73. changing patterns of recurrent disease in colorectal cancer

1
Tumour response to neoadjuvant therapy ranges from complete response to little or no response at all and is related with outcomes. The aim of this study was to determine the correlation between clinical, pathological pa- rameters and molecular biomarkers in diagnostic endoscopic biopsies with tumour regression grading in the resected specimens. Materials and methods: Ninety five patients with mid (56%) and low (44%) locally advanced rectal adenocarcinoma who received neoadjuvant radiotherapy with or without chemotherapy followed by radical surgical resection were included in the study. Mean age was 68 years. Sixty four (67%) were males and 31 (33%) females. Several clinical and pathological parameters were collected. Paraffin-embedded sections obtained in diag- nostic biopsies before therapy were assessed by immunohistochemical staining for p53, her-2, VEGFr, bcl-2, beta-catenin, COX-2, APAF-1 and Ki-67. These stains were correlated with T-downstaging and tumour re- gression grade (TRG) using Mandard’s scoring system on surgical speci- mens. Data were analyzed with chi-square and Spearman’s correlation tests. Results: Pathologic complete response was seen in 17% and T down- staging in 48.2%. There was correlation between TRG and pretreatment expression of bcl-2 (p¼0.04), beta-catenin (p¼0.03) and VEGFr (p¼0.04). T-downstaging was significantly associated with expression of APAF-1 (p¼0.04) and VEGFr (p¼0.03). We did not find any correlation with any other molecular marker (p53, her-2, COX-2, Ki-67), clinical and pathological parameters (age, gender, tumour location, pretreatment CEA level, interval to surgery), excepting histologic grade (p<0.001). Conclusions: Pathological and immunohistochemical evaluation of diagnostic biopsies may be a useful tool to predict tumour response to neoadjuvant therapy in patients with locally advanced rectal adenocarci- noma. 73. Changing patterns of recurrent disease in colorectal cancer I. Grossmann 1 , J.M. Klaase 1 , P.M. Doornbos 2 , G.H. de Bock 2 , T. Wiggers 3 1 Medisch Spectrum Twente, Surgery, Enschede, The Netherlands 2 UMC Groningen, Epidemiology, Groningen, The Netherlands 3 UMC Groningen, Surgery, Groningen, The Netherlands Introduction: Due to changes in staging and (neo)-adjuvant treatment of colorectal cancer (CRC), it is expected that the recurrence pattern, rel- evant for follow-up, changes as well. This study analyzes the incidence and time to recurrent disease (RD), the localization(s) and the eligibility for re- newed curative treatment. Materials and methods: A prospective consecutive cohort of CRC pa- tients treated with curative intent from 2007 till 2010 was analyzed (n¼511). This cohort was routinely staged before treatment with abdomi- nal CT and chest X-ray or CT and underwent (neo)-adjuvant treatment ac- cording to the current guidelines. Results: The incidence of RD was 15% for patients with stage 0-III disease and 19% when including curatively treated stage IV patients, after a median FU of 33 months. The annual incidences in the stage 0-III group (n¼472) were for year one 7.3%, year two 6.3%, year three 3.6%, year four 2.8% and year five 2.0%. In the stage IV group (n¼39) these were for year one 39% and year two 57%. The majority of RD was confined to one organ (59%) and 25% of patients were treated with curative intent. Conclusions: The incidence of RD has decreased significantly in com- parison to historical estimates of 30-50%. This decrease is probably due to improved staging before treatment, the decrease of local recurrences from rectal cancer and better adjuvant treatment in colon cancer. The annual in- cidences are the highest in the first two years but tend to retain in succeed- ing years for stage 0-III patients. The efforts to find RD with the intention to offer a second chance on cure do seem to be amenable. 74. The treatment of local recurrent rectal cancer in the TME Era S. Bosman 1 , F.A. HolmanMD 2 , R. Dudink 1 , H.J. Rutten 1 1 Catharina Hospital, Surgery, Eindhoven, The Netherlands 2 TweeStedenZiekenhuis, Surgery, Tilburg, The Netherlands Background: In recent years, an improvement in prognosis for patients with rectal cancer is achieved, partly due to the Total Mesorectal Excision (TME) technique, and the introduction of preoperative radiotherapy and che- motherapy. Despite improved outcomes, some patients develop locally re- current rectal cancer. The majority of patients with local recurrent rectal cancer have already received irradiation during the initial treatment for the primary tumour. This has led to the question whether reirradiation improves the local tumour response and survival or leads to late toxicity and a better outcome. The objective of this article is to evaluate the outcome of treatment in a large population patients with local recurrent rectal carcinoma. Materials and methods: The Catharina Hospital is a national referral centre for patients with recurrence rectal cancer. Patients were treated fol- lowing the TME rules whenever possible. Before surgery, patients under- went irradiation, re-irradiation, chemotherapy, a combination, or no neoadjuvant treatment. Patient follow up was enrolled in a database; com- plications post-operative, presence of local recurrence, metastasis and overall survival was reported. Follow-up ranged from 0 to 202 months with a median of 27 months. Results: From 1994 until 2011, 222 patients (mean age 63; 133 male, 89 female) with local recurrence were treated with curative intent. One hundred and two patients were reirradiated, the dose ranged from 2500 to 6000 centigrays (cGy), with a median dose of 4250 cGy. Two hundred and twenty two patients underwent surgery; in 57% (n¼126) of the surgi- cal procedures, a radical resection was achieved. On univariate cox regres- sion analysis, a radical resection showed high significance, compared with R1 or R2 resections; respectively (HR2.54 p¼0.000 and HR4.10 p¼0.000). The overall survival after five years was 35%. The five years cancer spe- cific survival was 41%. Fifty one percent developed local recurrence within five years and 46% developed distant metastases. The overall relapse free survival was 34%. Conclusions: Neoadjuvant treatment, re-irradiation or reirradiation combined with chemotherapy, has influence on cancer specific survival. However, radical resection is the main prognostic variable for oncological outcome. Even after TME surgery in combination with radiotherapy, treat- ment of local recurrence with reirradiation (in combination with chemo- therapy) is feasible and yields good oncological outcome. 75. Features on MRI after transanal endoscopic microsurgery in patients with rectal cancer G.L. Beets 4 , M.H. Martens 1 , M. Maas 2 , L.A. Heijnen 1 , D.M.J. Lambregts 2 , J.W.A. Leijtens 3 , R.G.H. Beets-Tan 2 1 Maastricht University Medical Centre, Surgery/Radiology, Maastricht, The Netherlands 2 Maastricht University Medical Centre, Radiology, Maastricht, The Netherlands 3 Laurentius Hospital, Surgery, Roermond, The Netherlands 4 Maastricht University Medical Centre, Surgery, Maastricht, The Netherlands Background: Standard treatment for rectal cancer is total mesorectal ex- cision (TME) with or without neo-adjuvant treatment. This major surgery is associated with significant morbidity and mortality. Transanal endoscopic microsurgery (TEM) is a minimally invasive technique for the local resection for T1 and selected T2 tumors and is associated with lower morbidity and mortality rates than TME. It is also an emerging option for good responders after chemoradiation. In most centres, the follow-up of patients treated with TEM includes regular MRI in addition to endoscopy. So far, rectal wall mor- phology on MRI after TEM has not yet been described. This study aimed to describe the rectal wall MRI morphology during short-term and long-term follow-up in patients that received TEM. Methods: Thirty-six patients had a post-TEM MRI in our center be- tween 2006 and 2011. For half of the patients (n¼19) only one post-oper- ative MRI was available in our institute. In 17 cases two or more MRIs were available. The MR morphology of the TEM site was studied on the consecutive MR examinations. 29 patients were primary treated with TEM, 7 patients had a long course of chemoradiation followed by TEM. 754 ABSTRACTS

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Page 1: 73. Changing patterns of recurrent disease in colorectal cancer

754 ABSTRACTS

Tumour response to neoadjuvant therapy ranges from complete response to

little or no response at all and is related with outcomes. The aim of this

study was to determine the correlation between clinical, pathological pa-

rameters and molecular biomarkers in diagnostic endoscopic biopsies

with tumour regression grading in the resected specimens.

Materials and methods: Ninety five patients with mid (56%) and low

(44%) locally advanced rectal adenocarcinoma who received neoadjuvant

radiotherapy with or without chemotherapy followed by radical surgical

resection were included in the study. Mean age was 68 years. Sixty four

(67%) were males and 31 (33%) females. Several clinical and pathological

parameters were collected. Paraffin-embedded sections obtained in diag-

nostic biopsies before therapy were assessed by immunohistochemical

staining for p53, her-2, VEGFr, bcl-2, beta-catenin, COX-2, APAF-1 and

Ki-67. These stains were correlated with T-downstaging and tumour re-

gression grade (TRG) using Mandard’s scoring system on surgical speci-

mens. Data were analyzed with chi-square and Spearman’s correlation

tests.

Results: Pathologic complete response was seen in 17% and T down-

staging in 48.2%. There was correlation between TRG and pretreatment

expression of bcl-2 (p¼0.04), beta-catenin (p¼0.03) and VEGFr

(p¼0.04). T-downstaging was significantly associated with expression of

APAF-1 (p¼0.04) and VEGFr (p¼0.03). We did not find any correlation

with any other molecular marker (p53, her-2, COX-2, Ki-67), clinical

and pathological parameters (age, gender, tumour location, pretreatment

CEA level, interval to surgery), excepting histologic grade (p<0.001).

Conclusions: Pathological and immunohistochemical evaluation of

diagnostic biopsies may be a useful tool to predict tumour response to

neoadjuvant therapy in patients with locally advanced rectal adenocarci-

noma.

73. Changing patterns of recurrent disease in colorectal cancer

I. Grossmann1, J.M. Klaase1, P.M. Doornbos2, G.H. de Bock2,

T. Wiggers3

1Medisch Spectrum Twente, Surgery, Enschede, The Netherlands2UMC Groningen, Epidemiology, Groningen, The Netherlands3UMC Groningen, Surgery, Groningen, The Netherlands

Introduction: Due to changes in staging and (neo)-adjuvant treatment

of colorectal cancer (CRC), it is expected that the recurrence pattern, rel-

evant for follow-up, changes as well. This study analyzes the incidence and

time to recurrent disease (RD), the localization(s) and the eligibility for re-

newed curative treatment.

Materials and methods: A prospective consecutive cohort of CRC pa-

tients treated with curative intent from 2007 till 2010 was analyzed

(n¼511). This cohort was routinely staged before treatment with abdomi-

nal CT and chest X-ray or CT and underwent (neo)-adjuvant treatment ac-

cording to the current guidelines.

Results: The incidence of RD was 15% for patients with stage 0-III

disease and 19% when including curatively treated stage IV patients, after

a median FU of 33 months. The annual incidences in the stage 0-III group

(n¼472) were for year one 7.3%, year two 6.3%, year three 3.6%, year

four 2.8% and year five 2.0%. In the stage IV group (n¼39) these were

for year one 39% and year two 57%. The majority of RD was confined

to one organ (59%) and 25% of patients were treated with curative intent.

Conclusions: The incidence of RD has decreased significantly in com-

parison to historical estimates of 30-50%. This decrease is probably due to

improved staging before treatment, the decrease of local recurrences from

rectal cancer and better adjuvant treatment in colon cancer. The annual in-

cidences are the highest in the first two years but tend to retain in succeed-

ing years for stage 0-III patients. The efforts to find RD with the intention

to offer a second chance on cure do seem to be amenable.

74. The treatment of local recurrent rectal cancer in the TME Era

S. Bosman1, F.A. HolmanMD 2, R. Dudink1, H.J. Rutten1

1 Catharina Hospital, Surgery, Eindhoven, The Netherlands2 TweeStedenZiekenhuis, Surgery, Tilburg, The Netherlands

Background: In recent years, an improvement in prognosis for patients

with rectal cancer is achieved, partly due to the Total Mesorectal Excision

(TME) technique, and the introduction of preoperative radiotherapy and che-

motherapy. Despite improved outcomes, some patients develop locally re-

current rectal cancer. The majority of patients with local recurrent rectal

cancer have already received irradiation during the initial treatment for the

primary tumour. This has led to the question whether reirradiation improves

the local tumour response and survival or leads to late toxicity and a better

outcome. The objective of this article is to evaluate the outcome of treatment

in a large population patients with local recurrent rectal carcinoma.

Materials and methods: The Catharina Hospital is a national referral

centre for patients with recurrence rectal cancer. Patients were treated fol-

lowing the TME rules whenever possible. Before surgery, patients under-

went irradiation, re-irradiation, chemotherapy, a combination, or no

neoadjuvant treatment. Patient follow up was enrolled in a database; com-

plications post-operative, presence of local recurrence, metastasis and

overall survival was reported. Follow-up ranged from 0 to 202 months

with a median of 27 months.

Results: From 1994 until 2011, 222 patients (mean age 63; 133 male,

89 female) with local recurrence were treated with curative intent. One

hundred and two patients were reirradiated, the dose ranged from 2500

to 6000 centigrays (cGy), with a median dose of 4250 cGy. Two hundred

and twenty two patients underwent surgery; in 57% (n¼126) of the surgi-

cal procedures, a radical resection was achieved. On univariate cox regres-

sion analysis, a radical resection showed high significance, compared with

R1 or R2 resections; respectively (HR2.54 p¼0.000 and HR4.10 p¼0.000).

The overall survival after five years was 35%. The five years cancer spe-

cific survival was 41%. Fifty one percent developed local recurrence within

five years and 46% developed distant metastases. The overall relapse free

survival was 34%.

Conclusions: Neoadjuvant treatment, re-irradiation or reirradiation

combined with chemotherapy, has influence on cancer specific survival.

However, radical resection is the main prognostic variable for oncological

outcome. Even after TME surgery in combination with radiotherapy, treat-

ment of local recurrence with reirradiation (in combination with chemo-

therapy) is feasible and yields good oncological outcome.

75. Features on MRI after transanal endoscopic microsurgery in

patients with rectal cancer

G.L. Beets4, M.H. Martens1, M. Maas2, L.A. Heijnen1,

D.M.J. Lambregts2, J.W.A. Leijtens3, R.G.H. Beets-Tan2

1Maastricht University Medical Centre, Surgery/Radiology, Maastricht,

The Netherlands2Maastricht University Medical Centre, Radiology, Maastricht,

The Netherlands3 Laurentius Hospital, Surgery, Roermond, The Netherlands4Maastricht University Medical Centre, Surgery, Maastricht,

The Netherlands

Background:Standard treatment for rectal cancer is totalmesorectal ex-

cision (TME) with or without neo-adjuvant treatment. This major surgery is

associated with significant morbidity and mortality. Transanal endoscopic

microsurgery (TEM) is aminimally invasive technique for the local resection

for T1 and selected T2 tumors and is associated with lower morbidity and

mortality rates than TME. It is also an emerging option for good responders

after chemoradiation. In most centres, the follow-up of patients treated with

TEM includes regular MRI in addition to endoscopy. So far, rectal wall mor-

phology on MRI after TEM has not yet been described.

This study aimed to describe the rectal wall MRI morphology during

short-term and long-term follow-up in patients that received TEM.

Methods: Thirty-six patients had a post-TEM MRI in our center be-

tween 2006 and 2011. For half of the patients (n¼19) only one post-oper-

ative MRI was available in our institute. In 17 cases two or more MRIs

were available. The MR morphology of the TEM site was studied on the

consecutive MR examinations. 29 patients were primary treated with

TEM, 7 patients had a long course of chemoradiation followed by TEM.