Radiation Oncology. Professor Jean-Philippe Pignol Head of Department

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1 Radiation Oncology I am proud to present this leaflet, which is only a brief excerpt of the incredibly broad research and education activities of the department of Radiation Oncology at Erasmus Medical Center. Yet it shows how much each of us is deeply committed to and passionate about improving the treatment of our patients. We are blessed with an unparalleled amount of resources available at Erasmus MC and with the diverse and highly sophisticated radiation treatment technologies available in our Department. However, our biggest strength remains our very committed and supportive staff. Over the years our Department has developed a strong research focus. We aim to increase radiation efficiency using novel radiosensitization strategies combining hyperthermia and DNA repair inhibition. At the same time, we focus on reducing treatment-induced side effects using high-precision robotic radiotherapy, hypofractionation, and dose distribution optimization and automation. Ongoing major technical developments include the building of HollandPTC, which is a Medical Delta shared proton therapy facility, and the creation of an intervention radiotherapy unit, enabling image guided and combined therapies such as hyperthermia and internal irradiation (brachytherapy). Our ambition is to eventually enable the clinical translation and evaluation of those inventions using novel clinical trial strategies and new techniques to measure patient s outcome. This will be done in close collaboration with many colleagues in other departments in the Erasmus MC and other Radiation Oncology Departments in The Netherlands, Europe and beyond. Professor Jean-Philippe Pignol Head of Department

2 Shafak Aluwini radiation oncologist As a radiation oncologist I specialize in treating prostate cancer. Our prostate center (Prostaatcentrum zuidwest Nederland), which is a collaboration between the Erasmus MC and the Sint Franciscus Gasthuis, clusters all expertise concerning prostate cancer. For patients, this means they can in principle get all advice and diagnostic tests in a single session. In addition, the collaboration increases our expertise, giving us the opportunity to offer treatments to almost all patients with prostate cancer. The prostate is located in a critical area, lying close to the bladder and the rectum with the urethra dissecting it. Our treatment therefore has to be careful in order not to negatively influence these organs. This is why we constantly seek for new means of irradiation that are more effective and yet less harmful to the surrounding tissue. For instance, we use a new method for internal irradiation called HDR brachytherapy. For this, a number of hollow tubes are inserted in the prostate, through which a radioactive iridium source passes at a controllable, yet variable speed. This means a higher radiation dose can be given at the site of the tumor, while healthy tissue can be spared. Our current Probach study investigates the effect of HDR brachytherapy on the short and long term side effects. A major publication this year was our article in the Lancet Oncology, in which we reported the first results of our HYPRO study comparing a regular treatment cycle of 39 external irradiations to a shortened cycle of 19 treatments. Unfortunately, the side effects during the first three months after treatment have increased significantly in the shortened cycle. The effect in the long term, however, is expected to be equal in both test groups, which in the end is more important. It is clear that this type of research is important to decide whether or not we can offer patients a shortened cycle of treatment. Erasmus MC-Radiation Oncology : review of an inspiring year This leaflet introduces you to some of the key achievements of the Department of Radiation Oncology at Erasmus MC Cancer Institute in We are introducing here only seven of the more than three hundred department employees who, each in their own field of expertise, have outstandingly contributed to the general mission of the department: offering more effective radiation treatment to cancer patients with as little side-effect as possible. You will read about research and education, proton therapy and hyperthermia, about the contribution of radiotherapists, the multidisciplinary way to treat prostate cancer, and the high tech possibilities of robotic radiotherapy. More than 5,000 patients were treated in the department of Radiotherapy during the past year. Whatever the reason you have been in contact with the Radiation Oncology Department, we are pleased to offer you this leaflet to give an overview of the department history, goals and current activities. 2

3 History Did you know that already in 1914 the Rotterdam Radiotherapy Institute (RTTI) was founded at the Bergweg in Rotterdam? Administration of ionizing radiation or X-rays as a treatment for cancer had only just started at that time. Remember that X-rays were first discovered just 20 years before in 1895, and the first radioactive source, radium, was isolated only in In 1940 the radiologist Daniel den Hoed became the director of the RTTI and under his supervision the institute developed into a renowned hospital. In 1960, the RTTI and the Rotterdam Rheumatism Foundation joined forces and the building of a new hospital at the Groene Hilledijk in Rotterdam was started. The Daniel den Hoed hospital, currently known as the Erasmus MC-Daniel den Hoed Cancer Center, was opened in 1965 and is still located where it started. Early in 2018, the Department will relocate from its historical location to a new building next to the Erasmus MC in the center of Rotterdam. The new Department will provide inside a luminous, appealing design and gigantic proportion space the most cutting edge technologies for research, education and patient care. Martine Franckena radiation oncologist As a radiation oncologist I treat patients with gynecological or urological tumors. In addition, I am the medical coordinator of the hyperthermia section. The effect of radiotherapy can be increased one and a half times by slightly heating the tumor, without aggravating the side-effects. Whether hyperthermia can be used depends mostly on the position of the tumor. In Rotterdam we are able to heat superficial tumors, e.g. breast or skin tumors, as well as tumors located in the pelvis or in the head and neck area. Other tumors, such as in the lungs or the head can unfortunately not yet be heated. In addition, the use of hyperthermia depends on the treatment it needs to enhance. Combining hyperthermia with chemotherapy strongly depends on the drug. With some drugs it is highly effective, but other drugs might lose their effect or become more toxic. The Erasmus MC can be regarded as the national center of expertise, even though hyperthermia itself is also done in other places. In Rotterdam, however, we are able to make patient specific schedules where we can monitor the best way of heating during the treatment. In addition, we now have a special MRI system that allows us to heat tumors inside the MRI scanner. To me, the commissioning of this new system is the most important event of the past year. Using this system we can investigate the mechanisms behind hyperthermia. It has already been shown that heating inhibits repair of DNA damage, increasing the effect of the treatment. But also the improved blood flow in the tumor can add to the effect of the treatment. The Dutch Cancer Foundation (Koningin Wilhelminafonds, KWF) has awarded me a large sum of money to set up a research project using the new MRI scanner. 3

4 Claire Wyman nanobiologist During radiotherapy DNA of tumor cells is being damaged, causing the cells to die. Just like healthy cells, tumor cells have multiple mechanisms to repair DNA damage. In my research group we try to find out precisely how these repair mechanisms work. Our results can then help to improve anti-cancer treatments such as radiotherapy. Repairing DNA damage in cells is done by proteins, tiny machines of a few nanometers. That is a thousand times smaller than a hair! To really understand how these proteins work, we would like to see what they are doing. That is not possible with a normal microscope. Fortunately, the Optical Imaging Center of the Erasmus MC has advanced microscopes that allow use to make pictures and movies of proteins inside a cell. Our research is being driven by curiosity, so we cannot tell in advance how it will benefit patients. On the other hand, fundamental research can also have surprising connections to the clinic. Researchers found that a certain repair protein got destroyed if cells were heated slightly. That result lit up the light bulbs: there already is a treatment for cancer that involves heating tumors, called hyperthermia. And indeed, the destruction of the repair protein turned out to be one of the explanations for the effectiveness of this treatment. This new insight allows optimizing existing hyperthermia treatments. To me, the most important result of this year was our publication in which we used the newest techniques to show how a particular individual protein is moving around in a cell. To compare, a fire truck cannot do anything until it gets to the fire. But how does it move through the busy traffic? The same question can be asked for repair proteins. Using experiments that really pushed the edges of what we could detect, we now visualized the movements of the protein in living cells. Patient care If you have a cup of coffee at the coffee corner in the outpatients clinic of the Erasmus MC-Daniel, you certainly have experienced the uninterrupted flow of patients and family members constantly coming and going. This activity is understandable if you know that some 85,000 radiation treatments were delivered last year and that most treatments are outpatient treatments. Under the inspirational leadership of a new Canadian head of department, Professor Jean-Philippe Pignol, who took the helm in August 2014, more than 300 employees contribute every day to patient care: radiation oncologists, radiotherapists, clinical physicists, nurses, secretaries, technical support and many others. Together they ensure flawless and top quality treatment for each individual patient. Prior to an actual irradiation many steps have already been taken. Some of these steps, such as the appointment with the specialist(s) and the making of a CT scan, are visible to the patients, but the majority of the work is done behind the scenes. In order to make a treatment plan, the tumor is meticulously delineated on the CT images, reconstructed in three dimensions and subsequently the radiation effect is simulated and optimized using very powerful computers and the optimal radiation dosage is calculated. 4

5 Joost Nuyttens radiation oncologist At Erasmus MC, multiple tumors are treated using the Cyberknife. In this machine, a linear accelerator is attached to a robotic arm which can move in virtually any direction. This allows us to irradiate the tumor from different angles and increases the precision of the treatment. The robot can also follow the movement of the tumor. Imagine a lung tumor moving up and down with respiration. The computer not only calculates the course of the respiratory movement, but can also adapt to changes, for instance if the patients starts breathing faster. The precision and the adaptive ability of the Cyberknife helps to reduce the damage inflicted upon healthy tissue. Other types of tumors can be treated with the Cyberknife as well. Pancreatic tumors, for instance, also follow the respiratory movement, but in addition stomach and bowel position vary with food intake. Their position changes every day. In our current study we make a scan shortly before irradiation begins and calculate the dose to the bowel and stomach. In the future we want to give a higher dose to the tumor if the intestines and the stomach are relatively far from it. This might shorten the total treatment or reduce the side effects. This year s major event is the commissioning of a CT-scanner in the same room as the Cyberknife, enabling us to study the exact dose given to the bowel and stomach. The treatment table with the patient moves from the CT scanner to the Cyberknife. The first patients are currently being treated in a clinical study and the preliminary results are promising. This study is being conducted by different departments in the Erasmus MC and underlines the effective collaboration between them. Research The optimal radiation dosage does not always equal the highest dose possible. The treatment plan aims to reach as many tumor cells as possible, but to also spare the surrounding tissue and minimize the treatment induced side effects. Scientific research and the application of new treatment strategies are both helping to achieve this. Take for example stereotactic irradiation, where narrow beams accurately aim from many different angles to the tumor that is accurately located in the 3 dimensional space. The department of Radiation Oncology in Rotterdam is the only Dutch department to possess robotic radiosurgery, and not one but two Cyberknives are available. These frameless robotic radiosurgery systems significantly increase the accuracy of treatments. The second Cyberknife went into operation this year and is the first in the world with an in-room CT scanner and the newly released micro-multileaf collimator. The department also investigates how to optimize internal irradiation techniques (such as brachytherapy) e.g. for the treatment of prostate cancer, how to apply hyperthermia (local heating of the tumor) and why it works, and the possibilities of proton therapy. To enable this latter form of therapy, Erasmus MC, the Technical University Delft and Leiden University jointly started building the Holland Particle Therapy Center in May The research of the Department of Radiation Oncology has resulted in a large number of publications in high impact journals. A report of the results of a clinical trial assessing the side effects following a shortened treatment cycle for prostate cancer patients has even been published in The Lancet Oncology. In addition, the department received several major peer review grants totaling several million of euros.

6 Marjon de Bruin sector manager Radiation therapists are involved in almost all aspects of radiotherapy treatment, both in preparation for treatment and in the actual treatment itself. They make the CT scan at the start of the treatment, co-determine the irradiation plan and operate the accelerators during the therapy. Each type of accelerator has its own team of therapists, and each team is led by a coordinator who in turn reports to me, the sector manager. In principal, each therapist has two working spots: one in the preparation process and one on an accelerator. Focus areas have been formed for areas such as CT and dose planning, to ensure that the teams have the same knowledge and apply the same strategies. As soon as we move to our new location next to the Erasmus MC hospital, only one type of accelerator will remain, so we will need to regroup our teams. One of the ideas is to group the therapists by specialization for a certain type of tumor, as is done by the radiation oncologists. For me the most important event of the last year was the arrival of our new head of department Jean-Philippe Pignol. He brought a breath of fresh air and started multiple important projects. One of them is Stop the beep. This project is meant to diminish the frequency of telephone contact between oncologists and therapists by making the processes involved in patient treatment more efficient. This leads to more research time for the oncologists, allows therapists to develop themselves by involvement in research and hopefully will increases job satisfaction. Another improvement is that we hired nurses who will be dedicated to the Radiation Oncology department, so we don t have to call upon nurses from other departments. Finally, we will start a palliative outpatient clinic, in which a special team will support the palliative care patients. Pignol set all of these projects in motion and gave the employees the energy to address the different issues. Education Treating tumors using the most advanced radiotherapy techniques requires welltrained specialists. The Department of Radiation Oncology is therefore strongly involved in education and training. It offers, among others, training for radiation oncologists and radiotherapists and is responsible for most oncology modules for undergraduate medical students. In addition, the department s specialists also share their knowledge and experience during in-service training modules. This year, the first training in the European School of Robotic Stereotactic Surgery was successfully started, and colleagues from all over the world learned how to practice radiosurgery and stereotactic body radiotherapy using the Cyberknife. 6

7 Mischa Hoogeman medical physicist For radiotherapy it is very important to precisely determine the location of the tumor using a CT-scan and an MRI-scan if needed. The treatment volume, which will be deduced from the images, is always larger than the tumor itself. This is necessary because tumor cells might be present in what appears to be healthy tissue and because the position of the tumor might change. The majority of our research focuses on mapping the mobility of tumors as accurately as possible and correcting for it with the aim of reducing the treatment volume. In one of our current research projects we study cervical tumors. The position of these tumors changes every day, since they are influenced by both the bladder and the rectum. Prior to the treatment course a patient specific library is created containing a series of treatment plans adjusted to the possible positions of the tumor. Just before the actual irradiation a CT scan is made and the treatment plan that fits this scan the best is taken out of the library, the socalled Plan of the Day. A very important event in 2015 was the start of the construction of the Holland Particle Therapy Center in Delft, in which we expect to treat the first patients with protons in the middle of Until now, proton therapy is not possible in The Netherlands, but it does have a significant advantage compared to radiotherapy with X-rays, as a proton beam only penetrates to a specific depth. This allows us to precisely focus the irradiation to the position of the tumor and spare the surrounding tissue. For proton therapy, image-guidance is even more important. If the protons stop a few millimeters sooner or later, part of the tumor will not be irradiated at all or an area of healthy tissue will receive the high dose that was meant for the tumor. 7

8 Manouk Olofsen radiation oncologist/education coordinator In addition to patient care and research, the Department of Radiation Oncology is also strongly involved in multiple educational programs. When I first started here, I treated patients, was involved in scientific research and did my share of teaching, but education stole my heart. So I stopped doing research and took up coordinating the different educational programs in the department: training for future radiation oncologists and radiotherapy teaching modules for medical students. In addition I teach radiotherapists and coordinate their training. The training for radiation oncologists is a national coordinated program. I am actively involved in the scientific association for radiation oncologists (NVRO) and thus in shaping the training and evaluating the individual training institutes. The guidelines drawn up by our government sometimes complicate our task, e.g. the number of training positions. This is determined by the government and forces us to train more specialists than necessary. As a result, some of the residents we trained are currently unemployed. To me as education coordinator, this is heartbreaking. Therefore, if possible, we stimulate our trainees to educate themselves in other aspects as well, or to actively involve themselves in research projects or educational activities of staff members. This will increase their chances of finding a job. In my view, the employment of Jean-Philippe Pignol as our new head of department might be the most important event of the year. The Board of Directors of the Erasmus MC did their job well. Our department has always dedicated itself to taking care of patients that come to us from a large region surrounding Rotterdam. This took up all of our time and left the specialists with hardly any time for scientific research. Jean-Philippe is showing us that by organizing our tasks differently, we can have time for research and still provide excellent patient care. We try to teach that to our residents too. Colofon 2015 Department of Radiation Oncology, Erasmus MC Text and editorial control: Marja Miedema, Erasmus MC Layout and portraits: Tom de Vries Lentsch, Erasmus MC Other images by: Levien Willemse; Department of Radiation Oncology; De Jong Gortemaker Algra Printing: Virtual Printer, Papendrecht Special thanks to: Olijn Tims, Lijanne Otto-Vollaard, Sanne Blinde, Jaap Jaspers, Renee Rijnsdorp.