The Advantage of Proton Therapy in Hypothalamic-Pituitary Axis and Hippocampus Avoidance for Children with Medulloblastoma.

PURPOSE: Craniospinal irradiation (CSI) improves clinical outcomes at the cost of long-term neuroendocrine and cognitive sequelae. The purpose of this pilot study was to determine whether hypothalamic-pituitary axis (HPA) and hippocampus avoidance (HPA-HA) with intensity-modulated proton therapy (IMPT) can potentially reduce this morbidity compared with standard x-ray CSI. MATERIALS AND METHODS: We retrospectively evaluated 10 patients with medulloblastoma (mean, 7 years; range, 4-14 years). Target volumes and organs at risk were delineated as per our local protocol and the ACNS0331 atlas. An experienced neuroradiologist verified the HPA and hippocampus contours. The primary objective was CSI and boost clinical target volume (CTV) covering 95% of the volume (D95) > 99% coverage with robustness. Described proton therapy doses in grays are prescribed using a biological effectiveness relative to photon therapy of 1.1. The combined prescribed dose in the boost target was 54 Gy. Secondary objectives included the HPA and hippocampus composite average dose (Dmean ≤ 18 Gy). For each patient, volumetric modulated arc radiotherapy (VMAT) and tomotherapy (TOMO) plans existed previously, and a new plan was generated with 3 cranial and 1 or 2 spinal beams for pencil-beam scanning delivery. Statistical comparison was performed with 1-way analysis of variance. RESULTS: Compared with standard CSI, HPA-HA CSI had statistically significant decreases in the composite doses received by the HPA (32.2 versus 17.9 Gy; P < .001) and hippocampi (39.8 versus 22.8 Gy; P < .001). The composite HPA Dmean was lower in IMPT plans (17.9 Gy) compared with that of VMAT (21.8 Gy) and TOMO (21.2 Gy) plans (P = .05). Hippocampi composite Dmean was also lower in IMPT plans (21 Gy) compared with that of VMAT (27.5 Gy) and TOMO (27.2 Gy) plans (P = .02). The IMPT CTV D95 coverage was lower in IMPT plans (52.8 Gy) compared with that of VMAT (54.6 Gy) and TOMO (54.6 Gy) plans (P < .001) The spared mean volume was only 1.35% (19.8 cm3) of the whole-brain CTV volume (1476 cm3). CONCLUSION: We found that IMPT has the strong potential to reduce the dose to the HPA and hippocampus, compared with standard x-ray CSI while maintaining target coverage. A prospective clinical trial is required to establish the safety, efficacy, and toxicity of this novel CSI approach.

Personalized 3D-printed anthropomorphic whole-body phantom irradiated by protons, photons, and neutrons.

The objective of this study was to confirm the feasibility of three-dimensionally-printed (3D-printed), personalized whole-body anthropomorphic phantoms for radiation dose measurements in a variety of charged and uncharged particle radiation fields. We 3D-printed a personalized whole-body phantom of an adult female with a height of 154.8 cm, mass of 90.7 kg, and body mass index of 37.8 kg/m2. The phantom comprised of a hollow plastic shell filled with water and included a watertight access conduit for positioning dosimeters. It is compatible with a wide variety of radiation dosimeters, including ionization chambers that are suitable for uncharged and charged particles. Its mass was 6.8 kg empty and 98 kg when filled with water. Watertightness and mechanical robustness were confirmed after multiple experiments and transportations between institutions. The phantom was irradiated to the cranium with therapeutic beams of 170-MeV protons, 6-MV photons, and fast neutrons. Radiation absorbed dose was measured from the cranium to the pelvis along the longitudinal central axis of the phantom. The dose measurements were made using established dosimetry protocols and well-characterized instruments. For the therapeutic environments considered in this study, stray radiation from intracranial treatment beams was the lowest for proton therapy, intermediate for photon therapy, and highest for neutron therapy. An illustrative example set of measurements at the location of the thyroid for a square field of 5.3 cm per side resulted in 0.09, 0.59, and 1.93 cGy/Gy from proton, photon, and neutron beams, respectively. In this study, we found that 3D-printed personalized phantoms are feasible, inherently reproducible, and well-suited for therapeutic radiation measurements. The measurement methodologies we developed enabled the direct comparison of radiation exposures from neutron, proton, and photon beam irradiations.

Risk of Cerebrovascular Events Among Childhood and Adolescent Patients Receiving Cranial Radiation Therapy: A Pediatric Normal Tissue Effects in the Clinic Normal Tissue Outcomes Comprehensive Review.

PURPOSE: Radiation-induced cerebrovascular toxicity is a well-documented sequelae that can be both life-altering and potentially fatal. We performed a meta-analysis of the relevant literature to create practical models for predicting the risk of cerebral vasculopathy after cranial irradiation. METHODS AND MATERIALS: A literature search was performed for studies reporting pediatric radiation therapy (RT) associated cerebral vasculopathy. When available, we used individual patient RT doses delivered to the Circle of Willis (CW) or optic chiasm (as a surrogate), as reported or digitized from original publications, to formulate a dose-response. A logistic fit and a Normal Tissue Complication Probability (NTCP) model was developed to predict future risk of cerebrovascular toxicity and stroke, respectively. This NTCP risk was assessed as a function of prescribed dose. RESULTS: The search identified 766 abstracts, 5 of which were used for modeling. We identified 101 of 3989 pediatric patients who experienced at least one cerebrovascular toxicity: transient ischemic attack, stroke, moyamoya, or arteriopathy. For a range of shorter follow-ups, as specified in the original publications (approximate attained ages of 17 years), our logistic fit model predicted the incidence of any cerebrovascular toxicity as a function of dose to the CW, or surrogate structure: 0.2% at 30 Gy, 1.3% at 45 Gy, and 4.4% at 54 Gy. At an attained age of 35 years, our NTCP model predicted a stroke incidence of 0.9% to 1.3%, 1.8% to 2.7%, and 2.8% to 4.1%, respectively at prescribed doses of 30 Gy, 45 Gy, and 54 Gy (compared with a baseline risk of 0.2%-0.3%). At an attained age of 45 years, the predicted incidence of stroke was 2.1% to 4.2%, 4.5% to 8.6%, and 6.7% to 13.0%, respectively at prescribed doses of 30 Gy, 45 Gy, and 54 Gy (compared with a baseline risk of 0.5%-1.0%). CONCLUSIONS: Risk of cerebrovascular toxicity continues to increase with longer follow-up. NTCP stroke predictions are very sensitive to model variables (baseline stroke risk and proportional stroke hazard), both of which found in the literature may be systematically erring on minimization of true risk. We hope this information will assist practitioners in counseling, screening, surveilling, and facilitating risk reduction of RT-related cerebrovascular late effects in this highly sensitive population.

Proton Radiotherapy Could Reduce the Risk of Fatal Second Cancers for Children with Intracranial Tumors in Low- and Middle-Income Countries.

PURPOSE: To test our hypothesis that, for young children with intracranial tumors, proton radiotherapy in a high-income country does not reduce the risk of a fatal subsequent malignant neoplasm (SMN) compared with photon radiotherapy in low- and middle-income countries. MATERIALS AND METHODS: We retrospectively selected 9 pediatric patients with low-grade brain tumors who were treated with 3-dimensional conformal radiation therapy in low- and middle-income countries. Images and contours were deidentified and transferred to a high-income country proton therapy center. Clinically commissioned treatment planning systems of each academic hospital were used to calculate absorbed dose from the therapeutic fields. After fusing supplemental computational phantoms to the patients' anatomies, models from the literature were applied to calculate stray radiation doses. Equivalent doses were determined in organs and tissues at risk of SMNs, and the lifetime attributable risk of SMN mortality (LAR) was predicted using a dose-effect model. Our hypothesis test was based on the average of the ratios of LARs from proton therapy to that of photon therapy ()(H0: = 1; H A : < 1). RESULTS: Proton therapy reduced the equivalent dose in organs at risk for SMNs and LARs compared with photon therapy for which the for the cohort was 0.69 ± 0.10, resulting in the rejection of H0 (P < .001, α = 0.05). We observed that the younger children in the cohort (2-4 years old) were at a factor of approximately 2.5 higher LAR compared with the older children (8-12 years old). CONCLUSION: Our findings suggest that proton radiotherapy has the strong potential of reducing the risk of fatal SMNs in pediatric patients with intracranial tumors if it were made available globally.

Application of a fast proton dose calculation algorithm to a thorax geometry.

Treatment planning in proton therapy requires the calculation of absorbed dose distributions on beam shaping components and the patient anatomy. Analytical pencil-beam dose algorithms commonly used are not always accurate enough. The Monte Carlo approach is more accurate but extremely computationally intensive. The Fast Dose Calculator, a track-repeating algorithm, has been proposed as an alternative fast and accurate dose calculation. In this work FDC is applied to a proton therapy patient thoracic anatomy.

Monte Carlo fast dose calculator for proton radiotherapy: application to a voxelized geometry representing a patient with prostate cancer.

The Monte Carlo method is used to provide accurate dose estimates in proton radiation therapy research. While it is more accurate than commonly used analytical dose calculations, it is computationally intense. The aim of this work was to characterize for a clinical setup the fast dose calculator (FDC), a Monte Carlo track-repeating algorithm based on GEANT4. FDC was developed to increase computation speed without diminishing dosimetric accuracy. The algorithm used a database of proton trajectories in water to calculate the dose of protons in heterogeneous media. The extrapolation from water to 41 materials was achieved by scaling the proton range and the scattering angles. The scaling parameters were obtained by comparing GEANT4 dose distributions with those calculated with FDC for homogeneous phantoms. The FDC algorithm was tested by comparing dose distributions in a voxelized prostate cancer patient as calculated with well-known Monte Carlo codes (GEANT4 and MCNPX). The track-repeating approach reduced the CPU time required for a complete dose calculation in a voxelized patient anatomy by more than two orders of magnitude, while on average reproducing the results from the Monte Carlo predictions within 2% in terms of dose and within 1 mm in terms of distance.

Stray radiation dose and second cancer risk for a pediatric patient receiving craniospinal irradiation with proton beams.

Proton beam radiotherapy unavoidably exposes healthy tissue to stray radiation emanating from the treatment unit and secondary radiation produced within the patient. These exposures provide no known benefit and may increase a patient's risk of developing a radiogenic cancer. The aims of this study were to calculate doses to major organs and tissues and to estimate second cancer risk from stray radiation following craniospinal irradiation (CSI) with proton therapy. This was accomplished using detailed Monte Carlo simulations of a passive-scattering proton treatment unit and a voxelized phantom to represent the patient. Equivalent doses, effective dose and corresponding risk for developing a fatal second cancer were calculated for a 10-year-old boy who received proton therapy. The proton treatment comprised CSI at 30.6 Gy plus a boost of 23.4 Gy to the clinical target volume. The predicted effective dose from stray radiation was 418 mSv, of which 344 mSv was from neutrons originating outside the patient; the remaining 74 mSv was caused by neutrons originating within the patient. This effective dose corresponds to an attributable lifetime risk of a fatal second cancer of 3.4%. The equivalent doses that predominated the effective dose from stray radiation were in the lungs, stomach and colon. These results establish a baseline estimate of the stray radiation dose and corresponding risk for a pediatric patient undergoing proton CSI and support the suitability of passively-scattered proton beams for the treatment of central nervous system tumors in pediatric patients.

The risk of developing a second cancer after receiving craniospinal proton irradiation.

The purpose of this work was to compare the risk of developing a second cancer after craniospinal irradiation using photon versus proton radiotherapy by means of simulation studies designed to account for the effects of neutron exposures. Craniospinal irradiation of a male phantom was calculated for passively-scattered and scanned-beam proton treatment units. Organ doses were estimated from treatment plans; for the proton treatments, the amount of stray radiation was calculated separately using the Monte Carlo method. The organ doses were converted to risk of cancer incidence using a standard formalism developed for radiation protection purposes. The total lifetime risk of second cancer due exclusively to stray radiation was 1.5% for the passively scattered treatment versus 0.8% for the scanned proton beam treatment. Taking into account the therapeutic and stray radiation fields, the risk of second cancer from intensity-modulated radiation therapy and conventional radiotherapy photon treatments were 7 and 12 times higher than the risk associated with scanned-beam proton therapy, respectively, and 6 and 11 times higher than with passively scattered proton therapy, respectively. Simulations revealed that both passively scattered and scanned-beam proton therapies confer significantly lower risks of second cancers than 6 MV conventional and intensity-modulated photon therapies.

A TRACK-REPEATING ALGORITHM FOR FAST MONTE CARLO DOSE CALCULATIONS OF PROTON RADIOTHERAPY.

Monte Carlo codes are utilized for accurate dose calculations in proton radiation therapy research. While they are superior in accuracy to commonly used analytical dose calculations, they require significantly longer computation times. The aim of this work is to characterize a Monte Carlo track-repeating algorithm to increase computation speed without compromising dosimetric accuracy. The track-repeating approach reduced the CPU time required for a complete dose calculation in voxelized patient anatomy by more than two orders of magnitude, while on average reproducing the results from the traditional Monte Carlo approach within 4% dose difference and within 1-mm distance to agreement.

REDUCING STRAY RADIATION DOSE FOR A PEDIATRIC PATIENT RECEIVING PROTON CRANIOSPINAL IRRADIATION.

The aim of this study was to quantify stray radiation dose from neutrons emanating from a proton treatment unit and to evaluate methods of reducing this dose for a pediatric patient undergoing craniospinal irradiation. The organ equivalent doses and effective dose from stray radiation were estimated for a 30.6-Gy treatment using Monte Carlo simulations of a passive scattering treatment unit and a patient-specific voxelized anatomy. The treatment plan was based on computed tomography images of a 10-yr-old male patient. The contribution to stray radiation was evaluated for the standard nozzle and for the same nozzle but with modest modifications to suppress stray radiation. The modifications included enhancing the local shielding between the patient and the primary external neutron source and increasing the distance between them. The effective dose from stray radiation emanating from the standard nozzle was 322 mSv; enhancements to the nozzle reduced the effective dose by as much as 43%. These results add to the body of evidence that modest enhancements to the treatment unit can reduce substantially the effective dose from stray radiation.

ANALYTICAL MODEL TO ESTIMATE EQUIVALENT DOSE FROM INTERNAL NEUTRONS IN PROTON THERAPY OF CHILDREN WITH INTRACRANIAL TUMORS.

This study developed a computationally efficient and easy-to-implement analytical model to estimate the equivalent dose from secondary neutrons originating in the bodies ('internal neutrons') of children receiving intracranial proton radiotherapy. A two-term double-Gaussian mathematical model was fit to previously published internal neutron equivalent dose per therapeutic absorbed dose versus distance from the field edge calculated using Monte Carlo simulations. The model was trained using three intracranial proton fields of a 9-year-old girl. The resulting model was tested against two intracranial fields of a 10-year-old boy by comparing the mean doses in organs at risk of a radiogenic cancer estimated by the model versus those previously calculated by Monte Carlo. On average, the model reproduced the internal neutron organ doses in the 10-year-old boy within 13.5% of the Monte Carlo at 3-10 cm from the field edge and within a factor of 2 of the Monte Carlo at 10-20 cm from the field edge. Beyond 20 cm, the model poorly estimated H/DRx, however, the values were very small, at <0.03 mSv Gy-1.

Reducing stray radiation dose to patients receiving passively scattered proton radiotherapy for prostate cancer.

Proton beam radiotherapy exposes healthy tissue to stray radiation emanating from the treatment unit and secondary radiation produced within the patient. These exposures provide no known benefit and may increase a patient's risk of developing a radiogenic second cancer. The aim of this study was to explore strategies to reduce stray radiation dose to a patient receiving a 76 Gy proton beam treatment for cancer of the prostate. The whole-body effective dose from stray radiation, E, was estimated using detailed Monte Carlo simulations of a passively scattered proton treatment unit and an anthropomorphic phantom. The predicted value of E was 567 mSv, of which 320 mSv was attributed to leakage from the treatment unit; the remainder arose from scattered radiation that originated within the patient. Modest modifications of the treatment unit reduced E by 212 mSv. Surprisingly, E from a modified passive-scattering device was only slightly higher (109 mSv) than from a nozzle with no leakage, e.g., that which may be approached with a spot-scanning technique. These results add to the body of evidence supporting the suitability of passively scattered proton beams for the treatment of prostate cancer, confirm that the effective dose from stray radiation was not excessive, and, importantly, show that it can be substantially reduced by modest enhancements to the treatment unit.

A comparison of the measured responses of a tissue-equivalent proportional counter to high energy heavy (HZE) particles and those simulated using the Geant4 Monte Carlo code.

Monte Carlo simulations of heavy ion interactions using the Geant4 toolkit were compared with measurements of energy deposition in a spherical tissue-equivalent proportional counter (TEPC). A spherical cavity with a physical diameter of 12.7 mm was filled with propane-based tissue-equivalent gas surrounded by a wall of A-150 tissue-equivalent plastic that was 2.54 mm to thick. Measurements and Monte Carlo simulations were used to record the energy deposition and the trajectory of the incident particle on an event-by-event basis for ions ranging in atomic number from 2 ((4)He) to 26 ((56)Fe) and in energy from 200 MeV/nucleon to 1000 MeV/nucleon. In the simulations, tracking of secondary electrons was terminated when the range of an electron was below a specified threshold. The effects of range cuts for electrons at 0.5 µm, 1 µm, 10 µm, and 100 µm were evaluated. To simulate an energy deposition influenced by large numbers of low energy electrons with large transverse momentum, it was necessary to track electrons down to range cuts of 10 µm or less. The Geant4 simulated data closely matched the measured data acquired using a TEPC for incident particles traversing the center of the detector as well as near the gas-wall interface. Values of frequency mean lineal energy and dose mean lineal energy were within 8% of the measured data. The production of secondary particles in the aluminum vacuum chamber had no effect on the response of the TEPC for (56)Fe at 1000 MeV/nucleon. The results of this study confirm that Geant4 can simulate patterns of energy deposition for existing microdosimeters and is valuable for improving the design of a new generation of detectors used for space dosimetry and for characterizing particle beams used in hadron radiotherapy.

Independent application of an analytical model for secondary neutron equivalent dose produced in a passive-scattering proton therapy treatment unit.

The purpose of this study was to independently apply an analytical model for equivalent dose from neutrons produced in a passive-scattering proton therapy treatment unit, H. To accomplish this objective, we applied the previously-published model to treatment plans of two pediatric patients. Their model accounted for neutrons generated by mono-energetic proton beams stopping in a closed aperture. To implement their model to a clinical setting, we adjusted it to account for the area of a collimating aperture, energy modulation, air gap between the treatment unit and patient, and radiation weighting factor. We used the adjusted model to estimate H per prescribed proton absorbed dose, D Rx , for the passive-scattering proton therapy beams of two children, a 9-year-old girl and 10-year-old boy, who each received intracranial boost fields as part of their treatment. In organs and tissues at risk for radiation-induced subsequent malignant neoplasms, T, we calculated the mass-averaged H, H T , per D Rx . Finally, we compared H T /D Rx values to those of previously-published Monte Carlo (MC) simulations of these patients' fields. H T /D Rx values of the adjusted model deviated from the MC result for each organ on average by 20.8 ± 10.0% and 44.2 ± 17.6% for the girl and boy, respectively. The adjusted model underestimated the MC result in all T of each patient, with the exception of the girl's bladder, for which the adjusted model overestimated H T /D Rx by 3.1%. The adjusted model provided a better estimate of H T /D Rx than the unadjusted model. That is, between the two models, the adjusted model reduced the deviation from the MC result by approximately 37.0% and 46.7% for the girl and boy, respectively. We found that the previously-published analytical model, combined with adjustment factors to enhance its clinical applicability, predicted H T /D Rx in out-of-field organs and tissues at risk for subsequent malignant neoplasms with acceptable accuracy. This independent application demonstrated that the analytical model may be useful broadly for clinicians and researchers to calculate equivalent dose from neutrons produced externally to the patient in passive-scattering proton therapy.

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

The purpose of this study was to develop a straightforward method of supplementing patient anatomy and estimating out-of-field absorbed dose for a cohort of pediatric radiotherapy patients with limited recorded anatomy. A cohort of nine children, aged 2-14 years, who received 3D conformal radiotherapy for low-grade localized brain tumors (LBTs), were randomly selected for this study. The extent of these patients' computed tomography simulation image sets were cranial only. To approximate their missing anatomy, we supplemented the LBT patients' image sets with computed tomography images of patients in a previous study with larger extents of matched sex, height, and mass and for whom contours of organs at risk for radiogenic cancer had already been delineated. Rigid fusion was performed between the LBT patients' data and that of the supplemental computational phantoms using commercial software and in-house codes. In-field dose was calculated with a clinically commissioned treatment planning system, and out-of-field dose was estimated with a previously developed analytical model that was re-fit with parameters based on new measurements for intracranial radiotherapy. Mean doses greater than 1 Gy were found in the red bone marrow, remainder, thyroid, and skin of the patients in this study. Mean organ doses between 150 mGy and 1 Gy were observed in the breast tissue of the girls and lungs of all patients. Distant organs, i.e. prostate, bladder, uterus, and colon, received mean organ doses less than 150 mGy. The mean organ doses of the younger, smaller LBT patients (0-4 years old) were a factor of 2.4 greater than those of the older, larger patients (8-12 years old). Our findings demonstrated the feasibility of a straightforward method of applying supplemental computational phantoms and dose-calculation models to estimate absorbed dose for a set of children of various ages who received radiotherapy and for whom anatomies were largely missing in their original computed tomography simulations.

Low- and middle-income countries can reduce risks of subsequent neoplasms by referring pediatric craniospinal cases to centralized proton treatment centers.

Few children with cancer in low- and middle-income countries (LMICs) have access to proton therapy. Evidence exists to support replacing photon therapy with proton therapy to reduce the incidence of secondary malignant neoplasms (SMNs) in childhood cancer survivors. The purpose of this study was to estimate the potential reduction in SMN incidence and in SMN mortality for pediatric medulloblastoma patients in LMICs if proton therapy were made available to them. For nine children of ages 2 to 14 years, we calculated the equivalent dose in organs or tissues at risk for radiogenic SMNs from therapeutic and stray radiation for photon craniospinal irradiation (CSI) in a LMIC and proton CSI in a high-income country. We projected the lifetime risks of SMN incidence and SMN mortality for every SMN site with a widely-used model from the literature. We found that the average total lifetime attributable risks of incidence and mortality were very high for both photon CSI (168% and 41%, respectively) and proton CSI (88% and 26%, respectively). SMNs having the highest risk of mortality were lung cancer (16%), non-site-specific solid tumors (16%), colon cancer (5.9%), leukemia (5.4%), and for girls breast cancer (5.0%) after photon CSI and non-site-specific solid tumors (12%), lung cancer (11%), and leukemia (4.8%) after proton CSI. The risks were higher for younger children than for older children and higher for girls than for boys. The ratios of proton CSI to photon CSI of total risks of SMN incidence and mortality were 0.56 (95% CI, 0.37 to 0.75) and 0.64 (95% CI, 0.45 to 0.82), respectively, averaged over this sample group. In conclusion, proton therapy has the potential to lessen markedly subsequent SMNs and SMN fatalities in survivors of childhood medulloblastoma in LMICs, for example, through regional centralized care. Additional methods should be explored urgently to reduce therapeutic-field doses in organs and tissues at risk for SMN, especially in the lungs, colon, and breast tissues.

The response of a spherical tissue-equivalent proportional counter to different heavy ions having similar velocities.

A tissue-equivalent proportional counter (TEPC) has been used as a dosimeter in mixed radiation fields. Since it does not measure LET directly, the response function must be characterized in order to estimate quality factor and thus equivalent dose for the incident radiation. The objectives of this study were to measure the response of a spherical TEPC for different high-energy heavy ions (HZE) having similar velocity and to determine how quality factors can be determined. Data were obtained at the HIMAC heavy ion accelerator for (4)He and (12)C at 220 +/- 5 MeV/nucleon (beta = 0.59) and (12)C, (16)O, (28)Si and (56)Fe at 376 +/- 15 MeV/nucleon (beta = 0.70). A particle spectrometer recorded the charge and position of each incident beam particle. Events with low energy deposition were observed for particles that passed through the wall of the TEPC but not through the sensitive volume. The frequency averaged lineal energy, y(f), was always less than the LET of the incident particles. The dose averaged lineal energy, y(D), was approximately equal to LET for particles with LET greater than 10 keV/mum, whereas y(D) was larger than LET for the lighter particles with lower LET. Part of this effect is due to detector resolution and energy straggling that increases the variance of the response function. Although the TEPC is not a LET spectrometer, it can provide real time measurements of dose and provide estimates of quality factors for HZE particles using averaged values of lineal energy.

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

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.

Reducing the cost of proton radiation therapy: the feasibility of a streamlined treatment technique for prostate cancer.

Proton radiation therapy is an effective modality for cancer treatments, but the cost of proton therapy is much higher compared to conventional radiotherapy and this presents a formidable barrier to most clinical practices that wish to offer proton therapy. Little attention in literature has been paid to the costs associated with collimators, range compensators and hypofractionation. The objective of this study was to evaluate the feasibility of cost-saving modifications to the present standard of care for proton treatments for prostate cancer. In particular, we quantified the dosimetric impact of a treatment technique in which custom fabricated collimators were replaced with a multileaf collimator (MLC) and the custom range compensators (RC) were eliminated. The dosimetric impacts of these modifications were assessed for 10 patients with a commercial treatment planning system (TPS) and confirmed with corresponding Monte Carlo simulations. We assessed the impact on lifetime risks of radiogenic second cancers using detailed dose reconstructions and predictive dose-risk models based on epidemiologic data. We also performed illustrative calculations, using an isoeffect model, to examine the potential for hypofractionation. Specifically, we bracketed plausible intervals of proton fraction size and total treatment dose that were equivalent to a conventional photon treatment of 79.2 Gy in 44 fractions. Our results revealed that eliminating the RC and using an MLC had negligible effect on predicted dose distributions and second cancer risks. Even modest hypofractionation strategies can yield substantial cost savings. Together, our results suggest that it is feasible to modify the standard of care to increase treatment efficiency, reduce treatment costs to patients and insurers, while preserving high treatment quality.

The response of a spherical tissue-equivalent proportional counter to different ions having similar linear energy transfer.

The response of a tissue-equivalent proportional counter (TEPC) to different ions having a similar linear energy transfer (LET) has been studied. Three ions, 14N, 20Ne and 28Si, were investigated using the HIMAC accelerator at the National Institute of Radiological Sciences at Chiba, Japan. The calculated linear energy transfer (LET( infinity )) of all ions was 44 +/- 2 keV/microm at the sensitive volume of the TEPC. A particle spectrometer was used to record the charge and position of each incident beam particle. This enabled reconstruction of the location of the track as it passed though the TEPC and ensured that the particle survived without fragmentation. The spectrum of energy deposition events in the TEPC could be evaluated as a function of trajectory through the TEPC. The data indicated that there are many events from particles that did not pass through the sensitive volume. The fraction of these events increased as the energy of the particle increased due to changes in the maximum energy of the delta rays. Even though the LET of the incident particles was nearly identical, the frequency-averaged lineal energy, y(F), as well as the dose-averaged lineal energy, y(D), varied with the velocity of the incident particle. However, both values were within 15% of LET in all cases.