The following article aims to highlight the importance of the assessment of frailty in patients affected by gynecological cancer and to discuss current data available on scores commonly used to predict adverse postoperative outcomes and overall survival in this group of patients. A narrative review was performed in Medline (PubMed) and Embase database until February 28, 2022. This study includes randomized and observational studies about patients undergoing non-emergent surgery for gynecological malignancies with preoperative frailty assessment. Fourteen studies, for a total of 85957 women, were included. The Modified Frailty Index (mFI) is the most commonly used tool for definition of frail patient. Results highlighted that frail patients had lower disease-free survival rates and overall survival rates than non-frail patients. Additionally, frail patients were more at risk of developing 30-day postoperative complications, non-home discharge and Intensive Care Unit admission than the other group. In gynecologic oncology, the assessment of the state of women's frailty is fundamental to predict adverse outcomes and to customize treatment strategies. Modified Frailty Index is the most used tool to assess the frailty state of gynecologic oncologic patients. We advise that this index should be part of the patients' standard evaluation and that it may be used in the daily practice to aid in shared decision making for tailored therapeutic strategies. In this manuscript we provide an update on the importance of the use of preoperative frailty scores to predict complications among patients treated for gynecological cancer.

IntroductionPancreatic cancer is associated with poor prognosis, and limited treatment options are available for the majority of patients. Natural killer (NK) cells in combination with antibodies inducing antibody-dependent cell-mediated cytotoxicity (ADCC) could be a highly effective new therapeutic option in pancreatic cancer. Accurate predictive preclinical models are needed to develop successful NK cell immunotherapy. Tumor organoids, in vitro 3D organ-like structures that retain important pathophysiological characteristics of the in vivo tumor, may provide such a model. In the current study, we assessed the cytotoxic potential of adoptive NK cells against human pancreatic cancer organoids. We hypothesized that NK cell anti-tumor responses could be enhanced by including ADCC-triggering antibodies.MethodsWe performed cytotoxicity assays with healthy donor-derived IL-2-activated NK cells and pancreatic cancer organoids from four patients. A 3D cytotoxicity assay using live-cell-imaging was developed and enabled real-time assessment of the response.ResultsWe show that NK cells migrate to and target pancreatic cancer organoids, resulting in an increased organoid death, compared to the no NK cell controls (reaching an average fold change from baseline of 2.1±0.8 vs 1.4±0.6). After 24-hours of co-culture, organoid 2D growth increased. Organoids from 2 out of 4 patients were sensitive to NK cells, while organoids from the other two patients were relatively resistant, indicating patient-specific heterogeneity among organoid cultures. The ADCC-inducing antibodies avelumab (anti-PD-L1) and trastuzumab (anti-HER2) increased NK cell-induced organoid cell death (reaching an average fold change from baseline of 3.5±1.0 and 4.5±1.8, respectively). Moreover, combination therapy with avelumab or trastuzumab resulted in complete disintegration of organoids. Finally, inclusion of ADCC-inducing antibodies was able to overcome resistance in NK-organoid combinations with low or no kill.DiscussionThese results support the use of organoids as a relevant and personalized model to study the anti-tumor response of NK cells in vitro and the potential of ADCC-inducing antibodies to enhance NK cell effector function.