Intra‐arterial chemoradiotherapy for locally advanced buccal mucosal cancer in an elderly patient with multiple comorbidities: A case report

Abstract Background The management of locally advanced oral cavity squamous cell carcinoma (LA‐OCScc) in elderly patients with multiple comorbidities is difficult. Case We report the case of an elderly patient with buccal mucosal squamous cell carcinoma as well as chronic renal dysfunction, hepatic cirrhosis, rheumatoid arthritis, and metachronous diffuse large B‐cell lymphoma. We performed radiation therapy (a total dose of 70 Gy in 35 fractions) and six cycles of intra‐arterial chemotherapy with 40 mg/m2 cisplatin per week. After treatment, the tumor completely disappeared, and there was no recurrence or deterioration of comorbidities during the 12‐month follow‐up period. Conclusion Intra‐arterial chemoradiotherapy may be a good treatment option for LA‐OCScc in elderly patients with multiple comorbidities.


| INTRODUCTION
Head and neck cancer is a common malignancy that causes more than 300 000 deaths per year worldwide. 1 Approximately 25% of patients with head and neck cancer are over the age of 70 years. 2,3 Various prognostic factors of head and neck cancer have been reported. Several factors, such as age, comorbidity, and human papilloma virus status, often have an influence on initial treatment strategy. [4][5][6] Surgery followed by postoperative chemoradiotherapy is the standard treatment for locally advanced oral cavity squamous cell carcinoma (LA-OCScc). Up-front surgery for LA-OCScc has been shown to provide a substantial survival benefit compared to definitive radiotherapy with or without chemotherapy in a small randomized trial 7 and several retrospective studies. [8][9][10] However, the number of patients with LA-OCScc receiving non-surgical treatment has been increasing. 5 In particular, patients aged 75 years or older have received non-surgical treatment more often than younger patients. 10 Concurrent chemoradiotherapy (CRT) is the most acceptable treatment approach for the non-surgical treatment of LA-OCScc. The standard treatment regimen consists of three cycles of cisplatin (100 mg/m 2 ) administered on days 1, 22, and 43 during radiotherapy (70 Gy in 35 fractions). 11,12 Since CRT improves survival outcomes achieved after radiotherapy alone, in addition to an increase in side effects, the management of toxicities has been important. 13,14 Several studies have shown that elderly patients can achieve outcomes similar to those of younger patients who receive aggressive treatments. 15,16 Nevertheless, elderly patients often receive less aggressive treatments, such as radiotherapy alone, compared with younger patients with the same disease status. 17 This tendency is remarkable in elderly patients with multiple comorbidities. In the elderly, complications such as renal dysfunction have a significant impact on life expectancy; therefore, it is important to make aggressive treatment choices if the patient can tolerate the treatment.
In a randomized controlled phase 3 trial in patients with locally advanced unresectable head and neck cancer, intra-arterial chemoradiotherapy (IA-CRT) was not superior to intravenous chemoradiotherapy (IV-CRT) in relation to outcomes, but rates of local control and overall survival were similar between the two groups. 18 Superselective intra-arterial chemotherapy (IA-CT) is divided into two types: selective arterial infusion through the femoral artery 19,20 or retrograde selective infusion via the superficial temporal artery (STA) and/or occipital artery (OA). [21][22][23] The former method is standard, but some studies have reported the risk of neurologic toxicity. 18,20 In contrast, the conventional method of catheterization through the STA is rarely associated with neurologic toxicity, but results in inadequate selectivity in some patients in whom the tumor was supplied by multiple arteries. Our previous report described treating head and neck cancer with multiple tumor-feeding arteries with retrograde superselective IA-CT using an external carotid arterial sheath (ECAS) system. 23 Superselective IA-CT using the ECAS system can be performed in elderly patients with carotid artery stenosis. However, there is insufficient evidence to show the efficacy and safety of retrograde intra-arterial chemotherapy with concurrent chemotherapy in elderly patients with multiple comorbidities. In this study, we report a case study using IA-CT with concurrent radiotherapy in an elderly patient with LA-OCScc as well as chronic renal dysfunction, hepatic cirrhosis, rheumatoid arthritis, and metachronous diffuse large B-cell lymphoma.

| CASE REPORT
A 76-year-old man was referred to Mie University Hospital due to exacerbation of swelling of the right buccal mucosa. He had a history of cirrhosis (Child-Pugh class B) and chronic renal dysfunction.
He was taking prednisolone for rheumatoid arthritis. In addition, he had maintained complete response for 3 years after treatment with six cycles of the rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone regimen for methotrexate-related malignant lymphoma (DLBCL). Physical examination revealed a mass of the right buccal mucosa (28 Â 25 mm) and a mucosal lesion on the soft palate ( Figure 1). He had redness and induration on the skin near the right corner of the mouth. Computed tomography (CT) with contrast showed an enhancing tumor in the right buccal mucosa, and the lesion was suspected to extend to the soft palate

| DISCUSSION
Although the treatment of an elderly patient with head and neck tumor with multiple comorbidities is challenging, IA-CRT is one of the curative treatments for inoperable patients. Here, we applied IA-CRT to a patient with LA-OCScc who was difficult to treat curatively due to age and basic diseases such as chronic renal failure and hepatic cirrhosis.
The standard treatment for LA-OCScc is surgery and postoperative radiotherapy with or without chemotherapy. According to previous reports on treatment outcomes of surgery with postoperative CRT in elderly patients with head and neck cancer, the 3-year overall survival (OS) and local control (LC) rates were 64% and 79%, respectively. 24 However, major surgery is less frequently offered to elderly patients because the incidence of medical complications is significantly increased due to the presence of degenerative conditions and comorbidities. 25 (Table 1). In a study of 134 patients treated with retrograde IA-CRT with weekly carboplatin or cisplatin, the 3-year LC and OS rates were 69% and 54%, respectively. 21 Mitsudo  In conclusion, radiotherapy combined with intra-arterial chemotherapy may be curative non-surgical treatment option for locally advanced oral cancer in elderly patients with multiple comorbidities. writingreview and editing (equal). Yoshihito Nomoto: Supervision (equal); writingreview and editing (equal).

ACKNOWLEDGEMENT
We would like to thank Editage (www.editage.jp) for English language editing.

CONFLICT OF INTEREST
The authors declare that they have no conflict of interest related to this study.

DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.

ETHICS STATEMENT
This case report does not require institutional review board approval, as it only includes one patient.