Salivary gland sparing in the treatment of head and neck cancer

Radiotherapy is an important component of the multimodality treatment of head and neck cancer. Although an effective treatment for many patients, it can have significant long-term sequelae. In particular, xerostomia – or dry mouth – caused by salivary gland injury is a serious problem suffered by most patients and leads to problems with oral comfort, dental health, speech and swallowing. This article explores the mechanisms behind radiation injury to the major salivary glands, as well as different strategies to minimize and alleviate xerostomia. This includes technical approaches to minimize radiation dose to salivary tissue, such as intensity-modulated radiotherapy and surgical transfer of salivary glands, as well as pharmacologic approaches to stimulate or protect the salivary tissue. The scientific literature will be critically examined to see what works and what strategies have been less effective in attempting to minimize xerostomia in head and neck cancer patients.     

Salivary gland sparing in the treatment of head and neck cancer

Radiotherapy is an important component of the multimodality treatment of head and neck cancer. Although an effective treatment for many patients, it can have significant long-term sequelae. In particular, xerostomia - or dry mouth - caused by salivary gland injury is a serious problem suffered by most patients and leads to problems with oral comfort, dental health, speech and swallowing. This article explores the mechanisms behind radiation injury to the major salivary glands, as well as different strategies to minimize and alleviate xerostomia. This includes technical approaches to minimize radiation dose to salivary tissue, such as intensity-modulated radiotherapy and surgical transfer of salivary glands, as well as pharmacologic approaches to stimulate or protect the salivary tissue. The scientific literature will be critically examined to see what works and what strategies have been less effective in attempting to minimize xerostomia in head and neck cancer patients.     

Does hyperbaric oxygen treatment have the potential to increase salivary flow rate and reduce xerostomia in previously irradiated head and neck cancer patients? A pilot study

Irradiated head and neck cancer survivors treated in the Hyperbaric Oxygen (HBO) Unit, Copenhagen University Hospital, spontaneously reported improvement of radiation-induced dry mouth feeling. The aim of this pilot study was to evaluate salivary flow rate and xerostomia before and after HBO in irradiated head and neck cancer patients. Eighty patients eligible for HBO treatment on the indication of prevention/treatment of osteoradionecrosis or soft tissue radiation injury were consecutively sampled, of whom 45 had hyposalivation (i.e. unstimulated whole saliva (UWS) flow rate <0.1ml/min), and 69 complained of xerostomia. UWS and stimulated whole saliva (SWS) were collected prior to and after 30 sessions of hyperbaric oxygen treatment over 6weeks. Xerostomia was assessed using the visual analogue scale (VAS). Each HBO session involved compression to 243kPa (2.4 ATA) for 90min while breathing 100% oxygen from a facemask or hood. There was a significant decrease in xerostomia (p<0.001) and slight increase in UWS (p<0.001) and SWS (p<0.001) flow rate, from before HBO as compared to after. Twenty-five of 45 patients with hyposalivation achieved an increased UWS flow rate after HBO. In 12 of these, the flow rates increased to levels not associated with hyposalivation. Patient-assessed improvement of xerostomia and slightly increased UWS and SWS secretion after HBO treatment suggest that HBO may have a beneficial effect on radiation-induced salivary gland damage.     

The prevention and treatment of radiotherapy - induced xerostomia

Efforts to reduce the severity of postradiotherapy xerostomia include the use of salivary substitutes to gain symptomatic relief, salivary gland stimulants, agents delivered to protect the glands during radiotherapy (RT), and physical means to partially spare the major salivary glands from RT while adequately irradiating tumor targets. These means include advanced RT treatment planning and salivary tissue transfer to nonirradiated areas. The relative potential gain from each of these strategies is discussed in this article. The combination of partial salivary gland sparing and radiation protectors/stimulants may provide additive or synergistic gains in reducing the severity of xerostomia.     

Upfront submandibular salivary gland transfer in pharyngeal cancers

Head and neck irradiation results in salivary dysfunction and subsequent xerostomia. Twenty two patients with squamous cancer of oropharynx or hypopharynx underwent contralateral submandibular salivary gland transfer (SMSGT) to submental triangle to shield it from subsequent radiotherapy. Resting salivary outputs of transferred and untransferred gland (control) were measured before and after SMSGT and following radiotherapy, by cannulating individual submandibular duct. They were compared by paired samples t-test. Following radiation therapy transferred gland retained 73% and untransferred gland (control) retained 27% of baseline salivary output. This significant difference in post-radiation salivary outputs suggests preservation of function of transferred salivary gland.     

Management of xerostomia related to radiotherapy for head and neck cancer

Xerostomia is a permanent and devastating sequela of head and neck irradiation, and its consequences are numerous. Pharmaceutical therapy attempts to preserve or salvage salivary gland function through systemic administration of various protective compounds, most commonly amifostine (Ethyol) or pilocarpine. When these agents are ineffective or the side effects too bothersome, patients often resort to palliative care, for example, with tap water, saline, bicarbonate solutions, mouthwashes, or saliva substitutes. A promising surgical option is the Seikaly-Jha procedure, a method of preserving a single submandibular gland by surgically transferring it to the submental space before radiotherapy. Improved radiation techniques, including intensity-modulated radiotherapy and tomotherapy, allow more selective delivery of radiation to defined targets in the head and neck, preserving normal tissue and the salivary glands. Acupuncture may be another option for patients with xerostomia. All of these therapies need to be further studied to establish the most effective protocol to present to patients before radiotherapy has begun.     

Intensity-modulated radiotherapy: Is xerostomia still prevalent?

Conformal radiation with intensity-modulated radiotherapy (IMRT) is a technique that potentially can minimize the dose to salivary glands and thereby decrease the incidence of xerostomia. Precise target determination and delineation is most important when using salivary gland-sparing techniques of IMRT. Reduction of xerostomia can be achieved by sparing the salivary glands on the uninvolved oral cavity and keeping the mean parotid gland dose of less than 26 to 30 Gy as a planning criterion if the treatment of disease is not compromised and parotid function preservation is desired.     

Radiation-induced xerostomia in patients with head and neck cancer: a literature review

A dry mouth or xerostomia is one of the most common complications during and after radiotherapy for head and neck cancer, because irreparable damage is caused to the salivary glands, which are included in the radiation fields. Xerostomia not only significantly impairs the quality of life of potentially cured cancer patients, it may also lead to severe and long-term oral disorders. Because management of xerostomia is rarely effective, prevention is paramount. Several strategies have been developed to avoid radiation-induced salivary dysfunction without compromising definitive oncologic treatment. These include salivary gland-sparing radiation techniques, such as 3-dimensional conformal or intensity-modulated radiotherapy, concomitant cytoprotectants, and surgical salivary gland transfer. However, these preventive approaches are not applicable to all patients, and comprehensive scientific research that incorporates new biological insights is warranted to optimize the therapeutic index of radiotherapy for head and neck cancer.     

唾液腺放射性损伤及其防护

放射治疗在头颈肿瘤的地位已得到广泛认同,但放疗并发症不容忽视,最常见的是放射性口干。其主要机制为放射诱导的唾液腺损伤,早期和晚期损伤的机制不同。目前对唾液腺放射防护的研究主要集中在放射防护剂、放射技术、基因转移技术等多个方面。     

Long-term effects of radiotherapy on taste and salivary function in man

The long-term effects of radiotherapy on taste and salivary function were studied in 13 patients treated by radiation 1–7 years previously for tumors of the head and neck. Taste function was quantitatively evaluated using a standard forced choice, three-stimulus-drop technique for the determination of detection and recognition thresholds and a forced-scaling technique for the determination of taste intensity responsiveness. Parotid salivary function was quantitatively evaluated by determination of flow rate and protein secretion rate. Nine of the 13 patients studied (69%) had measurable taste loss; every patient who had radiotherapy including the parotid glands had measurable salivary dysfunction. Our results demonstrate that curative courses of radiotherapy for tumours of the head and neck may result in long-term changes in taste and salivary function. From the present study, the maximum tolerance doses resulting in a 50% complication rate 5 years after treatment (TD 50/5) are estimated to be 40–65 Gy for xerostomia and 50–65 Gy for taste loss. Therefore, in a standard treatment regimen for tumors of the head and neck, with curative intent, gustatory and salivary gland tissues frequently sustain maximum tolerance injury.     

颌下腺移位术预防鼻咽癌放疗后口干燥症的长期效果

目的:评价颌下腺移位术预防鼻咽癌放疗后口干燥症的长期效果.方法:70例鼻咽癌患者随机分为试验组36例和对照组34例.试验组在行常规放疗前将颌下腺移位至颏下区,放疗时颏下区设置挡块.~(99)T_c核素扫描检测放疗前后颌下腺功能,测定放疗前后唾液分泌量,放疗后60个月进行口干程度问卷调查,统计5年生存率.结果:放疗后60个月:试验组颌下腺摄取、分泌功能均明显较对照组好,两者之间有显著性差异,P值分别为0.000和0.000;试验组和对照组唾液量的平均值分别为1.65g和0.73g(P=0.000);试验组中度至重度口干燥症的发生率亦显著低于对照组(12.9% vs 78.6%,P=0.000);试验组和对照组的5年生存率分别为86.1%和82.4%,两者之间无显著性差异(P=0.67).结论:颌下腺移位术不影响鼻咽癌远期疗效,预防鼻咽癌放疗后口干燥症的长期效果良好,可改善鼻咽癌患者放疗后的生存质量.     

颌下腺移位预防鼻咽癌放疗后口干燥症安全性评价的临床对照研究

目的:评价颌下腺移位术预防鼻咽癌放疗后口干燥症的安全性.方法:选择符合入选标准的鼻咽癌患者70例,分为试验组36例和对照组34例.试验组放疗前将颌下腺移位至颏下区,术后接受常规放疗,放疗时颏下区设置挡块.对照组直接行常规放疗.比较试验组和对照组的口干程度、5年颈淋巴结复发率及5年生存率.结果:放疗后60个月,对照组中度至重度口干燥症的发生率高于试验组(78.6% vs 12.9%),差异有统计学意义,P=0.000.试验组和对照组颈部淋巴结复发率分别为11.1%(4/36)和11.8%(4/34) ,两者之间差异无统计学意义,P=0.93.复发部位均在Ⅱ区.5年生存率试验组为86.1%(31/36),对照组82.4%(28/34),两者之间差异无统计学意义,P=0.67.结论:颌下腺移位术可预防鼻咽癌放疗后口干燥症,改善鼻咽癌患者放疗后的生存质量.颌下腺移位术预防鼻咽癌放疗后口干燥症不影响鼻咽癌远期疗效且安全可行.     

唾液腺放射性损伤及其防护

放射治疗在头颈肿瘤的地位已得到广泛认同,但放疗并发症不容忽视,最常见的是放射性口干。其主要机制为放射诱导的唾液腺损伤,早期和晚期损伤的机制不同。目前对唾液腺放射防护的研究主要集中在放射防护剂、放射技术、基因转移技术等多个方面。     

MR涎管成像对鼻咽癌放疗患者涎腺功能

目的 探究MR涎管成像用于评价鼻咽癌调强放疗患者涎腺功能的可行性。方法在放疗前、放疗结束时分别采集32例鼻咽癌患者腮腺和下颌下腺在静息及酸刺激下MR涎管成像图像,同时对涎管可见性及放射性口干进行评价,Spearman相关分析用于急性放射性口干评级与MR涎管成像评分关系的研究。结果 放疗后涎腺导管可见性、MR涎管成像评分均较放疗前降低(P=0.000、0.000)。非重度口干与重度口干相比,腮腺导管静息与刺激下MR涎管成像评分差值不同(P=0.009),下颌下腺导管静息与刺激下MR涎管成像评分差值也不同(P=0.005);腮腺导管静息与刺激下,以及下颌下腺导管静息与刺激下得分均相近(P=0.881、0.305、0.327、0.229)。Spearman相关分析显示急性口干与腮腺导管静息与刺激得分差值,以及下颌下腺导管静息与刺激得分差值均呈负相关(R=－0.472,P=0.006;R=－0.482,P=0.005)。结论 MR涎管成像评分与口干具有相关性,MR涎管成像可用于评价鼻咽癌放疗患者的涎腺功能。     

Radiation-related damage to dentition

Because of typical tissue reactions to ionising radiation, radiotherapy in the head and neck region usually results in complex oral complications affecting the salivary glands, oral mucosa, bone, masticatory musculature, and dentition. When the oral cavity and salivary glands are exposed to high doses of radiation, clinical consequences including hyposalivation, mucositis, taste loss, trismus, and osteoradionecrosis should be regarded as the most common side-effects. Mucositis and taste loss are reversible consequences, usually subsiding early post-irradiation, whereas hyposalivation is commonly irreversible. Additionally, the risk of rampant tooth decay with its sudden onset and osteonecrosis is a lifelong threat. Thus, early, active participation of the dental profession in the development of preventive and therapeutic strategies, and in the education and rehabilitation of patients is paramount in consideration of quality-of-life issues during and after radiotherapy. This Review focuses on the multifactorial causes of so-called radiation caries and presents possible treatment strategies to avoid loss of dentition.     

Prevention of radiation induced xerostomia by surgical transfer of submandibular salivary gland into the submental space.

BACKGROUND AND PURPOSE: Xerostomia is a significant morbidity of radiation treatment in the management of head and neck cancers. We hypothesized that the surgical transfer of one submandibular salivary gland to the submental space, where it can be shielded from radiation treatment (XRT), would prevent xerostomia. MATERIALS AND METHODS: We conducted a prospective Phase II clinical trial and the patients were followed clinically with salivary flow studies and the University of Washington Quality of Life questionnaire. RESULTS: We report the results on 76 evaluable patients. The salivary gland transfer was done in 60 patients. Nine patients (of 60) did not have postoperative XRT and in eight patients (of 60) the transferred gland was not shielded from XRT due to proximity of disease. The median follow up is 14 months. Of the 43 patients with the salivary gland transfer and post-operative XRT with protection of the transferred gland, 81% have none or minimal xerostomia, and 19% developed moderate to severe xerostomia. Three patients (6.9%) developed local recurrence, five patients (11.6%) developed distant metastases and five patients (11.6%) have died. There were no complications attributed to the surgical procedure. CONCLUSION: Surgical transfer of a submandibular salivary gland to the submental space preserves its function and prevents the development of radiation induced xerostomia.     

颌下腺移位术预防鼻咽癌放疗后口干燥症的近期效果

背景与目的:口干燥症是鼻咽癌放疗后最常见的后遗症之一,它严重影响患者放疗后的生存质量。本研究旨在探讨颌下腺移位术预防鼻咽癌放疗后口干燥症的临床效果。方法:共选择70例病例进行前瞻性非随机临床对照研究。试验组选择符合入选标准的鼻咽癌患者36例,在放疗前将颌下腺移位至颏下区,术后接受常规放疗,放疗时颏下区设置挡块。观察放疗中急性口腔粘膜反应,应用锝-99核素扫描检测放疗前后颌下腺功能的变化,测定放疗前后唾液分泌量的变化,放疗后3个月进行口干程度问卷调查。对照组(34例)不行颌下腺移位术,其余处理方法同试验组。将试验组的术侧与非术侧以及试验组与对照组的上述观察指标进行比较。结果:试验组急性口腔粘膜反应明显轻于对照组(P=0.007)。试验组放疗后3个月移位术侧颌下腺摄取、排泌功能均明显较未移位术侧者好,两者之间有非常显著性差异(P值分别为0.001和0.000);试验组颌下腺摄取、排泌功能均明显较对照组者好,两者之间有非常显著性差异(P值分别为0.004和0.000)。试验组放疗后唾液分泌量的平均值为1.41g,而对照组放疗后唾液分泌量平均值为0.71g。对照组76.5%的患者有中度至重度的口干燥症,试验组仅13.9%的患者有中度至重度的口干燥症,两者之间有非常显著性差异(P=0.000)。结论:颌下腺移位     

Dose and volume impact on radiation-induced xerostomia

Radiation-induced xerostomia consists in the chronic dryness of the mouth caused by parotid gland irradiation. Parotid glands produce approximately 60% of saliva while the rest is secreted by submandibular and accessory salivary glands. Methods of measuring the salivary output are essentially represented by 99mTc-pertechnate scintigraphy or simpler albeit less accurate methods in stimulated or unstimulated saliva. There are subjective and objective criteria of classification and grading of the secretion of saliva. Radiation-induced xerostomia, namely the residual salivary gland function is evidently associated with the mean dose absorbed. The salivary output tends to decrease after the end of radiotherapy. The partial dose-volume is substantially correlated with the mean dose to the whole gland. As for ipsilateral irradiation for head and neck cancer, conformal RT or IMRT allow to spare the contralateral parotid gland without increasing the risk of contralateral nodal recurrences. The monitoring system of late toxicity used by the authors is presented.     

Scintigraphy in prediction of the salivary gland function after gland-sparing intensity modulated radiation therapy for head and neck cancer

BACKGROUND AND PURPOSE: To evaluate salivary gland scintigraphy in prediction of salivary flow following radiation therapy. PATIENTS AND METHODS: Twenty patients diagnosed with head and neck cancer were treated with intensity modulated radiation therapy with an intention to spare the salivary gland function. The total quantitative saliva secretion was measured prior to and 6 and 12 months after therapy, and the function of the major salivary glands was monitored using Tc-99m-pertechnetate scintigraphy. Two models were designed for prediction of the post-treatment salivary flow: an average model, based on the average proportions of saliva produced by each of the four major glands in healthy subjects, and an individual model, based on saliva produced by each gland as measured by scintigraphy prior to therapy. These models were compared with volume-based (Lyman) normal tissue complication probability models using two published sets of model parameters. RESULTS: The D(50) for the parotid and the submandibular gland function assessed at 6 and 12 months after radiotherapy was approximately 39Gy. The scintigraphy-based individual model predicted well the measured post-treatment saliva flow rates. The correlation coefficient between the predicted stimulated and the measured saliva flow rate was 0.77 (p<0.0001) at 6 months and 0.55 (p=0.034) at 12 months after completion of radiotherapy. The relative changes in unstimulated and stimulated salivary flow rates showed similar dependency on the cumulative radiation dose. CONCLUSIONS: Salivary gland function assessed by scintigraphy prior to radiotherapy is useful in prediction of the residual salivary flow after radiotherapy.