氨磷汀在长期照射诱导引起口腔干燥中的?;ぷ饔米凼?美国2019

上传日期:2019-04-25 浏览次数:679次

本文是来自美国州立大学Sung Jun Ma, Charlotte I Rivers, Lucas M Serra, Anurag K Singh的研究成果。


AbstractXerostomia, or dry mouth, is a significant problem affecting quality of life in patients treated with radiation therapy for head and neck cancer. Strategies for reduction of xerostomia burden vary widely, with options including: sialagogue medications, saliva substitutes, acupuncture, vitamins, hyperbaric oxygen, submandibular gland transfer, and acupuncture or associated treatments. In this review, we sought to evaluate long-term outcomes of patients treated with various interventions for radiation-induced xerostomia. A literature search was performed using the terms “xerostomia” and “radiation” or “radiotherapy”; all prospective clinical trials were evaluated, and only studies that reported 1 year follow up were included. The search results yielded 2193 studies, 1977 of which were in English. Of those, 304 were clinical trials or clinical studies. After abstract review, 23 trials were included in the review evaluating the following treatment modalities: pilocarpine (three); cevimeline (one); amifostine (eleven); submandibular gland transfer (five); acupuncture like transcutaneous electrical nerve stimulation (ALTENS) (one); hyperbaric oxygen (one); and acupuncture (one). Pilocarpine, cevimeline, and amifostine have been shown in some studies to improve xerostomia outcomes, at the cost of toxicity. ALTENS has similar efficacy with fewer side effects. Submandibular gland transfer is effective but requires an elective surgery, and thus may not always be appropriate or practical. The use of intensity-modulated radiation therapy, in addition to dose deescalation in select patients, may result in fewer patients with late xerostomia, reducing the need for additional interventions.

口干是影响头颈癌放射治疗患者生活质量的一个重要问题。减少口干负担的策略各不相同,可选择包括:唾液替代品、针灸、维生素、高压氧、颌下腺转移和针灸或相关治疗。在这篇综述中,我们试图评估接受各种辐射性干燥症干预治疗的患者的长期预后。使用术语“干燥症”和“放射疗法”进行文献检索;评估所有前瞻性临床试验,仅包括报告1年随访的研究。搜索结果显示有2193项研究,其中1977年的研究是英文的。其中,304项是临床试验或临床研究。摘要综述后,23个试验被纳入综述,评估以下治疗方式:毛果芸香碱(3个);西维莫林(1个);氨磷?。?1个);颌下腺转移(5个);针刺样经皮神经电刺激(Altens)(1个);高压氧(1个);和针刺(1个)。一些研究显示,匹罗卡品、西维莫林和氨磷汀能改善干燥症的预后。针刺样经皮神经电刺激的疗效相似,副作用较少。颌下腺移植是有效的,但需要选择性手术,因此可能并不总是合适或实用的。使用调强放射治疗,除了在选定的患者中进行剂量去烫伤外,可能会减少晚期干骨病患者的数量,减少对额外干预的需要。

Although there have been prior reviews on the management of radiotherapy-induced xerostomia, to our knowledge there has been no review of the current literature with a focus on late xerostomia following radiotherapy for head and neck cancer. We found a very heterogeneous group of studies in this review, with many different modalities, doses, routes of administration, timing with respect to treatment, and differing quality of life (QOL) endpoints as well as different objective saliva measurements. In most of the studies reviewed above, amifostine appears to be beneficial in reducing the risk of long term xerostomia, although it likely requires IV administration. Severely limiting clinical utilization, however, toxicity was noted in close to half of the patients treated. Similarly toxicity limits the clinical utilization of pilocarpine and cevimeline, which have been shown to improve xerostomia, with treatment related adverse events exceeding 91.4% (20.4% grade 3) with cevimeline. In contrast, ALTENS treatment was shown to be as effective as pilocarpine, with fewer adverse events (20.8% in ALTENS group vs 61.6% in pilocarpine group). At 15 mo, the treatment response rate was significantly higher in the ALTENS group. ALTENS represents a non-invasive, well tolerated option for treatment of late xerostomia. However, ALTENS devices are not widely available and when offered in a clinical setting, require patients to travel to the clinic twice weekly for 12 wk. Both of these issues limit availability. To address this issue, Iovoli et al have described a case report of excellent improvement in dry mouth with home use of a new, cheap, commercially available device. Submandibular gland transfer has shown promise in several studies as mentioned above. The use of salivary gland transfer in select patients appears to be effective with regard to xerostomia prevention. Additionally, none of the studies evaluated here reported complications from surgery. However, the use of this procedure is somewhat limited based on several factors including patient selection criteria (for example, it would not be feasible in patients with bilateral positive neck nodes), experience of each surgeon and willingness to perform the procedure, as well as time constraints and potential delay of definitive treatment for an elective procedure. With the advancement of radiation delivery techniques, the use of IMRT has been shown to reduce dose to selected salivary glands, therefore sparing salivary function. It is generally thought that damage to major salivary glands (submandibular and parotid) is the major cause of xerostomia following radiation therapy, as evaluated with MRI, CT, and ultrasound. Pacholke et al retrospectively reviewed 210 patients with xerostomia at least one year following completion of radiation therapy, as measured by the University of Michigan xerostomia QOL score. Higher xerostomia scores were associated with higher salivary gland dose. On multivariate analysis, radiation technique was an independent predictor of xerostomia, favoring IMRT. The PARSPORT trial was a randomized phase III randomized controlled trial that assigned patients with pharyngeal squamous cell carcinoma to either conventional radiotherapy or parotid-sparing IMRT, and found a significant reduction in xerostomia in the IMRT group. In addition to IMRT, the use of intensity modulated proton beam therapy (IMPT) has also been studied in a 150 patient case-matched analysis comparing IMPT to IMRT. With respect to xerostomia, the authors found improved patient-reported symptoms at 3 mo, but no difference at 1 year. In many cases, however, complete sparing of the parotid or submandibular glands is not possible due to proximity of primary tumor or grossly involved lymph nodes. Recently, there is new evidence that sparing even a portion of the parotid gland may be helpful in preventing xerostomia. Parotid stem cells are thought to be capable of regenerating salivary function, and are located in a concentrated area in the parotid gland around the main salivary ducts, as demonstrated in a study in rats. In this same study, the  uthors identified a volume in the human parotid gland posterior to the mandible that was most associated with saliva production one year following radiation therapy, and demonstrated that it is possible to spare this area in some patients where sparing the entire parotid is not feasible. Because of the increasing incidence of HPV positive head and neck cancer, there has been interest in de-escalating therapy for this subset of patients. By reducing the total radiation dose, xerostomia may become less prevalent in this population, thus reducing the need for alternative treatment of salivary dysfunction. While pilocarpine, cevimeline and amifostine have been shown to improve late xerostomia outcomes, these treatments often cause side effects that are not tolerable for patients. ALTENS represents a less toxic alternative therapy for prevention of late xerostomia, but has not been widely available until recently. Similarly, submandibular gland transfer is effective, but may not be appropriate for all patients. Salivary gland sparing with improved radiation techniques (IMRT)—in particular sparing of parotid stem cells—is a practical way to reduce late salivary dysfunction. As IMRT becomes more widely available, in conjunction with potential dose deescalation, the need for alternative xerostomia treatments may become less relevant. 

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