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Varicella and zoster, produced by varicella-zoster virus (VZV), are associated with an increased risk of stroke that may be due to persistent inflammation and hypercoagulability. Because substance P is associated with inflammation, hypercoagulability, and atherosclerotic plaque rupture that may contribute to increased stroke risk after VZV infection, we measured serum substance P in simian varicella virus-infected rhesus macaques. We found significantly increased and persistent serum substance P concentrations during varicella and zoster compared with pre-inoculation, supporting the hypothesis that VZV-induced increases in serum substance P may contribute to increased stroke risk associated with VZV infection.

Targeting the CD47-signal-regulatory protein α (SIRPα) pathway represents a novel therapeutic approach to enhance anti-cancer immunity by promoting both innate and adaptive immune responses. Unlike CD47, which is expressed ubiquitously, SIRPα expression is mainly restricted to myeloid cells and neurons. Therefore, compared to CD47-targeted therapies, targeting SIRPα may result in differential safety and efficacy profiles, potentially enabling lower effective doses and improved pharmacokinetics and pharmacodynamics. The development of effective SIRPα antagonists is restricted by polymorphisms within the CD47-binding domain of SIRPα, necessitating pan-allele reactive anti-SIRPα antibodies for therapeutic intervention in diverse patient populations. We immunized wild-type and human antibody transgenic chickens with a multi-allele and multi-species SIRPα regimen in order to discover pan-allelic and pan-mammalian reactive anti-SIRPα antibodies suitable for clinical translation. A total of 200 antibodies were isolated and screened for SIRPα reactivity from which approximately 70 antibodies with diverse SIRPα binding profiles, sequence families, and epitopes were selected for further characterization. A subset of anti-SIRPα antibodies bound to both human SIRPα v1 and v2 alleles with high affinity ranging from low nanomolar to picomolar, potently antagonized the CD47/SIRPα interaction, and potentiated macrophage-mediated antibody-dependent cellular phagocytosis in vitro. X-ray crystal structures of five anti-SIRPα antigen-binding fragments, each with unique epitopes, in complex with SIRPα (PDB codes 6NMV, 6NMU, 6NMT, 6NMS, and 6NMR) are reported. Furthermore, some of the anti-SIRPα antibodies cross-react with cynomolgus SIRPα and various mouse SIRPα alleles (BALB/c, NOD, BL/6), which can facilitate preclinical to clinical development. These properties provide an attractive rationale to advance the development of these anti-SIRPα antibodies as a novel therapy for advanced malignancies. Abbreviations: ADCC: antibody-dependent cellular cytotoxicity; ADCP: antibody-dependent cellular phagocytosis; CFSE: carboxyfluorescein succinimidyl ester; Fab: fragment antigen binding; Fc: fragment crystallizable; FcγR: Fcγ receptor; Ig: immunoglobulin; IND: investigational new drug; MDM⊘: monocyte-derived macrophage; NOD: non-obese diabetic; scFv: single chain fragment variable; SCID: severe combined immunodeficiency; SIRP: signal-regulatory protein

Purpose Intraoperatively implanted Cesium-131 (131Cs) permanent seed brachytherapy is used to deliver highly localized re-irradiation in recurrent head and neck cancers. A single planar implant of uniform air kerma strength (AKS) seeds and 10 mm seed-to-seed spacing is used to deliver the prescribed dose to a point 5 mm or 10 mm perpendicular to the center of the implant plane. Nomogram tables to quickly determine the required AKS for rectangular and irregularly shaped implants were created and dosimetrically verified. By eliminating the need for a full treatment planning system plan, nomogram tables allow for fast dose calculation for intraoperative re-planning and for a second check method. Material and methods TG-43U1 recommended parameters were used to create a point-source model in MATLAB. The dose delivered to the prescription point from a single 1 U seed at each possible location in the implant plane was calculated. Implant tables were verified using an independent seed model in MIM Symphony LDR™. Implant tables were used to retrospectively determine seed AKS for previous cases: three rectangular and three irregular. Results For rectangular implants, the percent difference between required seed AKS calculated using MATLAB and MIM was at most 0.6%. For irregular implants, the percent difference between MATLAB and MIM calculations for individual seed locations was within 1.5% with outliers of less than 3.1% at two distal locations (10.6 cm and 8.8 cm), which have minimal dose contribution to the prescription point. The retrospectively determined AKS for patient implants using nomogram tables agreed with previous calculations within 5% for all six cases. Conclusions Nomogram tables were created to determine required AKS per seed for planar uniform AKS 131Cs implants. Comparison with the treatment planning system confirms dosimetric accuracy that is acceptable for use as a second check or for dose calculation in cases of intraoperative re-planning.

Purpose Permanent interstitial brachytherapy is an appealing treatment modality for patients with locoregional recurrent, resectable head and neck carcinoma (HNC), having previously received radiation. Cesium-131 (131Cs) is a permanent implant brachytherapy isotope, with a low average photon energy of 30 keV and a short half-life of 9.7 days. Exposure to medical staff and family members is low; patient isolation and patient room shielding are not required. This work presents a single institution’s implementation process of utilizing an intraoperative, permanent 131Cs implant for patients with completely resected recurrent HNC. Material and methods Fifteen patients receiving 131Cs permanent seed brachytherapy were included in this analysis. The process of pre-planning, selecting the dose prescription, seed ordering, intraoperative procedures, post-implant planning, and radiation safety protocols are described. Results Tumor volumes were contoured on the available preoperative PET/CT scans and a pre-implant treatment plan was created using uniform source strength and uniform 1 cm seed spacing. Implants were performed intraoperatively, following tumor resection. In five of the fifteen cases, intraoperative findings necessitated a change from the planned number of seeds and recalculation of the pre-implant plan. The average prescription dose was 56.1 ±6.6 Gy (range, 40-60 Gy). The average seed strength used was 2.2 ±0.2 U (3.5 ±0.3 mCi). Patients returned to a recovery room on a standard surgical floor and remained inpatients, without radiation safety restrictions, based on standard surgical recovery protocols. A post-implant treatment plan was generated based on immediate post-operative CT imaging to verify the seed distribution and confirm delivery of the prescription dose. Patients were provided educational information regarding radiation safety recommendations. Conclusions Cesium-131 interstitial brachytherapy is feasible and does not pose major radiation safety concerns; it should be considered as a treatment option for previously irradiated patients with recurrent, resectable HNC.

Purpose Permanent seed implant cesium-131 (131Cs) brachytherapy provides highly localized radiation for patients with recurrent head and neck cancer (HNC), who may be ineligible for external beam radiation therapy due to a high-risk of toxicity. As carotid blowout is a concern in the setting of re-irradiation, a dose to the carotid artery was examined for 131Cs brachytherapy implants. Material and methods Eleven patients were implanted with 131Cs adjacent to carotid at the time of resection for recurrent HNC. Vascularized tissue flaps were used in some patients. The carotid artery was contoured on the post-implant brachytherapy treatment plan, and the maximum carotid point dose and minimum carotid-seed distances are reported. The incidence of carotid blowout in the follow-up period was also measured. Results The maximum carotid dose was 77 ±52 Gy (range, 3-158 Gy). The closest seed to the carotid artery was 0.8 ±0.8 cm (range, 0.2-2.6 cm). One patient without a flap experienced carotid blowout, which was attributed to a non-healing wound rather than to high radiation doses. Conclusions Carotid artery doses from 131Cs are reported. Vascularized tissue flaps should be considered when planning 131Cs brachytherapy.

Background Implementation science frameworks aided the development of a new, evidence-based clinical physical therapy program. The purpose of this report is to describe the process of sustaining a clinical program in practice for over 4 years. We present a framework for integrating tools for sustainability with the Knowledge-to-Action model in the context of a proactive physical therapy (PAPT) program for individuals with early-stage Parkinson’s disease. Methods Sustainability of implementation strategies was addressed using the Dynamic Sustainability Framework and sustainability assessment tools. Repeated retrospective medical record reviews and phone interviews were used to evaluate the reach and adoption of the PAPT over 4 years. Characteristics of those who engaged with PAPT, implementation fidelity, and clinical effectiveness were assessed for year 1 and year 3. Sustainability was measured using RE-AIM, NHS Sustainability Model, and Clinical Sustainability Assessment Tool. Results Reach increased from 28 to 110 total patients per year and spread occurred from one to three sites. PAPT user age, sex, Hoehn and Yahr rating, time since diagnosis, and type of insurance were similar in year 1 and year 3 (p > 0.05). The program sustained its effect to help participants increase or maintain self-reported exercise (Y1, 95%; Y3, 100%). However, upon evaluation PAPT users in year 3 had longer time since symptom onset and worse UPDRS motor scores compared to the PAPT users in year 1 (p < 0.05). All sites sustained the core intervention components, with sustainability scores of 71/100 (± 9.9) on the NHS Sustainability Model and 6.1/7 (± 0.9) on the Clinical Sustainability Assessment Tool. Conclusions Integrating multiple sustainability models and assessments supported continued effectiveness, spread, and sustainment of PAPT for 4 years. Effective planning, anticipating common healthcare changes, and addressing sustainability determinants early in program implementation were essential aspects of long-term success.

Background The COVID-19 pandemic challenges our ability to safely treat breast cancer patients and requires revisiting current techniques to evaluate optimal strategies. Potential long-term sequelae of breast radiation have been addressed by deep inspiration breath-hold (DIBH), prone positioning, and four-dimensional computed tomography (4DCT) average intensity projection (AveIP)-based planning techniques. Dosimetric comparisons to determine the optimal technique to minimize the normal tissue dose for left-sided breast cancers have not been performed. Methods Ten patients with left-sided, early-stage breast cancer undergoing whole breast radiation were simulated in the prone position, supine with DIBH, and with a free-breathing 4DCT scan. The target and organs at risk (OAR) contours were delineated in all scans. Target volume coverage and OAR doses were assessed. One-way analysis of variance (ANOVA) and Kruskal-Wallis one-way ANOVA were used to detect differences in dosimetric parameters among the different treatment plans. Significance was set as p < 0.05. Results We demonstrate differences in heart and lung dose by the simulation technique. The mean heart doses in the prone, DIBH, and AveIP plans were 129 cGy, 154 cGy, and 262 cGy, respectively (p=0.02). The lung V20 in the prone, DIBH, and AveIP groups was 0.5%, 10.3% and 9.5%, respectively (p

New technologies and procedures have the potential to improve outcomes; however, initial implementation is often associated with a steep learning curve, decreased efficiency, and patient safety implications. Implementation of a real-time, ultrasound-based prostate high-dose rate brachytherapy procedure involved a multidisciplinary team composed of approximately 6-8 team members and numerous complex tasks. To characterize time spent on various aspects of the procedure and improve efficiency, the team developed a detailed process map, time study, and team debriefings. A benchmark was created based on an experienced institution which has performed >100 procedures annually. The process map was analyzed based on clinical tasks and treatment planning tasks. Over the course of 17 cases at a single institution, total procedure time ranged from 222 to 107 minutes. Implementation of the process map resulted in a reduction of total time by 52%. The implementation of a new procedure benefits from the integration and utilization of a process map. We were able to reduce procedure time significantly, which resulted in decreased time under general anesthesia, reduced risk of deep vein thrombosis, improved overall patient safety, patient throughput, and decreases in staffing demands.

Purpose To review brachytherapy use in recurrent head and neck carcinoma (RHNC) with focus on its efficacy and complication rates. Material and methods A literature search of PubMed, Ovid, Google Scholar, and Scopus was conducted from 1990 to 2017. Publications describing treatment of RHNC with brachytherapy with or without surgery were included. The focus of this review is on oncologic outcomes and the safety of brachytherapy in the recurrent setting. Results Thirty studies involving RHNC treatment with brachytherapy were reviewed. Brachytherapy as adjunctive treatment to surgical resection appears to be associated with an improved local regional control and overall survival, when compared with the published rates for re-irradiation utilizing external beam radiotherapy (RT) or brachytherapy alone. Safety data remains variable with different isotopes and dose rates with implantable brachytherapy demonstrating a tolerable side effect profile. Conclusions Although surgery remains a mainstay treatment for RHNC, intraoperative interstitial brachytherapy delivery as adjunctive therapy may improve the treatment outcome and may be associated with fewer complication rates as compared to reirradiation using external beam radiotherapy. Further investigations are required to elucidate the role of brachytherapy for RHNC.

Purpose High dose-rate (HDR) brachytherapy is commonly administered as a boost to external beam radiation therapy (EBRT). Our purpose was to compare toxicity with increasingly hypofractionated EBRT in combination with a single 15 Gy HDR boost for men with intermediate-risk prostate cancer. Methods and Materials Forty-two men were enrolled on this phase IB clinical trial to one of three EBRT dose cohorts: 10 fractions, seven fractions, or five fractions. Patients were followed prospectively for safety, efficacy, and health-related quality of life (Expanded Prostate Index Composite). Efficacy was assessed biochemically using the Phoenix definition. Results With a median follow up of 36 months, the biochemical disease-free survival was 95.5%. One man developed metastatic disease at 5 years. There was no significant minimally important difference in EPIC PRO for either urinary, bowel, or sexual domains. There was one acute Grade 3 GI and GU toxicity, but no late Grade 3 GU or GI toxicities. Conclusion Fifteen gray HDR brachytherapy followed by a five fraction SBRT approach results in high disease control rates and low toxicity similar to previously reported HDR protocols with significant improvement in patient convenience and resource savings. While mature results with longer follow up are awaited, this treatment approach may be considered a safe and effective option for men with intermediate-risk disease.

Hyperthermia (HT) has been shown to improve the clinical response of radiation therapy (RT) for cancer. The synergism is dramatically enhanced if HT and RT are combined simultaneously, but few technologies exist to apply treatments together. This study investigates feasibility of combining HT with RT using a thermobrachytherapy (TBT) balloon implant for treating a 5mm annular rim of at-risk tissue around a tumor resection cavity. For this approach, a balloon catheter was designed to deliver radiation from High Dose Rate brachytherapy simultaneously with HT delivered by filling a balloon with magnetic nanoparticles (MNP) and immersing the region in a radio frequency magnetic field. Temperature distributions in brain around the TBT balloon were simulated for typical brain blood perfusion using numerical modeling. A magnetic induction system was constructed and used to couple energy into MNP to heat tissue around balloon implants. Thermal dosimetry plans demonstrate our ability to heat a 5 mm annular rim of at-risk tissue around a brain tumor resection cavity between 40–48°C for 2–5 cm diameter balloon implants. The magnetic induction system produced rapid heating (>0.2°C/s) of MNP-filled balloons by depositing 0.6 W/ ml into the balloons with a magnetic field strength of 5.7 kA/m at 168 kHz, a level that has proven safe in previous clinical studies. These results demonstrate feasibility of using a thermobrachytherapy balloon implant for simultaneous heat and radiation treatment of tumor bed with both preclinical planning and experimental dosimetry.

CD47 is a widely expressed cell surface protein that functions as an immune checkpoint in cancer. When expressed by tumor cells, CD47 can bind SIRPα on myeloid cells, leading to suppression of tumor cell phagocytosis and other innate immune functions. CD47-SIRPα signaling has also been implicated in the suppression of adaptive antitumor responses, but the relevant cellular functions have yet to be elucidated. Therapeutic blockade of the CD47 pathway may stimulate antitumor immunity and improve cancer therapy. To this end, a novel CD47-blocking molecule, ALX148, was generated by fusing a modified SIRPα D1 domain to an inactive human IgG1 Fc. ALX148 binds CD47 from multiple species with high affinity, inhibits wild type SIRPα binding, and enhances phagocytosis of tumor cells by macrophages. ALX148 has no effect on normal human blood cells in vitro or on blood cell parameters in rodent and non-human primate studies. Across several murine tumor xenograft models, ALX148 enhanced the antitumor activity of different targeted antitumor antibodies. Additionally, ALX148 enhanced the antitumor activity of multiple immunotherapeutic antibodies in syngeneic tumor models. These studies revealed that CD47 blockade with ALX148 induces multiple responses that bridge innate and adaptive immunity. ALX148 stimulates antitumor properties of innate immune cells by promoting dendritic cell activation, macrophage phagocytosis, and a shift of tumor-associated macrophages toward an inflammatory phenotype. ALX148 also stimulated the antitumor properties of adaptive immune cells, causing increased T cell effector function, pro-inflammatory cytokine production, and a reduction in the number of suppressive cells within the tumor microenvironment. Taken together, these results show that ALX148 binds and blocks CD47 with high affinity, induces a broad antitumor immune response, and has a favorable safety profile.

DESCRIPTION OF THE PROBLEM The ACR accreditation process is a voluntary review that allows for an impartial peer evaluation of radiation oncology departments. Accreditation is a mechanism for departments to demonstrate to patients, providers, and payers adherence to recognized standards of care and quality performance. Among the goals of the process listed by the ACR are recognizing quality radiation oncology practices, as well as recommending potential practice improvements based on nationally recognized standards. As part of the accreditation process, an onsite survey of departmental facilities, staff, and procedures is carried out by board-certified radiation oncologists and medical physicists. During the onsite survey, the external reviewers interview key personnel, assess documentation of departmental policies and procedures, audit the department’s existing quality assurance and improvement program, and review patient records to assess adherence to nationally recognized clinical standards. Although quality of care is a challenging metric to assess in radiation oncology, accreditation programs focus on components of a department’s structure, process, and outcomes. Most quantifiable outcomes fall into the structure and process categories of quality assessment. Our department sought to quantify the quality improvement

Objective To examine the use and effect of the Battery of Rehabilitation Assessments and Interventions on evidence-based practice (EBP) over 6 years. Design Successive independent samples study. Setting Large rehabilitation system. Participants Successive samples of allied health clinicians (N=372) in 2009 (n=136), 2012 (n=115), and 2015 (n=121). Interventions The Battery of Rehabilitation Assessments and Interventions includes 2 components: (1) a process to synthesize, adapt, and make recommendations about the application of evidence; and (2) a process to implement the recommended practices in 3 levels of care. Main Outcome Measures To assess the effect of the project, surveys on EBP perspectives, use, and barriers were conducted before Battery of Rehabilitation Assessments and Interventions implementation and 3 and 6 years after implementation. Questions about effect of the project on clinical practice were included 3 and 6 years postimplementation. Results Survey data indicate the Battery of Rehabilitation Assessments and Interventions resulted in a significant increase in use of EBPs to make clinical decisions and justify care. As a result of the project, survey participants reported a substantial increase in use of outcome measures in 2012 (74%) and 2015 (91%) and evidence-based interventions in 2012 (62%) and 2015 (82%). In 2012, significant differences (P≤.01) in effect of the Battery of Rehabilitation Assessments and Interventions on practice were identified between therapists who were directly involved in the project and Interventions compared with uninvolved therapists. In 2015, no significant differences existed between involved and uninvolved therapists. Conclusions After 6 years of sustained implementation efforts, the Battery of Rehabilitation Assessments and Interventions expedited the adoption of EBPs throughout a large system of care in rehabilitation.

Purpose : Desire to improve efficiency and throughput inspired a review of the frequency and scope of our physics chart check procedures. Departmental policy mandates review of a patient’s treatment plan prior to port-filming, after first treatment and “weekly” every 3-5 fractions. This study examined the effectiveness of the “after-first” physics check with respect to improving patient safety and clinical efficiency. Methods and Materials : A shared spreadsheet was created to record errors discovered during patient-specific chart review following the first fraction of treatment and before the second fraction. First, entries were recorded and categorized from August 2014 through February 2015. Frequencies were assessed month-to-month. Next, utilizing these results, a continuous quality improvement (CQI) process following Deming’s Plan-Do-Study-Act (PDSA) methodology was generated. The first iteration of this PDSA was adding a dose tracking checklist item in the pre-treatment plan check assessment. A two-sided Fisher’s exact test was used to determine if there was a nonrandom association between the checklist implementation and incidence of dose tracking errors. Results : Analysis of recorded errors indicated an overall error rate of 3.4% over the 13 month period. The majority of errors related to discrepancies in documentation, followed by prescription, plan deficiency, and dose tracking-related errors. A two-sided Fisher’s exact test revealed a statistically significant decrease in dose tracking-related errors after implementing the checklist item (p = 0.0322, significance level = 0.05). Conclusions : This work indicates that this redundant secondary check is an effective QA process in our department. The first month spike in rates could be due to the Hawthorne/observer effect, but the consistent 3% error rate suggests the need for continuous quality improvement and periodical re-training on errors noted as frequent to improve awareness and quality of the initial chart review process, which may lead to improved treatment quality, patient safety and increased clinical efficiency.

ObjectivesThis study was conducted to determine the incidence of early stasis in radioembolization using resin yttrium-90 (Y-90) microspheres, to evaluate potential contributing factors, and to review initial imaging outcomes.MethodsPatients in whom early stasis occurred were compared with those in whom complete delivery was achieved for tumour type and vascularity, tumour:normal liver ratio (T:N ratio) at technetium-99m-macroaggregated albumin (Tc-99m-MAA) angiography, previous intra-arterial therapy, and infusion site (left, right or whole liver). Tumour response was evaluated at 3 months and defined according to whether a partial response and stable disease versus progressive disease were demonstrated.ResultsA total of 71 patients underwent 128 Y-90 infusions in which 26 (20.3%) stasis events occurred. Hypervascular and hypovascular tumours had similar rates of stasis (17.4% versus 27.8%; P = NS). The mean ± standard deviation T:N ratio was 3.03 ± 1.54 and 3.66 ± 2.79 in patients with and without stasis, respectively (P = NS). Stasis occurred in 14 of 81 (17.3%) and 12 of 47 (25.5%) infusions following previous intra-arterial therapy and in therapy-naïve territories, respectively (P = NS). Early stasis occurred in 15 of 41 (36.6%) left, 10 of 65 (15.4%) right and one of 22 (4.5%) whole liver infusions (P < 0.001). Rates of partial response and stable disease were similar in the stasis (88.3%) and non-stasis (76.0%) groups (P = NS).ConclusionsEarly stasis occurred in approximately 20% of infusions with similar incidences in hyper- and hypovascular tumours. Whole-liver therapy reduced the incidence of stasis. Stasis did not appear to affect initial imaging outcomes.

Low-dose rate brachytherapy (LDR-BT), involving implantation of radioactive seeds into the prostate, is an established monotherapy for most low-risk and select intermediate- and high-risk prostate cancer patients. High-dose rate brachytherapy (HDR-BT) is an advanced technology theorized to be more advantageous than LDR-BT from a radiobiological and radiophysics perspective, to the patient himself, and in terms of resource allocation. Studies of HDR-BT monotherapy have encouraging results in terms of biochemical control, patient survival, treatment toxicity and erectile preservation. However, there are still certain limitations that preclude recommending HDR-BT monotherapy for prostate cancer outside the setting of a clinical trial. HDR-BT monotherapy should be considered experimental at present.

Treatment of cervical cancer includes combination of external beam radiation therapy (EBRT) and brachytherapy (BRT). Traditionally, coronal images displaying dose distribution from a ring and tandem (RT) implant aid in construction of parametrial boost fields. This research aimed to evaluate a method of shaping parametrial fields utilizing contours created from the high-dose-rate (HDR) BRT dose distribution. Eleven patients receiving HDR-BRT via RT were identified. The BRT and EBRT CT scans were sent to FocalSim (v4.62)(®) and fused based on bony anatomy. The contour of the HDR isodose line was transferred to the EBRT scan. The EBRT scan was sent to CMS-XIO (v4.62)(®) for planning. This process provides an automated, potentially more accurate method of matching the medial parametrial border to the HDR dose distribution. This allows for a 3D-view of dose from HDR-BRT for clinical decision-making, utilizes a paperless process and saves time over the traditional technique.

Purpose: Post-implant dosimetry following prostate seed implantation (PSI) occasionally reveals suboptimal dosi- metric coverage of the gland. Published reports of re-implantation techniques have focused on earlier-generation tech- niques, including preplanned approaches and stranded seeds. The purpose of this case report is to describe a customizable approach to perform corrective re-implantation using loose seeds and intraoperative planning technique. Material and methods: This case report describes a 63-year-old male with favorable risk prostate adenocarcinoma receiving PSI. Thirty day post-implant dosimetric evaluation revealed suboptimal coverage of the base of the gland. Us- ing guidance from post-implant CT-images and real-time planning, the patient received a corrective re-implantation with intraoperative planning. Results: Post-implant dosimetry after re-implantation procedure with intraoperative planning yielded improved tar- get volume coverage that achieved standard dosimetric criteria. Conclusions: Re-implantation as a salvage treatment technique after sub-optimal PSI is a valid treatment option per- formed with intraoperative real-time planning. J Contemp Brachyther 2012; 4, 3: 176-181 DOI: 10.5114/jcb.2012.30684

To report the incidence of liver function test (LFT) toxicities after radioembolization with yttrium-90 ((90)Y) SIR-Spheres and review potential risk factors.Patients receiving (90)Y for radioembolization of primary or metastatic liver tumors had follow-up LFTs 29-571 days after treatment. The incidence and duration of bilirubin, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) toxicities were documented using common terminology criteria. Factors that were assessed included previous intra-arterial (IA) therapy, systemic chemotherapy, low tumor-to-normal liver tissue ratio at mapping angiography, vascular stasis, and higher prescribed (90)Y doses.There were 81 patients who underwent 122 infusions and had follow-up LFTs. Of 122 infusions, 71 (58%) were associated with toxicity. One patient died with radiation-induced liver disease. Grade 3 or greater toxicities occurred in seven (7%) patients after nine procedures. The median durations of laboratory elevations for bilirubin, AST, and ALT were 29 days, 29 days, and 20 days. Toxicity developed after 51 (71%) of 72 infusions with previous IA therapy versus 20 (40%) of 50 infusions in treatment-naïve areas (P = .0006). Absence of previous systemic therapy was associated with greater risk of toxicity versus previous chemotherapy (47% vs 66%, P = .03). Other factors were not associated with increased toxicity.Mild hepatotoxicity developed frequently after infusion of SIR-Spheres using the body surface area method, with normalization of LFTs in most patients. Grade 3 or greater toxicities were seen in10% of infusions. Toxicity was strongly associated with previous IA therapy.

Purpose Providing adequate dosimetric coverage of elongated, curvilinear incisions during adjuvant intensity-modulated radiation therapy (IMRT) after extrapleural pneumonectomy (EPP) for malignant pleural mesothelioma (MPM) creates technical challenges. We explored high-dose-rate (HDR) surface brachytherapy to supplement dose to multiple curvilinear incisions. This modality circumvents the technical limitations of relying on multiple en face electron fields while minimizing dose to adjacent normal tissues. Methods and Materials A 59-year-old man presented with a left-sided, Stage III, T3N2M0, epithelioid MPM. After undergoing a left EPP, adjuvant IMRT was recommended to improve local control. An eight-field IMRT plan was designed to encompass the postoperative hemithorax. Incisional scars were lengthy and extended beyond the hemithoracic target volume. Both en face electron and surface HDR plans were prepared and evaluated based on dosimetric coverage of the incisional scars, dose to normal tissues, reliability of setup, and treatment delivery. Results HDR was preferred. The patient was planned and treated in the right lateral decubitus position. HDR source catheters were placed along the incisions atop 5-mm bolus. A composite plan including IMRT and brachytherapy dose contributions was produced. Boosts of incisional scars were performed in six fractions (three fractions per week) of 3 Gy prescribed to 12 mm from the catheter. HDR brachytherapy was well tolerated. Conclusions Surface HDR brachytherapy is a viable option for supplemental dose to incisional scars at risk of local recurrence after EPP for MPM. Advantages over electron beam therapy include avoidance of field abutments and feathering, less tissue–bone interface dose uncertainty and reproducibility of treatment delivery.

OBJECTIVES To report outcomes after yttrium-90 microsphere brachytherapy for unresectable liver metastases from uveal melanoma and to evaluate factors predictive for overall survival (OS) and hepatic progression-free survival (PFS). METHODS A total of 71 patients were consecutively treated with microsphere brachytherapy for unresectable liver metastases from uveal melanoma between 2007 and 2012. Clinical, radiographic, and positron emission tomography-derived, functional tumor parameters were evaluated by log-rank test in univariate analysis and backwards stepwise multivariate Cox proportional hazards regression. OS and hepatic PFS were estimated by Kaplan-Meier analysis. RESULTS A total of 134 procedures were performed in 71 patients with a median age of 63 years (range, 23 to 91 y). Fifty-eight patients (82%) received microsphere brachytherapy as a salvage therapy. Median hepatic PFS and OS after microsphere brachytherapy were 5.9 months (range, 1.3 to 19.1 mo) and 12.3 months (range, 1.9 to 49.3 mo), respectively. Median OS times after diagnosis of liver metastases was 23.9 months (range, 6.2 to 69.0 mo). In univariate analysis, female sex, pretreatment metabolic tumor volume, and total glycolic activity (TGA) were significantly correlated with hepatic PFS and OS. In multivariate analysis, female sex and TGA retained significance as independent predictors of hepatic PFS and OS. A low pretreatment TGA (

PURPOSE: Prostate volume greater than 50 cc is traditionally a relative contraindication to pros- tate seed implantation (PSI), but there is little consensus regarding prostate size and clinical out- comes. We report biochemical control and toxicity after low-dose-rate PSI and compare outcomes according to the prostate size. METHODS AND MATERIALS: A total of 429 men who underwent low-dose-rate PSI between 1998 and 2009 were evaluated. Median followup was 38.7 months. Patients were classified by pros- tate volume into small, medium, and large subgroups. Differences were analyzed using the Man- neWhitney and Pearson's c 2 tests for continuous and categorical variables, respectively. Cox proportional hazards regression models were used to evaluate effect of prostate size on outcomes. RESULTS: Patient pretreatment factors were balanced between groups except for age (p 50.001). The 10-year actuarial freedom from biochemical failure for all patients treated with PSI was 96.3% with no statistically significant difference between large vs. small/medium prostate size (90% vs. 96.6%, p50.47). In a multivariate analysis, plan type (hazard ratio (HR) 50.25, p 50.03), dose to 90% of the gland (D90 :H R5 0.98, p50.02), volume receiving 200 Gy (V200 :H R50.98, p 50.026), and biologic effective dose (HR50.99, p 50.045), but not prostate size (HR52.27, p 50.17) were significantly associated with freedom from biochemical failure. Prostate size was not significantly associated with time to maximum American Urologic Association score. CONCLUSION: In men with large prostates, the PSI provides biochemical control and temporal changes in genitourinary toxicity that are comparable with men having smaller glands. Accurate dose optimization and delivery of PSI provides the best clinical outcomes regardless of gland size. Published by Elsevier Inc. on behalf of American Brachytherapy Society.

External beam radiation therapy (EBRT) combined with brachytherapy (BT) is an attractive treatment option for select patients with clinically localized prostate cancer. Either low- or high-dose rate BT may be combined with EBRT ('LDR-BT boost,' 'HDR-BT boost,' respectively). HDR-BT boost has potential theoretical benefits over LDR-BT boost or external beam radiation therapy monotherapy in terms of radiobiology, radiophysics and patient convenience. Based on prospective studies in this review, freedom from biochemical failure (FFBF) rates at 5 years for low-, intermediate- and high-risk patients have generally been 85-100%, 68-97%, 63-85%, respectively; late Radiotherapy and Oncology Group Grades 3 and 4 genitourinary and gastrointestinal toxicities are seen in

Studies of dose-escalated external beam radiation therapy (EBRT) and low dose rate brachytherapy (LDR-BT) have shown excellent rates of tumor control and cancer specific survival. Moreover, LDR-BT combined with EBRT (i.e. “LDR-BT boost”) is hypothesized to improve local control. While phase II trials with LDR-BT boost have produced mature data of outcomes and toxicities, high dose rate (HDR)-BT has been growing in popularity as an alternative boost therapy. Boost from HDR-BT has theoretical advantages over LDR-BT, including improved cancer cell death and better dose distribution from customization of catheter dwell times, locations, and inverse dose optimization. Freedom from biochemical failure rates at five years for low-, intermediate-, high-risk, and locally advanced patients have generally been 85–100%, 80–98%, 59–96%, and 34–85%, respectively. Late Radiation Therapy Oncology Group grade 3–4 toxicities have also been encouraging with

Purpose:To investigate the feasibility of using an inverse planning technique for CT-based ring and tandem high-dose rate brachytherapy of cervical cancer. Methods and Materials:Two patients previously treated with high-dose-rate brachytherapy for cervical cancer were retrospectively identified for this study. Each patient had five intracavitary insertions using CT/MR-compatible tandem and ring applicators. The 6Gy isodose lines from the original clinical plans were converted into a structure set (S6) using MIMvista. Inverse plans were then generated in Oncentra using the inverse planning simulated annealing (IPSA) with S6 as the optimization target. The dose to 0.1cm3, 1cm3, 5cm3 of bladder (DB0.1, DB1, and DB5) and rectum (DR0.1, DR1, DR5) were determined from the dose volume histogram (DVH). Percentage of physician drawn clinical target volume (CTV) and S6 coverage (V100CTV, V100S6) were also recorded. Results:The mean V100%CTV of the original clinical plans and the inverse plans were 88.14% and 87.57%. The mean V100%S6 of the original clinical plans and the inverse plans was 98.68% and 97.00%. The mean dose reduction for DB0.1, DB1 and DB5 were 5.4%, 5.4%, and 4.7%, respectively. The mean dose reduction for DR0.1, DR1 and DR5 were 6.4%, 5.5%, and 4.8%. Conclusions:This work demonstrated the feasibility of this structure-based inverse planning. It can achieve comparable CTV coverage while reducing dose to critical structures. Once template structure set is constructed, this procedure can not only reduce planning time, but improve quality assurance by standardizing the procedure. This approach can be directly extended to other applicator-based brachytherapy procedures.

Purpose: Permanent seed implants have traditionally been used to treat prostate, lung and head or neck cancers using I-125 and Pd-103. Cs-131, which has higher dose rate is being used to treat brain, head and/or neck cancers in our clinic, therefore, we chose to monitor the dose received by surgeons during the extensive procedure. The aims of this work are to assess the level of radiation exposure to surgeons and the instantaneous exposure at bedside and 1 m from patients. Methods: Ten patients received Cs-131 implants for recurrent brain,head and/or neck cancer; the median implanted activity, number of implanted seeds and prescription dose at 0.5 cm from the perpendicular plane of the implant were: 54.3 mCi (14.52 – 77); 19 (4 – 24) and 60 Gy (range 42 – 60) respectively. Radiation exposure was recorded at bedside and 1 m from the patient using Victoreen ion chamber (Fluke Biomedical, Cleveland, OH). Exposure to surgeons was measured using TLD (Mirion Technologies (GDS), Inc., USA). Results: The median equivalent dose rate at 1 m and bedside immediately following implantation were 1.49×10-2 mSv/h (8.77×10-3–2.63×10-2) and 7.76×10-2 mSv/h (3.1×10-2– 1.53×10-1) respectively. Median equivalent dose to surgeons’ hands was 0.60 mSv (0.33 – 1.48) and no doses were detected for whole-body. Surgical reconstruction for one patient was performed 71 days post-implant and resulted in zero exposure to surgeons. Conclusion: The recorded exposure rates were low when compared with the literature. Post procedure surveys at bed site and 1 m indicated that all patients were within safe limits for discharge (< 0.05 mSv/h at 1 m). However, as a precautionary measure, patients were advised to avoid direct contact with children and pregnant women within four weeks of the implant and stay at least at 3 ft from other people. Surgeons doses were well within occupational dose limits.

This article introduces the use of qualitative research techniques in the field of radiation oncology with respect to quality improvement initiatives. The qualitative techniques used in this research include field observations and in-depth, one-on-one interviews with radiation therapy technologists. The observations were conducted in a fast-paced academic institution. This high-pressure, high-throughput environment provided an interesting location for observation of behaviors, workflows, and areas of improvement. Qualitative research is a useful platform for formulating questions and addressing the environment on a larger scale. The information resulting from this research led to immediate changes that improved the efficiency and effectiveness of care provided to patients and identified future initiatives to improve patient safety and the timeliness of care provided. Overall, qualitative research proved to be an exceptional resource for identifying and evaluating a clinical department and demonstrated the usefulness of this method of research for future work.

Adoption and meaningful use of electronic health record (EHR) systems is an important national goal. We under- took a pilot study to determine the level of adoption and barriers to implementation of meaningful use (MU) of EHR systems as defined by the Centers for Medicare & Medicaid Services (CMS) in US radiation oncology practices. Materials and Methods: We administered a Web-based sur- veyinstrumenttoaconveniencesampleof40departmentsofradiation oncology. We determined the current status of EHR system use at each facility, attitudes toward EHR systems, knowledge of MU criteria, plans and barriers to implementation, and whether selected interven- tions would be helpful with regard to compliance with MU criteria. Results: Twenty-one of 40 radiation oncology facilities com- pleted the survey, for a 53% response rate. Respondents were mostly large academic practices with a median of six (range, one to 32) full-time physicians and 70 (range, eight to 650) patients treated daily. Most facilities (81%) currently used an EHR system. The majority (84%) of facilities were aware of MU criteria, and of these, 67% expected to imple- ment MU-compliant systems by the year 1 reporting deadline of October 1, 2011. The most frequently cited barriers to implementation were high cost, difficulty integrating with hospital systems, and a lack of national guidelines for implementation. Conclusion: Most large academic radiation oncology prac- tices have already incorporated EHR systems into practice and plan to meet MU requirements. Further work should focus on assessment of needs for smaller practices. Radiation oncology-specific guidelines may improve widespread adoption.

The purpose of this study was to assess the rate of recanalization and collateral vessel formation after side-branch embolization during mapping angiography for planned (90)Y radioembolization.Patients who underwent side-branch embolization at mapping angiography before (90)Y administration were included. Embolized vessels included the gastroduodenal artery, right gastric artery, and accessory arteries. Four interventional radiologists reviewed follow-up angiograms to assess recanalization and new collateral formation of embolized vessels. The time to recanalization or new collateral formation was tracked within 60 days and after the final arteriographic study. Differences in outcome among patients who had and those who had not undergone previous arterial directed therapy were reviewed.Fifty-six patients underwent side-branch embolization and follow-up arteriography; 124 treatments were performed after side-branch embolization (median, 2; range, 1-7), and the median follow-up period was 134 days (range, 7-684 days). Recanalization or new collateral vessel formation was found in 6 of 56 patients (10.7%) and in 8 of 56 patients (14.3%) 60 days after treatment or at final angiography, respectively. Embolization of 110 arteries was accomplished (42 gastroduodenal arteries, 46 right gastric arteries, and 22 accessory arteries). Two of 110 arteries (1.8%) recanalized, and four of 110 (3.6%) had new collateral vessels within 60 days. At final evaluation, 2 of 110 arteries (1.8%) had recanalized and 7 of 110 (6.4%) had new collaterals. Previous liver-directed therapy did not affect outcome (p0.05). No patient had symptomatic gastrointestinal ulceration.In more than 89% of patients, side-branch embolization provides durable occlusion for (90)Y radioembolization without collateral development or recanalization for a bilobar cycle of therapy. Further recanalization and collateral development at longer-term follow-up are minimal.

In light of concerns regarding the quality of radiation treatment delivery, we surveyed the practice of quality assurance peer review chart rounds at American academic institutions.An anonymous web-based survey was sent to the chief resident of each institution across the United States.The response rate was 80% (57/71). The median amount of time spent per patient was 2.7 minutes (range, 0.6-14.4). The mean attendance by senior physicians and residents was 73% and 93%, respectively. A physicist was consistently present at peer review rounds in 66% of departments. There was a close association between attendance by senior physicians and departmental organization: in departments with protected time policies, good attendance was 81% vs. 31% without protected time (p = 0.001), and in departments that documented attendance, attending presence was 69% vs. 29% in departments without documentation (p 0.05). More than 80% of institutions peer review all external beam therapy courses; however, rates were much lower for other modalities (radiosurgery 58%, brachytherapy 40%-47%). Patient history, chart documentation, and dose prescription were always peer reviewed in75% of institutions, whereas dosimetric details (beams, wedges), isodose coverage, intensity-modulated radiation therapy constraints, and dose-volume histograms were always peer reviewed in 63%, 59%, 42%, and 50% of cases, respectively. Chart rounds led to both minor (defined as a small multileaf collimator change/repeated port film) and major (change to dose prescription or replan with dosimetry) treatment changes. Whereas at the majority of institutions changes were rare (10% of cases), 39% and 11% of institutions reported that minor and major changes, respectively, were made to more than 10% of cases.The implementation of peer review chart rounds seems inconsistent across American academic institutions. Brachytherapy and radiosurgical procedures are rarely reviewed. Attendance by senior physicians is variable, but it improves when scheduling clashes are avoided. The potential effect of a more thorough quality assurance peer review on patient outcomes is not known.

The purpose of this study was to assess the safety and efficacy of radioembolization in the management of hepatic metastasis of uveal melanoma after failure of immunoembolization or chemoembolization.From January 2007 through April 2009, 32 patients underwent radioembolization therapy for hepatic metastasis of uveal melanoma. Pretreatment tumor burdens were divided into three categories: less than 25% (n = 25), 25-50% (n = 5), and greater than 50% (n = 2). Toxicity, extrahepatic disease, and hepatic tumor response were assessed 1 month and then every 3 months after treatment. Best radiographic response of hepatic metastasis was determined with the Response Evaluation Criteria in Solid Tumors criteria. Overall survival and progression-free survival of hepatic metastasis were estimated by Kaplan-Meier analysis. Differences in survival between subgroups were evaluated by log-rank test in univariate analysis.The clinical follow-up period ranged from 1.0 to 29.0 months (median, 10.0 months). The median overall survival was 10.0 months, and the progression-free survival of hepatic metastasis, 4.7 months. Twenty-two patients died 1.0-29.0 months (median, 5.8 months) after treatment owing to progression of liver disease (n = 13), extrahepatic disease (n = 4), or both (n = 5). Patients who had a pretreatment tumor burden less than 25% had longer median overall survival (10.5 vs 3.9 months, p = 0.0003) and progression-free survival (6.4 vs 3.0 months, p = 0.03) than patients who had a pretreatment tumor burden of 25% or greater. Patients who had a complete response (n = 1), partial response (n = 1), or stable disease (n = 18) had longer median overall survival (14.7 vs 4.9 months, p = 0.0006) and progression-free survival of hepatic metastasis (7.9 vs 3.1 months, p0.0001) than patients with tumor progression (n = 12). Self-limiting grade 1-2 systemic toxicity included tiredness (n = 9), indigestion (n = 2), and abdominal discomfort (n = 5). Grade 3-4 hepatic toxicity was attributed to tumor progression.Radioembolization is safe and effective salvage therapy for limited metastasis of uveal melanoma.

Purpose Delivering adequate dose to tracheal mucosa recurrence after multiple prior courses of surgery and radiation presented a challenge for radiation delivery. Tumor bed location and size, combined with previous doses to surrounding areas, complicated the use of external beam therapy with either photons or electrons. High-dose-rate (HDR) brachytherapy was explored to provide sufficient dose coverage. Methods and Materials A 45-year-old gentleman presented with recurrent head and neck cancer. After undergoing additional excision of gross tumor in the tracheal region, radiation was recommended to improve local control. The region of residual tumor was confined to a small superficial lesion at the posterior–superior aspect of the trachea, involving mucosa located along the bend of the trachea, immediately deep to the stoma. External beam treatment was discussed but was not recommended based on recurrence location in the prior radiation field and patient’s flexed chin position. HDR technique with a custom applicator was preferred. Results A three-dimensional HDR plan based on computed tomography used a single catheter optimized to cover gross tumor volume as delineated by physician. Prescribed dose was 5 Gy/fraction for six fractions (two fractions/wk). The applicator position was verified daily with computed tomography and physician setup approval before treatment. The patient was positioned on a wing board to allow access to the stoma. HDR brachytherapy was well tolerated. Conclusions Intraluminal HDR brachytherapy is a viable option for providing dose to region inside tracheal stoma. Advantages over photon and electron beam therapy include reduced dose to surrounding tissues previously irradiated, skin dose, and reproducibility of treatment delivery.

Purpose Intra-operative (real-time) treatment planning has been adapted by many institutions for low–dose rate prostate brachytherapy. Although this allows dosimetric planning to be done during the procedure, preplan imaging to obtain a prostate volume is essential to identify the number of seeds to ensure adequate volume coverage. Currently, there is no consensus regarding the most appropriate imaging to obtain this information. We conducted a retrospective study to compare how volumes obtained from preplan CT (p-CT) scans or preplan transrectal ultrasound (p-TRUS) correlated with real-time ultrasound and postimplant CT volumes and the difference in accuracy of seed estimation between these techniques. Methods and Materials Ninety-two patients underwent 125 I permanent seed implants at Thomas Jefferson University Hospital between February 2002 and August 2008. Fifty-one patients underwent p-TRUS before intra-operative planning and 41 patients were evaluated by p-CT. Results The median difference in volume between preimplant imaging and the intra-operative planning ultrasound was 3.59 and 5.2 cc for patients who underwent p-TRUS and p-CT, respectively. p-TRUS volumes more closely correlated with real-time intra-operative volumes ( R = 0.84 in all patients and R = 0.91 in hormone-naive patients) vs. p-CT ( R = 0.82). The median number of seeds wasted using p-CT was 18 vs. 7 using volumes derived from p-TRUS. Conclusions The number of seeds ordered could be more accurately obtained from p-TRUS volumes, and this translated into less seed wastage. Our findings indicate that p-TRUS is a more accurate and an economically superior alternative to p-CT imaging in the era of real-time ultrasound planning.

Purpose: To evaluate patient specific quality assurance (PSQA) for the delivery of volumetric modulated arc therapy (VMAT) by disease site. To compare planning-delivery system (PDS) PSQA pass rates in a dual vendor institution. Methods: PSQA is performed for VMAT plans using a ScandiDos Delta4 phantom. Verification plans are calculated using Varian Eclipse and Elekta Monaco treatment planning systems (TPS) for patients treated using Varian Truebeam and Elekta linear accelerators respectively. Individual arcs are delivered to the Delta4 phantoms and assessed using the gamma index pass criterion(3% Dose Deviation(DD%), 3mm Distance to Agreement(DTA),10% dose threshold and 90% gamma index). Results: A total of 287 VMAT plans and 680 arcs were analyzed. The passing rates for VMAT QA plans were 95% and 98% for head/neck and pelvis/prostate plans respectively, and 100% for chest/abdomen, spine, lung Stereotactic Body Radiotherapy (SBRT) and Stereotactic Radiosurgery(SRS) plans. Average gamma indices were: (99 ± 2) % for pelvis/prostate, chest/abdomen and lung SBRT plans, (97 ± 4) % for head and neck plans and (98 ± 3) % for spine plans. The average DD% and DTA pass rates ranged from 82% to 90% and 98% to 99% respectively for plans in different disease sites. Paired t-test analysis (two tails) indicated no significant differences in the gamma indices between plans delivered using different PDS; the P values were: 0.08, 0.45, and 0.94 for lung SBRT, head/neck and pelvis/prostate plans respectively. The statistical power for comparing PDS in different disease sites with an alpha of 0.05 is 1. Conclusion: The Gamma indices based on 3% DD%, 3 mm DTA and 10% dose threshold for the VMAT QA plans in all disease sites were well above 90%, suggesting the possibility of using a more stringent PSQA criterion. No significant differences were observed in the QA of VMAT plans delivered using different PDS.

Purpose: This study compares gamma passing rates for a cohort of similar intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) quality assurance (QA) plans to determine the equivalence of the patient specific QA plan delivery. The passing criterion is 90% gamma index with 3% dose difference (DD), 3mm distance-to-agreement (DTA) and a dose threshold of 10%. Methods: Gamma passing results of previously treated IMRT QA plans, delivered to Sun Nuclear MapCheck phantom, and VMAT QA plans, delivered to ScandiDos Delta4 phantom, are organized by anatomical site and treatment machine. Both Varian and Elekta machines are included. Pairs of IMRT and VMAT plans are matched based on site, machine, and PTV volume to ensure similar plan cohorts. A two-tailed t-test analysis of the data with an alpha of 0.05 determines if there exists a statistically significant difference. Power was calculated to detect a difference of 4%; all data sets were strong with above a 0.8 power. Results: The first data set consisting of 20 matched pairs of prostate plans was statistically insignificant (p-value=0.90, Power=0.99). The 14 matched pairs set of head and neck plans has a statistically significant Result (p-value=0.028, Power=0.88). The head and neck IMRT gamma indexes have a mean of 93.1% and range of 82%-100% while the VMAT gamma indexes have a mean of 96.7% and range of 92%-100%. The two combined data sets of matched plans had a statistically insignificant Result (p-value=0.073, Power=0.99). Conclusion: Overall, IMRT and VMAT have equivalent passing rates when comparing the gamma analysis using a passing criterion of 3% DD and 3mm DTA. When separated by site, prostate IMRT and VMAT plans have equivalent passing rates while head and neck plans have a statistically significant variation of passing rates. The passing rates for the two modalities are independent of delivery machine for matched PTV target volumes.