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Since the introduction of intensity-modulated radiation therapy (IMRT), new technologies have continued developing to achieve higher treatment efficacy and the lower side effects as possible. Recently, MR-Linac has also been introduced to clinical practice, enabling more precise image-guided radiation therapy (IGRT). However, no method has been developed to visualize the actual dose and site after X-ray irradiation. Imaging free radicals generated by irradiation will lead to better understanding of the treatment dose and site. We have been developing the free radical imaging methods using Dynamic Nuclear Polarization (DNP)-MRI with nitroxyl radicals as a redox probe (e.g. 4-Methacryloyloxy-2,2,6,6-tetramethylpiperidine-1-oxyl (Tempo methacrylate; TempoMC)). We previously demonstrated that the mixed solution of TempoMC and glutathione (GSH) was useful as a probe for quantitative detection of free radical reactions, allowing us to observe the redox reaction after irradiation clearly. In this study, we investigated the possibility of in vivo spatiotemporal visual verification of our X-ray visualization system based on redox reaction by in vivo DNP-MRI. We prepared balloon phantoms filled with 0.5 mL TempoMC/GSH solution which were made of a urinary catheter balloon and implanted in the abdominal cavity of mice. IMRT plan was prepared by the software used in daily clinical practice, and then each mouse was irradiated X-ray with 2.5Gy, 5.0Gy, and 10Gy by helical 3-D CRT and IMRT system. Free radical imaging by low filed type of DNP-MRI, ESR signal measurements, and MRI imaging were performed on the mice after irradiation. Balloon phantoms in the abdominal cavity of mice were well delineated on T1-weighted and T2-weighted MRI and clearly visualized by DNP-MRI. The DNP-MRI signal of TempoMC/GSH phantoms were decreased depending on prescribed irradiation dose. In addition, a linear relationship between the DNP-MRI signals and the irradiation dose was observed. EPR signal of remaining TempoMC radical in the balloon phantoms were decreased by irradiation and well corresponded to that of in vivo imaging data. DNP-MRI enables visual verification of IMRT in vivo. Quantitative visualization of irradiated dose from signal values is expected with the accumulation of data. Therefore, this study has potential for application to new systems such as MR-Linac for more precise radiotherapy. [ABSTRACT FROM AUTHOR]

Background: Stereotactic body radiotherapy (SBRT) is recognized as a curative treatment for oligometastasis. The spinal cord becomes the cauda equina at the lumbar level, and the nerves are located dorsally. Recently, a consensus has been reached that the cauda equina should be contoured as an organ at risk (OAR). Here, we examined the separate contouring benefits for the spinal canal versus the cauda equina only as the OAR., Materials and Methods: A medical physicist designed a simulation plan for 10 patients with isolated lumbar metastasis. The OAR was set with three contours: the whole spinal canal, cauda equina only, and cauda equina with bilateral nerve roots. The prescribed dose for the planning target volume (PTV) was 30 Gy/3 fx., Results: For the constrained QAR doses, D90 and D95 were statistically significant due to the different OAR contouring. The maximum dose ( D max ) was increased to the spinal canal when the cauda equina max was set to ≤ 20 Gy, but dose hotspots were observed in most cases in the medullary area. The D max and PTV coverage were negatively correlated for the cauda equina and the spinal canal if D max was set to ≤ 20 Gy for both., Conclusions: A portion of the spinal fluid is also included when the spinal canal is set as the OAR. Thus, the PTV coverage rate will be poor if the tumor is in contact with the spinal canal. However, the PTV coverage rate increases if only the cauda equina is set as the OAR., Competing Interests: Conflicts of interest The authors declare that they have no competing interests., (© 2023 Greater Poland Cancer Centre.)

Angiosarcoma of the scalp and face (ASF) is a rare, aggressive tumor often treated with multimodal therapy, including radiation therapy (RT). This study assessed RT outcomes for ASF and identified prognostic factors. Data from 68 non-metastatic ASF patients undergoing RT with or without other therapies were analyzed. Median radiation dose was 66 Gy in 33 fractions (interquartile range (IQR) 60-70 Gy in 28-35 fractions). Local control (LC), progression-free survival (PFS), and overall survival (OS) rates were calculated using Kaplan-Meier analysis. Multivariate analyses and adverse event evaluation were conducted. Median patient age was 75 years (IQR 71-80 years), with a median follow-up of 17 months (IQR 11-42 months). One-/three-year LC rates were 57/37%, PFS rates were 44/22%, and OS rates were 81/44%. Multivariate analyses showed that an equivalent dose in a 2 Gy fraction (EQD 2 ) >66 Gy correlated with improved LC (HR 2.35, 95% CI 1.03-5.32, p = 0.041). Combining chemotherapy (HR 2.43, 95% CI 1.08-5.46, p = 0.032) or surgery (HR 2.41, 95% CI 1.03-5.59, p = 0.041) improved PFS. No factors influenced OS. Late grade 3+ toxicities occurred in 1%, with one patient developing a grade 4 skin ulcer. These findings suggest that EQD 2 > 66 Gy and combining chemotherapy or surgery can enhance LC or PFS in ASF. Further prospective studies are needed to determine the optimal treatment strategy for this rare malignancy, particularly in elderly patients.

To examine the association of clinical, treatment, and dose parameters with late urinary toxicity after low-dose-rate brachytherapy (LDR-BT) for prostate cancer, we retrospectively studied patients with prostate cancer who underwent LDR-BT from January 2007 through December 2016. Urinary toxicity was assessed using the International Prostate Symptom Score (IPSS) and Overactive Bladder (OAB) Symptom Score (OABSS). Severe and moderate lower urinary tract symptoms (LUTS) were defined as IPSS ≥ 20 and ≥ 8, respectively; OAB was defined as a nocturnal frequency of ≥ 2 and a total OABSS of ≥ 3. In total, 203 patients (median age: 66 years) were included, with a mean follow-up of 8.4 years after treatment. The IPSS and OABSS worsened after 3 months of treatment; these scores improved to pretreatment levels after 18-36 months in most patients. Patients with a higher baseline IPSS and OABSS had a higher frequency of moderate and severe LUTS and OAB at 24 and 60 months, respectively. LUTS and OAB at 24 and 60 months were not correlated with the dosimetric factors of LDR-BT. Although the rate of long-term urinary toxicities assessed using IPSS and OABSS was low, the baseline scores were related to long-term function. Refining patient selection may further reduce long-term urinary toxicity.

Introduction: Pretreatment diagnosis by diffusion-weighted magnetic resonance imaging (DW-MRI) is useful to determine the effect of chemotherapy for gastric cancer. Here, we investigated the relationship among DW-MRI, endoscopy, and tumor markers., Patients: Eight patients underwent hemostatic radiotherapy (RT) for gastric cancer in this prospective study from 2019 to 2021. The patients completed MRI, endoscopy, and blood tests before RT; MRI, endoscopy, and blood tests 1 month after RT; and MRI and blood tests 3 months after RT. Correlations between changes in apparent diffusion coefficient (ADC) derived from DW-MRI and the tumor marker carcinoembryonic antigen (CEA) were investigated., Results: Univariate analysis of overall survival showed that sex and chemotherapy treatment were statistically significant factors. The CEA values before and 1 month after RT decreased significantly. There was no statistical difference between the CEA value 1 and 3 months after RT. The ADC value before and 1 month after RT increased significantly but not between 1 and 3 months after RT. Comparing the ratio of ADC before RT to 1 (or 3) month(s) after RT with that of CEA before RT to 1 (or 3) month(s) after RT, we found an inverse relationship between the two ratios., Conclusions: Therefore, changes in ADC and CEA are correlated. Additionally, 3 months after RT, the decrease in ADC appeared earlier than the decrease in CEA. ADC may indicate a biological change earlier than CEA, and the ratios of ADC and CEA may be important factors. These aspects warrant further confirmation in a larger sample population., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aim: This study aimed to examine the usefulness of seed density as a predictor of seed migration in patients with prostate cancer who received brachytherapy using Iodine-125 loose seed., Methods: From May 2006 to April 2016, 320 patients with localized prostate cancer underwent transperineal brachytherapy using iodine-125 loose seeds. Among them, 202 (63.1%) patients received brachytherapy monotherapy and 118 (36.9%) received combined brachytherapy and external beam radiotherapy. Seed density was calculated using the following formula: seed density = implanted seed number/prostate volume. All patients underwent radiography of the chest, abdomen and pelvis, and computed tomography at 1 day, 1 month, and 1 year after brachytherapy to evaluate the presence of seed migration., Results: In total, the number of implanted seeds was 21,876. Seed migration was detected in 92 (28.8%) patients. Of a total of 21,876 seeds, 144 (0.66%) showed migration. The number of needles, number of seeds, and seed density were significantly higher in the group with migration than in the group without migration ( p = 0.05). The ROC cutoff values for prostate volume, number of needles, number of seeds, and seed density were 20.9 cc, 21, 65, and 3.0, respectively. In the univariate analysis, prostate volume, number of needles, number of seeds, seed density, and treatment modality were all significant factors in predicting migration ( p = 0.05). In the multivariate analysis, seed density and treatment modality were significant factors in predicting migration ( p = 0.05)., Conclusion: Seed density is useful for predicting seed migration. In cases with seed density > 3.0, it is necessary to take measures such as considering the use of stranded seeds.

Background: Radiobiological daily changes within tumors are considered to be quite different between stereotactic radiotherapy (SRT) (e.g., 50 Gy in 4 fractions) and conventional radiotherapy (e.g., 60 Gy in 30 fractions). We aim to assess the optimal interval of irradiation in SRT and compare outcomes of daily irradiation with irradiation at two- to three-day intervals in SRT for patients with one to five brain metastases (BM)., Methods: This study is conducted as a multicenter open-label randomized phase II trial. Patients aged 20 or older with one to five BM, less than 3.0 cm diameter, and Karnofsky Performance Status ≥70 are eligible. A total of 70 eligible patients will be enrolled. After stratifying by the number of BMs (1, 2 vs. 3-5) and diameter of the largest tumor (< 2 cm vs. ≥ 2 cm), we randomly assigned patients (1:1) to receive daily irradiation (Arm 1), or irradiation at two- to three-day intervals (Arm 2). Both arms are performed with total dose of 27-30 Gy in 3 fractions. The primary endpoint is an intracranial local control rate, defined as intracranial local control at initially treated sites. We use a randomized phase II screening design with a two-sided α of 0∙20. The phase II trial is positive with p < 0.20. All analyses are intention to treat. This study is registered with the UMIN-clinical trials registry, number UMIN000048728., Discussion: This study will provide an assessment of the impact of SRT interval on local control, survival, and toxicity for patients with 1-5 BM. The trial is ongoing and is recruiting now., Trial Registration: UMIN000048728. Date of registration: August 23, 2022. https://center6.umin.ac.jp/cgi-bin/ctr/ctr&#95;view&#95;reg.cgi?recptno=R000055515 ., (© 2022. The Author(s).)

Background: In clinical practice, the organs at risk (OARs) should be carefully determined when performing pancreatic stereotactic body radiotherapy (SBRT). We conducted a simulation study to examine the effect of the stomach size on the radiation dose to the OARs when performing pancreatic SBRT., Methods: Twenty-five cases were included in this study. Pancreatic head and body tumors were 2-cm-sized pseudotumors, which were included as gross target volume (GTV) contours. The stomach, pancreas, small intestine, liver, kidneys, and spinal cord were considered as the OARs. The prescription dose for planning target volume (PTV) was 40 Gy/5fx, and the dose limit for the OARs was determined. The dose to X% of the OAR volume at X values of 0.1, 5.0, and 10.0 cc (DX) and the percentage of the OAR volume that received more than X Gy were recorded., Results: In terms of the radiation dose to the pancreatic body tumors, the stomach size was positively correlated with a dose of D10cc [correlation coefficient (r) = 0.5516) to the stomach. The r value between the radiation dose to the pancreatic head tumor and the stomach size was 0.3499. The stomach size and radiation dose to the head and body of the pancreas were positively correlated (pancreatic head D10cc: r = 0.3979, pancreatic body D10cc: r = 0.3209). The larger the stomach, the larger the radiation dose to the healthy portion of the pancreas outside the PTV., Conclusions: When performing pancreatic SBRT, the dose to the OARs depends on the stomach size. Reducing the dose to the stomach and pancreas can be achieved by shrinking the stomach., (© 2022. The Author(s).)

Background/aim: Nausea and vomiting are two of the most distressing adverse events of cancer radiotherapy. The aim of this study was to examine the control rate and risk factors associated with nausea and vomiting in patients with cervical cancer receiving radiotherapy., Patients and Methods: This retrospective study examined patients with cervical cancer who received radiotherapy alone or with concomitant cisplatin. Patients who received radiotherapy alone were not administered antiemetic premedication, while patients who received radiotherapy with concomitant weekly cisplatin (40 mg/m 2 ) were administered antiemetic therapy comprising granisetron and dexamethasone. Risk factors for non-complete response (CR) were identified using multivariate logistic regression analysis., Results: Multivariate analysis indicated that younger age and concomitant weekly cisplatin were significant factors associated with non-CR across 5 weeks of treatment in patients who received radiotherapy. The proportion achieving CR among younger patients (<65 years) who received radiotherapy alone or with concomitant cisplatin was significantly lower than that among older patients (≥65 years) (Concomitant cisplatin: 27% vs. 67%, p=0.049; Radiotherapy alone: 62% vs. 91%, p=0.166). However, the proportion of patients achieving CR across 5 weeks of treatment was insufficient in all groups except for those aged ≥ 65 years who received radiotherapy alone., Conclusion: Antiemetic prophylaxis should be considered for younger patients with cervical cancer undergoing radiotherapy alone. Further, neurokinin-1 receptor antagonist should be added to 5-hydroxytryptamine type-3 receptor antagonist and dexamethasone as antiemetic prophylactic therapy for patients with cervical cancer undergoing radiotherapy with concomitant weekly doses of 40 mg/m 2 cisplatin., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objectives: We aimed to compare dual-energy computed tomography (DECT) virtual monochromatic imaging (VMI) and iodine density imaging (IDI) of oral cancers in terms of visual scoring and tumour volume estimation., Materials and Methods: Nine patients diagnosed with oral cancer who underwent DECT VMI and IDI were enrolled. One radiation oncologist, one head and neck surgeon and nine oral surgeons evaluated image clarity and quality in each patient in terms of metal artefacts due to dental prosthesis, internal tumour structure, tumour-organ boundary and total quality of images for diagnosis. Tumour volume was estimated using VMI, IDI and magnetic resonance imaging (MRI)., Results: The mean score for image artefact was significantly higher for IDI than for VMI in three observers, the mean score for internal structure was significantly higher for IDI than for VMI in five, the mean score for tumour-organ boundary was significantly higher for IDI than for VMI in two and the mean score for total quality of images for diagnosis was significantly higher for IDI than for VMI in five. Standard deviation of estimated tumour volume was not significantly different between VMI and IDI, but that of MRI was significantly lowest in three images., Conclusions: In DECT for oral cancer, IDI has a visual image superior to VMI; thus, we recommend the use of IDI., Trial Registration: Clinical trial number: UMIN000038994., (© 2021. Japanese Society for Oral and Maxillofacial Radiology and Springer Nature Singapore Pte Ltd.)

Purpose: There has been an increase in the use of gold fiducial markers to ensure precise radiotherapy delivery in prostate cancer patients. However, metal artifacts may affect the quality of subsequent imaging used to assess disease status following treatment. In this study, we evaluated the effect of gold fiducial markers on magnetic resonance imaging (MRI), particularly on diffusion-weighted imaging (DWI)., Material and Methods: Among 57 patients with prostate cancer, 21 patients in whom two gold markers were placed in the prostate tumor with abnormal signal intensity on DWI were evaluated. The effect of the markers on DWI was evaluated on a scale of 1-5, with a high score indicating clinical usefulness. Change inapparent diffusion coefficient (ADC; 10 -3 mm 2 /s) from before to after marker placement was also evaluated., Results: The mean effect of the markers on DWI was 4.3 (standard deviation [SD] 1.3, range 2-5) points. The mean change in ADC was 0.045 (SD 0.041, range 0.025-0.089) × 10 -3 mm 2 /s., Conclusions: The gold fiducial markers demonstrated negligible effect on DWI quality. Therefore, gold markers do not affect MRI quality, particularly DWI, and may be used during follow-up in prostate cancer patients., (© 2020 John Wiley & Sons Australia, Ltd.)

In this retrospective cohort study, we evaluated the incidence of vascular events from carotid artery atherosclerosis after radiotherapy indication for laryngeal and hypopharyngeal cancer. From January 2007 to December 2016, we investigated 111 laryngeal/hypopharyngeal cancer patients who underwent curative radiotherapy and were followed up for ≥1 year (median follow-up duration, 60 months). We evaluated the incidence of vascular events from carotid artery atherosclerosis, defined as a transient ischemic attack or an atherothrombotic cerebral infarction, or from undergoing treatment such as carotid artery stenting for carotid artery stenosis. The median radiation dose was 66 Gy (range, 60-74); 48 patients (43.2%) received concurrent chemotherapy. The 5-year overall survival was 86.2%. Six patients required treatment for carotid artery disease. Carotid stenting was performed in three patients with carotid artery stenosis; three patients developed atherosclerotic cerebral infarction and received medical treatment, with a median of 51.7 months (range, 0.3-78.3) after radiotherapy initiation. The vascular event occurrence rate was 5.4% within 5 years and 10.7% within 8 years. In the univariate analysis, dyslipidemia, diabetes mellitus, and carotid calcification were significant factors for event occurrence. Because three out of six cases occurred out of the irradiated field, no carotid artery or carotid bulb dosimetric parameters showed significant correlation. As laryngeal/hypopharyngeal cancer patients, particularly with complications including dyslipidemia and diabetes mellitus, are at a high risk of carotid artery stenosis after radiotherapy, long-term carotid artery evaluation is necessary. Early intervention by stroke specialists can reduce the risk of fatal cerebral infarction., Competing Interests: None declared.

Objective: Standard treatment for progressive gastric cancer with bleeding includes hemostatic radiotherapy (RT); however, the only prospective study using a fixed dose with fractions during hemostatic RT did not introduce re-irradiation. Therefore, we determined the utility of RT including re-irradiation for gastric cancer., Methods: In this study, 31 patients with gastric cancer and bleeding were treated with an initial dose of 20 Gy/5 fractions for the whole stomach and a salvage dose of 15 Gy/5 fractions for the partial stomach. Patients achieving hemostasis, defined as a stable hemoglobin level within 30 days following irradiation, were considered responders, whereas those with no cessation of bleeding and those with re-bleeding within 30 days of irradiation were considered non-responders. We evaluated response rate, disease-free survival, overall survival (OS), re-irradiation, and adverse events (AEs)., Results: The response rate of initial RT was 80% (25/31). 6 of the 25 patients underwent re-irradiation, and all 6 were responders (100%). The median OS was significantly different among the entire cohort and one-time irradiation and re-irradiation groups (91, 76, and 112 days, respectively). No AEs of grade ≥3 were observed. Initial low-dose RT followed by reirradiation was effective in reducing AEs and did not cause any further AEs., Conclusion: Hemostatic RT was an effective approach with low toxicity, and re-irradiation was effective and tolerable, with no patients developing severe AEs. Further, randomized controlled studies are warranted to determine the ideal dose and number of fractions for initial RT in patients with gastric cancer and bleeding., Advances in Knowledge: In this prospective study on hemostatic radiotherapy for gastric cancer, the response rate was 80% using a fixed dose of 20 Gy/5 fractions and the salvage dose of 15 Gy for re-bleeding was effective. Future comparative studies should include other doses with 20 Gy as a control.

Bone-modifying agents (BMAs) are frequently used for the treatment of bone metastases. Both BMA and radiation therapy (RT) are effective; however, there are few studies that have evaluated the efficacy of the combination treatment. We evaluated the effectiveness of RT + BMA in breast cancer-induced osteolytic bone metastasis as compared to BMA alone. A total of 43 lesions in 25 patients were evaluated. The median follow-up period was 18 (range, 2-90) months. None of the lesions was treated with chemotherapy or molecular targeted drugs during the follow-up period for evaluating the local response. Patients with complete or partial response were considered as responders, while those with stable or progressive disease were considered as non-responders. The rate of response with RT + BMA was significantly higher than that with BMA alone (P = 0.001). The cumulative incidence rate of response at 6 months was 54.4% in the RT + BMA group and 27.5% in the BMA alone group. The median time to response was 4 (range, 2-11) months in the RT + BMA group and 6 (range, 4-16) months in the BMA alone group. The overall survival rate in the responder group (83.1% at 1 year) was significantly higher than that in the non-responder group (37.5% at 1 year) (P = 0.029). In conclusion, RT combined with BMA was found to be more effective than BMA alone for the treatment of osteolytic bone metastasis, which thereby improves the prognosis., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Stereotactic body radiotherapy (SBRT) delivers high-dose radiation to tumor tissues in few fractions, thereby reducing radiation damage to at-risk organs. There are more potential effects of SBRT owing to the higher biological equivalent dose delivered. Herein, we retrospectively analyzed its effectiveness and toxicity at our institution., Methods: Data from patients with hepatocellular carcinoma (HCC; n = 10) and liver metastases (n = 10) who underwent SBRT (total dose of 30-50 Gy in 5-10 fractions) between 2013 and 2016 were analyzed. Adverse events were recorded at the end of RT, 6 months after treatment, or upon death. Overall survival (OS) was calculated according to the biological effective dose (BED α/β = 10) and liver function (Child-Pugh [CP] classification 5 or 6 vs. 7 or 8) after SBRT, using Kaplan-Meier analyses., Results: Of the 20 patients, 6 declined the CP classification score after SBRT; grade 3 adverse events were not seen in any patient. A higher OS rate was seen in patients receiving a higher BED and in those with better CP classification after SBRT. Kaplan-Meier survival analysis yielded a median OS of 401 days and 1- and 2-year OS of 45% and 15%, respectively., Conclusion: The higher BED was significantly associated with tumor control, and there were no differences in the tumor control rate between HCC and metastatic tumors. Changes in CP scores after SBRT also affected the survival rate. Good liver function may permit multiple rounds of SBRT., (© 2019 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Intensity-modulated radiotherapy (IMRT) has been used for breast cancer as well as in field-in-field techniques. Few dosimetric comparison studies have been conducted using IMRT and volumetric modulated arc therapy (VMAT) for Japanese patients. We aimed to study such patients. Thirty-two patients with left-sided breast cancer were enrolled. We conducted the following five treatment plans: two field-static IMRT (2F-S-IMRT), four field-static IMRT (4F-S-IMRT), 40° dual partial arc VMAT (40d-VMAT), 80° dual partial arc VMAT (80d-VMAT) and 210° partial VMAT (210p-VMAT). We evaluated the following: level of coverage of planning target volume (PTV) of 95% for irradiation at a dose of 50 Gy (D95) and the percentage of the heart and left anterior descending artery (LAD) volume that received 10 Gy or more (V10). As a result, the coverage of 40d-VMAT for the prescribed PTV dose of D95 was significantly lower than that of the other treatment plans (P < 0.05). Regarding heart V10 and LAD V10, 2F-S-IMRT, 40d-VMAT and 80d-VMAT showed significantly lower dose than the other treatment plans (P < 0.05). In conclusion, among the five plans, 2F-S-IMRT is recommended for Japanese patients because of high coverage of D95 of PTV, low V10 of the heart and LAD and the monitor unit value was the lowest., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)