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  • Pain flare defined as a temporary

    2019-06-15

    Pain flare, defined as a “temporary worsening of bone pain in the treated metastatic site” [2], has been previously documented as a side effect of radiopharmaceutical and hormonal therapy [2,10,11]. Although it is a recognized side-effect of radiation treatment as well, only recent studies have attempted to accurately document its incidence in patients treated with EBRT or SBRT [2,4,7–13]. These studies report incidences reaching as high as 68% for SBRT and 44% for EBRT [8]. A qualitative study published by Hird et al. [14] discusses patient perspectives and the impact of pain flare on QOL. Overall, patients describe interference with daily activities and general functioning, as well as anxiety and worry regarding the success of the treatment. Typical pain flare management entails an increase in analgesic use, leaving the patient at risk of associated adverse events including dry mouth, drowsiness, and constipation [14]. Moreover, the majority of patients felt that their pain was not adequately relieved by increased analgesics. Rather, 85% of patients stated that the optimal management of pain flare requires prophylaxis [14]. Dexamethasone is an anti-inflammatory steroid medication that has been shown to be effective as a prophylactic agent against pain flare [4,8,12]. It is hypothesized that the dexamethasone reduces edema within the LDN193189 of the treated bone [15]. With a half life of 36–54h, it may be administered to patients throughout the duration of treatment and for a few days post treatment in order to curb the debilitating effects of pain flare [12].
    Methods
    Results A total of eleven studies published between 2005 and 2014 were identified as relevant. This includes nine full text articles and two abstract publications extracted from the ASTRO 2014. Seven studies investigated EBRT with two additionally investigating prophylactic treatment of pain flare with dexamethasone and one investigating prophylaxis with a methylprednisolone infusion. Four studies investigated pain flare resulting from stereotactic radiation therapy, only one of which included dexamethasone as a prophylactic agent. A summary of the studies and their characteristics is presented in Table 1. The incidence of pain flare, duration of pain flare, and possible use of dexamethasone, if applicable, is reported in Table 2.
    Discussion Bone pain as a result of bone metastases is a well documented occurrence in advanced cancer patients [2–4]. Palliative external beam radiation therapy, and more recently stereotactic body radiation therapy, are effective and well-tolerated treatments for the relief of cancer related bone pain [1,5,6]. Pain flare, a temporary exacerbation of pain closely following completion of treatment, is a recognized acute toxicity of both treatment techniques [2]. We completed a comprehensive review of the currently available literature documenting the incidence of pain flare and the prophylactic use of dexamethasone to decrease the incidence. The method of data collection is an inherently critical factor in study design and can greatly influence study results and their interpretation. It is particularly relevant to this current review when examining the widespread discrepancies in pain flare incidence, particularly among SBRT studies. Both Pan et al. [7] and Owen et al. [9] collected data retrospectively and reported incidence rates of 23% and 10%, respectively. These incidences are considerably less than the 68% reported by Chiang et al. [8] in 2013, in a study that employed prospective collection methods. Retrospective studies in general may be subject to recall bias, where patients do not accurately recall the events that they have experienced. Especially when the goal of treatment is to provide pain relief, these patients may be more focused on the improvement of their symptoms rather than the transient exacerbation of them. Noteworthy are that conventional EBRT studies obtained data prospectively and the collective incidence of pain flare was consistently around 40%.