Radiotherapy Dose Research Articles

Radiation therapy of renal cell carcinoma skeletal metastases – Does histologic subtype predict progression?: Renal cell histology and radiotherapy response

IntroductionThis investigation assessed whether the following factors were associated with radiographic local progression in bone metastases from renal cell carcinoma (RCC): (1) high-risk histologic features (2) lesional surgery (3) biologically effective dose (BED) of radiation therapy. Methods and materialsA single-institution database identified all patients who underwent surgery and radiation therapy for bone metastases from RCC to the appendicular skeleton and pelvis from 2006 to 2016. Thirty-six patients underwent radiotherapy for 80 metastases. While all patients had surgical stabilization, 17/36 also had lesional surgery to address the metastatic lesion. Progression of each individual lesion was determined using the application of RECIST criteria to imaging at last follow-up. ResultsThe rate of progressive disease was 8/25 (32%) in the high-risk group versus 5/55 (9%) in the standard-risk group (p ​= ​0.019). The rate of progression among high-risk metastases undergoing lesional surgery was 0/9 versus 8/16 (50%) having non-lesional surgery (p ​= ​0.0218). The rate of progression among standard-risk metastases undergoing lesional surgery was 1/16 (6%) versus 4/39 (10%) with non-lesional surgery (p ​= ​1.00). High-risk histologic features (OR: 10.592, 95% confidence interval: 1.347–83.271, p ​= ​0.025) and as well as a reduction in risk with every additional Gray of BED (OR: 0.902, 95% confidence interval: 0.827–0.984, p ​= ​0.021) were found to predict progressive disease. ConclusionsBone metastases from renal cell carcinoma with high-risk histologic features are associated with less favorable response to radiotherapy than those with standard-risk histology. Delivery of a higher BED was associated with lower odds of progression.

Consensus guidelines for the management of intracranial ependymoma for low- and middle-income countries.

This paper presents comprehensive consensus guidelines for the management of intracranial ependymoma, neoplasms arising from ependymal cells in the central nervous system's ventricular system, in low- and middleincome countries (LMICs). Acknowledging the distinct epidemiological patterns of ependymomas, notably their higher incidence in paediatric patients, and variable survival rates, these guidelines emphasize tailored management approaches for different age groups. An expert panel, comprising specialists in neuro-oncology, convened to address gaps in diagnosis and management within LMICs, considering the varying clinical presentation based on tumour size and location. Emphasizing surgical intervention as the cornerstone of treatment, the guidelines also address challenges such as intraoperative bleeding and tumour location impacting complete resection. The role of molecular subgrouping in stratifying treatment and predicting prognosis is highlighted, alongside a careful consideration of radiotherapy timing, dose, and volume based on risk factors. Chemotherapy's role, especially in paediatric cases, is explored. The paper synthesizes current research and expert opinions, including the need for standardisation, genetic testing, and exploration of less invasive treatment modalities, to address the unique healthcare infrastructure challenges in LMICs. The guidelines also emphasize multidisciplinary teams, aiming to bridge the care gap between high-income countries and LMICs, and improve survival rates and quality of life for patients with intracranial ependymoma. This article serves as a valuable resource for clinicians, researchers, and policymakers in Pakistan and beyond, facilitating the development of evidence-based strategies in diverse healthcare settings.

Factors associated with non-completion of palliative radiotherapy for spinal metastasis in patients with terminal cancer: a retrospective study.

Predictors of non-completion of radiotherapy (RT) should be identified to determine the optimal RT dose. Therefore, this study aimed to explore factors associated with non-completion of palliative RT in patients with terminal cancer. In this retrospective study, patients with terminal cancer who received RT (not including single-fraction RT) for relief of pain caused by spinal metastasis were categorized into complete and incomplete groups. Baseline characteristics, hematologic test data [e.g., total lymphocyte count (TLC)], performance status, palliative performance scale (PPS) score, psoas muscle index (PMI), Charlson comorbidity index, and age-adjusted Charlson comorbidity index of the patients were compared between the two groups. The complete group comprised 58 patients (median age: 68 years; female/male: 17/41; number of irradiation fractions: ≥2 to <10, 20 patients; 10, 34 patients; and >10, 4 patients), and the incomplete group comprised 9 patients (median age: 68 years; female/male: 3/6; number of irradiation fractions: ≥2 to <10, 2 patients; 10, 7 patients; and >10, 0 patient). The proportion of patient death within 1 week or 1 month was higher in the incomplete group than in the complete group. Compared with that in the incomplete group, TLC measured 1 week before RT (pre-TLC) and PMI recorded before RT were significantly higher in the complete group (P=0.013 and P=0.012, respectively). In multivariable analyses, pre-TLC was significantly associated with the incomplete group (P=0.048). Compared with the complete group, the incomplete group included several patients whose PPS scores rapidly decreased. Pre-TLC can predict non-completion of palliative RT in patients with terminal cancer.

64 Does dysphagia optimised radiation matter in the adjuvant setting

Although the issue has been relatively under-studied, the relationship between swallowing outcomes and radiotherapy dose to dysphagia and aspiration-related structures (DARS) may be different following definitive versus postoperative radiotherapy (PORT) for mucosal head and neck cancer (HNC). It also likely different across the head and neck subsites, given the variety of swallowing structures involved and surgical interventions performed. The goal of the presentation will be to provide an overview of swallowing outcomes and trajectories after surgery or surgery plus adjuvant radiotherapy for head and neck cancers, the potential organs at risk involved and the ability to spare them during radiotherapy planning, as well as the results of the interventions published to date and future directions.

The use of carbon fiber/polyetheretherketone (CF/PEEK) in pedicle screw fixation for spinal neoplasms-potential advantages in postoperative imaging and radiotherapy planning.

Titanium pedicle screw fixation complicates postoperative care in patients with spinal neoplasms due to postoperative imaging artefacts and dose perturbation. This study aims to measure the benefits of using carbon fiber/polyetheretherketone (CF/PEEK) pedicle fixation compared to titanium in postoperative imaging, radiotherapy planning and delivery for spinal neoplasms treated with conventional external beam radiotherapy with a commercial treatment planning system. The properties of CF/PEEK pedicle fixation systems were compared to titanium in radiotherapy dose planning accuracy and postoperative computed tomography (CT) image quality. Dose profiles through the screw, tulip and longitudinal axis of the screw were acquired with radiochromic films and compared to a collapsed cone algorithm simulation, to measure dose agreement. The image quality of postoperative CTs were compared by defining four regions of interest around the vertebrae and screws in water phantom models and previous planning CTs, and comparing calculated artefact indexes (AIs). CF/PEEK screws have non-inferior dosimetric prediction accuracy up to 50 mm beneath the screw for collapsed-cone algorithm planning systems. There is a statistically significant reduction in the absolute difference between calculated and measured dose at a depth of 2 mm beneath the screw. There is minimal attenuation with CF/PEEK relative to the surrounding dose, extending to 50 mm beneath the screw. There is a statistically significant improvement in CT imaging quality with reduced AIs in CF/PEEK fixation compared to titanium in both model and patient CT plans. CF/PEEK pedicle fixation can provide benefits in postoperative imaging and photon radiotherapy planning and delivery to patients with spinal neoplasms.

Observations of the effectiveness, dosage, and prognosis of intensity-modulated radiation therapy under ultrasonic guidance for cervical cancer patients.

Volumetric modulated arc therapy (VMAT) guided by ultrasound is a novel radiation therapy technique that facilitates the delineation of the tumor target area under image guidance, enhancing the precision of radiation therapy and maximizing the protection of surrounding tissues. The objective of this paper is to investigate the effectiveness of VMAT under ultrasonic guidance for cervical cancer patients and its impact on radiotherapy dosage and prognosis. A retrospective analysis encompassed 128 instances of cervical cancer patients who were admitted to our medical facility between April 2019 and April 2021. The patients were categorized into an observation cohort and a control cohort, depending on variations in treatment modalities post-admission. The control group underwent conventional radiotherapy, whereas the observation group received VMAT guided by ultrasound. Clinical efficacy, average radiation dosages (in the radiotherapy target area, rectum, and bladder), radiotherapy-related toxicities during treatment, and one-year survival rates were compared between the two groups. Additionally, variances in pre- and post-treatment serum levels of squamous cell carcinoma antigen (SCC-Ag), carcinoembryonic antigen (CEA), and carbohydrate antigen 724 (CA724) were subjected to assessment. When compared to the control group (64.52%), the observation cohort's comprehensive effectiveness rate was considerably greater (80.30%). The observation group saw lower average radiation exposures and a reduction in the post-treatment concentrations of CEA, SCC-Ag, and CA724. The overall incidence of adverse effects from radiation treatment also declined. The observation group had a greater one-year survival rate (90.48%) than the control group (73.33%). When comparing the observation cohort to the control group, Kaplan-Meier survival analysis showed a significantly higher one-year survival rate (Log-Rank = 6.530, P= 0.011). VMAT guided by ultrasound for patients with cervical cancer demonstrates promising short- and long-term treatment outcomes. It also leads to improvements in serum CEA, SCC-Ag, and CA724 levels, as well as reductions in the average radiation dosages to the radiotherapy target area, rectum, and bladder. This approach warrants attention from clinicians in clinical practice.

A Phase 1 Trial of Salvage Stereotactic Body Radiation Therapy for Radiorecurrent Prostate Cancer After Brachytherapy

NCT03253744 is a phase 1 trial with the primary objective to identify the maximum tolerated dose (MTD) of salvage stereotactic body radiation therapy (SBRT) in patients with local prostate cancer recurrence after brachytherapy. Additional objectives included biochemical control and imaging response. This trial was initially designed to test 3 therapeutic dose levels (DLs): 40 Gy (DL1), 42.5 Gy (DL2), and 45 Gy (DL3) in 5 fractions. Intensity modulation was used to deliver the prescription dose to the magnetic resonance imaging and prostate-specific membrane antigen-based positron emission tomography imaging-defined gross tumor volume while simultaneously delivering 30 Gy to an elective volume defined by the prostate gland. This phase 1 trial followed a 3+3 design with a 3-patient expansion at the MTD. Toxicities were scored until trial completion at 2 years post-SBRT using Common Terminology Criteria for Adverse Events version 5.0. Escalation was halted if 2 dose limiting toxicities occurred, defined as any persistent (>4 days) grade 3 toxicity occurring within the first 3 weeks after SBRT or any grade ≥3 genitourinary (GU) or grade 4 gastrointestinal toxicity thereafter. Between August 2018 and January 2023, 9 patients underwent salvage SBRT and were observed for a median of 22 months (Q1-Q3, 20-43 months). No grade 3 to 5 adverse events related to study treatment were observed; thus, no dose limiting toxicities occurred during the observation period. Escalation was halted by amendment given excellent biochemical control in DL1 and DL2 in the setting of a high incidence of clinically significant late grade 2 GU toxicity. Therefore, the MTD was considered 42.5 Gy in 5 fractions (DL2). One- and 2-year biochemical progression-free survival were 100% and 86%, representing a single patient in the trial cohort with biochemical failure (prostate-specific antigen [PSA] nadir + 2.0) at 20 months posttreatment. The MTD of salvage SBRT for the treatment of intraprostatic radiorecurrence after brachytherapy was 42.5 Gy in 5 fractions producing an 86% 2-year biochemical progression-free survival rate, with 1 poststudy failure at 20 months. The most frequent clinically significant toxicity was late grade 2 GU toxicity.

Impact of radiation dose distribution on nutritional supplementation needs in head and neck cancer radiotherapy: a voxel-based machine learning approach.

To investigate the relationship between nutritional supplementation and radiation dose to the pharyngeal constrictor muscles and larynx for head and neck (HN) cancer patients undergoing radiotherapy. We retrospectively analyzed radiotherapy (RT) dose for 231 HN cancer patients, focusing on the pharyngeal constrictors and larynx. We defined nutritional supplementation as feeding tube utilization or >10% weight loss from baseline within 90 days after radiotherapy completion. Using deformable image registration (DIR), we mapped each patient's anatomical structures to a reference coordinate system, and corresponding deformations were applied to dose matrices. Voxel doses were utilized as features for ridge logistic regression models, optimized through 5-fold cross-validation. Model performance was assessed with area under the curve of a receiver operating curve (AUC) and F1 score. We built and compared models using 1) pharyngeal constrictor voxels, 2) larynx voxels, 3) clinical factors and mean regional dose metrics, and 4) clinical factors and dose-volume histogram metrics. Test set AUCs were compared among the models, and feature importance was evaluated. DIR of the pharyngeal constrictors and larynx yielded mean Dice coefficients of 0.80 and 0.84, respectively. Pharyngeal constrictors voxels and larynx voxel models had AUC of 0.88 and 0.82, respectively. Voxel-based dose modeling identified the superior to middle regions of the pharyngeal constrictors and the superior region of larynx as most predictive of feeding tube use/weight loss. Univariate analysis found treatment setting, treatment laterality, chemotherapy, baseline dysphagia, weight, and socioeconomic status predictive of outcome. An aggregated model using mean doses of pharyngeal constrictors and larynx subregions had an AUC of 0.87 and the model using conventional DVH metrics had an AUC of 0.85 with p-value of 0.04. Feature importance calculations from the regional dose model indicated that mean doses to the superior-middle pharyngeal constrictor muscles followed by mean dose to the superior larynx were most predictive of nutritional supplementation. Machine learning modeling of voxel-level doses enables identification of subregions within organs that correlate with toxicity. For HN radiotherapy, doses to the superior-middle pharyngeal constrictors are most predictive of feeding tube use/weight loss followed by the doses to superior portion of the larynx.

Re-irradiation spine stereotactic body radiotherapy following high-dose conventional radiotherapy for metastatic epidural spinal cord compression: a retrospective study

Purpose We aimed to evaluate the efficacy and safety of re-irradiation stereotactic body radiation therapy (SBRT) in patients with metastatic epidural spinal cord compression (MESCC) following high-dose conventional radiotherapy.Materials and methods Twenty-one patients met the following eligibility criteria: with an irradiation history of 50 Gy2 equivalent dose in 2-Gy fractions (EQD2) or more, diagnosed MESCC in the cervical or thoracic spines, and treated with re-irradiation SBRT of 24 Gy in 2 fractions between April 2018 and March 2023. Prior treatment was radiotherapy alone, not including surgery. The primary endpoint was a 1-year local failure rate. Overall survival (OS) and treatment-related adverse events were assessed as the secondary endpoints. Since our cohort includes one treatment-related death (TRD) of esophageal perforation, the cumulative esophageal dose was evaluated to find the dose constraints related to severe toxicities.Results The median age was 68, and 14 males were included. The primary tumor sites (esophagus/lung/head and neck/others) were 6/6/7/2, and the median initial radiotherapy dose was 60 Gy2 EQD2 (range: 50–105 Gy2, 60–70/ > 70 Gy2 were 11/4). Ten patients underwent surgery followed by SBRT and 11 SBRT alone. At the median follow-up time of 10.4 months, 17 patients died of systemic disease progression including one TRD. No radiation-induced myelopathy or nerve root injuries occurred. Local failure occurred in six patients, with a 1-year local failure rate of 29.3% and a 1-year OS of 55.0%. Other toxicities included five cases of vertebral compression fractures (23.8%) and one radiation pneumonitis. The cumulative esophageal dose was recommended as follows: Dmax < 203, D0.035 cc < 187, and D1cc < 167 (Gy3 in biological effective dose).Conclusion Re-irradiation spine SBRT may be effective for selected patients with cervical or thoracic MESCC, even with high-dose irradiation histories. The cumulative dose assessment across the original and re-irradiated esophagus was recommended to decrease the risk of severe esophageal toxicities.

Digital twins in dosimetry and radiotherapy, a survey and some applications

Digital Twins (DTs) are emerging as a powerful tool in several applications, including Dosimetry and Radiotherapy (RT). Indeed, DTs have increased their effectiveness, up to the point that can be considered as virtual replicas of physical objects, processes, or systems. Through predictive modeling, DTs can determine optimal doses in radiation therapy, assist in defining personalized treatment schedules for individual patients, and monitor treatment responses. Moreover, DTs play a pivotal role in designing radioisotope production processes in the field of nuclear medicine. This can help to ensure the most effective treatment possible while minimizing the risk of side effects.As a frontier case example, DTs can be employed in the analysis of a possible new source for flash radiotherapy worth with respect to their effectiveness parameters like Radio-Biological Effectiveness (RBE) or cell Surviving Fraction (SF). Flash techniques involve the delivery of a high dose of radiation in a short time, reducing damage to surrounding healthy tissue while possibly increasing damage to malignant cells. DTs could be used to simulate and collect data about particle interactions with the treated tissues, optimizing the treatment and leading to improved outcomes.The most powerful tools that can be applied in DTs development are the Monte Carlo (MC) codes, particularly those with the highest capability of a detailed material/geometry description through an automatized spatial discretization approach like the one based on Unstructured Mesh (UM), allowing a common mathematical domain for both particle/radiation transport and thermal, fluid-dynamics and mechanical simulations. What comes out from various kind of applications is a common ground in terms of data management, phase space identification, simulation tools, that can be easily recognized even if spanning from cell response to technological devices, making realistic the perspective of the setup of general optimization procedures.

Radiomics for residual tumour detection and prognosis in newly diagnosed glioblastoma based on postoperative [11C] methionine PET and T1c-w MRI

Personalized treatment strategies based on non-invasive biomarkers have potential to improve patient management in patients with newly diagnosed glioblastoma (GBM). The residual tumour burden after surgery in GBM patients is a prognostic imaging biomarker. However, in clinical patient management, its assessment is a manual and time-consuming process that is at risk of inter-rater variability. Furthermore, the prediction of patient outcome prior to radiotherapy may identify patient subgroups that could benefit from escalated radiotherapy doses. Therefore, in this study, we investigate the capabilities of traditional radiomics and 3D convolutional neural networks for automatic detection of the residual tumour status and to prognosticate time-to-recurrence (TTR) and overall survival (OS) in GBM using postoperative [11C] methionine positron emission tomography (MET-PET) and gadolinium-enhanced T1-w magnetic resonance imaging (MRI). On the independent test data, the 3D-DenseNet model based on MET-PET achieved the best performance for residual tumour detection, while the logistic regression model with conventional radiomics features performed best for T1c-w MRI (AUC: MET-PET 0.95, T1c-w MRI 0.78). For the prognosis of TTR and OS, the 3D-DenseNet model based on MET-PET integrated with age and MGMT status achieved the best performance (Concordance-Index: TTR 0.68, OS 0.65). In conclusion, we showed that both deep-learning and conventional radiomics have potential value for supporting image-based assessment and prognosis in GBM. After prospective validation, these models may be considered for treatment personalization.

Deep match: A zero-shot framework for improved fiducial-free respiratory motion tracking

Background and purposeMotion management is essential to reduce normal tissue exposure and maintain adequate tumor dose in lung stereotactic body radiation therapy (SBRT). Lung SBRT using an articulated robotic arm allows dynamic tracking during radiation dose delivery. Two stereoscopic X-ray tracking modes are available – fiducial-based and fiducial-free tracking. Although X-ray detection of implanted fiducials is robust, the implantation procedure is invasive and inapplicable to some patients and tumor locations. Fiducial-free tracking relies on tumor contrast, which challenges the existing tracking algorithms for small (e.g., <15 mm) and/or tumors obscured by overlapping anatomies. To markedly improve the performance of fiducial-free tracking, we proposed a deep learning-based template matching algorithm – Deep Match. MethodDeep Match consists of four self-definable stages – training-free feature extractor, similarity measurements for location proposal, local refinements, and uncertainty level prediction for constructing a more trustworthy and versatile pipeline. Deep Match was validated on a 10 (38 fractions; 2661 images) patient cohort whose lung tumor was trackable on one X-ray view, while the second view did not offer sufficient conspicuity for tumor tracking using existing methods. The patient cohort was stratified into subgroups based on tumor sizes (<10 mm, 10–15 mm, and >15 mm) and tumor locations (with/without thoracic anatomy overlapping). ResultsOn X-ray views that conventional methods failed to track the lung tumor, Deep Match achieved robust performance as evidenced by >80 % 3 mm-Hit (detection within 3 mm superior/inferior margin from ground truth) for 70 % of patients and <3 mm superior/inferior distance (SID) ∼1 mm standard deviation for all the patients. ConclusionDeep Match is a zero-shot learning network that explores the intrinsic neural network benefits without training on patient data. With Deep Match, fiducial-free tracking can be extended to more patients with small tumors and with tumors obscured by overlapping anatomy.

Beam quality and the mystery behind the lower percentage depth dose in grid radiation therapy

Grid therapy recently has been picking momentum due to favorable outcomes in bulky tumors. This is being termed as Spatially Fractionated Radiation Therapy (SFRT) and lattice therapy. SFRT can be performed with specially designed blocks made with brass or cerrobend with repeated holes or using multi-leaf collimators where dosimetry is uncertain. The dosimetric challenge in grid therapy is the mystery behind the lower percentage depth dose (PDD) in grid fields. The knowledge about the beam quality, indexed by TPR20/10 (Tissue Phantom Ratio), is also necessary for absolute dosimetry of grid fields. Since the grid may change the quality of the primary photons, a new kq,q0\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${\\mathbf{k}}_{\\mathbf{q},{\\mathbf{q}}_{0}}$$\\end{document} should be evaluated for absolute dosimetry of grid fields. A Monte Carlo (MC) approach is provided to resolving the dosimetric issues. Using 6 MV beam from a linear accelerator, MC simulation was performed using MCNPX code. Additionally, a commercial grid therapy device was used to simulate the grid fields. Beam parameters were validated with MC model for output factor, depth of maximum dose, PDDs, dose profiles, and TPR20/10. The electron and photon spectra were also compared between open and grid fields. The dmax is the same for open and grid fields. The PDD with grid is lower (~ 10%) than the open field. The difference in TPR20/10 of open and grid fields is observable (~ 5%). Accordingly, TPR20/10 is still a good index for the beam quality in grid fields and consequently choose the correct kq,q0\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${\\mathbf{k}}_{\\mathbf{q},{\\mathbf{q}}_{0}}$$\\end{document} in measurements. The output factors for grid fields are 0.2 lower compared to open fields. The lower depth dose with grid therapy is due to lower depth fluence with scatter radiation but it does not impact the dosimetry as the calibration parameters are insensitive to the effective beam energies. Thus, standard dosimetry in open beam based on international protocol could be used.

Robotic Stereotactic Body Radiotherapy for Spine Metastasis Pain Relief

Spinal metastasis may occur in 40–70% of patients with cancer. Symptoms can vary from pain to spinal cord compression (SCC) and can affect their quality of life (QoL). Stereotactic body radiotherapy (SBRT) allows dose escalation of spinal tumor metastases, minimizing doses to organs at risk and improving pain control. The aim of this study is to retrospectively describe our institution’s experience with robotic SBRT (CyberKnife®, Accuray Incorporated, Sunnyvale, CA, USA) for spinal metastases, in terms of feasibility, oncological results, toxicities, and pain relief observed. In total, 25 patients with 43 lesions were assessed, most of them with dorsal metastases (48.8%). The median total dose was 27 Gy (16–35 Gy), the median number of fractions administered was 3 (1–5), and the median dose per fraction was 9 Gy. Pain was evaluated using the visual analogue scale at baseline and at the end of treatment. The statistically significant reduction in pain (p &lt; 0.01) was associated with the total dose of radiotherapy delivered (p &lt; 0.01). Only one patient developed grade 3 dermatitis. Female gender, adenocarcinoma tumors, and lack of previous surgery were associated with better response to SBRT (p &lt; 0.05). Robotic spine SBRT is feasible, well-tolerated, and improves patients’ QoL through a statistically significant reduction in pain, so it should be offered to patients at an early stage in their process.

A 15-Year Single-Institution Retrospective Study of Primary Pancreatic Cancer Treated with Non-Ablative Palliative Radiotherapy.

We studied the use of palliative radiotherapy (RT) among patients with primary, non-curable, locally advanced pancreatic cancer. In this subset of patients, with very poor survival, various palliative RT dose fractionation schemes are used; but, in the absence of a guideline, practice patterns vary, and dose choice is mainly based on the physician's intuition. We divided the patients into three groups, according to the dose fractionation schedules received: low (A), intermediate (B), and high (C) dose groups, to study the potential differences in outcome between the different dose prescriptions. Cohort: n = 184. Median age: 69 years. Male: n = 105 (57%), female: n = 79 (43%). Stage IV: n = 117 (64%). T4: n = 127 (69%). Tumor location: head: n = 109 (59%), body: n = 37 (20%), tail: n = 25 (14%), neck: n = 11 (6%), and uncinate: n = 2 (1%). Prior systemic therapy: n = 66 (36%). Most common dose fractionations received: 20 Gy in five fractions n = 67 (36%), 30 Gy in 10 fractions n = 49 (27%), and 8 Gy in one fraction n = 23 (13%). Group A: n = 33 (18%), median overall survival (OS) 19 days (95% CI 4-33). Group B: n = 84 (46%), median OS 52 days (95% CI 43-60). Group C: n = 67 (36%), median OS 126 days (95% CI 77-174). Median days to in-field progression: Group A 59 days (range 7-109), Group B 96 days (range 19-173), and Group C 97 days (range 13-475). To our knowledge, this is the largest reported retrospective cohort of patients receiving non-ablative palliative RT to treat their primary pancreatic tumors. Most patients had metastatic disease, T4 tumors of the pancreatic head and had not received prior systemic therapy. A significant survival benefit was seen favoring the high dose/longer RT fractionation group, presumably due to appropriate patient selection rather than an RT effect. Despite the relatively short median overall survival, one fifth of the patients were found to experience an in-field progression following RT.

Evaluating delivered radiation dose in intraoperative radiotherapy for breast cancer using TLD

The extra radiation that it delivers has been questioned by patients, physicians, and the public for early breast cancer patients of intraoperative radiotherapy (IORT). This investigation concerns a left breast Rando phantom with a lumpectomy cavity of 30 cm3 of left breast of Rando phantom made of polymethylmethacrylate (PMMA). Thermoluminescent dosimetry (TLD) was used to evaluate the extra radiation dose or air kerma (kair) rate under IORT from 20 Gy, 50 kV of an Xoft Axxent system. TLDs were first calibrated using 50 kV photons, and then inserted at phantom positions that were close to the positions of the represented organs and tissues. Equivalent doses (DT) delivered to the organ at risks (OAR) were evaluated according to ICRP 103. Entrance surface doses (ESD) or skin doses (Dskin) varied markedly among positions close to the lumpectomy cavity. The dose was 20 Gy at the surface of a balloon applicator and kair varied from 6.40 ± 0.92 Gy down to 1.20 ± 0.30 mGy along the left-right axis of the 17th slice of Rando. These experimental results are compared with those in the literature. The shielding effect of the tungsten-impregnated rubber was also evaluated. This study supports recommendations to patients, relatives, physicians and radiologists concerning IORT.

Immune Response following FLASH and Conventional Radiation in Diffuse Midline Glioma

Diffuse midline glioma (DMG) is a fatal tumor traditionally treated with radiation therapy (RT) and previously characterized as having a noninflammatory tumor immune microenvironment (TIME). FLASH is a novel RT technique using ultra-high dose rate that is associated with decreased toxicity and effective tumor control. However, the effect of FLASH and conventional (CONV) RT on the DMG TIME has not yet been explored. Here, we performed single-cell RNA sequencing (scRNA-seq) and flow cytometry on immune cells isolated from an orthotopic syngeneic murine model of brainstem DMG after the use of FLASH (90 Gy/sec) or CONV (2 Gy/min) dose-rate RT and compared to unirradiated tumor (SHAM). At day 4 post-RT, FLASH exerted similar effects as CONV in the predominant microglial (MG) population, including the presence of two activated subtypes. However, at day 10 post-RT, we observed a significant increase in the type 1 interferon α/β receptor (IFNAR+) in MG in CONV and SHAM compared to FLASH. In the non-resident myeloid clusters of macrophages (MACs) and dendritic cells (DCs), we found increased type 1 interferon (IFN1) pathway enrichment for CONV compared to FLASH and SHAM by scRNA-seq. We observed this trend by flow cytometry at day 4 post-RT in IFNAR+ MACs and DCs, which equalized by day 10 post-RT. DMG control and murine survival were equivalent between RT dose rates. Our work is the first to map CONV and FLASH immune alterations of the DMG TIME with single-cell resolution. Although DMG tumor control and survival were similar between CONV and FLASH, we found that changes in immune compartments differed over time. Importantly, although both RT modalities increased IFN1, we found that the timing of this response was cell-type and dose-rate dependent. These temporal differences, particularly in the context of tumor control, warrant further study.

Dependence of surface dose on atomic number in megavoltage photon beams.

Surface dose in megavoltage photon radiotherapy has a significant clinical impact on the skin-sparing effect. In previously published works, it was established that the presence of medium atomic number (Z) absorbers, such as tin, decreases the surface dose. It was concluded that high-Z absorbers, such as lead, increase the surface dose, relative to medium-Z absorbers, due to the increased contributions from photoelectrons and electron-positron pairs. The purpose of this investigation is to revisit these conclusions in the context of photon beams from modern linacs. A metric estimating the relative intensity of charged particles emitted in the forward direction, , was proposed using cross-sections for the photon interactions. The values were calculated for various absorbers using energy spectra of 6 and 10 MV photon beams from a Varian TrueBeam linac. Monte Carlo (MC) simulations were performed using TOPAS MC code to calculate the surface dose for various absorbers. Surface dose measurements were performed with 6 and 10 MV photon beams with tin and lead absorbers. The values were found to decrease as a function of Z for both 6 and 10 MV photon beams indicating that the surface dose from electrons emitted in the forward direction consistently decreases with increasing Z. With the increasing Z of the absorbers, both experimental and MC-calculated surface dose decreased without exhibiting a minimum at medium-Z absorbers. The surface dose for lead and tin was determined to be within 1% of each other for both 6 and 10 MV photon beams using MC simulations and experimental measurements. Therefore, no statistically significant difference in surface dose was found between the tin and lead absorbers disproving the presence of any minima in the surface dose versus the Z curve as has been reported in the literature. Surface dose for modern photon beams can be reduced using both medium and high Z absorbers since a consistent decrease in surface dose was found with increasing absorber Z.

The Trajectory of Oral Mucositis in Head and Neck Cancer Patients Undergoing Radiotherapy and its Influencing Factors

Background: Oral mucositis (OM) is a common and severe side effect of radiotherapy in head and neck cancer (HNC). The study aimed to investigate the longitudinal changes in OM and its influencing factors in patients with HNC during radiotherapy. Methods: This was a retrospective longitudinal observational study. From July 2022 to March 2023, patients with HNC undergoing radiation therapy were enrolled. OM, oral hygiene, oral infections, oral pain, feeding route, and laboratory indicators were measured at 7 times. The influencing factors of OM were analyzed using generalized estimation equations (GEEs). Results: A total of 160 patients were included in this study. The prevalence of severe OM at T0, T1, T2, T3, T4, T5, and T6 was 0, 0, 2.5%, 9.4%, 26.9%, 24.4%, and 26.9%, respectively. The prevalence of grade 1-2 OM at T0, T1, T2, T3, T4, T5, and T6 was 0, 16.3%, 53.1%, 65.1%, 61.9%, 70.7%, and 71.3%, respectively. Duration of diagnosis, clinical stage, N stage, M stage, surgery, diabetes, radiotherapy dose, oral hygiene, oral infection, oral pain, feeding route, and lymphocyte impacted OM significantly in the GEEs multivariate model. Conclusions: OM occurs in almost all patients with HNC who undergo radiotherapy. Changes in the severity of OM are a dynamic process, with the severity increasing with the cumulative radiotherapy dose. Specialist oral evaluation and oral care are needed to alleviate the severity of OM in HNC patients.

Predictive Factors Associated With Radiation Myelopathy in Pediatric Patients With Cancer: A PENTEC Comprehensive Review

Radiation myelitis (RM) is a rare complication of radiation therapy (RT). The Pediatric Normal Tissue Effects in the Clinic spinal cord task force aimed to identify RT dose effects and assess risk factors for RM in children. Through systematic review, we analyzed RT dose, fraction size, latency between completion of RT and toxicity, chemotherapy use, age when irradiated, and sex. We conducted literature searches of peer-reviewed manuscripts published from 1964 to June 2017 evaluating RM among children. Normality of variables was assessed with Kolmogorov-Smirnov or Shapiro-Wilk tests. Spearman's rank correlation coefficients were used to test correlations between RT dose/fraction size and latency between RT and development of toxicity. Of 1329 identified and screened reports, 144 reports were fully reviewed and determined to have adequate data for analysis; 16 of these reports had a total of 33 cases of RM with a median age of 13 years (range, 0.2-18) at the time of RT. The most common primary tumor histologies were rhabdomyosarcoma (n = 9), medulloblastoma (n = 5), and Hodgkin lymphoma (n = 2); the most common chemotherapy agents given were vincristine (n = 15), intrathecal methotrexate (n = 12), and intrathecal cytarabine (n = 10). The median RT dose and fraction size were 40 Gy (range, 24-57.4 Gy) and 1.8 Gy (range, 1.3-2.6 Gy), respectively. RT dose resulting in RM in patients who also received chemotherapy was lower than in those not receiving chemotherapy (mean 39.6 vs 49.7 Gy; P = .04). There was no association of age with RT dose. The median latency period was 7 months (range, 1-29). Higher RT dose was correlated with longer latency periods (P = .03) to RM whereas sex, age, fraction size, and chemotherapy use were not. Two of 17 patients with adequate follow-up recovered from RM; unfortunately, it was fatal in 6 of 15 evaluable patients. Complication probability modeling was not possible because of the rarity of events. This report demonstrates a relatively short latency from RT (with or without chemotherapy) to RM and a wide range of doses (including fraction sizes) associated with RM. No apparent association with age at the time of RT could be discerned. Chemotherapy appears to reduce spinal cord tolerance. Recovery from RM is rare, and it is often fatal.