Spijkervet Frederik K L, Brennan Michael T, Peterson Douglas E, Witjes Max J H, Vissink Arjan
Department of Oral & Maxillofacial Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Department of Oral Medicine, Carolinas Medical Center, Charlotte, NC.
J Natl Cancer Inst Monogr. 2019 Aug 1;2019(53). doi: 10.1093/jncimonographs/lgz006.
The deleterious effects of head and neck radiation on bone, with osteoradionecrosis (ORN) as the major disabling side effect of head and neck cancer treatment, are difficult to prevent and hard to treat. This review focuses on the current state of the science regarding the pathobiology, clinical impact, and management of ORN. With regard to the pathobiology underlying ORN, it is not yet confirmed whether the current radiation schedules by 3-dimensional conformal radiotherapy and intensity modified radiotherapy result in an unchanged, decreased, or increased risk of developing ORN when compared with conventional radiation treatment, the main risk factor being the total radiation dose delivered on any clinically significant surface of the mandible. With regard to the prevention of ORN, a thorough, early pre-irradiation dental assessment is still considered the first step to reduce the hazard of developing ORN post-radiotherapy, and hyperbaric oxygen (HBO) treatment reduces the risk of developing ORN in case of dental surgery in an irradiated field. With regard to the treatment of ORN, the focus is bidirectional: elimination of the necrotic bone and improving the vascularity of the normal tissues that were included in the radiation portal. The cure rate of limited ORN by conservative therapy is approximately 50%, and the cure rate of surgical approaches when conservative therapy has failed is approximately 40%. Whether it is effective to support conservative or surgical treatment with HBO as an adjuvant is not set. HBO treatment is shown to increase the vascularity of hard and soft tissues and has been reported to be beneficial in selected cases. However, in randomized clinical trials comparing the preventive effect of HBO on developing ORN with, eg, antibiotic coverage in patients needing dental surgery, the preventive effect of HBO was not shown to surpass that of a more conservative approach. More recently, pharmacologic management was introduced in the treatment of ORN with success, but its efficacy has to be confirmed in randomized clinical trials. The major problem of performing well-designed randomized clinical trials in ORN is having access to large numbers of patients with well-defined, comparable cases of ORN. Because many institutions will not have large numbers of such ORN cases, national and international scientific societies must be approached to join multicenter trials. Fortunately, the interest of funding organizations and the number researchers with an interest in healthy aging is growing. Research aimed at prevention and reduction of the morbidity of cancer treatment fits well within these programs.
头颈部放疗对骨骼的有害影响，以放射性骨坏死（ORN）作为头颈部癌症治疗的主要致残性副作用，难以预防且治疗困难。本综述聚焦于ORN的病理生物学、临床影响及管理方面的科学现状。关于ORN的病理生物学，与传统放疗相比，目前三维适形放疗和调强放疗的放疗方案是否会使ORN发生风险不变、降低或增加尚未得到证实，主要风险因素是下颌骨任何具有临床意义表面所接受的总辐射剂量。关于ORN的预防，全面、早期的放疗前牙科评估仍被视为降低放疗后发生ORN风险的首要步骤，高压氧（HBO）治疗可降低在放疗区域进行牙科手术时发生ORN的风险。关于ORN的治疗，重点是双向的：清除坏死骨并改善放疗野内正常组织的血管供应。保守治疗对局限性ORN的治愈率约为50%，保守治疗失败后手术治疗的治愈率约为40%。以HBO作为辅助支持保守或手术治疗是否有效尚无定论。HBO治疗可增加软硬组织的血管供应，据报道在某些病例中有益。然而，在比较HBO对ORN发生的预防效果与例如在需要牙科手术的患者中使用抗生素覆盖的随机临床试验中，未显示HBO的预防效果优于更保守的方法。最近，药物治疗被引入ORN的治疗并取得成功，但其疗效必须在随机临床试验中得到证实。在ORN中进行精心设计的随机临床试验的主要问题是能够获得大量具有明确、可比ORN病例的患者。由于许多机构不会有大量此类ORN病例，必须联系国家和国际科学协会以参与多中心试验。幸运的是，资助组织的兴趣以及对健康老龄化感兴趣的研究人员数量正在增加。旨在预防和降低癌症治疗发病率的研究非常适合这些项目。
