Search

Background: ‘ALARM’ is a systematic review of available literature aiming to provide updated information on the prevalence of Human Papillomavirus (HPV) in locally-regionally advanced (LA) and recurrent/metastatic (RM) head and neck cancer (HNC) worldwide. Methods: Electronic searches were conducted on clinicaltrials.gov, MEDLINE (via Pubmed), Embase and ASCO/ESMO journals of congresses for interventional studies (IS; phase I-III trials) as well as MEDLINE and Embase for non-interventional studies (NIS) of LA/RM HNC published between 01Jan2010 and 31Dec2020. Criteria for study selection included: availability of HPV prevalence data for patients with LA/RM HNC, patient enrollment from 01Jan2010 onwards, and oropharyngeal cancer (OPC) included among HNC types. HPV prevalence per study was calculated as proportion of HPV-positive (HPV+) over total number of HNC enrolled patients. For overall HPV prevalence across studies, mean of reported HPV prevalence rates across studies and pooled estimate, i.e., sum of all HPV+ patients over sum of all HNC patients enrolled, were assessed. Results: Eighty-one studies (62 IS; 19 NIS) were included in this evidence synthesis, representing 9607 LA/RM HNC cases, with an overall mean (pooled) HPV prevalence of 32.6% (25.1%). HPV prevalence was 44.7% (44.0%) in LA and 24.3% (18.6%) in RM. Among 2714 LA/RM OPC patients from 52 studies with available data, the mean (pooled) value was 55.8% (50.7%). The majority of published HPV prevalence data were derived from countries in Northern America and Europe, with overall HPV prevalence of 46.0% (42.1%) and 24.7% (25.3%) across studies conducted exclusively in these geographic regions, respectively. Mean (pooled) HPV prevalence in Northern Europe was 31.9% (63.1%), numerically higher than the European average. A “p16-based” assay was the most frequently reported HPV detection methodology (58.0%). Conclusion: Over the last decade, at least one quarter of LA/RM HNC and half of OPC cases studied in IS and NIS were HPV+, with variation across disease stages and geographic regions. This alarming burden is consistent with a potential implication of HPV in the pathogenesis of at least a subgroup of HNC. The observed rates underscore the relevance of HPV testing and prophylaxis to the prevention and management of these cancers. PROSPERO Number: CRD42021256876

Pancreatic neuroendocrine tumors (panNETs) are rare neoplasms with challenging disease management. We aimed to evaluate the progression-free survival (PFS) and overall response rate (ORR) in chemotherapy-naïve patients with unresectable or metastatic Grade (G) 1-2 panNETs treated with everolimus in the routine care in Greece.This was a multicenter, prospective, observational study. Eligible patients were recently (≤4 weeks) initiated on treatment with everolimus and were followed for up to 48 months.Nineteen eligible patients (mean age 55.1 years) were enrolled. All patients had metastatic disease and 84.2% had G2 panNET. Everolimus was initiated in combination with somatostatin analogues in 84.2% of the patients. The mean everolimus treatment duration was 21.5 months. The median Kaplan-Meier-estimated PFS was 20.4 months (95% confidence interval=14.1-41.5). The ORR was 27.8%. The rate of everolimus-related adverse events was 84.2% (Grade ≥3: 31.6%).Everolimus displayed clinical benefit and a predictable safety profile in pancreatic neuroendocrine tumors.

Immunoscore® is a digital pathology diagnostic immunoassay used to complement tumor node metastasis staging for the prediction of recurrence risk in patients with early-stage colon cancer. In combination with standard clinicopathological features, Immunoscore informs adjuvant chemotherapy decision-making for patients with early-stage colon cancer. Immunoscore has been validated in patients with stage II/III colon cancer and demonstrated to be a stronger prognostic factor for survival than tumor node metastasis staging alone. Immunoscore improves the prognostic definition of patients with colon cancer, the identification of those patients at high risk of tumor recurrence, and the ability to predict which patients will derive most benefit from the use of adjuvant chemotherapy. Immunoscore has robust analytical performance characteristics which include good interlaboratory reproducibility and overall assay precision.

BACKGROUND AND AIMS Immune checkpoint inhibitors (CPIs)—a landmark in cancer therapy—has been occasionally associated with immune-related nephropathy [1]. Acute interstitial nephritis is considered to be the most common underlying histological entity, according to recent literature [2]. METHOD We report on six patients, 58–73 years old, three women and three men who presented with acute kidney disease, while on immunotherapy with CPIs. Five of them carried the diagnosis of non-small cell lung carcinoma (NSCLC) and one the diagnosis of renal cell carcinoma. All received proton pump inhibitors and experienced one or more of immune-related adverse events (dermatitis, arthritis, colitis, hepatitis and pneumonitis), prior to nephropathy. All underwent kidney biopsy. RESULTS Two female patients, both with NSCLC, developed heavy nephrotic syndrome (serum albumin: 1.7–1.8 mg/dL and 24-h urine protein: 12–16 g), after 23–28 months on pembrolizumab monotherapy, which was withdrawn. In the first patient, kidney biopsy demonstrated histology consistent with a lupus like membranous nephropathy (Figure 1). She received corticosteroids with partial recovery. Rechallenge with pembrolizumab was attempted and well tolerated. Renal biopsy of the second patient demonstrated a secondary AA (+) amyloidosis (Figure 2). She showed increased levels of SAA (114 mg/L) and IL-1b (22.9 pg/mL). She received colchicine and moderate dose of corticosteroids with partial remission. Two other patients, with NSCLC and clear cell renal carcinoma respectively, demonstrated renal biopsy findings consistent with acute interstitial nephritis (serum creatinine 1.5–1.6 mg/dL). The first one was on pembrolizumab along with cisplatin and pemetrexed, while the second one was on pembrolizumab along with axitinib. Both received prednisolone (10–20 mg for 3 months approximately). Pembrolizumab was restarted thereafter. Their renal function remained stable. Finally, two patients with NSCLC, both men, disclosed acute renal failure (serum creatinine: 3.6- 5 mg/dL) without considerable albuminuria. Acute tubular injury (ATI) was the predominant histological finding (along with focal and mild interstitial inflammation). Both were on combined chemo- and immune- therapy. One on ipilimumab and nivolumab along with platinum and pemetrexed and the other on pembrolizumab and pemetrexed. ATI was attributed most probably to pemetrexed which was withdrawn. Corticosteroids were promptly stopped in the first patient. The second patient showed gradual improvement of his renal function without corticosteroid therapy. CONCLUSION CPIs can induce nephropathy other than acute interstitial nephritis. Renal biopsy showed diverse and unusual histological findings. Renal biopsy along with the clinical setting was helpful in choosing appropriate therapy and deciding on CPI's continuation or withdrawal.

This non-interventional, multicenter, prospective study aimed to evaluate the real-world activity of trabectedin, and its impact on symptom burden and quality of life in patients with advanced soft tissue sarcoma (aSTS) treated in routine clinical settings in Greece. Patients with histologically confirmed aSTS newly initiated on trabectedin were enrolled. The primary endpoint was progression-free survival (PFS) rate at 6 months. Secondary endpoints included PFS rate at 3 months, median PFS, objective response rate (ORR), disease control rate (DCR), overall survival (OS), and an assessment of the impact of treatment on health-related quality of life (HRQoL), cancer-related symptom burden and symptom interference with function, as well as all-cause treatment discontinuation rate. A total of 64 eligible patients from 13 Greek centers were evaluated. Patients received a median of three trabectedin cycles per patient (interquartile range [IQR]: 2.0–6.0). Median PFS was 6.6 months with 67.9% and 51.2% of patients free from progression at 3 and 6 months, respectively. ORR was 7.8% and DCR 21.9%. Median OS was 13.1 months. No significant changes from enrolment were noted in HRQoL scores. In total, 30 patients (46.9%) had at least one trabectedin-related adverse drug reaction (ADR) and 9 (14.1%) at least one serious ADR. The treatment discontinuation rate due to toxicity was 9.4%. These results suggest that trabectedin is an active treatment with clinically meaningful benefits in patients with aSTS with no new safety signals.

We reported the alveolar bone histology prior to dental extractions in cancer patients, who received bone-targeting agents (BTA).Fifty-four patients were included. Patients underwent extractions, and bone biopsies were taken.Extractions were performed due to pain, swelling, purulence, fistula, and numbness, not responding to treatment, in 40 patients (group A); extractions due to asymptomatic, non-restorable teeth, were performed in 14 patients (group B). Complete alveolar jaw bone histological necrosis was observed in 28 of 40 (70%) patients of group A and none of group B (p .001). The development of clinical osteonecrosis (MRON) was assessed in 44 patients; 10 patients, who were also treated with Low Level Laser Treatments-LLLT, were excluded from this analysis, as the alternative therapies were a confounding factor. Twelve patients, with alveolar bone histological necrosis prior to extraction, developed medication-related osteonecrosis of the jaw (MRONJ) compared with two patients with vital or mixed vital/non-vital bone (p .0007). BTAs1 year and concurrent targeted therapy were also significantly associated with MRONJ (p = .016 and p = .050).Pain, swelling, purulence, fistula, and numbness were significantly associated with complete bone histological necrosis prior to extractions and increased MRONJ development. Research is justified to explore whether histological necrosis represents an early stage of osteonecrosis.

BACKGROUND/AIM: Age may pertain to different tumor genotype characteristics which may interfere with treatment efficacy and prognosis. We investigated the distribution and prognostic effect of mutations and tumor infiltrating lymphocyte (stromal TIL density) in young (≤35 years) and elderly (>65 years) early breast cancer patients. MATERIALS AND METHODS: Paraffin tumor genotypes of all clinical subtypes from 345 patients were examined. RESULTS: A total of 638 mutations were detected in 221 patients (64.1%). Compared to young, elderly patients presented with lower TIL density (p

Highlights • DP-CAR: A rare, technically demanding operation with significant morbidity & mortality. • DP-CAR may provide curative (R0) resection of an otherwise unresectable cancer. • Our patient had optimal perioperative outcome and excellent histology result. • To the best of our knowledge this is the first DP-CAR case in Greece., Introduction Distal pancreatectomy with en bloc celiac axis resection (DP-CAR) is an operation technically demanding, uncommonly performed, even in high-volume pancreatic centers, which may offer a curative resection in patients with locally advanced cancer of the body of the pancreas, otherwise considered unresectable. Presentation of case We present, in clinical and technical detail, a patient with DP-CAR with a very good intraoperative and postoperative course, no complications, short hospital stay, and histology consistent with a curative resection. Discussion Because of the scarcity of DP-CAR, even high-volume individual centers have been able to gather relatively limited experience, and only in a time frame of more than a decade each. Conclusion DP-CAR can be curative for a minority of patients with pancreatic adenocarcinoma and is performed only in centers with a long, dedicated interest in advanced pancreatic surgery with a well-known track record in resection of borderline and locally advanced pancreatic cancer involving major peripancreatic veins.

Background: Globally 43.8 million people live with cancer. A 60% increase of cancer cases is estimated by 2040, with 29.4 million patients per year requiring therapy. Optimization of cancer management, using digital innovation, is urgently needed. CureCancer is a patient-centric/driven platform, which enables patients to self-create their profile, report symptoms, and communicate with physicians. We assessed CureCancer’s feasibility and patients’ and HCPs’ satisfaction. Methods: Patients from 9 Centers were asked to register at CureCancer, upload their data and complete a questionnaire on demographics, disease and treatment characteristics, and their satisfaction. Results: 159 patients were enrolled and 144 (90.6%) registered. 114 of 144 (79.1%), 63 males and 51 females, median age 54.5 years, completed the questionnaire. 64 patients were University and 35 were high School graduates. 46 patients had metastatic disease, 87 were on active treatment and 51 received supportive care. All patients also visited non-oncology HCPs. Nineteen patients changed work status and 49 had children below 24 years. Registration was “very/very much” easy for 98 (86.0 %) patients. File uploading was “very/very much” easy for 47 (41.2%) patients. Over 80% of patients and physicians preferred the digital way. 99 patients and all HCPs will recommend CureCancer to others. Easy data access, improved communication, feeling safe, treatment adherence, interventions from distance, particularly during covid-19 pandemic and saving time and money, were highly commented by patients and HCPs. Conclusion: CureCancer was feasible, and patients and HCPs were satisfied. Patients were successful to report information on their demographics, disease and treatment characteristics. They also disclosed the need to visit non-oncology HCPs during their cancer treatment and other socioeconomic issues. Integration of CureCancer in the routine practice is expected to improve cancer care and reduce cancer costs. Patients’ self-reporting, with CureCancer, can increase the accuracy of clinical trial results and map social/work/economic issues following cancer diagnosis to assist health care policy.

ImmunoscorePlain language summary Immunoscore

Front-line bevacizumab (BEV) in combination with taxanes offers benefit in progression-free survival (PFS) in metastatic breast cancer (mBC). The medical records of mBC patients, treated with front-line BEV-based chemotherapy, were retrospectively reviewed in order to generate real life safety and efficacy data. Patients with human epidermal growth factor receptor 2 (HER2)-negative mBC treated with front-line BEV in combination with chemotherapy were eligible. Maintenance therapy with BEV and/or hormonal agents was at the physicians’ discretion. Among the 387 included patients, the most common adverse events were anemia (61.9%, mainly grade 1), grade 3/4 neutropenia (16.5%), grade 1/2 fatigue (22.3%), and grade 1/2 neuropathy (19.6%). Dose reductions were required in 164 cycles (7.1%) and toxicity led to treatment discontinuation in 21 patients (5.4%). The median PFS and the median overall survival (OS) were 13.3 (95% CI: 11.7–14.8) and 32.3 months (95% CI: 27.7–36.9), respectively. Maintenance therapy, with hormonal agents (ET) and/or BEV, was associated with longer OS versus no maintenance therapy (47.2 versus 23.6 months; p < 0.001) in patients with hormone receptor (HR)-positive disease and BEV maintenance offered longer OS versus no maintenance in patients with HR-negative disease (52.8 versus 23.3; p = 0.023). These real-life data show that front-line BEV-based chemotherapy in HER2-negative mBC patients is an effective treatment with an acceptable toxicity profile. The potential benefit of maintenance treatment, especially ET, is important and warrants further research.

Stress-induced cardiomyopathy or takotsubo syndrome is a rare, nonischemic, heart condition resembling that of an acute coronary syndrome. Its distinctive feature is a transient wall motion abnormality occurring usually at the apical segment of the heart, with the degree of symptom manifestation and severity varying among patients. Although early data were supportive of a benign sequela and outcome, high degree of adverse events, such as acute heart failure and pulmonary edema, are anticipated, and the mortality rate approaches 5%. Hyperactivation of the sympathetic nervous system and adrenergic drugs have been pointed out as possible precipitators of the condition. Surgical procedures are a known cause of emotional and physical stress on patients, acting as an ideal substrate for the presentation of this syndrome. On occasion of a perioperative takotsubo syndrome case in a female patient during second-stage implant-based breast reconstruction, a review of the pertinent literature is presented. The acute onset and severity of the manifestations in this surgically uneventful procedure necessitated a multidisciplinary approach. Consequently, this report should raise awareness of the syndrome among plastic surgeons and anesthesiologists to promptly recognize and manage it effectively.

Purpose: We assessed CureCancer’s feasibility and patients’ and HCPs’ satisfaction. CureCancer is a patient-centric/driven platform, which enables patients to self-create their profile, report symptoms and communicate with physicians.Methods: Patients from 18 Centers were asked to register at CureCancer, upload their data and complete a questionnaire on demographics, disease and treatment characteristics, and their satisfaction. Results: 159 patients were enrolled and 144 (90.6%) registered. 114 of 144 (79.1%), 63 males and 51 females, median age 54.5 years, completed the questionnaire. 64 patients were University and 35 were high School graduates. 46 patients had metastatic disease, 87 were on active treatment and 51 received supportive care. All patients also visited non-oncology HCPs. Nineteen patients changed work status and 49 had children below 24 years. Registration was “very/very much” easy for 98 (86.0 %) patients. File uploading was “very/very much” easy for 47 (41.2%) patients. Over 80% of patients and physicians preferred the digital way. 99 patients and all HCPs will recommend CureCancer to others. Easy data access, improved communication, feeling safe, treatment adherence, interventions from distance, particularly during covid-19 pandemic and saving time and money, were highly commented by patients and HCPs. Conclusion: CureCancer was feasible and patients and HCPs were satisfied. File uploading changed to become more user friendly. Integration of CureCancer in the routine practice is expected to improve cancer care and reduce cancer costs. Patients’ self-reporting, with CureCancer, can increase the accuracy of clinical trial results and map social/work/economic issues following cancer diagnosis to assist health care policy.

This case demonstrates the importance of understanding that patients with malignant neoplasms may exhibit metastases in unexpected sites and illustrates the necessity of a thorough clinical examination and pathologic correlation.

Pancreatic cancer (PaC) induces a prothrombotic and hypercoagulable state. The aim of this study was to investigate the effect of tinzaparin in combination with chemotherapy. The PaCT (pancreatic cancer and tinzaparin) study was a retrospective observational study that collected data regarding progression free survival (PFS) in advanced or metastatic PaC patients who received thromboprophylaxis with tinzaparin during chemotherapy with nab-paclitaxel (N) and gemcitabine (G). The primary end point was to compare, from already published data, the PFS of patients receiving thromboprophylaxis with tinzaparin with the PFS of patients receiving chemotherapy with N–G but no thromboprophylaxis. Secondary end points were efficacy and safety of anticoagulation. In total, 110 PaC patients, 93% with advanced or metastatic disease, treated with N–G and tinzaparin (10,291 ± 1176 Anti-Xa IU, OD, median duration 8.7, IQR: 5.6–11.9 months) were enrolled. Of these, 52% were males and, the median age was 68 (40–86 years). The tumor was located to in the pancreatic head at in 45% of the patients. The median PFS was 7.9 months (IQR: 5.0–11.8 months). Out of 14 similar studies (involving 2994 patients) identified via systematic search, it was determined that the weighted PFS of patients receiving N–G but no anticoagulation was 5.6 months. Therefore, patients receiving tinzaparin had 39.54% higher PFS than patients without thromboprophylaxis (p &lt, 0.05). During the follow-up period of 18.3 ± 11.7 months, three (2.7%) thrombotic events were recorded while two clinically relevant non-major bleeding events occurred (1.9%). In conclusion, PFS in advanced PaC patients undergoing chemotherapy is positively impacted by anticoagulation. Thromboprophylaxis with tinzaparin in treatment dose is efficient and safe.

Background: Patients with pancreatic cancer (PC), which is not upfront resectable, but borderline, involving major peripancreatic vessels, have not been generally considered for surgery, considering that resection in such a setting may be futile. Materials and Methods: Retrospective analysis of prospectively collected data on patients with borderline pancreatic adenocarcinoma undergoing pancreatectomy en-block with portal and/or superior mesenteric vein resection in a tertiary referral center in Greece between January 2012 and February 2017. Follow-up was complete up to January 2018. Results: Twenty-four patients were included. Neoadjuvant therapy (NAT) was administered to only 38%, but more commonly in the second half of the group (58% vs. 17%, p = 0.035). It was associated with smaller tumor size (median: 2.5 vs. 4.2 cm, p

e18520 Background: Homologous Recombination deficiency (HRD) represents a distinct entity in OC. Clinical data suggest that treatment selection can be based on both BRCA1/2 mutations and bearing Genomic Instability Status (GIS). Testing for GIS is critical in order to expand patients’ pool for targeted treatment. Myriad my Choice, is currently the only FDA approved test that can detect HRD by assessing BRCA1/BRCA2 mutation and GIS status in OC tumor specimens using 3 biomarkers: loss of heterozygosity, telomeric allelic imbalance and large-scale state transitions. To address this need, HeSMO has initiated a national program to provide access to myChoice to newly diagnosed patients with high grade stage III/IV OC. Methods: Patients with newly diagnosed stage III/IV high grade OC were eligible to participate in this program. The specific performance characteristics of myChoice CDx assay were determined on FFPE tumor samples by the evaluation of a range of representative tumor BRCA1 and BRCA2 sequence variants (e.g. single nucleotide variants, insertions or deletions and variants in homopolymers), Large Rearrangements (e.g. deletions and duplications affecting single and multiple exons) and a representative range of GIS. The overall results are composed of two major components: GIS Status (positive or negative) and tumor (t) BRCA1/2 Status (positive or negative). The combined results form the basis of the overall interpretation of the myChoice CDx Myriad HRD Status. Results: From December 2020 to January 2022, 454 patients from all over the country were tested within this program. 220 patients (48.46%) had a positive GIS report and 179 (39.43%) had a negative one. Among GIS positive cases, 122 patients were tBRCAwt (26.87%) 78 patients were tBRCA mutated (17.18%) and 10 patients had suspected deleterious BRCA1/2 mutations (2.20%). Inconclusive was the report in 38 specimens (8.37%) and myChoice Lab failed to complete the analysis in 15 cases (3.30%). Furthermore, mutations were also detected in a number of other genes, including but not limited to, ATM, BRIP1, PALB2, RAD51C, RAD51D, FANCL, CHEK2. Conclusions: In our series, 48.46% of the patients with high grade OC tested as BRCA1/2 and/or GIS positive, in accordance with published data, underlying the clinical need to implement GIS testing in OC patients’ molecular evaluation. Apart from the significant implications for treatment possibilities in an expanded patients’ population, these results are important for cancer prevention. We strongly believe that our results will strengthen our efforts for reimbursement of such testing in high grade OC patients, and will serve as a roadmap for the establishment of local HRD testing solutions.

e18677 Background: Venous ThromboEmbolism (VTE), might be a challenge with a lot of negative consequences for patients with active cancer. VTE affects ongoing anticancer treatment, worsening morbidity and mortality, increases economic burden and escalates psychological distress. Incidence of VTE in patients with cancer reported 20%. Current guidelines recommend pharmacologic prophylaxis in ambulatory cancer patients with Khorana score ≥2. Methods: ACT4CAT is a prospective observational phase IV study conducted by HeSMO Greece, aiming to record the clinical practice of VTE prophylaxis in active cancer patients. Ambulatory patients who received thromboprophylaxis enrolled after signing informed consent. Study was approved by bioethics committee. Results: 691 patients from 19 oncology departments received thromboprophylaxis in 1st line 57.6%, 2nd line 14.8%, adjuvant 9.0% and neoadjuvant 7.5%. Age ≥65 found 55%, BMI≥30 17.5% and males 63%. Tumor types: gastrointestinal 45.4%, lung 25.8%, urological 11.6%, gynecological 6.0%, breast 4.2% and others 7.0%. High-Risk for Thrombosis Agents (HRTAs) received 87.2%, specifically: platinum agents (56.3%), antimetabolites (54.2%) and immunotherapy (12.1%). 54,5% of the anticancer agents had potential drug-drug interaction (DDI) with anticoagulation treatment. Thromboprophylaxis duration lasted 5.3±3.5 months. Main agents were: tinzaparin 89.6%, fondaparinux 6.0%, bemiparin 2.2%, enoxaparin 1.6%, apixaban 0.3% and rivaroxaban 0.3%. Intermediate thromboprophylaxis dose received 68% of patients, lower in adjuvant setting (45.2%), with a preference in metastatic cases (OR: 1.5 95% CI: 1.02-2.3, p = 0.026). 14 thrombotic events reported (efficacy: 98.0%, 95%CI: 96.6-98.8%) and 12 grade 1 bleeding (1.7%, 95%CI: 1.0-3.0%). Conclusions: Prevention of VTE in ambulatory patients with active cancer found effective and safe. Apart from the Khorana score, specific patient characteristics, metastasis, HRTAs and DDIs seemed that affect clinical decision for thromboprophylaxis mainly with LMWHs and often on intermediate dose regardless the clinical setting. Oncologists appeared informed that CAT is not negligible risk. Clinical trial information: NCT03909399. [Table: see text]

Objectives The aim of this study was to test the hypothesis that more intensive over standard anticoagulation administered during coronary angiography would significantly reduce rates of radial artery occlusion (RAO). Background RAO, although silent, remains a frequent and therefore worrisome complication following transradial coronary angiography. Anticoagulation is effective in reducing RAO, but the optimal heparin dose remains ill defined. Methods In this multicenter, randomized superiority trial, a high dose (100 IU/kg body weight administered in divided doses) and a standard dose (50 IU/kg body weight) of heparin during 5- or 6-F coronary angiography were compared. A total of 3,102 patients were randomized, of whom 1,836 patients not proceeding to percutaneous coronary intervention and without need for arterial access crossover entered the trial. Post-catheterization hemostasis did not follow a rigid protocol. Results A total of 102 early RAOs were found on ultrasonography (incidence 5.6%). In the high-dose heparin group, the rate of RAO was significantly lower compared with the standard-dose heparin group (27 [3.0%] vs. 75 [8.1%]; odds ratio: 0.35; 95% confidence interval: 0.22 to 0.55; p Conclusions High compared with standard heparin dose significantly reduced the rate of RAO in patients undergoing coronary angiography. High-intensity anticoagulation should be considered in transradial diagnostic procedures. (High [100IU/Kg] Versus Standard [50IU/Kg] Heparin Dose for Prevention of Forearm Artery Occlusion; NCT02570243 )

Background The advanced lung cancer inflammation index [ALI: body mass index × serum albumin/neutrophil-to-lymphocyte ratio (NLR)] reflects systemic host inflammation, and is easily reproducible. We hypothesized that ALI could assist guidance of non-small-cell lung cancer (NSCLC) treatment with immune checkpoint inhibitors (ICIs). Patients and methods This retrospective study included 672 stage IV NSCLC patients treated with programmed death-ligand 1 (PD-L1) inhibitors alone or in combination with chemotherapy in 25 centers in Greece and Germany, and a control cohort of 444 stage IV NSCLC patients treated with platinum-based chemotherapy without subsequent targeted or immunotherapy drugs. The association of clinical outcomes with biomarkers was analyzed with Cox regression models, including cross-validation by calculation of the Harrell's C-index. Results High ALI values (>18) were significantly associated with longer overall survival (OS) for patients receiving ICI monotherapy [hazard ratio (HR) = 0.402, P < 0.0001, n = 460], but not chemo-immunotherapy (HR = 0.624, P = 0.111, n = 212). Similar positive correlations for ALI were observed for objective response rate (36% versus 24%, P = 0.008) and time-on-treatment (HR = 0.52, P < 0.001), in case of ICI monotherapy only. In the control cohort of chemotherapy, the association between ALI and OS was weaker (HR = 0.694, P = 0.0002), and showed a significant interaction with the type of treatment (ICI monotherapy versus chemotherapy, P < 0.0001) upon combined analysis of the two cohorts. In multivariate analysis, ALI had a stronger predictive effect than NLR, PD-L1 tumor proportion score, lung immune prognostic index, and EPSILoN scores. Among patients with PD-L1 tumor proportion score ≥50% receiving first-line ICI monotherapy, a high ALI score >18 identified a subset with longer OS and time-on-treatment (median 35 and 16 months, respectively), similar to these under chemo-immunotherapy. Conclusions The ALI score is a powerful prognostic and predictive biomarker for patients with advanced NSCLC treated with PD-L1 inhibitors alone, but not in combination with chemotherapy. Its association with outcomes appears to be stronger than that of other widely used parameters. For PD-L1-high patients, an ALI score >18 could assist the selection of cases that do not need addition of chemotherapy., Highlights • ALI is prognostic and predictive for patients with advanced NSCLC treated with immunotherapy monotherapy, but not chemo-immunotherapy. • Its association with outcomes is stronger than that of other parameters (PD-L1 TPS, NLR, lung immune prognostic index, EPSILoN). • For PD-L1-high patients, an ALI score >18 could assist the selection of cases that do not need addition of chemotherapy.

We report a case of a 58-year-old female with ovarian cancer. The patient presented with ascites, and the biopsies revealed a low-grade adenocarcinoma, either a serous papillary ovarian cancer with peritoneal implants or a primary peritoneal carcinoma. She received neoadjuvant chemotherapy and after 5 cycles achieved partial response, and then, she underwent a total hysterectomy/bilateral salpingo-oophorectomy. The patient underwent germline gene-panel testing for the detection of mutations in cancer predisposing genes. A truncating mutation in the Fanconi anemia complementation group M (FANCM) gene was detected in heterozygosity, namely, p.Arg658Ter (c.1972C>T, rs368728266). The patient’s family history is unremarkable, with no reported cases of breast or ovarian cancer, a fact that can be attributed to the significant lower penetrance of FANCM mutations.

e21164 Background: The treatment of advanced non-small cell lung cancer (aNSCLC) has tremendously changed during the last few years, especially, since immune checkpoint inhibitors (ICIs) were incorporated in the daily clinical practice. However, clinical useful biomarkers remain an unmet need. Recently, our group established and proposed a new score, Patras Immunotherapy Score (PIOS), which was found to have predictive and prognostic value in a discovery group with aNSCLC patients treated with nivolumab or pembrolizumab. The objective of the current study was to validate our initial observation and confirm the clinical significance of PIOS formula in an external and multicentric cohort of aNSCLC patients. Methods: PIOS is a baseline formula derived by combining the following non-interventional clinical parameters, Performance Status (PS), Body Mass Index (BMI), age and Line Of Treatment (LOT) and it is calculated as PIOS = (PS×BMI)/(LOT×AGE). In the current multicenter study, 626 aNSCLC patients, treated with nivolumab or pembrolizumab monotherapy, were retrospectively selected, blindly to the clinical outcome, and enrolled. The primary endpoints of this study were to investigate the predictive and prognostic value of PIOS in terms of progression free survival (PFS), overall survival (OS) and best overall response. Results: Firstly, PIOS was associated with best overall response. Following a two-tier model, patients who had progressed (PD) had lower scores than those with stable disease (SD), partial response (PR) or complete response (CR) (p < 0.001). This association remained significant using a four-tier model (PD, SD, PR and CR) for evaluation of best overall response (p < 0.001). In addition, predictive significance of PIOS score also persisted using a binary logistic regression analysis, adjusted for disease stage and PD-L1 status (p = 0.002, OR 0.578, 95% CI 0.408-0.821). Furthermore, patients with higher PIOS score had longer PFS compared to patients with lower PIOS score (ΗΡ 0.621, 95% CI 0.470-0.821, p = 0.001), while multivariate analysis for PFS, adjusted for clinical stage and PD-L1, confirmed the predictive value of PIOS score (HR 0.651, 95% CI 0.492-0.863, p = 0.003). Moreover, PIOS score was also associated with prognosis (p < 0.001). The median OS for the favorable group was 778 days compared to 341 days for the unfavorable group with low PIOS score (HR = 0.608, 95% CI 0.482-0.766, p < 0.001) at univariate analysis. This association remained statistically significant (HR 0.620, 95% CI 0.492-0.783, p < 0.001) after adjusting for PD-L1 expression. Conclusions: These data provide further validation for PIOS as predictive and prognostic biomarker in aNSCLC patients treated with nivolumab or pembrolizumab monotherapy.

e18803 Background: Cancer Associated Thrombosis (CAT) is an increasing challenge for oncology patients since oncologists sometimes are reluctant to mitigate the risk with thromboprophylaxis. Active cancer patients while receiving chemotherapy have a 7fold risk of thrombosis compared with no cancer patients. Anticoagulation holds a prominent place in prevention of CAT usually with Low Molecular Weight Heparins (LMWHs). Methods: ACT4CAT is prospective observational study conducted by HeSMO across Greece, aiming to record the clinical practice of CAT prophylaxis in patients with solid tumors. Ambulatory, high thrombotic risk, active cancer patients who received thromboprophylaxis enrolled after signing informed consent. Results: Preliminary results collected from 18 oncology departments. From 431 enrolled patients 322 (65.4%) had completed the study. Tumor types included: lung 28.8%, gastrointestinal 39.8%, gynecological 7.0%, breast 4.4%, urological 7.0% and others 20%. Majority of patients (88.2%) received High-Risk for Thrombosis Chemotherapy Agents (HRTCAs) such as platinum agents (55.9%), antimetabolites (44.7%) and immunotherapy (12.6%). In 1st line were 62.1%, 2nd line 18.4%, adjuvant 8.9% and neoadjuvant 2.4%. The following table depicts: age, gender, metastatic disease, Khorana score ≥2 and HRTCAs. All patients received thromboprophylaxis for 5.3±3.6 months with: tinzaparin 90.8%, fondaparinux 5.5%, bemiparin 1.5%, enoxaparin 1.2%, apixaban 0.5% and rivaroxaban 0.5%. Intermediate doses received 70.9% of patients regardless clinical setting (1st, 2nd, adjuvant & neoadjuvant: 70.2%, 79.2%, 51.3% and 70.0% respectively, p = 0.0254), although intermediate doses were used more in metastatic stages (OR:2.4 95%CI: 1.4-4.2, p = 0.0028). Nine thrombotic events reported (2.1%, 95%CI: 1.1-3.9%), irrespective of clinical setting but with a trend towards prophylactic doses. Eleven grade 1 bleedings reported (2.6%, 95%CI: 1.4-4.5%), despite clinical setting or dose used. Conclusions: Thromboprophylaxis in ambulatory active cancer patients with high thrombotic risk is safe and effective. Oncologists are alerted about CAT negative influences in cancer patients’ prognosis. Apart from Khorana score, factors such as metastases, use of HRTCAs and drug-drug interactions influence the clinical decision of thromboprophylaxis in active cancer patients mainly with LMWHs and quite often with intermediate doses regardless clinical setting. Clinical trial information: NCT03909399. [Table: see text]

e14135 Background: CAT is the 2nd leading cause of death in oncology patients and there is need for thrombosis management across the natural history of cancer because of its dynamic nature. Anticoagulant therapy is the cornerstone of prevention and treatment, since thrombosis interferes with cancer treatment, increases health care resource utilization, imposes emotional and economic burden. Methods: A prospective observational study conducted by HeSMO across Greece, aiming to record the clinical practice of CAT prophylaxis in patients with solid tumors. Ambulatory, high risk for thrombosis, active cancer patients who received thromboprophylaxis are enrolled after signing informed consent. Results: Preliminary results are collected from 17 oncology departments. From the 272 enrolled patients, 176 (64.7%) have completed second visit (3-4 cycles of anticancer treatment). Primary cancers included: lung 31.3%, pancreas 26.1%, colorectal 13.6%, gynecological cancers 10.2%, stomach 7.8%, bladder 6.3%, and others.75.6% of the patients had metastatic disease. 1/3 of the patients were smokers or ex-smokers, and 33% underwent surgery. Most of patients (65.9%) were at 1st line treatment and 17.6% at 2nd line. The vast majority (90.3%) were treated with High-Risk for Thrombosis Chemotherapy Agents (HRTCAs) such as cisplatin etc. Regarding Khorana score, 65.1% had ≥2. In particular, 86.7% of patients with Khorana score ≤1 received HRTCAs while 95.4% of patients with score = 2.All patients received thromboprophylaxis, specifically: 93.0% tinzaparin, 5.2% fondaparinux and 1.8% other (enoxaparin, bemiparin) with average duration 5.3±3.1 months. 67.1% of the patients received higher than standard prophylactic doses. 3 patients (1.7%) experienced thrombotic events (2 DVT and 1 PE). These 3 patients had metastases and were treated with HRTCAs. Five grade 1 bleeding events were reported (2.8%). Conclusions: Thromboprophylaxis of CAT is both safe and effective. Oncologists are alerted about CAT negative influences in cancer patients’ prognosis. Apart from Khorana score, factors such as metastases, use of HRTCAs along with drug-drug interactions, increase the LMWHs usage often in higher than prophylactic doses in CAT management. Clinical trial information: NCT03909399.

The aim of this study was to test the hypothesis that more intensive over standard anticoagulation administered during coronary angiography would significantly reduce rates of radial artery occlusion (RAO).RAO, although silent, remains a frequent and therefore worrisome complication following transradial coronary angiography. Anticoagulation is effective in reducing RAO, but the optimal heparin dose remains ill defined.In this multicenter, randomized superiority trial, a high dose (100 IU/kg body weight administered in divided doses) and a standard dose (50 IU/kg body weight) of heparin during 5- or 6-F coronary angiography were compared. A total of 3,102 patients were randomized, of whom 1,836 patients not proceeding to percutaneous coronary intervention and without need for arterial access crossover entered the trial. Post-catheterization hemostasis did not follow a rigid protocol.A total of 102 early RAOs were found on ultrasonography (incidence 5.6%). In the high-dose heparin group, the rate of RAO was significantly lower compared with the standard-dose heparin group (27 [3.0%] vs. 75 [8.1%]; odds ratio: 0.35; 95% confidence interval: 0.22 to 0.55; p 0.001), without compromising safety. The time to achieve hemostasis was similar between groups. To avoid 1 RAO, the number of patients needed to treat in the high-dose heparin group was approximately 20. These results were corroborated by our integrated database, showing an 80% reduction of forearm artery occlusions in high versus low heparin dose patients and our updated meta-analysis of randomized controlled trials demonstrating significant benefit of higher over lower anticoagulation intensity.High compared with standard heparin dose significantly reduced the rate of RAO in patients undergoing coronary angiography. High-intensity anticoagulation should be considered in transradial diagnostic procedures. (High [100IU/Kg] Versus Standard [50IU/Kg] Heparin Dose for Prevention of Forearm Artery Occlusion; NCT02570243).

Relapsed urothelial cancer represents an unmet medical need. Vinflunine is a third-generation antimicrotubuline inhibitor and is currently the only approved drug for second-line treatment across the European Union. We conducted a retrospective analysis assessing the efficacy and safety of vinflunine in 71 Greek patients with relapsed urothelial cancer who were treated between 2005 and 2014. An overall 84% of our patients received vinflunine as second-line treatment, 77% had a performance status of Eastern Cooperative Oncology Group scale 0 or 1, and 30% had liver metastasis at the time of vinflunine administration. A median of four cycles of vinflunine were administered (range 1-16). The most common reported adverse events were constipation, fatigue, and anemia. Median progression-free survival was 6.2 months (95% confidence interval: 4.4-8.8) and overall survival was 11.9 months (95% confidence interval: 7.4-21). Two patients (3%) achieved a complete remission, seven a partial remission (10%), and 22 (31%) had stable disease according to an intention-to-treat analysis. Hemoglobin level less than 10 g/dl and Eastern Cooperative Oncology Group performance status greater than 1 were independent adverse prognostic factors. Stratification according to the Bellmunt risk model was also associated with progression-free survival and overall survival in our population. Vinflunine appears to be a safe and effective treatment modality for relapsed urothelial cancer. More effective therapies and more accurate prognostic algorithms should be sought.

5562 Background: The standard of care for Epithelial Ovarian cancer (EOC) is the combination of a taxane plus a platinum compound (TC) whereas the addition of bevacizumab (bev) to this regimen (TC-bev) has been shown to improve the PFS. Patients (pts) with ascites have more aggressive disease and less overall survival. The aim of the study was to evaluate the safety of the TC/bev regimen in the real life clinical practice. Methods: A multi-center observational study, approved by the ethics committees of the participating centers, including 314 pts with stage III/IV EOC, was conducted (11.2011-06.2014) in Greece. Two independent cohorts, with similar clinico-pathologic characteristics, were treated with front-line TC (n = 109) or TC/bev (n = 205) according to the physician’s choice. 83 (40.5%) and 40 (36.7%) in the TC/bev and TC groups presented with ascites. Results: Disease control was achieved in 90.7% and in 78.9% of patients treated with TC/bev and TC, respectively (p = 0.003). Pts with ascites treated with TC/bev experienced a better overall response rate (ORR) (68.7% Vs 55%) and less progression disease (PD) compared to patients receiving TC (13.2% Vs 30.8%). The median PFS in all pts was 21.5mo and 12.4mo (p < 0.001) and median PFS in ascites pts was 18.1mo and 10.3mo in the TC/bev and TC cohort , respectively (p < 0.001). The median OS was not reached in the TC/bev group and it was 36.9mo in the TC group, ( p = 0.059) while in the ascites pts also has not reached and it is 22.5m, respectively ( p = 0.023). The 3 year survival rate in all pts was 59.4% and 50.4% and in ascites pts was 55.3% and 30% in the TC/bev and TC respectively. Neutropenia was the most common grade 3/4 adverse event in 16.6% and 9.1% in TC/bev- and TC- treated patients ( p = 0.072) with no other adverse events > 5%. Conclusions: These real life data demonstrate that the combination of TC/bev represents an active and well tolerated regimen offering survival benefit in patients with stage III/IV EOC and especially in patients with ascites. Additional larger prospective studies are required to confirm these observations. Clinical trial information: NCT01982500.

Objective We examined trans-radial approach (TRA) use in coronary angiographies (CAs) as well as in percutaneous coronary interventions (PCIs) in specific regions of Greece, its distribution in public and private catheterization laboratories (CLs) and its preference by operators. Reliable data regarding the use of TRA are not available in Greece. Methods The study was performed in northern and central Greece, which constitutes 35.32% of the national population. This study focused on the years 2004, 2009 and 2013. Results There are 12 CLs. CAs performed using TRA were 0.43% in 2004, 12.28% in 2009 and 39.81% in 2013, whereas PCIs performed using TRA were 0.38%, 9.20% and 39.48%, respectively. Operators familiar with TRA, but who performed TRA electively, were 13.33% in 2004, 60.38% in 2009 and 42.37% in 2013. However, operators performing TRA routinely were 2.2%, 5.66%, and 49.15%, respectively. In 2013, there was a 3.76% decrease in CAs and 4.51% decrease in PCIs compared to 2009; in private CLs, there was a 29.63% decrease in CAs and 34.72% decrease in PCIs performed, which was contradictory to the 27.27% increase observed in CAs and 29.83% increase in PCIs in public CLs. Conclusions This is the first study to reveal the volumes and trends in interventions performed via TRA across central and northern Greece. TRA has gained a reputation among operators in both public and private CLs. Due to the financial crisis in Greece, catheterizations have been diminished, whereas private CLs have lost a great amount of their turnover.

Background: State health insurance authorities in Greece do not reimburse genetic testing for cancer predisposition. The Hellenic Society of Medical Oncology has launched and carries out a national program covering genetic testing for BRCA1/2 mutations detection, with the financial support of pharmaceutical industry. Aim: This analysis evaluates how, during this program, access to genetic testing transformed the oncologists' therapeutic approach toward their ovarian cancer patients and how the results impacted treatment decisions concerning PARP inhibitors. Adoption of testing by healthy relatives and timing of testing in the disease continuum were also evaluated. Methods: Adult patients with high-grade epithelial ovarian carcinoma, irrespectively of family history or age at diagnosis were eligible for this program. Genetic counseling was recommended before testing, and both were offered at no financial cost. First degree family members of pathogenic mutation carriers were also offered free counseling and testing. Results: From March 2015 through January 2018, 708 patients were enrolled and tested. One hundred and forty seven (20.7%) mutation carriers were identified, 102 (14.4%) in BRCA1 and 45 (6.3%) in BRCA2 gene. Testing was more often pursued at initial diagnosis (61%) than at recurrence (39%), as recorded for 409 patients with available relevant information. During the 1st year of the program, average monthly tests performed were 25.1, while during the 3rd year this number increased to 34.3 tests per month. Among patients who tested positive for deleterious BRCA1/2 mutations, relapse was reported in 58 patients, 94.8% of which (n= 55) received treatment with the PARP inhibitor olaparib as per its indication. Family members of 21 patients (14.3%), out of the 147 who tested positive, received genetic counseling and testing for the mutation identified in the context of the program. Conclusion: Free access to genetic testing for BRCA1/2 for ovarian cancer patients and genetic consultation facilitates testing uptake, affects common clinical practice & has major impact on patients and their families. Still, diffusion of genetic information and broader testing of family members require further efforts by the oncological community.

e15521Background: Bevacizumab (BEV) is an active antiangiogenic agent for the treatment of all patients (pts) with advanced colorectal cancer (CRC). We investigated the toxicity, compliance and sur...

Industrial scale-up of whey fermentation, promoted by raisin extracts, using free kefir-yeast cells is reported. The fermented whey would be exploited as raw material to produce kefir-like whey-based drinks, potable and fuel alcohol, as well as kefir-yeast biomass for use as baker's yeast. The scale-up process involved the development of a technology transfer scheme from lab-scale experiments to a successive series of increased capacity bioreactors (100, 3000 and 11,000 L). The development of this technology was supported by the six-fold promotion of whey fermentation by the addition of 1% black raisin extracts (optimum concentration found in this investigation), as well as by the formation of kefir-yeast in the form of easily precipitated granular biomass that led to the avoidance of centrifugal separators, which are equipment of high cost. A cost analysis showed a big reduction of the production cost of the aforementioned products in comparison with the market prices, attributed to the negligible cost of raw materials (whey) and the granular biomass formation.

Tumors arising at the lacrimal sac are extremely rare, as a limited number of cases have been reported worldwide. They are commonly primary and the majority of them are malignant and epithelial in origin. Adenocarcinomas account for a small percentage of these tumors. Treatment of local disease mainly includes complete surgical resection. However, metastatic disease has a poor prognosis and the development of new treatment strategies is highly important. Research efforts mainly focus on the identification of molecular targets for therapy. Herein, we describe for the first time a case of a patient with an Androgen Receptor expressing adenocarcinoma of the lacrimal sac that had an impressive response to abiraterone.