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Background Patient-specific dose prediction improves the efficiency and quality of radiation treatment planning and reduces the time required to find the optimal plan. In this study, a patient-specific dose prediction model was developed for a left-sided breast clinical case using deep learning, and its performance was compared with that of conventional knowledge-based planning using RapidPlan™. Methods Patient-specific dose prediction was performed using a contour image of the planning target volume (PTV) and organs at risk (OARs) with a U-net-based modified dose prediction neural network. A database of 50 volumetric modulated arc therapy (VMAT) plans for left-sided breast cancer patients was utilized to produce training and validation datasets. The dose prediction deep neural network (DpNet) feature weights of the previously learned convolution layers were applied to the test on a cohort of 10 test sets. With the same patient data set, dose prediction was performed for the 10 test sets after training in RapidPlan. The 3D dose distribution, absolute dose difference error, dose-volume histogram, 2D gamma index, and iso-dose dice similarity coefficient were used for quantitative evaluation of the dose prediction. Results The mean absolute error (MAE) and one standard deviation (SD) between the clinical and deep learning dose prediction models were 0.02 ± 0.04%, 0.01 ± 0.83%, 0.16 ± 0.82%, 0.52 ± 0.97, − 0.88 ± 1.83%, − 1.16 ± 2.58%, and − 0.97 ± 1.73% for D95%, Dmean in the PTV, and the OARs of the body, left breast, heart, left lung, and right lung, respectively, and those measured between the clinical and RapidPlan dose prediction models were 0.02 ± 0.14%, 0.87 ± 0.63%, − 0.29 ± 0.98%, 1.30 ± 0.86%, − 0.32 ± 1.10%, 0.12 ± 2.13%, and − 1.74 ± 1.79, respectively. Conclusions In this study, a deep learning method for dose prediction was developed and was demonstrated to accurately predict patient-specific doses for left-sided breast cancer. Using the deep learning framework, the efficiency and accuracy of the dose prediction were compared to those of RapidPlan. The doses predicted by deep learning were superior to the results of the RapidPlan-generated VMAT plan.

Background The aim of this study was to evaluate and compare the performance of intensity modulated radiation therapy (IMRT) plans, planned for low-field strength magnetic resonance (MR) guided linear accelerator (linac) delivery (labelled IMRT MRL plans), and clinical conventional volumetric modulated arc therapy (VMAT) plans, for the treatment of prostate cancer (PCa). Both plans used the original planning target volume (PTV) margins. Additionally, the potential dosimetric benefits of MR-guidance were estimated, by creating IMRT MRL plans using smaller PTV margins. Materials and methods 20 PCa patients previously treated with conventional VMAT were considered. For each patient, two different IMRT MRL plans using the low-field MR-linac treatment planning system were created: one with original (orig.) PTV margins and the other with reduced (red.) PTV margins. Dose indices related to target coverage, as well as dose-volume histogram (DVH) parameters for the target and organs at risk (OAR) were compared. Additionally, the estimated treatment delivery times and the number of monitor units (MU) of each plan were evaluated. Results The dose distribution in the high dose region and the target volume DVH parameters (D98%, D50%, D2% and V95%) were similar for all three types of treatment plans, with deviations below 1% in most cases. Both IMRT MRL plans (orig. and red. PTV margins) showed similar homogeneity indices (HI), however worse values for the conformity index (CI) were also found when compared to VMAT. The IMRT MRL plans showed similar OAR sparing when the orig. PTV margins were used but a significantly better sparing was feasible when red. PTV margins were applied. Higher number of MU and longer predicted treatment delivery times were seen for both IMRT MRL plans. Conclusions A comparable plan quality between VMAT and IMRT MRL plans was achieved, when applying the same PTV margin. However, online MR-guided adaptive radiotherapy allows for a reduction of PTV margins. With a red. PTV margin, better sparing of the surrounding tissues can be achieved, while maintaining adequate target coverage. Nonetheless, longer treatment delivery times, characteristic for the IMRT technique, have to be expected.

Background Online adaptive radiotherapy has the potential to reduce toxicity for patients treated for rectal cancer because smaller planning target volumes (PTV) margins around the entire clinical target volume (CTV) are required. The aim of this study is to describe the first clinical experience of a Conebeam CT (CBCT)-based online adaptive workflow for rectal cancer, evaluating timing of different steps in the workflow, plan quality, target coverage and patient compliance. Methods Twelve consecutive patients eligible for 5 × 5 Gy pre-operative radiotherapy were treated on a ring-based linear accelerator with a multidisciplinary team present at the treatment machine for each fraction. The accelerator is operated using an integrated software platform for both treatment planning and delivery. In all directions for all CTVs a PTV margin of 5 mm was used, except for the cranial/caudal borders of the total CTV where a margin of 8 mm was applied. A reference plan was generated based on a single planning CT. After aligning the patient the online adaptive procedure started with acquisition of a CBCT. The planning CT scan was registered to the CBCT using deformable registration and a synthetic CT scan was generated. With the support of artificial intelligence, structure guided deformation and the synthetic CT scan contours were adapted by the system to match the anatomy on the CBCT. If necessary, these contours were adjusted before a new plan was generated. A second and third CBCT were acquired to validate the new plan with respect to CTV coverage just before and after treatment delivery, respectively. Treatment was delivered using volumetric modulated arc treatment (VMAT). All steps in this process were defined and timed. Results On average the timeslot needed at the treatment machine was 34 min. The process of acquiring a CBCT, evaluating and adjusting the contours, creating the new plan and verifying the CTV on the CBCT scan took on average 20 min. Including delivery and post treatment verification this was 26 min. Manual adjustments of the target volumes were necessary in 50% of fractions. Plan quality, target coverage and patient compliance were excellent. Conclusions First clinical experience with CBCT-based online adaptive radiotherapy shows it is feasible for rectal cancer. Trial registration Medical Research Involving Human Subjects Act (WMO) does not apply to this study and was retrospectively approved by the Medical Ethics review Committee of the Academic Medical Center (W21_087 # 21.097; Amsterdam University Medical Centers, Location Academic Medical Center, Amsterdam, The Netherlands).

Purpose To investigate the dosimetric impact of deep learning-based auto-segmentation of organs at risk (OARs) on nasopharyngeal and rectal cancer. Methods and materials Twenty patients, including ten nasopharyngeal carcinoma (NPC) patients and ten rectal cancer patients, who received radiotherapy in our department were enrolled in this study. Two deep learning-based auto-segmentation systems, including an in-house developed system (FD) and a commercial product (UIH), were used to generate two auto-segmented OARs sets (OAR_FD and OAR_UIH). Treatment plans based on auto-segmented OARs and following our clinical requirements were generated for each patient on each OARs sets (Plan_FD and Plan_UIH). Geometric metrics (Hausdorff distance (HD), mean distance to agreement (MDA), the Dice similarity coefficient (DICE) and the Jaccard index) were calculated for geometric evaluation. The dosimetric impact was evaluated by comparing Plan_FD and Plan_UIH to original clinically approved plans (Plan_Manual) with dose-volume metrics and 3D gamma analysis. Spearman’s correlation analysis was performed to investigate the correlation between dosimetric difference and geometric metrics. Results FD and UIH could provide similar geometric performance in parotids, temporal lobes, lens, and eyes (DICE, p > 0.05). OAR_FD had better geometric performance in the optic nerves, oral cavity, larynx, and femoral heads (DICE, p p p = 0.05). Only one significant correlation was found between the mean dose of the femoral head and its HD index (R = 0.4, p = 0.01), there is no OARs showed strong correlation between its dosimetric difference and all of four geometric metrics. Conclusions Deep learning-based OARs auto-segmentation for NPC and rectal cancer has a nonsignificant impact on most PTV and OARs dose-volume metrics. Correlations between the auto-segmentation geometric metric and dosimetric difference were not observed for most OARs.

Background The Halcyon is a new machine from the Varian company. The purpose of this study was to evaluate the dosimetry of the Halcyon in treatment of bilateral breast cancer with volumetric modulated arc therapy. Methods On CT images of 10 patients with bilateral breast cancer, four Halcyon plans with different setup fields were generated, and dosimetric comparisons using Bonferroni’s multiple comparisons test were conducted among the four plans. Whole and partial arc plans on the Trilogy and the Halcyon, referred to as T-4arc, T-8arc, H-4arc and H-8arc, were designed. The prescription dose was 50 Gy in 2-Gy fractions. All plans were designed with the Eclipse version 15.5 treatment planning system. The dosimetric differences between whole and partial arc plans in the same accelerator were compared using the Mann–Whitney U test. The better Halcyon plan was selected for the further dosimetric comparison of the plan quality and delivery efficiency between the Trilogy and the Halcyon. Results Halcyon plans with high‐quality megavoltage cone beam CT setup fields increased the Dmean, D2 and V107 of the planning target volume (PTV) and the V5 and Dmean of the heart, left ventricle (LV) and lungs compared with other Halcyon setup plans. The mean dose and low dose volume of the heart, lungs and liver were significantly decreased in T-8arc plans compared to T-4arc plans. In terms of the V5, V20, V30, V40 and Dmean of the heart, the V20, V30, V40 and Dmean of the LV, the V30, V40, Dmax and Dmean of the left anterior descending artery (LAD), and the V5 and V40 of lungs, H-8arc was significantly higher than H-4arc (p 20 and V30 of lungs, there was no significant difference between the two accelerators. Compared with the Trilogy, plans on the Halcyon significantly increased the skin dose but also significantly reduced the delivery time. Conclusion For the Halcyon, the whole-arc plans have more dosimetric advantages than partial-arc plans in bilateral breast cancer radiotherapy. Although the mean dose of the heart and the skin dose are increased, the doses of the cardiac substructure and other OARs are comparable to the Trilogy, and the delivery time is significantly reduced.

Background Whole-brain radiotherapy (WBRT) remains an important treatment for over 200,000 cancer patients in the United States annually. Hippocampal-avoidant WBRT (HA-WBRT) reduces neurocognitive toxicity compared to standard WBRT, but HA-WBRT contouring and planning are more complex and time-consuming than standard WBRT. We designed and evaluated a workflow using commercially available artificial intelligence tools for automated hippocampal segmentation and treatment planning to efficiently generate clinically acceptable HA-WBRT radiotherapy plans. Methods We retrospectively identified 100 consecutive adult patients treated for brain metastases outside the hippocampal region. Each patient’s T1 post-contrast brain MRI was processed using NeuroQuant, an FDA-approved software that provides segmentations of brain structures in less than 8 min. Automated hippocampal segmentations were reviewed for accuracy, then converted to files compatible with a commercial treatment planning system, where hippocampal avoidance regions and planning target volumes (PTV) were generated. Other organs-at-risk (OARs) were previously contoured per clinical routine. A RapidPlan knowledge-based planning routine was applied for a prescription of 30 Gy in 10 fractions using volumetric modulated arc therapy (VMAT) delivery. Plans were evaluated based on NRG CC001 dose-volume objectives (Brown et al. in J Clin Oncol, 2020). Results Of the 100 cases, 99 (99%) had acceptable automated hippocampi segmentations without manual intervention. Knowledge-based planning was applied to all cases; the median processing time was 9 min 59 s (range 6:53–13:31). All plans met per-protocol dose-volume objectives for PTV per the NRG CC001 protocol. For comparison, only 65.5% of plans on NRG CC001 met PTV goals per protocol, with 26.1% within acceptable variation. In this study, 43 plans (43%) met OAR constraints, and the remaining 57 (57%) were within acceptable variation, compared to 42.5% and 48.3% on NRG CC001, respectively. No plans in this study had unacceptable dose to OARs, compared to 0.8% of manually generated plans from NRG CC001. 8.4% of plans from NRG CC001 were not scored or unable to be evaluated. Conclusions An automated pipeline harnessing the efficiency of commercially available artificial intelligence tools can generate clinically acceptable VMAT HA-WBRT plans with minimal manual intervention. This process could improve clinical efficiency for a treatment established to improve patient outcomes over standard WBRT.

Background The STAR-TReC trial is an international multi-center, randomized, phase II study assessing the feasibility of short-course radiotherapy or long-course chemoradiotherapy as an alternative to total mesorectal excision surgery. A new target volume is used for both (chemo)radiotherapy arms which includes only the mesorectum. The treatment planning QA revealed substantial variation in dose to organs at risk (OAR) between centers. Therefore, the aim of this study was to determine the treatment plan variability in terms of dose to OAR and assess the effect of a national study group meeting on the quality and variability of treatment plans for mesorectum-only planning for rectal cancer. Methods Eight centers produced 25 × 2 Gy treatment plans for five cases. The OAR were the bowel cavity, bladder and femoral heads. A study group meeting for the participating centers was organized to discuss the planning results. At the meeting, the values of the treatment plan DVH parameters were distributed among centers so that results could be compared. Subsequently, the centers were invited to perform replanning if they considered this to be necessary. Results All treatment plans, both initial planning and replanning, fulfilled the target constraints. Dose to OAR varied considerably for the initial planning, especially for dose levels below 20 Gy, indicating that there was room for trade-offs between the defined OAR. Five centers performed replanning for all cases. One center did not perform replanning at all and two centers performed replanning on two and three cases, respectively. On average, replanning reduced the bowel cavity V20Gy by 12.6%, bowel cavity V10Gy by 22.0%, bladder V35Gy by 14.7% and bladder V10Gy by 10.8%. In 26/30 replanned cases the V10Gy of both the bowel cavity and bladder was lower, indicating an overall lower dose to these OAR instead of a different trade-off. In addition, the bowel cavity V10Gy and V20Gy showed more similarity between centers. Conclusions Dose to OAR varied considerably between centers, especially for dose levels below 20 Gy. The study group meeting and the distribution of the initial planning results among centers resulted in lower dose to the defined OAR and reduced variability between centers after replanning. Trial registration The STAR-TReC trial, ClinicalTrials.gov Identifier: NCT02945566. Registered 26 October 2016, https://clinicaltrials.gov/ct2/show/NCT02945566).

Background The development of radiation pneumonitis (RP) after Stereotactic Body Radiotherapy (SBRT) is known to be associated with many different factors, although historical analyses of RP have commonly utilized heterogeneous fractionation schemes and methods of reporting. This study aims to correlate dosimetric values and their association with the development of Symptomatic RP according to recent reporting standards as recommended by the American Association of Physicists in Medicine. Methods We performed a single-institution retrospective review for patients who received SBRT to the lung from 2010 to 2017. Inclusion criteria required near-homogeneous tumoricidal (α/β = 10 Gy) biological effective dose (BED10) of 100–105 Gy (e.g., 50/5, 48/4, 60/8), one or two synchronously treated lesions, and at least 6 months of follow up or documented evidence of pneumonitis. Symptomatic RP was determined clinically by treating radiation oncologists, requiring radiographic evidence and the administration of steroids. Dosimetric parameters and patient factors were recorded. Lung volumes subtracted gross tumor volume(s). Wilcoxon Rank Sums tests were used for nonparametric comparison of dosimetric data between patients with and without RP; p-values were Bonferroni adjusted when applicable. Logistic regressions were conducted to predict probabilities of symptomatic RP using univariable models for each radiation dosimetric parameter. Results The final cohort included 103 treated lesions in 93 patients, eight of whom developed symptomatic RP (n = 8; 8.6%). The use of total mean lung dose (MLD) > 6 Gy alone captured five of the eight patients who developed symptomatic RP, while V20 > 10% captured two patients, both of whom demonstrated a MLD > 6 Gy. The remaining three patients who developed symptomatic RP without exceeding either metric were noted to have imaging evidence of moderate interstitial lung disease, inflammation of the lungs from recent concurrent chemoradiation therapy to the contralateral lung, or unique peri-tumoral inflammatory appearance at baseline before treatment. Conclusions This study is the largest dosimetric analysis of symptomatic RP in the literature, of which we are aware, that utilizes near-homogenous tumoricidal BED fractionation schemes. Mean lung dose and V20 are the most consistently reported of the various dosimetric parameters associated with symptomatic RP. MLD should be considered alongside V20 in the treatment planning process. Trial registration Retrospectively registered on IRB 398–17-EP.

Background Accurate and standardized descriptions of organs at risk (OARs) are essential in radiation therapy for treatment planning and evaluation. Traditionally, physicians have contoured patient images manually, which, is time-consuming and subject to inter-observer variability. This study aims to a) investigate whether customized, deep-learning-based auto-segmentation could overcome the limitations of manual contouring and b) compare its performance against a typical, atlas-based auto-segmentation method organ structures in liver cancer. Methods On-contrast computer tomography image sets of 70 liver cancer patients were used, and four OARs (heart, liver, kidney, and stomach) were manually delineated by three experienced physicians as reference structures. Atlas and deep learning auto-segmentations were respectively performed with MIM Maestro 6.5 (MIM Software Inc., Cleveland, OH) and, with a deep convolution neural network (DCNN). The Hausdorff distance (HD) and, dice similarity coefficient (DSC), volume overlap error (VOE), and relative volume difference (RVD) were used to quantitatively evaluate the four different methods in the case of the reference set of the four OAR structures. Results The atlas-based method yielded the following average DSC and standard deviation values (SD) for the heart, liver, right kidney, left kidney, and stomach: 0.92 ± 0.04 (DSC ± SD), 0.93 ± 0.02, 0.86 ± 0.07, 0.85 ± 0.11, and 0.60 ± 0.13 respectively. The deep-learning-based method yielded corresponding values for the OARs of 0.94 ± 0.01, 0.93 ± 0.01, 0.88 ± 0.03, 0.86 ± 0.03, and 0.73 ± 0.09. The segmentation results show that the deep learning framework is superior to the atlas-based framwork except in the case of the liver. Specifically, in the case of the stomach, the DSC, VOE, and RVD showed a maximum difference of 21.67, 25.11, 28.80% respectively. Conclusions In this study, we demonstrated that a deep learning framework could be used more effectively and efficiently compared to atlas-based auto-segmentation for most OARs in human liver cancer. Extended use of the deep-learning-based framework is anticipated for auto-segmentations of other body sites.

Background This retrospective German and Italian multicenter analysis aimed to compare the role of normofractionated stereotactic radiotherapy (nFSRT) to CyberKnife-based hypofractionated stereotactic radiotherapy (CK-hFSRT) for skull base meningiomas. Methods Overall, 341 patients across three centers were treated with either nFSRT or CK-hFSRT for skull base meningioma. Treatment planning was based on computed tomography (CT) and magnetic resonance imaging (MRI) following institutional guidelines. Most nFSRT patients received 33 × 1.8 Gy, and most CK-hFSRT patients received 5 × 5 Gy. The median follow-up time was 36 months (range: 1–232 months). Results In the CK-hFSRT group, the 1-, 3-, and 10-year local control (LC) rates were 99.4, 96.8, and 80.3%, respectively. In the nFSRT group, the 1-, 3-, and 10-year LC rates were 100, 99, and 79.1%, respectively. There were no significant differences in LC rates between the nFSRT and CK-hFSRT groups (p = 0.56, hazard ratio = 0.76, 95% confidence interval, 0.3–1.9). In the CK-hFSRT group, only one case (0.49%) of severe toxicity (CTCAE 4.0 ≥ 3) was observed. In the nFSRT group, three cases (2.1%) of grade III toxicity were observed. Conclusion This analysis of pooled data from three centers showed excellent LC and low side effect rates for patients treated with CK-hFSRT or nFSRT. The efficacy, safety, and convenience of a shortened treatment period provide a compelling case for the use of CK-hFSRT in patients with moderate size skull base meningioma and provided that OAR constraints are met.

Background In-vivo dosimetry (IVD) is a patient specific measure of quality control and safety during radiotherapy. With regard to current reporting thresholds for significant occurrences in radiotherapy defined by German regulatory authorities, the present study examines the clinical feasibility of superficial electron paramagnetic resonance (EPR) IVD of cumulative total doses applied to breast cancer patients treated with helical intensity-modulated radiotherapy (tomotherapy). Methods In total, 10 female patients with left- or right-sided breast cancer were enrolled in this prospective IVD study. Each patient received a hypofractionated whole breast irradiation. A total median dose of 42.4 Gy in 16 fractions (5 fractions per week) was prescribed to the planning target volume. The treatments were completely delivered using helical tomotherapy and daily image guidance via megavoltage CT (MVCT). For each patient, three EPR dosimeters were prepared and placed at distinct locations on the patient’s skin during the delivery of all fractions. Two dosimeters were placed next to the ipsilateral and contralateral mammilla and one dosimeter was placed ventrally to the thyroid (out-of-primary-beam). The total doses delivered to the dosimeters were readout after all fractions had been administered. The measured total dose values were compared to the planned dose values derived from the treatment planning system (TPS). Daily positional variations (displacement vectors) of the ipsilateral mammilla and of the respective dosimeter were analyzed with respect to the planned positions using the daily registered MVCT image. Results Averaged over all patients, the mean absolute dose differences between measured and planned total dose values (± standard deviation (SD)) were: 0.49 ± 0.85 Gy for the ipsilateral dosimeter, 0.17 ± 0.49 Gy for the contralateral dosimeter and -0.12 ± 0.30 Gy for the thyroid dosimeter. The mean lengths of the ipsilateral displacement vectors (± SD) averaged over all patients and fractions were: 10 ± 7 mm for the dosimeter and 8 ± 4 mm for the mammilla. Conclusion Superficial EPR IVD is suitable as additional safeguard for dose delivery during helical tomotherapy of breast cancer. Despite positional uncertainties in clinical routine, the observed dose deviations at the ipsilateral breast were on average small compared to national reporting thresholds for total dose deviations (i.e. 10%/4 Gy). EPR IVD may allow for the detection of critical dose errors during whole breast irradiations.

Background This study aimed to evaluate the clinical and dosimetric factors predictive of acute anal toxicity (AAT) after radiotherapy in prostate cancer (PCa) patients with or without hemorrhoids. Methods We analyzed data from 347 PCa patients (248 cases treated from July 2013 to November 2017 for training cohort and 99 cases treated in 2018 for validation cohort) treated with pelvic radiotherapy at a single institution. Anal canal dose–volume histogram was used to determine the prescribed dose. Univariate and multivariate analyses were used to evaluate the risk of AAT as a function of clinical and dosimetric factors. Results Totally, 39.5% (98/248) and 31.3% (31/99) of the PCa patients developed AAT in training and validation cohorts, respectively. The incidence of AAT was much higher in patients with hemorrhoids than in those without hemorrhoids in both training and validation cohorts. Hemorrhoids and volume received more than 20 Gy (V20) were valuated as independent factors for predicting AAT in training cohort. Similar results were also observed in our validation cohort. The combination of hemorrhoids and high anal canal V20 (> 74.93% as determined by ROC curves) showed the highest specificity and positive predictive values for predicting AAT in both training and validation cohorts. Conclusions AAT occurs commonly in PCa patients with hemorrhoids during and after pelvic radiotherapy. Hemorrhoids and anal canal V20 are independent predictors of AAT. These factors should be carefully considered during treatment planning to minimize the incidence of AAT.

Purpose Comparing radiation treatment plans by using the same safety margins and dose objectives for all techniques, to ascertain the optimal radiation technique for the stereotactic body radiotherapy (SBRT) of low-risk prostate cancer. Material and methods Treatment plans for 27 randomly selected patients were compared using intensity-modulated (IMRT) techniques as Sliding Window (SW), volumetric modulated arc therapy (VMAT), and helical tomotherapy (HT), as well as Cyber Knife (CK) system. The target dose was calculated to 36.25 Gy delivered in five fractions over 1 week. Dosimetric indices for target volume and organs at risk (OAR) as well as normal tissue complication probability (NTCP) of late rectal and urinary bladder toxicities were analyzed. Results The CK provided lower homogeneity in the target volume, but higher values for most of the conformity indices compared to the IMRT approaches. The SW demonstrated superior rectum sparing at medium-to-high dose range (V18 Gy - V32.6 Gy) compared to other techniques (p

Background The purpose of this study was to assess compliance with treatment planning in a dummy-run for a multicenter clinical trial involving patients with high-risk postoperative uterine cervical cancer using intensity-modulated radiation therapy (IMRT) (JCOG1402 trial). Methods For the dummy-run, we prepared a computed tomography dataset comprising two anonymized cases of post-hysterectomy cervical cancer. These were sent to the 47 participating institutions to assess institutional plan quality such as delineations and dose distributions. Results Central review showed 3 and 4 deviations per treatment plan on average. The deviations related to the nodal and vaginal cuff clinical target volume (CTV) delineation, which accounted for approximately 50% of the total deviations. The CTV vaginal cuff showed considerable differences in delineation compared with the nodal CTV. For the Dice similarity coefficient, case 1 showed a mean ± 1σ of 0.81 ± 0.03 and 0.60 ± 0.09 for the nodal and the CTV vaginal cuff, respectively, while these were 0.81 ± 0.04 and 0.54 ± 0.14, respectively, for case two. Of the 47 institutions, 10 were required to resubmit their treatment plan because the delineations, planning target volume margin, and required dose distributions were not in accordance with the JCOG1402 protocol. Conclusions The dummy-run test in postoperative uterine cervical cancer demonstrated substantial deviations in the delineations, particularly for the CTV vaginal cuff. The analysis data could provide helpful information on delineation and planning, allowing standardization of IMRT planning for postoperative uterine cervical cancer. Trial registration Japanese Clinical Trial Registry #: UMIN000027017 at https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000030672;language=J Electronic supplementary material The online version of this article (10.1186/s13014-019-1340-y) contains supplementary material, which is available to authorized users.

Background The aim of this study was to compare dose-volume histogram (DVH) with dose-mass histogram (DMH) parameters for treatment of left-sided breast cancer in deep inspiration breath-hold (DIBH) and free breathing (FB). Additionally, lung expansion and anatomical factors were analyzed and correlated to dose differences. Methods For 31 patients 3D conformal radiation therapy plans were retrospectively calculated on FB and DIBH CTs in the treatment planning system. The calculated doses, structures and CT data were transferred into MATLAB and DVHs and DMHs were calculated. Mean doses (Dmean), volumes and masses receiving certain doses (Vx, Mx) were determined for the left lung and the heart. Additionally, expansion of the left lung was evaluated using deformable image registration. Differences in DVH and DMH dose parameters between FB and DIBH were statistically analyzed and correlated to lung expansion and anatomical factors. Results DIBH reduced Dmean (DVH) and relative V20 (V20 [%]) of the left lung in all patients, on average by − 19 ± 9% (mean ± standard deviation) and − 24 ± 10%. Dmean (DMH) and M20 [%] were also significantly reduced (− 12 ± 11%, − 16 ± 13%), however 4 patients had higher DMH values in DIBH than in FB. Linear regression showed good correlations between DVH and DMH parameters, e.g. a dosimetric benefit smaller than 8.4% for Dmean (DVH) in DIBH indicated more irradiated lung mass in DIBH than in FB. The mean expansion of the left lung between FB and DIBH was 1.5 ± 2.4 mm (left), 16.0 ± 4.0 mm (anterior) and 12.2 ± 4.6 mm (caudal). No significant correlations were found between expansions and differences in Dmean for the left lung. The heart dose in DIBH was reduced in all patients by 53% (Dmean) and this dosimetric benefit correlated to lung expansion in anterior. Conclusions Treatment of left-sided breast cancer in DIBH reduced dose to the heart and in most cases the lung dose, relative irradiated lung volume and lung mass. A mass related dosimetric benefit in DIBH can be achieved as long as the volume related benefit is about ≥8–9%. The lung expansion (breathing pattern) showed no impact on lung dose, but on heart dose. A stronger chest breathing (anterior expansion) for DIBH seems to be more beneficial than abdominal breathing.

Background Although circular collimator arcs (CCA) and dynamic conformal arcs (DCA) are commonly used linear accelerator-based treatment planning techniques for intracranial stereotactic radiosurgery (SRS) of a small single lesion, these two techniques have not been rigorously compared in terms of tumor shape. Therefore, this study compared clinical CCA plans with re-planned DCA plans using conformity index (CI) and V12Gy (volume of normal brain tissue receiving 12 Gy or higher) from a perspective of asymmetry (Asym) of planning target volume (PTV). Methods Ninety-five clinical CCA plans delivered for a small single lesion with PTV size 6.12%. Conclusions The DCA technique is recommended when a lesion has PTV Asym > 6.12% regardless of PTV size. For lesions with PTV Asym ≤6.12%, a technique choice would depend on the preference of CI or V12Gy.

Background Peer review systems within radiation oncology are important to ensure quality radiation care. Several individualized methods for radiation oncology peer review have been described. However, despite the importance of peer review in radiation oncology barriers may exist to its effective implementation in practice. The purpose of this study was to quantify the rate of plan changes based on our group peer review process as well as the quantify amount of time and resources needed for this process. Methods Data on cases presented in our institutional group consensus peer review conference were prospectively collected. Cases were then retrospectively analyzed to determine the rate of major change (plan rejection) and any change in plans after presentation as well as the median time of presentation. Univariable logistic regression was used to determine factors associated with major change and any change. Results There were 73 cases reviewed over a period of 11 weeks. The rate of major change was 8.2% and the rate of any change was 23.3%. The majority of plans (53.4%) were presented in 6–10 min. Overall, the mean time of presentation was 8 min. On univariable logistic regression, volumetric modulated arc therapy plans were less likely to undergo a plan change but otherwise there were no factors significantly associated with major plan change or any type of change. Conclusion Group consensus peer review allows for a large amount of informative clinical and technical data to be presented per case prior to the initiation of radiation treatment in a thorough yet efficient manner to ensure plan quality and patient safety.

Background Most studies on synthetic computed tomography (sCT) generation for brain rely on in-house developed methods. They often focus on performance rather than clinical feasibility. Therefore, the aim of this work was to validate sCT images generated using a commercially available software, based on a convolutional neural network (CNN) algorithm, to enable MRI-only treatment planning for the brain in a clinical setting. Methods This prospective study included 20 patients with brain malignancies of which 14 had areas of resected skull bone due to surgery. A Dixon magnetic resonance (MR) acquisition sequence for sCT generation was added to the clinical brain MR-protocol. The corresponding sCT images were provided by the software MRI Planner (Spectronic Medical AB, Sweden). sCT images were rigidly registered and resampled to CT for each patient. Treatment plans were optimized on CT and recalculated on sCT images for evaluation of dosimetric and geometric endpoints. Further analysis was also performed for the post-surgical cases. Clinical robustness in patient setup verification was assessed by rigidly registering cone beam CT (CBCT) to sCT and CT images, respectively. Results All sCT images were successfully generated. Areas of bone resection due to surgery were accurately depicted. Mean absolute error of the sCT images within the body contour for all patients was 62.2 ± 4.1 HU. Average absorbed dose differences were below 0.2% for parameters evaluated for both targets and organs at risk. Mean pass rate of global gamma (1%/1 mm) for all patients was 100.0 ± 0.0% within PTV and 99.1 ± 0.6% for the full dose distribution. No clinically relevant deviations were found in the CBCT-sCT vs CBCT-CT image registrations. In addition, mean values of voxel-wise patient specific geometric distortion in the Dixon images for sCT generation were below 0.1 mm for soft tissue, and below 0.2 mm for air and bone. Conclusions This work successfully validated a commercially available CNN-based software for sCT generation. Results were comparable for sCT and CT images in both dosimetric and geometric evaluation, for both patients with and without anatomical anomalies. Thus, MRI Planner is feasible to use for radiotherapy treatment planning of brain tumours.

Background Segmentation is a crucial step in treatment planning that directly impacts dose distribution and optimization. The aim of this study was to evaluate the inter-individual variability of common cranial organs at risk (OAR) delineation in neurooncology practice. Methods Anonymized simulation contrast-enhanced CT and MR scans of one patient with a solitary brain metastasis was used for delineation and analysis. Expert professionals from 16 radiotherapy centers involved in brain structures delineation were asked to segment 9 OAR on their own treatment planning system. As reference, two experts in neurooncology, produced a unique consensual contour set according to guidelines. Overlap ratio, Kappa index (KI), volumetric ratio, Commonly Contoured Volume, Supplementary Contoured Volume were evaluated using Artiview™ v 2.8.2—according to occupation, seniority and level of expertise of all participants. Results For the most frequently delineated and largest OAR, the mean KI are often good (0.8 for the parotid and the brainstem); however, for the smaller OAR, KI degrade (0.3 for the optic chiasm, 0.5% for the cochlea), with a significant discrimination (p Association des Neuro-Oncologue d’Expression Française society performed better in all indicators compared to non-members (p p Conclusion Our study illustrates the heterogeneity in normal structures contouring between professionals. We emphasize the need for cerebral OAR delineation harmonization—that is a major determinant of therapeutic ratio and clinical trials evaluation.

As optic nerve sheath meningiomas (ONSM) are rare, there are no prospective studies. Our retrospective analysis focusses on a cohort of patients with uniform disease characteristics all treated with the same radiotherapy regimen. We describe treatment decision making, radiotherapy planning and detailed neuro-ophthalmological outcome of the patients. 26 patients with unilateral ONSM extending only to the orbit and the optic canal were evaluated for neuro-ophthalmological outcome. Radiation treatment was planned in a simultaneous integrated boost approach to gross tumor volume (GTV) + 2 mm / 5 mm to 54 Gy / 51 Gy in 1.8 Gy / 1.7 Gy fractions. Follow-up was done by specialized neuro-ophthalmologists. Visual acuity and visual field defects were evaluated after therapy as well as during follow-up. Interdisciplinary treatment decision for patients with ONSM follows a rather complex decision tree. Radiation treatment planning (equivalent uniform dose (EUD), maximum dose to the optic nerve) improved with experience over time. With this patient selection visual acuity as well as visual field improved significantly at first follow-up after treatment. For visual acuity this also applied to patients with severe defects before treatment. Long term evaluation showed 16 patients with improved visual function, 6 were stable, in 4 patients visual function declined. Interdisciplinary case discussion rated the visual decline as radiation-associated in two patients. With stringent patient selection radiotherapy for unilateral primary ONSM to 51 Gy / 54 Gy is safe and leads to significantly improved visual function. Interdisciplinary treatment decision and experience of the radiation oncology team play a major role.

Objective To assess the effects of various treatment planning parameters to identify the optimal gap distance for precise two-segment total body irradiation (TBI) using helical tomotherapy (HT) with fixed jaw mode. Methods and materials Data of a treatment plan for 8 acute leukemia patients (height range: 109–130 cm) were analyzed. All patients underwent total-body computed tomography (CT) with 5-mm slice thickness. A lead wire, placed at 10 cm above the patella, was used to mark the boundary between the two segments. Target volumes and organs at risk were delineated using a Varian Eclipse 10.0 physician’s workstation. Different distances between the lead wire and the boundary of the two targets were used. CT images were transferred to the HT workstation to design the treatment plans, by adjusting parameters, including the field width (FW; 2.5 cm, and 5 cm), pitch (0.287 and 0.430), modulation factor (1.8). The plans were superimposed to analyze the dose distributions in the overlap region when varying target gap distances, FWs, pitches to determine the optimal combinations. Results The pitch did not affect the dose distribution in the overlap region. The dose distribution in the overlap region was mostly homogeneous when the target gap distance was equal to the FW. Increased FW diminished the effect of the target gap distance on the heterogeneous index of the overlap region. Conclusions In two-segment TBI treatments by HT with Helix mode, a gap distance equal to the FW may achieve optimal dose distribution in the overlap region.

Purpose In this study, we employed a gated recurrent unit (GRU)-based recurrent neural network (RNN) using dosimetric information induced by individual beam to predict the dose-volume histogram (DVH) and investigated the feasibility and usefulness of this method in biologically related models for nasopharyngeal carcinomas (NPC) treatment planning. Methods and materials One hundred patients with NPC undergoing volumetric modulated arc therapy (VMAT) between 2018 and 2019 were randomly selected for this study. All the VMAT plans were created using the Monaco treatment planning system (Elekta, Sweden) and clinically approved: > 98% of PGTVnx received the prescribed doses of 70 Gy, > 98% of PGTVnd received the prescribed doses of 66 Gy and > 98% of PCTV received 60 Gy. Of these, the data from 80 patients were used to train the GRU-RNN, and the data from the other 20 patients were used for testing. For each NPC patient, the DVHs of different organs at risk were predicted by a trained GRU-based RNN using the information given by individual conformal beams. Based on the predicted DVHs, the equivalent uniform doses (EUD) were calculated and applied as dose constraints during treatment planning optimization. The regenerated VMAT experimental plans (EPs) were evaluated by comparing them with the clinical plans (CPs). Results For the 20 test patients, the regenerated EPs guided by the GRU-RNN predictive model achieved good consistency relative to the CPs. The EPs showed better consistency in PTV dose distribution and better dose sparing for many organs at risk, and significant differences were found in the maximum/mean doses to the brainstem, brainstem PRV, spinal cord, lenses, temporal lobes, parotid glands and larynx with P-values Conclusion The GRU-RNN-based DVH prediction method was capable of accurate DVH prediction. The regenerated plans guided by the predicted EUDs were not inferior to the manual plans, had better consistency in PTVs and better dose sparing in critical OARs, indicating the usefulness and effectiveness of biologically related model in knowledge-based planning.

Background Hypofractionated whole-breast irradiation is a standard adjuvant therapy for early-stage breast cancer. This study evaluates the plan quality and efficacy of an in-house-developed automated radiotherapy treatment planning algorithm for hypofractionated whole-breast radiotherapy. Methods A cohort of 99 node-negative left-sided breast cancer patients completed hypofractionated whole-breast irradiation with six-field IMRT for 42.56 Gy in 16 daily fractions from year 2016 to 2018 at a tertiary center were re-planned with an in-house-developed algorithm. The automated plan-generating C#-based program is developed in a Varian ESAPI research mode. The dose-volume histogram (DVH) and other dosimetric parameters of the automated and manual plans were directly compared. Results The average time for generating an autoplan was 5 to 6 min, while the manual planning time ranged from 1 to 1.5 h. There was only a small difference in both the gantry angles and the collimator angles between the autoplans and the manual plans (ranging from 2.2 to 5.3 degrees). Autoplans and manual plans performed similarly well in hotspot volume and PTV coverage, with the autoplans performing slightly better in the ipsilateral-lung-sparing dose parameters but were inferior in contralateral-breast-sparing. The autoplan dosimetric quality did not vary with different breast sizes, but for manual plans, there was worse ipsilateral-lung-sparing (V4Gy) in larger or medium-sized breasts than in smaller breasts. Autoplans were generally superior than manual plans in CI (1.24 ± 0.06 vs. 1.30 ± 0.09, p p Conclusions Our study presents a well-designed standardized fully automated planning algorithm for optimized whole-breast radiotherapy treatment plan generation. A large cohort of 99 patients were re-planned and retrospectively analyzed. The automated plans demonstrated similar or even better dosimetric quality and efficacy in comparison with the manual plans. Our result suggested that the autoplanning algorithm has great clinical applicability potential.

Purpose To ascertain the dosimetric performance of a new delivery system (the Halcyon system, H) equipped with dual-layer stacked multi-leaf collimator (MLC) for risk-adapted targets in cervix uteri cancer patients compared to another ring-based system in clinical operation (Helical Tomotherapy, HT). Methods Twenty patients were retrospectively included in a treatment planning study (10 with positive lymph nodes and 10 without). The dose prescription (45Gy to the primary tumour volume and a simultaneously integrated boost up to 55Gy for the positive patients) and the clinical planning objectives were defined consistently as recommended by an ongoing multicentric clinical trial. Halcyon plans were optimised for the volumetric modulated arc therapy. The plan comparison was performed employing the quantitative analysis of the dose-volume histograms. Results The coverage of the primary and nodal target volumes was comparable for both techniques and both subsets of patients. The primary planning target volume (PTV) receiving at least 95% of the prescription isodose ranged from 97.2 ± 1.1% (node-negative) to 99.1 ± 1.2% (node-positive) for H and from 96.5 ± 1.9% (node-negative) to 98.3 ± 0.9% (node-positive) for HT. The uncertainty is expressed at one standard deviation from the cohort of patient per each group. For the nodal clinical target volumes, the dose received by 98% of the planning target volume ranged 55.5 ± 0.1 to 56.0 ± 0.8Gy for H and HT, respectively. The only significant and potentially relevant differences were observed for the bowels. In this case, V40Gy resulted 226.3 ± 35.9 and 186.9 ± 115.9 cm3 for the node-positive and node-negative patients respectively for Halcyon. The corresponding findings for HT were: 258.9 ± 60.5 and 224.9 ± 102.2 cm3. On the contrary, V15Gy resulted 1279.7 ± 296.5 and 1557.2 ± 359.9 cm3 for HT and H respectively for node-positive and 1010.8 ± 320.9 versus 1203.8 ± 332.8 cm3 for node-negative. Conclusion This retrospective treatment planning study, based on the dose constraints derived from the Embrace II study protocol, suggested the essential equivalence between Halcyon based and Helical Tomotherapy based plans for the intensity-modulated rotational treatment of cervix uteri cancer. Different levels of sparing were observed for the bowels with H better protecting in the high-dose region and HT in the mid-low dose regions. The clinical impact of these differences should be further addressed.

Background Existing pencil beam analytical (PBA) algorithms for proton therapy treatment planning are not ideal for sites with heterogeneous tissue density and do not account for the spatial variations in proton relative biological effectiveness (vRBE). Using a commercially available Monte Carlo (MC) treatment planning system, we compared various dosimetric endpoints between proton PBA, proton MC, and photon treatment plans among patients with mediastinal lymphoma. Methods Eight mediastinal lymphoma patients with both free breathing (FB) and deep inspiration breath hold (DIBH) CT simulation scans were analyzed. The original PBA plans were re-calculated with MC. New proton plans that used MC for both optimization and dose calculation with equivalent CTV/ITV coverage were also created. A vRBE model, which uses a published model for DNA double strand break (DSB) induction, was applied on MC plans to study the potential impact of vRBE on cardiac doses. Comparative photon plans were generated on the DIBH scan. Results Re-calculation of FB PBA plans with MC demonstrated significant under coverage of the ITV V99 and V95. Target coverage was recovered by re-optimizing the PT plan with MC with minimal change to OAR doses. Compared to photons with DIBH, MC-optimized FB and DIBH proton plans had significantly lower dose to the mean lung, lung V5, breast tissue, and spinal cord for similar target coverage. Even with application of vRBE in the proton plans, the putative increase in RBE at the end of range did not decrease the dosimetric advantages of proton therapy in cardiac substructures. Conclusions MC should be used for PT treatment planning of mediastinal lymphoma to ensure adequate coverage of target volumes. Our preliminary data suggests that MC-optimized PT plans have better sparing of the lung and breast tissue compared to photons. Also, the potential for end of range RBE effects are unlikely to be large enough to offset the dosimetric advantages of proton therapy in cardiac substructures for mediastinal targets, although these dosimetric findings require validation with late toxicity data.

For 2018, the American Cancer Society estimated that there would be approximately 1.7 million new diagnoses of cancer and about 609,640 cancer-related deaths in the United States. By 2030 these numbers are anticipated to exceed a staggering 21 million annual diagnoses and 13 million cancer-related deaths. The three primary therapeutic modalities for cancer treatments are surgery, chemotherapy, and radiation therapy. Individually or in combination, these treatment modalities have provided and continue to provide curative and palliative care to the myriad victims of cancer. Today, CT-based treatment planning is the primary means through which conventional photon radiation therapy is planned. Although CT remains the primary treatment planning modality, the field of radiation oncology is moving beyond the sole use of CT scans to define treatment targets and organs at risk. Complementary tissue scans, such as magnetic resonance imaging (MRI) and positron electron emission (PET) scans, have all improved a physician’s ability to more specifically identify target tissues, and in some cases, international guidelines have even been issued. Moreover, efforts to combine PET and MR to define solid tumors for radiotherapy planning and treatment evaluation are also gaining traction. Keeping these advances in mind, we present brief overviews of other up-and-coming key imaging concepts that appear promising for initial treatment target definition or treatment response from radiation therapy.

Background A new strategy for making the appropriate choice of the representative optimization parameters in planning processes and accurate selection criteria during Pareto surface navigation for general multicriteria optimization (MCO) was recommended in the study. The purpose was to combine both benefits of AutoPlanning optimization and MCO (APMCO) for achieving an individual volumetric-modulated arc therapy (VMAT) plan according to the clinically achieved patient-specific tradeoff among conflicting priorities. The preclinical investigation of this optimization approach for nasopharyngeal carcinoma (NPC) radiotherapy was performed and compared to general MCO VMAT. Methods A total of 60 NPC patients with various stages were enrolled in this study. General MCO and APMCO plans were generated for each patient on the treatment planning system. The differences between two planning schemes were evaluated and compared. Results All plans were capable of achieving the prescription requirement. The planning target volume coverage and conformation number were remarkably similar between general MCO and APMCO plans. There were no significant differences in most of organs at risk (OARs) sparing. However, in APMCO plans, relatively remarkable decreases were observed in the mean dose (Dmean) to the glottic larynx and pharyngeal constrictor muscles. The reductions of average Dmean to the two OARs were 10.5% (p

Background Monte Carlo simulations were run to estimate the dose variations generated by thedifference arising from the chemical composition of the tissues. Methods CT datasets of five breast cancer patients were selected. Mammary gland was delineated as clinical target volume CTV, as well as CTV_lob and CTV_fat, being the lobular and fat fractions of the entire mammary gland. Patients were planned for volumetric modulated arc therapy technique, optimized in the Varian Eclipse treatment planning system. CT, structures and plans were imported in PRIMO, based on Monte Carlo code Penelope, to run three simulations: AdiMus, where the adipose and muscle tissues were automatically assigned to fat and lobular fractions of the breast; Adi and Mus, where adipose and muscle, respectively were assigned to the whole mammary gland. The specific tissue density was kept identical from the CT dataset. Differences in mean doses in the CTV_lob and CTV_fat structures were evaluated for the different tissue assignments. Differences generated by the tissue composition and estimated by Acuros dose calculations in Eclipse were also analysed. Results From Monte Carlo simulations, the dose in the lobular fraction of the breast, when adipose tissue is assigned in place of muscle, is overestimated by 1.25 ± 0.45%; the dose in the fat fraction of the breast with muscle tissue assignment is underestimated by 1.14 ± 0.51%. Acuros showed an overestimation of 0.98 ± 0.06% and an underestimation of 0.21 ± 0.14% in the lobular and fat portions, respectively. Reason of this dissimilarity resides in the fact that the two calculations, Monte Carlo and Acuros, differently manage the range of CT numbers and the material assignments, having Acuros an overlapping range, where two tissues are both present in defined proportions. Conclusion Although not clinically significant, the dose deposition difference in the lobular and connective fat fraction of the breast tissue lead to an improved knowledge of the possible dose distribution and homogeneity in the breast radiation treatment.

Background SBRT is standard therapy for early stage lung cancer. Toxicity in central tumors has been a concern. RTOG 0813 showed that central SBRT is safe and effective. We report our experience with central SBRT. Methods We reviewed the records of patients treated with SBRT for central lung tumors (

Background Peer review, especially prospective peer review, has been supported by professional organizations as an important element in optimal Radiation Oncology practice based on its demonstration of efficacy at detecting and preventing errors prior to patient treatment. Implementation of peer review is not without barriers, but solutions do exist to mitigate or eliminate some of those barriers. Methods Peer review practice at our institution involves three key elements: new patient conference, treatment planning conference, and chart rounds. The treatment planning conference is an adaptation of the group consensus peer review model from radiology which utilizes a group of peers reviewing each treatment plan prior to implementation. The peer group in radiation oncology includes Radiation Oncologists, Physician Residents, Medical Physicists, Dosimetrists, and Therapists. Thus, technical and clinical aspects of each plan are evaluated simultaneously. Results Though peer review is held in high regard in Radiation Oncology, many barriers commonly exist preventing optimal implementation such as time intensiveness, repetition, and distraction from clinic time with patients. Through the use of automated review tools and commitment by individuals and administration in regards to staffing, scheduling, and responsibilities, these barriers have been mitigated to implement this Group Consensus Peer Review model into a Radiation Oncology Clinic. Conclusion A Group Consensus Peer Review model has been implemented with strategies to address common barriers to effective and efficient peer review.

Background To appraise the dosimetric features and the quality of the treatment plan for radiosurgery of multiple brain metastases optimized with a novel automated engine and to compare with plans optimized for robotic-based delivery. Methods A set of 15 patients with multiple brain metastases was selected for this in silico study. The technique under investigation is the recently introduced HyperArc. For all patients, three treatment plans were computed and compared: i: a HyperArc; ii: a standard VMAT; iii) a CyberKnife. Dosimetric features were computed for the clinical target volumes as well as for the healthy brain tissue and the organs at risk. Results The data showed that the best dose homogeneity was achieved with the VMAT technique. HyperArc allowed to minimize the volume of brain receiving 4Gy (as well as for the mean dose and the volume receiving 12Gy, although not statistically significant). The smallest dose on 1 cm3 volume for all organs at risk is for CK techniques, and the biggest for VMAT (p

Background The purpose of this study was to demonstrate the feasibility of physician driven planning in intensity modulated radiotherapy (IMRT) with a multicriteria optimization (MCO) treatment planning system and template based plan optimization. Exploiting the full planning potential of MCO navigation, this alternative planning approach intends to improve planning efficiency and individual plan quality. Methods Planning was retrospectively performed on 12 brain tumor and 10 post-prostatectomy prostate patients previously treated with MCO-IMRT. For each patient, physicians were provided with a template-based generated Pareto surface of optimal plans to navigate, using the beam angles from the original clinical plans. We compared physician generated plans to clinically delivered plans (created by dosimetrists) in terms of dosimetric differences, physician preferences and planning times. Results Plan qualities were similar, however physician generated and clinical plans differed in the prioritization of clinical goals. Physician derived prostate plans showed significantly better sparing of the high dose rectum and bladder regions (p(D1)

Background: For irradiation treatment planning of meningiomas the use of PET-scans is well established. The most frequently used tracers are either based on amino acids or the somatostatin receptor ligand DOTATOC. Since up to now no inter-institutionally accepted standard PET-tracer has been defined, the aim of this study was to evaluate the influence of these different types of PET-tracers on the GTV-definition. Methods: Twenty-one patients suffering from intracranial meningiomas underwent CT, MRI, FET- and DOTATOC-PET. First, tumour extension was delineated after image-fusion of CT and MRI (GTV CT/MRI ). Then distinct GTVs based either on FET- or DOTATOC-PET were contoured and compared with each other as well with GTV CT/MRI . Results: Every tumour showed typical enhancement of DOTATOC, but two meningiomas remained FET-negative. The mean relative overlap volume of GTV FET and GTV DOTATOC was only 41.9% and there was a significantly stronger correlation between GTV CT/MRI and GTV DOTATOC than between GTV CT/MRI and GTV FET . Conclusions: Further investigations are necessary to clarify the minor conformity of DOTATOC- and FET-PET in meningiomas. Because of the receptor targeting, DOTATOC is known to be more specific for meningiomas and will remain the standard in our institution with the known limitation in areas nearby the pituitary gland.

Background This work explores how the choice of prescription isodose line (IDL) affects the dose gradient, target coverage, and treatment time for Gamma Knife radiosurgery when a smaller shot is encompassed within a larger shot at the same stereotactic coordinates (shot within shot technique). Methods Beam profiles for the 4, 8, and 16 mm collimator settings were extracted from the treatment planning system and characterized using Gaussian fits. The characterized data were used to create over 10,000 shot within shot configurations by systematically changing collimator weighting and choice of prescription IDL. Each configuration was quantified in terms of the dose gradient, target coverage, and beam-on time. By analyzing these configurations, it was found that there are regions of overlap in target size where a higher prescription IDL provides equivalent dose fall-off to a plan prescribed at the 50% IDL. Furthermore, the data indicate that treatment times within these regions can be reduced by up to 40%. An optimization strategy was devised to realize these gains. The strategy was tested for seven patients treated for 1–4 brain metastases (20 lesions total). Results For a single collimator setting, the gradient in the axial plane was steepest when prescribed to the 56–63% (4 mm), 62–70% (8 mm), and 77–84% (16 mm) IDL, respectively. Through utilization of the optimization technique, beam-on time was reduced by more than 15% in 16/20 lesions. The volume of normal brain receiving 12 Gy or above also decreased in many cases, and in only one instance increased by more than 0.5 cm3. Conclusions This work demonstrates that IDL optimization using the shot within shot technique can reduce treatment times without degrading treatment plan quality. Electronic supplementary material The online version of this article (10.1186/s13014-017-0919-4) contains supplementary material, which is available to authorized users.

Background The decrease in peripheral blood lymphocytes induced by radiation lessens the antitumour effect of the immune response, which might cause immunosuppression. We aimed to investigate the correlation between the decrease in peripheral blood lymphocytes during radiotherapy (RT) and the spleen irradiation dose in patients with hepatocellular carcinoma (HCC). Methods The subjects were 59 patients with HCC who had received RT from 2005 to 2014. The Min ALC (minimum value of absolute counts for peripheral blood lymphocytes) was collected from the routine workup for each patient prior to RT and weekly during RT. Spleen dose-volume variables, including the percentage of the organ volume receiving ≥ n Gy (Vn) and the mean spleen dose (MSD), were calculated using Eclipse treatment planning. Potential associations between dosimetric variables and the Min ALC were assessed by multiple linear regression analysis. Results Peripheral lymphocytes decreased during RT (P

Background To calculate the individualized fraction regime (IFR) in stereotactic body radiotherapy (SBRT) for non-small cell lung cancer (NSCLC) patients using the uncomplicated tumor control probability (UTCP, P+) function. Methods Thirty-three patients with peripheral lung cancer or lung metastases who had undergone SBRT were analyzed. Treatment planning was performed using the dose regime of 48 Gy in 4 fractions. Dose volume histogram (DVH) data for the gross tumor volume (GTV), lung, chest wall (CW) and rib were exported and the dose bin was multiplied by a certain percentage of the dose in that bin which ranged from 1 to 200% in steps of 1%. For each dose fraction, P+ values were calculated by considering the tumor control probability (TCP), radiation-induced pneumonitis (RIP), chest wall pain (CWP) and radiation-induced rib fracture (RIRF). UTCP values as a function of physical dose were plotted and the maximum P+ values corresponded to the optimal therapeutic gain. The IFR in 3 fractions was also calculated with the same method by converting the dose using the linear quadratic (LQ) model. Results Thirty-three patients attained an IFR using the introduced methods. All the patients achieved a TCP value higher than 92.0%. The IFR ranged from 3 × 10.8 Gy to 3 × 12.5 Gy for 3 fraction regimes and from 4 × 9.2 Gy to 4 × 10.7 Gy for 4 fraction regimes. Four patients with typical tumor characteristics demonstrated that the IFR was patient-specific and could maximize the therapeutic gain. Patients with a large tumor had a lower TCP and UTCP and a smaller fractional dose than patients with a small tumor. Patients with a tumor adjacent to the organ at risk (OAR) or at a high risk of RIP had a lower UTCP and a smaller fractional dose compared with patients with a tumor located distant from the OAR. Conclusions The proposed method is capable of predicting the IFR for NSCLC patients undergoing SBRT. Further validation in clinical samples is required.

Background This study clarified the mechanical performance of volumetric modulated arc therapy (VMAT) plans for prostate cancer generated with a commercial knowledge-based treatment planning (KBP) and whether KBP system could be applied clinically without any major problems with mechanical performance. Methods Thirty consecutive prostate cancer patients who underwent VMAT using extant clinical plans were evaluated. The mechanical performance and dosimetric accuracy of the single optimized KBPs, which were trained with other 51 clinical plans, were compared with the clinical plans. The mechanical performance metrics were mean field area (MFA), mean asymmetry distance (MAD), cross-axis score (CAS), closed leaf score (CLS), small aperture score (SAS), leaf travel (LT), modulation complexity score (MCSv), and monitor unit (MU). The γ passing rates were evaluated with ArcCheck and EBT3 film. Results The mean mechanical performance metrics (clinical plan vs. KBP) were as follows: 18.28 cm2 vs. 17.25 cm2 (MFA), 21.08 mm vs. 20.47 mm (MAD), 0.54 vs. 0.55 (CAS), 0.040 vs. 0.051 (CLS), 0.20 vs. 0.23 (SAS5mm), 458.5 mm vs. 418.8 mm (LT), 0.27 vs. 0.27 (MCSv), and 618.2 vs. 622.1 (MU), respectively. Significant differences were observed for CLS and LT. The average γ passing rates (clinical plan vs. KBP) were as follows: 99.0% vs. 99.1% (3%/3 mm) and 92.4% vs. 92.5% (2%/2 mm) with ArcCHeck, and 99.5% vs. 99.4% (3%/3 mm) and 95.2% vs. 95.4% (2%/2 mm) with EBT3 film, respectively. Conclusions The KBP used lower multileaf collimator (MLC) travel and more closed or small MLC apertures than the clinical plan. The KBP system of VMAT for the prostate cancer was acceptable for clinical use without any major problems.

Background Patient-specific distortions, particularly near tissue/air interfaces, require assessment for magnetic resonance (MR) only radiation treatment planning (RTP). However, patients are dynamic due to changes in physiological status during imaging sessions. This work investigated changes in subject-induced susceptibility distortions to pelvic organs at different bladder states to support pelvis MR-only RTP. Methods Pelvises of 9 healthy male volunteers were imaged at 1.0 Tesla (T), 1.5 T, and 3.0 T. Subject-induced susceptibility distortion field maps were generated using a dual-echo gradient-recalled echo (GRE) sequence with B0 field maps obtained from the phase difference between the two echoes acquired at several bladder volume states (3–4/subject, 32 overall). T2 turbo spin echo images were also acquired at each bladder state for organ delineation. Magnet central frequency was tracked over time. Distortion map differences and boxplots were computed to characterize changes within the clinical target volume (CTV), bladder, seminal vesicles, and prostate volumes. Results The time between the initial and final B0 maps was 42.6 ± 13.9 (range: 13.2–62.1) minutes with minimal change in magnet central frequency (0.02 ± 0.05 mm (range: − 0.06 – 0.12 mm)). Subject-induced susceptibility distortion across all bladder states, field strengths, and subjects was relatively small (1.4–1.9% of all voxels in the prostate and seminal vesicles were distorted > 0.5 mm). In the bladder, no voxels exhibited distortions > 1 mm. An extreme case acquired at 3.0 T with a large volume of rectal air yielded 27.4–34.6% of voxels within the CTVs had susceptibility-induced distortions > 0.5 mm across all time points. Conclusions Our work suggests that subject-induced susceptibility distortions caused by bladder/rectal conditions are generally small and subject-dependent. Local changes may be non-negligible within the CTV, thus proper management of filling status is warranted. Future work evaluating the impact of multiple models to accommodate for extreme status changes may be advantageous.

Background The use of the Monte Carlo (MC) method in radiotherapy dosimetry has increased almost exponentially in the last decades. Its widespread use in the field has converted this computer simulation technique in a common tool for reference and treatment planning dosimetry calculations. Methods This work reviews the different MC calculations made on dosimetric quantities, like stopping-power ratios and perturbation correction factors required for reference ionization chamber dosimetry, as well as the fully realistic MC simulations currently available on clinical accelerators, detectors and patient treatment planning. Conclusions Issues are raised that include the necessity for consistency in the data throughout the entire dosimetry chain in reference dosimetry, and how Bragg-Gray theory breaks down for small photon fields. Both aspects are less critical for MC treatment planning applications, but there are important constraints like tissue characterization and its patient-to-patient variability, which together with the conversion between dose-to-water and dose-to-tissue, are analysed in detail. Although these constraints are common to all methods and algorithms used in different types of treatment planning systems, they make uncertainties involved in MC treatment planning to still remain “uncertain”.

Background We hypothesized that dominant intraprostatic lesions (DILs) could be depictured by multimodal imaging techniques (MRI and/or PSMA PET/CT) in patients with primary prostate cancer (PCa) and investigated possible effects of radiotherapy (RT) dose distribution within the DILs on the patients’ outcome. Methods One hundred thirty-eight patients with localized prostate cancer (PCa) and visible DIL underwent primary external beam RT between 2008 and 2016 with an aimed prescription dose of 76 Gy to the whole prostate. Seventy-five patients (54%) additionally received androgen deprivation therapy. Three volumes were retrospectively generated: DIL using pretreatment MRI and/or PSMA PET/CT, prostatic gland (PG) and the subtraction between PG and DIL (SPG). The minimum dose (Dmin), maximum dose (Dmax) and mean dose (Dmean) in the three respective volumes were calculated. Biochemical recurrence free survival (BRFS) was considered in uni- and multivariate Cox regression analyses. An explorative analysis was performed to determine cut-off values for the three dose parameters in the three respective volumes. Results With a median follow-up of 45 months (14–116 months) 15.9% of patients experienced BR. Dmin (cut-off: 70.6 Gy, HR = 0.39, p = 0.036) applied to the DIL had an impact on BRFS in multivariate analysis, in contrast to the Dmin delivered to PG and SPG which had no significant impact (p > 0.05). Dmin was significantly (p 0.05). Conclusions The dose distribution within DILs defined by PSMA PET/CT and/or MRI is an independent risk factor for BR after primary RT in patients with PCa. These findings support the implementation of imaging based DIL interpretation for RT treatment planning, although further validation in larger patient cohorts with longer follow-up is needed.

Purpose The HyperArc VMAT (HA-VMAT) planning approach was newly developed to fulfill the demands of dose delivery for brain metastases stereotactic radiosurgery. We compared the dosimetric parameters of the HA-VMAT plan with those of the conventional VMAT (C-VMAT). Material and methods For 23 patients (1–4 brain metastases), C-VMAT and HA-VMAT plans with a prescription dose of 20–24 Gy were retrospectively generated, and dosimetric parameters for PTV (homogeneity index, HI; conformity index, CI; gradient index, GI) and brain tissue (V2Gy-V16Gy) were evaluated. Subsequently, the physical characteristics (modulation complexity score for VMAT, MCSV; Monitor unit, MU) of both treatment approaches were compared. Results HA-VMAT provided higher HI (1.41 ± 0.07 vs. 1.24 ± 0.07, p

Background Postoperative/adjuvant radiotherapy of advanced gastric cancer involves a large planning target volume (PTV) with multi-concave shapes which presents a challenge for volumetric modulated arc therapy (VMAT) planning. This study investigates the advantages of automated VMAT planning for this site compared to manual VMAT planning by expert planners. Methods For 20 gastric cancer patients in the postoperative/adjuvant setting, dual-arc VMAT plans were generated using fully automated multi-criterial treatment planning (autoVMAT), and compared to manually generated VMAT plans (manVMAT). Both automated and manual plans were created to deliver a median dose of 45 Gy to the PTV using identical planning and segmentation parameters. Plans were evaluated by two expert radiation oncologists for clinical acceptability. AutoVMAT and manVMAT plans were also compared based on dose-volume histogram (DVH) and predicted normal tissue complication probability (NTCP) analysis. Results Both manVMAT and autoVMAT plans were considered clinically acceptable. Target coverage was similar (manVMAT: 96.6 ± 1.6%, autoVMAT: 97.4 ± 1.0%, p = 0.085). With autoVMAT, median kidney dose was reduced on average by > 25%; (for left kidney from 11.3 ± 2.1 Gy to 8.9 ± 3.5 Gy (p = 0.002); for right kidney from 9.2 ± 2.2 Gy to 6.1 ± 1.3 Gy (p

Background Planning for Volumetric Modulated Arc Therapy (VMAT) may be time consuming and its use is limited by available staff resources. Automated multicriterial treatment planning can eliminate this bottleneck. We compared automatically created (auto) VMAT plans generated by Erasmus-iCycle to manually created VMAT plans for treatment of spinal metastases. Methods Forty-two targets in 32 patients were analyzed. Lungs and kidneys were defined as organs at risk (OARs). Twenty-two patients received radiotherapy on kidney levels, 17 on lung levels, and 3 on both levels. Results All Erasmus-iCycle plans were clinically acceptable. When compared to manual plans, planning target volume (PTV) coverage of auto plans was significantly better. The Homogeneity Index did not differ significantly between the groups. Mean dose to OARs was lower in auto plans concerning both kidneys and the left lung. One hotspot (>110% of D50%) occurred in the spinal cord of one auto plan (33.2 Gy, D50%: 30 Gy). Treatment time was 7% longer in auto plans. Conclusions Erasmus-iCycle plans showed better target coverage and sparing of OARs at the expense of minimally longer treatment times (for which no constraint was set). Electronic supplementary material The online version of this article (doi:10.1186/s13014-017-0767-2) contains supplementary material, which is available to authorized users.

There is a potential for adverse cardiovascular effects in long-term breast cancer survivors following adjuvant radiotherapy (RT). For this purpose, the deep inspiration breath-hold technique (DIBH) has been introduced into clinical practice, to maximally reduce the radiation dose to the heart. However, there are a variety of DIBH delivery techniques, patient positioning and visual patient feedback mechanisms. The aim of the present study was to evaluate the application of radiotherapy in DIBH using the CatalystTM/SentinelTM system, with a special emphasis on treatment planning and dosimetric plan comparison in free breathing (FB) and DIBH. A total of 13 patients with left-sided breast cancer following breast conserving surgery were included in this prospective clinical trial. For treatment application the CatalystTM/SentinelTM system (C-RAD AB, Uppsala, Sweden) was used and gating control was performed by an audio-visual patient feedback system. CT and surface data were acquired in FB and DIBH and dual treatment plans were created using Pencil Beam and Collapsed Cone Convolution. Dosimetric output parameters of organs at risk were compared using Wilcoxon signed-rank test. Central lung distance (CLD) was retrieved from iViewTM portal images during treatment delivery. The system contains a laser surface scanner (SentinelTM) and an optical surface scanner (CatalystTM) interconnected to the LINAC systems via a gating interface and allows for a continuous and touchless surface scanning. Overall, 225 treatment fractions with audio-visual guidance were completed without any substantial difficulties. Following initial patient training and treatment setup, radiotherapy in DIBH with the CatalystTM/SentinelTM system was time-efficient and reliable. Following dual treatment planning for all patients, nine of 13 patients were treated in DIBH. In these patients, the reduction of the mean heart dose for DIBH compared to FB was 52 % (2.73 to 1.31 Gy; p = 0.011). The maximum doses to the heart and LAD were reduced by 59 % (47.90 to 19.74 Gy; p = 0.008) and 75 % (38.55 to 9.66 Gy; p = 0.008), respectively. In six of the nine patients the heart completely moved out of the treatment field by DIBH. The standard deviation of the CLD varied between 0.12 and 0.29 cm (mean: 0.16 cm). The CatalystTM/SentinelTM system enabled a fast and reliable application and surveillance of DIBH in daily clinical routine. Furthermore, the present data show that using the DIBH technique during RT could significantly reduce high dose areas and mean doses to the heart. DRKS: DRKS00010929 registered on 5. August 2016.

Background To compare retrospectively generated gated plans to conventional internal target volume (ITV)-based plans and to evaluate whether gated radiotherapy provides clinically relevant dosimetric improvements to organs-at-risk (OARs). Methods Evaluation was performed of 150 stereotactic ablative radiotherapy treatment plans delivered to 128 early-stage (T1-T3 (

Purpose To build a new treatment planning approach that extends beyond radiation transport and IMRT optimization by modeling the radiation therapy process and prognostic indicators for more outcome-focused decision making. Methods An in-house treatment planning system was modified to include multiobjective inverse planning, a probabilistic outcome model, and a multi-attribute decision aid. A genetic algorithm generated a set of plans embodying trade-offs between the separate objectives. An influence diagram network modeled the radiation therapy process of prostate cancer using expert opinion, results of clinical trials, and published research. A Markov model calculated a quality adjusted life expectancy (QALE), which was the endpoint for ranking plans. Results The Multiobjective Evolutionary Algorithm (MOEA) was designed to produce an approximation of the Pareto Front representing optimal tradeoffs for IMRT plans. Prognostic information from the dosimetrics of the plans, and from patient-specific clinical variables were combined by the influence diagram. QALEs were calculated for each plan for each set of patient characteristics. Sensitivity analyses were conducted to explore changes in outcomes for variations in patient characteristics and dosimetric variables. The model calculated life expectancies that were in agreement with an independent clinical study. Conclusions The radiation therapy model proposed has integrated a number of different physical, biological and clinical models into a more comprehensive model. It illustrates a number of the critical aspects of treatment planning that can be improved and represents a more detailed description of the therapy process. A Markov model was implemented to provide a stronger connection between dosimetric variables and clinical outcomes and could provide a practical, quantitative method for making difficult clinical decisions.

Background Radiation therapy (RT) for a left-sided breast cancer often involves some incidental exposure of the heart and increase in the rate of major coronary events. One method to reduce the dose to the heart during a tangential breast irradiation is the deep inspiration breath hold (DIBH) technique. Our department adopted DIBH for selected left breast cancer patients with a maximum cardiac distance ≥ 10 mm. We evaluated the effect of the DIBH on cardiac dose compared to normal free breathing (FB). The secondary objective of our present study was to use modeled risk estimates to quantify the risk of coronary events after RT with DIBH. Methods and materials Thirty-two patients who underwent RT with DIBH at our hospital were retrospectively analyzed. For each patient, two computed tomography (CT) scans were acquired, FB-CT and DIBH-CT. Using a deformable image registration tool, the target volume was deformed from DIBH-CT to FB-CT, and conventional tangential treatment planning was performed, focusing on the equality of target coverage between the two plans. Doses to the heart, left anterior descending (LAD) artery, and ipsilateral lung were assessed. Results By using DIBH, the average mean heart dose was reduced from 724.1 cGy to 279.3 (p

Background Magnetic resonance imaging (MRI) has been incorporated as an adjunct to CT to take advantage of its excellent soft tissue contrast for contouring. MR-only treatment planning approaches have been developed to avoid errors introduced during the MR-CT registration process. The purpose of this study is to evaluate calculated dose distributions after incorporating a novel synthetic CT (synCT) derived from magnetic resonance simulation images into prostate cancer treatment planning and to compare dose distributions calculated using three previously published MR-only treatment planning methodologies. Methods An IRB-approved retrospective study evaluated 15 prostate cancer patients that underwent IMRT (n = 11) or arc therapy (n = 4) to a total dose of 70.2-79.2 Gy. Original treatment plans were derived from CT simulation images (CT-SIM). T1-weighted, T2-weighted, and balanced turbo field echo images were acquired on a 1.0 T high field open MR simulator with patients immobilized in treatment position. Four MR-derived images were studied: bulk density assignment (10 HU) to water (MRW), bulk density assignments to water and bone with pelvic bone values derived either from literature (491 HU, MRW+B491) or from CT-SIM population average bone values (300 HU, MRW+B300), and synCTs. Plans were recalculated using fixed monitor units, plan dosimetry was evaluated, and local dose differences were characterized using gamma analysis (1 %/1 mm dose difference/distance to agreement). Results While synCT provided closest agreement to CT-SIM for D95, D99, and mean dose (

Locoregional hyperthermia, i.e. increasing the tumor temperature to 40-45 degrees C using an external heating device, is a very effective radio and chemosensitizer, which significantly improves clinical outcome. There is a clear thermal dose-effect relation, but the pursued optimal thermal dose of 43 degrees C for 1 h can often not be realized due to treatment limiting hot spots in normal tissue. Modern heating devices have a large number of independent antennas, which provides flexible power steering to optimize tumor heating and minimize hot spots, but manual selection of optimal settings is difficult. Treatment planning is a very valuable tool to improve locoregional heating. This paper reviews the developments in treatment planning software for tissue segmentation, electromagnetic field calculations, thermal modeling and optimization techniques. Over the last decade, simulation tools have become more advanced. On-line use has become possible by implementing algorithms on the graphical processing unit, which allows real-time computations. The number of applications using treatment planning is increasing rapidly and moving on from retrospective analyses towards assisting prospective clinical treatment strategies. Some clinically relevant applications will be discussed.