Particle therapy for the curative treatment of children and young adults requires special demands on all ranks: Indication for treatment must be decided in an interdisciplinary setting, keeping in mind several important factors such as patient age, tumor type, staging and risk group, existing treatment concepts and running study protocols, as well as the special care necessary for small children requiring anesthesia for treatment. A strong focus must be set on target volume definition, delineation of organs at risk (OAR), choice of the optimal beam angles and dose distribution aiming at a reduction of dose to normal tissue. The reduction of integral dose is a main concern in pediatric radiation oncology, and the physical properties of ion beams offer a benefit compared with even advanced photon techniques due to the low dose deposition in the entry channel of the beam, and the high local dose deposition within the Bragg peak. Clinical evaluation and long-term data are currently being generated within several clinical protocols.
At HIT, treatment of pediatric patients with different indications was established since the beginning of patient treatment in 2009. Since then, 36 patients with different tumor entities were treated with proton and carbon ion radiotherapy. A streamlined clinical workflow for even very young children in anesthesia was established by a close collaboration with a dedicated team of anaesthesiologists for pediatric anesthesia. The strong collaboration with the neighboring departments of neurosurgery and pediatric oncology enable efficient and patient-oriented medical care. In all patients, few toxicities were observed, which were only mild and related to the size and anatomical lesion of the patients. Especially, frequent side effects such as hair loss in patients treated for brain tumors can be reduced significantly, depending on the location of the lesion. No severe acute or long-term side effects could be documented. Imaging response was observed in a number of patients, and all patients despite three remained stable during follow-up. Recurrences occurred in three patients, one child treated for a recurrence of a skull base rhabdomyosarcoma, and another patient developed meningeal spread along the craniospinal axis based on a cervical rhabdomyosarcoma, and in one patients with a glioblastoma. The safety and efficacy of proton and carbon ion treatments delivered by active rasterscanning could therefore be demonstrated.
The potential benefit of particle therapy for pediatric patients is the possibility to reduce integral dose, and thus reduce the risk for radiation-induced side effects, such as secondary malignancies. Is has been shown that taking into account several risk estimates, particle treatments compare favorably to photon treatments, especially when using beam scanning compared to beam scattering
[23, 24]. Several proton centers have reported excellent clinical outcome in various tumor entities:
At MGH in Boston, the treatment of patients with parameningeal rhabdomyosarcoma was studied based on elaborate treatment planning comparisons, evaluating the optimal treatment available
; In a group of 17 children treated with protons with a median age of 3.4 years (range, 0.4-17.6), a median dose of 50.4 Gy E was applied
. After a median follow-up time of 5 years, 59% remained failure-free, and overall survival was 64%. Late effects related to proton radiotherapy in the 10 recurrence-free patients included reduction in overall height in three patients, endocrinopathies (n = 2), mild facial hypoplasia (n = 7), failure of permanent tooth eruption (n = 3), dental caries (n = 5), and chronic nasal/sinus congestion in two patients. For Ewing’s sarcoma, as well, only mild side effects were observed in a group of 30 children, with tumors originating from various anatomical regions
. After a median proton dose of 54 Gy E, 3-years event-free survival rate was 60%, with local control and overall survival at 86% and 89%. Side effects included mostly mild reactions of the skin, despite four hematologic malignancies often observed after topoisomerase and anthacycline chemotherapy. For primary brain tumors, such as ependymomas, proton radiotherapy has shown convincing initial clinical results in 17 patients after a median follow-up of 26 months. Local control was 86%, and overall survival was 89%, with the extent of surgery being the most prominent prognostic factor
. Other studies have reported similarly convincing results for germ cell tumors, craniopharyngioma, bladder sarcoma as well as skull base tumors
[4–6, 26, 27].
To fully evaluate the long-term potential of particle therapy in pediatric patients requires much longer follow-up, which is the main downside in all current publications on particle therapy. Especially to completely understand the risk profile towards reduction of secondary malignancies, longer observation is required. Comparative data of protons and photons have suggested such a potential effect
. With respect to carbon ion radiotherapy and the distinct radiobiological properties, clinical implementation in pediatric patients should be applied cautiously due to a possible higher risk for treatment-induced secondary malignancies
. Therefore, this modality should be withheld for clinical situations in which the tumor is difficult to control with conventional low-LET-radiation, such as osteosarcoma. Therefore, in such a patient group the evaluation of carbon ion radiotherapy also in pediatric patients can be justified