Application Of Intraoperative Radiotherapy Research Articles

Использование интраоперационной лучевой терапии при комбинированном лечении операбельного рака лёгкого. Обзор

The treatment of non-small-cell lung cancer (NSCLC) continues to be a pressing issue. It is therefore necessary to advance and to put into practice the methods that will improve patients survival. The aim of the study was to estimate available information on application of intraoperative radiation therapy (IORT) in combined treatment of patients with NSCLC. The treatment plans, safety and tolerability of the treatment method were evaluated. From data analysis it became clear that IORT is a topical treatment for operable non-small cell lung cancer (NSCLC). The new technology has proved its effectiveness due to the reliable local control and significant improve the late survival of patients. During the IORT high one-off dose is selectively delivered to the tumor or tumor bed with maximum preservation of the adjacent normal tissues. The key point in planning radiation exposure during the IORT is to calculate accurately the single radiation dose. The reduction of local relapses and the improvement in overall survival are most likely due to the IORT damaging effect on possible tumor microfoci located in the bronchus cult, its surrounding tissues and lymphatic outflow pathways. To date, further study of the IORT effectiveness and feasibility will remain relevant. However, intraoperative irradiation has already proved to be an effective component of a multimodal approach to cancer treatment.

Application of Intraoperative Radiotherapy in Early-Stage Breast Cancer Patients in a Clinical Setting.

Background: Intraoperative radiation therapy (IORT) has gained popularity in recent years as an alternative to external beam whole breast radiation therapy (WBRT) for early-stage breast cancer. Here, we report 43-month recurrence and survival outcomes in a multiethnic cohort treated with IORT in a clinical context. Method: Two hundred and eleven patients with low-risk features were treated with IORT for early-stage breast cancer from 2014 to 2021. Selection criteria were based on Group Europeen de Curietherapie-European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) guidelines: preferably unifocal intraductal carcinoma (IDC), aged > 50, tumor size ≤ 2.0 cm, and without lymph node involvement. All patients received 20 Gy of radiation dose during the lumpectomy. Information on patient and tumor characteristics was collected. Results: The mean age of this cohort was 67.5 years; 95.2% of patients are Jewish, and the rest are Bedouins (4.7%). Most tumors were intraductal carcinoma (97.2%) and stage 1 (94.8%). The mean follow-up time was 43.4 months. Bedouins had larger tumor sizes (mean 1.21 vs. 1.13 cm) and were younger at diagnosis than Jewish patients (mean 65.4 vs. 67.6 years), although the differences are not significant. The overall recurrence rate was 1.4%. One case of local recurrence (0.5%) and two cases of metastasis (0.9%) were observed during the study period. One patient died from metastasis. Conclusion: Our findings suggest that IORT in selected low-risk patients can achieve an excellent prognosis with low rates of recurrence and metastasis.

A COMPACT NEUTRON GENERATOR FOR THE NIORT® TREATMENT OF SEVERE SOLID CANCERS

In the last four years, TheranostiCentre S.r.l., Berkion Technology LLC and ENEA have patented and fabricated a first prototype of a Compact Neutron Generator (CNG) currently under testing in the ENEA laboratories. Besides the usual applications in the field of materials irradiation, this CNG - producing neutrons of 2.45 MeV energy by using the DD fusion reaction - was conceived for the neutron irradiation of the solid cancer’s tumour bed by means of the Intra-Operative Radiotherapy (IORT) technique, the so-called neutron-IORT (nIORT®). The CNG is self-shielded and light-weight (~120 kg) making possible its remote handling by a robotic arm. Accurate Monte Carlo simulations, modelling the CNG and the “open wound” biological tissues near its irradiation window, demonstrated that the apparatus - operated at 100 kV-10 mA - supplies a neutron flux ~108 cm-2 s-1 and can deliver equivalent dose rates ~2 Gy (RBE)/min. Hence, it can administer very high dose levels in limited treatment times. This article briefly summarizes the main findings of this collaborative research study, the clinical rationales underpinning the nIORT® idea and the potential performances of the CNG for the treatment of solid cancer pathologies. Indeed, the CNG can be installed in an operating room dedicated to nIORT® treatments, without posing any environmental and safety issues. Monte Carlo simulations have been carried out by envisioning the CNG equipped with an IORT applicator, that is an applicator pipe with a tuneable diameter to be inserted in the surgical cavity. By foreseeing the clinical endpoints of the standard IORT protocols, the irradiation performances for potential nIORT® treatments - obtained with an applicator pipe of 6 cm diameter - are here reported for different regimes: from 10 up to 75 Gy (RBE), that can be administered in a single session of about 4 to 30 minutes. Besides the dose peak in the centre of the tumour bed, the almost isotropic neutrons emission allows to irradiate the surroundings side-walls of the tumour bed – usually filled by potential quiescent cancer cells (QCCs) – and therefore reducing the chances of local recurrences by improving the local control of the tumour. The rapid decrease in tissues depth of the dose profile (in few centimetres) will spare the neighbouring organs at risk from harmful radiations. Thus, the CNG apparatus developed for nIORT® applications can potentially improve the resectability rate of a given neoadjuvant cancer treatment and, generally, could satisfy all five R’s criteria of radiotherapy. Furthermore, in comparing with the current IORT techniques with electrons or low-keV X-rays, the nIORT® exploiting a high-flux neutrons beam of 2.45 MeV energy could lead to some significant clinical advantages due to its larger Linear Energy Transfer (LET, ~ 40 keV/m as average) and significantly higher Relative Biological Effectiveness (RBE 16) than all other forms of ionizing radiation.

Intraoperative radiation therapy for early-stage breast cancer: a single-institution experience.

BackgroundTo assess outcomes and toxicity after low-energy intraoperative radiotherapy (IORT) for early-stage breast cancer (ESBC).Materials and methodsWe reviewed patients with unilateral ESBC treated with breast-conserving surgery and 50-kV IORT at our institution. Patients were prescribed 20 Gy to the surface of the spherical applicator, fitted to the surgical cavity during surgery. Patients who did not meet institutional guidelines for IORT alone on final pathology were recommended adjuvant treatment, including additional surgery and/or external-beam radiation therapy (EBRT). We analyzed ipsilateral breast tumor recurrence, overall survival, recurrence-free survival and toxicity.ResultsAmong 201 patients (median follow-up, 5.1 years; median age, 67 years), 88% were Her2 negative and ER positive and/or PR positive, 98% had invasive ductal carcinoma, 87% had grade 1 or 2, and 95% had clinical T1 disease. Most had pathological stage T1 (93%) N0 (95%) disease. Mean IORT applicator dose at 1-cm depth was 6.3 Gy. Post-IORT treatment included additional surgery, 10%; EBRT, 11%; adjuvant chemotherapy, 9%; and adjuvant hormonal therapy, 74%. Median total EBRT dose was 42.4 (range, 40.05–63) Gy and median dose per fraction was 2.65 Gy. At 5 years, the cumulative incidence of ipsilateral breast tumor recurrence was 2.7%, the overall survival rate was 95% with no breast cancer-related deaths, and the recurrence-free survival rate was 96%. For patients who were deemed unsuitable for postoperative IORT alone and did not receive recommended risk-adapted EBRT, the IBTR rate was 4.7% versus 1.7% (p = 0.23) for patients who were either suitable for IORT alone or unsuitable and received adjuvant EBRT. Cosmetic toxicity data was available for 83%, with 7% experiencing grade 3 breast toxicity and no grade 4–5 toxicity.ConclusionsIORT for select patients with ESBC results in acceptable outcomes in regard to ipsilateral breast tumor recurrence and toxicity.

Low dose intraoperative radiation does positively influence recurrence after resection of retroperitoneal liposarcoma

Background: In retroperitoneal soft tissue sarcoma (STS) local recurrence (LR) rates are high. Application of intraoperative radiation therapy (IORT) has been frequently discussed. Still, the significance of IORT in multimodal treatment of retroperitoneal STS remains unclear.

Monte Carlo calculation of the TG-43 dosimetry parameters for the INTRABEAM source with spherical applicators

Objective: The relative TG-43 dosimetry parameters of the INTRABEAM (Carl Zeiss Meditec AG, Jena, Germany) bare probe were recently reported by Ayala Alvarez et al (2020 Phys. Med. Biol. 65 245041). The current study focuses on the dosimetry characterization of the INTRABEAM source with the eight available spherical applicators according to the TG-43 formalism using Monte Carlo (MC) simulations. Approach: This report includes the calculated dose-rate conversion coefficients that determine the absolute dose rate to water at a reference point of 10 mm from the applicator surface, based on calibration air-kerma rate measurements at 50 cm from the source on its transverse plane. Since the air-kerma rate measurements are not yet provided from a standards laboratory for the INTRABEAM, the values in the present study were calculated with MC. This approach is aligned with other works in the search for standardization of the dosimetry of electronic brachytherapy sources. As a validation of the MC model, depth dose calculations along the source axis were compared with calibration data from the source manufacturer. Main results: The calculated dose-rate conversion coefficients were 434.0 for the bare probe, and 683.5, 548.3, 449.9, 376.5, 251.0, 225.6, 202.8, and 182.6 for the source with applicators of increasing diameter from 15 to 50 mm, respectively. The radial dose and the 2D anisotropy functions of the TG-43 formalism were also obtained and tabulated in this document. Significance: This work presents the data required by a treatment planning system for the characterization of the INTRABEAM system in the context of intraoperative radiotherapy applications.

Monte Carlo calculation of the relative TG-43 dosimetry parameters for the INTRABEAM electronic brachytherapy source

The INTRABEAM system (Carl Zeiss Meditec AG, Jena, Germany) is an electronic brachytherapy (eBT) device designed for intraoperative radiotherapy applications. To date, the INTRABEAM x-ray source has not been characterized according to the AAPM TG-43 specifications for brachytherapy sources. This restricts its modelling in commercial treatment planning systems (TPSs), with the consequence that the doses to organs at risk are unknown. The aim of this work is to characterize the INTRABEAM source according to the TG-43 brachytherapy dosimetry protocol. The dose distribution in water around the source was determined with Monte Carlo (MC) calculations. For the validation of the MC model, depth dose calculations along the source longitudinal axis were compared with measurements using a soft x-ray ionization chamber (PTW 34013) and two synthetic diamond detectors (microDiamond PTW TN60019). In our results, the measurements in water agreed with the MC model calculations within uncertainties. The use of the microDiamond detector yielded better agreement with MC calculations, within estimated uncertainties, compared to the ionization chamber at points of steeper dose gradients. The radial dose function showed a steep fall-off close to the INTRABEAM source (10 mm) with a gradient higher than that of commonly used brachytherapy radionuclides (192Ir, 125I and 103Pd), with values of 2.510, 1.645 and 1.232 at 4, 6 and 8 mm, respectively. The radial dose function partially flattens at larger distances with a fall-off comparable to that of the Xoft Axxent® (iCAD, Inc., Nashua, NH) eBT system. The simulated 2D polar anisotropy close to the bare probe walls showed deviations from unity of up to 55% at 10 mm and 155°. This work presents the MC calculated TG-43 parameters for the INTRABEAM, which constitute the necessary data for the characterization of the source as required by a TPS used in clinical dose calculations.

Impact of spherical applicator diameter on relative biologic effectiveness of low energy IORT X-rays: A hybrid Monte Carlo study.

Low-kV IORT (Low kilovoltage intraoperative radiotherapy) using INTRABEAM machine and dedicated spherical applicators is a candidate modality for breast cancer treatment. The current study aims to quantify the RBE (relative biologic effectiveness) variations of emitted X-rays from the surface of different spherical applicators and bare probe through a hybrid Monte Carlo (MC) simulation approach. A validated MC model of INTRABEAM machine and different applicator diameters, based on GEANT4 Toolkit, was employed for RBE evaluation. To doing so, scored X-ray energy spectra at the surface of each applicator diameter/bare probe were used to calculate the corresponding secondary electron energy spectra at various distances inside the water and breast tissue. Then, MCDS (Monte Carlo damage simulation) code was used to calculate the RBE values according to the calculated electron spectra. Presence of spherical applicators can increase the RBE of emitted X-rays from the bare probe by about 22.3%. In return, changing the applicator diameter has a minimal impact (about 3.2%) on RBE variation of emitted X-rays from each applicator surface. By increasing the distance from applicator surface, the RBE increments too, so that its value enhances by about 10% with moving from 2 to 10mm distance. Calculated RBE values within the breast tissue were higher than those of water by about 4% maximum value. Ball section of spherical IORT applicators can affect the RBE value of the emitted X-rays from INTRABEAM machine. Increased RBE of breast tissue can reduce the prescribed dose for breast irradiation if INTRABEAM machine has been calibrated inside the water.

Intraoperative Radiation Therapy for Early-Stage Breast Cancer: A Single-Institution Experience

We assessed patient outcomes and toxicity after the use of intraoperative low-energy photon radiotherapy for select early-stage breast cancer (ESBC) patients. This is a retrospective review of patients with unilateral ESBC treated with breast-conservation surgery followed by low-energy photon intraoperative radiotherapy (IORT) at a single institution between 2010 and 2017. Institutional suitability guidelines included: age ≥ 50 years, invasive ductal carcinoma (IDC) with or without DCIS, grade 1 – 2 tumors < 3 cm, ER and or PR positive, Her2 negative, clinically node negative, no lymphovascular space invasion (LVSI), and negative margins (>2 mm). 20 Gy was prescribed to the surface of the spherical applicator fitted to the surgical cavity at surgery. Postoperative patients who did not meet institutional guidelines for IORT alone were recommended adjuvant treatment, including possible additional surgery, external-beam radiotherapy (EBRT), chemotherapy, and/or endocrine therapy. Kaplan-Meier estimates and Cox regression analysis were used to assess ipsilateral breast tumor recurrence (IBTR), overall survival (OS), and relapse-free survival (RFS). 201 patients were included with a median follow up of 5.1 years. Most patients met institutional guidelines for IORT for ESBC. The median age was 67 years; 88% were Her2 negative and ER positive and/or PR positive, 97% had IDC, 87% had grade 1 or 2 disease on biopsy, and 95% had T1 disease. On final pathology, 8% had LVSI, 25% had close (<2 mm) margins, and 3% had positive margins. Most had pathological T1 (93%) N0 (95%) disease. The median IORT applicator size was 4.5 cm with a mean dose at 1 cm depth of 6.3 Gy delivered over an average of 37 minutes. 10% of patients completed additional surgery, 11% additional EBRT, 9% adjuvant chemotherapy, and 74% received adjuvant hormonal therapy. The median total EBRT dose was 42.4 Gy (range 40.05 - 63 Gy) with a median dose of 2.65 Gy/fraction. The 5-year cumulative risk of IBTR was 2%. There was no statistically significant difference in IBTR between patients considered unsuitable by our institutional guidelines (p = 0.93) or by the 2016 ASTRO consensus guidelines (p = 0.26) compared to patients who were considered suitable for IORT alone, by respective guidelines. Of the 98 patients who did not meet institutional criteria based on final surgical pathology, 32% received adjuvant EBRT. Of the 9 patients who experienced IBTR, 5 patients did not undergo indicated EBRT. The 5-year OS rate was 95% with no breast cancer-related deaths. The 5-year RFS rate was 96%. 83% of patients had documented toxicity information and the overall highest reported grade 3 toxicity was 8%; seroma was the most common grade 3 toxicity (4%). IORT for select patients with ESBC has led to acceptable outcomes in regards to ipsilateral breast tumor recurrence and toxicity. We continue to recommend adjuvant EBRT for patients who do not meet IORT suitability criteria upon review of final pathology.

A prospective, single-arm, phase II clinical trial of intraoperative radiotherapy using a low-energy X-ray source for local advanced Laryngocarcinoma (ILAL): a study protocol

BackgroundLaryngocarcinoma (LC), in most cases a squamous cell carcinoma, accounts for 1 ~ 5% of the incidence of all tumors. At present, laryngocarcinoma is mainly managed with the integration of surgery and radio- and chemo-therapies. The current development trend of treatment is to improve the local control rate of tumor and the quality of life of patients. Intraoperative radiation therapy (IORT) is a radiotherapy that delivers single high dose irradiation at a close range to the tumor bed during the surgical operation process. It has particular radiobiological advantages in protecting normal surrounding tissues by directly applying the irradiation dose to the high-risk tumor bed area.Two forms of IORT, i.e., high dose rate (HDR) brachytherapy and external beam radiotherapy (EBRT, including electron and photono IORT), had been studied before the treatment of head and neck tumors (including laryngocarcinoma). However, no relevant assessment had been carried out on 50KV low-energy X-ray. We are convinced by certain arguments that the application of low-energy X-ray for intraoperative local radiotherapy of laryngocarcinoma can not only achieve the therapeutic effect of IORT but also reduce the incidence of high-energy irradiation related toxic and side effects. The purpose of this study is to observe the safety and short-term efficacy of IORT when used in conjunction with standard of care for the treatment of local advanced laryngocarcinoma (LAL).Methods/designIn consideration of the applications of precise targeted IORT in oncosurgery and in line with the application range and reference clinical medical guidances approved by SFDA (ZEISS radiosurgical operation system has been used for the treatment of solid tumors since 31 December, 2013 with an approval from SFDA), we have preliminarily planned the tumors suitable for IORT, determined the members of MDT in our hospital, improved the MDT diagnosis and treatment processes for the tumors, established the standards, indications and contraindications for the application of IORT, determined the indicators to be observed after the treatment of tumors with surgical operations plus IORT, and carried out follow-up visits and statistical analysis.This is a single-arm, prospective Phase II clinical trial of the treatment of LAL patients with IORT + EBRT. The study subjects are followed up for statistics and information of their acute/chronic toxic reactions and local control rate, DFS, and OS etc. The safety and short-term efficacy of the application of IORT as SIB for the treatment of LAL. The sample size of the study is 125 subjects.DiscussionThe safety and efficacy of IORT for the treatment of head and neck cancers have been proven in studies by multiple institutions (1–3). The purpose of this study is to investigate the maximum safe dose and short-term efficacy of IORT for providing a theoretical basis for clinical trials.Trial registrationTrial registration: Clinicaltrials.gov, NCT04278638. Registered 18 February 2020 - prospectively registered, https://clinicaltrials.gov/ct2/show/NCT04278638

Significance of intraoperative radiation therapy and high cumulative radiation doses in retroperitoneal soft tissue sarcoma

IntroductionIn retroperitoneal soft tissue sarcoma (STS) local recurrence (LR) rates remain high despite more aggressive surgical approaches. Since wide resection margins cannot be achieved in all patients, application of intraoperative radiation therapy (IORT) has been frequently discussed. Still, the significance of IORT in multimodal treatment of retroperitoneal STS remains unclear. Material and methodsPatients undergoing resection of primary or recurrent retroperitoneal STS at the University of Heidelberg Department of General, Visceral and Transplantation Surgery were retrospectively analyzed. Univariate Kaplan-Meyer and multivariate Cox regression analyses were performed to identify predictors of LR-free survival and to investigate the impact of IORT and high cumulative radiation doses. Analyses with propensity-score matched subgroups for IORT and cumulative radiation dose were performed to control for selection bias. Subgroup analyses for patients with retroperitoneal liposarcoma were likewise performed. Results272 patients were identified. Recurrent tumors, histology of dedifferentiated liposarcoma or unclassified sarcoma and microscopically incomplete resection were associated with decreased LR-free survival. In liposarcoma, only recurrent and dedifferentiated tumors were confirmed as poor prognostic factors concerning LR. IORT and cumulative radiation doses exceeding 60 Gy did not influence LR rates (estimated 5-year LR-free survival: IORT: 39%, non-IORT: 46%; p = 0.79). ConclusionIn this retrospective evaluation, additional application of IORT does not significantly influence oncological outcome in retroperitoneal soft tissue sarcoma. Randomized trials are needed to clarify the benefit of IORT.

Intraoperative radiotherapy for glioblastoma: an international pooled analysis

PurposeTo report the results of the first international pooled analysis of patients with glioblastoma treated with intraoperative radiotherapy (IORT) in addition to standard of care therapy. MethodsData from 51 patients treated at five centers in Germany, China and Peru were analyzed. All patients underwent tumor resection followed by a single application of IORT (10–40 Gy, prescribed to the applicator surface) with low-energy X-rays. Thereafter, standard adjuvant radiochemotherapy and maintenance chemotherapy were applied. Factors of interest were overall survival (OS), progression-free survival (PFS), local PFS (L-PFS; defined as appearance of new lesions ≤1 cm to the cavity border) and distant PFS (D-PFS; lesions >1 cm). The same endpoints were estimated at 1-, 2- and 3-years using the Kaplan-Meier method. Additionally, rates and severity (as per Common Terminology Criteria for Adverse Events Version 5.0) of radionecrosis (RN) were analyzed. ResultsThe median age was 55 years (range: 16–75) and the median Karnofsky Performance Status was 80 (20–100). At a median follow-up of 18.0 months (2–42.4), the median OS, PFS, L-PFS and D-PFS were 18.0 months (95% CI: 14.7–21.3), 11.4 months (95%CI: 7.58–15.22), 16 months (95%CI: 10.21–21.8) and 30.0 months (95%CI: 18.59 – 41.41), respectively. The estimated 1-, 2- and 3-year OS, PFS, L-PFS and D-PFS were 79.5%, 38.7% and 25.6%; 46.2%, 29.4%, and 5.9%; 60.9, 37.9%, and 12.6%; and 76.7%, 65.0%, and 39.0% respectively. First progression occurred locally in only 35.3% of cases. Grade 1 RN was detected in 7.8% and grade 3 in 17.6% of the patients. No grade 4 toxicity was reported and no treatment-related deaths occurred. ConclusionCompared to historical data, this pooled analysis suggests improved efficacy and safety of IORT with low-energy X-rays for newly diagnosed glioblastoma. Prospective data is warranted to confirm these findings.

Experts’ consensus on intraoperative radiotherapy for pancreatic cancer

Pancreatic cancer (PC), one of the most lethal malignancies, accounts for 8%–10% of digestive system cancers, and the incidence is increasing. Surgery, chemotherapy, and radiotherapy have been the main treatment methods but are not very effective. However, only 20% of patients have the opportunity to undergo surgical operation. Approximately 30–40% of patients present with locally advanced, unresectable pancreatic cancer because of invasion of mesenteric vessels or adjacent organs.The first patient with unresectable pancreatic cancer was treated with Intraoperative radiotherapy (IORT) in 1959 [1]. Since then, new surgical and radiotherapeutic techniques have been developed, clinical trials have provided new evidence, and intriguing long-term effects have emerged from global metadatabases. IORT has the advantages of more accurate target, better local control rate, less complications, longer survival time and better life quality. During the past decade, IORT has been applied in some hospitals in the world, but there is little agreement on technical details and standards. A guidelines of IORT in pancreatic cancer is therefore necessary and timely. To develop standardized criteria for the application of IORT in pancreatic cancer, the experts from China to discuss treatment methods and arrive at a consensus on the indications, contraindications, and preferred techniques of IORT in pancreatic cancer. This detailed and agreed technical description of IORT may have implications on training, assessment, quality control, and future research.

Comparing the physical and dosimetric characteristics of cylindrical and beam shaper intraoperative radiotherapy applicators

Intraoperative electron radiation therapy is one of the cancer treatment techniques that delivers high doses to the tumor bed by dedicated mobile accelerators such as LIAC. Two types of applicators (standard cylindrical applicators and beam shaper applicator) can be used with LIAC. The aim of this study was to investigate and compare the physical and dosimetric characteristics of emerging electrons from distal end of mentioned applicators. For this purpose, percentage depth dose, dose profiles and output factors were measured and compared. Furthermore, energy and angular distribution of electron beam at the exit of both applicator types were calculated by Monte Carlo simulation. A considerable difference was observed in both physical and dosimetric characteristics of emerging electrons from distal end of applicators under investigation which is mainly due to the presence of shielding blades in design of beam shaper applicator. This difference in both dosimetric and physical properties, can change the considered treatment planning procedure for patient irradiation during the employment of each studied applicator type.

Intraoperative Radiotherapy With the Intrabeam® Device for the Treatment of Resectable Pancreatic Adenocarcinoma

IntroductionThe application of intraoperative radiation therapy to the tumor bed after resection of pancreatic cancer has been shown to be beneficial in the local control of the disease. The objective of this study was to evaluate the preliminary outcomes after the application of a single intraoperative dose to the tumor bed with a new intraoperative radiotherapy device (Intrabeam®) in terms of viability, safety and short-term results. MethodsWe studied 5 patients who underwent pancreaticoduodenectomy for resectable pancreatic cancer in which a radiotherapy boost (5Gy) was intraoperatively applied to the tumoral bed using the portable Intrabeam® device, a low-energy point-source X-ray. Postoperative complications, hospital stay and mortality, recurrences and short-term survival were analyzed. ResultsMean patient age was 68 years. All patients had a T3-stage tumor and one of them N1. In 3 patients, R0 resection was performed, while R1 resection was conducted in 2. Perioperative mortality was 0%. The only complications included delayed gastric emptying and postoperative hemorrhage. There were no pancreatic fistulas. During follow-up (mean: 11.2 months), there was a relapse in the patient who had undergone R1 resection. ConclusionsThe application of radiotherapy with the Intrabeam® device in selected patients has not resulted in increased perioperative morbidity or mortality; therefore, this is a safe procedure for the treatment of resectable cancer.

Radioterapia intraoperatoria con Intrabeam® para el tratamiento del adenocarcinoma de páncreas resecable

IntroductionThe application of intraoperative radiation therapy to the tumor bed after resection of pancreatic cancer has been shown to be beneficial in the local control of the disease. The objective of this study was to evaluate the preliminary outcomes after the application of a single intraoperative dose to the tumor bed with a new intraoperative radiotherapy device (Intrabeam®) in terms of viability, safety and short-term results. MethodsWe studied 5 patients who underwent pancreaticoduodenectomy for resectable pancreatic cancer in which a radiotherapy boost (5Gy) was intraoperatively applied to the tumoral bed using the portable Intrabeam® device, a low-energy point-source X-ray. Postoperative complications, hospital stay and mortality, recurrences and short-term survival were analyzed. ResultsMean patient age was 68 years. All patients had a T3-stage tumor and one of them N1. In 3 patients, R0 resection was performed, while R1 resection was conducted in 2. Perioperative mortality was 0%. The only complications included delayed gastric emptying and postoperative hemorrhage. There were no pancreatic fistulas. During follow-up (mean: 11.2 months), there was a relapse in the patient who had undergone R1 resection. ConclusionsThe application of radiotherapy with the Intrabeam® device in selected patients has not resulted in increased perioperative morbidity or mortality; therefore, this is a safe procedure for the treatment of resectable cancer.

Intraoperative radiotherapy in patients with breast cancer treated by breast-conserving therapy.

To assess the safety, cosmetic effects, and clinical efficacy of breast-conserving surgery combined with intraoperative radiation therapy for the treatment of Chinese patients with breast cancer. Breast-conserving surgery combined with intraoperative radiation therapy was performed in 64 breast cancer patients. The postoperative short-term efficacy, safety, and cosmetic effects were assessed. Of the 64 patients, 1 case (1.6%) had local recurrence one year later, 7 cases (10.9%) had grade I postoperative radiation-induced lung injury, 10 cases (15.6%) had local hardening at the surgical sites, 8 cases (12.5 %) had changes in skin color, and 8 cases (12.5%) had pain at the surgical sites. Excellent or good levels of cosmetic effects were achieved in 95.3% of the patients. The application of intraoperative radiation therapy with breast-conserving surgery can yield satisfactory short-term curative efficacy, a high level of clinical safety, and good cosmetic effects.

Update on intraoperative radiotherapy: new challenges and issues.

Intraoperative radiotherapy (IORT) for breast cancer has challenged the standard external beam radiotherapy (EBRT) and has been shown to be non-inferior for treating early breast cancer in the past decade. Several technologies have been tested for IORT and various randomised controlled trials are still ongoing. Different methods of application of IORT have also been evaluated, from early breast cancer to tumour bed boost radiotherapy amongst high risk women. TARGIT-A and ELIOT trials have reported a low incidence of local recurrence and good survival in both arms. Moreover, mortality has been found to be lower amongst women who underwent partial breast radiotherapy compared to those treated with EBRT in a recent meta-analysis. Despite this, IORT has not been introduced in the current clinical practice as yet, and many clinicians do not mention this treatment option to patients awaiting breast cancer surgery. The scientific community does not unanimously support the effectiveness of IORT and still raises concerns about introducing IORT as a standard treatment option for breast cancer. Current evidence demonstrates that IORT is ready for roll-out; it is time to let well-selected and informed patients be offered this treatment option in the current clinical practice.

Our experience in intraoperative radiotherapy applications

Our experience in intraoperative radiotherapy applications

Clinical effect of intraoperative electron beam radiotherapy in treatment of unresectable locally advanced pancreatic cancer

Objective To assess the prognostic benefits of intraoperative radiotherapy (IORT) with electron beam among patients with unresectable locally advanced pancreatic cancer. Methods Between January 2009 and December 2014, 167 patients with unresectable locally advanced pancreatic cancer received IORT with electron beam (10-20 Gy) in our hospital. After surgery, 12 patients were treated with external beam radiotherapy, 56 patients with chemoradiotherapy (CRT), and 17 patients with chemotherapy. Overall survival (OS), local recurrence, and toxicities were retrospectively analyzed. The Kaplan-Meier method was used to calculate survival rates, the log-rank test was used for survival difference analysis and univariate prognostic analysis, and the Cox model was used for multivariate prognostic analysis. Results The follow-up rate was 100%. The median OS time was 10.3 months, and the 2-year OS rate was 22%. The median progression-free survival (PFS) time was 6.3 months, and the 2-year PFS rate was 9.9%. The cancer-specific survival (CSS) time was 11.2 months, and the 2-year CSS rate was 23.6%. In the patients treated with IORT alone at doses of 15 Gy, the median OS times were 6.2 months vs. 9.1 months vs. 22.2 months, and the 1-year OS rates were 10.0% vs. 39.6% vs. 74.4%(P=0.000). Among the patients receiving postoperative adjuvant therapy, those treated with IORT+ CRT had the best survival, with a median OS time of 11.6 months (P=0.033). The univariate analysis showed that IORT dose (P=0.000), tumor size (P=0.006), and IORT applicator diameter (P=0.007) were prognostic factors. The multivariate analysis showed that IORT dose (P=0.000) and IORT combined with CRT (P=0.006) were independent prognostic factors. Conclusions IORT with electron beam is an effective and safe treatment strategy for unresectable locally advanced pancreatic cancer. After protecting surrounding organs, increasing the IORT dose can improve the survival. IORT combined with CRT should be recommended because it improves survival for unresectable locally advanced pancreatic cancer without increasing toxicities. Key words: Pancreatic neoplasms/intraoperative radiotherapy; Intraoperative radiotherapy, electron beam; Pancreatic neoplasms/postoperative radiochemotherapy; Prognosis