Leveraging the Power of Electrons to Realize the Promise of FLASH*

The IntraOp® Mobetron® is a comprehensive electron therapy linear accelerator system with applications in intraoperative radiotherapy (IORT) and non-invasive treatment of skin cancer. Now Mobetron is the first to provide ultra-high dose rate (UHDR) electron therapy for preclinical and investigational studies of FLASH radiotherapy* on an established clinical radiotherapy platform. IntraOp’s advanced technology ushers in a new paradigm for cancer treatment by providing researchers an approach not possible before: Precision treatment in microseconds.

*Ultra-High Dose Rate (UHDR) functionality for FLASH Radiotherapy is for investigational use only and is not cleared for sale by the US FDA.

Empowering A New Renaissance in Radiotherapy

The advent of image-guidance significantly improved the precision of radiation therapy and advancements since continue to incrementally raise the efficacy of cancer treatment. However, the underlying theories and technologies have remained somewhat static for decades. To this point, radiation oncologists have only been able to control two key variables for improving treatment: fractionation and volume optimization. Breakthrough research from the CHUV, Lausanne-Switzerland introduces a third dimension: ultra-high dose rate irradiation and the “FLASH Effect”, for optimizing care based on new concepts in radiochemistry and radiobiology with the potential to revolutionize radiotherapy by making it safer and more effective.

The FLASH Effect Significantly Improves the Therapeutic Ratio for Curing Cancer

Therapeutic Index for FLASH Radiotherapy

The FLASH Effect Significantly Improves the Therapeutic Ratio for Curing Cancer

Therapeutic Index for FLASH Radiotherapy

Published Articles: FLASH Radiotherapy

Commissioning of an ultra-high dose rate pulsed electron beam medical LINAC for FLASH RT preclinical animal experiments and future clinical human protocols

The Mobetron device was evaluated with electron beams of 9 MeV in conventional (CONV) mode and of 6 and 9 MeV in UHDR mode (nominal energy). The acceptance was performed according to the acceptance protocol of the company. The commissioning consisted of determining the short- and long-term stability of the device, the measurement of percent depth dose curves (PDDs) and profiles at two different positions (with two different dose per pulse regimen) and for different collimator sizes, and the evaluation of the variability of these parameters when changing the pulse width and pulse repetition frequency. Measurements were performed using a redundant and validated dosimetric strategy with alanine and radiochromic films, as well as Advanced Markus ionization chamber for some measurements.

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Treatment of a first patient with FLASH-radiotherapy

When compared to conventional radiotherapy (RT) in pre-clinical studies, FLASH-RT was shown to reproducibly spare normal tissues, while preserving the anti-tumor activity. This marked increase of the differential effect between normal tissues and tumors prompted its clinical translation. In this context, we present here the treatment of a first patient with FLASH radiotherapy.

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Independent Reproduction of the FLASH Effect on the Gastrointestinal Tract: A Multi-Institutional Comparative Study

The ability of ultra-high dose rate FLASH radiation therapy (RT) to reduce normal tissue toxicity without affecting tumor response relative to conventional dose rate radiation therapy could fundamentally change the way we treat cancer. However, this field is still in its early stages, and the magnitude of the sparing effect between treatment centers differs greatly for reasons as yet unknown, which has put the robustness of the effect into question. In this study, we show that when similar irradiation beam parameter settings are used, the induced sparing effect is robust and reproducible across institutions. These settings should serve as a reference for further optimization of the FLASH effect.

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Dual beam-current transformer design for monitoring and reporting of electron ultra-high dose rate (FLASH) beam parameters

Two BCTs are integrated into the head of a FLASH Mobetron system, one located after the primary scattering foil and the other downstream of the secondary scattering foil. The response of the BCTs was evaluated individually to monitor beam output as a function of dose, scattering conditions, and ability to capture physical beam parameters such as pulse width (PW),pulse repetition frequency (PRF), and dose per pulse (DPP), and in combination to determine beam energy using the ratio of the lower-to-upper BCT signal.

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Implementation and validation of a beam-current transformer on a medical pulsed electron beam LINAC for FLASH-RT beam monitoring

Two beam current transformers (BCTs) were placed at the exit of a medical LINAC capable of UHDR irradiations. The BCTs were validated as monitoring devices by verifying beam parameters consistency between nominal values and measured values, determining the relationship between the charge measured and the absorbed dose, and checking the short- and long-term stability of the charge-absorbed dose ratio.

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The Therapeutic Potential of FLASH-RT for Pancreatic Cancer

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 may lead to one of the greatest breakthroughs in radiotherapy in decades. There is still much we hope to learn and understand about this phenomenon. We know that the next logical step is to begin human trials and are excited to be working with IntraOp on this initiative.

Jean Bourhis, MD, PhD.

Professor, Chief of Radiation Oncology at CHUV

The FLASH Effect

Leading researcher Marie-Catherine Vozenin, PhD explains that recent studies demonstrate how irradiation at ultra-high dose rates produce a biological “phenomena” that protects healthy tissue while delivering an iso-effective ability to control and kill tumors. This FLASH Effect has now been demonstrated in various animal studies and the first human treatment, consistently demonstrating lower toxicity to healthy tissue when compared with conventional radiation therapy. Many researchers are now turning their focus toward investigational and clinical trials of the FLASH Effect. With dose rates over 5,000 times higher than conventional radiotherapy, the Mobetron empowers researchers to study the FLASH Effect with electron energies of 6 MeV and 9 MeV and field sizes up to 10cm.

How Mobetron is Enabling Clinical Translation of FLASH

Clinical Translation Benefits of FLASH therapy

How Mobetron is Enabling Clinical Translation of FLASH

icons detailing the benefits of FLASH therapy

A Brief Visual History of FLASH

A timeline history of FLASH Radiotherapy (RT)

A Brief Visual History of FLASH

Timeline detailing the history of FLASH radiotherapy

First Human Treatment with FLASH Radiotherapy

Treatment delivered 15 Gy with no unexpected side effects and complete tumor clearance.

Before and After treatment photos using electron high-dose rate FLASH radiotherapy (FLASH RT)

Source: Bourhis et al. Radiotherapy and Oncology, 2019

Latest Research and Clinical Trials:

IntraOp is proud to be collaborating with leading researchers and institutions around the world to advance new technologies and research in FLASH therapy with a focus on translational studies to bring better care to patients safely and effectively.

Impulse Trial:

The Impulse Trial is the first in a series of trials led by Principle Investigator Professor Jean Bourhis (CHUV, Switzerland) to study the FLASH Effect in skin cancers.  The first in the series is a phase I dose escalation study of ultra-high dose rate irradiation with electrons in patients with skin metastases from melanoma.  This study is the first in the world to evaluate the potential of leveraging FLASH Effect to provide radiotherapy with curative intent to radio-resistant cancers.

Study Details:

  • Patients with skin metastases from melanoma
  • Dose escalation study to determine the maximum tolerated dose of FLASH therapy.
  • Enrollment is open now
  • Study uses a modified Mobetron with FLASH UHDR for investigational approval

Experts at CHUV Share Groundbreaking FLASH Radiotherapy Research

Our partners from CHUV (Lausanne University Hospital, Switzerland) are the world's leading researchers in FLASH radiotherapy. Watch as they present their findings on the FLASH Effect, provide clinical perspectives on this breakthrough therapy, and describe the forthcoming transition to clinical trials.

*Ultra-High Dose Rate (UHDR) functionality for FLASH Radiotherapy is for investigational use only and is not cleared for sale by the US FDA.

Leading Researchers Tell the Story of FLASH Radiotherapy

Marie-Catherine Vozenin, PhD, HDR
Chief of Radiation Oncology Research Lab Lausanne University Hospital | CHUV

What Comes Next: The Path to Clinical Trials

Raphael Moekckli, PhD, PD-MER
Head Physicist of Radiation Oncology, Lausanne University Hospital | CHUV

Clinical perspectives for FLASH Therapy

Jean Bourhis, MD, PhD
Professor, Chief of Radiation Oncology Lausanne University Hospital | CHUV

FLASH on a Versatile Platform

Compact. Effective. Scalable. New innovations such as FLASH make Mobetron an even more powerful solution for research and academic institutions. IntraOp’s FLASH technology incorporates into the established Mobetron platform enabling clinicians to use the Mobetron for routine clinical use while also researching FLASH with electrons in skin cancer and IORT indications.

We are extremely excited to partner with IntraOp to launch key investigations paving the way for future clinical implementation of FLASH-electrons in this setting. The existing data on FLASH-electrons, especially in the IORT setting, holds the potential of greatly enhancing the overall therapeutic ratio of radiation in a truly transformational manner.”

Arnab Chakravarti, MD

Chair and Professor of Radiation Oncology, Klotz Family Chair of Cancer Research and the Director of the Brain Tumor Program at the OSUCCC – James

The FLASH Renaissance Begins With Mobetron

IntraOp provides a flexible, effective, and efficient approach to studying FLASH with a focus on clinical translation.

IntraOp Mobetron for IORT Treatment - FLASH UHDR Controller for FLASH Radiotherapy - Mobetron SC for Skin Cancer treatment

  1. Favaudon V. et al. “Ultra-high doserate FLASH irradiation increases the differential response between normal and tumor tissue in mice”. Science Translation Medicine 2014
  2. Montay-Gruel P. et al. “Irradiation in a flash: Unique sparing of memory in mice after whole brain irradiation with dose rates above 100Gy/s”. Radiotherapy and Oncology 2017
  3. Vozenin M.C. et al. “The Advantage of FLASH Radiotherapy Confirmed in Mini-pig and Cat-cancer Patients”. Clinical Cancer Research 2019
  4. Bourhis J. et al. “Treatment of a first patient with FLASH-radiotherapy”. Radiotherapy and Oncology 2019

*Ultra-High Dose Rate (UHDR) functionality for FLASH Radiotherapy is for investigational use only and is not cleared for sale by the US FDA.

We look forward to sharing the ways FLASH with electrons is advancing the future of radiotherapy.


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