Angiotensin-converting enzyme inhibitors decrease the risk of radiation pneumonitis after stereotactic body radiation therapy

Harder, E.; Park, Henry S.; Nath, Sameer K.; Mancini, B.R.; Decker, Roy H.

doi:10.1016/j.prro.2015.07.003

Cited by 31 publications

(19 citation statements)

References 27 publications

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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: 56%

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: 56%

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

et al. 2017

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“…This is hypothesis generating, and supports the findings of recently published work looking at a broader patient population managed with lung SBRT. 17 …”

Section: Discussionmentioning

confidence: 99%

“…ACE-I usage was investigated owing to the evolving literature of its association with radiation pneumonitis (RP). 17,18 Tumor characteristics examined included histology (adenocarcinoma, squamous cell carcinoma, and not biopsied), T stage (T1a/T1b, T2a/T2b, and T3), tumor size, and tumor location. Treatment characteristics examined included method of mediastinal staging (positron emission tomography [PET]-CT with or without pathologic sampling), radiation dose per fraction, number of fractions delivered, and treatment delivery modality (intensity-modulated radiotherapy or volumetric arc therapy).…”

Section: Methodsmentioning

confidence: 99%

Stereotactic Body Radiotherapy for Early-stage Non–small-cell Lung Cancer in Patients 80 Years and Older: A Multi-center Analysis

Cassidy

Patel

Zhang

et al. 2017

Clinical Lung Cancer

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Stereotactic body radiotherapy (SBRT) for early-stage non–small-cell lung cancer use is evolving, with implementation in a rising geriatric oncologic population. Our study investigated the use of SBRT for non–small-cell lung cancer in 58 consecutive patients ≥ 80 years old at 4 academic centers. SBRT was well-tolerated with expected toxicity rates, excellent disease-specific outcomes, and patients with higher performance status deriving the greatest benefit. Background Stereotactic body radiotherapy (SBRT) is the standard of care for medically inoperable early-stage non– small-cell lung cancer. Despite the limited number of octogenarians and nonagenarians on trials of SBRT, its use is increasingly being offered in these patients, given the aging cancer population, medical fragility, or patient preference. Our purpose was to investigate the efficacy, safety, and survival of patients ≥80 years old treated with definitive lung SBRT. Methods Patients who underwent SBRT were reviewed from 2009 to 2015 at 4 academic centers. Patients diagnosed at ≥80 years old were included. Kaplan-Meier and multivariate logistic regression and Cox proportional hazard regression analyses were performed. Recursive partitioning analysis was done to determine a subgroup of patients most likely to benefit from therapy. Results A total of 58 patients were included, with a median age of 84.9 years (range, 80.1-95.2 years), a median follow-up time of 19.9 months (range, 6.9-64.9 months), a median fraction size of 10.0 Gy (range, 7.0-20.0 Gy), and a median number of fractions of 5.0 (range, 3.0-8.0 fractions). On multivariate analysis, higher Karnofsky performance status (KPS) was associated with higher local recurrence-free survival (hazard ratio [HR], 0.92; P < .01), regional recurrence-free survival (HR, 0.94; P < .01), and overall survival (HR, 0.91; P < .01). On recursive partitioning analysis, patients with KPS ≥75 had improved 3-year cancer-specific and overall survival (99.4% and 91.9%, respectively) compared with patients with KPS < 75 (47.8% and 23.6%, respectively; P < .01). Conclusion Definitive lung SBRT for early-stage non–small-cell lung cancer was efficacious and safe in patients ≥80 years old. Patients with a KPS of ≥75 derived the most benefit from therapy.

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“…It remains unclear whether this results from a direct effect of ACEIs/ARBs or whether these agents modulate tumor responses to other therapeutics. Additional studies have demonstrated an impact of ACEIs/ARBs on the normal tissue response to radiation therapy and resulting reduced rates of cardiopulmonary, renal, and brain toxicity after local or total body radiation or chemoradiation …”

Section: Introductionmentioning

confidence: 99%

Increased tumor response to neoadjuvant therapy among rectal cancer patients taking angiotensin‐converting enzyme inhibitors or angiotensin receptor blockers

Morris

Saha

Magnuson

et al. 2016

Cancer

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BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are commonly used antihypertensive medications that have been reported to affect aberrant angiogenesis and the dysregulated inflammatory response. Because of such mechanisms, it was hypothesized that these medications might affect the tumor response to neoadjuvant radiation in patients with rectal cancer. METHODS: One hundred fifteen patients who were treated with neoadjuvant radiation at the University of Wisconsin (UW) between 1999 and 2012 were identified. Univariate analyses were performed with anonymized patient data. In a second independent data set, 186 patients with rectal cancer who were treated with neoadjuvant radiation at the Queen's Medical Center of the University of Hawaii (UH) between 1995 and 2010 were identified. These data were independently analyzed as before. Multivariate analyses were performed with aggregate data. RESULTS: Among patients taking ACEIs/ARBs in the UW data set, a significant 3-fold increase in the rate of pathologic complete response (pCR) to neoadjuvant therapy (52% vs 17%, P 5 .001) was observed. This finding was confirmed in the UH data set, in which a significant 2-fold-increased pCR rate (24% vs 12%, P 5 .03) was observed. Identified patient and treatment characteristics were otherwise balanced between patients taking and not taking ACEIs/ ARBs. No significant effect was observed on pCR rates with other medications, including statins, metformin, and aspirin. Multivariate analyses of aggregate data identified ACEI/ARB use as a strong predictor of pCR (odds ratio, 4.02; 95% confidence interval, 2.06-7.82; P < .001). CONCLUSIONS: The incidental use of ACEIs/ARBs among patients with rectal cancer is associated with a significantly increased rate of pCR after neoadjuvant treatment. Cancer 2016;122:2487-95.

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Angiotensin-converting enzyme inhibitors decrease the risk of radiation pneumonitis after stereotactic body radiation therapy

Cited by 31 publications

References 27 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

Stereotactic Body Radiotherapy for Early-stage Non–small-cell Lung Cancer in Patients 80 Years and Older: A Multi-center Analysis

Increased tumor response to neoadjuvant therapy among rectal cancer patients taking angiotensin‐converting enzyme inhibitors or angiotensin receptor blockers

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