Sub theme 3.3
Improving accuracy and therapeutic ratio in radiation oncology

Goals of research: general outline
Scientific achievements
Future plans: special goals and approach
Running projects
Associated staff

Goals of research: general outline

In radiotherapy, treatment related morbidity may be substantial while on the other hand tumor control rates could be further improved. The investigations in this theme are focused on development of new technology and methods to enhance the therapeutic ratio. Depending on the specific tumor site or even the patient, this may be exploited to reduce radiation induced toxicity and/or increase the (effective) tumor dose. Major efforts are focused on identification and sparing of structures that may cause toxicity and on development and evaluation of new technology for more precise dose delivery.

Scientific achievements
  • Patient anatomy changes during a fractionated treatment (e.g. due to rectal filling variations, tumor shrinkage, etc.) are of major concern. To investigate the impact of these changes and solutions, a system for non-rigid image registration was developed and used to investigate deformations in the anatomies of head and neck cancer, cervix cancer and prostate cancer patients. Non-rigid image registration will be a major component for the investigations on dose painting and adaptive therapy (item 3. below).
  • For head and neck cancer, the department was among the first worldwide to extend investigations on radiation induced toxicity from xerostomia, to dysphagia and trismus. In a randomized trial, the positive effect of adjuvant hyperbaric oxygen treatment was clearly demonstrated. Together with external partners, a software module for auto-contouring of 3D image datasets was developed and evaluated. A system was developed for high precision, single vocal cord irradiation, using daily acquired cone beam CT-scans and advanced optimization and dose calculation algorithms.
  • For prostate cancer, the department was one of the initiators of a national randomized trial comparing the convential tumor dose with an enhanced dose, both regarding toxicity and tumor control. Patient accrual was completed and the first promising results were published. A system was developed for fast and accurate, daily repositioning of prostate patients, based on acquired images. It was demonstrated that the required safety margin to avoid partial tumor misses could be substantially reduced, resulting in a more focused dose delivery. The developed technology is now in clinical use in most Dutch radiotherapy centers. A new national trial has been initiated comparing conventional dose fractionation with hypofractionation.
  • For cervix cancer, extensive investigations have been started to study the impact of bladder filling variations on targer position and shape. The results will be used to investigate daily treatment interventions (item 3. below) 
  • For stereotactic, hypofractionated liver treatment, extensive investigations have created the possibility to individualize, and generally increase the delivered tumor dose. Excellent clinical results have been reported. Patients are referred from all over the Netherlands.
  • Robotic radiotherapy (Cyberknife) was introduced and optimized to treat with very small safety margins. Low stage lung tumors are now treated with ultra high doses and excellent clinical results.
  • Important progress has been made in mathematical optimization of beam angles. Clear advantages have already been observed for treatment plans for liver cancer patients. A system has been developed for combined optimization of beam angles and fluence profiles using multi-criteria optimization. First results of a new method for beam angle selection for robotic treatments do also point at clear advantages.
  • On all topics mentioned above, papers have appeared in the highest ranking journals of the field.

Future plans: special goals and approach
  • Together with the Delft University of Technology, the Netherlands Cancer Institute (NKI), and the Leiden University Medical Center (LUMC), Erasmus MC, and in particular the department of Radiation Oncology, is involved in founding a new particle therapy center (> 100.000.000,-). There are strong indications that with these particle beams (protons and light ions) highly superior dose distributions can be delivered to specific patient groups, both regarding the physical dose, as for the biological impact (light ions). A large research program is being set up to investigate the new opportunities.
  • Currently, in radiotherapy treatment planning it is assumed that the tumor is homogeneous, so all tumor areas should receive equal doses. Obviously, this is often not the case and new biological and functional imaging techniques are being developed and explored to identify tumor subvolumes that should receive higher doses. This type of dose delivery is called dose painting which can be realized using intensity modulated beams (IMRT), a speciality of the department. Dose painting based on biological/functional imaging will be a major research topic in the coming years.
  • Both for particle and photon beam therapy, image-guided, and adaptive radiotherapy will be major research topics. In adaptive therapy, medical images acquired during the course of a fractionated treatment will be used to adapt the treatment plan to optimally account for changes during the treatment. These changes can be anatomical (e.g. due to weight loss or tumor shrinkage), but also biological. To observe biological changes, repeat MRI/MRS, PET, and/or SPECT datasets will be acquired.

Most recent publications

1.      Early Hyperbaric Oxygen Therapy for Reducing Radiotherapy Side Effects: Early Results of a Randomized Trial in Oropharyngeal and Nasopharyngeal Cancer. Teguh DN, Levendag PC, Noever I, Voet P, van der Est H, van Rooij P, Dumans AG, de Boer MF, van der Huls MP, Sterk W, Schmitz PI. Int J Radiat Oncol Biol Phys. 2009 Apr 20. [Epub ahead of print]

2.      Méndez Romero A, Zinkstok RT, Wunderink W, van Os RM, Joosten H, Seppenwoolde Y, Nowak PJ, Brandwijk RP, Verhoef C, IJzermans JN, Levendag PC, Heijmen BJM. Stereotactic body radiation therapy for liver tumors: impact of daily setup corrections and day-to-day anatomic variations on dose in target and organs at risk. Int J Radiat Oncol Biol Phys. 2009 Apr 20. [Epub ahead of print]

3.      Hoogeman M, Prévost JB, Nuyttens J, Pöll J, Levendag P, Heijmen BJM. Clinical accuracy of the respiratory tumor tracking system of the cyberknife: assessment by analysis of log files. Int J Radiat Oncol Biol Phys. 2009; 74(1): 297-303.

4.      Stereotactic radiotherapy with real-time tumor tracking for non-small cell lung cancer: clinical outcome. van der Voort van Zyp NC, Prévost JB, Hoogeman MS, Praag J, van der Holt B, Levendag PC, van Klaveren RJ, Pattynama P, Nuyttens JJ. Radiother Oncol. 2009; 91(3): 296-300.

5.      Mutanga TF, de Boer JCJ, van der Wielen G, Wentzler D, Barnhoorn J, Incrocci L, Heijmen BJM. Stereographic Targeting in Prostate Radiotherapy: Speed and Precision by Daily Automatic Positioning Corrections Using kilovoltage/Megavoltage Image Pairs. Int J Radiat Oncol Biol Phys. 2008; 71(4): 1074-83.

6.      Results of fiberoptic endoscopic evaluation of swallowing vs. radiation dose in the swallowing muscles after radiotherapy of cancer in the oropharynx. Teguh DN, Levendag PC, Sewnaik A, Hakkesteegt MM, Noever I, Voet P, van der Est H, Sipkema D, van Rooij P, Baatenburg de Jong RJ, Schmitz PI. Radiother Oncol. 2008 Oct;89(1):57-63.

7.      Dysphagia disorders in patients with cancer of the oropharynx are significantly affected by the radiation therapy dose to the superior and middle constrictor muscle: a dose-effect relationship. Levendag PC, Teguh DN, Voet P, van der Est H, Noever I, de Kruijf WJ, Kolkman-Deurloo IK, Prevost JB, Poll J, Schmitz PI, Heijmen BJ. Radiother Oncol. 2007 Oct;85(1):64-73.

8.      Vásquez Osorio EM, Hoogeman MS, Al-Mamgani A, Teguh DN, Levendag PC, Heijmen BJM. Local anatomic changes in parotid and submandibular glands during radiotherapy for oropharynx cancer and correlation with dose, studied in detail with nonrigid registration. Int J Radiat Oncol Biol Phys. 2008; 70(3): 875-82.

9.      Seppenwoolde Y, Berbeco RI, Nishioka S, Shirato H, Heijmen BJM. Accuracy of tumor motion compensation algorithm from a robotic respiratory tracking system: a simulation study. Med Phys. 2007; 34(7): 2774-84. IF 3.5

10.  Breedveld S, Storchi PRM, Keijzer M, Heemink AW, Heijmen BJM. A novel approach to multi-criteria inverse planning for IMRT. Phys Med Biol. 2007; 52(20): 6339-53