The Value of Botox-A in Acute Radiation Proctitis: Results From a Phase I/II Study Using a Three-Dimensional Scoring System

Vuong, T.; Waschke, Kevin; Niazi, Tamim; Richard, Carole; Parent, Josée; Liberman, Sender; Mayrand, Serge; Loungnarath, Rasmy; Stein, Barry; Dević, Slobodan

doi:10.1016/j.ijrobp.2010.04.017

Cited by 11 publications

(5 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Encouraging results were reported by Stubblefield et al (31) using BTX in radiation fibrosis. Additional applications for BTX injections include management of genitourinary toxicities such as radiation cystitis (32) and proctitis (33). Furthermore, BTX is known to potentiate radiation therapy (34), which is desirable in a location such as the salivary glands, especially when nearby pathologic nodes are suspected.…”

Section: Discussionmentioning

confidence: 99%

Botulinum Toxin Confers Radioprotection in Murine Salivary Glands

Zeidan

Xiao

Cao

et al. 2016

International Journal of Radiation Oncology*Biology*Physics

View full text Add to dashboard Cite

Purpose Xerostomia is a common radiation sequela, which has a negative impact on the quality of life of patients with head and neck cancer. Current treatment strategies offer only partial relief. Botulinum toxins (BTX) have been successfully used in treating a variety of radiation sequelae such as cystitis, proctitis, fibrosis, and facial pain. The purpose of this study was to evaluate the effect of BTX on radiation-induced salivary gland damage. Methods and Materials We used a previously established model for murine salivary gland irradiation (IR). The submandibular glands (SMGs) of C5BL/6 mice (n=6/group) were injected with saline or BTX 72 hours before receiving 15 Gy of focal irradiation. Saliva flow was measured 3, 7, and 28 days after treatment. The SMGs were collected for immunohistochemistry, confocal microscopy, and Western blotting. A cytokine array consisting of 40 different mouse cytokines was used to evaluate cytokine profiles after radiation treatment. Results Irradiated mice showed a 50% reduction in saliva flow after 3 days, whereas mice preinjected with BTX had 25% reduction in saliva flow (P<.05). Cell death detected by TUNEL staining was similar in SMG sections of both groups. However, neutrophil infiltrate, detected by myeloperoxidase staining, was 3-fold lower for the BTX treated mice. A cytokine array showed a 2-fold upregulation of LPS-induced chemokine (LIX/CXCL5) 3 days after IR. BTX pretreatment reduced LIX levels by 40%. At 4 weeks after IR, the saline (control) group showed a 40% reduction in basal SMG weight, compared with 20% in the BTX group. Histologically, BTX-pretreated glands showed relative preservation of acinar structures after radiation. Conclusions These data suggest that BTX pretreatment ameliorates radiation-induced saliva dysfunction. Moreover, we demonstrate a novel role for CXCL5 in the acute phase of salivary gland damage after radiation. These results carry important clinical implications for the treatment of xerostomia in patients with head and neck cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

Botulinum Toxin Confers Radioprotection in Murine Salivary Glands

Zeidan

Xiao

Cao

et al. 2016

International Journal of Radiation Oncology*Biology*Physics

View full text Add to dashboard Cite

show abstract

“…More recent work has shown that increasing the dose of amifostine results in greater reduction of GI toxicity as determined by the EPIC bowel bothersome score during treatment and at 12 months after external prostate RT [ 47 ]. Lastly, the feasibility of rectal injections of Botox as a preventative measure against acute rectal toxicity has recently been studied based on Botox's effect on muscle spasticity, with future efficacy trials planned [ 48 ]. In total, there are a great deal more pharmaceutical compounds that have shown success in treating acute GI toxicity than treating late GI toxicity or preventing acute or late GI toxicity.…”

Section: Discussionmentioning

confidence: 99%

Systematic Review of the Relationship between Acute and Late Gastrointestinal Toxicity after Radiotherapy for Prostate Cancer

2015

View full text Add to dashboard Cite

A small but meaningful percentage of men who are treated with external beam radiation therapy for prostate cancer will develop late gastrointestinal toxicity. While numerous strategies to prevent gastrointestinal injury have been studied, clinical trials concentrating on late toxicity have been difficult to carry out. Identification of subjects at high risk for late gastrointestinal injury could allow toxicity prevention trials to be performed using reasonable sample sizes. Acute radiation therapy toxicity has been shown to predict late toxicity in several organ systems. Late toxicities may occur as a consequential effect of acute injury. In this systematic review of published reports, we found that late gastrointestinal toxicity following prostate radiotherapy seems to be statistically and potentially causally related to acute gastrointestinal morbidity as a consequential effect. We submit that acute gastrointestinal toxicity may be used to identify at-risk patients who may benefit from additional attention for medical interventions and close follow-up to prevent late toxicity. Acute gastrointestinal toxicity could also be explored as a surrogate endpoint for late effects in prospective trials.

show abstract

Section: Discussionmentioning

confidence: 99%

Botulinum Toxin Confers Radioprotection in Murine Salivary Glands

Zeidan

Xiao

Cao

et al. 2013

International Journal of Radiation Oncology*Biology*Physics

View full text Add to dashboard Cite

Purpose-Xerostomia is a common radiation sequela, which has a negative impact on the quality of life of patients with head and neck cancer. Current treatment strategies offer only partial relief. Botulinum toxins (BTX) have been successfully used in treating a variety of radiation sequelae such as cystitis, proctitis, fibrosis, and facial pain. The purpose of this study was to evaluate the effect of BTX on radiation-induced salivary gland damage.Methods and Materials-We used a previously established model for murine salivary gland irradiation (IR). The submandibular glands (SMGs) of C5BL/6 mice (n=6/group) were injected with saline or BTX 72 hours before receiving 15 Gy of focal irradiation. Saliva flow was measured 3, 7, and 28 days after treatment. The SMGs were collected for immunohistochemistry, confocal microscopy, and Western blotting. A cytokine array consisting of 40 different mouse cytokines was used to evaluate cytokine profiles after radiation treatment.Results-Irradiated mice showed a 50% reduction in saliva flow after 3 days, whereas mice preinjected with BTX had 25% reduction in saliva flow (P<.05). Cell death detected by TUNEL staining was similar in SMG sections of both groups. However, neutrophil infiltrate, detected by myeloperoxidase staining, was 3-fold lower for the BTX treated mice. A cytokine array showed a 2-fold upregulation of LPS-induced chemokine (LIX/CXCL5) 3 days after IR. BTX pretreatment reduced LIX levels by 40%. At 4 weeks after IR, the saline (control) group showed a 40% reduction in basal SMG weight, compared with 20% in the BTX group. Histologically, BTXpretreated glands showed relative preservation of acinar structures after radiation.Conclusions-These data suggest that BTX pretreatment ameliorates radiation-induced saliva dysfunction. Moreover, we demonstrate a novel role for CXCL5 in the acute phase of salivary

show abstract

The Value of Botox-A in Acute Radiation Proctitis: Results From a Phase I/II Study Using a Three-Dimensional Scoring System

Cited by 11 publications

References 44 publications

Botulinum Toxin Confers Radioprotection in Murine Salivary Glands

Botulinum Toxin Confers Radioprotection in Murine Salivary Glands

Systematic Review of the Relationship between Acute and Late Gastrointestinal Toxicity after Radiotherapy for Prostate Cancer

Botulinum Toxin Confers Radioprotection in Murine Salivary Glands

Contact Info

Product

Resources

About