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).