Imaging and angiogenesis of malignant lymphoma with dynamic MRI, H-MRS, P-MRS and FDG-PET/CT for staging, mid treatment assessment and outcome.

Malignant lymphoma constitute a heterogeneous group of diseases, derived from
either B- or T-cell lymphocytes at different stages of maturation and with
different pathogenic pathways and patterns of molecular alterations. Both
histology and the extend of the disease determines the choice of therapy.
Treatment often leads to remission but not always to cure. Within each
histological entity biological behaviour can be very diverse. In order to
improve treatment results, identification of risk profile and adequate
evaluation of the tumour is necessary. Evidence of the role of angiogenesis in
cancer, such as malignant lymphoma, is manifold. Microvessel density (MVD) in
malignant lymphoma correlates with malignancy grade and pro-angiogenetic
factors such as biochemical vascular endothelial growth factor (VEGF) can
function as an independent prognostic factor. From previous research with other
tumours dynamic magnetic resonance imaging with contrast (DCE-MRI) correlates
with perfusion, hence metabolism. MRS techniques enable the in vivo measurement
of metabolic aspects of tissue. H MRS demonstrates that that the signal of
choline is a hallmark of (agressive) tumour growth. P MRS findings correlate
with tumour perfusion and, hence with tumour angiogenesis.
Treatment response is currently monitored by [18F]-fluorodeoxyglucose positron
emission tomography fused with computed tomography (FDG-PET/CT). A disadvantage
being the radiation burden with its risk of inducing secondary malignancies in
the long term.

Evaluation of the vascularisation of malignant lymphoma and its change during
therapy with DCE-MRI. Furthermore evaluation of metabolite concentration
ratios and absolute measurements made with MRS techniques as a measurement of
vascularisation and predictor of response to treatment.

Prospective, observational non-randomized cohort investigation.
When there is no treatment option the patient will only get one DCE-MRI in
combination with MRS. A blood sample will be taken every three months to
determine the VEGF.
When a patient is considered for treatment an MRI exam will be acquired prior
to treatment, after 3 cycles of chemotherapy and after completion of treatment.
This exam will include a DCE-MRI exam and a 31P and 1H MR spectroscopy. For
practical reasons 31P MRS will only be performed on 10 patients with a
superficial lymph node mass. Blood withdrawal will take place prior to every
cycle of chemotherapy and after completion of treatment.

Patients will undergo a maximum of three DCE-MRI and a maximum of three MRS
examinations. This implies at the upmost 3 additional journeys to the hospital.
An intravenous canula will be placed for the administration of MRI-contrast,
Gadolinium, during the DCE-MRI examinations. In addition there will be several
blood withdrawals. If there is no treatment option blood will be withdrawn
every 3 months. If the patient is being treated it will be withdrawn prior to
every cycle of chemotherapy and after termination of the treatment. Whenever
possible in combination with the insertion of a canula for DCE-MRI or regular
blood withdrawal. A possible risk can be caused by Gadolinium although it is
relatively safe and being used in humans for many years. Possible side effects
which can occur are a warm sensation throughout the body, dry mouth and/or the
urge to urinate. These are considered to be minor and subdue mostly quick.
There is a small risk of an allergic reaction such as itching, red skinlesions
or sneezing. Although rare a more severe allergic reaction can occur such as
mucosal swelling, shortness of breath and/or drop in blood pressure. These
reactions can be adequately reversed with quick administration of medication.