2. Case report
A 55-year-old patient (height, 160 cm; weight, 52 kg; in good nutritional status) presented to our hospital because of an ulcer on the right tongue margin in June 2015. The patient had been previously diagnosed with endometrial atypical growth by the obstetrics and gynecology department of a nearby hospital in December 2012. The patient was neither a drinker nor a smoker and had no family history of cancer. An extraoral examination revealed no abnormal findings in the cervical lymph nodes, whereas intraoral examination using magnetic resonance imaging (MRI) showed an ulcerative lesion with a diameter of ∼22 mm on the right tongue margin (Fig. 1A). Infiltrative lesions showing a contrast effect with gadolinium were also observed in the area (Fig. 1B,C). Positron emission tomography (PET) showed high accumulation of fluorodeoxyglucose in the right tongue margin but not in other organs (Fig. 1D). Based on these findings and pathological evaluation of an intraoral biopsy specimen, we diagnosed the patient with stage II (T2N0M0) squamous cell carcinoma of the tongue 1.
In July 2015, the patient underwent partial right tongue resection under general anesthesia. Postoperative adjuvant therapy was not administered because the surgical margin was negative. Although no recurrence was found locally or in the neck, swelling of the right cervical region was observed in December 2015 and the patient was followed up by monthly MRI thereafter. The MRI performed in February 2016 showed that the right upper-internal jugular vein lymph node had a minor axis of ∼12 mm. The patient was then diagnosed with late cervical lymph node metastasis of tongue cancer because the MR image showed a region with moderate signal intensity that included a part of the low-signal region (Fig. 2A). In the same month, the patient underwent right total neck dissection under general anesthesia. Postoperative adjuvant therapy was administered this time because histopathological diagnosis did not detect extracapsular invasion in the right superior-internal jugular vein lymph node.
Follow-up was continued, and swelling was observed in the lower part of the patient’s right jaw in May 2016. Computed tomography (CT) showed that the right submandibular lymph node had become swollen with a minor axis of ∼15 mm and that the boundary with the surrounding area was unclear (Fig. 2B). Recurrence was confirmed after the patient was diagnosed with late cervical lymph node metastasis of tongue cancer, and chemoradiotherapy (cisplatin [cis-diamminedichloroplatinum II] total dose, 300 mg/m2; radiotherapy total dose, 66 Gy) was performed from the same month onward. The treatment resulted in a stable disease (Fig. 2C).
Chemotherapy with cetuximab began in September 2016. Cetuximab was initially administered at a dose of 400 mg/m2 and subsequently at 250 mg/m2 once weekly. Cisplatin was administered at 80 mg/m2 on Day 1, and fluorouracil was administered at 800 mg/m2 on Days 1–4. A CT scan was performed in December 2016, at the end of the three courses of cetuximab combination chemotherapy. The recurrent lymph node had disappeared and a complete response (CR) was hence recorded (Fig. 3A). Serious complications, including bone marrow suppression, and side effects were not detected. In addition, paronychia of the limbs was observed. Although it was considered to be a skin reaction triggered by cetuximab, it only caused mild pain and improved with the application of a moisturizer. Cetuximab alone was maintained from the same month onward at a dose of 250 mg/m2 administered once a week.
Another CT scan was performed in March 2017, three months after the maintenance administration of cetuximab alone was initiated, and it revealed that the right submandibular lymph node was swollen. Therefore, the treatment response was classified as progressive (Fig. 3B). Nivolumab therapy was then started at a dose of 3 mg/kg once every two weeks. Immune-related adverse events due to nivolumab were not observed. A CT scan was performed again in July 2017, after six doses of nivolumab had been administered, and it revealed a shrinkage of the right submandibular lymph node (Fig. 3C). The treatment response was categorized as partial, and nivolumab administration was continued.
However, in October 2017, after 14 courses with nivolumab, we observed swelling of the right submandibular gland and CT images showed a marked increase in the right submandibular lymph node (Fig. 3D). The patient was thus considered to have a progressive disease, and cetuximab combination chemotherapy was recontinued from the same month onward. The dose and dosing interval were the same as previously implemented. The next CT scan was performed in February 2018, after three courses with the readministration of cetuximab combination chemotherapy, and showed that the right submandibular recurrent lymph node was markedly reduced (Fig. 3E). From the same month onward, the patient received maintenance administration of cetuximab alone. The final CT scan was performed in March 2019, after 52 doses of cetuximab. The submandibular lymph node had disappeared, and CR was achieved (Fig. 3F). Cetuximab alone was still being administered as maintenance therapy 20 months later. PET has not detected any recurrence or metastasis, and the course has been uncomplicated (Fig. 4A, B).