Comparison of ultra-high versus conventional dose rate radiotherapy in a patient with cutaneous lymphoma

Gaide, Olivier; Herrera, Fernanda G.; Sozzi, Wendy Jeanneret; Jorge, Patrik Gonçalves; Kinj, Rémy; Bailat, Claude; Duclos, F.; Bochud, François; Germond, Jean‐François; Gondré, Maude; Boelhen, Till; Schiappacasse, Luis; Ozşahin, Mahmut; Moeckli, Raphaël; Bourhis, Jean

doi:10.1016/j.radonc.2021.12.045

Cited by 52 publications

(40 citation statements)

References 16 publications

(39 reference statements)

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“…Recently, radiation oncology departments worldwide have started implementing this technology at multiple levels geared toward early phase clinical trials in humans. To this end, a feasibility study with one patient has been published ( 9 ) recently followed by a negative report ( 10 ). In the same patient with a cutaneous lymphoma, no difference in terms of side effects and tumor response when a single dose of 15 Gy when delivered at 166 Gy/s versus conventional (0.08 Gy/s) dose rate.…”

Section: Introductionmentioning

confidence: 99%

Dose- and Volume-Limiting Late Toxicity of FLASH Radiotherapy in Cats with Squamous Cell Carcinoma of the Nasal Planum and in Mini Pigs

Bley

Wolf

Jorge

et al. 2022

Clinical Cancer Research

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Purpose: The FLASH effect is characterized by normal tissue sparing without compromising tumor control. Although demonstrated in various preclinical models, safe translation of FLASH-radiotherapy stands to benefit from larger vertebrate animal models. Based on prior results we designed a randomized phase III trial to investigate the FLASH effect in cat-patients with spontaneous tumors. In parallel, the sparing capacity of FLASH-RT was studied on mini-pigs using large field irradiation. Experimental Design: Cats with T1-T2, N0 carcinomas of the nasal planum were randomly assigned to 2 arms of electron irradiation: arm 1 was the standard of care (SoC) and used 10x4.8 Gy (90% isodose), arm 2 used 1x30 Gy (90% isodose) FLASH. Mini-pigs were irradiated using applicators of increasing size and a single surface dose of 31 Gy FLASH Results: In cats, acute side effects were mild and similar in both arms. The trial was prematurely interrupted due to maxillary bone necrosis which occurred 9-15 months after RT in 3/7 cats treated with FLASH-RT (43%), as compared to 0/9 cats treated with SoC. All cats were tumor-free at 1 year in both arms, with one cat progressing later in each arm. In pigs, no acute toxicity was recorded but severe late skin necrosis occurred in a volume-dependent manner (7-9 months) which later resolved. Conclusions: The reported outcomes point to the caveats of translating single-high-dose FLASH-RT and emphasizes the need for caution and further investigations.

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Section: Introductionmentioning

confidence: 99%

Dose- and Volume-Limiting Late Toxicity of FLASH Radiotherapy in Cats with Squamous Cell Carcinoma of the Nasal Planum and in Mini Pigs

Bley

Wolf

Jorge

et al. 2022

Clinical Cancer Research

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“…The results of the treatment were favorable where the patient exhibited no decrease in skin thickness and an equivalent tumor control compared to previously administered CONV-RT treatments [ 53 ]. In a different study on the same patient, two distinct tumors were treated to a dose of 15 Gy single fraction using either CONV or FLASH dose rates [ 54 ]. Both treatments gave comparable results in terms of acute and late effects as well as tumor control.…”

Section: Clinical Experiences With Flash-rtmentioning

confidence: 99%

The Therapeutic Potential of FLASH-RT for Pancreatic Cancer

Okoro

Schüler

Taniguchi

2022

Cancers

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Recent preclinical evidence has shown that ionizing radiation given at an ultra-high dose rate (UHDR), also known as FLASH radiation therapy (FLASH-RT), can selectively reduce radiation injury to normal tissue while remaining isoeffective to conventional radiation therapy (CONV-RT) with respect to tumor killing. Unresectable pancreatic cancer is challenging to control without ablative doses of radiation, but this is difficult to achieve without significant gastrointestinal toxicity. In this review article, we explore the propsed mechanisms of FLASH-RT and its tissue-sparing effect, as well as its relevance and suitability for the treatment of pancreatic cancer. We also briefly discuss the challenges with regard to dosimetry, dose rate, and fractionation for using FLASH-RT to treat this disease.

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“…The FLASH effect has been demonstrated in several animal studies of various types (fish eggs, mice, cats, mini‐pigs, etc. ), 2–7 and a first patient (skin melanoma) has been treated recently 8,9 . Although some FLASH effects have been also observed with photon 10 and proton 11 beams, the most established demonstrations were obtained with low‐energy electron beams (<20 MeV), limiting their current application to superficial tumors.…”

Section: Introductionmentioning

confidence: 99%

“…), [2][3][4][5][6][7] and a first patient (skin melanoma) has been treated recently. 8,9 Although some FLASH effects have been also observed with photon 10 and proton 11 beams, the most established demonstrations were obtained with low-energy electron beams (<20 MeV), limiting their current application to superficial tumors. New developments in compact highgradient accelerator techniques [12][13][14] and laser-driven electron beam technologies [15][16][17] allow to consider the use of very high-energy electron (VHEE, E > 70 MeV) beams [18][19][20] to address the penetration depth limitation and exploit the FLASH effect for the treatment of deepseated tumors.…”

Section: Introductionmentioning

confidence: 99%

Determination of the ion collection efficiency of the Razor Nano Chamber for ultra‐high dose‐rate electron beams

et al. 2022

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Background Ultra‐high dose‐rate (UHDR) irradiations (>40 Gy/s) have recently garnered interest in radiotherapy (RT) as they can trigger the so‐called “FLASH” effect, namely a higher tolerance of normal tissues in comparison with conventional dose rates when a sufficiently high dose is delivered to the tissue. To transfer this to clinical RT treatments, adapted methods and practical tools for online dosimetry need to be developed. Ionization chambers remain the gold standards in RT but the charge recombination effects may be very significant at such high dose rates, limiting the use of some of these dosimeters. The reduction of the sensitive volume size can be an interesting characteristic to reduce such effects. Purpose In that context, we have investigated the charge collection behavior of the recent IBA Razor™ Nano Chamber (RNC) in UHDR pulses to evaluate its potential interest for FLASH RT. Methods In order to quantify the RNC ion collection efficiency (ICE), simultaneous dose measurements were performed under UHDR electron beams with dose‐rate‐independent Gafchromic™ EBT3 films that were used as the dose reference. A dose‐per‐pulse range from 0.01 to 30 Gy was investigated, varying the source‐to‐surface distance, the pulse duration (1 and 3 μs investigated) and the LINAC gun grid tension as irradiation parameters. In addition, the RNC measurements were corrected from the inherent beam shot‐to‐shot variations using an independent current transformer. An empirical logistic model was used to fit the RNC collection efficiency measurements and the results were compared with the Advanced Markus plane parallel ion chamber. Results The RNC ICE was found to decrease as the dose‐per‐pulse increases, starting from doses above 0.2 Gy/pulse and down to 40% of efficiency at 30 Gy/pulse. The RNC resulted in a higher ICE for a given dose‐per‐pulse in comparison with the Markus chamber, with a measured efficiency found higher than 85 and 55% for 1 and 10 Gy/pulse, respectively, whereas the Markus ICE was of 60 and 25% for the same doses. However, the RNC shows a higher sensitivity to the pulse duration than the Advanced Markus chamber, with a lower efficiency found at 1 μs than at 3 μs, suggesting that this chamber could be more sensitive to the dose rate within the pulse. Conclusions The results confirmed that the small sensitive volume of the RNC ensures higher ICE compared with larger chambers. The RNC was thus found to be a promising online dosimetry tool for FLASH RT and we proposed an ion recombination model to correct its response up to extreme dose‐per‐pulses of 30 Gy.

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Comparison of ultra-high versus conventional dose rate radiotherapy in a patient with cutaneous lymphoma

Cited by 52 publications

References 16 publications

Dose- and Volume-Limiting Late Toxicity of FLASH Radiotherapy in Cats with Squamous Cell Carcinoma of the Nasal Planum and in Mini Pigs

Dose- and Volume-Limiting Late Toxicity of FLASH Radiotherapy in Cats with Squamous Cell Carcinoma of the Nasal Planum and in Mini Pigs

The Therapeutic Potential of FLASH-RT for Pancreatic Cancer

Determination of the ion collection efficiency of the Razor Nano Chamber for ultra‐high dose‐rate electron beams

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