The Role of Radiotherapy in the Treatment of Retroperitoneal Lymph Node Metastases from Colorectal Cancer

Figures & data

Table 1 Clinical and Pathologic Character of Patients

Characteristics	IRM Group N=40	ERM Group N=28
Age(years)
Median(range)	58(30–78)	54(28–66)
Gender (%)
Male	21(52.5%)	13(46%)
Female	19(47.5%)	15(54%)
ECOG performance status (%)
0	25(62.5%)	2(7%)
1	15(37.5%)	26(93%)
Primary Tumor (%)
Rectum	8(20%)	7(25%)
Colon	32(80%)	21(75%)
Initial TNM stage (%)
II	8(20%)	5(18%)
III	21(52.5%)	13(46%)
IV	7(17.5%)	9(32%)
Tumor grade (%)
G2: moderately differentiated	18(45%)	16(57%)
G3: poorly differentiated	12(30%)	12(43%)
RAS-BRAF mutations (%)
BRAF
BRAF mutant	2(5%)	0
BRAF wild type	16(40%)	19(68%)
Not done	22(55%)	9(32%)
KRAS
KRAS mutant	6(15%)	7(25%)
KRAS wild type	11(27.5%)	11(39%)
Not done	21(52.5%)	10(35.7%)
NRAS
NRAS mutant	0	0
NRAS wild type	2(5%)	4(14.3%)
Not done	38(95%)	24(85.7%)
Largest LN size(cm)
Range	1.2–4.2	1.3–5.8
Median	2.1	2.4

Abbreviations: ERM, extra-retroperitoneal metastases; ECOG, Eastern Cooperative Oncology Group performance status; IRM, isolated retroperitoneal lymph node metastases; LN, lymph node; RAS-BRAF, RAS gene and BRAF gene.

Table 2 Extra-Retroperitoneal Metastases Features

Location	ERM Group
Liver	17(61%)
No. of metastases
Mean±SD	2±3
Single liver mets	13(46%)
Radiotherapy to liver mets	2(7%)
Lung	7(25%)
No. of metastases
Mean±SD	1±6
Single lung mets	4(14%)
Radiotherapy to lung mets	0
Local recurrence	4(14%)
Radiotherapy to local recurrence	3(10%)
Other sites	6(21%)
Two sites of metastases	6(21%)
Pain	14(50%)
Ureteral obstruction	12(43%)

Abbreviations: ERM, extra-retroperitoneal metastases; Mets, metastases; SD, standard deviation.

Figure 1 Overall survival according to the presence or absence of extra-retroperitoneal metastases within the total study population.

Abbreviation: RPLN, retroperitoneal lymph node.

Figure 2 Progression-free survival according to the presence or absence of extra-retroperitoneal metastases within the total study population.

Abbreviation: RPLN, retroperitoneal lymph node.

Table 3 Univariate and Multivariate Cox Regression Analyses for PFS and OS in Isolated RPLNs

	UVA PFS	MVA PFS	UVA OS	MVA OS
	HR 95% CI P	HR 95% CI P	HR 95% CI P	HR 95% CI P
Age, year (≥50 vs.<50)	1.63 0.44–5.99 0.47	NI	0.71 0.11–4.42 0.71	NI
Sex (male vs female)	1.57 0.52–4.72 0.42	NI	3.21 0.57–17.9 0.19	NI
Primary site (colon vs rectum)	0.57 0.15–2.11 0.39	NI	0.37 0.04–3.25 0.37	NI
Tumor grade (G3 vs G2)	0.29 0.07–1.23 0.09	0.38 0.08–1.79 0.16	0.24 0.04–1.46 0.12	0.10 0.01–1.11 0.06
T-category (≤T3 vs >T4)	1.79 0.61–5.33 0.29	NI	1.09 0.25–4.77 0.91	NI
N-category (N2 vs N0–1)	0.19 0.05–0.71 0.01	0.18 0.04–0.79 0.02	0.11 0.01–1.07 0.05	0.14 0.01–1.31 0.08
RAS and BRAF status (wild type vs mutant type)	0.61 0.10–3.74 0.59	NI	1.27 0.07–21.8 0.87	NI
Interval, months (>12 vs≤12)	0.24 0.06–0.89 0.03	0.14 0.02–0.88 0.04	0.27 0.05–1.57 0.15	0.31 0.07–1.68 0.31
LN site (suprarenal vs infrarenal)	1.09 0.36–3.27 0.88	NI	3.98 0.46–34.4 0.21	NI
LN size (≤2cm vs >2cm)	4.87 1.15–20.6 0.03	9.04 0.97–83.5 0.05	0.52 0.05–5.08 0.57	NI
Radiation dose (<50 Gy vs≥50 Gy)	0.31 0.07–1.28 0.10	0.08 0.01–1.26 0.11	0.33 0.06–1.88 0.21	NI
RECIST (CR+PR vs SD+PD)	5.05 1.55–16.5 0.01	5.81 1.17–29.0 0.03	13.1 1.46–118 0.02	22.0 1.58–308 0.02
Targeted therapy (Yes vs No)	0.86 0.26–2.86 0.81	NI	2.45 0.29–21.1 0.41	NI
Targeted drug (cet vs bev)	0.74 0.07–8.41 0.81	NI	0.01 0–500 0.58	NI

Abbreviations: bev, bevacizumab; CI, confidence interval; CR, complete response; cet, cetuximab; HR, hazard ratio; LN, lymph node; MVA, multivariate analyses; mutant type, RAS-BRAF mutant; N, lymph node; NI, not included; OS, overall survival; PFS, progression-free survival; PR, partial response; PD, progressive disease; RPLN, retroperitoneal lymph node; RECIST, Response Evaluation Criteria in Solid Tumor; SD, stable disease; T, tumor; UVA, univariate analyses; wild type, RAS wild type.

Table 4 Univariate and Multivariate Cox Regression Analyses for PFS and OS in ERM Group

	UVA PFS	MVA PFS	UVA OS	MVA OS
	HR 95% CI P	HR 95% CI P	HR 95% CI P	HR 95% CI P
Age, year (≥50 vs<50)	1.74 0.51–5.98 0.38	NI	0.49 0.05–4.40 0.53	NI
Sex (male vs female)	0.52 0.16–1.66 0.27	NI	0.99 0.18–5.47 0.99	NI
Primary site (colon vs rectum)	0.83 0.26–2.63 0.75	NI	1.11 0.20–6.12 0.91	NI
Tumor grade (G3 vsG2)	1.91 0.60–6.09 0.27	NI	0.84 0.15–4.64 0.84	NI
T-category (≤T3 vs >T4)	0.36 0.10–1.29 0.12	0.40 0.12–1.34 0.10	0.58 0.09–3.71 0.58	NI
N-category (N2 vs N0–1)	0.22 0.05–0.92 0.04	0.22 0.05–0.92 0.05	0.34 0.06–2.09 0.24	NI
RAS and BRAF status (wild type vs mutant type)	1.26 0.29–5.33 0.75	NI	5.15 0.53–49.8 0.16	NI
Interval, months (>12 VS.≤12)	0.78 0.23–2.67 0.69	NI	1.63 0.27–9.85 0.59	NI
LN site(suprarenal vs. infrarenal)	0.09 0.02–0.49 0.01	0.1 0.02–0.55 0.01	0.39 0.07–2.24 0.29	NI
LN size(≤2 vs >2)	0.76 0.23–2.49 0.65	NI	2.17 0.37–12.5 0.39	NI
Radiation dose(<50 Gy vs≥50 Gy)	0.31 0.07–1.26 0.10	0.34 0.08–1.32 0.11	0.03 0.00–44.6 0.34	NI
Targeted therapy (Yes vs No)	1.08 0.32–3.67 0.90	NI	0.82 0.09–7.18 0.86	NI
Targeted drug (cet vs bev)	0.64 0.15–2.74 0.55	NI	1.17 0.18–7.49 0.87	NI
Extra-retroperitoneal metastases
Isolated lung metastases (yes vs no)	2.16 0.46–10.1 0.33	NI	1.89 0.21–17.1 0.57	NI
Isolated liver metastases (yes vs no)	0.20 0.06–0.74 0.02	0.23 0.06–0.86 0.03	0.27 0.05–1.51 0.14	NI
Number of ERM sites (≤1 vs >1)	1.46 0.39–5.57 0.58	NI	0.53 0.06–4.49 0.56	NI

Abbreviations: bev, bevacizumab; CI, credibility interval; CR, complete response; cet, cetuximab; ERM, extra-retroperitoneal metastases; HR, hazard ratio; LN, lymph node; MVA, multivariate analyses; mutant type, RAS-BRAF mutant; N, lymph node; NI, not included; OS, overall survival; PFS, progression-free survival; PR, partial response; PD, progressive disease; RECIST, Response Evaluation Criteria in Solid Tumor; SD, stable disease; T, tumor; UVA, univariate analyses; wild type, RAS wild type.