Predictive factors for response to neoadjuvant therapy in patients with oesophageal cancer.
BACKGROUND
Preoperative radio-chemotherapy (RCX) was introduced to improve the outcome of patients with oesophageal cancer (EC), but conflicting results have been released. Some 20-30% of patients show a complete pathological response, however, the perioperative morbidity and mortality is increased. To search for factors indicating response prior to the onset of RCX we investigated the proliferative activity (MIB-1), the expression of vascular endothelial growth factor (VEGF), and the capillary density (CD34) in samples of EC obtained by endoscopy prior to the start of the treatment.


METHODS
Forty-six (MIB-1) and 21 (VEGF, CD34) tissue specimens of ECs were available from 56 patients undergoing pretherapeutic endoscopy, RCX and surgery. Perioperative morbidity was divided into surgery and non-surgery related morbidity. MIB-1, VEGF and CD34 expression were investigated immunohistochemically. Multivariate analysis was carried out to prove independence of investigated variables.


RESULTS
Postoperative morbidity was noticed in 54 of 56 operated patients. Eight of 56 patients who received RCX died in hospital. Survival was significantly different between the group of complete responders (n=14) and non-responders (n=23; P=0.0026). None of the investigated tumour samples from patients with a complete response (CR) had a proliferation index of less than 45. Tumour samples from patients with a CR showed a VEGF expression of 10.7 compared with 36.58 of tumours with no response (P=0.035). CD34 expression showed a correlation with VEGF expression. The relation of mean indices of VEGF expression and proliferative activity in tumours from patients with complete, partial or no response was 10.7:58.8, 18.3:53.8 and 36.6:43.5, respectively.


CONCLUSIONS
According to these results, it may be expected that tumours with a VEGF/MIB-1 ratio of 1:6 or less prior to RCX will respond to this therapy.
Imdahl
A
A
Department of Surgery, Division of General Surgery, University of Freiburg, Hugstetterstrasse 55, 79106 Freiburg, Germany. imdahl@chir.ukl.uni-freiburg.de
Bognar
G
G
Schulte-Mönting
J
J
Schöffel
U
U
Farthmann
E H
EH
Ihling
C
C
D000230:Adenocarcinoma / Q000401:mortality / Q000628:therapy*; D000328:Adult; D000368:Aged; D000906:Antibodies / Q000276:immunology; D034961:Antigens, Nuclear; D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000628:therapy*; D017024:Chemotherapy, Adjuvant; D016228:Endothelial Growth Factors / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000401:mortality / Q000628:therapy*; D004947:Esophagus / Q000473:pathology*; D005260:Female; D005858:Germany / Q000453:epidemiology; D006801:Humans; D019394:Ki-67 Antigen; D008222:Lymphokines / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000096:biosynthesis; D011237:Predictive Value of Tests; D011300:Preoperative Care; D018714:Radiotherapy, Adjuvant; D013223:Statistics as Topic; D016019:Survival Analysis; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000906:Antibodies; D034961:Antigens, Nuclear; D016228:Endothelial Growth Factors; D019394:Ki-67 Antigen; D008222:Lymphokines; D009687:Nuclear Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors