Maurizio Vretenar ATS/DO

2. Introduction to NIMMS Next Ion Medical Machine Study at CERN Maurizio Vretenar ATS/DO

3. Why a new study for Ion Therapy • Proton therapy is now commercial, 4 companies offer turnkey treatment facilities (3 SC cyclotrons, one conventional synchrotron), and in competition with conventional radiation therapy (X-rays). Mainly used for paediatric tumours and some special cancers. • Light ion therapy (mainly carbon) is still in an early phase (13 facilities worldwide, 4 in Europe) in spite of several advantages with respect to proton therapy and to X-rays: • Active with hypoxic radio-resistant tumours (up to 3% of all tumours); • Increased dose conformity and reduced residual dose; • Expectations from recent exciting results on diffused cancers by combining ion therapy with immunotherapy. • The diffusion of ion therapy is primarily limited by the size and cost of accelerator and gantry. • An R&D programme based at CERN for critical technologies related to ion therapy acceleration could have a strong societal impact building on existing CERN competences and without competing with ongoing activities in Member States.

4. The potential of Ion Therapy • Ions have a well-definedniche in particletherapy: higher mass than protons, produce double-strand DNA breakingsthat are not repairable → active on hypoxic radio-resistanttumours (1-3%). Higher RBE and better dose conformitythan protons. • In future, this niche couldexpand as result of: • ongoing clinical trials; • new treatments combining particle therapy and immunotherapy: triggering the immune system with DNA fragments released from destroyed cells, to attack non-irradiated metastases across the body. • new techniques to solve range uncertainties (extension to “big killers”); • tests on non-cancer diseases. Constant growth of particle therapy facilities worldwide – about 15% delivering Carbon ions (4 in Europe, 5 in Japan, 2 in China). Courtesy Dr. HirohikoTsujii, MD Data from www.ptcog.ch

5. From PIMMS to NIMMS PIMMS = Proton-Ion Medical Machine Study • 1996 - 2000 collaborative study (CERN, TERA Foundation, Med-AUSTRON, Onkologie 2000) for the design of a cancer therapy synchrotron. • The PIMMS technical report was the foundation for the construction of the CNAO and MedAustron particle therapy centres. NIMMS = Next Ion Medical Machine Study 20 yearslater (and after the LHC construction!) CERN wants to play again a pivotal role in the design of a next generation of ion therapy accelerators. Council Strategy document on knowledgetransfer for the benefit of medical applications (6/2017): “A collaborative design study coordinated by CERN would contribute to the development of a new generation of compact and cost-effective light-ion medical accelerators. A new initiative of this type would leverage existing and upcoming CERN technologies and the Laboratory’s expertise in the fields of radiofrequency systems, advanced magnet design, superconducting materials, and beam optics. The possible launch of such a study is currently being explored by CERN experts and a proposal will be put forward and evaluated by CERN’s medical applications decision-making structure.” Idea: Use the (limited) KT Medical Application budget as seed money to set-uplarger collaborations.

6. From Archamps to the NIMMS Study The new CERN initiative isbased on the outcome of an International Workshop organised at Archamps in June 2018 (https://indico.cern.ch/event/682210/overview ): Accelerator • Lower cost, compared to present (~120 M€); • Higher beam intensities than present (1010ppp); • Reduced footprint, to about 1’000 m2; • Lower running costs. Delivery • Fast dose delivery (possibly with 3D feedback); • Equipped with a rotating gantry; • Using multiple ions; • With range calibration and diagnostics online. “Ideas and technologies for a next generation facility for medical research and therapy with ions”, Co-organized by CERN, ESI, GSI - 63 participants from accelerator and medical community. Requirementsfrom the particletherapycommunity: + having in mind a future transfer of the technology to industry!

7. Options for next generation ion therapy Superconducting synchrotron 90deg CCT-type magnets, Bmax 3.5T, ring 27m Linear accelerator Folded, 53m length, high rep. frequency and intensity, low emittance Superconducting gantry Two options being analysed: • Rotational CCT magnets (TERA) • Toroidal (L. Bottura, CERN) Size comparison: Superconducting (top left) vs. CNAO (bottomleft) and Medaustron (right)

8. Superconductingmagnets The main avenue to nextgeneration ion therapyissuperconductivity ! Superconductingmagnets are required for both a nextgeneration synchrotron and a nextgenerationgantry. (onlydifference in the aperture, synchrotron islargerbecause of high intensity). Ramp time islimited by the gantrymagnets Magnet Design Interest in CantedCosineTheta (CCT) design (LBNL, TERA, CERN for HL-LHC correctors, etc.) withnestedquadrupoles. NbTi, with option of future use of HTS. HIMAC SC synchrotron design (Japan) TERA synchrotron Design: CCT magnets 3.5T Aperture 60 mm Total circumference 27 m

9. The high-frequency linac option • Workplan initial phase: • end-to-end beamoptics design • finalise bend design • choice and design of intermediateenergy structures, choice of high-energy structure • define type and number of klystrons • + test of the MEDeGUNinjector, finalise design of RFQ. Present Design (430 MeV/u, CERN+TERA) Tot. length 53 m Tot. RF power 260 MW Optimised for power consumption Gradient 30 MV/m: higher values are possible but at the price of a drasticincrease in RF power. Bend: must containcavities to keepbeambunched S. Benedetti, A. Grudiev and A. Latina, Design of a 750 MHz IH structure for medical applications, Linac16

10. Strategy Instead of fully developing two alternative accelerator designs, concentrate CERN funding on the development of few key technologies corresponding to CERN core competences. Efficient use of the KT MA contribution: a) to provide the matching resources needed to attract funding from external sources, and b) to develop strategic components where CERN could have a scientific or industrial return. Idea: • A toolboxthatwillbefilledwith time with more instruments and tools. • At any moment an externalproject (or industry) canstep in and take the elementsthattheywant – accordingly to their goals, theirschedule and their budget. From the project management point of view, this requires a flexible structure that can be modulated depending on the results and on the availability of external contributions. Planning and resources well defined in the short term, more open for the long term.

11. NIMMS Plans for 2019/2021 The project plan for 2019/21 isstructured in 4 Workpackagescorresponding to key technologies. The first 3 WPs are carried on directly by CERN. The 4th Workpackageiscarried on by the SEEIIST with the collaboration of CERN:

12. Collaborations • CERN is collaborating with the SEEIIST (South East Europe International Institute for Sustainable Technologies), a new international partnership aiming at the construction of a particle therapy facility in South East Europe. • SEEIIST has received a preliminary funding of 1 M€ from the EC, part of which will be used to finance 2 FTEs working on ion therapy accelerator design for the next 18 months under the supervision of CERN (18pm for beam optics, 6pm for diagnostics and extraction + 6pm for magnet design). • Next step: EU Design Study proposal to the last call of H2020 Research Infrastructures, deadline November 2019, mobilising some 15-20 partners. 3 years duration 2020/23, 3 MEUR, co-funded. • The Design Studyis in preparation, expectedpartners are: CERN, GSI, CEA, U. Liverpool, INFN, CNAO, Medaustron, HIT, IAP, Cosylab, U. Melbourne + SEEIIST and otherpartners in the region. • Otherpartnersinterested in collaboratingwith CERN are fromIndia, Latvia, Iran, Sweden, etc. • A dedicated collaboration for the design of a superconducting gantry, possibly of the toroidal type, has been startedwith CNAO, INFN and MedAustron.