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The utility of Adaptive Radiotherapy (ART) in Head and Neck Squamous Cell Carcinoma (HNSCC) remains to be ascertained. While multiple retrospective and single-arm prospective studies have demonstrated its efficacy in decreasing parotid doses and reducing xerostomia, adequate randomized evidence is lacking. ReSTART (Reducing Salivary Toxicity with Adaptive Radiotherapy) is an ongoing phase III randomized trial of patients with previously untreated, locally advanced HNSCC of the oropharynx, larynx, and hypopharynx. Patients are randomized in a 1:1 ratio to the standard Intensity Modulated Radiotherapy (IMRT) arm {Planning Target Volume (PTV) margin 5 mm} vs. Adaptive Radiotherapy arm (standard IMRT with a PTV margin 3 mm, two planned adaptive planning at 10th and 20th fractions). The stratification factors include the primary site and nodal stage. The RT dose prescribed is 66Gy in 30 fractions for high-risk PTV and 54Gy in 30 fractions for low-risk PTV over six weeks, along with concurrent chemotherapy. The primary endpoint is to compare salivary toxicity between arms using salivary scintigraphy 12 months' post-radiation. To detect a 25% improvement in the primary endpoint at 12 months in the ART arm with a two-sided 5% alpha value and a power of 80% (and 10% attrition ratio), a sample size of 130 patients is required (65 patients in each arm). The secondary endpoints include acute and late toxicities, locoregional control, disease-free survival, overall survival, quality of life, and xerostomia scores between the two arms. The ReSTART trial aims to answer an important question in Radiation Therapy for HNSCC, particularly in a resource-limited setting. The uniqueness of this trial, compared to other ongoing randomized trials, includes the PTV margins and the xerostomia assessment by scintigraphy at 12 months as the primary endpoint. • The ReSTART, trial, evaluates the efficacy of adaptive radiotherapy in reducing xerostomia for HNSCC. • In the adaptive RT arm, two pre-planned adaptive planning are done at 10 and 20 fractions. • The CTV to PTV margin in the adaptive RT arm is 3 mm. • Primary hypothesis is a 25% benefit of 1-year salivary function, which is assessed by salivary scintigraphy. [ABSTRACT FROM AUTHOR]

For high-risk neuroblastoma, planning target volume coverage is often compromised to respect adjacent kidney tolerance. This trial investigated whether intensity-modulated arc radiotherapy techniques (IMAT) could facilitate dose escalation better than conventional techniques. Children with high-risk abdominal neuroblastoma referred for radiotherapy to the primary tumour site and involved regional lymph nodes were randomised to receive either standard dose (21 Gy in 14 fractions) or escalated dose (36 Gy in 24 fractions) radiotherapy. Dual planning with both a conventional anterior-posterior parallel opposed pair radiotherapy technique and an IMAT technique was performed. The quality of target volume and organ-at-risk delineation, and dosimetric plans, were externally reviewed. Dosimetric parameters were used to judge the superior technique for treatment. This feasibility trial was not powered to detect improvement in outcome with dose escalation. Between 2017 and 2020, 50 patients were randomised and dual-planned. The IMAT technique was judged more favourable in 48 patients. In all patients randomised to receive 36 Gy, IMAT would have permitted delivery of the full dose (median D50% 36.0 Gy, inter-quartile range 36.0–36.1 Gy) to the target volume, whereas dose compromise would have been required with conventional planning (median D50% 35.6 Gy, inter-quartile range 28.7–35.9 Gy). IMAT facilitates safe dose escalation to 36 Gy in patients receiving radiotherapy for neuroblastoma. The value of dose escalation is now being evaluated in a current prospective phase III randomised trial. • The standard tumour bed radiotherapy dose used for neuroblastoma is 21 Gy. • The optimal dose is uncertain, and a higher dose may lead to better local control. • Organ-at-risk tolerance may limit the desired dose to the target volume. • Intensity-modulated arc therapy facilitates better delivery of higher doses. [ABSTRACT FROM AUTHOR]

Radiomics is a promising tool for the development of quantitative biomarkers to support clinical decision-making. It has been shown to improve the prediction of response to treatment and outcome in different settings, particularly in the field of radiation oncology by optimising the dose delivery solutions and reducing the rate of radiation-induced side effects, leading to a fully personalised approach. Despite the promising results offered by radiomics at each of these stages, standardised methodologies, reproducibility and interpretability of results are still lacking, limiting the potential clinical impact of these tools. In this review, we briefly describe the principles of radiomics and the most relevant applications of radiomics at each stage of cancer management in the framework of radiation oncology. Furthermore, the integration of radiomics into clinical decision support systems is analysed, defining the challenges and offering possible solutions for translating radiomics into a clinically applicable tool. [ABSTRACT FROM AUTHOR]

Despite the breast being a mobile organ, there is currently no standard suitable immobilisation device to optimise radiotherapy for women with larger breasts treated after a wide local excision. The SuPPORT 4 All (S4A) bra was co-designed with patients and radiotherapy professionals. The purpose of this study was to test the feasibility of using the S4A bra in the existing breast cancer radiotherapy pathway. A randomised feasibility trial was conducted in a single institution; the primary feasibility endpoint was the recruitment of 50 participants. Efficacy endpoints were also tested, including assessment of skin reactions, dose to organs at risk and patient comfort. Fifty women were randomised to receive either standard radiotherapy with no immobilisation (control) or radiotherapy with the S4A bra (intervention). A separate planning study was undertaken on the cases randomised to receive the S4A bra. Participants in the intervention arm (S4A bra) underwent two planning computed tomography scans, one with the bra on and one without the bra; allowing direct comparison of organs at risk data for S4A bra versus no bra. All women who started radiotherapy wearing the S4A bra completed treatment with the bra; patient comfort did not change across the 3 weeks of treatment. Positional accuracy using the bra was comparable with existing published accuracy for methods without immobilisation. The mean ipsilateral lung doses showed some improvement when positioning with the S4A bra was compared with the no bra set-up (3.72 Gy versus 4.85 Gy for right-sided cases, 3.23 Gy versus 3.62 Gy for left-sided cases). The S4A bra is feasible to use in the radiotherapy pathway with good patient adherence. The S4A bra has potential to reduce dose to organs at risk (specifically ipsilateral lung dose) while maintaining good breast tissue coverage, and improved patient dignity, warranting further investigation on a larger scale. • The S4A bra is feasible to use in the breast cancer radiotherapy pathway. • In women with larger breasts, the S4A bra may reduce the mean ipsilateral lung dose. • The bra may allow greater breast coverage without increasing mean heart dose. • Patient compliance with use of the immobilisation bra was high. • Compliance with self-monitoring of skin reactions and breast changes was good. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Medical Imaging & Radiation Sciences is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Skin brachytherapy represents an excellent alternative treatment for patients with non-melanoma skin cancers. It offers superior conformity of dose distribution with rapid dose fall off, reducing the risk of radiotherapy-related treatment toxicity. A smaller treatment volume in brachytherapy, when compared with external beam radiotherapy, is conducive for hypofractionation, which is an attractive option for decreasing outpatient visits to the cancer centre, especially for elderly and frail patients. Skin brachytherapy is an excellent option to preserve function and cosmesis, especially in skin cancers located in the head and neck region. Electronic brachytherapy, image-guided superficial brachytherapy and 3D printed moulds are all emerging advances in skin brachytherapy. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Medical Imaging & Radiation Sciences is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

To report the final results of a dose-escalation study of volumetric intensity-modulated arc stereotactic radiosurgery (VMAT-SRS) boost after three-dimensional conformal radiation therapy in patients with spine metastases. Oligometastatic cancer patients bearing up to five synchronous metastases (visceral or bone, including vertebral ones) and candidates for surgery or radiosurgery were considered for inclusion. 25 Gy was delivered in 10 daily fractions (2 weeks) to the metastatic lesion, affected vertebrae and adjacent ones (one cranial and one caudal vertebra). Sequentially, the dose to spinal metastases was progressively increased (8 Gy, 10 Gy, 12 Gy) in the patient cohorts. Dose-limiting toxicities were defined as any treatment-related non-hematologic acute adverse effects rated as grade ≥3 or any acute haematological toxicity rated as ≥ 4 by the Radiation Therapy Oncology Group scale. Fifty-two lesions accounting for 40 consecutive patients (male/female: 29/11; median age: 71 years; range 40–85) were treated from April 2011 to September 2020. Most patients had a primary prostate (65.0%) or breast cancer (22.5%). Thirty-two patients received 8 Gy VMAT-SRS boost (total BED α/β10 : 45.6 Gy), 14 patients received 10 Gy (total BED α/β10 : 51.2 Gy) and six patients received 12 Gy (total BED α/β10 : 57.6 Gy). The median follow-up time was over 70 months (range 2–240 months). No acute toxicities > grade 2 and no late toxicities > grade 1 were recorded. The overall response rate based on computed tomography/positron emission tomography–computed tomography/magnetic resonance was 78.8%. The 24-month actuarial local control, distant metastases-free survival and overall survival rates were 88.5%, 27.1% and 90.3%, respectively. A 12 Gy spine metastasis SRS boost following 25 Gy to the affected and adjacent vertebrae was feasible with an excellent local control rate and toxicity profile. • A dose-finding trial focused on spinal metastases treated with radiosurgery boost following conventional radiotherapy is presented. • According to this analysis, this combined approach is safe with no impact on quality of life. • Treating the affected and adjacent vertebrae boosting the lesion site led to an excellent local control rate. [ABSTRACT FROM AUTHOR]

To use pre-treatment magnetic resonance imaging-based radiomics data with clinical data to predict radiation-induced temporal lobe injury (RTLI) in nasopharyngeal carcinoma (NPC) patients with stage T4/N0–3/M0 within 5 years after radiotherapy. This study retrospectively examined 98 patients (198 temporal lobes) with stage T4/N0–3/M0 NPC. Participants were enrolled into a training cohort or a validation cohort in a ratio of 7:3. Radiomics features were extracted from pre-treatment magnetic resonance imaging that were T1-and T2-weighted. Spearman rank correlation, the t -test and the least absolute shrinkage and selection operator (LASSO) algorithm were used to select significant radiomics features; machine-learning models were used to generate radiomics signatures (Rad-Scores). Rad-Scores and clinical factors were integrated into a nomogram for prediction of RTLI. Nomogram discrimination was evaluated using receiver operating characteristic analysis and clinical benefits were evaluated using decision curve analysis. Participants were enrolled into a training cohort (n = 139) or a validation cohort (n = 59). In total, 3568 radiomics features were initially extracted from T1-and T2-weighted images. Age, D max , D 1cc and 16 stable radiomics features (six from T1-weighted and 10 from T2-weighted images) were identified as independent predictive factors. A greater Rad-Score was associated with a greater risk of RTLI. The nomogram showed good discrimination, with a C-index of 0.85 (95% confidence interval 0.79–0.92) in the training cohort and 0.82 (95% confidence interval 0.71–0.92) in the validation cohort. We developed models for the prediction of RTLI in patients with stage T4/N0–3/M0 NPC using pre-treatment radiomics data and clinical data. Nomograms from these pre-treatment data improved the prediction of RTLI. These results may allow the selection of patients for earlier clinical interventions. • Interdisciplinary study that used pre-treatment MRI-based radiomics data for RTLI prediction in NPC patients. • Only included patients with stage T4/N0-3/M0 NPC, making the study more targeted. • Provide reliable risk stratification of RTLI by using non-invasive radiomics and clinical data. • Radiomics information was extracted from the routine MRI examinations without increasing healthcare costs. [ABSTRACT FROM AUTHOR]

Urinary toxicity is common following pelvic radiotherapy and can have a substantial negative effect on survivorship. Due to its prevalence and the increasing number of related clinical trials, localised prostate cancer radiotherapy is a useful illustrative tool to explore urinary toxicity. A good understanding of the interplay between anatomy, radiation-sensitive cell populations, and treatment sequencing is necessary for optimal outcomes. Emerging evidence suggests that the prostatic urethra is a radiation-sensitive structure, not only for stricture development, but also chronic irritative symptoms. Tools now exist not only to identify the urethra, but also to direct radiation dose away from the urethra, with early data suggesting that this reduces moderate-to-severe late urinary toxicity. Coupled with new evidence supporting dominant nodule microboosting and ultrahypofractionation as emerging standards of care, urethral sparing radiotherapy is a powerful tool against radiation induced urinary toxicity while also maximising disease control. [ABSTRACT FROM AUTHOR]

Previous studies with the majority of breast cancer (BC) patients treated up to 2000 provided evidence that radiation dose to the heart from radiotherapy (RT) was linearly associated with increasing risk for long-term cardiac disease. RT techniques changed substantially over time. This study aimed to investigate the dose-dependent cardiac risk in German BC patients treated with more contemporary RT. In a cohort of 11,982 BC patients diagnosed in 1998–2008, we identified 494 women treated with 3D-conformal RT who subsequently developed a cardiac event. Within a nested case-control approach, these cases were matched to 988 controls. Controls were patients without a cardiac event after RT until the index date of the corresponding case. Separate multivariable conditional logistic regression models were used to assess the association of radiation to the complete heart and to the left anterior heart wall (LAHW) with cardiac events. Mean dose to the heart for cases with left-sided BC was 4.27 Gy and 1.64 Gy for cases with right-sided BC. For controls, corresponding values were 4.31 Gy and 1.66 Gy, respectively. The odds ratio (OR) per 1 Gy increase in dose to the complete heart was 0.99 (95% confidence interval (CI): 0.94–1.05, P =.72). The OR per 1 Gy increase in LAHW dose was 1.00 (95% CI: 0.98–1.01, P =.68). Contrary to previous studies, our study provided no evidence that radiation dose to the heart from 3D-conformal RT for BC patients treated between 1998 and 2008 was associated with risk of cardiac events. • Dose-response analysis on cardiac late effects in irradiated breast cancer patients. • Nested case-control study with individual retrospective heart dosimetry. • Included 494 cases and 988 controls treated in 1998–2008 in Germany. • No association for cardiac late effects of 3D-conformal radiotherapy observed. • No association for the complete heart and left anterior heart wall observed. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Medical Imaging & Radiation Sciences is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose: Children's Oncology Group study ACNS1123 tested the efficacy of reduced dose and field of radiation therapy (RT) for patients with localized nongerminomatous germ cell tumors (NGGCT) who achieved a complete (CR) or partial response (PR) to chemotherapy. Here, we evaluate the quality of RT and patterns of failure for patients eligible for reduced RT in this phase 2 trial.Methods and Materials: Patients with localized NGGCT with CR/PR after induction chemotherapy received reduced RT to 30.6 Gy whole ventricular irradiation and 54 Gy tumor-bed total dose. An atlas was provided to assist with complex RT volumes. Early interventional review was performed for the initial RT plan. Complete RT plans for all patients and images of relapsed patients were centrally reviewed at completion of therapy.Results: Between May 2012 and September 2016, 107 eligible patients were enrolled and 66 achieved a CR/PR after induction chemotherapy (± second-look surgery) and were eligible for reduced RT. Median follow-up was 4.4 years. Median age was 11.0 years (3.7-21.6), and 75% were male. Progression-free survival and overall survival at 4 years were 87.9% ± 4.0% and 92.4% ± 3.3% for 66 evaluable patients, respectively. Eight patients relapsed: 6 with isolated spinal relapse and 2 with disease in the brain and spine. After central review, 62 (94%) patients had RT targets contoured and dose delivered per protocol. None of the patients with deviations (n = 4) have progressed.Conclusions: Patterns of failure suggest the spine is at risk for recurrence for patients with localized NGGCT who receive reduced RT after a CR/PR to induction chemotherapy. Although survival data are encouraging, the pattern of failure has influenced the next prospective trial design. RT compliance was excellent despite complexity of radiation volumes, suggesting that providing visual guidance in the form of an online atlas contributes to higher quality RT plans. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Medical Imaging & Radiation Sciences is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Medical Imaging & Radiation Sciences is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Artificial intelligence, and in particular deep learning using convolutional neural networks, has been used extensively for image classification and segmentation, including on medical images for diagnosis and prognosis prediction. Use in radiotherapy prognostic modelling is still limited, however, especially as applied to toxicity and tumour response prediction from radiation dose distributions. We review and summarise studies that applied deep learning to radiotherapy dose data, in particular studies that utilised full three-dimensional dose distributions. Ten papers have reported on deep learning models for outcome prediction utilising spatial dose information, whereas four studies used reduced dimensionality (dose volume histogram) information for prediction. Many of these studies suffer from the same issues that plagued early normal tissue complication probability modelling, including small, single-institutional patient cohorts, lack of external validation, poor data and model reporting, use of late toxicity data without taking time-to-event into account, and nearly exclusive focus on clinician-reported complications. They demonstrate, however, how radiation dose, imaging and clinical data may be technically integrated in convolutional neural networks-based models; and some studies explore how deep learning may help better understand spatial variation in radiosensitivity. In general, there are a number of issues specific to the intersection of radiotherapy outcome modelling and deep learning, for example translation of model developments into treatment plan optimisation, which will require further combined effort from the radiation oncology and artificial intelligence communities. • The use of deep learning for radiotherapy outcome prediction is reviewed. • Ten studies used convolutional neural networks and spatial dose for prediction. • Studies were generally small and single institutional, with lack of external validation. • Deep learning may explore spatial variation in radiosensitivity, but methodology underdeveloped. [ABSTRACT FROM AUTHOR]

To analyse dosimetric and clinical predictors for acute and late gastrointestinal toxicity following chemoradiotherapy of anal cancer. Consecutive patients with locally advanced (T2 ≥4 cm – T4 or N+) anal cancer were selected from an institutional database (n = 114). All received intensity-modulated radiotherapy with concomitant 5-fluorouracil and mitomycin C. Gastrointestinal toxicity was retrospectively graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 and bowel cavity, small bowel and large bowel were contoured. Dosimetric and clinical variables were tested for associations with acute grade ≥3 gastrointestinal toxicity and late grade ≥2 gastrointestinal toxicity using the Mann–Whitney test, area under receiver operating characteristic curve (AUC) and logistic regression. The median follow-up was 40 months. Acute grade ≥3 gastrointestinal toxicity was seen in 51 (44.7%) of the patients; late grade ≥2 gastrointestinal toxicity was seen in 36 of the patients (39.6% of 91 patients with >1 year recurrence-free follow-up). Bowel cavity V30Gy was the best dosimetric predictor for acute gastrointestinal toxicity (AUC 0.633; P = 0.02). Large bowel V20Gy was the best dosimetric predictor for late gastrointestinal toxicity (AUC 0.698; P = 0.001) but showed no association with acute gastrointestinal toxicity. In multivariate logistic regression, increasing age was significantly associated with acute gastrointestinal toxicity; smoking and large bowel V20Gy were significantly associated with late gastrointestinal toxicity. Patients who experienced acute grade ≥3 gastrointestinal toxicity were not at an increased risk of late grade ≥2 gastrointestinal toxicity (odds ratio 1.3; P = 0.55). Factors of importance for acute and late gastrointestinal toxicity were not the same. Bowel cavity V30Gy is a good metric to use for the prediction of acute gastrointestinal toxicity, but the results of our study indicate that individual large and small bowel loops need to be contoured for better prediction of late gastrointestinal toxicity. The role of the large bowel as an important organ at risk for late gastrointestinal toxicity merits further research. • Early and late gastrointestinal toxicity was common following chemoradiotherapy of anal cancer • Predictors for early and late gastrointestinal toxicity were not the same • Dose to large bowel (V20Gy) was the most important predictor for late gastrointestinal toxicity • Individual large bowel loops need to be contoured to predict late gastrointestinal toxicity [ABSTRACT FROM AUTHOR]

Interstitial brachytherapy (ISBT) plays an important role in the management of locally advanced gynaecological malignancies. However, the relationship between urinary toxicity and dose to the urethra is not well understood. We sought to evaluate the correlation between urethral dose and the incidence of genitourinary complications among patients undergoing vaginal high dose rate ISBT. Eighty-three patients treated with ISBT between August 2014 and April 2018 were retrospectively reviewed. CTCAE version 5.0 was used to grade toxicity. Individual treatment plans were evaluated to collect dose parameters. Urethral contours were added to the structure sets using a uniform 1 cm diameter brush and minimum doses to the hottest 0.1, 0.2 and 0.5 cm3 (D0.1cm3, D0.2cm3 and D0.5cm3) of the urethra were obtained. Total (ISBT ± external beam radiotherapy) equivalent doses in 2 Gy fractions (EQD2) received by the targets and organs at risk were calculated. Numerical counts (%) and medians (interquartile range) were used to characterise the data. Fisher's exact and the Mann–Whitney–Wilcox tests were used as appropriate. Receiver operator curve analysis was used to define the urethral threshold dose that correlated to genitourinary toxicity. The median age and follow-up times were 67 years (59–75) and 25 months (16–37), respectively. Patients had predominantly primary endometrial (49%) and vaginal (37%) cancer, with four (5%) patients with metastatic rectal cancer to the vagina. Twenty-four of 79 (30%) patients experienced acute genitourinary toxicity and 34 of 71 (48%) experienced late genitourinary toxicity. In both analyses, the median urethral dose was significantly higher among those with toxicity. Receiver operator curve analysis indicated that D0.1cm3, D0.2cm3 and D0.5cm3 of the urethra were associated with the development of toxicity at doses >78, >71 and >62 Gy, respectively. Urethral dose seems to predict genitourinary toxicity in ISBT of vaginal tumours. Further study with an expanded cohort and longer follow-up is warranted. • A review of 83 patients, treated with high dose rate interstitial brachytherapy, at a tertiary centre in Canada. • Urethral D0.1cm3, D0.2cm3 and D0.5cm3 correlated with the development of acute and late genitourinary toxicity. • This report supports the growing evidence in favour of establishing dose constraints for the urethra in HDR brachytherapy. • Prospective trials using patient-reported outcomes are needed to validate results of this study. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Medical Imaging & Radiation Sciences is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Ionising radiation causes secondary tumours and/or enduring cognitive deficits, especially in children. Proton radiotherapy reduces exposure of the developing brain in children but may still cause some lasting effects. Recent observations show that ultra-high dose rate radiation treatment (≥40 Gy/s), called the FLASH effect, is equally effective at tumour control but less damaging to surrounding tissue compared with conventional dose rate protons (0.03–3 Gy/s). Most studies on the FLASH effect in brain and other tissues with different radiation modalities (electron and photon radiation), show FLASH benefits in these preclinical rodent models, but the data are limited, especially for proton FLASH, including for dose, dose rate and neurochemical and neurobehavioural outcomes. Tests of neurocognitive outcomes have been limited despite clinical evidence that this is the area of greatest concern. The FLASH effect in the context of proton exposure is promising, but a more systematic and comprehensive approach to outcomes is needed. • Brain radiotherapy in children is associated with cognitive problems. • Protons may produce fewer cognitive deficits than photons. • High dose rate protons (FLASH) may cause fewer cognitive problems. • We review limitations of existing studies, and offer suggestions for improvements. • FLASH shows potential to improve cognitive outcomes but is not yet proven. [ABSTRACT FROM AUTHOR]

Purpose: Dexamethasone is commonly given during radiation therapy (RT) to manage toxicities. Our study examines if dexamethasone coadministration with RT inhibits the RT-induced antitumor T cell response in mouse.Methods and Materials: Intramuscularly implanted MC38 tumors were irradiated with 15 Gy after establishing for 7 days. Tumor bearing mice were administered dexamethasone using multiple schedules and doses. Peripheral lymphocyte reduction was monitored by complete blood count and intratumoral and tumor draining lymph node (tdLN) populations by flow cytometry. Effector phenotype and function of ex vivo stimulated tumor-infiltrating lymphocytes (TILs) and naïve splenocytes as well as in vivo TILs with or without dexamethasone were monitored by flow cytometry and ELISA.Results: Long course high dose, short course high dose, and short course human equivalent dose dexamethasone reduced peripheral lymphocytes yet did not inhibit survival after irradiation. Short course high dose administration decreased TIL and tdLN lymphocyte activation as well as tdLN mass but did not affect TIL frequencies or change tdLN cell population composition. Dexamethasone inhibited effector function of ex vivo stimulated naïve splenocytes and TILs, but magnitude of IFN-γ secretion was consistently higher in TILs regardless of dexamethasone dose. In vivo analysis of TILs after irradiation and HE dexamethasone treatment showed that TILs had a similar effector phenotype compared with vehicle controls.Conclusions: Dexamethasone reduces blood and tdLN lymphocytes. Dexamethasone also suppresses TIL activation/effector function yet does not affect survival in irradiated MC38 tumor bearing mice, which depend on RT-induced immune responses for therapy efficacy. Additional study in human subjects is warranted. [ABSTRACT FROM AUTHOR]

The standard of care for the definitive treatment of locoregionally advanced cervical cancer is external beam radiation therapy (EBRT) with concurrent chemotherapy followed by a brachytherapy boost. Historically, EBRT was delivered via a two-dimensional technique based primarily on bony landmarks. This gave way to three-dimensional conformal radiation therapy, which allows for dose calculation and adjustment based on individual tumour and patient anatomy. Further technological advances have established intensity-modulated radiation therapy (IMRT) as a standard treatment modality, given the ability to maintain tumoricidal doses to target volumes while reducing unwanted radiation dose to nearby critical structures, thereby reducing toxicity. Routine image guidance allows for increased confidence in patient alignment prior to treatment, and the ability to visualise the daily position of the targets and organs at risk has been instrumental in allowing safe reductions in treated volumes. Additional EBRT technologies, including proton therapy and stereotactic body radiation therapy, may further improve the therapeutic index. In the realm of brachytherapy, a shift from point-based dose planning to image-guided brachytherapy has been associated with improved local control and reduced toxicity, with additional refinement ongoing. Here we will discuss these advances, the supporting data and future directions. [ABSTRACT FROM AUTHOR]

Purpose: To develop a noninvasive prognostic imaging biomarker related to hypoxia to predict SABR tumor control.Methods and Materials: A total of 145 subcutaneous syngeneic Dunning prostate R3327-AT1 rat tumors were focally irradiated once using cone beam computed tomography guidance on a small animal irradiator at 225 kV. Various doses in the range of 0 to 100 Gy were administered, while rats breathed air or oxygen, and tumor control was assessed up to 200 days. Oxygen-sensitive magnetic resonance imaging (MRI) (T1-weighted, ΔR1, ΔR2*) was applied to 79 of these tumors at 4.7 T to assess response to an oxygen gas breathing challenge on the day before irradiation as a probe of tumor hypoxia.Results: Increasing radiation dose in the range of 0 to 90 Gy enhanced tumor control of air-breathing rats with a TCD50 estimated at 59.6 ± 1.5 Gy. Control was significantly improved at some doses when rats breathed oxygen during irradiation (eg, 40 Gy; P < .05), and overall there was a modest left shift in the control curve: TCD50(oxygen) = 53.1 ± 3.1 Gy (P < .05 vs air). Oxygen-sensitive MRI showed variable response to oxygen gas breathing challenge; the magnitude of T1-weighted signal response (%ΔSI) allowed stratification of tumors in terms of local control at 40 Gy. Tumors showing %ΔSI >0.922 with O2-gas breathing challenge showed significantly better control at 40 Gy during irradiation while breathing oxygen (75% vs 0%, P < .01). In addition, increased radiation dose (50 Gy) substantially overcame resistance, with 50% control for poorly oxygenated tumors. Stratification of dose-response curves based on %ΔSI >0.922 revealed different survival curves, with TCD50 = 36.2 ± 3.2 Gy for tumors responsive to oxygen gas breathing challenge; this was significantly less than the 54.7 ± 2.4 Gy for unresponsive tumors (P < .005), irrespective of the gas inhaled during tumor irradiation.Conclusions: Oxygen-sensitive MRI allowed stratification of tumors in terms of local control at 40 Gy, indicating its use as a potential predictive imaging biomarker. Increasing dose to 50 Gy overcame radiation resistance attributable to hypoxia in 50% of tumors. [ABSTRACT FROM AUTHOR]

Purpose: Advances in germline genetic testing have led to a surge in identification of ataxia-telangiectasia mutated (ATM) variant carriers among breast cancer patients, raising numerous questions regarding use of breast radiation therapy (RT) in this population.Methods: A literature search using PubMed identified articles assessing association(s) between the germline ATM variant status and the risk of toxicity after breast RT. An expert panel of breast radiation oncologists, genetic counselors, and basic scientists convened to review the association between ATM variants and radiation-induced toxicity or secondary malignancy risk and to determine any impact on breast RT recommendations.Results: Carriers of pathogenic variants in ATM have a 2- to 4-fold increased risk for developing breast cancer. ATM variants do not consistently increase risks of toxicities after RT, except possibly among patients with the single nucleotide variant c5557G>A (rs1801516), in whom a small increased risk for the development of both acute and late radiation effects has been identified. In most breast cancer patients with ATM variants, the excess 5-year absolute risk of developing a secondary contralateral breast cancer (CBC) after radiation is extremely low. The exception is in women younger than 45 years old with deleterious rare ATM missense variants, who may be at higher risk for developing a radiation-induced CBC over time.Conclusions: Adjuvant radiation is safe for most breast cancer patients who harbor ATM variants. The possible exceptions are patients with the variant c5557G>A (rs1801516) and patients younger than 45 years old with certain rare deleterious ATM variants, who may be at higher risk for developing CBC. These latter patients should be counseled regarding this potential risk, and every effort should be made to minimize the contralateral breast dose. However, the inconsistency of published data limits precise recommendations, magnifying the need for further prospective studies and the development of a centralized database cataloging RT outcomes and genetic status. [ABSTRACT FROM AUTHOR]

Purpose: Bolus use during postmastectomy radiation therapy doubles the risk of grade 2 and 3 skin toxicity. Despite its unknown benefit, bolus is often prescribed during postmastectomy radiation therapy for patients without skin involvement.Methods and Materials: For women with breast cancer receiving photon 3-dimensional conformal radiation therapy, bolus was used routinely for chest walls but was omitted for breast reconstructions by about half of radiation oncologists from 2007 to 2011. Eligible patients had newly diagnosed invasive breast cancers without skin involvement (pT1-4a, any-N, M0) treated with adjuvant or neoadjuvant radiation therapy. For the bolus and no-bolus groups, we compared the cumulative incidence of local recurrence (LR) and locoregional recurrence (LRR) with distant recurrence and death as competing risks and breast cancer mortality (BCM). Multivariable analysis of LR and BCM included stage, subtype, lymphovascular invasion, grade, margin status, beam energy, bolus use, hormone therapy, chemotherapy, and reconstruction.Results: Systemic therapy was used for 98% of the 1887 patients. The bolus group had 1569 patients and the no-bolus group had 318 patients. Bolus was used in 51% (281/550) of patients treated with reconstruction and 96% (1288/1337) of patients treated without reconstruction. The 10-year outcomes (95% confidence interval) in patients treated with and without bolus were, respectively: LR 1.9% (1.3-2.7) versus 0.9% (0.3-2.6), LRR 3.1% (2.3-4.0) versus 3.2% (1.6-5.5), and BCM 19.4% (17.3-21.6) versus 18.3% (13.9-23.2). On multivariable analysis, bolus use was not associated with better LR (hazard ratio = 1.4 [0.3-6.4]) or BCM (hazard ratio = 0.8 [0.5-1.2]).Conclusions: For patients treated with mastectomy, radiation therapy, and modern systemic therapy, the cumulative incidence of LR was low, with or without bolus. Because bolus use increases toxicity and does not reduce LR or BCM, it should no longer be used routinely for patients without skin involvement who receive systemic therapy. [ABSTRACT FROM AUTHOR]

This study aims to find out the reduction in radiation exposure rate in mobile X-ray examinations equipped with a Bluetooth wireless exposure switch system. This is a pre-experimental study. X-ray examination was simulated by exposing a radiographic phantom (Kyoto KagakuTM, CTU-41) using an X-ray mobile unit (CorsixTM R32-Italy). Exposures were performed using a developed Bluetooth wireless exposure switch with an exposure factor for lateral lumbar examination (85 kVp, 20 mAs, and 100 cm Source-Image Distance). Exposure rates were measured (RAMION survey meter) on various exposing positions to the X-ray source, repeated every 0,5 meters, up to 10 meters with no barrier, and up to 3 meters with a full barrier. The data were analyzed descriptively to find out the reduction trend. Radiation exposure rates (in mSv/h) at 0,5 meters to 4.5 meters were 2.17; 1.27; 0,64; 0.13, 0.07; 0.03, 0.01, 0.01, 0.01, 0.00, respectively, and 0.00 mSv/h until 10 meters. The longer the exposure time to the X-ray source, the lower the radiation exposure rate. There was a 100% reduction from 2.17 mSv/hour at 0.5 meters to 0 mSv/hour at 4.5 meters by using the Bluetooth wireless exposure switch system. The radiation exposure rate at the exposing position decreases significantly if using a Bluetooth wireless exposure switch system at 4.5 meters, so it is very prospective to be applied for safer X-ray mobile examination. [ABSTRACT FROM AUTHOR]

The study evaluates the adherence of Exposure Indices (EIs) produced in a busy Indonesian hospital to Manufacturer-Recommended Exposure Index (MREI) levels published by manufacturers and investigates the factors affecting these values. A total of 75304 EI values for abdomen, chest, pelvis, head, spine, and extremity examinations were evaluated in different CR systems (Philips DR Digital Diagnost, Carestream DRX-Evolution stationary, and Carestream DRX-Revolution mobile unit). These EI values were then compared to the manufacturers' recommendations for each specific examination. Data regarding the patient's gender and age, exposure control selection, and the use of a secondary radiation grid were also collected. The Mann-Whitney U test was employed following descriptive statistics to determine any significant findings. Evaluation of EIs suggests a large degree of non-compliance with manufacturer guidelines, with the proportion of over- and underexposures being as high as 97.3% and 98.4% for specific examinations, respectively. Significant differences (p<0.05) in EI values were shown for patient gender and age, exposure control selection, and the use of the secondary radiation grid. A large level of non-adherence to MREIs has been demonstrated in one of Indonesia's busiest hospitals, with factors such as patient gender and age, exposure control selection, and the use of secondary radiation grids being important determinants of EI levels. [ABSTRACT FROM AUTHOR]

External beam radiotherapy (EBRT), as part of a trimodality approach, is an attractive bladder-preserving alternative to radical cystectomy. Several EBRT regimens with different treatment volumes have been described with similar tumour control and, so far, clear recommendations on the optimal radiotherapy regimen and treatment volume are lacking. The current review summarises EBRT literature on dose prescription, fractionation as well as treatment volume in order to guide clinicians in their daily practice when treating patients with muscle-invasive bladder cancer. Taking into account literature on repopulation, continuous-course radiotherapy can be used safely in daily practice where a split-course should only be reserved for those patients who are fit enough to undergo a radical cystectomy in case of a poor early response. A recent meta-analysis has proven that hypofractionated radiotherapy is superior to conventional radiotherapy with regards to invasive locoregional control with similar toxicity profiles. In the absence of node-positive disease, the target volume can be restricted to the bladder. In order to compensate for organ motion, very large margins need to be applied in the absence of image-guided radiotherapy (IGRT). Therefore, the use of IGRT or an adaptive approach is recommended. Based on the available literature, one can conclude that moderate hypofractionated radiotherapy to a dose of 55 Gy in 20 fractions to the bladder only, delivered with IGRT, can be considered standard of care for patients with node-negative invasive bladder cancer. [ABSTRACT FROM AUTHOR]

Objective: To identify the incidence of radiation-induced urologic complication requiring procedural intervention following high-dose radiotherapy for cervical carcinoma, and to identify predictors of complication occurrence.Materials and Methods: We performed a retrospective chart review of cervical cancer patients undergoing radiotherapy with primary focus on procedural complications (Clavien-Dindo ≥ III). Clinical data were collected including radiation dose, procedure performed, timing of complication, and need for additional procedures. Univariate and multivariate logistic regression modeling was performed to assess predictive value of demographic and clinical variables.Results: A total of 126 patients with FIGO stage 1A2-4B cervical cancer were included in study analysis, with 18 patients experiencing procedural complication (14.3%). A total of 22 complications were identified, representing an average of 1.2 complications per patient with complication. The most common complications were ureteral stricture and radiation cystitis. The most common nononcologic procedures performed in the treatment of these complications were ureteral stenting, percutaneous nephrostomy tube placement, and cystoscopy. Notably, a total of 259 procedures were performed in the treatment of urologic complications, representing 14.4 procedures per patient and 24.6 procedures per patient with ureteral stricture. Logistic regression demonstrated active smoking at the time of diagnosis to be a predictor of procedural complication.Conclusion: Radiotherapy in the treatment of cervical cancer is associated with a high rate of urologic procedural complication. These complications often require numerous procedures and long-term management given their complexity. These findings suggest a need for awareness and plans for multidisciplinary management of urologic complications in this patient population. [ABSTRACT FROM AUTHOR]

Purpose: Our purpose was to evaluate normal tissue complication probability (NTCP) models for their ability to describe the increase in tolerance as the length of irradiated spinal nerve is reduced in a pig.Methods and Materials: Common phenomenological and semimechanistic NTCP models were fit using the maximum likelihood estimate method to dose-response data from spinal nerve irradiation studies in pigs. Statistical analysis was used to compare how well each model fit the data. Model parameters were then applied to a previously published dose distribution used for spinal cord irradiation in rats under the assumption of a similar dose-response.Results: The Lyman-Kutcher-Burman model, relative seriality, and critical volume model fit the spinal nerve data equally well, but the mean dose logistic and relative seriality models gave the best fit after penalizing for the number of model parameters. The minimum dose logistic regression model was the only model showing a lack of fit. When extrapolated to a 0.5-cm simulated square-wave-like dose distribution, the serial behaving models showed negligible increase in dose-response curve. The Lyman-Kutcher-Burman model and relative seriality models showed significant shifting of NTCP curves due to parallel behaving parameters. The critical volume model gave the closest match to the rat data.Conclusions: Several phenomenological and semimechanistic models were observed to adequately describe the increase in the radiation tolerance of the spinal nerves when changing the irradiated length from 1.5 to 0.5 cm. Contrary to common perception, model parameters suggest parallel behaving tissue architecture. Under the assumption that the spinal nerve response to radiation is similar to that of the spinal cord, only the critical volume model was robust when extrapolating to outcome data from a 0.5-cm square-wave-like dose distribution, as was delivered in rodent spinal cord irradiation research. [ABSTRACT FROM AUTHOR]

To investigate the time-to-event and the evolution of sacral insufficiency fractures in gynaecological patients receiving pelvic external beam radiotherapy (EBRT) in relation to dosimetric and imaging parameters across a spectrum of radiotherapy delivery techniques, and to develop a predictive model with a clinical nomogram to identify those at risk of sacral insufficiency fracture. Patients who received radical or adjuvant pelvic EBRT for gynaecological malignancy between 2014 and 2019 were identified. The data collected were: demographics and clinical details; radiotherapy planning data: dose, fractionation, technique (fixed-field intensity-modulated radiotherapy, adaptive arc, and non-adaptive arc), 60 Gy simultaneous integrated boost. Each plan was examined to determine the sacral dose in 5%/Gy 3 increments. Follow-up magnetic resonance scans were reviewed for insufficiency fractures, defined as linear low T1-weighted signal intensity with a high short-T1 inversion recovery (STIR) signal. The site of insufficiency fracture was recreated on the planning computed tomography, the dose to insufficiency fracture contours was recorded and insufficiency fractures were determined as healed with resolution of high STIR signal. Univariable analysis was conducted of the clinical variables. The area under the receiver operator characteristic curve and odds ratio of the risk prediction model with 95% confidence interval are reported with a nomogram for use in clinical practice. 115 patients were identified; the median imaging follow-up was 12 months (2–47). 37.4% developed sacral insufficiency fractures; 93.0% were detected within 12 months of EBRT. At the final radiological follow-up, 83.7% of insufficiency fractures remained active. The radiotherapy delivery technique was not associated with insufficiency fracture after adjusting for patient age (P = 0.115). The location of the 60 Gy simultaneous integrated boost planning target volume did not impact upon the site of insufficiency fracture or the dose received by the insufficiency fracture sites. Age and V40Gy 3 are predictors for insufficiency fracture and form the clinical risk model (receiver operator characteristic 0.72). Age and V40Gy 3 predict sacral insufficiency fractures; future work should focus on optimising radiotherapy planning with adoption of a bone-sparing planning approach for those patients at high risk of insufficiency fracture. • Sacral insufficiency fracture following pelvic external beam radiotherapy (EBRT) causes patient morbidity. • 37.4% of this cohort developed sacral insufficiency fractures; 93.0% were detected within 12 months of EBRT. • A prognostic model and clinical nomogram is presented together with strategies to mitigate sacral insufficiency fractures. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Medical Imaging & Radiation Sciences is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Medical Imaging & Radiation Sciences is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose: Recent voxel-based studies have shown that the dose to specific rectal and urethro-vesical subregions is predictive of toxicities after prostate cancer intensity modulated radiation therapy. The objective of this study was to validate the discriminatory power of these subregions with respect to the whole organs in a large independent population.Methods and Materials: The validation cohort consisted of 450 patients from the TROG03.04-RADAR trial treated with 3-dimensional conformal radiation therapy at 66 to 74 Gy. Previous voxel-based analyses identified an inferoanterior rectal subregion as predictive of rectal bleeding and 5 subregions in the urethra and the posterior and superior part of the bladder as predictive of urinary incontinence, dysuria, retention, and hematuria. In the validation cohort, these subregions were segmented in each patient's anatomy. Dose-volume histograms (DVHs) of the whole organs and the 6 subregions were compared bin-wise between patients with and without toxicities. The discriminatory power of DVHs for grade ≥2 toxicity endpoints was assessed using the area under the receiver operating characteristic curve (AUC).Results: Subregion DVHs were significantly different between patients with and without toxicities for late rectal bleeding (V44-V74), acute urinary incontinence (V68-V72), late dysuria (V56-V68), and late retention (V14-V64). The dose to the rectal subregion and the whole rectum were equally predictive of rectal bleeding (V68; AUC = 0.61). The doses to 3 out of the 5 urethro-vesical subregions were found to be more predictive than the dose to the whole bladder: in the urethra for acute incontinence (V71 AUC = 0.69 vs V71 AUC = 0.66), in the posterior part of the bladder for late dysuria (V65 AUC = 0.66 vs V68 AUC = 0.59), and late retention (V39 AUC = 0.74 vs no significant AUC).Conclusions: Three subregions located in the urethra and the bladder were successfully validated as more predictive of urinary toxicity than the whole bladder for urinary incontinence, retention, and dysuria. Sparing the posterior part of the bladder in particular in treatment planning may reduce the risk of late urinary retention. [ABSTRACT FROM AUTHOR]

Purpose: In a randomized focal dose escalation radiation therapy trial for prostate cancer (FLAME), up to 95 Gy was prescribed to the tumor in the dose-escalated arm, with 77 Gy to the entire prostate in both arms. As dose constraints to organs at risk had priority over dose escalation and suboptimal planning could occur, we investigated how well the dose to the tumor was boosted. We developed an anatomy-based prediction model to identify plans with suboptimal tumor dose and performed replanning to validate our model.Methods and Materials: We derived dose-volume parameters from planned dose distributions of 539 FLAME trial patients in 4 institutions and compared them between both arms. In the dose-escalated arm, we determined overlap volume histograms and derived features representing patient anatomy. We predicted tumor D98% with a linear regression on anatomic features and performed replanning on 21 plans.Results: In the dose-escalated arm, the median tumor D50% and D98% were 93.0 and 84.7 Gy, and 99% of the tumors had a dose escalation greater than 82.4 Gy (107% of 77 Gy). In both arms organs at risk constraints were met. Five out of 73 anatomic features were found to be predictive for tumor D98%. Median predicted tumor D98% was 4.4 Gy higher than planned D98%. Upon replanning, median tumor D98% increased by 3.0 Gy. A strong correlation between predicted increase in D98% and realized increase upon replanning was found (ρ = 0.86).Conclusions: Focal dose escalation in prostate cancer was feasible with a dose escalation to 99% of the tumors. Replanning resulted in an increased tumor dose that correlated well with the prediction model. The model was able to identify tumors on which a higher boost dose could be planned. The model has potential as a quality assessment tool in focal dose escalated treatment plans. [ABSTRACT FROM AUTHOR]

Purpose: Many patients with lung cancer are inactive due to their disease and underlying comorbidities, and activity levels can decline further during cancer therapy. Here we explore dosimetric predictors of activity decline in a cohort of patients who underwent continuous activity monitoring during definitive concurrent chemoradiotherapy (CRT) for locally advanced lung cancer.Methods and Materials: We identified patients who participated in prospective clinical trials involving the use of a commercial fitness tracker throughout the course of CRT. For each patient, we applied linear regression to log-transformed daily step counts to compute the weekly rate of activity change from 1 week before radiation therapy (RT) initiation to 2 weeks after RT completion. Clinical and dosimetric factors were tested as predictors of activity change using linear regressions.Results: Forty-six patient met the eligibility criteria. Median age was 66 years (range, 38-90). Pretreatment Eastern Cooperative Oncology Group performance status was 0, 1, and 2 for 17%, 70%, and 13%, respectively. Mean lung dose ranged from 5.0 to 23.5 Gy, mean esophagus dose from 1.1 to 39.6 Gy, and mean heart dose from 0.6 to 31.5 Gy. Median daily step count average was 5861 (interquartile range, 3540-8282) before RT and 3422 (interquartile range, 2364-5395) 2 weeks after RT completion. Rate of activity change was not significantly associated with age, performance status, or mean RT dose received by lungs or esophagus. In multivariate analysis, mean heart dose was significantly associated with rate of activity decline, with a 3.1% reduction in step count per week for every 10 Gy increase in mean heart dose (95% confidence interval: 0.5-5.7, P = .023).Conclusions: Extent of cardiac irradiation is associated with the rate of physical activity decline during CRT for lung cancer. Our novel finding contributes to the growing body of evidence that adverse effects of cardiac irradiation may be manifested at early time points. [ABSTRACT FROM AUTHOR]

Background: Radon and its progenies contribute significantly to the natural background radiation and cause several thousands of lung cancer cases per year worldwide. Moreover, patients with chronic inflammatory joint diseases are treated in radon galleries. Due to the complex nature of radon exposure, the doses associated with radon exposures are difficult to assess. Hence, there is a clear need to directly measure dose depositions from radon exposures to provide reliable risk estimates for radiation protection guidelines.Objectives: We aimed to assess tissue-specific radiation doses associated with radon activity concentrations, that deposit similar dose levels as the annual natural radon exposure or radon gallery visits.Methods: We exposed mice to defined radon concentrations, quantified the number of 53BP1 foci as a measure of induced DNA damage, and compared it with the number of foci induced by known doses of reference-type radiations. An image-based analysis of the 3-dimensional foci pattern provided information about the radiation type inflicting the DNA damage.Results: A 1-hour exposure to 440 kBq/m3 radon-induced DNA damage corresponding to a dose of ∼10 mGy in the lung and ∼3.3 mGy in the kidney, heart, and liver. A 1-hour exposure to 44 kBq/m3 provided values consistent with a linear relationship between dose and radon concentration. Two-thirds of the dose in the lung was caused by α-particles. The dose in the kidney, heart, and liver and one-third of the dose in the lung likely resulted from β- and γ-rays.Discussion: We found that radon exposures mainly lead to α-particle-induced DNA damage in the lung, consistent with the lung cancer risk obtained in epidemiologic studies. Our presented biodosimetric approach can be used to benchmark risk model calculations for radiation protection guidelines and can help to understand the therapeutic success of radon gallery treatments. [ABSTRACT FROM AUTHOR]

Purpose: To study the dosimetric risk factors for radiation-induced proximal bronchial tree (PBT) toxicity in patients treated with radiation therapy for non-small cell lung cancer (NSCLC).Methods and Materials: Patients with medically inoperable or unresectable NSCLC treated with conventionally fractionated 3-dimensional conformal radiation therapy (3DCRT) in prospective clinical trials were eligible for this study. Proximal bronchial tree (PBT) and PBT wall were contoured consistently per RTOG 1106 OAR-Atlas. The dose-volume histograms (DVHs) of physical prescription dose (DVHp) and biological effective dose (α/β = 2.5; DVH2.5) were generated, respectively. The primary endpoint was PBT toxicities, defined by CTCAE 4.0 under the terminology of bronchial stricture/atelectasis.Results: Of 100 patients enrolled, with a median follow-up of 64 months (95% confidence interval [CI], 50-78), 73% received 70 Gy or greater and 17% developed PBT toxicity (grade 1, 8%; grade 2, 6%; grade 3, 0%; and grade 4, 3%). The median time interval between RT initiation and onset of PBT toxicity was 8.4 months (95% CI, 4.7-44.1). The combined DVHs showed that no patient with a PBT maximum physical dose <65 Gy developed any PBT toxicity. Cox proportional hazards analysis and receiver operating characteristic analysis demonstrated that V75 of PBT was the most significant dosimetric parameter for both grade 1+ (P = .035) and grade 2+ (P = .037) PBT toxicities. The dosimetric thresholds for V75 of PBT were 6.8% and 11.9% for grade 1+ and grade 2+ PBT toxicity, respectively.Conclusions: V75 of PBT appeared be the most significant dosimetric parameter for PBT toxicity after conventionally fractionated thoracic 3DCRT. Constraining V75 of PBT can limit clinically significant PBT toxicity. [ABSTRACT FROM AUTHOR]

• Reirradiation is a treatment option for locoregionally recurrent NSCLC. • Evidence are actually limited and no analysis exists to guide its indication. • The current review explores the state of the art of reirradiation in this setting. • Reirradiation is feasible and can attain in selected patients long-term control. • Patients selection criteria and toxicity predictive factors were identified. The prognosis of lung cancer patients has improved in the last few years. Despite definitive therapy, local recurrence or a second primary tumour can occur in many patients within previously irradiated areas. Recent developement of more accurate techniques in radiation oncology allows delivery of high radiation dose to the tumor with the aim of improving local control, delaying disease progression and in some cases even curing. Nevertheless, the use of high dose in the reirradiation setting is not without risks, especially when treatment volumes overlap with previously irradiated tissues. The risk of adverse effects must be balanced with the choice of an effective treatment by selecting suitable candidates and the best radiation technique. In this systemic review efficacy and toxicity of reirradiation in locoregionally recurrent non-small-cell lung cancer is extensively discussed. Results indicate that reirradiation might be beneficial in well-selected patients. Prospective and high quality studies are necessary in this field. [ABSTRACT FROM AUTHOR]

Purpose: After publication of the radiation field design in the American College of Surgeons Oncology Group Z0011 trial, a radiation therapy quality assurance review was integrated into the Intergroup-Sentinel-Mamma (INSEMA) trial. We aimed to investigate the role of patient characteristics, extent of axillary surgery, and radiation techniques for dose distribution in ipsilateral axillary levels.Methods and Materials: INSEMA (NCT02466737) has randomized 5542 patients who underwent breast-conserving surgery. Of these, 276 patients from 108 radiation therapy facilities were included in the central review, using the planning records of the first 3 patients treated at each site.Results: Of the 276 patients, 41 had major deviations (ie, no axillary contouring or submission of insufficient records) leading to exclusion. A total of 235 (85.1%) radiation therapy planning records were delineated according to the INSEMA protocol, including 9 (3.8%) cases with minor deviations. At least 25% of INSEMA patients were unintentionally treated with ≥95% of the prescribed breast radiation dose in axillary level I. Approximately 50% of patients were irradiated with a median radiation dose of more than 85% of prescription dose in level I. Irradiated volumes and applied doses were significantly lower in levels II and III compared with level I. However, 25% of patients still received a median radiation dose of ≥75% of prescription dose to level II. Subgroup analysis revealed a significant association between incidental radiation dose in the axilla and obesity. Younger age, boost application, and fractionation schedule showed no impact on axillary dose distribution.Conclusions: Assuming ≥80% of prescribed breast dose as the optimal dose for curative radiation of low-volume disease in axillary lymph nodes, at least 50% of reviewed INSEMA patients received an adequate dose in level I, even with contemporary 3-dimensional techniques. Dose coverage was much less in axillary levels II and III, and far below therapeutically relevant doses. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Medical Imaging & Radiation Sciences is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Medical Imaging & Radiation Sciences is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Stereotactic ablative body radiotherapy doses for peripheral lung lesions caused high toxicity when used for central non-small cell lung cancer (NSCLC). To determine a safe stereotactic ablative body radiotherapy dose for central tumours, the phase I/II Radiation Therapy Oncology Group RTOG 0813 trial used 50 Gy/five fractions as a baseline. From 2013, 50 Gy/five fractions was adopted at the Beatson West of Scotland Cancer Centre for inoperable early stage central NSCLC. We report our prospectively collected toxicity and efficacy data. Patient and treatment characteristics were obtained from electronic medical records. Tumours were classed as moderately central or ultra-central tumours using published definitions. Toxicity was assessed in a centralised follow-up clinic at 2 weeks, 6 weeks, 3 months, 6 months, 1 year and 2 years after treatment. Fifty patients (31 women, 19 men, median age 75.1 years) were identified with T1-2N0M0 moderately central NSCLC; one patient had both an ultra-central and a moderately central tumour. Eighty-four per cent were medically unfit for surgery. Forty per cent had biopsy-proven NSCLC and 60% were diagnosed radiologically using 18-fluorodeoxyglucose positron emission tomography/computed tomography imaging. Fifty-six per cent of patients were Eastern Cooperative Oncology Group (ECOG) performance status 2 or worse. All patients received 50 Gy/five fractions on alternate days on schedule. Two patients died within 90 days of treatment, one from a chest infection, the other cause of death was unknown. There was one episode of early grade 3 oesophagitis and one grade 3 late dyspnoea. There was no grade 4 toxicity. Over a median follow-up of 25.2 months (range 1–70 months), there were 34 deaths: 18 unrelated to cancer and 16 due to cancer recurrence. The median overall survival was 27.0 months (95% confidence interval 20.6–35.9) and cancer-specific survival was 39.8 months (95% confidence interval 28.6, not reached). This study has shown that 50 Gy/five fractions is a safe dose and fractionation for early stage inoperable moderately central NSCLC, with outcomes comparable with other series, even with patients with a poor performance status. • Stereotactic radiotherapy for central lung cancer is associated with high toxicity. • 50 patients with central lung cancers were treated with 50 Gy in 5 fractions. • The overall grade 3 toxicity rate was 4% with 2 deaths within 90 days of treatment. • Median overall and cancer-specific survival was 27 and 39.8 months, respectively. • 50 Gy in 5 fractions is an acceptable treatment for moderately central lung cancer. [ABSTRACT FROM AUTHOR]

Purpose: Preclinical research into ultrahigh dose rate (eg, ≥40 Gy/s) "FLASH"-radiation therapy suggests a decrease in side effects compared with conventional irradiation while maintaining tumor control. When FLASH is delivered using a scanning proton beam, tissue becomes subject to a spatially dependent range of dose rates. This study systematically investigates dose rate distributions and delivery times for proton FLASH plans using stereotactic lung irradiation as the paradigm.Methods and Materials: Stereotactic lung radiation therapy FLASH-plans, using 244 MeV scanning proton transmission beams, with the Bragg peak behind the body, were made for 7 patients. Evaluated parameters were dose rate distribution within a beam, overall irradiation time, number of times tissue is irradiated, and quality of the FLASH-plans compared with the clinical volumetric-modulated arc therapy (VMAT) plans.Results: Sparing of lungs, thoracic wall, and heart in the FLASH-plans was equal to or better than that in the VMAT-plans. For a spot peak dose rate (SPDR, the dose rate in the middle of the spot) of 100 Gy/s, ∼40% of dose is delivered at FLASH dose rates, and for SPDR = 360 Gy/s this increased to ∼75%. One-hundred percent FLASH dose rate cannot be achieved owing to small contributions from distant spots with lower dose rates. The total irradiation time varied between 300 to 730 ms, and around 85% of the dose-receiving body volume was irradiated by either 1 or 2 beams.Conclusions: Clinical implementation of FLASH using scanning proton beams requires multiple treatment planning considerations: dosimetric, temporal, and spatial parameters all seem important. The FLASH efficiency of a scanning proton beam increases with SPDR. The methodology proposed in this proof-of-principle study provides a framework for evaluating the FLASH characteristics of scanning proton beam plans and can be adapted as FLASH parameters are better defined. It currently seems logical to optimize plans for the shortest delivery time, maximum amount of high dose rate coverage, and maximum amount of single beam and continuous irradiation. [ABSTRACT FROM AUTHOR]

The duodenum is a critical organ at risk while planning radiation for gastrointestinal cancers or para-aortic nodes from gynaecological cancers due to the close proximity to the target volumes. The aim of this study was to assess the dosimetric parameters of the duodenum received during radiotherapy to upper gastrointestinal and gynaecological malignancies and their correlation with clinical toxicity. All adult patients who were treated with radiotherapy for primary upper gastrointestinal cancers (liver, stomach, pancreas, gall bladder) and patients with gynaecological cancers who were treated with extended fields in view of para-aortic nodal involvement from 1 January 2010 to 31 July 2015 were considered for the study. The radiation dose prescription was 45 Gy to the elective clinical target volume and 52.5–60 Gy to the gross nodal volume. The planning computed tomography scan was retrieved and the dose–volume histogram parameters for the duodenum were extracted. The relative volumes of duodenum receiving a dose from 40 to 55 Gy in increments of 5 Gy (V40Gy, V45Gy, V50Gy, V55Gy) were also noted. Of the 258 patients assessed, 30 patients (12.1%) were detected to have grade 2–4 toxicities related to the duodenum as detected on endoscopy. Most had grade 3 toxicity – 18 patients were diagnosed with grade 3 toxicity and four patients had grade 4 toxicity. The most common toxicity noted was duodenal ulceration seen in 16 patients. The other toxicities were duodenal stricture in eight patients, duodenal perforation in five patients and one patient was reported to have duodenal fistula. The patients with duodenum receiving V55Gy ≥ 1 cm3 (7.7% versus 3.8%, P = 0.014) and V50Gy ≥ 4 cm3 (7.7% versus 3.8%, P = 0.014) had higher grade ≥2 duodenal toxicity. A threshold level of V55Gy ≥ 1 cm3 and V50Gy ≥ 4 cm3 for the duodenum is predictive of clinically significant grade 2 and higher toxicity and could serve as valid dose constraints for the duodenum. • The duodenum is a critical organ at risk during planning radiotherapy for the upper abdomen. • This study evaluated the dose–volume parameters for the duodenum in patients treated with radiation. • A positive correlation of V55Gy ≥ 1cm3 and V50Gy ≥ 4 cm3 was seen with grade 2 and higher duodenal toxicity. [ABSTRACT FROM AUTHOR]

Purpose: To develop and validate combined ion-beam with constant relative biological effectiveness (RBE) (CICR) particle therapy in single field arrangements for improved treatment efficacy, robustness, and normal tissue sparing.Methods and Materials: The PRECISE (PaRticle thErapy using single and Combined Ion optimization StratEgies) treatment planning system was developed to investigate clinical viability of CICR treatments. Single-field uniform dose (SFUD) with a single ion (proton [p], helium [He], or carbon [C]) and CICR (C-p and C-He) treatments were generated for 3 patient cases with a clinically prescribed dose of 3 Gy (RBE) per fraction. Spread-out Bragg peak plans were irradiated in homogenous and clinical-like settings using an anthropomorphic head phantom. A dosimetric and biological verification of CICRC-p treatments using a murine glioma cell line (GL261) was performed.Results: CICR treatment plans for the 3 patients presented highly uniform physical dose while reducing high dose-averaged linear energy transfer gradients compared with carbon ions alone. When considering uncertainty in tissue parameter (α/β)x assignment and RBE modeling, the CICRC-p treatment exhibited enhanced biophysical stability within the target volume, similar to protons alone. CICR treatments reduced dose to normal tissue surrounding the target, exhibiting similar or improved dosimetric features compared with SFUDHe. For both CICRC-p and SFUD treatments, measurements verified the planned dose in the target within ∼3%. Planned versus measured target RBE values were 1.38 ± 0.02 and 1.39 ± 0.07 (<1% deviation), respectively, for the CICRC-p treatment in heterogenous settings.Conclusions: Here, we demonstrate that by combining 2 (or more) ions in a single field arrangement, more robust biological and more conformal dose distributions can be delivered compared with conventional particle therapy treatment planning. This work constitutes the first dosimetric and biological verification of multi-ion particle therapy in homogeneous as well as heterogenous settings. [ABSTRACT FROM AUTHOR]

Background: Skin radiation injuries, especially radiation ulcers, are serious side effects caused by ionizing radiation during percutaneous coronary interventions (PCI). Because skin radiation injuries are closely associated with the peak skin dose, it is important to minimize the peak skin dose. The aim of the present study was to investigate the determinants of greater peak skin dose in current PCI.Methods: We included 707 consecutive coronary artery lesions, and divided them into an excess radiation group (n = 26; defined as peak skin dose ≥2 Gy) and a standard radiation group (n = 681; defined as peak skin dose <2 Gy). Clinical, lesion, and procedural characteristics were compared between the 2 groups. Univariate and multivariate logistic regression analyses were performed to identify determinants of the excess radiation group.Results: A multivariate logistic regression analysis revealed that body surface area (BSA) [0.1 m2 increase: odds ratio (OR) 1.39, 95% confidence interval (CI) 1.13-1.71, P < 0.01], PCI to a right coronary artery (RCA) (OR 3.11, 95% CI 1.35-7.17, P < 0.01), and PCI to a chronic total occlusion (CTO) (OR 6.69, 95% CI 2.65-16.87, P < 0.01) were significantly associated with the excess radiation group.Conclusions: Greater BSA, PCI to RCA lesions, and PCI to CTO lesions were significantly associated with excess radiation dose. The first step in the prevention of radiation injuries in current PCI will be to recognize these risk factors. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to assess the feasibility of carbon ion reirradiation (CIR) for recurrent head and neck cancer (HNC).Methods and Materials: This retrospective study included 229 patients with recurrent HNC who were treated with CIR between 2010 and 2017. We assessed progression-free survival, overall survival, pattern of failure, and toxicity. Of the primary tumors, 54.1% were adenoid cystic carcinomas, 26.2% were squamous cell carcinomas, 8.3% were adenocarcinomas, and 11.4% were other tumor entities.Results: The median radiation therapy interval was 3.9 years (range, 0.3-46.5 years), and patients received a median dose of 51 Gy (relative biological effectiveness [RBE]; range, 30-66 Gy [RBE]) in 3 Gy (RBE) fractions. The median cumulative lifetime dose after CIR was 132.8 Gy (range, 88.8-155.0 Gy). The median local progression-free survival after CIR was 24.2 months (95% confidence interval, 19.4-29.0 months), and the median overall survival was 26.1 months (95% confidence interval, 21.9-30.3 months). Serious acute toxicity (grade ≥3) after CIR included laryngeal edema, grade 4 (n = 2; 0.9%); dysphagia, grade 3 (n = 3; 1.3%); fistula, grade 3 (n = 1; 0.4%); and impaired hearing, grade 3 (n = 1; 0.4%). Late toxicities of grades 3 or higher (n = 18; 14.5%) included central nervous system necrosis, grades 4/3 (n = 1; 0.8%/n = 5; 4.0%); optic nerve disorder, grades 4/3 (n = 2; 1.6%/n = 2; 1.6%); impaired hearing, grade 3 (n = 5; 4.0%), osteonecrosis, grade 3 (n = 1; 0.8%); and carotid blowout, grade 4 (n = 1; 0.8%).Conclusions: In patients with locally recurrent HNC, CIR was a feasible, effective treatment with acceptable toxicity and good local control. Thus, CIR represented a valuable alternative to surgical salvage and palliative chemotherapy in selected patients. [ABSTRACT FROM AUTHOR]

Purpose: The treatment of nasopharyngeal carcinoma requires high radiation doses. The balance of the risks of local recurrence owing to inadequate tumor coverage versus the potential damage to the adjacent organs at risk (OARs) is of critical importance. With advancements in technology, high target conformality is possible. Nonetheless, to achieve the best possible dose distribution, optimal setting of dose targets and dose prioritization for tumor volumes and various OARs is fundamental. Radiation doses should always be guided by the As Low As Reasonably Practicable principle. There are marked variations in practice. This study aimed to develop a guideline to serve as a global practical reference.Methods and Materials: A literature search on dose tolerances and normal-tissue complications after treatment for nasopharyngeal carcinoma was conducted. In addition, published guidelines and protocols on dose prioritization and constraints were reviewed. A text document and preliminary set of variants was circulated to a panel of international experts with publications or extensive experience in the field. An anonymized voting process was conducted to rank the proposed variants. A summary of the initial voting and different opinions expressed by members were then recirculated to the whole panel for review and reconsideration. Based on the comments of the panel, a refined second proposal was recirculated to the same panel. The current guideline was based on majority voting after repeated iteration for final agreement.Results: Variation in opinion among international experts was repeatedly iterated to develop a guideline describing appropriate dose prioritization and constraints. The percentage of final agreement on the recommended parameters and alternative views is shown. The rationale for the recommendations and the limitations of current evidence are discussed.Conclusions: Through this comprehensive review of available evidence and interactive exchange of vast experience by international experts, a guideline was developed to provide a practical reference for setting dose prioritization and acceptance criteria for tumor volumes and OARs. The final decision on the treatment prescription should be based on the individual clinical situation and the patient's acceptance of optimal balance of risk. [ABSTRACT FROM AUTHOR]