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

The rapidly evolving field of radiomics has shown that radiomic features are able to capture characteristics of both tumor and normal tissue that can be used to make accurate and clinically relevant predictions. In the present study we sought to determine if radiomic features can characterize the adverse effects caused by normal tissue injury as well as identify if human embryonic stem cell (hESC) derived extracellular vesicle (EV) treatment can resolve certain adverse complications. A cohort of 72 mice (n = 12 per treatment group) were exposed to X-ray radiation to the whole lung (3 × 8 Gy) or to the apex of the right lung (3 × 12 Gy), immediately followed by retro-orbital injection of EVs. Cone-Beam Computed Tomography images were acquired before and 2 weeks after treatment. In total, 851 radiomic features were extracted from the whole lungs and

BACKGROUND: Genetic perturbation screens with single-cell readouts have enabled rich phenotyping of gene function and regulatory networks. These approaches have been challenging in vivo, especially in adult disease models such as cancer, which include mixtures of malignant and microenvironment cells. Glioblastoma (GBM) is a fatal cancer, and methods of systematically interrogating gene function and therapeutic targets in vivo, especially in combination with standard of care treatment such as radiotherapy, are lacking. RESULTS: Here, we iteratively develop a multiplex in vivo perturb-seq CRISPRi platform for single-cell genetic screens in cancer and tumor microenvironment cells that leverages intracranial convection enhanced delivery of sgRNA libraries into mouse models of GBM. Our platform enables potent silencing of drivers of in vivo growth and tumor maintenance as well as genes that sensitize GBM to radiotherapy. We find radiotherapy rewires transcriptional responses to genetic perturbations in an in vivo-dependent manner, revealing heterogenous patterns of treatment sensitization or resistance in GBM. Furthermore, we demonstrate targeting of genes that function in the tumor microenvironment, enabling alterations of ligand-receptor interactions between immune and stromal cells following in vivo CRISPRi perturbations that can affect tumor cell phagocytosis. CONCLUSION: In sum, we demonstrate the utility of multiplexed perturb-seq for in vivo single-cell dissection of adult cancer and normal tissue biology across multiple cell types in the context of therapeutic intervention, a platform with potential for broad application.

Meningiomas are the most common primary intracranial tumors in adults and are increasing in incidence due to the aging population and increased access to neuroimaging. While most exhibit nonmalignant behavior, a subset of meningiomas are biologically aggressive and are associated with treatment resistance, resulting in significant neurologic morbidity and even mortality. In recent years, meaningful advances in our understanding of the biology of these tumors have led to the incorporation of molecular biomarkers into their grading and prognostication. However, unlike other central nervous system (CNS) tumors, a unified molecular taxonomy for meningiomas has not yet been established and remains an overarching goal of the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy-Not Official World Health Organization (cIMPACT-NOW) working group. Additionally, clinical equipoise still remains on how specific meningioma cases and patient populations should be optimally managed. To address these existing gaps, members of the International Consortium on Meningiomas including field-leading experts, have prepared this comprehensive consensus narrative review directed toward clinicians, researchers, and patients. Included in this manuscript are detailed overviews of proposed molecular classifications, novel biomarkers, contemporary treatment strategies, trials on systemic therapies, health-related quality-of-life studies, and management strategies for unique meningioma patient populations. In each section, we discuss the current state of knowledge as well as ongoing clinical and research challenges to road map future directions for further investigation.

PurposeIn 2023 the American Urological Association (AUA) requested an Update Literature Review (ULR) to incorporate new evidence generated since the 2019 publication of this Guideline. The resulting 2024 Guideline Amendment addresses updated recommendations to provide guidance for the care of patients with incontinence after prostate treatment (IPT).Materials and methodsIn 2023, the IPT Guideline was updated through the AUA amendment process in which newly published literature is reviewed and integrated into previously published guidelines. There were 82 studies of interest initially identified in preliminary abstract review. Following full-text review, 17 studies met inclusion criteria and ultimately informed the statements of interest.ResultsThe Panel developed evidence- and consensus-based statements based on an updated review to provide guidance for the care of patients who experience IPT. These updates are detailed herein.ConclusionsAs prostate treatments are refined, a decreasing incidence of incontinence is anticipated. This Guideline will require further review as the diagnostic and treatment options for patients with IPT continue to evolve.

PURPOSE: CT Hounsfield Units (HUs) are converted to electron density using a calibration curve obtained from physical measurements of an electron density phantom. HU values assigned to an MRI-derived synthetic computed tomography (sCT) may present a different relationship with electron density compared to CT HU. Correct assignment of sCT HU values is critical for accurate dose calculation and delivery. The goals of this work were to develop a sCT calibration curve using patient data acquired on a clinically commissioned CT scanner and assess for CyberKnife- and volumetric modulated arc therapy (VMAT)-based MR-only treatment planning of prostate SBRT. METHODS: Same-day CT and MRI simulation in the treatment position were performed on 10 patients treated with SBRT to the prostate. Dixon in-phase and out-of-phase MRIs were acquired on a 3T scanner using a 3D T1-weighted gradient-echo sequence to generate sCTs using a commercial sCT algorithm. CT and sCT datasets were co-registered and HU values compared using mean absolute error (MAE). An optimized HU-to-density calibration curve was created based on average HU values across an institutional patient database for each of the four sCT tissue types. Clinical CyberKnife and VMAT treatment plans were generated on each patient CT and recomputed onto corresponding sCTs. Dose distributions computed using CT and sCT were compared using gamma criteria and dose-volume-histograms. RESULTS: For the optimized calibration curve, HU values were -96, 37, 204, and 1170 and relative electron densities were 0.95, 1.04, 1.1, and 1.7 for adipose, soft tissue, inner bone, and outer bone, respectively. The proposed sCT protocol produced total MAE of 94 ± 20HU. Gamma values mean ± std (min-max) were 98.9% ± 0.9% (97.1%-100%) and 97.7% ± 1.3% (95.3%-99.3%) for VMAT and CyberKnife plans, respectively. CONCLUSION: MRI-derived sCT using the proposed approach shows excellent dosimetric agreement with conventional CT simulation, demonstrating the feasibility of MRI-derived sCT for prostate SBRT treatment planning.

Cancer-related cognitive impairment (CRCI) is a consequence of chemotherapy and extracranial radiation therapy (ECRT). Our prior work demonstrated gliosis in the brain following ECRT in SKH1 mice. The signals that induce gliosis were unclear. Right hindlimb skin from SKH1 mice was treated with 20 Gy or 30 Gy to induce subclinical or clinical dermatitis, respectively. Mice were euthanized at 6 h, 24 h, 5 days, 12 days, and 25 days post irradiation, and the brain, thoracic spinal cord, and skin were collected. The brains were harvested for spatial proteomics, immunohistochemistry, Nanostring nCounter® glial profiling, and neuroinflammation gene panels. The thoracic spinal cords were evaluated by immunohistochemistry. Radiation injury to the skin was evaluated by histology. The genes associated with neurotransmission, glial cell activation, innate immune signaling, cell signal transduction, and cancer were differentially expressed in the brains from mice treated with ECRT compared to the controls. Dose-dependent increases in neuroinflammatory-associated and neurodegenerative-disease-associated proteins were measured in the brains from ECRT-treated mice. Histologic changes in the ECRT-treated mice included acute dermatitis within the irradiated skin of the hindlimb and astrocyte activation within the thoracic spinal cord. Collectively, these findings highlight indirect neuronal transmission and glial cell activation in the pathogenesis of ECRT-related CRCI, providing possible signaling pathways for mitigation strategies.

Prostate carcinoma is one of the most common cancers worldwide in men, with over 3 million men currently living with prostate carcinoma. In men, routine screening and successful treatment schemes, including radiation, prostatectomy, or hormone therapy, have allowed for high survivability. Dogs are recognized as one of the only mammals to spontaneously develop prostate neoplasia and are an important translational model. Within veterinary medicine, treatment options have historically been limited in efficacy or paired with high morbidity. Recently, less invasive treatment modalities have been investigated in dogs and people and demonstrated promise. Below, current treatment options available in dogs and people are reviewed, as well as a discussion of current and future trends within interventional treatment for canine PC.

Radiation therapy (RT) plays a crucial role in the treatment of head and neck cancers (HNCs). This paper emphasizes the importance of effective communication and collaboration between radiation oncologists and dental specialists in the HNC care pathway. It also provides an overview of the role of RT in HNC treatment and illustrates the interdisciplinary collaboration between these teams to optimize patient care, expedite treatment, and prevent post-treatment oral complications. The methods utilized include a thorough analysis of existing research articles, case reports, and clinical guidelines, with terms such as dental management, oral oncology, head and neck cancer, and radiotherapy included for this review. The findings underscore the significance of the early involvement of dental specialists in the treatment planning phase to assess and prepare patients for RT, including strategies such as prophylactic tooth extraction to mitigate potential oral complications. Furthermore, post-treatment oral health follow-up and management by dental specialists are crucial in minimizing the incidence and severity of RT-induced oral sequelae. In conclusion, these proactive measures help minimize dental and oral complications before, during, and after treatment.

BACKGROUND: Management strategies for metastatic castration-resistant prostate cancer (mCRPC) have rapidly shifted in recent years. As novel imaging and therapeutic approaches have made their way to the clinic, providers are encountering increasingly challenging clinical scenarios, with limited guidance from the current literature. MATERIALS AND METHODS: The US Prostate Cancer Conference (USPCC) is a multidisciplinary meeting of prostate cancer experts intended to address the many challenges of prostate cancer management. At the first annual USPCC meeting, areas of controversy and consensus were identified during a 2-day meeting that included expert presentations, full-panel discussions, and postdiscussion responses to questions developed by the USPCC cochairs and session moderators. RESULTS: This narrative review covers the USPCC expert discussion and perspectives relevant to mCRPC, including neuroendocrine/aggressive-variant prostate cancer (NEPC/AVPC). Areas of broad agreement identified among USPCC experts include the benefits of poly (ADP-ribose) polymerase (PARP) inhibitors for patients with BRCA1/2 mutations, the use of radioligand therapy in patients with prostate-specific membrane antigen (PSMA)-positive mCRPC, and the need for clinical trials that address real-world clinical questions, including the performance of novel therapies when compared with modern standard-of-care treatment. Ongoing areas of controversy and uncertainty included the appropriateness of PARP inhibitors in patients with non-BRCA1/2 mutations, the optimal definition of PSMA positivity, and systemic therapies for patients with NEPC/AVPC after progression on platinum-based therapies. CONCLUSIONS: The first annual USPCC meeting identified several areas of controversy in the management of mCRPC, highlighting the urgent need for clinical trials designed to facilitate treatment selection and sequencing in this heterogeneous disease state.

PURPOSE: Castration-sensitive prostate cancer (CSPC) is a complex and heterogeneous condition encompassing a range of clinical presentations. As new approaches have expanded management options, clinicians are left with myriad questions and controversies regarding the optimal individualized management of CSPC. MATERIALS AND METHODS: The US Prostate Cancer Conference (USPCC) multidisciplinary panel was assembled to address the challenges of prostate cancer management. The first annual USPCC meeting included experts in urology, medical oncology, radiation oncology, and nuclear medicine. USPCC co-chairs and session moderators identified key areas of controversy and uncertainty in prostate cancer management and organized the sessions with multidisciplinary presentations and discussion. Throughout the meeting, experts responded to questions prepared by chairs and moderators to identify areas of agreement and controversy. RESULTS: The USPCC panel discussion and question responses for CSPC-related topics are presented. Key advances in CSPC management endorsed by USPCC experts included the development and clinical utilization of gene expression classifiers and artificial intelligence (AI) models for risk stratification and treatment selection in specific patient populations, the use of advanced imaging modalities in patients with clinically localized unfavorable intermediate or high-risk disease and those with biochemical recurrence, recommendations of doublet or triplet therapy for metastatic CSPC (mCSPC), and consideration of prostate and/or metastasis-directed radiation therapy in select patients with mCSPC. CONCLUSIONS: CSPC is a diverse disease with many therapeutic options and the potential for adverse outcomes associated with either undertreatment or overtreatment. Future studies are needed to validate and clinically integrate novel technologies, including genomics, AI, and advanced imaging, to optimize outcomes among patients with CSPC.

Objective. In image-guided radiotherapy (IGRT), off-by-one vertebral body misalignments are rare but potentially catastrophic. In this study, a novel detection method for such misalignments in IGRT was investigated using densely-connected convolutional networks (DenseNets) for applications towards real-time error prevention and retrospective error auditing.Approach. A total of 4213 images acquired from 527 radiotherapy patients aligned with planar kV or MV radiographs were used to develop and test error-detection software modules. Digitally reconstructed radiographs (DRRs) and setup images were retrieved and co-registered according to the clinically applied alignment contained in the DICOM REG files. A semi-automated algorithm was developed to simulate patient positioning errors on the anterior-posterior (AP) and lateral (LAT) images shifted by one vertebral body. A DenseNet architecture was designed to classify either AP images individually or AP and LAT image pairs. Receiver-operator characteristic curves (ROC) and areas under the curves (AUC) were computed to evaluate the classifiers on test subsets. Subsequently, the algorithm was applied to the entire dataset in order to retrospectively determine the absolute off-by-one vertebral body error rate for planar radiograph guided RT at our institution from 2011-2021.Main results. The AUCs for the kV models were 0.98 for unpaired AP and 0.99 for paired AP-LAT. The AUC for the MV AP model was 0.92. For a specificity of 95%, the paired kV model achieved a sensitivity of 99%. Application of the model to the entire dataset yielded a per-fraction off-by-one vertebral body error rate of 0.044% [0.0022%, 0.21%] for paired kV IGRT including one previously unreported error.Significance. Our error detection algorithm was successful in classifying vertebral body positioning errors with sufficient accuracy for retrospective quality control and real-time error prevention. The reported positioning error rate for planar radiograph IGRT is unique in being determined independently of an error reporting system.

Aims: Magnetic resonance imaging (MRI)-only radiotherapy has emerged as a solution to address registration errors that can lead to missed dose delivery. However, the presence of systemic geometric distortion (SGD) stemming from gradient nonlinearity (GNL) and inhomogeneity of the main magnetic field (B[sub.0]) necessitates consideration. This study aimed to quantitatively assess residual SGD in 1.5T MRI simulation using a three-dimensional (3D) geometric distortion phantom and evaluate its impact on dosimetric accuracy for retrospective prostate cancer patients. Materials and Methods: Ten retrospective cases of prostate cancer patients treated with volumetric modulated arc radiotherapy (VMAT) were randomly selected. A geometric distortion phantom was scanned on a 1.5T MRI simulation using a 3D T1 volumetric interpolated breath-hold examination sequence, varying bandwidth (BW), and two-phase-encoding directions. Distortion maps were generated and applied to the original computed tomography (oriCT) plan to create a distorted computed tomography plan (dCT), and a dice similarity coefficient (DSC) was observed. Dosimetric accuracy was evaluated by recalculating radiation dose for dCT plans using identical beam parameters as oriCT. Results: The SGD increased with distance from the isocenter in all series. DSC exceeded 0.95 for all plans except the rectum. Regarding GNL's impact on dosimetric accuracy, most mean percentage errors for clinical target volume, planning target volume, and both femurs were under 2% in all plans, except for the bladder and rectum. Conclusion: SGD pre-evaluation is crucial and should be incorporated into a quality assurance program to ensure effective MRI-simulation performance before MRI-only treatment planning for prostate cancer. Keywords: Dosimetric accuracy, magnetic resonance imaging-only treatment planning, magnetic resonance imaging-simulation, systemic geometric distortion, Author(s): Korawig Chaknam [1]; Ladawan Worapruekjaru [2]; Sithiphong Suphaphong [2]; Nualjun Stansook [2]; Prapa Sodkokkruad [1]; Sawwanee Asavaphatiboon (corresponding author) [1] INTRODUCTION Magnetic resonance imaging (MRI) is increasingly integrated into [...]

Background: The induced activity is produced in the target, monitor chamber, flattening filter (FF), collimating jaws, etc., when a high-energy photon beam is utilized for radiation therapy. This may result in add-on exposure to radiation professionals. Objective: This study aims to measure the radiation level (RL) at the treatment plane due to induced activity in the linear accelerator head. Materials and Methods: In this study, RLs were measured close to the isocenter (I), LINAC head (H), and 0.5 m lateral to the isocenter (L) inside the radiation bunker. The RLs were measured for field sizes (FS) 5 cm x 5 cm, 10 cm x 10 cm, 20 cm x 20 cm, 30 cm x 30 cm, and 40 cm x 40 cm, using 50, 100, 200, 300, 400, 500, and 1000 monitor units (MUs) at above said locations inside the bunker using 10 mega-voltage (MV), 10 MV FF free, and 15 MV radiation beam. Results: RL increases with an increase in FS and MUs at all mentioned locations inside the bunker, except for 40 cm x 40 cm FS. The present study shows that RL increases with an increase in radiation beam energy, and there was significant RL inside the bunker at the mentioned location, even after the 1 min of high-energy radiation exposure. Conclusion: Therefore, treatment with a high-energy beam should be scheduled in the later evening of the working day and the jaw should be closed to a minimum before entering the bunker and a sufficient time gap should be followed to minimize the additional exposure due to induced activation in high-energy treatment. Keywords: Accelerator, high-energy X-rays, induced activity, neutron, radiation level, Author(s): Sonal Varshney (corresponding author) [1,2]; Lalit Kumar [3]; Umesh K. Dwivedi [1]; Pradeep Narayan [4] INTRODUCTION The Global Cancer Observatory 2020 estimated cancer incidence and mortality worldwide and deduced [...]

Objective: The aim of the study is to compare the accuracy of dose calculation for different dose calculation algorithms with different prescription points (air, tissue, air-tissue interface in carcinoma lung patients and bone, tissue, and bone-tissue interface in carcinoma buccal Mucosa tumors). Materials and Methods: Forty-one patients with carcinoma lung and buccal mucosa were retrospectively selected for this study. A three-dimensional conformal radiotherapy reference plan was created using the prescription point in the tissue with Monte Carlo (MC) algorithms for both the groups of patients. The reference plan was modified by changing the prescription point and algorithms in the tissue, air, air-tissue interface for lung patients and tissue, bone, and bone-tissue interface for buccal mucosa patients. The dose received by the target volume and other organs at risk (OAR) structures was compared. To find out the statistical difference between different prescription points and algorithms, the statistical tests were performed with repeated measures ANOVA. Results: The target volume receiving 95% dose coverage in lung patients decreased to -3.08%, -5.75%, and -1.87% in the dose prescription point at the air-tissue interface with the dose calculation algorithms like MC, collapsed cone (CC), and pencil beam (PB), respectively, compared to that of the MC tissue. Spinal cord dose was increased in the CC and PB algorithms in all prescription points in patients with lung and buccal mucosa. OAR dose calculated by PB in all prescription points showed a significant deviation compared to MC tissue prescription point. Conclusion: This study will help demonstrate the accuracy of dose calculation for the different dose prescription points with the different treatment algorithms in radiotherapy treatment planning. Keywords: Air-tissue interface, bone-tissue interface, dose calculation algorithms, dose prescription point, weight point, Author(s): Bharath Pandu (corresponding author) [1,2]; D. Khanna (corresponding author) [1]; Mohandass Palanisamy [3]; Saro Jacob [2]; Sherin Manichan [4] INTRODUCTION The goal of radiotherapy is to deliver an accurate [...]

Purpose: This study aims to investigate the radiation enhancement effects of ultrasound-stimulated microbubbles (USMB) with X-rays and nanoparticles on pancreatic cancer cells in vitro. Methods: Sonazoid™ microbubbles were used for USMB treatment with a commercially available ultrasound unit. The characterization of the microbubbles before and after ultrasound exposure with different mechanical parameters was evaluated microscopically. Two pancreatic cancer cell lines, MIAPaCa-2 and PANC-1, were treated with different concentrations of microbubbles in combination with 150 kVp X-rays and hydrogen peroxide-modified titanium dioxide nanoparticles. Cell viability was evaluated using a water-soluble tetrazolium dye and a colony formation assay. In addition, intracellular reactive oxygen species (ROS) induced by the combined treatment were assessed. Results: The number of burst microbubbles increased with ultrasound's higher mechanical index and the exposure time. A significant radiation enhancement effect with a significant increase in ROS levels was observed in MIAPaCa-2 cells treated with USMB and 6 Gy X-rays, whereas it was not significant in PANC-1 cells treated with the same. When a higher concentration of USMB was applied with X-rays, no radiation enhancement effects were observed in either cell line. Moreover, there was no radiation enhancement effect by USMB between cells treated with and without nanoparticles. Conclusions: The results indicate that USMB treatment can additively enhance the therapeutic efficacy of radiation therapy on pancreatic cancer cells, while the synergistic enhancement effects are likely to be cell type and microbubble concentration dependent. In addition, USMB did not improve the efficacy of nanoparticle-induced radiosensitization in the current setting. Keywords: Microbubbles, nanoparticles, radiation therapy, radiosensitizer, ultrasound, Author(s): Masao Nakayama (corresponding author) [1,2,3]; Ayaha Noda [4]; Hiroaki Akasaka [1,5]; Takahiro Tominaga [4]; Giulia McCorkell [2]; Moshi Geso [2]; Ryohei Sasaki [1] INTRODUCTION Microbubbles have been used clinically [...]

Objectives: The purpose of this study was to develop a prototype for controlling the water level of a three-dimensional (3D) water phantom using ultrasound sensors and Arduino technology and evaluate its performance in setting up the 3D water phantom for radiation beam measurements. Materials and Methods: A prototype consisted of an Arduino Nano board and two types of ultrasound sensors (US015 and SR04). The accuracy of both sensors was tested at various distances and the performance was evaluated through statistical analysis. The distance measurement test was performed rigorously at intervals of 2 cm from 5 cm to 21 cm, measuring an average error and a maximum deviation for each sensor. Results: Both sensors demonstrated the measurement accuracy within 2 mm. When using the traditional and prototype-based setup methods, the measured photon and electron beam profiles did not show any significant difference. This result suggests the equivalent setup capability when using these two different 3D water phantom setup methods. Conclusion: The ultrasound sensor-based prototype is demonstrated as a more effective device in maintaining the 3D water phantom setup consistently compared to the traditional method, which is prone to human error, and it will aid in facilitating precise phantom setup during the commissioning and routine quality assurance (QA) of linear accelerators in radiotherapy clinics. Keywords: Three-dimensional water phantom, quality assurance, ultrasonic sensors, water leveling, Author(s): Taehyung Kim [1,2]; Jeongun Kim [3]; Engchan Kim (corresponding author) [2] INTRODUCTION Radiation therapy is a precise medical procedure that utilizes high-energy radiation to treat diseases such as cancer. [...]

Opinion statementPSMA-PET has been a practice-changing imaging biomarker for the management of men with PCa. Research suggests improved accuracy over conventional imaging and other PET radiotracers in many contexts. With multiple approved PSMA-targeting radiotracers, PSMA PET will become even more available in clinical practice. Its increased use requires an understanding of the prospective data available and caution when extrapolating from prior trial data that utilized other imaging modalities. Future trials leveraging PSMA PET for treatment optimization and management decision-making will ultimately drive its clinical utility.

PURPOSE: The FLAME trial provides strong evidence that MR-guided external beam radiation therapy (EBRT) focal boost for localized prostate cancer increases biochemical disease-free survival (bDFS) without increasing toxicity. Yet, there are many barriers to implementation of focal boost. Our objectives are to systemically review clinical outcomes for MR-guided EBRT focal boost and to consider approaches to increase implementation of this technique. METHODS: We conducted literature searches in four databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guideline. We included prospective phase II/III trials of patients with localized prostate cancer underdoing definitive EBRT with MR-guided focal boost. The outcomes of interest were bDFS and acute/late gastrointestinal and genitourinary toxicity. RESULTS: Seven studies were included. All studies had a median follow-up of greater than 4 years. There were heterogeneities in fractionation, treatment planning, and delivery. Studies demonstrated effectiveness, feasibility, and tolerability of focal boost. Based on the Phoenix criteria for biochemical recurrence, the reported 5-year biochemical recurrence-free survival rates ranged 69.7-100% across included studies. All studies reported good safety profiles. The reported ranges of acute/late grade 3 + gastrointestinal toxicities were 0%/1-10%. The reported ranges of acute/late grade 3 + genitourinary toxicities were 0-13%/0-5.6%. CONCLUSIONS: There is strong evidence that it is possible to improve oncologic outcomes without substantially increasing toxicity through MR-guided focal boost, at least in the setting of a 35-fraction radiotherapy regimen. Barriers to clinical practice implementation are addressable through additional investigation and new technologies.

Technological advances in radiation oncology are oriented towards improving treatment precision and tumor control. Among these advances, magnetic-resonance-image-guided radiation therapy (MRgRT) stands out, with technological advances to deliver targeted treatments adapted to a tumors anatomy on the day while minimizing incidental exposure to organs at risk, offering an unprecedented therapeutic advantage compared to X-ray-based IGRT delivery systems. This new technology changes the traditional workflow in radiation oncology and requires an evolution in team coordination to administer more precise treatments. Once implemented, it paves the way for newer indication for radiation therapy to safely deliver higher doses than ever before, with better preservation of healthy tissues to optimize patient outcomes. In this narrative review, we assess the technical aspects of the novel linear accelerators that can deliver MRgRT and summarize the available published experience to date, focusing on oncological results and future challenges.

Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma, although it has many clinicopathological variants. Zosteriform MF is an extremely rare variant characterized by dermatomal distribution. To date, only six patients with zosteriform MF have been reported. We report a 57-year-old man with tumor-stage zosteriform MF localized on the left T4, T7-8, and bilateral L4 dermatomes for seven years after the first visit. Local skin-target therapy radiotherapy effectively led to complete remission, which was maintained with a combination of oral etretinate (30mg/day) and narrow-band ultraviolet B phototherapy. No other reports exist of zosteriform MF occurring in multiple dermatomes. We reviewed the literature to add to our understanding of the nature of rare variants of MF and discuss therapeutic options for zosteriform MF.

Esophageal cancer is one of the leading causes of cancer deaths globally with an incidence that is concentrated in specific hot spots in Eastern Asia, the Middle East, Eastern Africa, and South America. 10-year overall survival for patients treated with standard of care chemoradiation followed by surgical resection is below 40% highlighting the need for novel therapeutics to treat this disease. We assessed the effect of AMXI-5001, a novel small molecule poly ADP-Ribose polymerase (PARP) inhibitor and microtubule polymerization inhibitor on tumor growth inhibition in both in-vitro and in-vivo murine models. We found that AMXI-5001 was the most potent growth inhibitor of 8 out of 9 different esophageal carcinoma cell lines compared to other clinically available PARP inhibitors, Olaparib, Niraparib, Rucaparib, and Talazoparib. We then confirmed the previously described mechanism of action of AMXI-5001 as a PARP-inhibitor and microtubule polymerization inhibitor using both a PARP trapping assay and immunofluorescence. To further assess AMXI-5001s potential as a therapeutic for esophageal carcinoma we evaluated the effect of AMXI-5001 in combination with standard chemotherapy agents, Cisplatin and 5 Fluorouracil. We showed that AMXI-5001 synergistically inhibits growth in KYSE-70, a squamous esophageal cell line in combination with these drugs. In addition, we found that AMXI-5001 was an effective radiosensitizer, and squamous esophageal carcinoma cell lines treated 24 hours prior to external beam radiation showed significantly more growth inhibition compared to controls. Finally, we assessed the effect of AMXI-5001 monotherapy and in combination with radiotherapy in a xenograft mouse model implanted with subcutaneous KYSE-70 cells. Compared to vehicle control, and those treated with either AMXI-5001 alone or radiation alone, mice treated with both AMXI-5001 and radiation had significant tumor response. In conclusion, AMXI-5001 is an orally bioavailable dual-action PARP and microtubule polymerization inhibitor that holds promise in the treatment of esophageal carcinoma.

BackgroundRadiotherapy is an essential component of cancer treatment, yet many countries do not have adequate capacity to serve all patients who would benefit from it. Allocation systems are needed to guide patient prioritization for radiotherapy in resource-limited contexts. These systems should be informed by allocation principles deemed relevant to stakeholders. This study explores the ethical dilemmas and views of decision-makers engaged in real-world prioritization of scarce radiotherapy resources at a cancer center in Rwanda in order to identify relevant principles.MethodsSemi-structured interviews were conducted with a purposive sample of 22 oncology clinicians, program leaders, and clinical advisors. Interviews explored the factors considered by decision-makers when prioritizing patients for radiotherapy. The framework method of thematic analysis was used to characterize these factors. Bioethical analysis was then applied to determine their underlying normative principles.ResultsParticipants considered both clinical and non-clinical factors relevant to patient prioritization for radiotherapy. They widely agreed that disease curability should be the primary overarching driver of prioritization, with the goal of saving the most lives. However, they described tension between curability and competing factors including age, palliative benefit, and waiting time. They were divided about the role that non-clinical factors such as social value should play, and agreed that poverty should not be a barrier.ConclusionsMultiple competing principles create tension with the agreed upon overarching goal of maximizing lives saved, including another utilitarian approach of maximizing life-years saved as well as non-utilitarian principles, such as egalitarianism, prioritarianism, and deontology. Clinical guidelines for patient prioritization for radiotherapy can combine multiple principles into a single allocation system to a significant extent. However, conflicting views about the role that social factors should play, and the dynamic nature of resource availability, highlight the need for ongoing work to evaluate and refine priority setting systems based on stakeholder views.

Melanoma is a type of skin cancer that can be challenging to treat, especially in advanced stages. Radiotherapy is one of the main treatment modalities for melanoma, but its efficacy can be limited due to the radioresistance of melanoma cells. Recently, there has been growing interest in using high-Z metal nanoparticles (NPs) to enhance the effectiveness of radiotherapy for melanoma. This review provides an overview of the current state of radiotherapy for melanoma and discusses the physical and biological mechanisms of radiosensitization through high-Z metal NPs. Additionally, it summarizes the latest research on using high-Z metal NPs to sensitize melanoma cells to radiation, both in vitro and in vivo. By examining the available evidence, this review aims to shed light on the potential of high-Z metal NPs in improving radiotherapy outcomes for patients with melanoma. Graphical Abstract Article highlights Melanoma, a lethal skin cancer from melanocytes, causes 75% of skin cancer-related deaths worldwide. Rising incidence necessitates urgent interventions. Traditional treatments like surgery, chemotherapy, immunotherapy and radiotherapy (RT) have limitations. Nanomedicine, using nanoparticles (NPs) sized 1–100 nm, shows promise in enhancing cancer treatment, especially high-Z metal NPs (e.g., gold, platinum, gadolinium) in improving RT outcomes for melanoma. Radiotherapy for melanoma RT is vital for melanoma management, especially when surgery is not viable or cancer has spread. Combining RT with immune checkpoint inhibitors (ICI) improves outcomes in brain metastases. Fractionated RT enhances T cell responses, similar to vaccines. Studies suggest higher radiation doses may be more effective, with clinical studies indicating a median total dose of 30 Gy and BED >39.0 Gy10. High-Z metal NPs can enhance RT by targeting cancer cells precisely while sparing healthy tissue. High-Z metal NPs for radiotherapy of melanoma High-Z metal NPs like gold, magnetic iron oxide, gadolinium, copper-cysteamine and platinum enhance RT efficacy while preserving healthy tissue. Gold NPs enhance RT through unique properties like surface plasmon resonance. mIONs offer RT combined with hyperthermia, enhancing therapeutic outcomes. Gadolinium enhances MRI and RT, with AGuIX® NPs allowing precise imaging and targeted therapy. Other high-Z metals like copper-cysteamine and platinum enhance ROS production, improving treatment outcomes. Nanoparticle physicochemistry & radiosensitization Key design factors include material, size, shape, surface coating and charge. NP size affects biodistribution and clearance, with optimal sizes for tumor uptake being 20–60 nm. NP concentration and surface charge impact RT enhancement and cytocompatibility. Synthesis methods, including chemical, physical and green, ensure biocompatibility and reduced toxicity. Coatings improve stability and targeting, essential for passive and active strategies, enhancing treatment efficacy. Mechanisms of High-Z Metal NPs radiosensitization Radiosensitization involves physical, chemical and biological phases. High-Z metal NPs enhance RT through the photoelectric effect and sary electron production, increasing local radiation doses. They modulate chemical reactions, enhancing DNA damage and ROS production. Biologically, NPs disrupt cell cycles, delay DNA repair and induce oxidative stress, increasing tumor cell radiosensitivity. Conclusion High-Z metal nanoparticles show significant promise in enhancing radiotherapy for melanoma. Benefits include efficient x-ray absorption, targeted delivery and induction of oxidative stress. Key challenges like ensuring biocompatibility, understanding mechanisms and optimizing NP design need addressing before clinical translation. Continued research is essential for developing effective and safe NP-based therapies. Future perspectives Future prospects include using NPs for targeted radiation doses to melanoma cells, optimizing delivery strategies and conducting preclinical and clinical studies to validate efficacy and safety. Continued innovations in nanomedicine could lead to more targeted, effective and personalized cancer treatments, transforming oncology. [ABSTRACT FROM AUTHOR]

Background: During the day-night cycle, gravity and applied stress to the body mass and spine causes a decrease in body height, which is restored overnight. This diurnal spine length variation has not yet been quantified during radiotherapy. Therefore, we aimed to quantify diurnal spine length variation on cone beam CTs (CBCTs) of pediatric patients (< 18 years) who underwent radiotherapy. Methods: For this retrospective study, we included 32 patients (mean age 10.0, range 2.7–16.1 years) who received image guided radiotherapy between 2012 and 2018 in two institutes. Patients were included when they had two fractions per day, or when fractions were scheduled on varying time slots over the course of treatment. Daily CBCTs were registered to the planning CTs using two automatic registrations relative to the bony anatomy; one to vertebra T11 and one to vertebra L4. For each CBCT, the differences between the cranial-caudal (CC) position of the T11 and L4 vertebrae were calculated. To determine the diurnal spine length variation, the difference in vertebrae position between the morning and afternoon CBCTs was calculated. Furthermore, we investigated the possible correlation of diurnal spine length variation with the time slot differences (time interval) between CBCTs (Spearman's ρ). Results: Overall, the median spine length variation was -1.0 (range -3.9–0.1) mm, and we found a significant reduction in spine length over the day (p < 0.001) with substantial variations between patients. Time intervals between CBCTs ranging from 4.0 to 9.5 h were not correlated with spine length reduction (ρ=-0.01; p = 0.95). Conclusions: We found a small but significant reduction in spine length (vertebrae T11 to L4) over the course of day in pediatric patients undergoing radiotherapy, measured on CBCT imaging. Spine length reduction did not correlate with CBCT time intervals. However, our results indicate that diurnal spine length reduction could induce a setup error during treatment, and therefore should be considered in pediatric radiotherapy. [ABSTRACT FROM AUTHOR]

Background Purpose Methods Results Conclusions PET/CT and planning CT are commonly used medical images in radiotherapy for esophageal and nasopharyngeal cancer. However, repeated scans will expose patients to additional radiation doses and also introduce registration errors. This multimodal treatment approach is expected to be further improved.A new Transformer model is proposed to obtain pseudo‐PET/CT fusion images for esophageal and nasopharyngeal cancer radiotherapy.The data of 129 cases of esophageal cancer and 141 cases of nasopharyngeal cancer were retrospectively selected for training, validation, and testing. PET and CT images are used as input. Based on the Transformer model with a “focus‐disperse” attention mechanism and multi‐consistency loss constraints, the feature information in two images is effectively captured. This ultimately results in the synthesis of pseudo‐PET/CT fusion images with enhanced tumor region imaging. During the testing phase, the accuracy of pseudo‐PET/CT fusion images was verified in anatomy and dosimetry, and two prospective cases were selected for further dose verification.In terms of anatomical verification, the PET/CT fusion image obtained using the wavelet fusion algorithm was used as the ground truth image after correction by clinicians. The evaluation metrics, including peak signal‐to‐noise ratio, structural similarity index, mean absolute error, and normalized root mean square error, between the pseudo‐fused images obtained based on the proposed model and ground truth, are represented by means (standard deviation). They are 37.82 (1.57), 95.23 (2.60), 29.70 (2.49), and 9.48 (0.32), respectively. These numerical values outperform those of the state‐of‐the‐art deep learning comparative models. In terms of dosimetry validation, based on a 3%/2 mm gamma analysis, the average passing rates of global and tumor regions between the pseudo‐fused images (with a PET/CT weight ratio of 2:8) and the planning CT images are 97.2% and 95.5%, respectively. These numerical outcomes are superior to those of pseudo‐PET/CT fusion images with other weight ratios.This pseudo‐PET/CT fusion images obtained based on the proposed model hold promise as a new modality in the radiotherapy for esophageal and nasopharyngeal cancer. [ABSTRACT FROM AUTHOR]

Cone beam CT is integral to most modern radiotherapy treatments. The application of daily and repeat CBCT imaging can lead to high imaging doses over a large volume of tissue that extends beyond the treatment site. Hence, it is important to ensure exposures are optimised to keep doses as low as reasonably achievable, whilst ensuring images are suitable for the clinical task. This IPEM topical report presents the results of the first UK survey of dose indices in radiotherapy CBCT. Dose measurements, as defined by the cone beam dose index (CBDIw), were collected along with protocol information for seven treatment sites. Where a range of optimised protocols were available in a centre, a sample of patient data demonstrating the variation in protocol use were requested. Protocol CBDIw values were determined from the average dosimetry data for each type of linear accelerator, and median CBDIw and scan length were calculated for each treatment site at each centre. Median CBDIw values were compared and summary statistics derived that enable the setting of national dose reference levels (DRLs). A total of 63 UK radiotherapy centres contributed data. The proposed CBDIw DRLs are; prostate 20.6 mGy, gynaecological 20.8 mGy, breast 5.0 mGy, 3D-lung 6.0 mGy, 4D-lung 11.8 mGy, brain 3.5 mGy and head/neck 4.2 mGy. However, large differences between models of imaging system were noted. Where centres had pro-active optimisation strategies in place, such as sized based protocols with selection criteria, dose reductions on the 'average' patient were possible compared with vendor defaults. Optimisation of scan length was noted in some clinical sites, with Elekta users tending to fit different collimators for prostate imaging (relatively short) compared with gynaecological treatments (longest). This contrasts with most Varian users who apply the default scan length in most cases. [ABSTRACT FROM AUTHOR]

Background: Radiation therapy is an integral component of treatment that can predispose to carotid artery stenosis (CAS) and increase the risk of cerebrovascular events for head and neck cancer survivors. The utility of screening for CAS with carotid ultrasound in asymptomatic head and neck cancer survivors is unclear. Methods: In this prospective, cross-sectional pilot study, 60 patients who have no evidence of cancer at least 2 years from completion of RT will undergo screening carotid ultrasound to identify patients with high risk of cardiovascular events. Results: Outcomes will include clinically significant CAS, carotid intima-media thickness, acceptability/feasibility of screening, barriers to care and preliminary data on changes to medical management because of screening. Correlative multi-omics analyses will examine biomarkers of CAS after radiation therapy. Conclusion: The results of this study will provide valuable data on the prevalence of CAS and preliminary patient-centered data that will inform the design of a future large-scale, multi-site clinical trial. Clinical Trial Registration:NCT05490875 (ClinicalTrials.gov) Plain Language Summary Patients with head and neck cancer are often treated with radiation therapy. Radiation therapy can cause damage to the blood vessels in the neck. This damage can manifest as narrowing of the blood vessels like the carotid artery, which can lead to stroke. Currently, it is not clear if screening head and neck cancer survivors with ultrasound scans of the carotid arteries is feasible or acceptable to patients. This has also not been formally assessed using a prospective clinical trial. In this study, patients with a history of head and neck cancer who have no evidence of their cancer for at least 2 years since completion of their radiation therapy will be enrolled. They will undergo blood testing and a research ultrasound of the carotid arteries to check for narrowing and other findings that may signal a high risk of stroke or another cardiovascular event. Participants will complete surveys on their experience with the process and how likely they are to accept further screening or additional treatment if something is found. They will also complete surveys on their perception of their personal risk of stroke and barriers to care that would prevent them from getting screening ultrasounds. Patients will be followed for up to 6 months after the ultrasound to check for any changes in their medical care that occurred because of the screening ultrasound. Article highlights Carotid artery stenosis in head & neck cancer survivors treated with radiation therapy Radiotherapy for head and neck (HN) cancer may increase the risk of accelerated atherosclerosis and late carotid artery stenosis (CAS) in 25% of patients, and screening of asymptomatic stenosis may be useful and cost-effective in specific high-risk populations. If clinically significant stenosis is identified, risk reduction strategies such as optimal medical management with or without procedural intervention may reduce the risk of stroke. Data supporting the use of carotid ultrasound (CUS) for HN cancer survivors are sparse, and no guideline currently recommends CUS screening for asymptomatic patients. Carotid ultrasound surveillance for detection of asymptomatic carotid artery stenosis after head & neck radiotherapy CUS allows for cardiovascular risk stratification using stenosis and intima-media thickness measurements. Knowledge gaps with regard to the use of CUS screening in this population include patient acceptability, feasibility, and clinical utility. Rates of change in medical management for screen-detected carotid stenosis in HN cancer survivors have not been assessed in a prospective study. Pilot trial of carotid artery ultrasound in head & neck cancer survivors In this single-institution trial, 60 patients with a history of HN cancer treated with radiotherapy will undergo screening CUS. Patients will be evaluated for CAS (peak systolic velocity by Doppler ultrasonography), and intima-media thickness will be measured. Outcomes include patient acceptability, feasibility, barriers to care and perceived stroke risk among participants. In patients with clinically significant stenosis, the rate of resultant medical interventions (e.g., new medication, additional imaging or intervention) will be determined. Conclusion This prospective study for CUS screening in HN cancer survivors will obtain novel preliminary data to better understand the utility and feasibility of a CUS screening program. Preliminary results will inform future trials focused on the efficacy and cost-effectiveness of carotid artery ultrasound screening in this patient population. Correlative analysis will elucidate novel biomarkers and mechanisms of post-radiotherapy CAS. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Aim Methods Results Conclusion Health outcomes for Aboriginal and Torres Strait Islander people in Australia are significantly worse than in the non‐Indigenous population.To evaluate demographic factors and treatment (surgery and radiotherapy) rates for cervical cancer and to compare these between the Aboriginal and non‐Aboriginal populations to identify any differences in outcomes or modifiable treatment differences between the populations.Retrospective cohort analysis of all patients in the state of New South Wales, Australia, diagnosed with cervical cancer between 2009 and 2018 using linked registry, treatment, and death data.The crude incidence rate for cervical cancer in Aboriginal women in NSW (17.29/100,000) was more than double the rate among non‐Aboriginal women (6.77/100,000). Aboriginal women were diagnosed with cervical cancer, including metastatic disease, at a younger age. There was no significant difference in presentation stage, surgery or radiotherapy treatment rates, or overall survival at 5 years between the two populations.Although access to cancer care looks similar as an aggregate in Aboriginal versus non‐Aboriginal populations, there were disparities with reduced access to care (patients who did not receive either radiotherapy or surgery) among Aboriginal patients who were socioeconomically disadvantaged or residing in remote areas. The lower age of cancer diagnosis among Aboriginal women may have effects on survivorship, including negative effects on fertility, loss of income, and other personal, social, and economic consequences. Efforts to improve access to care, including screening, diagnosis, and treatment, should be targeted toward younger Aboriginal women and those who are socioeconomically disadvantaged or those residing in remote areas. [ABSTRACT FROM AUTHOR]

Background and purpose: Tumor bed (TB) is the residual cavity of resected tumor after surgery. Delineating TB from CT is crucial in generating clinical target volume for radiotherapy. Due to multiple surgical effects and low image contrast, segmenting TB from soft tissue is challenging. In clinical practice, titanium clips were used as marks to guide the searching of TB. However, this information is limited and may cause large error. To provide more prior location information, the tumor regions on both pre-operative and post-operative CTs are both used by the deep learning model in segmenting TB from surrounding tissues. Materials and methods: For breast cancer patient after surgery and going to be treated by radiotherapy, it is important to delineate the target volume for treatment planning. In clinical practice, the target volume is usually generated from TB by adding a certain margin. Therefore, it is crucial to identify TB from soft tissue. To facilitate this process, a deep learning model is developed to segment TB from CT with the guidance of prior tumor location. Initially, the tumor contour on the pre-operative CT is delineated by physician for surgical planning purpose. Then this contour is transformed to the post-operative CT via the deformable image registration between paired pre-operative and post-operative CTs. The original and transformed tumor regions are both used as inputs for predicting the possible region of TB by the deep-learning model. Results: Compared to the one without prior tumor contour information, the dice similarity coefficient of the deep-learning model with the prior tumor contour information is improved significantly (0.812 vs. 0.520, P = 0.001). Compared to the traditional gray-level thresholding method, the dice similarity coefficient of the deep-learning model with the prior tumor contour information is improved significantly (0.812 vs.0.633, P = 0.0005). Conclusions: The prior tumor contours on both pre-operative and post-operative CTs provide valuable information in searching for the precise location of TB on post-operative CT. The proposed method provided a feasible way to assist auto-segmentation of TB in treatment planning of radiotherapy after breast-conserving surgery. [ABSTRACT FROM AUTHOR]

Ewing sarcoma is a rare malignant neoplasm that primarily affects bone in children. Extraskeletal location is less common, while intradural extramedullary Ewing sarcoma (IEES) in adults is a casuistic phenomenon. Due to its rarity, a standardized treatment strategy for IEES has not been established. The clinical use of proton beam therapy (PBT) for craniospinal irradiation (CSI) in the treatment of IEES has not been reported in the literature. A 41-year-old previously healthy man presented with disabling gluteal and lower extremity pain, decreased sensation, and progressive paraparesis without sphincter dysfunction. Imaging showed intradural extramedullary spinal lesions. The patient underwent urgent surgery. Histology and immunohistochemistry suggested a poorly differentiated neuroendocrine tumor. Negative chromogranin staining and a high Ki67 index prompted further investigation. Next-generation sequencing later confirmed an EWSR1/FLI1 translocation, leading to the diagnosis of extraskeletal Ewing sarcoma. The patient received standardized chemotherapy with marked clinical improvement. PBT CSI was initiated but was interrupted due to COVID-19 and other complications. At 20 months follow-up, no recurrence was observed, and the patient reported an active life. Despite intra-spinal spread and multiple complications, intensive chemotherapy combined with PBT CSI led to a favorable outcome. CSI rather than focal radiotherapy should be considered for patients with IEES limited to the cerebrospinal axis. PBT may be used as an alternative to photon radiotherapy to better spare organs at risk. [ABSTRACT FROM AUTHOR]

The goal of the study was to assess the impact of deep inspiration breath hold technique (DIBH), surface-guided radiotherapy (SGRT), and daily kilovoltage cone-beam computed tomography (kV-CBCT) on the dose to organs at risk (OAR) in left-sided breast cancer radiotherapy. Twenty-six consecutive left-sided breast cancer patients treated using Volumetric Intensity Modulated Arc Therapy (VMAT), DIBH, SGRT, and a hypofractionated regimen were retrospectively evaluated in this study. Dose parameters were extracted from dose-volume histograms (DVH). The Wilcoxon Matched Pairs test was used to test dose parameters obtained in free breathing (FB) and DIBH for statistical significance. Multivariable analysis of variance (ANOVA) and receiver operating characteristics (ROC) analysis were used to identify parameters and cut-off points associated with the reduction of the mean heart dose (MHD) by DIBH. Based on published models, the risk of cardiac and lung toxicity (pneumonitis) using SGRT or daily kV-CBCT was estimated and compared. DIBH substantially reduced the MHD (median, 43.6%; range, 4.2% to 75.1%; P < 0.00001). The risk of cardiac toxicity using SGRT increased by 1%, compared to 3.6% to 20.5% using daily kV-CBCT. No significant difference in the risk of radiation-induced pneumonitis using SGRT versus daily kV-CBCT was detected. The ANOVA revealed the relative increase of the left lung volume by DIBH as the only significant impact factor for the MHD. The ROC analysis of this parameter showed an area under the curve (AUC) of 0.89 (95%CI, 0.71 to 0.98; P < 0.0001). DIBH can substantially reduce the MHD in left-sided breast cancer patients treated with modern radiotherapy techniques and hypofractionation. Patient setup using SGRT compared to daily kV-CBCT may be the preferred option for many patients. In our patient cohort, the relative reduction of the left lung volume by DIBH can be used as a predictor to select patients who benefit from DIBH. [ABSTRACT FROM AUTHOR]

Background Purpose Methods Results Conclusions Four‐dimensional computed tomography (4DCT) is an es sential tool in radiation therapy. However, the 4D acquisition process may cause motion artifacts which can obscure anatomy and distort functional measurements from CT scans.We describe a deep learning algorithm to identify the location of artifacts within 4DCT images. Our method is flexible enough to handle different types of artifacts, including duplication, misalignment, truncation, and interpolation.We trained and validated a U‐net convolutional neural network artifact detection model on more than 23 000 coronal slices extracted from 98 4DCT scans. The receiver operating characteristic (ROC) curve and precision‐recall curve were used to evaluate the model's performance at identifying artifacts compared to a manually identified ground truth. The model was adjusted so that the sensitivity in identifying artifacts was equivalent to that of a human observer, as measured by computing the average ratio of artifact volume to lung volume in a given scan.The model achieved a sensitivity, specificity, and precision of 0.78, 0.99, and 0.58, respectively. The ROC area‐under‐the‐curve (AUC) was 0.99 and the precision‐recall AUC was 0.73. Our model sensitivity is 8% higher than previously reported state‐of‐the‐art artifact detection methods.The model developed in this study is versatile, designed to handle duplication, misalignment, truncation, and interpolation artifacts within a single image, unlike earlier models that were designed for a single artifact type. [ABSTRACT FROM AUTHOR]

Prophylactic cranial irradiation (PCI) was recommended for limited‐stage small‐cell lung cancer (SCLC) patients with complete or partial response to primary chemoradiotherapy. But it is still controversial regarding its role in SCLC patients who have had radical resection. This meta‐analysis aims to evaluate the efficacy of PCI in resected SCLC patients. We searched PubMed, EMBASE, Web of Science, CENTRAl, and ClinicalTrials for controlled trials and cohort studies regarding PCI in postoperative SCLC patients. The correlation between PCI and post‐operative outcomes in SCLC patients, including survival and brain metastasis rate (BMR), was examined using hazard ratios (HRs) and risk ratios with corresponding 95% confidence intervals. Quality of studies was assessed by the Newcastle–Ottawa Scale (NOS), and publication bias was assessed by Begg's test. Meta‐analysis of eight studies with 2688 patients in total showed PCI was associated with improved overall survival (OS) for resected SCLC (HR: 0.65, 95% CI: 0.57–0.75, p < 0.01). In addition, subgroup analysis on three studies including 923 patients confirmed the protective role of postoperative PCI in N0 SCLC patients (HR: 0.79, 95% CI: 0.61–0.97, p < 0.05). There was also a significant reduction in BMR in the PCI group pooled from six studies (HR: 0.58, 95% CI: 0.40–0.85, p < 0.01). The use of PCI delayed brain recurrence and improved OS in patients with resected, stage I‐III SCLC. Importantly, patients with N0 SCLC can also benefit from postoperative PCI. In future studies, PCI's role in patients with resected N0 SCLC at different T stage may need to be explored. [ABSTRACT FROM AUTHOR]

Background: This study was conducted to better characterize the epidemiology, clinical outcomes, and current treatment patterns of de novo oligometastatic hormone‐sensitive prostate cancer (omHSPC) in the United States Veterans Affairs Health Care System. Methods: In this observational retrospective cohort study, 400 de novo metastatic hormone‐sensitive PC (mHSPC) patients diagnosed from January 2015 to December 2020 (follow‐up through December 2021) were randomly selected. omHSPC was defined as five or less total metastases (excluding liver) by conventional imaging. Kaplan–Meier methods estimated overall survival (OS) and castration‐resistant prostate cancer (CRPC)‐free survival from mHSPC diagnosis date and a log‐rank test compared these outcomes by oligometastatic status. Results: Twenty percent (79 of 400) of de novo mHSPC patients were oligometastatic. Most baseline characteristics were similar by oligometastatic status; however, men with non‐omHSPC had higher median prostate‐specific antigen at diagnosis (151.7) than omHSPC (44.1). First‐line (1L) novel hormonal therapy was similar between groups (20%); 1L chemotherapy was lower in omHSPC (5%) versus non‐omHSPC (14%). More omHSPC patients received metastasis‐directed therapy/prostate radiation therapy (14%) versus non‐omHSPC (2%). Median OS and CRPC‐free survival (in months) were higher in omHSPC versus non‐omHSPC (44.4; 95% confidence interval [CI], 33.9–not estimated vs. 26.2; 95% CI, 20.5–32.5, p =.0089 and 27.6; 95% CI, 22.1–37.2 vs. 15.3; 95% CI, 12.8–17.9, p =.0049), respectively. Conclusions: Approximately 20% of de novo mHSPC were oligometastatic, and OS was significantly longer in omHSPC versus non‐omHSPC. Although potentially "curative" therapy use was higher in omHSPC versus non‐omHSPC, the percentages were still relatively low. Future studies are warranted given potential for prolonged responses with multimodal therapy inclusive of systemic and local therapies. In this observational retrospective Veterans Affairs cohort study, 20% of men had de novo oligometastatic hormone‐sensitive prostate cancer (omHSPC). Although first‐line (1L) novel hormonal therapy was similar between groups, 1L chemotherapy use was lower in omHSPC, more omHSPC patients received metastasis‐directed therapy/prostate radiation therapy, and median overall survival and time to castration resistance was longer in men with omHSPC than non‐omHSPC. [ABSTRACT FROM AUTHOR]

Pencil-beam scanning proton therapy has been considered a potential modality for the 3D form of spatially fractionated radiation therapy called lattice therapy. However, few practical solutions have been introduced in the clinic. Existing limitations include degradation in plan quality and robustness when using single-field versus multifield lattice plans, respectively. We propose a practical and robust proton lattice (RPL) planning method using multifield and evaluate its dosimetric characteristics compared to clinically acceptable photon lattice plans. Seven cases previously treated with photon lattice therapy were used to evaluate a novel RPL planning technique using 2-orthogonal beams: a primary beam (PB) and a robust complementary beam (RCB) that deliver 67% and 33%, respectively, of the prescribed dose to vertices inside the gross target volume (GTV). Only RCB is robustly optimized for setup and range uncertainties. The number and volume of vertices, peak-to-valley dose ratios (PVDRs), and volume of low dose to GTV of proton and photon plans were compared. The RPL technique was then used in the treatment of 2 patients and their dosimetric parameters were reported. The RPL strategy was able to achieve the clinical planning goals. Compared to previously treated photon plans, the average number of vertices increased by 30%, the average vertex volume by 49% (18.2 ± 25.9 cc vs 12.2 ± 14.5 cc, P =.21), and higher PVDR (10.5 ± 4.8 vs 2.5 ± 0.9, P <.005) was achieved. In addition, RPL plans show more conformal dose with less low dose to GTV (V30%, 60.9% ± 7.2% vs 81.6% ± 13.9% and V10%, 88.3% ± 4.5% vs 98.6% ± 3.6% [ P <.01]). The RPL plan for 2 treated patients showed PVDRs of 4.61 and 14.85 with vertices-to-GTV ratios of 1.52% and 1.30%, respectively. A novel RPL planning strategy using a pair of orthogonal beams was developed and successfully translated to the clinic. The proposed method can generate better quality plans, a higher number of vertices, and higher PVDRs than currently used photon lattice plans. [ABSTRACT FROM AUTHOR]

This study aimed to compare the efficacy and safety of combining first-line chemoimmunotherapy with radiation therapy versus chemoimmunotherapy alone in patients with stage IVB esophageal squamous cell carcinoma (ESCC). We retrospectively examined 409 patients with stage IVB ESCC who received first-line chemotherapy and anti-PD-1 antibody, with or without radiation therapy of ≥40 Gy radiation dose to primary lesion, from 4 academic cancer centers between October 2018 and December 2022. Propensity score matching was conducted to minimize the potential confounding effects. In the overall cohort of 409 patients, the group that received additional radiation therapy had superior overall survival (OS) (hazard ratio [HR], 0.51; 95% CI, 0.39-0.66; P <.001) and progression-free survival (PFS) (HR, 0.52; 95% CI, 0.40-0.66; P <.001) compared to the group that received chemoimmunotherapy alone. After 1:1 propensity score matching, matching age, tumor location, and metastatic sites, a total of 250 patients were selected for further analysis. The results remained consistent and showed that the addition of radiation therapy significantly improved OS and PFS (median OS, 24.9 vs 14.6 months; P =.003; median PFS, 14.2 vs 10.6 months; P =.002). Multivariate Cox analysis including tumor location, T stage, metastatic sites, and treatment modality, revealed that radiation therapy was an independent prognostic factor for both OS (HR, 0.57; 95% CI, 0.41-0.81) and PFS (HR, 0.63, 95% CI, 0.47-0.86). Subgroup analyses revealed significant OS prolongation in patients with nonregional lymph node metastases only who received radiation therapy (HR, 0.49; 95% CI, 0.34-0.70). No OS survival benefit was observed in those with distant organ metastases (HR, 0.72; 95% CI, 0.46-1.13). Regarding safety, the group receiving additional radiation therapy had higher incidences of grade 3 to 4 lymphopenia (74.4% vs 17.7%, P <.001) and esophagitis (11.2% vs 2.4%, P =.006). The addition of radiation therapy to chemoimmunotherapy improved the survival of stage IVB ESCC patients with nonregional lymph node metastasis. [ABSTRACT FROM AUTHOR]

The focal radiation therapy (RT) boost technique was shown in a phase III randomized controlled trial (RCT) to improve prostate cancer outcomes without increasing toxicity. This technique relies on the accurate delineation of prostate tumors on MRI. A recent prospective study evaluated radiation oncologists' accuracy when asked to delineate prostate tumors on MRI and demonstrated high variability in tumor contours. We sought to evaluate the impact of contour variability and inaccuracy on predicted clinical outcomes. We hypothesized that radiation oncologists' contour inaccuracies would yield meaningfully worse clinical outcomes. Forty-five radiation oncologists and 2 expert radiologists contoured prostate tumors on 30 patient cases. Of these cases, those with CT simulation or diagnostic CT available were selected for analysis. A knowledge-based planning model was developed to generate focal RT boost plans for each contour per the RCT protocol. The probability of biochemical failure (BF) was determined using a model from the RCT. The primary metric evaluated was delta BF (DBF = Participant BF – Expert BF). An absolute increase in BF ≥5% was considered clinically meaningful. Eight patient cases and 394 target volumes for focal RT boost planning were included in this analysis. In general, participant plans were associated with worse predicted clinical outcomes compared to the expert plan, with an average absolute increase in BF of 4.3%. Of participant plans, 37% were noted to have an absolute increase in BF of 5% or more. Radiation oncologists' attempts to contour tumor targets for focal RT boost are frequently inaccurate enough to yield meaningfully inferior clinical outcomes for patients. [ABSTRACT FROM AUTHOR]

To study the late urinary toxicity in patients with prostate cancer with prior transurethral resection of prostate (TURP) and treated with hypofractionated prostate radiation therapy. Patients diagnosed with prostate cancer, with a prior TURP, and treated with moderate or extreme hypofractionated intensity-modulated radiation therapy (moderate hypofractionated radiation therapy [MHRT], stereotactic body radiation therapy [SBRT]), were included in this study. Severity and duration of urinary symptoms observed during serial follow-up after at least 3 months from radiation therapy were graded per National Cancer Institute Common Terminology Criteria for Adverse Events v5.0 using information from a prospectively maintained institutional database. Impact of hypofractionation and other potential contributory factors on cumulative grade 2+ late urinary toxicity was analyzed with univariable and multivariable binary logistic regression. A total of 203 eligible patients were included (MHRT = 114, 64-68 Gy/25#; SBRT = 89, 35-37.5 Gy/5#). Median time from TURP to radiation therapy was 10 months (IQR, 7-16 months), similar for MHRT and SBRT. Overall, mean cavity volume was 1.17 cc (IQR, 0.5-1.35 cc), whereas in MHRT and SBRT groups it was 1.03 cc (IQR, 0.4-1.15 cc) and 1.27 cc (IQR, 0.5-1.4 cc), respectively. At a median follow-up of 37 months, cumulative grade 3 and grade 2 late urinary toxicity was 8.4% (n = 17) and 23.2% (n = 47), respectively. Grade 3 symptoms were observed at median 29 months (IQR, 19-62 months) after radiation therapy completion, lasting for a median duration of 8 months (IQR, 2-14 months). Hematuria (6.4%) and urinary obstruction (3.4%) were the chief grade 3 symptoms. Multivariable analysis for age, diabetes, pelvic radiation therapy, fraction size, prostate volume, TURP to radiation therapy duration, and TURP cavity volume showed no significant association with late grade 2+ urinary toxicity. In this large cohort of patients with prior TURP and treated with hypofractionated prostate radiation therapy, incidence of severe late urinary adverse effects was <10%, mainly hematuria or urinary obstruction. Most of these were temporary, and no significant contributory factors were identified for late urinary morbidity after TURP and radiation therapy. [ABSTRACT FROM AUTHOR]

Memantine is standard in certain adults receiving brain radiation therapy (RT) to decrease cognitive impacts, but it is unknown whether pediatric patients can take, tolerate, and/or benefit from memantine. In this prospective single-arm feasibility study, we hypothesized that pediatric patients receiving central nervous system (CNS) RT would tolerate memantine with good adherence. Patients aged 4 to 18 years with a primary CNS malignancy (excluding World Health Organization grade 4 astrocytoma, glioblastoma) receiving intracranial RT were eligible. A 6-month memantine course was given during and after RT, with dose titration in 5 mg increments over 4 weeks targeting a weight-based maximum (0.4 mg/kg to the closest 5 mg), not to exceed 10 mg twice a day. The primary endpoint was to achieve 80% drug adherence rate in 80% of patients measured 1 month after RT. Secondary objectives included memantine feasibility at 3 and 6 months. Eighteen patients enrolled from 2020 to 2022 and were prescribed memantine with RT. The study closed early to avoid competing with the phase 3 randomized Children's Oncology Group study ACCL2031. No predefined stopping rules were met. One patient withdrew for cognition-altering substance use, leaving 17 patients available for analysis. One patient discontinued memantine after one dose due to nausea. For the remaining 16 patients, there was a median of 100% pill completion rate (range, 74%-100%; n = 9/17 with 100% adherence) at 1 month after RT, with 15/16 (94%) with adherence rates >80%. At the 3- and 6-month post-RT time points for secondary endpoints, the median adherence rates were 100% (range, 55%-100%) and 96% (range, 33%-100%), respectively. Grade 1 to 2 fatigue, headache, and nausea were the most common toxicity events, at least possibly related to the study drug (n = 27), without attributable grade 3+ events. Memantine is a feasible, safe, and well-tolerated addition to multimodality treatment for pediatric CNS malignancies. Results of ACCL2031 are awaited to define the value of memantine in this population. [ABSTRACT FROM AUTHOR]

Acute radiation dermatitis (ARD) is the most common side effect reported by patients undergoing radiation therapy (RT). Currently, the assessment of the severity of the reaction is based on the visual assessment of the skin, which is a subjective method, depending on many factors. The main aim of this study was to investigate the usefulness of hyperspectral imaging (HSI) in the assessment of ARD and find physiological factors that could be correlated with ARD. In this clinical pilot trial, weekly acquisitions of hyperspectral camera images of irradiated skin were performed for 5 weeks of RT and at the posttreatment follow-up visit which took place 30 to 40 days after the last fraction of RT. At the same time, the severity of radiodermatitis was assessed based on the criteria of the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE). The content and concentration of chromophores in irradiated skin were quantitatively determined using a hyperspectral camera. The use of HSI supported by image analysis and processing methods allowed for the determination of the content and distribution of hemoglobin and melanin in the irradiated skin. It was found that the hemoglobin concentration is correlated with the subjective assessment made according to the CTCAE protocol. HSI is a sensitive and specific method of analyzing the concentration of chromophores in the skin, including hemoglobin. A clear correlation was found between hemoglobin concentration and CTCAE v.5 scale because of which HSI can be considered as an objective method of skin assessment during RT. [ABSTRACT FROM AUTHOR]

Uveal melanoma (UM), although a rare malignancy, stands as the most prevalent intraocular malignancy in adults. Controversies persist regarding the dose dependency of local control (LC) through radiation therapy. This study sought to elucidate the significance of the prescription dose by employing time-dose-response models for patients with UM receiving photon-based stereotactic radiosurgery (SRS). The analysis included patients with UM treated between 2005 and 2019. All patients underwent single-fraction SRS. Datapoints were separated into 3 dose groups, with Kaplan-Meier analysis performed on each group, from which time-dose-response models for LC were created at 2, 4, and 7 years after SRS using maximum-likelihood fitted logistic models. Outcomes from 594 patients with 594 UMs were used to create time-dose-response models. The prescribed doses and the number of patients were as follows: 17 to 19 Gy (24 patients), 20 Gy (122 patients), 21 Gy (442 patients), and 22 Gy (6 patients). Averaged over all patients and doses, LC rates at 2, 4, and 7 years were 94.4%, 88.2%, and 69.0%, respectively. Time-dose-response models for LC demonstrated a dose-dependent effect, showing 2-year LC rates of more than 90% with 20 Gy and 95% with 22 Gy. For 4 years and a LC of 90%, a dose of approximately 21 Gy was required. After 7 years, the 21 Gy prescription dose was predicted to maintain a LC above 70%, sharply declining to less than 60% LC with 19 Gy and less than 40% with 18 Gy. In contrast to prior findings, the time-dose-response models for UM undergoing photon-based SRS emphasize the critical role of the prescription dose in achieving lasting LC. The dose selection must be carefully balanced against toxicity risks, considering tumor geometry and individual patient characteristics to tailor treatments accordingly. [ABSTRACT FROM AUTHOR]

Primary soft tissue sarcoma (STS) is rare, with many tumors occurring in extremities. Local management is limb-sparing surgery and preoperative/postoperative radiation therapy (RT) for patients at high risk of local recurrence. We prospectively investigated late normal tissue toxicity and limb function observed after intensity modulated RT (IMRT) in extremity STS. Patients with extremity STS, age ≥16 years. Two treatment cohorts: IMRT 50 Gy in 25 × 2 Gy fractions (preoperative) or 60/66 Gy in 30/33 × 2 Gy fractions (postoperative). The primary endpoint was the rate of grade ≥2 late soft tissue fibrosis (subcutaneous tissue) at 24 months after IMRT (Radiation Therapy Oncology Group late radiation morbidity scoring). One hundred sixty-eight patients were registered between March 2016 and July 2017. Of those, 159 (95%) received IMRT (106, 67% preoperative RT; and 53, 33% postoperative RT) with a median follow-up of 35.2 months (IQR, 32.9-36.6); 62% men, median age 58 years. Of 111 patients assessable for the primary endpoint at 24 months, 12 (10.8%; 95% CI, 5.7%-18.1%) had grade ≥2 subcutaneous fibrosis. The overall rate at 24 months of Radiation Therapy Oncology Group late skin, bone, and joint toxicity was 7 of 112 (6.3%), 3 of 112 (2.7%), and 10 of 113 (8.8%), respectively, and for Stern's scale edema was 6 of 113 (5.3%). More wound complications were observed with preoperative than postoperative RT (29.2% vs 3.8%). Overall survival at 24 months was 84.6%, and the local recurrence event rate at 24 months was 10%. The rate of grade ≥2 subcutaneous fibrosis at 24 months after IMRT was 10.8%, consistent with other recent trials of IMRT and lower than historically reported rates in patients treated with 3-dimensional conformal RT. This trial provides further evidence for the benefits of IMRT in this patient population. [ABSTRACT FROM AUTHOR]

The objective of this study was to characterize the conditional risk of developing grade 2+ urinary or gastrointestinal (GI) toxicity for patients treated with external beam radiation therapy in Radiation Therapy Oncology Group 0126. A secondary objective was to analyze baseline patient and treatment characteristics and determine their relevance in predicting toxicity both at the time of trial enrollment and at later points of follow-up. One thousand five hundred thirty-two patients with localized prostate cancer were enrolled between March 2002 and August 2008, of whom 1499 were eligible and included in data analysis with a median follow-up of 8.4 years (range, 0.02-13 years). Patients were treated with either 3-dimensional conformal radiation therapy or intensity-modulated radiation therapy according to institutional practice without the addition of androgen deprivation and randomized to receive either standard-dose radiation therapy of 70.2 Gy or dose-escalated radiation therapy of 79.2 Gy of radiation therapy to the prostate only with standard fractionation. Univariate and multivariate analyses were performed to determine whether initial factors were predictive of late toxicity at the time of treatment and at later time points. As patients proceed further from completion of radiation therapy without the development of toxicity, the subsequent risk of both grade 2+ genitourinary (GU) and GI toxicity decreases with time. At the time of enrollment, the risk of developing grade 2+ toxicity over the next 5 years was 9.57% and 17.89%, respectively. After 5 years of toxicity-free survival, the risk of developing grade 2+ GU or GI toxicity in the subsequent 5 years was 3.02% and 1.54%, respectively. Baseline treatment and patient-related factors predicted late toxicity both at trial enrollment and after 2 years of toxicity-free survivorship. Baseline urinary dysfunction and dose-escalated radiation therapy were associated with increased late GU toxicity. Acute GI toxicity and dose-escalated radiation therapy were associated with increased risk of late GI toxicity. Treatment with intensity-modulated radiation therapy was associated with reduced risk of either toxicity. The conditional risk of grade 2+ toxicities decreases as patients proceed further from treatment, with most toxicities occurring in the first few years after treatment completion. Baseline patient and treatment characteristics remain relevant at both enrollment and later time points. [ABSTRACT FROM AUTHOR]