[Multivariate analysis of the prognostic and predictive factors of response to concomitant radiochemotherapy in epidermoid cancers of the esophagus. Value of immunodetection of protein p53].
OBJECTIVE
The purpose of this study was to determine the prognostic value of the expression of protein p53, EGF receptors (EGR-R), cell proliferation antigen (Ki67) and DNA analysis by flow cytometry on per-endoscopic biopsies as well as the ability of these factors to predict response to concomitant chemoradiation in patients with squamous cell oesophageal carcinoma.


METHODS
Sixty-two patients with squamous cell oesophageal carcinoma were prospectively included in this study. For 58 patients (51 men, 7 women; mean age: 59.1 +/- 9.3 years), clinical response to chemoradiation was correlated with the findings of flow cytometry (ploidy, % of cells in S-phase) and immunohistochemistry (p53, EGF-R, Ki67). There were 4 patients in stage I, 14 in stage II, 27 in stage III, and 13 in stage IV. Chemoradiation (2 cycles associating continuous 5FU 800 mg/m2/24 h from D1 to 5 and from D22 to 26, Cisplatyl 70 mg/m2 on D1 and D22; 15 Gy/5d from D1 to 5 and from D22 to 26), was performed prior to surgery in 19 patients (group I) and as the only treatment in 39 patients (group II), with a third cycle from D43. Clinical response was defined as complete or incomplete, ascertained by endoscopy and biopsy, 2 to 3 weeks after the end of chemoradiation.


RESULTS
Mean survival in all 58 patients was 13.0 months. Survival was significantly longer in responders than in non responders (14.7 vs 9.6 months; P = 0.03). Among M0 patients, survival was not different in case of exclusive chemoradiation therapy or chemoradiation therapy followed by surgical excision (17.6 vs 13.0 months; NS). Monofactorial analysis showed that, in addition to response, the variables related to survival were stage, non-metastatic status, and absence of p53 surexpression. After multifactorial analysis according to the Cox model, the remaining variables were non-metastatic status, and absence of p53 surexpression. A complete response with negative biopsies was observed in 39 out of 58 patients, i.e. 67.3 +/- 12.1 % (group I: 12 out of 19; group II: 27 out of 39; NS). According to monofactorial analysis, 3 factors were predictive of complete response, i.e. non surexpression of p53 (P < 0.05) and tumour diameter (P = 0.04). After step-by-step logistic regression, non surexpression of p53 and tumour diameter continued to be predictive. The relative risk of a non-complete response was 5.46 if p53 was detected and 1.84 for each cm of added tumour diameter. These two factors were independent.


CONCLUSIONS
In this study the predictors of complete response were absence of p53 surexpression and tumour diameter ascertained by CT-scan. Flow cytometry and Ki67 antigen had no prognostic value and were not predictors of response.
Seitz
J F
JF
Unité d'Oncologie Digestive, Institut Paoli-Calmettes, Marseille.
Perrier
H
H
Monges
G
G
Giovannini
M
M
Gouvernet
J
J
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics / Q000401:mortality / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D004273:DNA, Neoplasm / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000401:mortality / Q000532:radiotherapy*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011300:Preoperative Care; D011379:Prognosis; D011446:Prospective Studies; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D004273:DNA, Neoplasm; D016159:Tumor Suppressor Protein p53
Analyse multifactorielle des facteurs pronostiques et prédictifs de réponse à la radiochimiothérapie concomitante dans les cancers épidermoïdes de l'oesophage. Intérêt de l'immunodétection de la protéine p53.