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Background: Intraprostatic local radiorecurrence (LRR) after definitive radiation is being increasingly identified due to the implementation of molecular positron emission tomography (PET)/computed tomography (CT) imaging for the evaluation of biochemical recurrence. Salvage high‐dose rate (HDR) brachytherapy offers a promising local therapy option, with encouraging toxicity and efficacy based on early series. Furthermore, the incorporation of advanced imaging allows for focal HDR to further reduce toxicity to maximise the therapeutic ratio. The objectives of the 'focal salvage HDR brachytherapy for locally recurrent prostate cancer in patients treated with prior radiotherapy' (F‐SHARP) trial are to determine the acute and late toxicity and efficacy outcomes of focal salvage HDR brachytherapy for LRR prostate cancer. Study Design: The F‐SHARP is a multi‐institutional two‐stage Phase I/II clinical trial of salvage focal HDR brachytherapy for LRR prostate cancer enrolling patients at three centres. Endpoints: The primary endpoint is the acute radiation‐related Grade ≥3 Common Terminology Criteria for Adverse Events (CTCAE, version 4.03) genitourinary (GU) and gastrointestinal (GI) toxicity rate, defined as within 3 months of brachytherapy. Secondary endpoints include acute and late CTCAE toxicity, biochemical failure, patterns of clinical progression, disease‐specific and overall survival, and health‐related quality of life, as measured by the International Prostate Symptom Score and 26‐item Expanded Prostate Cancer Index Composite instruments. Patients and Methods: Key eligibility criteria include: biopsy confirmed LRR prostate adenocarcinoma after prior definitive radiation therapy using any radiotherapeutic modality, no evidence of regional or distant metastasis, and cT1–3a Nx or N0 prostate cancer at initial treatment. All patients will have multiparametric magnetic resonance imaging and molecular PET/CT imaging if possible. In Stage 1, seven patients will be accrued. If there are two or more GI or GU Grade ≥3 toxicities, the study will be stopped. Otherwise, 17 additional patients will be accrued (total of 24 patients). For Stage 2, the cohort will expand to 62 subjects to study the efficacy outcomes, long‐term toxicity profile, quality of life, and compare single‐ vs multi‐fraction HDR. Transcriptomic analysis of recurrence biopsies will be performed to identify potential prognostic and predictive biomarkers. [ABSTRACT FROM AUTHOR]

Purpose: Currently, calculations of proton range in proton therapy patients are based on a conversion of CT Hounsfield units of patient tissues into proton relative stopping power. Uncertainties in this conversion necessitate larger proximal and distal planned target volume margins. Proton CT can potentially reduce these uncertainties by directly measuring proton stopping power. We aim to demonstrate proton CT imaging with complex porcine samples, to analyze in detail three‐dimensional regions of interest, and to compare proton stopping powers directly measured by proton CT to those determined from x‐ray CT scans. Methods: We have used a prototype proton imaging system with single proton tracking to acquire proton radiography and proton CT images of a sample of porcine pectoral girdle and ribs, and a pig's head. We also acquired close in time x‐ray CT scans of the same samples and compared proton stopping power measurements from the two modalities. In the case of the pig's head, we obtained x‐ray CT scans from two different scanners and compared results from high‐dose and low‐dose settings. Results: Comparing our reconstructed proton CT images with images derived from x‐ray CT scans, we find agreement within 1% to 2% for soft tissues and discrepancies of up to 6% for compact bone. We also observed large discrepancies, up to 40%, for cavitated regions with mixed content of air, soft tissue, and bone, such as sinus cavities or tympanic bullae. Conclusions: Our images and findings from a clinically realistic proton CT scanner demonstrate the potential for proton CT to be used for low‐dose treatment planning with reduced margins. [ABSTRACT FROM AUTHOR]

Cutaneous T-cell lymphoma (CTCL) is a chronic, debilitating disease that has a severe impact on quality of life. We present a patient with multiple CTCL lesions on the bilateral feet, which impaired his ability to ambulate. His lesions on both feet were successfully treated with a total of 8 Gy in two fractions via high-dose-rate surface brachytherapy using the Freiburg Flap applicator. The deeper aspects of the bulkier lesions on the left foot were boosted with electron beam therapy. The radiation therapy was well tolerated, and the patient was able to regain his mobility after completing radiation therapy. To our knowledge, there are few reports utilizing brachytherapy in treating CTCL. Our case describes treatment of larger, more extensive CTCL lesions than previously reported. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Rhabdomyosarcomas (RMSs) are the most common soft tissue tumors in the pediatric population. The American Brachytherapy Society provides recommendations for the use of brachytherapy (BRT) in the treatment of soft tissue sarcomas; yet, there are no clearly defined recommendations for the use of adjuvant BRT in treating RMSs in particular. Radiation therapy has an important role in maximizing local control, and BRT has the advantage over external beam radiation therapy of providing a high dose of radiation to the most susceptible area of recurrence, while delivering a lower dose to the surrounding normal tissue. Methods and Materials: This study examines a group of 8 pediatric patients with RMSs who were treated with temporary low-dose-rate 125I BRT and investigates the efficacy and side effects of such treatment. Results: The results demonstrate a local recurrence rate of 12.5%, with minimal side effects occurring in the patients who had no prior radiation history. Each patient's side effects are discussed. Conclusions: The high efficacy and ease of radiation protection for visitors establishes this as an effective treatment that is logistically convenient for patients and families. This is the first report of patients exclusively with RMSs being treated exclusively with 125I BRT and demonstrates promising results. [Copyright &y& Elsevier]

We report that a localized intracellular and extracellular Ca2+ mobilization occurs at the site of microscopic epithelial damage in vivo and is required to mediate tissue repair. Intravital confocal/two-photon microscopy continuously imaged the surgically exposed stomach mucosa of anesthetized mice while photodamage of gastric epithelial surface cells created a microscopic lesion that healed within 15 min. Transgenic mice with an intracellular Ca2+-sensitive protein (yellow cameleon 3.0) report that intracellular Ca2+ selectively increases in restituting gastric epithelial cells adjacent to the damaged cells. Pretreatment with U-73122, indomethacin, 2-aminoethoxydiphenylborane, or verapamil inhibits repair of the damage and also inhibits the intracellular Ca2+ increase. Confocal imaging of Fura-Red dye in luminal superfusate shows a localized extracellular Ca2+ increase at the gastric surface adjacent to the damage that temporally follows intracellular Ca2+ mobilization. Indomethacin and verapamil also inhibit the luminal Ca2+ increase. Intracellular Ca2+ chelation (1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid/acetoxymethyl ester, BAPTA/AM) fully inhibits intracellular and luminal Ca2+ increases, whereas luminal calcium chelation (N-(2-hydroxyetheyl)-ethylendiamin-N,N,N'-triacetic acid trisodium, HEDTA) blocks the increase of luminal Ca2+ and unevenly inhibits late-phase intracellular Ca2+ mobilization. Both modes of Ca2+ chelation slow gastric repair. In plasma membrane Ca-ATPase 1+/- mice, but not plasma membrane Ca-ATPase 4-/- mice, there is slowed epithelial repair and a diminished gastric surface Ca2+ increase. We conclude that endogenous Ca2+, mobilized by signaling pathways and transmembrane Ca2+ transport, causes increased Ca2+ levels at the epithelial damage site that are essential to gastric epithelial cell restitution in vivo. [ABSTRACT FROM AUTHOR]

Purpose: Accurate target definition is critical for the appropriate application of radiation therapy. In 2008, the Radiation Therapy Oncology Group (RTOG) published an international collaborative atlas to define the clinical target volume (CTV) for intensity modulated pelvic radiation therapy in the postoperative treatment of endometrial and cervical cancer. The current project is an updated consensus of CTV definitions, with removal of all references to bony landmarks and inclusion of the para-aortic and inferior obturator nodal regions.Methods and Materials: An international consensus guideline working group discussed modifications of the current atlas and areas of controversy. A document was prepared to assist in contouring definitions. A sample case abdominopelvic computed tomographic image was made available, on which experts contoured targets. Targets were analyzed for consistency of delineation using an expectation-maximization algorithm for simultaneous truth and performance level estimation with kappa statistics as a measure of agreement between observers.Results: Sixteen participants provided 13 sets of contours. Participants were asked to provide separate contours of the following areas: vaginal cuff, obturator, internal iliac, external iliac, presacral, common iliac, and para-aortic regions. There was substantial agreement for the common iliac region (sensitivity 0.71, specificity 0.981, kappa 0.64), moderate agreement in the external iliac, para-aortic, internal iliac and vaginal cuff regions (sensitivity 0.66, 0.74, 0.62, 0.59; specificity 0.989, 0.966, 0.986, 0.976; kappa 0.60, 0.58, 0.52, 0.47, respectively), and fair agreement in the presacral and obturator regions (sensitivity 0.55, 0.35; specificity 0.986, 0.988; kappa 0.36, 0.21, respectively). A 95% agreement contour was smoothed and a final contour atlas was produced according to consensus.Conclusions: Agreement among the participants was most consistent in the common iliac region and least in the presacral and obturator nodal regions. The consensus volumes formed the basis of the updated NRG/RTOG Oncology postoperative atlas. Continued patterns of recurrence research are encouraged to refine these volumes. [ABSTRACT FROM AUTHOR]

Purpose: Women remain underrepresented at all levels within the field of radiation oncology. We sought to study current female residents' experiences and concerns to inform interventions to promote gender equity. Furthermore, we evaluated interest in a professional society specifically for women radiation oncologists.Methods and Materials: An anonymous 76-item survey was designed and distributed to current women residents in radiation oncology in 2017-2018. Analyses describe personal, program, and family characteristics and experiences before and after joining the field.Results: Of 170 female residents surveyed, 125 responded (74% response rate). Over one-quarter were in programs with ≤2 female residents (29%) and ≤2 female attendings (29%). One-third (34%) reported having children. Over half (51%) reported that lack of mentorship affected career ambitions. Over half (52%) agreed that gender-specific bias existed in their programs, and over a quarter (27%) reported they had experienced unwanted sexual comments, attention, or advances by a superior or colleague. Only 5% reported no symptoms of burnout. Almost all (95%) agreed that radiation oncology is perceived as family friendly; however, only 52% agreed that it actually is. An overwhelming majority (90%) expressed interest in joining a professional group for women in radiation oncology.Conclusions: In the first study to our knowledge to focus specifically on the experiences of women residents in radiation oncology, a number of areas for potential improvement were highlighted, including isolation and underrepresentation, mentorship needs, bias and harassment, and gender-based obstacles such as need for support during pregnancy and motherhood. These findings support the organization of groups such as the Society for Women in Radiation Oncology, which seeks to target these needs to promote gender equity. [ABSTRACT FROM AUTHOR]

Purpose: Bladder-preserving curative radiation therapy (RT) has been established as an excellent treatment option for select patients with muscle-invasive bladder cancer (MIBC). However, some clinicians have concerns that good outcomes are only achievable at high-volume facilities (HVFs) and academic centers (ACs), questioning successful reproducibility of curative RT at smaller centers. This study sought to determine whether treatment at ACs or HVFs was associated with better overall survival (OS) than treatment at nonacademic centers or lower-volume facilities.Methods and Materials: We performed a retrospective cohort study of National Cancer Database patients (n=2763) with cT2 to cT4 N0 M0 transitional cell MIBC who received curative RT (60-70 Gy) with or without concurrent chemotherapy. Cox proportional hazards models were used to estimate the instantaneous hazard of death as a function of univariate and multivariate patient characteristics and clinical measures.Results: Univariate analysis showed that academic facility type was significantly associated with improved OS (hazard ratio [HR], 0.88; 95% confidence interval [CI] 0.79-0.98; P=.02) whereas higher case volume was not associated with improved survival (HR, 0.97; 95% CI 0.92-1.01; P=.15). Multivariate analysis showed no differences in OS for treatment at ACs versus nonacademic centers (HR, 0.94; 95% CI 0.84-1.06; P=.31) or HVFs versus lower-volume facilities (HR, 0.99; 95% CI 0.94-1.04; P=.60). The 2-year OS rate was 54.5% (95% CI 52.5%-56.4%), and the 5-year OS rate was 28.9% (95% CI 27.0%-30.8%).Conclusions: Although some providers are cautious about offering curative RT at all centers, this large hospital-based study suggests that facility type and volume are not significantly associated with OS for patients undergoing curative RT after we account for other clinically relevant risk factors. The results of this study demonstrate that curative RT in the treatment of MIBC may be considered for patients regardless of facility type or volume. [ABSTRACT FROM AUTHOR]

Purpose: We transitioned from a low-dose-rate (LDR) to a high-dose-rate (HDR) prostate brachytherapy program. The objective of this study was to describe our experience developing a prostate HDR program, compare the LDR and HDR dosimetry, and identify the impact of several targeted interventions in the HDR workflow to improve efficiency., Methods and Materials: We performed a retrospective cohort study of patients treated with LDR or HDR prostate brachytherapy. We used iodine-125 seeds (145 Gy as monotherapy, and 110 Gy as a boost) and preoperative planning for LDR. For HDR, we used iridium-192 (13.5 Gy × 2 as monotherapy and 15 Gy × 1 as a boost) and computed tomography-based planning. Over the first 18 months, we implemented several targeted interventions into our HDR workflow to improve efficiency. To evaluate the progress of the HDR program, we used linear mixed-effects models to compare LDR and HDR dosimetry and identify changes in the implant procedure and treatment planning durations over time., Results: The study cohort consisted of 122 patients (51 who received LDR and 71 HDR). The mean D90 was similar between patients who received LDR and HDR ( P = .28). HDR mean V100 and V95 were higher ( P < .0001), but mean V200 and V150 were lower ( P < .0001). HDR rectum V100 and D1cc were lower ( P < .0001). The HDR mean for the implant procedure duration was shorter (54 vs 60 minutes; P = .02). The HDR mean for the treatment planning duration dramatically improved with the implementation of targeted workflow interventions (3.7 hours for the first quartile to 2.0 hours for the final quartile; P < .0001)., Conclusions: We successfully developed a prostate HDR brachytherapy program at our institution with comparable dosimetry to our historic LDR patients. We identified several targeted interventions that improved the efficiency of treatment planning. Our experience and workflow interventions may help other institutions develop similar HDR programs.