Magnetic Resonance Lymphography with Ferumoxtran-10 for Pelvic Lymph Node Target Delineation in Bladder and Prostate Cancer

Abstract

Purpose/Objective: To determine the utility of Magnetic Resonance Imaging (MRI) with an ultra-small superparamagnetic iron oxide that delineates phagocytotic activity within lymph nodes as a means of lymph node target definition and to examine the patterns of lymph node metastases in prostate and bladder cancer to generate a nodal clinical target volume comprised of the nodal basins at risk of tumor spread. Materials/Methods: A single center trial was undertaken in 40 patients with histologically confirmed prostate (32) or bladder cancer (8). All patients underwent pre- and post- contrast MRI studies over two consecutive days. Axial images were obtained at 3 mm intervals through the pelvis. Ferumoxtran-10 (Combidex®: Advanced Magnetics, Inc, Cambridge, MA) was administered at 2.6 mg Fe/kg on the first day immediately after the initial MRI. The pelvic vasculature and lymph nodes were delineated from the origin of the inferior mesenteric artery to the ischial tuberosities using 3D modeling and image processing software (3D-DOCTOR®: Able Software Corp., Lexington, MA). Lymph node frequency and location relative to the adjacent vascular segments was analyzed. Nodes were ascertained to have metastases using previously demonstrated criteria and with clinicopathologic correlation in those patients undergoing pelvic lymph node dissection (Harisinghani et al. NEJM 2003;348:2491-9). The prostate cancer patients were treated with radiotherapy. However, patients with bladder cancer underwent radical cystectomy and pelvic lymph node dissection, allowing surgicopathologic correlation of the imaging results. Results: 40 patients were enrolled (see Table 1). In the patients with prostate cancer, 39 malignant nodes were identified. Metastases were situated in the following locations or vascular segments: obturator fossa (7); internal iliac (3); external iliac (11); common iliac (5); aortic/aortocaval (3); pararectal (6); and sacral (4). The median number of nodes excised at the time of cystectomy for those patients with bladder cancer was 29 (range 21 to 47). Pathologically, metastases were identified in the following locations or vascular segments: perivesicle (1); internal iliac (8); external iliac (6); common iliac (2); aortic/aortocaval (3); and pararectal (2). On post-contrast MRI imaging, a median of 27 (range 18 to 39) nodes was identified for both bladder and prostate cancer patients within the region occupied by the para-vesical, intercalating, para-rectal, pelvic sidewall, external iliac, common iliac, and pre-sacral lymph node basins. The maximum distance of these lymph nodes from the closest vessel was between 2.5 and 30 mm, with a mean distance of 7.5 mm.Table 1Patient Characteristics Conclusions: The use of MRI lymphography with ferumoxtran-10 provides an objective description of pertinent lymph node locations in a three-dimensional projection for pelvic IMRT and improves the precision of radiation treatment delivery. A uniform radial margin of expansion around the major pelvic vessels fails to adequately encompass all of the parietal and visceral lymph nodes at risk. Ferumoxtran-10 may be useful in the context of IMRT treatment planning as a means of identifying lymph nodes at risk of harbouring occult metastatic disease that should be included in the nodal CTV, and as a means of lowering the threshold for the detection of lymph node metastases that might be treated to a higher dose.