Search

Background Specific data regarding coronavirus disease 2019 (COVID-19) in patients with neuroendocrine neoplasms (NENs) are lacking. The aim of this study is to describe the characteristics of patients with NENs who tested severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive. Material and methods This is a worldwide study collecting cases of patients with NENs along with a positive nasopharyngeal swab reverse transcriptase-polymerase chain reaction (RT-PCR) test for SARS-CoV-2 between June 1, 2020, and March 31, 2021. Centres treating patients with NENs were directly contacted by the principal investigator. Patients with NENs of any primary site, grade and stage were included, excluding small-cell lung carcinoma and mixed adenoneuroendocrine carcinoma. Results Among 81 centres directly contacted, 88.8% responded and 48.6% of them declined due to lack of cases or interest. On March 31st, 2021, eight recruiting centres enrolled 89 patients. The median age was 64 years at the time of COVID-19 diagnosis. Most patients had metastatic, non-functioning, low-/intermediate-grade gastroenteropancreatic NENs on treatment with somatostatin analogues and radioligand therapy. Most of them had comorbidities. Only 8% of patients had high-grade NENs and 12% were receiving chemotherapy. Most patients had symptoms or signs of COVID-19, mainly fever and cough. Only 3 patients underwent sub-intensive treatment, whereas most of them received medical therapies, mostly antibiotics. In two third of cases, no changes occurred for the anti-NEN therapy. More than 80% of patients completely recovered without sequelae, whereas 7.8% patients died due to COVID-19. Conclusions Patients included in this study reflect the typical NEN population regardless of SARS-CoV-2. In most cases, they overcome COVID-19 without need of intensive care, short-term sequelae and discontinuation of systemic oncological therapy.

Neuroendocrine neoplasms (NENs) are a group of heterogeneous malignancies, arising from the neuroendocrine system. These neoplasms are divided into two distinct groups, the low-proliferating, well-differentiated neuroendocrine tumors (NETs), and the highly-proliferating, poorly-differentiated neuroendocrine carcinomas (NECs). Recent data demonstrate that the incidence of gastroenteropancreatic (GEP) neuroendocrine neoplasms, GEP-NETs and GEP-NECs, has increased exponentially over the last three decades. Although surgical resection is considered the best treatment modality, patients with GEP-NETs often present with advanced disease at diagnosis associated with a 5-year survival rate of 57% for well-differentiated tumors, and only 5.2% for small-cell tumors. Immunotherapy is a novel treatment approach, which has demonstrated effective and promising therapeutic results against several types of cancers. In the present study, we review the current ongoing clinical trials and to evaluate the efficacy of immunotherapy in GEP-NENs. Furthermore, we analyze the importance of tumor genetic profiling and its clinical implications in immunotherapy response.

Giannis Mountzios,1 Sofia Lampaki,2 Georgia-Angeliki Koliou,3 Athanassios Vozikis,4 Ioannis Kontogiorgos,4 Panagiotis Papantoniou,4 Margarita-Ioanna Koufaki,4 Eleni Res,5 Anastasios Boutis,6 Athina Christopoulou,7 Nicoleta Pastelli,8 Anastasios Grivas,9 Gerasimos Aravantinos,10 Efthalia Lalla,11 Georgios Oikonomopoulos,12 Anna Koumarianou,13 Dionisios Spyratos,2 Dimitrios Bafaloukos Snr,14 Georgios Rigakos,15 Pavlos Papakotoulas,6 George Fountzilas,16– 18 Helena Linardou19 1Fourth Department of Medical Oncology and Clinical Trials Unit Henry Dunant Hospital Center, Athens, Greece; 2Pulmonary Department, Lung Cancer Oncology Unit, Aristotle University of Thessaloniki, G. Papanicolaou Hospital, Thessaloniki, Greece; 3Section of Biostatistics, Hellenic Cooperative Oncology Group, Athens, Greece; 4Laboratory of Health Economics and Management, Department of Economics, University of Piraeus, Piraeus, Greece; 5Third Department of Medical Oncology, Agii Anargiri Cancer Hospital, Athens, Greece; 6First Department of Clinical Oncology, Theagenio Hospital, Thessaloniki, Greece; 7Medical Oncology Unit, S. Andrew Hospital, Patras, Greece; 8Department of Pathology, G. Papanicolaou Hospital, Thessaloniki, Greece; 9Second Department of Internal Medicine, Agios Savvas Cancer Hospital, Athens, Greece; 10Second Department of Medical Oncology, Agii Anargiri Cancer Hospital, Athens, Greece; 11Third Department of Clinical Oncology, Theagenio Hospital, Thessaloniki, Greece; 12Second Department of Medical Oncology, Metropolitan Hospital, Piraeus, Greece; 13Hematology-Oncology Unit, Fourth Department of Internal Medicine, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece; 14First Department of Medical Oncology, Metropolitan Hospital, Piraeus, Greece; 15Third Department of Medical Oncology, Hygeia Hospital, Athens, Greece; 16Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research/Aristotle University of Thessaloniki, Thessaloniki, Greece; 17Aristotle University of Thessaloniki, Thessaloniki, Greece; 18Department of Medical Oncology, German Oncology Center, Limassol, Cyprus; 19Fourth Oncology Department, Metropolitan Hospital, Athens, GreeceCorrespondence: Giannis MountziosFourth Department of Medical Oncology and Clinical Trials Unit, Henry Dunant Hospital Center, Messoghion Av. 107, Athens, 11526, GreeceTel +2106972000Email gmountzios@gmail.comPurpose: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the preferred first-line option for patients with advanced, EGFR-mutant non-small cell lung cancer (NSCLC). Afatinib, a second-generation irreversible EGFR-TKI, has been extensively used in Greece in this setting; however, real-world data regarding molecular epidemiology and financial implications of afatinib use are lacking.Materials and Methods: This was an observational, non-interventional, multicenter, retrospective cohort study, based on real-world data collected from the medical charts/records of patients treated with afatinib between 15/03/2015 and 25/06/2020 and were recorded on a web-based data capture system. Cox models were used to assess the prognostic significance of clinicopathological parameters with respect to clinical outcomes of interest. Cost analysis was conducted from a public third-payer perspective, and only direct medical costs reimbursed by the payer were considered.Results: A total of 59 patients were treated with afatinib for their EGFR mutation-positive advanced NSCLC; the median age was 61 years (range: 37– 91). Performance status was zero in 61%, and brain metastases were present in 13.6%. Forty-four patients (74.6%) had a deletion in exon 19 only, while nine (15.3%) had a mutation in exon 21, 8 of them in L858R and one in L861Q. At a median follow-up of 41.8 months (95% CI 35.9– 51.4), the median PFS was 14.3 months (95% CI 12.2– 16.4), and the median OS was 29 months (95% CI 25.6– 33.4). Corresponding values for patients with deletion 19 only were 14.3 months (95% CI 11.5– 18.5) and 28.1 months (95% CI 21.1– 32.6), respectively. The mean expenditure for the treatment of each patient equals € 25,333.68; with € 21,865.06 being attributed to drug acquisition costs, € 3325.35 to monitoring costs and € 143.27 to adverse event treatment-related costs.Conclusion: Long-term data in the real-world setting in Greece confirm activity, tolerability and cost-effectiveness of afatinib as first-line treatment of patients with advanced EGFR-mutant NSCLC.Clinical Trial Registration: Clinicaltrials.gov NCT04640870.Keywords: lung cancer, epidermal growth factor receptor, EGFR, afatinib, molecular epidemiology, cost-effectiveness

The efficacy of nab-paclitaxel in patients with metastatic breast cancer (MBC) has been demonstrated in randomized clinical trials. However, real-world evidence on effectiveness remains limited. The primary objective of this multicenter prospective study was to assess the overall response rate (ORR) of patients with MBC treated with nab-paclitaxel. Secondary objectives included progression-free survival (PFS), overall survival (OS) and quality of life, assessed with the Functional Assessment of Cancer Therapy-Breast (FACT-B) instrument. Eligible patients (N = 150; 36% with de novo MBC presentation) with a median age of 64.5 years were enrolled (86% were ER+, 33.3% (50/150) were ≥ 70 years of age and 53% were treated in the third or later line of treatment). A median of 6 cycles were administered but 26% of patients required dose reduction due to toxicity. The ORR was 26.7% [95% confidence interval (CI) 19.6–33.7], the median PFS was 6.2 months (95% CI 5.2–7.3), and the median OS 21.1 months (95% CI 17.2-not estimable). There was no statistical significant difference in the median PFS of patients

BACKGROUND/AIM Primary sarcomas of the lung (PSL) represent a rare, largely unknown entity. We herein present a retrospective study of 26 patients diagnosed with PSL. PATIENTS AND METHODS For a period of 10 years, the records of patients from 5 centers were gathered and analyzed. RESULTS Median age at diagnosis was 61.96 years (range=31-75 years). Eight patients (33.33%) had mediastinal node invasion (MNI). From 17 patients (70.83%) with localized disease, 11 patients (64.70%) underwent surgery. Recurrence rate was 72.72%. Median disease-free interval was 15 months. The median overall survival (OS) of patients with metastatic disease was 4 months and 10 months for the whole population. Only surgery had an impact on survival. CONCLUSION Prognosis of PSL is somber. The high proportion of patients with MNI at diagnosis may serve as an indication for surgical evaluation of mediastinum and raises the question whether patients with locoregional PSL should be treated with a more aggressive approach.

Introduction: Nanoparticle albumin-bound (nab)-paclitaxel (nab-P) is approved for the treatment of patients with metastatic breast cancer (MBC) who have failed first-line treatment for metastatic disease and for whom standard, anthracycline containing therapy is not indicated. Real-world evidence on the effectiveness of nab-P is sparse. From this perspective, this non-interventional study was designed to assess the impact of nab-P on the clinical outcomes and the quality of life of patients with MBC in the routine care of Greece. Materials and methods: This multicenter prospective study enrolled consented females with MBC initiated (≤7 days prior to enrollment) on nab-P according to physicians decision. Clinicopathologic parameters and patient-reported outcomes [Functional Assessment of Cancer Therapy-Breast (FACT-B)] were collected at approximately 9-week intervals during the first 12 months of study participation and approximately every 18 weeks thereafter, until the end of the study observation period (maximum 30 months). Results: Between April 2016 and October 2017, 150 eligible patients (99.3% Caucasian) were enrolled in the study in 16 oncology centers. The patients’ median age was 64.5 years (range: 30.7-84.0) and ECOG performance status was 0 in 66.4% and 1 in 26.2%. 45.3% of patients had ≥1 comorbidity (21.3% cardiovascular diseases). The median time elapsed since MBC diagnosis was 22.4 months, while 36.0% of patients were de novo metastatic. The distribution of hormone receptor (HR)/human epidermal growth factor receptor 2 (HER2) status was 74.6% HR+/HER2-, 11.9% HR-/HER2-, 11.2% HR+/HER2+, and 2.2% HR-/HER2+. Most commonly occurring metastatic sites were the bones (55.3%), lung (50.0%), and liver (40.0%). Prior taxane-based therapy was annotated in 40.0% of patients. Of the patients, 11.3% received nab-P as first, 36.0% as second, 23.3% as third, and 29.3% as fourth or further treatment line. A median of 6 cycles (range: 1-33) was administered; 42.7% of the patients completed >6 and 22.0% >8 cycles. Dose reductions were required for 26.0% of the patients, mainly due to toxicity. The objective response rate was 26.7% and the clinical benefit rate was 44.0%. After a median follow-up of 19.3 months, 92 patients had progressed and 57 had died (14 without progression). The median progression-free survival (PFS) was 6.2 months [95% confidence interval (CI): 5.2-7.3]. The 6- and 12-month PFS rates were 50.6% and 30.5%, respectively. The median overall survival was 21.1 months (95% CI: 17.2-not estimable). Liver [hazard ratio (HR): 1.81; 95% CI: 1.24-2.66] and lung (HR: 1.53; 95% CI: 1.04-2.25) metastases were associated with a higher risk of progression or death. No statistically significant change in the patients’ baseline FACT-B total score (median: 93.0) was observed. The serious and non-serious adverse event (AE) incidence rates were 12.7% and 48.0%, respectively with a total of 37 grade ≥3 AEs (not including disease progression) reported. Conclusion: This study generated real-world evidence on the effectiveness of nab-paclitaxel; no new safety signals emerged. Citation Format: Anna Koumarianou, Paris Makrantonakis, Flora Zagouri, Christos Papadimitriou, Athina Christopoulou, Epaminontas Samantas, Christos Christodoulou, Amanda Psyrri, Dimitris Bafaloukos, Gerasimos Aravantinos, Pavlos Papakotoulas, Sofia Baka, Charalampos Andreadis, Athanasios Alexopoulos, Iliada Bombolaki, Katerina Kampoli, Sofia Liori, Kiki Karvounis, Alexandros Ardavanis. Real-world multicenter, prospective study of the effects of nab-paclitaxel on clinical outcomes and quality of life of patients with metastatic breast cancer in Greece. The ‘ABReast’ study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-15-07.

Background: We evaluated the association between pathogenic mutations and overall survival (OS) in patients with cancer referred to Hellenic Cooperative Oncology Group-affiliated Departments. Patients and methods: Patients referred from 12/1980 to 1/2017 had molecular testing (for research) of archival tumor tissue collected at the time of first diagnosis (non-metastatic, 81%; metastatic, 19%). Tumor-specific gene panels (16-101 genes) were used to identify pathogenic mutations in clinically relevant genes. NGS genotyping was performed at the Laboratory of Molecular Oncology, Aristotle University of Thessaloniki. Annotation of mutations was performed at MD Anderson Cancer Center. Results: We analyzed 3,084 patients (median age, 57 years; men, 22%) with sequencing data. Overall, 1,775 (58% of 3,084) patients had pathogenic mutations. The median follow-up was 7.52 years (95% CI, 7.39-7.61). In patients with non-metastatic tumors, after stratification by tumor type, increasing age, higher grade, and histology other than adenocarcinoma were associated with shorter OS. OS was also shorter in patients with pathogenic TP53 (HR=1.36; p

The European Neuroendocrine Tumor Society (ENETS) promotes practices and procedures that aim to improve the standard of care delivered to patients diagnosed with or suspected of having neuroendocrine neoplasia (NEN). At its annual Scientific Advisory Board Meeting in 2018, experts in imaging, pathology and clinical care of patients with NEN drafted guidance for the standardised reporting of diagnostic studies critical to the diagnosis, grading, staging and treatment of NEN. These included pathology, radiology, endoscopy and molecular imaging procedures. In an iterative process, a synoptic reporting template for molecular imaging procedures was developed to guide personalised therapies. Following pilot implementation and refinement within the ENETS Center of Excellence network, harmonisation with specialist imaging societies including the Society of Nuclear Medicine, European Association of Nuclear Medicine and the International Cancer Imaging Society will be pursued. ispartof: JOURNAL OF NEUROENDOCRINOLOGY vol:34 issue:3 ispartof: location:United States status: published

Gastric cancer, the fifth most frequent cancer and the fourth leading cause of cancer deaths, accounts for a devastating death rate worldwide. Since the majority of patients with gastric cancer are diagnosed at advanced stages, they are not suitable for surgery and present with locally advanced or metastatic disease. Recent advances in immunotherapy have elicited a considerable amount of attention as viable therapeutic options for several cancer types. This work presents a summary of the currently ongoing clinical trials and critically addresses the efficacy of a large spectrum of immunotherapy approaches in the general population for gastric cancer as well as in relation to tumor genetic profiling.

Background Data on the safety and efficacy of immune checkpoint inhibitors (ICI) in patients with concurrent autoimmune diseases (AID) are limited. Methods We performed a retrospective multicenter review of medical records of patients with cancer and underlying AID who received ICI. The primary endpoint was progression-free survival (PFS). Results Among 123 patients with pre-existing AID who received ICI, the majority had been diagnosed with non-small cell lung cancer (NSCLC, 68.3%) and melanoma (14.6%). Most patients had a rheumatologic (43.9%), or an endocrine disorder (21.1%). Overall, 74 (60.2%) patients experienced an immune-related adverse event (irAE) after ICI initiation, AID flare (25.2%), or new irAE (35%). Frequent irAEs included thyroiditis, dermatitis and colitis. ICI was permanently discontinued due to unacceptable (8.1%) or fatal (0.8%) toxicity. In patients with NSCLC, corticosteroid treatment at the initiation of immunotherapy was associated with poor PFS (HR = 2.78, 95% CI 1.40–5.50, p = 0.003). The occurrence of irAE was associated with increased PFS (HR = 0.48, 95% CI 0.25–0.92, p = 0.026). Both parameters maintained their independent prognostic significance. Conclusions ICI in patients with cancer and pre-existing AID is associated with manageable toxicity that infrequently requires treatment discontinuation. However, since severe AID flare might occur, expected ICI efficacy and toxicity must be balanced. Clinical trial identifier NCT04805099

Simple Summary Non-small cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer cases, with few patients carrying driver mutations in the gene encoding for epidermal growth factor receptor (EGFR). Advances in translational research have established EGFR tyrosine kinase inhibitors (TKIs) as the standard first-line therapy for NSCLC patients with activating EGFR mutations. The aim of our observational study was to assess the frequency of T790M acquired resistance and predictors of its presence, in patients with EGFR-mutated locally advanced or metastatic NSCLC who have progressed in the first-line EGFR-TKI treatment setting with first- or second-generation TKIs and have undergone molecular testing in tissue and/or plasma biopsy. The study highlights the challenges of performing tissue re-biopsy in routine care settings, which can lead to patients considered non-eligible for certain therapies from which they can benefit, and merits further actions from the healthcare community, in order to establish re-biopsy as a standard procedure. Abstract Background: Real-world data on the molecular epidemiology of EGFR resistance mutations at or after progression with first- or second-generation EGFR-TKIs in patients with advanced NSCLC are lacking. Methods: This ongoing observational study was carried out by 23 hospital-based physicians in Greece. The decision to perform cobas® EGFR Mutation Test v2 in tissue and/or plasma at disease progression was made before enrollment. For patients with negative/inconclusive T790M plasma-based results, tissue re-biopsy could be performed. Results: Ninety-six (96) eligible patients were consecutively enrolled (median age: 67.8 years) between July-2017 and September-2019. Of the patients, 98% were tested upon progression using plasma and 2% using tissue/cytology biopsy. The T790M mutation was detected in 16.0% of liquid biopsies. Tissue re-biopsy was performed in 22.8% of patients with a T790M-negative plasma result. In total, the T790M positivity rate was 21.9%, not differing between patients on first- or second-generation EGFR-TKI. Higher (≥2) ECOG performance status and longer (≥10 months) time to disease progression following EGFR-TKI treatment initiation were associated with T790M positivity. Conclusions: Results from plasma/tissue-cytology samples in a real-world setting, yielded a T790M positivity rate lower than previous reports. Fewer than one in four patients with negative plasma-based testing underwent tissue re-biopsy, indicating the challenges in routine care settings.

Background Hereditary cancer predisposition syndromes are responsible for approximately 5–10% of all diagnosed cancer cases. In the past, single-gene analysis of specific high risk genes was used for the determination of the genetic cause of cancer heritability in certain families. The application of Next Generation Sequencing (NGS) technology has facilitated multigene panel analysis and is widely used in clinical practice, for the identification of individuals with cancer predisposing gene variants. The purpose of this study was to investigate the extent and nature of variants in genes implicated in hereditary cancer predisposition in individuals referred for testing in our laboratory. Methods In total, 1197 individuals from Greece, Romania and Turkey were referred to our laboratory for genetic testing in the past 4 years. The majority of referrals included individuals with personal of family history of breast and/or ovarian cancer. The analysis of genes involved in hereditary cancer predisposition was performed using a NGS approach. Genomic DNA was enriched for targeted regions of 36 genes and sequencing was carried out using the Illumina NGS technology. The presence of large genomic rearrangements (LGRs) was investigated by computational analysis and Multiplex Ligation-dependent Probe Amplification (MLPA). Results A pathogenic variant was identified in 264 of 1197 individuals (22.1%) analyzed while a variant of uncertain significance (VUS) was identified in 34.8% of cases. Clinically significant variants were identified in 29 of the 36 genes analyzed. Concerning the mutation distribution among individuals with positive findings, 43.6% were located in the BRCA1/2 genes whereas 21.6, 19.9, and 15.0% in other high, moderate and low risk genes respectively. Notably, 25 of the 264 positive individuals (9.5%) carried clinically significant variants in two different genes and 6.1% had a LGR. Conclusions In our cohort, analysis of all the genes in the panel allowed the identification of 4.3 and 8.1% additional pathogenic variants in other high or moderate/low risk genes, respectively, enabling personalized management decisions for these individuals and supporting the clinical significance of multigene panel analysis in hereditary cancer predisposition. Electronic supplementary material The online version of this article (10.1186/s12885-019-5756-4) contains supplementary material, which is available to authorized users.

Background: Real-world data on the molecular epidemiology of EGFR resistance mutations at or after progression with first- or second-generation EGFR-TKIs in patients with advanced NSCLC are lacking. Methods: This ongoing observational study was carried out by 23 hospital-based physicians in Greece. The decision to perform Cobas® EGFR Mutation Test v2 in tissue and/or plasma at disease progression was made before enrollment. For patients with negative/inconclusive T790M plasma-based results, tissue re-biopsy could be performed. Results: Ninety-six (96) eligible patients were consecutively enrolled (median age: 67.8 years) between July-2017 and September-2019. Of the patients, 98% were tested upon progression using plasma and 2% using tissue/cytology biopsy. The T790M mutation was detected in 16.0% of liquid biopsies. Tissue re-biopsy was performed in 22.8% of patients with a T790M-negative plasma result. In total, the T790M positivity rate was 21.9%, not differing between patients on first- or second-generation EGFR-TKI. Higher (≥2) ECOG performance status and longer (≥10 months) time to disease progression following EGFR-TKI treatment initiation were associated with T790M positivity. Conclusions: Results from plasma/tissue-cytology samples in a real-world setting, yielded a T790M positivity rate lower than previous reports. Fewer than one in four patients with negative plasma-based testing underwent tissue re-biopsy, indicating the challenges in routine care settings.

Objective: To evaluate the cost-effectiveness of trifluridine/tipiracil (FTD/TPI) compared with best supportive care (BSC) for the treatment of patients with metastatic gastric cancer(mGC), including gastroesophageal junction adenocarcinoma(GEJ), who have received at least two prior therapies for metastatic disease and are eligible for third-line treatment, in Greece.Methods: A partitioned survival model was locally adapted from a public payer perspective over a 10-year time horizon. Clinical, safety and utility data were extracted from literature. Resource consumption data obtained from a panel of local experts using a questionnaire developed for the study was combined with unit costs obtained from official sources. All costs reflect the year 2020 (€). Outcomes of the model were patients' life years (LYs) and quality-adjusted life years (QALYs), total costs and incremental cost-effectiveness ratio (ICER) per QALY and LY gained.Results: The total cost per patient was estimated to be €6,965 for FTD/TPI and €1,906 for BSC, while FTD/TPI was associated with 0.180 and 0.107 increments in LYs and QALYs, respectively, compared with BSC, resulting in an ICER of €47,144 per QALY gained and €28,112 per LY gained.Conclusion: FTD/TPI was estimated to be a cost-effective treatment option for eligible third line mGC patients, including GEJ in Greece.

The intracellular protozoan parasites of the Leishmania genus are responsible for Leishmaniases, vector borne diseases with a wide range of clinical manifestations. Leishmania (L.) donovani causes visceral leishmaniasis (kala azar), the most severe of these diseases. Along their biological cycle, Leishmania parasites undergo distinct developmental transitions including metacyclogenesis and differentiation of metacyclic promastigotes (MPs) to amastigotes. Metacyclogenesis inside the phlebotomine sandfly host’s midgut converts the procyclic dividing promastigotes to non-dividing infective MPs eventually injected into the skin of mammalian hosts and phagocytosed by macrophages where the MPs are converted inside modified phagolysosomes to the intracellular amastigotes. These developmental transitions involve dramatic changes in cell size and shape and reformatting of the flagellum requiring thus membrane and cytoskeleton remodeling in which phosphoinositide (PI) signaling and metabolism must play central roles. This study reports on the LDBPK_220120.1 gene, the L. donovani ortholog of LmjF.22.0250 from L. major that encodes a phosphatase from the “Atypical Lipid Phosphatases” (ALPs) enzyme family. We confirmed the expression of the LDBPK_220120.1 gene product in both L. donovani promastigotes and axenic amastigotes and showed that it behaves in vitro as a Dual Specificity P-Tyr and monophosphorylated [PI(3)P and PI(4)P] PI phosphatase and therefore named it LdTyrPIP_22 (Leishmaniad onovani Tyrosine PI Phosphatase, gene locus at chromosome 22). By immunofluorescence confocal microscopy we localized the LdTyrPIP_22 in several intracellular sites in the cell body of L. donovani promastigotes and amastigotes and in the flagellum. A temperature and pH shift from 25°C to 37°C and from pH 7 to 5.5, induced a pronounced recruitment of LdTyrPIP_22 epitopes to the flagellar pocket and a redistribution around the nucleus. These results suggest possible role(s) for this P-Tyr/PI phosphatase in the regulation of processes initiated or upregulated by this temperature/pH shift that contribute to the developmental transition from MPs to amastigotes inside the mammalian host macrophages.

Simple Summary Data on the prognostic and predictive value of germline cancer predisposing pathogenic/likely pathogenic variants (P/LPVs) in patients with pancreatic ductal adenocarcinoma is limited. This research was a study of germline testing of 62 cancer susceptibility genes in 549 unselected patients with pancreatic cancer. We reported a significant proportion of European patients with pancreatic cancer carrying P/LPVs in clinically significant genes, irrespectively of age, family history or disease stage. Importantly, P/LPVs were identified in pancreatic cancer-associated genes and in homologous recombination repair genes in 4.0% and 7.7% of patients, respectively. The presence of any P/LPVs was associated with improved overall survival univariately; however, it did not retain its independent prognostic significance in multivariate analysis. The presence of P/LPVs in homologous recombination repair genes did not predict benefit from platinum-based treatment. These results should be prospectively validated through universal genetic testing of patients with pancreatic cancer, taking into consideration the administration of newer treatments. Abstract Our aim was to determine the prevalence, prognostic and predictive role of germline pathogenic/likely pathogenic variants (P/LPVs) in cancer predisposing genes in patients with pancreatic ductal adenocarcinoma (PDAC). Germline testing of 62 cancer susceptibility genes was performed on unselected patients diagnosed from 02/2003 to 01/2020 with PDAC, treated at Hellenic Cooperative Oncology Group (HeCOG)-affiliated Centers. The main endpoints were prevalence of P/LPVs and overall survival (OS). P/LPVs in PDAC-associated and homologous recombination repair (HRR) genes were identified in 22 (4.0%) and 42 (7.7%) of 549 patients, respectively. P/LPVs were identified in 16 genes, including ATM (11, 2.0%) and BRCA2 (6, 1.1%), while 19 patients (3.5%) were heterozygotes for MUTYH P/LPVs and 9 (1.6%) carried the low-risk allele, CHEK2 p.(Ile157Thr). Patients carrying P/LPVs had improved OS compared to non-carriers (22.6 vs. 13.9 months, p = 0.006). In multivariate analysis, there was a trend for improved OS in P/LPV carriers (p = 0.063). The interaction term between platinum exposure and mutational status of HRR genes was not significant (p-value = 0.35). A significant proportion of patients with PDAC carries clinically relevant germline P/LPVs, irrespectively of age, family history or disease stage. The predictive role of these P/LPVs has yet to be defined. ClinicalTrials.gov Identifier: NCT03982446.

In two phase III trials, surufatinib, a novel oral tyrosine kinase inhibitor targeting immune cells and angiogenesis, was effective for treating pancreatic and extra-pancreatic neuroendocrine tumours. These findings further expand the therapeutic options for patients with gastro–entero–pancreatic, thymic and lung neuroendocrine tumours.

Recent advances in the field of immunotherapy have significantly prolonged the survival of patients with aggressive carcinomas, but the role of immunotherapy in neuroendocrine neoplasms (NENs) remains to be elucidated. We report a patient diagnosed with a well-differentiated grade 3 pancreatic NEN (pNEN) and type 3 liver metastases who received compassionate nivolumab as a fifth line treatment and achieved a durable partial response of more than 34 months. We have performed a systematic review to the literature on tumor microenvironment and potential biomarkers in the field of NEN including the tumor mutational burden, the tumor infiltrating lymphocytes, the programmed cell death ligand 1, and the mismatch repair system. The potential role of the immune system modulation together with a critical assessment of the recent phase II clinical studies in NEN including monotherapy with anti-PD-1/PD-L1 monoclonal antibodies, and combination therapies including anti-PD-1 along with anti-CTLA-4 monoclonal antibodies are also provided. Immunotherapeutics are gaining a post in the field of NENs in cases progressing during the course of the disease, dictating urgently the identification of biomarkers that will enable selection of NEN patients who may benefit from this treatment.

ObjectivePsychosocial interventions in families of children with cancer are considered an effective way of empowering family members to tackle the complex hurdles they face. The ability of parents to develop adaptive coping strategies during the child's treatment is not only important to their own mental and physical health, but also to their child's well-being and long-term adjustment with the disease.MethodsThe aim of this review was to evaluate the existing literature for the period from 2009 to 2017 on psychosocial interventions targeting families of children with cancer. We searched the PubMed database using the following combination of keywords: “cancer AND children AND (intervention OR training) AND (mothers OR primary caregivers OR parents OR fathers OR siblings).”ResultsAfter careful evaluation of 995 papers, 17 full-text papers were found to match our criteria (12 randomized controlled trials and 5 quasi-experimental studies). The quality of the studies was assessed using the Delphi score questionnaire, and the score of the reviewed studies ranged from 3 to 5. The findings suggest that most interventions reduced distress and improved coping strategies among participants. Interventions, mainly cognitive behavioral therapy and problem-solving skills training targeting maternal distress, were associated with improved adjustment outcomes in mothers of children with cancer.Significance of resultsPsychosocial interventions are helpful, and efforts should be made to promote them in a larger scale. Protocols should be implemented to ensure that all parents benefit. Computer-assisted methods may provide additional benefit by improving cancer-related knowledge and cancer-related communication.

Mesenteric fibrosis (MF) constitutes an underrecognized sequela in patients with small intestinal neuroendocrine neoplasms (SI-NENs), often complicating the disease clinical course. The aim of the present systematic review, carried out by Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology, is to provide an update in evolving aspects of MF pathogenesis and its clinical management in SI-NENs. Complex and dynamic interactions are present in the microenvironment of tumor deposits in the mesentery. Serotonin, as well as the signaling pathways of certain growth factors play a pivotal, yet not fully elucidated role in the pathogenesis of MF. Clinically, MF often results in significant morbidity by causing either acute complications, such as intestinal obstruction and/or acute ischemia or more chronic conditions involving abdominal pain, venous stasis, malabsorption and malnutrition. Surgical resection in patients with locoregional disease only or symptomatic distant stage disease, as well as palliative minimally invasive interventions in advanced inoperable cases seem clinically meaningful, whereas currently available systemic and/or targeted treatments do not unequivocally affect the development of MF in SI-NENs. Increased awareness and improved understanding of the molecular pathogenesis of MF in SI-NENs may provide better diagnostic and predictive tools for its timely recognition and intervention and also facilitates the development of agents targeting MF.

Background. During the last decade, significant improvement was made in systemic therapy of pancreatic adenocarcinoma (PAC). The impact of this progress in everyday clinical practice has not been fully described yet. The aim of the study was to investigate the pattern followed by Greek Medical Oncologists regarding the treatment of patients with PAC. Methods. This observational, noninterventional multicenter study recorded clinical data from the files of 200 active patients (alive and under treatment or follow-up) for a two-year period (November 2015 until November 2017) from 20 oncology centers around Greece. Results. In total, 51 (25.5%) patients underwent radical surgical resection of PAC, and 40 (78.4%) of them received adjuvant and 1 (2.0%) neoadjuvant chemotherapy. The median time to recurrence was 7.9 months, and median overall survival (OS), 20.2 months. First-line chemotherapy was administered to 193 (96.5%) patients. The majority of patients were treated with the combination of nab-paclitaxel-gemcitabine (NPG), 5-fluorouracil, leucovorin, irinotecan, oxaliplatin (FOLFIRINOX), or gemcitabine monotherapy. Of them, 39.5% responded to the treatment. Median OS and PFS were 14.1 months and 7.0 months, respectively. Second-line treatment was administered to 112 patients. The majority received NPG, FOLFIRINOX/capecitabine, oxaliplatin, irinotecan (CAPOXIRI), or 5-fluorouracil, leucovorin, oxaliplatin (FOLFOX)/capecitabine, oxaliplatin (CAPOX). Median OS with second-line treatment was 8.6 months, and median PFS, 5.5 months. The most common chemotherapy sequences were NPG as first-line followed by FOLFIRINOX/CAPOXIRI as second-line, NPG followed by FOLFOX/CAPOX, NPG followed by other regimens, and FOLFIRINOX/CAPOXIRI followed by NPG. Conclusion. This study described the significant improvement in prognosis of PAC patients receiving palliative chemotherapy and the relatively high rate of receipt of second-line chemotherapy, according to real-world data. However, due to the nonrandomized nature of the study, any comparison between different chemotherapy regimens should be regarded with caution.

Authors' Response to the Letter by Lamarca et al. Entitled "Temozolomide-Capecitabine Chemotherapy for Neuroendocrine Neoplasms : The Dilemma of Treatment Duration" Regarding "Activity and Safety of Standard and Prolonged Capecitabine/Temozolomide Administration in Patients with Advanced Neuroendocrine Neoplasms"

The majority of neuroendocrine tumours (NETs) are well-differentiated tumours that follow an indolent course, in contrast to a minority of poorly differentiated neuroendocrine carcinomas (NECs) which exhibit an aggressive course and assocaited with an overall short survival. Although surgery is the only curative treatment for NETs it is not always feasible,necessitating the application of other therapies including chemotherapy. Streptozotocin (STZ)-based regimens have long been used for advanced or metastatic well-to-moderately differentiated (G1-G2) NETs, especially those originating from the pancreas (pNETs). In poorly differentiated grade 3 (G3) tumours, platinum-based chemotherapy is recommended as first-line therapy, albeit without durable responses. Although data for temozolomide (TMZ)-based chemotherapy are still evolving, this treatment may replace STZ-based regimens in pNETs due to its better tolerability and side effect profile. In addition, there is evidence that TMZ could also be used in the subgroup of well-differentiated G3 NETs. There is less clear-cut evidence of a benefit for chemotherapy in intestinal NETs, but still evolving data suggest that TMZ may be efficacious in particular patients. In lung and thymic carcinoids, chemotherapy is reserved for patients with progressive metastatic disease in whom other treatment options are unavailable. Overall, chemotherapy is indicated in patients who have progressed on first-line treatment with somatostatin analogues, have extensive tumour load or exhibit rapid growth following a period of follow-up, and/or have a high proliferative rate; it may occasionally can be used in a neo-adjuvant setting. Prospective randomised studies are awaited to substantiate the role of chemotherapy in the therapeutic algorithm of NETs along with other evolving treatments.

Aim The aim of this analysis is to describe the clinicopathological characteristics of patients (pts) with esophageal cancer diagnosed in our unit. Background and methods Esophageal cancer (EC) is the eighth most common malignancy. Updated data indicate that rates of adenocarcinoma are increasing while the incidence of squamous-cell carcinoma is decreasing in industrialized countries. Epidemiologic data from Greek population are scarce. We analyzed the data of pts diagnosed with EC and treated in our unit from 2009 to 2019. Results Thirty-one pts were diagnosed with EC in our unit, 29 males and 2 females (ratio 14.5:1). Mean age of diagnosis was 62.90±11.19 (39-82) years. Eighteen pts were diagnosed with adenocarcinoma, representing the 58.1% of the sample. Seven pts (22.6%) had squamous-cell carcinoma and 6 pts (19.4%) were classified as “other”. Lower esophagus and gastroesophageal junction were the most common location (20 pts). Four pts had tumors located in the upper esophagus and 3 pts in the medium esophagus. Eleven pts had a previous diagnosis of Barret’s esophagus, of which 7 developed adenocarcinoma, 1 squamous-cell carcinoma and 2 neuroendocrine tumors. Four pts (12.9%) presented with metastases at diagnosis. Thirteen pts were treated in peripheral hospitals after diagnosis, so treatment and follow-up data are available for 18 pts. Of them, 4 pts underwent neoadjuvant chemotherapy and 2 pts received neoadjuvant chemoradiation. Downstaging was achieved in 3 pts (2 complete responses and 1 partial response). Most common treatments applied included radical radiotherapy with chemotherapy followed by surgery in some cases. Nine pts (55.5%) presented relapse with a mean time of progression-free survival of 10.44±9.18(2-29) months. With a mean follow-up of 13.48±14.08 (1-56) months, 4 pts are alive without disease, 8 pts are alive with disease and 6 pts deceased. Mean overall survival was 15.83±11.65(4-36) months. Conclusions EC is a heterogeneous disease with a changing epidemiologic trend. Data from our unit are superimposable to those described worldwide and may be representative of Greek population with EC. However, prospective data at national level are needed.

Introduction/Background Based largely on data from retrospective studies it has been postulated that chemotherapy has an aggravating effect on the cognitive function of breast cancer patients. Potential individual factors related to the effect of chemotherapy on cognitive function have been indicated, such as age-related cognitive dysfunction and stress. Elderly patients differ from non-elderly for higher cognitive related comorbidities, such as dementia, as well as for lower stress levels, indicating that chemobrain may affect differentially these two age groups. The aim of this review is to investigate the effect of stress and chemotherapy on the cognitive dysfunction and identify any potential age-related differences in breast cancer patients treated with adjuvant chemotherapy. Methodology A systematic review of the literature was carried out on Medline, Scopus and Web of Science. The inclusion criteria were original articles published in peer-reviewed journals, elderly and non-elderly patients with breast cancer, reporting on stress and at least one cognitive parameter pre- and/or post-treatment. Results Eight studies met the preset criteria and were further analyzed. 1253 women participated, of whom 800 breast cancer patients treated with surgery only, systemic treatment only, or both. Although all studies included a non-elderly breast cancer patient subpopulation, just two of the studies included patients over 65 years of age. All studies indicated a statistically significant association of stress with various domains of cognitive dysfunction in patients compared to controls, as shown by either self-completed questionnaires, neuropsychological testing or both. Age over 60 was linked to fewer cognitive difficulties mediated by lower levels of stress. Conclusion The evidence supports the association of stress with cognitive deficits in breast cancer patients, regardless of the type of cancer-related treatment. Therefore, stress should be addressed appropriately. Further research is needed to investigate the correlation of stress with cognitive function in elderly patients with breast cancer. Disclosure Nothing to disclose

Introduction/Background Stress, self-esteem and self-rated health are important parameters which have been extensively studied in breast cancer research. However, the correlations between these variables and the proportion of patients experiencing different stress and self-esteem levels are foggy. The aim of this study was to search for correlations between perceived stress, self-esteem and Self-Rated Health (SRH), as well as for their relationship with sociodemographic parameters in breast cancer patients treated with chemotherapy. Methodology The data were collected from 100 patients with breast cancer. Sociodemographic variables, the Perceived Stress Scale (PSS), a 1–5 Lickert scale measuring SRH and the Rosenberg Self-esteem Scale (RSES) were administrated. Pearson9s correlation, Independent Sample9s t-test and ANOVA were utilized. Differences in RSES and PSS levels were presented using proportions based on indicated cut-offs. Results The majority of patients were found to have normal self-esteem (72%), while a high proportion experienced low (38.4%) and mild perceived stress (34.3%). Severe stress was experienced only by 8.1% of the participants. The PSS and RSES scores were inversely correlated (P=0.005), while income satisfaction was positively correlated with SRH (P=0.000) and RSES (P=0.006), and inversely to PSS scores (P=0.033). There were also significant inverse associations between BMI and RSES (P=0.016) and between the number of children and PSS (P= 0.002). Higher PSS (P=0.032) and SRH (P=0.008) scores were recorded for those cohabitating. Finally, there was a significant association between smoking and SRH (P=0.021). Conclusion Only a minority of the participants experienced severe stress, while most of them had normal self-esteem levels. Stress was inversely associated with self-esteem, having more children and a higher income. No relationship between SRH and stress was observed. Future research on the identification of related parameters and the development of interventional programs to address stress should be intensified. Disclosure Nothing to disclose

Aim We retrospectively analyzed the medical files of patients treated with neuroendocrine neoplasms (NENs) of the esophagus in our unit. Background & Methods Esophageal NENs are rare and lacking functional symptoms. This results in a delay of diagnosis that may compromise patient survival. Numerous single cases are reported in literature, without a consensus on their management. The true incidence of esophageal NETs is unknown but evidence indicated geographic variability while smoking and alcohol abuse are the major risk factors. Men (60-70 years) are most commonly afflicted and usual symptoms include dysphagia and loss of appetite with consequent weight loss. The histologic subtypes reported in the literature include high or low-grade NETs and mixed neuroendocrine neoplasms (MINENs). Central pathology assessment significantly contributes to the accurate diagnosis and management. Personalised treatment depends on the grade, involved anatomic region and stage of disease and most commonly comprises combination chemotherapy and radiotherapy and rarely surgery. Results We report on three cases with localized esophageal NET diagnosed with endoscopic biopsies and staged with FDG or Gallium-PET CT scan. The mean age was 56, two were men and histologies included 1 MINEN (lower thoracic esophagus), 1 NET G3 (upper thoracic esophagus) and 1 NET G2 (middle thoracic esophagus). The patient with MINEN was stage 1b and was treated with complete esophagectomy and lymph nodal dissection without any further adjuvant therapy. Two patients with upper and middle thoracic esophagus were treated with combination chemotherapy and definitive IMRT radiotherapy. All patients remain disease free at 12 months follow up. Conclusion Localized esophageal NET are often diagnosed following endoscopic investigation. Long-term survival may be achieved with excellent quality of life after careful evaluation of the clinicopathologic characteristics by a dedicated multidisciplinary group.

Trastuzumab is an antibody used for the treatment of human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancers. Since trastuzumab is an internalizing antibody, two factors could play an important role in achieving high uptake and prolonged retention of radioactivity in HER2-positive tumors after radioiodination&mdash, residualizing capacity after receptor-mediated internalization and susceptibility to dehalogenation. To evaluate the contribution of these two factors, trastuzumab was radiolabeled using the residualizing reagent N-succinimidyl 4-guanidinomethyl-3-[*I]iodobenzoate ([*I]SGMIB) and the nonresidualizing reagent N-succinimidyl-3-[*I]iodobenzoate ([*I]SIB), both of which are highly dehalogenation-resistant. Paired-label uptake and intracellular retention of [125I]SGMIB-trastuzumab and [131I]SIB-trastuzumab was compared on HER2-expressing BT474 human breast carcinoma cells. Tumor uptake and normal tissue distribution characteristics for the two labeled conjugates were assessed in mice bearing BT474M1 xenografts. The internalization and intracellular retention of initially-bound radioactivity in BT474 cells was similar for the two labeled conjugates up to 4 h, but were significantly higher for [125I]SGMIB-trastuzumab at 6 and 24 h. Similarly, [*I]SGMIB labeling resulted in significantly higher uptake and retention of radioactivity in BT474M1 xenografts at all studied time points. Moreover, tumor-to-tissue ratios for [125I]SGMIB-trastuzumab were consistently higher than those for [131I]SIB-trastuzumab starting at 12 h postinjection. Thus, optimal targeting of HER2-positive breast cancers with a radioiodinated trastuzumab conjugate requires an acylation agent that imparts residualizing capacity in addition to high stability towards dehalogenation in vivo.

In spite of recent advances in the diagnosis and management of oesophageal cancer, the overall survival of the disease worldwide remains disappointingly low. In Greece and Cyprus, this may be partly due to a failure of health care providers to implement standardised treatment protocols in clinical practice. Development of clinical practice guidelines was undertaken as a joint project between the Hellenic Society of Medical Oncology (HeSMO) and Gastro-Intestinal Cancer Study Group (GIC-SG) in an effort to provide guidance for Greek and Cypriot clinicians in all aspects of the management of oesophageal cancer. A study group was formed comprising clinicians from different disciplines with a special interest in the management of oesophageal cancer. Following extensive review of the literature, the members of the group met in person and consensus statements were developed, which were later subjected to the Delphi survey process by invited national and international experts. Statements that achieved a rate of voting consensus 80% were adopted. Those that reached a voting consensus of 80% were revised or rejected. In total, 46 sentences were developed and subjected to the voting process. Of those, 45 sentences achieved a rate of consensus 80% during the first voting round. One sentence that did not reach a satisfactory rate of consensus was revised by the members of the study group and subsequently incorporated to the final statement. Forty-six recommendations covering all aspects of the management of oesophageal cancer and concise treatment algorithms are proposed by the Hellenic and Cypriot Oesophageal Cancer Study Group. In particular, centralisation of services, care by multidisciplinary teams and adherence to clinical guidelines are strongly recommended.

Digital ischemia has been rarely associated, as a paraneoplastic syndrome, with renal cancer. Since it can severely compromise the patients’ quality of life, early recognition is important, in order to optimally address it with currently available treatment options, such as tyrosine inhibitors. Digital ischemia may occur in the general population and it can be the result of other non-cancerous diseases; accordingly, a thorough and aggressive work-up is mandatory, together with appropriate therapeutic steps such as tyrosine kinase inhibitors, vasodilators, and antiaggregants. Herein, we report a 78-year-old male patient with a history of clear-cell renal-cell cancer, who presented in the emergency department with critical ischemia in the upper limbs.

Background Pericardial synovial sarcomas (PSS) are very rare tumors, with dismal prognosis and limited data. We describe the clinical features and identify prognostic factors of primary PSS. Case report We describe the case of a 56-year-old male patient with PSS managed by the multidisciplinary team of thoracic oncology. The therapeutic plan comprised surgery, chemotherapy, stereotactic radiosurgery and targeted therapy, with excellent results. Materials and methods Data from 37 cases reported in English during the past 20 years were gathered and analyzed. PSS was found to occur at a mean age of 36±17.082 (range=13-67) years. Survival analysis was performed on 20 cases with follow-up of at least 6 months. Conclusion Only complete resection of the tumor seems to be an independent prognostic factor. To our knowledge, this is the first report on the safety and effectivity of pazopanib in PSS and may provide guidance for similar cases in the future.

BACKGROUND Patients with stage II-III colorectal cancer (CRC) treated with adjuvant chemotherapy, gain a 25% survival benefit. In the context of personalized medicine, there is a need to identify patients with CRC who may benefit from adjuvant chemotherapy. Molecular profiling could guide treatment decisions in these patients. Thymidylate synthase (TYMS) gene polymorphisms, KRAS and BRAF could be included in the molecular profile under consideration. AIM To investigate the association of TYMS gene polymorphisms, KRAS and BRAF mutations with survival of CRC patients treated with chemotherapy. METHODS A retrospective study studied formalin-fixed paraffin-embedded tissues (FFPEs) of consecutive patients treated with adjuvant chemotherapy during January/2005-January/2007. FFPEs were analysed with PCR for the detection of TYMS polymorphisms, mutated KRAS (mKRAS) and BRAF (mBRAF). Patients were classified into three groups (high, medium and low risk) according to 5’UTR TYMS polymorphisms Similarly, based on 3’UTR polymorphism ins/loss of heterozygosity (LOH) patients were allocated into two groups (high and low risk of relapse, respectively). Cox regression models examined the associated 5-year survival outcomes. RESULTS One hundred and thirty patients with early stage CRC (stage I-II: 55 patients; stage III 75 patients; colon: 70 patients; rectal: 60 patients) were treated with surgery and chemotherapy. The 5-year disease free survival and overall survival rate was 61.6% and 73.9% respectively. 5’UTR polymorphisms of intermediate TYMS polymorphisms (2RG/3RG, 2RG/LOH, 3RC/LOH) were associated with lower risk for relapse [hazard ratio (HR) 0.320, P = 0.02 and HR 0.343, P = 0.013 respectively] and death (HR 0.368, P = 0.031 and HR 0.394, P = 0.029 respectively). The 3’UTR polymorphism ins/LOH was independently associated with increased risk for disease recurrence (P = 0.001) and death (P = 0.005). mBRAF (3.8% of patients) was associated with increased risk of death (HR 4.500, P = 0.022) whereas mKRAS (39% of patients) not. CONCLUSION Prospective validating studies are required to confirm whether 2RG/3RG, 2RG/LOH, 3RC/LOH, absence of ins/LOH and wild type BRAF may indicate patients at lower risk of relapse following adjuvant chemotherapy.

Soft tissue sarcomas (STS) are rare tumors; they do not even equate to 1% of all malignant tumor cases. One-fifth of all STS occur in the upper extremities, where epithelioid sarcoma, synovial sarcoma, clear cell sarcoma and malignant fibrohistiocytoma are the most frequent subtypes. Surgical resection is the cornerstone of treatment. However, accomplishment of optimal oncological and functional results of STS of the upper extremities may represent a challenge for hand surgeons, due to the complex anatomy. In several cases, preoperative therapies are needed to facilitate tumor resection and improve the oncological outcome. Oligometastatic disease may also be a challenging scenario as curative strategies can be applied. Radiotherapy and chemotherapy are commonly used for this purpose albeit with conflicting evidence. Novel drug combinations have also been approved in the metastatic setting, further improving the quality of life and survival of eligible patients. Thus, prior to any approach, every case should be individually discussed in sarcoma centers with specialized multidisciplinary tumor boards. The aim of the present review was to gather the multidisciplinary experiences of the available therapeutic strategies for STS of the upper extremities.

Comparisons between everolimus and sunitinib regarding their efficacy and safety in neuroendocrine neoplasms (NENs) are scarce. We retrospectively analysed the clinicopathological characteristics and outcomes in 92 patients with well-differentiated (WD) NEN of different origin (57 pancreatic NENs (PanNENs)), treated with molecular targeted therapy (MTT) with everolimus or sunitinib, first- (73:19) or second-line (sequential; 12:22) for progressive disease. Disease control rates (DCR: partial response or stable disease) at first-line were higher in all patients treated with everolimus than sunitinib (64/73 vs 12/19, P = 0.012). In PanNENs, DCR at first-line everolimus was 36/42 versus 9/15 with sunitinib (P = 0.062). Progression-free survival (PFS) at first-line everolimus was longer than sunitinib (31 months (95% CI: 23.1–38.9) vs 9 months (95% CI: 0–18.5); log-rank P P P = 0.951). Treatment with sunitinib (HR: 3.47; 95% CI: 1.5–8.3; P value: 0.005), KI67 >20% (HR: 6.38; 95% CI: 1.3–31.3; P = 0.022) and prior chemotherapy (HR: 2.71; 95% CI: 1.2–6.3; P = 0.021) were negative predictors for PFS at first line in multivariable and also confirmed at multi-state modelling analyses. Side effect (SE) analysis indicated events of serious toxicities (Grades 3 and 4: n = 13/85 for everolimus and n = 4/41 for sunitinib). Discontinuation rate due to SEs was 20/85 for everolimus versus 4/41 for sunitinib (P = 0.065). No additive toxicity of second-line MTT was confirmed. Based on these findings, and until reliable predictors of response become available, everolimus may be preferable to sunitinib when initiating MTT in progressive NENs.

BackgroundAnalysis 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.MethodsLiquid 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.ResultsAt 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.ConclusionsThis 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.

Aim: The objectives of this study were to validate the Patient Empowerment Strategies Questionnaire (PES-Q) in a Greek sample and to study its psychometric properties in a sample of patients diagnosed with chronic insomnia. Background: This is a validation of the PES-Q in Attikon General Hospital, School of Medicine, National and Kapodistrian University of Athens. The questionnaire was administered to 93 subjects aged between 18 and 85 years (mean age ± SD: 54.7 ± 15.2, 28% males). Methods: The criterion validity of the questionnaire was tested with the use of four specific criteria: the Athens Insomnia Scale, the Pittsburg questionnaire (Pittsburg Sleep Quality Index), the Depression, Anxiety and Stress Scale, and the Self-Esteem Scale. Findings: According to factor analysis results, the structure of the original scale was confirmed by the presence of one main factor in the Greek sample, explaining 40.1% of the variance of PES-Q queries. The questionnaire showed satisfactory reliability (Cronbach’s α = 0.887). The results of the current study suggest that the PES-Q may be used as an accurate psychometric instrument for the purposes of chronic insomnia. Future research should examine the psychometric qualities of the PES-Q Greek version in a larger sample.

e16205 Background: Data about neuroendocrine neoplasms (NENs) patients with SARS-CoV-2 are scanty and specific indications for clinical practice are missing. Our aim is to create an international registry about NENs patients affected by SARS-CoV-2 positivity to give a worldwide representation of the situation. Methods: This is an observational retrospective/prospective multicenter survey based on a direct email invitation. All types of NEN are eligible except SCLC and MiNEN. Patients fulfilling the inclusion criteria from March 1st, 2020 up to the end pf pandemic will be recruited. Electronic CRFs are filled out using the REDCap database. Local Institutional Review Board approval is required before data entry. Results: Eighty-one centers, 24 in and 57 outside Italy, representing 39 countries and 5 continents, were contacted. Fourteen centers did not respond and 15 declined the invitation. Among the remaining 52, 6 centers are currently recruiting and 8 are active but not recruiting yet. As of the current abstract submission deadline, 67 patients have been included, mostly GEP-NET (75%), non-functioning (86%), metastatic (85%) and on active treatment [47% somatostatin analogs (SSAs), 10% everolimus, 12% tirosin-kinase inhibitors (TKIs), 10% peptide receptor radionuclide therapy (PRRT), 15% chemotherapy]. Median age at NEN diagnosis was 57 years whilst the median age at SARS-CoV-2 diagnosis was 62 years. Almost all patients reported COVID-19-related symptoms, more commonly fever (67% of patients), cough (55%) and dyspnea (51%), in 28% of cases exertional and in 22% at rest. More than one third of patients (n, 24) had a pneumonia. The most common therapies for COVID-19 were antibiotics, steroids and hydroxychloroquine. Eleven patients (16%) needed oxygen therapy, three (4%) sub-intensive care and none intensive care. Fifty-six patients (84%) clinically recovered, six (9%) with sequelae, whereas five (7%) died. Among these latter 4 had a NET and 1 a NEC, and no patients have been receiving chemotherapy. With regard to the anti-tumor therapy no change occurred in 66% of patients, temporary interruption in 30%, and definitive discontinuation in 3%, 2% missing. Conclusions: Most of the NEN patients completely recovered from COVID-19, in many cases without any anti-tumor therapy adjustment. No clear correlations were observed with type, primary site and treatment of NEN. The recruitment is ongoing.