Proton beam therapy for hepatocellular carcinoma with bile duct invasion.

AIM: Hepatocellular carcinoma (HCC) with bile duct invasion (BDI) (BDIHCC) has a poor prognosis. Moreover, due to the paucity of reports, there is no consensus regarding optimal management of this clinical condition yet. The aim of this study was to clarify the efficacy and safety of proton beam therapy (PBT) for BDIHCC. METHODS: Between 2009 and 2018, 15 patients with BDIHCC underwent PBT at our institution. The overall survival (OS), local control (LC), and progression-free survival (PFS) curves were constructed using the Kaplan-Meier method. Toxicities were assessed using the Common Terminology Criteria of Adverse Events version 4.0. RESULTS: The median follow-up time was 23.4 months (range, 7.9-54.3). The median age was 71 years (range, 58-90 years). Many patients were Child A (n = 8, 53.3%) and most had solitary tumors (n = 11, 73.3%). Additionally, most patients had central type BDI (n = 11, 73%). The median tumor size was 4.0 cm (range, 1.5-8.0 cm). The 1-, 2-, and 3-year OS rates were 80.0%, 58.7% and 40.2%, respectively, and the corresponding LC and PFS rates were 93.3%, 93.3%, and 74.7% and 72.7%, 9.7%, and 0.0%, respectively. Acute grade 1/2 dermatitis (n = 7, 46.7%), and grades 2 (n = 1, 6.7%) and 3 (n = 1, 6.7%) cholangitis were observed. Late toxicities such as grade 3 gastric hemorrhage and pleural effusion were observed. No toxicities of grade 4 or higher were observed. CONCLUSIONS: PBT was feasible with tolerable toxicities for the treatment of BDIHCC.

Spinal changes after craniospinal irradiation in pediatric patients.

BACKGROUND: To evaluate long-term degenerative changes in bone and soft tissue after craniospinal irradiation (CSI). PROCEDURE: An analysis was performed for 892 vertebral bodies in 220 pediatric patients treated with CSI. To analyze vertebral growth, vertebral body height was calculated. Signal changes for vertebral bodies on MRI, scoliosis and kyphosis, degenerative changes of vertebral bones and discs, and wedging or vertebral height loss were analyzed on images, and factors that influenced these changes were investigated. RESULTS: Vertebral growth was significantly correlated with radiation dose and growth hormone (GH) deficiency. Growth rate was significantly worse at a dose >39 Gy. Fatty marrow change was found in 83% of patients, 31% had disc degenerative changes, 13% had degenerative changes of spinal bones, 17% had wedging or spinal height loss, and 27% had scoliosis. CONCLUSIONS: Vertebral bone growth was significantly reduced when high doses were administered, and adequate GH replacement was important for bone growth. Even with symmetrical irradiation, the risk of scoliosis is high after CSI. There was also frequent progression of spinal demineralization and degenerative changes after CSI. Therefore, careful attention should be paid to spinal symptoms as pediatric patients grow into adulthood.

Height after photon craniospinal irradiation in pediatric patients treated for central nervous system embryonal tumors.

BACKGROUND: We modeled height after craniospinal irradiation (CSI) in pediatric patients with central nervous system (CNS) embryonal tumors to identify factors that impair stature. PROCEDURE: During 1996-2012, 212 pediatric patients (131 male) with CNS embryonal tumors received postoperative CSI: 23.4 Gy (n = 147) or ≥36 Gy (n = 65), similar postirradiation chemotherapy, and were followed for at least 5 years without tumor progression or other event. The group was further characterized by age at CSI and hormone-replacement therapy received. Models were developed to identify factors associated with growth impairment and estimate final height. RESULTS: With median follow up of 10.2 years (range 5.0-20.4 years), the mean final height z-scores at 18 years of age, compared to United States standards, were -1.3 for female and -1.5 for male survivors. Younger age at the time of CSI, higher CSI dose, and female sex were associated with height impairment. Factors associated with higher growth rates before 15 years of age were older age at CSI, male sex, CSI dose < 36 Gy, replacement therapy for growth hormone (GH) and central adrenal insufficiency, and white race. Growth after age 15 in male survivors was associated with treatment of gonadotropin deficiency. Linear mixed-effects models were developed using clinical factors to estimate final height, demonstrate the unique growth curve of this cohort, and interactions between clinical variable and radiation dose. CONCLUSIONS: CSI significantly impaired height at current doses used to treat standard- or high-risk CNS embryonal tumors. Measures to reduce the impact of CSI on height should be sought, with our models serving as benchmarks.

Long-term follow-up after proton beam therapy for pediatric tumors: a Japanese national survey.

Proton beam therapy (PBT) is a potential new alternative to treatment with photon radiotherapy that may reduce the risk of late toxicity and secondary cancer, especially for pediatric tumors. The goal of this study was to evaluate the long-term benefits of PBT in cancer survivors. A retrospective observational study of pediatric patients who received PBT was performed at four institutions in Japan. Of 343 patients, 62 were followed up for 5 or more years. These patients included 40 males and 22 females, and had a median age of 10 years (range: 0-19 years) at the time of treatment. The irradiation dose ranged from 10.8 to 81.2 GyE (median: 50.4 GyE). The median follow-up period was 8.1 years (5.0-31.2 years). The 5-, 10- and 20-year rates for grade 2 or higher late toxicities were 18%, 35% and 45%, respectively, and those for grade 3 or higher late toxicities were 6%, 17% and 17% respectively. Univariate analysis showed that the irradiated site (head and neck, brain) was significantly associated with late toxicities. No malignant secondary tumors occurred within the irradiated field. The 10- and 20-year cumulative rates for all secondary tumors, malignant secondary tumors, and malignant nonhematologic secondary tumors were 8% and 16%, 5% and 13%, and 3% and 11%, respectively. Our data indicate that PBT has the potential to reduce the risk of late mortality and secondary malignancy. Longer follow-up is needed to confirm the benefits of PBT for pediatric tumors.

Registration error of the liver CT using deformable image registration of MIM Maestro and Velocity AI.

BACKGROUND: Understanding the irradiated area and dose correctly is important for the reirradiation of organs that deform after irradiation, such as the liver. We investigated the spatial registration error using the deformable image registration (DIR) software products MIM Maestro (MIM) and Velocity AI (Velocity). METHODS: Image registration of pretreatment computed tomography (CT) and posttreatment CT was performed in 24 patients with liver tumors. All the patients received proton beam therapy, and the follow-up period was 4-14 (median: 10) months. We performed DIR of the pretreatment CT and compared it with that of the posttreatment CT by calculating the dislocation of metallic markers (implanted close to the tumors). RESULTS: The fiducial registration error was comparable in both products: 0.4-32.9 (9.3 ± 9.9) mm for MIM and 0.5-38.6 (11.0 ± 10.0) mm for Velocity, and correlated with the tumor diameter for MIM (r = 0.69, P = 0.002) and for Velocity (r = 0.68, P = 0.0003). Regarding the enhancement effect, the fiducial registration error was 1.0-24.9 (7.4 ± 7.7) mm for MIM and 0.3-29.6 (8.9 ± 7.2) mm for Velocity, which is shorter than that of plain CT (P = 0.04, for both). CONCLUSIONS: The DIR performance of both MIM and Velocity is comparable with regard to the liver. The fiducial registration error of DIR depends on the tumor diameter. Furthermore, contrast-enhanced CT improves the accuracy of both MIM and Velocity. INSTITUTIONAL REVIEW BOARD APPROVAL: H28-102; July 14, 2016 approved.

Comorbidity and quality of life in childhood cancer survivors treated with proton beam therapy.

BACKGROUND: The rate of childhood cancer survival has recently reached >80%. Various adverse events among childhood cancer survivors (CCS) have been reported. Proton beams are able to avoid unnecessary irradiation to normal/vital organs. We conducted a quality of life (QOL) study for CCS who were treated with proton beam therapy (PBT). METHODS: We included those patients treated with PBT to the brain, head, or neck and who were ≤15 years old at the University of Tsukuba Hospital between 1983 and 2011. Clinical information was collected from medical records. Questionnaires including the Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scales (which assess health-related quality of life) were sent to the families/patients. RESULTS: Sixty patients were included. Median age at treatment was 6.2 years. The number of patients with status alive/dead/unknown was 32/24/4. Median follow-up period was 63.0 months (range, 48-340 months) for survivors. Questionnaires were sent to 25 families/patients and 19 were returned. PedsQL was assessed for 17 patients. Eleven of 32 living patients had at least one comorbidity grade 3/4. Average QOL score was above that for Japanese schoolchildren and adolescents. There was no correlation with comorbidity, and only longer time from treatment was correlated with a higher PedsQL score (P = 0.006). CONCLUSION: CCS who were treated with multimodal treatment using PBT had a higher QOL score. Higher score was related to longer time since treatment, regardless of comorbidity.

Proton beam therapy for pediatric ependymoma.

BACKGROUND: The aim of this study was to evaluate the efficacy of proton beam therapy for pediatric patients with ependymoma. METHODS: Proton beam therapy was conducted for six patients (three boys and three girls; age, 2-6 years; median, 5 years) with ependymoma. The tumors were WHO grades 2 and 3 in two and four patients, respectively. All patients underwent surgery (subtotal and gross total resection in three patients each) and proton beam therapy at doses of 50.4-61.2 GyE (median, 56.7 GyE). The mean doses to normal brain tissue in proton beam therapy and photon radiotherapy were simulated using the same treatment planning computed tomography images. RESULTS: All patients completed the planned irradiation. The follow-up period was 13-44 months (median, 24.5 months) from completion of proton beam therapy and all patients were alive at the end of this period. Local recurrence in the treatment field occurred in one patient at 4 months after proton beam therapy at 50.4 GyE. Alopecia and mild dermatitis occurred in all patients, but there was no severe toxicity. One patient had a once-off seizure after proton beam therapy and alopecia persisted in another patient for 31 months, but no patients had difficulty with daily life. The simulation showed that proton beam therapy reduces the dose to normal brain tissue by approximately half compared with photon radiotherapy. CONCLUSIONS: Proton beam therapy for pediatric ependymoma is safe, does not have specific toxicities, and can reduce irradiation of normal brain tissue.

Tailor-made treatment combined with proton beam therapy for children with genitourinary/pelvic rhabdomyosarcoma.

BACKGROUND: Rhabdomyosarcoma (RMS) is one of the most common soft tissue sarcomas among children. Patients who developed genitourinary/pelvic rhabdomyosarcoma (GU/P-RMS) have a higher complication ratio and relatively poorer event free survival, with local therapy being very important. While proton beam therapy (PBT) is expected to reduce co-morbidity, especially for children, this lacks firm evidence and analysis. We analyzed GU/P-RMS children who had undergone multimodal therapy combined with PBT at a single institution. METHOD: We retrospectively reviewed charts of children with GU/P-RMS treated from January 2007 to May 2013 at the University of Tsukuba Hospital who had undergone multimodal therapy with PBT. RESULTS: There were 5 children and their median age at diagnosis was 2.8 years (0.6-4.4 years). Primary sites were the bladder (2) and the prostate (3). All received neo-adjuvant chemotherapy and 3 underwent chemotherapy during PBT (Group Cx). All patients of Group Cx developed leukocytopenia (WBC <1000/µL). The median dose of PBT was 47.7 GyE (41.4-50.4 GyE). All patients survived by their last hospital visit (median, 36 months). CONCLUSIONS: We analyzed multimodal treatment combined with PBT applied for GU/P-RMS. PBT was well tolerated and could be a plausible choice instead of photon therapy for this population.

The Impact of Multileaf Collimator Size on Single Isocenter Dynamic Conformal Arcs-Based Radiosurgery for Brain Metastases.

PURPOSE: To compare the plan quality of stereotactic radiosurgery (SRS) between 2.5-mm and 5-mm multileaf collimator (MLC) and investigate the factors' influence on the differences by MLC size. METHODS: Seventy-six treatment plans including 145 targets calculated with a single isocenter multiple noncoplanar dynamic conformal arc (DCA) technique using automatic multiple brain metastases (MBM) treatment planning system. Conformity index (CI), gradient index (GI), lesion underdosage volume factor (LUF), healthy tissue overdose volume factor (HTOF), geometric conformity index (g), and mean dose to normal organs were compared between 2.5-mm and 5-mm MLC. Then the factors that influenced the differences of these parameters were investigated. The impact of target size was also investigated for CI and GI values of individual targets (n=145), and differences between 2.5-mm and 5-mm MLC were analyzed. RESULTS: All parameters except for LUF were significantly better in plans with 2.5 mm MLC. Target size was a significant factor for difference in HTOF, and distance between targets was a significant factor for difference in brain dose and GI. Among 145 metastases, the average inverse CI was 1.35 and 1.47 with 2.5-mm and 5-mm MLC, respectively (p<0.001). The average GI was 3.21 and 3.53, respectively (p<0.001). For individual targets, target size was a significant factor in CI and GI both with 2.5-mm and 5-mm MLC (p-value: <0.001, each). CI and GI were significantly better with 2.5-mm than 5-mm MLC. CI was almost >0.67 except for ≤5mm targets with 5-mm MLC. Also, GI was almost smaller than 3.0 for >10 mm targets both with 2.5-mm and 5-mm MLC. CONCLUSIONS: MBM with 5-mm MLC was almost fine. However, it may be better to use a conservative margin for larger metastases. It may also be better to avoid SRS with 5-mm MLC for patients with ≤5 mm target size.

Single isocenter dynamic conformal arcs-based radiosurgery for brain metastases: Dosimetric comparison with Cyberknife and clinical investigation.

Purpose: To compare the dosimetric quality of automatic multiple brain metastases planning (MBM) with that of Cyberknife (CK) based on the clinical tumor condition, such as the tumor number, size, and location. Methods: 76 treatment plans for 46 patients treated with CK were recalculated with the MBM treatment planning system. Conformity index (CI), homogeneity index (HI), gradient index (GI), lesion underdosage volume factor (LUF), healthy tissue overdose volume factor (HTOF), geometric conformity index (g) and mean dose to normal organs were compared between CK and MBM for tumor number, size, shape and distance from the brainstem or chiasm. Results: The results showed that the mean brain dose was significantly smaller in MBM than CK. CI did not differ between MBM and CK; however, HI was significantly more ideal in CK (p = 0.000), and GI was significantly smaller in MBM (P = 0.000). LUF was larger in CK (p = 0.000) and HTOF and g was larger in MBM (p = 0.003, and 0.012). For single metastases, CK had significantly better HTOF (p = 0.000) and g (p = 0.002), but there were no differences for multiple tumors. Brain dose in MBM was significantly lower and CI was higher for tumors < 30 mm (p = 0.000 and 0.000), whereas HTOF and g for tumors < 10 mm were significantly smaller in CK (p = 0.041 and p = 0.016). Among oval tumors, brain dose, GI and LUF were smaller in MBM, but HTOF and g were smaller in CK. There were no particular trends for tumors close to the brainstem, but HTOF tended to be smaller in CK (0.03 vs. 0.29, p = 0.068) for tumors inside the brainstem. Conclusions: MBM can reduce the brain dose while achieving a dose distribution quality equivalent to that with CK.

A systematic review and meta-analysis of radiotherapy and particle beam therapy for skull base chondrosarcoma: TRP-chondrosarcoma 2024.

Introduction: Chondrosarcoma is a rare malignant bone tumor. Particle beam therapy (PT) can concentrate doses to targets while reducing adverse events. A meta-analysis based on a literature review was performed to examine the efficacy of PT and photon radiotherapy for skull base chondrosarcoma. Methods: The meta-analysis was conducted using 21 articles published from 1990 to 2022. Results: After PT, the 3- and 5-year overall survival (OS) rates were 94.1% (95% confidence interval [CI]: 91.0-96.2%) and 93.9% (95% CI: 90.6-96.1%), respectively, and the 3- and 5-year local control rates were 95.4% (95% CI: 92.0-97.4%) and 90.1% (95% CI: 76.8-96.0%), respectively. Meta-regression analysis revealed a significant association of PT with a superior 5-year OS rate compared to three-dimensional conformal radiotherapy (p < 0.001). In the studies used in the meta-analysis, the major adverse event of grade 2 or higher was temporal lobe necrosis (incidence 1-18%, median 7%). Conclusion: PT for skull base chondrosarcoma had a good outcome and may be a valuable option among radiotherapy modalities. However, high-dose postoperative irradiation of skull base chondrosarcoma can cause adverse events such as temporal lobe necrosis.

An analysis of muscle growth after proton beam therapy for pediatric cancer.

Retardation of growth and development is a well-known late effect after radiotherapy for pediatric patients. The goal of the study was to examine the effect of proton beam therapy (PBT) on the growth of muscles included in the irradiated area. The subjects were 17 pediatric patients (age ≤ 5 years) who received PBT with a treatment field including a muscle on only one side out of a pair of symmetrical bilateral muscles and had imaging evaluations for at least 1 year after PBT. The thicknesses of the irradiated and non-irradiated (contralateral) muscles were measured retrospectively on CT or MRI axial images collected before and after PBT. The change of thickness divided by the period (years) for each muscle was compared between the irradiated and contralateral sides. Correlations of muscle growth with irradiation dose and age at the start of treatment were also evaluated. The median observation period was 39.2 months. The measurement sites included the erector spinae (n = 9), gluteus maximus (n = 5) and rhomboids + trapezius (n = 3) muscles. The average changes in muscle thickness were 0.24 mm/year on the irradiated side and 1.19 mm/year on the contralateral side, showing significantly reduced growth on the irradiated side (P = 0.001). Younger patients had greater muscle growth. Irradiation dose was not significant, but muscle growth tended to decrease as the dose increased, and muscles irradiated at >50 Gy (RBE) showed little growth. These results show that muscle growth is affected by PBT and that long-term follow-up is needed to evaluate muscle growth retardation.

Tumor Response on Diagnostic Imaging after Proton Beam Therapy for Hepatocellular Carcinoma.

BACKGROUND: Follow-up after treatment for hepatocellular carcinoma (HCC) can be mostly performed using dynamic CT or MRI, but there is no common evaluation method after radiation therapy. The purpose of this study is to examine factors involved in tumor reduction and local recurrence in patients with HCC treated with proton beam therapy (PBT) and to evaluate HCC shrinkage after PBT. METHODS: Cases with only one irradiated lesion or those with two lesions irradiated simultaneously were included in this study. Pre- and post-treatment lesions were evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) by measuring the largest diameter. RESULTS: The 6-, 12-, and 24-month CR + PR rates after PBT were 33.1%, 57.5%, and 76.9%, respectively, and the reduction rates were 25.1% in the first 6 months, 23.3% at 6-12 months, and 14.5% at 13-24 months. Cases that reached CR/PR at 6 and 12 months had improved OS compared to non-CR/non-PR cases. CONCLUSIONS: It is possible that a lesion that reached SD may subsequently transition to PR; it is reasonable to monitor progress with periodic imaging evaluations even after 1 year of treatment.

Late Changes in Renal Volume and Function after Proton Beam Therapy in Pediatric and Adult Patients: Children Show Significant Renal Atrophy but Deterioration of Renal Function Is Minimal in the Long-Term in Both Groups.

To compare late renal effects in pediatric and adult patients with malignancies after PBT involving part of the kidney. A retrospective study was conducted to assess changes in renal volume and function in 24 patients, including 12 children (1-14 years old) and 12 adults (51-80 years old). Kidney volumes were measured from CT or MRI images during follow-up. Dose-volume histograms were calculated using a treatment planning system. In children, the median volume changes for the irradiated and control kidneys were -5.58 (-94.95 to +4.79) and +14.92 (-19.45 to +53.89) mL, respectively, with a relative volume change of -28.38 (-119.45 to -3.87) mL for the irradiated kidneys. For adults, these volume changes were -22.43 (-68.7 to -3.48) and -21.56 (-57.26 to -0.16) mL, respectively, with a relative volume change of -5.83 (-28.85 to +30.92) mL. Control kidneys in children exhibited a marked increase in size, while those in adults showed slight volumetric loss. The percentage of irradiated volume receiving 10 Gy (RBE) (V10) and 20 Gy (RBE) (V20) were significantly negatively associated with the relative volume change per year, especially in children. The CKD stage based on eGFR for all patients ranged from 1 to 3 and no cases with severe renal dysfunction were found before or after PBT. Late effects on the kidneys after PBT vary among age groups. Children are more susceptible than adults to significant renal atrophy after PBT. V10 and V20 might serve as predictors of the degree of renal atrophy after PBT, especially in children. PBT has a minimal impact on deterioration of renal function in both children and adults.

Dose-volume histogram analysis for risk factors of radiation-induced rib fracture after hypofractionated proton beam therapy for hepatocellular carcinoma.

BACKGROUND: Radiation-induced rib fracture has been reported as a late complication after external radiotherapy to the chest. The purpose of this study was to clarify the characteristics and risk factors of rib fracture after hypofractionated proton beam therapy (PBT). MATERIAL AND METHODS: The retrospective study comprised 67 patients with hepatocellular carcinoma who were treated using PBT of 66 Cobalt-Gray-equivalents [Gy (RBE)] in 10 fractions. We analyzed the patients' characteristics and determined dose-volume histograms (DVHs) for the irradiated ribs, and then estimated relationships between risk of fracture and several dose-volume parameters. An irradiated rib was defined to be any rib included in the area irradiated by PBT as determined by treatment-planning computed tomography. RESULTS: Among the 67 patients, a total of 310 ribs were identified as irradiated ribs. Twenty-seven (8.7%) of the irradiated ribs developed fractures in 11 patients (16.4%). No significant relationships were seen between incidence of fracture and characteristics of patients, including sex, age, tumor size, tumor site, and follow-up period (p ≥ 0.05). The results of receiver operating characteristic curve analysis using DVH parameters demonstrated that the largest area under the curve (AUC) was observed for the volume of rib receiving a biologically effective dose of more than 60 Gy(3 )(RBE) (V60) [The equivalent dose in 2 Gy fractions (EQD2); 36 Gy(3)] and the AUCs of V30 to V120 (EQD2; 18-72 Gy(3)) and Dmax to D(10 cm)(3) were similar to that of V60. No significant relationships were seen for DVH parameters and intervals from PBT to incidence of fracture. CONCLUSION: DVH parameters are useful in predicting late adverse events of rib irradiation. This study identified that V60 was a most statistically significant parameter, and V30 to V120 and Dmax to D(10 cm)(3) were also significant and clinically useful for estimating the risk of rib fracture after hypofractionated PBT.

Abscopal effect with fever of unknown cause during radiotherapy: Two case reports and review of the literature.

The abscopal effect is a rare phenomenon that is defined as regression of tumor lesions distant from irradiation targets. At our department, two cases with an abscopal effect with fever of unknown cause (FUC) and an inflammatory response during radiotherapy were encountered. Radiotherapy is a local treatment; therefore, it rarely causes systemic side effects during radiotherapy, and if a patient develops a fever during radiotherapy, it is frequently considered tumor fever. We experienced 2 cases of FUC during irradiation followed by abscopal effect. The obvious relationship between the abscopal effect and the fever remains to be clarified. However, FUC during radiotherapy may be a hint to the abscopal effect, considering that immune response and cytokines are closely related to the abscopal effect.

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.

Risk Factors for Radiation Necrosis and Local Recurrence after Proton Beam Therapy for Skull Base Chordoma or Chondrosarcoma.

[Proposal] Here, we retrospectively evaluate risk factors for radiation necrosis and local recurrence after PBT for skull base chordoma or chondrosarcoma. [Patients and Methods] We analyzed 101 patients who received PBT for skull base chordomas and chondrosarcomas from January 1989 to February 2021. Multivariable logistic regression models were applied for local recurrence, temporal lobe radiation necrosis rates, and temporal lobe radiation necrosis. [Results] In multivariate analysis, chordoma and large tumor size were independent significant factors for local recurrence. The 1-, 2-, 3-, 4- and 5-year local recurrence rates were 3.9%, 16.9%, 20.3%, 28.5% and 44.0% for chordoma and 0%, 0%, 0%, 0% and 7.1% for chondrosarcoma, respectively. The local recurrence rates of small tumors (<30 mm) were 4.3%, 14.7%, 17.7%, 17.7% and 25.9%, and those for large tumors were 3.6%, 15.1%, 19.2%, 32.7% and 59.6%, respectively. In multivariate analysis, BED Gy10 and total dose were risk factors for radiation necrosis. [Conclusions] For skull base chordoma and chondrosarcoma, the risk factors of local recurrence were chordoma and large tumor size, and those of radiation necrosis were BED Gy10 and total dose, respectively. DVH analysis is needed to investigate the risk factors for brain necrosis in more detail.

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.