A 57-year-old woman (height, 164 cm; weight, 50 kg) was referred to Kachi Memorial Hospital, a psychiatric hospital, for the treatment of schizophrenia. An initial diagnosis of schizophrenia was made at the age of 18, and the patient was later repeatedly treated in several psychiatry hospitals. The patient was found to have PTC at the age of 40 and a left thyroid lobectomy was subsequently performed at Aichi Cancer Center Hospital. At 47 years of age, the patient showed pulmonary metastases and lymph node recurrences, and a completion total thyroidectomy and lymph node dissection were performed. After the operation, a whole-body scan with 10 mCi of RAI revealed no uptake in both pulmonary metastases and residual parapharyngeal metastases. An expert panel concluded there was no indication for high-dose RAI therapy and thus external radiation therapy was performed for Rouviere parapharyngeal lymph nodes. At 57 years of age, the patient showed metastases to cervical and mediastinal lymph nodes as well as lung metastases that had progressed. The trachea became narrowed by a para-tracheal metastatic lymph node compression. Therefore, sorafenib was started on an outpatient basis. After 2 weeks of sorafenib therapy, the patient was discovered unconscious at home and transferred to hospital by ambulance. Sorafenib therapy was then stopped. The patient was subsequently diagnosed with reversible posterior leukoencephalopathy syndrome (RPLS) by brain magnetic resonance imaging (MRI). External radiation therapy to the site of a tracheal stenosis in the neck and mediastinum was performed. However, the patient’s mental symptoms worsened, and she was referred and transferred to Kachi Memorial Hospital in July 2015.
Two months after hospital admission, the patient’s mental state stabilized. Although Kachi Memorial Hospital is a psychiatric hospital, the director is an endocrinologist and specialist in thyroid diseases. Furthermore, two endocrine surgeons worked at the hospital on a part-time basis. Therefore, the stage of thyroid cancer was evaluated and a treatment strategy formulated. According to computed tomography (CT), the largest recurrence sites were in cystic lymph nodes in the right para-tracheal space beyond the neck to the mediastinum. In addition, measurable solid recurrence sites existed, such as neck lymph nodes in the pre-laryngeal subcutaneous space, the right lobe of lung, and the left adrenal. A follow-up evaluation by CT after 2 months revealed such tumors to be enlarged (Fig. 1). After 2 months’ treatment for schizophrenia, the patient’s mental condition was good: she was calm and intelligent enough to spend most of the day reading English books written by Shakespeare, for example. However, the PTC was considered progressive enough to become lethal in the near future if an effective therapy was not tried. Therefore, we concluded that lenvatinib treatment should be started immediately. We explained the lenvatinib treatment to the patient including any possible adverse events. Accordingly, the patient agreed and gave written, informed consent.
Lenvatinib was commenced at a daily dose of 24 mg in November 2015. Other medications were 20 mg olanzapine, 4 mg risperidone, 3 mg flunitrazepam, 1 mg clonazepam, 100 μg levothyroxine sodium hydrate, 0.5 μg alfacalcidol, 48 μg lubiprostone, 1500 mg magnesium oxide, and 36 mg sennoside, per day, respectively. Hypertension was managed with daily 5 mg amlodipine besilate, and 20 mg azilsartan. Hand–foot syndrome with fever developed twice, and required a repeated discontinuation or a dose reduction of lenvatinib on each occasion (Fig. 1).
Before starting on lenvatinib, measurable solid recurrence sites for the cancer were noted in the neck lymph nodes in the pre-laryngeal subcutaneous space, right lobe of lung, and left adrenal, with maximal diameters of 33 mm, 32 mm, and 46 mm, respectively (Fig. 2, Nov/2015, A–C). Within 3 months after lenvatinib administration, the sum of tumor sizes was reduced by more than 30% and, thus, this was assessed as a partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 ([7], Fig. 2, Feb/2016, A–C). After 5 months, the neck cystic lesion ruptured spontaneously, and a small amount of bleeding occurred intermittently. Therefore, lenvatinib was stopped for 5 months.
During the discontinuation of lenvatinib, the tumors became enlarged, and neck lymph nodes and lung metastases regrew to almost 100% of the pre-treatment size (Fig. 1, Fig. 2, Sep/2016, A–C). Pre-laryngeal lymph node, lung, and adrenal tumors were not attached to large vessels, and the para-tracheal lymph nodes were mainly cystic. Thus, the endocrine team assessed that the risk of massive bleeding would be low, and lenvatinib was restarted at a dose of 10 mg a day in October 2016. After resuming lenvatinib, the patient showed only a few adverse events and therefore the medication was continued for another four and half years. However, it was discontinued in 2017 when her psychological condition worsened. After an improvement in psychological state, lenvatinib was restarted again after one month. Measurable tumors continued to be reduced in size, and a PR was observed until August 2020 (Figs. 1, 2 Aug/2020, A–C). However, in August 2020, a new bone metastasis in the sternum was found by CT scan (data not shown). Fortunately, the symptoms of bone metastasis were absent, and lenvatinib was continued despite progressive disease. Other than measurable lesions, cystic lymph nodes in the neck and mediastinum, and millions of tiny lung metastases, were also markedly reduced during lenvatinib treatment (Fig. 2D–F).
In February 2021, tumors in the neck and mediastinum, including the sternum, became enlarged, and the patient occasionally developed aspiration pneumonia. Lenvatinib was discontinued and restarted several times, being administered twice a week (10 mg/day) from April 2021 onwards. However, the multiple tumors progressively grew, and the patient’s general condition became worse, with multiple, large, cystic bone metastases evident. The patient subsequently passed away in June 2021.
