Dataset Information

A Novel Murine Model of a High Dose Brachytherapy-Induced Actinic Proctitis.

ABSTRACT:

Background

Radiation proctitis affects 1-20% of cancer patients undergoing radiation exposure due to pelvic malignancies, including prostate, gynecological and rectum cancers. The patients manifest rectal discomfort, pain, discharge, and bleeding. Notably, the efficacy of prophylactic measures remains controversial due to the lack of adequate animal models that mimic this condition.

Objective

The present study then aimed to develop a murine model of high-dose-rate (HDR) brachytherapy-induced proctitis.

Material/methods

C57BL/6 male mice were subjected to HDR (radiation source: iridium-192 [Ir-192]) through a cylindrical propylene tube inserted 2 cm far from the anal verge into the rectum. The animals received radiation doses once a day for three consecutive days (fractions of 9.5 Grays [Gy]), 3.0 mm far from the applicator surface. The sham group received only the applicator with no radiation source. The survival rate was recorded, and a colonoscopy was performed to confirm the tissue lesion development. Following euthanasia, samples of the rectum were collected for histopathology, cytokines dosage (IL-6 and KC), and immunohistochemical analysis (TNF-α and COX-2).

Results

HDR significantly reduced animals' survival ten days post first radiation exposure (14% survival vs. 100% in the non-irradiated group). Day seven was then used for further investigation. Mice exposed to radiation presented with rectum injury confirmed by colonoscopy and histopathology (P < 0.05 vs. the control group). The tissue damage was accompanied by an inflammatory response, marked by increased KC and IL-6 tissue levels, and immunostaining for TNF-α and COX-2 (P < 0.05 vs. control group).

Conclusions

We established a novel animal model of actinic proctitis induced by HDR brachytherapy, marked by inflammatory damage and low animal mortality.

SUBMITTER: Leite CHB

PROVIDER: S-EPMC8909144 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

A Novel Murine Model of a High Dose Brachytherapy-Induced Actinic Proctitis.

Leite Carlos Heli Bezerra CHB Lopes Carlos Diego Holanda CDH Leite Caio Abner Vitorino Gonçalves CAVG Terceiro Dulce Andrade DA Lima Gabriel Silva GS Freitas Jéssica Andrade JA Cunha Fernando Queiroz FQ Almeida Paulo Roberto Carvalho PRC Wong Deysi Viviana Tenazoa DVT Lima-Júnior Roberto César Pereira RCP

Frontiers in oncology 20220223

<h4>Background</h4>Radiation proctitis affects 1-20% of cancer patients undergoing radiation exposure due to pelvic malignancies, including prostate, gynecological and rectum cancers. The patients manifest rectal discomfort, pain, discharge, and bleeding. Notably, the efficacy of prophylactic measures remains controversial due to the lack of adequate animal models that mimic this condition.<h4>Objective</h4>The present study then aimed to develop a murine model of high-dose-rate (HDR) brachyther ...[more]

PMID: 35280725

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Project description:PurposeImage-guided high-dose-rate (HDR) prostate brachytherapy is a safe and effective treatment option for prostate cancer patients; however, some patients still experience acute and late genitourinary (GU) toxicity. Studies have shown that urethral dose is associated with the incidence and severity of GU toxicity. Therefore, a technique that can further spare the urethra while ensuring adequate target coverage is highly desirable. Intensity modulated brachytherapy (IMBT) designs, such as rotating shield brachytherapy (RSBT), offer ideal dosimetry theoretically but are challenging to implement clinically due to the need for high precision in moving the treatment delivery mechanisms synchronized with the source loading. In this study, we propose a novel relatively easy-to-implement solution based on the direction modulated brachytherapy (DMBT) design concept, which does not involve moving parts and works effectively with the ubiquitous 192Ir source.Materials and methodsThe popular Varian VS2000 (VS) and GammaMedPlus (GMP) 192Ir sources, with outer diameters of 0.6 mm and 0.9 mm, respectively, were simulated using the GEANT4 Monte Carlo (MC) simulation code. The novel DMBT needle concept consists of a 14-gauge nitinol needle, which houses a platinum shield inside. A single groove, consistent with the outer diameter of each source, was incorporated inside the platinum shield to accommodate the HDR source. The maximum thickness of the shield was 1.1 mm (0.8 mm) for the VS (GMP) source. To evaluate the effectiveness of the DMBT needle concept in reducing urethral dose, 6 patient cases were studied and DMBT plans were created by replacing two needles close to the urethra with the DMBT needles. The dosimetric comparisons between the DMBT and reference clinical plans were done by assessing the dose-volume histogram (DVH) planning criteria for the target coverage and organs-at-risk.ResultsThe MC results showed that the use of the novel DMBT needle design with the VS source (GMP source) could reduce the dose by 49.6% (39.2%) at 1 cm from the needle behind the platinum shield, as compared to the unshielded side. Additionally, when using the same DVH planning criteria as the original plan, the DMBT plan with the VS (GMP) source reduced the maximum urethral dose by 10.3% ± 5.6% (8.1% ± 5.0%) and 17.7% ± 14.2% (16.6% ± 13.3%) for 0 mm and 2 mm margins, respectively, while maintaining equivalent V90% and D100 target coverage.ConclusionThe novel DMBT technique offers a promising clinically implementable solution for sparing urethra, particularly in pre-apical region, without compromising the target coverage or increasing treatment time.

Project description:PurposeTo develop and validate a preliminary machine learning (ML) model aiding in the selection of intracavitary (IC) versus hybrid interstitial (IS) applicators for high-dose-rate (HDR) cervical brachytherapy.MethodsFrom a dataset of 233 treatments using IC or IS applicators, a set of geometric features of the structure set were extracted, including the volumes of OARs (bladder, rectum, sigmoid colon) and HR-CTV, proximity of OARs to the HR-CTV, mean and maximum lateral and vertical HR-CTV extent, and offset of the HR-CTV centre-of-mass from the applicator tandem axis. Feature selection using an ANOVA F-test and mutual information removed uninformative features from this set. Twelve classification algorithms were trained and tested over 100 iterations to determine the highest performing individual models through nested 5-fold cross-validation. Three models with the highest accuracy were combined using soft voting to form the final model. This model was trained and tested over 1,000 iterations, during which the relative importance of each feature in the applicator selection process was determined.ResultsFeature selection indicated that the mean and maximum lateral and vertical extent, volume, and axis offset of the HR-CTV were the most informative features and were thus provided to the ML models. Relative feature importances indicated that the HR-CTV volume and mean lateral extent were most important for applicator selection. From the comparison of the individual classification algorithms, it was found that the highest performing algorithms were tree-based ensemble methods - AdaBoost Classifier (ABC), Gradient Boosting Classifier (GBC), and Random Forest Classifier (RFC). The accuracy of the individual models was compared to the voting model for 100 iterations (ABC = 91.6 ± 3.1%, GBC = 90.4 ± 4.1%, RFC = 89.5 ± 4.0%, Voting Model = 92.2 ± 1.8%) and the voting model was found to have superior accuracy. Over the final 1,000 evaluation iterations, the final voting model demonstrated a high predictive accuracy (91.5 ± 0.9%) and F1 Score (90.6 ± 1.1%).ConclusionThe presented model demonstrates high discriminative performance, highlighting the potential for utilization in informing applicator selection prospectively following further clinical validation.

Dataset Information

A Novel Murine Model of a High Dose Brachytherapy-Induced Actinic Proctitis.

Background

Objective

Material/methods

Results

Conclusions

Publications

A Novel Murine Model of a High Dose Brachytherapy-Induced Actinic Proctitis.

Similar Datasets

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