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PurposeTo evaluate the feasibility to use a standard Ethos planning template to treat left-sided breast cancer with regional lymph nodes.Material/MethodsThe tuning cohort of 5 patients was used to create a planning template. The validation cohort included 15 patients treated for a locally advanced left breast cancer randomly enrolled. The Ethos planning template was tuned using standard 3 partial arc VMAT and two collimator rotation configurations: 45/285/345° and 30/60/330°. Re-planning was performed automatically using the template without editing. The study was conducted with a schedule of 42.3 Gy in 18 fractions to the breast/chestwall, internal mammary chain (IMC) and regional lymph nodes (“Nodes”). The PTV was defined as a 3D extension of the CTV with a margin of 7 mm, excluding the 5mm below the skin. The manual treatment plans were performed using Eclipse treatment planning system with AAA and PO algorithms (v15.6) and a manual arc VMAT configuration and imported in Ethos TPS (v1.1) for a dose calculation with Ethos Acuros algorithm. The automated plans were compared with the manual plans using PTV and CTV coverage, homogeneity and conformity indices (HI and CN) and doses to organs at risk (OAR) via DVH metrics. For each plan, the patient quality assurance (QA) were performed using Mobius3D and gamma index. Finally, two breast radiation oncologists performed a blinded assessment of the clinical acceptability of each of the three plans (manual and automated) for each patient.ResultsThe manual and automated plans provided suitable treatment planning as regards dose constraints. The dosimetric comparison showed the CTV_breast D99% were significantly improved with both automated plans (p< 0,002) while PTV coverage was comparable. The doses to the organs at risk were equivalent for the three plans. Concerning treatment delivery, the Ethos-45° and Ethos-30° plans led to an increase in MUs compared to the manual plans, without affecting the beam on time. The average gamma index pass rates remained consistently above 98% regardless of the type of plan utilized. In the blinded evaluation, clinicians 1 and 2 assessed 13 out of 15 plans for Ethos 45° and 11 out of 15 plans for Ethos 30° as clinically acceptable.ConclusionUsing a standard planning template for locally advanced breast cancer, the Ethos TPS provided automated plans that were clinically acceptable and comparable in quality to manually generated plans. Automated plans also dramatically reduce workflow and operator variability.

Purpose/objectivesAn artificial intelligence-based pseudo-CT from low-field MR images is proposed and clinically evaluated to unlock the full potential of MRI-guided adaptive radiotherapy for pelvic cancer care.Materials and methodIn collaboration with TheraPanacea (TheraPanacea, Paris, France) a pseudo-CT AI-model was generated using end-to-end ensembled self-supervised GANs endowed with cycle consistency using data from 350 pairs of weakly aligned data of pelvis planning CTs and TrueFisp-(0.35T)MRIs. The image accuracy of the generated pCT were evaluated using a retrospective cohort involving 20 test cases coming from eight different institutions (US: 2, EU: 5, AS: 1) and different CT vendors. Reconstruction performance was assessed using the organs at risk used for treatment. Concerning the dosimetric evaluation, twenty-nine prostate cancer patients treated on the low field MR-Linac (ViewRay) at Montpellier Cancer Institute were selected. Planning CTs were non-rigidly registered to the MRIs for each patient. Treatment plans were optimized on the planning CT with a clinical TPS fulfilling all clinical criteria and recalculated on the warped CT (wCT) and the pCT. Three different algorithms were used: AAA, AcurosXB and MonteCarlo. Dose distributions were compared using the global gamma passing rates and dose metrics.ResultsThe observed average scaled (between maximum and minimum HU values of the CT) difference between the pCT and the planning CT was 33.20 with significant discrepancies across organs. Femoral heads were the most reliably reconstructed (4.51 and 4.77) while anal canal and rectum were the less precise ones (63.08 and 53.13). Mean gamma passing rates for 1%1mm, 2%/2mm, and 3%/3mm tolerance criteria and 10% threshold were greater than 96%, 99% and 99%, respectively, regardless the algorithm used. Dose metrics analysis showed a good agreement between the pCT and the wCT. The mean relative difference were within 1% for the target volumes (CTV and PTV) and 2% for the OARs.ConclusionThis study demonstrated the feasibility of generating clinically acceptable an artificial intelligence-based pseudo CT for low field MR in pelvis with consistent image accuracy and dosimetric results.

PurposeThe aim of this study was to assess the feasibility of online adaptive radiotherapy with Ethos for breast cancer.Materials and methodsThis retrospective study included 20 breast cancer patients previously treated with TrueBeam. All had undergone breast surgery for different indications (right/left, lumpectomy/mastectomy) and were evenly divided between these four cases, with five extended cone beam computed tomography (CBCT) scans per patient. The dataset was used in an Ethos emulator to test the full adaptive workflow. The contours generated by artificial intelligence (AI) for the influencers (left and right breasts and lungs, heart) and elastic or rigid propagation for the target volumes (internal mammary chain (IMC) and clavicular lymph nodes (CLNs)) were compared to the initial contours delineated by the physician using two metrics: Dice similarity coefficient (DICE) and Hausdorff 95% distance (HD95). The repeatability of influencer generation was investigated. The times taken by the emulator to generate contours, optimize plans, and calculate doses were recorded. The quality of the scheduled and adapted plans generated by Ethos was assessed using planning target volume (PTV) coverage, homogeneity indices (HIs), and doses to organs at risk (OARs) via dose–volume histogram (DVH) metrics. Quality assurance (QA) of the treatment plans was performed using an independent portal dosimetry tool (EpiQA) and gamma index.ResultsOn average, the DICE for the influencers was greater than 0.9. Contours resulting from rigid propagation had a higher DICE and a lower HD95 than those resulting from elastic deformation but remained below the values obtained for the influencers: DICE values were 0.79 ± 0.11 and 0.46 ± 0.17 for the CLN and IMC, respectively. Regarding the repeatability of the influencer segmentation, the DICE was close to 1, and the mean HD95 was strictly less than 0.15 mm. The mean time was 73 ± 4 s for contour generation per AI and 80 ± 9 s for propagations. The average time was 53 ± 3 s for dose calculation and 125 ± 9 s for plan optimization. A dosimetric comparison of scheduled and adapted plans showed a significant difference in PTV coverage: dose received by 95% of the volume (D95%) values were higher and closer to the prescribed doses for adapted plans. Doses to organs at risk were similar. The average gamma index for quality assurance of adapted plans was 99.93 ± 0.38 for a 3%/3mm criterion.ConclusionThis study comprehensively evaluated the Ethos® adaptive workflow for breast cancer and its potential technical limitations. Although the results demonstrated the high accuracy of AI segmentation and the superiority of adapted plans in terms of target volume coverage, a medical assessment is still required.

BackgroundPrevious studies in 2D and in 3D conformal radiotherapy concludes that the maximal heart distance and the mean heart dose (MHD) are considered predictive of late cardiac toxicities. As the use of inverse-planned intensity modulated radiation therapy (IMRT) is increasing worldwide, we hypothesized that this 3D MHD might not be representative of heart exposure after IMRT for breast cancer (BC).MethodsPatients with left-sided BC and unfavorable cardiac anatomy received IMRT. Their treatment plan was compared to a virtual treatment plan for 3D conformal radiotherapy with similar target volume coverage (study A). Then, a second 3D conformal treatment plan was generated to achieve equivalent individual MHD obtained by IMRT. Then the heart and left anterior descending (LAD) coronary artery exposures were analyzed (study B). Last, the relationship between MHD and the heart volume or LAD coronary artery volume receiving at least 30Gy, 40Gy and 45Gy in function of each additional 1Gy to the MHD was assessed (study C).ResultsA significant decrease of heart and LAD coronary artery exposure to high dose was observed with the IMRT compared with the 3D conformal radiotherapy plans that both ensured adequate target coverage (study A). The results of study B and C showed that 3D MHD was not representative of similar heart substructure exposure with IMRT, especially in the case of high dose exposure.ConclusionsThe mean heart dose is not a representative dosimetric parameter to assess heart exposure following IMRT. Equivalent MHD values following IMRT and 3DRT BC treatment do not represent the same dose distribution leading to extreme caution when using this parameter for IMRT plan validation.

PurposeVolumetric Modulated Arc Therapy (VMAT) exhibits potent advantages regarding target volume coverage and protection of organs at risk, notably in the context of anatomical constraints. Nevertheless, reports concerning VMAT for the treatment of synchronous bilateral breast cancers (SBBC) have been scarce to date. As such, we conducted this observational study to assess efficacy, safety and feasibility of VMAT in SBBC.Materials and MethodsFrom August 2011 to December 2017, 54 consecutive patients with SBBC with or without axillary nodes involvement underwent a treatment protocol containing radiotherapy using VMAT. A total dose (TD) of 52.2Gy in 29 fractions was delivered to breast and internal mammary chain (IMC) nodes Planning Target Volume (PTV) plus, if applicable, a TD of 49.3Gy in 29 fractions to the supra- and infra-clavicular nodes PTV and a TD of 63.22Gy in 29 fractions to tumor boost PTV. Lungs, heart, esophagus, trachea, liver, thyroid and spinal cord were considered as organs at risk. VMAT feasibility and organ at risk sparing were evaluated by treatments planning of the 20 first enrolled patients. Tolerance and patients’ outcome were prospectively monitored by acute/late toxicities records and by the analysis of overall survival (OS), locoregional recurrence-free survival (LRFS) and recurrence-free survival (RFS).ResultsBreast, supraclavicular nodes and boost PTV coverage was adequate with at least 98% of PTV encompassed by more than 95% of the prescribed dose. Less than 90% of IMC PTV was encompassed by 95% of the prescribed dose. Mean lung dose was 12.3Gy (range: 7.7 – 18.7); mean heart dose was 10.7Gy (range: 6.2 – 22.3). Concerning acute toxicities, only 2 patients experienced grade 3 skin toxicity (3.7%) and only 1 patient developed grade 1 pneumonitis. After a median follow-up of 5.3 years, grade 2 fibrosis and/or shrinking was observed in 5 patients (10%), and grade 3 fibrosis in 1 patients (2%). The 5-year LRFS-rate, RFS-rate and OS were 98% [95% CI= 86.12-99.70%], 96% [95% CI= 84.63-98.96%] and 100%, respectively.

IntroductionStereotactic MR-guided adaptive radiotherapy (SMART) is an attractive modality of radiotherapy for pancreatic tumors. The objectives of this prospective registry study were to report the dosimetric benefits of daily adaptation of SMART and the first clinical results in pancreatic tumors.Materials and MethodsAll patients treated in our center with SMART for a pancreatic tumor were included. Patients were planned for five daily-adapted fractions on consecutive days. Endpoints were acute toxicities, late toxicities, impact of adaptive treatment on target volume coverage and organs at risk (OAR) sparing, local control (LC) rate, distant metastasis-free survival (DMFS), and overall survival (OS).ResultsThirty consecutive patients were included between October 2019 and April 2021. The median dose prescription was 50 Gy. No patient presented grade > 2 acute toxicities. The most frequent grade 1–2 toxicities were asthenia (40%), abdominal pain (40%), and nausea (43%). Daily adaptation significantly improved planning target volume (PTV) and gross tumor volume (GTV) coverage and OAR sparing. With a median follow-up of 9.7 months, the median OS, 6-month OS, and 1-year OS were 14.1 months, 89% (95% CI: 70%–96%), and 75% (95% CI: 51%–88%), respectively, from SMART completion. LC at 6 months and 1 year was respectively 97% (95% CI: 79–99.5%) and 86% (95% CI: 61%–95%). There were no grade > 2 late toxicities. With a median follow-up of 10.64 months, locally advanced pancreatic cancer (LAPC) and borderline resectable pancreatic cancer (BRPC) patients (22 patients) had a median OS, 6-month OS, and 1-year OS from SMART completion of 14.1 months, 76% (95% CI: 51%–89%), and 70% (95% CI: 45%–85%), respectively. Nine patients underwent surgical resection (42.1% of patients with initial LAPC and 33.3% of patients with BRPC), with negative margins (R0). Resected patients had a significantly better OS as compared to unresected patients (p = 0.0219, hazard ratio (HR) = 5.78 (95% CI: 1.29–25.9)).ConclusionSMART for pancreatic tumors is feasible without limiting toxicities. Daily adaptation demonstrated a benefit for tumor coverage and OAR sparing. The severity of observed acute and late toxicities was low. OS and LC rates were promising. SMART achieved a high secondary resection rate in LAPC patients. Surgery after SMART seemed to be feasible and might increase OS in these patients.

Purpose: This prospective registry study evaluated the feasibility of stereotactic magnetic resonance imaging (MRI)–guided radiation therapy for the local treatment of isolated prostate cancer recurrence within the gland or prostate bed after primary radiation therapy. Methods and Materials: Patients with isolated recurrence without any regional or distant extension after treatment by external radiation therapy of the prostate gland/bed or by prostate brachytherapy were included. A 173-second Fast Imaging with Steady state Precession (TrueFISP) sequence was used for MRI simulation, and the gross tumor volume was delineated using multimodal images. The initial treatment plan varied from 27.5 Gy in 5 fractions to 38.7 Gy in 9 fractions and was adapted at each session, if necessary. The primary endpoint was acute toxicities (according to the Common Terminology Criteria for Adverse Events v5.0 criteria). Secondary endpoints were the effects of the adaptive treatment on target volume coverage, late toxicities, and oncologic events. Results: Twenty patients were included. After a minimum follow-up of 6 months, grade 2 dysuria (from grade 1 at baseline; n = 1), grade 2 polyuria (n = 1), grade 1 urinary incontinence (n = 1), grade 1 urinary pain (n = 2), and grade 1 diarrhea (n = 1) were reported.All initial treatment plans met the tumor coverage objectives, with a mean 95% planning target volume value of 95.7%. No plan exceeded the bladder and rectum dose constraints, but 8 exceeded the urethra dose constraints because of urethra proximity to the planning target volume. The initial plan was adapted in 7 patients (35%). The tumor coverage improved by 3.7% compared with the predicted plan (P = .0001) without increase in the dose to organs at risk. The biochemical control rate for the whole cohort was 75% (15/20 patients) including the 4 patients who received androgen-deprivation therapy. Conclusions: MRI-guided reirradiation for isolated recurrence within the prostate or in the prostate bed appears to be safe with excellent dosimetric results.

Abstract Background Medical 3D printing has brought the manufacturing world closer to the patient’s bedside than ever before. This requires hospitals and their personnel to update their quality assurance program to more appropriately accommodate the 3D printing fabrication process and the challenges that come along with it. Results In this paper, we explored different methods for verifying the accuracy of a 3D printed anatomical model. Methods included physical measurements, digital photographic measurements, surface scanning, photogrammetry, and computed tomography (CT) scans. The details of each verification method, as well as their benefits and challenges, are discussed. Conclusion There are multiple methods for model verification, each with benefits and drawbacks. The choice of which method to adopt into a quality assurance program is multifactorial and will depend on the type of 3D printed models being created, the training of personnel, and what resources are available within a 3D printed laboratory.

Background: Monocentric cohorts suggested that radiation-induced CD8 T-lymphocyte apoptosis (RILA) can predict late toxicity after curative intent radiotherapy (RT). We assessed the role of RILA as a predictor of breast fibrosis (bf+) after adjuvant breast RT in a prospective multicenter trial. Methods: A total of 502 breast-cancer patients (pts) treated by conservative surgery and adjuvant RT were recruited at ten centers. RILA was assessed before RT by flow cytometry. Impact of RILA on bf+ (primary endpoint) or relapse was assessed using a competing risk method. Receiver–operator characteristic (ROC) curve analyses were also performed in intention to treat. This study is registered with ClinicalTrials.gov, number NCT00893035 and final analyses are presented here. Findings: Four hundred and fifty-six pts (90.8%) were included in the final analysis. One hundred and eight pts (23.7%) received whole breast and node irradiation. A boost dose of 10–16 Gy was delivered in 449 pts (98.5%). Adjuvant hormonotherapy was administered to 349 pts (76.5%). With a median follow-up of 38.6 months, grade ≥2 bf+ was observed in 64 pts (14%). A decreased incidence of grade ≥2 bf+ was observed for increasing values of RILA (p = 0.012). No grade 3 bf+ was observed for patients with RILA ≥12%. The area under the ROC curve was 0.62. For cut-off values of RILA ≥20% and

Systemic cancer therapies take into account breast cancer (BC) heterogeneity by targeting pathways specifically involved in some BC subtypes. On the other hand, BC intrinsic radiosensitivity is poorly understood and studied. Hence, radiotherapy personalization in BC is still “work in progress”. In this review, we will summarize the existing data on the management of axillary lymph nodes in BC, the impact of BC radiotherapy on axillary management, the indications for axillary radiotherapy, and biomarkers to predict patients’ outcome (tumor control and late toxicities) after axillary irradiation.

Background: The aim of this study was to describe the clinical implementation of the Calypso system with its potential impact on the treatment delivery. Materials and methods: The influence of the electromagnetic array was investigated on the kilovoltage cone beam computed tomography (kV-CBCT) image quality using the CATPHAN 504 CBCT images. Then, the QFix kVue Calypso couch top and the array attenuation, and their dosimetric influence on the Volumetric modulated arc therapy (VMAT) treatments of prostate was evaluated. Results: Regarding the image quality, a significant increase of noise (p < 0.01) was detected with the array in place, resulting in a significant decrease in signal noise ratio (SNR) (p < 0.01). No difference in absolute contrast was observed. Finally, there was a significant decrease in contrast noise ratio (CNR) (p < 0.01) even if the deviation was only of 2.5%. For the dosimetric evaluation, the maximum attenuation of the couch was 12.02% and 13.19% for X6 and X6 flattening filter free (FFF), respectively (configuration of rails out). Besides, the mean attenuation of the array was 1.15% and 1.67% for X6 and X6 FFF, respectively. For the VMAT treatment plans, the mean dose was reduced by 0.61% for X6 and by 0.31% for X6 FFF beams when using the electromagnetic array. Conclusions: The Calypso system does not affect significantly the kV-CBCT image quality and the VMAT plan dose distribution. [ABSTRACT FROM AUTHOR]

To evaluate the performance of a model-based optimisation process for volumetric modulated arc therapy, VMAT, applied to whole breast irradiation.A set of 150 VMAT dose plans with simultaneous integrated boost were selected to train a model for the prediction of dose-volume constraints. The dosimetric validation was done on different groups of patients from three institutes for single (50 cases) and bilateral breast (20 cases).Quantitative improvements were observed between the model-based and the reference plans, particularly for heart dose. Of 460 analysed dose-volume objectives, 13% of the clinical plans failed to meet the constraints while the respective model-based plans succeeded. Only in 5 cases did the reference plans pass while the respective model-based failed the criteria. For the bilateral breast analysis, the model-based plans resulted in superior or equivalent dose distributions to the reference plans in 96% of the cases.Plans optimised using a knowledge-based model to determine the dose-volume constraints showed dosimetric improvements when compared to earlier approved clinical plans. The model was applicable to patients from different centres for both single and bilateral breast irradiation. The data suggests that the dose-volume constraint optimisation can be effectively automated with the new engine and could encourage its application to clinical practice.

Ductal carcinoma in situ of the breast is associated with low mortality rates, but local relapse is a matter of concern in this disease. Risk factors for local relapse include young age, close or positive margins, and tumor necrosis. Whole breast irradiation following breast-conserving surgery for ductal carcinoma in situ significantly reduces the risk of local relapse as compared to breast-conserving surgery alone. Studies point to similar outcomes between breast-conserving surgery plus radiotherapy and mastectomy, in the absence of extensive disease. A complementary boost to the surgical bed improves outcomes for patients with invasive breast cancer. However, the effect of this strategy has never been prospectively reported for ductal carcinoma in situ. Two randomized controlled trials assessing this issue are ongoing. This paper represents an update on available literature about radiotherapy for DCIS with a special focus on the role of a radiotherapy boost to the tumor bed.