Radiation Delivery Research Articles

Cardiotoxicity following thoracic radiotherapy for lung cancer.

Radiotherapy is the standard of care treatment for unresectable NSCLC, combined with concurrent chemotherapy and adjuvant immunotherapy. Despite technological advances in radiotherapy planning and delivery, the risk of damage to surrounding thoracic tissues remains high. Cardiac problems, including arrhythmia, heart failure and ischaemic events, occur in 20% of patients with lung cancer who undergo radiotherapy. As survival rates improve incrementally for this cohort, minimising the cardiovascular morbidity of RT is increasingly important. Problematically, the reporting of cardiac endpoints has been poor in thoracic radiotherapy clinical trials, and retrospective studies have been limited by the lack of standardisation of nomenclature and endpoints. How baseline cardiovascular profile and cardiac substructure radiation dose distribution impact the risk of cardiotoxicity is incompletely understood. As Thoracic Oncology departments seek to expand the indications for radiotherapy, and as the patient cohort becomes older and more comorbid, there is a pressing need for cardiotoxicity to be comprehensively characterised with sophisticated oncology, physics and cardio-oncology evaluations. This review synthesises the evidence base for cardiotoxicity in conventional radiotherapy, focusing on lung cancer, including current data, unmet clinical needs, and future scientific directions.

Quantifying thermoplastic mask quality for precision radiotherapy in head and neck cancer: A 3D stress test and 6D-axis error analysis.

Patients with head and neck cancers often require radiotherapy, where immobilization devices like thermoplastic masks ensure precise radiation delivery by minimizing movement. However, the quality of these masks lacks standard reference data. This study aimed to establish institutional acceptance criteria for thermoplastic mask quality and quantify their effectiveness using a 3 dimensional stress test and verified the setup errors using daily megavoltage computed tomography (MVCT). Between April and June 2022, 30 patients underwent radiotherapy with thermoplastic masks. Four key facial points (forehead, bilateral cheekbones, and chin) were tested for supporting force. Mean forces ranged from 3.97 N to 8.8 N. MVCT was used to assess 6 dimensional-axis errors, with mean translational errors (x, y, z) of 0.32 mm, -1.09 mm, and 2.24 mm, respectively, and rotational errors (yaw, pitch, roll) of -0.12°, 0.22°, and 0.35°, respectively. The results demonstrated that the thermoplastic masks provided precise immobilization, minimizing setup errors in 6 dimensions. Our findings offer a quantifiable method to ensure high-quality immobilization during radiotherapy for patients with head and neck cancers.

Noise & mottle suppression methods for cumulative Cherenkov images of radiation therapy delivery.

Cherenkov imaging during radiotherapy provides a real time visualization of beam delivery on patient tissue, which can be used dynamically for incident detection or to review a summary of the delivered surface signal for treatment verification. Very few photons form the images, and one limitation is that the noise level per frame can be quite high, and mottle in the cumulative processed images can cause mild overall noise. This work focused on removing or suppressing noise via image postprocessing. Images were analyzed for peak-signal-to-noise and spatial frequencies present, and several established noise/mottle reduction algorithms were chosen based upon these observations. These included total variation minimization (TV-L1), non-local means filter (NLM), block-matching 3D (BM3D), alpha (adaptive) trimmed mean (ATM), and bilateral filtering. Each were applied to images acquired using a BeamSite camera (DoseOptics) imaged signal from 6x photons from a TrueBeam linac delivering dose at 600 MU/min incident on an anthropomorphic phantom and tissue slab phantom in various configurations and beam angles. The standard denoised images were tested for PSNR, noise power spectrum (NPS) and image sharpness. The average peak-signal-to-noise ratio (PSNR) increase was 17.4% for TV-L1. NLM denoising increased the average PSNR by 19.1%, BM3D processing increased it by12.1% and the bilateral filter increased the average PSNR by 19.0%. Lastly, the ATM filter resulted in the lowest average PSNR increase of 10.9%. Of all of these, the NLM and bilateral filters produced improved edge sharpness with, generally, the lowest NPS curve. For cumulative image Cherenkov data, NLM and the bilateral filter yielded optimal denoising with the TV-L1 algorithm giving comparable results. Single video frame Cherenkov images exhibit much higher noise levels compared to cumulative images. Noise suppression algorithms for these frame rates will likely be a different processing pipeline involving these filters incorporated with machine learning.

Cardiac motion in patients with ventricular tachycardia: potential implications for the treatment of patients candidates to stereotactic arrhythmia radio-ablation (STAR)

Abstract Background Stereotactic arrhythmia radio-ablation (STAR) has proven to be a valid alternative treatment for refractory ventricular tachycardia (VT) in patients who are unsuitable to undergo standard catheter ablation (CA). It consists in the application of external beam radiotherapy in a single dose of 25 Gy to the target areas. There is increased research activity on better understanding the complex and fast motion of the heart and on reducing radiation toxicity. Purpose In the context of an in silico study to evaluate the feasibility of STAR with protons in patients with VT, the initial findings related to cardiac motion on the first 10 patients are here presented. Methods Prior to CA, each patient underwent ECG gated CT scans in expiratory breath-hold, with and without contrast and reconstructed at 30% (systole) and 80% (diastole) of the cardiac R-R cycle. Contouring of the ablation target as a clinical target volume (CTV) for proton treatment planning was performed based on a standard electrophysiological study with 3D eletroanatomical mapping. Two different treatment plans were created: the first with only the diastolic CTV as target (gated treatment), the second including both diastolic and systolic CTVs to create an Internal Target Volume (ITV) in the hypothesis of non-gated treatment. Robust optimization was used to create the Planning Target Volume (PTV). Results The target volumes used for treatment planning are given in Table 1. The median CTV was 10.90 (2.93-36.94) cm3 for diastole and 14.26 (1.73-36.31) cm3 for systole. These volumes are somewhat smaller than those reported in patients treated previously with STAR: this difference may be due to the fact that no respiratory motion was included in the target contour and that the study population includes many patients referred for ventricular ectopic beats without structural heart disease, where the ablation target is expected to be smaller as compared to patients with VT in structural heart disease. Despite a small median difference between the diastolic and systolic CTV of 0.53 (0.03-9.61) cm3, the ITV approach resulted in a median increase in volume compared to the largest of the two CTVs of 29 % (1%-44%). When considering the proton range uncertainty and potential errors in patient positioning (PTV), the target is this time enlarged by a factor 2.9 (1.9-3.9). This data indicates that both cardiac motion and uncertainties in patient positioning before treatment will have a large impact on the treatment volume thus affecting the amount of surrounding tissue exposed to radiation. Conclusion The ablation target contour at systole and diastole are of similar magnitude but their non-overlap results in a large increase in treated volume when radiation delivery is not gated for cardiac motion. Further analysis shall investigate on a case-by-case basis the potential reduction in risk of healthy tissue toxicity with cardiac-gated proton delivery.Table 1

Targeting ventricular tachycardia originating from the anterolateral papillary muscle with stereotactic body radioablation therapy

Abstract Background Ventricular Tachycardia (VT) is prevalent in the setting of non-ischaemic cardiomyopathy (NICM), a heterogeneous group of conditions characterized by myocardial dysfunction in the absence of coronary artery disease. Challenges of catheter ablation to treat VT in NICM patients are well known, and recurrence rates can be as high as 58%. Stereotactic body radioablation therapy (SBRT) involves precise delivery of radiation to arrhythmogenic substrates, and represents a novel treatment to reduce recurrent implantable cardioverter defibrillator (ICD) therapies in patients with refractory VT. Though SBRT has shown preliminary effectiveness in reducing VT episodes, its effectiveness in NICM patients has not been widely evaluated. Purpose To evaluate SBRT effectiveness in NICM patients with scars at the basal anterolateral papillary muscle at a tertiary care center between November-December 2022. Methods Eligible patients had their VT substrate mapped using a single-use ECGI vest and a 4D-CT simulation scan. In addition, MRI scans were used to aid anatomical identification of the anterolateral papillary muscle which could not be seen on the non-contrast diagnostic CTs. SBRT was delivered in a single fraction of 25 Gy under image guidance. Effectiveness of the treatment was evaluated as changes in frequencies of total antitachycardia pacing (ATP) and ICD shock episodes from 6 months pre-, and within to 3, 6, and 12 months follow up post SBRT. Results Participants were 3 males with NICM, aged 56, 60, and 73 with previous dual chamber ICD implantation, 2 of whom had a history of VT ablation/ VT storm and paroxysmal atrial fibrillation. All participants had basal lateral scar, and were receiving beta blockers, mexiletine, and amiodarone with refractory VT before SBRT treatment. Prior to SBRT, ICD device interrogation showed a total of 119 (77, 7, and 35 in patients 1-3 respectively) ATPs, and 27 (10, 1, and 16 in patients 1-3 respectively) ICD shocks delivered. At 12 month follow-up, none of the participants experienced any episodes of ATP or ICD shock. Ejection fraction remained consistent pre-post SBRT. Conclusion SBRT showed remarkable success in reducing ATP and ICD shock episodes, facilitating uncomplicated 1 year follow-up in 3 male patients with NICM and VT from the anterolateral papillary muscle.

Clinical adoption of deep learning target auto-segmentation for radiation therapy: challenges, clinical risks, and mitigation strategies

Abstract Radiation therapy is a localized cancer treatment that relies on precise delineation of the target to be treated and healthy tissues to guarantee optimal treatment effect. This step, known as contouring or segmentation, involves identifying both target volumes and organs at risk on imaging modalities like CT, PET, and MRI to guide radiation delivery. Manual segmentation, however, is time-consuming and highly subjective, despite the presence of contouring guidelines. In recent years, automated segmentation methods, particularly deep learning models, have shown promise in addressing this task. However, challenges persist in their clinical use, including the need for robust quality assurance (QA) processes and addressing clinical risks associated with the use of the models. This review examines the challenges and considerations of the clinical adoption of deep learning target auto-segmentation in radiotherapy, focused on the target volume. We discuss potential clinical risks (e.g. over- and under-segmentation, automation bias, and appropriate trust), mitigation strategies (e.g. human oversight, uncertainty quantification, and education of clinical professionals), and we highlight the importance of expanding QA to include geometric, dose-volume, and outcome-based performance monitoring. While deep learning target auto-segmentation offers significant potential benefits, careful attention to clinical risks and rigorous QA measures are essential for its successful integration in clinical practice.

Advantages of single high-dose radiation therapy compared with conventional fractionated radiation therapy in overcoming radioresistance

Background Radioresistance is a major clinical challenge in cancer treatment, as it reduces the effectiveness of radiation therapy (RT). While advances in radiation delivery have enabled the clinical use of high-dose hypofractionated RT, its impact on radioresistant tumors remains unclear. This study aimed to compare the effects of single high-dose RT with conventional fractionated RT on radioresistant breast cancer cells and explore the underlying mechanisms. Methods Radioresistant cell lines were previously established by exposing SK-BR-3 and MCF-7 cells to 48 Gy and 70 Gy of radiation, respectively, in multiple fractions. We compared the effects of 2 Gy × 5 and 7 Gy × 1 fractions on these cells using clonogenic survival assays and western blot analysis. In vivo antitumor effects were assessed in SR tumor-bearing BALB/c mice irradiated with either 2 Gy × 5 or 7 Gy × 1 fractions. Results 7 Gy x1 was more efficient at killing radioresistant breast cancer cells than 2 Gy x5. Furthermore, the 7 Gy x1 fraction produced higher levels of reactive oxygen species (ROS) and decreased the expression of radioresistance factors such as p-STAT3, ACSL4, FOXM1, RAD51, Bcl-xL, and survivin. Consistent with the in vitro studies, the 7 Gy × 1 fraction also showed superior antitumor effects in SR tumor-bearing BALB/c mice. Conclusions Single high-dose RT offers superior advantages over conventional fractionated RT in regard to overcoming radioresistance, supporting its potential as a promising treatment for recurrent tumors.

Optimising PTV margins in oesophageal cancer radiotherapy: Amodern radiotherapy planning, treatment delivery and verification approach - A single institutional analysis.

Radiotherapy plays a key role in the multidisciplinary management of oesophageal cancers across neoadjuvant, definitive and palliative settings. Improved precision in radiotherapy planning and delivery techniques have allowed treating disease with tighter margins reducing toxicity. In this study, we examine the appropriateness of current practice in defining the planning target volume (PTV). This is a single institutional retrospective study of patients who received radiotherapy for oesophageal cancers using volumetric modulated arc therapy (VMAT) during 2020. All cone-beam computerised tomography (CBCT) scans were reviewed to assess whether PTV expansions appropriately accounted for tumour motion and interfractional variation. Of the 27 patients, 2 (7%), 5 (19%) and 20 (74%) had cervical, thoracic and distal/gastro-oesophageal junction (GOJ) disease, respectively. 16 (59%) had adenocarcinoma and 9 (33%) had squamous cell carcinoma. 9 of 20 distal/GOJ patients were planned and treated according to the institutional stomach filling protocol. 521/528 (98.7%) CBCTs demonstrated adequate target coverage. Cervical, thoracic and GOJ regions demonstrated adequate target coverage in 57/58, 96/97 and 368/373 CBCTs with median PTV expansions of 5, 7 and 7 mm, respectively. In four patients with GOJ disease, CBCT review identified five episodes where the target volume was insufficiently covered during the treatment course. In this single institutional retrospective study, for the vast majority of patients, our institutional practice of defining PTV margins achieved satisfactory target treatment. The interfractional variations observed in patients with GOJ tumours due to target motion and variable gastric volume, highlights the role of further refinements to motion management techniques in this cohort.

Exploring dual energy CT synthesis in CBCT-based adaptive radiotherapy and proton therapy: application of denoising diffusion probabilistic models

Background.Adaptive radiotherapy (ART) requires precise tissue characterization to optimize treatment plans and enhance the efficacy of radiation delivery while minimizing exposure to organs at risk. Traditional imaging techniques such as cone beam computed tomography (CBCT) used in ART settings often lack the resolution and detail necessary for accurate dosimetry, especially in proton therapy.Purpose.This study aims to enhance ART by introducing an innovative approach that synthesizes dual-energy computed tomography (DECT) images from CBCT scans using a novel 3D conditional denoising diffusion probabilistic model (DDPM) multi-decoder. This method seeks to improve dose calculations in ART planning, enhancing tissue characterization.Methods.We utilized a paired CBCT-DECT dataset from 54 head and neck cancer patients to train and validate our DDPM model. The model employs a multi-decoder Swin-UNET architecture that synthesizes high-resolution DECT images by progressively reducing noise and artifacts in CBCT scans through a controlled diffusion process.Results.The proposed method demonstrated superior performance in synthesizing DECT images (High DECT MAE 39.582 ± 0.855 and Low DECT MAE 48.540± 1.833) with significantly enhanced signal-to-noise ratio and reduced artifacts compared to traditional GAN-based methods. It showed marked improvements in tissue characterization and anatomical structure similarity, critical for precise proton and radiation therapy planning.Conclusions.This research has opened a new avenue in CBCT-CT synthesis for ART/APT by generating DECT images using an enhanced DDPM approach. The demonstrated similarity between the synthesized DECT images and ground truth images suggests that these synthetic volumes can be used for accurate dose calculations, leading to better adaptation in treatment planning.

Assessment of radiation pneumonitis and predictive factors in patients with locally advanced non-small cell lung cancer treated with chemoradiotherapy.

Radiation pneumonitis (RP) is a dose-limiting toxicity associated with increased mortality for patients with non-small cell lung cancer (NSCLC) treated with chemoradiotherapy (CRT). This study aims to assess the incidence of symptomatic RP (grade 2-5), rate of recovery and associated predictive factors. We performed a retrospective population-based study including 602 patients with NSCLC who were treated with CRT between 2002 and 2016. RP and rate of recovery were analysed using Common Terminology Criteria for Adverse Events version 4.0. Stepwise logistic regression was performed to analyse potential predictive factors for the two endpoints RP grade ≥ 2 and RP grade ≥ 3. A total of 136 (23%) patients developed symptomatic RP and 37 (6%) developed RP grade ≥ 3. A total of 67 (71%) recovered, whereas the remaining 27 (29%), with the major proportion of patients belonging to the RP grade ≥ 3 group, suffered from prevailing sequelae. On multivariable analysis, the selected model for predicting RP grade ≥ 2 included the factors V20, smoking status, average fractions per week and chemotherapy agent. V20 and age were selected factors for RP grade ≥ 3. The results suggest that regardless of all proposed factors predictive for RP, the most important influenceable significant factor still is dose to the lung. The main aim should be to avoid RP grade ≥ 3, where a substantial proportion of patients suffer from prevailing sequalae. Consequently, the technical improvement and precision of radiotherapy delivery should continue to focus on lung sparing techniques also in the ongoing immunotherapy-containing schedules where the risk of pneumonitis may be increased. e factor still is dose to the lung. Consequently, the technical improvement and precision of radiotherapy delivery should continue to focus on lung sparing techniques also in the ongoing immunotherapy-containing schedules where the risk of pneumonitis may be increased.

The Role of Ultrasound-Based Monitoring of Bladder Volume in Patients with Prostate Cancer during CyberKnife Stereotactic Radiosurgery

(1) Background: For patients irradiated due to prostate cancer, monitoring of bladder volume (BV) is crucial for accuracy of radiation delivery and minimizing exposure to surrounding healthy tissues. Due to the limited imaging capabilities of the CyberKnife system, ultrasound imaging plays a vital role in the monitoring of bladder filling. (2) Methods: A study was carried out in 142 prostate cancer patients treated with the CyberKnife system. Bladder ultrasound (US) was performed before each RTH session to assess real BV (rBV). The double US assessment of rBV was performed by two independent operators or a single operator during 177 and 495 RTH sessions, respectively, giving, in total, 1344 BV assessments. (3) Results: The mean BV in the first and second US assessment was 214.7 mL and 218.1 mL, respectively, while the mean planning bladder volume (pBV) was 340.8 mL. A pBV was significantly higher than an rBV. The mean difference between the US and CT assessment of BV was the smallest in the 100–349 mL group and the largest in the group above 349 mL. The Passing–Bablok regression results confirmed the reliability of the ultrasound (US) measurements. (4) Conclusions: The introduction of US-based BV assessment in patients irradiated due to prostate cancer using CyberKnife seems to be a crucial element in controlling the reproducibility of the treatment plan and should be a standard procedure. The pBV should be within the range of 200–300 mL. The US examination prior to CT scanning for planning is recommended to ensure the optimal range of BV for CT.

Minimizing human interference in an online fully automated daily adaptive radiotherapy workflow for bladder cancer

PurposeThe aim was to study the potential for an online fully automated daily adaptive radiotherapy (RT) workflow for bladder cancer, employing a focal boost and fiducial markers. The study focused on comparing the geometric and dosimetric aspects between the simulated automated online adaptive RT (oART) workflow and the clinically performed workflow.MethodsSeventeen patients with muscle-invasive bladder cancer were treated with daily Cone Beam CT (CBCT)-guided oART. The bladder and pelvic lymph nodes (CTVelective) received a total dose of 40 Gy in 20 fractions and the tumor bed received an additional simultaneously integrated boost (SIB) of 15 Gy (CTVboost). During the online sessions a CBCT was acquired and used as input for the AI-network to automatically delineate the bladder and rectum, i.e. influencers. These influencers were employed to guide the algorithm utilized in the delineation process of the target. Manual adjustments to the generated contours are common during this clinical workflow prior to plan reoptimization and RT delivery. To study the potential for an online fully automated workflow, the oART workflow was repeated in a simulation environment without manual adjustments. A comparison was made between the clinical and automatic contours and between the treatment plans optimized on these clinical (Dclin) and automatic contours (Dauto).ResultsThe bladder and rectum delineated by the AI-network differed from the clinical contours with a median Dice Similarity Coefficient of 0.99 and 0.92, a Mean Distance to Agreement of 1.9 mm and 1.3 mm and a relative volume of 100% and 95%, respectively. For the CTVboost these differences were larger, namely 0.71, 7 mm and 78%. For the CTVboost the median target coverage was 0.42% lower for Dauto compared to Dclin. For CTVelective this difference was 0.03%. The target coverage of Dauto met the clinical requirement of the CTV-coverage in 65% of the sessions for CTVboost and 95% of the sessions for the CTVelective.ConclusionsWhile an online fully automated daily adaptive RT workflow shows promise for bladder treatment, its complexity becomes apparent when incorporating a focal boost, necessitating manual checks to prevent potential underdosage of the target.

Oxygen Consumption In Vivo by Ultra-High Dose Rate Electron Irradiation Depends upon Baseline Tissue Oxygenation

Purpose: This study aimed to assess the impact of tissue oxygen levels on transient oxygen consumption induced by ultra-high dose rate (UHDR) electron radiation in murine flank and to examine the effect of dose rate variations on this relationship. Methods: Real-time oximetry using the phosphorescence quenching method and Oxyphor PdG4 molecular probe was employed. Continuous measurements were taken during radiation delivery on a UHDR-capable Mobetron linear accelerator (linac). Oxyphor PdG4 was administered into the subcutaneous tissue of the flank skin one hour before irradiation. Skin oxygen tension (pO2) was manipulated by adjusting oxygen content in the inhaled gas mixture and/or by vasculature compression. A skin surface radiation dose of 19.8±0.3Gy was verified using a calibrated semiconductor diode dosimeter. Dose rate was varied across the UHDR range by changing linac cone length and pulse repetition frequency (PRF). Results: The decrease in pO2 per unit dose during radiation delivery, termed oxygen consumption g-value (gO2, mmHg/Gy), was significantly influenced by tissue oxygen levels in the range 0-65mmHg under UHDR conditions. Within the 0-20mmHg range, gO2 exhibited a sharp increase with rising baseline pO2, plateauing at 0.26mmHg/Gy. Dose rate variations (mean values 25-1170Gy/s, per-pulse doses of 2.5-9.8Gy) were explored by varying both cone length and PRF (10-120Hz) with no significant changes in gO2. Conventional dose rate irradiation resulted in no discernible changes in pO2. Conclusions: The results show significant differences in the radiation-chemical effects of UHDR radiation between hypoxic and well-oxygenated tissues. Similar trends between earlier published in vitro and in vivo experiments presented herein suggest the chemical mechanisms driving the dependencies of gO2 on pO2 are similar, potentially underpinning the FLASH effect. Importantly, significant variations in baseline pO2 were observed in animals kept under identical conditions, underscoring the necessity to control and monitor tissue oxygen levels for preclinical investigations and future clinical applications of FLASH-RT.

Stereotactic Body Radiotherapy for Renal Cell Carcinoma-A Review of Use in the Primary, Cytoreductive and Oligometastatic Settings.

Renal cell carcinoma (RCC) has been increasing in incidence by around 1.5% per year for several years. However, the mortality rate has been decreasing by 1.6% per year, and this can be attributed to stage migration and improvements in treatment. One treatment modality that has emerged in recent years is stereotactic body radiotherapy (SBRT), which is an advanced radiotherapy technique that allows the delivery of high-dose radiation to the tumor while minimizing doses to the organs at risk. SBRT has developed a role in the treatment of early-stage, oligometastatic and oligoprogressive RCC. In localized disease, phase II trials and meta-analyses have shown that SBRT provides a very high probability of long-term local control with a low risk of severe late toxicity. In oligometastatic (OMD) RCC, the same level of evidence has similarly shown good local control and minimal toxicity. SBRT could also delay the necessity to start or switch systemic treatments. Medical societies have started to incorporate SBRT in their guidelines in the treatment of localized disease and OMD. A possible future role of SBRT involves cytoreduction. It is theorized that SBRT can lower tumor burden and enhance immune-related response, but it cannot be recommended until the results of the phase II trials are published.

National radiotherapy dosimetry audit in the UK – A vision and roadmap

Radiotherapy dosimetry audit is an important element in the overall quality assurance of radiotherapy delivery and has become established as best practice prior to implementation of new equipment, techniques or clinical trials.The Institute of Physics and Engineering in Medicine (IPEM) Interdepartmental Dosimetry Audit group (IDA) facilitates regional audits across the UK through a network of 8 regional chairs. This is a well-established and successful network utilising local staff resources and dosimetry equipment from each region to conduct audits for new radiotherapy equipment, techniques and annual reference audits. All dosimeters used are traceable to the National Physical Laboratory's (NPL) primary standard.NPL and the National Radiotherapy Trials Quality Assurance Group (RTTQA) perform audits for new techniques and clinical trials in the UK. The IPEM IDA, NPL and RTTQA have a joint vision of a national audit network so that comprehensive audits can be offered to all UK centres and bring together all UK dosimetry audit data within a centralised database to facilitate coordinated national audits. This will also allow centres to access and review their data for anonymous benchmarking against other UK centres to support quality improvement.Increasing the frequency and complexity of national audits to reflect current clinical practice is often inhibited by the cost of purchasing appropriate equipment. IPEM have now funded two phantoms that will enable national audits of gynae brachytherapy and head and neck external beam treatments through 2024–25.The aim of this Position Paper is to provide an update on the activities of the IPEM IDA and present the future vision and roadmap for the three UK dosimetry audit groups.

Impact of the radiotherapy rhythm on prognosis in nasopharyngeal carcinoma

Objective The role of chronoradiobiology in nasopharyngeal carcinoma (NPC) has not been fully elucidated. We sought to investigate the impact of radiotherapy rhythm on the survival outcomes of individuals to explore a chronomodulated radiation strategy to improve prognosis of NPC. Methods A cohort comprising non-metastatic NPC patients subjected to intensity-modulated radiotherapy at Fujian Cancer Hospital between Jan. 2016 and Dec. 2019 was assembled. Rhythmic fluctuation of radiotherapy (RFRT) was quantified based on the temporal distribution of radiation delivery. Cox proportional hazard model was performed to explore the impact of radiotherapy rhythm on all-cause mortality. The maximally selected rank statistics method was employed to discern an optimal cutoff. Sensitivity analyses were conducted to ensure the robustness of observed associations. Results Our analysis encompassed 2245 patients, with a median follow-up duration of 55 months, during which 315 individuals succumbed. Multivariate Cox regression analysis unveiled a significant correlation between prolonged RFRT and heightened mortality risk in NPC patients (HR, 1.17, 95% CI, 1.07-1.27, p < .001), a relationship robust to comprehensive adjustment for confounding variables. A cutoff value of 3 h was selected for potential clinical application, beyond which patients exhibited markedly poorer survival outcomes. Subgroup analyses consistently underscored the directional consistency of observed effects. Conclusion Our study sheds light on the potential advantages of scheduling radiotherapy sessions at consistent times. These findings have implications for optimizing radiotherapy schedules and warrant further investigation into personalized chronotherapy approaches in NPC management.

Feasibility of Biology-guided Radiotherapy (BgRT) Targeting Fluorodeoxyglucose (FDG) avid liver metastases

IntroductionBiology-guided radiotherapy (BgRT) is a novel radiation delivery approach utilizing fluorodeoxyglucose (FDG) activity on positron emission tomography (PET) imaging performed in real-time to track and direct RT. Our institution recently acquired the RefleXion X1 BgRT system and sought to assess the feasibility of targeting metastatic sites in various organs, including the liver. However, in order for BgRT to function appropriate, adequate contrast in FDG activity between the tumor and the background tissue, referred to as the normalized SUV (NSUV), is necessary for optimal functioning of BgRT.MethodsWe reviewed the charts of 50 lung adenocarcinoma patients with liver metastases. The following variables were collected: SUVmax and SUVmean for each liver metastasis, SUVmean and SUVmax at 5 and 10 mm radially from the lesion, and NSUV at 5 mm and 10 mm (SUVmax of the liver metastasis divided by SUV mean at 5 mm at 10 mm respectively).Results82 measurable liver metastases were included in the final analysis. The average SUVbackground of liver was 2.26 (95% confidence interval [CI] 2.17–2.35); average SUVmean for liver metastases was 5.31 (95% CI 4.87–5.75), and average SUVmax of liver metastases was 9.19 (95% CI 7.59–10.78). The average SUVmean at 5 mm and 10 mm radially from each lesion were 3.08 (95% CI 3.00-2.16) and 2.60 (95% CI 2.52–2.68), respectively. The mean NSUV at 5 mm and 10 mm were 3.13 (95% CI 2.53–3.73) and 3.69 (95% CI 3.00-4.41) respectively. Furthermore, 90% of lesions had NSUV greater than 1.45 at 5 mm and greater than 1.77 at 10 mm.ConclusionsThis is the first study to comprehensively characterize FDG contrast between the liver tumor and background, referred to as NSUV. Due to the high background SUV normally found in the liver, this work will be valuable for guiding optimization of BgRT for treating liver metastases in the future using the RefleXion® X1 and potentially other similar BgRT platforms.

Current Insights into Molecular Mechanisms and Potential Biomarkers for Treating Radiation-Induced Liver Damage.

Highly conformal delivery of radiation therapy (RT) has revolutionized the treatment landscape for primary and metastatic liver cancers, yet concerns persist regarding radiation-induced liver disease (RILD). Despite advancements, RILD remains a major dose-limiting factor due to the potential damage to normal liver tissues by therapeutic radiation. The toxicity to normal liver tissues is associated with a multitude of physiological and pathological consequences. RILD unfolds as multifaceted processes, intricately linking various responses, such as DNA damage, oxidative stress, inflammation, cellular senescence, fibrosis, and immune reactions, through multiple signaling pathways. The DNA damage caused by ionizing radiation (IR) is a major contributor to the pathogenesis of RILD. Moreover, current treatment options for RILD are limited, with no established biomarker for early detection. RILD diagnosis often occurs at advanced stages, highlighting the critical need for early biomarkers to adjust treatment strategies and prevent liver failure. This review provides an outline of the diverse molecular and cellular mechanisms responsible for the development of RILD and points out all of the available biomarkers for early detection with the aim of helping clinicians decide on advance treatment strategies from a single literature recourse.

Updates for newly diagnosed and recurrent glioblastoma: a review of recent clinical trials.

Glioblastoma (GBM) is the most common and devastating primary malignant brain tumor. We summarize recent advances in radiotherapy, immunotherapy, and targeted therapy approaches for the treatment of newly diagnosed and recurrent glioblastoma. We also introduce ongoing clinical trials. Recent clinical trials have explored multiple novel strategies to treat GBM including the use of oncoviruses, chimeric antigen receptor (CAR) T cell therapy, vaccines, radiotherapy, and novel drug delivery techniques to improves drug penetrance across the blood brain barrier. Approaches to improve drug delivery to brain tumors have the potential to expand treatment options of existing therapies that otherwise have poor brain tumor penetrance. Immunotherapy has been of keen interest in both newly diagnosed and recurrent glioblastoma. Vaccines SurVaxM and DCVax-L have shown initial promise in phase II and III trials, respectively. CAR T cell therapy trials are in their early phases but hold promise in both newly diagnosed and recurrent glioblastoma. Although progress to improve outcomes for GBM patients has been modest, multiple novel strategies utilizing combination therapies, focused ultrasound to improve drug delivery, and novel immunotherapies are underway.

Systematic review and recommendations for re-irradiation for intraprostatic radiorecurrent prostate cancer after definitive radiation therapy.

Intraprostatic recurrence (IRR) of prostate cancer after radiation therapy is increasingly identified. Our objective was to review the literature to determine the optimal workup for identifying IRR, the management options, and practical considerations for the delivery of re-irradiation as salvage local therapy. We performed a systematic review of available publications and ongoing studies on the topics of IRR, with a focus on salvage re-irradiation. Work up of biochemically recurrent prostate cancer includes PSMA PET/CT and multiparametric MRI, followed by biopsy to confirm IRR. Management options include continued surveillance, palliative hormonal therapy, and salvage local therapy. Salvage local therapy can be delivered using re-irradiation with low dose rate brachytherapy, high dose rate (HDR) brachytherapy, and stereotactic body radiotherapy (SBRT), as well as non-radiation modalities, such as cryotherapy, high-intensity focused ultrasound, irreversible electroporation and radical prostatectomy. Data demonstrate that HDR brachytherapy and SBRT have similar efficacy compared to the other salvage local therapy modalities, while having more favorable side effect profiles. Recommendations for radiation therapy planning and delivery using HDR and SBRT based on the available literature are discussed. Salvage re-irradiation is safe and effective and should be considered in patients with IRR.