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• Accurate organ at risk delineation is crucial during proton and photon therapy. • We developed an MR-based organs-at-risk autosegmentation atlas. • Autosegmentation enables contouring of 34 organs at risk in clinical practice. • This enables development of NTCP-models with limited interobserver variation. During radiotherapy treatment planning, avoidance of organs at risk (OARs) is important. An international consensus-based delineation guideline was recently published with 34 OARs in the brain. We developed an MR-based OAR autosegmentation atlas and evaluated its performance compared to manual delineation. Anonymized cerebral T1-weighted MR scans (voxel size 0.9 × 0.9 × 0.9 mm3) were available. OARs were manually delineated according to international consensus. Fifty MR scans were used to develop the autosegmentation atlas in a commercially available treatment planning system (Raystation®). The performance of this atlas was tested on another 40 MR scans by automatically delineating 34 OARs, as defined by the 2018 EPTN consensus. Spatial overlap between manual and automated delineations was determined by calculating the Dice similarity coefficient (DSC). Two radiation oncologists determined the quality of each automatically delineated OAR. The time needed to delineate all OARs manually or to adjust automatically delineated OARs was determined. DSC was ≥ 0.75 in 31 (91 %) out of 34 automated OAR delineations. Delineations were rated by radiation oncologists as excellent or good in 29 (85 %) out 34 OAR delineations, while 4 were rated fair (12 %) and 1 was rated poor (3 %). Interobserver agreement between the radiation oncologists ranged from 77-100 % per OAR. The time to manually delineate all OARs was 88.5 minutes, while the time needed to adjust automatically delineated OARs was 15.8 minutes. Autosegmentation of OARs enables high-quality contouring within a limited time. Accurate OAR delineation helps to define OAR constraints to mitigate serious complications and helps with the development of NTCP models. [ABSTRACT FROM AUTHOR]

• Intraoperative electron beam (IOERT) intercomparison of 6 sites was performed. • Mailed thermoluminescence dosimeters (TLDs) were used. • All absolute dose values, except one, and all energy values were well. • It is the structured and complete intercomparison of IOERT accelerators. 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. 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 d max with TLDs around d max and around depth of 50 % dose (R50). Absolute dose at 100 % and beam energy, expressed as R50, could be verified in this way. 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. All absolute dose values, except one of a non-reference beam, and all energy values were well within the measurement accuracy of RDS TLDs. [ABSTRACT FROM AUTHOR]

Purpose The purpose of this study was to compare the delivered dose to the expected intraoperative radiation therapy (IORT) dose with in vivo dosimetry. For IORT using electrons in accelerated partial breast irradiation, this is especially relevant since a high dose is delivered in a single fraction. Methods For 47 of breast cancer patients, in vivo dosimetry was performed with MOSFETs and/or GAFCHROMIC EBT2 films. A total dose of 23.33 Gy at d max was given directly after completing the lumpectomy procedure with electron beams generated with an IORT dedicated mobile accelerator. A protection disk was used to shield the thoracic wall. Results The results of in vivo MOSFET dosimetry for 27 patients and GAFROMIC film dosimetry for 20 patients were analysed. The entry dose for the breast tissue, measured with MOSFETs, (mean value 22.3 Gy, SD 3.4%) agreed within 1.7% with the expected dose (mean value 21.9 Gy). The dose in breast tissue, measured with GAFCHROMIC films (mean value 23.50 Gy) was on average within 0.7% (SD = 3.7%, range −5.5% to 5.6%) of the prescribed dose of 23.33 Gy. Conclusions The dose measured with MOSFETs and GAFROMIC EBT2 films agreed well with the expected dose. For both methods, the dose to the thoracic wall, lungs and heart for left sided patents was lower than 2.5 Gy even when 12 MeV was applied. The positioning time of GAFCHROMIC films is negligible and based on our results we recommend its use as a standard tool for patient quality assurance during breast cancer IORT. [ABSTRACT FROM AUTHOR]

Purpose: Intensity-modulated radiotherapy (IMRT) and dynamic conformal arc (DCA) are two state-of-the-art techniques for linac-based stereotactic radiotherapy (SRT) using the micromultileaf collimator. The purpose of this planning study is to examine the relative merits of these techniques in the treatment of intracranial tumors. Materials and Methods: SRT treatment plans were made for 25 patients with a glioma or meningioma. For all patients, we made an IMRT and a DCA plan. Plans were evaluated using: target coverage, conformity index (CI), homogeneity index (HI), doses in critical structures, number of monitor units needed, and equivalent uniform dose (EUD) in planning target volume (PTV) and critical structures. Results: In the overall comparison of both techniques, we found adequate target coverage in all cases; a better mean CI with IMRT in concave tumors (p = 0.027); a better mean HI with DCA in meningiomas, complex tumors, and small (< 92 mL) tumors (p = 0.000, p = 0.005, and p = 0.005, respectively); and a higher EUD in the PTV with DCA in convex tumors (gliomas) and large tumors (p = 0.000 and p = 0.003, respectively). In all patients, significantly more monitor units were needed with IMRT. The results of the overall comparison did not enable us to predict the preference for one of the techniques in individual patients. The DCA plan was acceptable in 23 patients and the IMRT plan in 19 patients. DCA was preferred in 18 of 25 patients. Conclusions: DCA is our preferred SRT technique for most intracranial tumors. Tumor type, size, or shape do not predict a preference for DCA or IMRT. [Copyright &y& Elsevier]

Abstract: Background and purpose: The underdose near air cavities in the head and neck region at photon energies of 4 MV and 6 MV was studied in search for clinical advantages of the 4 MV over 6 MV treatments. Materials and methods: The on-axis and off-axis dose distributions were measured with a parallel-plate ionization chamber and films in polystyrene phantoms containing an air cavity of appropriate size based on the results of computed tomography scans. Results: Although most results are similar for both energies, the 4 MV photon beams give a somewhat smaller underdose effect and a faster re-build up than the 6 MV. For both energies a significant underdose effect was observed at the edge of the field in the larynx phantom. This proved to be true for small and large fields, for smaller and larger cavities, for one-beam as well as parallel-opposed beams. Conclusion: For most clinically relevant situations there is no remarkable benefit in the use of either of the two energies. [Copyright &y& Elsevier]

Purpose: To evaluate the ipsilateral breast tumor recurrence (IBTR) after 2 accelerated partial breast irradiation (APBI) techniques (intraoperative electron radiation therapy [IOERT] and external beam APBI [EB-APBI]) in patients with early-stage breast cancer.Methods and Materials: Between 2011 and 2016, women ≥60 years of age with breast carcinoma or Ductal Carcinoma In Situ (DCIS) of ≤30 mm and cN0 undergoing breast-conserving therapy were included in a 2-armed prospective multicenter cohort study. IOERT (1 × 23.3 Gy prescribed at the 100% isodose line) was applied in 1 hospital and EB-APBI (10 × 3.85 Gy daily) in 2 other hospitals. The primary endpoint was IBTR (all recurrences in the ipsilateral breast irrespective of localization) at 5 years after lumpectomy. A competing risk model was used to estimate the cumulative incidences of IBTR, which were compared using Fine and Gray's test. Secondary endpoints were locoregional recurrence rate, distant recurrence, disease-specific survival and overall survival. Univariate Cox regression models were estimated to identify risk factors for IBTR. Analyses were performed of the intention to treat (ITT) population (IOERT n = 305; EB-APBI n = 295), and sensitivity analyses were done of the per-protocol population (IOERT n = 270; EB-APBI n = 207).Results: The median follow-up was 5.2 years (IOERT) and 5 years (EB-APBI). Cumulative incidence of IBTR in the ITT population at 5 years after lumpectomy was 10.6% (95% confidence interval, 7.0%-14.2%) after IOERT and 3.7% (95% confidence interval, 1.2%-5.9%) after EB-APBI (P = .002). The locoregional recurrence rate was significantly higher after IOERT than EB-APBI (12.1% vs 4.5%, P = .001). There were no differences between groups in other endpoints. Sensitivity analysis showed similar results. For both groups, no significant risk factors for IBTR were identified in the ITT population. In the per-protocol population, surgical margin status of the DCIS was the only significant risk factor for developing IBTR in both treatment groups.Conclusions: Ipsilateral breast tumor recurrences and locoregional recurrence rates were unexpectedly high in patients treated with IOERT, and acceptable in patients treated with EB-APBI. [ABSTRACT FROM AUTHOR]

Purpose: Breast cancer radiotherapy has been associated with an increased risk of cardiac toxicity. However, no data are available on the probability of developing coronary artery disease (CAD) in breast cancer patients when compared with healthy women. Therefore, baseline coronary artery calcium (CAC) scores, as an accepted tool to predict CAD, were determined and compared with the CAC scores of a healthy, asymptomatic cohort, the Multi-Ethnic Study of Atherosclerosis (MESA) cohort. Methods and Materials: Eighty consecutive patients with ductal carcinoma in situ or infiltrative breast cancer referred for radiotherapy after breast-conserving surgery were included in our study. Their cardiovascular risk profile was registered, and a 64 multislice CT scan was performed. The CAC scores of an unselected (Caucasian only) Radiotherapy Centre West (RCWEST) cohort, as well as of those of a selected (comorbidity and race adjusted) RCWEST cohort, were determined. The scores of both cohorts were compared with those of the female (Caucasian only) MESA cohort. Results: For the unselected RCWEST cohort (n = 62) we found significant (p < .01) higher scores for women in the 55–64 age category compared with those of the MESA cohort. In the selected cohort (n = 55) the CAC scores of the women in the age category 55–64 were significantly (p = .02) higher compared with the MESA cohort. No significant differences were noted in the other age categories. Conclusion: Both cohorts revealed that CAC scores in the 55–64 age category were significantly higher than the CAC scores in the asymptomatic (female) MESA population. These data suggest that breast cancer patients bear a higher risk of developing coronary heart disease before the start of radiotherapy. Therefore, measures to decrease cardiac dose further in breast cancer radiotherapy are even more important. [ABSTRACT FROM AUTHOR]

• IOERT-Boost should primarily be considered in higher risk patients. • Full dose IOERT is one feasible APBI technique for patients with low-risk criteria. • For both concepts acute and late toxicities are mild. • IOERT does minimally impair cosmetic outcome. • Dose prescription and technical prerequisites are well established and described. The aim of this review is to provide a comprehensive overview of the role of intraoperative radiation therapy with electrons (IOERT) in breast conserving therapy (BCT), both as partial breast irradiation (PBI) as well as anticipated boost ("IOERT-Boost"). For both applications, the criteria for patient selection, technical details/requirements, physical aspects and outcome data are presented. The largest evidence comes from Italian studies, especially the ELIOT randomized trial. Investigators showed that the rate of in-breast relapses (IBR) in the IOERT group was significantly greater than with whole breast irradiation (WBI), even when within the pre-specified equivalence margin. Tumour sizes >2 cm, involved axillary nodes, Grade 3 and triple negative molecular subtypes emerged as statistically significant predictors of IBR. For patients at low risk for in-breast recurrence (ASTRO/ESTRO recommendations), full dose IOERT was isoeffective with standard WBI. Hence, several national guidelines now include this treatment strategy as one of the standard techniques for PBI in carefully selected patients. The largest evidence for boost IOERT preceding WBI comes from pooled analyses performed by the European Group of the International Society of Intraoperative Radiation Therapy (ISIORT Europe), where single boost doses (mostly around 10 Gy) preceded whole-breast irradiation (WBI) with 50 Gy (conventional fractionation). At median follow-up periods up to ten years, local recurrence rates around 1% were observed for low risk tumours. Higher local relapse rates were described for grade 3 tumours, triple negative breast cancer as well as for patients treated after primary systemic therapy for locally advanced tumours. Even in this settings, long-term (>5y) local tumour control rates beyond 95% were achieved. These encouraging results are interpreted as being attributable to utmost precision in dose delivery (by avoiding a "geographic and/or temporal miss"), and the possible radiobiological superiority of a single high dose fraction, compared to the conventionally fractionated boost. IOERT also showed favourable results in terms of cosmetic outcome, assumedly thanks to the small treated volumes combined with complete skin sparing. [ABSTRACT FROM AUTHOR]

• Compared to VMAT and IMRT, IMPT significantly reduces the hippocampi doses. • Large dose reductions are also observed for normal brain and other organs at risk. • The results support consideration of IMPT for skull-base meningiomas >3 cm. Radiotherapy of skull-base meningiomas is challenging due to the close proximity of multiple sensitive organs at risk (OARs). This study systematically compared intensity modulated proton therapy (IMPT), non-coplanar volumetric modulated arc therapy (VMAT) and intensity modulated radiotherapy (IMRT) based on automated treatment planning. Differences in OARs sparing, with specific focus on the hippocampi, and low-dose delivery were quantified. Twenty patients, target diameter >3 cm, were included. Automated plan generation was used to calculate a VMAT plan with three non-coplanar arcs, an IMRT plan with nine non-coplanar beams with optimized gantry and couch angles, and an IMPT plan with three patient-specific selected non-coplanar beams. A prescription dose of 50.4 GyRBE in 28 fractions was used. The same set of constraints and prioritized objectives was used. All plans were rescaled to the same target coverage. Repeated measures ANOVA was used to assess the statistical significance of differences in OAR dose parameters between planning techniques. Compared to VMAT and IMRT, IMPT significantly improved dose conformity to the target volume. Consequently, large dose reductions in OARs were observed. With respect to VMAT, the mean dose and D 40% in the bilateral hippocampus were on average reduced by 48% and 74%, respectively (p ≤ 0.005). With IMPT, the mean dose in the normal brain and volumes receiving 20–30 Gy were up to 47% lower (p ≤ 0.01). When comparing IMPT and IMRT, even larger dose differences in those OARs were observed. For skull-base meningiomas IMPT allows for a considerable dose reduction in the hippocampi, normal brain and other OARs compared to both non-coplanar VMAT and IMRT, which may lead to a clinically relevant reduction of late neurocognitive side effects. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: In radiotherapy for left-sided breast cancer, Active Breathing Control enables a decrease of cardiac and Left Anterior Descending (LAD) coronary artery dose. We compared 3D-Conformal (3D-CRT) to Intensity Modulated Radiotherapy (IMRT) treatment plans based on free-breathing (FB) and breath-hold (BH). We investigated whether IMRT enables an additional decrease of cardiac dose in radiotherapy plans with and without BH. Methods and materials: Twenty patients referred for whole breast irradiation were included. The whole breast, heart and LAD-region were contoured. Four treatment plans were generated: FB_3D-CRT; FB_IMRT; BH_3D-CRT; BH_IMRT. Several doses were obtained from Dose Volume Histograms and compared. Results were compared statistically using the Wilcoxin Signed Rank Test. For heart and LAD-region, a significant dose reduction was found in BH (p <0.01). For both BH and FB, a significant dose reduction was found using IMRT (p <0.01). By using IMRT an average reduction of 5% was noted in the LAD-region for the volume receiving 20Gy. In 5 cases, the LAD-region remained situated in the vicinity of the radiation portals even in BH. Nevertheless, with IMRT the LAD dose was reduced in these cases. Conclusion: IMRT results in a significant additional decrease of dose in the heart and LAD-region in both breath-hold and free-breathing. [Copyright &y& Elsevier]

Purpose: To examine magnetic resonance imaging (MRI) and computed tomography (CT) for lumpectomy cavity (LC) volume delineation in supine radiotherapy treatment position and to assess the interobserver variability. Methods and Materials: A total of 15 breast cancer patients underwent a planning CT and directly afterward MRI in supine radiotherapy treatment position. Then, 4 observers (2 radiation oncologists and 2 radiologists) delineated the LC on the CT and MRI scans and assessed the cavity visualization score (CVS). The CVS, LC volume, conformity index (CI), mean shift of the center of mass (COM), with the standard deviation, were quantified for both CT and MRI. Results: The CVS showed that MRI and CT provide about equal optimal visibility of the LC. If the CVS was high, magnetic resonance imaging provided more detail of the interfaces of the LC seroma with the unaffected GBT. MRI also pictured in more detail the interfaces of axillary seromas (if present) with their surroundings and their relationship to the LC. Three observers delineated smaller, and one observer larger, LC volumes comparing the MRI- and CT-derived delineations. The mean ± standard deviation CI was 32% ± 25% for MRI and 52% ± 21% for CT. The mean ± standard deviation COM shift was 11 ± 10 mm (range 1–36) for MRI and 4 ± 3 mm (range 1–10) for CT. Conclusions: MRI does not add additional information to CT in cases in which the CVS is assessed as low. The conformity (CI) is lower for MRI than for CT, especially at a low CVS owing to greater COM shifts for MRI, probably caused by inadequate visibility of the surgical clips on magnetic resonance (MR) images. The COM shifts seriously dictate a decline in the CI more than the variability of the LC volumes does. In cases in which MRI provides additional information, MRI must be combined with the CT/surgical clip data. [ABSTRACT FROM AUTHOR]

Purpose: To examine MRI and CT for glandular breast tissue (GBT) volume delineation and to assess interobserver variability. Methods and Materials: Fifteen breast cancer patients underwent a planning CT and MRI, consecutively, in the treatment position. Four observers (two radiation oncologists and two radiologists) delineated the GBT according to the CT and separately to the MR images. Volumes, centers of mass, maximum extensions with standard deviations (SD), and interobserver variability were quantified. Observers viewed delineation differences between MRI and CT and delineation differences among observers. Results: In cranio-lateral and cranio-medial directions, GBT volumes were delineated larger using MRI when compared with those delineated with CT. Center of mass on MRI shifted a mean (SD) 17% (4%) into the cranial direction and a mean 3% (4%) into the dorsal direction when compared with that on the planning CT. Only small variations between observers were noted. The GBT volumes were approximately 4% larger on MRI (mean [SD] ratio MRI to CT GBT volumes, 1.04 [0.06]). Findings were concordant with viewed MRI and CT images and contours. Conformity indices were only slightly different; mean conformity index was 77% (3%) for MRI and 79% (4%) for CT. Delineation differences arising from personal preferences remained recognizable irrespective of the imaging modality used. Conclusions: Contoured GBT extends substantially further into the cranio-lateral and cranio-medial directions on MRI when compared with CT. Interobserver variability is comparable for both imaging modalities. Observers should be aware of existing personal delineation preferences. Institutions are recommended to review and discuss target volume delineations and to design supplementary guidelines if necessary. [ABSTRACT FROM AUTHOR]