European Organization for Research and Treatment of Cancer EORTC scoring system

Based on 25-year experience of the management of supradiaphragmatic early stage Hodgkin's lymphoma, the EORTC Lymphoma Group has defined treatment strategies based on prognostic factors with the objective of adapting the treatment aggressiveness (i.e., combined-modality therapy) to patients at high risk of treatment failure in order to avoid most treatment-related complications. In 1989, Tubiana and coworkers published the results of a multivariate analysis based on a total of 1579 patients enrolled into four successive randomized clinical trials over the 1964-1987 period.14 Six factors were proven to independently correlate with either disease-free survival or overall survival: age (<40, 40-49, >50 years), gender, number of nodal areas involved (1, 2 or 3, 4 or 5), histologic type (lymphocyte predominant or nodular sclerosing), B symptoms, and erythrocyte sedimentation rate (<30, 30-49, >50 mm/1st hour). The originality of the publication consisted in the discussion on the balance that exists between two types of riskā€”the risk of treatment failure because of too light treatment and that of long-term complications following extended field irradiation or combined-modality therapy using aggressive chemotherapy. After multivariate analysis, three prognostic groups were defined. The very favorable group included females aged 39 years or less, with stage I disease, lymphocyte predominant or nodular sclerosing histologic subtype, no B symptoms, and ery-throcyte sedimentation rate less than 30 mm/1st hour. They represented 6% of all patients. A simulation was performed to help in defining the unfavorable group of patients. Three options were discussed. Option A concerned patients aged 50 years or more, or with three or more nodal areas involved, or with no B symptoms and erythrocyte sedimentation rate more than or equal to 50 mm/1st hour, or with B symptoms and erythrocyte sedimentation rate more than or equal to 30 mm/1st hour. Forty-nine percent of patients were option A. Option B

had the same definition as option A except that only patients with four or five nodal areas involved were considered. Option B would include 38% of all patients. In option C, patients aged 50 years or more, or with four or five nodal areas involved, or patients aged 40-49 years with no B symptoms and erythrocyte sedimentation rate more than or equal to 50 mm/1st hour, or those with B symptoms and erythrocyte sedimentation rate more than or equal to 30 mm/1st hour were considered. Option C concerned 19% of patients. All other patients not fitting with very favorable or unfavorable definitions were considered in the favorable group, i.e., 45, 56, or 75% of all patients according to option A, B, or C, respectively. Based on the projected probability of disease-free survival and overall survival, option B was selected in the design of the H7 trial.15 However, in this trial the presence of bulky mediastinal involvement qualified patients as an unfavorable prognostic group, although this factor was not included in the overall prognostic study performed because it was not recorded.16 The EORTC scoring system, still in use since the H7 trial start, in particular in the two following trials H8 and H9, is presented in Table 70.2.17-19

Investigators who have defined a prognostic score they trust in are prone to use it in the design of the next study; they may also wait before its prognostic value is confirmed based on independent series. The design of the EORTC H7 trial was based on the newly defined EORTC scoring system; it also included an experimental strategy to test its validity. In the favorable group, patients were randomized to receive subtotal lymphoid and splenic irradiation (standard treatment) or six courses of EBVP (epirubicin, bleomycin, vinblastine, prednisone) followed by involved-field irradiation. In the unfavorable group, patients were randomized to receive six courses of MOPP/ABV (mechlorethamine, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, vinblastine) hybrid and involved-field irradiation (standard treatment) or six courses of EBVP and involved-field irradiation. Beside the treatment comparison within each prognostic group, the trial design tested the prognostic value of the scoring system by comparing the two groups of patients treated with EBVP and involved-field irradiation. It is the only example of an experimental prospective design made to assess the value of a prognostic score.

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