Intraoperative Radiotherapy Group Research Articles

Intraoperative radiotherapy in recurrent IDH-wildtype glioblastoma with gross total resection: A single-center retrospective study

BackgroundIsocitrate dehydrogenase-wildtype (IDHwt) glioblastoma (GBM) is one of the most aggressive primary brain tumors. The recurrence of GBM is almost inevitable. As an adjuvant option to surgery, intraoperative radiotherapy (IORT) is gaining increasing attention in the treatment of glioma. This study is aimed to evaluate the therapeutic efficacy of IORT on recurrent IDHwt GBM. MethodsIn total, 34 recurrent IDHwt GBM patients who received a second surgery were included in the analysis (17 in the surgery group and 17 in the surgery + IORT group). ResultsThe progression-free survival and overall survival after the second surgery were defined as PFS2 and OS2, respectively. The median PFS2 was 7.3 months (95% CI: 6.3–10.5) and 10.6 months (95% CI: 9.3–14.6) for those patients who received surgery and surgery + IORT, respectively. Patients in the surgery + IORT group also had a longer OS2 (12.8 months, 95% CI: 11.4–17.2) than those in the surgery group (9.3 months, 95% CI: 8.9–12.9). The Kaplan–Meier survival curves, analyzed by log-rank test, revealed a statistically significant difference in PFS2 and OS2 between both groups, suggesting that IORT plays an active role in the observed benefits for PFS2 and OS2. The effects of IORT on PFS2 and OS2 were further confirmed by multivariate Cox hazards regression analysis. Two patients in the surgery group developed distant glioma metastases, and no radiation-related complications were observed in the IORT group. ConclusionsThis study suggests that low-dose IORT may improve the prognosis of recurrent IDHwt GBM patients. Future prospective large-scale studies are needed to validate the efficacy and safety of IORT.

Comparison of intraoperative radiotherapy as a boost vs. simultaneously integrated boosts after breast-conserving therapy for breast cancer.

Currently, there are no data from randomized trials on the use of intraoperative radiotherapy (IORT) as a tumor bed boost in women at high risk of local recurrence. The aim of this retrospective analysis was to compare the toxicity and oncological outcome of IORT or simultaneous integrated boost (SIB) with conventional external beam radiotherapy (WBI) after breast conserving surgery (BCS). Between 2009 and 2019, patients were treated with a single dose of 20 Gy IORT with 50 kV photons, followed by WBI 50 Gy in 25 or 40.05 in 15 fractions or WBI 50 Gy with SIB up to 58.80-61.60 Gy in 25-28 fractions. Toxicity was compared after propensity score matching. Overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method. A 1:1 propensity-score matching resulted in an IORT + WBI and SIB + WBI cohort of 60 patients, respectively. The median follow-up for IORT + WBI was 43.5 vs. 32 months in the SIB + WBI cohort. Most women had a pT1c tumor: IORT group 33 (55%) vs. 31 (51.7%) SIB group (p = 0.972). The luminal-B immunophenotype was most frequently diagnosed in the IORT group 43 (71.6%) vs. 35 (58.3%) in the SIB group (p = 0.283). The most reported acute adverse event in both groups was radiodermatitis. In the IORT cohort, radiodermatitis was grade 1: 23 (38.3%), grade 2: 26 (43.3%), and grade 3: 6 (10%) vs. SIB cohort grade 1: 3 (5.1%), grade 2: 21 (35%), and grade 3: 7 (11.6%) without a meaningful difference (p = 0.309). Fatigue occurred more frequently in the IORT group (grade 1: 21.7% vs. 6.7%; p = 0.041). In addition, intramammary lymphedema grade 1 occurred significantly more often in the IORT group (11.7% vs. 1.7%; p = 0.026). Both groups showed comparable late toxicity. The 3- and 5-year local control (LC) rates were each 98% in the SIB group vs. 98% and 93% in the IORT group (LS: log rank p = 0.717). Tumor bed boost using IORT and SIB techniques after BCS shows excellent local control and comparable late toxicity, while IORT application exhibits a moderate increase in acute toxicity. These data should be validated by the expected publication of the prospective randomized TARGIT-B study.

Accelerated Partial Breast Irradiation vs. Intraoperative Radiation Therapy for Early-Stage Breast Cancer and Ductal Carcinoma In Situ

<h3>Purpose/Objective(s)</h3> Accelerated partial breast irradiation (APBI) delivered with intensity modulated radiation therapy (IMRT) over 5 fractions represents an attractive and convenient method of delivering adjuvant radiation therapy without compromising oncologic or aesthetic outcomes. Intraoperative radiation therapy (IORT) is another method of delivering radiation therapy to the lumpectomy cavity. Initial results reported in clinical trials utilizing IORT were encouraging; however, with longer follow up, higher rates of local recurrence have been observed in contrast to APBI. We report the outcomes of a large cohort of patients treated with 5 fraction APBI and IORT at our institution after undergoing breast conservation surgery (BCS) for stage 0-IIA breast cancer. <h3>Materials/Methods</h3> We performed a retrospective review of 482 patients with stage I-IIA stage breast cancer and ductal carcinoma in situ (DCIS) treated with lumpectomy and APBI at our institution. In total, 267 patients in our cohort received IMRT from December of 2015 to May of 2021 while 215 patients received IORT from October of 2011 to May of 2019. All patients in the IMRT group received 30 Gy in 5 fractions. All patients in the IORT group received 20 Gy in 1 fraction prescribed to the applicator surface delivered at the time of surgery without additional radiation. Kaplan-Meier analysis was used to estimate locoregional control (LRC) and overall survival (OS) among the 2 groups. <h3>Results</h3> Mean age at diagnosis of the patients was 67 years in the IMRT group and 71 years in the IORT cohort. The IMRT group included 220 patients with Stage I breast cancer (82%), 4 patients with Stage IIA breast cancer (1%), and 43 (16%) patients with DCIS. The IORT group had 198 (92%) with stage I breast cancer, 12 patients (6%) had Stage IIA breast cancer, and 5 patients (2%) had DCIS. After a median follow up of 16 months in the APBI group, only 1 (0.4%) patient experienced a local recurrence, and no patients experienced a regional or distant recurrence. After a median follow up of 55 months in the IORT group, 12 patients (5.6%) experienced a local recurrence, 1 patient (0.5%) experienced a nodal recurrence, and 4 patients (1.9%) experienced a distant recurrence. There was no significant statistical difference in hormonal therapy receipt between both groups (75.3% vs 76.7%, p=0.64). There was no significant difference in 2-year LRC between the APBI and the IORT groups (98.9% in the APBI group vs. 99% in the IORT group, p=0.32). There were no differences in 2-year OS between the two groups (99.6% vs 98.5%, p=0.33). The 5-year LRC was 92.7% in the IORT group. <h3>Conclusion</h3> In a large institutional series of patients with Stage 0-IIA breast cancer treated with BCS followed by 5 fraction APBI or IORT, despite having low risk features and high rates of endocrine therapy use, IORT was associated with high rates of locoregional recurrence of approximately 7% at 5 years. Longer term follow up is needed for comparative effectiveness observations between the two groups.

Intraoperative radiotherapy versus no radiotherapy for early stage low-risk breast cancer patients undergoing breast-conserving surgery: a propensity score matching study based on the SEER database.

To compare the effect of intraoperative radiotherapy (IORT) and no radiotherapy in early stage low-risk breast cancer patients undergoing breast-conserving surgery. According to the criteria recommended by ASTRO for patients eligible for IORT, we retrospectively selected women with early stage low-risk breast cancer who underwent breast-conserving surgery from 2010 to 2019 from the SEER database. Propensity score matching was used to balance the differences in baseline characteristics. The Kaplan-Meier method was used to calculate the overall survival (OS) and breast cancer-specific survival (BCSS) of patients, and the log-rank test was used to compare the differences. A total of 20,245 patients were included in the analysis, including 1738 in the IORT group and 18,507 in the no radiotherapy group, with a median follow-up of 41months. Before matching, the 5-year OS rates of the IORT group and the no radiotherapy group were 95.5% and 85.7% (p < 0.001), respectively, and the 5-year BCSS rates of the two groups were 99.6% and 98.3% (p < 0.001), respectively. After matching, the 5-year OS rates were 95.6% and 90.3% (p < 0.001) in the IORT group and the no radiotherapy group, respectively, and the 5-year BCSS rates were 99.5% and 99.1% (p = 0.028), respectively. Cox multivariate analysis of the original data showed that radiotherapy was an independent prognostic factor for both OS and BCSS (p < 0.05). For patients aged 50years or older with early stage low-risk breast cancer, IORT may be a better option, with improved BCSS compared to the elimination of radiotherapy. The study could not draw conclusions on OS, because underlying diseases may be unevenly distributed between the two groups.

Prognosis comparison between intraoperative radiotherapy and whole-breast external beam radiotherapy for T1-2 stage breast cancer without lymph node metastasis treated with breast-conserving surgery: A case-control study after propensity score matching.

BackgroundExternal beam radiotherapy (EBRT), an adjuvant to breast-conserving surgery (BCS), requires a long treatment period, is costly, and is associated with numerous complications. Large sample studies with long follow-up periods are lacking regarding whether intraoperative radiotherapy (IORT), an emerging radiotherapy modality, can replace EBRT for patients with T1–2 early stage breast cancer without lymph node metastasis treated with BCS.MethodsWe identified 270,842 patients with T1-2N0M0 breast cancer from 2000 to 2018 in the Surveillance, Epidemiology, and End Results (SEER) database. A total of 10,992 patients were matched by propensity score matching (PSM). According to the radiotherapy method, the patients were divided into the IORT and EBRT groups. Overall survival (OS) and breast cancer-specific survival (BCSS) rates were analyzed and compared between the IORT and EBRT groups by Kaplan–Meier analysis. Bilateral P < 0.05 was considered to indicate significance.ResultsAfter PSM, the survival analysis showed no significant differences in OS or BCSS rates between the IORT and EBRT groups. In the subgroup analysis, the IORT population diagnosed from 2010 to 2013 (HRs = 0.675, 95% CI 0.467–0.976, P = 0.037) or with T2 stage (HRs = 0.449, 95% CI 0.261–0.772, P = 0.004) had better OS rates, but in the overall population, the OS and BCSS rates were better in patients with T1 stage than in patients with T2 stage (P < 0.0001), and the proportion of chemotherapy was significantly higher in T2 stage than in T1 stage. Patients who had EBRT with unknown estrogen receptor had better OS rates (HRs = 3.392, 95% CI 1.368–8.407, P = 0.008). In addition, the IORT group had better BCSS rates for married (HRs = 0.403, 95% CI 0.184–0.881, P = 0.023), grade III (HRs = 0.405, 95% CI 0.173–0.952, P = 0.038), and chemotherapy-receiving (HRs = 0.327, 95% CI 0.116–0.917, P = 0.034) patients with breast cancer compared to the EBRT group.ConclusionIntraoperative radiotherapy results of non-inferior OS and BCSS rates, compared to those of EBRT, in patients with early stage breast cancer without lymph node metastasis treated with BCS, and IORT may provide substantial benefits to patients as an effective alternative to standard treatment. This finding provides new insights into radiotherapy strategies for early stage breast cancer.

The impact of intraoperative radiotherapy on breast cancer: focus on the levels of angiogenic factors

ObjectiveAngiogenesis is one of the hallmarks of cancers that is involved in tumor progression. Angiogenic factors induce the formation of new blood vessels and tumor extension, and finally reduce the survival of patients. Intraoperative radiotherapy (IORT), in which radiation is delivered to the tumor bed can kill cells and change tumor microenvironment. Here, we compared the impact of IORT on the levels of angiogenic factors in the blood and surgical wound fluids (SWF) of the breast cancer patients.Patients and methodsThree hundred sixty patients, who had undergone breast-conserving surgery between 2013 and 2018, were enrolled in IORT and non-IORT groups non-randomly. Blood and drained wound fluid (WF) samples were collected from the patients before and after surgery, followed by quantification of the amounts of TGF-β, EGF, FGF, VEGF, and DLL4 in the patients using ELISA.ResultsOur results were indicative of significant differences between the pre-surgery and post-surgery serum levels of EGF, DLL4, and VEGF. Furthermore, ROC analyses showed that TGF-β and DLL4 can differentiate of the early-stage from late-stage of the disease. Interestingly, the rate of the death and recurrence was reduced in IORT group.ConclusionsIn summary, IORT is a safe and effective treatment that can affect angiogenic factors and improve the overall- and recurrence-free survival of breast cancer patients.

Wound Fluid from Breast Cancer Patients Undergoing Intraoperative Radiotherapy Exhibits an Altered Cytokine Profile and Impairs Mesenchymal Stromal Cell Function.

Simple SummaryIntraoperative radiotherapy (IORT) is increasingly used in the therapy of early breast cancer. Besides the direct radiotoxic effects, IORT may add at inhibiting local recurrences by a modulation of the microenvironment. Our aim was to assess the impact of IORT in altering immunological responses and wound healing processes. Thus, we analyzed surgical wound fluid collected after breast conserving surgery with and without IORT concerning acute changes in immune cell populations and cytokine levels. Furthermore, their impact on functions of breast cancer cells and mammary mesenchymal stromal cells (MSC) was assessed. We found no changes in the immune cell composition, yet group-related differences in the expression levels of several cytokines. The application of the wound fluid in MSC cultures caused group-dependent differences in MSC proliferation, wound healing and migration with an alteration of the MSC secretome. Our findings help to elucidate the biological effects of IORT and to clarify the concomitant role of MSC.Intraoperative radiotherapy (IORT) displays an increasingly used treatment option for early breast cancer. It exhibits non-inferiority concerning the risk of recurrence compared to conventional external irradiation (EBRT) in suitable patients with early breast cancer. Since most relapses occur in direct proximity of the former tumor site, the reduction of the risk of local recurrence effected by radiotherapy might partially be due to an alteration of the irradiated tumor bed’s micromilieu. Our aim was to investigate if IORT affects the local micromilieu, especially immune cells with concomitant cytokine profile, and if it has an impact on growth conditions for breast cancer cells as well as mammary mesenchymal stromal cells (MSC), the latter considered as a model of the tumor bed stroma.42 breast cancer patients with breast-conserving surgery were included, of whom 21 received IORT (IORT group) and 21 underwent surgery without IORT (control group). Drainage wound fluid (WF) was collected from both groups 24 h after surgery for flow cytometric analysis of immune cell subset counts and potential apoptosis and for multiplex cytokine analyses (cytokine array and ELISA). It served further as a supplement in cultures of MDA-MB 231 breast cancer cells and mammary MSC for functional analyses, including proliferation, wound healing and migration. Furthermore, the cytokine profile within conditioned media from WF-treated MSC cultures was assessed. Flow cytometric analysis showed no group-related changes of cell count, activation state and apoptosis rates of myeloid, lymphoid leucocytes and regulatory T cells in the WF. Multiplex cytokine analysis of the WF revealed group-related differences in the expression levels of several cytokines, e.g., oncostatin-M, leptin and IL-1β. The application of WF in MDA-MB 231 cultures did not show a group-related difference in proliferation, wound healing and chemotactic migration. However, WF from IORT-treated patients significantly inhibited mammary MSC proliferation, wound healing and migration compared to WF from the control group. The conditioned media collected from WF-treated MSC-cultures also exhibited altered concentrations of VEGF, RANTES and GROα. IORT causes significant changes in the cytokine profile and MSC growth behavior. These changes in the tumor bed could potentially contribute to the beneficial oncological outcome entailed by this technique. The consideration whether this alteration also affects MSC interaction with other stroma components presents a promising gateway for future investigations.

Intraoperative radiotherapy in early breast cancer: Observational comparison with whole breast radiotherapy

IntroductionIn early breast cancer (EBC), a single dose of intraoperative radiotherapy (IORT) might be an option to standard whole breast radiotherapy (WBRT). However, there is no consensus about its use and clinical results. AimTo analyse the morbidity and oncological outcomes of IORT as monotherapy in EBC. MethodsA single centre observational analytic study was performed. A prospective IORT cohort (2015−17) and a retrospective WBRT cohort (2012−17) were selected following the same criteria: ≥ 45 y.o., invasive ductal carcinoma or variants, radiological tumour size ≤ 3cm, positive oestrogenic receptors, negative HER2, cN0; exclusion criteria: lymphovascular invasion, multicentricity/multifocality, BRCA mutation and neoadjuvant therapy. Clinical, histological, surgical, oncological characteristics and complications were collected. ResultsA total of 425 cases were selected: 217 in IORT cohort and 208 in WBRT cohort. Average age in IORT and WBRT groups was 67±9.5 and 64.8±9.9 y.o. respectively (p=0.01). ASA 3 risk score patients were 17.7% in IORT and 24 cases in WBRT (p=0.027). There were no differences in histological results or tumoral stage. Average follow up was 24.4±8 months in IORT and 50.5±18 months in WBRT (p<0.001). No differences were detected in local recurrence, metastases or mortality. Complications that required reintervention or hospitalization were similar in both groups. A total of 3 and 14 cases developed early severe dermatitis in IORT and WBRT groups respectively (p=0.01). ConclusionIORT as monotherapy in selected patients with EBC stands for an alternative option versus WBRT. It seems especially useful in advanced-age patients with severe comorbidities. IORT associates lesser early severe dermatitis.

Intraoperative Radiation Mitigates the Effect of Microscopically Positive Tumor Margins on Survival Among Pancreatic Adenocarcinoma Patients Treated with Neoadjuvant FOLFIRINOX and Chemoradiation.

Microscopically positive margins (R1) negatively impact survival in pancreatic ductal adenocarcinoma (PDAC). For patients with close/positive margins, intraoperative radiotherapy (IORT) can improve local control. The prognostic impact of an R1 resection in patients who receive total neoadjuvant therapy (TNT; FOLFIRINOX with chemoradiation) and IORT is unknown. Clinicopathologic data were retrospectively collected for borderline/locally advanced (BR/LA) PDAC patients who received TNT and underwent resection between 2011 and 2019. Disease-free (DFS) and overall survival (OS) measured from time of diagnosis were compared between groups. Two hundred one patients received TNT and were resected, with a median DFS and OS of 24months and 47months, respectively. Eighty-eight patients (44%) received IORT; of these, 69 (78%) underwent an R0 and 19 (22%) an R1 resection. There was no significant difference in clinicopathologic factors between the IORT and no-IORT groups, except for resectability status (LA: IORT 69%, no-IORT 53%, p = 0.021) and surgeons' concern for a positive/close margin. R1 resection was associated with worse DFS and OS in the no-IORT population. However, among patients who received IORT, there was no difference in DFS (R0: 29months, IQR 14-47 vs R1: 20months, IQR 15-28; p = 0.114) or OS (R0: 48months, IQR 25-not reached vs R1: 37months, IQR 30-47; p = 0.307) between patients who underwent R0 vs R1 resection. In multivariate analysis, within the IORT group, R1 resection was not associated with DFS or OS. IORT may mitigate the adverse effect of an R1 resection on DFS and OS in BR/LA PDAC patients receiving TNT.

Quality of Life Assessment After Conserving Breast Surgery and Intraoperative Radiotherapy (IORT) in Breast Cancer Patients Using the BREAST-Q Questionnaire

Background: In women undergoing breast surgery, Measurement of Patient Related Outcome Measures (PROMs) is important for improving the process of care, focusing on the patient's perspective. BREASTQ is a validated patient-reported outcome measure used increasingly in aesthetic and recostructive surgery. Only recently a breast conserving therapy module (BREASTQ-BCT) has been available. The aim of this study was to assess patient satisfaction and quality of life using BREAST-Q questionnaire in patients undergoing breast conserving surgery (BCS) plus IORT.Methods: Women undergoing BCS plus IORT for an early-stage breast cancer for at least a year were invited by telephone to partecipate. We scheduled dedicated outpatient visits to our center. The medical interviewer collected medical history information and administered the BREASTQ-BCT in paper format. Data were inserted in a de-identified database. Univariate regression analysis was used to identify clinicopathological variables associated with "satisfaction with breast" domain score.Results: Overall, 38 women completed the questionnaire. The domains of the questionnaire that obtained the lowest scores were ‘satisfaction with IORT information’ and ‘satisfaction with breasts’ (median score 59, IQR 55-73 and 51-69.5). Weight of specimen and vascular invasion were risk factors for lower ‘Satisfaction with breasts’ at univariate analysis. There was a moderate-strong correlation between 'satisfaction with the breasts' and 'psychosocial wellbeing' and 'Sexual wellbeing'.Conclusions: In this retrospective study, without a pre-operative questionnaire, changes in individuals’ satisfaction and quality of life could not be identified. A prospective study comparing BCS plus external RT group and BCS plus IORT group could be informative.

Intraoperative radiotherapy versus whole-breast external beam radiotherapy, and other factors associated with the prognosis of early breast cancer treated with breast-conserving surgery and radiotherapy: a retrospective study from SEER database.

BackgroundThis study was aimed to investigate the prognostic factors of early breast cancer treated with breast-conserving surgery (BCS) and radiotherapy. Besides, we focused our attention exclusively on the comparison of the impact on prognosis between intraoperative radiotherapy (IORT) and whole-breast external beam radiotherapy (EBRT).MethodsAn observational cohort study was performed on patients with Tis-2 N0–1 M0 breast cancer from the Surveillance, Epidemiology, and End Results (SEER) database who treated with BCS and radiotherapy. Cox regression analysis, Kaplan-Meier analysis, and propensity score matching (PSM) were used to estimate risk factors for overall survival (OS) and breast cancer-specific survival (BCSS).ResultsOf the 98,614 early breast cancer patients treated with BCS and radiotherapy, 97,164 (98.5%) patients underwent EBRT and 1,450 (1.5%) underwent IORT. Multivariable Cox regression analysis showed that early breast cancer patients with age ≥65, poor marital status, lack of medical insurance, histological grade III/IV (SEER 4 grades), high T stage, high N stage, and TNBC were associated with a decreased OS/BCSS, whereas ER-positive and PR-positive were associated with an improved OS/BCSS. No significant difference was observed in survival between IORT and EBRT groups (P=0.213 for OS, P=0.180 for BCSS), or between intraoperative beam radiation and intraoperative radioactive implants groups (P=0.319 for OS, P=0.972 for BCSS).ConclusionsOur study can help clinicians identify patients with poor prognosis after breast-conserving therapy. IORT may be an alternative to EBRT for early breast cancer patients who are unable to complete the long-term postoperative radiation treatment. Beam radiation and radioactive implants are both ideal alternatives for patients who choose IORT.

Impact of intraoperative radiotherapy on the perioperative period of patients after breast-conserving surgery.

To investigate the effect of intraoperative radiotherapy (IORT) in the perioperative period of patients after breast-conserving surgery (BCS). The clinical data of 100 patients with early breast cancer undergoing breast-conserving surgery (BCS) followed by treatment with IORT using the Intrabeam system (Carl Zeiss Meditec, Oberkochen, Germany) (BCS + IORT group, n=100) between June 2016 and December 2019 were analyzed and compared with the data of 60 matched patients who only underwent breast-conserving therapy over the same period (BCS group, n=60). The surgical settings and postoperative acute complications between the groups were assessed. There was no significant statistical difference between the groups in terms of age, tumor size, grading, lymph node status, hormone receptor status, and human epidermal growth factor receptor 2 (HER-2) status (P>0.05). The BCS + IORT group had a significantly longer surgery duration (P<0.05), but there was no significant statistical difference in terms of intraoperative blood loss, amount of bleeding, drainage tube removal time, postoperative length of hospitalization, incision suture removal time, or incidence of postoperative complications (P>0.05). IORT using the Intrabeam system safely delivers radiation therapy, is well-tolerated, has acceptable acute toxicity, and does not significant increase the risk of surgery or the incidence of perioperative complications.

Cardiac serum marker alterations after intraoperative radiotherapy with low-energy x-rays in early breast cancer as an indicator of possible cardiac toxicity

PurposeTo assess acute cardiac toxicity caused by intraoperative radiotherapy (IORT) with low-energy x‑rays for early breast cancer.MethodsWe prospectively analyzed pre- and postoperative troponin I and NT-proBNP in 94 women who underwent breast-conserving surgery between 2013 and 2017 at the Department of Gynecology and Obstetrics of the University Medical Center Mannheim, Germany. Thirty-nine women received IORT using low-energy x‑rays during breast-conserving surgery while 55 patients without IORT formed the control group. Demographic and surgical parameters as well as cardiac markers were evaluated.ResultsThere were no significant differences concerning age and side of breast cancer between the groups. Furthermore, no significant difference between the troponin I assays of the IORT and control groups could be found (preoperatively: 0.017 ± 0.006 ng/ml vs. 0.018 ± 0.008 ng/ml; p = 0.5105; postoperatively: 0.019 ± 0.012 ng/ml vs. 0.018 ± 0.010 ng/ml; p = 0.6225). N‑terminal fragment of B‑type natriuretic peptide (NT-proBNP) was significantly higher in the control group 24 h after surgery (preoperatively: 158.154 ± 169.427 pg/ml vs. 162.109 ± 147.343 pg/ml; p = 0.56; postoperatively: 168.846 ± 160.227 pg/ml vs. 232.527 ± 188.957 pg/ml; p = 0.0279).ConclusionTroponin I levels as a marker of acute cardiac toxicity did not show any significant differences in patients who received IORT during breast-conserving surgery compared to those who did not.

Safety and efficacy of INTRABEAM intraoperative radiotherapy for invasive thymoma.

Intraoperative radiotherapy (IORT) has been used to treat different residual solid tumors after tumor removal and has shown many advantages over other treatment methods. However, the use of IORT for invasive thymoma has not been reported. Therefore, in this study, we tried to determine the safety and efficacy of INTRABEAM IORT for the treatment of invasive thymoma.Among the patients admitted to our hospital from September to December 2016 who were diagnosed with invasive thymoma, 14 were selected as study subjects. With medical histories taken beforehand, 8 of these patients were diagnosed with Masaoka stage IIA and 6 with Masaoka stage IIB; furthermore, 5 of the patients were diagnosed with myasthenia gravis (MG). INTRABEAM radiation (8–10 Gy, low energy) was delivered to the postoperative tumor bed of each patient during surgery. The intra- and postoperative complications were observed and evaluated, and the improvement in symptoms was assessed. An additional 23 patients with stage II thymoma undergoing radical surgery from April to August 2016 were chosen as the control group.One month after the operation, only 1 patient in the IORT group had cough, increased levels of leucocytes and neutrophils, and pulmonary inflammation on chest computed tomography. Reactive inflammation and pleural effusion in the 2 groups were similar (P > .05). There was no significant difference between the 2 groups in the improvement of myasthenia gravis (P > .05). Postoperative chest computed tomography and routine blood examination at 3 and 12 months showed that all the patients recovered, with normal hemogram levels and no pulmonary fibrosis around the radiation field. In addition, ultrasonic cardiography and electrocardiography demonstrated no significant difference before or after surgery within the IORT group. At the end of the follow-up, all the patients were alive, no relapse or remote metastasis was observed in the IORT group, and 2 inpatients in the control group had experienced relapse at 24 and 26 months. There was a significant difference in disease-free survival between the 2 groups (P = .00).It is safe to administer low-energy INTRABEAM IORT at a dose of approximately 10 Gy in patients with stage II invasive thymoma. INTRABEAM IORT does not significantly increase operation- or radiation-related complications and has no significant effect on vital organs such as the lungs and heart. Its long-term efficacy is worth expecting.

Radioterapia intraoperatoria en cáncer de mama precoz: análisis observacional frente a radioterapia externa

IntroductionIn early breast cancer (EBC), a single dose of intraoperative radiotherapy (IORT) might be an option to standard whole breast radiotherapy (WBRT). However, there is no consensus about its use and clinical results. Aimto analyse the morbidity and oncological outcomes of IORT as monotherapy in EBC. MethodsA single centre observational analytic study was performed. A prospective IORT cohort (2015-17) and a retrospective WBRT cohort (2012-17) were selected following the same criteria: ≥ 45 y.o., invasive ductal carcinoma or variants, radiological tumour size ≤ 3 cm, positive oestrogenic receptors, negative HER2, cN0; exclusion criteria: lymphovascular invasion, multicentricity/multifocality, BRCA mutation and neoadjuvant therapy. Clinical, histological, surgical, oncological characteristics and complications were collected. ResultsA total of 425 cases were selected: 217 in IORT cohort and 208 in WBRT cohort. Average age in IORT and WBRT groups was 67±9.5 and 64.8 ± 9.9 y.o. respectively (p = 0.01). ASA 3 risk score patients were 17.7% in IORT and 24 cases in WBRT (p = 0.027). There were no differences in histological results or tumoral stage. Average follow up was 24.4 ± 8 months in IORT and 50.5 ± 18 months in WBRT (p < 0.001). No differences were detected in local recurrence, metastases or mortality. Complications that required reintervention or hospitalization were similar in both groups. A total of 3 and 14 cases developed early severe dermatitis in IORT and WBRT groups respectively (p = 0.01). ConclusionIORT as monotherapy in selected patients with EBC stands for an alternative option versus WBRT. It seems especially useful in advanced-age patients with severe comorbidities. IORT associates lesser early severe dermatitis.

Intra-operative radiation therapy as salvage treatment option for recurrent glioblastoma multiforme.

2535 Background: Glioblastoma multiforme (GBM) is an extremely aggressive cerebral tumor with poor prognosis. The majority of patients relapse after the initial surgery plus adjuvant radiation and chemotherapy. In case of recurrence there is no established standard therapy. The optimal techniques for salvage re-irradiation are unclear, so that procedure poses a challenge. In contrast to traditional external beam radiotherapy (EBRT) intra-operative radiotherapy (IORT) may improve patient’s outcome at the cost of minimal side effects and short treatment duration. Methods: A total of 30 patients were treated with recurrent GBM between August 2016 and June 2019. All patients underwent maximal safe resection; patients were divided into IORT and EBRT groups. 15 patients were included in each group with similar clinical characteristics. All patients in IORT group underwent maximal safe microsurgical resection with subsequent intraoperative balloon electronic brachytherapy (IBEB) and no further adjuvant treatment. IBEB was performed using Axxent electronic brachytherapy device (Xoft Electronic Brachytherapy (eBx) System, USA. Patients in EBRT group underwent same surgery followed by external beam radiotherapy. Contrast-enhanced brain MRI with perfusion was performed within 24 hours of surgery +/- brain PET-CT with 18-FDOPA and then every 3 months. Both groups were also assigned to subgroups (≤ 2.5cm3 and &gt; 2.5cm3) based on post-operative contrast-enhancing volume (POCEV). Median overall survival (OS) since diagnosis and local progression-free survival (locPFS) following the second surgery were analyzed. Possible toxicities and prognostic factors were also evaluated. Results: Median OS was 27 months in IORT group and 21 months in EBRT group. The locPFS range between 3.5 to 39 months in IORT group and only 2 to 10 months in group with EBRT. Kaplan-Meier OS curves in patients with POCEV ≤ 2.5cm3 showed more favorable outcomes for patients in the IORT group (p &lt; 0.05). In patients with POCEV &gt; 2.5cm3 the median OS was 17 months in IORT group and 13.5 months in EBRT group. Conclusions: IORT of recurrent GBM is feasible and provides encouraging local progression-free and overall survival; no high-grade radiation induced toxicities occur and further studies to establish this method are mandatory. The toxicity profile of additional IBEB was manageable. Maximal safe microsurgical resection is the most important prognostic factor and could determine the effectiveness of post-surgical IBEB.

Intraoperative radiotherapy for resectable advanced lower rectal cancer-final results of a randomized controlled trial (UMIN000021353).

Pelvic autonomic nerve preservation (PANP) is useful to preserve voiding and sexual function after rectal cancer surgery. The aim of this study was to investigate the benefit of intraoperative radiotherapy (IORT) to have complete PANP without affecting oncological outcomes. Patients undergoing potentially curative resection of the rectum were included. They were randomized to intraoperative radiotherapy of the completely preserved bilateral pelvic nerve plexuses (IORT group) or the control group without IORT, but with limited nerve preservation. The primary endpoint was pelvic sidewall recurrence. Moreover, patients' clinicopathologic parameters, postoperative complications, voiding function, and other oncologic outcomes were compared. From 79 patients, three were excluded from analysis, resulting in 38 patients in each group. Patients' demographic and pathological parameters were well balanced between the two groups. The trial was terminated prematurely in July 2017, because distant metastasis-free survivals were found to be significantly worse in the IORT group compared to the control group (odds ratio 2.554; 95% CI, 1.041 ~ 6.269; p= 0.041). Neither overall survival nor pelvic sidewall recurrence did differ between the two groups (overall survival: odds ratio 1.264; 95% CI, 0.523~3.051; p= 0.603/pelvic sidewall recurrence; odds ratio 1.350; 95% CI, 0.302~6.034; p= 0.694). Postoperative complications did not differ between the groups; however, the urinary function was significantly better in the IORT group in the short and long term. With the aid of IORT, complete PANP can be done without increase of pelvic sidewall recurrence; however, IORT may increase the incidence of distant metastases. Therefore, IORT cannot be recommended as a standard therapy to compensate less radical resection for advanced lower rectal cancer.

Intraoperative Boost Radiotherapy with 50 kV X-Rays Versus External Radiotherapy in Breast Cancer: Single-Center Experiences

Background: Intraoperative radiotherapy (IORT) within breast conserving surgery (BCS) is progressively utilized to deliver the optimal dose of radiotherapy immediately after the excision of cancer during the same operation to the well-vascularized tissue and to the margin of resected cancer to damage the cancer cells, which might remain nearby the tumor just on time without no delay as radical irradiation for particular cases or as boost dose for others. Methods: This study reports 54-month single-center experiences after introduction to deliver IORT (50 kV x-ray) as a tumor bed boost in BCS for breast cancer and comparison with external beam radiation therapy (EBRT). In this retrospective study, 255 patients (stages 1 - 3) with breast cancer were treated with BCS and IORT in the Cancer Research Center, Shahid Beheshti University of Medical Sciences (April 2014-September 2018). They received 20 Gy IORT as a boost compared with 321 patients in the same stages with EBRT. Results: Within 54 months, there were 3 (1.2%) occurrences of local recurrence in IORT patients compared with 8 (2.5%) local recurrences in EBRT patients (P = 0.361) and 12 (4.7%) metastasis in the IORT group vs. 20 (6.2%) in the EBRT group (P = 0.724). The 5-year disease-free survival (DFS) was 85.1% in the IORT group compared with 86% in the EBRT group. Conclusions: IORT tumor bed boost with 50 kV x-ray during breast conserving therapy had a better outcome, but it was not significant compared with EBRT.

Surgical Wound Fluids from Patients with Breast Cancer Reveal Similarities in the Biological Response Induced by Intraoperative Radiation Therapy and the Radiation-Induced Bystander Effect-Transcriptomic Approach.

In patients with breast cancer who undergo breast-conserving surgery (BCS), more than 90% of local recurrences occur in the same quadrant as the primary cancer. Surgical wound fluids (SWF) are believed to play a role in this process by inducing an inflammatory process in the scar tissue area. Despite strong clinical data demonstrating the benefits of intraoperative radiotherapy (IORT), the biological basis underlying this process remains poorly understood. Ionizing radiation (IR) directly affects cells by damaging DNA, thereby altering the cell phenotype. IR directly affects cancer cells and also influences unirradiated cells located nearby, a phenomenon known as the radiation-induced bystander effect (RIBE), significantly modifying the tumor microenvironment. We hypothesized that SWF obtained from patients after BCS and IORT would induce a radiobiological response (due to RIBE) in unirradiated cells, thereby modifying their phenotype. To confirm this hypothesis, breast cancer cells were incubated with SWF collected from patients after BCS: (1) without IORT (wound fluid (WF) group), (2) with IORT (radiotherapy wound fluid (RT-WF) group), and (3) WF with conditioned medium from irradiated cells (WF+RIBE group) and then subjected to microarray analysis. We performed gene set enrichment analysis to determine the biological processes present in these cells. This analysis showed that the RT-WF and WF+RIBE groups shared common biological processes, including the enhancement of processes involved in cell-cycle regulation, DNA repair, and oxidative phosphorylation. The WF group was characterized by overrepresentation of pathways involved in the INF-α and INF-γ response, inflammatory response, and the IL6 JAK/STAT3 signaling pathway. These findings show that MDA-MB-468 cells stimulated with surgical wound fluids obtained from patients who underwent BCS plus IORT and from cells stimulated with SWF plus RIBE share common biological processes. This confirms the role of the radiation-induced bystander effect in altering the biological properties of wound fluids.

Intraoperative radiotherapy as an immediate adjuvant treatment of rectal cancer due to limited access to external-beam radiotherapy

BackgroundNeoadjuvant external-beam radiotherapy (EBRT) with concomitant chemotherapy is the current standard-of-care for locally-advanced rectal cancer. Intraoperative radiotherapy (IORT) is to date only recommended for pelvic recurrences or incompletely resectable tumors. We here report on patients with stage II/III rectal cancer that were treated with IORT in a regional Russian university center due to limited access to EBRT.MethodsWe retrospectively analyzed data from patients that were diagnosed with locally-advanced rectal cancer and underwent surgery from December 2012 to October 2016 at a regional oncological center in Russia (Krasnodar). During this period, access to EBRT was limited due to a temporary lack of a sufficient number of EBRT facilities. Patients unable to travel to a distant radiotherapy site received IORT alone, those that could travel received neoadjuvant external beam (chemo-) radiotherapy. Factors of interest were tumor stage, tumor differentiation, resection status, surgery type and neoadjuvant or adjuvant chemotherapy. We assessed local progression-free survival (L-PFS), PFS and overall survival (OS).ResultsA total of 172 patients were included in this analysis. Of those, 92 (53.5%) were treated with IORT alone (median dose: 15 Gy [8.4–17 Gy]) and 80 (46.5%) received both neoadjuvant EBRT (median dose: 50.4 Gy [40–50.4 Gy]) and IORT (median dose: 15 Gy [15–17 Gy]). The median age was 65 years [33–82]. The median follow-up was 23 months [0–63 months]. The incidence of toxicity was low in both groups with an overall complication rate of 5.4%. Local PFS at 4 years was comparable with 59.4% in the IORT group and 65.4% in the IORT/EBRT group (p = 0.70). Similarly, there was no difference in OS or PFS (p = 0.66, p = 0.51, respectively).ConclusionsIORT is a valuable option for patients with locally-advanced rectal cancer in the absence of access to EBRT.