Can Angiotensin-Converting Enzyme Inhibitors Reduce the Incidence, Severity, and Duration of Radiation Proctitis?

Alashkham, Abduelmenem; Paterson, Catherine; Rauchhaus, Petra; Nabi, Ghulam

doi:10.1016/j.ijrobp.2015.09.013

Cited by 17 publications

(10 citation statements)

References 48 publications

(26 reference statements)

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“…This study showed a lower rate of grade 2 radiation pneumonitis (14% vs. 23%), but was not statistically significant as a result of being underpowered due to low accrual rates. Taken this study in context with the other published, albeit retrospective studies [25–28], the correlation that ABT decreases the incidence of late radiation toxicities within multiple organ systems [24–27] (gastrointestinal, lung, heart and kidney) and with different radiation regimens [28, 29] (standard [1.8–2 Gy] and high-dose, SBRT fractionation [> 5 Gy]) provides support that angiotensin may be part of a central targetable pathway critical in the development of late radiation effect.…”

Section: Discussionsupporting

confidence: 78%

Angiotensin receptor blockade: a novel approach for symptomatic radiation necrosis after stereotactic radiosurgery

et al. 2017

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Preclinical evidence suggests angiotensin blockade therapy (ABT) decreases late radiation toxicities. This study aims to investigate the association between ABT and symptomatic radiation necrosis (SRN) following stereotactic radiosurgery (SRS). Resected brain metastases (rBM) and arteriovenous malformation (AVM) patients treated with SRS from 2002 to 2015 were identified. Patients in the ABT cohort were on therapy during SRS and at 1-month follow up. Kaplan Meier method and cumulative incidence model were used to analyze overall survival (OS) and intracranial outcomes. 228 consecutive patients were treated with SRS: 111 with rBM and 117 with AVM. Overall, 51 (22.4%) patients were in the ABT group: 32 (28.8%) in the rBM and 19 (16.2%) in AVM cohorts. Baseline characteristics were similar, except for higher Graded Prognostic Analysis (3–4) in the rBM (ABT: 25.0% vs. non-ABT: 49.0%, p = 0.033) and median age in the AVM (ABT: 51.4 vs. non-ABT: 35.4, p < 0.001) cohorts. In both populations, OS and intracranial efficacy (rBM—local control; AVM—obliteration rates) were statistically similar between the cohorts. ABT was associated with lower 1-year SRN rates in both populations: rBM, 3.1 versus 25.3% (p = 0.003); AVM, 6.7 vs. 14.6% (p = 0.063). On multivariate analysis, ABT was a significant predictive factor for rBM (HR: 0.17; 95% CI 0.03–0.88, p = 0.035), but did not reach statistical significance for AVM (HR: 0.36; 95% CI 0.09–1.52, p = 0.165). ABT use appears to be associated with a reduced risk of SRN following SRS, without detriment to OS or intracranial efficacy. A prospective trial to validate these findings is warranted.

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Section: Discussionsupporting

confidence: 78%

Angiotensin receptor blockade: a novel approach for symptomatic radiation necrosis after stereotactic radiosurgery

et al. 2017

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“…It could be questioned why this study has included the use of angiotensin converting enzyme inhibitors as a covariant factor. Our previous study [35] reported that men who were hypertensive and on angiotensin converting enzyme inhibitors and underwent radical radiotherapy for prostate cancer were significantly less likely to have radiation induced proctitis. Although the mechanism of angiotensin converting enzyme inhibitors to reduce the incidence and risk of proctitis, further work is needed fully understand the hypothesised pathways in which these factors might affect radiation induced proctitis.…”

Section: Discussionmentioning

confidence: 96%

What is the impact of diabetes mellitus on radiation induced acute proctitis after radical radiotherapy for adenocarcinoma prostate? A prospective longitudinal study

Alashkham

Paterson

Hubbard

et al. 2019

Clinical and Translational Radiation Oncology

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BackgroundLong-term complications of diabetes include cardiovascular disease, retinopathy, nephropathy, and neuropathy. Diabetic patients with prostate cancer could be at a high risk of radiation-induced acute proctitis following radical radiotherapy. Our aims were to analyse the incidence, severity, and duration of radiation proctitis in diabetic patients treated by radical radiotherapy and combined androgen deprivation for prostate cancer.Material and methodsOn the bases of inclusion and exclusion criteria 716 patients with prostate cancer were retrospectively recruited. Patients were stratified into diabetic patients and non-diabetic patients. The incidence, severity, and duration of proctitis were the main outcomes. A polynomial ordered logistic regression was fitted to determine the influence of diabetes status, age, blood pressures medication, co-morbidities, Gleason score, PSA after treatment, and tumour stage on the grades of proctitis. Time to resolution per year was modelled as a negative binomial generalised linear model.ResultsThe overall mean age of patients was 67.44 (SD 6.77) years with a follow-up time of 3.36 (SD 2.05) years. Data exploratory analysis suggested that the only highly significant explanatory variable was the presence or absence of diabetes. Polynomial ordered logistic regression, however, showed that the presence (or not) of diabetes remained as the only significant predictor (t = −2.74; p = 0.0059) of severity of proctitis. A negative binomial generalised linear model showed that both grade of proctitis (z = −17.178; p < 0.001), and diabetes (z = −5.92; p < 0.001), were highly significant predictors of time to resolution.ConclusionsDiabetic patients were significantly more likely to have proctitis after radical radiation therapy for prostate cancer. Diabetes was significantly associated with an induced risk of radiation induced proctitis and also with deceleration of its resolution.

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“…To date, there are still a limited number of chemical RAs clinically used to minimize the severity and duration of toxicities associated with radiotherapy. Some other agents such as palifermin [121] , genistein [122] , angiotensin I-converting enzyme inhibitors [123] , melanin [124] , hemocyanin [125] and Vitamin D [126] showed a promising effect against the radiation toxicity, however there is a lack of high quality clinical studies for most of the agents described. The evaluation of safety and efficacy of these emerging agents are needed and their effects on tumor sensitivity should be verified [117] .…”

Section: Ra Its Categoris and Mechanisms Of Functionmentioning

confidence: 99%

Research and Development of Radioprotective Agents: A Mini-Review

Saaya

Katsube

Xie

et al. 2017

International Journal of Radiology

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The research and development (R&D) of radioprotective agents (RAs) have been conducting since seven decades ago, and the safety and protection against undesirable effects of ionizing radiation (IR) has become an important issue especially for the benefit of patients receiving the radiotherapy, in addition to the applications in nuclear industry, military, outer space exploration and accidental exposures. Although the technology advancement makes the radiotherapy a promising better treatment by maximizing the effect of IR to the cancer cells, there are still needs for improvement in minimizing the toxicity to the normal cells. Aiming at providing the new researchers in the radiation protection field with an overall view for R&D of the RAs, this mini-review elucidates in brief a general understanding of the IR and its effects on the cell, the concepts of radiotherapy and therapeutic ratio, the categories of RAs and their mechanisms, and discusses on the strategies and challenge for R&D of the RAs.

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Can Angiotensin-Converting Enzyme Inhibitors Reduce the Incidence, Severity, and Duration of Radiation Proctitis?

Cited by 17 publications

References 48 publications

Angiotensin receptor blockade: a novel approach for symptomatic radiation necrosis after stereotactic radiosurgery

Angiotensin receptor blockade: a novel approach for symptomatic radiation necrosis after stereotactic radiosurgery

What is the impact of diabetes mellitus on radiation induced acute proctitis after radical radiotherapy for adenocarcinoma prostate? A prospective longitudinal study

Research and Development of Radioprotective Agents: A Mini-Review

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