Anemia and long-term outcome in adjuvant and neoadjuvant radiochemotherapy of stage II and III rectal adenocarcinoma: The Freiburg experience (1989-2002)

doi:10.3748/wjg.v12.i12.1849

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Mar 28, 2006 (publication date) through Feb 6, 2025

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Colorectal Cancer

World J Gastroenterol. Mar 28, 2006; 12(12): 1849-1858
Published online Mar 28, 2006. doi: 10.3748/wjg.v12.i12.1849

Table 1 Patient characteristics

	Adjuvant radiochemotherapy n (%)	Neoadjuvant radiochemotherapy n (%)	All n (%)
Gender
Female	148 (63.5)	38 (71.7)	186 (65.0)
Male	85 (36.5)	15 (28.3)	100 (35.0)
Age
≤Median age of 62 yr	134 (57.5)	32 (60.4)	166 (58.0)
> Median age of 62 yr	99 (42.5)	21 (39.6)	120 (42.0)
Tumor location
Upper third	35 (15.1)	0 (0.0)	35 (12.2)
Middle third	100 (42.9)	23 (43.4)	123 (43.0)
Lower third	87 (37.3)	25 (47.2)	112 (39.2)
Not known	11 (4.7)	5 (9.4)	16 (5.6)
Surgical Resection
Anterior (LAR)	133 (56.8)	13 (24.6)	146 (51.0)
Abdominoperineal (APR)	100 (43.2)	40 (75.4)	140 (49.0)
R status
R0	197 (84.5)	37 (69.8)	234 (81.8)
R1	17 (7.3)	5 (9.4)	22 (7.7)
R2	4 (1.8)	2 (3.8)	6 (2.1)
not known	15 (6.4)	9 (17.0)	24 (8.4)
Stage
II	75 (32.2)	17 (32.1)	92 (32.2)
III	158 (67.8)	36 (67.9)	194 (67.8)
N stage
N0	74 (31.8)	17 (32.1)	91 (31.8)
N1	81 (34.8)	27 (50.9)	108 (37.8)
N2	78 (33.4)	9 (17.0)	87 (30.4)
Grading
G I	11 (4.7)	9 (17.0)	20 (7.0)
G II	161 (69.1)	29 (54.7)	190 (66.5)
G III	44 (18.9)	9 (17.0)	53 (18.5)
Not known	17 (7.3)	6 (11.3)	23 (8.0)
CEA
< 3 ng/mL	102 (43.8)	16 (30.2)	118 (41.3)
≥ 3 ng/mL	102 (43.8)	16 (30.2)	118 (41.3)
Not known	29 (12.4)	21 (39.6)	50 (17.4)
RTOG
RTOG 0	96 (41.2)	30 (56.6)	126 (44.1)
RTOG I	75 (32.2)	14 (26.4)	89 (31.1)
RTOG II	46 (19.7)	9 (17.0)	55 (19.2)
RTOG III	13 (5.6)	0 (0.0)	13 (4.6)
RTOG IV	3 (1.3)	0 (0.0)	3 (1.0)
RTOG V	0 (0.0)	0 (0.0)	0 (0.0)

Table 3 Survival rates and results of uni- and multivariate analysis (patient-related variables)

		OAS (%)	CSS (%)	DFS(%)	LRS (%)	DRS (%)
All stages II & III	5 yr / 10 yr:	47.0 / 36.0	60.0 / 52.0	41.4 /34.9	67.2 / 65.7	84.3 / 84.3
	at risk (5 yr / 10 yr):	78 / 34	81 / 36	69 / 34	72 / 46	74 / 34
	median survival:	1602		996
Gender
Male	5 yr / 10 yr:	49.2 / 36.3	64.9 / 56.8	24.7 / 12.9	73.1 / 73.1	85.1 / 85.1
Female	5 yr / 10 yr:	43.2 / 37.0	51.7 / 44.3	21.0 / 8.0	56.8 / 53.0	83.2 / 83.2
	uni- / multivariate: P =	0.93 / NS	0.16 / NS	0.17 / NS	0.01 / 0.018	0.66 / NS
	multivariate risk ratio:				male: 0.75
					(CI 0.59 – 0.95)
Age
< 62 yr	5 yr / 10 yr:	52.2 / 42.0	62.0 / 55.8	31.1 / 16.0	65.3 / 63.4	85.9 / 85.9
> 62 yr	5 yr / 10 yr:	41.0 / 27.0	57.1 / 42.6	13.6 / 5.1	70.4 / 70.4	80.2 / 80.2
*Median age	uni- / multivariate: P =	0.02 / NS	0.22 / 0.005	< 0.01 / NS	0.47 / NS	0.59 / NS
	multivariate risk ratio:		< 61 yr: 0.48
			(CI 0.28 – 0.80)
Staging
II	5 yr / 10 yr:	57.0 / 49.9	65.8 / 62.5	53.3 / 45.5	75.1 / 75.1	85.5 / 85.5
III	5 yr / 10 yr:	42.6 / 30.2	57.2 / 47.4	36.3 / 28.7	63.3 / 61.0	83.8 / 83.8
	uni- / multivariate: P =	0.02 / NS	0.09 / 0.009	0.02 / NS	0.06 / (0.07)	0.7 / NS
	multivariate risk ratio:		stage II: 0.45		stage II: 0.79
			(CI 0.21 – 0.84)		(CI 0.59 – 1.03)
Grading
II	5 yr / 10 yr:	50.6 / 39.7	62.0 / 55.1	49.3 / 41.7	73.3 / 70.7	86.8 / 86.8
III	5 yr / 10 yr:	40.7 / 36.6	55.3 / 49.8	23.3 / 23.3	58.8 / 58.8	64.4 / 64.4
	uni- / multivariate: P =	0.023 / (0.06)	0.07 / NS	< 0.01 / NS	0.04 / NS	< 0.01 / 0.04
	multivariate risk ratio:	G III: 1.68				G III: 2.87
		(CI 0.97 – 2.78)				(CI 1.08 – 7.01)

Risk ratio with confidence interval (CI) is given if multivariate analysis (step down analysis) revealed a significant result. Five- and 10- year survival rates are given as OAS, CSS, DFS, LRS and DRS.

Table 2 Anemia and hemoglobin values during radiotherapy (subgroup analysis of 192 patients)

	Adjuvant radiochemotherapy n (%)	Neoadjuvant radiochemotherapy n (%)	All n (%)
Anemia before RT
No	78 (47.6)	14 (50.0)	92 (47.9)
Yes	86 (52.4)	14(50.0)	100 (52.1)
Anemia after RT
No	102 (62.2)	8 (28.6)	110 (57.3)
Yes	62 (37.8)	20 (71.4)	82 (42.7)
Hemoglobin during RT
Hb increase	106 (64.6)	10 (35.7)	116 (60.4)
Hb decrease	58 (35.4)	18 (64.3)	76 (39.6)

Table 6 Anemia and hemoglobin increase versus decrease during radiotherapy (subgroup analysis of 199 patients with documented hemoglobin values before and after radiotherapy)

		OAS (%)	CSS (%)	DFS(%)	LRS (%)	DRS (%)
Anemia before RCT
No	5 yr / 10 yr:	44.6 / 31.4	66.4 / 66.4	41.5 / 33.7	76.6 / 76.6	74.9 / 74.9
Yes	5 yr / 10 yr:	49.5 / 47.2	55.4 / 45.6	48.5 / 39.2	61.5 / 59.6	88.1 / 88.1
	uni- / multivariate: P =	0.39 / NS	0.14 / NS	0.83 / 0.04	0.04 / NS	0.01 / NS
	multivariate risk ratio:			anemia present: 0.76
				(CI 0.57 – 0.99)
Anemia after RCT
No	5 yr / 10 yr:	47.5 / 34.0	57.4 / 48.4	42.5 / 34.7	87.6 / 87.6	62.7 / 60.7
Yes	5 yr / 10 yr:	47.0 / 41.5	64.7 / 59.3	39.6 / 35.9	80.0 / 80.0	73.0 / 73.0
	uni- / multivariate: P =	0.76 / NS	0.56 / NS	0.83 / NS	0.12 / NS	0.06 / NS
	multivariate risk ratio:
Hemoglobin (Hb) increase or decrease during RT
Hb increase	5 yr / 10 yr:	67.7 / 59.3	58.8 / 51.4	45.2 / 45.2	83.8 / 83.8	62.8 / 62.8
Hb decrease	5 yr / 10 yr:	35.3 / 35.3	38.7 / 33.9	36.2 / 36.2	73.9 / 73.9	75.9 / 75.9
	uni- / multivariate: P =	< 0.01 / NS	< 0.01 / NS	0.08 / 0.04	0.38 / NS	0.79 / NS
	multivariate risk ratio:			Hb decrease: 1.97
				(CI 1.02 – 3.43)

Survival rates and results of the uni- and multivariate analysis as well as risk ratio with confidence interval (CI) are given if multivariate analysis (step down analysis) revealed a significant result. Five- and 10-year survival rates are given as OAS, CSS, DFS, LRS and DRS

Table 7 Anemia and patient characteristics.

	Hb decreaseduring RTn (%)	P value
Age
≤ 62¹yr	42 (42.9)	0.31
> 62¹yr	32 (35.6)
Stage
II	18 (30.0)	0.07
III	56 (43.8)
Other serious diagnoses
No	38 (35.2)	0.17
Yes	36 (45.0)
BMI
≤ 24.2²	44 (50.0)	0.03
> 24.2²	18 (26.5)
Radiochemotherapy
Postoperative	56 (35.0)	0.03
Preoperative	18 (64.3)
Surgical Resection
LAR	42 (38.2)	0.96
APR	28 (37.8)
R status
R 0	24 (30.8)	0.04
R 1/2	10 (55.6)
Side effects
RTOG 0	8 (80.0)	0.27
RTOG I / II	62 (38.8)
RTOG III / IV	4 (22.2)

Results of chi-square test.

¹Median age,

²median BMI (body mass index).

Table 5 Results of uni- and multivariate analysis (other variables)

	OAS	CSS	DFS	LRS	DRS
N stage
uni- / multivariate: P =	0.009 / NS	0.05 / NS	0.06 / NS	0.09 / NS	0.15 / NS
CEA
uni- / multivariate: P =	< 0.001 / 0.007	< 0.001 / NS	< 0.001 / 0.001	< 0.001 / NS	0.55 / 0.055
multivariate risk ratio:	CEA increase: 1.37		CEA increase: 3.21		CEA decrease: 0.91
	(CI 1.09 – 1.73)		(CI 1.61 – 6.82)		(CI 0.76 – 1.00)
CA 19-9
uni- / multivariate: P =	< 0.001 / NS	0.033 / NS	0.22 / NS	0.79 / NS	0.62 / NS
Tumor location
uni- / multivariate: P =	0.34 / NS	0.43 / NS	0.4 / NS	0.83 / NS	0.37 / NS
Adherence to adjacent structures
uni- / multivariate: P =	< 0.001 / NS	0.004 / NS	< 0.001 / NS	0.13 / NS	0.019 / NS
BMI before RT
uni- / multivariate: P =	0.47 / NS	0.55 / NS	0.83 / NS	0.83 / NS	0.15 / NS
Smoking
uni- / multivariate: P =	0.79 / NS	0.49 / NS	0.71 / NS	0.22 / NS	0.31 / NS
Hkt before vs after RT
uni- / multivariate: P =	0.047 / NS	0.35 / NS	0.31 / NS	0.87 / NS	0.99 / NS
LDH before vs after RT
uni- / multivariate: P =	0.32 / NS	0.69 / NS	0.77 / NS	0.37 / NS	0.21 / NS

Table 4 Survival rates and results of uni- and multivariate analysis (treatment-related variables)

		OAS (%)	CSS (%)	DFS(%)	LRS (%)	DRS (%)
Adjuvant therapy
Postop RCT	5 yr / 10 yr:	47.6 / 35.6	59.0 / 48.4	40.2 / 34.0%	66.1 / 64.1	82.2 / 82.2
Preop RCT	5 yr / 10 yr:	43.9 / 38.0	62.6 / 62.6	45.4 / 39.3	69.8 / 69.8	92.8 / 92.8
	uni- / multivariate: P =	0.82 / NS	0.56 / NS	0.61 / NS	0.96 / NS	0.12 / NS
Protocol
NIH	5 yr / 10 yr:	60.7 / 45.2	72.5 / 59.4	49.8 / 44.2	84.1 / 84.1	73.2 / 73.2
ARO	5 yr / 10 yr:	26.9 / 21.5	45.6 / 36.5	24.5 / 16.3	67.6 / 67.6	64.0 / 64.0
	uni- / multivariate: P =	< 0.001 / NS	0.003 / 0.004	0.002 / NS	0.024 / NS	0.57 / NS
	multivariate risk ratio:		ARO: 2.66
			(CI 1.37 – 5.21)
Surgery	risk ratio:
LAR	5 yr / 10 yr:	36.4 / 25.9	49.5 / 41.1	27.8 / 22.7	64.7 / 64.7	81.3 / 81.3
APR	5 yr / 10 yr:	35.2 / 26.0	46.7 / 39.9	27.6 / 22.9	52.4 / 51.1	86.4 / 86.4
	uni- / multivariate: P =	0.4 / NS	0.51 / NS	0.27 / NS	0.015 / 0.039	0.6 / NS
	multivariate risk ratio:				LAR: 1.3
					(CI 1.01 – 1.60)
R status
R0	5 yr / 10 yr:	53.2 / 40.3	64.2 / 55.1	45.6 / 39.5	66.2 / 64.5	91.2 / 91.2
R1 or R2	5 yr / 10 yr:	14.2 / 14.2	20.7 / 20.7	17.3 / 17.3	62.9 / 62.9	51.2 / 51.2 5
	uni- / multivariate: P =	< 0.001 / NS	0.011 / (0.09)	< 0.001 / 0.026	0.95 / NS	< 0.001 / NS
	multivariate risk ratio:		R1/R2: 1.65	R1/R2: 3.45
			(CI 0.91 – 3.10)	(1.56 – 7.96)

Citation: Weissenberger C, Geissler M, Otto F, Barke A, Henne K, Plehn GV, Rein A, Müller C, Bartelt S, Henke M. Anemia and long-term outcome in adjuvant and neoadjuvant radiochemotherapy of stage II and III rectal adenocarcinoma: The Freiburg experience (1989-2002). World J Gastroenterol 2006; 12(12): 1849-1858
URL: https://www.wjgnet.com/1007-9327/full/v12/i12/1849.htm
DOI: https://dx.doi.org/10.3748/wjg.v12.i12.1849