Academic Center for Thoracic Oncology

Last updated: 365 days ago.

This ACE functions as an open and innovative group of people with a focus on preclinical, translational and clinical research for the treatment of (non) small cell lung cancer, thymoma, thymic carcinoma, and peritoneal mesothelioma

Global aim of the ACE Thoracic Oncology is to optimize the quality of health care in order to achieve the best patient outcomes on a regional, national and international level.

Specific aims:

- Develop specific tools to improve quality of life and survival of patients with thoracic malignancies

- Implement innovative research outcomes in the patient health care and evaluate the treatment effectiveness

- Invest in a strong collaboration on regional, national and international levels.

Academic Center of Excellence

Research Activities

Our multidisciplinary research group became leading in basic, translational, (pre)clinical studies of thoracic malignancies. The ACE is involved in over 70 clinical trials, which underlines the strong focus on development of new treatments and making new treatments available for patients. We use of a range of different approaches, including immunotherapeutic, epidemiologic and the genetic approach in innovative trials. The ACE conducts fundamental research, both investigator initiated as well as pharma initiated, on the field of thoracic surgery, radiotherapy, radiology, clinical oncology, nuclear medicine and pathology.

The department of pulmonary diseases has a long standing track record in preclinical oncology research. The aim of this department is focused on translational research. This has for instance resulted in the development of a murine model for mesothelioma where a new immunotherapeutic treatment has been developed: dendritic cell immunotherapy. This treatment option has been developed in the lab and has been introduced in humans in 3 early phase clinical studies and is now tested in a multicentre international phase III registration study. In the past years, 5 PhD graduates have been supervised and at present 5 PhD students are working of different projects on preclinical immune-oncology.

Furthermore, the department of pulmonary diseases also participates together with the department of medical oncology in the phase 1 clinical trial unit. This unit strives to perform trials with novel agents that could potentially benefit our patients. Within these trials we test novel treatment concepts, such immunotherapy with new drugs, targeted inhibition of molecules involved in cancer and combinations of known and novel drugs. In these trials we determine the dose we can administer to our patients safely and how the new drug is taken up by the body. Increasingly we also try to find early signs of activity of these novel agents, using improved imaging methods and biopsies of tumours.

An example with an immunotherapeutic research approach is an immune checkpoint inhibitor study; Multomab. Immune checkpoint inhibitor therapy have become key players in the treatment of many cancers. However, only a minority of cancer patients respond well and the treatment exerts immune related toxicity. Multomab is a study to prospectively collect blood from patients with different types of cancer planned to receive a monoclonal antibody as anti-cancer treatment. To date, over 500 cancer patients are included in the study, giving us the opportunity to research factors: e.g. tumour biology, immune status and pharmacokinetics. Hereby we have close collaboration with the department of medical oncology and tumour immunology, among other scientific top-notch collaborations. Eventually, the study will lead to better understanding of the treatment and the results will be translated in clinical practice.

Examples of smaller but important investigator initiated studies are:

In collaboration with clinical oncology:

· Tyrosine Kinase Inhibitors (TKI) essays

· Therapeutic drug monitoring (TDM)

· Start-TKI study

· CPCT/genomic

· SCLC

· Chemotherapy

· Multomab

In collaboration with Pathology:

· Tumour mutational burden (TMB)

· Cell free DNA analysis

· Case reports and case series

· SCLC circulating tumour DNA

In collaboration with Radiotherapy:

· NSCLC PEMBRO-RT

In collaboration with Neuro-oncology:

· NSCLC Brainmetastases

In collaboration with Nucleair Medicine:

· Start Cyclotron

In collaboration with Thoracic surgery:

· Shared decision making

· I-ELCART study

· Debulking-surgery

· HIPEC

· Immunotherapy

· Clinical N2 Disease NSCLC

· Onco Guideline

· Meta analyses overall survival chemoradiotherapy or chemotherapy

Type of

Collaborations

Different PIs in our ACE collaborate with various clinical and research partners both on national and international level. A regional disciplinary collaboration is the Comprehensive Cancer Network (CCN). The ACE thoracic oncology plays a leading role in this network. Once a month, a newsletter is sent to peripheral centres to inform them about ongoing studies and new developments. In addition, several times a year meetings are being held to discuss organizational and practical issues, leading to uniformization between the various hospitals in the CCN. In this, also patients advocacy Longkanker Nederland is actively involved. As an additional result, via this network patients are more often referred to the Erasmus MC when appropriate.

Within this ACE, a newly formed collaboration is the monthly RECIST meeting. These meetings are organized for the departments of pulmonary, radiology, thoracic surgery, pathology, radiotherapy and molecular sciences. The meetings give our colleagues the opportunity to discuss new developments and evaluate the ongoing studies. The meetings are often highly informative, and therefore also open for fellowships.

National collaborations in research with the leading oncology centres are present at multiple levels. The department of pulmonary diseases is active in the Dutch society for physicians in pulmonary and tuberculosis (NVALT), with two board memberships and also in the research society of the NVALT as board member.

Joint international research collaborations efforts exist between the department of pulmonary diseases and multiple international centres, such as Memorial Sloan Kettering Cancer centre in New York, The University Hospital Langone in New York, the Mount Sinai Hospital in New York, University Hospital Leicester, University Hospital Torino, University Hospital Lille and University Hospital Antwerp. Furthermore, our ACE is member of the exon 20 group, a special research collaboration for a rare genetic alteration in NSCLC.

Our ACE participates in the NIAZ, IKNL and WMO visitations. Furthermore, the ACE participates in the European Reference network on rare lung diseases (ERN-Lung), which strongly focusses on improving clinical care for patients all across Europe. The core network on mesothelioma is coordinated by our department.

Educational

Contributions

Education is an important tool to ensure excellent patient care by training current and future generations of physicans. This ACE focusses on education on several levels, from medical students to fellow specialists.

ACE Thoracic Oncology:

· Provides education to Bachelor's, Master's and PhD students

· Provides the opportunity for an official internship for medicine students in thoracic oncology, which includes lung oncology, immunotherapy, TKI treatment, mesothelioma, and research

· Provides the opportunity for (international) fellowships in tertiary outpatient and clinical thoracic oncology

· Organizing the Rotterdam Oncology & Thoracic Study group (ROTS) symposium. This symposium is organized for pulmonologists, thoracic surgeons, pathologists, radiotherapists, and nurses, to inform them about the highlights and new developments of the past year. Furthermore, (inter)national professionals are invited to present new techniques.

· Organizing the New York Dutch Lung Cancer Course. This course is an educational collaboration between the Erasmus MC and The Mount Sinai Hospital in NY where lung cancer screening was initiated. This hands on course is yearly organized for medical specialists and fellowships to learn about lung cancer screening, new developments and diagnostics.

· Organizing committee for the live ASCO meeting in The Netherlands for pulmonologists (Rotterdam ademt Chicago).

· Education of fellows in speciality training local in Erasmus MC and national.

· Co-Chair of the yearly education program for pulmonary oncology (Wengen Course)

The education programs of the ACE are reviewed by the participants and also externally. The Erasmus MC has an ongoing review of the education given to the medical students where the ACE members actively participate. There is a continuous adaptations of the program based on the feedback of the students. In general the scoring of the education to medical students is high.

As an example the New York Dutch Lung Cancer Course is year after year graded with an 8 or 9 by the participants. Also the Wengen course is highly appreciated by the participants. Last year the scoring was 8.3 in general, where the main appreciation is the fact that the course is really practice changing for the general pulmonologist.

Patient

Care Activities

Thoracic oncology is an area with progressive and rare diseases. With the ROBIJN method, the department of thoracic oncology covers 96% academic patient care. In addition to the existing acknowledgement as expert centre on mesothelioma since 2015, we were recognized in 2018 as an expert centre by the Dutch Federation of Universities (NFU) for the treatment of small cell lung cancer, thymoma, thymic carcinoma, and peritoneal mesothelioma.

We provide a multidisciplinary approach for adequate diagnosis and treatment. This involves weekly, well structured, multidisciplinary meetings to discuss patient cases (MDO's) with other centres. During these meeting, at least one thoracic surgeon, a specialist nurse, and a case manager are present, other disciplines are present if appropriate. As a results of these meetings, we are able to move quick in order to start the patients' treatment. Another additional benefit is that several disciplines within the ACE are able to discuss difficult cases and to take decisions for example on whether referral of patients to Erasmus MC is required and/or which treatment should be initiated. Altogether, the good collaboration within our ACE ensures that we can provide the patient with a high quality of health care and treatments that are according to the international guidelines.

Proof that our level of expertise is high is given by the NVALT. Since 2016, the NVALT appointed five medical centres in the Netherlands for the therapy of rare lung cancer mutations (incidence <5%), with the purpose to guarantee the highest quality of health care for these patients. Erasmus MC is one of these five centres, which entails that patients with rare lung cancer mutations from whole South-West region are to be referred us and for specific mutations even patients from the whole Netherlands and parts of Europe. Health insurers have conformed to this centralization of healthcare.

The NELSON trials, a pivotal trial on the benefit of lung cancer screening, was headed by the Erasmus MC. Many high impact papers presentations and multiple thesis were already a result of this study. Now that the mortality results of this study were recently presented, lung cancer screening is going to be implemented in many countries worldwide. In The Netherlands, the implementation of lung cancer screening is headed by members of the ACE.

Societal Relevance to Research, Education and Patient Care

Many thoracic malignancies have a poor prognosis: survival of patients is sometimes only several months to few years after diagnosis, despite aggressive treatments. Lung cancer for example has an incidence of >10,000 per year in the Netherlands alone, with a five year survival of only 19% (ref: Dutch Cancer Registration). Obviously, such diagnoses have a tremendous impact on patients, their relatives and society as a whole. There is an urgent need for treatments that increase survival while maintaining quality of life, not only for lung cancer, but also for other thoracic malignancies.

The ACE Thoracic Oncology is determined to continuously improve current- and develop new treatments in order to maintain the highest standard of care for patients. Our main focus is on quality of life, increasing survival and minimising side effects. As a tertiary referral centre, we facilitate peripheral centres in providing the best standard of care by organising and participating in MDOs.

We believe that an active dialogue with patients and their representatives, such as patient organisations, is essential in order to achieve this. We are working in close collaboration with patient organisations, such as Longkanker Nederland, Asbest Slachtoffers Vereniging Nederland and the European Cancer Patient Coalition. They are involved in our scientific research, from set up of new studies to participation in user committees of ongoing studies. They are also involved in communication to patients and the general public on our advances in scientific research and health care. At this moment, we are participating in a trial with Longkanker Nederland to further optimize the patients role in his treatment. Members of the ACE frequently provide lectures for patients, their representatives and general public.

Besides dissemination of our scientific advances to the scientific community via publications in peer reviewed journals and contributions to conferences, we believe that communication to patients and the general public is of outmost importance. As patients with thoracic malignancies represent a significant group within the population, it is of essence that these patients and their relatives are aware that advances are made in the field, and that there are many studies ongoing. In collaboration with the Erasmus MC press officers, we aim to communicate whenever appropriate. For example, a press release was aired after the presentation of the long awaited results of the NELSON study on lung cancer screening, which was picked up by the general press, resulting in articles in national newspapers Trouw and the Volkskrant as well as the TV news.

Viability of Research, Education and Patient Care

The ACE organizes (inter)national conferences for exchange of knowledge but also local in the hospital education programs are present for nurses research etc. Employees of different ages, backgrounds and experience bear knowledge about their specialism and educate each other also with international partners.

Frequent interaction with patient advocacy is present via combination visits of patients, and lecturing at conferences of patient organizations. PhD students are stimulated for international visits and careers.

Members of the ACE actively participate in (inter)national committees regarding thoracic oncology (DLCA, IKNL, IASLC, ATS, EORTC, ERS). They also serve as frequent (invited) speakers at international conferences. In order to optimal use the academic talent of medical specialists, they have followed courses, such as the leadership course for talented medical doctors.

The leading investigator is part of a number of international boards of guidelines. The pulmonologists, pathologists and surgeons do participate in the DLCA board section mesothelioma, oncology and surgery and are also involved in national guideline development. In addition they are involved in organizing national and international meetings, such as the dutch ASCO, ESMO and WCLC, where Thoracic Oncology news is transferred and taken by the implications for the Dutch situation.

We present a specific fellowship for thoracic oncology in a number of medical specialities to ensure broader education of thoracic oncology. The ACE is always investigating new innovative care programs and research projects to ensure optimal care and research. With the lungcancer screening program Erasmus MC is acknowledged as one of the leading centres in the world for the prevention of lungcancer. Also efforts are taken to create awareness on the health risks of asbestos exposure.

The department is involved in over 70 clinical trials, which underlines the strong focus on development of new treatments and making new treatments available for patients. The research of the ACE is sponsored by various funding agencies, such as ZonMw and the European Union, and societies involving community/patient foundations such as Stichting Coolsingel, Stichting Asbestkanker and the mesothelioma patient foundation from the United States.

Key and relevant publications of the last five years

  • De Goeje, P. L., Klaver, Y., Kaijen-Lambers, M. E., Langerak, A. W., Vroman, H., Kunert, A., ... & Hendriks, R. W. (2018). Autologous Dendritic Cell Therapy in Mesothelioma Patients Enhances Frequencies of Peripheral CD4 T Cells Expressing HLA-DR, PD-1, or ICOS. Frontiers in immunology, 9.
  • Visser, S., Huisbrink, J., van‘t Veer, N. E., van Toor, J. J., van Boxem, A. J. M., van Walree, N. C., ... & Aerts, J. G. J. V. (2018). Renal impairment during pemetrexed maintenance in patients with advanced non-small-cell lung cancer: a cohort study. European Respiratory Journal, 1800884.
  • Pedrosa, R. M., Mustafa, D. A., Aerts, J. G., & Kros, J. M. (2018). Potential molecular signatures predictive of lung cancer brain metastasis. Frontiers in oncology, 8, 159.
  • Cornelissen, R., & Aerts, J. G. (2018). Biomarkers in malignant mesothelioma—an unfulfilled need or a waste of resources?. Journal of thoracic disease, 10(Suppl 9), S1084.
  • Visser, S., de Mol, M., Cheung, K., van Toor, J. J., van Walree, N. C., Stricker, B. H., ... & Aerts, J. G. (2018). Treatment Satisfaction of Patients With Advanced Non–Small-cell Lung Cancer Receiving Platinum-based Chemotherapy: Results From a Prospective Cohort Study (PERSONAL). Clinical lung cancer.
  • Bins, S., Basak, E. A., El Bouazzaoui, S., Koolen, S. L., Oomen–de Hoop, E., van der Leest, C. H., ... & Aerts, J. G. J. V. (2018). Association between single-nucleotide polymorphisms and adverse events in nivolumab-treated non-small cell lung cancer patients. British journal of cancer, 118(10), 1296.
  • Costantini, A., Grynovska, M., Lucibello, F., Moisés, J., Pagès, F., Tsao, M. S., ... & Mazières, J. (2018). Immunotherapy: a new standard of care in thoracic malignancies?: A summary of the European Respiratory Society research seminar of the Thoracic Oncology Assembly. European Respiratory Journal, 51(2), 1702072.
  • Mokhles, S., Nuyttens, J. J. M. E., de Mol, M., Aerts, J. G. J. V., Maat, A. P. W. M., Birim, Ö., ... & Takkenberg, J. J. M. (2018). Treatment selection of early stage non-small cell lung cancer: the role of the patient in clinical decision making. BMC cancer, 18(1), 79.
  • Aerts, J. G., de Goeje, P. L., Cornelissen, R., Kaijen-Lambers, M. E., Bezemer, K., van der Leest, C., ... & Braakman, E. (2017). Autologous dendritic cells pulsed with allogeneic tumor cell lysate in mesothelioma: From mouse to human. Clinical Cancer Research, clincanres-2522.
  • Stoop, M. P., Visser, S., van Dijk, E., Aerts, J. G., Stricker, B. H., & Luider, T. M. (2018). High and individually variable enzymatic activity precludes accurate determination of pemetrexed, methotrexate and their polyglutamate metabolite concentrations in plasma. Journal of pharmaceutical and biomedical analysis, 148, 89-92.
  • Yousaf-Khan, A. U., van der Aalst, C. M., Aerts, J. G. J. V., den Bakker, M. A., & de Koning, H. J. (2017). Uniform and blinded cause of death verification of the NELSON lung cancer screening participants. Lung Cancer, 111, 131-134.
  • Dammeijer, F., Lau, S. P., van Eijck, C. H., van der Burg, S. H., & Aerts, J. G. (2017). Rationally combining immunotherapies to improve efficacy of immune checkpoint blockade in solid tumors. Cytokine & growth factor reviews, 36, 5-15.
  • Beije, N., Kraan, J., den Bakker, M. A., Maat, A. P., van der Leest, C., Cornelissen, R., ... & Sleijfer, S. (2017). Improved diagnosis and prognostication of patients with pleural malignant mesothelioma using biomarkers in pleural effusions and peripheral blood samples–a short report. Cellular Oncology, 40(5), 511-519.
  • Steendam, C. M., Dammeijer, F., Aerts, J. G., & Cornelissen, R. (2017). Immunotherapeutic strategies in non-small-cell lung cancer: the present and the future. Immunotherapy, 9(6), 507-520.
  • Mokhles, S., Maat, A. P., Aerts, J. G., Nuyttens, J. J., Bogers, A. J., & Takkenberg, J. J. (2017). Opinions of lung cancer clinicians on shared decision making in early-stage non-small-cell lung cancer. Interactive cardiovascular and thoracic surgery, 25(2), 278-284.
  • de Goeje, P. L., Smit, E. F., Waasdorp, C., Schram, M. T., Kaijen-Lambers, M. E., Bezemer, K., ... & Hegmans, J. P. (2017). Stereotactic Ablative Radiotherapy Induces Peripheral T-Cell Activation in Patients with Early-Stage Lung Cancer. American Journal of Respiratory and Critical Care Medicine, 196(9), 1224-1227.
  • de Mol, M., den Oudsten, B. L., Aarts, M., & Aerts, J. G. (2017). The distress thermometer as a predictor for survival in stage III lung cancer patients treated with chemotherapy. Oncotarget, 8(22), 36743.
  • Stoop, M. P., Visser, S., van Dijk, E., Aerts, J. G., Stricker, B. H., & Luider, T. M. (2016). A new quantification method for assessing plasma concentrations of pemetrexed and its polyglutamate metabolites. Journal of pharmaceutical and biomedical analysis, 128, 1-8.

PhD theses of the last five years

  • Joachim Aerts (oratie); Pulmonale oncologie niet immuun voor behandeling April 2015 https://repub.eur.nl/pub/93229/150424_Aerts-Joachim-GJV-ORATIE.pdf
  • Marlies Heuvers Improving lung cancer survival; Time to move on. June 2013 https://repub.eur.nl/pub/74994
  • Nanda Hoonreweg; Lung cancer screening in the Nelson trial; balancing harms and benefits November 2014 https://repub.eur.nl/pub/50089
  • Caroline Broos; T helper 17 cells and Regulatory T cells in Pulmonary Sarcoidosis : It takes two to tangle March 2017 https://repub.eur.nl/pub/98472/
  • Lysanne Lievense; Macrophages in Mesothelioma : Improving immunotherapy in pulmonary oncology March 2017 https://repub.eur.nl/pub/98474
  • Heleen Vroman; Heterogeniteit in astma : Implicaties voor dendritische cel activatie? June 2017 https://repub.eur.nl/pub/100318
  • Bobby Li; Group 2 Innate Lymphoid Cells in Allergic Airway Inflammation : Early Birds or Night Owls February 2018 https://repub.eur.nl/pub/104292/
  • Irma Tindemans; Notch Signaling During T Helper 2 Cell-Mediated Inflammation in Allergic Asthma March 2018 https://repub.eur.nl/pub/105791

Non-scientific publications related to the ACE

  • https://www.rtlnieuws.nl/lifestyle/gezondheid/artikel/4150461/komende-jaren-nog-ruim-9000-doden-door-asbest
  • https://www.gezondheidsnet.nl/kanker/nieuwe-techniek-bij-immunotherapie-asbestkanker
  • https://www.ad.nl/rotterdam/experiment-erasmus-mc-met-behandeling-asbestkanker~a55904ba/
  • https://www.rtlnieuws.nl/node/1137856
  • https://www.rtlnieuws.nl/nieuws/nederland/artikel/4430311/artsen-pleiten-voor-screening-longkanker-bij-ex-rokers
  • https://www.volkskrant.nl/wetenschap/screening-op-longkanker-bij-ex-rokers-zou-duizenden-doden-voorkomen-maar-deskundigen-zijn-sceptisch~be41757d/
  • https://www.nu.nl/gezondheid/5479844/ct-scan-kan-longkanker-in-gunstiger-stadium-ontdekken.html
  • https://www.trouw.nl/samenleving/screening-op-longkanker-redt-duizenden-levens~a43a9a94/
  • https://www.medicalfacts.nl/2017/03/15/unieke-samenwerking-kankerpatienten-behandelcentrum-immunotherapie-amphia/
  • https://www.volkskrant.nl/wetenschap/kankermedicijn-werkt-beter-met-cola~b5934753/
  • https://nos.nl/artikel/2056802-longkankermedicijn-niet-voor-elke-patient-beschikbaar.html

Principal coordinator(s)