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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]

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: 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.