ESTRO 36 Abstract Book

S50 ESTRO 36 2017 _______________________________________________________________________________________________

mean prostate volume was 37.9 cc (range 18-54). No patients experienced acute or late Grade 2+ GI toxicity. The percentage of acute Grade 2 GU toxicity were as follows; retention 62%, frequency 18%, urinary tract pain 6%. One patient required catheterization (acute G3) for one day post treatment and has been catheter-free since. Urinary retention is the only late Grade 2 GU toxicity that has been reported (n=6). Conclusion The use of mpMRI to define and further escalate dose to the DIL using HDR monotherapy is achievable with minimal acute toxicities. Further long term follow is required to determine efficacy of treatment, and impact on quality of life and late toxicities. SP-0103 The challenges of targeting tumour heterogeneity in the field of radiation oncology P. Lambin 1 , L. Dubois 2 , A. Yaromina 2 1 MAASTRO Clinic, Maastricht, The Netherlands 2 Maastricht University, Radiotherapy, Maastricht, The Netherlands There is no doubt that tumours are heterogeneous at genetic, biological and pathophysiological level. Intra- and intertumoural heterogeneity, on one hand, can facilitate the development of new anti-cancer therapies such as immunotherapies (1), radiation dose-painting strategies (2), and can also have great implications for biomarker discovery. On the other hand, it can hinder anti-cancer therapy success due to the presence of a resistant clone. Overall tumour heterogeneity quantified at the genetic level, tissue level or imaging level (e.g. imaging of tumour hypoxia, or radiomics), is a negative prognostic factor (3,4,5). Tumour heterogeneity creates several challenges that need to be overcome to achieve disease cure. It is unlikely that a single anti-cancer therapy will work alone for several reasons. First, the target is likely heterogeneously expressed throughout a tumour and primarily (intrinsically) resistant (radio- , chemo- or immuno-resistant) tumour cells are likely to be present within a tumour cell population. One example is heterogeneous expression of epidermal growth factor receptor targeted to monoclonal antibody cetuximab. In addition heterogeneous distribution of functional blood vessels may hamper uniform drug delivery. Secondly, changes of molecular profile of cancer cells as a consequence of tumour progression and therapy mediated selection pressure may lead to acquired resistance and activation of counteracting mechanisms by cancer cells. Up-regulation of immune checkpoints or exhaustion markers is an example of acquired resistance to immunotherapies. Thirdly, therapy becomes ineffective if a target gradually disappears while therapy progresses such as tumour hypoxia during fractionated irradiation due to tumour reoxygenation. These barriers also emphasize the need for the development of clinical tools for patient selection and for novel preferentially non-invasive (imaging) or minimally invasive (blood based) biomarkers for tumour monitoring during therapy to enable treatment modification or adaptation. We believe that there is room for new treatment options exploiting tumour heterogeneity. References: 1. Zegers CM et al. P. Radiotherapy combined with the immunocytokine (L19-IL2) provides long-lasting anti- tumor effects. Clin Cancer Res. 2015, 21(5):1151-60. 2. Trani D et al.Preclinical Assessment of Efficacy of Radiation Dose Painting Based on Intratumoral FDG-PET Uptake. Clin Cancer Res. 2015, 21(24):5511-8. 3. Lambin et al. Predicting outcomes in radiation oncology-multifactorial decision support systems. Nature Rev Clin Oncology. 2013;10(1):27-40. 4. Lambin et al. Radiomics: Extracting more information from medical images using advanced feature analysis. Eur J Cancer. 2012;48(4):441-6.

In this image a dominant intra-prostatic lesion (DIL) in the right posterolateral peripheral zone has been defined on both anatomical MRI sequences (top left) and on the diffusion weighted ADC map (top right). A dose-painting by contour method has been used to define the region for dose escalation. Treatment was performed using interstitial high dose-rate brachytherapy with 5mm catheter placement in the boost volume and 1cm spacing elsewhere (bottom left). The final dose distribution provides highly conformal dose escalation to the high risk region whilst delivering a standard dose to the remaining gland. In this plan, the dose escalation was designed to deliver 21 Gy to at least 95% of the boost PTV and 15 Gy to at least 95% of the remaining low-risk PTV. OC-0102 MRI assisted focal boost integrated with HDR monotherapy for low/intermediate risk prostate cancer L. Dalimonte 1 , J. Helou 2 , G. Morton 2 , H. Chung 2 , M. McGuffin 1 , A. Ravi 3 , A. Loblaw 2 1 Sunnybrook Health Sciences Centre University of Toronto, Radiation Therapy, Toronto, Canada 2 Sunnybrook Health Sciences Centre University of Toronto, Radiation Oncology, Toronto, Canada 3 Sunnybrook Health Sciences Centre University of Toronto, Medical Physics, Toronto, Canada Purpose or Objective There is growing evidence for the use of High Dose Rate (HDR) brachytherapy as monotherapy for the treated of low and intermediate risk prostate cancer patients. With the increasing availability of magnetic resonance imaging (MRI) there is an opportunity to further escalate dose to the dominant intraprostatic lesion (DIL). We report acute toxicity of this prospective Phase I/II trial. Material and Methods Eligible patients had low- and intermediate risk prostate cancer, IPSS < 16, were medically operable for HDR brachytherapy treatment and had an identified DIL on multiparametric MRI (mpMRI) prior to brachytherapy treatment. Patients were treated with 19 Gy delivered in one fraction to the whole prostate. A 0-5mm expansion was applied to the DIL to define the PTV DIL, with a DIL PTV D90 to receive > 23Gy based on previous experience. Toxicity was assessed using CTCAE v.4.0 at baseline, 6 weeks 3, 6, 9 and 12 months post brachytherapy. Results A total of 34 patients have undergone HDR monotherapy treatment with an integrated DIL boost with a median follow up of 6 months. The median age was 67 years (range 46-80). At presentation, median PSA was 6.1 ng/mL (2.5-16.4). Three, 26, and 6 patients had low, low intermediate and high intermediate risk disease. Baseline characteristics were PIRAD 5 (n=21) and PIRAD 4 (n=13),