Estimation of secondary cancer risk after radiotherapy in high-risk prostate cancer patients with pelvic irradiation.

We aimed to estimate the risk of secondary cancer after radiotherapy (RT) in high-risk prostate cancer (HRPC) patients with pelvic irradiation. Computed tomography data of five biopsy-proven HRPC patients were selected for this study. Two different planning target volumes (PTV1 and PTV2 ) were contoured for each patient. The PTV1 included the prostate, seminal vesicles, and pelvic lymphatics, while the PTV2 included only the prostate and seminal vesicles. The prescribed dose was 54 Gy for the PTV1 with a sequential boost (24 Gy for the PTV2 ). Intensity-modulated RT (IMRT) and volumetric modulated arc therapy (VMAT) techniques were used to generate treatment plans with 6 and 10 MV photon energies with the flattening filter (FF) or flattening filter-free (FFF) irradiation mode. The excess absolute risks (EARs) were calculated and compared for the bladder, rectum, pelvic bone, and soft tissue based on the linear-exponential, plateau, full mechanistic, and specific mechanistic sarcoma dose-response model. According to the models, all treatment plans resulted in similar risks of secondary bladder or rectal cancer and pelvic bone or soft tissue sarcoma except for the estimated risk of the bladder according to the full mechanistic model using IMRT(6MV;FF) technique compared with VMAT techniques with FFF options. The overall estimation of EAR indicated that the radiation-induced cancer risk due to RT in HRPC was lower for bladder than the rectum. EAR values ranged from 1.47 to 5.82 for bladder and 6.36 to 7.94 for rectum, depending on the dose-response models used. The absolute risks of the secondary pelvic bone and soft tissue sarcoma were small for the plans examined. We theoretically predicted the radiation-induced secondary cancer risk in HRPC patients with pelvic irradiation. Nevertheless, prospective clinical trials, with larger patient cohorts with a long-term follow-up, are needed to validate these model predictions.

Output factors of ionization chambers and solid state detectors for mobile intraoperative radiotherapy (IORT) accelerator electron beams.

PURPOSE: The electron energy characteristics of mobile intraoperative radiotherapy (IORT) accelerator LIAC® differ from commonly used linear accelerators, thus some of the frequently used detectors can give less accurate results. The aim of this study is to evaluate the output factors (OFs) of several ionization chambers (IC) and solid state detectors (SS) for electron beam energies generated by LIAC® and compare with the output factor of Monte Carlo model (MC) in order to determine the adequate detectors for LIAC® . METHODS: The OFs were measured for 6, 8, 10, and 12 MeV electron energies with PTW 23343 Markus, PTW 34045 Advanced Markus, PTW 34001 Roos, IBA PPC05, IBA PPC40, IBA NACP-02, PTW 31010 Semiflex, PTW 31021 Semiflex 3D, PTW 31014 Pinpoint, PTW 60017 Diode E, PTW 60018 Diode SRS, SNC Diode EDGE, and PTW 60019 micro Diamond detectors. Ion recombination factors (ksat ) of IC were measured for all applicator sizes and OFs were corrected according to ksat . The measured OFs were compared with Monte Carlo output factors (OFMC ). RESULTS: The measured OFs of IBA PPC05, PTW Advanced Markus, PTW Pinpoint, PTW microDiamond, and PTW Diode E detectors are in good agreement with OFMC . The maximum deviations of IBA PPC05 OFs to OFMC are -1.6%, +1.5%, +1.5%, and +2.0%; for PTW Advanced Markus +1.0%, +1.5%, +2.0%, and +2.0%; for PTW Pinpoint +2.0%, +1.6%, +4.0%, and +2.0%; for PTW microDiamond -1.6%, +2%, +1.1%, and +1.0%; and for PTW Diode E -+1.7%, +1.7%, +1.3%, and +2.5% for 6, 8, 10, and 12 MeV, respectively. PTW Roos, PTW Markus, IBA PPC40, PTW Semiflex, PTW Semiflex 3D, SNC Diode Edge measured OFs with a maximum deviation of +5.6%, +4.5%, +5.6%, +8.1%, +4.8%, and +9.6% with respect to OFMC , while PTW Diode SRS and IBA NACP-02 were the least accurate (with highest deviations -37.1% and -18.0%, respectively). CONCLUSION: The OFs results of solid state detectors PTW microDiamond and PTW Diode E as well as the ICs with small electrode spacing distance such as IBA PPC05, PTW Advanced Markus and PTW Pinpoint are in excellent agreement with OFMC . The measurements of the other detectors evaluated in this study are less accurate, thus they should be used with caution. Particularly, PTW Diode SRS and IBA NACP-02 are not suitable and their use should be avoided in relative dosimetry measurements under high dose per pulsed (DPP) electron beams.

Improvement of conformal arc plans by using deformable margin delineation method for stereotactic lung radiotherapy.

PURPOSE: Stereotactic body radiotherapy (SBRT) is an established treatment technique in the management of medically inoperable early stage non-small cell lung cancer (NSCLC). Different techniques such as volumetric modulated arc (VMAT) and three-dimensional conformal arc (DCA) can be used in SBRT. Previously, it has been shown that VMAT is superior to DCA technique in terms of plan evaluation parameters. However, DCA technique has several advantages such as ease of use and considerable shortening of the treatment time. DCA technique usually results in worse conformity which is not possible to ameliorate by inverse optimization. In this study, we aimed to analyze whether a simple method - deformable margin delineation (DMD) - improves the quality of the DCA technique, reaching similar results to VMAT in terms of plan evaluation parameters. METHODS: Twenty stage I-II (T1-2, N0, M0) NSCLC patients were included in this retrospective dosimetric study. Noncoplanar VMAT and conventional DCA plans were generated using 6 MV and 10 MV with flattening filter free (FFF) photon energies. The DCA plan with 6FFF was calculated and 95% of the PTV was covered by the prescription isodose line. Hot dose regions (receiving dose over 100% of prescription dose) outside PTV and cold dose regions (receiving dose under 100% of prescription dose) inside PTV were identified. A new PTV (PTV-DMD) was delineated by deforming PTV margin with respect to hot and cold spot regions obtained from conventional DCA plans. Dynamic multileaf collimators (MLC) were set to PTV-DMD beam eye view (BEV) positions and the new DCA plans (DCA-DMD) with 6FFF were generated. Three-dimensional (3D) dose calculations were computed for PTV-DMD volume. However, the prescription isodose was specified and normalized to cover 95% volume of original PTV. Several conformity indices and lung doses were compared for different treatment techniques. RESULTS: DCA-DMD method significantly achieved a superior conformity index (CI), conformity number (CIPaddick ), gradient index (R50% ), isodose at 2 cm (D2 cm ) and external index (CΔ) with respect to VMAT and conventional DCA plans (P < 0.05 for all comparisons). CI ranged between 1.00-1.07 (Mean: 1.02); 1.00-1.18 (Mean: 1.06); 1.01-1.23 (Mean 1.08); 1.03-1.29 (Mean: 1.15); 1.04-1.29 (Mean: 1.18) for DCA-DMD-6FFF, VMAT-6FFF, VMAT-10FFF DCA-6FFF and DCA-10FFF respectively. DCA-DMD-6FFF technique resulted significantly better CI compared to others (P = 0.002; < 0.001; < 0.001; < 0.001). R50% ranged between 3.22-4.74 (Mean: 3.99); 3.24-5.92 (Mean: 4.15) for DCA-DMD-6FFF, VMAT-6FFF, respectively. DCA-DMD-6FFF technique resulted lower intermediate dose spillage compared to VMAT-6FFF, though the difference was statistically insignificant (P = 0.32). D2 cm ranged between 35.7% and 67.0% (Mean: 53.2%); 42.1%-79.2% (Mean: 57.8%) for DCA-DMD-6FFF, VMAT-6FFF respectively. DCA-DMD-6FFF have significantly better and sharp falloff gradient 2 cm away from PTV compared to VMAT-6FFF (P = 0.009). CΔ ranged between 0.052 and 0.140 (Mean: 0.085); 0,056-0,311 (Mean: 0.120) for DCA-DMD, VMAT-6FFF, respectively. DCA-DMD-6FFF have significantly improved CΔ (P = 0.002). VMAT- V20 Gy , V2.5 Gy and mean lung dose (MLD) indices are calculated to be 4.03%, 23.83%, 3.42 Gy and 4.19%, 27.88%,3.72 Gy, for DCA-DMD-6FFF and DCA techniques, respectively. DCA-DMD-6FFF achieved superior lung sparing compared to DCA technique. DCA-DMD-6FFF method reduced MUs 44% and 33% with respect to VMAT-6FFF and 10FFF, respectively, without sacrificing dose conformity (P < 0.001; P < 0.001). CONCLUSIONS: Our results demonstrated that DCA plan evaluation parameters can be ameliorated by using the DMD method. This new method improves DCA plan quality and reaches similar results with VMAT in terms of dosimetric parameters. We believe that DCA-DMD is a simple and effective technique for SBRT and can be preferred due to shorter treatment and planning time.

Dosimetric comparison of stereotactic MR-guided radiation therapy (SMART) and HDR brachytherapy boost in cervical cancer.

PURPOSE: The standard of care in locally advanced cervical cancer (LACC) is concomitant chemoradiotherapy followed by high-dose-rate brachytherapy (HDR-BT). Although previous studies compared HDR-BT with stereotactic body radiotherapy (SBRT), there is scarce data regarding the dosimetric outcomes of stereotactic MR-guided adaptive radiation therapy (SMART) boost in lieu of HDR-BT. METHODS AND MATERIALS: In this single-institutional in-silico comparative study, LACC patients who were definitively treated with external beam radiotherapy followed by HDR-BT were selected. Target volumes and organs at risk (OARs) were delineated in MRI and HDR-planning CT. An HDR-BT and a SMART boost plan were generated with a prescribed dose of 28 Gy in four fractions for all patients. The HDR-BT and SMART boost plans were compared in regard to target coverage as well OARs doses. RESULTS: Mean EQD2 D90 to HR-CTV and IR-CTV for HDR-BT plans were 89.7 and 70.5 Gy, respectively. For SMART, the mean EQD2 D90 to HR-PTV, HR-CTV, and IR-CTV were 82.9, 95.4, and 70.2 Gy, respectively. The mean D2cc EQD2 of bladder, rectum, and sigmoid colon for HDR-BT plans were 86.4, 70.7, and 65.7 Gy, respectively. The mean D2cc EQD2 of bladder, rectum, and sigmoid colon for SMART plans were 81.4, 70.8, and 73.6 Gy, respectively. All dose constraints in terms of target coverage and OARs constraints were met for both HDR-BT and SMART plans. CONCLUSIONS: This dosimetric study demonstrates that SMART can be applied in cases where HDR-BT is not available or ineligible with acceptable target coverage and OAR sparing. However, prospective clinical studies are needed to validate these results.

Magnetic Resonance Imaging-Guided Stereotactic Body Radiation Therapy for Medically Inoperable Endometrial Cancer.

Endometrial carcinoma is the most frequently diagnosed gynecological cancer among women aged 50 and older in developed countries. In patients who are not amenable to surgery, radiotherapy results in improved survival with acceptable adverse effect profiles. Definitive stereotactic body radiotherapy (SBRT) as a monotherapy remains an unaddressed concept in the literature. Here, we present the case of an 86-year-old woman who was diagnosed with early-stage endometrial carcinoma and was medically inoperable due to cardiac comorbidities. She was treated with magnetic resonance imaging-guided online adaptive radiotherapy-based SBRT. She tolerated the treatment well, with mild increased vaginal discharge. Complete metabolic and radiological responses were obtained. She continues to be disease free in the first year of treatment with no long-term side effects. Our protocol presents promising results with a safe toxicity profile for inoperable early-stage endometrial cancer. Future studies are warranted in light of the current knowledge.

An ESTRO-ACROP guideline on quality assurance and medical physics commissioning of online MRI guided radiotherapy systems based on a consensus expert opinion.

OBJECTIVE: The goal of this consensus expert opinion was to define quality assurance (QA) tests for online magnetic resonance image (MRI) guided radiotherapy (oMRgRT) systems and to define the important medical physics aspects for installation and commissioning of an oMRgRT system. MATERIALS AND METHODS: Ten medical physicists and two radiation oncologists experienced in oMRgRT participated in the survey. In the first round of the consensus expert opinion, ideas on QA and commissioning were collected. Only tests and aspects different from commissioning of a CT guided radiotherapy (RT) system were considered. In the following two rounds all twelve participants voted on the importance of the QA tests, their recommended frequency and their suitability for the two oMRgRT systems approved for clinical use as well as on the importance of the aspects to consider during medical physics commissioning. RESULTS: Twenty-four QA tests were identified which are potentially important during commissioning and routine QA on oMRgRT systems compared to online CT guided RT systems. An additional eleven tasks and aspects related to construction, workflow development and training were collected. Consensus was found for most tests on their importance, their recommended frequency and their suitability for the two approved systems. In addition, eight aspects mostly related to the definition of workflows were also found to be important during commissioning. CONCLUSIONS: A program for QA and commissioning of oMRgRT systems was developed to support medical physicists to prepare for safe handling of such systems.

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.

Magnetic Resonance Image-Guided Hypofractionated Ablative Radiation Therapy for Hepatocellular Carcinoma With Tumor Thrombus Extending to the Right Atrium.

Hepatocellular carcinoma (HCC) presenting with tumor thrombus (TT) and inferior vena cava (IVC)/right atrium (RA) infringement point to an advanced-stage disease that is deemed inoperable. Stereotactic body radiotherapy is an emerging treatment option for this group of patients with promising outcomes in recent studies that are comparable to conventional treatment methods, namely, transarterial chemoembolization and transarterial radioembolization. Here, we report a case of HCC with RA extension through the IVC. The patient was referred to our clinic for treatment options, and he was found suitable for magnetic resonance imaging-guided radiotherapy (MRgRT). We treated the patient with MRgRT in five fractions to a total dose of 40 Gray. The tumor was tracked during the treatment sessions, and adaptive treatment planning was performed before each fraction. The patient tolerated the treatment well with no acute grade 3-4 toxicities. The last follow-up showed that the patient had a complete biochemical response and is now a candidate for an orthotopic liver transplant. To our knowledge, this report is the first to document the MRgRT treatment of an HCC with TT and RA extension. MRgRT is safe and feasible for this patient group and can be an effective bridging therapy for liver transplants.

Magnetic Resonance Imaging-Guided Online Adaptive Lattice Stereotactic Body Radiotherapy in Voluminous Liver Metastasis: Two Case Reports.

Lattice Radiotherapy (LRT) is a technique in which heterogeneous doses are delivered to the target so large tumors can have optimal doses of radiation without compromising healthy tissue sparing. To date, case reports and case series documented its application for bulky tumors mainly in the pelvic region. LRT not only provides dosimetric advantages but also promotes tumor control by triggering some radiobiological and immunological pathways. We report two cases of giant liver metastases for whom other treatment options were not suitable. We treated both patients with Magnetic Resonance Image-Guided Radiotherapy (MRgRT) with online adaptive LRT (OALRT) technique. Adaptive plans were generated before each fraction. Tumors were observed to have regressed interfractionally so the location and number of spheres were adapted to tumor size and daily anatomy of the surrounding organs at risk (OAR). Both patients had good treatment compliance without any Grade 3+ side effects. They are both under follow-up and report improvement. By reporting the first application of OALRT by using MRgRT in liver metastases, we show that MRgRT is a promising modality for LRT technique with better target and OAR visualization as well as online adaptive planning before each fraction according to the daily anatomy of the patient.

Magnetic Resonance Imaging-Guided Radiation Therapy for Early-Stage Gastric Mucosa-Associated Lymphoid Tissue Lymphoma.

Lymphoid neoplasia derived from mucosa-associated lymphoid tissue (MALT; also abbreviated as MALToma) is most commonly seen in the stomach. Radiotherapy (RT) is indicated in early-stage disease as a standard of care. With the advent of RT techniques, large field irradiation was replaced by involved site and involved field approaches. Magnetic resonance imaging-guided online adaptive RT (MRgRT) has the advantage of better soft tissue visualization, adaptive planning before each fraction, and online tumor tracking during treatment; hence, it could be a safe and effective choice for gastric MALToma patients. Herein, we investigated the interfractional changes in target and the impact of MRgRT on daily dosimetry in a gastric MALToma case. A patient diagnosed with MALToma who failed to respond to antibacterial treatment was referred to our clinic for RT. He was found to be suitable for MRgRT. We treated the patient with MRgRT in 20 fractions to a total dose of 30 Gy. Reoptimized adaptive plans were generated before each fraction since the coverages of the original plan were inadequate in each fraction. The patient showed good compliance and tolerated the treatment well. To our knowledge, this is the first documented case of a gastric MALToma treated with MRgRT. MRgRT is safe and feasible for this patient group with improved target coverage using small planning target volume margins. Without online adaptive planning, the target coverages would be inadequate and we would risk surrounding tissues to get higher doses.

Multi-Institutional Outcomes of Stereotactic Magnetic Resonance Image Guided Adaptive Radiation Therapy With a Median Biologically Effective Dose of 100 Gy10 for Non-bone Oligometastases.

Purpose: Randomized data show a survival benefit of stereotactic ablative body radiation therapy in selected patients with oligometastases (OM). Stereotactic magnetic resonance guided adaptive radiation therapy (SMART) may facilitate the delivery of ablative dose for OM lesions, especially those adjacent to historically dose-limiting organs at risk, where conventional approaches preclude ablative dosing. Methods and Materials: The RSSearch Registry was queried for OM patients (1-5 metastatic lesions) treated with SMART. Freedom from local progression (FFLP), freedom from distant progression (FFDP), progression-free survival (PFS), and overall survival (LS) were estimated using the Kaplan-Meier method. FFLP was evaluated using RECIST 1.1 criteria. Toxicity was evaluated using Common Terminology Criteria for Adverse Events version 4 criteria. Results: Ninety-six patients with 108 OM lesions were treated on a 0.35 T MR Linac at 2 institutions between 2018 and 2020. SMART was delivered to mostly abdominal or pelvic lymph nodes (48.1%), lung (18.5%), liver and intrahepatic bile ducts (16.7%), and adrenal gland (11.1%). The median prescribed radiation therapy dose was 48.5 Gy (range, 30-60 Gy) in 5 fractions (range, 3-15). The median biologically effective dose corrected using an alpha/beta value of 10 was 100 Gy10 (range, 48-180). No acute or late grade 3+ toxicities were observed with median 10 months (range, 3-25) follow-up. Estimated 1-year FFLP, FFDP, PFS, and OS were 92.3%, 41.1%, 39.3%, and 89.6%, respectively. Median FFDP and PFS were 8.9 months (95% confidence interval, 5.2-12.6 months) and 7.6 months (95% confidence interval, 4.5-10.6 months), respectively. Conclusions: To our knowledge, this represents the largest analysis of SMART using ablative dosing for non-bone OM. A median prescribed biologically effective dose of 100 Gy10 resulted in excellent early FFLP and no significant toxicity, likely facilitated by continuous intrafraction MR visualization, breath hold delivery, and online adaptive replanning. Additional prospective evaluation of dose-escalated SMART for OM is warranted.

Magnetic resonance image-guided stereotactic body radiation therapy for liver rhabdoid tumor in infancy: A case report.

Extracranial malignant rhabdoid tumors are rare and aggressive tumors that typically occur in the pediatric age group and have a poor prognosis. Herein, we report a case of a one year and five months old male infant who was referred with the diagnosis of malignant rhabdoid tumor of the liver. Magnetic resonance guided stereotactic body radiotherapy was administered with concomitant chemotherapy. Treatment was well tolerated with no severe acute side effects. A 40.8% volumetric reduction of the tumor was observed at the last fraction of MR guided radiotherapy.

Magnetic resonance image-guided hypofractionated ablative radiation therapy for extrahepatic cholangiocarcinoma: Plan adaptation in changing anatomy.

Extrahepatic cholangiocarcinoma is an aggressive malignancy of biliary duct epithelium which typically has a poor prognosis. Although surgical resection improves overall survival, many patients are deemed medically inoperable or have unresectable tumors. Herein, we report a case of an 84-year-old Caucasian male who was diagnosed with medically inoperable extrahepatic cholangiocarcinoma. Magnetic resonance image-guided hypofractionated ablative radiotherapy was administered which has the advantages of superior soft tissue resolution, better visualization of the target and organ at risk, daily online adaptive planning and continuous cine MR tracking of the target during irradiation. Concomitant chemotherapy was used. On the first fraction the patient presented with a broken arm that forced the patient take a treatment position much different than the one used for simulation CT and planning. The patient was able to finish the treatment without the need of another simulation by adapting the plan according to the new anatomy. The patient is being followed up until today and is alive with no evidence of disease.

Stereotactic MR-guided online adaptive radiation therapy (SMART) for the treatment of liver metastases in oligometastatic patients: initial clinical experience.

PURPOSE: We aimed to present our initial clinical experience on the implementation of a stereotactic MR-guided online adaptive radiation therapy (SMART) for the treatment of liver metastases in oligometastatic disease. MATERIALS AND METHODS: Twenty-one patients (24 lesions) with liver metastasis treated with SMART were included in this retrospective study. Step-and-shoot intensity-modulated radiotherapy technique was used with daily plan adaptation. During delivery, real-time imaging was used by acquiring planar magnetic resonance images in sagittal plane for monitoring and gating. Acute and late toxicities were recorded both during treatment and follow-up visits. RESULTS: The median follow-up time was 11.6 months (range, 2.2 to 24.6 months). The median delivered total dose was 50 Gy (range, 40 to 60 Gy); with a median fraction number of 5 (range, 3 to 8 fractions) and the median fraction dose was 10 Gy (range, 7.5 to 18 Gy). Ninety-three fractions (83.7%) among 111 fractions were re-optimized. No patients were lost to follow-up and all patients were alive except one at the time of analysis. All of the patients had either complete (80.9%) or partial (19.1%) response at irradiated sites. Estimated 1-year overall survival was 93.3%. Intrahepatic and extrahepatic progression-free survival was 89.7% and 73.5% at 1 year, respectively. There was no grade 3 or higher acute or late toxicities experienced during the treatment and follow-up course. CONCLUSION: SMART represents a new, noninvasive and effective alternative to current ablative radiotherapy methods for treatment of liver metastases in oligometastatic disease with the advantages of better visualization of soft tissue, real-time tumor tracking and potentially reduced toxicity to organs at risk.

Risk of symptomatic radiation necrosis in patients treated with stereotactic radiosurgery for brain metastases.

INTRODUCTIO: Stereotactic radiosurgery (SRS) is a treatment option in the initial management of patients with brain metastases. While its efficacy has been demonstrated in several prior studies, treatment-related complications, particularly symptomatic radiation necrosis (RN), remains as an obstacle for wider implementation of this treatment modality. We thus examined risk factors associated with the development of symptomatic RN in patients treated with SRS for brain metastases. PATIENTS AND METHODS: We performed a retrospective review of our institutional database to identify patients with brain metastases treated with SRS. Diagnosis of symptomatic RN was determined by appearance on serial MRIs, MR spectroscopy, requirement of therapy, and the development of new neurological complaints without evidence of disease progression. RESULTS: We identified 323 brain metastases treated with SRS in 170 patients from 2009 to 2018. Thirteen patients (4%) experienced symptomatic RN after treatment of 23 (7%) lesions. After SRS, the median time to symptomatic RN was 8.3 months. Patients with symptomatic RN had a larger mean target volume (p<0.0001), and thus larger V100% (p<0.0001), V50% (p<0.0001), V12Gy (p<0.0001), and V10Gy (p=0.0002), compared to the rest of the cohort. Single-fraction treatment (p=0.0025) and diabetes (p=0.019) were also significantly associated with symptomatic RN. CONCLUSION: SRS is an effective treatment option for patients with brain metastases; however, a subset of patients may develop symptomatic RN. We found that patients with larger tumor size, larger plan V100%, V50%, V12Gy, or V10Gy, who received single-fraction SRS, or who had diabetes were all at higher risk of symptomatic RN.

Magnetic resonance image-guided adaptive stereotactic body radiotherapy for prostate cancer: preliminary results of outcome and toxicity.

OBJECTIVE: Using moderate or ultra-hypofractionation, which is also known as stereotactic body radiotherapy (SBRT) for treatment of localized prostate cancer patients has been increased. We present our preliminary results on the clinical utilization of MRI-guided adaptive radiotherapy (MRgRT) for prostate cancer patients with the workflow, dosimetric parameters, toxicities and prostate-specific antigen (PSA) response. METHODS: 50 prostate cancer patients treated with ultra-hypofractionation were included in the study. Treatment was performed with intensity-modulated radiation therapy (step and shoot) technique and daily plan adaptation using MRgRT. The SBRT consisted of 36.25 Gy in 5 fractions with a 7.25 Gy fraction size. The time for workflow steps was documented. Patients were followed for the acute and late toxicities and PSA response. RESULTS: The median follow-up for our cohort was 10 months (range between 3 and 29 months). The median age was 73.5 years (range between 50 and 84 years). MRgRT was well tolerated by all patients. Acute genitourinary (GU) toxicity rate of Grade 1 and Grade 2 was 28 and 36%, respectively. Only 6% of patients had acute Grade 1 gastrointestinal (GI) toxicity and there was no Grade ≥ 2 GI toxicity. To date, late Grade 1 GU toxicity was experienced by 24% of patients, 2% of patients experienced Grade 2 GU toxicity and 6% of patients reported Grade 2 GI toxicity. Due to the short follow-up, PSA nadir has not been reached yet in our cohort. CONCLUSION: In conclusion, MRgRT represents a new method for delivering SBRT with markerless soft tissue visualization, online adaptive planning and real-time tracking. Our study suggests that ultra-hypofractionation has an acceptable acute and very low late toxicity profile. ADVANCES IN KNOWLEDGE: MRgRT represents a new markerless method for delivering SBRT for localized prostate cancer providing online adaptive planning and real-time tracking and acute and late toxicity profile is acceptable.

Time Analysis of Online Adaptive Magnetic Resonance-Guided Radiation Therapy Workflow According to Anatomical Sites.

PURPOSE: To document time analysis of detailed workflow steps for the online adaptive magnetic resonance-guided radiation therapy treatments (MRgRT) with the ViewRay MRIdian system and to identify the barriers to and solutions for shorter treatment times. METHODS AND MATERIALS: A total of 154 patients were treated with the ViewRay MRIdian system between September 2018 and October 2019. The time process of MRgRT workflow steps of 962 fractions for 166 treatment sites was analyzed in terms of patient and online adaptive treatment (ART) characteristics. RESULTS: Overall, 774 of 962 fractions were treated with online ART, and 83.2% of adaptive fractions were completed in less than 60 minutes. Sixty-three percent, 50.3%, and 4.2% of fractions were completed in less than 50 minutes, 45 minutes, and 30 minutes, respectively. Eight-point-three percent and 3% of fractions were completed in more than 70 minutes and 80 minutes, respectively. The median time (tmed) for ART workflow steps were as follows: (1) setup tmed: 5.0 minutes, (2) low-resolution scanning tmed: 1 minute, (3) high-resolution scanning tmed: 3 minutes, (4) online contouring tmed: 9 minutes, (5) reoptimization with online quality assurance tmed: 5 minutes, (6) real targeting tmed: 3 minutes, (7) beam delivery with gating tmed: 17 minutes, and (8) net total treatment time tmed: 45 minutes. The shortest and longest tmean rates of net total treatment time were 41.59 minutes and 64.43 minutes for upper-lung-lobe-located thoracic tumors and ultracentrally located thoracic tumors, respectively. CONCLUSIONS: To our knowledge, this is the first broad treatment-time analysis for online ART in the literature. Although treatment times are long due to human- and technology-related limitations, benefits offered by MRgRT might be clinically important. In the future, implementation of artificial intelligence segmentation, an increase in dose rate, and faster multileaf collimator and gantry speeds may lead to achieving shorter MRgRT treatments.

Artificial Intelligence in magnetic Resonance guided Radiotherapy: Medical and physical considerations on state of art and future perspectives.

Over the last years, technological innovation in Radiotherapy (RT) led to the introduction of Magnetic Resonance-guided RT (MRgRT) systems. Due to the higher soft tissue contrast compared to on-board CT-based systems, MRgRT is expected to significantly improve the treatment in many situations. MRgRT systems may extend the management of inter- and intra-fraction anatomical changes, offering the possibility of online adaptation of the dose distribution according to daily patient anatomy and to directly monitor tumor motion during treatment delivery by means of a continuous cine MR acquisition. Online adaptive treatments require a multidisciplinary and well-trained team, able to perform a series of operations in a safe, precise and fast manner while the patient is waiting on the treatment couch. Artificial Intelligence (AI) is expected to rapidly contribute to MRgRT, primarily by safely and efficiently automatising the various manual operations characterizing online adaptive treatments. Furthermore, AI is finding relevant applications in MRgRT in the fields of image segmentation, synthetic CT reconstruction, automatic (on-line) planning and the development of predictive models based on daily MRI. This review provides a comprehensive overview of the current AI integration in MRgRT from a medical physicist's perspective. Medical physicists are expected to be major actors in solving new tasks and in taking new responsibilities: their traditional role of guardians of the new technology implementation will change with increasing emphasis on the managing of AI tools, processes and advanced systems for imaging and data analysis, gradually replacing many repetitive manual tasks.

Patient-Reported Tolerance of Magnetic Resonance-Guided Radiation Therapy.

PURPOSE: Magnetic resonance-guided radiation therapy (MRgRT) has been incorporated into a growing number of clinical practices world-wide, however, there is limited data on patient experiences with MRgRT. The purpose of this study was to prospectively evaluate patient tolerance of MRgRT using patient reported outcome questionnaires (PRO-Q). METHODS: Ninety patients were enrolled in this prospective observational study and treated with MRgRT (MRIdian Linac System, ViewRay Inc. Oakwood Village, OH, United States) between September 2018 and September 2019. Breath-hold-gated dose delivery with audiovisual feedback was completed as needed. Patients completed an in-house developed PRO-Q after the first and last fraction of MRgRT. RESULTS: The most commonly treated anatomic sites were the abdomen (47%) and pelvis (33%). Respiratory gating was utilized in 62% of the patients. Patients rated their experience as positive or at least tolerable with mean scores of 1.0-2.8. The most common complaint was the temperature in the room (61%) followed by paresthesias (57%). The degree of anxiety reported by 45% of the patients significantly decreased at the completion of treatment (mean score 1.54 vs. 1.36, p = 0.01). Forty-three percent of the patients reported some degree of disturbing noise which was improved considerably by use of music. All patients appreciated their active role during the treatment. CONCLUSION: This evaluation of PROs indicates that MRgRT was well-tolerated by our patients. Patients' experience may further improve with adjustment of room temperature and noise reduction.

Multichannel Film Dosimetry for Quality Assurance of Intensity Modulated Radiotherapy Treatment Plans Under 0.35 T Magnetic Field.

Purpose To evaluate the intensity modulated radiotherapy (IMRT) quality assurance (QA) results of the multichannel film dosimetry analysis with single scan method by using Gafchromic™ EBT3 (Ashland Inc., Covington, KY, USA) film under 0.35 T magnetic field. Methods Between September 2018 and June 2019, 70 patients were treated with ViewRay MRIdian® (ViewRay Inc., Mountain View, CA) linear accelerator (Linac). Film dosimetry QA plans were generated for all IMRT treatments. Multichannel film dosimetry for red, green and blue (RGB) channels were compared with treatment planning system (TPS) dose maps by gamma evaluation analysis. Results The mean gamma passing rates of RGB channels are 97.3% ± 2.26%, 96.0% ± 3.27% and 96.2% ± 3.14% for gamma evaluation with 2% DD/2 mm distance to agreement (DTA), respectively. Moreover, the mean gamma passing rates of RGB channels are 99.7% ± 0.41%, 99.6% ± 0.59% and 99.5% ± 0.67% for gamma evaluation with 3% DD/3 mm DTA, respectively. Conclusion The patient specific QA using Gafchromic™ EBT3 film with multichannel film dosimetry seems to be a suitable tool to implement for MR-guided IMRT treatments under 0.35 T magnetic field. Multichannel film dosimetry with Gafchromic™ EBT3 is a consistent QA tool for gamma evaluation of the treatment plans even with 2% DD/2 mm DTA under 0.35 T magnetic field presence.