Trial Information

To Assess the Feasibility and Impact of Computed Tomotherapy (CT) and Magnetic Resonance Imaging (MRI) Fusion on Radiation Treatment Planning for Ten Patients With Cancer of the Cervix

Rationale/Background:

For a long time diagnostic imaging has been used in planning radiation treatment for the
carcinoma of the cervix, although it is not the essential part of FIGO staging work up. In
the past, treatment planning was based on examination under anesthesia (EUA) findings and
standard portals were used. Various studies have shown high risks of geographical miss
and/or inappropriate tumor coverage (up to >70%) with the use of standard portals, which was
related to poor local control. Increasingly, diagnostic/planning CT and MRI imaging are used
to plan radiation treatment.

Most patients with invasive carcinoma of the cervix, who are not candidates for radical
hysterectomy, are treated by radiotherapy, often with concomitant chemotherapy with a
curative intent. Amongst those patients, where cure is not achieved, there are a significant
proportion who fail first or only in the pelvis. Higher doses of radiation would be expected
to reduce this risk. With conventional radiotherapy, higher doses of radiation result in a
higher rate of complications. New technology available at the Cross Cancer Institute
(tomotherapy + intensity modulated radiation therapy [IMRT]) would be expected to permit
higher doses of radiation to be delivered but avoid the increased risk of complications.
Accurate definition of clinical target volume, composed of the cervix, uterus, gross primary
tumor and the regional lymphatic drainage is required for accurate treatment planning. The
MRI imaging is expected to be valuable in this regard. Demonstrating this is the immediate
aim of this study. The investigators' long term aim will be to replace conventional external
beam radiotherapy with helical tomotherapy. They expect to be able to apply increasing doses
of radiation to the GTV + CTV and monitor short-term treatment effects with biological
imaging, principally magnetic resonance spectroscopy (MRS). Eventually the investigators
hope to be able to individualize radiation doses based in part on biological imaging, before
and during treatment.

In their center the investigators routinely perform diagnostic and planning CT scans of
almost all Ca. cervix patients before radiation treatment planning. This study will involve
one additional MRI scan of the pelvis, which will take about 30 minutes to perform; this
process has potential benefit in the treatment planning.

Studies comparing imaging modalities for diagnostic accuracy:

There are studies in which CT and MRI scans were performed preoperatively and results were
compared with surgical-pathological outcome to confirm their diagnostic accuracy in terms of
tumor detection, parametrial invasion, lymph node status and adjacent organ involvement. MRI
was consistently reported to be more accurate than CT scan in terms of tumor delineation and
normal organ localization. This is also true for a meta-analysis of 17 eligible studies.

Studies Comparing Imaging Modalities for Treatment Planning:

Not surprisingly CT planning was shown to be superior over standard field technique for
external beam radiation therapy (EBRT) and brachytherapy planning for ca cervix patients.
There was less chance of geographical miss by using an imaging modality for planning.
Studies comparing MRI and CT for treatment planning showed that MRI led to significant
changes in field borders.

Image Fusion:

Harms W et al from Germany studied the fusion of CT and MRI images from sixteen patients who
were treated by interstitial (n=12) and endocavitary (n=4) brachytherapy for recurrent
cervix, head and neck, sarcoma and vulva carcinoma. They compared conventional
3D-brachytherapy planning based on CT-information alone to brachytherapy planning based on
fused CT and MRI data. They measured the accuracy of image fusion using predefined
corresponding landmarks in the CT and MRI data. They found that an automated algorithm was
robust and reliable (mean registration error 1.8 mm, range 0.8-4.1 mm, SD 0.9 mm); tumor
visualization was difficult using CT alone; and brachytherapy treatment planning based on
fused CT and MRI data enabled better definition of target volume and critical structures as
compared to treatment planning based on CT alone.

Patients and Methods:

Ten patients with a histological diagnosis of cervix carcinoma who are to receive treatment
at the Cross Cancer Institute will be enrolled in this fusion study. They will go through
the usual investigations prior to treatment planning, including CT imaging. In addition,
patients will have an MRI of the pelvis which takes approximately about 30 minutes.

CT and MRI imaging will be fused using fusion software. Treatment planning for standard four
field box technique and tomotherapy will be done on CT images as usual and subsequently on
fused images. Tumor coverage and normal organ doses will be recorded and compared. Tumor
control probabilities and normal tissue complication probabilities will be calculated for
the different plans to facilitate objective comparisons.

Conclusion:

Most patients with invasive carcinoma of the cervix, who are not candidates for a radical
hysterectomy, are often treated by concomitant chemo-radiation with a curative intent.
Patients who cannot achieve a cure with this treatment fail first or only in the pelvis. The
higher doses of radiation would be expected to reduce this risk, which cannot be achieved
with conventional radiotherapy due to higher rates of complications. Tomotherapy based
treatment planning would be expected to obtain higher doses of radiation to be delivered but
avoid the measured risk of complications. More accurate definition of clinical target
volume, composed of the cervix, uterus, gross primary tumor and the regional lymphatic
drainage is required for accurate treatment planning. Currently the investigators are
planning on the basis of CT scan only in their center; MRI scan is consistently shown to be
superior over CT for treatment. Fusing MRI and CT images are expected to delineate
structures more accurately compared to CT alone and therefore will be valuable in accurate
treatment planning to deliver higher doses to CTV without increasing treatment related
complications.

Objectives:

1. To assess the feasibility of image fusion between MRI and CT for radiotherapy (RT)
planning in Ca. Cervix

2. To determine the added value of fused MRI and CT over CT alone for RT planning.