Intraoperative Electron Radiotherapy Research Articles

Calibration and validation of a bleeding detector for beveled PMMA applicators in electron intraoperative radiotherapy

This study aimed to calibrate and validate a capacitive-sensor bleeding detector, originally designed for flat applicators, with beveled applicators (bPMMA), which are among the most commonly used applicators in intraoperative radiotherapy with electron mobile linacs. The detector will help prevent dose misadministration during irradiation in the event of fluid accumulation in the applicator, thus allowing for appropriate intervention. The handicap with employing this detector for bPMMA stems from the fact that the level of accumulated fluid depends on both the tilting angle and orientation of the applicator. Furthermore, the fluid remains accumulated at the bottom corner of the applicator, reducing the sensitivity of the sensor. A 5-strip capacitive sensor has been used, attached to a 4 cm diameter 30° beveled applicator with a tilting angle range from 0° to 30°. The sensor is read out using dedicated electronics, including a Wheatstone bridge circuit, amplifier, filter stages, and microcontroller. To calculate the sensitivity of the sensor, a prior calibration of the circuit has been carried out in order to obtain the relationship between the output voltage of the conditioning circuit and the height of the fluid present in the applicator for different inclinations. Using the average sensitivity over the inclination range of interest can provide accurate measurements of the estimated fluid height up to 12 mm, with a maximum deviation of approximately 2.0 mm and less than 1.0 mm for the 5 mm clinic threshold. The use of the mean sensitivity is a practical approach for detecting bleeding in beveled applicators because it simplifies the measurement process by avoiding the need to obtain detector sensitivity for each inclination and orientation of the applicator, which would be complex if not impractical in clinical use.

Preliminary study on the correlation between accelerated current and dose in water for an electron-based LINAC

Purpose: Intraoperative electron radiotherapy (IOeRT) is considered the first clinical translation of FLASH with electrons. A crucial aspect is represented by the precise dose monitoring and measurement; to this aim, we propose a method fully based on Monte Carlo (MC) simulation that uses as input the beam current measurement and the beam optics simulation. To validate this approach, we chose the NOVAC11 (produced by Sordina IORT Technologies SpA) accelerator, which provides a well-studied model.Methods: We used FLUKA and FRED MC software to simulate in detail the geometry of the NOVAC11 and the coupled applicator usually adopted in clinical practice to deliver the dose in the surgical bed. The simulation results of the longitudinal and off-axis profiles and dose per pulse obtained in a water phantom with different applicators are compared to the experimental data.Results: A very good agreement not only for the relative dosimetry in both the longitudinal and off-axis profiles, with a gamma index pass rate of 100% with 3%/3 mm acceptance criteria, but also for the absolute dosimetry was obtained.Conclusion: The results completely validate the MC description of the system and provide a reliable evaluation of the dose per pulse and output factor with an accuracy of the order of few % for different sets of applicator diameters and lengths.

On the need of in vivo verifications as quality control for intraoperative electron radiotherapy in breast cancer.

Intraoperative electron radiotherapy (IOERT) is a technique aiming to deliver radiotherapy during oncological surgery. In breast IOERT, the applicator and shielding disc placement are correlated with organs at risk (OAR) irradiation, in vivo verification of these parameters is scarcely reported. The aim of our study is to report and analyze possible causes of the misalignment using radiochromic films and compare our results to others reported in the bibliography. From November 2019 to April 2023, in vivo verifications were performed for 33 patients. IOERT was performed using a LIAC 10MeV (Sordina, Italy) electron accelerator. We attached a radiochromic film to the upper side of the polytetrafluoroethylene cover of the shielding disc. The percentage of the irradiation area outside the disc was recorded and various parameters (applicator angulations, prescription depth, tumor location and breast size) were analyzed to find possible correlations. For 29 patients, 20Gy were prescribed while 10Gy were prescribed to 4 patients. The average irradiated area outside the disc was 19% (0-56%) corresponding to a surface of 4.5 cm2 (0-17.4 cm2). The applicator of 5cm was used for most of the patients. The mean prescription depth was 1.4cm (0.5-2.5cm). We found no correlation between the analyzed parameters and misalignment. This study confirms the presence and magnitude of the misalignments. We strongly recommend in vivo verifications as a quality check during IOERT procedures. The misalignment has no correlation with tumor localization parameters, so the solution could be based on technical improvements of the applicator.

Intra-operative radiation for pancreatic cancer: Initial experience at the Hadassah Medical Center.

634 Background: Prognosis following surgery for pancreatic cancer (PC) remains poor. Local recurrence is common and negatively impacts survival rate. In an effort to improve local control and potentially improve survival, we have adopted a strategy of adding intra-operative electron radiation therapy (IOeRT) to selected patients undergoing pancreatic resection (PR) for PC. Here we report our initial experience with this treatment modality. Methods: 14 patients (10 male, 4 female), age between 44 - 81 years (mean 66.17), who underwent PR (Head 7, Body7) between 1/2021-1/2023 were included in this analysis. Patients selected for IOeRT included patients that according to surgeon assessment were at risk not to achieve satisfactory resection margins by surgery alone. All had resectable or borderline resectable disease according to standard criteria. 8 patients underwent pre-op chemotherapy followed by stereotactic body radiotherapy (SBRT) to a dose of 25-40 Gy in 5 fractions to the tumor and regional lymphatics followed by PR (5 Whipple, 3 distal pancreatectomy) and IOeRT, 3 patients received preop SBRT followed by PR (3 distal pancreatectomy) + IOeRT, 2 patients underwent PR (whipple 1, distal pancreatectomy 1) + IoeRT, and 1 received neoadjuvant chemotherapy followed by SBRT only and did not undergo surgery due to tumor progression. Immediately following resection, mobile IOeRT accelerator using a 40-80mm applicator with a level of 0-15 degrees was directed at the tumor bed deemed at high risk for recurrence. 10-20 Gy was delivered using 6-8 MeV electrons to the 90% isodose line at the discretion of the treating radiation oncologist. Data including serial imaging, genomic analysis, radiation protocol, complications, pathological results and outcome was collected for analysis. Results: Mean follow up was 9.7 months (2-21). 8 patients are alive: 7 pts with no evidence of disease and 1 pt with liver metastases. 6 patients died: 4 with distant metastatic disease, 1 from disease progression prior to surgery and 1 from early post-op sepsis. Negative surgical margins were achieved in 10 patients of which 2 mutated BRCA gene carriers showed complete pathological response (both who received combined neoadjuvant chemotherapy followed by SBRT). Post-operative complications possibly attributed to RT included hepatic artery occlusion (1 pt), portal vein stenosis (1 pt) and prolonged GI tract dysfunction (1pt). Conclusions: Combining RT with resection appears feasible and safe. Our data possibly show a reduction in local recurrence following resection of PC, however, longer follow up is necessary. Refinements in patient selection and treatment protocol may further improve outcomes. Larger scale studies are required to determine the benefit of this modality.

Post-operative complications following dose adaptation of intra-operative electron beam radiation therapy in locally advanced or recurrent rectal cancer.

The benefit of intra-operative radiotherapy (IORT) in the treatment of locally advanced rectal cancer (LARC) or locally recurrent rectal cancer (LRRC) lie in its ability to provide high-dose of radiation to limited at-risk volume, thereby eliminating microscopic disease and decreasing toxicity. A comparative study between high-dose-rate (HDR) brachytherapy, named intra-operative brachytherapy (IOBT), and intra-operative electron radiotherapy (IOERT) was performed showing favorable LRFS after IOBT, possibly due to a higher surface dose that is inherent in IOBT technique. The IOERT technique in Catharina Hospital Eindhoven was adapted to increase the surface dose, aiming to improve local control. Post-operative complications due to an increased radiation dose remain the matter of concern. This retrospective study was performed to compare complication rates before and after adapted IOERT dose. All patients undergoing surgery with IOERT for LARC or LRRC from September 2019 until July 2023, were considered. Patients selected until August 31, 2021 were included in control cohort (n = 108), and those chosen from September 1, 2021 onwards were included in intervention cohort (n = 92). Perioperative and (major) post-operative complications were classified retrospectively, during admission, at 30 days, and at 90 days. In LARC patients, a decrease in post-operative complications was observed (p = 0.009). 19% of LARC patients experienced major post-operative surgical complications, i.e., Clavien-Dindo grade 3b-5, regardless of treatment group. No difference in major 90-day complications was noted (p = 0.142). In LRRC patients, the use of induction chemotherapy decreased from 78% to 29% (p < 0.001), which complicated comparison. However, no difference in major post-operative complications was observed at 30 days (p = 0.222) or 90 days (p = 0.977) after surgery. Increased surface dose of IOERT does not seem to lead to an increase in post-operative complications. Further research is needed to evaluate the efficacy of dose adaptation in IOERT to improve local oncological control rates. Routine evaluation of CTCAE scores in follow-up will help uncover possible long-term radiation-induced toxicity.

Design and performance validation of a novel 3d printed thin-walled and transparent electron beam applicators for intraoperative radiation therapy with beam energy up to 12 MeV.

A high-energy electron accelerator is used in the treatment of patients in the so-called intraoperative electron radiotherapy (IOERT). The work aimed to present the results of the validation of a new design of an electron beam applicator for use in IOERT. A novel solution was described along with the design optimization method based on Monte Carlo simulations. In this solution, the applicator consists of two parts. The lower exchangeable part collimates the therapeutic field. Measurements were made based on the International Electrotechnical Commission (IEC) standard recommendations. The measurement described in the standard has been adapted to the specificity of the intraoperative accelerator Source to Skin Distance - of 60 cm and applicators with a circular cross-sectional area. Measurements were performed for nominal beam energies of 6, 10, and 12 MeV and two therapeutic field diameters of 6 and 10 cm. The dose due to stray X-ray radiation in all energies is less than 0.3% and increases for energies from 6 to 12 MeV by 2.9 times from 0.1 for 6MeV to 0.29 for 12 MeV. The average dose due to leakage radiation also shows an increasing trend and is higher for a 6 cm diameter applicator. Validation confirmed the usefulness of the novel applicator design for clinical applications. Thanks to the use of 3D printing, it was possible to make applicators that are transparent, biocompatible and, at the same time, light and form a beam field with therapeutically useful accuracy, and the leakage radiation does not exceed normative recommendations.

First clinical application of image-guided intraoperative electron radiation therapy with real time intraoperative dose calculation in recurrent rectal cancer: technical procedure

Intraoperative radiation therapy (IORT) is a radiation technique applying a single fraction with a high dose during surgery. We report the first abdomino-pelvic application of an image-guided intraoperative electron radiation therapy with intraoperative real time dose calculation based on the individual intraoperative patient anatomy. A patient suffering from locoregionally recurrent rectal cancer after treatment with neoadjuvant re-chemoradiation was chosen for this approach. After surgical removal of the recurrence, an adequate IORT applicator was placed as usual. A novel mobile imaging device (ImagingRing, MedPhoton) was positioned around the patient covering the region to be treated with the IORT-applicator in place. It allowed the acquisition of three-dimensional intraoperative cone-beam computed tomography images suitable for dose calculation using an automated scaling (heuristic object and head scatter as well as hardening corrections) of Hounsfield units. After image acquisition confirmed the correct applicator position, the images were transferred to our treatment planning system for intraoperative dose calculation. Treatment could be accomplished using the calculated dose distribution. We herein describe the details of the procedure including necessary adjustments in the typically used IORT equipment and work flow. We further discuss the pros and cons of this new approach generally overcoming a decade long limitation of IORT procedures as well as future perspectives regarding IORT treatments.

Comparison of mammography and ultrasound findings in the follow-up of patients with breast cancer treated with segmental mastectomy followed by intraoperative electron radiotherapy versus external whole breast radiotherapy

This study aims to describe imaging findings in patients treated with intraoperative electron radiotherapy and compare them with those detected in patients treated with external whole breast radiotherapy (WBRT). The study population consisted of 25 patients who received intraoperative radiotherapy [IORT (21 Gy)] as single-dose radiotherapy and a control group of 25 patients who received WBRT at the same institution. Mammography and ultrasound (US) findings were divided into three groups: minor, intermediate, and advanced. On mammography, mass lesions were considered advanced, and asymmetries or architectural distortions were considered intermediate. Oil cysts, linear scars, and the increase in parenchymal density were considered minor findings. On US, irregular non-mass lesions were considered advanced, and circumscribed hypoechoic lesions or planar irregular scars with shadowing were considered intermediate. Oil cysts, fluid collections, or linear scars were considered minor findings. On mammography, skin thickening (P = 0.001), edema (P < 0.001), increased parenchymal density (P < 0.001), dystrophic calcifications (P = 0.045), and scar/distortion (P = 0.005) were significantly more common in the WBRT group. On US, irregular non-mass lesions, which made interpretation considerably difficult, were significantly more common in the IORT group (P = 0.004). Dominant US findings were fluid collections and postoperative linear or planar scars in the WBRT group. Minor findings were more common in low-density breasts, and major findings (intermediate and advanced) were more common in high-density breasts on both mammographies (P = 0.011) and US (P = 0.027) in the IORT group. Ill-defined non-mass lesions detected on US in the IORT group have not been defined previously. Radiologists should be aware of these lesions because they can be confusing, especially in early follow-up studies. This study has found that minor findings are seen more frequently in low-density breasts, while major findings are more common in high-density breasts in the IORT group. This has not been reported before, and further studies with more cases are needed to verify these results.

Evaluation of intraoperative breast radiotherapy on local recurrence: a Brazilian cohort

Purpose Assess the local recurrence rate and global survival rate among women diagnosed with breast cancer who underwent intraoperative electron radiotherapy (IOERT) between 2007 and 2017, in a single private healthcare setting in Belo Horizonte, Brazil. Material and Methods This is a retrospective study based on medical records about the outcomes of patients submitted to breast-conserving surgery followed by IOERT. The collected variables included the patient’s profile and tumor features, IOERT isodose, and outcomes. The quantitative data were presented in tables of frequency. The survival curves were created with the Kaplan-Meier method. In all tests, the adopted relevance level was 5%. The analyses were carried out with SPSS version 25.0. Results and Conclusions The samples consisted of 78 patients, among which a total of 14 (17.9%) recurrences were observed. The median time of recurrence was 49 months after the IOERT was performed. Of the 78 patients analyzed, 13 (16.7%) died, 5 (6.4%) of which were due to breast cancer. The global survival rate in 5 years was 94.9% and 90.4% in 10 years. The local recurrence rate in 5 years was 89.7% and 86.4% in 10 years. Our findings revealed a higher local recurrence rate than the literature data. However, our results also showed that patients classified as low-risk had an overall survival of 5 and 10 years similar to other studies in the literature, reaffirming that low-risk women can benefit from IOERT. Given this finding, it is reaffirmed that rigorous eligibility criteria for IOERT are critical to reducing local recurrence.

Evaluating the induced photon contamination by different breast IOERT shields using Monte Carlo simulation.

Avoiding the underlying healthy tissue over-exposure during breast intraoperative electron radiotherapy (IOERT) is owing to the use of some dedicated radioprotection disks during patient irradiation. The originated contaminant photons from some widely used double-layered shielding disks including PMMA+Cu, PTFE+steel, and Al+Pb configurations during the breast IOERT have been evaluated through a Monte Carlo (MC) simulation approach. Produced electron beam with energies of 6, 8, 10, and 12 MeV by a validated MC model of Liac12 dedicated IOERT accelerator was used for disk irradiations. Each of above-mentioned radioprotection disks was simulated inside a water phantom, so that the upper disk surface was positioned at R90 depth of each considered electron energy. Simulations were performed by MCNPX (version 2.6.0) MC code. Then, the energy spectra of the contaminant photons at different disk surfaces (upper, middle, and lower one) and relevant contaminant dose beneath the studied disks were determined and compared. None of studied shielding disks show significant photon contamination up to 10 MeV electron energy, so that the induced photon dose by the contaminant X-rays was lower than those observed in the disk absence under the same conditions. In return, the induced photon dose at a close distance to the lower disk surface exceeded from calculated values in the disk absence at 12 MeV electron energy. The best performance in contaminant dose reduction at the energy range of 6-10 MeV belonged to the Al+Pb disk, while the PMMA+Cu configuration showed the best performance in this regard at 12 MeV energy. Finally, it can be concluded that all studied shielding disks not only don't produce considerable photon contamination but also absorb the originated X-rays from electron interactions with water at the electron energy range of 6-10 MeV. The only concern is related to 12 MeV energy where the induced photon dose exceeds the dose values in the disk absence. Nevertheless, the administered dose by contaminant photons to underlying healthy tissues remains beneath the tolerance dose level by these organs at the entire range of studied electron energies.

Full-Dose Intraoperative Electron Radiotherapy for Early Breast Cancer: Evidence from a Single Center’s Experience

To evaluate the clinical response rate and cosmetic outcome after full-dose intraoperative electron radiotherapy (IOERT) in early breast cancer (BC) treated with conserving surgery. Inclusion criteria were: &gt;60 years old, clinical tumor size ≤2 cm, luminal A carcinoma, patological negative lymph nodes, excluded lobular carcinoma histology. IOERT was delivered with a dose of 21 Gy at 90% isodose. Clinical, cosmetic and/or instrumental follow-up were performed 45 days after IOERT, 6 months after the first check, and every 12 months thereafter. Acute and late toxicities were assessed with the CTCAE v.4.03 and EORTC-RTOG scales, respectively. Cosmetic outcome was evaluated using the Harvard/NSABO/RTOG Breast Cosmesis Grading Scale. Overall, 162 consecutive patients were included in this analysis (median follow-up: 54 months, range: 1–98 months). The overall response rate was 97.5% (CI 95%: 0.93–0.99%). Locoragional relapse occurred in 2.5% of patients. No patient showed distant metastases. No patient showed radiation-related acute complications, with 3.7% showing late G2–3 toxicity. Only 3.7% of patients showed poor cosmetic results. Our data confirmed that IOERT is a feasible and valid therapeutic option in low-risk BC patients treated with lumpectomy. A low local recurrence rate combined with good cosmetic results validates the settings of our operative method in routinely clinical practice.

Comparing Oncologic Outcomes and Toxicity for Combined Modality Therapy vs. Carbon-Ion Radiotherapy for Previously Irradiated Locally Recurrent Rectal Cancer.

No standard treatment paradigm exists for previously irradiated locally recurrent rectal cancer (PILRRC). Carbon-ion radiotherapy (CIRT) may improve oncologic outcomes and reduce toxicity compared with combined modality therapy (CMT). Eighty-five patients treated at Institution A with CIRT alone (70.4 Gy/16 fx) and eighty-six at Institution B with CMT (30 Gy/15 fx chemoradiation, resection, intraoperative electron radiotherapy (IOERT)) between 2006 and 2019 were retrospectively compared. Overall survival (OS), pelvic re-recurrence (PR), distant metastasis (DM), or any disease progression (DP) were analyzed with the Kaplan-Meier model, with outcomes compared using the Cox proportional hazards model. Acute and late toxicities were compared, as was the 2-year cost. The median time to follow-up or death was 6.5 years. Median OS in the CIRT and CMT cohorts were 4.5 and 2.6 years, respectively (p ≤ 0.01). No difference was seen in the cumulative incidence of PR (p = 0.17), DM (p = 0.39), or DP (p = 0.19). Lower acute grade ≥ 2 skin and GI/GU toxicity and lower late grade ≥ 2 GU toxicities were associated with CIRT. Higher 2-year cumulative costs were associated with CMT. Oncologic outcomes were similar for patients treated with CIRT or CMT, although patient morbidity and cost were lower with CIRT, and CIRT was associated with longer OS. Prospective comparative studies are needed.

Outcomes of surgical resection and intraoperative electron radiotherapy for patients with para-aortic recurrences of gastrointestinal and gynecologic malignancies

BackgroundPara-aortic lymph node (PALN) metastases from primary pelvic malignancies are often treated with resection, but recurrence is common. We report toxicity and oncologic outcomes for patients with PALN metastases from gastrointestinal and gynecologic malignancies treated with resection and intraoperative electron radiotherapy (IORT).MethodsWe retrospectively identified patients with recurrent PALN metastases who underwent resection with IORT. All patients were included in the local recurrence (LR) and toxicity analyses. Only patients with primary colorectal tumors were included in the survival analysis.ResultsThere were 26 patients with a median follow up of 10.4 months. The rate of para-aortic local control (LC) was 77% (20/26 patients) and the rate of any cancer recurrence was 58% (15/26 patients). Median time from surgery and IORT to any recurrence was 7 months. The LR rate for those with positive/close margins was 58% (7/12 patients) versus 7% (1/14 patients) for those with negative margins (p = 0.009). 15% (4/26 patients) developed surgical wound and/or infectious complications, 8% (2/26 patients) developed lower extremity edema, 8% (2/26 patients) experienced diarrhea, and 19% (5/26 patients) developed an acute kidney injury. There were no reported nerve injuries, bowel perforations, or bowel obstructions. For patients with primary colorectal tumors (n = 19), the median survival (OS) was 23 months.ConclusionsWe report favorable LC and acceptable toxicity for patients receiving surgical resection and IORT for a population that has historically poor outcomes. Our data show disease control rates similar to literature comparisons for patients with strong risk factors for LR, such as positive/close margins.

Long-term results of breast cancer patients who received IOERT as boost during BCS: A single-institution retrospective analysis.

Intraoperative electron radiotherapy (IOERT) applied as boost to the tumor bed during breast conserving surgery is advantageous in terms of local recurrence in breast cancer patients. In addition, it has other advantages over the adjuvant boost RT such as no risk of tumor bed change, ease of sequencing radiotherapy chemotherapy, and reduced workload of the radiotherapy clinic. This study aimed to evaluate the long-term results of our patients who were treated with this method in our institution and are still being followed up. One hundred and three patients enrolled in this study received IOERT equivalent to 10 Gy as boost during BCS and were subsequently given adjuvant WBI according to the biological subtype of the tumor systemic therapy. These patients were analyzed using their files and hospital records. Patients were evaluated for overall survival, local recurrence, distant metastasis, and cosmetic outcome (using LENT-SOMA scale). Median age was 53,5 (27-74), mean follow-up time was 75 (48-106) months. Mean pathological tumor size was 18 mm (4-30), 90 of the patients had invasive ductal carcinoma, eight of them were lobular and five of them had mixed histological structure. Ninety-three of the patients presented histological grade II, 15 grade III; 74 patients were luminal A-like, 15 luminal B-like, eight HER2 positive and six triple negative breast cancer. According to the LENT-SOMA scale, 35 had grade 0, 42 each had grade I, 23 had grade II, and two had grade III. All patients underwent whole breast irradiation after surgery, 81 received chemotherapy and 90 endocrine therapy. There was one local recurrence, distant recurrence was seen in four patients and one patient died of non-breast cancer causes. Overall survival was %99, and event free survival %96. IOERT for breast cancer treatment during BCS is a safe option with low chronic toxicity and the cosmetic outcome gets better over time.

IOeRT in retroperitoneal sarcoma: Towards more organ preservation with comparable oncological outcomes

BackgroundRetroperitoneal sarcomas (RPS) present a surgical challenge with high rates of local recurrence (LR). We investigated the role of intraoperative electron radiotherapy (IOeRT) in reducing LR after surgical resection of RPS. MethodsA retrospective analysis of all patients who underwent surgical resection for RPS between 2014 and 2021 at a tertiary academic referral center (n = 172). Patients included underwent surgical resection of their RPS and received IOeRT (n = 36) and were compared by case control matching to patients with similar tumor characteristics (recurrence status and tumor grade) that did not receive IOeRT (n = 36). ResultsThe median length of hospitalization was 8 days (range, 4–34) in the IOeRT group and 10 days (range, 2–42) in the non-IOeRT group (p = 0.25). The mean operating room (OR) time was 4h (±1.3) and 4h (±1.9) in the IOeRT and non-IOeRT groups respectively, (p = 0.37). Complete resection with R0 margins was achieved in 30 patients (83.3%) and 24 patients (66.6%) in the IOeRT and non-IOeRT groups, respectively (p = 0.1). R1 resection was achieved in 6 patients (16.6%) and 12 patients (33.3%) respectively, (p = 0.1). The resected organ weighted score was significantly different between the groups; score 0 observed in 19 (52.7%) patients in the IOeRT group and 3 (8.3%) in the non-IOeRT group (p < 0.001), score 1 observed in 7 (19.4%) in the IOeRT group and 17 (47.2%) in the non-IOeRT group (p = 0.012). The rate of severe complications (CD score>3) did not differ between the groups, 5 (13.8%) patients in the IOeRT group and 9 (25%) patients in the non-IOeRT group (p = 0.23). No radiation associated complications were noted. The 2-year local recurrence free survival (LRFS) was 75.9% in the IOeRT group and 60.3% in the non-IOeRT group (p = 0.4). The 2-year IOeRT field recurrent free survival (IRFS) was 88.4% in the IOeRT group and 60.3% in the non-IOeRT group (p = 0.04). ConclusionsThe use of IOeRT did not increase the rate of surgical complications and was associated with superior local control in the radiation field, improved organ preservation without an impact on overall survival.

Whole Breast Irradiation Versus Intraoperative Electron Radiation Therapy for Breast Conserving Therapy: A Large Mature Single Institution Matched-Pair Evaluation of True Local Relapse, Progression Free Survival, and Overall Survival

Comparative outcome data after intraoperative radiation therapy and whole breast irradiation (WBI) for breast cancer at >10 years median follow-up are rare. We present a mature, single-institution, matched-pair comparison reporting survival and relapse rates in patients treated with either modality. Complete data sets for 258 intraoperative electron radiation therapy (IOERT) patients treated between 2000 and 2010 were matched with 258 patients postoperatively treated with WBI by age/histology/tumor size, grading/lymph-node-status/hormone receptors/type of adjuvant therapy/surgical margins, and treatment date. Relapse at surgical intervention site was classified as true local recurrence (LR). All recurrences in the treated breast (any quadrant) were classified as ipsilateral recurrence (IR). Median follow-up was 157 months (12-251) for the IOERT group and 154 months (31-246) for the WBI group. Cumulative incidence of IR at 5, 10, and 15 years was 2.4%, 7.9%, and 12.7% for IOERT and 1.2%, 4.1%, and 5.0% for WBI (P=.02). Cumulative incidence of LR at 5, 10, and 15 years was 1.6%, 5.1%, and 8.3% for IOERT and 0.4%, 2.1%, and 2.5% for WBI (P=.02). No differences in overall survival, disease-free survival, second cancer incidence, or cardiac events were recorded in either treatment group. Outcome was better in the accelerated partial breast irradiation (APBI)-suitable group than in the APBI-unsuitable group (2009 criteria) (cumulative incidence of IR at 5, 10, and 15 years was 0% vs 7.3%, 6.1% vs 13.3%, and 7.3% vs 19.9% for IOERT and 0% vs 1.8%, 2.0% vs 3.9%, and 3.1% vs 3.9% for WBI) and in the revised APBI-suitable group than in the APBI-cautionary group (2017 criteria) (cumulative incidence of IR at 5, 10, and 15 years was 1.1% vs 6.4%, 6.2% vs 13.3%, and 7.8% vs 27.5% for IOERT and 1.7% vs 0%, 4.1% vs 4.4%, and 5.4% vs 4.4% for WBI). The IR and LR rate were higher after IOERT than after WBI for the American Society for Radiation Oncology suitable patient group, although without reaching statistical significance. Thus, IOERT could be an alternative to WBI upon stringent patient selection, but patients should be counseled carefully about the potential for increased IR rate with IOERT. Second cancer incidence and cardiac events did not differ between IOERT and WBI.

Estimating the skin dose near to the applicator and acute toxicity in breast cancer patients: An intraoperative electron radiotherapy technique.

Intraoperative electron radiation therapy (IOERT) is one of the most recently popular therapeutic methods for breast cancer. This study aimed to measure the skin dose near the applicator during IOERT of breast cancer patients, as well as, the incidence of acute toxicity after surgery. Thirty-six female patients participated in the current study with the prescribed dose of 21 and 12 Gy for IOERT as full and boost, respectively. The skin dose was investigated based on different applicator sizes, tumor bed thicknesses, and monitor units (MUs). The energy was chosen 8 MeV, and EBT3 film was used for the dosimetric process. In addition, the acute toxicity included healing time for the surgical wound, scaling of the skin, itching, necrosis, redness as well as seroma formation for 1 week and 1 month were recorded. The results were compared to those of 22 patients who underwent the surgery without IOERT. The highest skin dose for the patients was obtained 2.09 Gy, which is lower than the threshold dose (6 Gy). Furthermore, the findings showed that the average skin dose was higher in bigger applicator sizes and MU and lower tumor bed thicknesses. The average of wound healing for the patient underwent IOERT and without the use of IOERT (as the control group) was 19.32 and 11.67 days, respectively. One month after surgery, the volume of aspirated seroma was higher in the patients who performed IOERT compared to the control group (250 ml vs. 200 ml). It is notable that there were not observed any redness, itching, scaling, and necrosis in both investigated groups. Owing to the results, the skin dose during IOERT was lower than the recommended level. The dose of IOERT as a full was higher than boost which can be related to the lower number of the patients in full method; however, there was a well-tolerated without severe acute complication, especially seroma formation and wound healing time in both full and boost methods.

Dosimetric characteristics of the LIAC intraoperative radiotherapy beams: Assessment of sensitivity to measurement errors at the commissioning phase

Commissioning of the LIAC intraoperative electron radiotherapy (IOERT) unit relies on the vendor's SWL-LIAC software. This software simulates the percentage depth-doses (PDDs), off-axis dose profiles and relative output factors (ROFs) for all beams based on a small set of input measurements. To date, the impact of various possible measurement errors during commissioning on LIAC dosimetric characteristics has not been studied in detail. We aimed to assess the sensitivity of the dosimetric characteristics of the ‘LIAC 12 MeV’ IOERT unit beams to various measurement errors in the commissioning phase by obtaining the magnitude of the influence of each error.The required SWL-LIAC inputs (PDDs of applicator diameters 3, 7, and 10 cm and open field) were measured with intentional applicator misalignments including 1° rotation or lateral (2 mm) or vertical (±2 mm) displacements. Also, inaccurate water surface definition for the detector was simulated by using PDDs that were shifted by ±2 mm. The errors were applied one at a time. To identify the most influential errors, the computed relative dosimetric characteristics resulting from such erroneous measurement conditions were compared to the corresponding ‘error-free’ ones. The depths of 90% and 50% doses (R90 and R50, respectively) were investigated further.All the resulting errors in R90, R50, flatness, symmetry and penumbra were within 3.9 mm, 2.8 mm, 4.3%, 4.6% and 3.5 mm, respectively. The overall averages of the absolute differences in these indices from the error-free fields were 0.8 mm, 0.8 mm, 0.6%, 0.4% and 0.5 mm, respectively. Errors in water surface definition for the detector had 4.4 to 22 times greater influence on PDDs than the other errors. The corresponding values for the profiles were 1.3–5.8 times. Among the errors in applicator alignment, PDDs and profiles were more affected by rotational and vertical ‘stand-in’ applicator misalignments, respectively. The R90 and R50 values were less affected by the errors in the small (3 and 4 cm diameter) and 45° bevelled applicators.To conclude, on average, the studied errors caused relatively small changes in beam characteristics although the maximum magnitudes of the observed errors were fairly substantial. Among the investigated errors, defining the water surface inaccurately has the largest impact on the dosimetric characteristics. Overall, sensitivity to the studied errors was found to be greatest with large-diameter flat applicators and/or lower electron energies. Although individual errors in applicator alignment have less effect on dosimetric characteristics compared to water surface error, given that these errors may occur simultaneously during dosimetry, special attention should be paid to placing the applicator correctly at the surface. Special set-up aids, such as our in-house tool for aligning applicators, are therefore indicated. The findings also further highlight the need for checking the water level periodically in long-term dosimetry procedures.

Systematic review of intraoperative radiation therapy for head and neck cancer.

Multidisciplinary treatments with surgery, radiation therapy, and chemotherapy are the cornerstones in the management of locally advanced head and neck malignancies. In most cases, radiation is delivered via external beam radiation therapy (EBRT). Intraoperative radiation therapy (IORT), on the other hand, is the delivery of precise doses of radiation to selected target volumes within the exposed surgical field while at the operating room. Most studies on its use on head and neck cancers are limited to single-institutional retrospective case series. We performed a systematic review to consolidate the existing literature on IORT for head and neck malignancies. Fifty-two studies representing a mixed population of 2,389 patients were included in this review. IORT via electrons (intraoperative electron radiation therapy), brachytherapy (intraoperative high dose-rate brachytherapy) or photons was administered in numerous settings, but most commonly as part of a reirradiation regimen following salvage surgery for recurrent tumours. Often, additional EBRT was also planned postoperatively. This review illustrates that IORT is a promising treatment modality in head and neck cancer. Multiple single-institutional studies spanning several decades have demonstrated benefit in terms of local control with reasonable toxicity. However, randomised trials comparing it with current standards of care are still needed.

Intraoperative electron radiotherapy in early invasive ductal breast cancer: 6-year median follow-up results of a prospective monocentric registry

BackgroundIntraoperative electron radiotherapy (IOERT) can be used to treat early breast cancer during the conservative surgery thus enabling shorter overall treatment times and reduced irradiation of organs at risk. We report on our first 996 patients enrolled prospectively in a registry trial.MethodsAt Jules Bordet Institute, from February 2010 onwards, patients underwent partial IOERT of the breast. Women with unifocal invasive ductal carcinoma, aged 40 years or older, with a clinical tumour size ≤ 20 mm and tumour-free sentinel lymph node (on frozen section and immunohistochemical analysis). A 21 Gy dose was prescribed on the 90% isodose line in the tumour bed with the energy of 6 to 12 MeV (Mobetron®-IntraOp Medical).ResultsThirty-seven ipsilateral tumour relapses occurred. Sixteen of those were in the same breast quadrant. Sixty patients died, and among those, 12 deaths were due to breast cancer. With 71.9 months of median follow-up, the 5-year Kaplan–Meier estimate of local recurrence was 2.7%.ConclusionsThe rate of breast cancer local recurrence after IOERT is low and comparable to published results for IORT and APBI. IOERT is highly operator-dependent, and appropriate applicator sizing according to tumour size is critical. When used in a selected patient population, IOERT achieves a good balance between tumour control and late radiotherapy-mediated toxicity morbidity and mortality thanks to insignificant irradiation of organs at risk.