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.
ReviewEvidence-based organ-sparing radiotherapy in head and neck cancer
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 (75)
- et al.
Head and neck cancer
Lancet
(2008) - et al.
Reassessment of the role of induction chemotherapy for head and neck cancer
Lancet Oncol
(2006) - et al.
Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: three meta-analyses of updated individual data. MACH-NC Collaborative Group. Meta-Analysis of Chemotherapy on Head and Neck Cancer
Lancet
(2000) - et al.
Hyperfractionated or accelerated radiotherapy in head and neck cancer: a meta-analysis
Lancet
(2006) - et al.
Impact of adding concomitant chemotherapy to hyperfractionated accelerated radiotherapy for advanced head and neck squamous cell carcinoma
Int J Radiat Oncol Biol Phys
(2009) Toxicity in head and neck cancer: a review of trends and issues
Int J Radiat Oncol Biol Phys
(2000)- et al.
Evidence behind use of intensity-modulated radiotherapy: a systematic review of comparative clinical studies
Lancet Oncol
(2008) Beware the swing and a miss: baseball precautions for conformal radiotherapy
Int J Radiat Oncol Biol Phys
(2008)- et al.
Recurrence in region of spared parotid gland after definitive intensity-modulated radiotherapy for head and neck cancer
Int J Radiat Oncol Biol Phys
(2008) - et al.
Radiotherapy for head and neck cancer—is the “next level” down?
Int J Radiat Oncol Biol Phys
(2009)
Impact of radiation-induced xerostomia on quality of life after primary radiotherapy among patients with head and neck cancer
Int J Radiat Oncol Biol Phys
Preservation of parotid function after external beam irradiation in head and neck cancer patients: a feasibility study using 3-dimensional treatment planning
Int J Radiat Oncol Biol Phys
Parotid gland sparing in patients undergoing bilateral head and neck irradiation: techniques and early results
Int J Radiat Oncol Biol Phys
The impact of dose on parotid salivary recovery in head and neck cancer patients treated with radiation therapy
Int J Radiat Oncol Biol Phys
Two-year longitudinal study of parotid salivary flow rates in head and neck cancer patients receiving unilateral neck parotid-sparing radiotherapy treatment
Oral Oncol
A prospective study of salivary function sparing in patients with head-and-neck cancers receiving intensity-modulated or three-dimensional radiation therapy: initial results
Int J Radiat Oncol Biol Phys
Xerostomia and its predictors following parotid-sparing irradiation of head-and-neck cancer
Int J Radiat Oncol Biol Phys
Preserved salivary output and xerostomia-related quality of life in head and neck cancer patients receiving parotid-sparing radiotherapy
Oral Oncol
Preservation of parotid function with uncomplicated conformal radiotherapy
Radiother Oncol
Evaluation of salivary gland function after treatment of head-and-neck tumors with intensity-modulated radiotherapy by quantitative pertechnetate scintigraphy
Int J Radiat Oncol Biol Phys
Preservation of oral health-related quality of life and salivary flow rates after inverse-planned intensity-modulated radiotherapy (IMRT) for head-and-neck cancer
Int J Radiat Oncol Biol Phys
Intensity modulated radiotherapy for head and neck cancer: evidence for preserved salivary gland function
Radiother Oncol
Dose-volume modelling of salivary function in patients with head-and-neck cancer receiving radiotherapy
Int J Radiat Oncol Biol Phys
Intensity-modulated radiotherapy significantly reduces xerostomia compared with conventional radiotherapy
Int J Radiat Oncol Biol Phys
Xerostomia and quality of life after intensity-modulated radiotherapy vs conventional radiotherapy for early-stage nasopharyngeal carcinoma: initial report on a randomized controlled clinical trial
Int J Radiat Oncol Biol Phys
Dose, volume and function relationships in parotid salivary glands following conformal and intensity-modulated irradiation of head and neck cancer
Int J Radiat Oncol Biol Phys
Dose-response relationships within the parotid gland after radiotherapy for head and neck cancer
Radiother Oncol
Quality of life after parotid-sparing IMRT for head-and-neck cancer: a prospective longitudinal study
Int J Radiat Oncol Biol Phys
Matched case-control study of quality of life and xerostomia after intensity-modulated radiotherapy or standard radiotherapy for head-and-neck cancer: initial report
Int J Radiat Oncol Biol Phys
Grading xerostomia by physicians or by patients after intensity-modulated radiotherapy of head-and-neck cancer
Int J Radiat Oncol Biol Phys
How should we measure and report radiotherapy-induced xerostomia?
Semin Radiat Oncol
Patterns of loco-regional recurrence following parotid-sparing conformal and segmental intensity-modulated radiotherapy for head and neck cancer
Int J Radiat Oncol Biol Phys
Recurrences after conformal parotid-sparing radiotherapy for head and neck cancer
Radiother Oncol
Predictive factors of local-regional recurrences following parotid sparing intensity modulated or 3D conformal radiotherapy for head and neck cancer
Radiother Oncol
Recurrences near base of skull after IMRT for head and neck cancer: implications for target delineation in high neck and for parotid gland sparing
Int J Radiation Oncology Biol Phys
Level II lymph nodes and radiation-induced xerostomia
Int J Radiat Oncol Biol Phys
CT-based delineation of lymph node levels and related CTVs in the node-negative neck: DAHANCA, EORTC, GORTEC, NCIC, RTOG consensus guidelines
Radiother Oncol
Cited by (126)
Dosimetric and radiobiological analyses of a de-escalation strategy for elective nodal regions in human papillomavirus-associated oropharyngeal cancer
2023, Technical Innovations and Patient Support in Radiation OncologyDevelopment and Clinical Implementation of an Automated Virtual Integrative Planner for Radiation Therapy of Head and Neck Cancer
2023, Advances in Radiation OncologyCitation Excerpt :Radiation therapy (RT) is a cornerstone of head and neck (HN) cancer treatment. Intensity modulated radiation therapy (IMRT) has improved treatment accuracy and reduced RT-associated morbidity.1-10 HN IMRT manual optimization is resource-intensive and variable, with heavy reliance upon physician and facility expertise.11-16
Radiomics and radiogenomics in head and neck squamous cell carcinoma: Potential contribution to patient management and challenges
2021, Cancer Treatment ReviewsCitation Excerpt :Table 5 summarizes radiomic publications addressing prediction of CRT-related toxicity in HNSCC patients [79–84]. Xerostomia is a frequent side effect of radiotherapy with a non-negligible impact on quality of life and few options for management in clinical practice [85,86]. The bulk of radiomic studies [79–81] have focused on analyzing features extracted from the salivary glands to predict this sequela.
A randomized phase III trial for alleviating radiation-induced xerostomia with chewing gum
2020, Radiotherapy and Oncology