Showing papers by "Kristoffer Petersson published in 2020"

Ultra-High Dose Rate (FLASH) Radiotherapy: Silver Bullet or Fool's Gold?

Abstract: Radiotherapy is a cornerstone of both curative and palliative cancer care. However, radiotherapy is severely limited by radiation-induced toxicities. If these toxicities could be reduced, a greater dose of radiation could be given therefore facilitating a better tumor response. Initial pre-clinical studies have shown that irradiation at dose rates far exceeding those currently used in clinical contexts reduce radiation-induced toxicities whilst maintaining an equivalent tumor response. This is known as the FLASH effect. To date, a single patient has been subjected to FLASH radiotherapy for the treatment of subcutaneous T-cell lymphoma resulting in complete response and minimal toxicities. The mechanism responsible for reduced tissue toxicity following FLASH radiotherapy is yet to be elucidated, but the most prominent hypothesis so far proposed is that acute oxygen depletion occurs within the irradiated tissue. This review examines the tissue response to FLASH radiotherapy, critically evaluates the evidence supporting hypotheses surrounding the biological basis of the FLASH effect, and considers the potential for FLASH radiotherapy to be translated into clinical contexts.

The FLASH effect depends on oxygen concentration.

Abstract: Objective:Recent in vivo 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 ...

A Quantitative Analysis of the Role of Oxygen Tension in FLASH Radiation Therapy

Abstract: Purpose Recent demonstrations of normal tissue sparing by high-dose, high-dose-rate FLASH radiation therapy have driven considerable interest in its application to improve clinical outcomes. However, significant uncertainty remains about the underlying mechanisms of FLASH sparing and how deliveries can be optimized to maximize benefit from this effect. Rapid oxygen depletion has been suggested as a potential mechanism by which these effects occur, but this has yet to be quantitatively tested against experimental data. Methods and Materials Models of oxygen kinetics during irradiation were used to develop a time-dependent model of the oxygen enhancement ratio in mammalian cells that incorporates oxygen depletion. The characteristics of this model were then explored in terms of the dose and dose-rate dependence of the oxygen enhancement ratio. This model was also fit to experimental data from both in vitro and in vivo data sets. Results In cases of FLASH radiation therapy, this model suggests that oxygen levels can be depleted by amounts that are sufficient to affect radiosensitivity only in conditions of intermediate oxygen tension, with no effect seen at high or very low initial oxygen levels. The model also effectively reproduced the dose, dose rate, and oxygen tension dependence of responses to FLASH radiation therapy in a range of systems, with model parameters compatible with published data. Conclusions Oxygen depletion provides a credible quantitative model to understand the biological effects of FLASH radiation therapy and is compatible with a range of experimental observations of FLASH sparing. These results highlight the need for more detailed quantification of oxygen depletion under high-dose-rate radiation exposures in relevant systems and the importance of oxygen tension in target tissues for FLASH sparing to be observed.

Understanding High-Dose, Ultra-High Dose Rate, and Spatially Fractionated Radiation Therapy.

Abstract: The National Cancer Institute's Radiation Research Program, in collaboration with the Radiosurgery Society, hosted a workshop called Understanding High-Dose, Ultra-High Dose Rate and Spatially Fractionated Radiotherapy on August 20 and 21, 2018 to bring together experts in experimental and clinical experience in these and related fields. Critically, the overall aims were to understand the biological underpinning of these emerging techniques and the technical/physical parameters that must be further defined to drive clinical practice through innovative biologically based clinical trials.

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

Abstract: 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. This was done by modeling the drop-in ion-collection efficiency of the chamber with increasing dose-per-pulse values, so that the ion recombination effect could be considered. The raw transmission chamber signal was extracted from the linear accelerator and its response was measured using radiochromic film at different dose rates/dose-per-pulse values, at a source-to-surface distance of 100 cm. An increase of the polarizing voltage, applied over the transmission chamber, by a factor of 2 and 3, improved the ion-collection efficiency, with corresponding increased efficiency at the highest dose-per-pulse values by a factor 1.4 and 2.2, respectively. The drop-in ion-collection efficiency with increasing dose-per-pulse was accurately modeled using a logistic function fitted to the transmission chamber data. The performance of the model was compared to that of the general theoretical Boag models of ion recombination in ionization chambers. The logistic model was subsequently used to correct for ion recombination at dose rates ranging from conventional to ultra-high, making the transmission chamber useful as a real-time monitor for the dose delivery of FLASH electron beams in a clinical setup.

Corrigendum: Ultra-High Dose Rate (FLASH) Radiotherapy: Silver Bullet or Fool's Gold?

Abstract: [This corrects the article DOI: 10.3389/fonc.2019.01563.].

Palliative short-course hypofractionated radiotherapy followed by chemotherapy in esophageal adenocarcinoma: the phase II PALAESTRA trial

Abstract: Background: The majority of patients with incurable esophageal adenocarcinoma suffer from dysphagia. We assessed a novel treatment strategy with initial short-course radiotherapy followed by chemotherapy with the primary aim to achieve long-term relief of dysphagia. Methods: This phase II trial included treatment-naive patients with dysphagia due to esophageal adenocarcinoma not eligible for curative treatment. External beam radiotherapy with 20 Gy in five fractions to the primary tumor was followed by four cycles of chemotherapy (FOLFOX regimen). Dysphagia was assessed using a five-grade scale. Results: From October 2014 to May 2018 a total of 29 patients were enrolled. The rate of dysphagia improvement was 79%, median duration of improvement 6.7 months (12.2 months for responders) and median overall survival 9.9 months. In the pre-specified per protocol analysis (23 patients) the rate of dysphagia improvement was 91%, median duration of improvement 12.2 months (14.0 months for responders) and median overall survival 16.0 months. The most common grade 3–4 adverse events were neutropenia (29%), infection (25%), anorexia (11%), esophagitis (11%) and fatigue (11%). Conclusion: Initial palliative short-course radiotherapy followed by chemotherapy is a promising treatment strategy that can provide long-lasting relief of dysphagia in patients with esophageal adenocarcinoma.