ESTRO 36 Abstract Book

S50 ESTRO 36 _______________________________________________________________________________________________

SP-0098 What is the purpose of surgical metastasectomy and do we achieve it? T. Treasure 1 1 UCL Cancer Institute, Clinical Operational Research Unit, London, United Kingdom Is the purpose palliation? Earlier detection of metastases, and selection for operations to remove them, systematically targets asymptomatic patients - who have no symptoms to palliate. There have been very many follow-up studies but none document symptomatic benefit. [Thorac Surg Clin 2016;26:79; Eur J Cardiothorac Surg 2016;50:792] Intervention is explicitly offered with curative intent. Is cure often achieved? There has never been a study with any form of control group to test survival difference. On the other hand there have been multiple trials (16 RCTs to date) of increasing intensity of monitoring to find asymptomatic patients for metastasectomy with curative intent. A systematic review capably done by an international multidisciplinary team, including skills in oncology, surgical research, data analysis and guideline development, found no benefit but instead an excess of harm done.[Br J Surg 2016;103:1259] Metastasectomy appears to be an example of over diagnosis leading to harm by over treatment. [Ending Medical Reversal. Baltimore, Johns Hopkins University Press, 2015] Scholars of the history of medicine recognise that over time, disease states have been ‘framed’ and reframed as the sophistication of diagnostic methods escalated from clinical examination and morbid anatomy; through microscopy, bacteriology, clinical chemistry and haematology; and now to extraordinary advances in imaging. This has resulted in a new diagnostic frame ‘oligometastatic cancer’ which is operationally defined by excluding patients with more metastases than can be treated by surgical resection or ablative methods.[J R Soc Med 2012;105:242] This results in selection of patients at the less aggressive end of the spectrum of metastatic disease and hence naturally determined to be longer survivors. So benefits of metastasectomy may be an illusion. [JAMA Oncol 2015;1:787] SP-0099 What is the indication and what is the aim of clinical treatment: radiotherapy E. Lartigau 1 1 Centre Oscar Lambret, Lille, France Oligometastatic disease is considered Today to be amenable to combined systemic and local treatment in order to increase local control, decrease tumor burden and potentially increase survival. Stereotactic body radiotherapy has been successfully used in the treatment of brain metastases for more than 3 decades and is now widely used for bone, lung and liver metastases. For example in our Department, the feasibility, efficacy, and toxicity of SBRT as been evaluated for treatment of unresectable hepatic or lung metastases regardless of their primary tumor site for patients with a history of aggressive systemic chemotherapy. Local control has been demonstrated as excellent (66.1% at 2 years) even if disease-free survival rates remains low (10%, 95% CI: 4– 20%). SBRT is well tolerated with few toxicities and possible in aging patients. There is today a wide consensus on the local role of SBRT in oligometastatic disease. Current step is to optimize the combination with systemic treatments (chemotherapy and targeted agents). A new door has been more recently opened on the potential role of early SBRT together with immunotherapy in order to increase treatment response by neo antigens production following high dose RT, or by immune activation after low dose. Clinical studies are ongoing exploring this new path ways.

SP-0100 Oligometastastic cancer: a therapeutic challenge K. Van der Hoeven UMC St Radboud Nijmegen, The Netherlands

Abstract not received

Symposium with Proffered Papers: Targeting tumour heterogeneity

SP-0101 Using heterogeneous brachytherapy dose distributions to target tumour cell heterogeneity R. Alonzi 1 1 Mount Vernon Hospital, Senior lecturer and consultant in clinical oncology, Northwood Middlesex, United Kingdom Some tumour characteristics, such as hypoxia, vascularity, cellular proliferation or clonogen density, can be mapped geographically using functional imaging techniques or by using systematic biopsies with subsequent immunohistochemistry or molecular characterisation. The ability to assimilate this functional information into the radiotherapy planning process poses a number of challenges, but the technology to achieve biological conformity is widely available and routinely used in most radiotherapy departments. The potential gains in therapeutic ratio from the precision targeting of areas of intrinsic resistance makes focused dose escalation an exciting field of study and will be the principal theme of this presentation. Higher administered radiation doses can overcome intrinsic radio-resistance. However, dose escalation to the entire tumour volume may not always be possible. Increasing the tumour dose will inevitably increase the dose to the surrounding critical normal tissues leading to worse acute and late toxicity. Focused dose escalation is based upon the principle that areas of tumour with relative radio-resistance can be overcome by administering a higher biologically effective radiation dose (BED). This can be achieved either by giving a higher total dose or higher dose per fraction. For focused dose escalation, brachytherapy offers some major advantages over external beam techniques. One of the key features of brachytherapy is that the irradiation only affects a very localised area around each radiation source as dose falls off rapidly, obeying the inverse square law. This feature has been exploited for many years and makes brachytherapy the most conformal of all radiotherapy techniques. As long as the sources are precisely placed within the tumour, there is minimal exposure to radiation of healthy tissues further away from the sources. This allows very high doses to be administered to the target volume. Also, patient set-up and tumour motion are less relevant because the radiation sources move with the tumour and therefore retain their correct position; this increases the confidence that the radiation has been delivered in accordance with the required plan. Brachytherapy plans are inhomogeneous by their very nature, with high dose regions surrounding each source and lower dose regions where there is maximum geometrical separation between sources. By carefully manipulating source positions and dwell times, the non- uniform dose distribution can be shaped to match a biological risk map. The brachytherapy implant technique may have to be adapted to accommodate this.