International Journal of Radiation Oncology*Biology*Physics
Physics contributionMapping pelvic lymph nodes: Guidelines for delineation in intensity-modulated radiotherapy
Introduction
Whole pelvic nodal radiotherapy (RT) has a key role in the management of many pelvic malignancies and may improve both locoregional control and survival. The lymph nodes are included in the radiation target volume when the tumor stage and grade indicate a significant risk of microscopic nodal metastases or if overt node involvement is already present. Treatment, which is traditionally delivered using a four-field technique defined by bony landmarks, is associated with a dose-limiting incidence of acute and late toxicity (1, 2, 3). In addition, despite large volumes of normal tissue being encompassed, conventional planning increases the risk of a geographic miss (4, 5).
Planning studies comparing intensity-modulated RT (IMRT) with conventional approaches for pelvic RT have demonstrated the volume of small bowel, rectum, and bladder receiving high doses can be reduced by 20–50% (6, 7, 8). The initial clinical studies treating gynecologic malignancies with IMRT have reported a corresponding reduction in acute and late GI toxicity (9, 10). However, one factor that has prevented widespread implementation of pelvic IMRT has been the lack of a validated method for defining the nodal clinical target volume (CTV).
The probability of a node containing metastases is assessed with CT and MRI using size criteria, usually a nodal short axis diameter >1 cm, but the sensitivity of this method is only 40–70% (11, 12, 13). Unenlarged nodes may still contain tumor deposits; therefore, it is necessary to include all lymph nodes within the draining regions in the CTV. Most “normal size” lymph nodes are too small to be visualized directly with standard imaging, and delineation of the CTV depends on their relationship to other pelvic structures.
Anatomic studies have demonstrated that pelvic lymph nodes lie adjacent to major blood vessels. These are relatively well visualized on conventional imaging and can, with a margin, be used as a surrogate target for lymph nodes. Debate is ongoing about whether the use of a uniform margin around the blood vessels is the appropriate method to define the CTV for nodal regions. The question as to what margin will ensure the maximal nodal, but minimal normal tissue, coverage has not been satisfactorily answered, and different groups have used margins varying from 5 to 20 mm (6, 9, 14, 15).
Ultrasmall particles of iron oxide (USPIO) are a novel class of MRI contrast agent developed for the assessment of lymph nodes. Initial clinical studies have reported USPIO-enhanced MRI improves the sensitivity, whilst maintaining a high specificity, for the detection of nodal metastases for head-and-neck, lung, and pelvic tumors (16, 17, 18, 19, 20, 21). The nanoparticles, which are administered intravenously, are taken up by macrophages within benign lymph nodes. The magnetic susceptibility effects of the iron oxide causes a marked loss in the signal intensity of normally functioning nodes on T2- and T2*-weighted sequences, resulting in a black appearance. This makes the nodes easily visible on the postcontrast images (Fig. 1).
The purposes of this study were first to map the distribution of normal pelvic lymph nodes in relation to the blood vessels using the USPIO contrast agent; second, to use these data to determine the margin needed around the blood vessels to allow full coverage of the lymph nodes while achieving maximal sparing of normal tissue; and third, to propose guidelines for pelvic lymph node definition that can be applied to standard CT imaging for three-dimensional planning techniques.
Section snippets
Methods and materials
Twenty patients with gynecologic (12 cervical and 8 endometrial) tumors underwent preoperative assessment of their pelvic lymph nodes with USPIO contrast medium (Sinerem, Guerbet, Roissy, France and Combidex, Advanced Magnetics Inc., Cambridge, MA). The local research ethics committee approved the study, and the Medical Controls Agency (United Kingdom) approved off-license use of USPIO. All patients were >18 years old and provided written informed consent. MRI of the pelvis was performed with
Results
In total, 1216 nodal contours were evaluated in 20 patients. The median number of nodal contours identified was 58 per patient (range, 30–101). The distribution of the nodal groups is presented in Table 1. The external iliac group had the greatest number of nodes identified, with a total of 627 contours, evenly distributed among the three subgroups as 196 medial, 241 anterior, and 190 lateral external iliac nodes. We visualized 303 obturator, 144 internal iliac, and 135 common iliac nodal
Discussion
Intensity-modulated RT has great potential for normal tissue sparing and dose escalation when treating pelvic tumors. The CTV usually comprises the primary tumor, or tumor bed, structures at risk of direct tumor spread, such as the parametrium, and the draining lymph node regions. The pelvic lymph nodes, however, are difficult to delineate, because most cannot be visualized on CT or MRI, but still may contain metastases. Consistent and accurate target volume definition is essential, because
Conclusion
Using MRI with USPIO, the pelvic lymph node distribution was mapped and a relation to the pelvic blood vessels defined. Because blood vessels are readily seen on standard CT imaging, these are suitable as a surrogate lymph node target. Guidelines for the accurate definition of different nodal CTV groups using a standardized target definition have been proposed.
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This research was supported by the X-Appeal Fund, Royal College of Radiologists, and The BUPA Foundation, UK.