Elsevier

The Lancet Oncology

Volume 11, Issue 1, January 2010, Pages 85-91
The Lancet Oncology

Review
Evidence-based organ-sparing radiotherapy in head and neck cancer

https://doi.org/10.1016/S1470-2045(09)70231-1Get rights and content

Summary

Intensification of radiotherapy treatment for locally advanced head and neck cancer by use of altered fractionation schedules or concomitant chemotherapy has resulted in substantially improved locoregional control and survival. However, these improvements have come at the cost of increased acute, and late, toxic effects. The application of technological advances, such as intensity-modulated radiotherapy, is expected to further improve the therapeutic index of radiotherapy for head and neck cancer, by limiting toxicity and possibly by increasing locoregional control. However, the organ-sparing potential of such highly conformal radiotherapy techniques relies heavily on the appropriate selection and accurate delineation of the crucial organs at risk, with the application of rigorous dose constraints during planning. Because xerostomia and dysphagia are the main causes of decreased quality of life after radiotherapy for head and neck cancer, the prevention of these two complications will form the focus of this review.

Introduction

Head and neck cancer (HNC) is a common disease, representing about 6% of all malignancies and yearly accounting for an estimated 47 560 new cases in the USA alone and at least 500 000 worldwide.1 Treatment for HNC is highly complex, not only because of the variety of disease subsites, but also because of the intricate anatomy, with normal and tumoral structures often in close proximity, and the importance of preserving organ function. Although radiotherapy and surgery remain the two main treatment options, systemic therapy has recently become an integral part of multidisciplinary treatment.2, 3, 4, 5 Choice of treatment modality depends on patient factors, primary site, clinical stage, and resectability of the tumour.

About two-thirds of patients are diagnosed with locoregionally advanced disease, the management of which remains a clinical challenge.2 Intensification of radiotherapy treatment for advanced HNC, using altered fractionation schedules or concomitant chemotherapy, has resulted in significantly improved locoregional control and survival.5, 6, 7 However, these improvements come at the cost of increased toxicity.7, 8 Currently, no further treatment intensification seems possible, because there are no effective techniques to prevent serious late complications.9

The introduction of conformal radiotherapy with three-dimensional (3D) treatment planning on computed tomography (CT) scans signified the first major improvement over conventional two-dimensional (2D) radiotherapy, where the treatment portals are based on a radiographic simulation film. By use of intensity-modulated radiotherapy (IMRT), high-dose areas can be sculpted around the target volumes, with steep dose fall-off immediately outside these regions, thus allowing even more conformal radiation dose delivery (figure). Usually, five to seven non-opposing, coplanar beams are combined to produce an optimised dose distribution—ie, one that ensures target coverage by the prescribed radiation dose while reducing doses to the organs at risk. The expedient use of IMRT evidently decreases toxicity and can increase locoregional control via dose-escalation.10

Organs at risk in the head and neck region include the spinal cord, brainstem, salivary glands, swallowing structures, and mandible. For nasopharyngeal cancer, the optic nerves, chiasm, and temporal lobes of the brain are also at risk. Exceeding the tolerances of these structures can lead to cord or brainstem dysfunction, xerostomia, dysphagia, osteoradionecrosis, blindness, or brain necrosis. Thus, organ-sparing radiotherapy needs appropriate selection and accurate delineation of many avoidance structures. However, defining dose–response curves, which allow the definition of reliable radiation-dose constraints below which a complication is unlikely to occur, is a complicated process. Most available data are based on retrospective analyses, which often insufficiently correct for confounding clinical factors, and which use different endpoints to define a complication in disparate patient populations. Because of these drawbacks, these analyses do not allow definitive conclusions.

Moreover, there is increasing concern that inappropriate sparing of normal tissue, perhaps due to an overemphasis in the recent published work on toxicity prevention rather than on tumour eradication, could lead to avoidable marginal recurrences.11, 12, 13 Shielding clinically negative, at-risk regions from elective radiation to prevent damage to healthy tissue should be approached with extreme care: adequate selection of patients is of crucial importance and locoregional recurrences need to be carefully assessed and reported.

The aim of this review is to present the current evidence behind organ-sparing radiotherapy techniques. Because it is clear that both xerostomia and dysphagia are the main causes of decreased quality of life after radiotherapy for HNC, the prevention of these two complications will form the focus of this review.14

Section snippets

Xerostomia

Xerostomia is thought to be the most prominent complication after radiotherapy for HNC. Radiation-induced damage to the salivary glands changes the volume, consistency, and pH of secreted saliva from thin secretions with a neutral pH to thick and tenacious secretions with increased acidity.15 Patients have oral discomfort or pain, find it difficult to speak, chew, or swallow, and run an increased risk of dental caries or oral infection. Ultimately, these problems can lead to decreased

Dysphagia

Swallowing dysfunction after radiotherapy is correlated with compromised quality of life, and can lead to life-threatening complications, such as aspiration pneumonia.57, 58 Because the risk of radiation-induced dysphagia is associated with the use of accelerated fractionation schedules and, especially, concomitant chemotherapy, its incidence has considerably increased in recent years.59, 60, 61 Concomitant chemotherapy in particular is associated with a high incidence of early and late

Conclusion

In patients with HNC who are treated with IMRT or other highly conformal radiotherapy techniques, it is important that all relevant normal structures at risk are delineated to predict potential complications and that the available radiation-dose constraints are respected. Currently, sparing the contralateral parotid gland should be attempted in selected patients, by holding a mean dose threshold of 26 Gy. Sparing of the ipsilateral parotid gland has low priority, especially if level II

Search strategy and selection criteria

References for this review were identified by searches of Medline and PubMed using each organ at risk (eg, “parotid gland”, “submandibular gland”, etc) or complication (eg, “xerostomia”, “dysphagia”, etc), as well as “radiotherapy” and “head and neck cancer” as search terms. The reference lists from all retrieved articles were also assessed for relevant publications. Only papers published in English between January, 1990, and June, 2009, were included.

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