Case 7
A 55-year-old male presented with cough, neck pain, and eventually “throat tightness” in September 2016. There was no history of radiation exposure. Neck Computerized Tomography (CT) indicated concern for tracheal invasion, esophageal invasion, and strap muscle invasion. There was involvement of the prevertebral soft tissues and there may be subtle erosion along the anterior cortex of T1. In November 2016, biopsy was consistent with anaplastic thyroid cancer but poor tissue quality.
The patient started with fluorouracil, doxorubicin, and cyclophosphamide. The tumour recurred a year later in the patient’s chest wall and distant metastases to the lung were subsequently detected.
In December 2016 the patient received CDDP with radiotherapy. In January 2017 there was evidence of persistent disease and episode of massive haemoptysis and the patient received nab-paclitaxel/carboplatin/pembrolizumab. In March 2017 disease progression was diagnosed with intracardiac and soft tissue extremity masses, and biopsy of soft tissue mass performed while also lenvatinib + pembrolizumab treatment started. In May 2017 the patient was admitted for respiratory failure with clear disease progression
NTRK gene fusion testing
NGS was performed on DNA extracted from the soft tissue mass biopsy that revealed the presence of ETV6-NTRK3 gene fusion. All clinically significant variants detected are shown below.
TRK inhibitor treatment
The patient enrolled on an entrectinib clinical trial and started with a daily, oral dose of 600mg in November 2017. On Cycle 1, Day 15 visit, the patient showed significant clinical improvement and was discharged from hospital. There was a decrease in multiple soft tissue masses (largest 6.5 cm to 2 cm in diameter) and oxygen requirement went from 10L/min to 2L/min.
The patient responded for 12 months at which time entrectinib was stopped, at which point paclitaxel was administered but the patient did not respond, and performance status started declining.
The patient elected not to have further treatment and died shortly after that (approximately 6 months after stopping entrectinib).
Response during treatment with entrectinib (29% decrease in tumor size since baseline as measured by RECIST 1.1)
18/02/2017: Innumerable pulmonary nodules (yellow/orange included) through both lungs with larger coalescing mass in the Left lung/perihilar region (green). The right lower lobe nodule indicated by the (orange) * is the same nodule between all three scans
BASELINE: 5/5/2017: Large left perihilar/parenchymal mass (green) has continued to grow in size associated increasing malignant pericardial effusion (blue), increased right ventricular mass (red), Although the is decrease in over tumor burden to the lungs with many nodules regressing in size, there are scattered nodules/mass that had continue to grow through treatment including the right middle lobe now conglomerate disease (yellow) . The right lower lobe nodule indicated by the (orange) * is the same nodule between all three scans.
05/06/2017: decreased size and infiltration of the left perihilar/parenchymal mass (Green) with decreased malignant pericardial effusion (blue). The right ventricular mass persists (but is somewhat smaller in size). The right middle mass like consolidation has decreased as well as the size of many pulmonary nodules.
Clinical interpretation and impact of NTRK gene fusion testing
This case demonstrates that ETV6-NTRK3 is the most common rearrangement in PTC. However, it should be noted that its prevalence in adults with PTC is very low (<1%) but it is the second most common rearrangement seen in radiation-associated PTC [1].
The case also demonstrates that responses can occur in heavily pretreated patients.
References
1. Leeman-Neill RJ, Kelly LM, Liu P et al. ETV6-NTRK3 is a common chromosomal rearrangement in radiation-associated thyroid cancer. Cancer 2014;120(6):799-807.