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Background: ESMO COVID-19 and CAncer REgistry (ESMO-CoCARE) is an international collaborative registry-based, cohort study gathering real-world data from Europe, Asia/Oceania and Africa on the natural history, management and outcomes of patients with cancer infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Patients and methods: ESMO-CoCARE captures information on patients with solid/haematological malignancies, diagnosed with coronavirus disease 2019 (COVID-19). Data collected since June 2020 include demographics, comorbidities, laboratory measurements, cancer characteristics, COVID-19 clinical features, management and outcome. Parameters influencing COVID-19 severity/recovery were investigated as well as factors associated with overall survival (OS) upon SARS-CoV-2 infection. Results: This analysis includes 1626 patients from 20 countries (87% from 24 European, 7% from 5 North African, 6% from 8 Asian/Oceanian centres), with COVID-19 diagnosis from January 2020 to May 2021. Median age was 64 years, with 52% of female, 57% of cancer stage III/IV and 65% receiving active cancer treatment. Nearly 64% patients required hospitalization due to COVID-19 diagnosis, with 11% receiving intensive care. In multivariable analysis, male sex, older age, Eastern Cooperative Oncology Group (ECOG) performance status ≥2, body mass index (BMI)

BACKGROUND: Telomerase Reverse Transcriptase (TERT) is increasingly important in the molecular characterization of malignant gliomas. Its role differs between low and high grade gliomas and its association with other biomarkers and treatment outcome is still under investigation. MATERIAL AND METHODS: In the present study, 115 patients at a median age of 46 years diagnosed from 2004 to 2017 with malignant glioma were studied. For all patients, we had information on their clinical and pathological characteristics, on their therapy and on: IDH1 expression (IHC or PCR), MGMT methylation (PCR), BRAF expression (IHC or PCR), expression of EGFRvIII (IHC or real time PCR), expression of ATRX (IHC), co-deletion of 1p/19q (MLPA), p53 expression (IHC). For TERT, DNA was isolated from formalin fixed paraffin embedded tissue and mutation analysis was performed using Nested PCR. Finally, sequence analysis was performed by Sanger sequencing. RESULTS: Of the 115 patients 77 were diagnosed with GBM, 11 with an astrocytoma grade III and 9 with an astrocytoma grade II, while 9 had grade III oligodendroglioma and 3 grade II oligodendroglioma. Median overall survival was 33,5 months for all patients, while glioblastoma patients had the worst survival (20,9 months). Patients with a mutation in IDH1 had a median overall survival of 78,8 months, much longer than the 42 months of IDH wild-type patients. Glioma patients with an MGMT methylation had also a longer median overall survival (42,7 months) than those with unmethylated MGMT (20,3 months). TERT promoter mutations were observed in 75 out of 115 patients. Of these, C228T mutation was detected in 59 patients, C250T mutation in 15 and C127 mutation in only 1 patient. Patients with a TERT mutation were older, they were diagnosed with glioblastoma or oligodendroglioma rather than astrocytoma and they were usually found to be IDH wild-type, the latter being the parameter most significantly associated with survival. TERT promoter mutation was a negative prognostic factor for the entire population, as well as for the high grade gliomas while we were not able to take any safe conclusion regarding low grade gliomas. CONCLUSION: The prognostic role of TERT concerning both the histological subtype of glioma and the other molecular markers has been demonstrated in this rather representative study. The potential therapeutic targeting of TERT and the study of its predictive role in both chemotherapy and radiotherapy will be the main axes of further research.

This study examined the dimensions of burden perceived by key-relatives of patients suffering from schizophrenia spectrum disorder by the development of an instrument, the Family Burden Scale (FBS) and the underlying predictors. One hundred and seventy one primary caregivers, living with 158 patients suffering from chronic psychotic illness and maintained on community basis in Athens area, were interviewed by the use of FBS supplemented by the Family Atmosphere Scale and GHQ. Construction procedure and factor analysis of FBS produced a scale of 23 items in four factors, three of them measuring objective and the fourth one, subjective burden. The scale was also proved to be reliable and valid. Forty-five percent of primary caregivers reported high levels of burden. Psychological impairment (high GHQ scores) was related with high levels of burden and negative family atmosphere. Previous admissions and duration of illness were also found to predict burden. The results suggest that FBS differentiates objective from subjective burden. Psychological well being of carers is affected by the dimensions of perceived burden.

Aim: The reported prevalence of MET overexpression varies from 25-55% in non-small cell lung cancer (NSCLC) and clinical correlations are emerging slowly. In a well-defined NSCLC cohort of the Lungscape program, we explore the epidemiology, the natural history of IHC MET positivity and its association to OS, RFS and TTR. Methods: Resected stage I-III NSCLC identified based on the quality of clinical data and FFPE tissue availability were assessed for MET expression using immunohistochemistry (IHC) on TMAs (CONFIRM anti total c-MET assay, clone SP44, Ventana BenchMark platform). All cases were analysed at participating pathology laboratories using the same protocol, after passing an external quality assurance program. MET positive status is defined as ≥ 50% of tumor cells staining with 2+ or 3+ intensity. Results: A total of 2709 cases are included in the iBiobank and will be analysed. IHC MET expression is currently available for 1552 patients, with positive MET IHC staining in 380 cases [24.5%; IHC 3+ in 157 cases (41.3%) and 2+ in 223 cases (58.7%)]. The cohort of 1552 patients includes 48.2%, 44.7% and 4.4% cases of adenocarcinoma, squamous and large cell histologies, respectively. IHC MET status was independent of stage, age and smoking history. Significant differences in MET positivity were associated with gender (32% vs. 21% for female vs. male, p Conclusions: The preliminary results for this large multicentre European cohort describe a prevalence of MET overexpression that seems lower than previous observations in NSCLC, such as reported for the OAM4971g trial, suggesting potential biological differences between surgically resected and metastatic disease. Analysis for the full cohort is ongoing and results will be presented. Disclosure: L. Bubendorf: Disclosures: Stock ownership: Roche Advisory boards: Roche, Pfizer Research support: Roche; K. Schulze: Full time employee of Roche; A. Das-Gupta: I am a full time employee of Roche. All other authors have declared no conflicts of interest.

Background: HER2 positivity is most frequently assessed by a combination of immunohistochemical (IHC) and in situ hybridization (ISH) testing. We previously reported (Dowsett et al, J Clin Oncol, 2009, 27, 2962) in the HERA trial that the degree of benefit from trastuzumab in the 1 year arm and the prognosis in the no-trastuzumab (observation) arm was unaffected by the level of HER2 amplification above the cut-off of 2.0 (HER2/CEP17 ratio). We have now assessed whether IHC staining intensity, which is a measure of the protein target for trastuzumab, had an effect on prognosis or benefit from treatment. Patients and method: 3,401 patients were HER2 positive either by being assessed as IHC 3+ positive or with a FISH ratio of >2.0 in the central laboratory for the HERA trial (Kassel, Germany). We conducted a case-control analysis in which 425 patients were identified as the cases by their experiencing a disease-free survival (DFS) event in the 1-year (n=168) or observation (n=257) arms after a median 2 years’ follow-up. The cases were matched to controls (850 controls, 1:2 ratio). Images were collected using the Ariol image analysis system (Genetix Ltd.) of tissue sections stained by the DAKO HercepTest in the central laboratory. Images were analysed for degree of staining intensity which was quantified as a continuous variable. Relationship of staining intensity with FISH copy number and FISH HER2/CEP17 ratio were assessed. The impact of HER2 staining intensity on risk of a disease-free event was determined using a conditional logistic regression model in SAS 9.2. Results: Image intensity results were available on 381 (89.6%) cases and 755 (88.8%) controls. There were highly significant correlations between HER2 staining intensity and copy number in the whole population (Spearman Correlation, r=0.464, P Conclusion: In tumours overexpressing HER2, gene copy number is more significantly related to IHC staining intensity than HER2/CEP17 ratio. Like degree of amplification, IHC staining intensity does not relate to prognosis of HER2 positive chemotherapy-treated patients or to the benefit they derive from 1 year of adjuvant trastuzumab. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD10-01.

Background The prevalence of ALK gene rearrangement (ALK+) in European patients with non-small cell lung cancer (NSCLC) is unknown. The Lungscape project provides a platform to evaluate its expression and clinical significance in a large cohort of patients with resected NSCLC from 13 European sites in 11 countries. Methods Participating sites retrospectively identified cases of NSCLC with clinical demographic and outcome data, and available tissue for research according to predefined protocol criteria. Local ethical and regulatory approvals were adhered to. Clinical data were entered to a central, secure database. Accepted cases on the basis of completeness of clinical data were assessed for ALK expression using immunohistochemistry (IHC) using antibody clone 5A4 (Novocastra) and an H-score modified after Ruschoff et al. All cases were analysed at participating clinical pathology laboratories using the same protocol, control tissue microarray and after passing an external quality assurance exercise. Results To date 998 cases of adenocarcinoma have been accepted to the database and ALK IHC results are available for 743 (74%). Positive IHC staining is present in 54 cases (7.3%) with IHC 3+ in 17 cases (2.3%), 2+ in 6 cases and 1+ in 31 cases. The median H-score is 45 (range 1-300) with homogeneous staining in 30% of cases and heterogeneous staining in at least 70% of cases. In total there are 38% women and 62% men, the proportion of stage I, II and III is 55, 23 and 22 % respectively, 16% of cases are never smokers and 99% Caucasian ethnicity. The median age of all cases (n = 998) is 65 years (range 23 - 86) and for IHC + 63.2 years. With respect to gender and smoking status 11% of women, 5.6% of men, 13% of never-smokers, 5.3% of former smokers and 9.3% of current smokers demonstrated positive IHC for ALK. Conclusions The preliminary results for this large multicentre European cohort demonstrate a prevalence of ALK assessed by IHC of 7.3%, with IHC 3+ expression in 2.3% of cases. Correlation of IHC scores with fluorescent in situ hybridisation, clinical demographics and outcomes is ongoing and will be presented. Disclosure All authors have declared no conflicts of interest.

Background The Lungscape project aims at building a virtual biobank to facilitate an international high-quality analysis of large numbers of tumors for molecular alterations linked to clinical and biological characteristics captured in the iBiobank. Methods Retrospective radically resected stage I-III non-small cell lung cancer cases from 15 ETOP centers, with mandatory comprehensive clinical annotations including at least 2 years of FU have been reviewed and captured. Results This first set of 1614 cases was enriched in adenocarcinoma (61.8%), with 28.8% of squamous and 4.9% of large cell histologies. Median age is 65 yrs, 37.6% are women, and respectively 13.9%, 33.5% and 49.6% are never, current and former smokers. Stage distribution is: IA 23.7%, IB 25.8%, IIA 16.4%, IIB 11.6%, IIIA 20.8%, IIIB 1.7%. At last FU, 52.8% of patients were still alive, with a median FU of 5.3 yrs. PFS No. of patients 5 years (95% C.I.) Median (mos) (95% C.I.) TOTAL 1614 46 (43.3, 48.6) 49.0 ( 43.9, 55.2) Stage Ia 382 64.5 (59.1, 60.5) NR Ib 417 55.4 (50.3, 60.5) 78.0 IIa 264 44.8 (38.4, 51.3) 46.9 IIb 187 39.2 (31.6, 46.8) 33.7 IIIa 335 20.0 (15.2, 24.8) 17.5 IIIb 28 11.9 (0.0, 25.3) 10.1 OS 1614 52.0 (49.3, 54.7) 64.2 (57.3, 76.9) Stage Ia 382 70.0 (64.9, 75.2) NR Ib 417 60.6 (55.5, 65.7) NR IIa 264 50.5 (43.8, 57.1) 62.2 IIb 187 43.7 (36.0, 51.4) 43.3 IIIa 335 29.3 (23.9, 34.7) 29.0 IIIb 28 10.3 (0.0, 27.1) 20.2 Conclusion This is the first large-scale series based on 7th TNM classification reporting on OS and PFS in the context of European standards of care. These data confirm the discriminative capacity of the 7th TNM with a potentially somewhat superior outcome. Histologies other than adenocarcinoma are currently actively being captured. Complete data including PFS and TTP - never reported before - as well as OS based on the expected 2400 patients correlated to stage, gender, smoking status, histology and age will be provided. This complete clinical dataset will be invaluable to investigate the impact of molecular characteristics on outcome. It will allow building future hypothesis for prospective evaluation of new treatment strategies and help in the development of a molecularly refined TNM. Disclosure All authors have declared no conflicts of interest.