Brachytherapy Research Articles

Unexpected Anti-tumor Effect of Selective Internal Radiation Therapy and Radiofrequency Ablation Followed by Immune Checkpoint Inhibitors for Hepatocellular Carcinoma

Introduction: Hepatocellular carcinoma (HCC) has become an increasingly serious health problem worldwide. Combining immune checkpoint inhibitors (ICIs) for HCC with local treatments can produce synergistic effects. Although the abscopal effect was noted in 1953, most studies on this phenomenon have been conducted in the context of external beam radiotherapy (EBRT). The incidence of the abscopal effect induced by selective internal radiation therapy (SIRT) alone is lower. This research reports a case of a patient with multifocal HCC who received SIRT plus radiofrequency ablation (RFA) followed by ICI therapy. During the subsequent course of ICI therapy, an anti-tumor effect was detected in the left hepatic lobe, far from the site targeted by the local treatments. Case Presentation: The abscopal effect has recently attracted widespread attention because ICIs can enhance this phenomenon. However, little is known about the relationship between inducing the abscopal effect and local treatment against HCC. A 76-year-old male patient presented with multifocal HCC. During hepatic angiography, MRI showed multiple HCCs in both lobes of the liver. Selective internal radiation therapy was performed on a tumor with a diameter of approximately 80 millimeters in the right lobe. A month later, RFA was conducted on another tumor in the right lobe, approximately 30 mm in diameter, and ICI therapy was administered on the second day post-RFA. Hepatic arterial phase imaging of contrast-enhanced magnetic resonance performed 10 months after SIRT showed the disappearance of the tumor in the left liver lobe. Conclusions: This case highlights that the combination of multiple local treatment methods with ICI therapy can enhance the anti-tumor immune response and benefit patients with multifocal

The experience of transarterial embolisation for metastsatic NET at queen Elizabeth Hospital Birmingham and future possible role of selective internal radiation therapy

The experience of transarterial embolisation for metastsatic NET at queen Elizabeth Hospital Birmingham and future possible role of selective internal radiation therapy

Case Report: Successful Treatment of Solitary Fibrous Tumor with Selective Internal Radiation Therapy (SIRT)

Background: This case report details the innovative use of selective internal radiation therapy (SIRT) with Yttrium-90 resin microspheres to treat a 73-year-old woman with a solitary fibrous tumor (SFT), a rare and challenging tumor type. SFTs often present significant treatment difficulties, especially in cases of recurrence or metastasis, as systemic therapies typically show limited effectiveness. This report explores SIRT as an alternative therapeutic approach for SFTs with liver metastasis. Methods: The patient initially presented with a pelvic mass, which was surgically resected. However, metastatic disease later developed in the liver. After experiencing severe side effects from targeted therapy with sunitinib, the patient was selected for treatment with SIRT as an alternative. Results: Following the SIRT intervention, the patient demonstrated a substantial reduction in tumor size and significant relief from symptoms. This outcome suggests SIRT’s effectiveness as a targeted treatment for metastatic SFT. Conclusions: To our knowledge, and based on an extensive literature review, this is the first reported instance of treating SFT with SIRT. This case provides new insights into SIRT’s potential as a therapeutic strategy, particularly for patients for whom conventional treatments are either ineffective or intolerable. The success observed here underscores SIRT’s potential as a less invasive, locally targeted treatment option, offering hope for similar cases.

Comprehensive Analysis of the Potential Toxicity of Magnetic Iron Oxide Nanoparticles for Medical Applications: Cellular Mechanisms and Systemic Effects

Owing to recent advancements in nanotechnology, magnetic iron oxide nanoparticles (MNPs), particularly magnetite (Fe3O4) and maghemite (γ-Fe2O3), are currently widely employed in the field of medicine. These MNPs, characterized by their large specific surface area, potential for diverse functionalization, and magnetic properties, have found application in various medical domains, including tumor imaging (MRI), radiolabelling, internal radiotherapy, hyperthermia, gene therapy, drug delivery, and theranostics. However, ensuring the non-toxicity of MNPs when employed in medical practices is paramount. Thus, ongoing research endeavors are essential to comprehensively understand and address potential toxicological implications associated with their usage. This review aims to present the latest research and findings on assessing the potential toxicity of magnetic nanoparticles. It meticulously delineates the primary mechanisms of MNP toxicity at the cellular level, encompassing oxidative stress, genotoxic effects, disruption of the cytoskeleton, cell membrane perturbation, alterations in the cell cycle, dysregulation of gene expression, inflammatory response, disturbance in ion homeostasis, and interference with cell migration and mobility. Furthermore, the review expounds upon the potential impact of MNPs on various organs and systems, including the brain and nervous system, heart and circulatory system, liver, spleen, lymph nodes, skin, urinary, and reproductive systems.

Brachytherapy for cervical cancer: from intracavitary to interstitial technique

Cervical cancer is a common malignant tumor of female reproductive system. Radiation therapy is one of the main methods of cervical cancer treatment, of which brachytherapy is an essential and important part of radiation therapy for locally advanced cervical cancer. With the rapid development of imaging technologies such as computed tomography (CT) and magnetic resonance imaging (MRI), brachytherapy for cervical cancer has gradually developed from traditional two-dimensional image-guided technology to three-dimensional image-guided technology. And there are more and more treatment methods, including intracavitary brachytherapy, interstitial brachytherapy, and intracavitary combined interstitial implantation brachytherapy. We performed a PubMed search for introduce the application progress of intracavity, implantation, intracavity combined implantation brachytherapy and radioactive seed implantation, and discuss the dosimetric feasibility of internal and external fusion irradiation.

A Novel Anthropometric Phantom for Rapid Radiological Triage: A Quick Sort Triage Solution.

Rapidly identifying individuals who have received internal radiation exposure above action guidelines is crucial for mitigating health risks and addressing public concerns immediately following a radiological event involving the dispersal of radioactive materials. This study describes a novel triage method using a conventional Geiger-Mueller (GM) detector to select those individuals from the large group of persons who may have received an intake of radioactive material at levels corresponding to one Clinical Decision Guide (CDG). The triage method involves placing a portable GM detector against the lower anterior torso of a sitting person as they bend over to surround the detector with their body. The response of the GM detector is evaluated using a new, specially designed anthropometric phantom that simulates combined tissues of the lower thorax and gastrointestinal (GI) tract and is fabricated with a tissue substitute material that matches the overall radiological properties of human tissue present in this body region. The phantom has four separate layers of tissue substitute material with ports to accommodate a single GM detector at the center and one or more sealed radioactive sources that can be arranged to characterize the detector response for a variety of source distributions, including a "hot spot." In this study, the response of a Ludlum Model 133-4 GM detector was evaluated using sealed sources of 232Th and 137Cs to determine the measurement efficiency for a quantity of activity present in the abdomen within a few hours post-intake equivalent to 1 CDG. Results demonstrate that the Quick Sort triage procedure using a single GM detector placed against the abdomen of a person can reliably detect internal deposition resulting from an intake equivalent to 1 CDG for 232Th or a significantly lower activity of 137Cs within a few hours following a radiological incident. The evaluation was performed over a wide range of photon energies, so the Quick Sort triage procedure is expected to be suitable for most fission products distributed uniformly within the abdomen or as a single "hot spot."

Re-evaluation of F-FDG absorbed and effective dose in adult and pediatric phantoms using DoseCalcs Monte Carlo platform: a validation study.

Positron emission tomography (PET) using F-FDG is a well-known modality for the diagnosis of various diseases in patients of different ages, sexes, and states of health, which implies that internal radiation dosimetry is highly desired for different phantom anatomies. In this study, we validate "DoseCalcs," a new Monte Carlo platform that combines personalized internal dosimetry calculations with Monte Carlo simulations. To achieve that, we used the specific absorbed fraction (SAF) calculated by DoseCalcs and those from ICRP publication 133 to estimate the absorbed dose per injected activity (AD/IA) and effective dose per injected activity (ED/IA) for F-FDG. The investigation focused on various voxelized phantoms representing different age groups, including adult male and female, and pediatric phantoms of various ages, from newborn to 15 years old. Using the DoseCalcs Monte Carlo platform, we have simulated the emission of F-FDG positrons based on the energy spectrum provided in ICRP publication 107. The results demonstrated the impact of anatomical differences and different organ/tissue compositions on radiation absorption, with significant variations in the AD/IA across different phantoms. Interestingly, organs/tissues near the emission source showed higher AD/IA, highlighting the anatomical dependence on the phantom. When our results were compared to established reference data, especially from ICRP128, most organs/tissues had good agreement. Still, some cases have shown differences. This shows how important it is to use accurate radionuclide data and biokinetic modeling in internal dosimetry calculations. Furthermore, we compared AD/IA and ED/IA values calculated in newborns by DoseCalcs with those derived from alternative codes, MCNP and EGSnrc. While the results generally exhibited consistency, subtle variations underscored the influence of biokinetics modeling choices and computational methodologies. Overall, this research contributes valuable insights into the precision of internal dosimetry calculations using "DoseCalcs-Gui" by providing one platform for Monte Carlo simulation and personalized internal dosimetry in nuclear medicine. The DoseCalcs platform is free for research and available for download at www.github.com/TarikEl/DoseCalcs-Gui .

Quality assurance of internal mammary node irradiation in the DBCG IMN2 study

Purpose/objectiveThe Danish Breast Cancer Group (DBCG) IMN2 study investigated the gain from internal mammary node irradiation (IMNI) in node-positive breast cancer (BC) patients. IMNI was indicated in right-sided patients, but not in left-sided. Target volume delineations were based on bony landmarks in contrast to the contemporary vessel-based ESTRO consensus guideline. Our objective was to compare IMNI doses in right-sided versus left-sided patients. Material/methodsTreatment plans and delineated structures including CTVn_IMN (IMN_old) from 2008 to 14 were collected from the DBCG RT Nation study. During the study period, IMN_old was only delineated in right-sided patients. Right and left-sided CTVn_IMN structures were auto-segmented following the ESTRO guidelines (IMN_ESTRO). Due to cranial discordance between IMN_old and IMN_ESTRO, the IMN_ESTRO models were separated into IMN_ESTRO_cranial and IMN_ESTRO_intercostal space(IC)1-3, IC1-4, and IC4_only. ResultsTreatment plans for 2,837 patients were available (62.5 % of patients in the IMN2 study). In right-sided patients, the median IMN_old dose coverage (92.4 %) was higher than IMN_ESTRO (71.7 %), p < 0.001. Dose coverage in IMN_ESTRO_IC1-3 was comparable to IMN_old. Comparing IMN_ESTRO_IC1-3 in all patients by laterality, the median CTVn_V90% was 94.6 % (IQR 64.8–100.0) in right-sided patients and 20.4 % (IQR 0.9–55.8) in left-sided patients, p < 0.001. For right-sided patients, CTV_V90% was 82.3 % in IMN_ESTRO_IC4_only.Median mean heart doses were lower in right-sided patients (1.2 Gy) than in left-sided (2.3 Gy), p < 0.001. Median mean lung doses were higher in right-sided patients (16.0 Gy) than in left-sided (12.7 Gy), p < 0.001. ConclusionFor IMN_ESTRO_IC1-3, we found a significantly higher IMN dose coverage in right-sided than in left-sided patients supporting treatment according to study guidelines.

Feasibility of balloon rectal spacer implantation in HDR and LDR brachytherapy for prostate cancer treatment

PurposeThis study evaluates the use of a biodegradable balloon rectal spacer in two prostate cancer patients undergoing Low Dose Radiation (LDR) and salvage High Dose Radiation (HDR) brachytherapy. The spacer aims to reduce radiation dose to adjacent organs, particularly the rectum, in patients previously treated with radiation. MethodsThe balloon spacer was implanted transperineally under transrectal ultrasonography (TRUS) guidance in two patients. For the LDR case (73-year-old, intermediate-risk), the balloon was placed post-implant with 55 iodine-125 seeds delivering 145 Gy. For the HDR case (66-year-old, high-risk), the balloon was placed one week before treatment, which delivered 23 Gy in two weekly fractions using 16 channels. ResultsThe balloon provided a 14-15mm separation between rectum and prostate. In the LDR case, prostate D90 was 149.1Gy (102.83%), V100 was 91.95%, and rectum D30 was 23.93Gy (16.50%). For the HDR case, prostate D90 was 11.63Gy (105.79%), V100 was 93.63%, and rectum D0.5cc was 8.04Gy (73.15%). Both patients tolerated the treatment well, with no observed postoperative complications at 6-month follow-up. ConclusionsThe use of a rectal balloon spacer in both salvage HDR and LDR brachytherapy is feasible and safe, allowing for controlled placement and providing rectal protection from high radiation doses.

Thermodynamics of Giant Molecular Clouds: The Effects of Dust Grain Size

The dust grain size distribution (GSD) likely varies significantly across star-forming environments in the Universe, but its impact on star formation remains unclear. This ambiguity arises because the GSD interacts nonlinearly with processes like heating, cooling, radiation, and chemistry, which have competing effects and varying environmental dependencies. Processes such as grain coagulation, expected to be efficient in dense star-forming regions, reduce the abundance of small grains and increase that of larger grains. Motivated by this, we investigate the effects of similar GSD variations on the thermochemistry and evolution of giant molecular clouds (GMCs) using magnetohydrodynamic simulations spanning a range of cloud masses and grain sizes, which explicitly incorporate the dynamics of dust grains within the full-physics framework of the STARFORGE project. We find that grain size variations significantly alter GMC thermochemistry: the leading-order effect is that larger grains, under fixed dust mass, GSD dynamic range, and dust-to-gas ratio, result in lower dust opacities. This reduced opacity permits interstellar radiation field and internal radiation photons to penetrate more deeply. This leads to rapid gas heating and inhibited star formation. Star formation efficiency is highly sensitive to grain size, with an order-of-magnitude reduction when grain size dynamic range increases from 10−3–0.1 μm to 0.1–10 μm. Additionally, warmer gas suppresses low-mass star formation, and decreased opacities result in a greater proportion of gas in diffuse ionized structures.

Metastatic insulinoma—outcomes in the current era

Abstract Background Multimodal interventions in neuroendocrine tumors appear to have a beneficial impact on survival. Metastatic insulinoma is associated with hypoglycemia and, historically, a shortened life expectancy. Methods The authors retrospectively analyzed the clinical outcomes of patients with metastatic insulinomas treated at a tertiary care center between 2006 and 2023. Results Clinical data on 14 patients with metastatic insulinoma (metastases to the liver, skeleton, and lung) were reviewed in this descriptive study. The patients underwent various treatments including surgery; liver directed therapies (embolization, selective internal radiotherapy), somatostatin analogs; targeted agents (everolimus); systemic chemotherapy (capecitabine/temozolomide; carboplatin/etoposide); external beam radiation; and peptide receptor radiotherapy. Seven subjects died during follow-up. The time of the 7 deaths ranged from 2.5 to 10.4 years (median time to death was 8.2 years). This compares to previous reports of median survival of about 2 years. Seven subjects are alive 1.2-12.3 years after diagnosis. Hypoglycemia was well-controlled and did not cause the deaths. Conclusions Multimodal interventions in metastatic insulinoma can be effective in managing hypoglycemia. The patients on multimodal treatments also lived a long time when considering previous published reports of median survival of just 2 years. Our findings challenge previous assumptions regarding clinical outcomes in this patient population.

The production study of Auger emitters in platinum group metal for radiotherapy

Targeted radioisotope therapy (TRT) is a type of internal radiotherapy that combines radiation therapy and targeted therapy to eliminate cancer cells without damaging healthy tissue. Radionuclides attached to targeting molecules travel to cancer cells and emit radiation in the form of beta-ray emitting nuclides and alpha nuclides. A third type of nuclide called Auger emitter can be used in a treatment called Auger therapy. Dr Tomoyuki Ohya, Department of Advanced Nuclear Medicine Sciences, Institute for Quantum Medical Sciences (iQMS), National Institutes for Quantum Science and Technology (QST), Japan, is interested in Auger therapy as a radiotherapy that only affects the tissues that require treatment. Challenges associated with this treatment are the short range of Auger electrons, meaning that they must be precisely targeted in order to be effective. With a view to overcoming this, Ohya is focusing on Pd-103 and Rh-103m as optimal nuclides for Auger therapy. He is working to develop a technology to facilitate high-quality, large-scale manufacturing that can be applied to the clinical use of Auger therapy, enhancing its efficiency and rendering its use on a wide scale possible. In one project, Ohya investigated the potential of developing an efficient and reliable method for producing Rh-103m. Due to its short half-life it needs to be produced by a generator for clinical use. As the anion-exchange resins used in previously developed generators are no longer commercially available, Ohya and the team prepared and tested generators using commercially available anion-exchange resins.

PO0248: MRI-Guided Intensity-Modulated Radiotherapy Boost in Gynecologic Cancers for Patients Unsuitable for Brachytherapy (BT): A Case Series

PO0248: MRI-Guided Intensity-Modulated Radiotherapy Boost in Gynecologic Cancers for Patients Unsuitable for Brachytherapy (BT): A Case Series

Current status of the working environment of brachytherapy in Japan: a nationwide survey-based analysis focusing on radiotherapy technologists and medical physicists.

Brachytherapy (BT), especially in high dose rate (HDR), has become increasingly complex owing to the use of image-guided techniques and the introduction of advanced applicators. Consequently, radiotherapy technologists and medical physicists (RTMPs) require substantial training to enhance their knowledge and technical skills in image-guided brachytherapy. However, the current status of the RTMP workload, individual abilities and quality control (QC) of BT units in Japan remains unclear. To address this issue, we conducted a questionnaire survey from June to August 2022 in all 837 radiation treatment facilities in Japan involving RTMPs. This survey focused on gynecological cancers treated with HDR-BT (GY-HDR) and permanent prostate implantation using low-dose-rate BT (PR-LDR). The responses revealed that the average working time in the overall process for HDR varied: 120min for intracavitary BT and 180min for intracavitary BT combined with interstitial BT. The QC implementation rate, in accordance with domestic guidelines, was 65% for GY-HDR and 44% for PR-LDR, which was lower than the 69% observed for external beam radiation therapy (EBRT). Additionally, the implementation rate during regular working hours was low. Even among RTMP working in facilities performing BT, the proportion of those able to perform QC for BT units was ~30% for GY-HDR and <20% for PR-LDR, significantly lower than the 80% achieved for EBRT. This study highlights the vulnerabilities of Japan's BT unit QC implementation structure. Addressing these issues requires appropriate training of the RTMP staff to safely perform BT tasks and improvements in practical education and training systems.

Automated planning of curved needle channels in 3D printed patient-tailored applicators for cervical cancer brachytherapy.

Purpose&#xD;Patient-tailored intracavitary/interstitial (IC/IS) brachytherapy (BT) applicators may increase dose conformity in cervical cancer patients. Current configuration planning methods in these custom applicators rely on manual specification or a small set of (straight) needles. This work introduces and validates a two-stage approach for establishing channel configurations in the 3D printed patient-tailored ARCHITECT applicator. &#xD;&#xD;Methods&#xD;For each patient, the patient-tailored applicator shape was based on the first BT application with a commercial applicator and integrated connectors to a commercial (Geneva) intrauterine tube and two lunar ring channels. First, a large candidate set was generated of channels that steer the needle to desired poses in the target region and are contained in the applicator. The channels' centrelines were represented by Bézier curves. Channels running between straight target segments and entry points were optimised and refined to ensure (dynamic) feasibility. Second, channel configurations were selected using geometric coverage optimisation. This workflow was applied to establish patient-tailored geometries for twenty-two patients previously treated using the Venezia applicator. Treatment plans were automatically generated using the in-house developed algorithm BiCycle. Plans for the clinically used configuration, TPclin, and patient-tailored configuration, TParch, were compared.&#xD;&#xD;Results&#xD;Channel configurations could be generated in clinically feasible time (median: 2651s, range 1826-3812s). All TParchand TPclinplans were acceptable, but planning aims were more frequently attained with patient-tailored configurations (115/132 versus 100/132 instances). Median CTVIRD98and bladderD2cm3doses significantly improved (p< 0.001 andp< 0.01 respectively) in TParchplans in comparison with TPclinplans, and in approximately half of the patients dosimetric indices improved. &#xD;&#xD;Conclusion&#xD;Automated patient-tailored BT channel configuration planning for 3D printed applicators is clinically feasible. A treatment planning study showed that all plans met planning limits for the patient-tailored configurations, and in selected cases improved the plan quality in comparison with commercial applicator configurations.&#xD.

Assessment of radiological risk to workers and members of the public from the operation of a groundwater treatment plant in Jordan

ABSTRACT The study aimed to evaluate the radiation doses received by workers at a pilot water treatment plant (WTP) in Jordan. It also examined the concentrations of gross alpha, gross beta, and radium activities in both groundwater and treated water, along with a radiological risk assessment for the waste generated by the treatment process. The radioactivity levels of gross alpha and gross beta in the groundwater were found to exceed the established drinking water limits. In the pilot WTP, two methods were applied for water treatment, namely, ceramic ultra-filtration (CUF) and reverse osmosis (RO), both of which produced treated water that met drinking water quality standards. The annual effective dose from external radiation exposure to the WTP workers was found to be less than 0.007 mSv y−1 (during the filters backwash operation). However, the average annual dose from internal radiation due to inhalation of radon released from groundwater reached 3.2 mSv y−1, exceeding the 1 mSv y−1 limit. Therefore, monitoring radon levels in workplaces is recommended. Radioisotope concentrations in the waste (sludge) stockpiles exceeded clearance levels, requiring them to be treated as radioactive waste. Overall, the WTP successfully produced drinking water that met quality standards, and the methods used could be replicated in other locations.

Dosimetric benefit and clinical feasibility of deep inspiration breath-hold and volumetric modulated arc therapy-based postmastectomy radiotherapy for left-sided breast cancer

To evaluate the dosimetric benefits and clinical feasibility of deep inspiratory breath-hold (DIBH) combined with volumetric modulated arc therapy (VMAT) in left-sided postmastectomy radiotherapy (PMRT). Eligible patients with left-sided breast cancer undergoing DIBH-based PMRT were prospectively included. Chest wall, supra/infraclavicular fossa, and/or internal mammary node irradiation (IMNI) were planned with a prescription dose of 43.5 Gy in 15 fractions. VMAT plans were designed on free breathing (FB)—and DIBH-CT to compare dosimetric parameters in heart, left anterior descending artery (LAD) and lung. Cone-beam computed tomography (CBCT) was performed before and after treatment to evaluate inter- and intra-fractional setup errors. Heart position and dose variations during treatment were estimated by fusing CBCT with DIBH-CT scans.Twenty patients were included with 10 receiving IMNI. In total, 193 pre-treatment and 39 pairs pre- and post-treatment CBCT scans were analyzed. The Dmean, Dmax, and V5−40 of the heart, LAD, and left lung were significantly lower in DIBH than FB (p < 0.05 for all), except for V5 of LAD (p = 0.167). The cardiopulmonary dosimetric benefits were maintained regardless of IMNI. The inter- and intra-fractional setup errors were < 0.3 cm; and the overall estimated PTV margins were < 1.0 cm. During treatment, the mean dice similarity coefficient of heart position and the mean ratio of heart Dmean between CBCT and DIBH-CT plans was 0.95 (0.88–1.00) and 100% (70.6–119.5%), respectively. DIBH-VMAT could effectively reduce the cardiopulmonary doses with acceptable reproducibility and stability in left-sided PMRT regardless of IMNI.

LI-RADS radiation-based treatment response algorithm for HCC: what to know and how to use it.

Locoregional treatments (LRT) continue to advance for hepatocellular carcinoma (HCC). Selective internal radiation therapy (SIRT) or transarterial radioembolization (TARE) with radioactive 90 Yttrium (Y90) microspheres is currently widely accepted, and external beam and stereotactic body radiation (EBRT/SBRT) are increasingly used as LRT1-5. Assessment of treatment response after these radiation-based therapies can be challenging, given that the adjacent liver also undergoes treatment related changes, inflammatory changes occur, and there is a variable time for response to develop. In 2017, the liver imaging reporting and data system (LI-RADS) workgroup initially developed a single algorithm for the imaging assessment of treatment response encompassing all types of locoregional therapies, the LI-RADS treatment response (LR-TR) algorithm. Recognizing that response and imaging patterns differ between radiation and non-radiation based therapies, the LR-TR working group recently updated the algorithm to reflect the unique characteristics of tumor response for therapies involving radiation. This article aims to elucidate the changes in the new version of the LI-RADS TR, with a guide for algorithm utilization and illustration of expected and unexpected findings post liver directed therapies for HCC.

Efficacy and safety of bevacizumab in neoadjuvant and concurrent chemoradiotherapy for refractory cervical cancer patients.

A platinum-based concurrent chemoradiotherapy (CCRT) is the standard treatment for refractory cervical cancer (CC). However, the recurrence of disease and the occurrence of metastasis remain prevalent. We observed the long-term efficacy and safety of bevacizumab combined with neoadjuvant chemotherapy (NACT) and CCRT in refractory CC. A total of 62 patients with refractory CC were enrolled in this study from January 2016 to December 2019. The NACT regimen included bevacizumab (7.5 mg/kg), docetaxel (75 mg/m2), and cisplatin (75 mg/m2), administered tri-weekly for 2 cycles. The CCRT regimen included bevacizumab (7.5 mg/kg) and cisplatin (75 mg/m2), administered tri-weekly for 2 cycles. A dose of 45-50 Gy was prescribed for external beam radiotherapy (EBRT), while 30-35 Gy in 4-5 fractions was prescribed for brachytherapy (BT). Among the patients, 21 patients (33.9%) were at stages IIB-IIIB, 8 patients (12.9%) were at stage IIIC1, 19 patients (30.6%) were at stage IIIC2, and 14 patients (22.6%) were at stage IVB. Pelvic, para-aortic, supraclavicular, and inguinal lymph node metastases were discovered in 41 patients (66.1%). The median follow-up was 49.8 months (12.3-82.7 months). The median tumor volumes pre-treatment, after NACT, and before BT were 84.64 ± 53.15 cm3, 1.64 ± 13.15 cm3, and 0 ± 1.5 cm3, respectively. Complete clinical response (cCR) rates after NACT and EBRT were 35.5% and 66.1%, respectively. Four years after the diagnosis, the overall survival (OS) rate was 78.6%, the local region-free survival (LRFS) rate was 91.3%, the disease-free survival (DFS) rate was 70.6%, and the distant metastasis-free survival (DMFS) rate was 81.4%. A total of 29 patients (46.8%) experienced grade 3/4 hematological toxicity, 3 patients (4.8%) experienced grade 3 gastrointestinal toxicities, and none experienced grade 5 adverse events. Bevacizumab combined with NACT and CCRT significantly improved cCR and OS in refractory CC with acceptable toxicity.

Sequencing microsphere selective internal radiotherapy after external beam radiotherapy for hepatocellular carcinoma: proof of concept of a synergistic combination.

This study aims to explore the synergistic effects of combining Stereotactic Body Radiation Therapy (SBRT) and Selective Internal Radiation Therapy (SIRT) in that specific sequence for treating hepatocellular carcinoma (HCC), particularly in patients at high risk of radiation-induced liver disease (RILD). We analyzed a case of a patient with HCC who was treated with SBRT at our institution. A virtual 90Y dose distribution was added using our in-house -BLINDED FOR REVIEW- model to keep a minimum dose to the healthy liver tissue. BED and EUD metrics were calculated to harmonize the dose distributions of SBRT and SIRT. Our radiation biology-based models suggest that the combination of SBRT and SIRT could maintain effective tumor control while reducing the dose to normal liver tissue. Specifically, an SBRT plan of 10 Gy x 3 fractions combined with SIRT yielded comparable tumor control probability to an SBRT-only plan of 10 Gy x 5 fractions. The combination of SBRT and SIRT is a promising treatment strategy for HCC patients at high risk of RILD. While the LQ model and associated formalisms provide a useful starting point, further studies are needed to account for factors beyond these models. Nonetheless, the potential for significant dose reduction to normal tissue suggests that this combination therapy could offer substantial clinical benefits. This article presents a proposal to combine SBRT and SIRT, in this specific order, for HCC, discussing its advantages. A framework for future research into optimizing combination therapy for HCC is provided, utilizing a novel HCC vascular model to simulate 90Y doses.