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Purpose: To evaluate the interfractional reproducibility of respiration-induced lung tumors motion, defined by their centroids and the intrafractional target motion range. Methods and Materials: Twentythree pairs of four-dimensional/computed tomography scans were acquired for 22 patients. Gross tumor volumes were contoured, Clinical target volumes (CTVs) were generated. Geometric data for CTVs and lung volumes were extracted. The motion tracks of CTV centroids, and CTV edges along the cranio-caudal, anterior-posterior, and lateral directions were evaluated. The Pearson correlation coefficient for motion tracks along the cranio-caudal direction was determined for the entire respiratory cycle and for five phases about the end of expiration. Results: The largest motion extent was along the cranio-caudal direction. The intrafractional motion extent for five CTVs was <0.5 cm, the largest motion range was 3.59 cm. Three CTVs with respiration-induced displacement >0.5 cm did not exhibit the similarity of motion, and for 16 CTVs with motion >0.5 cm the correlation coefficient was >0.8. The lung volumes in corresponding phases for cases that demonstrated CTVs motion similarity were reproducible. No correlation between tumor size and mobility was found. Conclusion: Target motion reproducibility seems to be present in 87% of cases in our dataset. Three cases with dissimilar motion indicate that it is advisable to verify target motion during treatment. The adaptive adjustment to compensate the possible interfractional shifts in a target position should be incorporated as a routine policy for lung cancer radiotherapy. [ABSTRACT FROM AUTHOR]

Purpose: The global cancer burden and mortality rates are increasing, with significant disparities in access to care in low- and middle-income countries (LMICs). This study aimed to identify radiology and radiation therapy needs in LMICs from the perspective of departmental and institutional leaders., Methods and Materials: A survey was developed and conducted by the American Association of Physicists in Medicine Global Needs Assessment Committee and the American Association of Physicists in Medicine International Council. The survey, organized into 5 sections (Introduction, Infrastructure Needs, Education Needs, Research Needs, and General Information), was open to respondents from March 1, to August 16, 2022., Results: A total of 175 responses were received from 6 global regions: Africa (31.4%), the Americas (17.7%), the Eastern Mediterranean (14.3%), Europe (9.1%), Southeast Asia (23.4%), and the Western Pacific (4.0%). The greatest reported need was for new or updated equipment, particularly positron emission tomography/computed tomography imaging technology. There was also a high demand for clinical and equipment training. Approximately 25% of institutions reported a lack of radiology-based cancer screening programs because of high health care costs and a shortage of specialized equipment. Many institutions that expressed interest in research face funding and grant challenges., Conclusions: The findings highlight critical areas where organizations can support LMICs in enhancing radiology and radiation therapy services to mitigate the growing cancer burden., (© 2024 The Author(s).)

Purpose: To evaluate the intra-fractional tumor motion in lung stereotactic body radiotherapy (SBRT) with deep inspiration breath-hold (DIBH), and to investigate the adequacy of the current planning target volume (PTV) margins., Methods: Twenty-eight lung SBRT patients with DIBH were selected in this study. Among the lesions, twenty-three were at right or left lower lobe, two at right middle lobe, and three at right or left upper lobe. Post-treatment gated cone-beam computed tomography (CBCT) was acquired to quantify the intra-fractional tumor shift at each treatment. These obtained shifts were then used to calculate the required PTV margin, which was compared with the current applied margin of 5 mm margin in anterior-posterior (AP) and right-left (RL) directions and 8 mm in superior-inferior (SI) direction. The beam delivery time was prolonged with DIBH. The actual beam delivery time with DIBH (T beam&#95;DIBH ) was compared with the beam delivery time without DIBH (T beam&#95;wo&#95;DIBH ) for the corresponding SBRT plan., Results: A total of 113 treatments were analyzed. At six treatments (5.3%), the shifts exceeded the tolerance defined by the current PTV margin. The average shifts were 0.0 ± 1.9 mm, 0.1±1.5 mm, and -0.5 ± 3.7 mm in AP, RL, and SI directions, respectively. The required PTV margins were determined to be 4.5, 3.9, and 7.4 mm in AP, RL, and SI directions, respectively. The average T beam&#95;wo&#95;DIBH and T beam&#95;DIBH were 2.4 ± 0.4 min and 3.6 ± 1.5 min, respectively. The average treatment slot for lung SBRT with DIBH was 25.3 ± 7.9 min., Conclusion: Intra-fractional tumor motion is the predominant source of treatment uncertainties in CBCT-guided lung SBRT with DIBH. The required PTV margin should be determined based on data specific to each institute, considering different techniques and populations. Our data indicate that our current applied PTV margin is adequate, and it is possible to reduce further in the RL direction. The time increase of T beam&#95;DIBH , relative to the treatment slot, is not clinically significant., (© 2024 The Author(s). Journal of Applied Clinical Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Purpose: With proper beam setup and optimization constraints in the treatment planning system, volumetric modulated arc therapy (VMAT) can improve target dose coverage and conformity while reducing doses to adjacent structures for whole breast radiation therapy. However, the low-dose bath effect on critical structures, especially the heart and the ipsilateral lung, remains a concern. In this study, we present a VMAT technique with the jaw offset VMAT (JO-VMAT) to reduce the leakage and scatter doses to critical structures for whole breast radiation therapy., Materials and Methods: The data of 10 left breast cancer patients were retrospectively used for this study. CT images were acquired on a CT scanner (GE, Discovery) with the deep-inspiration breath hold (DIBH) technique. The planning target volumes (PTVs) and the normal structures (the lungs, the heart, and the contralateral breast) were contoured on the DIBH scan. A 3D field-in-field plan (3D-FiF), a tangential VMAT (tVMAT) plan, and a JO-VMAT plan were created with the Eclipse treatment planning system. An arc treatment field with the x-jaw closed across the central axis creates a donut-shaped high-dose distribution and a cylinder-shaped low-dose volume along the central axis of gantry rotation. Applying this setup with proper multi-leaf collimator (MLC) modulation, the optimized plan potentially can provide sufficient target coverage and reduce unnecessary irradiation to critical structures. The JO-VMAT plans involve 5-6 tangential arcs (3 clockwise arcs and 2-3 counterclockwise arcs) with jaw offsets. The plans were optimized with objective functions specified to achieve PTV dose coverage and homogeneity; For organs at risk (OARs), objective functions were specified individually for each patient to accomplish the best achievable treatment plan. For tVMAT plans, optimization constraints were kept the same except that the jaw offset was removed from the initial beam setup. The dose volume histogram (DVH) parameters were generated for dosimetric evaluation of PTV and OARs., Results: The D 95% to the PTV was greater than the prescription dose of 42.56 Gy for all the plans. With both VMAT techniques, the PTV conformity index (CI) was statistically improved from 0.62 (3D-FiF) to 0.83 for tVMAT and 0.84 for JO-VMAT plans. The difference in the homogeneity index (HI) was not significant. The D max to the heart was reduced from 12.15 Gy for 3D-FiF to 8.26 Gy for tVMAT and 7.20 Gy for JO-VMAT plans. However, a low-dose bath effect was observed with tVMAT plans to all the critical structures including the lungs, the heart, and the contralateral breast. With JO-VMAT, the V 5Gy and V 2Gy of the heart were reduced by 32.7% and 15.4% compared to 3D-FiF plans. Significantly, the ipsilateral lung showed a reduction in mean dose (4.65-3.44 Gy) and low dose parameters (23.4% reduction for V 5Gy and 10.7% reduction for V 2Gy ) for JO-VMAT plans compared to the 3D-FiF plans. The V 2Gy dose to the contralateral lung and breast was minimal with JO-VMAT techniques., Conclusion: A JO-VMAT technique was evaluated in this study and compared with 3D-FiF and tVMAT techniques. Our results showed that the JO-VMAT technique can achieve clinically comparable coverage and homogeneity and significantly improve dose conformity within PTV. Additionally, JO-VMAT eliminated the low-dose bath effect at all OARs evaluation metrics including the ipsilateral/contralateral lung, the heart, and the contralateral breast compared to 3D-FiF and tVMAT. This technique is feasible for the whole breast radiation therapy of left breast cancers., (© 2024 The Author(s). Journal of Applied Clinical Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

We hypothesize that the injection of JP4-039, a mitochondria-targeted nitroxide, prior to irradiation of the mouse retina may decrease apoptosis and reduce neutrophil and macrophage migration into the retina. In our study, we aimed to examine the effects of JP4-039 in the mouse retina using fluorescent microscopy, a terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, and flow cytometry. Forty-five mice and one eye per mouse were used. In Group 1, fluorescent microscopy was used to determine retinal uptake of 10 µL (0.004 mg/µL) of intravitreally injected BODIPY-labeled JP4-039 at 0, 15, and 60 min after injection. In Group 2, the TUNEL assay was performed to investigate the rate of apoptosis after irradiation in addition to JP4-039 injection, compared to controls. In Group 3, flow cytometry was used to determine the extent of inflammatory cell migration into the retina after irradiation in addition to JP4-039 injection, compared to controls. Maximal retinal uptake of JP4-039 was 15 min after intravitreal injection ( p < 0.0001). JP4-039-treated eyes had lower levels of retinal apoptosis (35.8 ± 2.5%) than irradiated controls (49.0 ± 2.7%; p = 0.0066) and demonstrated reduced migration of N1 cells (30.7 ± 11.7% vs. 77.7 ± 5.3% controls; p = 0.004) and M1 cells (76.6 ± 4.2 vs. 88.1 ± 3.7% controls, p = 0.04). Pretreatment with intravitreally injected JP4-039 reduced apoptosis and inflammatory cell migration in the irradiated mouse retina, marking the first confirmed effect of this molecule in retinal tissue. Further studies may allow for safety profiling and potential use for patients with radiation retinopathy.

Most school-based prevention curricula for young children fail to address multiple types of abuse and limit instruction to a single day, despite evidence that polyvictimization is common and children learn better when allowed to practice material repeatedly. This study utilized a cluster randomized control trial design to evaluate a multi-abuse prevention program, the Monique Burr Foundation for Children (MBF) Child Safety Matters®, based on varying lesson structure. Participants included nine Florida schools consisting of 843 children in grades K-2. Schools were randomized within cluster to implement in two lessons, four lessons, or after study data collection (i.e., control group). Lessons averaged 34 minutes ( SD = 8.8 minutes) in length for 2-lesson group and 23.6 minutes ( SD = 6.9 minutes) for the 4-lesson condition. Knowledge was assessed before implementation and on average 11 weeks after implementation. There were no statistical differences between clusters. Controlling for pre-test scores, schools in the four-lesson group scored highest on a measure of knowledge of potentially risky and unsafe situations ( M = 69.68, SE = .80) on post-test, followed by schools in the two-lesson group ( M = 67.31, SE = .77), followed by schools in the control group ( M = 62.92, SE = .76). Results support use of more frequent, shorter lessons for prevention programs and the promise of addressing multiple forms of child victimization., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Despite recent advances in cancer therapy, ovarian cancer remains the most lethal gynecological cancer worldwide, making it crucial and of the utmost importance to establish novel therapeutic strategies. Adjuvant radiotherapy has been assessed historically, but its use was limited by intestinal toxicity. We recently established the role of Limosilactobacillus reuteri in releasing IL-22 (LR-IL-22) as an effective radiation mitigator, and we have now assessed its effect in an ovarian cancer mouse model. We hypothesized that an LR-IL-22 gavage would enable intestinal radioprotection by modifying the tumor microenvironment and, subsequently, improving overall survival in female C57BL/6MUC-1 mice with widespread abdominal syngeneic 2F8cis ovarian cancer. Herein, we report that the LR-IL-22 gavage not only improved overall survival in mice when combined with a PD-L1 inhibitor by inducing differential gene expression in irradiated stem cells but also induced PD-L1 protein expression in ovarian cancer cells and mobilized CD8+ T cells in whole abdomen irradiated mice. The addition of LR-IL-22 to a combined treatment modality with fractionated whole abdomen radiation (WAI) and systemic chemotherapy and immunotherapy regimens can facilitate a safe and effective protocol to reduce tumor burden, increase survival, and improve the quality of life of a locally advanced ovarian cancer patient.

Purpose/objectives: (A) To examine the alignment accuracy of CBCT guidance for brain metastases with off centered isocenters, (B) to test dose delivery and targeting accuracy for single isocenter treatments with multiple brain metastases. We report the results of the end-to-end test for Truebeam stereotactic radiosurgery (SRS)., Materials/methods: An anthropomorphic CT head phantom was drilled with five MOSFET inserts and two PTW Pinpoint chamber inserts. The phantom was simulated, planned, and delivered. For the purpose of comparing the accuracy of alignment, CBCTs were acquired with the isocenter centered and offset superiorly 8 cm, inferiorly 8 cm, anteriorly 7 cm, posteriorly 7 cm, and right 5 cm. There were six degrees of freedom corrections applied to the plans, as well as intentional rotational and translational errors for dose comparisons. Dose accuracy checks were performed with MOSFET and PTW Pinpoint chamber, and targeting accuracy was assessed with GafChromic films., Result: (A) Compared to centered CBCT, off-centered CBCT scan showed some alignment errors, with a maximum difference of 0.6-degree pitch and 0.9 mm translation when the phantom was placed 8 cm inferior off center. (B) For the single isocenter plan, measured doses of the five MOSFET were 95%-100% of the planned dose, whereas the multiple isocenter plans were 96%-100%. With intentional setup errors of 1-degree pitch, doses were 97.1%-100.4% compared to the perfect setup. The same was found for the two pinpoint chamber readings with 1-degree rotation and 1 mm translation. (C) Targeting accuracy for targets at the isocenter is 0.67 mm, within the machine specification of 0.75 mm. Targeting accuracy for isocenters 6-12 cm away from the target is in the range 0.67-1.18 mm., Conclusion: (A) Single isocenter HyperArc treatments for multiple brain metastases are feasible and targeting accuracy is clinically acceptable. (B) The vertex in a cranial scan is very important for proper alignment., (© 2023 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Prevalent PET imaging reconstructs 2γ-photon pairs emitted after an annihilation from para-positronium (p-Ps) and rejects 3γ events from ortho-positronium (o-Ps) as noises. The 3γ/2γ decay ratio is ~ 3/7 in human body theoretically but in fact significantly lower due to pick-off process, hence PET imaging quality is well controlled. In a PET-MR hybrid unit, the MR magnetic field alters positronium decay patterns through magnetic quenching: all o-Ps and excited p-Ps states are split into finer quantum states under strong magnetic field, thus transitions between some triplet and singlet finer states (m z  = 0) were no longer forbidden, thus some o-Ps converts to p-Ps spontaneously by emitting hyperfine split (HFS) photons, which also drops 3γ/2γ ratio hence helps PET imaging quality. However, inverse magnetic quenching might also occur if any external source of HFS frequencies is nearby, thus many p-Ps convert to o-Ps by absorbing those HFS photons (induced HFS transitions). This will dramatically increase 3γ/2γ ratio and hence degrade PET imaging quality instantaneously. The HFS spectrum lies in a broad range of microwaves, from 0.02 to 200 GHz. To prevent inverse magnetic quenching, it is necessary to block external microwave sources outside the hybrid vault, by adding a thin metal layer at all directions of the vault. This could be achieved by adopting the metallic Faraday Cage, which was originally for MR shielding, with possible amendment if necessary. The frequencies of excitation pulses in MR imaging overlap with HFS spectrum, however, the chance for mutual interference during hybrid imaging is small, hence there seems no need to veto each other during hybrid scans., (© 2023. The Author(s).)

Background/aim: Patients with radiation sensitive Fanconi anemia (FA) are presenting with cancers of the oral cavity, oropharynx, and other anatomic locations., Materials and Methods: Animal models for cancer in FA mice used orthotopic tumors from wild type mice. We derived a cancer cell line from Fanca-/- mice by topical application of the chemical carcinogen dimethyl benzanthracene (DMBA)., Results: A Fanca-/- mouse rhabdomyosarcoma was derived from a Fanca-/- (129/Sv) mouse. The in vitro clonogenic survival of the Fanca-/- clone 6 cancer cell line was consistent with the FA genotype. Transplanted tumors demonstrated hypoxic centers surrounded by senescent cells., Conclusion: This Fanca-/- mouse syngeneic cancer should provide a valuable resource for discovery and development of new normal tissue radioprotectors for patients with FA and cancer., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Motivational deficits in schizophrenia may interact with foundational cognitive processes including learning and memory to induce impaired cognitive proficiency. If such a loss of synergy exists, it is likely to be underpinned by a loss of synchrony between the brains learning and reward sub-networks. Moreover, this loss should be observed even during tasks devoid of explicit reward contingencies given that such tasks are better models of real world performance than those with artificial contingencies. Here we applied undirected functional connectivity (uFC) analyses to fMRI data acquired while participants engaged in an associative learning task without contingencies or feedback. uFC was estimated and inter-group differences (between schizophrenia patients and controls, n = 54 total, n = 28 patients) were assessed within and between reward (VTA and NAcc) and learning/memory (Basal Ganglia, DPFC, Hippocampus, Parahippocampus, Occipital Lobe) sub-networks. The task paradigm itself alternated between Encoding, Consolidation, and Retrieval conditions, and uFC differences were quantified for each of the conditions. Significantly reduced uFC dominated the connectivity profiles of patients across all conditions. More pertinent to our motivations, these reductions were observed within and across classes of sub-networks (reward-related and learning/memory related). We suggest that disrupted functional connectivity between reward and learning sub-networks may drive many of the performance deficits that characterize schizophrenia. Thus, cognitive deficits in schizophrenia may in fact be underpinned by a loss of synergy between reward-sensitivity and cognitive processes., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to report., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Infectious disease outbreaks have always presented challenges to the operation of healthcare systems. In particular, the treatment of cancer patients within Radiation Oncology often cannot be delayed or compromised due to infection control measures. Therefore, there is a need for a strategic approach to simultaneously managing infection control and radiotherapy risks., Purpose: To develop a systematic risk management method that uses mathematical models to design mitigation efforts for control of an infectious disease outbreak, while ensuring safe delivery of radiotherapy., Methods: A two-stage failure mode and effect analysis (FMEA) approach is proposed to modify radiotherapy workflow during an infectious disease outbreak. In stage 1, an Infection Control FMEA (IC-FMEA) is conducted, where risks are evaluated based on environmental parameters, clinical interactions, and modeling of infection risk. occupancy risk index (ORI) is defined as a metric for infection transmission risk level in each room, based on the degree of occupancy. ORI, in combination with ventilation rate per person (R p ), is used to provide a broad infection risk assessment of workspaces. For detailed IC-FMEA of clinical processes, infection control failure mode (ICFM) is defined to be any instance of disease transmission within the clinic. Infection risk priority number (IRPN) has been formulated as a function of time, distance, and degree of protective measures. Infection control measures are then systematically integrated into the workflow. Since the workflow is perturbed by infection control measures, there is a possibility of introducing new radiotherapy failure modes or increased likelihood of existing failure modes. Therefore, in stage 2, a conventional radiotherapy FMEA (RT-FMEA) should be performed on the adjusted workflow., Results: The COVID-19 pandemic was used to illustrate stage 1 IC-FMEA. ORI and R p values were calculated for various workspaces within a clinic. A deep inspiration breath hold (DIBH) CT simulation was used as an example to demonstrate detailed IC-FMEA with ICFM identification and IRPN evaluation. A total of 90 ICFMs were identified in the DIBH simulation process. The calculated IRPN values were found to be progressively decreasing for workflows with minimal, moderate, and enhanced levels of protective measures., Conclusion: The framework developed in this work provides tools for radiotherapy clinics to systematically assess risk and adjust workflows during the evolving circumstances of any infectious disease outbreak., (© 2023 American Association of Physicists in Medicine.)

Irradiation can be an effective treatment for ovarian cancer, but its use is limited by intestinal toxicity. Thus, strategies to mitigate toxicity are important and can revitalize the current standard of care. We previously established that LR-IL-22 protects the intestine from WAI. We now hypothesize that LR-IFN-β is an effective radiation protector and mitigator and is rapidly cleared from the digestive tract, making it an option for intestinal radioprotection. We report that the gavage of LR-IFN-β during WAI provides improved intestinal barrier integrity and significantly preserves the numbers of Lgr5+GFP+ intestinal stem cells, improving survival. The rapid clearance of the genetically engineered probiotic from the digestive tract renders it a safe and feasible radiation mitigator. Therefore, the above genetically engineered probiotic is both a feasible and effective radiation mitigator that could potentially revolutionize the management of OC patients. Furthermore, the subsequent addition of platinum/taxane-based chemotherapy to the combination of WAI and LR-IFN-β should reduce tumor volume while protecting the intestine and should improve the overall survival in OC patients.

Portal dosimetry is one option for verification of volumetric-modulated arc therapy (VMAT) planning for multiple brain metastases. However, due to the changing response of the portal imager with photon beam energy, the dose transmitted through closed multileaf collimator (MLC) leaves or narrow MLC gaps may be underestimated by the imager. We present a simple method for correcting for these effects that may be implemented within the Eclipse treatment planning system. We recalculated the predicted portal dose with and without this correction for 20 multiple brain met VMAT plans. Before the correction, 3/20 composite plan fields passed our standard quality assurance (QA) criteria (54/80 individual fields); the average gamma passing rate for the composite plans was 76.9 ± 16.6%, and the average gamma value across the composite plans was 0.67 ± 0.23. After correction, 20/20 composite plan fields passed the QA criteria (80/80 individual fields); the average gamma passing rate for composite plans was 99.2 ± 1.4%, the average gamma value across the composite plans was 0.33 ± 0.90. A measure of plan complexity, the average leaf pair opening could be correlated to the gamma analysis results for the uncorrected plans but not for the corrected plans., (© 2022 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

Purpose: The aim of this work was to test the implementation of small field dosimetry following TRS-483 and to develop quality assurance procedures for the experimental determination of small field output factors (SFOFs)., Materials and Methods: Twelve different centers provided SFOFs determined with various detectors. Various linac models using the beam qualities 6 MV and 10 MV with flattening filter and without flattening filter were utilized to generate square fields down to a nominal field size of 0.5 cm × 0.5 cm. The detectors were positioned at 10 cm depth in water. Depending on the local situation, the source-to-surface distance was either set to 90 cm or 100 cm. The SFOFs were normalized to the output of the 10 cm × 10 cm field. The spread of SFOFs measured with different detectors was investigated for each individual linac beam quality and field size. Additionally, linac-type specific SFOF curves were determined for each beam quality and the SFOFs determined using individual detectors were compared to these curves. Example uncertainty budgets were established for a solid state detector and a micro ionization chamber., Results: The spread of SFOFs for each linac and field was below 5% for all field sizes. With the exception of one linac-type, the SFOFs of all investigated detectors agreed within 10% with the respective linac-type SFOF curve, indicating a potential inter-detector and inter-linac variability., Conclusion: Quality assurance on the SFOF measurements can be done by investigation of the spread of SFOFs measured with multiple detectors and by comparison to linac-type specific SFOFs. A follow-up of a measurement session should be conducted if the spread of SFOFs is larger than 5%, 3%, and 2% for field sizes of 0.5 cm × 0.5 cm, 1 cm × 1 cm, and field sizes larger than 2 cm × 2 cm, respectively. Additionally, deviations of measured SFOFs to the linac-type-curves of more than 7%, 3%, and 2% for field sizes 0.5 cm × 0.5 cm, 1 cm × 1 cm, and field sizes larger than 1 cm × 1 cm, respectively, should be followed up., (© 2022 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Purpose: Biology-guided radiotherapy (BgRT) is a new external beam radiation therapy modality combining PET-CT with a linear accelerator that has the potential to track and treat one or more tumors in real-time. The use of PET and radiopharmaceutical tracers introduces new processes that are different from the existing treatment processes. In this study, we have developed a process map for the clinical implementation of a prototype BgRT machine., Methods: A team of 13 members from various radiation therapy disciplines at our institution participated in developing a prospective process map for a prototype BgRT machine. The methodology provided by the AAPM TG 100 report was followed. In particular, the steps unique to the BgRT workflow, using hypofractionated stereotactic body radiation therapy with fluorodeoxyglucose radiolabeled with fluorine-18 (FDG) to guide beam delivery, were analyzed., Results: The multi-disciplinary team in the department of radiation oncology at our institution developed a prospective process map for the clinical BgRT workflow. By focusing on the appropriate level of detail, 15 major subprocesses, 133 steps, and 248 substeps were identified and the process map was agreed upon as being useful, implementable, and manageable. Seventy-four steps from nine subprocesses, 55.6% of the whole process, were analyzed to be the BgRT unique steps. They originate mainly from: (1) acquiring multiple PET images at the BgRT machine with separate patient visits, (2) creating a unique biological treatment volume for BgRT plan (PTV BgRT ), and (3) BgRT plan optimization and treatment delivery using PET images., Conclusion: Using BgRT to irradiate multiple metastases in the same session will impact clinical workflow, thus a graphical process map depicting the new clinical workflow with an appropriate level of detail is critical for efficient, safe, and high-quality care. The prospective process map will guide the successful setup and use of the new BgRT system., (© 2022 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

(1) Background: The systemic administration of therapeutic agents to the intestine including cytokines, such as Interleukin-22 (IL-22), is compromised by damage to the microvasculature 24 hrs after total body irradiation (TBI). At that time, there is significant death of intestinal microvascular endothelial cells and destruction of the lamina propria, which limits drug delivery through the circulation, thus reducing the capacity of therapeutics to stabilize the numbers of Lgr5+ intestinal crypt stem cells and their progeny, and improve survival. By its direct action on intestinal stem cells and their villus regeneration capacity, IL-22 is both an ionizing irradiation protector and mitigator. (2) Methods: To improve delivery of IL-22 to the irradiated intestine, we gavaged Lactobacillus-reuteri as a platform for the second-generation probiotic Lactobacillus-reuteri -Interleukin-22 (LR-IL-22). (3) Results: There was effective radiation mitigation by gavage of LR-IL-22 at 24 h after intestinal irradiation. Multiple biomarkers of radiation damage to the intestine, immune system and bone marrow were improved by LR-IL-22 compared to the gavage of control LR or intraperitoneal injection of IL-22 protein. (4) Conclusions: Oral administration of LR-IL-22 is an effective protector and mitigator of intestinal irradiation damage.

Purpose: Previous studies have suggested that the dose immediately outside the PTV may impact the incidence of distant metastases after stereotactic body radiation therapy (SBRT) for patients with early-stage non-small cell lung cancer (NSCLC). In particular, Diamant et al. [1,2] reported a correlation between the mean EQD2 of a 30 mm shell around the PTV and both local control and the rate of distant metastases. In this study, we assess this parameter and others in a series of patients with radiographically presumed or biopsy-proven early-stage NSCLC treated at our institution with stereotactic body radiotherapy (SBRT) between 2017 and 2019., Materials/methods: We reviewed the dosimetry, local control, regional nodal relapse, and rate of distant metastases for 304 patients with 325 lesions treated with SBRT at our institution. Dosimetric parameters investigated include the prescribed dose, minimum and mean doses to the PTV, conformity index, and the mean EQD2 to a 30 mm shell around the PTV. Time to each event was defined from date of last fraction of SBRT to date of event, with event-free patients censored at last radiographic follow-up. Univariate (UVA) Cox regression analysis was performed on the collected parameters to assess for correlation with regional nodal relapse and rate of distant metastases., Results: There was no significant correlation between the mean EQD2 dose to a 30 mm shell around the PTV and the rate of distant metastases. On UVA Cox proportional hazards analysis, positive predictors of reduced incidence of distant metastases were PTV <22 cc (vs. ≥22 cc, p = 0.01) and GTV <10 cc (vs. ≥10 cc, p < 0.01), with GTV <10 cc also being a positive predictor of reduced incidence of regional nodal relapse (p < 0.01). In the subset of patients treated with 4-5 fractions, mean EQD2 dose to the 30 mm shell around the PTV ≥21 Gy was associated with increased incidence of distant metastases (HR 2.42, 95% CI 1.06-5.53, p = 0.04), differing from prior data from Diamant et al. CONCLUSIONS: We did not observe a correlation between the rate of distant metastases and dose outside the PTV, as reported by other groups; rather, we noted an opposite trend in patients treated with 4-5 fractions. Our data show additional correlations between distant metastases and tumor size., Competing Interests: Conflicts of interest None declared., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Purpose: Halcyon linear accelerators employ intensity-modulated radiation therapy (IMRT) and stereotactic body radiation therapy (SBRT) techniques. The Halcyon offers translational, but not rotational, couch correction, which only allows a 3 degrees of freedom (3-DOF) correction. In contrast, the TrueBeam (TB) linear accelerator offers full 6-DOF corrections. This study aims to evaluate the difference in treatment plan quality for single thoracic or lumbar vertebral segment SBRT between the Halcyon and TB linear accelerators. In addition, this study will also investigate the effect of patient rotational setup errors on the final plan quality., Methods: We analyzed 20 patients with a single-level spine metastasis located between the T7 and L5 vertebrae near the spinal canal. The median planning target volume was 52.0 cm 3 (17.9-138.7 cm 3 ). The median tumor diameter in the axial plane was 4.6 cm (range 1.7-6.8 cm), in the sagittal plane was 3.3 cm (range 2-5 cm). The prescription doses were either 12-16 Gy in 1 fraction or 18-24 Gy in 3 fractions. All patients were treated on the TB linear accelerator with a 2.5 mm Multi-Leaf Collimator (MLC) leaf width. Treatment plans were retrospectively created for the Halcyon, which has a 5 mm effective MLC leaf width. The 20 patients had a total of 50 treatments. Analysis of the 50 cone beam computed tomography (CBCT) scans showed average rotational setup errors of 0.6°, 1.2°, and 0.8° in pitch, yaw, and roll, respectively. Rotational error in roll was not considered in this study, as the original TB plans used a coplanar volumetric modulated arc therapy (VMAT) technique, and each 1° of roll will contribute an error of 1/360. If a plan has 3 arcs, the contribution from errors in roll will be < 0.1%. To simulate different patient setup errors, for each patient, 12 CT image datasets were generated in Velocity AI with different rotational combinations at a pitch and yaw of 1°, 2°, and 3°, respectively. We recalculated both the TB and Halcyon plans on these rotated images.  The dosimetric plan quality was evaluated based on the percent tumor coverage, the Conformity Index (CI), Gradient Index (GI), Homogeneity index (HI), the maximum dose to the cord/cauda, and the volume of the cord/cauda receiving 8, 10, and 12 Gy (V8Gy, V10Gy and V12Gy). Paired t-tests were performed between the original and rotated plans with a significance level of 0.05., Results: The Eclipse based VMAT plans on Halcyon achieved a similar target coverage (92.3 ± 3.0% vs. 92.4 ± 3.3%, p = 0.82) and CI (1.0 ± 0.1 vs. 1.1 ± 0.2, p = 0.12) compared to the TB plans. The Gradient index of Halcyon is higher (3.96 ±0.8) than TB (3.85 ±0.7), but not statistically significant. The maximum dose to the spinal cord/cauda was comparable (11.1 ± 2.8 Gy vs. 11.4 ± 3.6 Gy, p = 0.39), as were the V8Gy, V10Gy and V12Gy to the cord/cauda. The dosimetric influence of patient rotational setup error was statistically insignificant for rotations of up to 1° pitch/yaw (with similar target coverage, CI, max cord/cauda dose and V8Gy, V10Gy, V12Gy for cord/cauda). The total number of monitor units (MUs) for Halcyon (4998 ± 1688) was comparable to that of TB (5463 ± 2155) (p = 0.09)., Conclusions: The Halcyon VMAT plans for a single thoracic or lumbar spine metastasis were dosimetrically comparable to the TB plans. Patient rotation within 1° in the pitch and yaw directions, if corrected by translation, resulted in insignificant dosimetric effects. The Halcyon linear accelerator is an acceptable alternative to TB for the treatment of single thoracic or lumbar spinal level metastasis, but users need to be cautious about the patient rotational setup error.  It is advisable to select patients appropriately, including only those with the thoracic or lumbar spine involvement and keeping at least 2 mm separation between the target and the cord/cauda. More margin is needed if the distance between the isocenter and cord/cauda is larger. It is advisable to place the planning isocenter close to the spinal canal to further mitigate the rotational error., Summary: We simulated various scenarios of patient setup errors with different rotational combinations of pitch and yaw with 1°, 2°, and 3°, respectively. Rotation was corrected with translation only to mimic the Halcyon treatment scenario. Using the Halcyon for treating a tumor in a single thoracic or lumbar vertebral segment is feasible, but caution should be noted in patients requiring rotational corrections of > 1° in the absence of 6-DOF correction capabilities., (© 2021 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

The purpose of this study is to predict the collision clearance distance of stereotactic cones with treatment setup devices in cone-based stereotactic radiosurgery (SRS). The BrainLAB radiosurgery system with a Frameless Radiosurgery Positioning Array and dedicated couch top was targeted in this study. The positioning array and couch top were scanned with CT simulators, and their outer contours of were detected. The minimum clearance distance was estimated by calculating the Euclidian distances between the surface of the SRS cones and the nearest surface of the outer contours. The coordinate transformation of the outer contour was performed by incorporating the Beam's Eye View at a planned arc range and couch angle. From the minimum clearance distance, the collision-free gantry ranges for each couch angle were sequentially determined. An in-house software was developed to calculate the clearance distance between the cone surface and the outer contours, and thus determine the occurrence of a collision. The software was extensively tested for various combinations of couch and arc angles at multiple isocenter locations for two combinations of cone-couch systems. A total of 50 arcs were used to validate the calculation accuracies of the software for each system. The calculated minimum distances and collision-free angles from the software were verified by physical measurements. The calculated minimum distances were found to agree with the measurements to within 0.3 ± 0.9 mm. The collision-free arc angles from the software also agreed with the measurements to within 1.1 ± 1.1° with a 5-mm safety margin for 20 arcs. In conclusion, the in-house software was able to calculate the minimum clearance distance with <1.0 mm accuracy and to determine the collision-free arc range for the cone-based BrainLab SRS system., (© 2020 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

The same fractionation scheme of accelerated partial breast irradiation (APBI) with brachytherapy is usually applied to APBI patients without considering the radiaton effect on the planning target and organs at risk (OARs) for an individual patient. The purpose of this study is to report the results of optimization of the fractionation scheme by evaluating the radiation effect on target and OARs with a modified linear-quadratic model, universal survival curve (USC), based on dose-volume histograms (DVHs). Ten breast patients treated with multilumen balloon brachytherapy were selected. The minimum skin and chest wall/rib (CW/rib) spacing ranged from 2.5 to 14.3 mm and from 0.5 to 25.0 mm, respectively. The USC model parameters were set as: (1) breast:α = 0.3, β = 0.05; (2) skin: acute reaction α = 0.101, β = 0.009; late reaction α = 0.064, β = 0.029; (3) CW/rib: α = 0.3, β = 0.12. Boundary dose D t was 6 Gy for both target and OARs. The relation between radiation effects on the target (E T ) and OARs (E OAR ) were plotted for fraction numbers (N) from 1 to 20. If E T is set at a certain value, the fractionation that results in a minimum E OAR value corresponds to the optimal fractionation. The results show that the optimal fractionation is different for different OAR damage effects. For most of the patients, N = 2 is best for minimizing skin acute reactions while N = 20 is best for minimizing skin late reactions. N varies from 3 to 20 among patients for minimizing CW/rib toxicity. The determined unique optimal N for treatment delivery was found to vary from 1 to 20 among these 10 patients resulted from balancing the different damage effects considering the spatial dose for a given patient geometry. Optimal fractionation can be achieved for an individual patient by evaluating the radiation effect on tumor and OARs with the USC model based on the patient specific DVHs with APBI brachytherapy., Competing Interests: Declaration of Competing Interests None., (Copyright © 2019 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.)

Mitigation of total-body irradiation (TBI) in C57BL/6 mice by two drugs, which target apoptosis and necroptosis respectively, increases survival compared to one drug alone. Here we investigated whether the biomarker (signature)directed addition of a third anti-ferroptosis drug further mitigated TBI effects. C57BL/6NTac female mice (30-33 g) received 9.25 Gy TBI, and 24 h or later received JP4-039 (20 mg/kg), necrostatin-1 (1.65 mg/kg) and/or lipoxygenase-15 inhibitor (baicalein) (50 mg/kg) in single-, dual- or three-drug regimens. Some animals were sacrificed at days 0, 1, 2, 3, 4 or 7 postirradiation, while the majority in each group were maintained beyond 30 days. For those mice sacrificed at the early time points, femur bone marrow, intestine (ileum), lung and blood plasma were collected and analyzed for radiation-induced and mitigator-modified levels of 33 pro-inflammatory and stress response proteins. Each single mitigator administered [JP4-039 (24 h), necrostatin-1 (48 h) or baicalein (24 h)] improved survival at day 30 after TBI to 25% ( P = 0.0432, 0.2816 or 0.1120, respectively) compared to 5% survival of 9.25 Gy TBI controls. Mice were administered the drug individually based on weight (mg/kg). Drug vehicles comprised 30% cyclodextrin for JP4-039 and baicalein, and 10% Cremphor-EL/10% ethanol/80% water for necrostatin-1; thus, dual-vehicle controls were also tested. The dual-drug combinations further enhanced survival: necrostatin-1 (delayed to 72 h) with baicalein 40% ( P = 0.0359); JP4-039 with necrostatin-1 50% ( P = 0.0062); and JP4-039 with baicalein 60% ( P = 0.0064). The three-drug regimen, timed to signature directed evidence of onset after TBI of each death pathway in marrow and intestine, further increased the 30-day survival to 75% ( P = 0.0002), and there was optimal normalization to preirradiation levels of inflammatory cytokine and stress response protein levels in plasma, intestine and marrow. In contrast, lung protein levels were minimally altered by 9.25 Gy TBI or mitigators over 7 days. Significantly, elevated intestinal proteins at day 7 after TBI were reduced by necrostatin-1-containing regimens; however, normalization of plasma protein levels at day 7 required the addition of JP4-039 and baicalein. These findings indicate that mitigator targeting to three distinct cell death pathways increases survival after TBI.

We evaluated daily setup reproducibility of deep inspiration breath hold (DIBH) using mega voltage (MV) imaging for left breast cancer radiation therapy. Analysis of 109 left breast cancer patients across UPMC Hillman Cancer Center network treated using DIBH technique with daily MV imaging was done. Patient characteristics, MV imaging procedure used and inter-fraction directional shifts were collected. For the statistical analyses, we separated all patients into 2 groups in each of the following 3 categories; (1) obese (BMI ≥ 30) vs nonobese, (2) mastectomy vs lumpectomy, (3) internal mammary node (IMN) treatment vs no IMN treatment. The group mean inter-fraction directional shifts were as following: (1) 0.7 mm (superior), 0.8 mm (inferior); (2) 0.65 mm (left), 0.64 mm (right); (3) 0.89 mm (anterior), 0.83 mm (posterior). Also, any directional shift ≥ 2 mm, ≥ 3 mm, ≥ 4 mm, ≥ 5 mm, ≥ 10 mm was found to be 52.9%, 37.6%, 30.9%, 21.9%, 3.7% of total fractions, respectively. In the stratified analysis, obese patients had larger directional shifts (p < 0.05) and highly associated with number of fractions for ≥ 5 mm in any directional shift compared to nonobese patients (29% vs 17%; p = 0.04). DIBH setup for left breast cancer treatment at our large cancer center network was reproducible with any mean directional shifts less than 1.0 mm using MV imaging. Daily imaging would be more beneficial for obese patients compared to nonobese patients., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2019 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.)

Purpose: To compare the doses calculated by the Analytical Anisotropic Algorithm (AAA), Acuros dose-to-medium, and Acuros dose-to-water for the patients with lung cancer treated at our institution and show that further investigation and clarification are needed about what dose specifications should be used for NRG clinical trials., Methods and Materials: Twenty-one patients with lung cancer who previously received intensity modulated radiation therapy or volumetric modulated arc therapy-based treatments at our institution were analyzed by recalculating their plans for each one with the AAA algorithm (reviewed and approved by our radiation oncologists) and with both reporting modes of the Acuros algorithm. All plans used the same monitor units as the original approved plan and a 2.5-mm grid size. For each patient, D 100 of clinical target volume (CTV) and CTV coverage ratios in each plan were compared, and dose distributions and dose-volume histograms calculated by AAA, Acuros dose-to-water (D w,m ), and Acuros dose-to-medium (D m,m ) were compared as well., Results: Differences between CTV D 100 calculated by AAA and Acuros D m,m were larger than the differences between AAA and Acuros XB D w,m for all patients. When D 100 of CTV was evaluated, the largest difference between AAA and Acuros D m,m was 14.12% and between AAA and Acuros XB D w,m was 3.68%. The average differences between the CTV D 100 calculated by AAA and Acuros D m,m was 5.39%. Coverage ratio between Acuros D m,m and AAA ranges from 51.08% to 100% with an average of 91.32%; coverage ratio between Acuros D w,m and AAA ranges from 87.2% to 100.41% with average of 98.94%; coverage ratio between Acuros D m,m and Acuros D w,m ranges from 58.58% to 100% with an average of 92.03%., Conclusions: The present study shows large and systematic differences in doses calculated by AAA and Acuros D m,m . Therefore, further investigation and clarification are needed about which dose reporting mode should be used., (Copyright © 2019 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Purpose: Varian Halcyon linear accelerator version 2 (The Halcyon 2.0) was recently released with new upgraded features. The aim of this study was to report our clinical experience with Halcyon 2.0 for a dual-isocenter intensity-modulated radiation therapy (IMRT) planning and delivery for gynecological cancer patients and examine the feasibility of in vivo portal dosimetry., Methods: Twelve gynecological cancer patients were treated with extended-field IMRT technique using two isocenters on Halcyon 2.0 to treat pelvis and pelvic/or para-aortic nodes region. The prescription dose was 45 Gy in 25 fractions (fxs) with simultaneous integrated boost (SIB) dose of 55 or 57.5 Gy in 25 fxs to involved nodes. All treatment plans, pretreatment patient-specific QA and treatment delivery records including daily in vivo portal dosimetry were retrospectively reviewed. For in vivo daily portal dosimetry analysis, each fraction was compared to the reference baseline (1st fraction) using gamma analysis criteria of 4 %/4 mm with 90% of total pixels in the portal image planar dose., Results: All 12 extended-field IMRT plans met the planning criteria and delivered as planned (a total of 300 fractions). Conformity Index (CI) for the primary target was achieved with the range of 0.99-1.14. For organs at risks, most were well within the dose volume criteria. Treatment delivery time was from 5.0 to 6.5 min. Interfractional in vivo dose variation exceeded gamma analysis threshold for 8 fractions out of total 300 (2.7%). These eight fractions were found to have a relatively large difference in small bowel filling and SSD change at the isocenter compared to the baseline., Conclusion: Halcyon 2.0 is effective to create complex extended-field IMRT plans using two isocenters with efficient delivery. Also Halcyon in vivo dosimetry is feasible for daily treatment monitoring for organ motion, internal or external anatomy, and body weight which could further lead to adaptive radiation therapy., (© 2019 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

Purpose: The purpose of this study was to study the correlation between intraoperative and postimplant dosimetry. We investigated the correlation between prostate (V 150 ) and urethra (D 30 , D 5 ) dose limits, and whether it is possible to increase prostate D 90 and V 100 in intraoperative planning without violating postimplant urethra and rectum dose limits., Methods and Materials: Seventy-nine patients who underwent real-time ultrasound-guided prostate implants using intraoperative planning from 2013 to 2017 were analyzed. Forty-one of the 79 implants were 125 I as monotherapy and the remainder was 103 Pd as boost to external beam radiation therapy or external beam radiation therapy plus androgen deprivation therapy. Prescriptions followed the guidelines of AAPM TG-137. The urethra was catheterized during intraoperative implantation and postimplant imaging to facilitate the urethra identification. T2-cubed MRI and CT were acquired on the same day and about 1 month after the low-dose-rate procedure, and MRI was later fused with the CT scan for accurate delineation of the prostate and postimplant dosimetry evaluation. An institutionally based peer-review process and document procedure were established based on national recommendations. Correlation of dose parameters: D 90 , V 150 , V 100 of prostate, D 30 , D 5 of urethra, and V 100 of rectum between intraoperative and postimplant plans were evaluated., Results: D 90 and V 100 declined for all implants between intraoperative and postimplant dosimetry. On average, D 90 declined by 17.5% and 21.7% for 125 I and 103 Pb implants, respectively. V 100 declined for all implants between intraoperative and postimplant dosimetry but less pronounced. Prostate V 150 and urethra D 30 and D 5 also showed different tendency of decline. Of the 79 implants, 60 did not meet the postimplant dosimetry target for prostate (V 150  ≤ 50%), and 46 of the 60 implants met the optimal dosimetry targets for both D 30 (<125%) and D 5 (<150%), and the other 14 of the 60 implants failed to meet either the D 30 or the D 5 limits. All the implants met the postimplant target dose for rectum: V 100 ≤ 1.3 cc., Conclusion: Intraoperative implant dosimetry could not accurately predict postimplant dosimetry; however, to avoid underdosage of prostate, intraoperative D 90 should be close to 120% of prescribed dose and V 100 needs to be close to 100% of prescribed dose. Prostate V 150 > 50% does not necessarily indicate the violation of urethra D 30 and D 5 dose limits. For most of the implants, target intraoperative D 90 and V 100 could be raised without violating urethra D 30 and D 5 limits recommended by American Brachytherapy Society in postimplant evaluation., (Copyright © 2018 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: A new type of linear accelerator (linac) was recently introduced into the market by a major manufacturer. Our institution is one of the early users of this preassembled and preconfigured dual-layer multileaf collimator (MLC), ring-gantry linac - Halcyon™ (1st version). We performed a set of full acceptance testing and commissioning (ATC) measurements for three Halcyon machines and compared the measured data with the standard beam model provided by the manufacturer. The ATC measurements were performed following the guidelines given in different AAPM protocols as well as guidelines provided by the manufacturer. The purpose of the present work was to perform a risk assessment of the ATC process for this new type of linac and investigate whether the results obtained from this analysis could potentially be used as a guideline for improving the design features of this type of linac., Methods: AAPM's TG100 risk assessment methodology was applied to the ATC process. The acceptance testing process relied heavily on the use of a manufacturer-supplied phantom and the automated analysis of electronic portal imaging device (EPID) images. For the commissioning process, a conventional measurement setup and process (e.g., use of water tank for scanning) was largely used. ATC was performed using guidelines recommended in various AAPM protocols (e.g., TG-106, TG-51) as well as guidelines provided by the manufacturer. Six medical physicists were involved in this study. Process maps, process steps, and failure modes (FMs) were generated for the ATC procedures. Failure modes and effects analysis (FMEA) were performed following the guidelines given in AAPM TG-100 protocol. The top 5 and top 10 highest-ranked FMs were identified for the acceptance and commissioning procedures, respectively. Quality control measures were suggested to mitigate these FMs., Results: A total of 38 steps and 88 FMs were identified for the entire ATC process. Fourteen steps and 34 FMs arose from acceptance testing. The top 5 FMs that were identified could potentially be mitigated by the manufacturer. For commissioning, a total of 24 steps and 54 potential FMs were identified. The use of separate measurement tools that are not machine-integrated has been identified as a cause for the higher number of steps and FMs generated from the conventional ATC approach. More than half of the quality control measures recommended for both acceptance and commissioning could potentially be incorporated by the manufacturer in the design of the Halcyon machine., Conclusion: This paper presents the results of FMEA and quality control measures to mitigate the FMs for the ATC process for Halcyon machine. Unique FMs that result from the differences in the ATC guidelines provided by the vendor and current conventional protocols, and the challenges of performing the ATC due to the new linac features and ring-gantry design were highlighted for the first time. The FMs identified in the present work along with the suggested quality control measures, could potentially be used to improve the design features of future ring-gantry type of linacs that are likely to be preassembled, preconfigured, and heavily reliant on automation and image guidance., (© 2019 American Association of Physicists in Medicine.)

Purpose: The goal of this work is to provide a large and consistent set of data for detector-specific output correction factors, k Q clin , Q ref f clin , f ref , for small static fields for seven solid-state detectors and to determine field output factors, Ω Q clin , Q ref f clin , f ref , using EBT3 radiochromic films and W1 plastic scintillator as reference detectors on two different linear accelerators and four megavoltage photon beams. Consistent measurement conditions and recommendations given in the International Code of Practice TRS-483 for small-field dosimetry were followed throughout the study., Methods: Ω Q clin , Q ref f clin , f ref were determined on two linacs, Elekta Versa HD and Varian TrueBeam, for 6 and 10 MV beams with and without flattening filter and for nine fields ranging from 0.5 × 0.5 cm 2 to 10 × 10 cm 2 . Signal readings obtained with EBT3 radiochromic films and W1 plastic scintillator were fitted by an analytical function. Volume averaging correction factors, determined from two-dimensional (2D) dose matrices obtained with EBT3 films and fitted to bivariate Gaussian function, were used to correct measured signals. k Q clin , Q ref f clin , f ref were determined empirically for six diodes, IBA SFD, IBA Razor, PTW 60008 P, PTW 60012 E, PTW 60018 SRS, and SN EDGE, and a PTW 60019 microDiamond detector., Results: Field output factors and detector-specific k Q clin , Q ref f clin , f ref are presented in the form of analytical functions as well as in the form of discrete values. It is found that in general, for a given linac, small-field output factors need to be determined for every combination of beam energy and filtration (WFF or FFF) and field size as the differences between them can be statistically significant (P < 0.05). For different beam energies, the present data for k Q clin , Q ref f clin , f ref are found to differ significantly (P < 0.05) from the corresponding data published in TRS-483 mostly for the smallest fields (<1.5 cm). For the PTW microDiamond detector, statistically significant differences (P < 0.05) between k Q clin , Q ref f clin , f ref values were found for all investigated beams on an Elekta Versa HD linac for field sizes 0.5 × 0.5 cm 2 and 0.8 × 0.8 cm 2 . Significant differences in k Q clin , Q ref f clin , f ref between beams of a given energy but with and without flattening filters are found for measurements made in small fields (<1.5 cm) at a given linac. Differences in k Q clin , Q ref f clin , f ref are also found when measurements are made at different linacs using the same beam energy filtration combination; for the PTW microDiamond detector, these differences were found to be around 6% and were considered as significant., Conclusions: Selection of two reference detectors, EBT3 films and W1 plastic scintillator, and use of an analytical function, is a novel approach for the determination of Ω Q clin , Q ref f clin , f ref for small static fields in megavoltage photon beams. Large set of k Q clin , Q ref f clin , f ref data for seven solid-state detectors and four beam energies determined on two linacs by a single group of researchers can be considered a valuable supplement to the literature and the TRS-483 dataset., (© 2018 The Authors. Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

Purpose: Underutilization of hypofractionated whole-breast irradiation (HF-WBI) in large-breasted women may be partially explained by concerns about dose heterogeneity. Although modern planning may mitigate this issue, validated dosimetric guidelines are lacking. Our clinical pathway mandates hypofractionation, guided by institutional dosimetric criteria for plan evaluation. We examined acute radiation dermatitis rates with HF-WBI in large-breasted patients when our guidelines are followed and evaluated factors predictive for dermatitis., Methods and Materials: Patients with whole-breast clinical target volumes (WB-CTV) of ≥1000 cm 3 treated with HF-WBI were reviewed. WB-CTV V105, V107, and V110 were assessed. Our guidelines recommend limiting V105 to <10% to 15% and V110 to 0%. The highest grade of acute dermatitis was recorded. Potential clinical and dosimetric predictors of dermatitis were analyzed using logistic regression., Results: From 2012 to 2017, 505 breasts in 502 patients were treated with HF-WBI. The median WB-CTV was 1261.3 cm 3 (interquartile range [IQR], 1115.3-1510.0). Most plans (99%) delivered 42.56 Gy in 16 fractions. A cavity boost of 10 Gy in 4 fractions was delivered in 99% of plans. Electrons were used in 69% of boost plans. Three-dimensional field-in-field technique was used in 68% of plans and inverse-planned intensity modulated radiation therapy in 32%. The median WB-CTV V105 was 9.7% (IQR, 5.6%-13.3%); the median WB-CTV V107 was 0.8% (IQR, 0.0%-2.5%). The WB-CTV V110 was 0% in 97.4% of plans (median, 0.0%; IQR, 0.0%-0.0%). Grade 1, 2, and 3 dermatitis rates were 55.0%, 40.8%, and 3.4%, respectively. On multivariate analysis, age >64 years (P = .016; odds ratio [OR] 4.0; 95% confidence interval [CI], 1.3-12.3), WB-CTV >1500 cm 3  (P = .006; OR, 4.3; 95% CI, 1.5-12.3), body mass index ≥34 (P = .044; OR, 3.9; 95% CI, 1.0-14.5), and WB-CTV V105 >10% (P = .011; OR, 5.3; 95% CI, 1.5-19.3) predicted for grade 3 dermatitis., Conclusions: With our institutional dosimetric guidelines, grade 3 dermatitis rates with HF-WBI in large-breasted women was <5%. WB-CTV V105 should be optimized to <10% to keep grade 3 dermatitis rates <2%., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: A joint IAEA/AAPM international working group has developed a Code of Practice (CoP) for the dosimetry of small static fields used in external megavoltage photon beam radiotherapy, published by the IAEA as TRS-483. This summary paper introduces and outlines the main aspects of the CoP., Methods: IAEA TRS-483 is a condensation of the wide range of different approaches that have been described in the literature for the reference dosimetry of radiotherapy machines with nominal accelerating potential up to 10 MV that cannot establish the conventional 10 cm × 10 cm reference field, and for the determination of field output factors for relative dosimetry in small static photon fields. The formalism used is based on that developed by Alfonso et al. [Med Phys. 2008;35:5179-5186] for this modality., Results: Three introductory sections describe the rationale and context of the CoP, the clinical use of small photon fields, and the physics of small-field dosimetry. In the fourth section, definitions of terms that are specific to the CoP (as compared to previous CoPs for broad-beam reference dosimetry, such as IAEA TRS-398 and AAPM TG-51) are given; this section includes a list of the symbols and equivalences between IAEA and AAPM nomenclature to facilitate the practical implementation of the CoP by end users of IAEA TRS-398 and AAPM TG-51. The fifth section summarizes the equations and procedures that are recommended in the CoP and the sixth section provides an overview of the methods used to derive the data provided in IAEA TRS-483., Conclusions: This is the first time an international Code of Practice for the dosimetry of small photon fields based on comprehensive data and correction factors has been published. This joint IAEA/AAPM CoP will ensure consistent reference dosimetry traceable to the international System of Units and enable common and internationally harmonized procedures to be followed by radiotherapy centers worldwide for the dosimetry of small static megavoltage photon fields., (© 2018 American Association of Physicists in Medicine.)

Background: The purpose of this study was to present our evaluation of the cost-effectiveness of salvage therapies for patients with recurrent head and neck cancer., Methods: A Markov model was developed with 5 salvage treatment strategies: (1) platinum-based chemotherapy alone; (2) chemotherapy plus cetuximab; (3) stereotactic body radiotherapy (SBRT) alone; (4) SBRT plus cetuximab; and (5) intensity-modulated radiotherapy (IMRT) plus chemotherapy. Clinical parameters were obtained from comprehensive literature review and 2016 Medicare reimbursement. Strategies were compared using the incremental cost-effectiveness ratio (ICER), with effectiveness in quality-adjusted life years (QALYs), and evaluated with a willingness-to-pay (WTP) threshold of $100 000 per QALY gained., Results: In the base case analysis, no treatment strategy was cost-effective at a WTP threshold. The most cost-effective therapy was SBRT alone with $150 866 per QALY gained. If median survival of SBRT alone was ≥11 months, SBRT was considered to be cost-effective., Conclusion: None of the treatment strategies were cost-effective. However, SBRT-based reirradiation has potential to be cost-effective., (© 2018 Wiley Periodicals, Inc.)

Purpose: The International Atomic Energy Agency (IAEA) and the American Association of Physicists in Medicine (AAPM) have jointly published a new code of practice (CoP), TRS483, for the dosimetry of small static photon fields used in external beam radiotherapy. It gave recommendations on how to perform reference dosimetry in nonstandard machine-specific reference (msr) fields and measure field output factors in small fields. The purpose of this work was to perform a dosimetric evaluation of the recommendations given in this CoP., Methods: All measurements were done in a Varian TrueBeam™ STx linear accelerator. Five ionization chambers were used for beam quality measurements, four Farmer type ionization chambers for performing reference dosimetry and two diodes for performing field output factor measurements. Field output factor measurements were done for fourteen field sizes (ranging from 0.5 cm × 0.5 cm to 10 cm × 10 cm). Beam energies used were: 6 MV WFF, 6 MV FFF, 10 MV WFF, and 10 MV FFF. Where appropriate, results from this study were compared with those obtained from the recommendations given in the IAEA TRS398 CoP, AAPM TG51 and TG51 Addendum protocols., Results: Beam quality measurements show that for all beam energies and for equivalent square msr field sizes ranging from 4 cm × 4 cm to 10 cm × 10 cm, agreement between calculated and measured values of TPR 20,10 (10) was within 0.6%. When %dd(10,10) X was used as beam quality specifier, the agreement was found to be within 0.8%. Absorbed dose to water per unit monitor unit at the depth of maximum dose z max in a beam of quality Q, Dw,Qzmax/MU, was determined using both %dd(10,10) X and TPR 20,10 (10) as beam quality specifiers. Measured ratios of D w,Q (z max )/MU, determined using the two approaches, ranged between 0.999 and 1.000 for all the beam energies investigated. Comparison with TRS398, TG51 and TG51 addendum protocols show that depending on beam energy, the mean values of the ratios TRS398/TRS483, TG51/TRS483, and TG51 Addendum/TRS483 of D w,Q (z max )/MU determined using both approaches show excellent agreement with TRS398 CoP (to within 0.05%); agreement with TG51 and TG51 addendum was to within 0.3% for all four beam energies investigated. Field output factors, determined using the two methods recommended in the TRS483 CoP, showed excellent agreement between the two methods. For the 1 cm collimator field size, the mean value of the field output factor obtained from an average of the two detectors investigated was found to be 2% lower than the mean value of the uncorrected ratio of readings., Conclusion: For beams with and without flattening filters, the values of D w,Q (z max )/MU obtained following the new CoP are found to be consistent with those obtained using TRS398, TG51 and TG51 addendum protocols to within 0.3%. Field output factors for small beams can be improved when the correction factors for different detectors included in TRS483 are appropriately incorporated into their dosimetry., (© 2018 American Association of Physicists in Medicine.)

The use of small fields in radiation therapy techniques has increased substantially in particular in stereotactic radiosurgery (SRS) and stereotactic body radiation therapy (SBRT). However, as field size reduces further still, the response of the detector changes more rapidly with field size, and the effects of measurement uncertainties become increasingly significant due to the lack of lateral charged particle equilibrium, spectral changes as a function of field size, detector choice, and subsequent perturbations of the charged particle fluence. This work presents a novel 3D dose volume-to-point correction method to predict the readings of a 0.015 cc PinPoint chamber (PTW 31014) for both small static-fields and composite-field dosimetry formed by fixed cones on the CyberKnife ® M6 ™ machine. A 3D correction matrix is introduced to link the 3D dose distribution to the response of the PinPoint chamber in water. The parameters of the correction matrix are determined by modeling its 3D dose response in circular fields created using the 12 fixed cones (5 mm-60 mm) on a CyberKnife ® M6 ™ machine. A penalized least-square optimization problem is defined by fitting the calculated detector reading to the experimental measurement data to generate the optimal correction matrix; the simulated annealing algorithm is used to solve the inverse optimization problem. All the experimental measurements are acquired for every 2 mm chamber shift in the horizontal planes for each field size. The 3D dose distributions for the measurements are calculated using the Monte Carlo calculation with the MultiPlan ® treatment planning system (Accuray Inc., Sunnyvale, CA, USA). The performance evaluation of the 3D conversion matrix is carried out by comparing the predictions of the output factors (OFs), off-axis ratios (OARs) and percentage depth dose (PDD) data to the experimental measurement data. The discrepancy of the measurement and the prediction data for composite fields is also performed for clinical SRS plans. The optimization algorithm used for generating the optimal correction factors is stable, and the resulting correction factors were smooth in the spatial domain. The measurement and prediction of OFs agree closely with percentage differences of less than 1.9% for all the 12 cones. The discrepancies between the prediction and the measurement PDD readings at 50 mm and 80 mm depth are 1.7% and 1.9%, respectively. The percentage differences of OARs between measurement and prediction data are less than 2% in the low dose gradient region, and 2%/1 mm discrepancies are observed within the high dose gradient regions. The differences between the measurement and prediction data for all the CyberKnife based SRS plans are less than 1%. These results demonstrate the existence and efficiency of the novel 3D correction method for small field dosimetry. The 3D correction matrix links the 3D dose distribution and the reading of the PinPoint chamber. The comparison between the predicted reading and the measurement data for static small fields (OFs, OARs and PDDs) yield discrepancies within 2% for low dose gradient regions and 2%/1 mm for high dose gradient regions; the discrepancies between the predicted and the measurement data are less than 1% for all the SRS plans. The 3D correction method provides an access to evaluate the clinical measurement data and can be applied to non-standard composite fields intensity modulated radiation therapy point dose verification.