Data for this review were identified by searches of PubMed and selected references from relevant articles with the search terms “head neck cancer”, “induction”, “chemotherapy”, “radiation”, “radiotherapy”, “randomised”, “chemoradiotherapy”, “organ preservation”, “neoadjuvant”. The same terms were used in a search limited to “reviews”. Abstracts from the American Society of Clinical Oncology Annual Meetings (2001–05) were also searched for these terms. Papers published from 1984 onwards
ReviewReassessment of the role of induction chemotherapy for head and neck cancer
Introduction
Head and neck cancers are a complex group of diseases defined by variations in histological features, anatomical location, and cause (figure 1).1 There are about 500 000 new cases per year worldwide, fewer than 10% of which occur in the USA.2 Given the heterogeneity of head and neck cancer, decision-making to select treatment is complicated. About 60% of patients have locally advanced disease (ie, stages III or IV, according to the AJCC [American Joint Committee on Cancer] system) at diagnosis. The precise definition of advanced-stage disease varies with subsite; most patients have a large primary tumour (ie, >4 cm) and involvement of regional nodes. Stage IV disease is classified as resectable, unresectable, or metastatic, with only about 5% of patients in the latter group at presentation.
Although treatment of head and neck cancer was once the realm of surgeons and radiation oncologists, over the past two decades medical oncologists have become an integral part of the treatment team. Improvements in radiotherapy and reconstructive surgical techniques as well as effective non-surgical curative treatment approaches have relegated radical surgeries that left patients with severe cosmetic deformity, functional impairment, and attendant psychosocial sequelae to the past. Current best practices need a multidisciplinary team approach that uses sequenced and concurrent combinations of the three modalities.
The results of these advances are site-specific and stage-specific, and include improvements in survival and quality of life through organ preservation. Current standards of care include primary chemoradiotherapy for unresectable disease, advanced nasopharyngeal cancer, and resectable disease where organ preservation is desirable; chemotherapy is added to postoperative radiotherapy for patients with high-risk pathological features.
Section snippets
Epidemiology and Survival
Historical survival data suggest that multimodality treatments cure at most 50% of patients with locally advanced disease. About 35% of patients have local recurrence and die from complications of locoregional disease; the remaining 15% die of distant disease. Although these numbers are sobering, they perhaps do not represent effects of recent shifts in the epidemiology of head and neck squamous-cell cancer and recent improvements in treatment.
More recent survival analyses incorporate
Improvement in treatment approach
Given both the increased complexity and potential toxic effects of combined treatment,12, 13 historical and current data must be analysed to determine how to become more selective when applying treatments. Characteristics of both the patient and the tumour—eg, tumour stage, location, and biology and host pharmacogenomics—may be used for this purpose.
Selection of patients and treatments can be optimised for the use of induction chemotherapy added to chemoradiotherapy in the setting of locally
Treatment of locally advanced disease
The first step in the development of multimodality care involved the use of postoperative radiotherapy in patients with adverse pathological features (ie, involved regional nodes; positive resection margin; and perineural, lymphatic, or vascular invasion). Although not proven with randomised studies, the approach has long been the standard of care since work by Lundahl and Huang.21 Variations in radiotherapy dosing, fractionation, and scheduling were also tested, but standard treatment remains
Rationale for induction chemotherapy
There are several theoretical advantages to preceding definitive local treatment (ie, chemoradiotherapy or surgery) with induction chemotherapy, including the potential of systemic treatment to suppress development of distant metastases, and the hypothesis that subsequent local treatment is more effective after reduction of tumour volume. Together, these benefits lower the risk of recurrence. Cisplatin-based induction chemotherapy leads to high objective responses, including complete responses
Induction chemotherapy in practice
Randomised studies of induction chemotherapy followed by surgery or radiotherapy compared with definitive local treatment alone date back two decades (table 1). They are numerous, but the results are easily summarised. Apart from two published trials,19, 20 induction chemotherapy had no benefit in survival compared with local treatment (surgery, radiotherapy, or chemoradiotherapy) alone, although many reported a reduction in distant metastases in patients allocated chemotherapy (table 1). By
Future directions
After several decades of studies involving thousands of patients, the role of induction chemotherapy remains controversial. The current interest in reassessing induction chemotherapy, however, is in the context of adding a more effective three-drug regimen of a taxane, cisplatin, and fluorouracil to a treatment that improves locoregional control—specifically, chemoradiotherapy. Before incorporating this treatment into clinical practice, it is imperative that a gain in survival is shown.
Conclusion
In the 1980s, induction chemotherapy before surgery or radiotherapy was the focus for integration of chemotherapy into the management of newly diagnosed patients. These studies, in the main, showed that local control was not improved, but that chemotherapy did suppress metastases. Although survival was not improved, it also was not jeopardised and larynx preservation was established. Clinical research initiatives in the 1990s investigated concurrent platinum-based chemoradiotherapy. This
Search strategy and selection criteria
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Multifocal regression and pathologic response predicts recurrence after neoadjuvant chemotherapy in head and neck squamous cell carcinoma
2021, Oral OncologyCitation Excerpt :Neoadjuvant chemotherapy (NAC) induces a response in the majority of patients with head and neck squamous cell carcinoma (HNSCC) [1].
Target Volume Definition for Intensity-modulated Radiotherapy after Induction Chemotherapy and Patterns of Treatment Failure after Sequential Chemoradiotherapy in Locoregionally Advanced Oropharyngeal Squamous Cell Carcinoma
2013, Clinical OncologyCitation Excerpt :Recent encouraging results from the TAX 324 study, showing a survival benefit with the addition of docetaxel to cisplatin and 5-fluorouracil, have generated renewed interest in the use of induction chemotherapy in locoregionally advanced SCC of the head and neck (SCCHN) [1]. Induction chemotherapy produces high response rates of 60–90% in SCCHN, including complete responses [2]. It may eradicate micrometastatic disease at distant sites and reduce tumour volume before chemoradiation (CRT) [2].
Epithelial-mesenchymal transition transcription factor ZEB1/ZEB2 co-expression predicts poor prognosis and maintains tumor-initiating properties in head and neck cancer
2013, Oral OncologyCitation Excerpt :HNC-related death is primarily caused by cervical lymph node metastasis and occasionally by distant organ metastasis.2 Despite improvements in the diagnosis and management of HNC, long-term survival rates have improved only marginally over the past decade.3 To improve the survival rate of HNC patients, investigations to elucidate the mechanism of the tumorigenesis of HNC are urgently needed.
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