrospective study of consecutive patients undergoing neck reoperation for recurrent/persistent DTC in a referral cancer center. Response after reoperation was defined according to the 2015 American Thyroid Association guidelines.
One hundred sixty-one DTC patients were enrolled (64% females, median age 35 years, 96% papillary DTC). Initial stage was pT3 in 43% and pT4 in 10%, pN1 in 74%. Aggressive histology was present in 25% of the patients, in both primary and persistent/recurrent tumor. Four patients had no malignancy in the reoperative specimen, and 1 patient died due to postoperative hematoma and was excluded from further analysis. Following reoperation, 15 patients (10%) had persistent structural disease, 16 (10%) had biochemical incomplete response, 26 (17%) had indeterminate response, and 99 (63%) had complete response (CR), among whom 24 relapsed later. After a median follow-up of 5 years, only 83 patients (53%) had CR without the need for further treatments. The rate of permanent complications was: hypoparathyroidism 2%, laryngeal nerve palsy 0.6%, other 6%. Age ≥45 years, aggressive histology, and lymph node ratio ≥0.6 at initial surgery were independent risk factors for incomplete response after reoperation. Male sex, aggressive histology, and ≥10 metastases at reoperation were independent risk factors of secondary relapse following CR achieved with reoperation.
A careful risk-benefit analysis should guide surgical decision, particularly in patients with risk factors for incomplete response.
Anaplastic thyroid cancer (ATC) is a rare lethal disease. Lenvatinib is an off-label therapeutic option for ATC in most countries, except in Japan. The aim of this multicenter retrospective survey ...was to analyze the efficacy and the toxicity profile of off-label lenvatinib treatment in all adults advanced ATC patients, in France. Of the 23 patients analysed (14 males; mean age 64 years), 15 were pure ATC and 8 were mixed tumors (i.e. with a differentiated or poorly differentiated component). Prior treatments included neck external beam irradiation in 74%, at least one line of chemotherapy in 22 cases, two lines of chemotherapy in 11 patients, other TKI in 4 cases. A central RECIST assessment was performed. Since lenvatinib initiation, median PFS was 2.7 months (95% CI; 1.9-3.5) and median OS was 3.1 months (95% CI; 0.6-5.5). OS was significantly longer in case of mixed tumors compared with pure ATC (6.3 vs 2.7 months, P = 0.026). Best tumor response was partial response in two cases and stable disease in seven. Clinical improvement was achieved in seven patients. Lethal adverse events occurred in three patients, consisting in haemoptysis in two cases and pneumothorax in one case. Among long-surviving ATC patients (>6 months), four underwent biopsy of distant metastasis, revealing poorly differentiated histology; three of them had initial mixed ATC histology. Efficacy of lenvatinib appears limited, although pure vs mixed ATC disclose differences in disease aggressiveness and treatment response. Long-surviving ATC patients might benefit from biopsy of persistent disease, searching for histological transition or molecular target.
We investigated the activities of an ImmunoTOX board, an academic, multidisciplinary group of oncologists and organ specialists that adopts a real-life, case-by-case approach in the management of ...patients with immune-related adverse events (irAEs).
The ImmunoTOX assessment board was set up in 2016 at Gustave Roussy in France. It meets every 2 weeks to discuss the case-by-case management of patients presenting with irAEs. Here, we describe the ImmunoTOX board's activities between 2016 and 2019.
Over study period, 398 requests (concerning 356 patients) were submitted to the ImmunoTOX board. Most of the requests concerned the putative causal link between immunotherapy and the irAE (n = 148, 37%), followed by possible retreatment after temporary withdrawal because of an adverse event (n = 109, 27%), the clinical management of complex situations (n = 100, 25%) and the initiation of immunotherapy in patients with pre-existing comorbidities (n = 41, 10%). The ImmunoTOX board discerned 273 irAEs. The five organ systems most frequently involved by irAEs were lung (n = 58, 21%), gastrointestinal tract (n = 36, 13%), liver or biliary tract (n = 33, 12%), musculoskeletal system (n = 27, 10%), and nervous system (n = 23, 8%). The time to occurrence was shorter for severe irAEs (grade III and VI) than for mild irAEs (grades I and II), with medians of 47 and 91 days, respectively (p = 0.0216).
The main medical needs in the management of irAEs involved the lung organ. Severe irAEs were expected to occur earlier than mild irAEs. This real-life study can help to better estimate medical needs and therefore help to assess the management of irAEs.
•Severe irAEs (grade III-IV) occurred earlier than mild irAEs (grade I-II) in this study.•The main medical needs in the management of immune-related adverse events (irAEs) involved the lung organ.•Rechallenge after previous irAE was assessed as feasible in 65% of cases.•Initiation of immunotherapy in patients with autoimmune comorbidity was assessed as feasible in 93% of cases.•A multidisciplinary approach could help to better appraise and manage irAEs in real life.
Multiple endocrine neoplasia type 2B is a rare syndrome caused mainly by Met918Thr germline RET mutation, and characterised by medullary thyroid carcinoma, phaeochromocytoma, and extra-endocrine ...features. Data are scarce on the natural history of multiple endocrine neoplasia type 2B. We aimed to advance understanding of the phenotype and natural history of multiple endocrine neoplasia type 2B, to increase awareness and improve detection.
This study was a retrospective, multicentre, international study in patients carrying the Met918Thr RET variant with no age restrictions. The study was done with registry data from 48 centres globally. Data from patients followed-up from 1970 to 2016 were retrieved from May 1, 2016, to May 31, 2018. Our primary objectives were to determine overall survival, and medullary thyroid carcinoma-specific survival based on whether the patient had undergone early thyroidectomy before the age of 1 year. We also assessed remission of medullary thyroid carcinoma, incidence and treatment of phaeochromocytoma, and the penetrance of extra-endocrine features.
345 patients were included, of whom 338 (98%) had a thyroidectomy. 71 patients (21%) of the total cohort died at a median age of 25 years (range <1-59). Thyroidectomy was done before the age of 1 year in 20 patients, which led to long-term remission (ie, undetectable calcitonin level) in 15 (83%) of 18 individuals (2 patients died of causes unrelated to medullary thyroid carcinoma). Medullary thyroid carcinoma-specific survival curves did not show any significant difference between patients who had thyroidectomy before or after 1 year (comparison of survival curves by log-rank test: p=0·2; hazard ratio 0·35; 95% CI 0.07-1.74). However, there was a significant difference in remission status between patients who underwent thyroidectomy before and after the age of 1 year (p<0·0001). There was a significant difference in remission status between patients who underwent thyroidectomy before and after the age of 1 year (p<0·0001). In the other 318 patients who underwent thyroidectomy after 1 year of age, biochemical and structural remission was obtained in 47 (15%) of 318 individuals. Bilateral phaeochromocytoma was diagnosed in 156 (50%) of 313 patients by 28 years of age. Adrenal-sparing surgery was done in 31 patients: three (10%) of 31 patients had long-term recurrence, while normal adrenal function was obtained in 16 (62%) patients. All patients with available data (n=287) had at least one extra-endocrine feature, including 106 (56%) of 190 patients showing marfanoid body habitus, mucosal neuromas, and gastrointestinal signs.
Thyroidectomy done at no later than 1 year of age is associated with a high probability of cure. The reality is that the majority of children with the syndrome will be diagnosed after this recommended age. Adrenal-sparing surgery is feasible in multiple endocrine neoplasia type 2B and affords a good chance for normal adrenal function. To improve the prognosis of such patients, it is imperative that every health-care provider be aware of the extra-endocrine signs and the natural history of this rare syndrome. The implications of this research include increasing awareness of the extra-endocrine symptoms and also recommendations for thyroidectomy before the age of 1 year.
None.
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