Evaluation of Ethos intelligent optimization engine for left locally advanced breast cancer.

Purpose: To evaluate the feasibility to use a standard Ethos planning template to treat left-sided breast cancer with regional lymph nodes. Material/Methods: The 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. Results: The 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. Conclusion: Using 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.

Feasibility study of adaptive radiotherapy with Ethos for breast cancer.

Purpose: The aim of this study was to assess the feasibility of online adaptive radiotherapy with Ethos for breast cancer. Materials and methods: This 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. Results: On 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. Conclusion: This 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.

A multi-centric evaluation of self-learning GAN based pseudo-CT generation software for low field pelvic magnetic resonance imaging.

Purpose/objectives: An 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 method: In 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. Results: The 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. Conclusion: This 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.

A prospective registry study of stereotactic magnetic resonance guided radiotherapy (MRgRT) for primary liver tumors.

BACKGROUND AND PURPOSE: Stereotactic body radiation therapy (SBRT) has demonstrated safe and effective results for primary liver tumors. Magnetic Resonance guided Radiotherapy (MRgRT) is an innovative radiotherapy modality for abdominal tumors. The aim of this study is to report on acute and late toxicities and initial oncological results for primary liver tumors treated with MRgRT. MATERIALS AND METHODS: We prospectively included in our cohort all patients treated by MRgRT for a primary liver tumor at the Montpellier Cancer Institute. The primary endpoint was acute and late toxicities assessed according to CTCAE v 5.0. The mean prescribed dose was 50 Gy in 5 fractions. RESULTS: Between October 2019 and April 2022, MRgRT treated 56 patients for 72 primary liver lesions. No acute or late toxicities of CTCAE grade greater than 2 attributable to radiotherapy were noted during follow-up. No cases of radiation-induced liver disease (RILD), either classical or non-classical, occurred. After a median follow-up of 13.2 months (95% CI [8.8; 15.7]), overall survival was 85.1% (95% CI: [70.8; 92.7]) at 1 year and 74.2% at 18 months (95% CI [52.6; 87.0]). Local control was 98.1% (95% CI: [87.4; 99.7]) and 94.7% (95% CI: [79.5; 98.7]) at 12 and 18 months, respectively. Among the HCC subgroup, no local recurrences were observed. CONCLUSION: MRgRT for primary liver tumors is safe without severe adverse events and reach excellent local control. Numerous studies are underway to better assess the value of MRI guidance and adaptive process in these indications.

Implementation of the Calypso system: a commissioning experience.

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.

Robustness of Breast Margins with Volumetric Modulated Arc Therapy without a Six-Degrees-of-Freedom Couch: A Dosimetric Evaluation.

In our hospital, a TrueBeam linear accelerator and the PerfectPitch 6-degrees-of-freedom (6-DOF) couch (Varian), with 7 mm margins, are used for volumetric modulated arc therapy (VMAT) of breast cancer (BC). This study tested whether a 3-degrees-of-freedom (3-DOF) couch, i.e., without rotation compensation (such as the Halcyon couch), affected dose metrics. A total of 446 daily extended cone beam computed tomography (CBCT) data of 20 patients who received VMAT for BC were used to recalculate the treatment plans with the session registration (6-DOF) and a simulated matching with 3-DOF. The initial plan provided significantly better coverage for internal mammary chain and clavicular lymph node clinical target volumes (CTVs) than the 6-DOF and 3-DOF CBCT plans. The volumes receiving 110% of the prescribed dose (V110%) were increased for all CTVs with the 6-DOF and 3-DOF CBCT plans, but the difference was significant only for the breast/chest wall CTV (p < 0.05; paired samples t-test). Protection of the heart and lungs was comparable among plans. The dose volume histograms based on the 6-DOF and 3-DOF data were similar for CTVs and organs at risk. Therefore, with a 7 mm margin, VMAT and a 3-DOF couch can be used for BC treatment without any compromise in delivery accuracy.

Stereotactic MR-Guided Radiotherapy for Liver Metastases: First Results of the Montpellier Prospective Registry Study.

Liver stereotactic body radiotherapy (SBRT) is a local treatment that provides good local control and low toxicity. We present the first clinical results from our prospective registry of stereotactic MR-guided radiotherapy (MRgRT) for liver metastases. All patients treated for liver metastases were included in this prospective registry study. Stereotactic MRgRT indication was confirmed by multidisciplinary specialized tumor boards. The primary endpoints were acute and late toxicities. The secondary endpoints were survival outcomes (local control, overall survival (OS), disease-free survival, intrahepatic relapse-free survival). Twenty-six consecutive patients were treated for thirty-one liver metastases between October 2019 and April 2022. The median prescribed dose was 50 Gy (40-60) in 5 fractions. No severe acute MRgRT-related toxicity was noted. Acute and late gastrointestinal and liver toxicities were low and mostly unrelated to MRgRT. Only 5 lesions (16.1%) required daily adaptation because of the proximity of organs at risk (OAR). With a median follow-up time of 17.3 months since MRgRT completion, the median OS, 1-year OS and 2-year OS rates were 21.7 months, 83.1% (95% CI: 55.3-94.4%) and 41.6% (95% CI: 13.5-68.1%), respectively, from MRgRT completion. The local control at 6 months, 1 year and 2 years was 90.9% (95% CI: 68.3-97.7%). To our knowledge, we report the largest series of stereotactic MRgRT for liver metastases. The treatment was well-tolerated and achieved a high LC rate. Distant relapse remains a challenge in this population.

Efficacy, safety, and feasibility of volumetric modulated arc therapy for synchronous bilateral breast cancer management.

Purpose: Volumetric 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 Methods: From 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). Results: Breast, 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.

Magnetic Resonance-Guided Reirradiation for Local Recurrence within the Prostate or in the Prostate Bed: One-Year Clinical Results of a Prospective Registry Study.

Around 33% of patients treated by EBRT or brachytherapy will present a biochemical recurrence. SBRT is a new option for the treatment of patients with local-only recurrence. MRgRT seems to be interesting for the treatment of these recurrences. This article presents the one-year late tolerance and biochemical recurrence-free survival results of a prospective registry study. Patients with intraprostatic (or in the prostate bed) recurrence were treated with 5 to 9 fractions (median dose of 30 Gy in 5 fractions) with the MRIdian® system. PSA level and toxicities were evaluated before treatment and at three, six and 12 months after treatment. Thirty-seven patients with a median age of 74.5 years old were treated between 21 October 2019 and 7 December 2020. Acute tolerance was excellent with no grade >2 toxicities. Twelve months after treatment, we observed an increase of grade 1−2 dysuria (46% vs. 13% before treatment) and grade 1 polyuria (73% vs. 7%). The six, nine and 12-months biochemical-recurrence free survival were 97.3%, 86.5% and 65.0%. Fifteen patients (40%) presented a biochemical recurrence. Nine of these 15 patients (60%) had a persistent disease within the treated volume. In conclusion, MRgRT is safe and has promising survival results.

Stereotactic MR-Guided Radiotherapy for Pancreatic Tumors: Dosimetric Benefit of Adaptation and First Clinical Results in a Prospective Registry Study.

Introduction: Stereotactic 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 Methods: All 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). Results: Thirty 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)). Conclusion: SMART 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.

Stereotactic MR-Guided Adaptive Radiotherapy for Pancreatic Tumors: Updated Results of the Montpellier Prospective Registry Study.

Introduction: Stereotactic MR-guided Adaptive RadioTherapy (SMART) is a novel process to treat pancreatic tumors. We present an update of the data from our prospective registry of SMART for pancreatic tumors. Materials and methods: After the establishment of the SMART indication in a multidisciplinary board, we included all patients treated for pancreatic tumors. Primary endpoints were acute and late toxicities. Secondary endpoints were survival outcomes (local control, overall survival, distant metastasis free survival) and dosimetric advantages of adaptive process on targets volumes and OAR. Results: We included seventy consecutive patients in our cohort between October 2019 and April 2022. The prescribed dose was 50 Gy in 5 consecutive fractions. No severe acute SMART related toxicity was noted. Acute and late Grade ≤ 2 gastro intestinal were low. Daily adaptation significantly improved PTV and GTV coverage as well as OAR sparing. With a median follow-up of 10.8 months since SMART completion, the median OS, 6-months OS, and 1-year OS were 20.9 months, 86.7% (95% CI: (75−93%), and 68.6% (95% CI: (53−80%), respectively, from SMART completion. Local control at 6 months, 1 year, and 2 years were, respectively, 96.8 % (95% CI: 88−99%), 86.5 (95% CI: 68−95%), and 80.7% (95% CI: 59−92%). There was no grade > 2 late toxicities. Locally Advanced Pancreatic Cancers (LAPC) and Borderline Resectable Pancreatic Cancers (BRPC) patients (52 patients) had a median OS, 6-months OS, and 1-year OS from SMART completion of 15.2 months, 84.4% (95% CI: (70−92%)), and 60.5% (95% CI: (42−75%)), respectively. The median OS, 1-year OS, and 2-year OS from initiation of induction chemotherapy were 22.3 months, 91% (95% CI: (78−97%)), and 45.8% (95% CI: (27−63%)), respectively. Twenty patients underwent surgical resection (38.7 % of patients with initially LAPC) with negative margins (R0). Conclusion: To our knowledge, this is the largest series of SMART for pancreatic tumors. The treatment was well tolerated with only low-grade toxicities. Long-term OS and LC rates were achieved. SMART achieved high secondary resection rates in LAPC patients.

Stereotactic MR-Guided Radiotherapy for Adrenal Gland Metastases: First Clinical Results.

Stereotactic MR-guided Radiotherapy (MRgRT) is an interesting treatment option for adrenal gland metastases (AGM). We reviewed data from 12 consecutive patients treated with MRgRT for an AGM in our center between 14 November 2019 and 17 August 2021. Endpoints were tolerance assessment, the impact of adaptive treatment on target volume coverage and organs at risk (OAR) sparing, local control (LC), and overall survival (OS). The majority of patients were oligometastatic (58.3%), with 6 right AGM, 5 left AGM and 1 left and right AGM. The prescribed dose was 35 to 50 Gy in 3 to 5 fractions. The median PTV V95% on the initial plan was 95.74%. The median V95% of the PTVoptimized (PTVopt) on the initial plan was 95.26%. Thirty-eight (69%) fractions were adapted. The PTV coverage was significantly improved for adapted plans compared to predicted plans (median PTV V95% increased from 89.85% to 91.17%, p = 0.0478). The plan adaptation also significantly reduced Dmax for the stomach and small intestine. The treatment was well tolerated with no grade > 2 toxicities. With a median follow-up of 15.5 months, the 1−year LC and OS rate were 100% and 91.7%. Six patients (50%) presented a metastatic progression, and one patient (8.3%) died of metastatic evolution during the follow-up. Adaptation of the treatment plan improved the overall dosimetric quality of MRI-guided radiotherapy. A longer follow-up is required to assess late toxicities and clinical results.

Different meaning of the mean heart dose between 3D-CRT and IMRT for breast cancer radiotherapy.

Background: Previous 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). Methods: Patients 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). Results: A 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. Conclusions: The 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.

Image-Guided Liver Stereotactic Body Radiotherapy Using VMAT and Real-Time Adaptive Tumor Gating: Evaluation of the Efficacy and Toxicity for Hepatocellular Carcinoma.

Liver SBRT is a therapeutic option for the treatment of HCC in patients not eligible for other local therapies. We retrospectively report the outcomes of a cohort of consecutive patients treated with SBRT for HCC at the Montpellier Cancer Institute. Between March 2013 and December 2018, 66 patients were treated with image-guided liver SBRT using VMAT and real-time adaptive tumor gating in our institute. The main endpoints considered in this study were local control, disease-free survival, overall survival, and toxicity. The median follow-up was 16.8 months. About 66.7% had prior liver treatment. Most patients received 50 Gy in five fractions of 10 Gy. No patient had local recurrence. Overall survival and disease-free survival were, respectively, 83.9% and 46.7% at one year. In multivariate analysis, the diameter of the lesions was a significant prognostic factor associated with disease-free survival (HR = 2.57 (1.19-5.53) p = 0.02). Regarding overall survival, the volume of PTV was associated with lower overall survival (HR = 2.84 (1.14-7.08) p = 0.025). No grade 3 toxicity was observed. One patient developed a grade 4 gastric ulcer, despite the dose constraints being respected. Image-guided liver SBRT with VMAT is an effective and safe treatment in patients with inoperable HCC, even in heavily pre-treated patients. Further prospective evaluation will help to clarify the role of SBRT in the management of HCC patients.

Magnetic Resonance-Guided Reirradiation for Local Recurrence Within the Prostate or in the Prostate Bed: Preliminary Results of a Prospective Registry Study.

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.

Quality assurance program and early toxicities in the phase III BONBIS randomized trial evaluating the role of a localized radiation boost in ductal carcinoma in situ.

PURPOSE: To describe the quality assurance (QA) program and early toxicities in the phase III randomized trial BONBIS (NCT00907868) on the role of a localized radiation boost in ductal carcinoma in situ (DCIS). MATERIALS AND METHODS: From November 2008 to July 2014, 2004 patients were randomized in arm A (only whole breast radiotherapy, WBRT) and arm B (WBRT + boost). The QA program involved 44 participant centers that performed the dummy run (DR). Compliance and uniformity of clinical target volume (CTV) delineations, and dose prescription and delivery according to the BONBIS trial radiotherapy guidelines were analyzed. Acute toxicities (during and up to 3 months after radiotherapy completion, NCI-CTCAE v3.0 classification) were evaluated in 1929 patients. RESULTS: The differences in whole breast CTV (CTV1) and planning target volume (PTV1) were ≤10%, and the differences in boost CTV (CTV2) and PTV (PTV2) were ≥20% compared with the reference DR values; 95% of the prescribed dose encompassed 98.7% and 100% of the median CTV1 and CTV2. Grade ≥2 breast erythema (38.3% vs. 22.4% of grade 2 and 5.4% vs. 2.1% of grade 3, p < 0.001), grade ≥2 dermatitis (2.8% vs. 0.7%, p < 0.001), and grade 2 hyperpigmentation (6.9% vs. 3.6%, p = 0.005) were more frequent in arm B than arm A. No acute lung or cardiac toxicity was observed. Smoking history, large breast size, and large breast CTV were strong predictive factors of grade ≥2 acute skin toxicities. CONCLUSIONS: The QA program showed deviations in breast and tumor bed delineation. The boost significantly increased acute skin toxicities.

Prostate hypofractionated radiotherapy (62Gy at 3.1Gy per fraction) with injection of hyaluronic acid: final results of the RPAH1 study.

OBJECTIVES: The present multicenter Phase II study evaluated the rate of late grade ≥2 gastrointestinal (GI) toxicities at 3 years, after hypofractionated radiotherapy (HFR) of prostate cancer with injection of hyaluronic acid (HA) between the prostate and the rectum. METHODS: Between 2010 and 2013, 36 patients with low- or intermediate-risk prostate cancer were treated by HFR/IMRT-IGRT. 20 fractions of 3.1 Gy were delivered, 5 days per week for a total dose of 62 Gy. A transperineal injection of 10cc of HA was performed between the rectum and the prostate. Late toxicities were evaluated between 3 and 36 months after the end of treatment (CTCAE v4). RESULTS: Median pretreatment prostate-specific antigen was 8 ng ml-1. Among the 36 included patients, 2 were not evaluated because they withdrew the study in the first 3 months of follow-up, and 4 withdrew between 3 and 36 months, the per protocol population was therefore composed.Late grade ≥2 GI toxicities occurred in 4 (12%) patients with 3 (9%) Grade 2 rectal bleedings and one diarrhoea. Therefore, the inefficacy hypothesis following Fleming one-stage design cannot be rejected. None of the patients experienced late Grade 3-4 toxicities. Among the 30 patients completing the 36 months' visit, none still had a grade ≥2 GI toxicity. Late grade ≥2 genitourinary (GU) toxicities occurred in 14 (41%) patients. The most frequent toxicities were dysuria and pollakiuria. Four patients still experienced a grade ≥2 GU toxicity at 36 months.The biochemical relapse rate (nadir +2 ng ml-1) was 6% (2 patients). Overall, HA was very well tolerated with no pain or discomfort. CONCLUSION: Despite the inefficacy of HA injection was not rejected, we observed the absence of Grade 3 or 4 rectal toxicity as well as a rate of Grade 2 rectal bleeding below 10% at 36 months of follow-up. Late urinary toxicities are the most frequent but the rate decreases largely at 3 years. ADVANCES IN KNOWLEDGE: With an injection of HA, hypofractionated irradiation in 4 weeks is well tolerated with no Grade 3 or 4 GI toxicity and a rate of Grade 2 rectal bleeding below 10% at 36 months of follow-up.

Intraoperative partial irradiation for highly selected patients with breast cancer: Results of the INTRAOBS prospective study.

PURPOSE: To evaluate our long-term experience on one-day breast intraoperative radiotherapy (IORT) given as sole radiation treatment to selected patients with breast cancer. METHODS AND MATERIALS: Inclusion criteria of INTRAOBS study (prospective observational study) were: ER+ T1N0 unifocal ductal carcinoma; absence of lymphovascular invasion or of extensive intraductal component (Scarff-Bloom-Richardson grade III and HER2+++ excluded). Two different linacs were used (20Gy/1 fraction): one dedicated electron linac (

Long-term follow-up experience in anal canal cancer treated with Intensity-Modulated Radiation Therapy: Clinical outcomes, patterns of relapse and predictors of failure.

BACKGROUND AND PURPOSE: To assess the long-term outcomes of patients with squamous cell carcinoma of the anal canal (SCCAC) treated with Intensity-Modulated Radiation Therapy (IMRT). MATERIAL AND METHODS: From 2007 to 2015, 193 patients were treated by IMRT for SCCAC. Radiotherapy delivered 45 Gy in 1.8 Gy daily-fractions to the primary tumor and elective nodal areas, immediately followed by a boost of 14.4-20 Gy to the primary tumor and involved nodes. Concurrent chemotherapy with 5-FU-mitomycin (MMC) or cisplatin was added for locally advanced tumors. Survivals were estimated by Kaplan-Meier method. Locoregional (LR) relapses were precisely assessed. Prognostic factors were evaluated by uni- and multivariate analyses. Late toxicity was scored according to the Common Toxicity Criteria for Adverse Events v4.0. RESULTS: Median follow-up was 70 months (range, 1-131). Forty-nine men (25%) and 144 women (75%) were analyzed. Median age was 62 years. Tumor stages were I, II, III and IV in 7%, 24%, 63% and 6% of cases, respectively. Chemotherapy was delivered in 167 patients (87%), mainly MMC (80%). Five-year OS, DFS, CFS and LR control rates were 74%, 68%, 66% and 85%, respectively. Forty-one patients (21%) had a relapse: 22 were LR, mostly in-field (68%). Predictors for LR failure were exclusive radiotherapy, chemotherapy lacking MMC and treatment breaks >3 days. Overall late toxicity ≥grade 2 occurred in 43% of patients, with 24% grade 3 and one case of grade 4 (hematuria). CONCLUSION: CRT with IMRT assures excellent local control in locally advanced SCCAC with manageable long-term toxicity. Multicentric prospective trials are required to reinforce those results.

Tracking, gating, free-breathing, which technique to use for lung stereotactic treatments? A dosimetric comparison.

BACKGROUND: The management of breath-induced tumor motion is a major challenge for lung stereotactic body radiation therapy (SBRT). Three techniques are currently available for these treatments: tracking (T), gating (G) and free-breathing (FB). AIM: To evaluate the dosimetric differences between these three treatment techniques for lung SBRT. MATERIALS AND METHODS: Pretreatment 4DCT data were acquired for 10 patients and sorted into 10 phases of a breathing cycle, such as 0% and 50% phases defined respectively as the inhalation and exhalation maximum. GTVph, PTVph (=GTVph + 3 mm) and the ipsilateral lung were contoured on each phase.For the tracking technique, 9 fixed fields were adjusted to each PTVph for the 10 phases. The gating technique was studied with 3 exhalation phases (40%, 50% and 60%). For the free-breathing technique, ITVFB was created from a sum of all GTVph and a 3 mm margin was added to define a PTVFB. Fields were adjusted to PTVFB and dose distributions were calculated on the average intensity projection (AIP) CT. Then, the beam arrangement with the same monitor units was planned on each CT phase.The 3 modalities were evaluated using DVHs of each GTVph, the homogeneity index and the volume of the ipsilateral lung receiving 20 Gy (V 20Gy). RESULTS: The FB system improved the target coverage by increasing D mean (75.87(T)-76.08(G)-77.49(FB)Gy). Target coverage was slightly more homogeneous, too (HI: 0.17(T and G)-0.15(FB)). But the lung was better protected with the tracking system (V 20Gy: 3.82(T)-4.96(G)-6.34(FB)%). CONCLUSIONS: Every technique provides plans with a good target coverage and lung protection. While irradiation with free-breathing increases doses to GTV, irradiation with the tracking technique spares better the lung but can dramatically increase the treatment complexity.