Determining Out-of-Field Doses and Second Cancer Risk From Proton Therapy in Young Patients—An Overview

Abstract

Proton therapy has the potential to provide survival and tumor control outcomes comparable and frequently superior to photon therapy. This has led to a significant concern in the medical physics community on the risk for the induction of second cancers in all patients and especially in younger patients, as they are considered more radiosensitive than adults and have an even longer expected lifetime after treatment. Thus, our purpose is to present an overview of the research carried out on the evaluation of out-of-field doses linked to second cancer induction and the prediction of this risk. Most investigations consisted of Monte Carlo simulations in passive beam facilities for clinical scenarios. These works established that equivalent doses in organs could be up to 200 mSv or 900 mSv for a brain or a craniospinal treatment, respectively. The major contribution to this dose comes from the secondary neutrons produced in the beam line elements. Few works focused on scanned-beam facilities, but available data show that, for these facilities, equivalent doses could be between 2 and 50 times lower. Patient age is a relevant factor in the dose level, especially for younger patients (by means of the size of the body) and, in addition, in the predicted risk by models (due to the age dependence of the radiosensitivity). For risks, the sex of the patient also plays an important role, as female patients show higher sensitivity to radiation. Thus, predicted risks of craniospinal irradiation can range from 8% for a 15-year-old male patient to 58% for a 2-year-old female patient, using a risk model from a radiological protection field. These values must be taken with caution due to uncertainties in risk models, and then dosimetric evaluation of stray radiation becomes mandatory in order to complement epidemiological studies and be able to model appropriate dose–response functions for this dose range. In this sense, analytical models represent a useful tool and some models have been implemented to be used for young patients. Research carried out so far confirmed that proton beam therapy reduces the out-of-field doses and second cancer risk. However, further investigations may be required in scanned-beam delivery systems.

Range shifter contribution to neutron exposure of patients undergoing proton pencil beam scanning

“…As discussed before, in terms of spot size, it is preferable to choose a position as close as possible to the patient. However, studies in passive scatter facilities have showed the decrease of organ doses by increasing the air gap 10 . A similar behavior is expected in the case of the RS and, therefore, an optimal configuration in terms of proton dose distribution within the target is unfavorable in terms of neutron production and thus unwanted dose deposition in organs at risk.…”

“…The proton beam scored after the RS presented a component of higher energies in comparison to the NRS plan. Since the neutron production increases with proton energy, 10 these more energetic protons in the RS plan explain why doses due to the neutrons originated in the phantom are generally higher than in the NRS plan (as illustrated by the values of equivalent doses in organ in Table 1). Nevertheless, the more energetic protons are producing more high energy neutrons which are forward directed and not likely to contribute to doses to distant organs and tissues.…”

Secondary neutron dosimetry for conformal FLASH proton therapy

“…Proton therapy has gained increasing interest in past decades as it offers superior dose conformity and reduces the adverse effects on healthy tissues compared to photon radiotherapy 1 . The use of proton therapy has been shown to reduce the incidence of secondary cancers in long‐term survivors, making it a more favorable option especially for pediatric patients and patients with localized tumors 2–5 . Since 2014, the concept of FLASH therapy has emerged as a promising approach to greatly reduce the toxicity in radiotherapy treatments by delivering an ultra‐high dose rate (UHDR) of radiation exceeding 40 Gy/s 6,7 .…”

Modelling the influence of radiosensitivity on development of second primary cancer in out-of-field organs following proton therapy for paediatric cranial cancer

“…As long-term follow-up and prospective clinical studies are difficult to conduct, more consideration has been given to modelling studies to determine risk of SPC in children (for latest review see Romero-Expósito et al 8 and references within). Mathematical prediction of SPC can be somewhat contentious as parameters associated with increased risk are based on historically collected data from high irradiation incidents and adult populations.…”