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Highlights • A total of 88 patients experienced light flashes among 416 who received photon radiotherapy and 205 who received proton beam therapy in our prospective study. • The frequency of light flashes during radiotherapy was associated with the retina dose and younger age, and were commonly blue or white light for brain or head and neck irradiation. • Light flashes were seen by only 35/524 patients (6.7%) without retinal irradiation, but by 13/33 (39.4%) and 41/64 (64.1%) with retinal maximum isodose lines of 10–50% and 60–100%, respectively. • Totals of 52, 15, 15, 9, 16 and 8 patients sensed light of blue, purple, yellow, red, white and other colors, respectively., Background Patients who receive radiation therapy sometimes complain of a light flash during irradiation. The details of the characteristics of this light have not been described. Purpose To evaluate light flashes during photon and proton radiotherapy. Methods and Materials A prospective observational study was performed in all adult patients (≥20 years old) who received photon and proton therapy at two centers between January 2019 and August 2020, except for patients who could not communicate and those with visual abnormality. Evaluations were obtained for the presence or absence of light flashes, light darkness (7 levels), light intensity (5 levels), frequency, light movement, light flashing, and time seeing the light, using a weekly checklist. Results A total of 650 courses were examined for 621 patients, of whom 416 received photon radiotherapy and 205 received proton beam therapy. The checklist indicated that 88 patients (16.1%) sensed light during photon or proton radiotherapy. In multivariate logistic regression analysis, the factors that were significantly associated with a light flash were a higher retina dose and younger age (p

Hepatocellular carcinoma (HCC) located in the caudate lobe (caudate HCC) is rare; however, patients with this type of tumour have poorer prognoses than those with HCC in other segments. Despite many published reports on the clinical usefulness of proton beam therapy (PBT) for HCC, data on the clinical outcomes of patients undergoing PBT for caudate HCC remain scarce. Therefore, the present study aimed to investigate the outcomes of this group of patients. Thirty patients with caudate HCC who underwent definitive PBT between February 2002 and February 2014 were retrospectively analysed. The total irradiation doses ranged from 55 to 77 (median 72.6) Gy relative biological dose. The median follow-up period was 37.5 (range, 3.0–152.0) months. The overall survival (OS) rates at one, three and five years were 86.6%, 62.8% and 46.1%, respectively. According to univariate and multivariate analyses, Child-Pugh A (P

Highlights • Proton beam therapy is likely to be safe for liver hemangiomas because, in our experience. • Proton beam therapy achieves good local control for liver hemangiomas without causing severe hepatic damage. • Proton beam therapy expected to minimize the risk of late adverse events., Background Hepatic hemangiomas are benign tumors with a favorable prognosis, but giant hepatic hemangiomas can cause abdominal symptoms and are indicated for treatment. Most cases are treated with surgery, but radiotherapy has also been used. However, to date, there have been no reports of proton beam therapy for a hepatic hemangioma. Case presentation A 46-year-old woman had a tumor of 80 × 80 mm in the left medial lobe of the liver, which was diagnosed as a giant hemangioma based on the contrast pattern. Therapy was required for a giant hepatic hemangioma with symptoms, but the patient refused blood transfusion due to religious reasons, which made surgical resection difficult. Therefore, she was referred to our hospital for proton beam therapy. At her first visit, liver function was Child-Pugh A (5 points) and there was no elevation of tumor markers. Proton beam therapy of 28.6 Gy (RBE) given in 13 fractions was performed without interruption. The only observed acute radiation toxicity was Grade 1 dermatitis. One year after proton beam therapy, the hemangioma had significantly decreased, and a complete response has been maintained for 15 years based on ultrasound and MRI. Conclusion This case is the first reported use of proton beam therapy for a hepatic hemangioma. The outcome suggests that this treatment may be effective for a giant liver hemangioma.

Highlights • A cervical desmoid tumor could be successfully controlled with proton therapy. • Desmoid tumors commonly occur in the limbs and trunk, rarely in the neck. • Proton beam therapy was selected to reduce radiation related adverse events., Desmoid tumors are benign, but may have a locally invasive tendency that commonly results in local recurrence. Most occur on the body trunk or extremities, whereas a head and neck desmoid tumor is relatively rare. The efficacy of radiotherapy has been suggested and 50–60 Gy is used for unresectable or recurrent desmoid tumors, but there are few reports of use of particle beam therapy. However, since this tumor occurs more often in younger patients compared to malignant tumors and the prognosis is favorable, there may be an advantage of this therapy. We treated a male patient with a head and neck recurrent desmoid tumor with proton beam therapy (PBT) at a dose of 60 Gy (RBE). This patient underwent surgical resection as initial treatment, but the tumor recurred only six months after surgery, and resection was performed again. After PBT, the tumor gradually shrank and complete remission has been achieved for 10 years without any severe late toxicity. Here, we report the details of this case, with a review of the literature. We suggest that PBT may reduce the incidence of second malignant tumors by reducing the dose exposure around the planning target volume.

Light flash and odor during radiotherapy are well-known phenomena. Two prospective observational studies have indicated that 55% of patients observed a light flash during irradiation of the retina and 27% of patients sensed an odor during radiotherapy for the nasal cavity. A prospective observational study was performed in all patients at our hospital who received total body irradiation (TBI) between January 2019 to October 2021. Light flash and odor during TBI were examined using the same method as that used in previous studies. A total of 32 patients received TBI during the study period. The patients had a median age of 41 (18–60) years, and included 20 males and 12 females. A survey checklist showed that 14 patients (44%) sensed light and 14 patients (44%) sensed odor during TBI,. The color of the light during irradiation was yellow in six cases, white in four cases, and blue in four cases. The intensity of the light was 2–5 (median 3, 1 is very weak, 5 is very strong) and the time over which the light flash was felt was 4–60 s (median 10 s). Two patients each sensed smells of plastic, ozone and bleach, and others sensed one smell each. The intensity of the odor was 1–4 (median 3, 1 is very weak, 5 is very strong) and the time over which the odor was sensed was 1–25 s (median 3 s). We conclude that light flashes and odors are each sensed by 44% of patients during TBI. Various types of light flashes and odors were reported in this study.

Patients often report a sense of smell during radiation therapy (RT), but the details of these events are not well understood. The purpose of the study was to evaluate events of smell during photon RT and proton beam therapy (PBT).The subjects were all adult patients (≥20 years old) treated with photon RT or PBT at two centers from January 2019 to August 2020, with the exclusion of those with communication difficulties or olfactory abnormality. The presence of smell, odor type, intensity (five levels), and time period was examined prospectively using a weekly checklist.A total of 649 courses were examined in 620 patients who received photon RT (n=415) or PBT (n=205). A smell during the procedure was sensed by 51 patients (8.2%). In multivariate logistic regression analysis, nasal cavity dose (p=0.002), age (p0.001), and photon RT (p=0.018) were identified as significant factors associated with a sense of smell. Smell occurred in only 23/515 patients (4.5%) in whom the nasal cavity was not irradiated, but in 4/19 (21.1%) and 24/86 (27.9%) with nasal cavity maximum isodose lines of 10%-50% and 60%-100%, respectively. Patients who received photon RT sensed a smell (43/415; 10.4%) more frequently than those treated with PBT (8/205; 3.9%). Of the 51 patients who sensed a smell, 32 (63%) reported a burnt smell, eight (16%) a chemical smell, two (4%) a sour smell, and nine another smell (copier machine, sweet, garbage, etc.).The sense of a smell appears to be common during RT and this sensation is significantly associated with the nasal cavity dose, younger age, and photon RT.

Background This study was conducted to evaluate late toxicities in adolescent and young adult (AYA) patients who received photon or proton therapy. Methodology A total of 106 AYA patients who received proton and photon therapy and were followed-up for more than two years were retrospectively evaluated. The median age of patients was 22 years (range, 15-29 years). A total of 47 patients were male and 59 were female. A total of 35 and 71 patients received photon and proton therapy, respectively. All but one patient received radiotherapy with curative intent. The target disease was benign and malignant in 28 and 78 patients, respectively. Results The median follow-up period in all patients was 62 months (range: 24-293 months). Grade 3 or higher toxicity was observed in 20 patients. There was one case of grade 5 toxicity (myelodysplastic syndrome), which was probably due to chemotherapy. No other secondary cancers were observed. Regarding life events, 15 and 88 patients were married and unmarried at the start of radiotherapy, respectively. Of the 88 unmarried patients, five were married after radiotherapy. Occupation and education were evaluated in 71 patients. Of the 71 patients, 33 were students, 21 were employed, and 16 were unemployed. Of the 33 students, eight were employed and 11 were at a higher educational grade after radiotherapy. Of the 21 employed patients, 17 had the same jobs and four had lost their jobs after radiotherapy. For the 16 unemployed patients, all remained unemployed. Conclusions This study is one of the largest studies to focus on life after radiation therapy among AYAs and suggests that cancer treatment has an influence on life events.

Background/aim Curing local recurrence of rectal cancer (LRRC) is difficult with conventional photon radiotherapy. Proton beam therapy (PBT) on the other hand, has unique physical characteristics that permit higher doses to LRRC while minimizing side effects on surrounding organs. However, the efficacy of PBT on controlling rectal cancer recurrence has not yet been reported. This study aimed to evaluate clinical outcomes and toxicities of PBT for LRRC. Patients and methods Clinical outcomes were retrospectively evaluated for 12 patients with 13 total lesions that had received PBT for LRRC at our institute. Results The median follow-up period from the initiation of PBT was 35.6 months. The 3-year local control, progression-free survival and overall survival rates were 80.2%, 10.4% and 73.8%, respectively. Median survival time was 67.1 months. There were no severe acute or late adverse events. Conclusion PBT could be a safe and effective treatment method for LRRC.

Background/Aim: This multi-institutional study aimed to investigate the efficacy and feasibility of proton beam therapy (PBT) for renal cell carcinoma (RCC) in Japan. Patients and Methods: The survival, local control, and toxicities in 22 RCC patients treated between 2001 and 2016 at 6 Japanese PBT institutes were analyzed. Results: The 22 patients comprised 20 men and had a median age of 67 (range=42-88) years. The total irradiation dose was 60-79.6 Gy (relative biological effectiveness). Over a median follow-up of 37 months, the 3-year overall and disease-specific survival rates were 95% and 100%, respectively, and no recurrence occurred. No patient experienced grade 3 or higher adverse events. The serum blood urea nitrogen (p=0.25) and creatinine levels (p=0.95) were not significantly affected, although the mean estimated glomerular filtration rate was reduced by 7.1±11.2 ml/min/1.73 m(2). Conclusion: Despite the small number of patients, high-dose PBT can control RCC while maintaining their renal function with high probability, and could be and alternative curative therapy especially for inoperable patients.

Purpose: Malignant fibrous histiocytoma (MFH) is one of the most common soft tissue sarcomas. The standard treatment is adequate surgical resection; in addition, radiation therapy plays a major role in perioperative treatment in most cases. Herein, we report the case of a patient with a large MFH who was successfully treated with combined proton beam therapy (PBT) and local hyperthermia (LH). Case Presentation: A 60-year-old man presented with a 6×4-cm mass on his left thigh. Histopathology and immunohistochemistry indicated MFH, and he refused limb amputation. He received treatment with PBT at a dose at 72 GyE in 18 fractions. To cover the entire large target lesion, we used a patch-field protocol. He also concurrently received 7 courses of LH. The combination therapy achieved long-term local control without severe acute or late toxicity during the 7-year follow-up period. Conclusions: This case suggests that the combination of PBT and LH may be an option as a limb-preserving treatment for large inoperable MFH in the extremities.

Simple Summary Radiotherapy has a key role in treatment of pediatric cancer and has greatly improved survival in recent years. However, vertebrae are often included in the irradiated area, and this may affect growth after treatment. In this study, we examined the relationship of the dose of proton beam therapy with subsequent growth of 353 vertebral bodies in 23 children (10 boys, 13 girls) with a median age at treatment of 4 years old and a median observation period of 13.9 months. Most importantly, we found that the growth rate of vertebral bodies decreased even at a low proton beam therapy dose, which indicates the need for careful planning of the irradiation area in this patient population. Growth inhibition was clearly dose-dependent, and proton beam therapy had the same growth inhibitory effect as photon radiotherapy, at least within the irradiated field. Abstract Impairment of bone growth after radiotherapy for pediatric bone cancer is a well-known adverse event. However, there is limited understanding of the relationship between bone growth and irradiation dose. In this study, we retrospectively analyzed bone growth impairment after proton beam therapy for pediatric cancer. A total of 353 vertebral bodies in 23 patients under 12 years old who received proton beam therapy were evaluated. Compared to the non-irradiated vertebral body growth rate, the irradiated vertebral body rate (%/year) was significantly lower: 77.2%, 57.6%, 40.8%, 26.4%, and 14.1% at 10, 20, 30, 40, and 50 Gy (RBE) irradiation, respectively. In multivariate analysis, radiation dose was the only factor correlated with vertebral body growth. Age, gender, and vertebral body site were not significant factors. These results suggest that the growth rate of the vertebral body is dose-dependent and decreases even at a low irradiated dose. This is the first report to show that proton beam therapy has the same growth inhibitory effect as photon radiotherapy within the irradiated field.

Proton beam therapy (PBT) is a curative treatment for hepatocellular carcinoma (HCC), because it can preserve liver function due to dose targeting via the Bragg peak. However, the degree of direct liver damage by PBT is unclear. In this study, we retrospectively analyzed liver/biliary enzymes and total bilirubin (T-Bil) as markers of direct liver damage during and early after PBT in 300 patients. The levels of these enzymes and bilirubin were almost stable throughout the treatment period. In patients with normal pretreatment levels, aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), and T-Bil were abnormally elevated in only 2 (1.2%), 1 (0.4%), 0, 2 (1.2%), and 8 (3.5%) patients, respectively, and in 8 of these 13 patients (61.5%) the elevations were temporary. In patients with abnormal pretreatment levels, the levels tended to decrease during PBT. GGT and T-Bil were elevated by 1.62 and 1.57 times in patients who received 66 Gy (RBE) in 10 fractions and 74 Gy (RBE) in 37 fractions, respectively, but again these changes were temporary. These results suggest that direct damage to normal liver caused by PBT is minimal, even if a patient has abnormal pretreatment enzyme levels.

Background: Androgen deprivation therapy (ADT) combined with radiation therapy benefits intermediate- and high-risk prostate cancer (PC) patients. The optimal ADT duration in combination with high-dose proton beam therapy (PBT) remains unknown. Methods: Intermediate- and high-risk PC patients treated with PBT combined with ADT for various durations were analyzed retrospectively. To assess the relationship between ADT and biochemical relapse-free (bRF) rate, Cox proportional hazards models including T stage, prostate specific antigen (PSA) level, Gleason score (GS), and total radiation dose were used. Results: In the intermediate-risk PC patients (n = 520), ADT use improved bRF (HR 0.49, 95% CI 0.26&ndash, 0.93, p = 0.029), especially in those with multiple intermediate-risk factors (T2b&ndash, 2c, PSA 10&ndash, 20 ng/mL, and GS 7). In the high-risk PC patients (n = 555), a longer ADT duration (&gt, 6 months) conferred a benefit for bRF (HR 0.54, 95% CI 0.32&ndash, 0.90, p = 0.018), which was most apparent in patients with multiple high-risk factors (T3a&ndash, 4, PSA &gt, 20 ng/mL, and GS &ge, 8) treated with ADT for &ge, 21 months. Conclusions: Short-term (&le, 6 months) ADT is beneficial for intermediate-risk PC patients, but likely unnecessary for those with a single risk factor, whereas ADT for &gt, 6 months is necessary for high-risk PC patients and ADT for &ge, 21 months might be optimal for those with multiple risk factors in combination of high-dose PBT.

Background The effectiveness of proton beam therapy (PBT) as initial treatment for patients with unresectable intrahepatic cholangiocarcinoma (ICC) is unclear, particularly as related to ICC histological subtypes. We performed this study to address this gap in knowledge. Methods Thirty-seven patients with unresectable ICC who underwent PBT as their initial treatment were evaluated. Twenty-seven patients had Child-Pugh class A liver function, 11 exhibited jaundice, and 10 had multiple tumors. Nineteen, 7, and 11 tumors were classified as mass forming (MF), periductal infiltrating (PI), and intraductal growth (IG) types, respectively, based on gross appearance in imaging studies. Patients were classified into the curative group (n = 25) and palliative group (n = 12) depending on whether the planning target volume covered all the macroscopic tumors. Results The 1- and 2-year overall survival rates were 60.3, and 41.4%, respectively; the median survival time (MST) was 15 months for all patients. The MSTs for curative and palliative groups were 25 and 7 months, respectively. Curative treatment and adjuvant chemotherapy significantly improved overall survival, while the presence of periductal infiltrating type tumors was a negative prognostic factor. In the curative group, the 1- and 2-year local control rates were 100 and 71.5%, respectively, while the 1-, and 2-year progression-free survival rates were 58.5, and 37.6%, respectively. No severe acute toxicities were observed. Three patients experienced grade 3 biliary tract infection, although it was unclear whether this was radiotherapy-related. Conclusion PBT may yield to improve survival and local tumor control among patients with unresectable ICC.