HDR brachytherapy versus robotic-based and linac-based stereotactic ablative body radiotherapy in the treatment of liver metastases – A dosimetric comparison study of three radioablative techniques

Characterizing the landscape of clinical trials including brachytherapy can provide an overview of the current status and research trends which may guide further areas of investigation.We queried 449,849 clinical trials from the ClinicalTrials.gov registry using brachytherapy-related keywords from 1980 to 2023, yielding 245 multi-arm and 201 single-arm, brachytherapy trials. Multi-arm and single-arm brachytherapy trials were compared using 12 trial protocol elements.The number of trials including brachytherapy has increased over time, with over 60% of trials registered in 2010 onwards. The majority of clinical trials were Phase 2 or 3, evaluated both safety and efficacy, and were funded by academic sponsors. The most common tumor sites evaluated in brachytherapy clinical trials include prostate, cervix, liver, endometrium, and breast.There remains continued interest in clinical trials including brachytherapy focused on evaluation of novel delivery systems, treatment planning, and new indications. More brachytherapy clinical trials are needed to define the optimal clinical utilization and advance prospective research in this field. 

Review of brachytherapy clinical trials: a cross-sectional analysis of ClinicalTrials.gov

Introduction Surgical resection is gold standard for treatment of liver metastasis, locally ablative techniques including computer tomography (CT)-guided interstitial high-dose-rate (HDR) brachytherapy (CT-BRT) and stereotactic body radiotherapy (SBRT) have gained prominence as alternatives, offering comparable outcomes in selected patients. We aim to compare CT-BRT and SBRT - based on dosimetric analysis. Material and methods Patients who underwent CT-BRT for oligometastatic, ≤4cm liver metastases between 2018 and 2024 were eligible. SBRT plans for Halcyon (SBRTh) and TrueBeam (SBRTtb) were prepared virtually. In the CT-BRT group CTV was equal to PTV, for SBRTh and SBRTtb planning, a 5 mm margin was applied to CTV to create PTV. Dose calculation was carried out with the TG-43 algorithm for CT-BRT and Anisotropic Analytical Algorithm for SBRTh and SBRTtb group. Descriptive statistics were used to compare the data. The Wilcoxon pairwise order test was utilized to compare dependent groups. Results CT-BRT resulted in a more favorable dose distribution within PTVs for Dmean, D50, and D90, while SBRT showed better results for D98 and V27.5Gy. No significant differences were observed for V25Gy between CT-BRT and SBRTtb, but SBRTh favored over CT-BRT. For OARs, CT-BRT plans showed better values for V5, V10, and V11.6Gy in the uninvolved liver volume. There were no significant differences in dose distribution for the duodenum, bowel, and heart. SBRT modalities performed better in the kidney. CT-BRT had improved dose distribution in the esophagus, great vessels, ribs, skin, spinal cord, and stomach compared to SBRT. Conclusions CT-BRT could be a viable alternative to SBRT for certain patients with liver malignancies. 

Radiotherapy as a metastasis directed therapy for liver oligometastases - comparative analysis between CT-guided interstitial HDR brachytherapy and two SBRT modalities performed on double-layer and single layer LINACs

Radiotherapy of the liver, lung, and other inner organs can be performed percutaneously and noninvasively by using modern stereotactic body radiotherapy (SBRT) strategies. The efficacy of these noninvasive approaches has been demonstrated in numerous tumor locations. Another option for applying high single doses is interstitial brachytherapy (iBT). Here, a radioactive source, for example, iridium-192, is inserted directly into the tumor through a catheter. iBT allows the delivery of very high doses of radiation in a single fraction, and, owing to the steep dose gradient, organs at risk can be efficiently spared. The available evidence suggests that this minimally invasive treatment is particularly advantageous in the treatment of large tumors (although substantial superiority of iBT compared with SBRT regarding the sparing of the surrounding tissue seems to decline with increasing lesion size) and owing to its repeatability.

Introduction: Why and When Radiotherapy with iBT? When SBRT?

In unresectable hepatocellular carcinoma several local ablative treatments are available. Among others, radiation based treatments such as stereotactic body radiotherapy (SBRT) and high-dose rate interstitial brachytherapy (HDR BT) have shown good local control rates. We conducted a dose comparison between actually performed HDR BT versus virtually planned SBRT to evaluate the respective clinically relevant radiation exposure to uninvolved liver tissue. Moreover, dose coverage and conformity indices were assessed. Overall, 46 treatment sessions (71 lesions, 38 patients) were evaluated. HDR BT was applied in a single fraction with a dose prescription of 1 × 15 Gy. D98 was 17.9 ± 1.3 Gy, D50 was 41.8 ± 8.1 Gy. The SBRT was planned with a prescribed dose of 3 × 12.5 Gy (65%-Isodose), D98 was 50.7 ± 3.1 Gy, D2 was 57.0 ± 2.3 Gy, and D50 was 55.2 ± 2.3 Gy. Regarding liver exposure Vliver10GyBT was compared to Vliver15.9GySBRT, Vliver16.2GySBRT (EQD2 equivalent doses), and Vliver20GySBRT (clinically relevant dose), all results showed significant differences (p < .001). In a case by case analysis Vliver10GyBT was smaller than Vliver20GySBRT in 38/46 cases (83%). Dmean of the liver was significantly smaller in BT compared to SBRT (p < .001). GTV volume was correlated to the liver exposure and showed an advantage of HDR BT over SBRT in comparison of clinically relevant doses, and for EQD2 equivalent doses. The advantage was more pronounced for greater liver lesions The Conformity Index (CI) was significantly better for BT, while Healthy Tissue Conformity Index (HTCI) and Conformation Number (CN) showed an advantage for SBRT (p < .001). HDR BT can be advantageous in respect of sparing of normal liver tissue as compared to SBRT, while providing excellent target conformity.

/pdf/comparison-of-liver-exposure-in-ct-guided-high-dose-rate-hdr-57kay6q28u.pdf

Comparison of liver exposure in CT-guided high-dose rate (HDR) interstitial brachytherapy versus SBRT in hepatocellular carcinoma

Several radiotherapeutic approaches for patients with oligotopic malignant liver lesions unfit for surgical resection exist. The most advanced competitive techniques are high-dose-rate (HDR) brachytherapy, Cyberknife, volume-modulated-arc therapy (VMAT) and Tomotherapy. We evaluated the optimal technique by a planning study for a single ablative dose with different lesion sizes.
 We compared dose distributions of HDR-brachytherapy with stereotactic ablative radiotherapy using the Cyberknife, VMAT or Tomotherapy. Tumor-control-probabilities (TCP), normal-tissue-complication-probabilities (NTCP) were determined in a theoretical framework applying a single dose of 20 Gy (demanding 95% coverage) for intrahepatic lesions of 1–5 cm in size. We evaluated therapeutic ratios by TCP (mean dose in the lesion) relative to high-dose (conformality) or low-dose liver exposition in dependency on the lesion size for each technique. In addition, we considered treatment times and accuracy (clinical target volume vs planning target volume). HDR-brachtherapy has the highest therapeutic ratios with respect to high-dose as well as low-dose liver exposition even for extended lesions, and the Cyberknife being suited second best. However, for lesions ≥ 3 cm diameter the therapeutic ratios of all ablative techniques are increasingly converging, and better tolerance and shorter treatment times of noninvasive external techniques become more important. On the other hand, mean tumor doses of HDR-brachytherapy of near 60 Gy are unattainable by the other techniques gaining only 22–34 Gy, and the conformality of HDR-brachytherapy is still rather good for lesions ≥ 3 cm diameter. HDR-brachytherapy is by far the most effective technique to treat intrahepatic lesions by a single fraction, but sparing of the surroundings declines with increasing lesion size and approaches the benchmarks of external beam radiosurgery techniques. External beam radiotherapy has the advantage to use suitable fractionation schedules.

/pdf/radiotherapeutic-treatment-options-for-oligotopic-malignant-k4a8jqv2h0.pdf

Radiotherapeutic treatment options for oligotopic malignant liver lesions.

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Radiotherapeutic treatment options for oligotopic malignant liver lesions.