Recent Developments at CNAO
The Centro Nazionale di Adroterapia Oncologica (CNAO) in Pavia represents a unique institutional model, defined by its robust interdisciplinary collaboration uniting physics, medicine, research, education, and industry. Established by the Ministry of Health and supported by a network of universities, research institutes, hospitals, and public entities, CNAO exemplifies how shared effort translates scientific knowledge and research into effective care for oncological patients. CNAO holds the distinction of being the sole centre in Italy capable of providing oncological treatments using both protons and carbon ions.
As of mid-2025, CNAO had treated approximately 5,700 patients. The centre serves about 600 new patients annually, amounting to 11,000 annual hadrontherapy sessions, with roughly 50 patients undergoing treatment each day.
The treatments provided are largely reimbursed by the Italian National Health System (SSN) under the established list of eligible pathologies, referred to as the Essential Levels of Assistance (LEA) for hadrontherapy. This list encompasses a range of complex and often radioresistant tumours, including: skull base and spinal chordomas and chondrosarcomas, adenoid cystic carcinomas of the salivary glands, sino-nasal carcinomas, brainstem tumours and meningiomas, soft tissue and bone sarcomas (all sites), tumours of the orbit, including ocular melanoma, recurrent tumours (re-treatments), tumours in patients with immunological disorders. Three years ago, a programme for treating paediatric patients was initiated. Today, about 80 children are treated yearly, with a significant number requiring full anaesthesia.
The efficacy of CNAO’s patient collection and selection system stems from intense collaboration with the national hospital network. While less than 5% of patients are self-referred via the CNAO Medical Service, 60% arrive through the top ten referring hospital centres, with the remainder coming from other hospitals and clinics across Italy. Patient selection is a critical, rigorous process guided by multidisciplinary discussion among medical doctors and organ experts, ensuring a shared, personalized therapeutic plan aligned with updated guidelines.
The core technology of CNAO is the circular particle accelerator known as a synchrotron, which is approximately 80 meters long. This accelerator, whose design was compacted to fit within a hospital environment by the TERA Foundation, derives from the Proton-Ion Medical Machine Study (PIMMS) developed at CERN. It routinely accelerates protons and carbon ions. Recently, a new ion source has been installed, in collaboration with INFN, to produce new high-current ion beams, starting with helium, which is presently in the advanced commissioning phase.
The complete high-technology setup includes three ion sources, a linear injector (linac), the synchrotron itself, five high-energy beam transfer lines (leading to three clinical treatment rooms and one research room), and robotic patient positioning equipment.
CNAO is currently undergoing a significant expansion to enhance its research and clinical capabilities, reinforcing its position as a leading global centre.
The Marie™ system by Leo Cancer Care (https://leocancercare.com/), intended for installation in CNAO’s third treatment room, introduces an innovative approach centred on treating patients in a seated or semi-seated position. The system utilizes a sophisticated 6-Degrees-of-Freedom (DOF) robotic Patient Positioning System (PPS) which can rotate the patient continuously by 360° relative to a horizontal, fixed beam. Furthermore, the system incorporates a diagnostic-quality, Dual-Energy CT scanner for precise imaging and verification. Crucially, the seated position and rotation enable the introduction of Arc Therapy for particle radiation, allowing for dosimetric optimization and sub-millimetric precision in dose conformity to the target.
CNAO is also implementing a new Hitachi Protontherapy system. It addresses the need for greater angular flexibility in treatment delivery, particularly in paediatric oncology. The technological core is a compact Hitachi synchrotron with multi-energy extraction capability, and a 360° rotating gantry for ultra-precise tumour irradiation from any angle, minimizing the dose delivered to growing healthy tissues, and potentially reducing the necessity for prolonged patient sedation. The system supports a large scanning area up to 30×40 cm2 for seamlessly treating large neoplasms.
CNAO is also pioneering in Italy the establishment of a hospital-based facility for Boron Neutron Capture Therapy (BNCT), an experimental treatment using low-energy neutron beams. This therapy is highly selective at the cellular level, offering new hope for widespread, inoperable, or radioresistant tumours.
The mechanism involves administering a Boron-10 carrying drug, such as Borophenylalanine (BPA), which tumour cells preferentially absorb. Subsequent irradiation with epithermal neutrons triggers a nuclear reaction, generating highly destructive alpha and lithium ions that deposit their energy within a radius of less than 10 micrometers, thereby destroying only the cells that have accumulated the boron.
The new facility will utilize the Tandem Accelerator technology manufactured by TLS Company (https://taelifesciences.com/) and will operate BNCT in two rooms: one for clinical use and one for research.
Research is a fundamental pillar of CNAO, tightly integrated with clinical practice and training. Every year, beam time is devoted to external groups to perform research in domains spanning from physics to radiobiology, from detector technology to the effects of radiation on materials. For example, in 2024, more than 600 hours of beam time were delivered to experiments, mainly during nights and weekends. The main final goal is the continuous improvement in hadrontherapy efficacy and the development of new personalized strategies for complex tumours. The expansion project is designed to integrate CNAO’s clinical competencies with cutting-edge experimental infrastructures and a broad variety of particle beams.
CNAO operates with 170 staff members and maintains a strong network of national and international collaborations. The collective expertise, ranging from physics and technology to medicine and research, is fundamental to making CNAO a centre of excellence for the benefit of patients.
