Systemic Therapy

Systemic Therapy

Clinical Outline

Educational Clips from TIROxMDS

1. Systemic Therapies

A. Neoadjuvant Systemic Therapy

B. Bridging Chemotherapy

C. Concomitant Chemotherapy

2. Persistent or Unresectable Disease

A. Radiation

= Primers in Thyroidology

= Journal Club Presentation

= Case-based Discussion (inc. roundtables)

= Grand Rounds Lectureship

• 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
  • Anaplastic Thyroid Cancer
    • Diagnostic Procedures
    • Initial Staging & Treatment Planning
    • Surgical Management
    • Systemic Therapy
    • End of Life Care
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Management Recommendations

1. Systemic Therapies

Clinical trial enrollment should be encouraged for all patients diagnosed with ATC.^​1–3​

Urgent assessment of BRAF^V600E mutation and extended molecular profiling is strongly recommended as it may identify potential targets for therapy.^​1–3​

A. Neoadjuvant Systemic Therapy

For stage IVA, IVB consider external beam radiotherapy (EBRT) preferably intensity modulated radiotherapy (IMRT) with concomitant chemotherapy when appropriate or molecularly targeted neoadjuvant therapy (for example dabrafenib/trametinib for BRAF^V600E mutations; selpercatinib or pralsetinib for RET-Fusion positive tumours; and larotrectinib or entrectinib for patients with NTRK gene fusion-positive tumours).^​1,2​

B. Bridging Chemotherapy

Among ATC patients with unresectable or advanced disease who wish to consider aggressive therapy, cytotoxic chemotherapy may be started as an initial and potentially bridging approach until mutational profiling results and/or mutationally specified therapies become available.^​1​

EXPERT COMMENTARY OR EDUCATIONAL CONTENT : UPFRONT SHORT COURSE EBRT

C. Concomitant Chemotherapy

In BRAF nonmutated patients, radiation therapy with concurrent chemotherapy should be considered in an effort to maintain the airway in patients with low burden of metastatic disease.^​1–3​

Cytotoxic chemotherapy can usually be started within a week of surgery, provided sufficient healing, while subsequent chemoradiation is planned.^​1​

The use of concomitant cytotoxic chemotherapy involving a Taxane (paclitaxel or docetaxel), or anthracyclines (doxorubicin) or platin (cisplatin or carboplatin), should be considered in patients treated with definitive intention radiation.^​1–4​

2. Persistent or Unresectable Disease

Patients who have undergone R2 resection or have unresectable but nonmetastatic disease with good performance status can be offered standard fractionation IMRT with concomitant systemic therapy. In BRAF^V600E-mutated ATC, combined BRAF/MEK inhibitors can be considered as an alternative.^​1–3​

In BRAF^V600E-mutated IVC and in unresectable IVB ATC patients who decline radiation therapy, initiation of BRAF/MEK inhibitors (dabrafenib plus trametinib) is recommended over other systemic therapies if available.^​1–3​

In NTRK or RET fusion ATC patients with stage IVC disease, it is advisable to initiate a TRK inhibitor (either larotrectinib or entrectinib) or RET inhibitor (either selpercatinib or pralsetinib), preferably in a clinical trial, if available.^​1–3​

In IVC ATC patients with high PD-L1 expression, checkpoint (PD-L1, PD1) inhibitors can be considered first-line therapy in the absence of other actionable alterations or as later line therapy, preferably in the context of a clinical trial.^​1–3​

In metastatic ATC patients lacking other therapeutic options including clinical trials, suggest considering cytotoxic chemotherapy including a taxane and/or an anthracycline or taxane with or without cis- or carboplatin.^​1–4​

In patients with ATC with bone metastasis, intravenous bisphosphonate infusions or subcutaneous RANK ligand inhibitor should be considered.^​1​

A. Radiation

For locally advanced disease, patients with R0/R1 resections with minimal co-morbid illnesses and M0 disease, consider postoperative EBRT +/- chemotherapy soon after the diagnosis is made.^​1–4​

For unresectable (R2/M1), BRAF wild-type disease , palliative EBRT may be considered.^​1–3​

Due to its rapid growth, accelerated fraction radiation has the potential to limit tumor growth that may occur during the course of radiation therapy.^​1​

In general, preoperative radiation is  not recommended.^​1​

Following thyroidectomy, if  anaplastic thyroid cancers are incidentally detected post-operative radiation therapy is not recommended.^​1​

Lower-doses of radiotherapy may provide a  palliative benefit for patients with poor performance status.^​1​ Radiotherapy should be considered as  palliative treatment for bone metastases, spinal cord compression, brain metastases^​1–3​ and post obstructive pneumonia and hemoptysis due to endobronchial lesions.^​1​

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