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Reducing dysphagia with palliative 2D high-dose-rate brachytherapy improves survival in esophageal cancer.

ABSTRACT: Purpose:The goal of this study was to assess the effectiveness of dysphagia relief and overall survival in patients with advanced esophageal cancer treated with palliative high-dose-rate (HDR) brachytherapy (BT) without computed tomography-based planning. Material and methods:Palliative 2D HDR-BT was used to treat 93 patients with advanced or incurable esophageal cancer in a regional cancer center from October 2010 to December 2016. Before the treatment patients presented the following grades of dysphagia: 0 - 0%, I - 57%, II - 33.3%, III - 6.5%, IV - 3.2%. The planned dose was 22.5 Gy in 3 fractions. The median age of patients was 65 years (45-88). Squamous cell carcinoma was diagnosed in 59.4%, adenocarcinoma in 22.6%, and other histological types of tumors in 6.7% of cases. The histopathological report was unknown in 11.3% of patients. Results:The mean follow-up was 5.0 months (range 1-43). The median tumor length was 72.5 mm. Due to BT dysphagia was significantly decreased: grade 0 - 38.7%, I - 31.2%, II - 20.4%, IV - 1.1% (p < 0.001). Dysphagia relief was achieved in 55% of patients and lasted for a mean time of 4.6 months; stabilization occurred in 31% and deterioration in 14%. The patients with partial or complete dysphagia relief lived longer (5.8 vs. 4.1 months, p = 0.02). The patients with a length of the tumor less than 72.5 mm, histopathologically confirmed adenocarcinoma or after dilatation with a metal stent subsequently to BT had improved overall survival as well (7.1 vs. 3.6; 8.0 vs. 4.1; 6.5 vs. 4.0 months, respectively; p < 0.05). The primary localization and primary grade of dysphagia were not factors that influenced the survival of patients. The logistic regression model did not reveal any predictors for treatment response. Conclusions:2D HDR-BT reduces dysphagia and prolongs survival in patients who respond to the treatment. It meets the assumption of palliative treatment for advanced esophageal cancer because of its simplicity and effectiveness.

SUBMITTER: Burchardt W

PROVIDER: S-EPMC6964340 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Reducing dysphagia with palliative 2D high-dose-rate brachytherapy improves survival in esophageal cancer.

Burchardt Wojciech W Chyrek Artur A Burchardt Ewa E Bielęda Grzegorz G Trojanowski Maciej M Chicheł Adam A

Journal of contemporary brachytherapy 20191225 6

<h4>Purpose</h4>The goal of this study was to assess the effectiveness of dysphagia relief and overall survival in patients with advanced esophageal cancer treated with palliative high-dose-rate (HDR) brachytherapy (BT) without computed tomography-based planning.<h4>Material and methods</h4>Palliative 2D HDR-BT was used to treat 93 patients with advanced or incurable esophageal cancer in a regional cancer center from October 2010 to December 2016. Before the treatment patients presented the foll ...[more]

PMID: 31969911

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Project description:To compare the outcomes of localized prostate cancer treatment with high-dose-rate brachytherapy (HDR-BT) and low-dose-rate brachytherapy (LDR-BT), we examined 924 patients treated with HDR-BT + external beam radiotherapy (EBRT) and 500 patients treated with LDR-BT ± EBRT using multi-institutional retrospective data. The HDR-BT treated advanced disease with more hormonal therapy than LDR-BT. To reduce background selection bias, we performed inverse probability of treatment weighting (IPTW) analysis using propensity scores and excluded patients with T3b-4 disease/ initial prostate-specific antigen (PSA) levels > 50 ng/ml. The actuarial 5-year biochemical control rates (5y-bNED) were 96.3% and 95.7% in the HDR-BT and LDR-BT groups, respectively. The corresponding values were 100% and 96.5% in the low-risk group; 97.4% and 97.1% in the intermediate-risk group (97.2% and 97% in the higher titer group and 97.5% and 94.6% in the lower titer group, respectively); and 95.7% and 94.9% in the selected high-risk group, respectively. IPTW correction indicated no significant difference among the groups. The 5y-bNED in the HDR-BT + EBRT, LDR-BT + EBRT, and LDR-BT alone groups were 96.3%, 95.5%, and 97%, respectively (P = 0.3011). The corresponding values were 97.4%, 94.7%, and 96.6% (P = 0.1004) in the intermediate-risk group (97.5%, 100%, and 94.5% in the lower titer group [P = 0.122] and 97.2%, 96.2%, and 100% [P = 0.664] in the higher titer group, respectively) and 95.7%, 95.5%, and 100% (P = 0.859) in the high-risk group, respectively. The HDR-BT group showed a lower incidence of acute grade ≥ 2 genitourinary toxicities; the incidence of other early and late grade ≥ 2 toxicities were similar between the HDR-BT and LDR-BT groups. Acute genitourinary toxicity predicted the occurrence of late genitourinary toxicity. EBRT increased the risk of grade ≥ 2 gastrointestinal toxicity. HDR-BT + EBRT is a good alternative to LDR-BT ± EBRT for low-, intermediate-, and selected high-risk patients.

Project description:We have previously shown that the antimalarial agent chloroquine can abrogate the lethal cellular effects of low-dose-rate (LDR) radiation in vitro, most likely by activating the ataxia-telangiectasia mutated (ATM) protein. Here, we demonstrate that chloroquine treatment also protects against lethal doses of LDR radiation in vivo.C57BL/6 mice were irradiated with a total of 12.8 Gy delivered at 9.4 cGy/hour. ATM null mice from the same background were used to determine the influence of ATM. Chloroquine was administered by two intraperitoneal injections of 59.4 ?g per 17 g of body weight, 24 hours and 4 hours before irradiation. Bone marrow cells isolated from tibia, fibula, and vertebral bones were transplanted into lethally irradiated CD45 congenic recipient mice by retroorbital injection. Chimerism was assessed by flow cytometry. In vitro methylcellulose colony-forming assay of whole bone marrow cells and fluorescence activated cell sorting analysis of lineage depleted cells were used to assess the effect of chloroquine on progenitor cells.Mice pretreated with chloroquine before radiation exhibited a significantly higher survival rate than did mice treated with radiation alone (80% vs. 31%, p = 0.0026). Chloroquine administration before radiation did not affect the survival of ATM null mice (p = 0.86). Chloroquine also had a significant effect on the early engraftment of bone marrow cells from the irradiated donor mice 6 weeks after transplantation (4.2% vs. 0.4%, p = 0.015).Chloroquine administration before radiation had a significant effect on the survival of normal but not ATM null mice, strongly suggesting that the in vivo effect, like the in vitro effect, is also ATM dependent. Chloroquine improved the early engraftment of bone marrow cells from LDR-irradiated mice, presumably by protecting the progenitor cells from radiation injury. Chloroquine thus could serve as a very useful drug for protection against the harmful effects of LDR radiation.

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Project description:CivaTech Oncology Inc. (Durham, NC) has developed a novel low-dose rate (LDR) brachytherapy source called the CivaSheet.TM The source is a planar array of discrete elements ("CivaDots") which are directional in nature. The CivaDot geometry and design are considerably different than conventional LDR cylindrically symmetric sources. Thus, a thorough investigation is required to ascertain the dosimetric characteristics of the source. This work investigates the repeatability and reproducibility of a primary source strength standard for the CivaDot and characterizes the CivaDot dose distribution by performing in-phantom measurements and Monte Carlo (MC) simulations. Existing dosimetric formalisms were adapted to accommodate a directional source, and other distinguishing characteristics including the presence of gold shield x-ray fluorescence were addressed in this investigation. Primary air-kerma strength (SK ) measurements of the CivaDots were performed using two free-air chambers namely, the Variable-Aperture Free-Air Chamber (VAFAC) at the University of Wisconsin Medical Radiation Research Center (UWMRRC) and the National Institute of Standards and Technology (NIST) Wide-Angle Free-Air Chamber (WAFAC). An intercomparison of the two free-air chamber measurements was performed along with a comparison of the different assumed CivaDot energy spectra and associated correction factors. Dose distribution measurements of the source were performed in a custom polymethylmethacrylate (PMMA) phantom using GafchromicTM EBT3 film and thermoluminescent dosimeter (TLD) microcubes. Monte Carlo simulations of the source and the measurement setup were performed using MCNP6 radiation transport code. The CivaDot SK was determined using the two free-air chambers for eight sources with an agreement of better than 1.1% for all sources. The NIST measured CivaDot energy spectrum intensity peaks were within 1.8% of the MC-predicted spectrum intensity peaks. The difference in the net source-specific correction factor determined for the CivaDot free-air chamber measurements for the NIST WAFAC and UW VAFAC was 0.7%. The dose-rate constant analog was determined to be 0.555 cGy h-1 U-1 . The average difference observed in the estimated CivaDot dose-rate constant analog using measurements and MCNP6-predicted value (0.558 cGy h-1 U-1 ) was 0.6% ± 2.3% for eight CivaDot sources using EBT3 film, and -2.6% ± 1.7% using TLD microcube measurements. The CivaDot two-dimensional dose-to-water distribution measured in phantom was compared to the corresponding MC predictions at six depths. The observed difference using a pixel-by-pixel subtraction map of the measured and the predicted dose-to-water distribution was generally within 2-3%, with maximum differences up to 5% of the dose prescribed at the depth of 1 cm. Primary SK measurements of the CivaDot demonstrated good repeatability and reproducibility of the free-air chamber measurements. Measurements of the CivaDot dose distribution using the EBT3 film stack phantom and its subsequent comparison to Monte Carlo-predicted dose distributions were encouraging, given the overall uncertainties. This work will aid in the eventual realization of a clinically viable dosimetric framework for the CivaSheet based on the CivaDot dose distribution.

Dataset Information

Reducing dysphagia with palliative 2D high-dose-rate brachytherapy improves survival in esophageal cancer.

Publications

Reducing dysphagia with palliative 2D high-dose-rate brachytherapy improves survival in esophageal cancer.

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