Inter-Institutional Comparison of Personalized Risk Assessments for Second Malignant Neoplasms for a 13-Year-Old Girl Receiving Proton versus Photon Craniospinal Irradiation

Abstract

Children receiving radiotherapy face the probability of a subsequent malignant neoplasm (SMN). In some cases, the predicted SMN risk can be reduced by proton therapy. The purpose of this study was to apply the most comprehensive dose assessment methods to estimate the reduction in SMN risk after proton therapy vs. photon therapy for a 13-year-old girl requiring craniospinal irradiation (CSI). We reconstructed the equivalent dose throughout the patient’s body from therapeutic and stray radiation and applied SMN incidence and mortality risk models for each modality. Excluding skin cancer, the risk of incidence after proton CSI was a third of that of photon CSI. The predicted absolute SMN risks were high. For photon CSI, the SMN incidence rates greater than 10% were for thyroid, non-melanoma skin, lung, colon, stomach, and other solid cancers, and for proton CSI they were non-melanoma skin, lung, and other solid cancers. In each setting, lung cancer accounted for half the risk of mortality. In conclusion, the predicted SMN risk for a 13-year-old girl undergoing proton CSI was reduced vs. photon CSI. This study demonstrates the feasibility of inter-institutional whole-body dose and risk assessments and also serves as a model for including risk estimation in personalized cancer care.

A review of dosimetric and toxicity modeling of proton versus photon craniospinal irradiation for pediatrics medulloblastoma

“…Mu et al [21] noted that the mean lung dose was not significantly reduced with PrT. This was later supported by Zhang et al [20] and Taddei et al [27] who concluded that SMR after PrT was generally reduced with the exception of the lungs. Girls were found to have higher LAR of lung cancer than boys resulting from a greater proportion of their lungs received more dose due to their smaller physical stature, as mentioned previously.…”

“…Eight of fifteen articles [20][21][22][25][26][27][28][29]] that compared SMR between Proton-and Photon-CSI, highlighted that Proton-CSI yielded lower SMR for most organs when compared to 3DCRT, IMRT and VMAT (Table 4 and supplementary appendix C). VMAT and IMRT led to highest SMR amongst all radiation techniques [21,22,29].…”

“…Substantial evidence points to greater SMR after Photon-CSI than Proton-CSI [20][21][22][25][26][27][28][29], with 3DCRT reported to increase SMR by 2-15 times when compared to PrT [21,22,25,26,28,29]. However, direct inter-study comparison of SMR was complicated by the variations in risk models used.…”

A Review of Radiotherapy-Induced Late Effects Research after Advanced Technology Treatments

“…( 38 ). An empirical model was developed for photon CSI ( 93 , 94 ) to model out-of-field radiation exposures. That model parameterized measured data in an approach conceptually similar to that of Stovall et al ( 95 ).…”

Supplemental computational phantoms to estimate out-of-field absorbed dose in photon radiotherapy

“…In an effort to balance speed, accuracy, and available resources, Taddei et al (2013) created an anthropomorphic measurement-based analytical model to accurately estimate the out-of-field dose for children receiving craniospinal irradiation (CSI). They later applied this model in subsequent studies that compared risks of SMNs in proton CSI versus photon CSI (Taddei et al 2015, Taddei et al 2018). This approach was innovative in that a computationally inexpensive and fast method to calculate out-of-field dose could be applied to many patients if missing anatomy were made available.…”