Intraoperative radiotherapy after neurosurgical resection of brain metastases as institutional standard treatment- update of the oncological outcome form a single center cohort after 117 procedures.

PURPOSE: Stereotactic radiotherapy (SRT) is the predominant method for the irradiation of resection cavities after resection of brain metastases (BM). Intraoperative radiotherapy (IORT) with 50 kV x-rays is an alternative way to irradiate the resection cavity focally. We have already reported the outcome of our first 40 IORT patients treated until 2020. Since then, IORT has become the predominant cavity treatment in our center due to patients´ choice. METHODS: We retrospectively analyzed the outcomes of all patients who underwent resection of BM and IORT between 2013 and August 2023 at Augsburg University Medical Center (UKA). RESULTS: We identified 105 patients with 117 resected BM treated with 50 kV x-ray IORT. Median diameter of the resected metastases was 3.1 cm (range 1.3 - 7.0 cm). Median applied dose was 20 Gy. All patients received standardized follow-up (FU) including three-monthly MRI of the brain. Mean FU was 14 months, with a median MRI FU for patients alive of nine months. Median overall survival (OS) of all treated patients was 18.2 months (estimated 1-year OS 57.7%). The observed local control (LC) rate of the resection cavity was 90.5% (estimated 1-year LC 84.2%). Distant brain control (DC) was 61.9% (estimated 1-year DC 47.9%). Only 16.2% of all patients needed WBI in the further course of disease. The observed radio necrosis rate was 2.6%. CONCLUSION: After 117 procedures IORT still appears to be a safe and appealing way to perform cavity RT after neurosurgical resection of BM with low toxicity and excellent LC.

Acute and Long-Term Toxicity after Planned Intraoperative Boost and Whole Breast Irradiation in High-Risk Patients with Breast Cancer-Results from the Targeted Intraoperative Radiotherapy Boost Quality Registry (TARGIT BQR).

In the context of breast cancer treatment optimization, this study prospectively examines the feasibility and outcomes of utilizing intraoperative radiotherapy (IORT) as a boost in combination with standard external beam radiotherapy (EBRT) for high-risk patients. Different guidelines recommend such a tumor bed boost in addition to whole breast irradiation with EBRT for patients with risk factors for local breast cancer recurrence. The TARGIT BQR (NCT01440010) is a prospective, multicenter registry study aimed at ensuring the quality of clinical outcomes. It provides, for the first time, data from a large cohort with a detailed assessment of acute and long-term toxicity following an IORT boost using low-energy X-rays. Inclusion criteria encompassed tumors up to 3.5 cm in size and preoperative indications for a boost. The IORT boost, administered immediately after tumor resection, delivered a single dose of 20 Gy. EBRT and systemic therapy adhered to local tumor board recommendations. Follow-up for toxicity assessment (LENT SOMA criteria: fibrosis, teleangiectasia, retraction, pain, breast edema, lymphedema, hyperpigmentation, ulceration) took place before surgery, 6 weeks to 90 days after EBRT, 6 months after IORT, and then annually using standardized case report forms (CRFs). Between 2011 and 2020, 1133 patients from 10 centers were preoperatively enrolled. The planned IORT boost was conducted in 90%, and EBRT in 97% of cases. Median follow-up was 32 months (range 1-120, 20.4% dropped out), with a median age of 61 years (range 30-90). No acute grade 3 or 4 toxicities were observed. Acute side effects included erythema grade 1 or 2 in 4.4%, palpable seroma in 9.1%, punctured seroma in 0.3%, and wound healing disorders in 2.1%. Overall, chronic teleangiectasia of any grade occurred in 16.2%, fibrosis grade ≥ 2 in 14.3%, pain grade ≥ 2 in 3.4%, and hyperpigmentation in 1.1%. In conclusion, a tumor bed boost through IORT using low-energy X-rays is a swift and feasible method that demonstrates low rates in terms of acute or long-term toxicity profiles in combination with whole breast irradiation.

Intraoperative radiation therapy for brain metastasis in a pregnant patient: a case report.

We present the rare case of a 42-year-old woman with oligometastatic lung adenocarcinoma in her first trimester of pregnancy who was treated for brain metastases with metastasectomy and intraoperative radiation therapy (IORT) using the INTRABEAM® system (Zeiss AG, Jena, Germany). This case underscores the potential of IORT in optimizing cancer treatment while safeguarding fetal health in pregnant patients.

Biological effects of intraoperative radiation therapy: histopathological changes and immunomodulation in breast cancer patients.

Introduction: Intraoperative radiation therapy (IORT) delivers a single accelerated radiation dose to the breast tumor bed during breast-conserving surgery (BCS). The synergistic biologic effects of simultaneous surgery and radiation remain unclear. This study explores the cellular and molecular changes induced by IORT in the tumor microenvironment and its impact on the immune response modulation. Methods: Patients with hormone receptor (HR)-positive/HER2-negative, ductal carcinoma in situ (DCIS), or early-stage invasive breast carcinoma undergoing BCS with margin re-excision were included. Histopathological evaluation and RNA-sequencing in the re-excision tissue were compared between patients with IORT (n=11) vs. non-IORT (n=11). Results: Squamous metaplasia with atypia was exclusively identified in IORT specimens (63.6%, p=0.004), mimicking DCIS. We then identified 1,662 differentially expressed genes (875 upregulated and 787 downregulated) between IORT and non-IORT samples. Gene ontology analyses showed that IORT was associated with the enrichment of several immune response pathways, such as inflammatory response, granulocyte activation, and T-cell activation (p<0.001). When only considering normal tissue from both cohorts, IORT was associated with intrinsic apoptotic signaling, response to gamma radiation, and positive regulation of programmed cell death (p<0.001). Using the xCell algorithm, we inferred a higher abundance of γδ T-cells, dendritic cells, and monocytes in the IORT samples. Conclusion: IORT induces histological changes, including squamous metaplasia with atypia, and elicits molecular alterations associated with immune response and intrinsic apoptotic pathways. The increased abundance of immune-related components in breast tissue exposed to IORT suggests a potential shift towards active immunogenicity, particularly immune-desert tumors like HR-positive/HER2-negative breast cancer.

Impact on the estimated dose of different tissue assignment strategies during partial breast irradiations with INTRABEAM.

PURPOSE: Partial breast irradiations with electronic brachytherapy or kilovoltage intraoperative radiotherapy devices such as Axxent or INTRABEAM are becoming more common every day. Breast is mainly composed of glandular and adipose tissues, which are not always clearly disentangled in planning breast CTs. In these cases, breast tissues are replaced with an average soft tissue, or even water. However, at kilovoltage energies, this may lead to large differences in the delivered dose, due to the dominance of photoelectric effect. Therefore, the aim of this work was to study the effect on the dose prescribed in breast with the INTRABEAM device using different soft tissue assignment strategies that would replace the adipose and glandular tissues that constitute the breast in cases where these tissues cannot be adequately distinguished in a CT scan. METHODS AND MATERIALS: Dose was computed with a Monte Carlo code in five patients with a 3 cm diameter INTRABEAM spherical applicator. Tissues within the breast were assigned following six different strategies: one based on the TG-43 recommendations, representing the whole breast as water of unity density, another one also water-based but with CT derived density, and the other four also based on CT-derived densities, using a single tissue resulting from different mixes of glandular and adipose tissues. These were compared against the reference dose computed in an accurately segmented CT, following TG-186 recommendations. Relative differences and dose ratios between the reference and the other tissue assignment strategies were obtained in three regions of interest inside the breast. RESULTS AND CONCLUSIONS: Dose planning in water-based tissues was found inaccurate for breast treatment with INTRABEAM, as it would incur in up to 30% under-prescription of dose. If accurate soft tissue assignments in the breast cannot be safely done, a single-tissue composition of 80% adipose and 20% glandular tissue, or even a 100% adipose tissue, would be recommended to avoid dose under-prescription.

Cost-effectiveness of intraoperative radiation therapy versus intensity-modulated radiation therapy for the treatment of early breast cancer: a disinvestment analysis.

BACKGROUND: Adjuvant radiotherapy represents a key component in curative-intent treatment for early-stage breast cancer patients. In recent years, two accelerated partial breast irradiation (APBI) techniques are preferred for this population in our organization: electron-based Intraoperative radiation therapy (IORT) and Linac-based External Beam Radiotherapy, particularly Intensity-modulated radiation therapy (IMRT). Recently published long-term follow-up data evaluating these technologies have motivated a health technology reassessment of IORT compared to IMRT. METHODS: We developed a Markov model to simulate health-state transitions from a cohort of women with early-stage breast cancer, after lumpectomy and adjuvant APBI using either IORT or IMRT techniques. The cost-effectiveness from a private health provider perspective was assessed from a disinvestment point of view, using life-years (LYs) and recurrence-free life-years (RFLYs) as measure of benefits, along with their respective quality adjustments. Expected costs and benefits, and the incremental cost-effectiveness ratio (ICER) were reported. Finally, a sensitivity and scenario analyses were performed to evaluate the cost-effectiveness using lower IORT local recurrence and metastasis rates in IORT patients, and if equipment maintenance costs are removed. RESULTS: IORT technology was dominated by IMRT in all cases (i.e., fewer benefits with greater costs). Despite small differences were found regarding benefits, especially for LYs, costs were considerably higher for IORT. For sensitivity analyses with lower recurrence and metastasis rates for IORT, and scenario analyses without equipment maintenance costs, IORT was still dominated by IMRT. CONCLUSIONS: For this cohort of patients, IMRT was, at least, non-inferior to IORT in terms of expected benefits, with considerably lower costs. As a result, IORT disinvestment should be considered, favoring the use of IMRT in these patients.

IOeRT conventional and FLASH treatment planning system implementation exploiting fast GPU Monte Carlo: The case of breast cancer.

Partial breast irradiation for the treatment of early-stage breast cancer patients can be performed by means of Intra Operative electron Radiation Therapy (IOeRT). One of the main limitations of this technique is the absence of a treatment planning system (TPS) that could greatly help in ensuring a proper coverage of the target volume during irradiation. An IOeRT TPS has been developed using a fast Monte Carlo (MC) and an ultrasound imaging system to provide the best irradiation strategy (electron beam energy, applicator position and bevel angle) and to facilitate the optimisation of dose prescription and delivery to the target volume while maximising the organs at risk sparing. The study has been performed in silico, exploiting MC simulations of a breast cancer treatment. Ultrasound-based input has been used to compute the absorbed dose maps in different irradiation strategies and a quantitative comparison between the different options was carried out using Dose Volume Histograms. The system was capable of exploring different beam energies and applicator positions in few minutes, identifying the best strategy with an overall computation time that was found to be completely compatible with clinical implementation. The systematic uncertainty related to tissue deformation during treatment delivery with respect to imaging acquisition was taken into account. The potential and feasibility of a GPU based full MC TPS implementation of IOeRT breast cancer treatments has been demonstrated in-silico. This long awaited tool will greatly improve the treatment safety and efficacy, overcoming the limits identified within the clinical trials carried out so far.

Intraoperative radiotherapy combined with spinal stabilization surgery-a novel treatment strategy for spinal metastases based on a first single-center experiences.

INTRODUCTION: Current treatment of spinal metastases (SM) aims on preserving spinal stability, neurological status, and functional status as well as achieving local control. It consists of spinal surgery followed by radiotherapy and/or systemic treatment. Adjuvant therapy usually starts with a delay of a few weeks to prevent wound healing issues. Intraoperative radiotherapy (IORT) has previously been successfully applied during brain tumor, breast and colorectal carcinoma surgery but not in SM, including unstable one, to date. In our case series, we describe the feasibility, morbidity and mortality of a novel treatment protocol for SM combining stabilization surgery with IORT. METHODS: Single center case series on patients with SM. Single session stabilization by navigated open or percutaneous procedure using a carbon screw-rod system followed by concurrent 50 kV photon-IORT (ZEISS Intrabeam). The IORT probe is placed via a guide canula using navigation, positioning is controlled by IOCT or 3D-fluroscopy enabling RT isodose planning in the OR. RESULTS: 15 (8 female) patients (71 ± 10y) received this treatment between 07/22 and 09/23. Median Spinal Neoplastic Instability Score was 8 [7-10] IQR. Most metastasis were located in the thoracic (n = 11, 73.3%) and the rest in the lumbar (n = 4, 26.7%) spine. 9 (60%) patients received open, 5 (33%) percutaneous stabilization and 1 (7%) decompression only. Mean length of surgery was 157 ± 45 min. Eleven patients had 8 and 3 had 4 screws placed. In 2 patients radiotherapy was not completed due to bending of the guide canula with consecutive abortion of IORT. All other patients received 8 Gy isodoses at mdn. 1.5 cm [1.1-1.9, IQR] depth during 2-6 min. The patients had Epidural Spinal Cord Compression score 1a-3. Seven patients (46.7%) experienced adverse events including 2 surgical site infection (one 65 days after surgery). CONCLUSION: 50 kV photon IORT for SM and consecutive unstable spine needing surgical intervention is safe and feasible and can be a promising technique in selected cases.

Combined Ultrahypofractionated Whole-Breast Irradiation and IORT-Boost: A Safety and Feasibility Analysis.

BACKGROUND: The current standard of local treatment for patients with localized breast cancer (BC) includes whole breast irradiation (WBI) after breast-conserving surgery (BCS). Ultrahypofractionated WBI schemes (1-week treatment) were shown not to be inferior to the standard WBI. Tumor bed boost using photon intraoperative radiotherapy (IORT) is safe and feasible in combination with standard WBI. The aim of the present study is to assess, for the first time, the feasibility and safety of combining photon IORT with ultrahypofractionated WBI. METHODS: Patients diagnosed with low-risk early BC candidates for BCS were included in this prospective study. IORT was administered at a dose of 20 Gy to the surface's applicator, and WBI was administered 3-5 weeks after surgery at a total dose of 26 Gy in five consecutive days. RESULTS: From July 2020 to December 2022, seventy-two patients diagnosed with low-risk early BC and treated in our institution were included in this prospective study. All patients completed the proposed treatment, and no severe acute or late grade 3 toxicity was observed 3 and 12 months after WBI, respectively. CONCLUSIONS: Our results confirm for the first time that the combination of ultrafractionation WBI and photon-IORT after BCS is a feasible and safe option in patients with early BC.

An Adjustable Wireless Backhaul Link Selection Algorithm for LEO-UAV-Sensor-Based Internet of Remote Things Network.

Internet of Remote Things (IoRT) networks utilize the backhaul links between unmanned aerial vehicles (UAVs) and low-earth-orbit (LEO) satellites to transfer the massive data collected by sensors. However, the backhaul links change rapidly due to the fast movement of both the UAVs and the satellites, which is different from conventional wireless networks. Additionally, due to the various requirements of IoRT multiservices, the system performance should be comprehensively considered. Thus, an adjustable wireless backhaul link selection algorithm for a LEO-UAV-sensor-based IoRT network is proposed. Firstly, an optimization model for backhaul link selection is proposed. This model uses Q, which integrates the remaining service time and capacity as the objective function. Then, based on the snapshot method, the dynamic topology is converted into the static topology and a heuristic optimization algorithm is proposed to solve the backhaul link selection problem. Finally, the proposed algorithm is compared with two traditional algorithms, i.e., maximum service time and maximum capacity algorithms. Numerical simulation results show that the proposed model can achieve better system performance, and the overload of the satellites is more balanced. The algorithm can obtain a trade-off between remaining service time and capacity by dynamically adjusting model parameters. Thus, the adjustable backhaul link selection algorithm can apply to multiservice IoRT scenarios.

Intraoperative electron beam intercomparison of 6 sites using mailed thermoluminescence dosimetry: Absolute dose and energy.

PURPOSE: In 2018, the Netherlands Commission on Radiation Dosimetry subcommittee on IORT initiated a limited intercomparison of electron IORT (IOERT) in Belgium and The Netherlands. The participating institutions have enough variability in age, type of equipment, and in dose calibration protocols. METHODS: In this study, three types of IOERT-dedicated mobile accelerators were represented: Mobetron 2000, LIAC HWL and LIAC. Mobetron produces electron beams with energies of 6, 9 and 12 MeV, while LIAC HWL and LIAC can deliver 6, 8, 10 and 12 MeV electron beams. For all energies, the reference beam (10 cm diameter, 0° incidence) and 5 cm diameter beams were measured, as these smaller beams are used more frequently in clinic. The mailed TLD service from the Radiation Dosimetry Services (RDS, Houston, USA) has been used. Following RDS' standard procedures, each beam was irradiated to 300 cGy at dmax with TLDs around dmax and around depth of 50 % dose (R50). Absolute dose at 100 % and beam energy, expressed as R50, could be verified in this way. RESULTS: All absolute doses and energies under reference conditions were well within RDS-stated uncertainties: dose deviations were <5 % and deviations in R50 were <5 mm. For the small 5 cm beams, all results were also within acceptance levels except one absolute dose value. Deviations were not significantly dependent on manufacturer, energy, diameter and calibration protocol. CONCLUSIONS: All absolute dose values, except one of a non-reference beam, and all energy values were well within the measurement accuracy of RDS TLDs.

Non-Terrestrial Networks for Energy-Efficient Connectivity of Remote IoT Devices in the 6G Era: A Survey.

The Internet of Things (IoT) is gaining popularity and market share, driven by its ability to connect devices and systems that were previously siloed, enabling new applications and services in a cost-efficient manner. Thus, the IoT fuels societal transformation and enables groundbreaking innovations like autonomous transport, robotic assistance, and remote healthcare solutions. However, when considering the Internet of Remote Things (IoRT), which refers to the expansion of IoT in remote and geographically isolated areas where neither terrestrial nor cellular networks are available, internet connectivity becomes a challenging issue. Non-Terrestrial Networks (NTNs) are increasingly gaining popularity as a solution to provide connectivity in remote areas due to the growing integration of satellites and Unmanned Aerial Vehicles (UAVs) with cellular networks. In this survey, we provide the technological framework for NTNs and Remote IoT, followed by a classification of the most recent scientific research on NTN-based IoRT systems. Therefore, we provide a comprehensive overview of the current state of research in IoRT and identify emerging research areas with high potential. In conclusion, we present and discuss 3GPP's roadmap for NTN standardization, which aims to establish an energy-efficient IoRT environment in the 6G era.

Postoperative Complications Following Lumpectomy With Intraoperative X-Ray Radiation Therapy: A Retrospective Comparative Study.

BACKGROUND: Lumpectomy with intraoperative radiation (IORT) is a relatively new modality for the treatment of early breast cancer. IORT delivers targeted radiation to the tumor bed and obviates the need for external beam radiation (EBRT) in 85% of the cases. IORT is being used increasingly around the world, however information regarding early and late postoperative complications associated with the procedure is limited. AIM: To describe and compare complication rates after lumpectomy and IORT with those seen after lumpectomy and EBRT or lumpectomy alone. METHODS: Clinical, demographic, and histopathological data were collected from electronic medical records and a retrospectively maintained database. Postoperative complications were compared for patients undergoing lumpectomy with IORT, lumpectomy with EBRT, and lumpectomy alone over the same period. RESULTS: A total of 445 patients were included in the study: 113 underwent lumpectomy with IORT, 253 had lumpectomy followed by EBRT, and 79 had Lumpectomy alone. Postoperative seroma was documented in 74 patients (65%) after IORT,87 (34%) after EBRT, and 9 (11%) after lumpectomy alone (P = .000). Surgical site infection requiring antibiotic treatment was diagnosed in 26 patients (23%) after IORT, 38 (15%) after EBRT, and 5 (6%) after lumpectomy alone (P = .013). Postoperative erythema was documented in 39 patients (34%) after IORT, 40 (16%) after EBRT, and 5 (6%) after lumpectomy alone (P = .000). Postoperative minor complications such as scar and breast deformity, edema, Mondor's syndrome, and chronic tenderness, were documented in 62 patients (55%) after IORT, 119 (47%) after EBRT, and 13 (17%) after lumpectomy alone (P = .000). The average follow-up was 14 months. CONCLUSIONS: IORT is associated with an increased rate of postoperative complications compared to EBRT or lumpectomy alone. Most complications are minor and transient. We hypothesize that the increased occurrence of complications may also be attributed to overreporting, which is associated with the introduction of a new technology. Educating physicians and patients about potential complications and their course may help establish expectations and improve the management of postoperative complications.

Intraoperative radiation therapy with 50 kV x-rays: A multi-institutional review.

This report covers clinical implementation of a low kV intraoperative radiation therapy (IORT) program with the INTRABEAM® System (Carl Zeiss Meditec AG, Jena, Germany). Based on collective user experience from eight institutions, we discuss best methods of INTRABEAM quality assurance (QA) tests, commissioning measurements, clinical workflow, treatment planning, and potential avenues for research. The guide provides pertinent background information and clinical justification for IORT. It describes the INTRABEAM system and commissioning measurements along with a TG100 risk management analysis to ensure safety and accuracy of the IORT program. Following safety checks, dosimetry measurements are performed for verification of field flatness and symmetry, x-ray output, and depth dose. Also discussed are dose linearity checks, beam isotropy, ion chamber measurements, calibration protocols, and in-vivo dosimetry with optically stimulated luminescence dosimeters OSLDs, and radiochromic film. Emphasis is placed on the importance of routine QA procedures (daily, monthly, and annual) performed at regular intervals for a successful IORT program. For safe and accurate dose delivery, tests of important components of IORT clinical workflow are emphasized, such as, dose prescription, pre-treatment QA, treatment setup, safety checks, radiation surveys, and independent checks of delivered dose. Challenges associated with in-vivo dose measurements are discussed, along with special treatment procedures and shielding requirements. The importance of treatment planning in IORT is reviewed with reference to a Monte Carlo-based commercial treatment planning system highlighting its main features and limitations. The report concludes with suggested topics for research including CT-based image-guided treatment planning and improved prescription dose accuracy. We hope that this multi-institutional report will serve as a guidance document on the clinical implementation and use of INTRABEAM IORT.

Efficacy and Safety of Intraoperative Radiotherapy for High-Grade Gliomas: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: High-grade gliomas (HGGs) are aggressive tumors of the central nervous system that cause significant morbidity and mortality. Despite advances in surgery and radiation therapy (RT), HGG still has a high incidence of recurrence and treatment failure. Intraoperative radiotherapy (IORT) has emerged as a promising therapeutic approach to achieve local tumor control while sparing normal brain tissue from radiation-induced damage. METHODS: A systematic review and meta-analysis were conducted following PRISMA guidelines to evaluate the use of IORT for HGG. Eligible studies were included based on specific criteria, and data were independently extracted. Outcomes of interest included complications, IORT failure, survival rates at 12 and 24 months, and mortality. RESULTS: Sixteen studies comprising 436 patients were included. The overall complication rate after IORT was 17%, with significant heterogeneity observed. The IORT failure rate was 77%, while the survival rates at 12 and 24 months were 74% and 24%, respectively. The mortality rate was 62%. CONCLUSION: This meta-analysis suggests that IORT may be a promising adjuvant treatment for selected patients with HGG. Despite the high rate of complications and treatment failures, the survival outcomes were comparable or even superior to conventional methods. However, the limitations of the study, such as the lack of a control group and small sample sizes, warrant further investigation through prospective randomized controlled trials to better understand the specific patient populations that may benefit most from IORT. However, the limitations of the study, such as the lack of a control group and small sample sizes, warrant further investigation. Notably, the ongoing RP3 trial (NCT02685605) is currently underway, with the aim of providing a more comprehensive understanding of IORT. Moreover, future research should focus on managing complications associated with IORT to improve its safety and efficacy in treating HGG.

Outcomes and complications of intraoperative radiotherapy versus external beam radiotherapy for early breast cancer.

BACKGROUND: Intraoperative radiotherapy (IORT) is an alternative for external beam radiotherapy (EBRT) for early stage breast cancer (BC). Herein, we compared outcomes, postoperative and post-radiation complications of IORT and EBRT. METHODS: We conducted a cohort study to compare complications of IORT and EBRT in patients. A checklist of the complications of IORT and EBRT, was used to assess and post-radiation complications and outcomes. RESULTS: Overall, 264 women (121 in IORT and 143 in EBRT group) with a mean (SD) age of 55 ± 8.6 years analyzed in this study. The IORT group (quadrantectomy + SLNB + IORT) had more severe post-operative pain compared to the EBRT group (quadrantectomy + SLNB) (OR = 1.929, 95% CI: 1.116-3.332). Other postoperative complications, including edema, erythema, seroma, hematoma, and wound complications were not significantly different between the IORT and EBRT groups. EBRT was associated with higher rates post-radiation complications, including erythema (95.8% vs. 21.5%), skin dryness (30.8% vs. 12.4%), pruritus (26.6% vs. 17.4%), hyperpigmentation (48.3% vs. 9.9%), and telangiectasia (1.4% vs. 0.8%). Multivariate analysis showed that erythema, skin dryness and pruritus, and hyperpigmentation were more severe in the EBRT group, while breast induration was higher in the IORT group (OR = 4.109, 95% CI: 2.242-7.531). Excellent, good, and fair cosmetic outcome was seen in 11.2%, 72%, and 16.8% of the patients in the EBRT group and 29.8%, 63.6%, and 6.6% in the IORT group, respectively, suggesting that the cosmetic outcome was significantly better in the IORT group (P < .001). There wasn't statistically significant difference in recurrence-free survival and overall survival rates between two groups of patients who received either IORT or EBRT (P = .953, P = .56). CONCLUSION: IORT is considered to have lower post-radiation complications and better cosmetic outcomes in breast cancer patients. Therefore, IORT might be used as the treatment of choice in eligible patients.

Clinical Outcomes of Breast-Conserving Surgery with Synchronous 50-kV X-ray Intraoperative Partial Breast Irradiation in Patients Aged 64 Years or Older with Low-Risk Breast Cancer.

Background: Breast-conserving surgery with synchronous 50-kV X-ray intraoperative radiation therapy (TARGIT-IORT) is a convenient form of partial breast irradiation; however, the existing literature supports a wide range of local control rates. Objectives: We investigated the treatment effectiveness and toxic effects of TARGIT-IORT in a patient cohort aged 64 years or older with low-risk breast cancer. Design: Retrospective analysis. Methods: Patients who received breast-conserving surgery with synchronous TARGIT-IORT at a single institution from 2016 to 2019 were reviewed. Additional whole breast irradiation was recommended at the discretion of the treating radiation oncologist. Baseline patient demographics and treatment details were recorded. Acute and chronic toxicities, measured using the Common Terminology Criteria for Adverse Events version 3.0 or 4.0 and breast cosmetic outcomes, using the Harvard Cosmesis score, were recorded. Locoregional recurrence, distant metastasis, and overall survival were recorded, and 5-year rates were estimated using the Kaplan-Meier method. Results: 61 patients were included with a median follow-up of 3.5 years and median age of 72 years. Eight (13%) patients received additional whole breast irradiation, and fifty-four (89%) received adjuvant hormone therapy. There were no local, regional, or distance recurrences. One patient died of complications from COVID-19 infection. Grade 2 + acute and chronic toxicities were observed in 6 (12%) and 7 (14%) patients, respectively. One patient experienced a grade 3 acute toxicity. Cosmetic outcome was "excellent" or "good" in 45 (92%) patients. Conclusions: Breast TARGIT-IORT was well tolerated and conferred excellent disease control in this cohort of patients with low-risk breast cancer. While continued follow-up is required, TARGIT-IORT may be an appropriate treatment option for this population.

Five Fraction Accelerated Partial Breast Irradiation Versus Intraoperative Radiation Therapy for Early-Stage Breast Cancer.

PURPOSE/OBJECTIVE(S): Accelerated partial breast irradiation (PBI) delivered in 5 fractions with intensity modulated radiation therapy (IMRT) has been shown to have comparable clinical outcomes to whole breast irradiation with reduced toxicity profiles. In contrast, intraoperative radiation therapy (IORT) offers patients the potential to complete adjuvant radiation therapy in a single treatment. While early data were promising, concerns exist regarding long-term rates of local recurrence after IORT. We present a comparison of 5 fraction PBI versus IORT. MATERIALS/METHODS: We performed a retrospective review of 473 patients with early-stage breast cancer treated at a single institution from 2011 to 2021 with 258 receiving PBI and 215 receiving IORT. PBI patients received 30 Gy in 5 fractions delivered with IMRT. IORT patients received 20 Gy in 1 fraction prescribed to the applicator surface at surgery using the low-energy TARGIT technique. RESULTS: Mean age was 71 years old (IQR:67-74) for IORT patients and 67 years old (IQR:62-72) for PBI patients. Median follow up was 5.7 years (IQR:4.2-7.0) for IORT patients and 2.4 years (IQR:1.8-3.3) for PBI patients (P < .001). Recurrence at any time (locoregional and distant) was seen in 7.9% (n = 17) of patients receiving IORT as compared to 0.8% (n = 2) of patients receiving PBI. IORT was associated with reduced rates of locoregional relapse free survival at 5 years (93.6% vs. 99.4%, P = .05) with no difference in overall survival(92.8% vs. 95.1%, P = .99). CONCLUSION: Low-energy TARGIT IORT was associated with higher rates of locoregional recurrence compared to PBI. These outcomes, consistent with other series and current guidelines, suggest a limited role for low-energy IORT as monotherapy.

Case Report: Bilateral targeted intraoperative radiotherapy: a safe and effective alternative for synchronous bilateral breast cancer.

Background: The incidence of bilateral breast cancer (BBC) ranges from 1.4% to 11.8%. BBC irradiation is a challenge in current clinical practice due to the large target volume that must be irradiated while minimizing the dose to critical organs. Supine or prone breast techniques can be used, with the latter providing better organ sparing; both, however, result in lengthy treatment times. The use of Intra-operative radiotherapy (IORT) in breast cancer patients who choose breast conservation has been highlighted in previous studies, but there is a scarcity of literature analyzing the utility and applicability of IORT in BBC. This case series aims to highlight the applicability of administering bilateral IORT in patients with BBC. Case reports: Five patients with bilateral early-stage breast cancer (or DCIS) were treated with breast-conserving surgery followed by bilateral IORT. Of the 10 breast cancers, 8 were diagnosed as either DCIS or IDC, while the other 2 were diagnosed as invasive lobular carcinoma and invasive carcinoma, respectively. During surgery, all patients received bilateral IORT. Furthermore, 1 patient received external beam radiation therapy after her final pathology revealed grade 3 DCIS. The IORT procedure was well tolerated by all five patients, and all patients received aromatase inhibitors as adjuvant therapy. Additionally, none of these patients showed evidence of disease after a 36-month median follow-up. Conclusion: Our findings demonstrate the successful use of IORT for BCS in patients with BBC. Furthermore, none of the patients in our study experienced any complications, suggesting the feasibility of the use of IORT in BBC. Considering the benefits of improved patient compliance and a reduced number of multiple visits, IORT may serve as an excellent patient-centered alternative for BBC. Future studies are recommended to reinforce the applicability of IORT in patients with BBC.

Intraoperative radiotherapy after resection of brain metastases located in the posterior fossa. Analysis of postoperative morbidity and mortality in a single center cohort.

INTRODUCTION: In order to improve surgical outcome and accelerate the adjuvant oncologic therapy, intraoperative Radiotherapy (IORT) has become a treatment option in oncologic surgery for various diseases including glioma and brain metastasis (BM). BMs are often located in the cranial posterior fossa (PF) requiring specific surgical considerations due to its complex anatomy. Up until now, data on IORT for BMs is limited and detailed description in the use of IORT for lesions in the PF is lacking. Our aim is to provide more insight into this emerging treatment strategy. METHODS: We performed a retrospective analysis of patients receiving surgery for BMs and undergoing IORT at our institution. Each patient was discussed at the interdisciplinary tumor board decision before the intervention. Patient characteristics, functional status (Karnofsky Performance Score, KPS) before and after surgery, disease (recursive partitioning analysis, lesion size) and operative parameters were analyzed. Adverse events (AE) were recorded up until 30 days after the intervention and rated according to the Clavien Dindo Rating scale. RESULTS: Nine patients (5 female) were included. None underwent prior radiotherapy (RT). Mean age was 66 ± 11 years. Preoperative median KPS was 80%. Mean BM diameter was 3.2 ± 0.9 cm. There was no statistically significant deterioration of the functional status after the intervention. Two patients experienced AEs with both of them needing revision surgery. CONCLUSION: Surgery for BMs with IORT in the PF seems safe and feasible. Further studies are needed to evaluate the influence of IORT on long-term outcome after BM surgery.