Head and neck cancer – general principles

Chapter 21 Head and neck cancer – general principles



Christopher D. Scrase



Chapter contents



Introduction


Demographics


Aetiology


Prevention and early diagnosis


Tumour types


Presentation


Investigation


Nutrition


Dentition


Indications for radiotherapy


Definitive radiotherapy 

Postoperative radiotherapy 

Palliative radiotherapy 

Radiotherapy planning


Immobilization 

Target volumes


Definitive radiotherapy 

Postoperative radiotherapy 

Radiotherapy technique


Conformal radiotherapy (3DCRT) 

Intensity modulated and image guided radiotherapy in head and neck cancers 

What is intensity modulated radiotherapy? 

How is intensity modulated radiotherapy achieved? 

Treatment planning in IMRT 

The scope of IMRT in head and neck tumours 

Pitfalls to intensity modulated radiotherapy 

IGRT 

Dose and fractionation


Definitive radiotherapy 

Postoperative radiotherapy 

Chemotherapy in head and neck cancer


Concurrent chemotherapy and definitive radiotherapy 

Concurrent chemotherapy and postoperative radiotherapy 

Induction chemotherapy 

Chemotherapy in the palliative setting


Toxicity of treatment


Acute toxicity 

Late toxicity 

Molecular oncology – future developments


Further reading



Introduction


‘Head and neck cancer’ is a rather inaccurate term for describing cancers of the upper aerodigestive tract – tumours of the facial skin and the brain are not conventionally included. They are a diverse group, comprising oral cancers, as well as those of the oropharynx, larynx, nasopharynx and hypopharynx; also the paranasal sinuses, salivary glands and ear. The overall incidence is approximately 11 cases per 100   000 per year in England and Wales, although there are regional variations. The incidence is increasing at present (see the ‘aetiology’ section of this chapter). Although the treatment for these areas is often highly specialized, they also have many features in common with regard to investigation, diagnosis and management. Perhaps more than any other anatomical site, the concept of multidisciplinary team working is paramount in head and neck cancer and it is essential that the team members are involved as early as possible to provide the best outcome in terms of tumour control, maintaining function and acceptable cosmesis. Radiotherapy, and to an increasing extent chemotherapy, are now widely used, either as primary therapy or postoperative treatments.



Demographics


Head and neck cancers make up 4–5% of all new cancers. The incidence is higher in males than females, although the ratio is different for specific cancers: oral cavity (2:1), larynx (4:1), but these numbers are changing due to an increasing incidence of smoking in women. The majority of head and neck cancers present beyond the fifth decade with an average age of onset of 60 years. Cancers of the head and neck are more commonly found in people from the lower social classes and this is multifactorial with higher incidences of smoking and alcoholism, late presentation, poor oral hygiene, inadequate diet etc. It is linked to delayed diagnosis and worse outcome.



Aetiology


The most important risk factor in the development of head and neck cancers is tobacco. Smoking or chewing tobacco is associated with 85–90% of head and neck malignancies. Alcohol intake has also been shown to cause an increase in this group of cancers. There is also a synergistic effect of combining alcohol and tobacco with regard to developing cancers in this site. There is also a clear increase in the incidence of second malignancy of the head and neck and other sites (lung, oesophagus) in persistent smokers.


Other risk factors in head and neck cancers have been suggested including poor oral hygiene, dental disease and trauma from badly fitted dentures, though direct causation has not been demonstrated. Viral infections have also been investigated for a role in the aetiology of head and neck cancers. There is a very strong association with Epstein-Barr virus infection and nasopharyngeal cancer. There is an increasing incidence of human papilloma virus (HPV) associated oropharyngeal and oral tumours, particularly in the USA. Such tumours develop in younger patients and have a distinctive pathological appearance – basaloid and predominantly poorly differentiated carcinoma. Immunosuppression is known to be a risk factor for malignancy and this includes cancers of the head and neck. Tertiary syphilis is another predisposing factor, although the authors have never knowingly seen a patient – but this rare disease is increasing in frequency again, and needs to be remembered.


Pre-malignant conditions also exist which predispose for the development of head and neck cancers. These are most commonly seen in the oral cavity and include leukoplakia (white patches) which carry an approximately 5% risk of progressing to invasive malignancy and, more sinisterly, erythroplakia. Regular specialist follow up is therefore essential. Lichen planus with dysplastic features can also become malignant and requires monitoring.


Radiation exposure is also a risk factor for developing head and neck cancers. A previous history of radiotherapy treatment should be sought in newly diagnosed patients. It will also have an impact on any future radiotherapy treatment options.



Prevention and early diagnosis


When diagnosed early, head and neck cancer has quite good chances for cure, but at present there is no established screening programme. It has been shown that targeted education in the primary sector with general practitioners and dentists has had some impact on early referral for oral cancers. This is important as patients presenting with advanced disease have a poorer prognosis.


Tobacco cessation is also an important factor in preventing head and neck cancers. The prevalence of cigarette smoking has fallen by over 20% in men over the last 20 years (Figure 21.1). Aggressive treatment of pre-malignant conditions is important in reducing the incidence of invasive cancer.


image

Figure 21.1 Prevalence of smoking 1974–2002.



Tumour types


The majority (over 90%) of cancers of the head and neck are squamous cell carcinomas (SCC) arising from mucosal cells. They are usually graded into well-, moderate- or poorly-differentiated on the basis of their histological assessment (mitoses, pleomorphism). Poorly-differentiated tumours tend to metastasize to lymph nodes more frequently than well-differentiated lesions. The remainder are made up of small numbers of adenocarcinoma, lymphoma (these are treated by a different team in most institutions), sarcoma, melanoma and various salivary gland tumours (muco-epidermoid, adenoid cystic, acinic tumours). It is essential that a histological diagnosis is confirmed before treatment to ensure the correct management and a specialist head and neck pathologist must be part of the multidisciplinary team.



Presentation


The majority of cases of head and neck cancer present symptomatically. The symptoms therefore depend on the primary site and the adjacent structures that may be involved. This may be a visible lesion in the oral cavity – leucoplakia, erythroplakia or non-healing ulcer – or may relate to a swelling or mass in the oropharynx, hypopharynx or larynx. There may be hoarseness, difficulty swallowing, discomfort or pain on eating, referred aural pain, trismus or cranial nerve palsies. The onset of these symptoms is an indication for urgent referral to a head and neck department. More non-specific symptoms of weight loss, anorexia or generalized discomfort can also be seen in this group of patients.


A common presentation of head and neck cancer is with lymph node metastases in the neck. The histology may be confirmed by FNA (fine needle aspiration) or biopsy. A thorough search for a potential primary tumour is required. However, in a number of patients, this remains occult and treatment must then be planned to cover potential sites of origin.



Investigation


Patients presenting with possible head and neck cancer should be referred urgently to a specialist head and neck oncology team. The work-up requires confirmation of the histological diagnosis and full examination under anaesthetic of the aerodigestive tract for accurate staging and to exclude second primary lesions. Cross-sectional imaging with computed tomography (CT) or magnetic resonance imaging (MRI) with contrast enhancement is also essential for staging purposes detailing anatomical extent of the primary lesion and any nodal involvement. Imaging of the chest with chest x-ray or CT is required to exclude pulmonary metastases or a synchronous lung primary. There may be a synchronous primary in up to 10% of head and neck cancer patients and these are often tobacco related. The incidence of distant metastases is reported between 5 and 30% and the majority is in the lung, although very occasionally bone or liver secondaries are found. The occurrence of metastases correlates with increasing stage of the primary tumour and the number, size and bilaterality of lymph node involvement at presentation. Positron emission tomography (PET) is increasingly used in staging head and neck cancer, and offers possibly exciting opportunities, but its exact role remains to be defined. It offers potential for patients with cervical lymphadenopathy and an occult primary but, perhaps, at present, its main use is assessment following radiotherapy to look for residual or persisting disease.


All head and neck cancer patients should be discussed in a multidisciplinary meeting at the time of diagnosis and staging to determine the optimum treatment. The choice is usually between radical surgery ± postoperative radiotherapy (or chemoradiotherapy) or primary radical radiotherapy (or concurrent chemoradiation) with possible neck dissection for residual disease. The decision is usually determined by the site of the primary tumour, the size of the primary tumour, evidence of lymph node involvement and patients’ co-morbidity or individual preference. Before embarking on any radical treatment options, there are a number of preparatory steps that need to be assessed.



Nutrition


Head and neck cancer patients have many reasons to be malnourished prior to diagnosis of their malignancy. Many have a background of excessive alcohol intake, the tumour may have resulted in impaired swallowing function or caused oral discomfort. The success of any radical treatment is compromised by inadequate nutrition and morbidity is also increased. It is essential that all head and neck cancer patients have assessment by a specialist dietician prior to any treatment. They may require enteral feeding prior to treatment and will certainly need it following surgery. Patients receiving radical radiotherapy will usually have a course of treatment over many weeks and will develop mucositis and dysphagia in the acute phase. Nasogastric tube or percutaneous gastrostomy should be actively considered in all patients, especially those with large treatment fields and are essential for patients being considered for concurrent chemoradiation where the acute toxicity is usually increased. It is also important for the dietetic input to continue regularly throughout the treatment course – patients need to be weighed weekly, outcome data show ongoing weight loss to be a negative prognostic factor – and in the recovery phase following treatment which may last many weeks. Close monitoring should therefore continue during the follow-up period until tube feeding is no longer required and patients have returned to sufficient oral intake and proven maintained weight.



Dentition


Patients receiving radical radiotherapy for head and neck cancers will often have treatment fields involving part or all of the mandible and the salivary glands. Following radiotherapy, these patients are often left with xerostomia. Saliva has a protective role in neutralizing oral acids and reducing dental caries. Tooth decay and dental problems can be increased post-radiotherapy. Patients need to have a full dental assessment prior to radiotherapy. The ideal is for review by a restorative dentist or maxillofacial team to remove teeth if required. Any problem teeth should be removed and, as this typical patient population has often neglected their oral hygiene, many end up with a dental clearance. Dental extractions should be done a minimum of 2 weeks before commencing radiotherapy. Edentulous patients should be reviewed to ensure dentures are well fitting and will not aggravate their radiotherapy reaction by movement.


When taking consent from patients for radiotherapy, they must be counselled about the risks of dental problems following the treatment and, in particular, osteoradionecrosis of the mandible which can develop spontaneously but is more likely after dental procedures, particularly extractions (Figure 21.2). Patients need to be encouraged to use fluoride mouthwash or gel daily and to have regular dental check-ups – and if dental work is considered necessary it should be performed by specialist hospital dental teams in view of the high risk of complications.


image

Figure 21.2 Orthopantomogram (OPT) of mandible showing osteoradionecrosis on right side.



Indications for radiotherapy



Definitive radiotherapy


The chief aim in using radiotherapy in head and neck cancer is organ preservation. In early laryngeal cancer, equivalent cure rates are attainable with radical radiotherapy and laryngectomy, but the former has the clear advantage of normal voice preservation. In some sites, radiotherapy is the only option or preferred option due to the inaccessible nature of the primary, e.g. nasopharyngeal cancer.



Postoperative radiotherapy


The purpose of postoperative radiotherapy is to improve locoregional control. It has recently been estimated that cancer-specific and overall survival at 5 years might be improved by about 10% with postoperative radiotherapy.


There are a number of indications for postoperative radiotherapy (Table 21.1). In some cases, postoperative radiotherapy is mandatory, in other situations the real benefit to the patient is less clear.


Table 21.1 Indications for postoperative radiotherapy






Positive (involved) resection margins


Extracapsular lymph node spread


Close resection margins, i.e. <5   mm


Invasion of soft tissues


≥2 nodes involved


>1 positive nodal group (i.e. level)


Involved node >3   cm in diameter


Vascular invasion


Perineural invasion


Poor differentiation


Stage III/IV


Multicentric primary


Oral cavity/oropharynx tumours with involved nodes at level IV/V


Carcinoma in situ/dysplasia at resection margin/‘field changes’


Guidelines for cervical nodal irradiation in squamous cell carcinoma of the head and neck.


Reproduced with kind permission of Dr M. Henk and the CHART steering committee


Postoperative radiotherapy should ideally commence within 6 weeks of surgery as evidence suggests an inferior outcome if started later than this.



Palliative radiotherapy


As a general rule, radiotherapy should be used with curative intent and with standard curative doses. On occasions, however, patients will not be fit to undergo any form of radical radiotherapy and radiotherapy can provide useful symptom relief.



Radiotherapy planning


Once radiotherapy has been decided as the treatment modality for head and neck patients, there are a number of steps required prior to commencing. Patients need to be informed of all possible side effects (see Toxicity of treatment) and to give consent.



Immobilization


The next step is to consider immobilization. Tumours in the head and neck may be relatively small compared to other anatomical sites and they are also often adjacent to several critical normal structures. It is therefore essential for accurate treatment delivery that patients have good quality reproducible immobilization. In general, this involves an individual shell to cover the head, neck and, sometimes, the shoulders. These shells are commonly either thermoplastic or rigid Perspex and are created specifically for the patient during the planning phase. The patient then has subsequent imaging in the mask. Although the thermoplastic shells sometimes appear more flexible, they can still provide an accurate set-up. Occasionally, stereotactic frames or relocatable devices may be used but these are not usually required for most head and neck patients. Mould room staff who make the shell also require information about the patient’s position (usually supine) and the orientation of the neck. This is important and is determined by the site one intends to irradiate and needs consideration of the intended beam arrangement: an extended neck position would be required for treatment of the parotid bed and middle/inner ear to facilitate the exiting posterior oblique field below the contralateral eye. It is also necessary to consider whether the patient requires a mouth bite or tongue depressor. A mouth bite is used to push the tongue out of the treatment volume, e.g. maxillary antral tumours. A tongue depressor is used to push the tongue into the treatment volume, e.g. oral tongue tumours.


The most important issue of any immobilization device is to know what the reproducibility of set-up is for any particular patient. All centres should know the accuracy of their set-up for a particular device as this is the information required for determining the margin from clinical target volume (CTV) to planning target volume (PTV). In practice, an accuracy of 3–5   mm can be expected with existing devices.



Target volumes



Definitive radiotherapy


When radiotherapy (with or without chemotherapy) is the definitive treatment, a gross tumour volume (GTV) is present and a planning CT scan will allow it to be delineated combined with information from the examination under anaesthesia (EUA), histology and other diagnostic imaging. Help from a specialist radiologist is recommended. The CTV is to account for microscopic spread. Overtly involved nodes should be included in that CTV. Occult lymph node metastases occur in up to 20–30% of the N0 neck patients, so prophylactic irradiation is required for many head and neck tumours and is delineated as a separate CTV. The sites where this is not considered are early glottic or subglottic cancers (T1/T2 disease) (Table 21.2). The likelihood of nodal involvement has been widely studied and it is clear that the probability increases with site of primary, size of primary and differentiation.


Table 21.2 Indications for nodal irradiation by tumour site





















Indications Irradiation
Oral cavity  
T2N0 with well-lateralized primary Levels I and II on the same side
T2N1 with well-lateralized primary Levels I to V on the same side
T2N0 with primary approaching midline, all T3N0 and T4N0 Levels I, II and III bilaterally
All others Levels I to V bilaterally

















Oropharynx  
T2N0 tonsil Levels I and II on the same side
T2N1 tonsil Levels I to V on the same side
T2N0 other sites Levels I, II and III bilaterally
All others Levels I to V bilaterally







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Mar 7, 2016 | Posted by in GENERAL RADIOLOGY | Comments Off on Head and neck cancer – general principles

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Nasopharynx  
Squamous cell carcinoma T1 – T4 N0