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.

Moderately hypofractionated proton beam therapy for localized prostate cancer: 5-year outcomes of a phase II trial.

The usefulness of moderately hypofractionated radiotherapy for localized prostate cancer has been extensively reported, but there are limited studies on proton beam therapy (PBT) using similar hypofractionation schedules. The aim of this prospective phase II study is to confirm the safety of a shortened PBT course using 70 Gy relative biological effectiveness (RBE) in 28 fractions. From May 2013 to June 2015, 102 men with localized prostate cancer were enrolled. Androgen deprivation therapy was administered according to risk classification. Toxicity was assessed using Common Terminology Criteria for Adverse Events version 4.0. Of the 100 patients ultimately evaluated, 15 were classified as low risk, 43 as intermediate risk, and 42 as high risk. The median follow-up time of the surviving patients was 96 months (range: 60-119 months). The 5-year cumulative incidences of grade 2 gastrointestinal/genitourinary adverse events were 1% (95% CI: 0.1-6.9) and 4% (95% CI: 1.5-10.3), respectively; no grade ≥ 3 gastrointestinal/genitourinary adverse events were observed. The current study revealed a low incidence of late adverse events in prostate cancer patients treated with moderately hypofractionated PBT of 70 Gy (RBE) in 28 fractions, indicating the safety of this schedule.

Re-Irradiation With Proton Beam Therapy for Localized Perineural Spread Following Presacral Recurrence in Sigmoid Colon Cancer: A Case Report.

This report describes the effective management of localized perineural spread (PNS) to the sacral peripheral nerves following a presacral recurrence of colon cancer using proton beam therapy (PBT). The patient, a male in his 60s with a history of sigmoid colon cancer treated with laparoscopic Hartmann's procedure, presented with presacral recurrence two years post-surgery. Radical resection was deemed infeasible, leading to a combined treatment of PBT (75 Gy relative biological effectiveness (RBE) in 25 fractions) and capecitabine. However, three years post-PBT, magnetic resonance imaging revealed swelling of the left S2 nerve with abnormal fluorodeoxyglucose uptake, indicating localized PNS. Re-irradiation with PBT (75 Gy RBE in 25 fractions) was conducted, carefully considering the overlap with the previous PBT field and aiming to minimize dosage to adjacent organs. At 1.5 years post-reirradiation, the patient remained free of recurrence. This case underscores the potential efficacy of PBT and emphasizes the need for further research to assess its broader applicability in comparable situations.

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.

Methyl-11C-L-methionine positron emission tomography for radiotherapy planning for recurrent malignant glioma.

OBJECTIVE: To investigate differences in uptake regions between methyl-11C-L-methionine positron emission tomography (11C-MET PET) and gadolinium (Gd)-enhanced magnetic resonance imaging (MRI), and their impact on dose distribution, including changing of the threshold for tumor boundaries. METHODS: Twenty consecutive patients with grade 3 or 4 glioma who had recurrence after postoperative radiotherapy (RT) between April 2016 and October 2017 were examined. The study was performed using simulation with the assumption that all patients received RT. The clinical target volume (CTV) was contoured using the Gd-enhanced region (CTV(Gd)), the tumor/normal tissue (T/N) ratios of 11C-MET PET of 1.3 and 2.0 (CTV (T/N 1.3), CTV (T/N 2.0)), and the PET-edge method (CTV(P-E)) for stereotactic RT planning. Differences among CTVs were evaluated. The brain dose at each CTV and the dose at each CTV defined by 11C-MET PET using MRI as the reference were evaluated. RESULTS: The Jaccard index (JI) for concordance of CTV (Gd) with CTVs using 11C-MET PET was highest for CTV (T/N 2.0), with a value of 0.7. In a comparison of pixel values of MRI and PET, the correlation coefficient for cases with higher JI was significantly greater than that for lower JI cases (0.37 vs. 0.20, P = 0.007). D50% of the brain in RT planning using each CTV differed significantly (P = 0.03) and that using CTV (T/N 1.3) were higher than with use of CTV (Gd). V90% and V95% for each CTV differed in a simulation study for actual treatment using CTV (Gd) (P = 1.0 × 10-7 and 3.0 × 10-9, respectively) and those using CTV (T/N 1.3) and CTV (P-E) were lower than with CTV (Gd). CONCLUSIONS: The region of 11C-MET accumulation is not necessarily consistent with and larger than the Gd-enhanced region. A change of the tumor boundary using 11C-MET PET can cause significant changes in doses to the brain and the CTV.

A Case of Circumscribed Choroidal Hemangioma Treated With Proton Beam Therapy and Followed Up for 15 Years.

Circumscribed choroidal hemangiomas are rare and benign tumors but often have a progressive course and are complicated by retinal detachment and glaucoma. The effectiveness of external radiation for large tumors that are difficult to treat with photodynamic therapy was recently reported; however, few studies have conducted long-term follow-ups. We encountered a case of localized choroidal hemangioma that was treated with proton beam therapy and followed up for 15 years. A 37-year-old man was diagnosed with a 10 × 4 mm circumscribed choroidal hemangioma involving the macular area with retinal detachment. Proton beam therapy was performed at 26.4 Gy relative biological effectiveness (RBE) in 8 fractions. The choroidal hemangioma gradually shrank over three years, and the retinal detachment also improved. A cataract developed on the affected side 11 years after irradiation, and eye coordination issues developed 15 years after irradiation. Glaucoma was not observed during the follow-up period; however, visual acuity did not recover, and the patient developed light perception. Although vision was not preserved, proton beam therapy effectively shrank the tumor and maintained quality of life.

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.

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.

A case of massive hemoptysis caused by lung cancer saved by V-V ECMO and hemostasis achieved by radiotherapy.

Massive hemoptysis is one of the fatal complications of lung cancer. There is no established standard treatment method for it, and it often causes sudden suffocation, and some cases may be difficult to save. A 63-year-old man was admitted to the hospital with dyspnea, and developed massive hemoptysis from lung cancer shortly after admission. The tumor had obstructed the right main bronchus and had invaded the right pulmonary artery. Surgery and interventional radiology were judged impossible. The patient was successfully saved by the introduction of Veno-Venous Extra Corporeal Membrane Oxygenation (V-V ECMO), and hemostasis was obtained by radiotherapy. Two months after completion of radiotherapy, he was weaned off the ventilator and discharged on his own. He died of increased peritoneal dissemination and other complications 1 year and 1 month later, but no recurrence of hemoptysis was noted until his death. We experienced a case of massive hemoptysis in which V-V ECMO and radiation therapy succeeded in saving life and stopping bleeding. The use of V-V ECMO by emergency care teams and multimodality therapy, including radiotherapy, were effective for massive hemoptysis from lung cancer.

Proton Beam Therapy for Hepatocellular Carcinoma: Multicenter Prospective Registry Study in Japan.

PURPOSE: A prospective multicenter registry study was started May 2016 in Japan to evaluate the efficacy and safety of proton beam therapy (PBT) for hepatocellular carcinoma (HCC). METHODS AND MATERIALS: Patients who received PBT for HCC from May 2016 to June 2018 were registered in the database of the Particle Beam Therapy Committee and Subcommittee of the Japanese Society for Radiation Oncology. Overall survival (OS), progression-free survival (PFS), and local recurrence were evaluated. RESULTS: Of the 755 registered patients, 576 with initial PBT and no duplicate cancer were evaluated. At final follow-up, 322 patients were alive and 254 had died. The median follow-up period for survivors was 39 months (0-58 months). The median OS time of the 576 patients was 48.8 months (95% CI, 42.0-55.6 months) and the 1-, 2-, 3-, and 4-year OS rates were 83.8% (95% CI, 80.5%-86.6%), 68.5% (64.5%-72.2%), 58.2% (53.9%-62.2%), and 50.1% (44.9%-55.0%), respectively. Recurrence was observed in 332 patients, including local recurrence in 45 patients. The median PFS time was 14.7 months (95% CI, 12.4-17.0 months) and the 1-, 2-, 3-, and 4-year PFS rates were 55.2% (95% CI, 51.0%-59.2%), 37.5% (33.5%-41.5%), 30.2% (26.3%-34.2%), and 22.8% (18.5%-27.4%), respectively. The 1-, 2-, 3-, and 4-year OS rates were significantly higher for tumor size <5 versus 5 to 10 cm (P < .001) and <5 versus ≥10 cm (P < .001); Child-Pugh score A/B versus C (P < .001); and distance of the tumor from the gastrointestinal tract <1 versus 1 to 2 cm (P < .008) and <1 versus >2 cm (P < .001). At final follow-up, 27 patients (4.7%) had late adverse events of grade 3 or higher, with liver failure (n = 7), and dermatitis (n = 7) being most common. CONCLUSIONS: This multicenter prospective data registry indicated that PBT for HCC gives good therapeutic effects (3-year local control rate of 90%) with a low risk of severe late adverse events.

Long-term follow-up of unresectable adenoid cystic carcinoma of the trachea and bronchus treated with high-dose proton beam therapy: A report of two cases.

Adenoid cystic carcinoma (ACC) of the trachea is a rare disease that is slow growing and has a risk of distant metastasis. The standard treatment for ACC of the trachea is surgery, but this tumor is often unresectable. In definitive radiotherapy using photons for unresectable ACC of the trachea, it is sometimes difficult to deliver a sufficient dose to the target without exceeding the tolerable dose to the surrounding normal tissues. Here, we report two cases of ACC of the trachea that received a high dose (74 Gy [relative biological effectiveness]) of proton beam therapy and achieved long-term survival.

Patterns of care for brachytherapy in Japan.

This study aimed to assess the current state of brachytherapy (BT) resources, practices and resident education in Japan. A nationwide survey was undertaken encompassing 177 establishments facilitating BT in 2022. Questionnaires were disseminated to each BT center, and feedback through online channels or postal correspondence was obtained. The questionnaire response rate was 90% (159/177), and every prefecture had a response in at least one center. The number of centers in each prefecture ranged from 0.6 to 3.6 (median: 1.3) per million population. The annual number of patients in each center ranged from 0 to 272 (median: 31). While most prefectures provided intracavitary (IC) BT for gynecological cancers and interstitial (IS) BT for prostate cancer, only one-third of the prefectures provided IS BT for cancer sites other than the prostate. The institutional image-guided BT implementation rate was 71%. IC and IS BT was performed for 15.4% of IC BT cases of gynecological cancer. Only 47% of the BT training centers answered that they could provide adequate training in BT for residents. The most common reason for this finding was the insufficient number of patients in each center. The results show that, although BT has achieved uniformity in terms of facility penetration, new technologies are not yet widespread enough. Furthermore, IS BT, which requires advanced skills, is limited to a few BT centers, and considerable number of BT training centers do not have sufficient caseloads to provide the necessary experience for their residents.

Multimodal treatment with chemoradiotherapy, regional hyperthermia and interstitial brachytherapy for a huge locally advanced cervical cancer: A case report.

A female patient in her 50 s was found to have a 10-cm tumor resulting from locally advanced cervical cancer (LACC). Three-year relapse-free survival was achieved following a multimodal treatment strategy integrating chemoradiotherapy (CRT), regional hyperthermia (RHT), and interstitial brachytherapy (ISBT). Given the large size of the tumor, enhancement of the geometrical dose distribution was anticipated using ISBT. However, delivery of a sufficient dose to the high-risk clinical target volume was predicted to be challenging. Thus, RHT was incorporated to potentially augment the overall treatment effect. This unique combination of CRT, RHT and ISBT may be promising for management of large LACC and warrants further investigation.

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.

Proton therapy (PT) combined with concurrent chemotherapy for locally advanced non-small cell lung cancer with negative driver genes.

PURPOSE: To discuss the optimal treatment modality for inoperable locally advanced Non-Small Cell Lung Cancer patients with poor physical status, impaired cardio-pulmonary function, and negative driver genes, and provide clinical evidence. MATERIALS AND METHODS: Retrospective analysis of 62 cases of locally advanced non-small cell lung cancer patients with negative driver genes treated at Tsukuba University Hospital(Japan) and Qingdao University Affiliated Hospital(China).The former received proton therapy with concurrent chemotherapy, referred to as the proton group, with 25 cases included; while the latter underwent X-ray therapy with concurrent chemoradiotherapy followed by 1 year of sequential immunomodulatory maintenance therapy, referred to as the X-ray group, with 37 cases included.The treatment response and adverse reactions were assessed using RECIST v1.1 criteria and CTCAE v3.0, and radiotherapy planning and evaluation of organs at risk were performed using the CB-CHOP method.All data were subjected to statistical analysis using GraphPad Prism v9.0, with a T-test using P < 0.05 considered statistically significant. RESULTS: (1)Target dose distribution: compared to the X-ray group, the proton group exhibited smaller CTV and field sizes, with a more pronounced bragg peak.(2)Organs at risk dose: When comparing the proton group to the X-ray group, lung doses (V5, V20, MLD) and heart doses (V40, Dmax) were lower, with statistical significance (P < 0.05), while spinal cord and esophagus doses showed no significant differences between the two groups (P > 0.05).(3)Treatment-related toxicities: The incidence of grade 3 or higher adverse events in the proton group and X-ray group was 28.6% and 4.2%, respectively, with a statistically significant difference (P < 0.05). In terms of the types of adverse events, the proton group primarily experienced esophagitis and pneumonia, while the X-ray group primarily experienced pneumonia, esophagitis, and myocarditis. Both groups did not experience radiation myelitis or esophagotracheal fistula.(4)Efficacy evaluation: The RR in the proton group and X-ray group was 68.1% and 70.2%, respectively (P > 0.05), and the DCR was 92.2% and 86.4%, respectively (P > 0.05), indicating no significant difference in short-term efficacy between the two treatment modalities.(5)Survival status: The PFS in the proton group and X-ray group was 31.6 ± 3.5 months (95% CI: 24.7 ~ 38.5) and 24.9 ± 1.55 months (95% CI: 21.9 ~ 27.9), respectively (P > 0.05), while the OS was 51.6 ± 4.62 months (95% CI: 42.5 ~ 60.7) and 33.1 ± 1.99 months (95% CI: 29.2 ~ 37.1), respectively (P < 0.05).According to the annual-specific analysis, the PFS rates for the first to third years in both groups were as follows: 100%, 56.1% and 32.5% for the proton group vs. 100%, 54.3% and 26.3% for the X-ray group. No statistical differences were observed at each time point (P > 0.05).The OS rates for the first to third years in both groups were as follows: 100%, 88.2%, 76.4% for the proton group vs. 100%, 91.4%, 46.3% for the X-ray group. There was no significant difference in the first to second years (P > 0.05), but the third year showed a significant difference (P < 0.05). Survival curve graphs also depicted a similar trend. CONCLUSION: There were no significant statistical differences observed between the two groups in terms of PFS and OS within the first two years. However, the proton group demonstrated a clear advantage over the X-ray group in terms of adverse reactions and OS in the third year. This suggests a more suitable treatment modality and clinical evidence for populations with frail health, compromised cardio-pulmonary function, post-COVID-19 sequelae, and underlying comorbidities.

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.

Retrospective Analysis of the Areas Responsible for Light Flash and Odor During Proton Beam Therapy and Photon Therapy.

Background Abnormal sensations were frequently experienced by patients who received irradiation of the brain or head and neck region. We have previously suggested correlations with irradiation of the nasal cavity and retina. Purpose We performed a retrospective dose-volume histogram analysis focused on the brain and head and neck tumor to examine the relationship between these abnormal sensations and the details of irradiation. Methods Multivariate logistic regression models were applied for the presence or absence of light flash and odor. Gender, age, radiotherapy method (proton beam therapy vs. photon radiotherapy), dose of retina, optic nerve, chiasmatic gland, pituitary, nasal cavity, oral cavity, frontal lobe, parietal lobe, occipital lobe, temporal lobe, amygdala, and hippocampus were set as candidates of explanatory variables. Results Light flash and odor during radiotherapy have been suggested to be associated with younger age and retina and nasal cavity irradiation. Multivariate analyses including dose-volume histograms indicated that light flash was related to age, chiasmatic gland irradiation, and pituitary dose, and odor was related to age and nasal cavity irradiation. Conclusion Our results indicate that light flash during radiotherapy is caused by irradiation of the visual pathway and that odor is caused by irradiation of the nasal cavity or olfactory bulb.

Proton Beam Therapy versus Radiofrequency Ablation for Patients with Treatment-Naïve Single Hepatocellular Carcinoma: A Propensity Score Analysis.

Introduction: Proton beam therapy (PBT) is known to be an effective locoregional treatment for hepatocellular carcinoma (HCC). However, few comparative studies in treatment-naïve cases have been reported. The aim of this study was to compare the survival outcomes of PBT with those of radiofrequency ablation (RFA) in patients with treatment-naïve solitary HCC. Methods: Ninety-five consecutive patients with treatment-naïve HCC, a single nodule measuring ≤5 cm in diameter, and a Child-Pugh score of ≤8 who were treated with PBT at the University of Tsukuba Hospital between 2001 and 2013 were enrolled in the study. In addition, 836 patients with treatment-naïve HCC treated by RFA at the University of Tokyo Hospital during the same period were analyzed as controls. Recurrence-free survival (RFS) and overall survival (OS) were compared in 83 patient pairs after propensity score matching. Results: The 1-year, 3-year, and 5-year RFS rates were 86.6%, 49.5%, and 35.5%, respectively, in the PBT group and 59.5%, 34.0%, and 20.9% in the RFA group (p = 0.058); the respective OS rates were 97.6%, 77.8%, and 57.1% in the PBT group and 95.1%, 81.7%, and 67.7% in the RFA group (p = 0.16). Regarding adverse effects, no grade 3 or higher adverse events were noted in the PBT; however, two grade 3 adverse events occurred within 30 days of RFA in the RFA group: one hemoperitoneum and one hemothorax. Discussion: After propensity score matching, PBT showed no significant difference in RFS and OS compared to RFA. PBT can be an alternative for patients with solitary treatment-naïve HCC.