Statistics Fellowship

This past June, Monia Ouali completed a two year fellowship in the Statistics Department at EORTC Headquarters. This fellowship supported by the EORTC Soft Tissue and Bone Sarcoma Group allowed Ms. Ouali, under the supervision of Dr. Martine Van Glabbeke, to study the statistical methodology of cancer clinical trials and carry out projects to identify prognostic factors and predictive factors in soft tissue sarcoma. Specifically, she performed retrospective analyses using the EORTC Soft Tissue and Bone Sarcoma Group’s (STBSG) database of 12 STBSG trials.

In one project Ms. Ouali investigated the relationship between sarcoma tumors and ifosfamide treatment in first line therapy. She described the population and then performed a prognostic factor analysis to identify subgroups of patients with favorable overall survival (OS), progression free survival (PFS), or response of treatment independently of outcome to ifosfamide-containing treatment. She also performed a predictive factor analysis to identify subgroups of patients who benefit more from ifosfamide-containing treatment than other patients.

Doxorubicin and ifosamide are two drugs currently used in the treatment of advanced sarcomas. Doxorubicin appears to be the most active drug in the treatment of soft tissue sarcomas, but treatment with doxorubicin is limited due to cumulative cardiotoxicity. Unfortunately none of the tested anthracyline analogs has been shown to be superior or comparable to doxorubicin. Ifosfamide has also been demonstrated to be active in second line chemotherapy, although its activity is definitively lower than that observed in first line chemotherapy. To date the optimal dose and scheduling of ifosfamide administration with respect to tumor effect and quality of life are unknown. Therefore, Monia assessed the independent prognostic and predictive factors for outcome of ifosamide chemotherapy.

Ifosfamide combined with doxorubicin is favorable for response to treatment and PFS, but there is no effect on OS. Synovial sarcoma (histological subtype) is favorable, whereas GIST (gastrointestinal stromal tumor) is unfavorable for response and PFS, but there is no effect on OS. Other factors differ importantly. A high tumor grade is favorable for response but unfavorable for OS. The results of this work were presented orally at ASCO 2009, and publication of these results is in preparation.

With the same database and using similar methodology, Monia also investigated the prognostic factors and described the populations in the following studies:

• Lung metastases in patients receiving first line therapy of advanced soft tissue sarcomas;
• Patients with an advanced neurogenic sarcoma versus other histological cell types;
• Patients with a primary versus recurrent tumor in first line therapy of advanced soft tissue sarcomas.

Ms. Ouali’s fellowship also investigated the prognostic and predictive factors for patients treated by adjuvant chemotherapy in two EORTC-STBSG studies. Adjuvant chemotherapy is intended to eradicate distant micrometastases after curative local treatment, but no significant survival benefit has been demonstrated thus far in randomized trials or in meta-analyses. Results of her analysis show that large tumor size, high histological grade, and marginal resection were independent, significant adverse prognostic factors for both OS and PFS. Treatment has an independent favorable prognostic value for PFS. This study confirms previously documented prognostic factors in completely resected soft tissue sarcoma. Males, patients older than 40 years, and patients with a marginal resection benefited more from adjuvant chemotherapy than did others. Tumor size and histological grade had no predictive value for the benefit of chemotherapy. Patients in the adverse prognostic subgroups are not necessarily those who benefited the most from adjuvant chemotherapy. The quality of initial surgery seems to be the most important prognostic and predictive factor for the benefit (marginal resection) or not (radical resection) of adjuvant chemotherapy for PFS and OS. Results of this work were presented as a poster communication at ASCO 2009 and a manuscript is in preparation. Following this study and using similar methods, Monia also investigated prognostic factors in an adolescent and young adult patient population versus patients aged over 30 years (poster presentation at ASCO 2009).

Ms. Ouali received her Applied Science Degree in Mathematics and Informatics and her
License in Mathematical Sciences from the University Montpellier II, Montpellier, France, and she earned her MSc in Statistics and Informatics from the University Aix-Marseille I, Marseille, France. In addition to her research, during her fellowship Monia availed herself of numerous opportunities to follow EORTC sponsored scientific and statistics sessions.

Ms. Ouali will remain at EORTC Headquarters as biostatistician in the EORTC Statistics Department. She will be involved, among other things, with two retrospective analyses in soft tissue sarcomas. One of these analyses concerns metastases versus primary tumors and the other concerns the toxicities due to doxorubicin.

The EORTC is pleased to have Ms. Ouali join the EORTC Headquarters Staff.

John Bean