ESTRO 36 Abstract Book

S152 ESTRO 36 2017 _______________________________________________________________________________________________

room for quality improvement in this increasingly influential research area. SP-0297 Method of development of ESMO Magnitude of Clinical Benefit applicable for radiotherapy? E.G.E. De Vries 1 , R. Sullivan 2 , N.I. Cherny 3 1 UMCG University Medical Center Groningen, Department of Medical Oncology, Groningen, The Netherlands 2 Institute of Cancer Policy, Kings Health Partners Integrated Cancer Centre- King's College London, London, United Kingdom 3 Shaare Zedek Medical Center, Cancer Pain and Palliative Medicine Service- Department of Medical Oncology, Jerusalem, Israel The value of any new therapeutic strategy or treatment is determined by the magnitude of its clinical benefit balanced against its cost. Evidence for clinical benefit from new treatment options is derived from clinical research, in particular phase III randomised trials, which generate unbiased data regarding the efficacy, benefit and safety of new therapeutic approaches. Until recently, there was no standard tool for grading the magnitude of clinical benefit of cancer therapies, which may range from trivial (median progression-free survival advantage of only a few weeks) to substantial (improved long-term survival). Indeed, in the absence of a standardised approach for grading the magnitude of clinical benefit, conclusions and recommendations derived from studies are often hotly disputed and very modest incremental advances have often been presented, discussed and promoted as major advances or 'breakthroughs'. Recognising the importance of presenting clear and unbiased statements regarding the magnitude of the clinical benefit from new therapeutic approaches derived from high-quality clinical trials, the European Society for Medical Oncology (ESMO) has developed a validated and reproducible tool to assess the magnitude of clinical benefit for cancer medicines, the ESMO Magnitude of Clinical Benefit Scale (ESMO-MCBS). An ESMO Task Force to guide the development of the grading scale was established in March 2013. A first- generation draft scale was developed and adapted through a ‘snowball’ method based upon previous work of Task Force members who had independently developed preliminary models of clinical benefit grading. The first- generation scale was sent for review by 276 members of the ESMO faculty and a team of 51 expert biostatisticians. The second-generation draft was formulated based on the feedback from faculty and biostatisticians and the conceptual work of Alberto Sobrero regarding the integration of both hazard ratio (HR), prognosis and absolute differences in data interpretation [J Clin Oncol 2009, Clin Cancer Res 2015]. The second-generation draft was applied in a wide range of contemporary and historical disease settings by members of the ESMO-MCBS Task Force, the ESMO Guidelines Committee and a range of invited experts. Results were scrutinized for face validity, coherence and consistency. Where deficiencies were observed or reported, targeted modifications were implemented and the process of field testing and review was repeated. This process was repeated through 13 redrafts of the scale preceding the current one (ESMO- MCBS v1.0). The final version and fielded testing results were reviewed by selected members of the ESMO faculty and the ESMO Executive Board. Version 1.0 appeared in 2015 (Cherny et al. Ann Oncol). This tool thus provides a rational, structured and consistent approach to derive a relative ranking of the magnitude of clinically meaningful benefit that can be expected from a new anti-cancer treatment. The ESMO- MCBS is an important first step to the critical public policy issue of value in cancer care, helping to frame the appropriate use of limited public and personal resources to deliver cost-effective and affordable cancer care. The

ESMO-MCBS is a dynamic tool and its criteria will be revised on a regular basis. The next version will include also an approach to grade the clinical benefit data derived from the registration trials of medications approved on the basis of these single arm studies. Currently the grading of newly registered drugs is included in ESMO-guidelines. A similar approach to develop a scale can potentially be used for other treatment or diagnostic areas in oncology including radiotherapy. For a scale grading radiotherapy, there will likely be a number of similarities and differences versus a scale for drug treatment. Factors taken into account for the radiotherapy scale might well include the adjuvant and curative outcomes: overall survival, disease free survival, local recurrence free survival, pathological complete response and non- curative/palliative outcomes such as: single symptom relief (complete response, partial response, relief duration of response), control of hemorrhage, relief of obstruction, effects on skeletal events (pain, fracture) and neurological function. We anticipate methodological challenges in the relative weighting and scoring of palliative outcomes form localized radiotherapy as distinct from systemic therapies. SP-0298 For the motion B. Raaymakers 1 1 UMC Utrecht, Department of Radiation Oncology, Utrecht, The Netherlands The common ground for proton and photon guidance, that is MRI and CBCT guidance, is the desire to localize the target and the surrounding structures in order to improve the spatial accuracy of dose delivery. This is especially important to better target and to minimize the high dose volumes which are leading to the most acute toxicity and are often dose limiting. With modern accelerators, both proton- and photon therapy can generate a conformal high dose volume, while image guidance is the most important parameter on delivering this high dose volume to the correct position and with that minimize this high dose volume. Doing so, also hypo-fractionated treatments for more and more tumor sites can become feasible. MRI guidance is superior because: 1) Soft-tissue guidance of MRI will out-perform CBCT based set-up 2) MRI provides dynamic imaging to track breathing and peristalsis without the need for retrospective binning 3) MRI enables daily full re-planning 4) MRI provides intra-fraction (volumetric) imaging for dose reconstruction and plan adaptation 5) Integrated MRI provides functional response assessment during the course of radiotherapy CBCT has greatly improved radiotherapy by offering 3D imaging just prior to radiation delivery, these images can be used for improved patient set up and assessment of the breathing pattern. These data, even though they have limited soft-tissue contrast, are acquired just prior to treatment. Using these instead of relying on pre- treatment images of days (if not weeks) old, provides much more representative information on the target and surrounding structures and will improve patient set-up. With MRI integrated in the radiotherapy system, all the aims from CBCT guidance can be brought to the next level. MRI offers soft-tissue contrast, so one can much better distinguish tumor from surrounding tissues. Also dynamic MRI can provide 4D anatomical data with high temporal resolution (e.g. 3Hz) to detect breathing and peristaltic Debate: This house believes that proton guided photons (online MR guided therapy) will be superior to photon guided protons (CBCT proton therapy)