PMC5937622_01
Selected CT images of the lymph nodes for every treatment modality. (a-d), (e-h), (i-l), (m-p), (q-t), (u-x), and (y-ab) represent CT scans #1, #2, #3, #4, #5, #9, and #19 in supplemental Figure 1, respectively. Arrowheads in the 1st to 4th columns show the obturator lymph nodes, common iliac lymph nodes, para-aortic lymph node #1, and para-aortic lymph node #2, respectively. CT: computed tomography, GC: chemotherapy using gemcitabine and cisplatin, RNU: radical nephroureterectomy, GP: chemotherapy using gemcitabine and paclitaxel, and RT: radiotherapy.
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fig1
Magnetic resonance imaging suggested the ureteral tumor (21 x 13 mm) had invaded the muscle layer, but not the periureteric fat (Figure S1). In order to control the apparent obturator LN metastasis (17.5 +- 0.5 mm, Figure 1(a), Table S1), the patient was given 6 courses of chemotherapy with gemcitabine (1,000 mg/m2, days 1, 8, and 15) and cisplatin (70 mg/m2, day 2) (GC-chemotherapy, GC #1-6). Other LNs, which subsequently showed enlargement, were within normal size (<1.0 cm) before GC-chemotherapy (Figures 1(b)-1(d)). Although the obturator LN significantly shrunk to 8.4 +- 1.1 mm (Figure 1(e)), the left common iliac LN enlarged from 6.6 +- 0.4 to 11.0 +- 0.4 mm (Figure 1(f)). The two para-aortic LNs, which later expanded, remained within the normal size range (6.4 +- 0.3 and 7.1 +- 0.8 mm, resp., Figures 1(g)-1(h)). However, we could not remove the enlarged LN behind the common iliac artery (* in Figure 1(f)) owing to vascular adherence, probably caused by stent-graft implantation for the treatment of aortic aneurism (Figure 1(f)). At 1.5 months after the surgery, CT revealed no recurrence to the obturator lymph node (Figure 1(i)), but the remaining common iliac LN enlarged to 22.2 +- 0.8 mm (Figure 1(j)). Furthermore, the sizes of the two para-aortic LNs significantly increased to 12.7 +- 0.9 mm (para-aortic LN #1, Figure 1(k)) and 17.1 +- 0.8 mm (para-aortic LN #2, Figure 1(l)). The common iliac LN and para-aortic LN #2 shrank, to 15.5 +- 0.9 mm (Figure 1(n)) and 7.9 +- 0.6 mm (Figure 1(p)), respectively, but the para-aortic LN #1 did not (Figure 1(o)). After the additional 2 courses of GC-chemotherapy (GC #9-10), both obturator LN and para-aortic LN #1 remained within the normal size range (Figures 1(q) and 1(s)), whereas the sizes of the common iliac LN (23.0 +- 0.7 mm, Figure 1(r)) and para-aortic LN #2 (11.9 +- 0.4 mm, Figure 1(t)) increased. No recurrence was observed at the site of the obturator LN resection (Figure 1(u)), while those of the common iliac LN (5.8 +- 0.7 mm, Figure 1(v)) and para-aortic LN #1 (5.8 +- 0.6 mm, Figure 1(w)) significantly decreased; however, the size of the para-aortic LN #2 grew (21.5 +- 0.3 mm, Figure 1(x)). No recurrence was observed at the site of the extracted obturator LN (Figure 1(y)) with no regrowth reported in the two LNs that were irradiated as part of the consolidative therapy (Figures 1(z) and 1(aa)). Remarkably, the para-aortic LN #2 that presumably contained chemoresistant cancer cells significantly shrunk to normal size after salvage radiotherapy (5.4 +- 0.5 mm, Figure 1(ab)).
Irradiation conditions for the lymph nodes. (a) Frontal view of CT image reconstruction; RF1 was set based on CTV1 and 2 as standard radiation. (b) Left anterior oblique view of CT image reconstruction; RF2 was set based on CTV2 as a radiation boost. CT: computed tomography, RF: radiation field, GTV: gross tumor volume, CTV: clinical target volume, Ao: aorta, IVC: inferior vena cava, Kid: right kidney, ob: obturator lymph node, ci: left common iliac lymph node, and pa: para-aortic lymph node.
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fig2
Computed tomography (CT) showed a contrast-enhanced tumor in the lower ureter (data not shown), left hydronephrosis (data not shown) and an enlarged left obturator lymph node (18 mm in diameter, Figure S2). The treatment efficacy was evaluated by CT imaging (Figure S2), in which the sizes of the LNs were retrospectively measured by HK, SS, TO, and AK (Table S1) and compared by statistical analysis (Student's t-test). As consolidative therapy for the left common iliac LN and para-aortic LN #1 as well as salvage therapy for the para-aortic LN #2, the patient underwent aggressive extra-beam radiotherapy utilizing 10 megavolts photons from a linear accelerator employing a 3-dimensional conformal technique (Figure 2). The patient underwent two patterns of radiotherapy: (A) standard irradiation from the frontal and posterior positions (40 Gy/20 fractions, green-lined area in Figure 2(a)) and (B) boost irradiation from the oblique position (20 Gy/10 fractions, yellow-lined area in Figure 2(b)). During standard irradiation, the gross tumor volume (GTV), identified on CT of the target metastasized lesions in the area, included the para-aortic LN #2 and the left common iliac LNs (para-aortic LN #2 and the left common iliac artery/vein, black-dotted lines in Figure 2(a)). CTV2 in Figure 2(a)). CTV1 was defined by the aorta (Ao), inferior vena cava (IVC), and left common iliac artery/vein with 7 mm margins where metastatic cells possibly existed in the lymphatic system, while CTV2 was defined by the GTVs with a 5 mm margin (pink-circled area in Figure 2(a)). Subsequently, both actual radiation fields, RF1 and RF2, were set based on CTV1 and CTV2, excluding the right kidney, spinal cord, and bowel (green- and yellow-lined areas in Figures 2(a) and 2(b), resp.).