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.

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.

The Role of Intraoperative Radiotherapy Treatment of Locally Advanced Rectal Cancer.

Intraoperative radiation therapy (IORT) has been used in the treatment of locally advanced and recurrent rectal cancers for the last several decades. Given the heterogeneity of patients treated and different indications for use and dosing at different institutions, it has been difficult to discern if IORT adds any appreciable benefit to standard of care therapies. Herein, the rationale for IORT in rectal cancer is discussed along with the most modern and best available data in 2023. IORT is likely indicated in patients with locally advanced and locally recurrent rectal cancer with threatened margins (R0 or R1 resection) to help improve local control. High-quality imaging and multidisciplinary discussion are necessary to ensure optimal patient selection. Appropriate counseling of the patient and excellent team communication are of the utmost importance given the challenging nature of these cases and the prognostic implications of R1 and R2 resections in this patient population.

Outcome assessment of intraoperative radiotherapy for brain metastases: results of a prospective observational study with comparative matched-pair analysis.

PURPOSE: Intraoperative radiation therapy (IORT) is an emerging alternative to adjuvant stereotactic external beam radiation therapy (EBRT) following resection of brain metastases (BM). Advantages of IORT include an instant prevention of tumor regrowth, optimized dose-sparing of adjacent healthy brain tissue and immediate completion of BM treatment, allowing an earlier admission to subsequent systemic treatments. However, prospective outcome data are limited. We sought to assess long-term outcome of IORT in comparison to EBRT. METHODS: A total of 35 consecutive patients, prospectively recruited within a study registry, who received IORT following BM resection at a single neuro-oncological center were evaluated for radiation necrosis (RN) incidence rates, local control rates (LCR), distant brain progression (DBP) and overall survival (OS) as long-term outcome parameters. The 1 year-estimated OS and survival rates were compared in a balanced comparative matched-pair analysis to those of our institutional database, encompassing 388 consecutive patients who underwent adjuvant EBRT after BM resection. RESULTS: The median IORT dose was 30 Gy prescribed to the applicator surface. A 2.9% RN rate was observed. The estimated 1 year-LCR was 97.1% and the 1 year-DBP-free survival 73.5%. Median time to DBP was 6.4 (range 1.7-24) months in the subgroup of patients experiencing intracerebral progression. The median OS was 17.5 (0.5-not reached) months with a 1 year-survival rate of 61.3%, which did not not significantly differ from the comparative cohort (p = 0.55 and p = 0.82, respectively). CONCLUSION: IORT is a safe and effective fast-track approach following BM resection, with comparable long-term outcomes as adjuvant EBRT.

Intraoperative or postoperative stereotactic radiotherapy for brain metastases: time to systemic treatment onset and other patient-relevant outcomes.

PURPOSE: Intraoperative radiotherapy (IORT) has become a viable treatment option for resectable brain metastases (BMs). As data on local control and radiation necrosis rates are maturing, we focus on meaningful secondary endpoints such as time to next treatment (TTNT), duration of postoperative corticosteroid treatment, and in-hospital time. METHODS: Patients prospectively recruited within an IORT study registry between November 2020 and June 2023 were compared with consecutive patients receiving adjuvant stereotactic radiotherapy (SRT) of the resection cavity within the same time frame. TTNT was defined as the number of days between BM resection and start of the next extracranial oncological therapy (systemic treatment, surgery, or radiotherapy) for each of the groups. RESULTS: Of 95 BM patients screened, IORT was feasible in 84 cases (88%) and ultimately performed in 64 (67%). The control collective consisted of 53 SRT patients. There were no relevant differences in clinical baseline features. Mean TTNT (range) was 36 (9 - 94) days for IORT patients versus 52 (11 - 126) days for SRT patients (p = 0.01). Mean duration of postoperative corticosteroid treatment was similar (8 days; p = 0.83), as was mean postoperative in-hospital time (11 versus 12 days; p = 0.97). Mean total in-hospital time for BM treatment (in- and out-patient days) was 11 days for IORT versus 19 days for SRT patients (p < 0.001). CONCLUSION: IORT for BMs results in faster completion of interdisciplinary treatment when compared to adjuvant SRT, without increasing corticosteroid intake or prolonging in-hospital times. A randomised phase III trial will determine the clinical effects of shorter TTNT.

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

BACKGROUND AND OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Patient satisfaction after nipple-sparing mastectomy with intraoperative radiotherapy and breast reconstruction for breast cancer.

INTRODUCTION: The use of nipple-sparing mastectomy (NSM) combined with breast reconstruction is increasing in breast cancer surgeries despite its controversial safety profile. To reduce the recurrence rate of tumors in the nipple-areola complex (NAC), we used intraoperative radiotherapy (IORT). The purpose of this study was to explore patients' feedback on this novel treatment strategy. PATIENTS AND METHODS: From January 2014 to May 2018, eligible patients with breast cancer were enrolled in this study and separated into 2 groups. Patients in the NSM group underwent IORT to the NAC flap, and patients in the skin-sparing mastectomy (SSM) group underwent SSM and breast reconstruction. The postoperative satisfaction was collected and assessed using the Breast-Q reconstruction questionnaire and a standardized questionnaire; this was compared between the 2 groups. RESULTS: There were 46 patients (52 NSMs) in the NSM group and 20 patients (22 SSMs) in the SSM group. The breast-Q scores were higher in the NSM group than the SSM group, with trends for a 'higher satisfaction with breasts' (67.39 ± 20.59 vs. 55.00 ± 19.33; p = 0.026) and 'higher sexual well-being' (61.74 ± 22.24 vs. 49.50 ± 20.12; p = 0.039). All the patients recognized the importance of nipple preservation. Thirty-seven women (80.40%) were satisfied or very satisfied with the appearance and shape of the NAC in the NSM group, while 38/46 women (82.60%) were very unsatisfied or unsatisfied with the sensitivity of the nipples. CONCLUSIONS: The Breast-Q scores showed great satisfaction with breasts and sexual well-being in the NSM group. However, more effort should be made in improving postoperative NAC sensitivity.

Early Therapeutic Interventions for Newly Diagnosed Glioblastoma: Rationale and Review of the Literature.

PURPOSE OF REVIEW: Glioblastoma is the commonest primary brain cancer in adults whose outcomes are amongst the worst of any cancer. The current treatment pathway comprises surgery and postoperative chemoradiotherapy though unresectable diffusely infiltrative tumour cells remain untreated for several weeks post-diagnosis. Intratumoural heterogeneity combined with increased hypoxia in the postoperative tumour microenvironment potentially decreases the efficacy of adjuvant interventions and fails to prevent early postoperative regrowth, called rapid early progression (REP). In this review, we discuss the clinical implications and biological foundations of post-surgery REP. Subsequently, clinical interventions potentially targeting this phenomenon are reviewed systematically. RECENT FINDINGS: Early interventions include early systemic chemotherapy, neoadjuvant immunotherapy, local therapies delivered during surgery (including Gliadel wafers, nanoparticles and stem cell therapy) and several radiotherapy techniques. We critically appraise and compare these strategies in terms of their efficacy, toxicity, challenges and potential to prolong survival. Finally, we discuss the most promising strategies that could benefit future glioblastoma patients. There is biological rationale to suggest that early interventions could improve the outcome of glioblastoma patients and they should be investigated in future trials.

Intraoperative radiotherapy during awake craniotomies: preliminary results of a single-center case series.

Awake craniotomies are performed to avoid postoperative neurological deficits when resecting lesions in the eloquent cortex, especially the speech area. Intraoperative radiotherapy (IORT) has recently focused on optimizing the oncological treatment of primary malignant brain tumors and metastases. Herein, for the first time, we present preliminary results of IORT in the setting of awake craniotomies. From 2021 to 2022, all patients undergoing awake craniotomies for tumor resection combined with IORT were analyzed retrospectively. Demographical and clinical data, operative procedure, and treatment-related complications were evaluated. Five patients were identified (age (mean ± standard deviation (SD): 65 ± 13.5 years (y)). A solid left frontal metastasis was detected in the first patient (female, 49 y). The second patient (male, 72 y) presented with a solid metastasis on the left parietal lobe. The third patient (male, 52 y) was diagnosed with a left temporoparietal metastasis. Patient four (male, 74 y) was diagnosed with a high-grade glioma on the left frontal lobe. A metastasis on the left temporooccipital lobe was detected in the fifth patient (male, 78 y). After awake craniotomy and macroscopic complete tumor resection, intraoperative tumor bed irradiation was carried out with 50 kV x-rays and a total of 20 Gy for 16.7 ± 2.5 min. During a mean follow-up of 6.3 ± 2.6 months, none of the patients developed any surgery- or IORT-related complications or disabling permanent neurological deficits. Intraoperative radiotherapy in combination with awake craniotomy seems to be feasible and safe.

Sole adjuvant intraoperative breast radiotherapy in Taiwan: a single-center experience.

INTRODUCTION: Intraoperative radiotherapy (IORT) is more convenient than standard whole breast external beam radiotherapy (EBRT) as a sole adjuvant radiotherapy for breast cancer. The impact of age on breast cancer course and treatment strategy is still under investigation, and the peak age for breast cancer in Taiwan is much younger than that in Western countries. We aimed to review the oncological outcomes of sole IORT compared with standard EBRT in a country with younger breast cancer patients. PATIENTS AND METHODS: We reviewed patients with invasive breast cancer who received breast-conserving surgery (BCS) from September 2014 to December 2016. The clinicopathologic characteristics and oncological outcomes of eligible patients who received EBRT or IORT as sole adjuvant radiotherapy after BCS were collected and reviewed. RESULTS: A total of 170 patients were enrolled with a mean follow-up time of 3.53 ± 0.82 years. The risk of locoregional recurrence was 2.44% for EBRT versus 10.64% for IORT (p = 0.024). IORT was a significant risk factor of locoregional recurrence (p = 0.005). The hazard ratios (HRs) for locoregional recurrence in the IORT group compared with the EBRT group were significantly higher in non-suitable risk group patients (HR = 7.02, p = 0.009) and in patients under 50 years old (HR = 10.42, p = 0.011). CONCLUSIONS: Locoregional recurrence was significantly higher in patients who received IORT than in those who underwent EBRT. IORT should not be used alone in patients under 50 years old who do not belong to a suitable group.

IOERT versus external beam electrons for boost radiotherapy in stage I/II breast cancer: 10-year results of a phase III randomized study.

BACKGROUND: Intraoperative radiotherapy with electrons (IOERT) boost could be not inferior to external beam radiotherapy (EBRT) boost in terms of local control and tissue tolerance. The aim of the study is to present the long-term follow-up results on local control, esthetic evaluation, and toxicity of a prospective study on early-stage breast cancer patients treated with breast-conserving surgery with an IOERT boost of 10 Gy (experimental group) versus 5 × 2 Gy EBRT boost (standard arm). Both arms received whole-breast irradiation (WBI) with 50 Gy (2 Gy single dose). METHODS: A single-institution phase III randomized study to compare IOERT versus EBRT boost in early-stage breast cancer was conducted as a non-inferiority trial. Primary endpoints were the evaluation of in-breast true recurrences (IBTR) and out-field local recurrences (LR) as well as toxicity and cosmetic results. Secondary endpoints were overall survival (OS), disease-free survival (DFS), and patient's grade of satisfaction with cosmetic outcomes. RESULTS: Between 1999 and 2004, 245 patients were randomized: 133 for IOERT and 112 for EBRT. The median follow-up was 12 years (range 10-16 years). The cumulative risk of IBTR at 5-10 years was 0.8% and 4.3% after IOERT, compared to 4.2% and 5.3% after EBRT boost (p = 0.709). The cumulative risk of out-field LR at 5-10 years was 4.7% and 7.9% for IOERT versus 5.2% and 10.3% for EBRT (p = 0.762). All of the IOERT arm recurrences were observed at > 100 months' follow-up, whereas the mean time to recurrence in the EBRT group was earlier (55.2 months) (p < 0.05). No late complications associated with IOERT were observed. The overall cosmetic results were scored as good or excellent in physician and patient evaluations for both IOERT and EBRT. There were significantly better scores for IOERT at all time points in physician and patient evaluations with the greatest difference at the end of EBRT (p = 0.006 objective and p = 0.0004 subjective) and most narrow difference at 12 months after the end of EBRT (p = 0.08 objective and p = 0.04 subjective analysis). CONCLUSION: A 10-Gy IOERT boost during breast-conserving surgery provides high local control rates without significant morbidity. Although not significantly superior to external beam boosts, the median time to local recurrences after IOERT is prolonged by more than 4 years.

Health-related quality of life of early-stage breast cancer patients after different radiotherapy regimens.

PURPOSE: To evaluate and compare health-related quality of life (HRQL) of women with early-stage breast cancer (BC) treated with different radiotherapy (RT) regimens. METHODS: Data were collected from five prospective cohorts of BC patients treated with breast-conserving surgery and different RT regimens: intraoperative RT (IORT, 1 × 23.3 Gy; n = 267), external beam accelerated partial breast irradiation (EB-APBI, 10 × 3.85 Gy; n = 206), hypofractionated whole breast irradiation(hypo-WBI, 16 × 2.67 Gy; n = 375), hypo-WBI + boost(hypo-WBI-B, 21-26 × 2.67 Gy; n = 189), and simultaneous WBI + boost(WBI-B, 28 × 2.3 Gy; n = 475). Women ≥ 60 years with invasive/in situ carcinoma ≤ 30 mm, cN0 and pN0-1a were included. Validated EORTC QLQ-C30/BR23 questionnaires were used to asses HRQL. Multivariable linear regression models adjusted for confounding (age, comorbidity, pT, locoregional treatment, systemic therapy) were used to compare the impact of the RT regimens on HRQL at 12 and 24 months. Differences in HRQL over time (3-24 months) were evaluated using linear mixed models. RESULTS: There were no significant differences in HRQL at 12 months between groups except for breast symptoms which were better after IORT and EB-APBI compared to hypo-WBI at 12 months (p < 0.001). Over time, breast symptoms, fatigue, global health status and role functioning were significantly better after IORT and EB-APBI than hypo-WBI. At 24 months, HRQL was comparable in all groups. CONCLUSION: In women with early-stage breast cancer, the radiotherapy regimen did not substantially influence long-term HRQL with the exception of breast symptoms. Breast symptoms are more common after WBI than after IORT or EB-APBI and improve slowly until no significant difference remains at 2 years posttreatment.

Intraoperative radiotherapy boost as part of breast-conservation therapy for breast cancer: a single-institution retrospective analysis.

BACKGROUND: There are currently no data from randomized controlled trials on the use of intraoperative radiotherapy (IORT) as a tumor bed boost as part of a breast-conservation approach for breast cancer. This study retrospectively reviewed the safety and efficacy of IORT as a boost treatment at a tertiary cancer center. METHODS: From 2015 to 2019, patients underwent breast-conserving surgery with axillary lymph node staging and a single dose of 20 Gy IORT with 50-kV photons, followed by whole-breast irradiation (WBI) and adjuvant systemic therapy (if applicable). Patients were followed for assessment of acute and late toxicities (using the Common Terminology Criteria for Adverse Events version 5.0) at 3-6-month intervals. Outcomes included ipsilateral (IBTR) and contralateral breast progression-free survival (CBE), distant metastasis-free survival (DMFS), and overall survival (OS). RESULTS: Median follow-up for the 214 patients was 28 (range 2-59) months. Most patients had T1 disease (n = 124) and were clinically node negative. Only few patients had high-grade and/or triple-negative disease. The vast majority of patients underwent sentinel node biopsy, and 32 (15%) required re-resection for initially positive margins. Finally, all tumor bed margins were clear. Nine (4.2%) and 48 (22.4%) patients underwent neoadjuvant and adjuvant chemotherapy, respectively. WBI was predominantly performed as conventionally fractionated WBI (n = 187, 87.4%), and the median time from BCS to WBI was 54.5 days. IORT was delivered with a single dose of 20 Gy. The median WBI dose was 50 Gy (range 29.4-50.4 Gy). No patients experienced grade 4 events; acute grade 3 toxicities were limited to 17 (8%) cases of radiation dermatitis. Postoperative toxicities were mild. After WBI only one case of late grade ≥ 2 events was reported. There were two recurrences in the tumor bed and one contralateral breast event. CONCLUSION: This investigation provides additional preliminary data supporting the using of IORT in the boost setting and corroborates the existing literature. These encouraging results should be prospectively validated by the eventual publication of randomized studies such as TARGIT­B.

A phase II trial proposal of total neoadjuvant treatment with primary chemotherapy, stereotactic body radiation therapy, and intraoperative radiation therapy in borderline resectable pancreatic adenocarcinoma.

BACKGROUND: The current management guidelines recommend that patients with borderline resectable pancreatic adenocarcinoma (BRPC) should initially receive neoadjuvant chemotherapy. The addition of advanced radiation therapy modalities, including stereotactic body radiation therapy (SBRT) and intraoperative radiation therapy (IORT), could result in a more effective neoadjuvant strategy, with higher rates of margin-free resections and improved survival outcomes. METHODS/DESIGN: In this single-center, single-arm, intention-to-treat, phase II trial newly diagnosed BRPC will receive a "total neoadjuvant" therapy with FOLFIRINOX (5-fluorouracil, irinotecan and oxaliplatin) and hypofractionated SBRT (5 fractions, total dose of 30 Gy with simultaneous integrated boost of 50 Gy on tumor-vessel interface). Following surgical exploration or resection, IORT will be also delivered (10 Gy). The primary endpoint is 3-year survival. Secondary endpoints include completion of neoadjuvant treatment, resection rate, acute and late toxicities, and progression-free survival. In the subset of patients undergoing resection, per-protocol analysis of disease-free and disease-specific survival will be performed. The estimated sample size is 100 patients over a 36-month period. The trial is currently recruiting. TRIAL REGISTRATION: NCT04090463 at clinicaltrials.gov.

Intraoperative radiotherapy vs concurrent chemoradiotherapy in the treatment of patients with locally advanced pancreatic cancer.

PURPOSE: The purpose of the multi-institutional retrospective study was to evaluate whether intraoperative radiotherapy (IORT) has advantages in the treatment of patients with locally advanced pancreatic cancer (LAPC) compared with concurrent chemoradiotherapy (CCRT). PATIENTS AND METHODS: A total of 103 patients with LAPC whom was treated with IORT (Arm A; n = 50) or CCRT (Arm B; n = 53) from 2015.6 to 2016.7 were retrospectively identified. Data on feasibility, toxicity, and overall survival (OS) were evaluated. RESULTS: Most factors of the two cohorts were similar. The severe adverse events (grade 3 and 4) patients in Arm B were higher than patients in Arm A (34% vs 0%). Disease progression was noted in 38 patients (76%) in Arm A and 37 patients (69.8%) in Arm B. The median survival of patients in Arm A and B were 15.3 months (95% CI, 13.0-17.6 months) and 13.8 months (95% CI, 11.0-16.6 months), respectively. The 1-year survival rate were 66.3% in Arm A (95% CI, 52.3%-80.2%) and 60.9% in Arm B (95% CI, 46.4%-75.4%). There was no significant difference in OS between patients treated with IORT and with CCRT (p = 0.458). CONCLUSION: Our results demonstrated that patients with LAPC treated with IORT showed fewer adverse events, less treatment time, and high feasibility compared to CCRT. Although, IORT has no advantages in survival and tumor control compared with CCRT.

A prospective single-institution study of intraoperative radiotherapy (IORT) for early-stage breast cancer.

Intraoperative radiation therapy (IORT) is an option for breast-conserving therapy in early-stage breast cancer. IORT is given in one fraction at the time of surgery and eliminates the need for adjuvant external beam radiation therapy. However, previous trials indicate increased local failure rates compared with whole-breast irradiation, which engenders controversy around the appropriate use of IORT. We conducted a prospective study of patients diagnosed with early-stage breast cancer (T1-T2, N0-N1) at the University of Oklahoma Health Sciences Center (OUHSC) between 2013 and 2017 and treated with lumpectomy followed by intraoperative radiation therapy (IORT). Data collected included stage of disease, tumor location, histology, tumor markers, lymph node status, surgical margin size, recurrence, cosmetic outcomes, and length of follow-up. In-breast tumor recurrence rate (IBTR) in the 77 evaluable patients was 3.9% (3 patients). Margins were close (1 mm or less) in all three recurrent patients, and two were initially diagnosed with DCIS. Recurrence rates in our patients were comparable to prior reports. All recurrences were in patients with close margins indicating that this may represent a predictive feature for exclusion from IORT; additional studies are essential to determine the recurrence rates among patients treated with IORT and to identify potential predictors of IORT eligibility.

Verification of electron beam parameters in an intraoperative linear accelerator using dosimetric and radiobiological response methods.

BACKGROUND: The availability of linear accelerators (linac) for research purposes is often limited and therefore alternative radiation sources are needed to conduct radiobiological research. The National Centre for Radiation Research in Poland recently developed an intraoperative mobile linac that enables electron irradiation at energies ranging from 4 to 12 MeV and dose rates of 5 or 10 Gy/min. The present study was conducted to evaluate the electron beam parameters of this intraoperative linac and to verify the set-up to evaluate out-of-field doses in a water phantom, which were determined through dosimetric and biological response measurements. MATERIALS AND METHODS: The distribution of radiation doses along and across the radiation beam were measured in a water phantom using a semiconductor detector and absolute doses using an ionisation chamber. Two luminal breast cancer cell lines (T-47D and HER2 positive SK-BR-3) were placed in the phantom to study radiation response at doses ranging from 2 to 10 Gy. Cell response was measured by clonogenic assays. RESULTS AND CONCLUSION: The electron beam properties, including depth doses and profiles, were within expected range for the stated energies. These results confirm the viability of this device and set-up as a source of megavoltage electrons to evaluate the radiobiological response of tumour cells.

Intraoperative radiotherapy for breast cancer treatment efficiently targets the tumor bed preventing breast adipose stromal cell outgrowth.

OBJECTIVES: Mesenchymal stromal cells (MSC) in bone marrow have been shown to be radioresistant, which is related to pronounced DNA repair mechanisms. Intraoperative radiotherapy (IORT) during breast-conserving surgery for early breast cancer is an innovative technique applying low energy x­ray to the tumor bed immediately after removal of the tumor. IORT is considered to reduce the risk of local tumor recurrence by directly targeting cells of the tumor bed and altering the local microenvironment. Aim of this study was to investigate whether IORT affects the outgrowth potential of breast adipose tissue-derived MSC (bASC) as part of the tumor bed. MATERIALS AND METHODS: After surgical tumor resection, biopsies of the tumor bed were taken before (pre IORT) and after IORT (post IORT) and processed applying well-established protocols for ASC isolation and characterization. RESULTS: In all, 95% of pre IORT tumor bed samples yielded persistently outgrowing bASC with typical ASC characteristics: fibroblastoid morphology, proliferation, adipogenic and osteogenic differentiation and ASC surface marker expression. However, none of the post IORT samples yielded persistent outgrowth of bASC. CONCLUSIONS: After breast-conserving surgery, approximately 90% of local recurrences emerge in close proximity to the initial tumor bed, potentially reflecting a significant contribution of the tumor bed to relapse. Our data show that IORT, besides the proven effect on breast cancer cells, efficiently modifies the tumor environment by having an impact on tumor bed bASC. This effect on tumor bed stromal cells might contribute to reduce the risk of tumor relapse and metastases.

Long-term outcome after intraoperative radiotherapy as a boost in breast cancer.

PURPOSE: To investigate long-term oncological outcome and incidence of chronic side effects in patients with breast cancer and intraoperative radiotherapy given as an upfront boost (IORT boost). METHODS: Retrospective analysis of 400 patients with an IORT boost with low-energy X­rays (20 Gy), subsequent whole-breast irradiation (46-50 Gy), and annual oncological follow-up. Side effects were prospectively evaluated (LENT-SOMA scales) over a period of up to 15 years. Side effects scored ≥grade 2 at least three times during follow-up were judged to be chronic. RESULTS: The median age was 63 years (30-85) and the median follow-up was 78 months (2-180) after IORT boost. In 15 patients a local recurrence occurred, resulting in a local recurrence rate at 5, 10, and 15 years of 2.0%, 6.6%, and 10.1%, respectively. The overall survival rates at 5, 10, and 15 years were 92.1%, 81.8%, and 80.7%, respectively. The most common high-grade side effects were fibrosis (21%) and pain (8.6%). The majority of side effects occurred within the first 3 years. The actuarial rates of chronic fibrosis were 19.1% and 21.1% at 5 and ≥8 years, of chronic pain 8.6% at ≥4 years, of chronic edema of the breast 2.4% at ≥2 years, of chronic lymphedema 0.0% at 5 and 10 years, and of chronic hyperpigmentation 0.5% at ≥2 years. Side effects were similar or less than expected from an external beam boost. CONCLUSION: IORT boost appears to be a highly efficient and safe method for upfront delivery of the tumor bed boost in high-risk breast cancer patients.

Efficacy analysis of intraoperative radiotherapy in patients with early-stage breast cancer.

BACKGROUND: To analyze the clinical efficacy of intraoperative radiotherapy (IORT) after breast-conserving surgery (BCS) in patients with early-stage breast cancer (BC), and to investigate the relationship between its influencing factors and clinical efficacy and prognosis. METHODS: A total of 73 patients with early-stage BC who underwent IORT after BCS in our hospital were selected in this research. RESULTS: Kaplan-Meier survival analysis was used to analyze the related factors of BCS and IORT of disease-free survival (DFS) and overall survival (OS). It was found that only age (χ2 = 14.035, P = 0.003) was statistically positively correlated with the patient's DFS, and local recurrence and metastasis rate and mortality were higher in patients over 70 years old. Log rank test was used to analyze multiple factors. Only the diameter of the applicator (χ2 = 70.378, P < 0.05) was statistically significant with wound complications, and the larger the diameter, the higher incidence of wound complications. The remaining risk factors did not increase the incidence of wound complications. COX multivariate analysis showed that age was an independent risk factor for DFS rate and the risk factor had no significant effect on the OS rate of patients undergoing IORT after BCS. CONCLUSIONS: IORT may be a safe form of treatment for the selected patients with early-stage BC, and can achieve satisfactory esthetic effect. Larger applicator diameters may increase the incidence of wound complications. Age is an independent risk factor for DFS in early-stage BC patients undergoing IORT after BCS.