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CORRESPONDENCE
Year : 2013  |  Volume : 9  |  Issue : 4  |  Page : 718-720

Thermochemoradiotherapy using superselective intra-arterial infusionfor N3 cervical lymph node metastases of tongue cancer


1 Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
2 Department of Oral and Maxillofacial Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan

Date of Web Publication11-Feb-2014

Correspondence Address:
Kenji Mitsudo
Department of Oral and Maxillofacial Surgery, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama Kanagawa 236-0004
Japan
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.126465

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 > Abstract 

A case of squamous cell carcinoma of the tongue with advanced N3 cervical lymph node metastases in an 80-year-old female is reported. The patient was treated with a combination of radiotherapy (2 Gy/day, total 60 Gy), superselective intra-arterial chemotherapy via a superficial temporal artery and a femoral artery (docetaxel, total 124 mg; cisplatin, total 135 mg), and four sessions of hyperthermia for cervical lymph node metastases. The tumor responded well to therapy, and 18-fluorodeoxyglucose uptake in both primary and neck lesions disappeared on positron emission tomography-computed tomography. The patient has shown no clinical or radiological evidence of local recurrence or distant metastases 6 years after the end of treatment. Advanced oral cancer patients with N3 cervical lymph node metastases are particularly difficult to treat and have a poor prognosis. This method of thermochemoradiotherapy seems a promising modality for patients with N3 cervical lymph node metastases of oral cancer.

Keywords: Hyperthermia, intra-arterial infusion, N3 cervical lymph node metastases, oral cancer, thermochemoradiotherapy


How to cite this article:
Nishiguchi H, Mitsudo K, Yamamoto N, Tohnai I. Thermochemoradiotherapy using superselective intra-arterial infusionfor N3 cervical lymph node metastases of tongue cancer. J Can Res Ther 2013;9:718-20

How to cite this URL:
Nishiguchi H, Mitsudo K, Yamamoto N, Tohnai I. Thermochemoradiotherapy using superselective intra-arterial infusionfor N3 cervical lymph node metastases of tongue cancer. J Can Res Ther [serial online] 2013 [cited 2019 Nov 22];9:718-20. Available from: http://www.cancerjournal.net/text.asp?2013/9/4/718/126465


 > Introduction Top


Oral cancer patients with cervical lymph node metastases are particularly difficult to treat, especially when cervical lymph node metastases exceed 6 cm (N3), and have a poor prognosis. Hyperthermia (HT) has generally been limited to cervical lymph node metastases accessible with a radiofrequency system using external application, in combination with synergistic chemoradiotherapy. There have been a few clinical trials of patients with head and neck squamous cell carcinoma with N3 cervical lymph node metastases treated with thermoradiotherapy plus systemic chemotherapy, [1],[2] but survival and locoregional control rates were unsatisfactory. Superselective intra-arterial chemotherapy for head and neck cancer has the advantage of delivering high concentrations of the chemotherapeutic agents to the primary tumor and metastatic cervical lymph nodes. A case of squamous cell carcinoma of the tongue with N3 cervical lymph node metastases treated with thermochemoradiotherapy using superselective intra-arterial chemotherapy via a superficial temporal artery (STA) and a femoral artery with Seldinger's method is reported.


 > Case Report Top


An 80-year-old woman with an enlarging left-sided neck mass and tongue pain was referred in January 2006. Oral examination showed an ulcerative mass with induration at the left lateral border of the tongue [Figure 1]a. The patient also had a large left-sided neck mass (80 × 45 mm) [Figure 1]b. The tongue mass was biopsied and diagnosed as well-differentiated squamous cell carcinoma. Contrast-enhanced computed tomography (e-CT) showed a well-demarcated mass at the left edge of the tongue that crossed the midline [Figure 2]a and a multiple ring-enhanced mass at levels I, II, III, and IV of the left cervical area [Figure 2]b. Positron emission tomography-computed tomography (PET-CT) demonstrated high 18-fluorodeoxyglucose (FDG) uptake at the cervical lymph nodes (SUVmax 7.15) [Figure 2]c. The distant metastasis work-up was negative.
Figure 1: Clinical appearance at initial presentation, showing an ulcerative mass with induration, measuring 55 × 42 mm at the left lateral border of the tongue (a) and a large neck mass on the left side (b)

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Figure 2: E-CT shows a well-demarcated mass at the left tongue (a, arrows) and a multiple ring-enhanced mass that measured 80 × 45 mm at the left neck (b). PET-CT shows abnormal FDG uptake (SUVmax 7.15) of the left neck mass (c)

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Since the patient rejected radical surgery, definitive thermochemoradiotherapy using superselective intra-arterial infusion was planned. The feeding arteries of the tongue tumor were bilateral lingual and facial arteries; those of the N3 cervical lymph nodes were the left facial artery, superior thyroid artery, and transverse cervical artery. Catheterization from the STA was performed using the method of Fuwa and Tohnai. [3],[4] Two catheters were inserted superselectively into the left thyrolinguofacial trunk and right facial artery via bilateral STAs. The right catheter was re-placed into the lingual artery when the total irradiation dose reached 30 Gy. After catheterization, flow-check digital subtraction angiography (DSA) and angio-computed tomography (angio-CT) were performed to confirm enhancement of the feeding area and to assist in appropriate catheter placement [Figure 3]. Docetaxel (DOC) and cisplatin (CDDP) were injected in a bolus through the intra-arterial catheter from the STAs during radiotherapy. In addition, DOC was injected into the left transverse cervical artery three times via the femoral artery for N3 cervical lymph node metastases [Figure 4]. The total doses were 124 mg/body for DOC and 135 mg/body for CDDP. Sodium thiosulfate (1 g/m 2 ) was administered intravenously to provide effective CDDP neutralization after CDDP was given. Radiotherapy was planned after appropriate immobilization using a thermoplastic mask and three-dimensional CT-based techniques. The total dose delivered to the primary tumor and the metastatic N3 lymph node sites was 60 Gy/30 fractions. Four sessions of HT were given for cervical lymph node metastases. HT was administered for 50 min within 30 min after each session of chemoradiotherapy using a radiofrequency capacitive heating device (Thermox 1000, OMRON, Tokyo, Japan). Tumor temperatures were monitored by thermometric probes in the central skin surface of the neck tumor, and mean maximum and minimum temperatures were 43.3°C and 41.5°C, respectively. Grade 3 neutropenia, oral mucositis, and dermatitis associated with treatment were observed following therapy (National Cancer Institute-Common Toxicity Criteria for Adverse Events v3.0). No major complications, such as cerebral infarctions or other neurological complications, occurred. Both primary tumor and N3 neck disease responded well [Figure 5]a and b and FDG uptake on PET-CT in both sites disappeared after treatment [Figure 5]c and d. The patient has shown no clinical or radiological evidence of local recurrence or distant metastasis 6 years after treatment.
Figure 3: The tip of the catheter is inserted superselectively into the left thyrolinguofacial trunk (a). Angio-CT shows that the N3 lymph node metastases corresponds to the enhancement from the thyrolinguofacial trunk (b) and the transverse cervical artery (c, arrow)

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Figure 4: Treatment schedule. (Lt., left; Rt., right; CT, chemotherapy; RT, radiotherapy; HT, hyperthermia; D, docetaxel; C, cisplatin; STA, superficial temporal artery; TLF, thyrolinguofacial trunk; LA, lingual artery; FA, facial artery; TCA, transverse cervical artery; Fe. A, femoral artery)

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Figure 5: After completion of thermochemoradiotherapy, both the primary lesion (a) and N3 neck disease (b) responded well. Physiological uptake of FDG was continued in the primary and neck lesion, and calcification in the metastatic lymph nodes was seen (d, arrows) on PET-CT. FDG uptake in both sides disappeared (c and d)

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 > Discussion Top


Superselective intra-arterial chemotherapy via the STA has become feasible for daily concurrent radiotherapy and chemotherapy for advanced head and neck cancer, with a high clinical efficacy. [5] The superficial temporal approach is a technically simple and easy method for inserting a catheter into the branches of the external carotid artery, such as the lingual, facial, occipital, or maxillary arteries. However, it is impossible to insert a catheter into the superior and inferior thyroid, ascending cervical, and transverse cervical arteries. Patients with cervical lymph node metastasis at level III, IV, or V do not obtain sufficient effects using superselective intra-arterial chemotherapy via the STA. In these cases, the transfemoral approach with Seldinger's method enables catheter insertion into target arteries and facilitates the administration of anticancer agents into the arteries. [6],[7] In this case, the target arteries for the primary focus and cervical lymph node metastases were the lingual, facial, superior thyroid, and transverse cervical arteries; thus, it was necessary to approach both the superficial temporal and transfemoral arteries for superselective intra-arterial infusion.

HT is a physical treatment with fewer side effects than chemotherapy and radiotherapy, and repeated treatments should be feasible without cumulative toxic side effects. Radioresistant cells, such as hypoxic cells, low pH cells, and cells in late S phase, are thermosensitive. [8] Moreover, radiotherapy and numerous chemotherapeutic agents display complementary synergistic effects with HT. [1],[9] Large-volume lymph node metastases usually display poor perfusion that results in central hypoxic conditions, anaerobic glycolysis, and low pH. Therefore, combination CRT with HT should improve the clinical outcomes of large lymph node metastases, and superficial metastatic neck nodes seem to be suitable for HT.

In this case, good long-term results were achieved with radiotherapy and HT in combination with superselective intra-arterial DOC and CDDP chemotherapy. Therefore, this method seems a promising modality for patients with N3 cervical lymph node metastases of oral cancer.

 
 > References Top

1.Serin M, Erkal HS, Cakmak A. Radiation therapy, cisplatin and hyperthermia in combination in management of patients with carcinomas of the head and neck with N2 or N3 metastatic cervical lymph nodes. Radiother Oncol 1999;50:103-6.  Back to cited text no. 1
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2.Tohnai I, Hayashi Y, Mitsudo K, Shigetomi T, Ueda M, Ishigaki T. Prognostic evaluation of preoperative thermochemoradiotherapy for N(3) cervical lymph node metastases of oral cancer. Oncology 2002;62:234-40.  Back to cited text no. 2
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3.Tohnai I, Fuwa N, Hayashi Y, Kaneko R, Tomaru Y, Hibino Y, et al. New superselective intra-arterial infusion via superficial temporal artery for cancer of the tongue and tumour tissue platinum concentration after carboplatin (CBDCA) infusion. Oral Oncol 1998;34:387-90.  Back to cited text no. 3
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4.Fuwa N, Ito Y, Matsumoto A, Kamata M, Kodaira T, Furutani K, et al. A combination therapy of continuous superselective intraarterial carboplatin infusion and radiation therapy for locally advanced head and neck carcinoma. Phase I study. Cancer 2000;89:2099-105.  Back to cited text no. 4
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5.Mitsudo K, Shigetomi T, Fujimoto Y, Nishiguchi H, Yamamoto N, Furue H, et al. Organ preservation with daily concurrent chemoradiotherapy using superselective intra-arterial infusion via a superficial temporal artery for T3 and T4 head and neck cancer. Int J Radiat Oncol Biol Phys 2011;79:1428-35.  Back to cited text no. 5
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6.Lee YY, Wallace S, Dimery I, Goepfert H. Intraarterial chemotherapy of head and neck tumors. AJNR Am J Neuroradiol 1986;7:343-8.  Back to cited text no. 6
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7.Robbins KT, Storniolo AM, Kerber C, Seagren S, Berson A, Howell SB. Rapid superselective high-dose cisplatin infusion for advanced head and neck malignancies. Head Neck 1992;14:364-71.  Back to cited text no. 7
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8.Hahn GM, Shiu EC. Adaptation to low pH modifies thermal and thermo-chemical responses of mammalian cells. Int J Hyperthermia 1986;2:379-87.  Back to cited text no. 8
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9.Hahn GM. Potential for therapy of drug and hyperthermia. Cancer Res 1979;39:2264-8.  Back to cited text no. 9
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  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]



 

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