Neoplasms

All Conditions

Symptoms and General Pathology

Carcinoma

Neoplasm Metastasis

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Ching-Ting Tan, MD, PhD

Investigate the final diagnosis and treatment result of metastatic cervical carcinoma of unknown primary

Carcinoma of unknown primary (CUP) is defined as biopsy-proven metastasis of an epithelial malignancy in the absence of an identifiable primary site after complete history and physical examination, basic laboratory studies, chest X-ray and additional directed studies indicated by positive findings during the initial work-up. It is characterized by its slow local development and its high metastatic potential.1,2 Patients with CUP represent 4-10% of all new cancer patients.3,4 The presenting sites of metastasis identified pathologically, radiographically or by physical examination were found most frequently in the lymph nodes (37.1%), followed by the liver, bone, lung, pleura/pleural space, brain, peritoneum, adrenal and skin. Of the lymph nodes of metastasis, the supraclavicular cervical area is the leading site (31.3%), followed by the mediastinum, axilla, retroperitonium, and inguina.5 The incidence of metastatic cervical CUP (MCCUP) varies between 2% and 9% of all head and neck cancers.6-8 The level of cervical metastatic involvement may give some clue as to the likely primary site. A submandibular mass (level I) would most commonly be related to a primary in the oral cavity or skin. Level II nodes, including the jugulodigastric node, may point to a primary in the oral cavity, oropharynx, or supraglottic larynx. Tumours of the nasopharynx generally spread to level II or the posterior triangle, as well as retropharyngeal nodes. Middle and lower jugular nodes (levels III and IV) are more likely related to a laryngeal or hypopharyngeal cancer. Metastatic disease restricted to the supraclavicular region is often due to an infraclavicular primary site.9 The prognosis is different according to the involved lymph node level and possible primary site. Modern cancer management relies heavily on recognition of the primary tumor; thus the absence of a primary site poses major diagnostic and therapeutic problems. The patient benefits from identification of the initial tumor site because postoperative irradiation ports may be reduced and because surveillance for recurrence may be improved.10 In order to identify the likely primary site of MCCUP and compare the prognoses of known and unknown primary groups, we report the results according to the different levels of metastatic cervical lymph nodes.

The Final Diagnosis and Treatment Result of Metastatic Cervical Carcinoma of Unknown Primary

National Taiwan University Hospital

Respiratory Tract (Lung and Bronchial) Diseases

Ear, Nose, and Throat Diseases

Recurrence

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Head and Neck Neoplasms

Laryngeal Diseases

Neoplasms, Squamous Cell

Antineoplastic Agents

All Drugs and Chemicals

Cisplatin

Alkylating Agents

Stereotactic Body Radiation Therapy (SBRT) and Cisplatin. Starting Dose: 6 Gy/ Fraction 5/ Total 30 Gy/ Cisplatin 15 mg/m\^2

Cisplatin 15 mg/m\^2 prior to each fraction

All participants will be treated every other day (excluding Saturday/Sunday). Starting Dose: 6 Gy/ Fraction 5/ Total 30 Gy.

Stereotactic Body Radiation Therapy (SBRT)

Jimmy Caudell, M.D., Ph.D.

This study involves another course of radiation (called re-irradiation) to the participant's tumor. The type of radiation is called stereotactic body radiation therapy (SBRT). The purpose of this study is to compare the effects, good and/or bad, of different doses of SBRT given along with the chemotherapy drug, cisplatin. The researchers want to see which dose of radiation will work best in controlling the growth of head/neck cancer. The usual treatment for head/neck cancer that has grown is surgery and/or more radiation with various chemotherapy drugs.

Stereotactic Body Radiation Therapy (SBRT) is a relatively new radiation technique in which a few very high doses of radiation are delivered to small, well-defined tumors. It has been used effectively in other cancers like lung and liver. The goal is to deliver a radiation dose that is high enough to kill the cancer while limiting radiation to surrounding healthy organs. The daily dose of radiation is 2-3 times greater than conventional radiotherapy, but it is given for only 5 days over a 2 week period. Conventional radiotherapy is given over 6-7 weeks. The chemotherapy drug, cisplatin is used as a radiation sensitizer and will be given before each of the 5 radiation treatments.

Stereotactic Body Radiotherapy and Concurrent Cisplatin for Re-Irradiation of Unresectable, Recurrent Squamous Cell Carcinomas of Head and Neck

A Phase I Dose Escalation Trial of Stereotactic Body Radiotherapy and Concurrent Cisplatin for Re-Irradiation of Unresectable, Recurrent Squamous Cell Carcinomas of the Head and Neck

The traditional 3+3 dose escalation method will be utilized for this phase I study, with up to 3 sequential cohorts. The maximal tolerated dose (MTD) of Stereotactic Body Radiation Therapy (SBRT) radiation dose associated with a ≤ 33% probability of dose-limiting toxicity (DLT). DLT is defined as any grade 4 or greater toxicity, per The Common Terminology Criteria for Adverse Events v4 (CTCAE v4) that occurs within 3 months from the start of SBRT.

Local control is defined as lack of progression as defined radiographically or pathologically proven within the SBRT treated area. This will be calculated via Kaplan-Meier method. Response and progression will be evaluated in this study using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) \[Eur J Ca 45:228-247, 2009\]. Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes are used in the RECIST criteria.

Overall survival will be calculated from the end of SBRT treatment to time of death or last contact via Kaplan-Meier method.

H. Lee Moffitt Cancer Center and Research Institute

Gland and Hormone Related Diseases

Rare Diseases

Thyroid Neoplasms

Thyroid Diseases

Lymphatic Metastasis

Neoplastic Processes

Endocrine System Diseases

Endocrine Gland Neoplasms

Thyroid Cancer, Medullary

Central Nervous System Depressants

Anesthetics

Percutaneous Laser Ablation for the treatment of metastatic cervical lymph nodes with \> 0.8 cm diameter with biopsy-proven diagnosis of differentiated thyroid carcinoma or medullary thyroid carcinoma.

Percutaneous cryoablation for the treatment of metastatic cervical lymph nodes with \> 0.8 cm diameter with biopsy-proven diagnosis of differentiated thyroid carcinoma or medullary thyroid carcinoma.

Percutaneous radio frequency ablation for the treatment of metastatic cervical lymph nodes with \> 0.8 cm diameter with biopsy-proven diagnosis of differentiated thyroid carcinoma or medullary thyroid carcinoma.

Single session with Diode laser ablation system; one or two applicators will be used for treatments; one to three illuminations; fixed output power of 3 watts (W); pullback technique; delivered energy: 1200-1800 Joules (J) varying according to tumor volume; treatment under local anesthesia +- conscious or moderate sedation;

Laser ablation

Single session with Argon-based cryoablation system; one 17 Gauge (G) V-probe applicator will be used for treatments; fixed gas delivery of 100%; treatment under local anesthesia +- conscious or moderate sedation;

Cryoablation

Single session with radiofrequency generator; one 17 Gauge (G) V-tip applicator with a 1 to 4cm active tip; moving-shot technique or multiple overlapping shot technique with 60 Watts (W) output power; treatment under local anesthesia +- conscious or moderate sedation;

Radiofrequency ablation

Ricardo MC Freitas, PhD

Ana O Hoff, PhD

Talita R Vincunas

Marco AV Kulcsar, PhD

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.

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.

Thermal Ablation of Cervical Metastases From Thyroid Carcinoma

Ultrasound Guided Percutaneous Thermal Ablation of Cervical Metastases From Thyroid Carcinoma

De-identified individual participant data for all primary and secondary outcomes measures will be made available.

defined as the ability to target the nodule and to perform ablation as preoperatively planned

Evaluation of minor and major complication rates, immediately after ablation; and one- and four-weeks post-ablation by telephone call.

Minor and major complication rates \[Designed as a safety issue: Yes\]. The safety endpoint for this study is to assess the incidence and severity of procedure or device-related adverse events, as reported by the Common Terminology Criteria of Adverse Events - CTCAE V5. 2017 Version.

Defined as the complete absence of color Doppler or, if applicable when tumors over 1.0 cm diameter, enhancement by contrast-enhanced ultrasound in the treated nodule

Absence of enhancement is expected in treated cervical lymph nodes after local ablative therapy in comparison to pre-treatment enhancement pattern. Partial enhancement may indicate residual tumoral tissue requiring new ablation session

Quantitative measurements of nodule stiffness designated by the most representative region of interest within the nodule estimating of Young's modulus in kilopascal (KPa) and shear wave velocity in centimetres per second (cm/s) of treated cervical lymph nodes after local ablative therapy in comparison to pre-treatment pattern.

The best response is defined as a subject having local disease control related to lymph node volume reduction or volume stability in percentage will be assessed by ultrasound measurement in comparison to pre-treatment volume.

Number of patients with tumor marker response: defined in negative thyroglobulin, calcitonin, or carcinoembryonic antigen (CEA) levels or anti-thyroglobulin antibodies

Number of patients with additional therapies: Additional therapies for persistent/recurrent local disease associated with the index tumor (s) under study or new cervical lymph node metastases.

Number of patients with complications, side effects and tolerability in each ablation technique.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
The Final Diagnosis and Treatment Result of Metastatic Cervical Carcinoma of Unknown Primary	NCT00302588	Metastasis Cerv...		20 Years - 75 Years	National Taiwan University Hospital
Stereotactic Body Radiotherapy and Concurrent Cisplatin for Re-Irradiation of Unresectable, Recurrent Squamous Cell Carcinomas of Head and Neck	NCT02158234	Squamous Cell C...	Cisplatin Stereotactic Bo...	18 Years -	H. Lee Moffitt Cancer Center and Research Institute
Stereotactic Body Radiotherapy and Concurrent Cisplatin for Re-Irradiation of Unresectable, Recurrent Squamous Cell Carcinomas of Head and Neck	NCT02158234	Squamous Cell C...	Cisplatin Stereotactic Bo...	18 Years -	H. Lee Moffitt Cancer Center and Research Institute
Thermal Ablation of Cervical Metastases From Thyroid Carcinoma	NCT04522570	Thyroid Neoplas... Well-Differenti... Medullary Thyro... Lymph Node Meta...	Laser ablation Cryoablation Radiofrequency ...	18 Years -	Instituto do Cancer do Estado de São Paulo

Spots Global Cancer Trial Database for cervical lymph nodes