Human thioredoxin-1 (TRX) is a target-selective disulfide reductase with antioxidant, anti-inflammatory, and regulatory functions that mitigates cellular stresses in various organ systems, providing a compelling rationale for therapeutic use as a broad-spectrum cell protectant. However, clinical application of recombinant TRX (rhTRX) is constrained by rapid clearance and proliferative intracellular activity. To overcome these limitations, a rationally designed TRX variant, ORP100S, was engineered for enhanced stability, prolonged extracellular target engagement, and improved protective function, with development of novel single-turnover insulin reduction and hybrid-immunocapture LC-MS assays. ORP100S demonstrates high-yield expression in E. coli (16 g L-1) and exhibits significant in vivo mitigating effects when administered subcutaneously to rodents and non-human primates exposed to otherwise-lethal total-body ionizing radiation. Compared to native TRX, ORP100S displays improved pharmacokinetic and pharmacodynamic properties without promoting murine or human cancer cell proliferation. Additionally, ORP100S protects hematopoietic stem/progenitor cells (HSPCs) from chemotherapy-induced toxicity in vitro and in vivo synergistically with co-administered granulocyte-macrophage colony-stimulating factor (GM-CSF). Mechanistic studies revealed that ORP100S modulates the Kruppel-like factor 4 (KLF4)-p53 pathway to selectively inhibit ferroptosis in HSPCs but not cancer cells. These findings highlight the potential of ORP100S as a novel therapeutic agent for mitigating acute radiation injury and improving the safety and efficacy of chemotherapy without compromising antitumor activity.

Wake Forest University School of Medicine (WFUSM) hosts the Radiation Late Effects Cohort (RLEC), a unique cohort of previously irradiated rhesus monkeys gathered from multiple institutions over twenty years. Supported by the National Institutes of Health's National Institute of Allergy and Infectious Diseases (NIH/NIAID) Radiation/Nuclear program, it serves as a resource for the Centers for Medical Countermeasures against Radiation Consortium (CMCRC) and the wider biomedical research community. These animals act as a national resource for examining the long-term effects of radiation exposure. Since its establishment in 2007, the RLEC has studied 328 macaques, including 270 exposed to external beam ionizing radiation and 58 controls. Results to date reveal a multisystemic pattern of chronic illness, including metabolic disease and diabetes mellitus, hypertension, higher rates of cancers, long-term immune impairment, myocardial disease, cerebrovascular disease, low body weight, gonadal injury with reduced sex steroid output, cataracts, osteopenia, renal disease, compromised intestinal barrier function, and ongoing systemic inflammation. This summary highlights the essential aspects of the RLEC, the significant achievements of researchers using this resource, and the potential for further investigation of this unique animal population and its associated resources.

The thymus is critical for the development and selection of T cells with a diverse range of non-self-reactive antigen receptors. Both the thymus and circulating T cells can be damaged by acute exposure to ionizing radiation, leading to dose-dependent lymphopenia, a temporarily increased risk of infection that can be life-threatening, and long-term disruptions in T cell homeostasis and function. Currently, there are no biomedical countermeasures available to prevent radiation-induced T cell lymphopenia or other T cell defects caused by radiation. Therefore, preclinical models of radiation-induced thymic injury are necessary for testing countermeasures. Adult mice and non-human primates (NHP) that are subjected to whole-body or thorax irradiation are suitable models for this purpose. However, findings from these models may not directly apply to juveniles, given the significant changes in thymus size and function during childhood. To address this, we characterized the effects of 10 Gy whole-thorax irradiation on the thymus of pediatric rhesus macaque NHPs. Computed tomography (CT) assessments of thymic density and volume were used as in vivo indicators of thymic injury, but they did not correlate with the changes in thymic weight observed 19 weeks after irradiation. Histopathological staining revealed that whole-thorax irradiation caused disruption of thymic architecture, evident four months post-irradiation in some animals. Molecular analyses showed that radiation led to a decrease in thymic output, reduced diversity of T cell antigen receptors, and an over-representation of certain receptor sequences indicative of extensive clonal expansion. Overall, this work demonstrates the usefulness of the NHP whole-thorax irradiation model-commonly employed in lung radiobiology research-in studying radiation-induced thymic injury in children and in developing medical countermeasures.

OBJECTIVE:Gamma Knife radiosurgery (GKRS) is a treatment option for refractory trigeminal neuralgia (TN). However, there is a paucity of data regarding the effectiveness of GKRS for relapsing TN following microvascular decompression (MVD). The aim of this study was to characterize the response rate, complications, pain relief durability, and predictors of pain relapse for salvage GKRS following MVD for TN. METHODS:A retrospective study of all patients who received GKRS for Burchiel type 1 TN (TN1) or type 2 TN (TN2) pain at Wake Forest University School of Medicine was conducted. Pain was measured using the Barrow Neurological Institute (BNI) pain intensity score. After an initial pain response of BNI scores I-III, a BNI score of IV or V constituted relapse. Durability of pain relief was characterized using the Kaplan-Meier estimator. Predictors of relapse were investigated using Cox regression models. Statistical significance was set at p < 0.05. RESULTS:Of 2065 patients with TN1 or TN2, 59 had GKRS post-MVD. Forty-nine (83.1%) of these patients experienced a BNI pain score of I-III at the first follow-up post-GKRS. The median time to relapse was 1.75 years; freedom rates from relapse were 77%, 45.9%, and 30.7% at 1, 2, and 5 years, respectively. Radiofrequency ablation prior to MVD significantly decreased the likelihood of an initial response to salvage GKRS (Fisher's exact test, p = 0.02). After controlling for baseline and clinical characteristics, facial numbness significantly decreased the likelihood of pain relapse (Cox regression, HR 0.15, 95% CI 0.03-0.73; p = 0.01). Conversely, a worse initial pain response significantly increased the likelihood of pain relapse (Cox regression, HR 3.64, 95% CI 1.02-12.95; p = 0.04). Pain relapse within 24 months of the original MVD did not predict durability of pain relief following salvage GKRS (Cox regression, HR 0.94, 95% CI 0.40-2.22; p = 0.89). The overall toxicity rate of salvage GKRS was 35.6%. CONCLUSIONS:Salvage GKRS presents an effective, noninvasive option for recurring TN after MVD, with a comparable response rate to primary GKRS or MVD, and a favorable complications profile relative to salvage MVD. Patients with postoperative facial numbness and a better initial pain response may experience more durable pain relief following salvage GKRS.

Organic dosimeters offer unique advantages over traditional technologies, and they can be used to expand the capabilities of current radiation detection systems. In-depth knowledge of the mechanisms underlying the interaction between radiation and organic materials is essential for their widespread adoption. Here, we identified and quantitatively characterized the electronic traps generated during the operation of radiation dosimeters based on organic field-effect transistors. Spectral analysis of the trap density of states, along with optical and structural studies, revealed the origin of trap states as local structural disorder within the crystalline films. Our results provide new insights into the radiation-induced defects in organic dosimeters, and pave the way for the development of more efficient and reliable radiation detection devices.

Cardiac exposure to ionizing radiation can damage both the microvasculature and coronary arteries, as well as increase the long-term risk of heart disease, myocardial fibrosis, and conduction abnormalities. Therapeutic agents capable of promoting recovery from radiation injury to the heart are limited. Growth hormone is linked to improved cardiac function following injury. Here, we leveraged a cynomolgus macaque model to determine the long-term outcomes of recombinant human growth hormone (rhGH) therapy on the heart following low-dose ionizing radiation. Macaques were exposed to 2 Gy radiation, treated with rhGH for one month, and assessed after 2 years. Overall, plasma lipid profile, cardiac function, and coronary artery disease were similar between rhGH and placebo treated animals. However, a subgroup of rhGH-treated animals exhibited more extensive atherosclerotic plaques in the coronary arteries. Together, these findings indicate that transient human growth hormone therapy subsequent to a single low dose of ionizing radiation involving the heart does not result in long-term changes to plasma cholesterol but may promote exacerbated coronary artery disease in a subset of individuals.

The ACR Intersociety Committee meeting of 2022 (ISC-2022) was convened around the theme of "Recovering From The Great Resignation, Moral Injury and Other Stressors: Rebuilding Radiology for a Robust Future." Representatives from 29 radiology organizations, including all radiology subspecialties, radiation oncology, and medical physics, as well as academic and private practice radiologists, met for 3 days in early August in Park City, Utah, to search for solutions to the most pressing problems facing the specialty of radiology in 2022. Of these, the mismatch between the clinical workload and the available radiologist workforce was foremost-as many other identifiable problems flowed downstream from this, including high job turnover, lack of time for teaching and research, radiologist burnout, and moral injury.

Rationale and objectives: The accurate, non-invasive, and rapid measurement of renal cortical fibrosis is needed for well-defined benchmarks of permanent injury and for use of anti-fibrotic agents. It is also needed for non-invasive and rapid assessment of the chronicity of human renal diseases. Materials and methods: We have used a non-human primate model of radiation nephropathy to develop a novel method of size-corrected CT imaging to quantify renal cortical fibrosis. Results: Our method has an area under the receiver operating curve of 0.96, which is superior to any other non-invasive method of measuring renal fibrosis. Conclusion: Our method is suitable for immediate translation to human clinical renal diseases.

Introduction: Rhesus macaques share extensive similarities with humans including immune cell populations, regulatory mechanisms, and targets for cancer immunotherapy but also naturally develop cancers at similar life stages. Hence, treating rhesus macaques with spontaneous tumors bears enormous potential as model for human cancer immunotherapy. Material and Methods: We identified 2 female rhesus macaques, 23.6y (CRC_1) and 20.3y (CRC_2) old with naturally occurring colorectal cancer by imaging and clinical assessments. We collected a pre-treatment tumor biopsy in CRC_1 prior to treatment with 8 Gy intensity-modulated radiotherapy (IMRT) to the proximal portion of the tumor and 2 mg/kg i.v. pembrolizumab. The second candidate (CRC_2) was not tumor biopsy-eligible due to anemia and was treated with pembrolizumab alone. We collected blood and peripheral lymph nodes (LNs) pre- and on-treatment and complete tissue collection was performed at the 3w time point including tumor-adjacent mesenteric LNs. Follow-up assessments include IHC (e.g. CD3, CD20, IBA1), flow cytometry, cytokine assessment in plasma, and transcriptomics of LN and tumor samples. Results and Discussions: Imaging revealed focal thickening of the proximal colonic wall with disrupted architecture in CRC_1 and focal colonic thickening and an enlarged adjacent LN in CRC_2. Both tumors displayed mismatch repair-deficiency (MLH1 & PMS2 loss) and a drastic reduction in infiltrating CD3 cells in neoplastic areas compared to adjacent healthy colon. On treatment, tumor-associated LNs demonstrated a mild increase in CD20+ cells in the medullary sinuses of both patients and increased follicle numbers with normal follicular architecture in reference to peripheral LNs. In both patients there was an increased number of tertiary lymphoid structures (TLS) surrounding the tumors, predominately populated with CD20+ cells and with Ki67+ germinal centers, profoundly so in CRC_2. Moreover, IBA1+ cells abundantly infiltrated both tumors but showed a higher aggregation within the stromal elements of the neoplasms. A gradient of histologic differentiation was evident in CRC_1 and coincided with a reduction of TLS, IBA1+ cell abundance, and CD3+ cell infiltration in those areas which were poorly differentiated. Within the irradiated tumor of CRC_1, there were abundant apoptotic cells which stained positively with cleaved caspase 3 at the 3w time point. Circulating blood counts as preliminary peripheral read-out revealed a reduction in circulating lymphocytes in both patients beginning at 3d (CRC_1) resp. 6d (CRC_2) and a sharp increase in monocytes at 3d in unirradiated patient CRC_2. Conclusion: The immunological and tumoral response to pembrolizumab and radiotherapy matches the clinical response in humans and enables an unprecedented examination of the peripheral and local lymph node response. Citation Format: Simon Deycmar, George W. Schaaf, Brendan J. Johnson, J. Daniel Bourland, James D. Ververs, Christopher T. Whitlow, J. Mark Cline. Naturally occurring colorectal cancer in rhesus macaques as model for human cancer immunotherapy: a first report on pembrolizumab ± radiotherapy. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5203.

The purpose of this study is to further validate the utility of our previously developed CNN in an alternative small animal model of BM through transfer learning. Unlike the glioma model, the BM mouse model develops multifocal intracranial metastases, including both contrast enhancing and non-enhancing lesions on DCE MRI, thus serving as an excellent brain tumor model to study tumor vascular permeability. Here, we conducted transfer learning by transferring the previously trained GBM CNN to DCE MRI datasets of BM mice. The CNN was re-trained to learn about the relationship between BM DCE images and target permeability maps extracted from the Extended Tofts Model (ETM). The transferred network was found to accurately predict BM permeability and presented with excellent spatial correlation with the target ETM PK maps. The CNN model was further tested in another cohort of BM mice treated with WBRT to assess vascular permeability changes induced via radiotherapy. The CNN detected significantly increased permeability parameter Ktrans in WBRT-treated tumors (p < 0.01), which was in good agreement with the target ETM PK maps. In conclusion, the proposed CNN can serve as an efficient and accurate tool for characterizing vascular permeability and treatment responses in small animal brain tumor models.

When I became the 2022 AAPM President I was Professor of Radiation Oncology, Physics and Biomedical Engineering at Wake Forest School of Medicine and University, Winston-Salem, NC, where I've been working for the last 26+ years. As for all AAPM Presidents, I served on many AAPM committees prior to becoming president-elect. My AAPM roles started in the late 1980s with TG-41 (HDR – I was a graduate student at the time and had designed a dedicated HDR suite for a new building), and then continued. Selected roles include Science/Ed Council Liaison, Hyperthermia (it was Hot at the time), Chair of the Inaugural Electronic Media Communication Committee (1997–2002; we decided all of the aapm.org policies and details, technologies for Headquarters - it was much fun), WC2000 Editorial Board, AE-Medical Physics, AIP DBOSS (my first introduction to the American Institute of Physics), International/African Affairs and IOMP Delegate at various times, Chair/Past Chair of MICRO, Board Member At-Large, TG-178 (Gamma Radiosurgery), JBMC/JsBMC, AIP Board of Directors (2009–2020), various Ad Hocs including MedPhys Match, Editor Team Review, and MedPhys 3.0, roles in peer societies such as ABR and SDAMPP, and then during 2022 with my presidential term there were several other ex officio committee memberships. The AAPM presidency role brings opportunities and challenges to address - on some of these the president makes decisions and for others, in AAPM's shared leadership model, the Executive Committee (the five Officers and the Executive Director, known as EXCOM) and the Board of Directors provide their counsel and direction on how to proceed. I formed an ad hoc committee to explore future revenue sources, given the forecast for decreases in AAPM's three main revenue sources. With a number of members interested and desiring to learn about artificial intelligence (AI), another ad hoc committee was formed to provide fundamental AI education for the medical physics community (AI boot camp approach). Global and national issues were on the forefront for AAPM during 2022, including the continuing impact of COVID on AAPM meetings, use of virtual presentations during in-person meetings, and societal issues of diversity, equity and inclusion and their considerations for AAPM meetings and the practice of medical physics. The 2022 AAPM Annual Meeting in Washington, DC, had my selected theme of “Celebrating Medical Physics - Transforming Human Health.” We Celebrated! the first in-person annual meeting since 2019 (virtual meetings had been held in 2020 and 2021), and in the President's Symposium, subtitled “Important Conversations”, I presented the challenge to Transform human health in both the seemingly small and loomingly large activities that we undertake as medical physicists – our work, makes a difference, for patient care. I chose guest speakers that focused on humanity, with two personal accounts on the impact of severe disease, in this case Alzheimer's and Cancer, on ones’ lives, to remind us that while medical physics is about technology applied to human health, our field is ultimately about people. The design elements of the 2022 Annual Meeting motif were carefully conceived, which Headquarters staff creatively brought to life (Figure 1). The motif reflects the medical physicist's contributions of critical thinking, problem solving and scholarship. The AAPM Presidency is deeply rewarding and an immense honor for the opportunity to serve AAPM and the medical physics community. It is also a significant time commitment and effort. The Executive Committee members serve as closest colleagues for ongoing activities, the Board sets the overall vision and strategic plan, and AAPM Headquarters Staff and all of our AAPM member volunteers contribute daily to make AAPM's mission go forward. AAPM is a volunteer-driven association, and within EXCOM, with 1-year terms in the presidential chain being somewhat fleeting, we have agreed to the high priority for continuity of AAPM's mission across our individual terms - to collectively provide for AAPM's future. My AAPM colleagues, thank you for the opportunity to serve you as the 2022 AAPM President.

Thrombocytopenia, hemorrhage, anemia, and infection are life-threatening issues following accidental or intentional radiation exposure. Since few therapeutics are available, safe and efficacious small molecules to mitigate radiation-induced injury need to be developed. Our previous study showed the synthetic TLR2/TLR6 ligand fibroblast stimulating lipopeptide (FSL-1) prolonged survival and provided MyD88-dependent mitigation of hematopoietic acute radiation syndrome (H-ARS) in mice. Although mice and humans differ in TLR number, expression, and function, nonhuman primate (NHP) TLRs are like those of humans; therefore, studying both animal models is critical for drug development. The objectives of this study were to determine the efficacy of FSL-1 on hematopoietic recovery in small and large animal models subjected to sublethal total body irradiation and investigate its mechanism of action. In mice, we demonstrate a lack of adverse effects, an easy route of delivery (subcutaneous) and efficacy in promoting hematopoietic progenitor cell proliferation by FSL-1. NHP given radiation, followed a day later with a single subcutaneous administration of FSL-1, displayed no adversity but showed elevated hematopoietic cells. Our analyses revealed that FSL-1 promoted red blood cell development and induced soluble effectors following radiation exposure. Cytologic analysis of bone marrow aspirates revealed a striking enhancement of mononuclear progenitor cells in FSL-1-treated NHP. Combining the efficacy of FSL-1 in promoting hematopoietic cell recovery with the lack of adverse effects induced by a single administration supports the application of FSL-1 as a viable countermeasure against H-ARS.

Computed tomography (CT) imaging has been used to diagnose radiation-induced lung injury for decades. However, histogram-based quantitative tools have rarely been applied to assess lung abnormality due to radiation-induced lung injury (RILI). Here, we used first-order summary statistics to derive and assess threshold measures extracted from whole lung histograms of CT radiodensity in rhesus macaques. For the present study, CT scans of animals exposed to 10 Gy of whole thorax irradiation were utilized from a previous study spanning 2–9 months postirradiation. These animals were grouped into survivors and non-survivors based on their clinical and experimental endpoints. We quantified the change in lung attenuation after irradiation relative to baseline using three density parameters; average lung density (ALD), percent change in hyper-dense lung volume (PCHV), hyperdense volume as a percent of total volume (PCHV/TV) at 2-month intervals and compared each parameter between the two irradiated groups (non-survivors and survivors). We also correlated our results with histological findings. All the three indices (ALD, PCHV, PCHV/TV) obtained from density histograms showed a significant increase in lung injury in non-survivors relative to survivors, with PCHV relatively more sensitive to detect early RILI changes. We observed a significant positive correlation between histologic pneumonitis scores and each of the three CT measurements, indicating that CT density is useful as a surrogate for histologic disease severity in RILI. CT-based three density parameters, ALD, PCHV, PCHV/TV, may serve as surrogates for likely histopathology patterns in future studies of RILI disease progression.

Background Rhesus macaques share extensive similarities with humans including immune cell populations, regulatory mechanisms, and targets for cancer immunotherapy, but also naturally develop cancers at similar life stages. Treating rhesus macaques with spontaneous tumors bears enormous potential as a model for human cancer immunotherapy. Methods For this study (figure 1), we recruited 2 female rhesus macaques with naturally-occurring colorectal cancer (CRC): 23.6y (CRC_1) and 20.3y (CRC_2) old. We collected a pre-treatment tumor biopsy in CRC_1 prior to treatment with 8 Gy intensity-modulated radiotherapy (IMRT) to the proximal portion of the tumor and 2 mg/kg i.v. pembrolizumab. The second candidate (CRC_2) was not tumor biopsy-eligible and treated with pembrolizumab alone. Sampling consisted of blood and peripheral lymph nodes (LNs) pre- and on-treatment and complete tissue collection at the 3w endpoint. Follow-up analysis consisted of flow cytometry (PBMCs), IHC, and transcriptomics. Results Morphologically, both tumors presented with focal thickening of the proximal colonic wall, and were mismatch repair deficiency. Flow cytometry of PBMCs revealed a strong response of CD4 and CD8 in aPD1+IMRT-treated CRC_1, acutely driven by TEMRA (CD45RA+CD62L-) at 3d and replaced by the increasing Tem population (CD45RA- CD62L-) at the later time points. This was accompanied by an increase of OX40+ (2w, strongest in CD4) and PD1+ T cells (3w, strongest in CD8). aPD1-only CRC_2 presented with a much milder PBMC response, only limited expansion of Tem, a reduced OX40+ upregulation, and no elevation in PD1+ towards the 3w endpoint. IHC revealed a mild treatment response composed of a reduction of CD4/FoxP3, and increase of high endothelial venules (MECA-79) was observed in peripheral LNs of CRC_1. Additionally, we observed an initial reduction of CD3, CD8, and CD20 staining in peripheral LNs of CRC_2 at 1w, followed by a mild expansion at the later time point. Following therapy, extensive numbers of TLS were observed adjacent to both CRCs, consisting primarily of CD20+ B cells with germinal centers (Ki67+ and PD1+ cells), and T cell zones (CD3+/CD4+/CD4+FoxP3+/CD8+). Both tumors were depleted of CD3+ T cells, particularly in more poorly differentiated regions. Notably, IBA1+ macrophages extensively infiltrated both tumors and were enriched at the tumor margins and the TLS periphery. Conclusions In rhesus CRCs, we observed similar immune-depleted phenotypes and response to aPD1±IMRT as described in humans, enabling an unprecedented opportunity to dissect the impact of the tumor microenvironment on the acute and long-term response and resistance. Ethics Approval All procedures were approved by the WFSM Institutional Animal Care and Use Committee, in compliance with the U.S. Animal Welfare Act, The Guide for the Care and Use of Laboratory Animals, the Office of Laboratory Animal Welfare, and Public Health Service Policy. WFSM is accredited by the Association for the Assessment and Accreditation of Laboratory Animal Care, International (AAALACi).

PURPOSE:Data on the efficacy and safety of stereotactic radiosurgery (SRS) for treatment of radiation-induced meningiomas (RIMs) are limited. METHODS:A single institution database of Cobalt-60 SRS cases from 08/1999 to 10/2020 was reviewed. Radiation-induced meningiomas were identified using Cahan's criteria. Endpoints included overall survival (OS), progression free survival (PFS), local control (LC), treatment failure, and treatment toxicity. Univariate and multivariate analyses were performed using cox proportional hazard models. RESULTS:A total of 29 patients with 86 RIM lesions were identified. Median follow-up after SRS was 59 months. The median dose prescribed to the 50% isodose line was 14 Gy (range 12-20 Gy). The actuarial 5-yr OS and PFS were 96% and 68%, respectively. Patients treated for recurrent RIMs had a significantly lower PFS (45% vs 94% at 3 yr, p < 0.005) than patients treated in the upfront setting. Patients with presumed or WHO grade I RIMs had a significantly greater PFS (3-year PFS 96% vs 20%) than patients with WHO grade II RIMs (p < 0.005). On a per-lesion basis, local control (LC) at 1-, 3-, and 5-yrs was 82%, 76%, 74%, respectively. On multivariate analysis, female gender was associated with improved LC (p < 0.001), while marginal doses > 14 Gy were associated with worse local control (p < 0.001). Grade I-III toxicity following treatment was 9.0%. CONCLUSIONS:Stereotactic radiosurgery is a safe and effective treatment option for radiographic RIMs, WHO grade I RIMs, or lesions treated in the upfront setting. WHO grade II lesions and recurrent lesions are at increased risk for disease progression.

The American Association of Physicists in Medicine (AAPM) formed Task Group 178 (TG-178) to perform the following tasks: review in-phantom and in-air calibration protocols for gamma stereotactic radiosurgery (GSR), suggest a dose rate calibration protocol that can be successfully utilized with all gamma stereotactic radiosurgery (GSR) devices, and update quality assurance (QA) protocols in TG-42 (AAPM Report 54, 1995) for static GSR devices. The TG-178 report recommends a GSR dose rate calibration formalism and provides tabulated data to implement it for ionization chambers commonly used in GSR dosimetry. The report also describes routine mechanical, dosimetric, and safety checks for GSR devices, and provides treatment process quality assurance recommendations. Sample worksheets, checklists, and practical suggestions regarding some QA procedures are given in appendices. The overall goal of the report is to make recommendations that help standardize GSR physics practices and promote the safe implementation of GSR technologies.

PurposeRadiation-induced lung injury (RILI) is a progressive condition with an early phase (radiation pneumonitis) and a late phase (lung fibrosis). RILI may occur after partial-body ionizing radiation exposures or internal radioisotope exposure, with wide individual variability in timing and extent of lung injury. This study aimed to provide new insights into the pathogenesis and progression of RILI in the nonhuman primate (NHP) rhesus macaque model.Methods and MaterialsWe used an integrative approach to understand RILI and its evolution at clinical and molecular levels in 17 NHPs exposed to 10 Gy of whole-thorax irradiation in comparison with 3 sham-irradiated control NHPs. Clinically, we monitored respiratory rates, computed tomography (CT) scans, plasma cytokine levels, and bronchoalveolar lavage (BAL) over 8 months and lung samples collected at necropsy for molecular and histopathologic analyses using RNA sequencing and immunohistochemistry.ResultsElevated respiratory rates, greater CT density, and more severe pneumonitis with increased macrophage content were associated with early mortality. Radiation-induced lung fibrosis included polarization of macrophages toward the M2-like phenotype, TGF-β signaling, expression of CDKN1A/p21 in epithelial cells, and expression of α-SMA in lung stroma. RNA sequencing analysis of lung tissue revealed SERPINA3, ATP12A, GJB2, CLDN10, TOX3, and LPA as top dysregulated transcripts in irradiated animals. In addition to transcriptomic data, we observed increased protein expression of SERPINA3, TGF-β1, CCL2, and CCL11 in BAL and plasma samples.ConclusionsOur combined clinical, imaging, histologic, and transcriptomic analysis provides new insights into the early and late phases of RILI and highlights possible biomarkers and potential therapeutic targets of RILI. Activation of TGF-β and macrophage polarization appear to be key mechanisms involved in RILI.