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Purpose: Helical tomotherapy is a complex delivery technique, integrating CT image guidance and intensity modulated radiotherapy in a single system. The integration of the CT detector ring on the gantry not only allows patient position verification but is also often used to perform various QA procedures. This convenience lacks the rigor of a machine-independent QA process. Methods: In this article, a Si strip detector, known as the Dose Magnifying Glass (DMG), was used to perform machine-independent QA measurements of the multileaf collimator alignment, leaf open time threshold, and leaf fluence output factor (LFOF). Results: The DMG measurements showed good agreements with EDR2 film for the MLC alignment test while the CT detector agrees well with DMG measurements for leaf open time threshold and LFOF measurements. The leaf open time threshold was found to be approximately 20 ms. The LFOF measured with the DMG agreed within error with the CT detector measured LFOF. Conclusions: The DMG with its 0.2 mm spatial resolution coupled to TERA ASIC allowed real-time high temporal resolution measurements of the tomotherapy leaf movement. In conclusion, DMG was shown to be a suitable tool for machine-independent QA of a tomotherapy unit. [ABSTRACT FROM AUTHOR]

Purpose: Sparing the hippocampus during cranial irradiation poses important technical challenges with respect to contouring and treatment planning. Herein we report our preliminary experience with whole-brain radiotherapy using hippocampal sparing for patients with brain metastases.Methods and Materials: Five anonymous patients previously treated with whole-brain radiotherapy with hippocampal sparing were reviewed. The hippocampus was contoured, and hippocampal avoidance regions were created using a 5-mm volumetric expansion around the hippocampus. Helical tomotherapy and linear accelerator (LINAC)-based intensity-modulated radiotherapy (IMRT) treatment plans were generated for a prescription dose of 30 Gy in 10 fractions.Results: On average, the hippocampal avoidance volume was 3.3 cm(3), occupying 2.1% of the whole-brain planned target volume. Helical tomotherapy spared the hippocampus, with a median dose of 5.5 Gy and maximum dose of 12.8 Gy. LINAC-based IMRT spared the hippocampus, with a median dose of 7.8 Gy and maximum dose of 15.3 Gy. On a per-fraction basis, mean dose to the hippocampus (normalized to 2-Gy fractions) was reduced by 87% to 0.49 Gy(2) using helical tomotherapy and by 81% to 0.73 Gy(2) using LINAC-based IMRT. Target coverage and homogeneity was acceptable with both IMRT modalities, with differences largely attributed to more rapid dose fall-off with helical tomotherapy.Conclusion: Modern IMRT techniques allow for sparing of the hippocampus with acceptable target coverage and homogeneity. Based on compelling preclinical evidence, a Phase II cooperative group trial has been developed to test the postulated neurocognitive benefit. [ABSTRACT FROM AUTHOR]

Purpose: This report describes routine machine quality assurance (QA) (daily, monthly, and annual QA) tests for the Zap-X ® Gyroscopic Radiosurgery ® platform., Methods: Following the recommendations of the American Association of Physicists in Medicine Task Group (AAPM TG)-142 and Medical Physics Practice guideline (MPPG) 8.b, routine machine QA tests for the Zap-X system were implemented. The implementation included (1) daily, monthly, and annual QA tests encompassing dosimetry, mechanical, safety and imaging tests, (2) QA methods of each test specific to the Zap-X, (3) a tolerance value for each test, and (4) necessary QA equipment., Results: Baseline values and key results of daily, monthly, and annual QA tests are presented in this report. This report also discusses QA tests not adopted from TG 142 or MPPG 8.b (e.g., distance indicator) due to unique features of the Zap-X system as well as additional QA tests added from the vendor's recommendations (e.g., self-check) and from TG-135 recommendations (e.g., monthly end-to-end testing) because of similarities between Zap-X and CyberKnife systems., Conclusions: The comprehensive information on routine machine QA tests presented in this report will assist Zap-X teams in other Neurosurgery centers or Radiation Oncology clinics in establishing and maintaining their QA programs until AAPM endorsed guidelines become available., (© 2024 The Author(s). Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

Purpose: This study investigates potential failure modes and conducts failure mode and effects analysis (FMEA) and fault tree analysis (FTA) on the administration of 177 Lu $^{177}{\rm Lu}$ DOTATATE (LUTATHERA) and 177 Lu $^{177}{\rm Lu}$ PSMA-617 (PLUVICTO). The quality management (QM) process in radiopharmaceutical therapies (RPTs) requires collaboration between nuclear medicine (NM) and radiation oncology (RO) departments. As part of a multi-institutional study, we surveyed various departments to identify and analyze failure modes, leading to a proposed comprehensive QM program. RPT teams in RO or NM clinics can benefit from this study by continually improving their practice., Methods: We reviewed the literature to investigate the administration of Pluvicto and Lutathera, focusing on prospective procedural failures and potential failure modes (PFMs) and their outcomes. We distributed an FMEA survey to multiple experienced centers in 177 Lu $^{177}{\rm Lu}$ -based RPTs and calculated risk priority number (RPN) for various PFM. We conducted an FTA using this information to pinpoint the root causes of potential failures., Results: The findings from the literature review and survey responses on the prospective study have identified several critical areas at risk of failure. These areas include non-optimized treatment delivery, inadequate patient monitoring, and lack of safety training, leading to radiation contamination from the dose excreted by the patients after treatment administration. A segmented FTA was created based on the FMEA results, focusing on radiation contamination with a high RPN value., Conclusion: By identifying the root causes of failures and proposing targeted improvements to the existing QM measures, this analysis enhances safety in treatment delivery of 177 Lu $^{177}{\rm Lu}$ -based RPTs. Given the limited number of prospective risk analysis studies in RPTs, our research addresses the necessity for more such studies and recommends methods to apply this study to other RPTs., (© 2024 The Author(s). Journal of Applied Clinical Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Recurrent high-grade intracranial malignancies have a grim prognosis and uniform management guidelines are lacking. Re-irradiation is underused due to concerns about irreversible side effects. Pulsed-reduced dose rate radiotherapy (PRDR) aims to reduce toxicity while improving tumor control by exploiting dose-rate effects. We share our initial experience with temporally modulated pulsed proton re-irradiation (TMPPR), focusing on workflow, safety, feasibility, and outcomes for the first patient cohort. TMPPR was administered to patients with recurrent or progressive central nervous system malignancies using intensity modulated proton therapy with three fields. Patient and treatment data were collected, responses categorized using RANO assessment, and toxicities graded using CTCAE v5.0. Five patients received TMPPR between October 2022 and May 2023, with a median age of 54 years (Range: 32-72), and a median time from initial radiotherapy to re-RT of 23 months (Range 14-40). Treatment was completed without delay, with a median dose of 60 GyRBE in 30 fractions. Initial treatment response assessment showed complete (n = 1) or partial (n = 3) responses. Limited toxicity was observed, primarily grade 2 alopecia and one case of radiation necrosis graded at 2. This early experience demonstrates the feasibility of TMPPR delivery, highlighting the importance of prospective evaluations in the re-irradiation setting., (© 2024. The Author(s).)

Background: Stereotactic radiosurgery (SRS) for patients with brain metastases (BM) is associated with a risk of distant intracranial failure (DIF). This study evaluates the impact of integrating dedicated 3D-TSE sequences to MPRAGE in BM detection and DIF prolongation in a histology-agnostic patient cohort., Methods: The study population included adults treated with SRS from February 2019 to January 2024 who underwent MPRAGE alone or dual-sequence with the addition of 3D-TSE starting from February 2020. Median times to DIF were estimated using the Kaplan-Meier method., Results: The 216 study patients who underwent 332 SRS courses for 1456 BM imaged with MPRAGE and 3D-TSE (primary cohort) were compared to a control cohort (92 patients, 135 SRS courses, 462 BM). In the session-wise analysis, the median time to DIF between the cohorts was significantly prolonged in the primary vs. control cohorts (11.4 vs. 6.8 months, p=0.029), more pronounced in the subgroups with 1-4 metastases (14.7 vs. 8.1 months, p=0.008) and with solitary BM (36.4 vs. 10.9 months, p=0.001). While patients relapsing on immunotherapy or targeted therapy did not significantly benefit from 3D-FSE (7.2 vs. 5.7 months, p=0.280), those who relapsed on chemotherapy or who were off systemic therapy (including synchronous metastases) exhibited a trend towards longer time to DIF with 3D-TSE integration (14.7 vs. 7.9 months, p=0.057)., Conclusions: Implementing 3D-TSE sequences into SRS practice increases BM detection across all patients and translates into clinical relevance by prolonging time to DIF, particularly in those with limited intracranial disease and those not receiving CNS-active agents., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Purpose: Surgically targeted radiation therapy (STaRT) with Cesium-131 seeds embedded in a collagen tile is a promising treatment for recurrent brain metastasis. In this study, the biological effective doses (BED) for normal and target tissues from STaRT plans were compared with those of external beam radiotherapy (EBRT) modalities., Methods: Nine patients (n = 9) with 12 resection cavities (RCs) who underwent STaRT (cumulative physical dose of 60 Gy to a depth of 5 mm from the RC edge) were replanned with CyberKnife Ⓡ (CK), Gamma Knife Ⓡ (GK), and intensity modulated proton therapy (IMPT) using an SRT approach (30 Gy in 5 fractions). Statistical significance comparing D95% and D90% in BED 10Gy (BED 10Gy 95% and BED 10Gy 90%) and to RC + 0 to + 5 mm expansion margins, and parameters associated with radiation necrosis risk (V8 3Gy , V10 3Gy , V12 3Gy and V24 3Gy ) to the normal brain were evaluated by a Wilcoxon-signed rank test., Results: For RC + 0 mm, median BED 10Gy 90% for STaRT (90.1 Gy 10 , range: 64.1-140.9 Gy 10 ) was significantly higher than CK (74.3 Gy 10 , range:59.3-80.4 Gy 10 , p = 0.04), GK (69.4 Gy 10 , range: 59.8-77.1 Gy 10 , p = 0.005), and IMPT (49.3 Gy 10 , range: 49.0-49.7 Gy 10 , p = 0.003), respectively. However, for the RC + 5 mm, the median BED 10Gy 90% for STaRT (34.1 Gy 10 , range: 22.2-59.7 Gy 10 ) was significantly lower than CK (44.3 Gy 10 , range: 37.8-52.4 Gy 10 ), and IMPT (46.6 Gy 10 , range: 45.1-48.5 Gy 10 ), respectively, but not significantly different from GK (34.1 Gy 10 , range: 22.8-47.0 Gy 10 ). The median V24 3Gy was significantly higher in CK (11.7 cc, range: 4.7-20.1 cc), GK(6.2 cc, range: 2.3-11.9 cc) and IMPT (19.9 cc, range: 11.1-36.6 cc) compared to STaRT (1.1 cc, range: 0.0-7.8 cc) (p < 0.01)., Conclusions: This comparative analysis suggests a STaRT approach may treat recurrent brain tumors effectively via delivery of higher radiation doses with equivalent or greater BED up to at least 3 mm from the RC edge as compared to EBRT approaches., Competing Interests: Disclosure Tugce Kutuk: None. Rupesh Kotecha: Honoraria from Accuray Inc., Elekta AB, ViewRay Inc., Novocure Inc., Elsevier Inc., Brainlab, Kazia Therapeutics, Castle Biosciences, and institutional research funding from Medtronic Inc., Blue Earth Diagnostics Ltd., Novocure, Inc., GT Medical Technologies, AstraZeneca, Exelixis, ViewRay, Inc., Brainlab, Cantex Pharmaceuticals, and Kazia Therapeutics. Roberto Herrera: None. DJay J Wieczorek: None. Zachary W. Fellows: None. Vibha Chaswal: None. Alonso La Rosa: None. Vivek Mishra: None. Michael W McDermott: Consultant Deinde Medical and Stryker Medical. Vitaly Siomin: None. Minesh P Mehta: Consulting fees from Karyopharm, Sapience, Zap, Mevion, Xoft, BOD Oncoceutics, Kazia Therapeutics; stock in Chimerix. Alonso N Gutierrez: Honoraria from ViewRay, Inc., Elekta AB, IBA AB. Ranjini Tolakanahalli: None., (Copyright © 2024 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

To assess the impact of Strut Adjusted Volume Implant (SAVI) catheter digitization variability on dosimetric evaluation parameters of HDR breast brachytherapy treatment plans. Four clinically approved SAVI cases were chosen for this digitization variability analysis. All patients were implanted with 6-1 SAVI device. Six experienced physicists independently digitized SAVI catheters. Plans utilizing significant peripheral loading were used for this study where SAVI catheters were near the chest wall and/or skin. After digitization was completed for each case by each physicist, the original clinical dwell times were copied over for comparison. This ensured that only variability among plans is the digitization of SAVI catheters by different users. The original plan that went through two physicists' checks and one physician's review was considered the "ground truth" plan to which all other plans were compared. Plans were evaluated on planning parameters for lumpectomy cavity's PTV&#95;Eval D90, V150, V200 and for the OARs (Chest-Wall/Ribs and Skin), on D 0.03cc , D 0.1cc , D 1cc , D 2cc . Additionally, a visualization window setting-based uncertainty test was performed on the same 4 cases. Our results showed that the average and maximum dwell positional digitization uncertainties were 0.36 and 0.75 mm, respectively. Average PTV&#95;Eval D90 was 97.11+/-2.93 %, V150 was 23.10+/-4.25 cc, V200 was 11.88+/-1.93 cc. All OAR constraints were met on all plans - Chest-Wall/Ribs (CW/Ribs) and Skin D 0.03cc was 103.40+/-9.23 % and 93.60+/-6.14 %, respectively. Aggregate analysis across all plans shows a clinically nonsignificant spread around the mean for all parameters considered. The robustness of SAVI treatment plans to minor variation in catheter digitization was proved through our multiuser study. Our study showed that SAVI planning constraints are stable within reasonable variation of digitization differences. Such uncertainty analysis is useful in standardization of digitization practices in a department and in defining action levels on digitization fixing request during a 2nd check., Competing Interests: Declaration of competing interest All authors and contributors involved in this process of carrying out this or writing the manuscript for this study have no conflicts of interests to disclose. Cite Sources of Support (if applicable): This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors., (Copyright © 2024. Published by Elsevier Inc.)

Single-fraction stereotactic radiosurgery (SRS) or fractionated SRS (FSRS) are well established strategies for patients with limited brain metastases. A broad spectrum of modern dedicated platforms are currently available for delivering intracranial SRS/FSRS; however, SRS/FSRS delivered using traditional CT-based platforms relies on the need for diagnostic MR images to be coregistered to planning CT scans for target volume delineation. Additionally, the on-board image guidance on traditional platforms yields limited inter-fraction and intra-fraction real-time visualization of the tumor at the time of treatment delivery. MR Linacs are capable of obtaining treatment planning MR and on-table MR sequences to enable visualization of the targets and organs-at-risk and may subsequently help identify anatomical changes prior to treatment that may invoke the need for on table treatment adaptation. Recently, an MR-guided intracranial package (MRIdian A3i BrainTx TM ) was released for intracranial treatment with the ability to perform high-resolution MR sequences using a dedicated brain coil and cranial immobilization system. The objective of this report is to provide, through the experience of our first patient treated, a comprehensive overview of the clinical application of our institutional program for FSRS adaptive delivery using MRIdian's A3i BrainTx system-highlights include reviewing the imaging sequence selection, workflow demonstration, and details in its delivery feasibility in clinical practice, and dosimetric outcomes., Competing Interests: Conflict of Interest All remaining authors declare no conflicts of interest., (Copyright © 2024 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.)

Introduction: This study compares four management paradigms for large brain metastasis (LMB): fractionated SRS (FSRS), staged SRS (SSRS), resection and postoperative-FSRS (postop-FSRS) or preoperative-SRS (preop-SRS)., Methods: Patients with LBM (≥ 2 cm) between July 2017 and January 2022 at a single tertiary institution were evaluated. Primary endpoints were local failure (LF), radiation necrosis (RN), leptomeningeal disease (LMD), a composite of these variables, and distant intracranial failure (DIF). Gray's test compared cumulative incidence, treating death as a competing risk with a random survival forests (RSF) machine-learning model also used to evaluate the data., Results: 183 patients were treated to 234 LBMs: 31.6% for postop-FSRS, 28.2% for SSRS, 20.1% for FSRS, and 20.1% for preop-SRS. The overall 1-year composite endpoint rates were comparable (21 vs 20%) between nonoperative and operative strategies, but 1-year RN rate was 8 vs 4% (p = 0.012), 1-year overall survival (OS) was 48 vs. 69% (p = 0.001), and 1-year LMD rate was 5 vs 10% (p = 0.052). There were differences in the 1-year RN rates (7% FSRS, 3% postop-FSRS, 5% preop-SRS, 10% SSRS, p = 0.037). With RSF analysis, the out-of-bag error rate for the composite endpoint was 47%, with identified top-risk factors including widespread extracranial disease, > 5 total lesions, and breast cancer histology., Conclusion: This is the first study to conduct a head-to-head retrospective comparison of four SRS methods, addressing the lack of randomized data in LBM literature amongst treatment paradigms. Despite patient characteristic trends, no significant differences were found in LF, composite endpoint, and DIF rates between non-operative and operative approaches., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Significant improvements within radioembolization imaging and dosimetry permit the development of an accurate and personalized pretreatment plan using technetium 99m-labeled macroaggregated albumin ( 99 m Tc-MAA) and single-photon emission computed tomography (SPECT) combined with anatomical CT (SPECT/CT). Despite these potential advantages, the clinical transition to pretreatment protocols with SPECT/CT is hindered by their unknown safety constraints. This study aimed to address this issue by establishing novel dose limits for 99 m Tc-MAA SPECT/CT to enable quantitative pretreatment planning., Methods and Materials: Stratification criteria to determine images most viable for dosimetry analysis were created from a cohort of 85 patients. SPECT/CT, cone beam CT, and activity calculations derived from the local deposition method were used to create an accurate pretreatment protocol. Planar and SPECT/CT images were compared using linear regression and modified Bland-Altman analyses to convert accepted planar dose limits to SPECT/CT. To validate these new dose limits, activity calculations based on SPECT/CT were compared with those calculated with the body surface area and planar methods for three treatment plans., Results: A total of 38 of 85 patients were deemed viable for dosimetry analysis. SPECT yielded greater lung shunt fractions (LSFs) than planar imaging when LSFs were <4.89%, whereas SPECT yielded lower LSFs than planar imaging when LSFs were >4.89%. Planar to SPECT/CT dose conversions were 0.76×, 0.70×, and 0.55× for the whole liver, normal liver, and lungs, respectively. Patients with SPECT LSFs ≤4.89% were safely treated with the direct application of planar lung dose limits. Activity calculations with the newly established SPECT/CT dose limits were greater than those of the body surface area method by a median range of 33.1% to 61.9% and were lower than planar-based activity calculations by a median range of 12.5% to 13.7% for the whole liver and by 29.4% to 32.2% for the normal liver., Conclusions: This study demonstrated a safe method for translating dose limits from 99 m Tc-MAA planar imaging to SPECT/CT. A robust pretreatment protocol was further developed guided by the current knowledge in the field. Established SPECT/CT dose limits safely treated 97.5% of patients and permitted the application of independent pretreatment planning with 99 m Tc-MAA SPECT/CT., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background and Purpose: Implementing any radiopharmaceutical therapy (RPT) program requires a comprehensive review of system readiness, appropriate workflows, and training to ensure safe and efficient treatment delivery. A quantitative assessment of the dose delivered to targets and organs at risk (OAR) using RPT is possible by correlating the absorbed doses with the delivered radioactivity. Integrating dosimetry into an established RPT program demands a thorough analysis of the necessary components and system fine-tuning. This study aims to report an optimized workflow for molecular radiation therapy using 177 Lu with a primary focus on integrating patient-specific dosimetry into an established radiopharmaceutical program in a radiation oncology setting., Materials and Methods: We comprehensively reviewed using the Plan-Do-Check-Act (PDCA) cycle, including efficacy and accuracy of delivery and all aspects of radiation safety of the RPT program. The GE Discovery SPECT/CT 670DR™ system was calibrated per MIM protocol for dose calculation on MIM SurePlan™ MRT software. Jaszcak Phantom with 15-20 mCi of 177 Lu DOTATATE with 2.5 µM EDTA solution was used, with the main energy window defined as 208 keV ±10% (187.6 to 229.2 keV); the upper scatter energy window was set to 240 keV ±5% (228 to 252 keV), while the lower scatter energy window was 177.8 keV ±5% (168.9 to 186.7 keV). Volumetric quality control tests and adjustments were performed to ensure the correct alignment of the table, NM, and CT gantry on SPECT/CT. A comprehensive end-to-end (E2E) test was performed to ensure workflow, functionality, and quantitative dose accuracy., Results: Workflow improvements and checklists are presented after systematically analyzing over 400 administrations of 177 Lu-based RPT. Injected activity to each sphere in the NEMA Phantom scan was quantified, and the MIM Sureplan MRT reconstruction images calculated activities within ±12% of the injected activity. Image alignment tests on the SPECT/CT showed a discrepancy of more than the maximum tolerance of 2.2 mm on any individual axis. As a result of servicing the machine and updating the VQC and COR corrections, the hybrid imaging system was adjusted to achieve an accuracy of <1 mm in all directions., Conclusion: Workflows and checklists, after analysis of system readiness and adequate training for staff and patients, are presented. Hardware and software components for patient-specific dosimetry are presented with a focus on hybrid image registration and correcting any errors that affect dosimetric quantification calculation. Moreover, this manuscript briefly overviews the necessary quality assurance requirements for converting diagnostic images into dosimetry measurement tools and integrating dosimetry for RPT based on 177 Lu., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 George, Tolakanahalli, Aguirre, Kim, Samuel and Mishra.)

Purpose: This is the first reporting of the MRIdian A3i TM intracranial package (BrainTx TM ) and benchmarks the end-to-end localization and dosimetric accuracy for commissioning an magnetic resonace (MR)-guided stereotactic radiosurgery program. We characterized the localization accuracy between MR and radiation (RT) isocenter through an end-to-end hidden target test, relative dose profile intercomparison, and absolute dose validation., Methods and Materials: BrainTx consists of a dedicated head coil, integrated mask immobilization system, and high-resolution MR sequences. Coil and baseplate attenuation was quantified. An in-house phantom (Cranial phantOm foR magNetic rEsonance Localization of a stereotactIc radiosUrgery doSimeter, CORNELIUS) was developed from a mannequin head filled with silicone gel, film, and MR BB with pinprick. A hidden target test evaluated MR-RT localization of the 1×1×1 mm 3 TrueFISP MR and relative dose accuracy in film for a 1 cm diameter (International Electrotechnical Commission (IEC)-X/IEC-Y) and 1.5 cm diameter (IEC-Y/IEC-Z) spherical target. Two clinical cases (irregular-shaped target and target abutting brainstem) were mapped to the CORNELIUS phantom for feasibility assessment. A 2-dimensional (2D)-gamma compared calculated and measured dose for spherical and clinical targets with 1 mm/1% and 2 mm/2% criteria, respectively. A small-field chamber (A26MR) measured end-to-end absolute dose for a 1 cm diameter target., Results: Coil and baseplate attenuation were 0.7% and 2.7%, respectively. The displacement of MR to RT localization as defined through the pinprick was 0.49 mm (IEC-X), 0.27 mm (IEC-Y), and 0.51 mm (IEC-Z) (root mean square 0.76 mm). The reproducibility across IEC-Y demonstrated high fidelity (<0.02 mm). Gamma pass rates were 97.1% and 95.4% for 1 cm and 1.5 cm targets, respectively. Dose profiles for an irregular-shaped target and abutting organ-at-risk-target demonstrated pass rates of 99.0% and 92.9%, respectively. The absolute end-to-end dose difference was <1%., Conclusions: All localization and dosimetric evaluation demonstrated submillimeter accuracy, per the TG-142, TG-101, MPPG 9.a. criteria for SRS/SRT systems, indicating acceptable delivery capabilities with a 1 mm setup margin., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Radiotherapy for ultracentral lung tumors represents a treatment challenge, considering the high rates of high-grade treatment-related toxicities with stereotactic body radiation therapy (SBRT) or hypofractionated schedules. Accelerated hypofractionated magnetic resonance-guided adaptive radiation therapy (MRgART) emerged as a potential game-changer for tumors in these challenging locations, in close proximity to central organs at risk, such as the trachea, proximal bronchial tree, and esophagus. In this series, 13 consecutive patients, predominantly male ( n = 9), with a median age of 71 (range (R): 46-85), underwent 195 MRgART fractions (all 60 Gy in 15 fractions) to metastatic ( n = 12) or primary ultra-central lung tumors ( n = 1). The median gross tumor volumes (GTVs) and planning target volumes (PTVs) were 20.72 cc (R: 0.54-121.65 cc) and 61.53 cc (R: 3.87-211.81 cc), respectively. The median beam-on time per fraction was 14 min. Adapted treatment plans were generated for all fractions, and indications included GTV/PTV undercoverage, OARs exceeding tolerance doses, or both indications in 46%, 18%, and 36% of fractions, respectively. Eight patients received concurrent systemic therapies, including immunotherapy (four), chemotherapy (two), and targeted therapy (two). The crude in-field loco-regional control rate was 92.3%. No CTCAE grade 3+ toxicities were observed. Our results offer promising insights, suggesting that MRgART has the potential to mitigate toxicities, enhance treatment precision, and improve overall patient care in the context of ultracentral lung tumors.

Purpose: This study evaluates the outcomes of recurrent brain metastasis treated with resection and brachytherapy using a novel Cesium-131 carrier, termed surgically targeted radiation therapy (STaRT), and compares them to the first course of external beam radiotherapy (EBRT)., Methods: Consecutive patients who underwent STaRT between August 2020 and June 2022 were included. All patients underwent maximal safe resection with pathologic confirmation of viable disease prior to STaRT to 60 Gy to a 5-mm depth from the surface of the resection cavity. Complications were assessed using CTCAE version 5.0., Results: Ten patients with 12 recurrent brain metastases after EBRT (median 15.5 months, range: 4.9-44.7) met the inclusion criteria. The median BED 10Gy 90% and 95% were 132.2 Gy (113.9-265.1 Gy) and 116.0 Gy (96.8-250.6 Gy), respectively. The median maximum point dose BED 10Gy for the target was 1076.0 Gy (range: 120.7-1478.3 Gy). The 6-month and 1-year local control rates were 66.7% and 33.3% for the prior EBRT course; these rates were 100% and 100% for STaRT, respectively (p < 0.001). At a median follow-up of 14.5 months, there was one instance of grade two radiation necrosis. Surgery-attributed complications were observed in two patients including pseudomeningocele and minor headache., Conclusions: STaRT with Cs-131 presents an alternative approach for operable recurrent brain metastases and was associated with superior local control than the first course of EBRT in this series. Our initial clinical experience shows that STaRT is associated with a high local control rate, modest surgical complication rate, and low radiation necrosis risk in the reirradiation setting., (Copyright © 2023 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study is to investigate inter-planner plan quality variability using a manual forward planning (MFP)- or fast inverse planning (FIP, Lightning)-approach for single brain lesions treated with the Gamma Knife ® (GK) Icon™., Methods: Thirty patients who were previously treated with GK stereotactic radiosurgery or radiotherapy were selected and divided into three groups (post-operative resection cavity, intact brain metastasis, and vestibular schwannoma [10 patients per group]). Clinical plans for the 30 patients were generated by multiple planners using FIP only (1), a combination of FIP and MFP (12), and MFP only (17). Three planners (Senior, Junior, and Novice) with varying experience levels re-planned the 30 patients using MFP and FIP (two plans per patient) with planning time limit of 60 min. Statistical analysis was performed to compare plan quality metrics (Paddick conformity index, gradient index, number of shots, prescription isodose line, target coverage, beam-on-time (BOT), and organs-at-risk doses) of MFP or FIP plans among three planners and to compare plan quality metrics between each planner's MFP/FIP plans and clinical plans. Variability in FIP parameter settings (BOT, low dose, and target max dose) and in planning time among the planners was also evaluated., Results: Variations in plan quality metrics of FIP plans among three planners were smaller than those of MFP plans for all three groups. Junior's MFP plans were the most comparable to the clinical plans, whereas Senior's and Novice's MFP plans were superior and inferior, respectively. All three planners' FIP plans were comparable or superior to the clinical plans. Differences in FIP parameter settings among the planners were observed. Planning time was shorter and variations in planning time among the planners were smaller for FIP plans in all three groups., Conclusions: The FIP approach is less planner dependent and more time-honored than the MFP approach., (© 2023 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

For patients with newly diagnosed glioblastoma, the current standard-of-care includes maximal safe resection, followed by concurrent chemoradiotherapy and adjuvant temozolomide, with tumor treating fields. Traditionally, diagnostic imaging is performed pre- and post-resection, without additional dedicated longitudinal imaging to evaluate tumor volumes or other treatment-related changes. However, the recent introduction of MR-guided radiotherapy using the ViewRay MRIdian A3i system includes a dedicated BrainTx package to facilitate the treatment of intracranial tumors and provides daily MR images. We present the first reported case of a glioblastoma imaged and treated using this workflow. In this case, a 67-year-old woman underwent adjuvant chemoradiotherapy after gross total resection of a left frontal glioblastoma. The radiotherapy treatment plan consisted of a traditional two-phase design (46 Gy followed by a sequential boost to a total dose of 60 Gy at 2 Gy/fraction). The treatment planning process, institutional workflow, treatment imaging, treatment timelines, and target volume changes visualized during treatment are presented. This case example using our institutional A3i system workflow successfully allows for imaging and treatment of primary brain tumors and has the potential for margin reduction, detection of early disease progression, or to detect the need for dose adaptation due to interfraction tumor volume changes., Competing Interests: Conflicts of Interest M.P.M: Consulting Fees from Karyopharm, KAzia Therapeutics, Sapience, Zap, Mevion, Xoft; BOD Oncoceutics; Stock in Chimerix. RK: Honoraria from Accuray Inc., Elekta AB, ViewRay Inc., Novocure Inc., Elsevier Inc., Brainlab, Kazia Therapeutics, Castle Biosciences, and institutional research funding from Medtronic Inc., Blue Earth Diagnostics Ltd., Novocure Inc., GT Medical Technologies, AstraZeneca, Exelixis, ViewRay Inc., Brainlab, Cantex Pharmaceuticals, and Kazia Therapeutics. KM: reports ownership interest in a company that provides consulting services on image guided radiation therapy technology (MR Guidance, LLC.). She received travel reimbursement/consulting fees/speaking fees/grants from ViewRay Inc. ANG: Honoraria from ViewRay, Inc., Elekta AB, IBA AB. YO: Trial Support: Chimerix, MimiVax LLC, Karyopharm; Consulting: Istari Oncology, PharPoint Research, Novocure; DSMB: GammaTile, Actuate. MSA: Consultation: Bayer, Novocure, Kiyatec, Insightec, GSK, Xoft, Nuvation, Cellularity, SDP Oncology, Apollomics, Prelude, Janssen, Tocagen, Voyager Therapeutics, Viewray, Caris Lifesciences, Pyramid Biosciences, Anheart Therapeutics, Varian Medical Systems. Scientific Advisory Board: Cairn Therapeutics, Pyramid Biosciences, ModifiBio. Stock shareholder: Mimivax, Cytodyn, MedInnovate Advisors LLC. All remaining authors declare no conflicts of interest., (Copyright © 2023 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.)

Purpose: This article describes our experience in implementation of superficial radiation therapy (SRT) using SRT-100 Vision™ for non-melanoma skin cancer., Methods: Following the American Association of Physicists in Medicine Task Group-61 protocol, absolute output (absorbed dose to water at surface (cGy/min)) was measured for three energies (50, 70, and 100 kV) and for six applicators (1.5-5.0 cm in diameter). Percent depth dose (PDD) and profiles were also measured. Timer testing and ultrasound testing were performed. A treatment time calculation worksheet was created. Quality assurance (QA) of SRT-100 Vision was implemented. After treatment workflow for our clinic was developed, end-to-end (E2E) testing was performed using a Rando phantom. Considerations for treatment using SRT-100 Vision were made., Results: Absolute output (cGy/min) decreases as energy increases and applicator size decreases. Due to scatter from the applicator, PDD at depths ≤5 mm does not follow conventional trends but PDD at depths ≥15 mm increases with increasing applicator size. Profiles for the 5 cm applicator do not have strong dependence on depth except profiles at 5 mm for 50 kV. Timer/end errors are negligible for all three energies. Ultrasound images confirm allowed field of view and depth as well as no image artifacts and spatial integrity. Daily, monthly and annual QA of SRT-100 Vision implemented in our clinic is listed in a table format. E2E testing results (<1%) demonstrate the functionality and performance of our treatment workflow. Our considerations for SRT treatment include patient, applicator size and energy selections, patient setup, and shields., Conclusions: This article is expected to serve as guidance for Radiation Oncology and/or Dermatology clinics aspiring to initiate an SRT program in their clinics., (© 2023 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

Objectives: The objective of this study is to evaluate the user-defined optimization settings in the Fast Inverse Planning (FIP) optimizer in Leksell GammaPlan® and determine the parameters that result in the best stereotactic radiosurgery (SRS) plan quality for brain metastases, benign tumors, and arteriovenous malformations (AVMs)., Methods: Thirty patients with metastases and 30 with benign lesions-vestibular schwannoma, AVMs, pituitary adenoma, and meningioma-treated with SRS were evaluated. Each target was planned by varying the low dose (LD) and beam-on-time (BOT) penalties in increments of 0.1, from 0 to 1. The following plan quality metrics were recorded for each plan: Paddick conformity index (PCI), gradient index (GI), BOT, and maximum organ-at-risk (OAR) doses. A novel objective score matrix was calculated for each target using a linearly weighted combination of the aforementioned metrics. A histogram of optimal solutions containing the five best scores was extracted., Results: A total of 7260 plans were analyzed with 121 plans per patient for the range of LD/BOT penalties. The ranges of PCI, GI, and BOT across all metastatic lesions were 0.58-0.97, 2.1-3.8, and 8.8-238 min, respectively, and were 0.13-0.97, 2.1-3.8, and 8.8-238 min, respectively, for benign lesions. The objective score matrix showed unique optimal solutions for metastatic lesions and benign lesions. Additionally, the plan metrics of the optimal solutions were significantly improved compared to the clinical plans for metastatic lesions with equivalent metrics for all other cases., Conclusion: In this study, FIP optimizer was evaluated to determine the optimal solution space to maximize PCI and minimize GI, BOT and OAR doses simultaneously for single metastatic/benign/non-neoplastic targets. The optimal solution chart was determined using a novel objective score which provides novice and expert planners a roadmap to generate the most optimal plans efficiently using FIP., (© 2023 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

We evaluated the effect of lesion number and volume for brain metastasis treated with SRS using GammaKnife ® ICON™ (GK) and CyberKnife ® M6™ (CK). Four sets of lesion sizes (<5 mm, 5-10 mm, >10-15 mm, and >15 mm) were contoured and prescribed a dose of 20 Gy/1 fraction. The number of lesions was increased until a threshold mean brain dose of 8 Gy was reached; then individually optimized to achieve maximum conformity. Across GK plans, mean brain dose was linearly proportional to the number of lesions and total GTV for all sizes. The numbers of lesions needed to reach this threshold for GK were 177, 57, 29, and 10 for each size group, respectively; corresponding total GTVs were 3.62 cc, 20.37 cc, 30.25 cc, and 57.96 cc, respectively. For CK, the threshold numbers of lesions were 135, 35, 18, and 8, with corresponding total GTVs of 2.32 cc, 12.09 cc, 18.24 cc, and 41.52 cc respectively. Mean brain dose increased linearly with number of lesions and total GTV while V8 Gy, V10 Gy, and V12 Gy showed quadratic correlations to the number of lesions and total GTV. Modern dedicated intracranial SRS systems allow for treatment of numerous brain metastases especially for ≤10 mm; clinical evidence to support this practice is critical to expansion in the clinic.

Given the positive results from recent randomized controlled trials in patients with oligometastatic, oligoprogressive, or oligoresidual disease, the role of radiotherapy has expanded in patients with metastatic non-small cell lung cancer (NSCLC). While small metastatic lesions are commonly treated with stereotactic body radiotherapy (SBRT), treatment of the primary tumor and involved regional lymph nodes may require prolonged fractionation schedules to ensure safety especially when treating larger volumes in proximity to critical organs-at-risk (OARs). We have developed an institutional MR-guided adaptive radiotherapy (MRgRT) workflow for these patients. We present a 71-year-old patient with stage IV NSCLC with oligoprogression of the primary tumor and associated regional lymph nodes in which MR-guided, online adaptive radiotherapy was performed, prescribing 60 Gy in 15 fractions. We describe our workflow, dosimetric constraints, and daily dosimetric comparisons for the critical OARs (esophagus, trachea, and proximal bronchial tree [PBT] maximum doses [D 0.03cc ]), in comparison to the original treatment plan recalculated on the anatomy of the day (i.e., predicted doses). During MRgRT, few fractions met the original dosimetric objectives: 6.6% for esophagus, 6.6% for PBT, and 6.6% for trachea. Online adaptive radiotherapy reduced the cumulative doses to the structures by 11.34%, 4.2%, and 5.62% when comparing predicted plan summations to the final delivered summation. Therefore, this case study presets a workflow and treatment paradigm for accelerated hypofractionated MRgRT due to the significant variations in daily dose to the central thoracic OARs to reduce treatment-related toxicity associated with radiotherapy., (Copyright © 2023 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.)

Total body irradiation (TBI) is used with chemotherapy to induce immunosuppression for hematopoietic cell transplantation and is often administered using lead blocks to minimize lung dose in adults and children. This technique is challenging in infants and young children. A 13-month-old female with acute lymphoblastic leukemia (ALL) was treated with fractionated TBI to a dose of 12 Gy in eight fractions delivered twice daily. Multiple TBI techniques for delivering treatment were considered. Ultimately, treatment using helical tomotherapy was selected in order to spare and accurately quantify the dose to the lung, meet lung dose constraints, and ensure adequate TBI dose coverage. With anesthesia, this technique provided a comfortable and reproducible set-up for the young child. The treatment plan was delivered with intensity-modulated radiotherapy, where 96.4% of the target volume received a prescription dose with a total beam-on time of 16.8 minutes. The mean lung dose was 7.7 Gy for a total lung volume of 245cc. This report describes the challenges faced during the treatment planning and delivery, and how they were resolved., Competing Interests: The authors have declared financial relationships, which are detailed in the next section., (Copyright © 2022, Abraham et al.)

Background: Stereotactic radiosurgery (SRS) is increasingly used for brain metastases (BM) patients, but distant intracranial failure (DIF) remains the principal disadvantage of this focal therapeutic approach. The objective of this study was to determine if dedicated SRS imaging would improve lesion detection and reduce DIF., Methods: Between 02/2020 and 01/2021, SRS patients at a tertiary care institution underwent dedicated treatment planning MRIs of the brain including MPRAGE and SPACE post-contrast sequences. DIF was calculated using the Kaplan-Meier method; comparisons were made to a historical consecutive cohort treated using MPRAGE alone (02/2019-01/2020)., Results: 134 patients underwent 171 SRS courses for 821 BM imaged with both MPRAGE and SPACE (primary cohort). MPRAGE sequence evaluation alone detected 679 lesions. With neuroradiologists evaluating SPACE and MPRAGE, an additional 108 lesions were identified (p < 0.001). Upon multidisciplinary review, 34 additional lesions were identified. Compared to the historical cohort (103 patients, 135 SRS courses, 479 BM), the primary cohort had improved median time to DIF (13.5 vs. 5.1 months, p = 0.004). The benefit was even more pronounced for patients treated for their first SRS course (18.4 vs. 6.3 months, p = 0.001). SRS using MPRAGE and SPACE was associated with a 60% reduction in risk of DIF compared to the historical cohort (HR: 0.40; 95% CI: 0.28-0.57, p < 0.001)., Conclusions: Among BM patients treated with SRS, a treatment planning SPACE sequence in addition to MPRAGE substantially improved lesion detection and was associated with a statistically significant and clinically meaningful prolongation in time to DIF, especially for patients undergoing their first SRS course., Competing Interests: Conflicts of interest Tugce Kutuk: None. Kevin J. Abrams: Consultant: Keystone Heart, Viz.Ai Stock: Keystone Heart, Viz.Ai, Cleerly. Martin C Tom: Honoraria from ViewRay. Institutional research funding from Blue Earth Diagnostics. Ltd. Personal fees from Elsevier. Charif Sidani: None. Haley Appel: Honoraria for Novocure Inc. Matthew D Hall: Honorarium from Accuray, Inc. Proton Collaborative Group Executive Committee Institutional Representative and Voting Member, Miami Cancer Institute (unpaid). Grant Funding: Live Like Bella Pediatric Cancer Research Initiative, Florida Department of Health Grant 8LA04. Ranjini Tolakanahalli: None. D Jay J Wieczorek: None. Alonso N Gutierrez: Honoraria from ViewRay, Inc., Elekta AB, IBA. Muni Rubens: None. Michael W McDermott: Consultant Deinde Medical and Stryker Medical. Manmeet S Ahluwalia: Receipt of grants/research supports: Astrazeneca, Abbvie, BMS, Bayer, Incyte, Pharmacyclics, Novocure, Merck. Stock shareholder: Doctible, Mimivax. Receipt of honoraria or consultation fees: Elsevier, Wiley, Abvvie, VBI Vaccines, Bayer, karyopharm, Tocagen, Forma therapeutics. Minesh P Mehta: Consulting Fees from Karyopharm, Sapience, Zap, Mevion, Xoft; BOD Oncoceutics; Stock in Chimerix. Rupesh Kotecha: Honoraria from Accuray Inc., Elekta AB, ViewRay Inc., Novocure Inc., Elsevier Inc., and Brainlab and institutional research funding from Medtronic Inc., Blue Earth Diagnostics Ltd., Novocure Inc., GT Medical Technologies, AstraZeneca, Exelixis, ViewRay Inc., and Brainlab., (Copyright © 2022 Elsevier B.V. All rights reserved.)

We compared the clinical outcomes of BM treated with mask immobilization with zero-SM (i.e., zero-PTV) to standard zero-SM frame immobilization SRS. Consecutive patients with BM, 0.5−2.0 cm in maximal diameter, treated with single-fraction SRS (22−24 Gy) during March 2019−February 2021 were included. Univariable and multivariable analysis were performed using the Kaplan−Meier method and Cox proportional hazards regression. A total of 150 patients with 453 BM met inclusion criteria. A total of 129 (28.5%) lesions were treated with a zero-SM mask immobilization and 324 (71.5%) with zero-SM frame immobilization. Frame immobilization treatments were associated with a higher proportion of gastrointestinal and fewer breast-cancer metastases (p = 0.024), and a higher number of treated lesions per SRS course (median 7 vs. 3; p < 0.001). With a median follow up of 15 months, there was no difference in FFLF between the mask and frame immobilization groups on univariable (p = 0.29) or multivariable analysis (p = 0.518). Actuarial FFLF at 1 year was 90.5% for mask and 92% for frame immobilization (p = 0.272). Radiation necrosis rates at 1 year were 12.5% for mask and 4.1% for frame immobilization (p = 0.502). For BM 0.5−2.0 cm in maximal diameter treated with single-fraction SRS using 22−24 Gy, mask immobilization with zero SM produces comparable clinical outcomes to frame immobilization. The initial findings support omitting a SM when using mask immobilization with this treatment approach on a Gamma Knife® Icon™.

Purpose: The objective was to describe PRDR outcomes and report EQD2 OAR toxicity thresholds., Methods: Eighteen patients with recurrent primary CNS tumors treated with PRDR at a single institution between April 2017 and September 2021 were evaluated. The radiotherapy details, cumulative OAR doses, progression-free survival (PFS), overall survival (OS), and toxicities were collected., Results: The median PRDR dose was 45 Gy (range: 36-59.4 Gy); the median cumulative EQD2 prescription dose was 102.7 Gy (range: 93.8-120.4 Gy). The median cumulative EQD2 D 0.03cc for the brain was 111.4 Gy (range: 82.4-175.2 Gy). Symptomatic radiation necrosis occurred in three patients, for which the median EQD2 brain D 0.03cc was 115.9 Gy (110.4-156.7 Gy). The median PFS and OS after PRDR were 6.3 months (95%CI: 0.9-11.6 months) and 8.6 months (95%CI: 4.9-12.3 months), respectively. The systematic review identified five peer-reviewed studies with a median cumulative EQD2 prescription dose of 110.3 Gy. At a median follow-up of 8.7 months, the median PFS and OS were 5.7 months (95%CI: 2.1-15.4 months) and 6.7 months (95%CI: 3.2-14.2 months), respectively., Conclusion: PRDR re-irradiation is a relatively safe and feasible treatment for recurrent primary CNS tumors. Despite high cumulative dose to OARs, the risk of high-grade, treatment-related toxicity within the first year of follow-up remains acceptable.

To compare stereotactic radiosurgery (SRS) plan quality metrics of manual forward planning (MFP) and Elekta Fast Inverse Planning™ (FIP)-based inversely optimized plans for patients treated with Gamma Knife®. Clinically treated, MFP SRS plans for 100 consecutive patients (115 lesions; 67 metastatic and 48 benign) were replanned with the FIP dose optimizer based on a convex linear programming formulation. Comparative plans were generated to match or exceed the following metrics in order of importance: Target Coverage (TC), Paddick Conformity Index (PCI), beam-on time (BOT), and Gradient Index (GI). Plan quality metrics and delivery parameters between MFP and FIP were compared for all lesions and stratified into subgroups for further analysis. Additionally, performance of FIP for multiple punctate (<4 mm) metastatic lesions on a subset of cases was investigated. A Wilcoxon signed-rank test for non-normal distributions was used to assess the statistical differences between the MFP and FIP treatment plans. Overall, 76% (87/115) of FIP plans showed a statistically significant improvement in plan quality compared to MFP plans. As compared to MFP, FIP plans demonstrated an increase in the median PCI by 1.1% (p<0.01), a decrease in GI by 3.7% (p< 0.01), and an increase in median number of shots by 74% (p< 0.01). TC and BOT were not statistically significantly different between MFP and FIP plans (p>0.05). FIP plans showed a statistically significant increase in use of 16 mm (p< 0.01) and blocked shots (p< 0.01), with a corresponding decrease in 4 mm shots (p< 0.01). Use of multiple shots per coordinate was significantly higher in FIP plans (p<0.01). The FIP optimizer failed to generate a clinically acceptable plan in 4/115 (3.5%) lesions despite optimization parameter changes. The mean optimization time for FIP plans was 5.0 min (Range: 1.0 - 10.0 min). In the setting of multiple punctate lesions, PCI for FIP was significantly improved (p<0.01) by changing the default low-dose/BOT penalty optimization setting from a default of 50/50 to 75-85/40. FIP offers a significant reduction in manual effort for SRS treatment planning while achieving comparable plan quality to an expert planner-substantially improving overall planning efficiency. FIP plans employ a non-intuitive increased use of blocked sectors and shot-in-shot technique to achieve high quality plans. Several FIP plans failed to achieve clinically acceptable treatments and warrant further investigation., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The objective of this study was to evaluate the impact of the time interval between planning imaging and stereotactic radiosurgery (SRS) delivery on tumor volumes and spatial anatomic displacements of brain metastases (BM)., Methods: Consecutive patients diagnosed with BM treated with SRS over a 3-year period were evaluated. Only patients who underwent an institutionally standardized diagnostic MRI (MRI-1) and a treatment planning MRI (MRI-2) were included. The impact of histology, inter-scan time interval, lesion location, tumor volume, and diameter were evaluated on final lesion diameter, volume, anatomic displacement, and ultimate need for change in management (ie, expanding margins, rescanning)., Results: 101 patients (531 lesions) with a median inter-scan time interval of 8 days (range: 1-42 days) met the inclusion criteria. The median percentage increase in BM diameter and volume were 9.5% (IQR: 2.25%-24.0%) and 20% (IQR: 0.7%-66.7%). Overall, 147 lesions (27.7%) in 57 patients (56.4%) required a change in management. There was a statistically significant relationship between initial tumor diameter (cm) and change in management (OR: 2.69, 95% CI: 1.93-3.75; P < .001). Each day between MRI-1 and MRI-2 was associated with a change in management with an OR of 1.05 (95% CI: 1.03-1.07; P < .001)., Conclusions: Changes in tumor diameter, volume, and spatial position occur as a function of time. Planning imaging for SRS is recommended to occur in close temporal proximity to treatment; for those with delays, a larger setup margin may need to be used to ensure tumor coverage and account for positional changes., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Neuro-Oncology and the European Association of Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

This study focuses on predicting breathing pattern, which is crucial to deal with system latency in the treatments of moving lung tumors. Predicting respiratory motion in real-time is challenging, due to the inherent chaotic nature of breathing patterns, i.e. sensitive dependence on initial conditions. In this work, nonlinear prediction methods are used to predict the short-term evolution of the respiratory system for 62 patients, whose breathing time series was acquired using respiratory position management (RPM) system. Single step and N-point multi step prediction are performed for sampling rates of 5 Hz and 10 Hz. We compare the employed non-linear prediction methods with respect to prediction accuracy to Adaptive Infinite Impulse Response (IIR) prediction filters. A Local Average Model (LAM) and local linear models (LLMs) combined with a set of linear regularization techniques to solve ill-posed regression problems are implemented. For all sampling frequencies both single step and N-point multi step prediction results obtained using LAM and LLM with regularization methods perform better than IIR prediction filters for the selected sample patients. Moreover, since the simple LAM model performs as well as the more complicated LLM models in our patient sample, its use for non-linear prediction is recommended., (Copyright © 2015 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Purpose: Local failure rates after radiation therapy (RT) for locally advanced non-small-cell lung cancer (NSCLC) remain high. Consequently, RT dose intensification strategies continue to be explored, including hypofractionation, which allows for RT acceleration that could potentially improve outcomes. The maximum-tolerated dose (MTD) with dose-escalated hypofractionation has not been adequately defined., Patients and Methods: Seventy-nine patients with NSCLC were enrolled on a prospective single-institution phase I trial of dose-escalated hypofractionated RT without concurrent chemotherapy. Escalation of dose per fraction was performed according to patients' stratified risk for radiation pneumonitis with total RT doses ranging from 57 to 85.5 Gy in 25 daily fractions over 5 weeks using intensity-modulated radiotherapy. The MTD was defined as the maximum dose with ≤ 20% risk of severe toxicity., Results: No grade 3 pneumonitis was observed and an MTD for acute toxicity was not identified during patient accrual. However, with a longer follow-up period, grade 4 to 5 toxicity occurred in six patients and was correlated with total dose (P = .004). An MTD was identified at 63.25 Gy in 25 fractions. Late grade 4 to 5 toxicities were attributable to damage to central and perihilar structures and correlated with dose to the proximal bronchial tree., Conclusion: Although this dose-escalation model limited the rates of clinically significant pneumonitis, dose-limiting toxicity occurred and was dominated by late radiation toxicity involving central and perihilar structures. The identified dose-response for damage to the proximal bronchial tree warrants caution in future dose-intensification protocols, especially when using hypofractionation., Competing Interests: Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Purpose: Prediction methods for breathing patterns, which are crucial to deal with system latency in treatments of moving lung tumors using state-space methodologies based on non-linear dynamics are contrasted to linear predictive methods., Method and Materials: In our previous work we established that breathing patterns can be described as a 5-6 dimensional nonlinear, stationary and deterministic system that exhibits sensitive dependence on initial conditions. In this work, nonlinear prediction methods are used to predict the short-term evolution of the respiratory system for 3 patients. Single step and N-point multi step prediction are performed for sampling rates of 5Hz, 10Hz, and 30Hz. We compare the employed nonlinear prediction methods with respect to prediction accuracy to Infinite Impulse Response (IIR) prediction filters. The simplest form of local prediction is finding similar segments of scalar time series data in a higher dimensional embedding space. Hence, we predict the future value x(t)of N-time steps ahead by simply finding the average of nearest neighbor points to the point x(t) in the past and using them to estimate x(t+N), yielding a local average model (LAM). Local linear models (LLM) which are linear autoregressive models that hold only for a region around the target point formed by the nearest neighbor points is combined with a set of linear regularization techniques to solve ill-posed regression problems are also implemented., Results: For all sampling frequencies, both single step and N-point multi step prediction results obtained using LAM and LLM with regularization methods are better than IIR prediction filters for the selected sample patients., Conclusions: The use of non-linear prediction methods for predicting the breathing pattern of lung cancer patients may lead to improved, robust and accurate long-term prediction to account for system latencies., (© 2012 American Association of Physicists in Medicine.)

This study highlights the use of adaptive planning to accommodate testicular shielding in helical tomotherapy for malignancies of the proximal thigh. Two cases of young men with large soft tissue sarcomas of the proximal thigh are presented. After multidisciplinary evaluation, preoperative radiation therapy was recommended. Both patients were referred for sperm banking and lead shields were used to minimize testicular dose during radiation therapy. To minimize imaging artifacts, kilovoltage CT (kVCT) treatment planning was conducted without shielding. Generous hypothetical contours were generated on each "planning scan" to estimate the location of the lead shield and generate a directionally blocked helical tomotherapy plan. To ensure the accuracy of each plan, megavoltage fan-beam CT (MVCT) scans were obtained at the first treatment and adaptive planning was performed to account for lead shield placement. Two important regions of interest in these cases were femurs and femoral heads. During adaptive planning for the first patient, it was observed that the virtual lead shield contour on kVCT planning images was significantly larger than the actual lead shield used for treatment. However, for the second patient, it was noted that the size of the virtual lead shield contoured on the kVCT image was significantly smaller than the actual shield size. Thus, new adaptive plans based on MVCT images were generated and used for treatment. The planning target volume was underdosed up to 2% and had higher maximum doses without adaptive planning. In conclusion, the treatment of the upper thigh, particularly in young men, presents several clinical challenges, including preservation of gonadal function. In such circumstances, adaptive planning using MVCT can ensure accurate dose delivery even in the presence of high-density testicular shields., (Published by Elsevier Inc.)

Purpose: To demonstrate that Recurrence quantification analysis (RQA) can be used as a quantitative decision making tool to classify patients breathing pattern and select treatment strategy for maneuvering the tumor motion : (a) MIP based treatment (b) 4D treatment using non-linear prediction only (c) 4D treatment non-linear control prediction and breathing control., Method and Materials: In our previous work we established that breathing patterns can be described as a 5-6 dimensional nonlinear, stationary and deterministic system that exhibits sensitive dependence on initial conditions. Recurrence plots enable one to investigate an m-dimensional state space trajectory through a two-dimensional representation of its recurrences where the value of a specific pixel is 1 if the distance between the two corresponding trajectory points is less than a threshold value ε. Important measures calculated are: Recurrence Rate (RR), %Determinism, Divergence, Shannon Entropy, LMean, and Renyi entropy (K2). Time Resolved RQA: By implementing a sliding window design, each of the above calculated parameters is computed multiple times. Alignment of those parameters with the time series reveals details not obvious in the 1 -dimensional time series data. The breathing pattern for seven randomly chosen volunteers were recorded using the RPM system for 15 minutes. Non-linear prediction was performed and the normalized root mean square error (NRMSE) was calculated for each of the volunteer data., Results: The threshold value ε was chosen such that the Recurrence Rate was equal to 1%. There is a strong correlation of NRMSE with Entropy, Determinism and LMean. Time resolved RR locates strong Unstable Periodic Orbits(UPOs), i.e. patterns of uninterrupted equally spaced diagonal lines., Conclusions: RQAs could prove to be a very powerful tool for design of personalized treatment regimen. Entropy, Determinism in conjunction with strong UPOs can be used to determine if patients are suitable candidates for prediction and chaos control., (© 2012 American Association of Physicists in Medicine.)

Purpose: To design a methodology based on numerical phantom for reconstruction of dose delivered to moving lung tumors., Methods: MatlabTM 7.6 was used to generate a 4D numerical lung phantom (NLP). Customer parameter files were used as input to this NLP, which consists of multiple ellipsoids representing body, lung, cord and tumor. In this study, we studied the impact of varying breathing pattern on a left lower lobe tumor, where the tumor motion was simulated on the daily breathing pattern of the patient acquired using real time positioning management (RPMTM) system from Varian Medical Systems. Based on the daily breathing pattern, the original RPM signal and the original tumor trajectory, 5 sets of motion trajectories were simulated. This was then used to build 10 different phases of the numerical phantom. Average Intensity Projection (AIP) was then generated from the different phases. The actual delivered dose on the 5 AIP sets were compared to the intended dose on the original planning AIP image set., Results: The mean target coverage (TC) recomputed on the 5 AIP sets was approximately 18% lower than the TC for the planning AIP image set. The mean homogeneity index (HI) recomputed on the 5 sets, was approximately 5 times higher than HI for the planning AIP image set. The lung NTDmean dose was approximately 9.5 Gy3 and did not differ much., Conclusions: The presented numerical simulation framework may assist in monitoring the changes in dose accumulation due to changes in the patient's breathing on a daily basis. This can also be used for validation of new motion tracking algorithms and its impact of dose coverage., (© 2012 American Association of Physicists in Medicine.)

The underlying requirements for successful implementation of any efficient tumour motion management strategy are regularity and reproducibility of a patient's breathing pattern. The physiological act of breathing is controlled by multiple nonlinear feedback and feed-forward couplings. It would therefore be appropriate to analyse the breathing pattern of lung cancer patients in the light of nonlinear dynamical system theory. The purpose of this paper is to analyse the one-dimensional respiratory time series of lung cancer patients based on nonlinear dynamics and delay coordinate state space embedding. It is very important to select a suitable pair of embedding dimension 'm' and time delay 'τ' when performing a state space reconstruction. Appropriate time delay and embedding dimension were obtained using well-established methods, namely mutual information and the false nearest neighbour method, respectively. Establishing stationarity and determinism in a given scalar time series is a prerequisite to demonstrating that the nonlinear dynamical system that gave rise to the scalar time series exhibits a sensitive dependence on initial conditions, i.e. is chaotic. Hence, once an appropriate state space embedding of the dynamical system has been reconstructed, we show that the time series of the nonlinear dynamical systems under study are both stationary and deterministic in nature. Once both criteria are established, we proceed to calculate the largest Lyapunov exponent (LLE), which is an invariant quantity under time delay embedding. The LLE for all 16 patients is positive, which along with stationarity and determinism establishes the fact that the time series of a lung cancer patient's breathing pattern is not random or irregular, but rather it is deterministic in nature albeit chaotic. These results indicate that chaotic characteristics exist in the respiratory waveform and techniques based on state space dynamics should be employed for tumour motion management.

X-ray scatter is a significant problem in cone-beam computed tomography when thicker objects and larger cone angles are used, as scattered radiation can lead to reduced contrast and CT number inaccuracy. Advances have been made in x-ray computed tomography (CT) by incorporating a high quality prior image into the image reconstruction process. In this paper, we extend this idea to correct scatter-induced shading artifacts in cone-beam CT image-guided radiation therapy. Specifically, this paper presents a new scatter correction algorithm which uses a prior image with low scatter artifacts to reduce shading artifacts in cone-beam CT images acquired under conditions of high scatter. The proposed correction algorithm begins with an empirical hypothesis that the target image can be written as a weighted summation of a series of basis images that are generated by raising the raw cone-beam projection data to different powers, and then, reconstructing using the standard filtered backprojection algorithm. The weight for each basis image is calculated by minimizing the difference between the target image and the prior image. The performance of the scatter correction algorithm is qualitatively and quantitatively evaluated through phantom studies using a Varian 2100 EX System with an on-board imager. Results show that the proposed scatter correction algorithm using a prior image with low scatter artifacts can substantially mitigate scatter-induced shading artifacts in both full-fan and half-fan modes.

Use of helical TomoTherapy-based MVCT imaging for adaptive planning is becoming increasingly popular. Treatment planning and dose calculations based on MVCT require an image value to electron density calibration to remain stable over the course of treatment time. In this work, we have studied the dosimetric impact on TomoTherapy treatment plans due to variation in image value to density table (IVDT) curve as a function of target degradation. We also have investigated the reproducibility and stability of the TomoTherapy MVCT image quality over time. Multiple scans of the TomoTherapy "Cheese" phantom were performed over a period of five months. Over this period, a difference of 4.7% in the HU values was observed in high-density regions while there was no significant variation in the image values for the low densities of the IVDT curve. Changes in the IVDT curves before and after target replacement were measured. Two clinical treatment sites, pelvis and prostate, were selected to study the dosimetric impact of this variation. Dose was recalculated on the MVCTs with the planned fluence using IVDT curves acquired before and after target change. For the cases studied, target replacement resulted in an overall difference of less than 5%, which can be significant for hypo-fractionated cases. Hence, it is recommended to measure the IVDT curves on a monthly basis and after any major repairs/replacements.

Cone-beam computed tomography (CBCT) has been clinically used to verify patient position and to localize the target of treatment in image-guided radiation therapy (IGRT). However, when the chest and the upper abdomen are scanned, respiratory-induced motion blurring limits the utility of CBCT. In order to mitigate this blurring, respiratory-gated CBCT, i.e. 4D CBCT, was introduced. In 4D CBCT, the cone-beam projection data sets acquired during a gantry rotation are sorted into several respiratory phases. In these gated reconstructions, the number of projections for each respiratory phase is significantly reduced. Consequently, undersampling streaking artifacts are present in the reconstructed images, and the image contrast resolution is also significantly compromised. In this paper, we present a new method to simultaneously achieve both high temporal resolution ( approximately 100 ms) and streaking artifact-free image volumes in 4D CBCT. The enabling technique is a newly proposed image reconstruction method, i.e. prior image constrained compressed sensing (PICCS), which enables accurate image reconstruction using vastly undersampled cone-beam projections and a fully sampled prior image. Using PICCS, a streak-free image can be reconstructed from 10-20 cone-beam projections while the signal-to-noise ratio is determined by a denoising feature of the selected objective function and by the prior image, which is reconstructed using all of the acquired cone-beam projections. This feature of PICCS breaks the connection between the temporal resolution and streaking artifacts' level in 4D CBCT. Numerical simulations and experimental phantom studies have been conducted to validate the method.

Cone-beam computed tomography (CBCT) using an "on-board" x-ray imaging device integrated into a radiation therapy system has recently been made available for patient positioning, target localization, and adaptive treatment planning. One of the challenges for gantry mounted image-guided radiation therapy (IGRT) systems is the slow acquisition of projections for cone-beam CT (CBCT), which makes them sensitive to any patient motion during the scans. Aiming at motion artifact reduction, four-dimensional CBCT (4D CBCT) techniques have been introduced, where a surrogate for the target's motion profile is utilized to sort the cone-beam data by respiratory phase. However, due to the limited gantry rotation speed and limited readout speed of the on-board imager, fewer than 100 projections are available for the image reconstruction at each respiratory phase. Thus, severe undersampling streaking artifacts plague 4D CBCT images. In this paper, the authors propose a simple scheme to significantly reduce the streaking artifacts. In this method, a prior image is first reconstructed using all available projections without gating, in which static structures are well reconstructed while moving objects are blurred. The undersampling streaking artifacts from static structures are estimated from this prior image volume and then can be removed from the phase images using gated reconstruction. The proposed method was validated using numerical simulations, experimental phantom data, and patient data. The fidelity of stationary and moving objects is maintained, while large gains in streak artifact reduction are observed. Using this technique one can reconstruct 4D CBCT datasets using no more projections than are acquired in a 60 s scan. At the same time, a temporal gating window as narrow as 100 ms was utilized. Compared to the conventional 4D CBCT reconstruction, streaking artifacts were reduced by 60% to 70%.