Hypoxia-induced complement component 3 promotes aggressive tumor growth in the glioblastoma microenvironment.

Glioblastoma (GBM) is the most aggressive form of glioma with a high rate of relapse despite intensive treatment. Tumor recurrence is tightly linked to radio-resistance, which in turn is associated with hypoxia. Here, we discovered a strong link between hypoxia and local complement signaling using publicly available bulk, single-cell, and spatially resolved transcriptomic data from patients with GBM.

Long-term toxicity and efficacy of FLASH radiotherapy in dogs with superficial malignant tumors.

Introduction: FLASH radiotherapy (RT) has emerged as a promising modality, demonstrating both a normal tissue sparing effect and anticancer efficacy. We have previously reported on the safety and efficacy of single fraction FLASH RT in the treatment of oral tumors in canine cancer patients, showing tumor response but also a risk of radiation-induced severe late adverse effects (osteoradionecrosis) for doses ≥35 Gy. Accordingly, the objective in this study was to investigate if single fraction high dose FLASH RT is safe for treating non-oral tumors.

Evaluation of superficial xenograft volume estimation by ultrasound and caliper against MRI in a longitudinal pre-clinical radiotherapeutic setting.

Background: Accurate tumor volume estimation is important for evaluating the response to radionuclide therapy and external beam radiotherapy as well as to other pharmaceuticals. A common method for monitoring the growth of subcutaneous tumors in pre-clinical models and assessing the treatment response is to measure the tumor length and width by external calipers to estimate its volume. This procedure relies on an assumption of a spheroidal tumor shape wherein the tumor depth equals the width and can yield considerably inaccuracies.

Investigating Ras homolog gene family member C (RhoC) and Ki67 expression following external beam radiation therapy show increased RhoC expression in relapsing prostate cancer xenografts.

Ras homolog gene family member C (RhoC) is a GTPase involved in cell migration, implicated in epithelial-mesenchymal transition and treatment resistance and metastasis of cancer. For example, RhoC has been shown to be involved in resistance to radiation in cervical carcinoma. Here, the effect of X-ray irradiation on RhoC expression in prostate cancer (PCa) xenografts was investigated in both xenografts in regression and relapse.

Comparable survival in rats with intracranial glioblastoma irradiated with single-fraction conventional radiotherapy or FLASH radiotherapy.

Background: Radiotherapy increases survival in patients with glioblastoma. However, the prescribed dose is limited by unwanted side effects on normal tissue. Previous experimental studies have shown that FLASH radiotherapy (FLASH-RT) can reduce these side effects.

Reconfiguring a Plane-Parallel Transmission Ionization Chamber to Extend the Operating Range into the Ultra-High Dose-per-pulse Regime.

This study aims to investigate the feasibility of enhancing the charge collection efficiency (CCE) of a transmission chamber by reconfiguring its design and operation. The goal was to extend the range of dose-per-pulse (DPP) values with no or minimal recombination effects up to the ultra-high dose rate (UHDR) regime. The response of two transmission chambers, with electrode distance of 1 mm and 0.

Beam control system and output fine-tuning for safe and precise delivery of FLASH radiotherapy at a clinical linear accelerator.

Introduction: We have previously adapted a clinical linear accelerator (Elekta Precise, Elekta AB) for ultra-high dose rate (UHDR) electron delivery. To enhance reliability in future clinical FLASH radiotherapy trials, the aim of this study was to introduce and evaluate an upgraded beam control system and beam tuning process for safe and precise UHDR delivery.

Materials And Methods: The beam control system is designed to interrupt the beam based on 1) a preset number of monitor units (MUs) measured by a monitor detector, 2) a preset number of pulses measured by a pulse-counting diode, or 3) a preset delivery time.

Evaluation of single-fraction high dose FLASH radiotherapy in a cohort of canine oral cancer patients.

Background: FLASH radiotherapy (RT) is a novel method for delivering ionizing radiation, which has been shown in preclinical studies to have a normal tissue sparing effect and to maintain anticancer efficacy as compared to conventional RT. Treatment of head and neck tumors with conventional RT is commonly associated with severe toxicity, hence the normal tissue sparing effect of FLASH RT potentially makes it especially advantageous for treating oral tumors. In this work, the objective was to study the adverse effects of dogs with spontaneous oral tumors treated with FLASH RT.

Evaluation of intensity-modulated electron FLASH radiotherapy in a clinical setting using veterinary cases.

Purpose: The increased normal tissue tolerance for FLASH radiotherapy (FLASH-RT), as compared to conventional radiotherapy, was first observed in ultra-high dose rate electron beams. Initial clinical trials in companion animals have revealed a high risk of developing osteoradionecrosis following high-dose single-fraction electron FLASH-RT, which may be related to inhomogeneities in the dose distribution. In the current study, we aim to evaluate the possibilities of intensity-modulated electron FLASH-RT in a clinical setting to ensure a homogeneous dose distribution in future veterinary and human clinical trials.

Surface guided electron FLASH radiotherapy for canine cancer patients.

Background: During recent years FLASH radiotherapy (FLASH-RT) has shown promising results in radiation oncology, with the potential to spare normal tissue while maintaining the antitumor effects. The high speed of the FLASH-RT delivery increases the need for fast and precise motion monitoring to avoid underdosing the target. Surface guided radiotherapy (SGRT) uses surface imaging (SI) to render a 3D surface of the patient.

Combined anti-C1-INH and radiotherapy against glioblastoma.

Background: A more effective immune response against glioblastoma is needed in order to achieve better tumor control. Radiotherapy can induce anti-tumor mediated immune reactions, in addition to its dose response effects. The complement system can function as a bridge between innate and adaptive immune responses.

Comparable Long-Term Tumor Control for Hypofractionated FLASH Versus Conventional Radiation Therapy in an Immunocompetent Rat Glioma Model.

Purpose: To ensure a clinical translation of FLASH radiation therapy (FLASH-RT) for a specific tumor type, studies on tumor control and toxicity within the same biological system are needed. In this study, our objective was to evaluate tumor control and toxicity for hypofractionated FLASH-RT and conventional radiation therapy (CONV-RT) in an immunocompetent rat glioma model.

Methods And Materials: Fisher 344 rats (N = 68) were inoculated subcutaneously with NS1 glioma cells and randomized into groups (n = 9-10 per group).

Long-term anti-tumor effects following both conventional radiotherapy and FLASH in fully immunocompetent animals with glioblastoma.

Radiotherapy can induce an immunological response. One limiting factor is side effects on normal tissue. Using FLASH radiotherapy, side effects could possibly be reduced.

Robustness Assessment of Images From a 0.35T Scanner of an Integrated MRI-Linac: Characterization of Radiomics Features in Phantom and Patient Data.

Radiomics entails the extraction of quantitative imaging biomarkers (or radiomics features) hypothesized to provide additional pathophysiological and/or clinical information compared to qualitative visual observation and interpretation. This retrospective study explores the variability of radiomics features extracted from images acquired with the 0.35 T scanner of an integrated MRI-Linac.

Impact of combining vitamin C with radiation therapy in human breast cancer: does it matter?

Vitamin C may impact the efficiency of radiation therapy (RT) in breast cancer. The effects of RT alone or in combination with vitamin C in SKBR3, MDA-MB-231, and MCF7 cells were compared using clonogenic assay, proliferation assay (MTT), cell cycle analysis, and Western blot. Vitamin C use was assessed in 1803 breast cancer patients 2002-2017 in relation to clinicopathological features and recurrences after RT.

Cancer Cells Can Exhibit a Sparing FLASH Effect at Low Doses Under Normoxic Conditions.

Background: Irradiation with ultra-high dose rate (FLASH) has been shown to spare normal tissue without hampering tumor control in several studies. Few cell lines have been investigated , and previous results are inconsistent. Assuming that oxygen depletion accounts for the FLASH sparing effect, no sparing should appear for cells irradiated with low doses in normoxia.

Artificial intelligence and the medical physics profession - A Swedish perspective.

Background: There is a continuous and dynamic discussion on artificial intelligence (AI) in present-day society. AI is expected to impact on healthcare processes and could contribute to a more sustainable use of resources allocated to healthcare in the future. The aim for this work was to establish a foundation for a Swedish perspective on the potential effect of AI on the medical physics profession.

Establishment and Initial Experience of Clinical FLASH Radiotherapy in Canine Cancer Patients.

FLASH radiotherapy has emerged as a treatment technique with great potential to increase the differential effect between normal tissue toxicity and tumor response compared to conventional radiotherapy. To evaluate the feasibility of FLASH radiotherapy in a relevant clinical setting, we have commenced a feasibility and safety study of FLASH radiotherapy in canine cancer patients with spontaneous superficial solid tumors or microscopic residual disease, using the electron beam of our modified clinical linear accelerator. The setup for FLASH radiotherapy was established using a short electron applicator with a nominal source-to-surface distance of 70 cm and custom-made Cerrobend blocks for collimation.

Correction for Ion Recombination in a Built-in Monitor Chamber of a Clinical Linear Accelerator at Ultra-High Dose Rates.

In the novel and promising radiotherapy technique known as FLASH, ultra-high dose-rate electron beams are used. As a step towards clinical trials, dosimetric advances will be required for accurate dose delivery of FLASH. The purpose of this study was to determine whether a built-in transmission chamber of a clinical linear accelerator can be used as a real-time dosimeter to monitor the delivery of ultra-high-dose-rate electron beams.

Surface-guided tomotherapy improves positioning and reduces treatment time: A retrospective analysis of 16 835 treatment fractions.

Purpose: In this study, we have quantified the setup deviation and time gain when using fast surface scanning for daily setup/positioning with weekly megavoltage computed tomography (MVCT) and compared it to daily MVCT.

Methods: A total of 16 835 treatment fractions were analyzed, treated, and positioned using our TomoTherapy HD (Accuray Inc., Madison, USA) installed with a Sentinel optical surface scanning system (C-RAD Positioning AB, Uppsala, Sweden).

Increased effect of two-fraction radiotherapy in conjunction with IDO1 inhibition in experimental glioblastoma.

Objectives: The aim of the study was to investigate therapeutic efficacy of single- or two-fraction radiotherapy in conjunction with IDO1-inhibition in a syngeneic rat glioblastoma model. IDO is known to cause immunosuppression through breakdown of tryptophan in the tumor microenvironment.

Methods: Gene expression analyses of IDO in glioblastoma were performed with data from publicly available datasets.

Analysis of early respiratory-related mortality after radiation therapy of non-small-cell lung cancer: feasibility of automatic data extraction for dose-response studies.

To examine the feasibility of automatic data extraction from clinical radiation therapy (RT) databases at four hospitals to investigate the impact of mean lung dose (MLD) and age on the risk of early respiratory-related death and early overall death for patients treated with RT for non-small-cell lung cancer (NSCLC). We included adult patients with NSCLC receiving curatively intended RT between 2002 and 2017 at four hospitals. A script was developed to automatically extract RT-related data.

Growth pattern of experimental glioblastoma.

Glioblastoma multiforme (GBM) is an aggressive primary brain malignancy with a very poor prognosis. Researchers employ animal models to develop potential therapies. It is important that these models have clinical relevance.

The FLASH effect depends on oxygen concentration.

Objective: Recent results have shown prominent tissue sparing effect of radiotherapy with ultra-high dose rates (FLASH) compared to conventional dose rates (CONV). Oxygen depletion has been proposed as the underlying mechanism, but data to support this have been lacking. The aim of the current study was to compare FLASH to CONV irradiation under different oxygen concentrations .

Modifying a clinical linear accelerator for delivery of ultra-high dose rate irradiation.

Objectives: The purpose of this study was to modify a clinical linear accelerator, making it capable of electron beam ultra-high dose rate (FLASH) irradiation. Modifications had to be quick, reversible, and without interfering with clinical treatments.

Methods: Performed modifications: (1) reduced distance with three setup positions, (2) adjusted/optimized gun current, modulator charge rate and beam steering values for a high dose rate, (3) delivery was controlled with a microcontroller on an electron pulse level, and (4) moving the primary and/or secondary scattering foils from the beam path.