Clinical Controversies: Proton Therapy for Pediatric Tumors

Abstract

Despite the claim in the published literature, the introduction of proton therapy for children is not analogous to the evolution of conformal photon irradiation relying on the understanding of the impact of altered dose distributions. The differences in radiobiological effect when comparing photons to protons means that we are comparing a known entity to an unknown entity: the dose-volume histogram for proton therapy might mean something substantially different than the dose-volume histogram for photon therapy. The multifaceted difference between the two modalities supports the argument for careful evaluation, follow-up and clinical trials with adverse event monitoring when using proton therapy in children. We review the current data on the outcome of proton therapy in a range of pediatric tumours and compare them to the often excellent results of photon therapy in the setting of multidisciplinary management of childhood cancer. It is hoped that the apparent dosimetric advantage of proton therapy over photons will lead to improved indications for therapy, disease control and functional outcomes. While physical dose distribution is of clear importance, the multimodality management of children by an expert pediatric oncology team and the availability of ancillary measures that improve the quality of treatment delivery may be more important than the actual beam. In addition, current estimates of the benefit of proton therapy over photon therapy based on toxicity reduction will only be realized when survivorship has been achieved. Once substantive data proton therapy data become available, it will be necessary to demonstrate benefit in clinically relevant outcome measures in comparison to best existing photon outcome data. Such an effort will require improved funding and appreciation for late effects research. Only real clinical outcome data combined with better understanding of the radiobiological differences between protons and photons will help us to further reduce side effects in children and exploit the full curative potential of this relatively new modality.

New challenges in high-energy particle radiobiology

“…[140][141][142] Breast cancer is indeed the most frequent cancer in females, and if proven, superior CPT could have a much larger use than in the past. The advantage here is not in the TCP, but in the reduced normal tissue toxicity, and this advantage, already considered the main justification for paediatric use of protons, 107 is likely to be decisive in the future of CPT. In space, a mission to Mars would bring the total dose around 1 Sv, 143 a region where epidemiological data suggest an increase of cardiovascular diseases.…”

“…This is a critical issue for paediatric patients, a group that is often referred to proton therapy because much normal tissue can be spared compared with X-rays and, therefore, toxicity is reduced. 107 For these patients, the risk of second cancer is, however, substantial and the genetic predisposition to cancer very likely because the tumour was expressed at a young age. 108 This problem will be discussed in the next section.…”

Controversy over the Use of Proton Therapy for the Treatment of Tumors of Central Nervous Systém

“…Vysvětlení lze nalézt v publikaci Merchanta [27], který udává u dětských pa cientů s ependymomem průměrnou dávku na mozek 10 Gy při užití fotonové terapie a 7-8 Gy při PBT se stejným rizikem subnormálních kognitivních funkcí.…”

“…Při ozařování kraniospinální osy dochází k vyš-šímu šetření srdce a endokrinních žláz. Nicméně rozdíly v dávkové distribuci jsou mimo rozsah měřitelných změn v radiační toxicitě [27]. Hypoteticky by PBT mohla vést k nižšímu poškození neurokognitivních funkcí a sníženému riziku sekundárních malignit.…”

Proton radiotherapy should be further developed in Poland

“…The efficacy studies for proton beam radiotherapy on CNS cancers indicate high rates of overall survival [17]. Reducing the number of complications to healthy organs has been confirmed in numerous dosimetric and modelling studies showing decreased risks of: cardiac toxicity [19], premature radiotherapy-related ovarian failure [20], ototoxicity [21] or cognitive impairment [22]. Indeed, the first clinical data has now emerged on improved Health-Related Quality of Life (HRQoL) in patients after receiving proton irradiation in childhood compared to photon therapy [23].…”