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  • Title: [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].
    Author: Seitz JF, Perrier H, Monges G, Giovannini M, Gouvernet J.
    Journal: Gastroenterol Clin Biol; 1995 May; 19(5):465-74. PubMed ID: 7589997.
    Abstract:
    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.
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