Clinical trial NCT04522570: Thermal Ablation of Cervical Metastases From Thyroid Carcinoma
Official title: Ultrasound Guided Percutaneous Thermal Ablation of Cervical Metastases From Thyroid Carcinoma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Thyroid Neoplasia
Well-Differentiated Thyroid Cancer
Medullary Thyroid Cancer
Lymph Node Metastases
Keywords: differentiated thyroid cancer
medullary thyroid cancer
cervical lymph nodes
contrast-enhanced ultrasound
thermal ablation
laser ablation
radiofrequency ablation
cryoablation
elastography
Lead sponsor: Instituto do Cancer do Estado de São Paulo
Sponsor class: OTHER
First posted: 2020-08-21
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will evaluate the clinical response and safety of ultrasound guided percutaneous thermal ablation of lymph node metastases from thyroid carcinoma as an alternative to surgical treatment.

The ablation of cervical lymph node metastases from differentiated thyroid carcinoma or medullary thyroid carcinoma will be directed to lesions larger than 0.8 cm, using ultrasound-guided radiofrequency ablation (RFA), laser ablation (LA) or cryoablation (Cryo) techniques, randomly assigned. Clinical and ultrasound monitoring will be carried out during 24 months, with examinations before the ablation procedure, immediately after including contrast-enhanced ultrasound (CEUS) when applicable, and B-mode, color Doppler and Shear-Wave elastography ultrasound follow up with 6, 12, and 24 months.

Detailed description: Thyroidectomy is the main treatment of well differentiated thyroid carcinoma. Residual or recurrent cervical metastases are common (9-20% of patients during long-term follow up). Thermal ablation of cervical metastatic lymph nodes from thyroid carcinoma has been proposed in research centers as an option for the treatment of patients who remain with metastatic disease in cervical lymph nodes, despite thyroidectomy with or without neck dissection associated with radioiodine treatment. Potential advantages from percutaneous thermal ablation are related to less complication rates, less morbidity, possibility of outpatient treatment modality, and less global treatment costs when compared to the surgical approach.

Aims of the study:

1. To evaluate safety and efficacy of ultrasound-guided thermal ablation in the treatment of cervical lymph node metastases from differentiated thyroid carcinoma
2. To evaluate the best response to thermal ablation defined as lymph node reduction or volume stability after ablation
3. To evaluate the CEUS patterns of lymph nodes before and after ablation
4. To evaluate the elastography patterns of lymph nodes before and after ablation
5. To evaluate the tumor marker response after ablation
6. To evaluate the contribution of thermal ablation to decrease additional therapeutic procedures
7. To compare differences between LA, RFA and cryoablation in terms of complications, side effects and tolerability

Patients with cervical metastatic lymph nodes from differentiated thyroid carcinoma or medullary thyroid carcinoma who meet the eligibility criteria and who have been determined to be an appropriate candidate for local ablation therapy will be offered enrollment into the study. Patients agreeing to participate will become subjects of the study if they read and sign an informed consent form.

Treatment will be performed using three different ablation technologies (laser ablation, RFA or cryoablation) in a randomly assignment fashion.

Subjects will have up to six simultaneous treated lesions larger than 0.8 cm diameter with positive fine-needle aspiration biopsy. Ultrasound (and CEUS when applicable) will be performed over 24 months follow up in order to evaluate efficacy. Baseline and follow-up data will be collected for each subject via a web-based electronic data collection tool.

In case of recurrent disease treated by any ablative technique in patients who did not undergo previous neck dissection, a rescue neck dissection will be performed; in case of recurrent disease treated by any ablative technique in patients who underwent previous neck dissection, a new ablative technique approach will be considered.

Eligibility criteria: Inclusion Criteria:

* 18 years of age or older
* Patients with fine needle aspiration biopsy (FNAb)-proven metastatic cervical lymph nodes at levels I, II, III, IV, V, VI or VII from differentiated thyroid carcinoma or medullary thyroid carcinoma who underwent total thyroidectomy and subsequent radioiodine therapy, in case of differentiated thyroid carcinoma.
* Patients considered high surgical risk candidate or patients who are informed about the ablation therapy and prefers it instead surgery;
* Patients with metastatic cervical lymph nodes over 0.8 cm diameter and under 4.0 cm diameter; no more than 6 simultaneous cervical nodal metastases;
* Cervical recurrences in previously lateral neck dissection patients for differentiated thyroid carcinoma or medullary thyroid carcinoma over 0.8 cm diameter.

Exclusion Criteria:

* Age under 18 years
* Uncorrectable coagulopathy;
* Inconclusive or benign cytologic specimens;
* Pregnancy or breast-feeding;
* Anaplastic or poor-differentiated thyroid carcinoma;
* Partial thyroidectomy
* Cervical tumors not considered to surgery (invading vessels, nerves, larynx or trachea);
* Serious medical illness, including any of the following: uncontrolled angina, myocardial infarction, cerebrovascular event within 6 months prior to the baseline visit, uncontrolled congestive heart failure;
* Participation in other studies that could affect the primary endpoint

Primary outcomes:
measure: Evaluation of technical feasibility
timeFrame: immediately after the procedure
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of thermal ablation of thyroid carcinoma cervical lymph node metastases
timeFrame: up to 4 weeks post-ablation
Secondary outcomes:
measure: Evaluation of technical success
timeFrame: immediately after the procedure
measure: Evaluation of contrast-enhanced ultrasound pattern after thermal ablation therapy
timeFrame: 12 months
measure: Evaluation of elastography pattern after thermal ablation therapy
timeFrame: 24 months
measure: Best response to the thermal ablation therapy
timeFrame: 24 months
measure: Evaluation of tumor marker response
timeFrame: 24 months
measure: Evaluation of additional therapies
timeFrame: 24 months
measure: Outcomes among thermal ablation therapies
timeFrame: 24 months
Other outcomes:
Locations:
city: São Paulo
country: Brazil
facility: Instituto do Cancer do Estado de São Paulo
Study officials:
affiliation: Instituto do Cancer do Estado de São Paulo
name: Ricardo MC Freitas, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hong YR, Luo ZY, Mo GQ, Wang P, Ye Q, Huang PT. Role of Contrast-Enhanced Ultrasound in the Pre-operative Diagnosis of Cervical Lymph Node Metastasis in Patients with Papillary Thyroid Carcinoma. Ultrasound Med Biol. 2017 Nov;43(11):2567-2575. doi: 10.1016/j.ultrasmedbio.2017.07.010. Epub 2017 Aug 12.
citation: Guenette JP, Tuncali K, Himes N, Shyn PB, Lee TC. Percutaneous Image-Guided Cryoablation of Head and Neck Tumors for Local Control, Preservation of Functional Status, and Pain Relief. AJR Am J Roentgenol. 2017 Feb;208(2):453-458. doi: 10.2214/AJR.16.16446. Epub 2016 Nov 15.
citation: Guang Y, Luo Y, Zhang Y, Zhang M, Li N, Zhang Y, Tang J. Efficacy and safety of percutaneous ultrasound guided radiofrequency ablation for treating cervical metastatic lymph nodes from papillary thyroid carcinoma. J Cancer Res Clin Oncol. 2017 Aug;143(8):1555-1562. doi: 10.1007/s00432-017-2386-6. Epub 2017 Mar 24.
citation: Wang L, Ge M, Xu D, Chen L, Qian C, Shi K, Liu J, Chen Y. Ultrasonography-guided percutaneous radiofrequency ablation for cervical lymph node metastasis from thyroid carcinoma. J Cancer Res Ther. 2014 Nov;10 Suppl:C144-9. doi: 10.4103/0973-1482.145844.
citation: Mauri G, Cova L, Ierace T, Baroli A, Di Mauro E, Pacella CM, Goldberg SN, Solbiati L. Treatment of Metastatic Lymph Nodes in the Neck from Papillary Thyroid Carcinoma with Percutaneous Laser Ablation. Cardiovasc Intervent Radiol. 2016 Jul;39(7):1023-30. doi: 10.1007/s00270-016-1313-6. Epub 2016 Feb 24.
citation: Papini E, Bizzarri G, Bianchini A, Valle D, Misischi I, Guglielmi R, Salvatori M, Solbiati L, Crescenzi A, Pacella CM, Gharib H. Percutaneous ultrasound-guided laser ablation is effective for treating selected nodal metastases in papillary thyroid cancer. J Clin Endocrinol Metab. 2013 Jan;98(1):E92-7. doi: 10.1210/jc.2012-2991. Epub 2012 Nov 12.
citation: Baudin E, Schlumberger M. New therapeutic approaches for metastatic thyroid carcinoma. Lancet Oncol. 2007 Feb;8(2):148-56. doi: 10.1016/S1470-2045(07)70034-7.
citation: Monaco F. Classification of thyroid diseases: suggestions for a revision. J Clin Endocrinol Metab. 2003 Apr;88(4):1428-32. doi: 10.1210/jc.2002-021260. No abstract available.
citation: Hegedus L. Clinical practice. The thyroid nodule. N Engl J Med. 2004 Oct 21;351(17):1764-71. doi: 10.1056/NEJMcp031436. No abstract available.