Evaluation of Advanced Disease

Evaluation of Advanced Disease

Clinical Outline

Educational Clips from TIROxMDS

1. Radiotherapy

A. Adjuvant Treatment

B. Recurrent or Persistent Disease

C. Distant Metastatic Disease

2. Other Locally Ablative Modalities in Metastatic Disease

3. Systemic Therapy

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• Care Recommendations
  • Differentiated Thyroid Cancer
    • Initial Evaluation of Thyroid Nodules
    • Initial Management
    • Initial Staging & Response to Therapy
    • Systemic Therapy
    • Use of Radioactive Iodine
    • Recurrent & Persistent Disease
  • Medullary Thyroid Cancer
    • Initial Evaluation of Thyroid Nodules Suspicious of MTC
    • Surgical Management
    • Evaluation of Advanced Disease
    • Management of Specific Clinical Scenarios
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    • Initial Staging & Treatment Planning
    • Surgical Management
    • Systemic Therapy
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Management Recommendations

In patients with elevated calcitonin (Ctn) levels after initial surgical treatment consider distant metastasis. Note: first Ctn level measurement recommended to be 60 to 90 days after surgery then every 6 months. Imaging techniques to detect persistent or recurrent MTC besides neck US, may include neck and chest CT, three-phase contrast-enhanced CT, contrast-enhanced MRI, US of the liver, bone scintigraphy, MRI of the spine and pelvis.^​1–3​

// Discordance: calcitonin (Ctn) levels > 150 pg/ml vs. 500 pg/mL //

¹⁸FDG-PET and ¹⁸F-DOPA-PET/CT or ⁶⁸Ga-DOTATATE are additional imaging modalities, considering that selection criteria and medico-economic evaluation are required before being used routinely in clinical practice.^​1–3​

Laparoscopic or open evaluation and biopsy of the liver is recommended to exclude occult metastases before subjecting a patient to an extensive loco-regional surgery with curative intent.^​2​

// Expert commentary: Laparoscopic or open evaluation for liver biopsy liver is rarely performed and not necessary with modern imaging technologies available. //

The growth rate in patients with distant metastasis should be evaluated according to RECISTv1.1, with Ctn and CEA doubling time evaluated. Increasing tumor markers in the absence of structural disease progression are not considered as an indication for treatment with systemic therapy.^​1–3​

Somatic genotyping to determine RET mutational status is recommended in patients with advanced MTC who are germline RET wild-type or in whom germline RET status is unknown.^​1​

// Expert commentary: Where Selpercatinib and/or Pralsetinib are available, somatic RET genotyping is recommended in sporadic MTC. //

1. Radiotherapy

A. Adjuvant Treatment

Consider therapeutic external beam radiotherapy (EBRT) [Intensity modulated radiotherapy (IMRT) is recommended] for incomplete tumor resection when additional attempts at surgical resection have been ruled out.^​1,2​

Postoperative adjuvant EBRT (IMRT recommended) to the neck and mediastinum should be considered in patients at high risk for local recurrence based on microscopic or macroscopic residual MTC, extrathyroidal extension, or extensive lymph node metastases, and those at risk of airway obstruction. The potential benefits must be weighed against the acute and chronic toxicity associated with the therapy.

// Discordance: Only ATA guidelines endorse. NCCN guidelines are not rarely recommended. //

B. Recurrent or Persistent Disease

EBRT (IMRT is recommended) can be considered for unresectable disease.^​1​

C. Distant Metastatic Disease

EBRT/IMRT/Stereotactic body radiotherapy (SBRT) to metastatic disease recommended for symptom control.^​1–3​

2. Other Locally Ablative Modalities in Metastatic Disease

Patients with MTC who have fractures or impending fractures require treatment. Therapeutic options include surgery, thermoablation (radiofrequency or cryotherapy), cement injection, and EBRT.^​1–3​

Surgical resection should be considered in patients with large solitary lung metastases. Radiofrequency ablation should be considered when the metastases are peripheral and small. ^​1–3​

Surgical resection should be considered in patients with large, isolated hepatic metastases. Chemoembolization should be considered in patients with disseminated tumors less than 30 mm in size involving less than a third of the liver.^​1–3​

If possible cutaneous metastases should be excised surgically. Multiple cutaneous lesions are best treated by EBRT or ethanol injection.^​1–3​

3. Systemic Therapy

For unresectable locoregional disease that is symptomatic or progressing by RECIST and asymptomatic distant metastatic MTC progressing by RECIST, treatment with kinase inhibitor therapy is appropriate. Vandetanib or cabozantinib are appropriate regardless of genotype. Selpercatinib or Pralsetinib are appropriate for germline or somatic RET mutation-positive cases. Pembrolizumab is available in high tumor mutational burden (≥ 10 mut/Mb) cases. Lenvatinib and sorafenib may be utilized for unresectable disease if specific targeted therapy is not identified or available.^​1–4​

For symptomatic distant metastatic MTC, treatment with kinase inhibitor therapy is preferred. Vandetanib or Cabozantinib are appropriate regardless of genotype. Selpercatinib or Pralsetinib are appropriate for germline or somatic RET mutation-positive cases. Other regimens that may be considered beyond first-line include other kinase inhibitors (e.g. sorafenib, sunitinib, Lenvatinib or pazopanib), dacarbazine/5FU or doxorubicin +/- cisplatin chemotherapy, or pembrolizumab in high tumor mutational burden (≥ 10 mut/Mb) cases. Radionuclide therapy, such as with somatostatin-labeled radiopharmaceuticals, may be an option in selected cases. ^​1–4​

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