Incidence of Radiation-induced Nausea and Vomiting: A Prospective Single-institution Pilot Study.

Radiation-induced nausea and vomiting (RINV) is a frequent adverse event that occurs in patients undergoing radiotherapy. However, research on RINV is underrepresented. This prospective single-institution exploratory pilot study investigated the incidence of RINV according to the irradiation site and observed the efficacy of symptomatic antiemetic treatment in controlling symptoms of RINV. The primary outcomes were the proportions of emesis-free days and nausea-free days. The secondary endpoints included the time to the first episode of RINV, frequency of vomiting, and severity of nausea, including its impact on eating habits and weight loss. Fifteen patients were enrolled in each group (minimal, low, and moderate emetogenic risk). All patients received greater than 20 Gy in five fractions. Evaluation was based on weekly questionnaires completed by patients during routine clinic visits. Nausea and vomiting occurred in 11 and 0 patients, respectively. Six of 15 patients in the minimal-risk group, 1 in the low-risk group, and 4 in the moderate-risk group experienced nausea. Although all 11 symptomatic patients were offered antiemetics, only 3 used them, who reported satisfactory control of nausea. The percentage of emesis-free days for all patients was 100% and the percentage of nausea-free days for the 11 patients who developed RINV was 38%. An unexpectedly high percentage of patients in the minimal-risk group experienced nausea; all had breast cancer. Future studies should investigate factors beyond the irradiation site, including the characteristics of the patient and the treatment, to better predict an individual's risk of RINV.

The impact of the COVID-19 pandemic on radiotherapy delivery in Japan: An observational study based on the national database.

BACKGROUND: This study analyzed the impact of the coronavirus disease 2019 (COVID-19) pandemic on radiotherapy delivery in Japan using a high-quality Japanese national database based on universal health coverage. METHODS: We performed a retrospective observational study using National Database of Health Insurance Claims and Specific Health Checkups of Japan open data focused on radiotherapy between fiscal year (FY) 2019 and FY2020 and the number of COVID-19 cases from the Ministry of Health, Labour, and Welfare. We statistically analyzed the relationship between the number of COVID-19 cases and the number of radiotherapy deliveries in Japan as a whole and by prefecture. RESULTS: The total number of external beam radiotherapy (EBRT) fractions was 4,472,140 in FY2019 and 4,227,673 in FY2020 (-5.8%). EBRT courses were 250,395 in FY2019 and 240,329 in FY2020 (-4.0%), stereotactic radiotherapy courses were 27,619 in FY2019 and 31,786 in FY2020 (+15.1%), and single-fraction palliative radiotherapy courses were 4124 in FY2019 and 5255 in FY2020 (+21.5%). The total number of breast and prostate hypofractionated radiotherapy (HFRT) fractions was 155,773 and 48,188 in FY2019, and 200,256 and 84,230 in FY2020 (+28.6% and +74.8%), respectively. In the Pearson correlation analysis, EBRT fractions were lower, and breast HFRT fractions were higher in prefectures with more COVID-19 cases. CONCLUSIONS: Overall, radiotherapy delivery in Japan was relatively stable after the pandemic, with an increase in HFRT. Also, EBRT fractions decreased, and breast HFRT were more likely to be used in prefectures with more COVID-19 cases.

Dosimetric comparison of rectal dose-reductive techniques in intra-cavitary brachytherapy for cervical cancer: A retrospective analysis.

Purpose: Rectal complications in radiotherapy for cervical cancer can highly affect quality of life and correlate with rectal dose. Vaginal gauze packing (VP) and rectal retraction (RR) are widely used for rectal dose reduction in high-dose-rate brachytherapy. We aimed to perform a dosimetric comparison of these two methods for three-dimensional image-guided adaptive brachytherapy. Material and methods: We retrospectively examined 50 patients with cervical cancer treated with definitive radiotherapy, including intra-cavitary brachytherapy, performed with VP and RR. We extracted two fractions for each patient: one fraction with VP and the next fraction with RR, and then compared dose-volume parameters. In total, 50 fractions each were analyzed in VP and RR groups. Dose to 90% (D90) of high-risk clinical target volume (HR-CTV), and minimum dose to most exposed 2.0 cm3 of other organs at risk (D2cm3) for the rectum and bladder were determined from planning computed tomography. Results: There were no significant differences between VP and RR in D90 of HR-CTV (mean: 7.479 Gy and 7.652 Gy, respectively, p = 0.172). The D2cm3 values for the rectum (mean: 4.234 Gy vs. 4.627 Gy, p = 0.008) and bladder (mean: 5.959 Gy vs. 6.690 Gy, p < 0.001) were significantly lower with VP compared with RR. Conclusions: VP reduced the dose to the rectum and bladder when compared with RR without impairing the dose to CTV.

Phase I study of neoadjuvant S-1 plus cisplatin with concurrent radiation for biliary tract cancer (Tokyo Study Group for Biliary Cancer: TOSBIC02).

Aim: Neoadjuvant chemoradiotherapy may improve survival in patients with advanced cholangiocarcinoma. This Phase I study aimed to determine the recommended dose of neoadjuvant chemoradiotherapy and decide whether to move to a Phase II study. Methods: Patients diagnosed with resectable stage II-IVa cholangiocarcinoma were administered cisplatin (40 [level 0], 50 [level 1 as starting dose], or 60 [level 2] mg/m2), 80 mg/m2 of S-1, and 50.4 Gy of external beam radiation. The recommended dose was defined as a dose one-step lower than the maximum-tolerated dose, which was defined when dose-limiting toxicity was observed in three or more of the six patients. Results: Twelve patients were eligible from November 2012 to May 2016. Ten patients had perihilar cholangiocarcinoma and two patients had distal cholangiocarcinoma. Dose-limiting toxicity was observed in one of the first six patients at level 1 and two of the next six patients at level 2; thus, the maximum-tolerated dose was not determined even at level 2 and the recommended dose was determined as level 2. Four patients had partial response, four patients had stable disease, and two patients had progression of disease because of liver metastases. Finally, nine patients underwent radical surgery and seven cases achieved R0 resection. However, five cases suffered biliary leakage and one suffered intrahospital death due to rupture of the hepatic artery. Conclusion: We determined the recommended dose of neoadjuvant chemoradiotherapy for resectable cholangiocarcinoma. However, we terminated the trial due to a high incidence of morbidity and unexpected mortality.

Factors associated with quality of life in patients receiving palliative radiotherapy for bone metastases: a secondary cross-sectional analysis of data from a prospective multicenter observational study.

OBJECTIVE: To identify factors significantly associated with quality of life (QOL) and determine if these associations are strong enough to predict certain aspects of QOL without measuring them. METHODS: We conducted an exploratory secondary analysis of baseline data of 224 patients (enrolled between December 2020 and March 2021) from a previously published prospective observational study on radiotherapy for bone metastases at 26 centres. Using univariable linear regression, we assessed the association between patient/treatment factors and QOL scale scores as measured by the European Organization for Research and Treatment of Cancer (EORTC) QOL Questionnaire Core 15-Palliative (QLQ-C15-PAL) and the EORTC QOL Questionnaire Bone Metastases module (QLQ-BM22). RESULTS: Age and sex were not significantly associated with QOL. Worse performance status, higher pain scores, and opioid and single-fraction use were significantly associated with most QOL scales; these four factors were associated with worse global QOL, worse functioning status, and more severe symptoms. The coefficients of determination for most QOL scales were less than 0.2, indicating that most of the variability in QOL scores was not explained by any of the explanatory variables. CONCLUSION: Performance status, pain intensity, and opioid and single-fraction use were significantly associated with most QOL scales. However, the associations were not strong enough to estimate QOL. ADVANCES IN KNOWLEDGE: To date, the association between treatment factors and QOL in patients with bone metastases has not been fully studied. We identified the factors that were significantly associated with QOL and found that these associations were not strong enough to predict QOL.

Evaluation of dose perturbations around iodine-125 seed sources in supplemental external beam prostate radiotherapy.

We investigated dose perturbations caused by 125I seeds in patients undergoing supplemental external beam radiotherapy (EBRT) for prostate cancer. We examined two types of nonradioactive seed models: model 6711 and model STM1251. All experiments were performed using a water-equivalent phantom. Radiochromic film was used to measure the dose distributions adjacent to the seeds upstream and downstream of the external beam source. Single and clusters of multiple seeds were placed in slots in a solid water (SW) slab to measure dose perturbations with separate versus dense seed placement at beam energies of 6 or 10 MV. Monte Carlo simulations (MCSs) were also performed to include the theoretical basis against film dosimetry. Distinct patterns of dose enhancement (buildup [BU]) were upstream, and dose reduction (builddown [BD]) were downstream of the radiation source. Model 6711 with lower photon beam energies produced larger dose perturbations of BU and BD than the model STM1251. The results showed the same tendency with different seed placements and beam energies. However, these differences were not observed in the rotational irradiation measurement, which replicated a clinical plan. Dose perturbations around seeds result in dose enhancement and dose reduction with varying impact depending on the photon beam energy and seed type. This has the potential to cancel out these perturbations using multiple beam direction fields.

Income and Employment of Patients at the Start of and During Follow-up After Palliative Radiation Therapy for Bone Metastasis.

Purpose: The aim of this study was to understand the income and employment status of patients at the start of and during follow-up after palliative radiation therapy for bone metastasis. Methods and Materials: From December 2020 to March 2021, a prospective multi-institutional observational study was conducted to investigate income and employment of patients at the start of administration of radiation therapy for bone metastasis and at 2 and 6 months after treatment. Of 333 patients referred to radiation therapy for bone metastasis, 101 were not registered, mainly because of their poor general condition, and another 8 were excluded from the follow-up analysis owing to ineligibility. Results: In 224 patients analyzed, 108 had retired for reasons unrelated to cancer, 43 had retired for reasons related to cancer, 31 were taking leave, and 2 had lost their jobs at the time of registration. The number of patients who were in the working group was 40 (30 with no change in income and 10 with decreased income) at registration, 35 at 2 months, and 24 at 6 months. Younger patients (P = 0), patients with better performance status (P = 0), patients who were ambulatory (P = .008), and patients with lower scores on a numerical rating scale of pain (P = 0) were significantly more likely to be in the working group at registration. There were 9 patients who experienced improvements in their working status or income at least once in the follow-up after radiation therapy. Conclusions: The majority of patients with bone metastasis were not working at the start of or after radiation therapy, but the number of patients who were working was not negligible. Radiation oncologists should be aware of the working status of patients and provide appropriate support for each patient. The benefit of radiation therapy to support patients continuing their work and returning to work should be investigated further in prospective studies.

The impact of the COVID-19 pandemic on radiotherapy in Japan: nationwide surveys from May 2020 through June 2021.

A longitudinal online questionnaire survey on the impact of coronavirus disease 2019 (COVID-19) on the operation of radiotherapy departments in Japan was conducted. Approximately 26.1-70.9% of the radiotherapy departments participated, and their responses were collected in May, July and November 2020, and February and June 2021. The survey results revealed that while the number of patients receiving radiotherapy decreased in 41.2% and 30.7% of institutions in May 2020 and June 2021, respectively, it increased in 4% and 16.8% of institutions in May 2020 and June 2021, respectively. There were a few institutions limiting or postponing patient treatments in June 2021. The hypofractionated regimen was used more during the pandemic than during the pre-pandemic period, particularly for the treatment of breast and prostate cancers as well as for palliation. Infection control measures for patients and staff were followed. Approximately 20% of the respondent institutions had cases of patients with COVID-19 infection receiving radiotherapy. Most institutions encountered challenges in the continuous provision of radiotherapy for patients with COVID-19. In conclusion, COVID-19 had a multifaceted impact on the operations of radiotherapy departments in Japan. Further follow-up and analysis are warranted to understand the long-term impact of COVID-19 on radiotherapy.

Practical guidelines of online MR-guided adaptive radiotherapy.

The first magnetic resonance (MR)-guided radiotherapy system in Japan was installed in May 2017. Implementation of online MR-guided adaptive radiotherapy (MRgART) began in February 2018. Online MRgART offers greater treatment accuracy owing to the high soft-tissue contrast in MR-images (MRI), compared to that in X-ray imaging. The Japanese Society for Magnetic Resonance in Medicine (JSMRM), Japan Society of Medical Physics (JSMP), Japan Radiological Society (JRS), Japanese Society of Radiological Technology (JSRT), and Japanese Society for Radiation Oncology (JASTRO) jointly established the comprehensive practical guidelines for online MRgART. These guidelines propose the essential requirements for clinical implementation of online MRgART with respect to equipment, personnel, institutional environment, practice guidance, and quality assurance/quality control (QA/QC). The minimum requirements for related equipment and QA/QC tools, recommendations for safe operation of MRI system, and the implementation system are described. The accuracy of monitor chamber and detector in dose measurements should be confirmed because of the presence of magnetic field. The ionization chamber should be MR-compatible. Non-MR-compatible devices should be used in an area that is not affected by the static magnetic field (outside the five Gauss line), and their operation should be checked to ensure that they do not affect the MR image quality. Dose verification should be performed using an independent dose verification system that has been confirmed to be reliable through commissioning. This guideline proposes the checklists to ensure the safety of online MRgART. Successful clinical implementation of online MRgART requires close collaboration between physician, radiological technologist, nurse, and medical physicist.

Applying Artificial Neural Networks to Develop a Decision Support Tool for Tis-4N0M0 Non-Small-Cell Lung Cancer Treated With Stereotactic Body Radiotherapy.

PURPOSE: Clear evidence indicating whether surgery or stereotactic body radiation therapy (SBRT) is best for non-small-cell lung cancer (NSCLC) is lacking. SBRT has many advantages. We used artificial neural networks (NNs) to predict treatment outcomes for patients with NSCLC receiving SBRT, aiming to aid in decision making. PATIENTS AND METHODS: Among consecutive patients receiving SBRT between 2005 and 2019 in our institution, we retrospectively identified those with Tis-T4N0M0 NSCLC. We constructed two NNs for prediction of overall survival (OS) and cancer progression in the first 5 years after SBRT, which were tested using an internal and an external test data set. We performed risk group stratification, wherein 5-year OS and cancer progression were stratified into three groups. RESULTS: In total, 692 patients in our institution and 100 patients randomly chosen in the external institution were enrolled. The NNs resulted in concordance indexes for OS of 0.76 (95% CI, 0.73 to 0.79), 0.68 (95% CI, 0.60 to 0.75), and 0.69 (95% CI, 0.61 to 0.76) and area under the curve for cancer progression of 0.80 (95% CI, 0.75 to 0.84), 0.72 (95% CI, 0.60 to 0.83), and 0.70 (95% CI, 0.57 to 0.81) in the training, internal test, and external test data sets, respectively. The survival and cumulative incidence curves were significantly stratified. NNs selected low-risk cancer progression groups of 5.6%, 6.9%, and 7.0% in the training, internal test, and external test data sets, respectively, suggesting that 48% of patients with peripheral Tis-4N0M0 NSCLC can be at low-risk for cancer progression. CONCLUSION: Predictions of SBRT outcomes using NNs were useful for Tis-4N0M0 NSCLC. Our results are anticipated to open new avenues for NN predictions and provide decision-making guidance for patients and physicians.

Mean heart dose-based normal tissue complication probability model for pericardial effusion: a study in oesophageal cancer patients.

We investigated the normal tissue complication probability (NTCP) of the incidence of pericardial effusion (PCE) based on the mean heart dose (MHD) in patients with oesophageal cancer treated with definitive chemoradiotherapy. The incidences of PCE in any grade (A-PCE) and symptomatic PCE (S-PCE) were evaluated separately. To identify predictors for PCE, several clinical and dose-volume parameters were analysed using a receiver operating characteristic (ROC) curve and multivariate regression analysis. To validate its clinical applicability, the generated NTCP model was compared to the Lyman-Kutcher-Burman (LKB) model. Among 229 eligible patients, A-PCE and S-PCE were observed in 100 (43.7%) and 18 (7.9%) patients, respectively. MHD showed a preferable area under the curve (AUC) value for S-PCE (AUC = 0.821) and A-PCE (AUC = 0.734). MHD was the only significant predictor for A-PCE; MHD and hypertension were selected as significant factors for S-PCE. The estimated NTCP, using the MHD-based model, showed excellent correspondence to the LKB model in A-PCE and S-PCE. The NTCP curve of A-PCE was gentler than that of S-PCE and had no threshold. The MHD-based NTCP model was simple but comparable to the LKB model for both A-PCE and S-PCE. Therefore, the estimated NTCP may provide clinically useful parameters for predicting PCE.

Effects of sample size and data augmentation on U-Net-based automatic segmentation of various organs.

Deep learning has demonstrated high efficacy for automatic segmentation in contour delineation, which is crucial in radiation therapy planning. However, the collection, labeling, and management of medical imaging data can be challenging. This study aims to elucidate the effects of sample size and data augmentation on the automatic segmentation of computed tomography images using U-Net, a deep learning method. For the chest and pelvic regions, 232 and 556 cases are evaluated, respectively. We investigate multiple conditions by changing the sum of the training and validation datasets across a broad range of values: 10-200 and 10-500 cases for the chest and pelvic regions, respectively. A U-Net is constructed, and horizontal-flip data augmentation, which produces left and right inverse images resulting in twice the number of images, is compared with no augmentation for each training session. All lung cases and more than 100 prostate, bladder, and rectum cases indicate that adding horizontal-flip data augmentation is almost as effective as doubling the number of cases. The slope of the Dice similarity coefficient (DSC) in all organs decreases rapidly until approximately 100 cases, stabilizes after 200 cases, and shows minimal changes as the number of cases is increased further. The DSCs stabilize at a smaller sample size with the incorporation of data augmentation in all organs except the heart. This finding is applicable to the automation of radiation therapy for rare cancers, where large datasets may be difficult to obtain.

Radiation dose rate variations in different measurement scenarios after prostate 125I brachytherapy.

PURPOSE: This study aimed to directly compare different measurement scenarios using a supplemental radiation exposure measurement data set. MATERIALS AND METHODS: Two sets of measurement scenarios comparing different body postures, such as standing and chair sitting positions, and different measurement directions, such as anterior and posterior directions, were assessed for radiation dose rate variations in this study at the Tokyo Medical Center, Japan. The estimated precaution time for holding children in the spoon position while sitting was also calculated. RESULTS: Different radiation dose rate measurement scenarios showed different variation tendencies. Radiation dose rate measurement showed higher mean values of measured radiation dose tendency in the standing position than in the sitting positions. The measurement from the anterior direction showed a slightly lower tendency than that from the posterior direction. Assuming a dose limit of 1 mSv, the precaution time calculated for children being held in the spoon position for a certain duration every day was 51.5 (range, 12.5-152.2) minutes. CONCLUSIONS: Our study presented a supplemental radiation exposure measurement data set and directly compared different measurement scenarios. Several trends in radiation exposure variations were found in the measurement scenarios at different body postures and different measurement directions. Our study data set could be a useful source of concrete information regarding radiation safety and contribute to the review and revision of public guidance in the future.

Proton beam therapy for children and adolescents and young adults (AYAs): JASTRO and JSPHO Guidelines.

Children and adolescents and young adults (AYAs) with cancer are often treated with a multidisciplinary approach. This includes use of radiotherapy, which is important for local control, but may also cause adverse events in the long term, including second cancer. The risks for limited growth and development, endocrine dysfunction, reduced fertility and second cancer in children and AYAs are reduced by proton beam therapy (PBT), which has a dose distribution that decreases irradiation of normal organs while still targeting the tumor. To define the outcomes and characteristics of PBT in cancer treatment in pediatric and AYA patients, this document was developed by the Japanese Society for Radiation Oncology (JASTRO) and the Japanese Society of Pediatric Hematology/Oncology (JSPHO).

Phase 1 study of plerixafor in combination with total body irradiation-based myeloablative conditioning for allogeneic hematopoietic stem cell transplantation.

Plerixafor, a CXCR4 inhibitor, has the potential to mobilize leukemic cells, which may contribute to their chemosensitization. This phase 1 study evaluated the safety of myeloablative conditioning combined with plerixafor for allogeneic hematopoietic stem cell transplantation (HSCT). Patients with high-risk leukemia undergoing allogeneic HSCT after total body irradiation (TBI, 12 Gy)-based myeloablative conditioning were eligible; 9 patients were enrolled. The study was performed using a 3 + 3 design with an escalating total dose of plerixafor. Plerixafor was given subcutaneously 8 h before TBI and chemotherapeutic agents. Plerixafor was successfully escalated to the maximum dose (0.72 mg/kg) without dose-limiting toxicities. Underlying diseases were acute myelogenous and lymphoblastic leukemia, chronic myeloid leukemia, and myelodysplastic syndrome. As adverse events, plerixafor administration was associated with transient Grades 2-3 diarrhea (n = 7) and abdominal pain (n = 4). In 6 patients, leukemic cell mobilization into the peripheral blood by plerixafor was confirmed by a morphological or molecular method. All patients achieved neutrophil engraftment and 5 were alive in remission at a follow-up after 30-40 months. Plerixafor-combined myeloablative conditioning for allogeneic HSCT was well tolerated. Leukemic-cell mobilization into peripheral blood was observed in half of the patients. Further study is required to evaluate the efficacy and safety of this concept.

Simple low-cost approaches to semantic segmentation in radiation therapy planning for prostate cancer using deep learning with non-contrast planning CT images.

PURPOSE: Deep learning has shown great efficacy for semantic segmentation. However, there are difficulties in the collection, labeling and management of medical imaging data, because of ethical complications and the limited number of imaging studies available at a single facility. This study aimed to find a simple and low-cost method to increase the accuracy of deep learning semantic segmentation for radiation therapy of prostate cancer. METHODS: In total, 556 cases with non-contrast CT images for prostate cancer radiation therapy were examined using a two-dimensional U-Net. Initially, all slices were used for the input data. Then, we removed slices of the cranial portions, which were beyond the margins of the bladder and rectum. Finally, the ground truth labels for the bladder and rectum were added as channels to the input for the prostate training dataset. RESULTS: The highest mean dice similarity coefficients (DSCs) for each organ in the test dataset of 56 cases were 0.85 ± 0.05, 0.94 ± 0.04 and 0.85 ± 0.07 for the prostate, bladder and rectum, respectively. Removal of the cranial slices from the original images significantly increased the DSC of the rectum from 0.83 ± 0.09 to 0.85 ± 0.07 (p < 0.05). Adding bladder and rectum information to prostate training without removing the slices significantly increased the DSC of the prostate from 0.79 ± 0.05 to 0.85 ± 0.05 (p < 0.05). CONCLUSIONS: These cost-free approaches may be useful for new applications, which may include updated models and datasets. They may be applicable to other organs at risk (OARs) and clinical targets such as elective nodal irradiation.

Relationship between radiation doses and erectile function deterioration in patients with localized prostate cancer treated with permanent prostate brachytherapy.

OBJECTIVES: To investigate the relationship between radiation doses in prostate brachytherapy and deterioration of erectile function in patients with localized prostate cancer. METHODS: A longitudinal survey study was carried out among 261 prostate cancer patients who received prostate brachytherapy. A total of 48 patients were potent at baseline and they did not receive any supplemental therapy preoperatively. Dosimetry parameters of the whole prostate gland, prostate apex, urethra and rectum were collected using the VariSeed 8.0 treatment planning system (Varian Medical Systems, Palo Alto, CA, USA). We carried out a logistic regression analysis to clarify the relationship between radiation doses and erectile function deterioration, which was assessed using the International Index of Erectile Function-15 questionnaire. RESULTS: The median patient age was 66 years (range 53-70 years) with a median follow-up time of 44 months (36-71 months). The mean total International Index of Erectile Function-15 score decreased from 49.9 at baseline to 34.7 after 12 months (P < 0.001), but gradually plateaued within 36 months. Erectile function deterioration was noted in 32 (66.7%) patients 36 months after prostate brachytherapy. In an analysis of risk factors for erectile function deterioration after prostate brachytherapy, age ≥70 years (P = 0.029), prostate V100 ≥95% (P = 0.024), apex V100 ≥95% (P = 0.024), apex V150 ≥70% (P = 0.009) and apex D90 ≥150 Gy (P = 0.011) correlated with erectile function deterioration. A multivariate analysis identified an age of ≥70 years (odds ratio 7.91, P = 0.024) and apex V150 ≥70% (odds ratio 7.75, P = 0.007) as independent risk factors for erectile function deterioration after prostate brachytherapy. CONCLUSIONS: An excessive radiation dose, particularly to the prostate apex area, and an advanced age might have a negative impact on the preservation of potency after prostate brachytherapy.

2-Nitroimidazoles induce mitochondrial stress and ferroptosis in glioma stem cells residing in a hypoxic niche.

Under hypoxic conditions, nitroimidazoles can replace oxygen as electron acceptors, thereby enhancing the effects of radiation on malignant cells. These compounds also accumulate in hypoxic cells, where they can act as cytotoxins or imaging agents. However, whether these effects apply to cancer stem cells has not been sufficiently explored. Here we show that the 2-nitroimidazole doranidazole potentiates radiation-induced DNA damage in hypoxic glioma stem cells (GSCs) and confers a significant survival benefit in mice harboring GSC-derived tumors in radiotherapy settings. Furthermore, doranidazole and misonidazole, but not metronidazole, manifested radiation-independent cytotoxicity for hypoxic GSCs that was mediated by ferroptosis induced partially through blockade of mitochondrial complexes I and II and resultant metabolic alterations in oxidative stress responses. Doranidazole also limited the growth of GSC-derived subcutaneous tumors and that of tumors in orthotopic brain slices. Our results thus reveal the theranostic potential of 2-nitroimidazoles as ferroptosis inducers that enable targeting GSCs in their hypoxic niche.

Comparison of prostate verification with implanted gold markers in tissue surrounding the prostate and pelvic bony anatomy for external beam radiation therapy following low-dose-rate brachytherapy: a prospective clinical trial.

We aimed to investigate whether gold marker implantation in the tissue surrounding the prostate could accurately monitor setup errors during external beam radiation therapy (EBRT) following low-dose-rate (LDR) brachytherapy. Thirty-eight patients had confirmed intermediate- or high-risk prostate cancer and received EBRT following LDR brachytherapy. In >175 computed tomography imaging sessions, the average values of the weekly setup error during EBRT to the prostate centroid at the time of gold marker matching in the surrounding tissue of the prostate and pelvic bone matching were measured and then compared using the Wilcoxon signed-rank test. Gold marker matching in the surrounding tissue of the prostate estimated setup errors better than those estimated by bone matching (3D displacement = 2.7 ± 2.0 vs 3.8 ± 2.6 mm, P < 0.01). Overall, the standard deviation of systematic (Σ) and random (σ) setup error was lower with gold marker matching than with bone matching (3D displacement = 1.8 and 1.1 mm vs 2.1 and 1.6 mm, respectively). With gold marker matching, the setup error of the position of the prostate centroid was smaller, and the optimal setup margin was lower than that with bone matching (2Σ + 0.7σ and 2.5Σ + 0.7σ of 3D displacement = 4.3 and 5.2 mm vs 5.3 and 6.4 mm, respectively). This high-precision radiotherapy approach placing gold markers in the surrounding tissue of the prostate can allow more accurate setup during EBRT following LDR brachytherapy.