Intraoperative electron beam intercomparison of 6 sites using mailed thermoluminescence dosimetry: Absolute dose and energy.

PURPOSE: In 2018, the Netherlands Commission on Radiation Dosimetry subcommittee on IORT initiated a limited intercomparison of electron IORT (IOERT) in Belgium and The Netherlands. The participating institutions have enough variability in age, type of equipment, and in dose calibration protocols. METHODS: In this study, three types of IOERT-dedicated mobile accelerators were represented: Mobetron 2000, LIAC HWL and LIAC. Mobetron produces electron beams with energies of 6, 9 and 12 MeV, while LIAC HWL and LIAC can deliver 6, 8, 10 and 12 MeV electron beams. For all energies, the reference beam (10 cm diameter, 0° incidence) and 5 cm diameter beams were measured, as these smaller beams are used more frequently in clinic. The mailed TLD service from the Radiation Dosimetry Services (RDS, Houston, USA) has been used. Following RDS' standard procedures, each beam was irradiated to 300 cGy at dmax with TLDs around dmax and around depth of 50 % dose (R50). Absolute dose at 100 % and beam energy, expressed as R50, could be verified in this way. RESULTS: All absolute doses and energies under reference conditions were well within RDS-stated uncertainties: dose deviations were <5 % and deviations in R50 were <5 mm. For the small 5 cm beams, all results were also within acceptance levels except one absolute dose value. Deviations were not significantly dependent on manufacturer, energy, diameter and calibration protocol. CONCLUSIONS: All absolute dose values, except one of a non-reference beam, and all energy values were well within the measurement accuracy of RDS TLDs.

Narrowing the difference in dose delivery for IOERT and IOBT for locally advanced and locally recurrent rectal cancer.

Purpose: Intra-operative radiotherapy (IORT) has been used as a tool to provide a high-dose radiation boost to a limited volume of patients with fixed tumors with a likelihood of microscopically involved resection margins, in order to improve local control. Two main techniques to deliver IORT include high-dose-rate (HDR) brachytherapy, termed 'intra-operative brachytherapy' (IOBT), and electrons, termed 'intra-operative electron radiotherapy' (IOERT), both having very different dose distributions. A recent paper described an improved local recurrence-free survival favoring IOBT over IOERT for patients with locally advanced or recurrent rectal cancer and microscopically irradical resections. Although several factors may have contributed to this result, an important difference between the two techniques was the higher surface dose delivered by IOBT. This article described an adaptation of IOERT technique to achieve a comparable surface dose as dose delivered by IOBT. Material and methods: Two steps were taken to increase the surface dose for IOERT: 1. Introducing a bolus to achieve a maximum dose on the surface, and 2. Re-normalizing to allow for the same prescribed dose at reference depth. Conclusions: We describe and propose an adaptation of IOERT technique to increase surface dose, decreasing the differences between these two techniques, with the aim of further improving local control. In addition, an alternative method of dose prescription is suggested, to consider improved comparison with other techniques in the future.

Intraoperative Electron Beam Radiation Therapy (IOERT) Versus High-Dose-Rate Intraoperative Brachytherapy (HDR-IORT) in Patients With an R1 Resection for Locally Advanced or Locally Recurrent Rectal Cancer.

PURPOSE: Intraoperative radiation therapy (IORT), delivered by intraoperative electron beam radiation therapy (IOERT) or high-dose-rate intraoperative brachytherapy (HDR-IORT), may reduce the local recurrence rate in patients with locally advanced and locally recurrent rectal cancer (LARC and LRRC, respectively). The aim of this study was to compare the oncological outcomes between both IORT modalities in patients with LARC or LRRC who underwent a microscopic irradical (R1) resection. METHODS: All consecutive patients who received IORT because of an R1 resection of LARC or LRRC between 2000 and 2016 in two tertiary referral centers were included. In LARC, a resection margin of ≤2 mm was considered R1. A resection margin of 0 mm was considered R1 in LRRC. RESULTS: In total, 215 patients with LARC were included, of whom 151 (70%) received IOERT and 64 (30%) received HDR-IORT; in addition, 158 patients with LRRC were included, of whom 112 (71%) received IOERT and 46 (29%) received HDR-IORT. After multivariable analyses, the overall survival was not significantly different between the two IORT modalities. The local recurrence-free survival was significantly longer in patients treated with HDR-IORT, both in LARC (hazard ratio [HR], 0.496; 95% CI, 0.253-0.973; P = .041) and LRRC (HR, 0.567; 95% CI, 0.349-0.920; P = .021). In patients with LARC, major postoperative complications were similar for both IORT modalities (IOERT, 30%; HDR-IORT, 27%), whereas in patients with LRRC, the incidence of major postoperative complications was higher after HDR-IORT (IOERT, 26%; HDR-IORT, 46%). CONCLUSIONS: This study showed a significantly better local recurrence-free survival in favor of HDR-IORT in patients with an R1 resection for LARC or LRRC. Optimization of the IOERT technique seems warranted.

ESTRO/ACROP IORT recommendations for intraoperative radiation therapy in primary locally advanced rectal cancer.

Carcinoma of the rectum is a heterogeneous disease. The clinical spectrum identifies a subset of patients with locally advanced tumours that are close to or involve adjoining structures, such as the sacrum, pelvic sidewalls, prostate or bladder. Within this group of patients categorized as "locally advanced", there is also variability in the extent of disease with no uniform definition of resectability. A practice-oriented definition of a locally advanced tumour is a tumour that cannot be resected without leaving microscopic or gross residual disease at the resection site. Since these patients do poorly with surgery alone, irradiation and chemotherapy have been added to improve the outcome. Intraoperative irradiation (IORT) is a component of local treatment intensification with favourable results in this subgroup of patients. International guidelines (National Comprehensive Cancer Network (NCCN) guidelines) currently recommend the use of IORT for rectal cancer resectable with very close or positive margins, especially for T4 and recurrent cancers. We report the ESTRO-ACROP (European Society for Radiotherapy and Oncology - Advisory Committee on Radiation Oncology Practice) recommendations for performing IORT in primary locally advanced rectal cancer.

ESTRO/ACROP IORT recommendations for intraoperative radiation therapy in locally recurrent rectal cancer.

Multimodal strategies have been implemented for locally recurrent rectal cancer scheduled for complete surgical resection. Irradiation and systemic therapy have been added to improve the oncological outcome, as surgery alone was associated with a poor prognosis. Intraoperative irradiation (IORT) is a component of irradiation intensification. Long-term cancer control and a higher survival rate were consistently reported in patients who had IORT as a component of their multidisciplinary treatment. The experience reported by expert IORT groups is reviewed and recommendations to guide clinical practice are explained in detail.

Photons, protons or carbon ions for stage I non-small cell lung cancer - Results of the multicentric ROCOCO in silico study.

PURPOSE: To compare dose to organs at risk (OARs) and dose-escalation possibility for 24 stage I non-small cell lung cancer (NSCLC) patients in a ROCOCO (Radiation Oncology Collaborative Comparison) trial. METHODS: For each patient, 3 photon plans [Intensity-modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT) and CyberKnife], a double scattered proton (DSP) and an intensity-modulated carbon-ion (IMIT) therapy plan were created. Dose prescription was 60 Gy (equivalent) in 8 fractions. RESULTS: The mean dose and dose to 2% of the clinical target volume (CTV) were lower for protons and ions compared with IMRT (p < 0.01). Doses to the lungs, heart, and mediastinal structures were lowest with IMIT (p < 0.01), doses to the spinal cord were lowest with DSP (p < 0.01). VMAT and CyberKnife allowed for reduced doses to most OARs compared with IMRT. Dose escalation was possible for 8 patients. Generally, the mediastinum was the primary dose-limiting organ. CONCLUSION: On average, the doses to the OARs were lowest using particles, with more homogenous CTV doses. Given the ability of VMAT and CyberKnife to limit doses to OARs compared with IMRT, the additional benefit of particles may only be clinically relevant in selected patients and thus should be carefully weighed for every individual patient.

Infrastructure and distributed learning methodology for privacy-preserving multi-centric rapid learning health care: euroCAT.

Machine learning applications for personalized medicine are highly dependent on access to sufficient data. For personalized radiation oncology, datasets representing the variation in the entire cancer patient population need to be acquired and used to learn prediction models. Ethical and legal boundaries to ensure data privacy hamper collaboration between research institutes. We hypothesize that data sharing is possible without identifiable patient data leaving the radiation clinics and that building machine learning applications on distributed datasets is feasible. We developed and implemented an IT infrastructure in five radiation clinics across three countries (Belgium, Germany, and The Netherlands). We present here a proof-of-principle for future 'big data' infrastructures and distributed learning studies. Lung cancer patient data was collected in all five locations and stored in local databases. Exemplary support vector machine (SVM) models were learned using the Alternating Direction Method of Multipliers (ADMM) from the distributed databases to predict post-radiotherapy dyspnea grade [Formula: see text]. The discriminative performance was assessed by the area under the curve (AUC) in a five-fold cross-validation (learning on four sites and validating on the fifth). The performance of the distributed learning algorithm was compared to centralized learning where datasets of all institutes are jointly analyzed. The euroCAT infrastructure has been successfully implemented in five radiation clinics across three countries. SVM models can be learned on data distributed over all five clinics. Furthermore, the infrastructure provides a general framework to execute learning algorithms on distributed data. The ongoing expansion of the euroCAT network will facilitate machine learning in radiation oncology. The resulting access to larger datasets with sufficient variation will pave the way for generalizable prediction models and personalized medicine.

Distributed learning: Developing a predictive model based on data from multiple hospitals without data leaving the hospital - A real life proof of concept.

PURPOSE: One of the major hurdles in enabling personalized medicine is obtaining sufficient patient data to feed into predictive models. Combining data originating from multiple hospitals is difficult because of ethical, legal, political, and administrative barriers associated with data sharing. In order to avoid these issues, a distributed learning approach can be used. Distributed learning is defined as learning from data without the data leaving the hospital. PATIENTS AND METHODS: Clinical data from 287 lung cancer patients, treated with curative intent with chemoradiation (CRT) or radiotherapy (RT) alone were collected from and stored in 5 different medical institutes (123 patients at MAASTRO (Netherlands, Dutch), 24 at Jessa (Belgium, Dutch), 34 at Liege (Belgium, Dutch and French), 48 at Aachen (Germany, German) and 58 at Eindhoven (Netherlands, Dutch)). A Bayesian network model is adapted for distributed learning (watch the animation: http://youtu.be/nQpqMIuHyOk). The model predicts dyspnea, which is a common side effect after radiotherapy treatment of lung cancer. RESULTS: We show that it is possible to use the distributed learning approach to train a Bayesian network model on patient data originating from multiple hospitals without these data leaving the individual hospital. The AUC of the model is 0.61 (95%CI, 0.51-0.70) on a 5-fold cross-validation and ranges from 0.59 to 0.71 on external validation sets. CONCLUSION: Distributed learning can allow the learning of predictive models on data originating from multiple hospitals while avoiding many of the data sharing barriers. Furthermore, the distributed learning approach can be used to extract and employ knowledge from routine patient data from multiple hospitals while being compliant to the various national and European privacy laws.

Prototyping a large field size IORT applicator for a mobile linear accelerator.

The treatment of large tumors such as sarcomas with intra-operative radiotherapy using a Mobetron is often complicated because of the limited field size of the primary collimator and the available applicators (max Ø100 mm). To circumvent this limitation a prototype rectangular applicator of 80 x 150 mm(2) was designed and built featuring an additional scattering foil located at the top of the applicator. Because of its proven accuracy in modeling linear accelerator components the design was based on the EGSnrc Monte Carlo simulation code BEAMnrc. First, the Mobetron treatment head was simulated both without an applicator and with a standard 100 mm applicator. Next, this model was used to design an applicator foil consisting of a rectangular Al base plate covering the whole beam and a pyramid of four stacked cylindrical slabs of different diameters centered on top of it. This foil was mounted on top of a plain rectangular Al tube. A prototype was built and tested with diode dosimetry in a water tank. Here, the prototype showed clinically acceptable 80 x 150 mm(2) dose distributions for 4 MeV, 6 MeV and 9 MeV, obviating the use of complicated multiple irradiations with abutting field techniques. In addition, the measurements agreed well with the MC simulations, typically within 2%/1 mm.

Recommendations on detectors and quality control procedures for brachytherapy beta sources.

BACKGROUND AND PURPOSE: It is estimated that one third of the institutes applying clinical beta sources does not perform independent dosimetry. The Netherlands commission on radiation dosimetry (NCS) recently published recommended quality control procedures and detectors for the dosimetry of beta sources. The main issues of NCS Report 14 are summarized here. MATERIALS AND METHODS: A dosimetry survey was performed among 23 institutes in The Netherlands and Belgium. Well ionization chambers, a plastic scintillator, plane-parallel ionization chamber, diode and radiochromic film were used for determination of source strength (dose rate at reference distance) and uniformity of intravascular and ophthalmic sources. The source strength of multiple sources of each type was measured and compared with the source strength specified by the manufacturer. RESULTS: The standard deviation of the difference between measured and specified source strength was mostly about 3%, but varied between 0.8 and 15.8% depending on factors such as source type, detector, phantom and manufacturers calibration. The average non-uniformity was about 7% for intravascular sources and 20% for ophthalmic sources. It is estimated that the total relative standard uncertainty can be kept below +/-4% (1 sigma) with all detectors tested. Maximum deviations in source strength of 10% and a non-uniformity below 10% (intravascular) and 30% (ophthalmic) are recommended. CONCLUSIONS: Dosimetric and non-dosimetric quality control procedures on beta sources are recommended. They enable standardized measurements, including the determination of relative source strength and non-uniformity. Absolute calibrations depend on the future introduction of primary standards for clinical beta sources.

Quality control of brachytherapy equipment in the Netherlands and Belgium: current practice and minimum requirements.

BACKGROUND AND PURPOSE: Brachytherapy is applied in 39 radiotherapy institutions in The Netherlands and Belgium. Each institution has its own quality control (QC) programme to ensure safe and accurate dose delivery to the patient. The main goal of this work is to gain insight into the current practice of QC of brachytherapy in The Netherlands and Belgium and to reduce possible variations in test frequencies and tolerances by formulating a set of minimum QC-requirements. MATERIALS AND METHODS: An extensive questionnaire about QC of brachytherapy was distributed to and completed by the 39 radiotherapy institutions. A separate smaller questionnaire was sent to nine institutions performing intracoronary brachytherapy. The questions were related to safety systems, physical irradiation parameters and total time spent on QC. The results of the questionnaires were compared with recommendations given in international brachytherapy QC reports. RESULTS: The answers to the questionnaires showed large variations in test frequencies and test methods. Furthermore, large variations in time spent on QC exist, which is mainly due to differences in QC-philosophy and differences in the available resources. CONCLUSIONS: Based on the results of the questionnaires and the comparison with the international recommendations, a set of minimum requirements for QC of brachytherapy has been formulated. These guidelines will be implemented in the radiotherapy institutions in The Netherlands and Belgium.