Radiation Delivery Research Articles

Modern radiotherapy for breast cancer: Update and new developments

AbstractThe delivery of radiotherapy for breast cancer has evolved significantly over the years. The aim of this review is to highlight important developments and current concepts. Postoperative hypofractionated three-dimensional conformal or intensity-modulated photon radiotherapy continues to be the standard application after breast-conserving surgery to improve local control. New therapy techniques in deep inspiration breath hold or physical-biological advantages of proton beam therapy offer innovative therapy methods with regard to the protection of normal tissue and reduced cardiotoxicity. Ultra-hypofractionated therapy concepts and the integration of a simultaneous integrated boost in hypofractionated therapy concepts also enable the duration of treatment to be reduced to a few days or weeks. In low-risk constellations, the radiation volume may also be de-escalated to partial breast irradiation, and if life expectancy is severely restricted at the same time, the omission of postoperative radiotherapy might be critically discussed. The oncological benefit of an irradiation of the regional lymph node regions continues to be confirmed in locally advanced, node-positive carcinomas and further enables the omission of surgical axillary lymph node dissection with low morbidity in individualized therapy approaches.

First-in-human trial using mixed-reality visualization for patient setup during breast or chest wall radiotherapy

BackgroundThe purpose of this study is to assess the feasibility of mixed-reality (MixR) visualization for patient setup in breast and chest wall radiotherapy (RT) by performing a first-in-human clinical trial comparing MixR with a 3-point alignment.MethodsIRB approval was granted for a study incorporating MixR during the setup process for patients undergoing proton (n = 10) or photon (n = 8) RT to the breast or chest wall. For each patient, MixR was utilized for five fractions and compared against another five fractions using 3-point alignment. During fractions with MixR, the patient was aligned by at least one therapist wearing a HoloLens 2 device who was able to guide the process by simultaneously and directly viewing the patient and a hologram of the patient’s surface derived from their simulation CT scan. Alignment accuracy was quantified with cone-beam CT (CBCT) for photon treatments and CBCT plus kV/kV imaging for proton treatments. Registration time was tracked throughout the setup process as well as the amount of image guidance (IGRT) utilized for final alignment.ResultsIn the proton cohort, the mean 3D shift was 0.96 cm using 3-point alignment and 1.18 cm using MixR. An equivalence test indicated that the difference in registration accuracy between the two techniques was less than 0.5 cm. In the photon cohort, the mean 3D shift was 1.18 cm using 3-point alignment and 1.00 cm using MixR. An equivalence test indicated that the difference in registration accuracy was less than 0.3 cm. Minor differences were seen in registration time and the amount of IGRT utilization.ConclusionsMixR for patient setup for breast cancer RT is possible at the level of accuracy and efficiency provided by a 3-point alignment. Further developments in marker tracking, feedback, and a better understanding of the perceptual challenges of MixR are needed to achieve a similar level of accuracy as provided by modern surface-guided radiotherapy (SGRT) systems.Trial registrationClinicalTrials.gov, UFHPTI 2015-BR05: Improving Breast Radiotherapy Setup and Delivery Using Mixed-Reality Visualization, NCT05178927.

OGC SO06 - Novel Non-metallic Fiducial marker for Radiotherapy in Oesophageal Cancer

Abstract Background Early oesophageal tumours are technically difficult to delineate on the planning computed tomography (pCT) for Image Guided Radiotherapy (IGRT). We describe the use of a novel non-metallic fiducial marker for this purpose. Method Non-metallic fiducial marker (NFM) (BioXmark) was used in 17 patients from April 2021 to November 2022 for marking tumour site prior to radical or palliative radiotherapy. NFM was injected in the sub-mucosal plane using fluoroscopy under general anaesthesia, with the patient supine and using regular injection catheter and syringes. After the initial series, further modifications to the technique improved the injection and shortened operative time. These include left lateral positioning, an ultra-fine injection catheters and micro-dosing syringes. Feedback from the treating radiation oncologists was sought for all the patients. Results Injection was successful in all the patients. In the initial series before the modifications to the technique, often the marker was a larger than anticipated due to a combination of poor visibility when the patients were supine and use of larger bore injection catheters. Once the patient position was changed along with the changes in the injection catheters and the syringes, marking was very precise. Conclusion Previously used fiducial markers are gold based. While these were visible on pCTs, they are known to cause distortion along with being expensive and cumbersome to inject. In comparison, NFM is easy to inject without the artefacts seen with metallic markers. We refined the technique further by changing the patient’s position to left lateral which afforded a improved fluoroscopic visibility. Introducing finer injection catheters and micro-dosing syringes further led to usage of lesser volume and precise marking respectively. In summary we present a series of patients whose early oesophageal tumours were marked with a NFM aiding precise delivery of radiotherapy.

Toxicity assessment following conventional radiation therapy and pulsed low dose rate radiation therapy: an in vivo animal study

BackgroundPulsed low dose rate radiotherapy (PLDR) is a new radiation delivery method, in which the fractional dose is divided into sub-fractional doses with periodical time breaks in between. The goal of our study is to assess the toxicity on healthy tissues resulting from PLDR as compared to conventional radiotherapy (CRT) using the same physical X-ray dose.MethodsWe analyzed the weight and survival time for CRT and PLDR groups and studied the inflammatory cytokine transforming Growth Factor-β (TGF-β), usually released following irradiation. Histopathological and immunohistochemical analyses were conducted for intestinal and bone marrow tissues from rats subjected to 8 Gy whole- body irradiation using CRT and PLDR techniques. We investigated genotoxicity by performing a comet assay (CA) in splenic tissues.ResultsOur findings showed an improvement in survival time with PLDR versus CRT by 82%.The mean survival time for CRT rats’ group was 6.3 days, while it was 35.9 days for PLDR group.The weight of CRT group decreased gradually by 3.7%, while weight of PLDR group increased gradually by 2.4%.CRT resulted in more cellular atrophy in bone marrow and intestinal tissues than in PLDR treatments as shown by hematoxylin and eosin staining analysis. In addition, the transforming growth factor-β (TGF-β) expression in bone marrow and intestinal tissues of CRT was higher than those expressed in tissues from PLDR as demonstrated by the Immuno reactive score (IRS). It was10(0.53) and 9.8(0.55) for BM and intestinal tissues, respectively from CRT group and 5.8(0.63) for PLDR for both tissues. The measured CA parameters were larger with CRT compared to PLDR, where the Tail Length (TL), Tail DNA % (TD%) and Tail Moment (TM) measurements were 25.4(3.4), 56.5(7.6) % and 20.5(3.5) for CRT, 7.3(1.9), 30.0(7.2) % and 5.7(1.8) for PLDR, with P value 0.000064, 0.0004 and 0.00017, respectively.ConclusionThis study indicates that PLDR can reduce the toxicity on normal tissues compared to CRT.

Comparison of Patient-Specific Quality Assurance Devices in Radiation Therapy

This study aimed to compare the results of patient-specific quality assurance (PSQA) between MapCHECK and Octavius for radiation therapy. A total of 50 patients with passing PSQA results were included. The point dose difference (DD) and gamma passing rate (GPR) were analyzed to evaluate the agreement between the measured and planned data, and the PSQA results from the two quality assurance (QA) devices were compared for all cases. The DDs and GPRs were within the tolerance ranges in all of the cases. The average GPR difference between the two detectors was statistically significant for the brain and the H&N values for the gamma criteria were 3%/3 mm, 2%/2 mm, and 1%/1 mm. These PSQA systems can be used interchangeably for routine PSQA during the delivery of radiation therapy.

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

Purpose.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.Approach.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-1incident 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.Results.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.Conclusion.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.

CTNI-63. RHENIUM (186RE) OBISBEMEDA (RHENIUM NANOLIPOSOME,186RNL) FOR THE TREATMENT OF LEPTOMENINGEAL METASTASES (LM): SUMMARY OF THE PHASE 1 DOSE ESCALATION STUDY AND PHASE 2 ADMINISTERED DOSE SELECTION

Abstract BACKGROUND Leptomeningeal metastases (LM) is a devastating systemic cancer complication most often seen with breast, lung, and melanoma, with limited treatment options and poor survival. Rhenium (186Re) Obisbemeda (186RNL) provides the combination of effective therapeutic beta radiation, simultaneous gamma-decay for imaging, and ~90-hour physical half-life for optimal radiation delivery. A summary of the Phase 1 dose escalation study, expected to be completed, will be presented. METHODS ReSPECT-LM is a Phase 1 dose escalation study for patients with LM from any primary cancer. Adult patients are given a single dose of 186RNL via intraventricular catheter (Ommaya reservoir) in an outpatient setting to determine the maximum tolerated/feasible dose (MTD/MFD), safety, and tolerability. Seven administered dose cohorts in a 3 + 3 design, from 6.6 mCi to 109.96 mCi, were anticipated. RESULTS For the first 5 cohorts, doses were well-tolerated; most AEs were Grade 1 and 2 with 1 DLT (Cohort 5) at time of abstract submission. CSF tumor cell enumeration assays were performed with a maximum reduction over baseline seen at Day 28. Radiation absorbed doses were calculated for the ventricles, cranial subarachnoid space, and spinal fluid and showed a linear increase with administered dose, with liver and spleen remaining low. Neurological symptoms were reported to improve. We expect the Phase 1 conclusion and the RP2D to be determined for conference reporting; additionally, based on duration of benefit seen during the Phase 1, a multidose paradigm will be initiated to extend benefit. CONCLUSION A single dose of 186RNL for patients with LM has been well-tolerated, with high absorbed doses to the treatment area, acceptable organ doses, and promising clinical improvement and reductions in tumor cell count. Phase 2 is expected to begin enrollment by Q4 2024. Additionally, based on these data, a Phase 1 multidose study is planned to be initiated this year.

Radiation induced liver injury (RILI) evaluation using longitudinal computed tomography (CT) in image‐guided precision murine radiotherapy

AbstractPurposeWe aim to perform image‐guided, dose‐escalated, well‐controlled liver‐irradiated animal studies and subsequently evaluate radiation induced liver injury (RILI) using longitudinal CT.MethodsEighteen 6–8 weeks mice were divided into three groups: control, 15Gy and 30Gy irradiated groups. The animal protocol was approved by the animal care ethics committee of our institution. Precision radiotherapy started with CT simulation, followed by treatment planning using volumetric modulated arc therapy (VMAT), image guidance with cone beam CT (CBCT) and radiation delivery on a medical linear accelerator. Weekly CT was conducted on the same CT simulator using same scanning parameters. At the end of fifth week, all mice were sacrificed, and histological staining was performed. Body weight, liver volume, HU values and histogram distributions were analyzed.ResultsBody weight of irradiation groups was significantly reduced compared to that of the control group (p<0.05). Liver volume in irradiated groups was reduced too. The average liver HU was significantly reduced in irradiated groups (HU mean = 62±3, 48±6, and 36±8 for the control, 15Gy and 30Gy respectively; p control vs. 15Gy < 0.05, p control vs. 30Gy < 0.05). A linear relationship between liver HU and radiation dose was found. Furthermore, HU histogram changes with time and dose showed not only density but also structure might be affected by radiation. HE and Masson Trichrome staining confirmed histological change and increased collagen deposition in irradiated liver.ConclusionLongitudinal unenhanced CT is a useful imaging tool to evaluate the severity and progression of radiation induced liver injury.

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.

Enhancement of reactive oxygen species production by ultra-short electron pulses.

The development of laser-driven accelerators-on-chip has provided an opportunity to miniaturize devices for electron radiotherapy delivery. Laser-driven accelerators produce highly time-compressed electron pulses, on the 100 fs to 1 ps scale. This delivers electrons at high peak power yet low average beam current compared with conventional delivery devices, which generate pulses of approximately 3 µs. The biophysical effects of this time structure, however, are unclear. Here, we use a Monte Carlo simulation approach to explore the effects of the electron beam time structure on the production of reactive oxygen species (ROS) in water. Our results show a power law increase in the generation of hydroxyl ions per deposited electron with decreasing pulse length over the pulse length range of 10 µs to 100 fs. Similar trends were observed for hydrogen peroxide, superoxide, hydroperoxyl, hydronium and solvated electrons. In practical terms, this indicates a fourfold increase in the efficiency of free radical production for sub-picosecond pulses, relative to that of conventional microsecond pulses, for the same number of deposited electrons.

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.

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.

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.

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.

Improving the Timely Delivery of Postoperative Radiation in Head and Neck Cancer

The time that elapses between a patient's ablative tumor resection and indicated adjuvant radiation has a significant impact on an individual's local tumor control and survival, and its optimization is in the best interest of the patient. Furthermore, it is a recognized treatment-related quality metric that can have bearing on future provider compensation. Despite these important driving considerations, compliance rates with established goals are low, recently measured to be <50%. Making meaningful and lasting improvements in this requires a system-based approach. This article seeks to provide clinicians practical tools to apply lean health care and flow management principles to identify chief obstacles to timely care in their systems, and effective strategies to overcome common bottlenecks.