Hitting the Mark: Introducing state-of-the-art MRI for precision radiotherapy of glioblastoma

One of the fundamentals of glioblastoma management is radiotherapy, where
ionizing radiation is aimed towards a specific target area in the brain to
inhibit further tumor growth. As these brain tumors are notorious for their
extensive tumor infiltration, where tumor grows beyond the tumor that is
visible on conventional magnetic resonance imaging (MRI), this target area,
defined as the clinical target volume (CTV), consists of the visible tumor plus
a 1.5-cm isotropic safety margin. In the majority of cases, this unspecific CTV
margin adequately covers tumor infiltration, but inevitably also includes
considerable amounts of healthy tissue. Radiation-induced side-effects like
headaches, nausea, fatigue and cognitive decline can substantially affect the
quality of life for these patients.
An opportunity arises to indirectly visualize tumor infiltration with
state-of-the-art advanced MRI (aMRI) techniques, providing additional
information on physiology rather than only showing anatomical information
through conventional MRI. A workflow has been developed to create a CTV based
on these aMRI scans (CTVbio) rather than an isotropic expansion. With the
additional information that aMRI provides, it could be possible to more
accurately define what needs to be targeted and thus minimize damage to healthy
tissue. In this research, the aim is to assess the potential of integrating
aMRI into radiotherapy target delineation for patients with a glioblastoma by
comparing the pattern of failure (coverage of first tumor recurrence by the
radiotherapy plan) and the expected radiation dose to organs at risk between
the CTVbio and the 1.5-cm CTV. It is hypothesized that the CTVbio can result in
decreased radiation dose to organs at risk, whilst having similar pattern of
failure.

Primary objective:
• To demonstrate that the probability for reduced coverage of the recurrence
volume by a radiotherapy plan based on a CTVbio, compared to the clinical
radiotherapy plan (1.5-cm CTV), is lower than 0.20.

Secondary objectives:
• To illustrate a reduction in dose to organs at risk with a radiotherapy plan
based on a conceptual CTVbio compared to the clinical radiotherapy plan (1.5-cm
CTV).
• To evaluate the synergistic information that each individual aMRI-scan
provides for the identification of tumor infiltration.
• To explore the association between pathophysiological changes on aMRI and
future tumor recurrence.

In this prospective cohort study, the clinical standard MRI session used for
radiotherapy planning of glioblastoma patients will be extended with aMRI
techniques that assess altered oxygenation, angiogenesis and increased protein
concentration. Radiation treatment (and patient follow-up) will occur according
to the clinical standard, i.e. using the 1.5-cm CTV for radiotherapy planning.
The aMRI-scans will be used to create a theoretical CTVbio and corresponding
radiotherapy plan. Pattern-of-failure analysis and assessment of dose to organs
at risk will be done to compare the radiotherapy plan based on the 1.5-cm CTV
with the (theoretical) radiotherapy plan based on the CTVbio. Additionally,
various theoretical CTVs based on different combinations of aMRI-scans are
generated to explore the added value of the different aMRI techniques. Lastly,
the signal intensities on the aMRI-scans at the site of tumor recurrence are
compared with contralateral normal-appearing white matter.

The patients have the burden of prolonged scan time (+ 20 minutes, total scan
time will be approximately 45 minutes instead of 25 minutes) during their
standard radiotherapy planning MRI-scan. The remainder of their clinical care
will not be altered: Radiotherapy will be given to these patients based on
standard 1.5-cm CTVs. Follow-up will follow the clinical protocol. There will
be no personal benefit for the patients in this research project.