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A Robust Oxygen Microbubble Radiosensitizer for Iodine-125 Brachytherapy.

ABSTRACT: Iodine-125 (¹²⁵I) brachytherapy, a promising form of radiotherapy, is increasingly applied in the clinical treatment of a wide range of solid tumors. However, the extremely hypoxic microenvironment in solid tumors can cause hypoxia-induced radioresistance to ¹²⁵I brachytherapy, resulting in therapeutic inefficacy. In this study, the aim is to sensitize hypoxic areas in solid tumors using ultrasound-activated oxygen microbubbles for ¹²⁵I brachytherapy. A modified emulsion freeze-drying method is developed to prepare microbubbles that can be lyophilized for storage and easily reconstituted in situ before administration. The filling gas of the microbubbles is modified by the addition of sulfur hexafluoride to oxygen such that the obtained O₂/SF₆ microbubbles (OS MBs) achieve a much longer half-life (>3×) than that of oxygen microbubbles. The OS MBs are tested in nasopharyngeal carcinoma (CNE2) tumor-bearing mice and oxygen delivery by the OS MBs induced by ultrasound irradiation relieve hypoxia instantly. The post-treatment results of brachytherapy combined with the ultrasound-triggered OS MBs show a greatly improved therapeutic efficacy compared with brachytherapy alone, illustrating ultrasound-mediated oxygen delivery with the developed OS MBs as a promising strategy to improve the therapeutic outcome of ¹²⁵I brachytherapy in hypoxic tumors.

SUBMITTER: Peng S

PROVIDER: S-EPMC8025033 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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A Robust Oxygen Microbubble Radiosensitizer for Iodine-125 Brachytherapy.

Peng Sheng S Song Ruyuan R Lin Qingguang Q Zhang Yanling Y Yang Yuanzhong Y Luo Ma M Zhong Zhihui Z Xu Xiaonan X Lu Ligong L Yao Shuhuai S Zhang Fujun F

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20210210 7

Iodine-125 (125I) brachytherapy, a promising form of radiotherapy, is increasingly applied in the clinical treatment of a wide range of solid tumors. However, the extremely hypoxic microenvironment in solid tumors can cause hypoxia-induced radioresistance to 125I brachytherapy, resulting in therapeutic inefficacy. In this study, the aim is to sensitize hypoxic areas in solid tumors using ultrasound-activated oxygen microbubbles for 125I brachytherapy. A modified ...[more]

PMID: 33854878

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Project description:BackgroundTumor regression of uveal melanomas (UMs) after radiotherapy has been reported as a valuable prognostic factor for metastasis and metastatic death. But its effect on prognosis is questionable. The purpose of this study was to summarize the regression features of uveal melanoma after iodine-125 plaque brachytherapy and the relationship with prognosis.MethodsAdult uveal melanoma patients who only received iodine-125 plaque brachytherapy between December 2009 and March 2018 at the Beijing Tongren Hospital, Capital Medical University were enrolled in this study. The regression rate was calculated as the percent change in tumor height, and each eye was classified for four main regression patterns: Decrease (D), Stable (S), Others (O), and Increase (I), according to the trend of height change. Statistical analysis was performed using one-way ANOVA and chi-square test, univariate and multivariate logistic regression, and Kaplan-Meier analysis.ResultsA total of 139 patients was included in the study. The median follow-up was 35 months. Regression patterns status was pattern D in 65 tumors (46.8%), pattern S in 50 tumors (36.0%), pattern O in 6 tumors (4.3%), and pattern I in 18 tumors (12.9%). Reductions of tumor mean height for each follow-up visit were 5.26% (3 months), 10.66% (6 months), 9.37% (12 months), and 14.68% (18 months). A comparison (D vs. S vs. O vs. I) revealed the preoperative height of pattern I was significantly lower than the pattern D, S and O (mean: 7.24 vs. 7.30 vs. 6.77 vs. 5.09 mm, respectively; P = 0.037). LBD (largest basal diameter) was strongly associated with the metastasis (P = 0.03). However, an association between the tumor regression and subsequent melanoma-related metastasis and mortality could not be confirmed (P = 0.66 and P = 0.27, respectively). The tumor regression rate increased with increasing tumor height (P = 0.04) and decreased with increasing of LBD (P = 0.01).ConclusionOur study showed a lack of association between the prognosis and the regression of uveal melanomas following I-125 plaque radiotherapy. The LBD and original height of the tumor have predictive value in tumor regression rate, and LBD was positively associated with metastasis.

Project description:PurposeTo investigate chronological changes in lower urinary tract symptoms (LUTS) in patients who received iodine-125 brachytherapy (BT) for prostate cancer.MethodsWe enrolled 706 patients who received BT. Of these, 265 (38%) received BT combined with external beam radiation therapy (EBRT). An International Prostate Symptom Score (IPSS), IPSS quality of life (IPSS-QOL) score, and overactive bladder symptom score (OABSS) were recorded before BT (baseline, BL), and 1, 3, 6, 12, 24, 36, 48, and 60 months after BT. The sum of frequency (2), urgency (4) and nocturia (7) of the IPSS questionnaire was defined as the storage symptoms score, whereas the sum of emptying (1), intermittency (3), weak stream (5), and hesitancy (6) was defined as the voiding symptom score.ResultsTotal IPSS significantly increased at 3 months following BT compared with BL (mean score: 17.1 vs. 7.99, P < 0.001) and returned to BL by 36 months. The storage symptom score did not return to BL 36 months after BT. Total OABSS significantly increased 3 months after BT compared with BL (mean score: 6.52 vs. 3.45, P < 0.001), and returned to BL 48 months after BT. The IPSS-QOL score was the highest score (mean score: 2.46 vs. 3.9, P < 0.001) 3 months after BT and returned to BL 48 months after BT, however the IPSS-QOL score was lower than BL (mean score: 2.01 vs 2.46, P < 0.001) at 60 months. The risk factors for LUTS within 1 year after BT were BL IPSS (P < 0.001) and PV (P < 0.001). Patients who received combined EBRT experienced transient storage symptoms 24 and 36 months after BT, whereas those who received BT alone did not. However, the storage symptom score of the patients who received combined EBRT was improving 48 months after BT and eventually showed no significant difference compared with those treated with BT alone.ConclusionThree months after BT, LUTS, including storage symptoms, deteriorated the most but improved with time. The urinary symptom in patients who received combined EBRT can potentially flare again in 24 and 36 months after BT. Knowledge of changes in LUTS associated with BT may influence treatment recommendations and enable patients to make better-informed decisions.

Project description:BackgroundThere is currently no widely-accepted consensus for the management of hepatocellular carcinoma with portal vein tumor thrombus. We evaluate the safety and efficacy of ultrasound-guided percutaneous brachytherapy with iodine-125 seeds for the treatment of hepatocellular carcinoma with portal vein-branch tumor thrombus (PVBTT).MethodsSixty-nine hepatocellular carcinoma patients with PVBTT were enrolled; 34 received transarterial chemoembolization (TACE) combined with iodine-125 seeds implanted in the PVBTT; 35 were treated with TACE alone. Adverse events, objective response rate, disease control rate, progression-free survival, and overall survival were compared between the two groups. Tumor responses of PVBTT and intrahepatic tumor were correlated. Multivariate and subgroup analyses were conducted for overall survival.ResultsNo grade 3 or 4 adverse events were recorded, and there was no difference in grade 1 or 2 adverse events between the two groups. Objective response rate and disease control rate for PVBTT were 58.9 and 91.2%, respectively, in the combined treatment group, which were significantly greater than the 5.7 and 54.3% rates, respectively, in the TACE-alone group (both p's ≤ 0.001). Intrahepatic tumor response was positively correlated with the PVBTT response (γ = 0.782, p < 0.01). Survival outcomes were better in the combined treatment group than in the TACE-alone group: the median progression-free survival for PVBTT was 9 months versus 3 months (HR = 0.187 [95% CI: 0.101, 0.345], p < 0.001), and the median overall survival was 11 months versus 7 months (HR = 0.448 [95% CI: 0.265, 0.758], p = 0.003). Multivariate analysis revealed that application of brachytherapy and lower grade PVBTT (Vp1 + Vp2 vs. Vp3) were protective predictors of overall survival. In stratified analysis, the benefit of overall survival was more significant in the subgroup of PVBTT Vp1 + Vp2 rather than in Vp3.ConclusionsThe combination of iodine-125 seed brachytherapy guided by ultrasound and TACE is a convenient, safe, and effective treatment for patients with HCC and PVBTT, conferring a better survival benefit than TACE alone.

Dataset Information

A Robust Oxygen Microbubble Radiosensitizer for Iodine-125 Brachytherapy.

Publications

A Robust Oxygen Microbubble Radiosensitizer for Iodine-125 Brachytherapy.

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