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Local recurrence after rectal cancertreatment
Danijela Scepanovic, Andrea Masarykova, Martina Lukacovicova, Andrea Hurakova,
Zuzana Dolinska, Margita Pobijakova
Department of Radiation Oncology, National Oncological Institute of Slovakia,
Bratislava, Slovakia
Background
Local recurrence is a major problem after rectalcancer surgery. Local recurrence rates historicallyvary between 15% and 45%. The introduction oftotal mesorectal excision (TME) as treatment forpatients with rectal cancer has led to an improvedlocal control and survival when compared withhistorical controls.
Purpose
To analyze local recurrence rates in ourpatients treated with preoperative
radiotherapy with/withoutchemotherapy followed by TME or non
TME surgery.
Material and methods
Two hundred fifty patients (pts) were enrolledbetween January 2004 and December 2010.
Median age was 62 years (min=26, max=83). There were 83 female and 167 male. To be eligible, patients had to have histologically
confirmed adenocarcinoma of the rectum, withoutevidence of distant metastases, and the inferiormargin of the tumor had to be located not fartherthan 15 cm from the anal verge.
Initially, 96% of patients had locally advanced stageof disease (T3/T4N0, any TN+).
Material and methodsLocation tumors in rectum
4-8cm51%
0-4cm18%
12-15cm5%
8-12cm26%
Material and methodsInitial TNM stage
T10%
T3N+55%
T2N+4%
T45%
T324%
T24%
T4N+8%
T1T2T3T4T2N+T3N+T4N+
Material and methodsRadiotherapy
All patients had preoperativeradiotherapy (RT)with a total dose of 45-50.4Gy in 25-28 fractions for5 to 5.5 weeks
020406080
100120140160180200
to 45Gy over 45Gy
No
Material and methodsChemotherapy
Chemotherapy (CT) was performed concomitantly with RT:
1. 5-fluorouracil – 168 patients
2. capecitabine – 72 patients
3. without CT – 10 patients
0
20
40
60
80
100
120
140
160
180
5-fluorouracil capecitabine without CT
No
Material and methodsSurgery
Six weeks after RT/CT patients were operated with:
1. Total mesorectal excision (TME)=118 patients
2. Non total mesorectal excision (nonTME)=132 patients
ResultsLocal recurrence rate (LRR)
Median follow-up time = 48 months(range, 12 to 96 months).
The cumulative proportion of localrecurrence was 6.8% for all group of
patients (250):1.1. TME group TME group –– 0.8%0.8%
2.2. nonTMEnonTME group group –– 6%6% p=0.0022
ResultsSites of recurrence
22
1
12
0 2 4 6 8 10 12 14
presacral
multisites
anastomosis
nonTMETME
No
ResultsInfluence of tumor distance from
the anal verge on LRR
0
1
2
3
4
5
6
7
0-4cm 4-8cm 8-12cm 12-15cm
TMEnonTME
p=0.1442
p=0.660
p=0.1604
No
Results Influence of dose irradiation on
LRR
0
2
4
6
8
10
12
to 45Gy over 45Gy
TMEnonTME
p=0.0410
p=0.0298
p=1.0000
No
Results Influence of chemotherapy type on
LRR
0
2
4
6
8
10
12
TMEnonTME
p=0.0287
p=0.2750 p=1.0000
p=0.56255-FU capecitabine without CT
p=0.1419
No
Results Influence of postoperative stage on
LRR
pT0 pT1 pT2 pT3 pT4 anyTN+0
1
2
3
4
5
6
7
TMEnonTME
p=0.3644
p=0.1341No
Results Influence of resection margins on
LRR
0
2
4
6
8
10
12
R negative R positive
TMEnonTME
p=0.0009
p=0.0196No
Results Influence of lymphovascular
invasion on LRR
0
2
4
6
8
10
12
LVI negative LVI positive
TMEnonTME
p=0.0427
p=0.0196
p=0.2550
No
Results Influence of KRAS on LRR
0
0,5
1
1,5
2
2,5
3
KRAS negative KRAS mutant
TMEnonTME
p=0.5125
p=0.0252
p=1.0000
No
ResultsTime to progression (TTP)
36
48
monthsnonTMETME
min=12; max=96
min=10; max=96
Results Distant metastases
Fifty one patients Fifty one patients had distant had distant metastases in metastases in whole group of whole group of patients:patients:
1. TME group=162. nonTME group=35
0
2
4
6
8
10
12
14
livermetastases
lungmetastases
liver/lung lung/bones bones
TMEnonTME
p=0.3451
p=0.3294
p=1
p=1 p=0.5810
p=0.0121
No
Results Influence of KRAS on distant
metastases KRAS analysis was KRAS analysis was
performed in 111 performed in 111 patients (44.4%) and patients (44.4%) and distant metastases distant metastases occurred in 24 patients occurred in 24 patients (22%):(22%):
KRAS negative:KRAS negative:1. TME group=82. nonTME group=10 KRAS mutant:1. TME group=42. nonTME=2 0
2
4
6
8
10
12
KRAS negative KRAS mutant
TMEnonTME
p=0.0194
p=0.5686
p=0.2147
No
Results5 years DFS
0
10
20
30
40
50
60
70
80
90
100
0 to 12 12 to 24 24 to 36 36 to 48 48 to 60 60 to 72 72 to 84 84 to 96
TMEnonTME
months
%
p=0.0025
Results5 years OS
0
10
20
30
40
50
60
70
80
90
100
0 to 12 12 to 24 24 to 36 36 to 48 48 to 60 60 to 72 72 to 84 84 to 96
TMEnonTME
months
%
p=0.0012
ResultsSurvival
In the group of patients with TME died 15 patients while in the group with nonTME died 39 patients
The association between groups of patients and outcome is considered to be very statistically significant (p=0.0012)
Conclusions
1. Radiotherapy followed by TME has beenshown to significantly reduce localrecurrence rates in our patients.
2. There was very statistically significant difference between TME and nonTMEgroups of pts regarding DFS and OS.
3. The strong criteria for identifying low risk group of pts for LR were:
Negative resection margins (p=0.0009) and TME (p=0.0022).