Marc Gignoux

Preoperative radiotherapy as adjuvant treatment in rectal cancer. Final results of a randomized study of the European Organization for Research and Treatment of Cancer (EORTC).

A randomized clinical trial was conducted by the European Organization for Research and Treatment for Cancer (EORTC) Gastrointestinal Cancer Cooperative Group to study the effectiveness of irradiation therapy administered in a dosage of 34.5 Gy, divided into 15 daily doses of 2.3 Gy each before radical surgery for rectal cancer (T2, T3, T4, NX, MO). Four hundred sixty-six patients were entered in the clinical trial between June 1976 and September 1981. Tolerance and side effects of pre- operative irradiation were acceptable. The overall 5-year survival rates were similar in both groups. When considering only the 341 patients treated by surgery with a curative aim, the 5-year survival rates were 59.1% and 69.1% in the control group and in the combined modality group, respectively (p = 0.08). The local recurrence rates at 5 years were 30% and 15% in the control group and the adjuvant radiotherapy group, respectively (p = 0.003). Although this study did not show preoperative radiotherapy to have a statistically significant benefit on overall survival, it does have a clear effect on local control of rectal cancer. Therefore, before performing radical surgery, this adjuvant therapy should be administered to patients who have locally extended rectal cancer.

Preoperative radiotherapy in esophageal carcinoma: A meta-analysis using individual patient data (oesophageal cancer collaborative group)

PURPOSE The existing randomized evidence has failed to conclusively demonstrate the benefit or otherwise of preoperative radiotherapy in treating patients with potentially resectable esophageal carcinoma. This meta-analysis aimed to assess whether there is benefit from adding radiotherapy prior to surgery. METHODS AND MATERIALS This quantitative meta-analysis included updated individual patient data from all properly randomized trials (published or unpublished) comprising 1147 patients (971 deaths) from five randomized trials. RESULTS With a median follow-up of 9 years, the hazard ratio (HR) of 0.89 (95% CI 0.78-1.01) suggests an overall reduction in the risk of death of 11% and an absolute survival benefit of 3% at 2 years and 4% at 5 years. This result is not conventionally statistically significant (p = 0.062). No clear differences in the size of the effect by sex, age, or tumor location were apparent. CONCLUSION Based on existing trials, there was no clear evidence that preoperative radiotherapy improves the survival of patients with potentially resectable esophageal cancer. These results indicate that if such preoperative radiotherapy regimens do improve survival, then the effect is likely to be modest with an absolute improvement in survival of around 3 to 4%. Trials or a meta-analysis of around 2000 patients would be needed to reliably detect such an improvement (15-->20%).

Palliative therapy of inoperable oesophageal carcinoma with radiotherapy and methotrexate: Final results of a controlled clinical trial☆

Between May 1976 and January 1982, 170 patients were entered in a randomized study comparing a combined treatment consisting of methotrexate followed by irradiation versus radiotherapy alone in patients with non metastatic inoperable oesophageal cancer. Methotrexate was administered subcutaneously in 4 days to a total dose of 24 mg/m2. Radiotherapy was performed, in both groups, at a dose of 56.25 Gy in 25 fractions (5 weeks). The administration of methotrexate did not lead to an increased intolerance to radiotherapy but severe hematological toxicities were observed in 7.8% of the cases. No difference in the duration of survival was detected. Initial performance status of the patients and their weight loss prior to entry on trial were the factors that were most predictive of the patients prognosis.

Treatment of Adenocarcinoma of the Pancreas With Somatostatin and Gonadoliberin (Luteinizing Hormone-Releasing Hormone)

Experimental studies have shown a significant inhibition of adenocarcinoma of the pancreas by gonadoliberin (luteinizing hormone-releasing hormone [LH-RH]) and somatostatin. The aim of this prospective randomized study was to compare the potential value of somatostatin (250 micrograms every 8 hours), LH-RH (3.75 mg monthly), or combined, to a control group. One hundred sixty-three patients with adenocarcinoma of the pancreas who did not undergo resection for cure were divided into 4 groups that did not differ in terms of clinical, biologic, or pathologic data. The mean survival times were 6 months in the LH-RH plus somatostatin group, 5.5 months in the LH-RH group, 4.3 months in the control group, and 3.8 months in the somatostatin group. However, the life-table analyses for all randomized patients, and separately according to sex, the lymph node extension, and metastatic spread were not different between groups. Improvement of patient status was observed in 20% of the patients receiving hormone therapy without any difference noted between the treatment regimens. These disappointing results may be explained by the degree of extension of pancreatic carcinoma in the patients studied. The results suggest that different hormone therapy regimens might be considered according to the age and the sex of patients, as well as to the presence or absence of hormone receptors.

Controlled clinical trial for the treatment of patients with inoperable esophageal carcinoma: a study of the EORTC Gastrointestinal Tract Cancer Cooperative Group.

Radiotherapy is the usual treatment for inoperable esophageal carcinoma. Results published before 1976, when this trial was begun were very modest, except for those of Pearson [1], The 1-year survival rate varies from 15% to 30%, and 5-year survival rates were about 5% [2–7].

Prognostic factors in resectable gastric cancer: Results of EORTC study no. 40813 on FAM adjuvant chemotherapy

AbstractBackground: The high incidence of locoregional recurrences and distant metastases after curative surgery for gastric cancer calls for improved locoregional control and systemic adjuvant treatment. Methods: In a randomized clinical trial on adjuvant FAM2 chemotherapy, quality of surgery was evaluated by comparing surgical and pathology data. Univariate and multivariate analysis was made to evaluate the effect of prognostic factors on survival and time of recurrence in relation to patients, tumor, and therapy. Results: Of 314 patients randomized from 28 European institutions, 159 comprised the control and 155 the FAM2 group. After a median follow-up of 80 months, no statistically significant difference was found between survivals. However, for recurrence time, treated patients had a significant advantage over controls (p=0.02). At univariate analysis, statistically significant differences in survival and time to progression emerged for T, N, disease stage, and “adequacy” of surgery. The multivariate analysis retained preoperative Hb level, T, N, and “adequacy” of surgery for time of survival; and T, N, “adequacy” of surgery and adjuvant chemotherapy for recurrence time. Conclusions: Disease stage is the most important prognostic factor. “Adequate” surgery has an important effect. Adjuvant FAM2 delayed time of recurrence, but did not influence overall survival.

Prospective and Controlled Studies on Multidisciplinary Treatment in Gastrointestinal Cancer

The Gastrointestinal Tract Cooperative Group of the EORTC has been conducting prospective and controlled studies in multidisciplinary treatment since 1973. There are now 39 institutions in the Netherlands, Germany, Switzerland, Italy, Spain, France, Israel, and Belgium contributing to the various clinical trials. They have already registered 1,350 patients, of whom 950 are evaluable for the studies. Seven clinical trials are still in progress or already closed. The purpose of this paper is to review these studies briefly.