Postoperative cosmetic outcome of intraoperative radiotherapy in comparison to whole breast radiotherapy in early stage breast cancer; a retrospective cohort study.

BACKGROUND: In this study, we aim to evaluate the cosmetic outcome differences between Intraoperative electron beam radiation therapy (IOERT) and whole breast radiotherapy (WBR) with further investigation of boosted IOERT. METHODS: This retrospective cohort study was conducted in two referral centers in Tehran, Iran. 116 women aged 30 to 79 with early-stage breast cancer (T0-2N0-1M0) eligible for breast conservation were divided into two groups of 58 based on the intervention they received, and further subgroups were defined based on receiving boosted IOERT. Patients in both groups underwent breast conservation surgery and those in the IOERT group received either a 21 Gy radical dose (radical IOERT) or 12 Gy boosted electron beam radiotherapy and a routine fractionated dose of 50 Gy in 25 sessions of WBR (boosted IOERT). Those in the WBR group were administered 50Gy in 32 sessions. Physician-assessed cosmetic outcome was defined as the primary result and incidence of fat necrosis and fibrosis and post-operative chronic pain were secondary outcomes. RESULTS: Post-operative cosmetic outcome scores and chronic pain, showed no significant difference between the two groups. The median cosmetic score in both groups was 9. Fat necrosis and fibrosis had significantly higher rates in the IOERT group (P. VALUE: 0.001). However, the majority (21/34 or 61.8%) of this complication was observed in the boosted IOERT subgroup and no statistical significance was recorded between the radical IOERT subgroup and the WBR group. CONCLUSIONS: In early-stage breast cancer treatment, radical IOERT has noninferiority compared to WBR in terms of cosmesis. Regarding fat necrosis and fibrosis, boosted IOERT was associated with higher rates in comparison to other groups. Therefore, radical IOERT seems to be a better treatment option for selected patients.

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

BACKGROUND: Intraoperative 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. METHODS: At 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). RESULTS: Thirty-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%. CONCLUSIONS: The 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.

Adenoid cystic carcinoma of the breast and intraoperative electron radiotherapy: single case report and review of literature.

Adenoid cystic carcinoma (ACC) of the breast is a very rare neoplasm. It presents a triple-negative phenotype in most cases, but its prognosis is generally considered to be better than other breast cancers with the same immunohistochemical pattern. Due to its controversial features, no data are available in the literature regarding a consensus approach for ACC treatment, especially for subtypes with worse prognosis like solid basaloid ACC. We present for the first time a rare case of ACC with multifocal presentation treated with breast-conservative surgery and intraoperative electron radiotherapy, thus supporting this treatment of ACC in selected patients like young women affected by the solid basaloid variant who commonly present a worse prognosis. In this case, no local or systemic recurrence was detected after 30 months of follow-up.

Plain language summary Breast cancer is a large group of tumors with different and specific features. Because of its variety, no univocal guidelines are available to medical doctors for the treatment of this disease, especially for the rarest presentations. This is the case for breast adenoid cystic carcinoma, a rare tumor which accounts for less than 0.1% of all breast cancers and about which few instructions for its therapeutic approach or prognosis are described in the literature. This case report describes our experience using partial breast resection in combination with a specific protocol of intraoperative radiation for the treatment of an aggressive variant of breast adenoid cystic carcinoma. Good cosmetic results and no recurrence of the disease were shown, suggesting that a conservative approach could avoid unnecessary total breast resection as supported by some previous authors.

Intraoperative electron radiation therapy after salvage surgery in gynecological cancers and retroperitoneal sarcomas: outcomes and adverse effects.

Background: Salvage surgery is considered an option for isolated recurrences of retroperitoneal and pelvic tumors, in patients who have undergone previous radiotherapy. In order to increase local control intra operative electron radiation therapy (IOERT) can be used in these patients to administer additional radiation dose. We evaluated the outcomes and adverse effects in patients with retroperitoneal sarcoma and gynecologic tumors after salvage surgery and IOERT. Materials and methods: Twenty patients were retrospectively analyzed. Twenty-three IOERT treatments were performed after surgery. Six (30%) were sarcoma and 14 (70%) were gynecological carcinoma. Administered dose depended on previous dose received with external beam radiotherapy (EBRT) and proximity to critical structures. The toxicities were scored using the Common Terminology Criteria for Adverse Events version 4.0. Results: The median age of the patients was 51 years (range 34-70). After a median follow-up of 32 months (range 1-68), in the sarcoma group the local control rate was 66.6%; while in the gynecological group the local control rate was 64.3%. In relation to late toxicity, one patient had a Grade 2 vesicovaginal fistula, and one patient presented Grade 4 enterocolitis and enteric intestinal fistula. Conclusions: IOERT could have a role in the treatment of retroperitoneal sarcomas in primary tumors after EBRT, as it may suggest a benefit in local control or recurrences after surgical resection in those at high risk of microscopic residual disease. The addition of IOERT to salvage resection for isolated recurrence of gynecologic cancers suggest favorable local control in cases with concern for residual microscopic disease.

Comparing the performance of some dedicated radioprotection disks in breast intraoperative electron radiotherapy: a Monte Carlo study.

Radiation-shielding of healthy tissue is mandatory in breast intraoperative electron radiotherapy (IOERT). In this regard, dedicated radioprotection disks have been introduced. The aim of this study was to evaluate and compare the performance of three radioprotection disks widely used for breast IOERT. A Monte Carlo simulation approach was used for this purpose. The considered disks included Al + Pb, PMMA + Copper, and PTFE + Steel. They were stimulated by means of the MCNPX Monte Carlo code at depths around R100 and R90 of different electron energies in a water phantom, and their impact on the dosimetric properties of the therapeutic beam was evaluated in both correct and upside down disk placements. The electron energy spectrum immediately above and below each disk was calculated and analyzed. Furthermore, performance characteristics of the studied disks such as backscatter factors (BSFs) and transmission factors (TFs) at different electron energies were determined and compared. The results show that the Al + Pb disk most effectively attenuates the beam, while at the same time exhibits maximum BSF values. Employing the PMMA + Copper disk can minimize the BSF value but at the expense of an increased TF. The Al + Pb disk showed the best performance from the radiation protection viewpoint, while its highest BSF values could lead to perturbation of dose homogeneity within the target volume. PTFE + Steel disk showed an intermediate performance regarding the electron backscattering and transmission among the studied disks. The reverse placement of each disk can substantially increase the BSF value as compared to the correct situation but had less impact on the TF value.

Practical issues regarding angular and energy response in in vivo intraoperative electron radiotherapy dosimetry.

AIM: To estimate angular response deviation of MOSFETs in the realm of intraoperative electron radiotherapy (IOERT), review their energy dependence, and propose unambiguous names for detector rotations. BACKGROUND: MOSFETs have been used in IOERT. Movement of the detector, namely rotations, can spoil results. MATERIALS AND METHODS: We propose yaw, pitch, and roll to name the three possible rotations in space, as these unequivocally name aircraft rotations. Reinforced mobile MOSFETs (model TN-502RDM-H) and an Elekta Precise linear accelerator were used. Two detectors were placed in air for the angular response study and the whole set of five detectors was calibrated as usual to evaluate energy dependence. RESULTS: The maximum readout was obtained with a roll of 90° and 4 MeV. With regard to pitch movement, a substantial drop in readout was achieved at 90°. Significant overresponse was measured at 315° with 4 MeV and at 45° with 15 MeV. Energy response is not different for the following groups of energies: 4, 6, and 9 MeV; and 12 MeV, 15 MeV, and 18 MeV. CONCLUSIONS: Our proposal to name MOSFET rotations solves the problem of defining sensor orientations. Angular response could explain lower than expected results when the tip of the detector is lifted due to inadvertent movements. MOSFETs energy response is independent of several energies and differs by a maximum of 3.4% when dependent. This can limit dosimetry errors and makes it possible to calibrate the detectors only once for each group of energies, which saves time and optimizes lifespan of MOSFETs.

Minimally invasive surgery using intraoperative electron-beam radiotherapy for the treatment of soft tissue sarcoma of the extremities with tendon involvement.

BACKGROUND: When a soft tissue sarcoma (STS) is located at the distal part of an extremity and involves the tendon, a wide excision usually causes severe functional disability. We therefore developed a minimally invasive surgical technique using intraoperative electron-beam radiotherapy (IOERT) to reduce the incidence of post-operative functional disability in patients with peri-/intra-tendinous STS. We assessed the clinical outcomes of the novel minimally invasive surgery. METHODS: The study population included five patients who received treatment for distal extremity STSs. After elevating the tumor mass, including the tendon and nerve from the tumor bed with a wide margin, a lead board was inserted beneath the tumor mass to shield the normal tissue. IOERT (25-50 Gy) was then applied, and the tumor excised with care taken to maintain the continuity of the tendon. RESULTS: In a desmoid patient, local recurrence was observed outside the irradiated field. No cases of neuropathy or bone necrosis were observed. The mean limb function score was excellent in all patients. None of the high-grade sarcoma patients had local recurrence or distant metastasis. CONCLUSIONS: Although the current study is only a pilot study with a small number of patients, it shows that this minimally invasive procedure has the potential to become a standard treatment option for selected patients. TRIAL REGISTRATION: H17-250 (registered 2 November 2005) and H25-250 (modified from H17-250, registered 5 December 2013).

Six-year outcome of a prospective study evaluating tumor bed boost with intra-operative electron irradiation followed by whole-breast irradiation for early-stage breast cancer.

A prospective study was performed for patients with early-stage breast cancer in which a single fraction of intraoperative electron irradiation (IOERT) was given to the tumor bed, followed by conventional fractionated whole-breast irradiation (WBRT). Patients with T1/T2N0 breast cancer underwent lumpectomy and sentinel lymph node biopsy. A tumor bed boost of 10 Gy of IOERT using 6-12 MeV electrons was administered by a dedicated mobile linear accelerator in the operating room. After adequate wound healing, 48 Gy WBRT was given to the whole breast in 24 fractions. Fifty-two patients were enrolled between February 2003 and January 2005. At a median follow-up of 79 months, there were two local relapses. The 6-year actuarial overall survival and distant control rates were 89% and 96%, respectively. At last follow-up, cosmesis was graded as excellent or good in 45 (87%), fair in five (10%), and poor in two patients (4%), respectively. Difficulty in wound healing occurred in two patients who had additional surgery later. One patient developed significant fibrosis after aspiration of a symptomatic seroma. The result of this pilot study shows the feasibility of using IOERT as the tumor bed boost in lieu of 6-8 days of standard electron beam treatment with good local control and cosmetic results. However, late surgical intervention of the lumpectomy bed may result in more pronounced tissue fibrosis and wound healing difficulty.

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

INTRODUCTION: 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. METHODS: From November 2019 to April 2023, in vivo verifications were performed for 33 patients. IOERT was performed using a LIAC 10 MeV (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. RESULTS: For 29 patients, 20 Gy were prescribed while 10 Gy 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 5 cm was used for most of the patients. The mean prescription depth was 1.4 cm (0.5-2.5 cm). We found no correlation between the analyzed parameters and misalignment. CONCLUSION: 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.

Evaluation of RADIANCE Monte Carlo algorithm for treatment planning in electron based Intraoperative Radiotherapy (IOERT).

PURPOSE: To perform experimental as well as independent Monte Carlo (MC) evaluation of the MC algorithm implemented in RADIANCE version 4.0.8, a dedicated treatment planning system (TPS) for 3D electron dose calculations in intraoperative radiation therapy (IOERT). METHODS AND MATERIALS: The MOBETRON 2000 (IntraOp Medical Corporation, Sunnyvale, CA) IOERT accelerator was employed. PDD and profiles for five cylindrical plastic applicators with 50-90 mm diameter and 0°, 30° beveling were measured in a water phantom, at nominal energies of 6, 9 and 12 MeV. Additional PDD measurements were performed for all the energies without applicator. MC modeling of the MOBETRON was performed with the user code BEAMnrc and egs_chamber of the MC simulation toolkit EGSnrc. The generated phase space files of the two 0°-bevel applicators (50 mm, 80 mm) and three energies in both RADIANCE and BEAMnrc, were used to determine PDD and profiles in various set-ups of virtual water phantoms with air and bone inhomogeneities. 3D dose distributions were also calculated in image data sets of an anthropomorphic tissue-equivalent pelvis phantom. Image acquisitions were realized with a CT scanner (Philips Big Bore CT, Netherlands). Gamma analysis was applied to quantify the deviations of the RADIANCE calculations to the measurements and EGSnrc calculations. Gamma criteria normalized to the global maximum were investigated between 2%, 2 mm and 3%, 3 mm. RESULTS: RADIANCE MC calculations satisfied the gamma criteria of 3%, 3 mm with a tolerance limit of 85% passing rate compared to in- water phantom measurements, except for the dose profiles of the 30° beveled applicators. Mismatches lay in surface doses, in umbra regions and in the beveled end of the 30° applicators. A very good agreement to the EGSnrc calculations in heterogeneous media was observed. Deviations were more pronounced for the larger applicator diameter and higher electron energy. In 3D dose comparisons in the anthropomorphic phantom, gamma passing rates were higher than 96 % for both simulated applicators. CONCLUSIONS: RADIANCE MC algorithm agrees within 3%, 3 mm criteria with in-water phantom measurements and EGSnrc MC dose distributions in heterogeneous media for 0°-bevel applicators. The user should be aware of missing scattering components and the 30° beveled applicators should be used with attention.

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.

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.

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.

Outcomes of Breast Intraoperative Electron Beam Radiotherapy (IOeRT) : Case Series of Single Institute Experience in Saudi Arabia.

INTRODUCTION: 85-90% of local recurrences after breastconserving surgery occurs within the index quadrant. Intraoperative radiotherapy may be a good alternative for eligible patients avoiding long course of adjuvant radiation. PATIENTS AND METHODS: Eligible patients were early stage node negative at least 50 years at time of inclusion, unicentric less than 30mm in diameter any hormone receptor status. 21 Gy was delivered intraoperatively, biologically equivalent to 58 to 60 Gy in standard fractionation using electron beam to 90% isodose line. Cosmetic, Oncological and Patient Satisfaction Evaluation of treated Patients between March 2018 and August 2020 at the King Khalid university hospital, using the IOeRT (Mobetron® ). Evaluation done at a combined clinic between surgical and radiation oncology teams at the end of the follow up period before publication. RESULTS: 15 female patients were evaluable with mean follow up period 33.8 months (19-48 months). Mean Age 56.4 years (50-65 years). Mean tumor size 1.213 cm. Majority of patients were T1. 2 patients showed Sentinel lymph node positive.21 Gy was delivered intraoperatively.4 Patients (26.7%) received adjuvant postoperative external beam radiation therapy (EBRT). 2 patients due to being in Caution group due to positive extensive Ductal carcinoma in situ (DCIS). External beam radiation was 40 Gy/15 fractions/3 weeks using three dimensional radiation therapy (3DCRT). Cosmetically, Apart from one patient score 9 due to presence of keloid scar formation, most patients were in range of 0-3 according to physician evaluation and Modified Hollander's score otherwise, No more than score 3 in any of the patients was detected. Oncologically, Till the time of publication no local or distant relapses was detected. As a patient experience, 100 % of patients were satisfied. CONCLUSION: Breast IOERT is a convenient, safe and a valid treatment modality as an option for patients who are otherwise appropriate candidates for APBI. Proper patient selection should focus on clinicopathologic factors predictive of negative nodes and negative margins. Careful assessment of preoperative mammographic and other imaging studies for features, such as extent of calcifications, may be helpful.

Optimization of the regularization parameter in the Dual Annealing method used for the reconstruction of energy spectrum of electron beam generated by the AQURE mobile accelerator.

INTRODUCTION: The shape of the energy spectrum is an essential component of any electron beam Monte Carlo model. Due to specialized equipment and the long measurement time for the direct methods for determining the energy spectrum, attractive alternatives are backward spectrum reconstructions from the measured data. One such approach is solving the first-degree Fredholm integral equation with appropriate regularization. It makes it possible to calculate the depth distribution as the sum of the distributions from monoenergetic beams. This study aims to determine the optimal value of the regularization parameter for the problem of determining the spectrum of the electron beam produced by a mobile accelerator used during intraoperative radiotherapy. MATERIAL AND METHODS: The Geant4 package was used to generate the distributions of deep doses for monoenergetic beams for two models with different degrees of complexity, i.e. simple (theoretical) and full (for the mobile accelerator). The dose distributions for four different shapes of energy spectrum (for each model) were obtained similarly. They were established as the reference data for further calculations. The Dual Annealing optimization method was used to obtain the reconstructed spectrum. The multiple optimizations that differ by the regularization parameter (ranging from 0 to 1) were performed. For each reconstruction, similarity indicators of the energy spectrum and the dose distribution to the referenced data were calculated to determine the optimal regularization parameters. RESULTS: Optimal regularization parameters determined by similarity indicators for the spectrum and the dose distribution differ for geometry models considered in the study. The regularization parameter for the simple geometry ranged from 0.03 to 0.05, while for full geometry, they were from 0.05 to 0.06. The results for conventional linear accelerators found in the literature range from 0.5 to 1.1. CONCLUSION: The Dual Annealing optimization method can be effectively used to solve the Fredholm equation with Tikhonov regularization to reconstruct an electron beam's energy spectrum. The regularization parameter value depends on the beam-forming system. Its value for the mobile accelerator considered in the study ranges from 0.05 to 0.06, depending on the nominal beam energy value.

Intra-Operative Electron Radiation Therapy: An Update of the Evidence Collected in 40 Years to Search for Models for Electron-FLASH Studies.

INTRODUCTION: The clinical practice and outcome results of intraoperative electron radiation therapy (IOeRT) in cancer patients have been extensively reported over 4 decades. Electron beams can be delivered in the promising FLASH dose rate. METHODS AND MATERIALS: Several cancer models were approached by two alternative radiobiological strategies to optimize local cancer control: boost versus exclusive IOeRT. Clinical outcomes are revisited via a bibliometric search performed for the elaboration of ESTRO/ACROP IORT guidelines. RESULTS: In the period 1982 to 2020, a total of 19,148 patients were registered in 116 publications concerning soft tissue sarcomas (9% of patients), unresected and borderline-resected pancreatic cancer (22%), locally recurrent and locally advanced rectal cancer (22%), and breast cancer (45%). Clinical outcomes following IOeRT doses in the range of 10 to 25 Gy (with or without external beam fractionated radiation therapy) show a wide range of local control from 40 to 100% depending upon cancer site, histology, stage, and treatment intensity. Constraints for normal tissue tolerance are important to maintain tumor control combined with acceptable levels of side effects. CONCLUSIONS: IOeRT represents an evidence-based approach for several tumor types. A specific risk analysis for local recurrences supports the identification of cancer models that are candidates for FLASH studies.

Intra-Operative Electron Radiation Therapy (IOERT) Anticipated Boost in Breast Cancer Treatment: An Italian Multicenter Experience.

In breast cancer, the use of a boost to the tumor bed can improve local control. The aim of this research is to evaluate the safety and efficacy of the boost with intra-operative electron radiotherapy (IOERT) in patients with early-stage breast cancer undergoing conservative surgery and postoperative whole breast irradiation (WBI). The present retrospective multicenter large data were collected between January 2011 and March 2018 in 8 Italian Radiation Oncology Departments. Acute and late toxicity, objective (obj) and subjective (subj) cosmetic outcomes, in-field local control (LC), out-field LC, disease-free survival (DFS) and overall survival (OS) were evaluated. Overall, 797 patients were enrolled. IOERT-boost was performed in all patients during surgery, followed by WBI. Acute toxicity (≥G2) occurred in 179 patients (22.46%); one patient developed surgical wound infection (G3). No patients reported late toxicity ≥ G2. Obj-cosmetic result was excellent in 45%, good in 35%, fair in 20% and poor in 0% of cases. Subj-cosmetic result was excellent in 10%, good in 20%, fair in 69% and poor in 0.3% of cases. Median follow-up was 57 months (range 12-109 months). At 5 years, in-field LC was 99.2% (95% CI: 98-99.7); out-field LC 98.9% (95% CI: 97.4-99.6); DFS 96.2% (95% CI: 94.2-97.6); OS 98.6% (95% CI: 97.2-99.3). In conclusion, IOERT-boost appears to be safe, providing excellent local control for early-stage breast cancer. The safety and long-term efficacy should encourage use of this treatment, with the potential to reduce local recurrence.

Long-Term Outcomes Using Electron IOERT APBI for Early Stage Breast Cancer: The Verona University Hospital Experience.

METHODS AND MATERIALS: From July 2006 to December 2015, 295 patients suitable for breast-conserving therapy entered a single-arm phase II study and were treated with IOERT as radical treatment. Inclusion criteria were age >50, postmenopausal status, cT1N0M0 stage, grade G1-G2, positive estrogen receptor status; unicentric and unifocal disease, histologically proven invasive ductal carcinoma no previous breast irradiation, good performance status. RESULTS: With a median follow-up of 7.1 years (95% CI, 6.5;7.4) 6 women (2.0%) experienced a true local recurrence (reappearance of the tumour in the same quadrant). Five-year overall survival and local recurrence-free survival were 96% (95% CI, 92.9;97.8) and 94.9% (95% CI, 91.6;97.0) respectively. CONCLUSION: Our trial suggests that, in highly selected early stage breast cancers, a single-dose IOERT can be safely delivered with excellent results and very low long-term recurrence rates.

Long-Term Outcome of Centrally Located Hepatocellular Carcinomas Treated by Radical Resection Combined With Intraoperative Electron Radiotherapy (IOERT).

PURPOSE: To explore the feasibility and safety of centrally located hepatocellular carcinoma (CL-HCC) treated by narrow-margin resection combined with intraoperative electron radiotherapy (IOERT). METHODS AND MATERIALS: From November 2009 to November 2016, 37 consecutive patients were treated with IOERT as adjuvant treatment during narrow-margin resection for CL-HCC. Long-term outcomes, adverse events for surgery, and acute and chronic toxicities were analyzed. RESULTS: The median follow-up was 57.82 months (range, 3.75-111.41 months). A total dose of 15 Gy (range 12 to 17Gy) (prescribed at the 90% isodose) was delivered with a 0.9cm (range 0.8-1.2 cm) median treatment depth targeting the narrow-margin. The 1-year, 3-year and 5-year OS rates were 91.39%, 88.34% and 88.34%, respectively. The 1-year, 3-year and 5-year DFS rates were 80.81%, 68.59% and 54.17%, respectively. In the univariate analysis, none of the treatment characteristics were predictive of overall survival. Fifteen (40.5%) patients suffered from a recurrence event. No patient had marginal recurrence. The 1-year, 3-year and 5-year intrahepatic recurrence rates were 19.75%, 25.92% and 39.58%, respectively. The 1-year, 3-year and 5-year extrahepatic recurrence rates were 2.7%, 5.95% and 9.87%, respectively. There was no 30-day surgical-related death. Three patients had grade 4, and 28 patients had grade 3 alanine aminotransferase (ALT) levels, and seven patients had grade 4, and 30 patients had grade 3 aspartate transaminase (AST) levels. All of them returned to normal within four months. There was no acute radiation-induced liver injury during follow-up. There were no acute or chronic toxicities associated with IOERT. CONCLUSION: IOERT for narrow-margin CL-HCC may achieve good long-term survival outcomes, without significantly increasing acute and chronic toxicities. An IOERT dose of 15Gy may be the safest and most feasible. IOERT might be considered as an adjuvant therapy for CL-HCC patients with a narrow-margin.

Hypofractionated Whole Breast Irradiation and Boost-IOERT in Early Stage Breast Cancer (HIOB): First Clinical Results of a Prospective Multicenter Trial (NCT01343459).

Background and purpose: To investigate intraoperative electron radiation therapy (IOERT) as a tumor bed boost during breast conserving surgery (BCS) followed by hypofractionated whole breast irradiation (HWBI) on age-correlated in-breast recurrence (IBR) rates in patients with low- to high-risk invasive breast cancer. Material and methods: BCS and IOERT (11.1 Gy) preceded a HWBI (40.5 Gy) in 15 fractions. Five-year IBR-rates were compared by a sequential ratio test (SQRT) with best evidences in three age groups (35−40 y and 41−50 y: 3.6%, >50 y: 2%) in a prospective single arm design. Null hypothesis (H0) was defined to undershoot these benchmarks for proof of superiority. Results: Of 1445 enrolled patients, 326 met exclusion criteria, leaving 1119 as eligible for analysis. After a median follow-up of 50 months (range 0.7−104), we detected two local recurrences, both in the age group >50 y. With no observed IBR, superiority was demonstrated for the patient groups 41−50 and >50 y, respectively. For the youngest group (35−40 y), no appropriate statistical evaluation was yet possible due to insufficient recruitment. Conclusions: In terms of five-year IBR-rates, Boost-IOERT followed by HWBI has been demonstrated to be superior in patients older than 50 and in the age group 41−50 when compared to best published evidence until 2010.