FLASH radiotherapy is an emerging cancer treatment that delivers radiation at extremely high dose rates within a fraction of a second. This innovative radiation delivery technique, dramatically faster than conventional radiotherapy, reduces radiation injury to surrounding healthy tissues while effectively targeting malignant tumour cells.
Preclinical studies of laboratory animals have demonstrated that FLASH radiotherapy is at least equivalent to conventional radiotherapy, and may produce better anti-tumour effects in some types of cancer. The biological “FLASH effect”, which is observed for ultrahigh-dose rate (UHDR) irradiations, spares normal tissue compared with conventional dose rate (CDR) irradiations, while retaining the tumour toxicity.
With FLASH radiotherapy opening up the therapeutic window, it has potential to benefit patients requiring radiotherapy. As such, efforts are underway worldwide to overcome the clinical challenges for safe adoption of FLASH into clinical practice. As the FLASH effect has been mostly investigated using broad UHDR electron beams, which have limited range and are best suited for treating superficial lesions, one important challenge is to find a way to effectively treat deep-seated tumours.
In a proof-of-concept treatment planning study, researchers in Switzerland demonstrated that a hybrid approach combining UHDR electron and CDR photon radiotherapy may achieve equivalent dosimetric effectiveness and quality to conventional radiotherapy, for the treatment of glioblastoma, pancreatic cancer and localized prostate cancer. The team, at Lausanne University Hospital and the University of Lausanne, report the findings in Radiotherapy and Oncology.
Combined device
This hybrid treatment could be facilitated using a linear accelerator (linac) with the capability to generate both UHDR electron beams and CDR photon beams. Such a radiotherapy device could eliminate concerns relating to the purchase, operational and maintenance costs of other proposed FLASH treatment devices. It would also overcome the logistical hurdles of needing to move patients between two separate radiotherapy treatment rooms and immobilize them identically twice.
For their study, the Lausanne team presumed that such a dual-use clinically approved linac exists. This linac would deliver a bulk radiation dose by a UHDR electron beam in a less conformal manner to achieve the FLASH effect, and then deliver conventional intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT) to enhance dosimetric target coverage and conformity.
Principal investigator Till Böhlen and colleagues created a machine model that simulates 3D-conformal broad electron beams with a homogeneous parallel fluence. They developed treatments that deliver a single broad UHDR electron beam with case-dependent energy of between 20 and 250 MeV for every treatment fraction, together with a CDR VMAT to produce a conformal dose delivery to the planning target volume (PTV).
The tumours for each of the three cancer cases required simple, mostly round PTVs that could be covered by a single electron beam. Each plan’s goal was to deliver the majority of the dose per treatment with the UHDR electron beam, while achieving acceptable PTV coverage, homogeneity and sparing of critical organs-at-risk.
Plan comparisons
The researchers assessed the plan quality based on absorbed dose distribution, dose–volume histograms and dose metric comparisons with the CDR reference plans used for clinical treatments. In all cases, the hybrid plans exhibited comparable dosimetric quality to the clinical plans. They also evaluated dose metrics for the parts of the doses delivered by the UHDR electron beam and by the CDR VMAT, observing that the hybrid plans delivered the majority of the PTV dose, and large parts of doses to surrounding tissues, at UHDR.
“This study demonstrates that hybrid treatments combining an UHDR electron field with a CDR VMAT may provide dosimetrically conformal treatments for tumours with simple target shapes in various body sites and depths in the patient, while delivering the majority of the prescribed dose per fraction at UHDR without delivery pauses,” the researchers write.
Will ultrahigh dose rates transform radiotherapy in a FLASH?
In another part of the study, the researchers estimated the potential FLASH sparing effect achievable with their hybrid technique, using the glioblastoma case as an example. They assumed a FLASH normal tissue sparing scenario with an onset of FLASH sparing at a threshold dose of 11 Gy/fraction, and a more favourable scenario with sparing onset at 3 Gy/fraction. The treatment comprised a single-fraction 15 Gy UHDR electron boost, supplemented with 26 fractions of CDR VMAT. The two tested scenarios showed a FLASH sparing magnitude of 10% for the first scenario and more substantial 32% sparing of brain tissues of for the second.
“Following up on this pilot study focusing on feasibility, the team is currently working on improving the joint optimization of the UHDR and CDR dose components to further enhance plan quality, flexibility and UHDR proportion of the delivered dose using the [hybrid] treatment approach,” Böhlen tells Physics World. “Additional work focuses on quantifying its biological benefits and advancing its technical realization.”
