MR-sequence optimization and workflow development for treatment guidance, using the integrated MR scanner of the MR-Linac system. Towards MR-guided adaptive radiation therapy.

In today's clinical practice, radiation therapy is based on a CT scan obtained
during the treatment planning phase, which is sometimes co-registered with a
diagnostic MRI scan. The dose distribution is calculated and optimized based on
the organ configuration that was present at the day of scanning. During the
course of radiotherapy, however, both the tumor and organs at risk (OAR) are
variable in position, shape and size between fractions, or during beam delivery
within one treatment fraction. Around the clinical target volume (CTV) a safety
margin is created to account for these geometric uncertainties and ensure that
the tumor receives the prescribed dose. Direct integration of imaging at the
linear accelerator enables daily monitoring of patient positioning, tumor
position, and alterations in patient anatomy. Image guided radiotherapy (IGRT)
enables the detection and immediate correction of such deviations and increases
the precision of delivery. Current adaptive protocols rely upon a standard
CT-based workflow and (cone-beam) CT-based image guidance. MRI has superior
soft-tissue contrast over CT and seems a very promising modality to integrate
in the radiation treatment process, facilitating better visualization of the
tumor and OAR during treatment.
The Netherlands Cancer Institute (NKI-AVL) is a member of the Elekta MR-Linac
consortium, which has the objective to introduce the MR-Linac (MRL), a linear
accelerator with an integrated MRI scanner.
The MRL will be able to use MRI images acquired just prior to treatment for
online image guidance and plan adaptation and during treatment for treatment
monitoring and gating. The MRL opens up the possibility to reduce uncertainties
in the shape and position of the tumor and OAR both before and during
treatment, and therefor might allow for reduced margins. More accurate
irradiation would potentially allow for a reduction of toxicity and/or dose
escalation to the tumor.
The MRI scanner of the MRL is based on the diagnostic 1.5 Tesla Ingenia
scanner, manufactured by Philips, and modified for integration with the
accelerator. The imaging capacity is similar to that of the diagnostic scanner,
but the modifications have an impact on image quality. The purpose of imaging
at the MRL is treatment guidance. This involves monitoring of the motion and
deformation of a known structure and monitoring of response of the cancer and
normal tissue to irradiation. For these purposes, dedicated scan protocols need
to be developed for all clinical applications. A secondary aim is to develop
clinical workflows for MRI-guided adaptive radiotherapy.

Primary:
To optimize MR-sequence protocols for MR-guided adaptive radiotherapy, using
the integrated Phillips MRI scanner of the MR-Linac (MRL) system.

Secondary:
To develop an optimal MRL workflow for online MRI-guided adaptive radiotherapy

The patients will undergo MRI exams at baseline and during fractionated
radiotherapy, with a maximum of five additional MRI exams per patient. A
baseline MRI exam is not necessary when a pre-treatment diagnostic MR scan of
good quality is available for comparison. For hypofractionated schedules, MRI
exams will be performed at the day of each fraction. Patients will be treated
in the usual fashion according to the currently used CT-based workflows, with
CT simulation. At the same time, an MR-simulation as well as serial re-imaging
will be performed at the integrated Philips MR scanner of the Elekta MRL
system.

Patients will undergo an MRI exam up to a maximum of 5 times. The scan duration
will be approximately 30 minutes per exam, during which multiple sequences can
be scanned. The MRI exams will include both anatomical and functional sequences
and may include administration of Gadolinium contrast agent (Dotarem). At
baseline the glomerular filtration rate (GFR) will be determined, and contrast
agents will only be admitted when renal function is adequate (GFR > 60
ml/min/1.7m2). No more than once a week contrast agents will be admitted.
No adverse effects are known of the administration of a repeated dose after a
previous exam. No risk has been reported of repeated MRI exams.

Patients will undergo a MRI exam up to a maximum of 5 times. During the MRI
exam 15 ml of the contrast agent Dotarem (Gadoteric acid, concentration 0.5M)
may be administered intravenously. No adverse effects are known of the
administration of a repeated dose after a previous exam. No risk has been
reported of repeated MRI exams. The repeat MRI exams cause a negligible risk
for patients.