LAUSR

We thank Dr Iavazzo et al. for their interest in our paper [1]. We agree that the outcomes of patients with advanced mucinous ovarian carcinoma (MOC) are extremely poor. Our paper underlines the pivotal role of achieving complete cytoreduction [2]. Unfortunately, response to adjuvant therapy is disappointing. In terms of intravenous chemotherapy, recent multi-institutional retrospective data suggest that a gastro-intestinal regimen may be superior to the carboplatin paclitaxel combination [3]. We agree with Dr Iavazzo et al. that heated intraperitoneal chemotherapy (HIPEC) appears to be a promising therapeutic avenue given the remarkable 5-year survival (69.6%) among 77 patients with MOC and peritoneal carcinomatosis managed with cytoreductive surgery and HIPEC reported by the PSOGI Working Group [4]. However, authors did not clarify whether central pathology review was performed [4]. In the GOG 241 trial, 53% of tumors were reclassified as metastatic MOC [5]. Application of strict pathologic criteria and discrimination of patients with pure MOC from those with a gastro-intestinal primary is pivotal in future efforts to clarify the role of HIPEC. Selecting the appropriate intraperitoneal chemotherapy agent can also be challenging. Extrapolated from the aforementioned study 5-FU or oxaloplatin may be more appropriate compared to cisplatin. Targeted therapy is another promising treatment avenue. Mutations to the KRAS and HER2-neu genes have been detected among patients MOCs and could be targeted with cetuximab and trantuzumab [6, 7]. In addition, Src kinase inhibition and combination of PI3K/mTOR and MEK inhibition should be explored in future clinical trials given reported in vitro and in vivo anti-tumor activity [8, 9]. Immunotherapy is also less explored management option. Evaluation for PD-L1 expression or mismatch repair deficiency can be assessed and guide off-label use of programmed death-ligand 1 inhibitors. CAR-T cell therapy, targeting antigens specific to MOC such as MUC5A, could be investigated in vivo models. Similar to prior reports, we recommend the performance of comprehensive tumor molecular testing in each patient diagnosed with advanced MOC to identify potential molecular targets [10]. Given the rarity of advanced stage MOC and the difficulty in establishing correct pathological diagnosis, we agree that international collaborations are necessary. The creation of an international registry with tumor repository following central pathology review can aid in elucidating the management of these patients and serve as a platform for multiinstitutional collaborations.