Clinical Investigation
Thermochemoradiation Therapy Using Superselective Intra-arterial Infusion via Superficial Temporal and Occipital Arteries for Oral Cancer With N3 Cervical Lymph Node Metastases

https://doi.org/10.1016/j.ijrobp.2012.02.057Get rights and content

Purpose

To evaluate the therapeutic results and histopathological effects of treatment with thermochemoradiation therapy using superselective intra-arterial infusion via the superficial temporal and occipital arteries for N3 cervical lymph node metastases of advanced oral cancer.

Methods and Materials

Between April 2005 and September 2010, 9 patients with N3 cervical lymph node metastases of oral squamous cell carcinoma underwent thermochemoradiation therapy using superselective intra-arterial infusion with docetaxel (DOC) and cisplatin (CDDP). Treatment consisted of hyperthermia (2-8 sessions), superselective intra-arterial infusions (DOC, total 40-60 mg/m2; CDDP, total 100-150 mg/m2) and daily concurrent radiation therapy (total, 40-60 Gy) for 4-6 weeks.

Results

Six of 9 patients underwent neck dissection 5-8 weeks after treatment. In four of these 6 patients, all metastatic lymph nodes, including those at N3, were grade 3 (non-viable tumor cells present) or grade 4 (no tumor cells present) tumors, as classified by the system by Shimosato et al (Shimosato et al Jpn J Clin Oncol 1971;1:19-35). In 2 of these 6 patients, the metastatic lymph nodes were grade 2b (destruction of tumor structures with a small amount of residual viable tumor cells). The other 3 patients did not undergo neck dissection due to distant metastasis after completion of thermochemoradiation therapy (n=2) and refusal (n=1). The patient who refused neck dissection underwent biopsy of the N3 lymph node and primary sites and showed grade 3 cancer. During follow-up, 5 patients were alive without disease, and 4 patients died due to pulmonary metastasis (n=3) and noncancer-related causes (n=1). Five-year survival and locoregional control rates were 51% and 88%, respectively.

Conclusions

Thermochemoradiation therapy using intra-arterial infusion provided good histopathologic effects and locoregional control rates in patients with N3 metastatic lymph nodes. However, patients with N3 metastatic lymph nodes experienced a high rate of distant metastases.

Introduction

Patients with head-and-neck squamous cell carcinoma with advanced cervical metastases present a treatment dilemma because their prognosis is generally considered poor. When cervical lymph node metastases exceed 6 cm in the largest diameter (N3), treatment of these metastases is extremely difficult and often results in poor prognoses (1). The use of hyperthermia (HT) has generally been confined to treatment of cervical lymph node metastases, accessible with a radiofrequency system using external application, and in combination with synergistic chemoradiation therapy (CRT). HT is appealing because it is a physical treatment with fewer side effects than chemotherapy or radiation therapy. Repeated HT treatments should be feasible without concern for cumulative toxic side effects. Preoperative thermochemoradiation therapy has been shown to reduce N3 cervical lymph node metastases to surgically treatable sizes and to result in high clinical and pathological responses and improved survival rates (2).

A method of superselective intra-arterial infusion via a superficial temporal artery (STA) was developed 3, 4. This treatment can be used to provide daily concurrent radiation therapy and chemotherapy for patients with advanced head-and-neck cancer. This method has been used in the clinical setting since 1996 for organ preservation and improvement of treatment of patients with advanced head and neck cancer 3, 5; however, this method showed insufficient effects on cervical lymph node metastases, especially N2 and N3 disease. There have been a few clinical trials of patients with head-and-neck squamous cell carcinoma with N3 cervical lymph node metastases who were treated with thermoradiation therapy plus systemic chemotherapy, but no trials using thermoradiation therapy plus superselective intra-arterial chemotherapy have been reported. The present study evaluated the therapeutic results and histopathological effects of thermochemoradiation therapy using superselective intra-arterial infusion via STA and an occipital artery (OA) in patients with N3 cervical lymph node metastases of advanced oral cancer.

Section snippets

Patients

Between April 2005 and September 2010, 9 patients with stage T2-T4 N3 squamous cell carcinoma of the oral cavity and no evidence of distant metastasis when initially evaluated underwent intra-arterial CRT combined with HT at the Department of Oral and Maxillofacial Surgery of the Nagoya Graduate School of Medicine, Nagoya, and the Yokohama City Graduate School of Medicine, Yokohama, Japan (Table 1). Patients were required to have an Eastern Cooperative Oncology Group performance status (//ecog.dfci.harvard.edu/general/perf_stat.html

HT treatment

The median number of HT treatments was 4 (range, 2-8 sessions), the median maximum temperature in the central surface of the N3 disease was 43.4°C (range, 43.1°C-44.0°C), and the median minimum temperature was 42.2°C (range, 39.6°C-43.0°C) (Table 1).

Treatment results and pathological responses

Pathological responses and outcomes are shown in Table 2. For all patients, the median follow-up was 37 months (range, 7-70 months). Therapy as described above was completed in all patients. No major complications, such as cerebral infarctions or

Discussion

Superselective intra-arterial chemotherapy for head and neck cancer has the advantage of delivering a high concentration of chemotherapeutic agents to the tumor bed, and it is divided into 2 types: one type is selective arterial infusion through the femoral artery by Seldinger's method 9, 10; and the other type is retrograde selective infusion via STA and OA 3, 4, 5, 7. Of note, retrograde superselective intra-arterial infusion has become feasible for daily concurrent radiation therapy and

Conclusions

In conclusion, the present study has demonstrated that thermochemoradiation therapy using intra-arterial infusion provided good histopathologic effects and LRC rates for patients with advanced oral cancer with N3 cervical lymph node metastases. However, patients with N3 metastatic lymph nodes had a high rate of distant failure. Adjuvant chemotherapy after definitive treatment is recommended to reduce the risk of distant metastases for all patients with N3 disease.

Acknowledgment

The authors thank Dr Masaharu Hata and Dr Suomi Kurihara, Department of Radiology, for performing the radiation therapy and hyperthermia treatments.

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