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ESMO Open — Health & Fitness
ESMO Open

ESMO Open is the European Society for Medical Oncology’s online-only, peer-reviewed Open Access journal, dedicated to publishing high-quality medical research and educational content from all disciplines of oncology, with a focus on innovative clinical and translational cancer research.
The journal is published by BMJ on behalf of ESMO.
http://esmoopen.bmj.com/
* The purpose of this podcast is to educate and to inform. The content of this podcast does not constitute medical advice and it is not intended to function as a substitute for a healthcare practitioner’s judgement, patient care or treatment. The views expressed by contributors are those of the speakers. BMJ does not endorse any views or recommendations discussed or expressed on this podcast. Listeners should also be aware that professionals in the field may have different opinions. By listening to this podcast, listeners agree not to use its content as the basis for their own medical treatment or for the medical treatment of others.

Copyright: © 643134

Latest Episodes:

Immune checkpoint inhibitors for every non-small cell lung cancer patient Jul 17, 2018

Show notes

Several phase III trials on immune checkpoint inhibitor therapy in non-small cell lung cancer were recently published and changed the clinical practice Here, non-small cell lung cancer has to be categorized first according to the presence of activating mutations and second according to the programmed cell death ligand 1 (PDL1) expression. Approximately 25% of patients present with a driver mutation and should be treated with tyrosine kinase inhibitors as the first line treatment strategy for metastatic non-small cell lung cancer. Approximately 75% of patients do not present with a driver mutation and should be treated according to the presence of PDL1 expression. Patients with high PDL1 (≥ 50% of tumor cells) expression are candidates for immune checkpoint inhibitor monotherapy, although a combination with chemotherapy can be suggested in patients with high tumor load and fast progressing disease. Patients with intermediate (1-49% of tumor cells) PDL1 expression are on the other hand candidates for the combination of chemotherapy with immune checkpoint inhibitor therapy according to the recently published data. Further, combination of immune checkpoint inhibitor-based therapy with chemotherapy and bevacizumab could be an option in patients with a driver mutation after the failure of available tyrosine kinase inhibitors. Listen to the podcast with Professor Johan Vansteenkiste, MD (Respiratory Oncology Unit and Trial Unit; Department of Respiratory Diseases

University Hospitals KU Leuven; Catholic University Leuven, Belgium) and read the full Abstract on the ESMO Open website.

Epigenetic Biomarkers in Cancer Jun 26, 2018

Show notes

Epigenetic biomarkers are emerging across tumor types in cancer research. Aberrant DNA methylation in tumors results in silencing of distinct genes. This modification is very stable and therefore can reliably be assessed and used as a diagnostic but also prognostic biomarker. Recently, DNA methylation was validated as an additional diagnostic biomarker in brain tumors. Here, the methylation profile allowed precise clinical diagnosis associated with the survival prognosis. Therefore, the addition of DNA methylation profiles to routine diagnostic assessment in cancer diagnosis might be promising to ensure accurate diagnosis and support treatment decisions. Further, predictive epigenetic biomarkers were identified as MGMT methylation was repeatably shown to associate with response to alkylating chemotherapy. Several current research efforts are concentrating on the identification of new diagnostic as well as predictive biomarkers in various types of cancer. This podcast with Professor Gerda Egger (Department of Pathology, Medical University of Vienna and Ludwig Boltzmann Institute Applied Diagnostics) provides an overview of the current routinely used biomarkers as well as an outlook on what is on the horizon in epigenetic biomarkers.

Read the Abstract on the ESMo Open website: https://esmoopen.bmj.com/content/3/5/e000416.

Questions asked in everyday practice: Immune Checkpoint Inhibitors Jun 04, 2018

Show notes

Immunotherapy has been approved for several indications in Oncology, resulting in an increasing number of physicians that use it to treat their patients. In this podcast, Teresa Amaral, member of the ESMO YOC, interviews Professor John Haanen (Head of the Division of Medical Oncology and Staff Scientist in the Division of Immunology; Professor of Translational Immunotherapy of Cancer at Leiden University Medical Centre, the Netherlands) on the topic: “Questions asked in everyday practice: Immune Checkpoint Inhibitors”. Currently, there is no consensus about how long should we treat patients with immunotherapy and the optimal duration might also be different considering the tumor type (e.g. melanoma, NSCLC). In some patients, stopping early due to adverse events doesn’t seem to be detrimental, but the follow-up time is still short to make definitive assumptions. When treating a patient with a previous autoimmune disease, several aspects need to be considered, namely, which type of immunosuppression is the patient receiving now, in which dosage and how long has the autoimmune disease been stable. Patients that received a solid organ transplant pose an extra challenge. For patients that develop grade 4 autoimmune adverse events, re-treatment with immunotherapy should be extensively discussed. In case of severe autoimmune toxicity that does not respond to the treatments referred in the guidelines, and if the treating physician is not experienced with escalating immunosuppressive therapy, consultation with other centers with more familiarity and expertise on this topic should be considered.

Read the abstract on the ESMO Open website: http://dx.doi.org/10.1136/esmoopen-2018-000395.

Macrophage repolarization therapy in colorectal cancer May 23, 2018

Show notes

Although highly successful in other entities, immune checkpoint inhibition has so far only shown limited efficacy in an unselected population of colorectal cancer patients. The particular composition of the inflammatory microenvironment of colorectal cancer, characterized by a low density of tumor-infiltrating-lymphocytes and no PDL1 expression on the tumor cells, might explain this resistance. Indeed, colorectal cancer with microsatellite instability responds much better to immune checkpoint inhibitors and present with a much higher infiltration with T-cells. Dense infiltration with tumor-associated macrophages at the invasion margin is a further characteristic of the inflammatory microenvironment in colorectal cancer potentially causing the limited response to immune checkpoint inhibitors. Interestingly, PDL1 expression can be frequently observed on these tumor-associated macrophages at the invasion margin, which potentially reduce the infiltration with T cells. Interfering with this population of myeloid cells is a possible new immune modulating treatment approach, although more insight on the exact underlying mechanisms causing tumor supportive or suppressive behavior of the myeloid cells is needed. Here, therapeutic approaches combining immune checkpoint inhibitor modulating the T cells function and specific modulators of the tumor-associated macrophages might be successful and should be investigated in future clinical trials.

Listen to the podcast with Professor Niels Halama, MD (Department of Medical Oncology and Internal Medicine VI, National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany) and read the Abstract on the ESMO Open website: https://esmoopen.bmj.com/content/3/5/e000426.

New therapeutic anti-CEA anti-CD3 bispecific antibody in colorectal cancer Apr 16, 2018

Show notes

Colorectal cancer has a strong interaction with the immune system as underlined by the high prognostic impact of tumor infiltrating lymphocytes in the tumor core as well as the infiltration margin in the localized setting. However in the metastatic scenario the vast majority of these tumors - the 95% lacking deficiencies in the missmatch repair sustem- demonstrated to be immune-elusive. The new therapeutic bispecific anti-CEA anti CD3 antidobody CEA-TCB is therefore a new, promising immune modulating therapy currently evaluated in clinical studies in colorectal cancer. The CEA-TCB has a 2-to-1 binding ratio, with one domain of the antibody binding directly to CD3 on T cells while the remaining two binding domains simultaneously bind to CEA molecules on the tumor cells. The CEA-TCB induces T-cell engagement and activation, with T-cell proliferation at the site of activation. Two phase 1 trials with CEA-TCB have been presented this year, one as a single-drug trial, the other in combination with the PD-L1 inhibitor Azetolizumab, with promising results. The two studies are debated regarding inclusion, results and toxicity. Finally, the future of CEA-TCB and its impact on Colorectal Cancer treatment are discussed in this podcast. The interview to Guillem Argilés (Gastrointestinal Malignancies Program, Vall d’Hebron University Hospital, Barcelona, Spain) is conducted by the ESMO Open Editor of multimedia and social media Laurids Poulsen.

Read the abstract on the ESMO Open website: http://dx.doi.org/10.1136/esmoopen-2018-000377.

Recent advances in adjuvant therapy for melanoma patients Feb 01, 2018

Show notes

In the last decade, we have seen a significant change in the therapeutic landscape for advanced melanoma. Recently, results from two trials evaluating immunotherapy and targeted therapy in the adjuvant setting (completely resected stage III/IV) were published. In this podcast, Teresa Amaral, member of the ESMO YOC, talks with Professor Jeffrey Weber, Professor of Oncology and Deputy Director of the Laura and Isaac Perlmutter Cancer Center, about the recent developments in adjuvant therapies for patients with melanoma. Professor Weber also gives some insight on this data's impact on the treatment of real-world patients. Currently, there is enough evidence to support adjuvant treatment in patients with resected Stage IIIB/C-IV melanoma. As for Stage II patients, this option should be considered in some selected cases (e.g. T ≥ 4mm with the presence of ulceration). In both of the above-mentioned trials, patients were treated for a maximum of 12 months. Although a shorter treatment duration (e.g. 6 months) might result in the same benefit, it is unclear that a trial comparing 12 months to 6 months of therapy will be conducted to show equivalence, since it would be a very large trial requiring prolonged follow-up. So, for now, 12 months of adjuvant therapy is the standard. It is difficult to compare the results from both trials in patients with BRAF mutated melanoma since the populations treated were different but overlapping. Nonetheless, both therapies showed good results in the population of BRAF mutated stage III patients. What is clearly different is the safety profile and type of administration. Choosing one treatment over the other must also consider patient and physicians’ preferences. For patients that have a recurrence while receiving adjuvant therapy, changing from targeted therapy to immunotherapy and vice versa is probably the best approach." You can hear the full interview also on the ESMO Open homepage: http://esmoopen.bmj.com/. The related papers here: http://www.nejm.org/doi/full/10.1056/NEJMoa1708539 and http://www.nejm.org/doi/full/10.1056/NEJMoa1708539

http://www.nejm.org/doi/full/10.1056/NEJMoa1709030.

New therapeutic targets in the inflammatory microenvironment Sep 05, 2017

Show notes

In this podcast, Editor Anna Berghoff speaks to Professor Eric Tartour (Department of Immunology; Hôpital Européen Georges Pompidou) about new therapeutic targets in the inflammatory microenvironment. The introduction of immune checkpoint inhibitors introduced a new era of oncology. The CTLA4 or PD1/PDL1 axis targeting immune checkpoint inhibitors have shown remarkable and long lasting responses in a variety of tumor types, Here, the biology of immune checkpoint inhibitors is outlined including the main site of action for the different immune checkpoint inhibitor types. Further, other possible immune checkpoints like LAG3 and other cells types including macrophages and NK cells as future directions for immune modulating therapies are discussed. Combination approaches including immune checkpoint inhibitors and chemotherapy or radiotherapy are currently investigated for their synergistic efficacy and preliminary data has shown promising results.

Read the Abstract on the ESMO Open website: http://esmoopen.bmj.com/content/3/1/e000310.

Immunotherapy in lung cancer Jul 26, 2017

Show notes

Immune Checkpoint inhibitors have become an important treatment option in patients with metastatic lung cancer. This podcast gives an overview on the current evidence of immune checkpoint inhibitors in patients with non-small cell lung cancer. Based on the phase III data, patients with PDL1 expression >50% are candidates for 1st line pembrolizumab if there are no contraindications. Currently, PDL1 expression as assessed by immunohistochemistry is the most validated biomarker although other biomarkers including mutational load, neo-antigen presence or tumor infiltrating lymphocytes are currently under investigation. Importantly, the side effect profile of immune checkpoint inhibitors does not differ in lung cancer patients. Studies are currently investigating the value of immune checkpoint inhibitors for patients with small cell lung cancer. Several currently on-going studies are investigating the combination of chemo-/radiotherapy and immune checkpoint inhibitors in patients with lung cancer.

Read the abstract on the ESMO Open website: http://esmoopen.bmj.com/content/3/1/e000311.

ESMO Leaders Generation Programme – an alumni insight Jun 26, 2017

Show notes

Several alumni of the European Society for Medical Oncology (ESMO) Leaders Generation Programme introduce the scope, aims and goals of the program. The ESMO Leaders Generation Programme was designed to shape the future of the oncology profession as well as the future of ESMO. This exciting and intensive course has been specifically created for young oncologists to provide them a specific training needed for future leadership. Covered topics include ESMO and the world of oncology as well as the development of personal skills especially in the areas of communication, leadership and career development. All qualified medical or clinical oncologists working in Europe who are ESMO members and aged between 31 and 45 years are invited to apply for the program. The course is divided into two parts and provides a variety of interactive training as well as mentoring by experts in the field of oncology. Applications can be filled out on the ESMO homepage. The alumni give detailed insights on their most valuable ESMO Leaders Generation Programme experience and encourage applying to the program. Participants in this podcast conducted by Editor Anna Berghoff: - Guillem Argiles and Leticia De Mattos Arruda (Department of Medical Oncology, Vall d'Hebron University Hospital and Institute of Oncology , Barcelona , Spain); - Carmen Criscitiello (Division of Early Drug Development, European Institute of Oncology, Milano, Italy); - Matteo Lambertini (Department of Medicine, Institut Jules Bordet and Université Libre de Bruxelles (ULB), Brussels, Belgium).

Read the Abstract on the ESMO Open website: http://esmoopen.bmj.com/content/3/1/e000312.

Heterogeneity of colon cancer: from bench to bedside Jun 14, 2017

Show notes

Professor Marco Merlano, Oncology Department Santa Croce e Carle, General Hospital, Italy, is the leading author of the ESMO Open article ‘Heterogeneity of colon cancer: from bench to bedside’, summarised in this podcast. Abstract The large bowel shows biomolecular, anatomical and bacterial changes that proceed from the proximal to the distal tract. These changes account for the different behaviour of colon cancers arising from the diverse sides of the colon–rectum as well as for the sensitivity to the therapy, including immunotherapy. The gut microbiota plays an important role in the modulation of the immune response and differs between the right colon cancer and the left colorectal cancer. The qualitative and quantitative difference of the commensal bacteria between the right side and the left side induces epigenetic changes in the intestinal epithelial cells as well as in the resident immune population. The second player in the pathological homeostasis of colorectal cancer is the differences of the genetic features of cancer cells and the different effects that microsatellite instability, chromosomal instability and the CpG island methylator phenotype induce on the immunological organisation of the tumour microenvironment. The third player is the immunological composition of the tumour microenvironment, which changes under the influence of both genetic structures and gut microbiota. All these three players influence each other. This review describes these three aspects, highlights their interactions and discusses data from reported clinical trials.

Read the full article on the ESMO Open website: http://esmoopen.bmj.com/content/2/3/e000218.

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