Treatment of a first patient with FLASH-radiotherapy

Jean Bourhis; Wendy Jeanneret Sozzi; Patrik Gonçalves Jorge; Olivier Gaide; Claude Bailat; Fréderic Duclos; David Patin; Mahmut Ozsahin; François Bochud; Jean-François Germond; Raphaël Moeckli; Marie-Catherine Vozenin

doi:10.1016/j.radonc.2019.06.019

Treatment of a first patient with FLASH-radiotherapy

Radiother Oncol. 2019 Oct:139:18-22. doi: 10.1016/j.radonc.2019.06.019. Epub 2019 Jul 11.

Affiliations

¹ Department of Radiation Oncology, Lausanne University Hospital and University of Lausanne, Switzerland; Radiation Oncology Laboratory, Department of Radiation Oncology. Lausanne University Hospital and University of Lausanne, Switzerland. Electronic address: jean.bourhis@chuv.ch.
² Department of Radiation Oncology, Lausanne University Hospital and University of Lausanne, Switzerland.
³ Department of Radiation Oncology, Lausanne University Hospital and University of Lausanne, Switzerland; Radiation Oncology Laboratory, Department of Radiation Oncology. Lausanne University Hospital and University of Lausanne, Switzerland; Institute of Radiation Physics, Lausanne University Hospital and University of Lausanne, Switzerland.
⁴ Department of Dermatology, Lausanne University Hospital and University of Lausanne, Switzerland.
⁵ Institute of Radiation Physics, Lausanne University Hospital and University of Lausanne, Switzerland.
⁶ Department of Radiation Oncology, Lausanne University Hospital and University of Lausanne, Switzerland; Radiation Oncology Laboratory, Department of Radiation Oncology. Lausanne University Hospital and University of Lausanne, Switzerland.

PMID: 31303340
DOI: 10.1016/j.radonc.2019.06.019

Abstract

Background: 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-RT.

Material & methods: A 75-year-old patient presented with a multiresistant CD30+ T-cell cutaneous lymphoma disseminated throughout the whole skin surface. Localized skin RT has been previously used over 110 times for various ulcerative and/or painful cutaneous lesions progressing despite systemic treatments. However, the tolerance of these RT was generally poor, and it was hypothesized that FLASH-RT could offer an equivalent tumor control probability, while being less toxic for the skin. This treatment was given to a 3.5-cm diameter skin tumor with a 5.6-MeV linac specifically designed for FLASH-RT. The prescribed dose to the PTV was 15 Gy, in 90 ms. Redundant dosimetric measurements were performed with GafChromic films and alanine, to check the consistency between the prescribed and the delivered doses.

Results: At 3 weeks, i.e. at the peak of the reactions, a grade 1 epithelitis (CTCAE v 5.0) along with a transient grade 1 oedema (CTCAE v5.0) in soft tissues surrounding the tumor were observed. Clinical examination was consistent with the optical coherence tomography showing no decrease of the thickness of the epidermis and no disruption at the basal membrane with limited increase of the vascularization. In parallel, the tumor response was rapid, complete, and durable with a short follow-up of 5 months. These observations, both on normal skin and on the tumor, were promising and prompt to further clinical evaluation of FLASH-RT.

Conclusion: This first FLASH-RT treatment was feasible and safe with a favorable outcome both on normal skin and the tumor.

Keywords: Clinical translation; Differential effect; FLASH-RT; Normal tissue protection.

Publication types

Case Reports
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Drug Resistance, Neoplasm
Humans
Lymphoma, T-Cell, Cutaneous / radiotherapy*
Male
Organ Sparing Treatments / methods
Radiotherapy / methods
Radiotherapy Dosage
Skin Neoplasms / radiotherapy*
Treatment Outcome