Effect of timing of surgery on survival after preoperative hyperfractionated accelerated radiotherapy (HART) for locally advanced rectal cancer (LARC): Is it a matter of days?

Figures & data

Figure 1.  Overall survival, cancer specific survival, disease free survival and local control are plotted as a function of GD. If GD > 5 days see dotted line.

Table I.  Contingency analysis for patient- and tumor related characteristics of potential prognostic importance (introduced as categorical data) by gap duration. A significant association between GD and any these characteristics a two-tailed Fisher's exact test yields a p-value ≤0.05. D.a.m.- distance to anal margin. APR-abdominoperineal resection. T. volume-tumor volume (assessed on pathological specimens).

	GD ≤ 5 days	GD > 5 days	Fisher's test p-value
Female	33	53	0.59
Male	70	94
Age < 64	48	69	1.00
Age ≥ 64	55	78
CEA ≤ 5 ng/ml	63	101	0.22
CEA > 5 ng/ml	40	46
D.a.m ≤ 5 cm	50	81	0.37
D.a.m.>5 cm	53	66
cT < 4	80	126	0.13
cT4	23	21
APR	45	63	0.90
Other than APR	58	84
Different.<3	79	91	0.02
Differentiation≥ 3	24	56
Clearance < 3 mm	25	38	0.88
Clearance ≥ 3 mm	78	109
pT > 2	75	106	1.00
pT ≤ 2	28	41
Downstaging	42	53	0.51
No downstaging	61	94
pN +	47	71	0.70
pN0	56	76
No vascular invasion	78	115	0.65
Vascular invasion +	25	32
Resection R0	88	118	0.32
Resection R+	15	29
T. volume ≤ 20cc *	72	102	1.00
T. volume > 20cc	31	45

Cut-off value for volume correponds to the 75^th percenrtile (*).

Table II.  Univariate analysis of patient and treatment related characteristics. The cut-off values are tabulated for each of the parameters. If rated SS▵ there is a statistically significant difference between the strata with a p-value of ≤0.05 log-rank test. NS* = difference not reaching a p-value <0.05 (log-rank) but reaching a p = 0.03 with the Wilcoxon test. APR - abdominoperineal resection; LAR - low anterior resection; d.a.m. - distance to anal margin; clear - clearance i.e. lateral resection margin; VI - vascular invasion; GD-gap duration in days.

		OS	CSS	DFS	OS
Age	≤64	SS
CEA	≤5 ng/ml	SS		SS
d.a.m	>5 cm			SS
cT		SS	SS	SS	SS
GD	≤5 days	SS	SS	SS
Surg.	APR vs LAR			SS
Clear	<3 mm	SS	SS	SS	SS
ypT	T1–2 vs T3–4	SS	SS	SS
ypN	+ vs −	SS	SS	SS
VI	+ vs −	SS	SS	SS
R0	R0 vs R1–2	SS	NS*	SS	SS

Table III.  Univariate analysis for the parameter GD. The cut-off value of ≤5 days is used to define the two strata. For the 2- and 5-years results, in the upper line are tabulated the values for the subgroup with a GD ≤ 5 days, whereas the lower line represents the patients with a GD > 5 days. If the median is not reached, this is labelled NR in the table. All survival figures are given in % with the corresponding standard error.

	p-value	2-years	5-years	Median
OS	0.002	75%±0.05	47%±0.06	51 months
		88%±0.03	69%±0.05	NR
CSS	0.0007	81%±0.04	57%±0.06	NR
		94%±0.02	82%±0.04
DFS	0.0003	55%±0.05	41%±0.05	28 months
		82%±0.03	62%±0.05	NR
LC	NS	90%±0.03	90%±0.03	NR
		96%±0.02	93%±0.03

Table IV.  Multivariate analysis of patient and tumor related factors. The second column corresponds to the cut-off value. For each of the parameters the p-value is listed (upper line) with the Risk Ratio (RR) and corresponding confidence limits (CL) (lower line). If the factor is not kept in the final model, this factor is mentioned in the table as not significant (NS). GD - gap duration; VI - vascular invasion; a.m. - anal margin. Patients in the defined subgroup have a better prognosis if the RR < 1.

	OS	CSS	DFS	LC
Age	0.02 0.77 (0.61–0.96)	NS	NS	NS
≤ 64
Distance to a.m.	NS	NS	0.002 0.73 (0.59–0.89)	NS
> 5 cm
CEA	NS	NS	0.04 0.81 (0.66–0.99)	NS
≤ 5 ng/ml
GD	0.0002 1.51 (1.21–1.88)	0.0009 1.57 (1.20–2.06)	0.0002 1.46 (1.20–1.79)	NS
≤ 5 days
Clearance	0.008 0.74 (0.59–0.92)	NS	NS	0.002 0.45 (0.26–0.74)
> 3 mm
pN	0.0000 0.60 (0.47–0.75)	0.0002 0.57 (0.41–0.77)	0.0000 0.61 (0.49–0.75)	NS
− vs +
VI	NS	0.01 0.69 (0.52–0.91)	0.04 0.80 (0.65–0.99)	NS
− vs +