Changing the landscape of European School of Oncology-European Society for Medical Oncology masterclasses in clinical oncology during the COVID-19 pandemic.

Aims: This study aimed to assess the participants' evaluation of the European School of Oncology-European Society for Medical Oncology virtual masterclasses in clinical oncology (MCOs) organized during the pandemic in 2021. Materials & methods: The participants answered an online evaluation questionnaire at the end of each MCO to evaluate the content and organization of the MCO. Results: The clinical session and case presentation scores ranged between 4.6 and 4.8 over 5. The participants strongly agreed that the MCOs offered updates to improve their knowledge and practice in 68-83% and 52-76%, respectively; 74-90% of the participants considered the quality of the meetings to be excellent. Conclusion: The participants were satisfied with the virtual MCOs during the COVID-19 pandemic. Virtual MCO may be an acceptable alternative educational modality in specific circumstances.

In 2002, the European School of Oncology (ESO) established masterclasses in clinical oncology (MCOs) and provided 41 in-person courses over the past two decades. As the COVID-19 pandemic forced travel restrictions and social distancing, the ESO and the European Society for Medical Oncology (ESMO) adapted the traditional MCOs to create virtual MCOs presented on e-ESO, an ESO e-learning platform. To date, five virtual MCOs have been organized for oncologists from western Europe, Latin America, Arab countries and southern Europe, the Baltic and Eurasia, eastern Europe and the Balkans. This study aimed to assess the participants' evaluation of the ESO-ESMO virtual MCOs organized during the pandemic in 2021 and to compare the participants' evaluation with that of previous in-person MCOs conducted between 2002 and 2019.

Eight-Year Experience of the Certificate of Competence and Advanced Studies Program Organized by the European School of Oncology.

The Certificate of Competence and Advanced Studies Program is an academically recognized postgraduate program that is organized by the European School of Oncology in collaboration with the University of Ulm and the University of Zurich. It is a part-time educational activity that aims to provide physicians and scientists with advanced knowledge in the management of patients with breast cancer, lymphoma, and lung cancer. The program encloses three attendance seminars and four to five e-learning modules that extend over 12 to 14 months. To be certified, participants have to pass an online test after each module followed by a final certification exam at the end of the program. This article reports on the 8-year experience of the 166 graduated fellows who have attended the program.

The Contribution of the European School Of Oncology Education to the Central Asian and Caucasian Regions.

The European School of Oncology (ESO) organizes educational activities within Europe, the Mediterranean region, Central Asia, and the Caucasus. In this paper, we report on the participation of oncologists from Uzbekistan, Kazakhstan, Kirgizstan, Tajikistan, Azerbaijan, Georgia, and Armenia in various ESO activities including the masterclass, courses, refresher courses, conventions, conferences, consensus conferences, clinical training centers fellowship program, and the medical students' courses in oncology. Over the last 15 years, 428 oncologists and medical students have successfully attended one or more of the above activities organized in various European countries. This article details the implementation and coordination of the ESO educational events in the Central Asian and the Caucasian regions.

ESO-ESSO-ESTRO Multidisciplinary Course in Oncology for Medical Students: 4 Years of Experience (2016-2019).

The ESO-ESSO-ESTRO Multidisciplinary Course in Oncology is intended to fill the gap of the undergraduate fragmented oncology education, to provide insight into all theoretical and practical aspects of oncology, and to encourage future professional choices towards an oncology discipline. Students are exposed to (a) preclinical cancer topics; (b) natural history of the disease; (c) laboratory diagnostic tests; (d) medical, radiation, surgical, and palliative treatment; and (e) direct or through multidisciplinary patients' approach. Students are obliged to attend (i) all theoretical lectures, (ii) clinical case presentations, (iii) laboratories and ward visits, and (iv) to prepare and present a specific project under supervision. Participation is limited to 24 medical students who are selected through a competitive application process. Between 2016 and 2019, 96 students from 29 countries have attended. Data analysis derived from a given questionnaire demonstrates that most of the participants have declared that (1) they have achieved their expectations and objectives, (2) they have highly rated both clinical and non-clinical teaching oncological topics, and (3) they have been stimulated in developing a professional career in the field of oncology.

Genomic correlates of response and resistance to immune checkpoint inhibitors in carcinomas of unknown primary.

BACKGROUND: Cancers of unknown primary (CUP) are highly aggressive tumours with limited molecular characterization. These tumours can be particularly sensitive to immune checkpoint inhibitors (ICI) by mounting a seemingly more effective anti-tumour immune response. Unlike other tumour lineages, the biological basis and clinical efficacy of ICI in CUP remain largely unknown. MATERIALS AND METHODS: The cBioPortal database was accessed to select eligible cases from the MSK-IMPACTTM Clinical Sequencing Cohort. The tumour cell genomic correlates of response and resistance to ICI in patients with CUP were compared to those with ICI-eligible tumours: cervical cancer, gastric cancer, renal cell carcinoma, hepatocellular carcinoma, non-small-cell lung cancer, melanoma, Merkel cell carcinoma and urothelial bladder cancer. RESULTS: Among a total of 234 patients with CUP, the identified genomic alterations were mainly mutation correlates of resistance to ICI, notably mutations in oncogenic signalling pathways including KRAS, STK11 and EGFR (24.7%, 10.9% and 4.2%, respectively). Compared to other tumours considered eligible for ICI, CUP presents a higher prevalence of alterations in the oncogenic signalling pathways KRAS and STK11. CUP patients treated with ICI had similar median overall survival with and without genomic correlates of response and resistance to ICI. An exploratory analysis showed that patients with TMB >10 mutations had a trend for better outcomes. CONCLUSIONS: A tumour mutation burden >10 mutations per megabase can provide a potential genomic correlate of response to ICI in patients with CUP. Further research is warranted to validate these findings.

Educational contribution of the College of the European School of Oncology to the Latin American Oncologists.

The European School of Oncology (ESO) offers a wide range of educational activities in Europe, the Middle East and Latin America. International experts are invited to provide proper education in the diagnosis and treatment of patients with cancer according to a holistic model of care. This activity is currently structured in the ESO College (ESCO) through masterclasses in clinical oncology, international conferences, clinical training centers fellowship programs, certificate of competence and advanced studies, patients' advocacy events, e-learning sessions and medical students' courses in oncology. This institutional profile highlights the ESO-ESCO educational activities dedicated to Latin American oncologists and reports on the experience of the 869 participants that have attended these programs.

The management of patients with cancer of unknown primary in middle-income countries: an ESO-AROME survey.

Aim: To report on the management strategies in patients with cancer of unknown primary (CUP) in middle-income countries. Methods: We conceived a survey of 20 items concerning the management of patients with CUP in daily clinical practice. Only participants from lower- and higher-middle-income countries, as per the World Bank Classification, were eligible for this study. Results: The indications for the first-line treatment did not differ between the two economic regions, whereas those for second-line treatment were more prevalent in higher-middle-income countries. The use of targeted therapy based on immunohistochemistry alone was higher in lower-middle-income countries, although the access to CUP classifiers was similar between the two regions. Conclusions: Proper recommendations must ensure that the economic burden is minimized and that other benefits outweigh the limited survival benefit achieved in patients with CUP.

ESO-ESMO Masterclass in Clinical Oncology: Analysis and Evaluation of the Learning Self-Assessment Test.

Masterclass in Clinical Oncology (MCO) represents the "key educational event" of European School of Oncology's (ESO) teaching program. MCO in collaboration with European Society for Medical Oncology (ESMO) is a multidisciplinary and clinical oriented educational event offered mainly to young oncologists worldwide. It provides full immersion in oncology with clinical case presentations and a Learning Self-Assessment Test (LSAT).LSAT is consisting of 45 multiple choice questions on an electronic platform referring to the material taught during the MCO. Three questions related to their topics are requested in advance from each faculty member. The major intentions of LSAT are the following: (a) the learning reflection of the massive information given during 4-5 days of intensive teaching and (b) to offer the opportunity to the participants to prepare themselves for their National Boards or for ESMO examination.In this article, we are analyzing and evaluating the results of LSAT from the ESO-ESMO Central European MCOs. We used the information of Central European MCOs for analysis due to the homogeneity of the available data. We assessed the level of participants' knowledge in relation to their oncology specialty or to their country of origin and the level of the quality of faculty teaching.

Clinical Case Presentation and Discussion During ESO-ESMO Masterclass: a 10-Year Interactive Educational Experience.

In this article, we report on the clinical case presentations that have been delivered during the ESO or ESO-ESMO Masterclasses in Clinical Oncology in the last 10 years. Masterclasses have been held in three different geographical continents including Europe, Middle East, and Latin America, in which participants had to submit a clinical case and present it either in front of a tumor board (multidisciplinary-like sessions) or in small groups. Clinical case presentation is a unique part of the educational program preparing young oncologists to present and discuss their own patients with distinguished experts. In each Masterclass, between 40 and 55 clinical cases-depending on the number of participants-are presented. All presentations are assessed and evaluated by faculty members as well as by the rest of the participants.

Cancer of unknown primary: Incidence rates, risk factors and survival among adolescents and young adults.

Cancer of unknown primary (CUP) is a clinical challenge especially when it occurs in adolescents and young adults (AYA), aged 15-39 years, due to the sparse data in this population. The available data has not described the population-based epidemiological features of CUP among AYA. Therefore, we collected patient information from the Surveillance, Epidemiology and End Results (SEER) registry, 1990-2015. Age, gender, ethnic, five pathological classification groups were assessed along with an aggregate level socioeconomic status (SES) index and population density at the county level. Incidence rates, modeled relative risks and survival of AYA patients with CUP were assessed. Among 2,480 AYA patients, 907 met the definition of standard pathology classifications. The majority of AYA patients with CUP had a neuroendocrine, squamous cell and poorly differentiated carcinomas with 0.4 cases per 1,000,000 population. AYA living in areas with the highest SES level had the highest risks of CUP; adjusted relative risks (ARR) of 1.17 (95% CI 1.0-1.4) and 1.99 (95% CI 1.5-2.6), respectively. AYA living in nonmetropolitan areas had a lower risk of CUP (ARR = 0.16; 95% CI 0.1-0.2). The incidence of differentiated neoplasms has been decreasing slower than undifferentiated neoplasms since the early 1990s. The median overall survival (OS) was 11 months (95% CI 9-13 months) with squamous CUP having the longest median OS 16 years (95% CI 3-24 years). In conclusion, this analysis answers several gaps in the knowledge of CUP among AYA and provides a platform to better understand this disease and its management within this group.

Exploring the biological hallmarks of cancer of unknown primary: where do we stand today?

Cancer of unknown primary (CUP) affects a small percentage of the general population. Nonetheless, a substantial number of these patients have a poor prognosis and consequently succumb to their illness within a year of diagnosis. The natural history of CUP is characterised by early metastasis from the unknown primary site, aggressive course and resistance to conventional chemotherapy. Unfortunately, the processes by which this orphan disease originates and progresses have not been fully elucidated and its biology remain unclear. Despite the conceptual progress in genetic and molecular profiling made over the past decade, recognition of the genetic and molecular abnormalities involved in CUP, as well as the identification of the tissue of origin remain unresolved issues. This review will outline the biology of CUP by exploring the hallmarks of cancer in order to rationalise the complexities of this enigmatic syndrome. This approach will help the reader to understand where research efforts currently stand and the pitfalls of this quest.

Veliparib in ovarian cancer: a new synthetically lethal therapeutic approach.

Epithelial ovarian cancer (EOC) accounts for nearly 90% of all ovarian malignancies. The standard therapeutic strategy includes cytoreductive surgery and neo (adjuvant) platinum-based chemotherapy. Relapse of advanced high grade serous ovarian cancer (HGSOC) is related to the development of drug resistance. A defective DNA damage response is a defining hallmark of HGSOC. Poly (ADP-ribose) polymerase (PARP) inhibitors exploit this deficiency through synthetic lethality and have emerged as promising anticancer therapies, especially in breast cancer gene (BRCA1 or BRCA2) mutation carriers. Apart from inducing synthetic lethality, PARP inhibitors have also been shown to trap PARP1 and PARP2 on DNA, leading to PARP-DNA complexes. This "PARP trapping" potentiates synergism between PARP inhibition and both alkylating agents and platinum-based chemotherapy. However, there are remarkable differences in the ability of PARP inhibitors to trap PARP, based on the size and structure of each separate molecule. Since monotherapy with PARP inhibitors is unlikely to induce cancer cell death in BRCA-proficient tumors, the efficacy of PARP inhibitors could be potentially optimized when combined with DNA-damaging agents, or with molecular targeted agents that also impair mechanisms of DNA repair. Olaparib, rucaparib, and niraparib have all obtained US Food and Drug Administration (FDA) and/or European Medicines Agency (EMA) approval in ovarian cancer in different settings. Veliparib does not yet have an approved label; nevertheless, there are currently promising results available in preclinical and early clinical settings. This comprehensive review summarizes the mechanism of action of veliparib and provides an overview of its early and ongoing clinical investigations.

Synovial Sarcoma: A Complex Disease with Multifaceted Signaling and Epigenetic Landscapes.

PURPOSE OF REVIEW: Aside from a characteristic SS18-SSX translocation identified in almost all cases, no genetic anomalies have been reliably isolated yet to drive the pathogenesis of synovial sarcoma. In the following review, we explore the structural units of wild-type SS18 and SSX, particularly as they relate to the transcriptional alterations and cellular pathway changes imposed by SS18-SSX. RECENT FINDINGS: Native SS18 and SSX contribute recognizable domains to the SS18-SSX chimeric proteins, which inflict transcriptional and epigenetic changes through selective protein interactions involving the SWI/SNF and Polycomb chromatin remodeling complexes. Multiple oncogenic and developmental pathways become altered, collectively reprogramming the cellular origin of synovial sarcoma and promoting its malignant transformation. Synovial sarcoma is characterized by complex epigenetic and signaling landscapes. Identifying the operational pathways and concomitant genetic changes induced by SS18-SSX fusions could help develop tailored therapeutic strategies to ultimately improve disease control and patient survivorship.

The clinical training centers fellowships: a European School of Oncology career development program (2013-2019).

Aim: This article refers to the European School of Oncology Clinical Training Centers (CTCs) program, which is a granted Fellowships program dedicated to young oncologists in training. Materials & methods: A total of 74 fellowships were offered by several CTCs during the last 7 years. Candidates were enrolled for 3-6 months of training rotations as fellows or observers in more than 30 training programs in well known Cancer Centers around Europe. Fellowships were covering medical, surgical, radiation and pediatric oncology specialties, laboratory diagnostic training and experimental, translational and clinical research. Fellows originated from Europe, Latin America and Mediterranean Africa. Results: Analysis of the questionnaire assessment showed that 95.5% of the fellows evaluated CTC programs with an 'excellent' or 'very good' score, while 100% declare that they had reached their objectives. Conclusion: The European School of Oncology CTC program designed for an additional practical education abroad meets the needs of young oncologists.

Advances in the management of brain metastases from cancer of unknown primary.

Cancer of unknown primary accounts for 3-5% of all cancers for which an adequate investigation does not identify the primary tumor. The particular subset of brain metastasis in cancer of unknown primary (BMCUP) is a clinical challenge that lacks standardized diagnostic and therapeutic options. It is diagnosed predominantly in male patients in the sixth decade of age with complaints of headache, neurological dysfunction, cognitive and behavioral disturbances and seizures. The therapeutic approach to patients with BMCUP relies on local control and systemic treatment. Surgery or stereotactic radiosurgery and/or whole brain radiation therapy seems to be the cornerstone of the treatment approach to BMCUP. Systemic therapy remains essential as cancers of unknown primary are conceptually metastatic tumors. The benefits of chemotherapy were disappointing whereas those of targeted therapies and immune checkpoint inhibitors remain to be evaluated. In this Review, we address the advances in the diagnosis and treatment of BMCUP.

Comparison of second-line treatments of recurrent and/or metastatic squamous cell carcinoma of the head and neck.

AIM: The literature lacks direct evidence comparing the different regimens evaluated in the second-line treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). METHODS: We conducted a network meta-analysis (NMA) of the randomized controlled Phase III trials reporting on the second-line drug treatment options in R/M SCCHN. RESULTS: The eligible trials included 11 regimens among which six targeted therapies, two immune checkpoint inhibitors and three chemotherapy regimens. Only nivolumab has shown statistically significant superiority over methotrexate in terms of overall survival (HR: 0.64; 95% CI: 0.43-0.96) and objective response rate (OR: 2.51; 95% CI: 1.07-5.86). CONCLUSION: Based on the efficacy and safety outcomes of this network meta-analysis, nivolumab seems the most favorable regimen inthe management of R/M SCCHN.

Familial cancer of unknown primary.

Cancer of unknown primary site (CUP) is a deadly disease diagnosed through metastases at various organs without primary tumor identification. Despite the major molecular and technological advances, the carcinogenesis of CUP remains enigmatic which hampers adequate study design of treatments leading to survival improvement. To date, the pathogenesis of CUP is still debatable with one hypothesis considering CUP simply a group of metastatic tumors with unidentified primaries and another considering it a distinct entity with specific genetic and phenotypic aberrations. Familial CUP seems to favor the first hypothesis due to common genetic predisposition factors between known primaries and CUP. Two clinical implications may be withdrawn from the pathogenesis of familial clustering of CUP. The detailed family history and environmental risk factors may orient towards the primary tumor identification. Smoking avoidance and adherence to general population guidelines for cancer screening would be strongly encouraged.

Sense of Coherence and Defense Style Predict Sleep Difficulties in Early Non-metastatic Colorectal Cancer.

BACKGROUND: Sleep disturbances are common in cancer patients, but little is known about the complex interplay between the background psychological profile, coping with health stressors capacities and psychological distress in the formation of sleep difficulties in colorectal cancer. AIMS: To study the course and to identify psychological predictors of sleep difficulties in early non-metastatic colorectal cancer patients over a one-year period. METHODS: In this 1-year prospective study, we assessed in 84 early non-metastatic colorectal cancer patients the association of psychological distress (SCL-90-R), sense of coherence (SOC-29), and defense styles (Defense Style Questionnaire) with sleep difficulties (SCL-90-R) in multiple regression models. Eighty-two patients with breast cancer and 50 patients with cancer of unknown primary site served as disease controls, and 84 matched for age and sex alleged healthy individuals served as healthy controls. RESULTS: Colorectal cancer patients presented more sleep difficulties compared to healthy participants but fewer than patients with breast cancer and cancer of unknown primary site. Colorectal cancer patients' trouble falling asleep (p = 0.033) and wakening up early in the morning (p < 0.001) deteriorated over time. Sleep that was restless or disturbed was independently associated with low SOC (p = 0.046) and maladaptive defenses (p = 0.008). Anxiety symptoms (p < 0.001) predicted deterioration in trouble falling asleep, while depressive symptoms (p = 0.022) and self-sacrificing defense style (p = 0.049) predicted deterioration in wakening up early in the morning. CONCLUSIONS: Psychological parameters and coping with health stressors capacities are independently associated with sleep difficulties in colorectal cancer patients, indicating the need for psychological interventions aiming at improving adjustment to the disease.