Thermochemotherapy of lower lip squamous cell carcinoma without metastases: An experience of 31 cases

Summary

Introduction

The aim of this study was to evaluate the efficacy, functional and aesthetic results, and safety of a novel treatment, thermochemotherapy, for lower lip squamous cell carcinoma (LLSCC) without metastases.

Patients and Methods

A combination of local hyperthermia delivered by a 915 MHz microwave heating system and the chemotherapy of pingyangmycin (bleomycin A(5) hydrochloride) (PYM) and methotrexate (MTX), was administered to 31 patients of LLSCC twice per week for a period of 4.5–7.5 weeks. Patients with complete response (CR) have been followed up for a full five-year period, whereas partial response (PR) patients were excluded for further analysis. The local control of tumour, functional and cosmetic outcomes, recurrence, regional lymph node and distant metastases, and complications were assessed by clinical and imaging examination.

Results

Clinical CR was observed in twenty-nine (93.55%) patients and PR in two (6.45%), the total response rate was 100%, while the adverse effects were extremely minimal and tolerable in all 31 patients including 6 elderly patients with a compromised general condition. All 29 CR, including 8 extensive lesions, achieved excellent cosmetic and functional preservation. During the follow-up period, local relapse was seen in 1 case, 1 patient died, and the remainder obtained a complete remission.

Conclusion

This clinical study suggests that thermochemotherapy may be a feasible treatment for primary LLSCC without cervical metastases, especially for patients with extensive lesions and a compromised general condition.

Introduction

Squamous cell carcinoma is the most frequent histological type of malignant lip tumour in human, as it represents more than 95% of all cases (Zitsch et al., 1995, Myers and Suen, 1996). Lip squamous cell carcinoma occurs frequently on the lower lip of middle-aged and elderly males who have a history of chronic sun exposure and the habit of smoking (Eastcott, 1963). The behaviour of the lower lip squamous cell carcinoma (LLSCC) is locally destructive, rarely producing metastases and has little effect on survival. LLSCC can be treated with diverse methods: surgical excision (Salgarelli et al., 2005, Kalantar-Hormozi and Khorvash, 2006, Kovács, 2006, Lung et al., 2007, Schiefke et al., 2008), brachytherapy and external beam radiotherapy (Freeman et al., 1964, Lovett et al., 1990, Guinot et al., 2003, Rovirosa-Casino et al., 2006, Lung et al., 2007, Schiefke et al., 2008), chemo-surgery with Mohs (Mohs, 1956), electrofulguration (Lovett et al., 1990), photodynamic therapy (Chen et al., 2005, Vesnaver and Dovsak, 2006), and continuous intra-arterial infusion (Kovács, 2006Wu et al., 2007), which are regarded as effective treatment options. However, all modalities possess their advantages and disadvantages. Standard surgical excision with adequate margins is usually recommended as the technique of choice for lower lip carcinomas especially when in the early stage because of the advantage of complete extirpation of the tumour, avoidance of radiation complications, and rapid recovery. However, the management of the resulting lower lip defect remains a significant reconstructive challenge, requiring meticulous preoperative planning and surgical technique to optimize the functional and cosmetic outcome. It has been reported that there have been no major advances in lower lip reconstruction; rather, continued improvement of accepted techniques (Coppit et al., 2004). Radiotherapy has also been widely employed many years ago in the treatment of these lesions. Nevertheless, radiation complications are frequently observed (Baker, 1990, de Visscher et al., 1999). Besides, the following technical parameters need consideration: total dose, dose per fraction, type of frequency used, utilization of bolus and size of the treated region (Freeman et al., 1964, Lovett et al., 1990, Guinot et al., 2003, Rovirosa-Casino et al., 2006). The electrofulguration destroys tissue locally; but its use precludes anatomo-pathological examination and study of the resection margin. In addition, its effect produces a poor aesthetic result (Lovett et al., 1990). Although chemotherapy has been favoured in view of its cosmetic and oral functional results, the adverse effects of chemotherapeutic agents are an important issue yet to be solved. In addition, it's curative effect is not as good (Wu et al., 2007). The management of LLSCC, especially when advanced, remains a significant challenge. Depending on its site, it must offer the best efficacy and the best functional and aesthetic results along with the fewest side effects.

According to recent promising clinical trials in the several published series, hyperthermia, particularly in conjunction with chemo or radiotherapy (Overgaard et al., 1995; Hoshina et al., 1997, Yasumoto et al., 2004), was useful for the treatment of human malignant tumours. These were characterized by treatment of a wide range of lesions with minimal adverse effect events and adjacent tissue damage, and thus allowed good functional and aesthetic results. In addition, hyperthermic treatment is especially suitable for human head and neck cancer, as it is easy to perform thermoregulation when compared with deep organs such as the liver and pancreas (Hoshina et al., 1997, Yasumoto et al., 2004). To the best of our knowledge, however, no similar study of hyperthermia in combination with chemotherapy for lower lip carcinomas can be found in the literature.

Pingyangmycin (PYM), the single component of bleomycin A₅, is an anticancer agent that is refined from Streptomyces pingyangensis and shows a strong damage function to squmaous cell carcinoma. PYM mixed with methotrexate (MTX) can be used to treat oral cancer (Qiu, 1989). In the present study, 31 patients who suffered from LLSCC but no metastases were treated using a novel thermochemotherapy, microwave local hyperthermia combined with PYM and MTX chemotherapy in West China Stomatological Hospital of Sichuan University from October 1998 to December 2002. The efficacy, functional and aesthetic results, usefulness, and safety of thermochemotherapy were assessed for this patient group.