- Patients with undifferentiated thyroid cancer have poor outcomes and lack effective treatments.
- Immunotherapy may be effective in undifferentiated thyroid cancer, and more research and exploration is needed.
Troublesome undifferentiated cancer
Undifferentiated thyroid cancer (ATC) accounts for only 1% to 2% of all thyroid cancers, but it is the most malignant, progresses very rapidly, metastasizes at a very early stage, and has very poor patient outcomes, with half of patients surviving only 3 to 5 months.
Overall, the treatment of ATC is tricky. Many patients have distant metastases by the time they are diagnosed, and there are few effective treatments. Where resection is possible, surgery is still the first choice. If surgery is lost, physicians may first consider radiation therapy. Undifferentiated carcinoma hardly takes up iodine and is not sensitive to chemotherapy, so radioactive iodine (RAI) therapy and chemotherapy are generally not used. Currently, targeted drugs for undifferentiated cancer are in clinical research and have not entered clinical use.
Immunotherapy, especially the new class of drugs represented by PD-1/PD-L1 inhibitors, is a hot topic in oncology treatment. After their success with melanoma, they are being gradually applied to other cancers, and thyroid cancer is one of them. A recently reported case from abroad showed significant efficacy of immunotherapy in undifferentiated thyroid cancer.
Mr. A’s experience: Immunotherapy works well
This is a 62-year-old male patient from abroad, whom we will call Mr. A.
Mr. A saw his doctor for an enlarged mass on the right side of his neck, and was diagnosed with papillary thyroid cancer on the right side. This is a highly differentiated thyroid cancer that does not invade lymph or nerves and usually has a good outcome. However, a whole-body radionuclide scan showed tumor activity at the base of the thyroid, and he was subsequently treated with RAI. Nine months after the initial diagnosis, due to recurrent lump enlargement, Mr. A underwent another lymph node dissection of his neck, which revealed hypofractionated adenocarcinoma in 1 of 23 lymph nodes and extra-lymph node invasion, and his doctor determined that his cancer was undifferentiated thyroid cancer.
After diagnosis, the initial treatment plan was cisplatin in combination with adriamycin chemotherapy every 3 weeks for 2 courses. Unfortunately, Mr. A tolerated the chemotherapy poorly and developed lung metastases. So he had to try paclitaxel and undergo gene sequencing to see if there was a suitable therapeutic target. The sequencing results showed a BRAF V600E gene mutation, and the targeted drug vemurafenib was available. In addition, immunohistochemistry showed PD-L1 positivity, suggesting that PD-1/PD-L1 inhibitor therapy could be tried.
Mr. A started taking verofenib and within a few days the lymph node mass in his neck started to shrink, but a new mass appeared in the middle of his neck and grew rapidly, and cancer metastases appeared in his left clavicle and upper lobe of his left lung. The doctor then gave him the immune drug nivolumab (nivolumab) again. After he developed increased joint pain, his doctor discontinued verofinib and treated him with only nivolumab alone. Surprisingly, his symptoms improved and the tumors that had metastasized to his clavicle and lungs shrank.
In the end, Mr. A received a total of 12 courses of nabumab and was in clinical remission for almost 2 years (20 months); adverse effects included nausea, vomiting, diarrhea, and acute colitis, but were tolerable.
Conclusion: Immunotherapy for ATC, still needs to be explored
Mr. A’s case is an isolated case, and it cannot yet be assumed that immunotherapy is feasible for other thyroid cancers. Whether and to what extent immunotherapy is effective in other ATC patients will require more cases and more studies. But this is at least a good start, so let’s wait and see.