Thirty years of proton therapy at Institut Curie

Since the first proton accelerator, built on the initiative of Frédéric Joliot in 1954, the management of this type of radiation has made great strides at Institut Curie. Its clinical use began in 1991 with treatment of the first eye tumors, before beginning to treat adult and pediatric brain tumors (in 1993), young children under the age of 5 requiring general anesthesia (in 1996), then moving to a broader field of treatment, including pelvic, chest and spinal tumors, with the installation of a rotating treatment arm, in a third treatment room that opened in 2010. These successive developments have made Institut Curie’s proton therapy center the third most important in the world, in terms of the number of patients treated since it opened. Its development is closely linked to past and present collaborations with Institut Curie’s Research Center, with regional scientific and medical contributors such as the IPN, the CEA, Institut Gustave Roussy and AP-HP.

And today, physicians, physicists and researchers are still working to enable increasing numbers of patients to receive treatment using this special radiation.

A very precise dose

As with other photon radiotherapy techniques, proton therapy involves irradiating tumors to destroy them. But the physical properties of protons offer very high precision. Rémi Dendale, oncological radiotherapist and director of the proton therapy center, explains:

The ionizing beam passes through other tissues before reaching the tumor. With protons, the dose can be delivered to the tumor in a single very narrow beam, and it does not come back out.

This ability to focus precisely reduces the total irradiation dose to which the body is exposed, which explains why it is useful in pediatrics. Tumors of the head and brain are important indications for this technique.

In this way we spare healthy brain tissue, and thus reduce the risk of disrupting neurocognitive acquisition and the risk of secondary cancer for young patients, the majority of whom will be cured

continues Rémi Dendale. Since 2017 Institut Curie has been performing craniospinal irradiation. This innovative approach enables treatment of certain tumors of the nervous system that require the brain and the rest of the central nervous system (spinal cord and dural sac) to be treated. This technique completely spares the organs in the chest and abdomen using IMPT (Intensity modulated proton therapy) irradiation. The proton therapy center at Orsay is the only center in France to use this approach since 2017.

In children and young adults, physicians offer proton therapy for mediastinal Hodgkin’s lymphoma, a form of blood cancer where the lymph nodes are affected. “Proton therapy lets us irradiate the lymph nodes and reduce the dose delivered to the heart,” explains Rémi Dendale. This proton therapy technique requires respiratory control via spirometry to avoid mobility of the organs related to breathing; this combination helps further reduce cardio-pulmonary toxicity. Institut Curie at Orsay is the only proton therapy center in France since 2018 to offer this treatment technique.

Generally speaking, proton therapy is offered when the tumor is close to sensitive organs. In adults this includes ophthalmic cancers, tumors of the head and neck, and certain tumors of the pelvic region and chest in young adults.

Ophthalmic tumors remain the most important indications for the center, which offers a dedicated treatment room. It represents an alternative to enucleation since it allows most patients to preserve their eye, and many of them to save their vision. The proton therapy center at Institut Curie is the leading center worldwide in terms of total number of ophthalmology patients treated and numbers of patients treated annually.

Moreover, via its practitioners from the Oncology department, Institut Curie is taking part in a national reflection on extending indications to proton therapy, so that more patients can receive this treatment.

The future of proton therapy

Technological innovation is producing ever-more precise devices. Since 2017, one of the treatment rooms has been equipped with pencil beam scanning (PBS), a beam delivery technique that improves the precision and distribution of the dose. This technique enables us to treat certain chest tumors after the team has assessed the benefit compared with classic radiotherapy. The institute takes part in national and international clinical trials for childhood and adult tumors at the base of the skull, soon to be extended to the esophagus and pancreas.

Other projects, conducted on the proton therapy site in collaboration with Institut Curie’s Research Center, are looking at new ways to distribute the beam, such as FLASH irradiation (dose delivered in a very short time, 10,000 times briefer than with classic radiotherapy) and MINIBEAMS (specific spatial distribution of the dose in the form of “peaks and valleys”). These techniques are highly promising in clinical settings for the near future. They have already shown a reduction in toxicity of healthy tissues, with effectiveness on tumors preserved in preclinical trials.

The future of proton therapy also involves artificial intelligence software and integrated imaging systems.

Research and clinical trials show that we are going to be treating more and more patients in the future. We need to anticipate investments and prepare ramp-up of the proton therapy center

concludes Rémi Dendale.

Key figures

10,724 patients were treated from September 1991 to December 2020. These successive developments have made Institut Curie’s proton therapy center the third most important in the world, in terms of the number of patients treated since it opened.

In ophthalmology

• Only 10 centers worldwide practice proton therapy in ophthalmology and Curie is the largest in terms of total number of patients.
• A total of 7,500 patients were treated from the beginning to December 2020
• An average of 360 patients a year (306 in 2020 but the pandemic changed some treatments)
• Examples of pathologies treated are intra-ocular tumors, uveal tumors, choroidal melanoma (represents 70% of patients), benign eye tumors, choroidal hemangioma and malignant conjunctive tumors.

In pediatrics

• A total of 970 patients were treated from the beginning in December 2020
• An average of 100 patients a year, increasing (104 in 2020, 110 in November 2021)
• One quarter of these children are treated under general anesthesia, with a majority of children under the age of 5. The other young patients are awake.
• Examples of diseases treated include tumors of the head, ependymoma, craniopharyngioma, germ-cell tumors, medulloblastoma, sarcoma, chordoma of the base of the skull and the spinal column, Hodgkin’s lymphoma and ocular tumors
• In the case of craniospinal irradiation (innovative techniques that spares the tissues of the chest and abdomen), the procedure has existed since 2017 (4 patients treated). 21 patients were treated in 2021.

Chest tumor in adults 

• Proton therapy is proposed for chest tumors where there is a risk of irradiating the heart or other vital internal organs (mediastinal tumors, Hodgkin’s lymphoma, thymomas, soft-tissue sarcoma) since 2018
• 8 patients treated in 2018, 9 in 2019, 16 in 2020

Examples of other indications in adults include tumors at the base of the skull, meningioma, craniopharyngioma, sarcoma of the head, spinal column and pelvis.