Lifetime attributable risk of radiation-induced secondary cancer from proton beam therapy compared with that of intensity-modulated X-ray therapy in randomly sampled pediatric cancer patients

To investigate the amount that radiation-induced secondary cancer would be reduced by using proton beam therapy (PBT) in place of intensity-modulated X-ray therapy (IMXT) in pediatric patients, we analyzed lifetime attributable risk (LAR) as an in silico surrogate marker of the secondary cancer after these treatments. From 242 pediatric patients with cancers who were treated with PBT, 26 patients were selected by random sampling after stratification into four categories: (i) brain, head and neck, (ii) thoracic, (iii) abdominal, and (iv) whole craniospinal (WCNS) irradiation. IMXT was replanned using the same computed tomography and region of interest. Using the dose-volume histograms (DVHs) of PBT and IMXT, the LARs of Schneider et al. were calculated for the same patient. All the published dose-response models were tested for the organs at risk. Calculation of the LARs of PBT and IMXT based on the DVHs was feasible for all patients. The means +/- standard deviations of the cumulative LAR difference between PBT and IMXT for the four categories were (i) 1.02 +/- 0.52% (n = 7, P = 0.0021), (ii) 23.3 +/- 17.2% (n = 8, P = 0.0065), (iii) 16.6 +/- 19.9% (n = 8, P = 0.0497) and (iv) 50.0 +/- 21.1% (n = 3, P = 0.0274), respectively (one tailed t-test). The numbers needed to treat (NNT) were (i) 98.0, (ii) 4.3, (iii) 6.0 and (iv) 2.0 for WCNS, respectively. In pediatric patients who had undergone PBT, the LAR of PBT was significantly lower than the LAR of IMXT estimated by in silico modeling. Although a validation study is required, it is suggested that the LAR would be useful as an in silico surrogate marker of secondary cancer induced by different radiotherapy techniques

General ion recombination effect in a liquid ionization chamber in high-dose-rate pulsed photon and electron beams

Liquid ionization chambers (LICs) are highly sensitive to dose irradiation and have small perturbations because of their liquid-filled sensitive volume. They require a sensitive volume much smaller than conventional air-filled chambers. However, it has been reported that the collection efficiency has dependencies on the dose per pulse and the pulse repetition frequency of a pulsed beam. The purpose of this study was to evaluate in detail the dependency of the ion collection efficiency on the pulse repetition frequency. A microLion (PTW, Freiburg, Germany) LIC was exposed to photon and electron beams from a TrueBeam (Varian Medical Systems, Palo Alto, USA) linear accelerator. The pulse repetition frequency was varied, but the dose per pulse was fixed. A theoretical evaluation of the collection efficiency was performed based on Boag’s theory. Linear correlations were observed between the frequency and the relative collection for all energies of the photon and electron beams. The decrease in the collected charge was within 1% for all the flattened photon and electron beams, and they were 1.1 and 1.8% for the 6 and 10 MV flattening filter-free photon beams, respectively. The theoretical ion collection efficiency was 0.990 for a 10 MV flattened photon beam with a dose rate of 3 Gy·min−1. It is suggested that the collected charge decreased because of the short time intervals of the beam pulse compared with the ion collection time. Thus, it is important to correctly choose the pulse repetition frequency, particularly when flattening filter-free mode is used for absolute dose measurements

3D‐printable lung phantom for distal falloff verification of proton Bragg peak

In proton therapy, the Bragg peak of a proton beam reportedly deteriorates when passing though heterogeneous structures such as human lungs. Previous studies have used heterogeneous random voxel phantoms, in which soft tissues and air are randomly allotted to render the phantoms the same density as human lungs, for conducting Monte Carlo (MC) simulations. However, measurements of these phantoms are complicated owing to their difficult‐to‐manufacture shape. In the present study, we used Voronoi tessellation to design a phantom that can be manufactured, and prepared a Voronoi lung phantom for which both measurement and MC calculations are possible. Our aim was to evaluate the effectiveness of this phantom as a new lung phantom for investigating proton beam Bragg peak deterioration. For this purpose, we measured and calculated the percentage depth dose and the distal falloff widths (DFW) passing through the phantom. For the 155 MeV beam, the measured and calculated DFW values with the Voronoi lung phantom were 0.40 and 0.39 cm, respectively. For the 200 MeV beam, the measured and calculated DFW values with the Voronoi lung phantom were both 0.48 cm. Our results indicate that both the measurements and MC calculations exhibited high reproducibility with plastinated lung sample from human body in previous studies. We found that better results were obtained using the Voronoi lung phantom than using other previous phantoms. The designed phantom may contribute significantly to the improvement of measurement precision. This study suggests that the Voronoi lung phantom is useful for simulating the effects of the heterogeneous structure of lungs on proton beam deterioration

Lifetime attributable risk of radiation-induced secondary cancer from proton beam therapy compared with that of intensity-modulated X-ray therapy in randomly sampled pediatric cancer patients

To investigate the amount that radiation-induced secondary cancer would be reduced by using proton beam therapy (PBT) in place of intensity-modulated X-ray therapy (IMXT) in pediatric patients, we analyzed lifetime attributable risk (LAR) as an in silico surrogate marker of the secondary cancer after these treatments. From 242 pediatric patients with cancers who were treated with PBT, 26 patients were selected by random sampling after stratification into four categories: (i) brain, head and neck, (ii) thoracic, (iii) abdominal, and (iv) whole craniospinal (WCNS) irradiation. IMXT was replanned using the same computed tomography and region of interest. Using the dose–volume histograms (DVHs) of PBT and IMXT, the LARs of Schneider et al. were calculated for the same patient. All the published dose–response models were tested for the organs at risk. Calculation of the LARs of PBT and IMXT based on the DVHs was feasible for all patients. The means ± standard deviations of the cumulative LAR difference between PBT and IMXT for the four categories were (i) 1.02 ± 0.52% (n = 7, P = 0.0021), (ii) 23.3 ± 17.2% (n = 8, P = 0.0065), (iii) 16.6 ± 19.9% (n = 8, P = 0.0497) and (iv) 50.0 ± 21.1% (n = 3, P = 0.0274), respectively (one tailed t-test). The numbers needed to treat (NNT) were (i) 98.0, (ii) 4.3, (iii) 6.0 and (iv) 2.0 for WCNS, respectively. In pediatric patients who had undergone PBT, the LAR of PBT was significantly lower than the LAR of IMXT estimated by in silico modeling. Although a validation study is required, it is suggested that the LAR would be useful as an in silico surrogate marker of secondary cancer induced by different radiotherapy techniques

A validated proton beam therapy patch-field protocol for effective treatment of large hepatocellular carcinoma

Development of a curative local treatment for large hepatocellular carcinoma (HCC) is an important issue. Here, we investigated the dose homogeneity, safety and antitumor effectiveness of proton beam therapy (PBT) using a patch-field technique for large HCC. Data from nine patients (aged 52–79 years) with large HCC treated with patch-field PBT were investigated. The cranial–caudal diameters of the clinical target volumes (CTVs) were 15.0–18.6 cm (median 15.9). The CTV was divided cranially and caudally while both isocenters were aligned along the cranial–caudal axis and overlap of the cranial and caudal irradiation fields was set at 0–0.5 mm. Multileaf collimators were used to eliminate hot or cold spots. Total irradiation doses were 60–76.4 Gy equivalents. Irradiation doses as a percentage of the prescription dose (from the treatment planning system) around the junction were a minimum of 93–105%, a mean of 99–112%, and a maximum of 105–120%. Quality assurance (QA) was assessed in the cranial and caudal irradiation fields using imaging plates. Acute adverse effects of Grade 3 were observed in one patient (hypoalbuminemia), and a late adverse effect of Grade 3 was observed in one patient (liver abscess). Child–Pugh class elevations were observed in four patients (A to B: 3; B to C: 1). Overall survival rates at 1 and 2 years were 55 and 14%, respectively, with a median overall survival of 13.6 months. No patients showed local recurrence. Patch-field PBT supported by substantial QA therefore is one of the treatment options for large HCC

Synchronization of light flash with the irradiation pulse in proton beam therapy: A case report

The correlation between sensory light flash and proton beam delivery was evaluated by measuring the timing of pulse beam delivery and light flash sensing using an event recorder in an 83-year-old patient receiving proton beam therapy (PBT) for nasopharyngeal adenoid cystic carcinoma. The treatment dose was 65 Gy (RBE) in 26 fractions with 2 ports, and both beams included the visual pathway (retina, optic nerve, chiasma). Measurements were obtained in 13 of the 26 fractions. The patient sensed a light flash in all 13 fractions and pressed the recorder button for 426 of the 430 pulsed beam deliveries, giving a sensing rate of 99.1%. The median duration of button-pressing of 0.3 s was almost the same as that of the beam pulse of 0.2 s, with a reaction time lag of 0.35 s. These results suggest a consistency between light flash during PBT and the timing of irradiation

A Retrospective Study of Renal Growth Changes after Proton Beam Therapy for Pediatric Malignant Tumor

The purpose of this study was to analyze renal late effects after proton beam therapy (PBT) for pediatric malignant tumors. A retrospective study was performed in 11 patients under 8 years of age who received PBT between 2013 and 2018. The kidney was exposed in irradiation of the primary lesion in all cases. Kidney volume and contour were measured on CT or MRI. Dose volume was calculated with a treatment-planning system. The median follow-up was 24 months (range, 11–57 months). In irradiated kidneys and control contralateral kidneys, the median volume changes were −5.63 (−20.54 to 7.20) and 5.23 (−2.01 to 16.73) mL/year; and the median % volume changes at 1 year were −8.55% (−47.52 to 15.51%) and 9.53% (−2.13 to 38.78%), respectively. The median relative volume change for irradiated kidneys at 1 year was −16.42% (−52.21 to −4.53%) relative to control kidneys. Kidneys irradiated with doses of 10, 20, 30, 40, and 50 GyE had volume reductions of 0.16%, 0.90%, 1.24%, 2.34%, and 8.2% per irradiated volume, respectively. The larger the irradiated volume, the greater the kidney volume was lost. Volume reduction was much greater in patients aged 4–7 years than in those aged 2–3 years. The results suggest that kidneys exposed to PBT in treatment of pediatric malignant tumor show continuous atrophy in follow-up. The degree of atrophy is increased with a higher radiation dose, greater irradiated volume, and older age. However, with growth and maturation, the contralateral kidney becomes progressively larger and is less affected by radiation

A Retrospective Study of Renal Growth Changes after Proton Beam Therapy for Pediatric Malignant Tumor

The purpose of this study was to analyze renal late effects after proton beam therapy (PBT) for pediatric malignant tumors. A retrospective study was performed in 11 patients under 8 years of age who received PBT between 2013 and 2018. The kidney was exposed in irradiation of the primary lesion in all cases. Kidney volume and contour were measured on CT or MRI. Dose volume was calculated with a treatment-planning system. The median follow-up was 24 months (range, 11–57 months). In irradiated kidneys and control contralateral kidneys, the median volume changes were −5.63 (−20.54 to 7.20) and 5.23 (−2.01 to 16.73) mL/year; and the median % volume changes at 1 year were −8.55% (−47.52 to 15.51%) and 9.53% (−2.13 to 38.78%), respectively. The median relative volume change for irradiated kidneys at 1 year was −16.42% (−52.21 to −4.53%) relative to control kidneys. Kidneys irradiated with doses of 10, 20, 30, 40, and 50 GyE had volume reductions of 0.16%, 0.90%, 1.24%, 2.34%, and 8.2% per irradiated volume, respectively. The larger the irradiated volume, the greater the kidney volume was lost. Volume reduction was much greater in patients aged 4–7 years than in those aged 2–3 years. The results suggest that kidneys exposed to PBT in treatment of pediatric malignant tumor show continuous atrophy in follow-up. The degree of atrophy is increased with a higher radiation dose, greater irradiated volume, and older age. However, with growth and maturation, the contralateral kidney becomes progressively larger and is less affected by radiation