Elsevier

European Journal of Cancer

Volume 51, Issue 17, November 2015, Pages 2596-2603
European Journal of Cancer

Induction chemotherapy prior to surgery with or without postoperative radiotherapy for oral cavity cancer patients: Systematic review and meta-analysis

https://doi.org/10.1016/j.ejca.2015.08.007Get rights and content

Highlights

  • This is a systematic review and meta-analysis involving oral cavity cancer patients only.

  • Induction chemotherapy before surgery did not improve clinical outcomes.

  • There may be a survival benefit from induction chemotherapy in the cN2 subgroup.

Abstract

Background

Locoregionally advanced oral cavity cancers are aggressive tumours with high risk of relapse after definitive treatment. This study was performed to assess the effectiveness and safety of induction chemotherapy prior to surgery for untreated oral cavity cancer patients.

Material and methods

Only prospective phase III randomised studies comparing induction chemotherapy followed by surgery with or without postoperative radiotherapy (Chemo Group) compared with surgery with or without postoperative radiotherapy (Control Group) were eligible. Two of the authors independently selected and assessed the studies regarding eligibility criteria and risk of bias.

Results

Two studies were selected. A total of 451 patients were randomly assigned to Chemo Group (n = 226) versus Control Group (n = 225). Most patients had tumours at clinical stages III/IV (89.1%). Both trials were classified as having low risk of bias. No significant overall benefit in favour of induction chemotherapy was found regarding loco-regional recurrence, disease-free survival and overall survival. A subgroup analysis of individual data from cN2 patients showed statistically significant overall survival benefit in favour of induction chemotherapy. The included studies did not directly compare toxicity between the groups and no statistical analysis was performed regarding safety outcomes.

Conclusions

Based on the available studies, induction chemotherapy when administered before surgery with curative intent did not improve clinical outcomes in locoregionally advanced oral cavity cancer patients. Clinically assessed N2 patients might benefit from induction chemotherapy.

Introduction

Squamous cell carcinoma is the most common cancer that occurs in the oral cavity, with an estimated 300,000 new cases worldwide each year [1], [2], [3]. Locoregionally advanced oral cavity cancers are aggressive tumours with elevated probabilities of relapse after definitive treatment with surgery or radiotherapy (RT). Therefore, a multimodal approach combining surgery and postoperative radiotherapy or chemoradiotherapy has been proposed [4].

There are insufficient reports from phase III prospective randomised clinical studies to show an ideal approach for patients with locally advanced oral cavity malignancies. Guidelines and treatment options are based upon studies that included a majority of patients with primary cancers at other head and neck sites and also retrospective data.

In general, the primary therapy for locally advanced oral cavity squamous cell carcinoma (SCC) usually involves surgery followed by radiotherapy and chemotherapy (in the setting of high-risk pathological features such as positive resection margins, and extracapsular nodal spread). Upfront chemoradiation is an option for patients who decline surgery, have unresectable tumour and/or are medically inoperable [5]. Nevertheless, overall survival and tumour control are disappointing, because approximately 50% of the patients will die after 5 years from diagnosis, due to local and/or systemic recurrences [6]. Although improvement in surgical techniques and use of adjuvant treatments have been observed, the 5-year survival rate has not improved considerably in recent years, persisting at 55% [7], [8].

New treatment strategies for locally advanced oral cavity SCC have been tested, including preoperative chemotherapy. Induction chemotherapy might reduce tumour burden, ameliorate tumour-related symptoms and improve surgical results. Moreover, induction chemotherapy could treat micrometastatic disease early on, potentially leading to improved overall clinical outcomes [9].

This study was performed to assess the effectiveness and safety of induction chemotherapy prior to surgery for untreated oral cavity SCC patients.

Section snippets

Study design

This was a systematic review carried out in accordance with The Cochrane Collaboration Handbook of Interventions Systematic Reviews [10]. The manuscript was arranged using the PRISMA Statement as reporting guidance [11].

Criteria for considering studies for this review

We included trials that assessed any induction chemotherapy strategy followed by surgery with or without postoperative radiotherapy compared with surgery with or without postoperative radiotherapy. Only randomised controlled trials were considered. Cluster or crossover designs

Study selection and characteristics of the included studies

The flowchart of the retrieved studies and the characteristics of included studies are presented in Fig. 1 and Table 1, respectively. Three papers, reporting two studies fulfilled the eligibility criteria (Bossi et al. [12], Licitra et al. [13], Zhong et al. [14]).

451 patients were randomly assigned to induction chemotherapy followed by surgery with or without radiotherapy (n = 226), versus surgery with or without radiotherapy (n = 225). Most of the patients were male (75.8%); tumours at clinical

Discussion

Standard management for advanced oral cavity SCC comprises a multidisciplinary approach including surgery and postoperative radiotherapy associated or not with chemotherapy. Despite technical improvements in the involved therapeutic modalities [15], [16], [17], long-term overall survival and tumour control are still unsatisfactory [8], [9].

The use of chemotherapy in advanced head and neck SCC has shown a significant advantage in terms of overall survival, when delivered concurrently with

Conflict of interest statement

None.

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