The objective: to increase the effectiveness of treatment of patients with benign and borderline epithelial ovarian tumors (EOT) after conservative operations performed based on the definition of a high risk group for recurrence and malignancy according to the molecular expression profile of the markers p53, Ki-67, estrogen receptors (ER), CD34 and E-cadherin and inclusion in the complex anti-relapse therapy of the immunomodulating drug Glutoxim. Materials and methods. A clinical examination of 60 patients of reproductive age with EOT was performed, which were treated with organ-sparing surgical treatment (main group). Of these 60 patients, 30 women (subgroup I) were diagnosed with benign EOT (BEOT), the remaining 30 women (subgroup II) were diagnosed with borderline EOT (BoEOT) Ia and Ib stages in FIGO. In removed tumors after routine histopathological examination, the molecular profile was determined by immunohistochemically determining the protein regulator of apoptosis p53, proliferation index (PI) by Ki-67 expression, estrogen receptors — ER, microvessel density by CD34 expression and E-cadherin intercellular adhesion protein. Based on the molecular profile determination data, the removed tumor was ranked as high or low risk of recurrence and malignancy. Patients from the high-risk group for relapse and malignancy according to the molecular profile data included the immunomodulating drug Glutoxim in the complex anti-relapse therapy - intramuscularly 10 mg daily for 2 weeks with a course repeated every six months for 3 years. The control group consisted of 64 patients with BEOT and BoEOT, who underwent conservative surgical treatment without further anti-relapse treatment. Results. During the molecular profile study, it was found that high risk of recurrence and malignancy had EOT with p53 expression (LI ≥15%), high proliferative activity of cells with Ki-67 expression (PI ≥10%), low estrogen reception (LI ER < 49.5%), high density of microvessels on the expression of CD34 (IM ≥40 mv /mm2), low level of intercellular adhesion on the expression of E-cadherin (LI <59%). Molecular profile characterizing a high risk of recurrence and malignancy, in most cases was inherent in BoEOT. The purpose of a comprehensive anti-relapse treatment with the inclusion of the immunomodulatory drug Glutoxim (intramuscularly daily at 10 mg for 2 weeks) after performing of sparing conservative surgical treatment with a repetition of the course every six months in patients at high risk of relapse and malignancy according to molecular profile data has reduced the relapse of EOT to 6.7% in patients of the main group compared with 20.3% in the control group during three years of follow-up observation of patients. The difference is statistically significant (p <0.05). Conclusion. In order to prevent cases of recurrence and malignancy in patients with EOT at high risk of relapse and malignancy according to molecular profile data after a sparing surgical treatment that preserves their reproductive function, it is recommended that Glutoxim is administered in complex anti-relapse therapy at 10 mg intramuscularly per every day for 2 weeks with a repetition of the course every six months for 3 years. Key words: benign epithelial ovarian tumors, borderline epithelial ovarian tumors, high risks of recurrence and malignancy, anti-relapse therapy, reproductive function, Glutoxim.
Protocol for a single-arm confirmatory trial of adjuvant chemoradiation for patients with high-risk rectal submucosal invasive cancer after local resection: Japan Clinical Oncology Group Study JCOG1612 (RESCUE study)