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obp.20 PH GUI TED KALL WELL Bartho clinica pelvic ic ma lymph s of 3, es ana olume l tissu he no ly. Th th a 10 covera Conclusion: Blood vessels with a modified 7-mm margin offer a good surrogate target for pelvic lymph nodes. By making appropriate adjustments, coverage of specific nodal groups may be increased and the volume of normal W ma bo inc sta no pre fou ate (1– be ris (IM de de Th R of Lo 83 blu P Int. J. Radiation Oncology Biol. Phys., Vol. 63, No. 5, pp. 1604–1612, 2005 Copyright © 2005 Elsevier Inc. tissue irradiated decreased. On the basis of these findings, recommended guidelines for outlining pelvic nodes have been produced. © 2005 Elsevier Inc. Pelvic lymph nodes, Clinical target volume, Intensity-modulated radiotherapy, Iron oxide particles. INTRODUCTION hole pelvic nodal radiotherapy (RT) has a key role in the nagement of many pelvic malignancies and may improve th locoregional control and survival. The lymph nodes are luded in the radiation target volume when the tumor ge and grade indicate a significant risk of microscopic dal metastases or if overt node involvement is already sent. Treatment, which is traditionally delivered using a r-field technique defined by bony landmarks, is associ- d with a dose-limiting incidence of acute and late toxicity 3). In addition, despite large volumes of normal tissue ing encompassed, conventional planning increases the k of a geographic miss (4, 5). Planning studies comparing intensity-modulated RT RT) with conventional approaches for pelvic RT have monstrated the volume of small bowel, rectum, and blad- r receiving high doses can be reduced by 20–50% (6–8). e initial clinical studies treating gynecologic malignan- cies 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% (11–13). 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 rela- tively well visualized on conventional imaging and can, with a margin, be used as a surrogate target for lymph eprint requests to: Alexandra Taylor, F.R.C.R., Department Radiotherapy, St. Bartholomew’s Hospital, West Smithfield, ndon EC1A 7AE, United Kingdom. Tel: (�44)-20-7601- 53; Fax: (�44)-20-7601-8364; E-mail: alexandra.taylor@ for Therapeutic Radiology and Oncology (ASTRO), Atlanta, GA, October 3–7, 2004. This research was supported by the X-Appeal Fund, Royal College of Radiologists, and The BUPA Foundation, UK. doi:10.1016/j.ijr YSICS CONTRIBUTION MAPPING PELVIC LYMPH NODES: INTENSITY-MODULA ALEXANDRA TAYLOR, F.R.C.R.,* ANDREA G. ROC AND MELANIE E. B. PO Departments of *Radiotherapy and †Radiology, St. Purpose: To establish guidelines for delineating the mapping the location of lymph nodes in relation to the Methods and Materials: Twenty patients with gynecolog with administration of iron oxide particles. All visible were generated for each patient using modified margin nodal contours were then overlaid and individual nod within each clinical target volume and planning target v that could provide maximal nodal, but minimal norma Results: In total, 1216 nodal contours were evaluated. T using vessel margins of 3, 5, 7, 10, and 15 mm, respective volume was 146.9 cm3 with a 7-mm margin, 190 cm3 wi Minor modification to the 7-mm margin ensured 99% eyonder.co.uk resented at the 46th Annual Meeting of the American Society R Ac 1604 05.05.062 DELINES FOR DELINEATION IN RADIOTHERAPY , F.R.C.R.,† RODNEY H. REZNEK, F.R.C.R.,† , M.D., F.R.C.R.* lomew’s Hospital, London, United Kingdom l target volume for pelvic nodal irradiation by anatomy. lignancies underwent magnetic resonance imaging nodes were outlined. Five clinical target volumes 5, 7, 10, and 15 mm around the iliac vessels. The lyzed for coverage. The volume of normal tissue was also measured to aid selection of the margin e, coverage. dal coverage was 56%, 76%, 88%, 94%, and 99% e mean volume of bowel within the planning target -mm margin, and 266 cm3 with a 15-mm margin. ge of the pelvic nodes. Printed in the USA. All rights reserved 0360-3016/05/$–see front matter eceived Jan 9, 2005, and in revised form May 27, 2005. cepted for publication May 31, 2005. no ma defi ma tiss dif (6, cla lym en a h he pa up ne los T2 pe co of usi det ful spa pel CT h nod d imag de adm Fig nan Ma ves 1605Pelvic lymph nodes for IMRT ● A. TAYLOR et al. des. Debate is ongoing about whether the use of a uniform rgin around the blood vessels is the appropriate method to ne the CTV for nodal regions. The question as to what rgin will ensure the maximal nodal, but minimal normal ue, coverage has not been satisfactorily answered, and ferent groups have used margins varying from 5 to 20 mm 9, 14, 15). Ultrasmall particles of iron oxide (USPIO) are a novel ss of MRI contrast agent developed for the assessment of ph nodes. Initial clinical studies have reported USPIO- hanced MRI improves the sensitivity, whilst maintaining igh specificity, for the detection of nodal metastases for ad-and-neck, lung, and pelvic tumors (16–21). The nano- rticles, which are administered intravenously, are taken by macrophages within benign lymph nodes. The mag- tic susceptibility effects of the iron oxide causes a marked Fig. 1. Axial magnetic resonance images of pelvis with lymp contrast. (b) Lymph nodes have high signal on T2*-weighte T2*-weighted images after ultrasmall particles of iron oxi . 2. Gradient echo T2*-weighted axial pelvic magnetic reso- ce image after ultrasmall particles of iron oxide administration. rgins of 3, 5, 7, 10, and 15 mm drawn around pelvic blood sels, and nodal contours overlaid in yellow. rato s in the signal intensity of normally functioning nodes on - and T2*-weighted sequences, resulting in a black ap- arance. This makes the nodes easily visible on the post- ntrast images (Fig. 1). The purposes of this study were first to map the distribution normal pelvic lymph nodes in relation to the blood vessels ng the USPIO contrast agent; second, to use these data to ermine the margin needed around the blood vessels to allow l coverage of the lymph nodes while achieving maximal ring of normal tissue; and third, to propose guidelines for vic lymph node definition that can be applied to standard imaging for three-dimensional planning techniques. es indicated (arrows). (a) T2-weighted images without es before contrast. (c) Decrease in signal intensity on inistration improved visibility of lymph nodes. . 3. Axial magnetic resonance image of external iliac region posed of lateral nodes (EI lat) lateral to external iliac artery (a), erior nodes (EI ant) anteriomedial to external iliac vein (v), and dial nodes (EI med) medial and directly posterior to vein. Obtu- Fig com ant me r (obt) nodes lie between internal and external iliac vessels. T tria lym Ro bri stu pro and per we Af nod con we 1606 I. J. Radiation Oncology ● Biology ● Physics Volume 63, Number 5, 2005 METHODS AND MATERIALS wenty patients with gynecologic (12 cervical and 8 endome- l) tumors underwent preoperative assessment of their pelvic ph nodes with USPIO contrast medium (Sinerem, Guerbet, issy, France and Combidex, Advanced Magnetics Inc., Cam- dge, MA). The local research ethics committee approved the dy, and the Medical Controls Agency (United Kingdom) ap- ved off-license use of USPIO. All patients were �18 years old provided written informed consent. MRI of the pelvis was formed with axial T2-weighted fast spin echo and T2*- ighted gradient-echo (GE) sequences taken at 4-mm increments. ter the scan, intravenous USPIO was administered, and the al imaging sequences were repeated after 24–36 h. The post- trast T2* images were co-registered with the precontrast T2- Fig. 4. Modified 7-mm contour to ensure coverage of lymp in lateral and posterior spaces. (b) Contour must extend ful nodes, extend anterior border along iliopsoas muscle (i-p extending medial contour around external iliac vessels po contour. This strip should be 18 mm wide. CI � common i � anterior external iliac; EI med � medial external iliac; ighted and T2* scans. This enabled positive identification of the nal ph nodes by demonstrating a change in signal intensity be- en the matched images. When delineating nodes, agreement s required between two observers—a radiation oncologist and a iologist. All pelvic nodes were contoured and measured on the tcontrast T2* images (Fig. 2). ymph nodes were assigned to a nodal group depending on their ition in relation to the blood vessels. The common iliac nodes adjacent to the common iliac vessels from the aortic bifurcation the division of the common iliac artery into the external and ernal iliac branches. The internal iliac nodes lie in relation to the ernal iliac vessels and their branches and tributaries. The exter- iliac nodes surround the external iliac vessels until they pass ough the inguinal ligament. This group is subdivided into the dial, anterior, and lateral subgroups (Fig. 3). The medial exter- groups (red outline). (a) Common iliac nodes can lie lvic sidewall. (c) To cover distal lateral external iliac dditional 10 mm. (d) Obturator region covered by rly, parallel to pelvic sidewall, to join internal iliac � internal iliac; EI lat � lateral external iliac; EI ant obturator. lym twe wa rad pos L pos are to int int nal thr me h node ly to pe ) by a sterio liac; II Obt � iliac nodes are medial and directly posterior to the external iliac vei art ext Th and ant bel per hol T ma for ine enc ves unt sin obt clu ove bes E gen del wh and aor by E mo ach vol the obt gen CT tie 58 gro the co 19 no 13 ha sac ne dia we 7 ( aro ma ere 88 No L Co Me An La Ob Int Pre 0– To 30– * Co Me An La Ob Int Pre To 1607Pelvic lymph nodes for IMRT ● A. TAYLOR et al. n; the anterior external iliac nodes sit in the sulcus between the ery and vein and anteromedial to the artery; and the lateral ernal iliac nodes extend laterally from the external iliac artery. e obturator nodes lie within the triangle between the external internal iliac vessels. The presacral nodes are situated directly erior to the sacrum and are subdivided into the subaortic nodes, ow the aortic bifurcation over the sacral promontory, and the irectal nodes, found within the mesorectal fascia in the sacral low. he pelvic blood vessels were outlined, and three-dimensional rgins of 3, 5, 7, 10, and 15 mm were used, creating five CTVs each patient. In the lower pelvis, the obturator nodes would vitably be inadequately covered by vessel expansion alone. To ompass this region, the medial contour around the external iliac sel was continued posteriorly, parallel to the pelvic sidewall, il it joined the internal iliac contour (Fig. 4d). This created a gle volume on each side of the pelvis that would incorporate the urator region with varying width. Muscle and bone were ex- ded from each volume. The lymph node outlines were then rlaid on each CTV to determine which margin would result in t coverage of the node (Fig. 2). ach CTV was expanded uniformly by an additional 10 mm to erate the planning target volumes (PTV). The rectum was ineated from the anal margin to the sigmoid flexure, and the ole bladder was contoured. The bowel (comprising the large small intestine) was outlined on all slices up to the level of the tic bifurcation. The volume of each normal structure overlapped the CTV and PTV was measured. ach nodal group was examined to assess whether a simple dification to the CTV could improve nodal coverage and ieve maximal sparing of normal tissues. To determine the ume width necessary to cover the obturator region adequately, distance from the pelvic sidewall to the medial border of each Table 1. Distribution and s ymph node group Total Contours per p Mean mmon iliac* 135 10.4 dial external iliac 196 9.8 terior external iliac 241 12.1 teral external iliac 190 9.5 turator 303 15.2 ernal iliac 144 7.2 sacral 7 0.4 tal 1216 60.8 Common iliac region imaged in 13 patients. Table 2. Lymph node contours cove Lymph node group 3 mm (%) 5 mm mmon iliac (n � 135) 41 (30.3) 90 ( dial external iliac (n � 196) 122 (62.2) 167 ( terior external iliac (n � 241) 124 (51.4) 190 ( teral external iliac (n � 190) 16 (8.4) 41 ( turator (n � 303) 275 (90.1) 295 ( ernal iliac (n � 144) 105 (72.9) 135 ( sacral (n � 7) 0 (0) 0 ( tal (n � 1216) 683 (56.2) 918 ( urator node was also measured. This information was used to erate the proposed guidelines for delineating the pelvic nodal V. RESULTS In total, 1216 nodal contours were evaluated in 20 pa- nts. The median number of nodal contours identified was per patient (range, 30–101). The distribution of the nodal ups is presented in Table 1. The external iliac group had greatest number of nodes identified, with a total of 627 ntours, evenly distributed among the three subgroups as 6 medial, 241 anterior, and 190 lateral external iliac des. We visualized 303 obturator, 144 internal iliac, and 5 common iliac nodal contours, although only 13 patients d imaging to assess this region adequately. Only 7 pre- ral nodes were identified, 3 overlying the sacral promi- nce and 4 in the perirectal fascia. The median short axis meter of the lymph nodes was 3.6 mm. Very few nodes re enlarged, with only 30 (2.5%) measuring �8 mm and 0.6%) �10 mm. The number of nodes fully encompassed by a margin und the blood vessels increased correspondingly with the rgin size. The percentage of lymph node contours cov- d by a 3-, 5-, 7-, 10-, and 15-mm margin was 56%, 76%, %, 94%, and 99%, respectively (Table 2). rmal tissue coverage The volume of normal tissue within each CTV and PTV shown in Table 3. The PTV created with the 15-mm lymph node contours (n) Short axis diameter (mm) nge Median SD Range 22 3.9 1.5 1.3–9.0 19 3.7 2.0 1.1–12.1 20 3.5 1.4 1.1–8.5 23 4.1 1.7 1.1–11.0 43 3.7 1.6 1.4–11.5 22 2.7 1.0 1.1–6.1 2 101 3.6 1.6 1.1–12.1 margin around blood vessels 7 mm (%) 10 mm (%) 15 mm (%) 123 (91.1) 135 (100) 135 (100) 193 (98.4) 196 (100) 196 (100) 227 (94.2) 241 (100) 241 (100) 76 (40) 123 (64.7) 178 (93.7) 302 (99.7) 303 (100) 303 (100) 142 (98.6) 144 (100) 144 (100) 3 (42.9) 3 (42.9) 3 (42.9) 1066 (87.7) 1145 (94.2) 1200 (98.7) is red by (%) 66.7) 85.2) 78.8) 21.6) 97.3) 93.8) 0) 75.7) ize of atient Ra 2– 2– 4– 3– 3– 1– ma 17 tis an the 7 wi ex som wi Ly ma fai no inc 7-m en mi cre rea the no for are ma spa Th ve the bra ma of sid thr dia ex no wi sio of soa no the clu ve CT wi bo a s no 7-m sid mm wa 15 wi in me pre rget vo e of n 7 m Bo 32 Bla 3 Re 0 e of 7 m Bo 146 Bla 21 Re 7 Ly 1608 I. J. Radiation Oncology ● Biology ● Physics Volume 63, Number 5, 2005 rgin included 266 cm3 of bowel, 41 cm3 of bladder, and cm3 of rectum. A 10-mm margin reduced the normal sue encompassed to 190 cm3 of bowel, 28 cm3 of bladder, d 10 cm3 of rectum, and a 7-mm margin further reduced volumes to 147 cm3 of bowel, 21 cm3 of bladder, and cm3 of rectum. In view of the large volume of bowel thin the 15-mm PTV, the lymph nodal coverage was amined further to assess whether a margin �15 mm, with e modification, could maximize normal tissue sparing thout compromising nodal coverage. mph node groups The coverage of each nodal group by the different vessel rgins was assessed (Table 2). Even a 15-mm margin led to cover fully the lateral external iliac and presacral des. Excluding these two groups, all other nodes were luded by a 10-mm expansion and �95% nodes by a m expansion. The 150 nodal contours incompletely compassed by a 7-mm margin were scrutinized to deter- ne which simple adjustments to this volume would in- ase nodal coverage. Of these nodes, 93 (62%) were dily visible on the T2 precontrast scans. The results of required modifications are summarized below for each dal group, with the provision that all enlarged, and there- e visible, nodes were also included in the CTV (Table 4). Common iliac nodes. Although the common iliac nodes usually situated in direct contact with the vessels, they y also lie some distance away in the posterior and lateral ces. Because of this, a nonuniform margin is necessary. e CTV should be drawn 7-mm anterior and medial to the ssels; however, posterolaterally, it must be extended to psoas muscle and vertebral body (Fig. 4a). Internal iliac nodes. The internal iliac vessels have many nches, and all need to be included in the CTV. A 7-mm rgin around these vessels will provide coverage of 100% the nodes provided the lateral border reaches to the pelvic ewall (Fig. 4b). External iliac nodes. The external iliac nodes consist of ee connecting subgroups—the lateral, anterior, and me- l groups. Although a 7-mm margin uniformly around the ternal iliac vessels covers all the medial and anterior Table 3. Volume of normal structures within clinical ta Total volume A. Mean volum 3 mm (%) 5 mm (%) wel 643.7 5.9 (0.9) 16.8 (2.6) dder 131.0 0.7 (0.3) 2.1 (1.0) ctum 44.4 0.2 (0.2) 0.5 (0.7) Total volume B. Mean volum 3 mm (%) 5 mm (%) wel 643.7 95.6 (15.4) 120.7 (19.4) dder 131.0 13.1 (7.5) 16.7 (9.8) ctum 44.4 3.9 (6.8) 5.5 (19.9) des, the lateral external iliac nodes are poorly covered, * th only 40% completely encompassed. Additional exten- n of only the anterior margin by another 10 mm (a total 17 mm from the vessel) anterolaterally along the iliop- s muscle would include �99% of the external iliac des. A nonuniform margin around the vessel should, refore, be used (Fig. 4c). Obturator nodes. The obturator nodes would not be in- ded by uniform expansion of the vessel contour, unless a ry large margin were used. In this study, the potential Vs were designed to cover this region with varying dths by joining the corresponding medial and lateral rders of the internal and external iliac contours, creating ingle volume on each side of the pelvis. All obturator des were covered by joining the contours created with the m vessel margin. The average distance from the pelvic ewall required to cover the nodes was 8 mm (range, 2–21 ; SD, 3.6). Therefore, a volume along the pelvic side- ll to encompass 95% of the lymph nodes needs a width of mm, and 99% nodes would be covered with an 18-mm- de strip (Fig. 4d). Presacral nodes. Very few sacral nodes were identified this study. A uniform vessel margin is not an appropriate thod to cover these nodes, and it is necessary to cover the sacral region specifically, if indicated by the tumor site lumes (CTV) and planning target volumes (PTV) ormal structure within CTV (cm3) m (%) 10 mm (%) 15 mm (%) .4 (5.1) 63.2 (10.2) 123.3 (19.9) .9 (1.9) 7.4 (3.8) 14.3 (7.7) .9 (1.4) 2.2 (3.6) 5.4 (9.7) normal structure within PTV (cm3) m (%) 10 mm (%) 15 mm (%) .9 (23.7) 190.3 (30.8) 265.9 (42.9) .2 (12.8) 28 (17.5) 40.6 (26.5) .2 (13.3) 10.4 (19.9) 17.1 (34.1) Table 4. Recommend modifications to margins mph node group Recommended margins* mmon iliac 7-mm margin around vessels; extend posterior and lateral borders to psoas and vertebral body ternal iliac 7-mm margin around vessels; extend anterior border by additional 10- mm anterolaterally along iliopsoas muscle to include lateral external iliac nodes turator Join external and internal iliac regions with 18-mm-wide strip along pelvic sidewall erna