The guidelines issued by the International Lymphoma Radiation Oncology Group (ILROG) open up new opportunities for the use of proton radiotherapy in leukemia.
ILROG’s recommendations newly apply also to patients with initial involvement of CNS (positive finding in the cerebrospinal fluid) or patients with a relapsed disease related to CNS who are planned for allogeneic transplantation or have CNS involvement and do not respond to chemotherapy or biological treatment.
If patients diagnosed with leukemia have infiltration of their central nervous system (CNS) or extramedullary involvement (myelosarcoma) and their attending hematologist-oncologist recommends radiotherapy, proton therapy is a suitable choice. This is confirmed both by the newly updated recommendations of the international expert group ILROG, and dosimetric comparisons of the existing forms of available radiotherapy.
CNS leukemia ranks among the latest diagnoses suitable for proton therapy. This is because the central nervous system (i.e. the brain and the spinal cord) is separated from the blood stream by a safety barrier, the hemato-encefalic barrier (blood–brain barrier), where the substances which are admitted into the CNS are selected. Some substance molecules, including pharmaceuticals, thus enter the CNS only to a limited extent or not at all. In some cases, the CNS can become the source of disease relapse because some cells are not exposed to the effects of chemotherapy or biological treatment. It may therefore become the reason why tumorous cells start spreading in the body again.
Due to the limited possibilities of systemic treatment, it is advisable to irradiate the whole area of the central nervous system. It is namely irradiation of the brain, spinal cord and the area where the cerebrospinal fluid circulates, i.e. the craniospinal axis. The objective is to get rid of leukemic cells in these hard-to-access areas, including those that are not sensitive to chemotherapy or biological treatment.
Irradiation of the craniospinal axis is beneficial especially for those patients who have, despite intensive systemic treatment, a positive finding of leukemic cells in the cerebrospinal fluid, patients who had a positive finding in the cerebrospinal fluid already at diagnosis and who are high-risk in terms of involvement of the central nervous system in the future. It is also beneficial for patients with tumorous leukemic lesions in the brain or spinal cord. According to the new recommendations, these patients should preferably have the entire area of the craniospinal axis irradiated.
In the said cases, the use of proton radiotherapy instead of conventional radiation may reduce adverse effects that previously significantly deteriorated the quality of life when older technology was used. This concerns primarily nausea, vomiting, fatigue, pain during swallowing and aphthae in the oral cavity. That is why radiotherapy was not commonly used in such patients and if used, lower radiation doses were applied especially because of toxicity concerns related to older radiation technology. It has been found that irradiation of the CNS as a high-risk area improves the chances of recovery in high-risk patients. The new recommendations of ILROG have identified groups of patients who will benefit from the inclusion of craniospinal axis radiotherapy in their therapeutic scheme for the treatment of leukemia. Proton radiotherapy further allows for lower-dose irradiation of organs in front of vertebral bodies, minimal irradiation of the lungs, the heart, esophagus, intestinal villi, kidneys, liver, and the urinary bladder, which significantly reduces the possibility of late toxicity of these organs. Patients also better tolerate irradiation of the craniospinal axis.
In such cases, proton radiotherapy has substantial benefits when compared with other forms of radiotherapy. These include no radiation strain on organs in front of vertebral bodies and minimal systemic toxicity (reduced occurrence of nausea, vomiting, diarrhoea). Proton radiotherapy is suitable for highly pre-treated patients (patients after a few rounds of chemotherapy) with necessary reduction of the dose to which the lungs, intestinal villi, heart and other organs are exposed.
Treatment at PTC is usually done in the prone position with the patient lying with their arms along their sides. Irradiation of the entire area takes 9–12 sessions (fractions) applied to the area of the whole craniospinal axis. In some patients, the riskiest areas, such as apparent tumor lesions, are saturated until the total number of 15–18 doses is reached. Irradiation takes place on all business days and may be accompanied by slight swallowing difficulties, fatigue, and a decrease in the number of blood cells.