PURPOSE: The aim of our study was to elucidate the impact of bevacizumab added to neoadjuvant chemotherapy (NACT) on the tumor immune microenvironment and correlate the changes with the clinical outcome of the patients.EXPERIMENTAL DESIGN: Immunohistochemistry and multiplex immunofluorescence for lymphoid and myeloid lineage markers were performed in matched tumor samples from 23 ovarian cancer patients enrolled in GEICO 1205/NOVA clinical study before NACT and at the time of interval cytoreductive surgery.RESULTS: Our results showed that the addition of bevacizumab to NACT plays a role mainly on lymphoid populations at the stromal compartment, detecting a significant decrease of CD4+ T cells, an increase of CD8+ T cells and an upregulation effector/regulatory cells ratio (CD8+/CD4+FOXP3+). None of the changes observed were detected in the intra-epithelial site in any arm (NACT or NACT-bevacizumab). No differences were found in myeloid lineage (macrophages-like). The percentage of Treg populations and effector/regulatory cell ratio in the stroma were the only two variables significative associated with PFS.CONCLUSIONS: The addition of bevacizumab to NACT did not have an impact on PFS in the GEICO 1205 study. However, at cellular level, changes in CD4+, CD8+lymphocyte populations, and CD8+/CD4+FOXP3 ratio have been detected only at the stromal site. Based on our results, we hypothesize about the existence of mechanisms of resistance that could prevent the trafficking of T effector cells into the epithelial component of the tumor as a potential explanation for the lack of efficacy of ICI in the first line of advanced EOC.

Background Intraoperative ultrasound (IOUS) guided conservative surgery has been shown to reduce rates of positive margins in breast cancer. The aim of the study is to evaluate the feasibility of using IOUS to assess superficial/anterior margins in nipple and skin sparing mastectomy (NSM/SSM) and its impact on reducing rates of positive margins. Methods This prospective study includes all breast cancer patients who had an indication for NSM/SSM at our Institution. Superficial margin width was measured by IOUS before surgery and the area marked on the skin. Same measurement was performed afterwards in the mastectomy specimen. Any superficial margin < 5 mm was re-excised intraoperatively following the mark on the skin. Results Fifty-nine patients were included, 47 patients (79.7%) underwent NSM, and 12 patients (20.3%) a SSM. Of the 59 patients, 23 (38.98%) had margins ¿5 mm and 36 patients (61.02%) had margins of ¿5 mm. Of the 36 patients with superficial margins ¿5 mm, 20 had margins <2 mm, and 6 of them had intraoperative involved superficial margins in final pathology. However, after IOUS-guided re-excision, final pathology showed no involved margins. A 2 mm margin was set as the cut-off point for performing an intraoperative re-excision. IOUS guided re-excisions for intraoperative margins ¿2 mm significantly reduced the risk of close/positive margins in final pathology, p < 0.0001. Conclusion The results showed that IOUS margin evaluation significantly reduced the rate of superficial positive margins in NSM/SSM. It is feasible and effective and may avoid challenging reoperations and/or additional radiation therapy for positive margins.