F-SHARP: a Phase I/II trial of focal salvage high-dose-rate brachytherapy for Radiorecurrent prostate cancer.

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.

ACR Appropriateness Criteria® Malignant or Aggressive Primary Musculoskeletal Tumor-Staging and Surveillance: 2022 Update.

Malignant or aggressive primary musculoskeletal tumors are rare and encompass a wide variety of bone and soft tissue tumors. Given the most common site for metastasis from these primary musculoskeletal tumors is to the lung, chest imaging is integral in both staging and surveillance. Extrapulmonary metastases are rarely encountered with only a few exceptions. Following primary tumor resection, surveillance of the primary tumor site is generally recommended. Local surveillance imaging recommendations differ between primary tumors of bone origin versus soft tissue origin. This document consolidates the current evidence and expert opinion for the imaging staging and surveillance of these tumors into five clinical scenarios. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer-reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances in which peer-reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

Implications of Medical Board Certification Practices on Family Planning and Professional Trajectory for Early Career Female Radiation Oncologists.

PURPOSE: Our purpose was to evaluate the effect of the current structure and schedule of the American Board of Radiology (ABR) radiation oncology initial certification (RO-IC) examinations, with a primary focus on implications for family planning and early professional barriers among female radiation oncologists. METHODS AND MATERIALS: A survey was conducted of crowdsourced ABR candidates and diplomates for radiation oncology between June and July of 2020. The primary study cohort was early career female radiation oncologists of the 2016 through 2021 graduating classes. RESULTS: The survey response rate of early career female radiation oncologists was 37% (126 of an estimated 337). Among this cohort, 58% (73 of 126) reported they delayed or are currently delaying/timing pregnancy or adoption to accommodate the annual schedule of the 4 qualifying and certifying examinations required to achieve board certification in radiation oncology. One in every 3 respondents who had attempted to become pregnant reported experiencing infertility (25 of 79, 32%). Women who reported intentionally delaying pregnancy to accommodate the ABR RO-IC examination schedule were significantly more likely to experience infertility (46% vs 18%, P = .008). Seven women (6%) reported at least a 1-year delay in sitting for a RO-IC examination due to an unavoidable scheduling conflict related to childbirth and/or the peripartum period. A majority reported that full board certification had a significant effect on achieving academic promotion or professional partnership (52%), annual compensation (54%), and nonclinical professional commitments (58%) - these rates mirror those of surveyed early career male counterparts (n = 101). CONCLUSIONS: The current structure and scheduling of the ABR RO-IC examinations imposes noteworthy hurdles for many female radiation oncologists when entering the workforce. The recent transition to virtual examination platforms creates an important opportunity to increase flexibility in the structure and scheduling of the board examination process to improve equitable board certification practices.

A Systematic Review and Meta-analysis of the Impact of Radiation-Related Lymphopenia on Outcomes in High-Grade Gliomas.

Supriya MallickIntroduction Malignant gliomas are the most common primary malignant brain tumors and are typically treated with maximal safe surgical resection followed by chemoradiation. One of the unintended effects of radiation is depletion of circulating lymphocyte pool, which has been correlated with inferior overall survival outcomes. Methods A comprehensive and systematic searches of the PubMed, Cochrane Central, and Embase databases were done to assess the studies that have reported radiation-related lymphopenia in high-grade gliomas. Hazard ratios (HRs), odds ratios (OR), and mean differences were represented with Forest plots comparing patients with severe lymphopenia and no severe lymphopenia. Review Manager Version 5.3 (The Nordic Cochrane Centre, Copenhagen, Denmark) was used for the analysis. Results Nineteen studies were included in the final systematic review and 12 studies were included in the meta-analysis. The odds of developing severe lymphopenia were 0.39 (95% CI:0.19, 0.81, I 2 = 94%, p = 0.01). Patients with severe lymphopenia were at increased risk of death with a pooled HR = 2.19 (95% CI: 1.70, 2.83, I 2 = 0%, p <0.00001) compared to patients with no severe lymphopenia. The mean difference in survival between patients with severe lymphopenia and no severe lymphopenia was -6.72 months (95% CI: -8.95, -4.49, I 2 = 99%, p <0.00001), with a better mean survival in the no severe lymphopenia group. Conclusion Radiation-induced severe lymphopenia was associated with poor overall survival and increased risk of death. Photon therapy, larger planning target volume, higher brain dose, higher hypothalamus dose, and female gender were associated with increased risk of severe lymphopenia.

A comparison of proton stopping power measured with proton CT and x-ray CT in fresh postmortem porcine structures.

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.

Socioeconomic Disparities in Non-Small Cell Lung Cancer With Brain Metastases at Presentation: A Population-Based Study.

OBJECTIVE/BACKGROUND: The purpose of this study was to characterize the impact of household income disparities in the survival of patients with non-small cell lung cancer (NSCLC) presenting with brain metastasis on a population-based level. METHODS: This is a population-based cohort study using the Surveillance, Epidemiology, and End Results (SEER) database from 2010-2016 including 15,808 NSCLC patients presenting with brain metastasis. RESULTS: This study comprises 15,808 adult patients with NSCLC presenting with brain metastases having an age range 64 ± 10 years with 51% male, 76% white, 52% married, 61% insured, and with 85% of lung adenocarcinoma histopathology. The 1-, 2- and 5-year survival rates for living in the lower household income quartile were 21%, 10%, and 3%, respectively, for the second quartile 24%, 10%, and 3%; for the third quartile 28%, 14%, and 4%; and for the top quartile 31%, 17%, and 4%, respectively. Multivariate Cox proportional hazard analysis showed that living in a higher quartile household income county is associated with increased survival (P < 0.0001), hazard ratio 0.87, 95% confidence interval (0.82-0.92). CONCLUSIONS: This population-based study suggests that living in higher median household income counties is associated with increased survival time and reduced risk of mortality for patients with NSCLC who have brain metastases present at diagnosis, independent of other factors. These findings underscore the importance of ensuring adequate and easy access to care for all patients, irrespective of their economic background.

Dosimetric assessment of brass mesh bolus and transparent polymer-gel type bolus for commonly used breast treatment delivery techniques.

We investigated skin dose enhancements of brass mesh bolus (BMB) and a recently developed transparent polymer-gel bolus (PGB) for clinically relevant breast treatment delivery techniques. The dose enhancement of the breast surface with BMB and PGB were compared to that of tissue-equivalent bolus. Three breast treatment plans were generated on CT scans of an anthropomorphic chest phantom: tangential step-and-shoot 3D conformal (3DCRT) planned using Field-in-Field (FiF), tangential sliding-window 3DCRT using Electronic Compensator (EC), and volumetric modulated arc therapy (VMAT). All plans were created using 6 MV photons and a prescription dose (Rx) of 180 cGy per fraction. Skin doses of all 3 plans were measured with radiochromic films, separately delivered in triplicate. Each plan was delivered to the phantom without bolus, and then with BMB (1 or 2 layers; 3 or 10 mm tissue-equivalent), PGB, and Superflab (3, 5, and 10 mm tissue-equivalent). Doses were determined by reading the radiochromic films with a flatbed scanner, and analyzing the images using a calibration curve for each specific batch. For all bolus types and plans, surface doses averaged over the 3 measurements were between 88.4% and 107.4% of Rx. Without bolus, average measured skin doses were between 51.2% and 64.2% of Rx. Skin doses with BMB and PGB were comparable to that with tissue-equivalent bolus. Over all 3 treatment delivery techniques, using BMB resulted in average skin doses of 92.8% and 102.1% for 1- and 2 layers, respectively, and using PGB results in average skin doses of 94.8%, 98.2%, and 99.7% for 3, 5, and 10-mm tissue-equivalent, respectively. The average measured skin doses with BMB and PGB agreed within ± 3% compared to the tissue-equivalent thickness bolus. We concluded that BMB and PGB are clinically equivalent in skin dose enhancement for breast treatment as the 3, 5, and 10 mm tissue-equivalent bolus.

NRG Oncology/RTOG Consensus Guidelines for Delineation of Clinical Target Volume for Intensity Modulated Pelvic Radiation Therapy in Postoperative Treatment of Endometrial and Cervical Cancer: An Update.

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.

A Survey Study of Female Radiation Oncology Residents' Experiences to Inform Change.

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.

#WomenWhoCurie: Leveraging Social Media to Promote Women in Radiation Oncology.

The proportion of female trainees in radiation oncology has generally declined despite increasing numbers of female medical students; as a result, radiation oncology is among the bottom 5 specialties in terms of the percentage of female applicants. Recently, social media has been harnessed as a tool to bring recognition to underrepresented groups within medicine and other fields. Inspired by the wide-reaching social media campaign of #ILookLikeASurgeon to promote female physicians, members of the Society for Women in Radiation Oncology penned a new hashtag and launched the #WomenWhoCurie social media campaign on Marie Curie's birthday November 7th, as part of their strategy to raise public awareness. From November 6, 2018 until November 10, 2018, the #WomenWhoCurie hashtag delivered 1,135,000 impressions, including 408 photos from all over the world including United States, Spain, Canada, France, Australia, Ireland, the United Kingdom, Mexico, Japan, the Netherlands, India, Ecuador, Panama, Brazil, and Nigeria. Alongside continued gender disparity research, social media should continue to be used as a tool to engage the community and spur conversations to formulate solutions for gender inequity.

Transitioning From a Low-Dose-Rate to a High-Dose-Rate Prostate Brachytherapy Program: Comparing Initial Dosimetry and Improving Workflow Efficiency Through Targeted Interventions.

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.

Extensive Cutaneous T-Cell Lymphoma of the Feet Treated with High-Dose-Rate Brachytherapy and External Beam Radiation.

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.

The Impact of Academic Facility Type and Case Volume on Survival in Patients Undergoing Curative Radiation Therapy for Muscle-Invasive Bladder Cancer.

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.

Concurrent chemotherapy is associated with improved survival in elderly patients with bladder cancer undergoing radiotherapy.

BACKGROUND: The current study was conducted to compare the overall survival (OS) of concurrent chemoradiotherapy (CCRT) versus radiotherapy (RT) alone in elderly patients (those aged ≥80 years) with muscle-invasive bladder cancer (MIBC). METHODS: Patients aged ≥80 years with cT2-4, N0-3, M0 transitional cell MIBC who were treated with curative RT (60-70 Gray) or CCRT were identified in the National Cancer Data Base. Univariable and multivariable frailty survival analyses, as well as 1-to-1 propensity score matching, were used to isolate the association between CCRT and OS. RESULTS: A total of 1369 patients who were treated with RT from 2004 through 2013 met eligibility criteria: 739 patients (54%) received RT alone and 630 patients (46%) received CCRT. The median age of the patients was 84 years (range, 80-90 years). The median follow-up was 21 months. The 2-year OS rate was 48%. When comparing CCRT with RT alone, the 2-year OS rate was 56% versus 42% (P<.0001), respectively. Multivariable analysis demonstrated that CCRT (hazard ratio [HR], 0.74; 95% confidence interval [95% CI], 0.65-0.84 [P<.0001]) and a higher RT dose (HR, 0.78; 95% CI, 0.67-0.90 [P<.001]) were associated with improved OS. T4 disease was associated with worse OS (HR, 1.42; 95% CI, 1.15-1.76 [P = .001]). After using 1-to-1 propensity score matching, there remained an OS benefit for the use of CCRT (HR, 0.77; 95% CI, 0.67-0.90 [P<.001]). CONCLUSIONS: CCRT is associated with improved OS compared with the use of RT alone in elderly patients with MIBC, independent of Charlson-Deyo comorbidity score, suggesting that CCRT should be used in this population. Cancer 2017;123:3524-31. © 2017 American Cancer Society.

Establishing a targeted plan for prophylactic dental extractions in patients with laryngeal cancer receiving adjuvant radiotherapy.

OBJECTIVE: The purpose of this study was to determine dose delivered to individual mandibular tooth-bearing regions during adjuvant intensity-modulated radiotherapy for laryngeal cancers. STUDY DESIGN: Twenty patients with laryngeal cancer treated with intensity-modulated radiotherapy were included. Individual mandibular tooth-borne areas were manually contoured. Average doses were calculated for individual teeth. RESULTS: Doses to individual teeth increased with more posterior location. Highest dose was observed for third molar (M3) (43.1 Gy; P < .001). Doses to molars and premolars correlated with T- and N-stage (P = .007; P < .001, respectively). For ipsilateral nodal disease, there was no difference between the doses to ipsilateral teeth and contralateral teeth. Only in N2 c tumors, dose was above our threshold for extraction for M3 only (51.5 Gy). CONCLUSIONS: T- and N-stage drive dose to individual mandibular tooth-borne areas. With the exception of the posterior molars, particularly in node-positive patients, radiation exposure falls below the threshold reported for pre-RT tooth extractions (50 Gy). We concluded that a more conservative approach to prophylactic tooth extraction with a greater emphasis on dental management may be warranted for the prevention of osteoradionecrosis in patients with laryngeal cancer receiving adjuvant RT.

Efficacy and morbidity of temporary (125)I brachytherapy in pediatric rhabdomyosarcomas.

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 (125)I 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 (125)I BRT and demonstrates promising results.

In vivo epithelial wound repair requires mobilization of endogenous intracellular and extracellular calcium.

We report that a localized intracellular and extracellular Ca(2+) 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 Ca(2+)-sensitive protein (yellow cameleon 3.0) report that intracellular Ca(2+) 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 Ca(2+) increase. Confocal imaging of Fura-Red dye in luminal superfusate shows a localized extracellular Ca(2+) increase at the gastric surface adjacent to the damage that temporally follows intracellular Ca(2+) mobilization. Indomethacin and verapamil also inhibit the luminal Ca(2+) increase. Intracellular Ca(2+) chelation (1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid/acetoxymethyl ester, BAPTA/AM) fully inhibits intracellular and luminal Ca(2+) increases, whereas luminal calcium chelation (N-(2-hydroxyetheyl)-ethylendiamin-N,N,N'-triacetic acid trisodium, HEDTA) blocks the increase of luminal Ca(2+) and unevenly inhibits late-phase intracellular Ca(2+) mobilization. Both modes of Ca(2+) 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 Ca(2+) increase. We conclude that endogenous Ca(2+), mobilized by signaling pathways and transmembrane Ca(2+) transport, causes increased Ca(2+) levels at the epithelial damage site that are essential to gastric epithelial cell restitution in vivo.