Pain Flare‐Effect Prophylaxis With Corticosteroids on Bone Radiotherapy Treatment: A Systematic Review

Abstract

BackgroundRadiotherapy for metastatic bone pain can induce a transitory increase in pain known as pain flare. Several studies have described the use of prophylactic corticosteroids to prevent pain flare. However, the role and efficacy of corticosteroids to prevent pain flare remain unclear.PurposeTo summarize the available evidence with regard to the efficacy and toxicity of prophylactic corticosteroids for the prevention of pain flare.MethodsThis was a systematic review (PROSPERO protocol CRD42018090351) of peer‐reviewed studies published in the Cochrane, Medline, and Scopus databases through September 2018. Studies carried out in adult patients treated with radiotherapy for bone metastases who received prophylactic corticosteroids to prevent pain flare were eligible for inclusion. The Cochrane Collaboration tool was used to assess risk of bias. The evidence grade was determined according to the GRADEpro tool.ResultsA total of 4,407 studies were identified. Of these, 4 clinical trials (CT) and 1 prospective cohort study met the inclusion criteria. The overall incidence of pain flare was 28%, and 21% vs. 37% in the prophylaxis vs. non‐prophylaxis groups; the relative risk reduction was 43%. In the 3 studies that compared corticosteroids to placebo, the relative risk reductions were 25%, 67%, and 72%. The most common treatment regimen was oral dexamethasone at 8 mg once daily from the first day of radiotherapy for 5 days. One study administered methylprednisolone. No severe toxicity was reported in any of the studies.ConclusionsOverall, the findings of this systematic review indicate that glucocorticoids appear to be an effective prophylactic treatment to prevent pain flare in patients undergoing radiotherapy for bone metastases. New CT are needed to confirm these results and to determine the optimal dose of dexamethasone.

Clinical Predictors for Analgesic Response to Radiotherapy in Patients with Painful Bone Metastases

“…Corticosteroids are known to reduce inflammation and are proposed to reduce the incidence of pain flares after RT. 36,37 One potential explanation for corticosteroids being a negative predictor for RT response is that the anti-inflammatory effect of RT is already induced by the corticosteroids which reduce the additional effect of RT. Corticosteroids are widely administered to patients with metastatic cancer disease and if has a negative impact on RT response, this could lead to a change in clinical practice.…”

ESTRO ACROP guidelines for external beam radiotherapy of patients with uncomplicated bone metastases

“…Pain flare can be managed by symptomatic measures such as paracetamol and dexamethasone. In the management of pain flare, only studies comparing prophylactic use of glucocorticoid vs. placebo have been performed [74]. The SC.23 randomized trial showed that prophylactic use of dexamethasone in patients with bone metastases undergoing a single dose of 8 Gy significantly reduced the pain flare incidence from 35% (with placebo) to 26% (with 8 mg dexamethasone for five days) [75].…”

Manipulation of different phytochemical classes against inflammation induced by radiations

“…Whereas RT is destroying or damaging cancer cells, it initiates inflammation cascade through the body organ sand oxidative cellular damage. Thus, the issue that flashes across the mind whether there is a possibility to counteract these harmful effects through phytochemical manipulation for such an essential treatment for enormous suffering cancer patients [23,24] .…”

“…Although systemic corticosteroids e.g. (dexamethasone; glucocorticoids) have been an approved treatment to the harmful effects resulting from RT, but patients receiving corticosteroids have suffered from many health issues as the long term use of such medication led to immunosuppression and consequently may cause some chronic diseases such as diabetes and other heart disorders or serious microorganism invasion [23] . Additionally, new research contexts have to be worked on to find safe and yet effective substitute for corticosteroids.…”

“…classes [29] The mode of action and structure-activity relationship of plant phytochemicalsasradioprotective, antioxidant and anti-inflammatory agents Fig. 3: Proposed mechanism for the radioprotective effects of phytochemicals against, oxidative stress response and inflammation [23]. .…”