ESMO/ASCO Recommendations for a Global Curriculum in Medical Oncology Edition 2023.

The European Society for Medical Oncology (ESMO) and ASCO are publishing a new edition of the ESMO/ASCO Global Curriculum (GC) with contributions from more than 150 authors. The purpose of the GC is to provide recommendations for the training of physicians in medical oncology and to establish a set of educational standards for trainees to qualify as medical oncologists. This edition builds on prior ones in 2004, 2010, and 2016 and incorporates scientific advances and input from an ESMO/ASCO survey on GC adoption conducted in 2019, which revealed that GC has been adopted or adapted in as many as two thirds of the countries surveyed. To make GC even more useful and applicable, certain subchapters were rearranged into stand-alone chapters, that is, cancer epidemiology, diagnostics, and research. In line with recent progress in the field of multidisciplinary cancer care new (sub)chapters, such as image-guided therapy, cell-based therapy, and nutritional support, were added. Moreover, this edition includes an entirely new chapter dedicated to cancer control principles, aiming to ensure that medical oncologists are able to identify and implement sustainable and equitable cancer care, tailored to local needs and resources. Besides content renewal, modern didactic principles were introduced. GC content is presented using two chapter templates (cancer-specific and non-cancer-specific), with three didactic points (objectives, key concepts, and skills). The next step is promoting GC as a contemporary and comprehensive document applicable all over the world, particularly due to its capacity to harmonize education in medical oncology and, in so doing, help to reduce global disparities in cancer care.

ESMO/ASCO Recommendations for a Global Curriculum in Medical Oncology Edition 2023.

The European Society for Medical Oncology (ESMO) and ASCO are publishing a new edition of the ESMO/ASCO Global Curriculum (GC) with contributions from more than 150 authors. The purpose of the GC is to provide recommendations for the training of physicians in medical oncology and to establish a set of educational standards for trainees to qualify as medical oncologists. This edition builds on prior ones in 2004, 2010, and 2016 and incorporates scientific advances and input from an ESMO ASCO survey on GC adoption conducted in 2019, which revealed that GC has been adopted or adapted in as many as two thirds of the countries surveyed. To make GC even more useful and applicable, certain subchapters were rearranged into stand-alone chapters, that is, cancer epidemiology, diagnostics, and research. In line with recent progress in the field of multidisciplinary cancer care new (sub)chapters, such as image-guided therapy, cell-based therapy, and nutritional support, were added. Moreover, this edition includes an entirely new chapter dedicated to cancer control principles, aiming to ensure that medical oncologists are able to identify and implement sustainable and equitable cancer care, tailored to local needs and resources. Besides content renewal, modern didactic principles were introduced. GC content is presented using two chapter templates (cancer-specific and non-cancer-specific), with three didactic points (objectives, key concepts, and skills). The next step is promoting GC as a contemporary and comprehensive document applicable all over the world, particularly due to its capacity to harmonize education in medical oncology and, in so doing, help to reduce global disparities in cancer care.

Real-world outcomes of immunotherapy with or without chemotherapy in first-line treatment of advanced non-small cell lung cancer.

Background: Immunotherapy alone (mono-IT) or combined with chemotherapy (chemo-IT) has recently become the cornerstone of first-line treatment for advanced non-small cell lung cancer (NSCLC) patients. Here, real-world outcomes of first-line mono-IT and chemo-IT of advanced NSCLC treated within routine clinical practice at a single academic center in the Central Eastern European (CEE) region are presented. Materials and methods: A total of 176 consecutive patients with advanced NSCLC treated with mono-IT (118 patients) or chemo-IT (58 patients) were included. At the participating institution, all medical data relevant for providing oncology care are collected prospectively and in a standardized manner using purposely created pro-forms. Adverse events (AEs) were recorded and graded according to Common Terminology Criteria for Adverse Events (CTCAE). The Kaplan-Meier method was used to estimate median overall survival (mOS) and median duration of treatment (mDOT). Results: The 118 patients in the mono-IT cohort had a median age of 64 years, most were male (59%), 20% had ECOG PS ≥2, and 14% had controlled CNS metastases at baseline. With a median follow-up time (mFU) of 24.1 months, the mOS was 19.4 months (95% CI, 11.1-27.6), and the mDOT was 5.0 months (95% CI, 3.5-6.5). The 1-year OS was 62%. The 58 patients in the chemo-IT cohort had a median age of 64 years, most were male (64%), 9% had ECOG PS ≥2, and 7% had controlled CNS metastases at baseline. With a mFU of 15.5 months, the mOS was 21.3 months (95% CI, 15.9-26.7), and the mDOT was 12.0 months (95% CI, 8.3-15.6). The 1-year OS was 75%. Adverse events of severe grade were recorded in 18% and 26% of patients, and immunotherapy discontinuation due to AEs occurred in 19% and 9% in the mono-IT and chemo-IT groups, respectively. No treatment-related deaths were recorded. Conclusion: The results from the present real-world observational study from a CEE country suggest similar effectiveness and safety of first-line mono-IT and chemo-IT in patients with advanced NSCLC to those observed in randomized clinical trials. However, continuous follow-up will offer better insight into the magnitude of long-term benefits in routine clinical practice.

European Groundshot-addressing Europe's cancer research challenges: a Lancet Oncology Commission.

Cancer research is a crucial pillar for countries to deliver more affordable, higher quality, and more equitable cancer care. Patients treated in research-active hospitals have better outcomes than patients who are not treated in these settings. However, cancer in Europe is at a crossroads. Cancer was already a leading cause of premature death before the COVID-19 pandemic, and the disastrous effects of the pandemic on early diagnosis and treatment will probably set back cancer outcomes in Europe by almost a decade. Recognising the pivotal importance of research not just to mitigate the pandemic today, but to build better European cancer services and systems for patients tomorrow, the Lancet Oncology European Groundshot Commission on cancer research brings together a wide range of experts, together with detailed new data on cancer research activity across Europe during the past 12 years. We have deployed this knowledge to help inform Europe's Beating Cancer Plan and the EU Cancer Mission, and to set out an evidence-driven, patient-centred cancer research roadmap for Europe. The high-resolution cancer research data we have generated show current activities, captured through different metrics, including by region, disease burden, research domain, and effect on outcomes. We have also included granular data on research collaboration, gender of researchers, and research funding. The inclusion of granular data has facilitated the identification of areas that are perhaps overemphasised in current cancer research in Europe, while also highlighting domains that are underserved. Our detailed data emphasise the need for more information-driven and data-driven cancer research strategies and planning going forward. A particular focus must be on central and eastern Europe, because our findings emphasise the widening gap in cancer research activity, and capacity and outcomes, compared with the rest of Europe. Citizens and patients, no matter where they are, must benefit from advances in cancer research. This Commission also highlights that the narrow focus on discovery science and biopharmaceutical research in Europe needs to be widened to include such areas as prevention and early diagnosis; treatment modalities such as radiotherapy and surgery; and a larger concentration on developing a research and innovation strategy for the 20 million Europeans living beyond a cancer diagnosis. Our data highlight the important role of comprehensive cancer centres in driving the European cancer research agenda. Crucial to a functioning cancer research strategy and its translation into patient benefit is the need for a greater emphasis on health policy and systems research, including implementation science, so that the innovative technological outputs from cancer research have a clear pathway to delivery. This European cancer research Commission has identified 12 key recommendations within a call to action to reimagine cancer research and its implementation in Europe. We hope this call to action will help to achieve our ambitious 70:35 target: 70% average 10-year survival for all European cancer patients by 2035.

Perspectives for Cancer Care and Research in Central and Eastern Europe.

BACKGROUND: Discrepancies between the outcomes of cancer patients between Western European and Central and Eastern European (CEE) countries have often been observed. Despite the enormous economic and civilizational progress made in these countries after the abolishment of the communist regime, structural problems persist. SUMMARY: The present article reviews the domains of medical oncology education, human resources in oncology, cancer care, and clinical research in CEE in order to comprehensively assess the current situation and needs, describe important initiatives, and also propose ways to improving cancer outcomes in the region. Activities are under way to address these issues in national action plans to divert funding into oncology-related education, research, the purchase of equipment, and the attainment of modern hospital organization and structures. KEY MESSAGE: Over the past more than 30 years, CEE countries have made enormous economic and societal progress. Nevertheless, challenges especially in the health care sector persist.

Accelerating the Development and Validation of Liquid Biopsy for Early Cancer Screening and Treatment Tailoring.

Liquid biopsy (LB) is a minimally invasive method which aims to detect circulating tumor-derived components in body fluids. It provides an alternative to current cancer screening methods that use tissue biopsies for the confirmation of diagnosis. This paper attempts to determine how far the regulatory, policy, and governance framework provide support to LB implementation into healthcare systems and how the situation can be improved. For that reason, the European Alliance for Personalised Medicine (EAPM) organized series of expert panels including different key stakeholders to identify different steps, challenges, and opportunities that need to be taken to effectively implement LB technology at the country level across Europe. To accomplish a change of patient care with an LB approach, it is required to establish collaboration between multiple stakeholders, including payers, policymakers, the medical and scientific community, and patient organizations, both at the national and international level. Regulators, pharma companies, and payers could have a major impact in their own domain. Linking national efforts to EU efforts and vice versa could help in implementation of LB across Europe, while patients, scientists, physicians, and kit manufacturers can generate a pull by undertaking more research into biomarkers.

Population pharmacokinetics of cisplatin in small cell lung cancer patients guided with informative priors.

PURPOSE: Cisplatin-etoposide treatment is recommended as a first line in small cell lung cancer patients (SCLC). However, the prognosis is poor and the dosing is not tailored beyond the body surface area, which is related with indeterminate cisplatin exposure-response relationship. We aimed to evaluate cisplatin pharmacokinetics (PK) and the exposure to unbound cisplatin in SCLC patients using the informative priors, and assess the relationship between the cisplatin exposure and probability of neutropenia. METHODS: Observational clinical study was performed including 17 cisplatin-treated SCLC patients. External population cisplatin PK models were identified and NONMEM® software and $PRIOR subroutine were used for the model evaluation. The bias and precision of the model-predicted cisplatin concentrations were evaluated. The best models were combined in a final model including several sets of informative priors, which was used to estimate individual cisplatin exposure, analyze the relationship between the exposure and neutropenia and simulate several cisplatin dosing regimens in a virtual patient cohort. RESULTS: The models by Urien with the informative priors best fitted the data. The individual cisplatin exposure ranged between 2430 and 4560 µg*h/L. There was a trend of increasing probability of neutropenia and febrile neutropenia with increasing cisplatin exposure. Approximately 50%, 75% and 90% of patients receiving 60 mg/m2, 70 mg/m2 and 80 mg/m2, respectively, achieved the previously identified exposure threshold of 2860 µg*h/L. CONCLUSION: We developed a tool to individualize cisplatin dosing based on the estimated probability of neutropenia. The benefit of more intense dosing regimens in SCLC patients should be further assessed.

Real-life long-term outcomes of upfront surgery in patients with resectable stage I-IIIA non-small cell lung cancer.

BACKGROUND: Treatment of early-stage non-small cell lung cancer (NSCLC) is rapidly evolving. When introducing novelties, real-life data on effectiveness of currently used treatment strategies are needed. The present study evaluated outcomes of stage I-IIIA NSCLC patients treated with upfront radical surgery in everyday clinical practice, between 2010-2017. PATIENTS AND METHODS: Data of 539 consecutive patients were retrieved from a prospective hospital-based registry. All diagnostic, treatment and follow-up procedures were performed at the same thoracic oncology centre according to the valid guidelines. The primary outcome was overall survival (OS) analysed by clinical(c) and pathological(p) TNM (tumour, node, metastases) stage. The impact of clinicopathological characteristics on OS was evaluated using univariable (UVA) and multivariable regression analysis (MVA). RESULTS: With a median follow-up of 53.9 months, median OS and 5-year OS rate in the overall population were 90.4 months and 64.4%. Five-year OS rates by pTNM stage I, II and IIIA were 70.2%, 60.21%, and 49.9%, respectively. Both cTNM and pTNM stages were associated with OS; but only pTNM retained its independent prognostic value (p = 0.003) in MVA. Agreement between cTNM and pTNM was 69.0%. Next to pTNM, age (p = 0.001) and gender (p = 0.004) retained their independent prognostic value for OS. CONCLUSIONS: The study showed favourable outcomes of resectable stage I-IIIA NSCLC treated with upfront surgery in real-life. Relatively low agreement between cTNM and pTNM stages and independent prognostic value of only pTNM, observed in real-life data, suggest that surgery remains the most accurate provider of the anatomical stage of disease and important upfront therapy.

Real-world experience with capmatinib in MET exon 14-mutated non-small cell lung cancer (RECAP): a retrospective analysis from an early access program.

Background: Patients with non-small cell lung cancer (NSCLC) presenting with mesenchymal-epithelial transition (MET) exon 14 skipping mutation have an unfavorable prognosis with standard treatments. Capmatinib is a selective MET inhibitor, which showed promising efficacy in this patient population in early trials. Methods: We performed a retrospective, international, multicenter efficacy and safety analysis in patients with NSCLC treated with capmatinib in an early access program between March 2019 and December 2021. Results: Data from 81 patients with advanced MET exon 14 mutated NSCLC treated with capmatinib in first- or later-line therapy were analyzed. Median age was 77 years (range, 48-91), 56% were women, 86% had stage IV disease, and 27% had brain metastases. For all patients, the objective response rate (ORR) to capmatinib was 58% (95% CI, 47-69), whereas it was 68% (95% CI, 50-82) in treatment-naïve and 50% (95% CI, 35-65) in pretreated patients. The median progression-free survival was 9.5 months (95% CI, 4.7-14.3), whereas it was 10.6 months (95% CI, 5.5-15.7) in first-line and 9.1 months (95% CI, 3.1-15.1) in pretreated patients. After a median follow-up of 11.0 months, the median overall survival was 18.2 months (95% CI, 13.2-23.1). In patients with measurable brain metastases (n = 11), the intracranial ORR was 46% (95% CI, 17-77). Capmatinib showed a manageable safety profile. Grade ⩾ 3 treatment-related adverse events included peripheral edema (13%), elevated creatinine (4%), and elevated liver enzymes (3%). Conclusion: In patients with MET exon 14 skipping mutation, capmatinib showed durable systemic and intracranial efficacy and a manageable safety profile. This analysis confirms previously reported phase II data in a real-world setting.

Identifying the Steps Required to Effectively Implement Next-Generation Sequencing in Oncology at a National Level in Europe.

Next-generation sequencing (NGS) may enable more focused and highly personalized cancer treatment, with the National Comprehensive Cancer Network and European Society for Medical Oncology guidelines now recommending NGS for daily clinical practice for several tumor types. However, NGS implementation, and therefore patient access, varies across Europe; a multi-stakeholder collaboration is needed to establish the conditions required to improve this discrepancy. In that regard, we set up European Alliance for Personalised Medicine (EAPM)-led expert panels during the first half of 2021, including key stakeholders from across 10 European countries covering medical, economic, patient, industry, and governmental expertise. We describe the outcomes of these panels in order to define and explore the necessary conditions for NGS implementation into routine clinical care to enable patient access, identify specific challenges in achieving them, and make short- and long-term recommendations. The main challenges identified relate to the demand for NGS tests (governance, clinical standardization, and awareness and education) and supply of tests (equitable reimbursement, infrastructure for conducting and validating tests, and testing access driven by evidence generation). Recommendations made to resolve each of these challenges should aid multi-stakeholder collaboration between national and European initiatives, to complement, support, and mutually reinforce efforts to improve patient care.

The ESSO core curriculum committee update on surgical oncology.

INTRODUCTION: Surgical oncology is a defined specialty within the European Board of Surgery within the European Union of Medical Specialists (UEMS). Variation in training and specialization still occurs across Europe. There is a need to align the core knowledge needed to fulfil the criteria across subspecialities in surgical oncology. MATERIAL AND METHODS: The core curriculum, established in 2013, was developed with contributions from expert advisors from within the European Society of Surgical Oncology (ESSO), European Society for Radiotherapy and Oncology (ESTRO) and European Society of Medical Oncology (ESMO) and related subspeciality experts. RESULTS: The current version reiterates and updates the core curriculum structure needed for current and future candidates who plans to train for and eventually sit the European fellowship exam for the European Board of Surgery in Surgical Oncology. The content included is not intended to be exhaustive but, rather to give the candidate an idea of expectations and areas for in depth study, in addition to the practical requirements. The five elements included are: Basic principles of oncology; Disease site specific oncology; Generic clinical skills; Training recommendations, and, lastly; Eligibility for the EBSQ exam in Surgical Oncology. CONCLUSIONS: As evidence-based care for cancer patients evolves through research into basic science, translational research and clinical trials, the core curriculum will evolve, mature and adapt to deliver continual improvements in cancer outcomes for patients.

Immunotherapy for Metastatic Non-Small Cell Lung Cancer: Real-World Data from an Academic Central and Eastern European Center.

BACKGROUND: Immunotherapy with immune checkpoint inhibitors (ICIs) recently became the standard treatment for patients with advanced non-small cell lung cancer (NSCLC). Here, we present the first results of a real-world observational study on the effectiveness of ICI monotherapy in patients with advanced NSCLC treated at a single academic center in a Central and Eastern European (CEE) country. MATERIALS AND METHODS: Overall, 66 consecutive patients with advanced NSCLC treated with ICIs in everyday clinical practice, either with first-line pembrolizumab (26 patients) or second-line atezolizumab, nivolumab, or pembrolizumab (40 patients), from August 2015 to November 2018, were included. All data were retrieved from a hospital lung cancer registry, in which the data is collected prospectively. RESULTS: Included patients had a median age of 64 years, most were male (55%), 6% were in performance status ≥2, and 18% had controlled central nervous system metastases at baseline. In first-line, the median progression-free survival (mPFS) was 9.3 months, while the median overall survival (mOS) was not reached. The 1-year overall survival (OS) was 62%. In second-line, the mPFS and mOS were 3.5 months and 9.9 months, respectively, with a 1-year OS of 35%. In the overall population, adverse events of any grade were recorded in 79% of patients and of severe grade (3-4) in 12% of patients. CONCLUSION: The first real-world outcomes of NSCLC immunotherapy from a CEE country suggest comparable effectiveness to those observed in clinical trials and other real-world series, mainly coming from North America and Western European countries. Further data to inform on the real-world effectiveness of immunotherapy worldwide are needed. IMPLICATIONS FOR PRACTICE: Immunotherapy is a standard treatment of advanced non-small cell lung cancer (NSCLC). The real-world data on immunotherapy are still limited. This article presents the first data on the effectiveness of mono-immunotherapy with immune checkpoint inhibitors for patients with advanced NSCLC treated at a single academic center in a Central and Eastern European country. The survival rates and toxicity are comparable to those achieved in randomized clinical trials and other real-world series, coming mainly from North American and Western European countries. There is a pressing need to gather further data on the effectiveness of immunotherapy in everyday practice worldwide.

Gene Expression Levels of the Prolyl Hydroxylase Domain Proteins PHD1 and PHD2 but Not PHD3 Are Decreased in Primary Tumours and Correlate with Poor Prognosis of Patients with Surgically Resected Non-Small-Cell Lung Cancer.

BACKGROUND: Hypoxia correlates with poor prognosis in several cancer types, including lung cancer. Prolyl hydroxylase domain proteins (PHDs) play a role in cell oxygen sensing, negatively regulating the hypoxia-inducible factor (HIF) pathway. Our study aim was to evaluate PHD1, PHD2 and PHD3 mRNA expression levels in primary tumours and normal lungs of non-small-cell lung cancer (NSCLC) patients and to correlate it with selected regulators of HIF signalling, with clinicopathological characteristics and overall survival (OS). METHODS: Tumour tissue samples were obtained from 60 patients with surgically resected NSCLC who were treated with radical surgery. In 22 out of 60 cases, matching morphologically normal lung tissue was obtained. PHD1, PHD2 and PHD3 mRNA expressions were measured using RT-qPCR. RESULTS: The PHD1 and PHD2 mRNA levels in primary tumours were significantly decreased compared to those in normal lungs (both p < 0.0001). PHD1 and PHD2 expression in tumours was positively correlated (rs = 0.82; p < 0.0001) and correlated well with HIF pathway downstream genes HIF1A, PKM2 and PDK1. Decreased PHD1 and PHD2 were associated with larger tumour size, higher tumour stage (PHD1 only) and squamous cell carcinoma. Patients with low PHD1 and patients with low PHD2 expression had shorter OS than patients with high PHD1 (p = 0.02) and PHD2 expression (p = 0.01). PHD1 showed borderline independent prognostic values in multivariate analysis (p = 0.06). In contrast, we found no associations between PHD3 expression and any of the observed parameters. CONCLUSIONS: Our results show that reduced expression of PHD1 and PHD2 is associated with the development and progression of NSCLC. PHD1 could be further assessed as a prognostic marker in NSCLC.

Prognostic impact of PD-1 and PD-L1 expression in malignant pleural mesothelioma: an international multicenter study.

BACKGROUND: Programmed cell death 1/programmed death ligand 1 (PD-1/PD-L1) immune-checkpoint blockade is a promising new therapeutic strategy in cancer. However, expression patterns and prognostic significance of PD-L1 and PD-1 are still controversial in human malignant pleural mesothelioma (MPM). METHODS: Formalin-fixed paraffin-embedded (FFPE) tumor samples from 203 MPM patients receiving standard treatment without immunotherapy were collected from 5 European centers. PD-L1 and PD-1 expression of tumor cells (TCs) and tumor-infiltrating lymphocytes (TILs) were measured by immunohistochemistry and correlated with clinical parameters and long-term outcome. RESULTS: High (>10%) PD-L1 TC and PD-1 TILs expressions were found in 18 (8%) and 39 (24%) patients, respectively. PD-L1 was rarely expressed by TILs [≥1%, n=13 (8%); >10%, n=1]. No significant associations were found between the PD-L1 or PD-1 expression of TCs or TILs and clinicopathological parameters such as stage or histological subtype. Notably, patients with high (>10%) TC-specific PD-L1 expression exhibited significantly worse median overall survival (OS) (6.3 vs. 15.1 months of those with low TC PD-L1 expression; HR: 2.51, P<0.001). In multivariate cox regression analysis adjusted for clinical parameters, high TC PD-L1 expression (>10%) proved to be an independent negative prognostic factor for OS (HR: 2.486, P=0.005). There was no significant correlation between PD-L1 or PD-1 expression of TILs and OS. CONCLUSIONS: In this multicenter cohort study, we demonstrate that high (>10%) PD-L1 expression of TCs independently predicts worse OS in MPM. Further studies are warranted to investigate the value of PD-L1/PD-1 expression as a marker for treatment response in MPM patients receiving immunotherapy.

Sequential afatinib and osimertinib in patients with EGFR mutation-positive non-small-cell lung cancer: final analysis of the GioTag study.

Aim: Final overall survival (OS) and time on treatment analysis of patients with EGFR mutation-positive non-small-cell lung cancer (NSCLC) who received sequential afatinib and osimertinib. Patients & methods: Patients (n = 203) had T790M-positive disease following first-line afatinib and started osimertinib treatment ≥10 months before data entry. Primary outcome was time on treatment; OS analysis was exploratory. Results: Median time on treatment with afatinib and osimertinib was 27.7 months (90% CI: 26.7-29.9). Median OS was 37.6 months (90% CI: 35.5-41.3); median OS was 41.6 and 44.8 months in Del19-positive patients and Asian patients, respectively. Conclusion: In real-world clinical practice, sequential afatinib and osimertinib was associated with encouraging outcomes in patients with EGFR mutation-positive NSCLC, especially in Del19-positive patients and Asian patients. Clinical Trial Registration: NCT03370770 (ClinicalTrials.gov).

Access to Novel Drugs for Non-Small Cell Lung Cancer in Central and Southeastern Europe: A Central European Cooperative Oncology Group Analysis.

BACKGROUND: Treatment of non-small cell lung cancer (NSCLC) improved substantially in the last decades. Novel targeted and immune-oncologic drugs were introduced into routine treatment. Despite accelerated development and subsequent drug registrations by the European Medicinal Agency (EMA), novel drugs for NSCLC are poorly accessible in Central and Eastern European (CEE) countries. MATERIAL AND METHODS: The Central European Cooperative Oncology Group conducted a survey among experts from 10 CEE countries to provide an overview on the availability of novel drugs for NSCLC and time from registration to reimbursement decision in their countries. RESULTS: Although first-generation epidermal growth factor receptor tyrosine kinase inhibitors were reimbursed and available in all countries, for other registered therapies-even for ALK inhibitors and checkpoint inhibitors in first-line-there were apparent gaps in availability and/or reimbursement. There was a trend for better availability of drugs with longer time from EMA marketing authorization. Substantial differences in access to novel drugs among CEE countries were observed. In general, the availability of drugs is not in accordance with the Magnitude of Clinical Benefit Scale (MCBS), as defined by the European Society for Medical Oncology (ESMO). Time spans between drug registrations and national decisions on reimbursement vary greatly, from less than 3 months in one country to more than 1 year in the majority of countries. CONCLUSION: The access to novel drugs for NSCLC in CEE countries is suboptimal. To enable access to the most effective compounds within the shortest possible time, reimbursement decisions should be faster and ESMO MCBS should be incorporated into decision making.

Time to access to novel anticancer drugs and the correlation with ESMO-Magnitude of Clinical Benefit Scale in Slovenia.

Objectives: Timely access to novel anticancer drugs is challenging and value frameworks such as the European Society of Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) could assist in drug prioritization. We assessed the overall time to access to novel anticancer drugs in Slovenia and its correlation with ESMO-MCBS scores.Methods: Anticancer drugs with European Medicines Agency marketing authorization (EMA MA), applying for national reimbursement approval (NRA) in the period 2008-2018 with assigned ESMO-MCBS score, were included. Publically available data from EMA and the Slovenian National Health Insurance Institute were used for time calculations.Results: Among 53 studied drugs; a majority (47) of them obtained reimbursement approval within the observed time. The median time to EMA MA was 397 (range 98-615) days with the NRA requiring additional 422 (range 154-892) days. Neither time to EMA MA nor NRA correlated with ESMO-MCBS substantial clinical benefit (p = 0.332 and p = 0.965, respectively).Conclusions: In Slovenia, time to access to novel anticancer drugs exceeds two years and, more importantly, is equally long for drugs with or without substantial clinical benefit. Integration of the ESMO-MCBS into reimbursement deliberations could improve access to drugs with substantial clinical benefit.

Expression of FGFR1-4 in Malignant Pleural Mesothelioma Tissue and Corresponding Cell Lines and its Relationship to Patient Survival and FGFR Inhibitor Sensitivity.

Malignant pleural mesothelioma (MPM) is a devastating malignancy with limited therapeutic options. Fibroblast growth factor receptors (FGFR) and their ligands were shown to contribute to MPM aggressiveness and it was suggested that subgroups of MPM patients could benefit from FGFR-targeted inhibitors. In the current investigation, we determined the expression of all four FGFRs (FGFR1-FGFR4) by immunohistochemistry in tissue samples from 94 MPM patients. From 13 of these patients, we were able to establish stable cell lines, which were subjected to FGFR1-4 staining, transcript analysis by quantitative RT-PCR, and treatment with the FGFR inhibitor infigratinib. While FGFR1 and FGFR2 were widely expressed in MPM tissue and cell lines, FGFR3 and FGFR4 showed more restricted expression. FGFR1 and FGFR2 showed no correlation with clinicopathologic data or patient survival, but presence of FGFR3 in 42% and of FGFR4 in 7% of patients correlated with shorter overall survival. Immunostaining in cell lines was more homogenous than in the corresponding tissue samples. Neither transcript nor protein expression of FGFR1-4 correlated with response to infigratinib treatment in MPM cell lines. We conclude that FGFR3 and FGFR4, but not FGFR1 or FGFR2, have prognostic significance in MPM and that FGFR expression is not sufficient to predict FGFR inhibitor response in MPM cell lines.

Definition of Synchronous Oligometastatic Non-Small Cell Lung Cancer-A Consensus Report.

INTRODUCTION: Improved outcome has been shown in patients with synchronous oligometastatic (sOM) NSCLC when treated with radical intent. As a uniform definition of sOM NSCLC is lacking, we developed a definition and diagnostic criteria by a consensus process. METHODS: A pan-European multidisciplinary consensus group was established. Consensus questions were built on the basis of current controversies, and definitions were extracted from a survey, cases and a systematic review. This statement was formulated during a consensus meeting. RESULTS: It was determined that definition of sOM NSCLC is relevant when a radical treatment that may modify the disease course (leading to long-term disease control) is technically feasible for all tumor sites with acceptable toxicity. On the basis of the review, a maximum of five metastases and three organs was proposed. Mediastinal lymph node involvement was not counted as a metastatic site. Fludeoxyglucose F 18 positron emission tomography-computed tomography and brain imaging were considered mandatory. A dedicated liver magnetic resonance imaging scan was advised for a solitary liver metastasis, and thoracoscopy and biopsies of distant ipsilateral pleural sites were recommended for a solitary pleural metastasis. For mediastinal staging, fludeoxyglucose F 18 positron emission tomography-computed tomography was deemed the minimum requirement, with pathological confirmation recommended if this influences the treatment strategy. Biopsy of a solitary metastatic location was mandated unless the multidisciplinary team is of the opinion that the risks outweigh the benefits. CONCLUSION: A multidisciplinary consensus statement on the definition and staging of sOM NSCLC has been formulated. This statement will help to standardize inclusion criteria in future clinical trials.