Adult cancers
For adults, proton therapy is currently indicated for tumors with high ballistic and radiobiological constraints. Some indications are currently consensual and validated by the French health authorities.
So-called "radioresistant" tumors are also indications for proton therapy, as they require high radiation doses to ensure tumor control, especially if they are close to organs whose tolerance is limiting.
Indications are discussed on a case-by-case basis, on the basis of a complete medical file and comparative dosimetry. The decision is validated by a specialized Multidisciplinary Consultation Meeting (RCP).
Chondrosarcomas / Chordomas
Chondrosarcomas are malignant cartilage tumors. They account for 20% of malignant bone and cartilage tumors. They occur mainly in adults between the ages of 50 and 70. They mainly affect the pelvis, bones such as the femur and humerus, and more rarely the spinal column and base of the skull.
In the latter two anatomical locations, they are difficult to treat because of their proximity to major organs. Surgery is therefore often incomplete, but it can be combined with proton therapy, which delivers a dose sufficient to halt tumor progression.
Chordomas represent 1 to 4% of malignant bone tumors, which are assimilated to sarcomas although they are not part of them. They occur after the age of 30, and most often around the age of 60. They affect the spinal column, in particular the sacrum (60%) and the base of the skull (25%), or other parts of the spine. They are generally slow-growing, but have a propensity to recur after surgery.
Chondrosarcomas and chordomas of the skull base and spine, other sarcomas or tumors requiring high doses of radiotherapy (sometimes referred to as "radioresistant") close to the spine, and therefore to the spinal cord and skull base, are therefore key indications for proton therapy. Proton therapy is well established in these indications, thanks to its physical superiority over conventional photon irradiation techniques.
Proton therapy treatment of other types of sarcoma with complex anatomical locations is open to discussion.
ENT tumors
Tumors of the ENT sphere for which proton therapy is a feasible treatment are periorbital tumors, or tumors reaching the skull base or cavernous sinuses, or tumors with intracranial extension, or extensive perineural tumors in patients treated with curative intent and long life expectancy.
Based on clinical studies, squamous cell carcinomas, cavitary cancers and cancers of the facial sinuses appear to be indications that could benefit from proton therapy in terms of therapeutic efficacy and acute and late toxicities. These indications need to be discussed in advance at a multidisciplinary consultation meeting (réunion de concertation pluridisciplinaire - RCP). These treatments are carried out as part of clinical research trials.
Paraspinal tumors
Tumors close to the spine, in the thorax or abdomen, which are not very mobile, may also be suitable for proton therapy.
If considered, this indication must be discussed on the basis of a complete medical file during a specialized Multidisciplinary Consultation Meeting (RCP).
Curative re-irradiation
With the improvement in treatments and life expectancy for cancer patients, it is becoming increasingly common to have to treat a patient again in an area that has already been treated with radiotherapy.
In these situations, however, local treatment is limited by the dose already received from previous irradiation of healthy tissue adjacent to the tumor. To deliver a dose that is once again effective against the tumour without generating severe toxicity, proton therapy can be proposed. This limits irradiation of healthy tissues to medium or low doses.
Proton therapy considerably reduces intermediate doses to pre-irradiated healthy tissues, a limiting factor in delivering a curative dose for a second time.Proton therapy can achieve substantial tissue sparing and avoid toxicity, sometimes by dose escalation.
For example, in the particular case of radiation-induced sarcomas arising after childhood irradiation for retinoblastoma, re-irradiation may be the only approach to local treatment. In this situation of predisposition to radiation-induced tumors, proton therapy is to be preferred.
Eye tumor
Certain tumors of the eye and the orbit, the area of the facial mass that contains the eye, can be difficult to treat. In fact, the optic nerves and other structures of the eye itself, such as the retina, are sensitive to radiotherapy.
Melanomas of the eye, in particular, require high doses of radiotherapy, which can be delivered by proton therapy or brachytherapy, depending on the situation. Ocular melanomas are a major indication for proton therapy, with the aim of treating the tumor while preserving sight whenever possible. The possibility of preserving sight also depends on technical specificities that need to be assessed in order to best decide on the treatment site.
The two other French proton therapy centers in Orsay and Nice have the appropriate equipment and long-standing expertise in the treatment of these eye melanomas.
Other potential locations & prospects
Many other potential indications for proton therapy have been identified and are or will be the subject of clinical research protocols.
Certain less aggressive brain tumors (meningiomas, paragangliomas, also known as chemodectomas, neurinomas, also known as schwannomas, craniopharyngiomas, etc.) may benefit from proton therapy to improve neurocognitive preservation, i.e. long-term memory and brain flexibility.
Tumors with a good prognosis and a five-year survival of 90% or more, for which it is important to limit sequelae toxicities in long-surviving patients, particularly in cardiology, are potential applications for proton therapy. This is the case, for example, with Hodgkin's disease of cervical-mediastinal localization.
This could also be the case for cancers of the left breast with lymph node invasion of the internal mammary chain: with current techniques, the heart, located behind the left breast, receives a small dose of irradiation. Even this low dose has been identified as responsible for cardiac toxicity. The breast and lymph nodes are irradiated more homogeneously and at a more optimal dose using protons than using photons, even with intensity modulation. The average dose delivered to the heart is lower with protons than with photons, and remains acceptable even when irradiating the internal mammary chain. However, the lack of clinical data from irradiated patients means that it is not possible to formally conclude that proton therapy cures more patients, or that it reduces the rate of late cardiac complications. Its theoretical and physical advantages will have to be evaluated in clinical trials.
Childhood cancers
Thanks to its ballistic qualities, proton therapy exposes children to a much lower dose near and far ("integral") to the tumor than conventional photon radiotherapy.
Its main assets are the reduction of local, acute and late toxicities, functional sequelae (auditory, endocrine, cognitive) and very long-term carcinogenic risks.
Medulloblastoma and other primitive neuroectodermal tumors
After leukemia, brain tumors are the most common childhood tumors, accounting for around 20% of the total. Among them, medulloblastoma is one of the most frequent, accounting for around a quarter.
It is located in the posterior cerebral fossa and develops at the expense of the cerebellum, generally in its medial part. Highly aggressive, it rapidly induces balance disorders, followed by compression of the cranial nerves located further forward, in the brain stem (continuation of the spinal cord into the brain = risk of paralysis of the eyes and face, reduced hearing...). In the final stage, tumour cells can invade the entire CSF (cerebrospinal fluid), bathing the brain and spinal cord.
Intensive treatment generally begins with surgical resection, followed by a combination of chemotherapy and radiotherapy, spread over several months. The particularity of radiotherapy lies in the need to "cover" the entire cranio-spinal axis (brain + medulla + ponytail), with a higher dose of radiation in the region most at risk: the cerebellum.
Long-term survival of localized forms is around 70%.
Craniospinal irradiation is a recent development in France, due to its complexity and the almost indispensable use of the new "spot scanning" technology. It will certainly make it possible to significantly limit the doses delivered to neighboring tissues (eyes, ears, facial bones, teeth, thyroid gland, organs of the thorax, abdomen and pelvis), and even to the spinal column itself in some cases.
Dose superimposition delivered at the end of treatment to the posterior fossa alone is, on the other hand, simpler, and has been widely used since the introduction of protons in pediatrics in the 2000s.
- Irradiation schedule: daily sessions, spread over approximately 6 weeks.
Gliomas
Gliomas account for more than half of all brain tumors in children, and are located preferentially in the cerebral cortex and its deep structures (optic tract, thalamus, floor of the fourth ventricle).
Unlike in adults, most of these are benign in histology, and therefore compatible with prolonged survival (around 80%), where quality of life is paramount. A notable exception is malignant gliomas of the brain stem, which are generally very aggressive, and for which radiotherapy has an essentially symptomatic effect.
In deep benign forms, with a cystic and/or solid appearance on imaging, which can be considerable in size, radiotherapy is quite often used as first-line treatment in older children, or after prolonged evaluation of the efficacy of chemotherapy in younger children.
Proton therapy is the treatment of choice for benign forms of the disease. Foreign dosimetric studies are abundant, and suggest a substantial reduction in toxicity on sensory organs and hormonal secretions, and perhaps an improvement in intellectual performance.
Irradiation schedule:
- Mild forms: daily sessions, spread over approximately 5 to 6 weeks
- Malignant forms: daily sessions, spread over approximately 3 to 6 weeks
Ependymomas
Representing around 10% of all brain tumors, ependymomas are most often found in the medial part of the posterior cerebral fossa, within the fourth ventricle, but may extend into the latter and down into the cervical spinal canal, complicating radiotherapy techniques. They can occur in very young children (particularly in the hemispheres).
The aggressiveness of ependymomas is partly determined by their histological appearance, with diffuse anaplastic forms being the most malignant. These and less aggressive but incompletely operated forms should be irradiated.
Studies are currently underway to demonstrate the impact of increased radiation doses on tumor control.
There are a number of reasons why proton therapy should be chosen, when all or part of these are present (young age, technical complexity, need for dose escalation).
- Irradiation schedule : Daily sessions, spread over approximately 6 to 7 weeks.
Craniopharyngioma
A craniopharyngioma is a benign but progressive tumor located in the central region of the skull base (pituitary gland). It is a rare brain tumor in children (5-10%), never diagnosed in children under 5.
This tumor progressively compresses neighboring organs: the optic nerve and chiasma, with the risk of partial or total blindness; the pituitary gland and hypothalamus, or "floor of the fourth ventricle", with the risk of hormonal disturbances and sensations of hunger and thirst; and the brain, with the immediate risk of intracranial hypertension, and the more distant risk of memory and behavioral disorders.
Treatment is mainly surgical, but radiotherapy is often used as a complement.
There is interesting French and international experience in minimizing the dose received at this crossroads of critical organs.
- Irradiation schedule : Daily sessions, spread over approximately 6 weeks.
Rhabdomyosarcomas and other mesenchymal sarcomas
Mesenchymal sarcomas, including rhabdomyosarcoma, account for 5-10% of pediatric tumors.
Occurring in soft tissues (muscles, nerves, fat, vessels, etc.), mesenchymal sarcomas affect all age groups, from infancy to adolescence. Rhabdomyosarcoma is the most common form of mesenchymal sarcoma, under the age of 5 and in adolescence.
Mesenchymal sarcomas occur virtually anywhere in the body. The main sites affected are the head and neck, particularly the orbital region, or adjacent to the base of the skull (parameningeal forms), and the genito-urinary region (bladder, vagina and uterus in girls, prostate and testicular envelopes in boys). Apart from the local site, the disease can spread to lymph nodes (particularly in the "alveolar" type) and distant organs (lungs, bones, etc.).
Left untreated, the disease can progress rapidly, leading to signs of local compression (blindness, urinary retention, etc.), followed by distant dissemination. Treatment is usually a combination of local and general chemotherapy, plus local treatment (surgery and/or radiotherapy). In purely local cases, long-term survival is around 70%.
Proton therapy is particularly well-suited to "high" cancers (skull base, orbit, ENT). New technologies ("spot scanning") mean that treatment of "lower" sites (abdomen, pelvis) can be envisaged in the near future.
- Irradiation schedule: Daily sessions, spread over approximately 5 to 6 weeks.
Neuroblastoma
Neuroblastoma is a malignant tumor of the peripheral (sympathetic) nervous system, located on the front of the spinal column.
It is relatively common (approx. 10% of tumours), mainly affecting very young children (average age: 2 years), and often behaves aggressively, when molecular markers are present (MYCN oncogene amplification), in the form of metastases (bone) at diagnosis, or during progression. Radiotherapy and surgery play only a supporting role to a treatment mainly based on chemotherapy.
When radiotherapy is indicated, doses are relatively low, but the position of the tumor in contact with highly radiosensitive organs (kidneys, liver, spine) justifies the use of proton therapy, as shown by several dosimetric publications.
- Irradiation schedule: Daily sessions, spread over approximately 2 to 3 weeks.
Other pediatric tumors
There are many other types of tumor, generally very rare, for which, once the indication for irradiation has been established by specialists, there is no consensus on the optimal technique.
In such cases, we recommend a thorough dosimetric study comparing the best photonic and proton techniques, followed by a collegial assessment of the potential clinical impact.