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Analysis of circulating tumor nucleic acids in plasma of Non-Small Cell Lung Cancer (NSCLC) patients is the most widespread and documented form of \"liquid biopsy\" and provides real-time information on the molecular profile of the tumor without an invasive tissue biopsy. Liquid biopsy analysis was requested by the referral physician in 121 NSCLC patients at diagnosis and was performed using a sensitive Next Generation Sequencing assay. Additionally, a comparative analysis of NSCLC patients at relapse following EGFR Tyrosine Kinase Inhibitor (TKIs) treatment was performed in 50 patients by both the cobas and NGS platforms. At least one mutation was identified in almost 49% of the cases by the NGS approach in NSCLC patients analyzed at diagnosis. In 36 cases with paired tissue available a high concordance of 86.11% was observed for clinically relevant mutations, with a Positive Predictive Value (PPV) of 88.89%. Furthermore, a concordance rate of 82% between cobas and the NGS approach for the EGFR sensitizing mutations (in exons 18, 19, 21) was observed in patients with acquired resistance to EGFR TKIs, while this concordance was 94% for the p.T790M mutation, with NGS being able to detect this mutation in three 3 additional patients. This study indicates the feasibility of circulating tumor nucleic acids (ctNA) analysis as a tumor biopsy surrogate in clinical practice for NSCLC personalized treatment decision making. The use of new sensitive NGS techniques can reliably detect tumor-derived mutations in liquid biopsy and provide clinically relevant information both before and after targeted treatment in patients with NSCLC. Thus, it could aid physicians in treatment decision making in clinical practice.

Cancer-associated thrombosis (CAT), the second leading cause of death in patients with cancer can be treated with low molecular weight heparin (LMWH) according to guidelines. A multicenter prospective observational study was carried out to record anti-thrombotic treatment practice, assess thrombosis recurrence and bleeding, and identify potential risk factors. Adult patients from 18 Oncology Departments throughout Greece were followed-up for 12 months. A total of 120 patients with CAT receiving anticoagulant treatment were enrolled (35% incidental); 85% were treated for more than 6 months, 95.8% were treated with tinzaparin and smaller percentages with other agents. Thrombosis recurred in three patients and there was minor bleeding in four patients. Bleeding was associated with high body mass index (>35 kg/m ), trauma history, renal insufficiency and bevacizumab use. Incidental thrombosis contributes significantly to CAT burden. Long-term use of LMWH seems to be effective and safe. Several risk factors associated with bleeding should be considered during anti-coagulation therapy planning.

BackgroundPDAC is recognized as a highly thrombogenic tumor; thus, low-molecular-weight heparin (LMWH) is routinely used for PDAC patients. Based on the combinatorial therapy approach to treating highly malignant and refractory cancers such as PDAC, we hypothesized that LMWHs could augment the effectiveness of immune checkpoint inhibitors and induce an efficient antitumoral activity.1 MethodsBxPC-3, PANC-1, and MIA-PaCa2 were incubated alone or in combination with Tinzaparin (T) and/or Nab-Paclitaxel (A) and/or Gemcitabine (G) and/or Nivolumab (NI), Pembrolizumab (PE) and/or Ipilimumab (IPI). The effect of these regimes on various signaling pathways controlling proliferation and apoptosis was identified in vitro through Western blot. Cell viability was measured with MTT assay. NOD/SCID mice will be used to generate xenografts with the PANC-1 cell line. Human peripheral blood mononuclear cells (PBMCs) from healthy donors will be injected to give mice a human-like immune system.2 ResultsIn a triple combinatorial scheme, NI/PE+IPI+T, the protein levels of VEGFR2 were decreased (0.1 to 0.7 folds) in a dose-dependent way in mtKRAS PC cell lines (PANC1 and MIAPACA2). The number of PANC-1 cells was decreased around 40% in a triple combinatorial scheme of T+IPI+(NI or PE) after 48 hours. The triple combination of Gemcitabine + Nab-paclitaxel + Tinzaparin leads to a decrease in tumor size relative to control by 51% and relative to Nab-P + G by 15%. The combination of chemotherapy, immunotherapy, and Tinzaparin leads to a reduction in tumor size compared to control by up to 60%. Tinzaparin contributes an additional 20% Preliminary data show that the quadruple therapeutic regimen increases the percentage of CD8+ cells from 5% to 27% and decreases Tregs’ percentage from 9.5% to 4% (in TILs).ConclusionsIn vitro experiments show a decrease in the cell viability of PC cell lines and a reduction in the protein levels of VEGFR2 in mtKRAS cell lines. In vivo experiments with NOD/SCID mice and humanized NOD/SCID mice show a significant reduction in tumor volume in the combination therapy regimens with Tinzaparin. Possible mechanisms for these effects include an increase in CD8+ cells, a decrease in Tregs cells, a reduction in VEGFR-2 expression, and an increase in cancer cell apoptosis. This synergistic strategy can create new avenues for the treatment of patients with pancreatic cancer, achieving a better clinical outcome and greater survival.ReferencesBokas A, Papakotoulas P, Sarantis P, Papadimitropoulou A, Papavassiliou AG, Karamouzis MV. Mechanisms of the Antitumor Activity of Low Molecular Weight Heparins in Pancreatic Adenocarcinomas. Cancers (Basel). 2020;12(2):432. Published 2020 Feb 13. doi:10.3390/cancers12020432.Chen Q, Wang J, Liu WN, Zhao Y. Cancer Immunotherapies and Humanized Mouse Drug Testing Platforms. Transl Oncol. 2019;12(7):987–995. doi:10.1016/j.tranon.2019.04.020.

Atrial fibrillation (AF) may often pre-exist in patients with newly diagnosed cancer or occur with increased frequency shortly after cancer diagnosis. Patients with active cancer and AF have a particularly high risk of thromboembolic complications, as both conditions carry a risk of thrombosis. Thromboembolic risk is determined by several factors, including advanced age, sex (females), cancer histology (adenocarcinomas), location (e.g., pancreas, stomach), advanced stage, anticancer regimens (e.g., platinum compounds, anti-angiogenic therapies, immune modulators), comorbidities (e.g., obesity, kidney disease) and concurrent therapies (e.g., surgery, central catheters). Physicians are often reluctant to prescribe anticoagulants to patients with active cancer and AF, mainly due to fear of bleeding complications, which is partly related to the paucity of evidence in the field. Decision making regarding anticoagulation for the prevention of ischemic stroke and systemic embolism in patients with active cancer and AF may be challenging and should not simply rely on the risk prediction scores used in the general AF population. By contrast, the administration and choice of anticoagulants should be based on the comprehensive, individualized and periodic evaluation of thromboembolic and bleeding risk, drug-drug interactions, patient preferences and access to therapies.

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and a tumor with a broad spectrum of targeted therapies already available or in clinical trials. Thus, molecular characterization of the tumor using next generation sequencing (NGS) technology, has become a key tool for facilitating treatment decisions and the clinical management of NSCLC patients. The performance of a custom 23 gene multiplex amplification hot spot panel, based on Ion AmpliSeq™ technology, was evaluated for the analysis of tumor DNA extracted from formalin-fixed and paraffin-embedded (FFPE) tissues. Furthermore, the Ion AmpliSeq™ RNA Fusion Lung Cancer Research Panel was used for fusion RNA transcript analysis. The mutation spectrum of the tumors was determined in a cohort of 502 patients with NSCLC using the aforementioned targeted gene panels. The panel used for tumor DNA analysis in this study exhibited high rates (100%) of sensitivity, specificity and reproducibility at a mutation allelic frequency of 3%. At least one DNA mutation was detected in 374 patients (74.5%) and an RNA fusion was identified in 16 patients, (3.2%). In total, alterations in a cancer-driver gene were identified (including point mutations, gene rearrangements and MET amplifications) in 77.6% of the tumors tested. Among the NSCLC patients, 23% presented a mutation in a gene associated with approved or emerging targeted therapy. More specifically, 13.5% (68/502) presented a mutation in a gene with approved targeted therapy (EGFR, ALK, ROS1) and 9.4% (47/502) had an alteration in a gene related to emerging targeted therapies (ERBB2, BRAF, MET and RET). Furthermore, 51.6% of the patients had a mutation in a gene that could be related to an off label therapy or indicative for access to a clinical trial. Thus, the targeted NGS panel used in this study is a reliable approach for tumor molecular profiling and can be applied in personalized treatment decision making for NSCLC patients.

Introduction/BackgroundHigh-intermediate and high-risk endometrial cancer cases are associated with increased risk for lymph node invasion. Main objective of the present study was to report the overall rate of pelvic and paraaortic lymph node invasion in these cases.MethodologyA retrospective single-center study was observed regarding the period 2019–2022. In this study we included cases with high-intermediate and high-risk endometrial cancer cases in which full surgical staging with pelvic and para-aortic lymphadenectomy was performed, either open or laparoscopically. Epidemiological and histopathological characteristics of patients were recorded. Primary outcome was the rate of overall lymph node invasion as well as the rate of invasion in pelvic and para-aortic lymph nodes separately. Univariate regression analysis was also performed to identify histopathological parameters being significantly associated with risk for lymph node invasionResultsThere were overall 22 cases identified during the period. Mean age of patients were 65.9 years, while final stage was assessed to be stage ≥ IIIA in 71.4% of cases (n=15). Overall rate of lymph node invasion was 59.1% (n=13), while relative rates for pelvic and para-aortic lymph nodes were 59.1% (13/22) and 50.0% relatively (11/22). Rates did not differ significantly between sub-groups of high-intermediate and high risk patients, ranging between 46.2% and 61.5%. LVSI was assessed to be independent factor of lymph node invasion (P=.03).ConclusionHigh-intermediate and high risk endometrial cancer cases are associated with high rates of pelvic and para-aortic lymph node invasion. Surgical staging still remains the procedure of choice in this category of patients to identify lymph node metastasis and therafter tailor adjuvant treatment.

Introduction/BackgroundDebulking surgery for advanced-stage ovarian cancer is potentially the most challenging surgical procedure in the context of gynaecological oncological care. Such cases are continuously referred to specialized Units and ESGO accreditation may act attractively for patients and referring departments. Main objective of the present study is to report the evolution of debulking surgeries after the first ESGO accreditation of a Northern Greek Gynaecologic Oncology Unit at the end of 2020.MethodologyA prospective observational cohort was performed concerning patients treated with a diagnosis of advanced-stage ovarian cancer. Epidemiological, histopathological and surgical reports of all patients were prospectively recorded in a computerized database, based on the recommendations of ESGO for advanced-stage ovarian cancer surgery. The present study concerns patients treated between 2020–2022. Rate of optimal cytoreduction, primary and interval debulking surgery, histological subtype of patients as well as evolution of number of cases throughout study period were set in the center of our analysis.ResultsThere were overall 98 patients operated during study period, of which 28 in 2020, 33 in 2021 and 37 in 2022. Mean age of patients was 61.8 years. Overall complete cytoreduction rate was 79.5% (78/98 patients). This rate remained stable during the overall period (82.1% vs. 78.8% vs 78.4% respectively, P=NS). Primary debulking surgery rate was 68.4% (67/98 cases), the rate also remaining stable during the overall period (71.4%, 72.3% and 67.6% respectively, P=NS). Rates of complete cytoreduction were comparable between primary cytoreductive and interval debulking surgeries (79.7% vs. 79.3%, P=NS). The main histopathological diagnosis was high-grade serous carcinoma (66/98 cases, 67.3%). Finally, there was observed an overall 32.4% increase of treated cases between 2020 and 2022.ConclusionESGO accreditation for individual fellowship lead to significant increase of advanced-stage ovarian cancer patients treated in our Department, with a relative maintenance and upgrade of provided services level.DisclosuresAuthors have nothing to disclose

Introduction/BackgroundLaparoscopic para-aortic lymphadenectomy is a procedure performed for staging purposes. Retroperitoneal approach is an alternative approach, potentially superior to intraperitoneal regarding bowel dysfunction and hemorrhage. Main purpose of the present study was to present the main intraoperative, postoperative and short-term survival outcomes of first relative cases treated with this approach in an ESGO-certified Gynecologic Oncology Center.MethodologyΑ prospective observational cohort was performed during 2020–2022. Epidemiological, histopathological characteristics and indications of the procedure were reviewed. Primary outcomes were intraoperative and postoperative complications, namely hemorrhage, vessel injury, need for transfusion, bowel injury, postoperative bowel dysfunction, perinephral hematoma, total hemoglobin drop, hospitalization duration. Short-term survival outcomes were also reviewed.ResultsThere were overall 8 cases in which laparoscopic retroperitoneal para-aortic lymphadenectomy was attempted. Median age was 52 years, median BMI 26.4. Indications were restaging for apparent early-stage ovarian cancer (n=3), surgical staging of high-risk apparent early-stage endometrial cancer (n=2), restaging for concomitant early-stage endometrial and ovarian cancer (n=1), staging for apparent advanced-stage cervical (n=1) and staging for potential lymph-node recurrence of previously treated vulvar cancer (n=1). All operations were performed by ESGO-certified physicians (S.P, N=6 and F.G, N=2). Method was abandoned in one case in which diagnostic laparoscopy for apparent early-stage serous endometrial cancer revealed diffuse omental metastasis and conversion was decided. Median surgical time was 135 minutes. Median number of resected nodes was 15. No major intraoperative and postoperative complication was observed. There was only 1 case of subcutaneous hematoma observed on 1st postoperative day, treated conservatively with compression. Median haemoglobin reduction was 2.3 gr/dl. Median hospitalization duration was 2 days. The total of patients remains free of recurrence and alive during follow-up period (5–29 months).ConclusionLaparoscopic retroperitoneal para-aortic lymphadenectomy is a safe and effective method, which is associated with low rates of intraoperative and postoperative complications along with favorable oncological outcomes.DisclosuresAll Authors have nothing to disclose

Introduction/BackgroundSentinel node is indicated for staging of low and intermediate risk patients of apparent early-stage endometrial cancer. Main objective of the present cohort was to evaluate the surgical and histopathological outcomes of the first 30 cases in which sentinel node was performed in our ESGO-accredited Department.MethodologyΑ prospective cohort study was conducted during 2020–2022 including the first 30 patients with early-stage endometrial cancer in which sentinel node technique was performed. All cases included in the present study were supervised by certified Gynaecologic Oncologist of Endoscopic Surgeon (S.P, F.G or K.D respectively). Epidemiological, surgical and histopathological outcomes of patients were recorded in a computerized database. Primary outcome of the study was to assess rates of any sentinel detection, bilateral or unilateral detection as well as to record main intraoperative and postoperative complications. Secondary outcome was to report final FIGO staging along with main histopathologic parameters.ResultsMean patients’ age was 64.5 years. Technique was performed laparoscopically in 28 cases and with laparotomy in 2 cases. At least one sentinel node was detected in all cases of the cohort. Macroscopic bilateral detection was achieved in 28 cases (93.3%), while histologically confirmed detection in 24 cases (80.0%). Non-detection concerned left side in 4 cases and right side in 2 cases. No major intraoperative or postoperative complication was observed in these cases. There was 1 case in which sentinel node was positive for nodal involvement (3.3%) and was upstaged to IIIC. Final FIGO staging was IA in 33.3% of patients (10/30), IB in 60.0% of patients (18/30), II in 6.7% of patients (2/30) and IIIC in 3.3% (1/30).ConclusionSentinel node is safe and effective technique with high rates of nodal status detection. Current ESGO guidelines necessitating the performance of technique in apparent early-stage endometrial cancer cases should be widely implemented by ESGO-accredited Departments.DisclosuresAuthors have nothing to disclose

Introduction/BackgroundTo present the video of the laparoscopic procedure of a fertility-sparing surgery performed in a 28-year old patient leading to the final diagnosis of non-invasive stage IIIA borderline tumor.MethodologyMedical elements and video files were reviewed in order to present medical history and final video of the procedure. Windows movie maker was used in order to create the final video originated from the original files.ResultsA 28-year old patient was admitted with a suspicious mass of 89x76 diameter originated from the right ovary. CA-125 was 53 IU/mL. MRI and transvaginal U/S rather posed the suspicion for a borderline ovarian tumour. No indication of extraovarian disease was made. The decision for fertiity-sparing surgery was made for the patient, including right salpingoophorectomy, peritoneal cytology, peritoneal and omental biopsies. Laparoscopy indicated not only the presence of the right ovarian tumour but also the presence of a left ovarian implant, which was also resected conservatively in order to retain the maximum of left ovarian tissue. Masses were oncologically removed into laparoscopic endobag. The final pathological diagnosis was non-invasive borderline bilateral tumor, however the presence of a vascular omental invasion was also detected upgrading final staging to IIIA. Based on current ESGO recommendations, patient decided to continue with plan of fertilty preservation and has already performed ovarian cryopreservation leading to retrieval of 11 eggs after two consequent stimulations.. Decision of laparoscopic re-operation for contralateral salpingoophorectomy and omentectomy to reassure oncological safety has been made.ConclusionLaparoscopic surgery for non-invasive advanced-stage borderline tumour is feasible and may give the possibility for fertility preservation.DisclosuresAuthors have nothing to disclose.