Monitoring MRI changes before and during Radiotherapy Treatment of Brain Tumors

The accuracy of irradiation of brain tumors may be influenced by the time
interval between treatment preparation and delivery, due to anatomical changes
during treatment. We studied tumor position shifts and its relations to
peritumoral volume edema changes over time, as seen on MRI.
We evaluated 26 patients who underwent stereotactic radiosurgery (SRS) for
brain metastases in our institution. We evaluated the occurrence of a tumor
shift between the diagnostic MRI and radiotherapy planning MRI. For 42 brain
metastases the tumor and peritumoral edema were delineated on the contrast
enhanced T1weighted and FLAIR images of both the diagnostic MRI and planning
MRI examinations. Center of Mass (CoM) shifts and tumor border were evaluated.
We evaluated the influence of steroids on peritumoral edema and tumor volume
and the correlation with CoM and tumor border changes.
The median values of the CoM shifts and of the maximum distances between the
tumor borders obtained from the diagnostic MRI and radiotherapy planning MRI
were 1.3 mm (maximum shift of 5.0 mm) and 1.9 mm (maximum distance of 7.4 mm),
respectively. We found significant correlations between the absolute change in
edema volume and the tumor shift of the CoM (p<0.001) and tumor border
(p=0.040).
Because shifts may have a significant impact on the local dose coverage we
changed our clinical workflow and reduced the time between the planning MRI and
start of SRS.
Based on these results we became also interested in investigating potential
changes in tumor volume, tumor location and peri-tumoral edema occurring before
the start and during fractionated irradiation in both patients with primary
brain tumors and patients with brain metastases. For this reason we included in
our current treatment protocol another MRI half way the treatment schedule. For
both brain metastasis and primary brain tumors we observed significant changes
of the target volume (increase of volume) half way the treatment and in more
than 10% of the patients the treatment plan needed adaptation. However, since
we only have the MRI repeated half way through the treatment we cannot
determine whether this is the optimal time point to repeat the MRI. For this
reason we want to continue this strategy of repeating the MRI during RT.
Besides issues related of tumor shift, repeated MRI during radiation therapy
can provide further possibilities to evaluate and optimize radiation treatment
efficacy by monitoring more structural tumor changes.
For this purpose we want to execute functional MRI sequences during and before
RT. Different aspects of the tumor can be characterized using functional MRI
techniques, which may be important for predicting treatment outcome. The
aspects include the permeability of the blood vessels in the tumor, the
perfusion rate in the tumor and the cellularity (impact on diffusion) of the
tumor. We expect that these treatment related effects will vary between tumors
and patients and may provide an important parameter to optimize and
individualize radiotherapy treatment.

Primary objective: To establish anatomical variations (position, shape, size)
and functional MRI parameters (permeability, perfusion and diffusion) in the
target volume before and during fractional radiotherapy treatment for brain
lesions.

Secondary objective: To correlate pre- and per-treatment anatomical variations
(position, shape, size) and functional MRI parameters (permeability, perfusion
and diffusion) to treatment outcome (e.g. progression/regression/radiation
necrosis of the radiated tumor on follow-up MRI) in order to make a sample size
calculation for a future study of imaging marker discovery.

This is a primarily a registration study. It is estimated that for 10% of the
patients the tumor coverage on the repeated MRI is not optimal anymore due to
growth or shift of the tumor. In these cases an intervention is needed by
adaptation of the treatment plan.

1-3 extra MRIs

The main burden for the patient is that the number of MRI*s will be extended
from 2 to 5 and the injection of contrast agents. An additional visit to the
hospital is needed for the first scan. The practitioner may have more
diagnostic information available during treatment and subjects in this study
will have a better control of their target volume during and before
radiotherapy. This may imply that target regions will be adapted during (or
before) radiotherapy. Whether this has clinical relevance is unknown and will
as such be explained to the patients.