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Background and purpose Breath hold is increasingly used for cardiac sparing in left-sided breast cancer irradiation. We have developed a fast automated method to verify breath hold stability in each treatment fraction. Material and methods We evaluated 504 patients treated with breath hold. Moderate deep inspiration breath hold was audio-guided. Medial and lateral large tangential field segments were delivered in a single breath hold and movieloops of these fields were acquired with an EPID. The thoracic wall position was automatically detected in each frame and the full range of thoracic wall motion (RTWM) was determined. If the RTWM >4 mm more than 3 times, the patient was excluded from breath hold treatment if further coaching did not yield improvement. Results Unstable breath hold was observed in 2.8% of the patients. However, this frequency dropped from 9.5% in the first 6 months to 1.6% in the subsequent 16 months. The 97% of patients with proper breath hold showed excellent stability: the average RTWM was 0.9 ± 0.5 mm. The reproducibility of the breath hold depth was confirmed by (1) the small difference between the thoracic wall positions in the medial and lateral fields within one fraction and (2) the setup errors of breath hold patients showed no significant differences with those of right-sided breast patients. Conclusions We have developed and clinically applied an imaging tool to automatically determine stability of breath holds in each treatment fraction during beam delivery. [ABSTRACT FROM AUTHOR]

Abstract: Background and purpose: We are developing a technique for highly focused vocal cord irradiation in early glottic carcinoma to optimally treat a target volume confined to a single cord. This technique, in contrast with the conventional methods, aims at sparing the healthy vocal cord. As such a technique requires sub-mm daily targeting accuracy to be effective, we investigate the accuracy achievable with on-line kV-cone beam CT (CBCT) corrections. Materials and methods: CBCT scans were obtained in 10 early glottic cancer patients in each treatment fraction. The grey value registration available in X-ray volume imaging (XVI) software (Elekta, Synergy) was applied to a volume of interest encompassing the thyroid cartilage. After application of the thus derived corrections, residue displacements with respect to the planning CT scan were measured at clearly identifiable relevant landmarks. The intra- and inter-observer variations were also measured. Results: While before correction the systematic displacements of the vocal cords were as large as 2.4±3.3mm (cranial–caudal population mean±SD Σ), daily CBCT registration and correction reduced these values to less than 0.2±0.5mm in all directions. Random positioning errors (SD σ) were reduced to less than 1mm. Correcting only for translations and not for rotations did not appreciably affect this accuracy. The residue random displacements partly stem from intra-observer variations (SD=0.2–0.6mm). Conclusion: The use of CBCT for daily image guidance in combination with standard mask fixation reduced systematic and random set-up errors of the vocal cords to <1mm prior to the delivery of each fraction dose. Thus, this facilitates the high targeting precision required for a single vocal cord irradiation. [Copyright &y& Elsevier]

Abstract: Background and Purpose: To quantify respiratory motion of the vocal cords during normal respiration using 4D-CT. The final goal is to develop a technique for single vocal cord irradiation (SVCI) in early glottic carcinoma. Sparing the non-involved cord and surrounding structures has the potential to preserve voice quality and allow re-irradiation of recurrent and second primary tumors. Material and methods: Four-dimensional CTs of 1mm slice thickness from 10 early glottic carcinoma patients were acquired. The lateral dimensions of the air gap separating the vocal cords were measured anteriorly, at mid-level and posteriorly at each phase of the 4D-CTs. The corresponding anterior–posterior gaps were similarly measured. Cranio-caudal vocal cords movements during breathing were derived from the shifts of the arythenoids. Results: The population-averaged mean gap size±the corresponding standard deviation due to breathing (SDB) for the lateral gaps was 5.8±0.7mm anteriorly, 8.7±0.9mm at mid-level, and 11.0±1.3mm posteriorly. Anterior–posterior gap values were 21.7±0.7mm, while cranio-caudal shift SDB was 0.8mm. Conclusion: Vocal cords breathing motions were found to be small relative to their separation. Hence, breathing motion does not seem to be a limiting factor for SVCI. [Copyright &y& Elsevier]

Abstract: Purpose: To determine adequate three-dimensional (3D) margins around the clinical target volume (CTV) of oropharyngeal cancers. Methods and materials: The CTV, bounded by implanted markers, was recorded under fluoroscopy in antero-posterior (AP) and lateral view. The peak-to-peak motion was measured in lateral, AP and cranio–caudal (CC) directions. Results: During swallowing, the mean amplitude of motion measured was 9.4mm (0.9–18.5) and 4.1mm (0.6–11.4) in AP view in the CC and lateral direction, respectively; and 8.6mm (0.5–16.5) and 7.6mm (0.9–14.5) in lateral view in the CC and AP direction, respectively. In the non-swallowing period the motion was 1.5mm (0.3–3.2) and 1mm (0.4–3.6) in AP view in the CC and lateral direction, respectively; and 1.3mm (0.4–3.1) and 1.3mm (0.4–3.4) in lateral view in the CC and AP direction, respectively. This motion was believed to be due to breathing. Conclusion: If swallowing can be suppressed during CT acquisition, the contribution to the internal margin for this motion is negligible. Breathing related motion is also believed to be of limited clinical relevance in current practice. However, it might become of importance in future, with further reduction of margins. [Copyright &y& Elsevier]

• Radiotherapy innovations in the Netherlands changed rapidly over time. • All radiotherapy centres experience comparable innovation implementation challenges. • Sharing experiences, not only on content, but also on hurdles, is no common practice. • A web-based platform has been designed as a first step to stimulate mutual learning. Previous research among Dutch radiotherapy centres (RTCs) showed that 69% of innovations was simultaneously implemented in 7/19 centres, with a success rate of 51%. However, no structure to share lessons learned about the implementation process existed. Therefore, a national Taskforce Implementation (TTI) was raised to stimulate efficient implementation of innovations. The aim of the current study was to develop and pilot-evaluate a website for facilitating mutual learning on implementation issues. First, we made an inventory in all Dutch RTCs on their 10 most valuable innovations between 2019 and 2022. In-depth interviews, structured according to the Consolidated Framework for Implementation Research, were performed on the four most mentioned topics. A website was built, and pilot evaluated 1 year after the launch, using a qualitative survey amongst the TTI members. In 13/18 centres, 19 interviews were conducted on 1) automation, 2) patient participation, 3) adaptive radiotherapy 4) surface guided radiotherapy and tracking. Most innovations (13/16) were implemented with a delay, with many comparable challenges: e.g. shortage of personnel (7/16) and prioritization of projects (9/16). The website allows users to upload and search for projects, including implementation experiences. After 1 year, 14 projects were uploaded. The qualitative evaluation was largely positive with room for improvement, i.e.75 % would recommend the website to others. This study showed that RTCs experience comparable challenges when implementing innovations, thereby underlining the need for a platform to share implementation-lessons learned. The first concept of this platform was evaluated positively. [ABSTRACT FROM AUTHOR]

Abstract: Background and purpose: Pretreatment verification with an electronic portal imaging device is an important part of our patient-specific quality assurance program for advanced treatment techniques. Up to now, this verification has been performed for over 400 IMRT patient plans. For every treatment field, a 2D portal dose image (PDI) is measured and compared with a predicted PDI. Often it is not straightforward to interpret dose deviations found in these 2D comparisons in terms of clinical implications for the patient. Therefore, a method to derive the 3D patient dose based on the measured PDIs was implemented. Methods and materials: For reconstruction of the 3D patient dose, the actual fluences delivered by the accelerator are derived from measured portal dose images using an iterative method. The derived fluence map for each beam direction is then used as input for the treatment planning system to generate an adapted 3D patient dose distribution. The accuracy of this method was assessed by measurements in a water phantom. Clinical evaluation of the 3D dose reconstruction was performed for 17 IMRT patients with different tumor sites. Dose differences with respect to the original treatment plan were evaluated in individual CT slices using dose difference maps and a 3D γ analysis and by comparing dose-volume histograms (DVHs). Results: The measurements indicated that the accuracy of the 3D dose reconstruction was within 2%/2mm. For the patients observed dose differences with respect to the original plan were generally within 2%, except at the field edges and in the sharp dose gradients around the planning target volume (PTV). Gamma analysis showed that the dose differences were within 2%/2mm for more than 95% of the points in all cases. Differences in DVH parameters for the PTV and organs at risk were also within 2% in nearly all cases. Conclusion: A method to derive actual delivered fluence maps from measured PDIs and to use them to reconstruct the 3D patient dose was implemented. The reconstruction eases the estimation of the clinical relevance of observed dose differences in the pretreatment measurements. [Copyright &y& Elsevier]

Abstract: Background and purpose: In our clinic a QA program for IMRT verification, fully based on dosimetric measurements with electronic portal imaging devices (EPID), has been running for over 3 years. The program includes a pre-treatment dosimetric check of all IMRT fields. During a complete treatment simulation at the linac, a portal dose image (PDI) is acquired with the EPID for each patient field and compared with a predicted PDI. In this paper, the results of this pre-treatment procedure are analysed, and intercepted errors are reported. An automated image analysis procedure is proposed to limit the number of fields that need human intervention in PDI comparison. Materials and methods: Most of our analyses are performed using the γ index with 3% local dose difference and 3mm distance to agreement as reference values. Scalar parameters are derived from the γ values to summarize the agreement between measured and predicted 2D PDIs. Areas with all pixels having γ values larger than one are evaluated, making decisions based on clinically relevant criteria more straightforward. Results: In 270 patients, the pre-treatment checks revealed four clinically relevant errors. Calculation of statistics for a group of 75 patients showed that the patient-averaged mean γ value inside the field was 0.43±0.13 (1SD) and only 6.1±6.8% of pixels had a γ value larger than one. With the proposed automated image analysis scheme, visual inspection of images can be avoided in 2/3 of the cases. Conclusion: EPIDs may be used for high accuracy and high resolution routine verification of IMRT fields to intercept clinically relevant dosimetric errors prior to the start of treatment. For the majority of fields, PDI comparison can fully rely on an automated procedure, avoiding excessive workload. [Copyright &y& Elsevier]

• A higher radiation dose to the anorectum is associated with increased overall GI toxicity. • Increasing the dose to the anorectum should be weighed against the benefit of focal dose escalation. • Further increasing the dose to the tumor without increasing the anorectal dose should be explored. The phase III FLAME trial (NCT01168479) showed an increase in five-year biochemical disease-free survival, with no significant increase in toxicity when adding a focal boost to external beam radiotherapy (EBRT) for localized prostate cancer [Kerkmeijer et al. JCO 2021]. The aim of this study was to investigate the association between delivered radiation dose to the anorectum and gastrointestinal (GI) toxicity (grade ≥2). All patients in the FLAME trial were analyzed, irrespective of treatment arm. The dose–effect relation of the anorectal dose parameters (D2cm3 and D50%) and GI toxicity grade ≥2 in four years of follow-up was assessed using a mixed model analysis for repeated measurements, adjusted for age, cardiovascular disease, diabetes mellitus, T-stage, baseline toxicity grade ≥1, hormonal therapy and institute. A dose–effect relation for D2cm3 and D50% was observed with adjusted odds ratios of 1.17 (95% CI 1.13–1.21, p < 0.0001) and 1.20 (95% CI 1.14–1.25, p < 0.0001) for GI toxicity, respectively. Although there was no difference in toxicity between study arms, a higher radiation dose to the anorectum was associated with a statistically significant increase in GI toxicity following EBRT for prostate cancer. This dose–effect relation was present for both large and small anorectal volumes. Therefore, further increase in dose to the anorectum should be weighed against the benefit of focal dose escalation for prostate cancer. [ABSTRACT FROM AUTHOR]

• Focal intraprostatic lesion SBRT boosting is associated with low acute toxicity. • No acute grade ≥3 toxicity was reported in the phase II hypo-FLAME trial. • SBRT for PCa is attractive to both patients and radiation oncology departments. Local recurrences after radiotherapy for prostate cancer (PCa) often originate at the location of the macroscopic tumour(s). Since PCa cells are known to be sensitive to high fraction doses, hypofractionated whole gland stereotactic body radiotherapy (SBRT) in conjunction with a simultaneous ablative microboost to the macroscopic tumour(s) within the prostate could be a way to reduce the risk of local failure. We investigated the safety of this treatment strategy. Patients with intermediate or high risk PCa were enrolled in a prospective phase II trial, called hypo-FLAME. All patients were treated with extreme hypofractionated doses of 35 Gy in 5 weekly fractions to the whole prostate gland with an integrated boost up to 50 Gy to the multiparametric (mp) MRI-defined tumour(s). Treatment-related toxicity was measured using the CTCAE v4.0. The primary endpoint of the trial was treatment-related acute toxicity. Between April 2016 and December 2018, 100 men were treated in 4 academic centres. All patients were followed up for a minimum of 6 months. The median mean dose delivered to the visible tumour nodule(s) on mpMRI was 44.7 Gy in this trial. No grade ≥3 acute genitourinary (GU) or gastrointestinal (GI) toxicity was observed. Furthermore, 90 days after start of treatment, the cumulative acute grade 2 GU and GI toxicity rates were 34.0% and 5.0%, respectively. Simultaneous focal boosting to the macroscopic tumour(s) in addition to whole gland prostate SBRT is associated with acceptable acute GU and GI toxicity. [ABSTRACT FROM AUTHOR]

• SBRT represents a valid treatment option for men with low/intermediate risk PCa. • Adding a focal boost to the intraprostatic tumor may improve disease control. • A focal boost might have favourable toxicity compared to whole-gland dose-escalation. • Currently, SBRT with a focal boost for PCa should be restricted to clinical trials. Stereotactic body radiotherapy (SBRT) for prostate cancer (PCa) is gaining interest by the recent publication of the first phase III trials on prostate SBRT and the promising results of many other phase II trials. Before long term results became available, the major concern for implementing SBRT in PCa in daily clinical practice was the potential risk of late genitourinary (GU) and gastrointestinal (GI) toxicity. A number of recently published trials, including late outcome and toxicity data, contributed to the growing evidence for implementation of SBRT for PCa in daily clinical practice. However, there exists substantial variability in delivering SBRT for PCa. The aim of this topical review is to present a number of prospective trials and retrospective analyses of SBRT in the treatment of PCa. We focus on the treatment strategies and techniques used in these trials. In addition, recent literature on a simultaneous integrated boost to the tumor lesion, which could create an additional value in the SBRT treatment of PCa, was described. Furthermore, we discuss the multicenter consensus of the FLAME consortium on SBRT for PCa with a focal boost to the macroscopic intraprostatic tumor nodule(s). [ABSTRACT FROM AUTHOR]

• The overall treatment time of focal boosted prostate SBRT can safely be reduced. • No acute grade ≥3 toxicity was reported for the semi-weekly (hypo-FLAME 2.0) schedule. • Less grade 2 GU toxicity was found for the once- compared to the semi-weekly schedule. • Patients should be counselled about short-term benefits of a protracted schedule. The hypo-FLAME trial showed that once-weekly (QW) focal boosted prostate stereotactic body radiotherapy (SBRT) is associated with acceptable acute genitourinary (GU) and gastrointestinal (GI) toxicity. Currently, we investigated the safety of reducing the overall treatment time (OTT) of focal boosted prostate SBRT from 29 to 15 days. Patients with intermediate- and high-risk prostate cancer were treated with SBRT delivering 35 Gy in 5 fractions to the whole prostate gland with an iso-toxic boost up to 50 Gy to the intraprostatic lesion(s) in a semi-weekly (BIW) schedule. The primary endpoint was radiation-induced acute toxicity (CTCAE v5.0). Changes in quality of life (QoL) were examined in terms of proportions achieving a minimal clinically important change (MCIC). Finally, acute toxicity and QoL scores of the BIW schedule were compared with the results of the prior QW hypo-FLAME schedule (n = 100). Between August 2020 and February 2022, 124 patients were enrolled and treated BIW. No grade ≥3 GU or GI toxicity was observed. The 90-days cumulative incidence of grade 2 GU and GI toxicity rates were 47.5% and 7.4%, respectively. Patients treated QW scored significant less grade 2 GU toxicity (34.0%, p = 0.01). No significant differences in acute GI toxicity were observed. Furthermore, patients treated QW had a superior acute bowel and urinary QoL. Semi-weekly prostate SBRT with iso-toxic focal boosting is associated with acceptable acute GU and GI toxicity. Based on the comparison between the QW and BIW schedule, patients should be counselled regarding the short-term advantages of a more protracted schedule. Registration number ClinicalTrials.gov: NCT04045717. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: This study investigates (i) the effect of verification protocols on treatment accuracy and PTV margins for partial breast and boost breast radiotherapy with short fractionation schema (15 fractions), (ii) the effect of deformation of the excision cavity (EC) on PTV margin size, (iii) the imaging dose required to achieve specific PTV margins. Methods and materials: Verification images using implanted EC markers were studied in 36 patients. Target motion was estimated for a 15 fraction partial breast regimen using imaging protocols based on on-line and off-line motion correction strategies (No Action Level (NAL) and the extended NAL (eNAL) protocols). Target motion was used to estimate a PTV margin for each protocol. To evaluate treatment errors due to deformation of the excision cavity, individual marker positions were obtained from 11 patients. The mean clip displacement and daily variation in clip position during radiotherapy were determined and the contribution of these errors to PTV margin calculated. Published imaging dose data were used to estimate total dose for each protocol. Finally the number of images required to obtain a specific PTV margin was evaluated and hence, the relationship between PTV margins and imaging dose was investigated. Results: The PTV margin required to account for excision cavity motion, varied between 10.2 and 2.4mm depending on the correction strategy used. Average clip movement was 0.8mm and average variation in clip position during treatment was 0.4mm. The contribution to PTV margin from deformation was estimated to be small, less than 0.2mm for both off-line and on-line correction protocols. Conclusion: A boost or partial breast PTV margin of ∼10mm, is possible with zero imaging dose and workload, however, patients receiving boost radiotherapy may benefit from a margin reduction of ∼4mm with imaging doses from 0.4cGy to 25cGy using an eNAL protocol. PTV margin contributions from deformation errors are likely to be small in comparison to other sources of error, i.e., set up or delineation. [Copyright &y& Elsevier]