Evaluating the impact of prescription isodose line on plan quality using Gamma Knife inverse planning.

The impact of selection of prescription isodose line (IDL) on plan quality has not been well evaluated during inverse planning (IP). In this study, a total of 180 IP plans at five levels of IDL were generated for 30 brain metastases (BMs). For each BM, one round of IP was performed with typical IP settings, followed by a quick fine-tuning to ensure the same target coverage and comparable conformality index. The impact of the IDL on the quality metrics (selectivity, gradient index [GI], and treatment time) was evaluated. The decrease of selectivity and increase of GI meant inferior target dose conformality and more dose spillage. Additionally, a metric directly correlated to the treatment time was proposed. For all cases, the mean GI decreased monotonically as IDL decreased from 70% to 30%, and the decreasing rate was significantly different based on tumor size. The mean selectivity and number of shots decreased monotonically as IDL decreased for all the tumors. From 70% to 30% IDL, the decreasing rate of the mean selectivity was 2.8% (p = 0.020), 7.7% (p = 0.005), and 15.4% (p = 0.020) and that of the number of shots was 75.4% (p = 0.001), 73.2% (p = 0.001), and 50.7% (p = 0.009), for the large, medium, and small tumors, respectively. For the medium and small tumor groups, the mean treatment time increased monotonically when IDLs decreased (increasing rate was 80.0% [p = 0.002] for medium tumors [p = 0.001] and 130.8% [p = 0.001] for small tumors from 70% to 30%). For the large tumors, the mean treatment time was the shortest at 50% IDL (59.0 min) and higher at 70% (65.9 min) and 30% (71.9 min). Overall, the GammaPlan chose smaller sectors for plans with lower IDLs except for the large size group.

caTissue Suite to OpenSpecimen: Developing an extensible, open source, web-based biobanking management system.

The National Cancer Institute (NCI) Cancer Biomedical Informatics Grid® (caBIG®) program established standards and best practices for biorepository data management by creating an infrastructure to propagate biospecimen resource sharing while maintaining data integrity and security. caTissue Suite, a biospecimen data management software tool, has evolved from this effort. More recently, the caTissue Suite continues to evolve as an open source initiative known as OpenSpecimen. The essential functionality of OpenSpecimen includes the capture and representation of highly granular, hierarchically-structured data for biospecimen processing, quality assurance, tracking, and annotation. Ideal for multi-user and multi-site biorepository environments, OpenSpecimen permits role-based access to specific sets of data operations through a user-interface designed to accommodate varying workflows and unique user needs. The software is interoperable, both syntactically and semantically, with an array of other bioinformatics tools given its integration of standard vocabularies thus enabling research involving biospecimens. End-users are encouraged to share their day-to-day experiences in working with the application, thus providing to the community board insight into the needs and limitations which need be addressed. Users are also requested to review and validate new features through group testing environments and mock screens. Through this user interaction, application flexibility and interoperability have been recognized as necessary developmental focuses essential for accommodating diverse adoption scenarios and biobanking workflows to catalyze advances in biomedical research and operations. Given the diversity of biobanking practices and workforce roles, efforts have been made consistently to maintain robust data granularity while aiding user accessibility, data discoverability, and security within and across applications by providing a lower learning curve in using OpenSpecimen. Iterative development and testing cycles provide continuous maintenance and up-to-date capabilities for this freely available, open-access, web-based software application that is globally-adopted at over 25 institutions.

A Statewide Multi-Institutional Study of Asymptomatic Pretreatment Testing of Radiation Therapy Patients for SARS-CoV-2 in a High-Incidence Region of the United States.

PURPOSE: Our purpose was to establish the prevalence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in asymptomatic patients scheduled to receive radiation therapy and its effect on management decisions. METHODS AND MATERIALS: Between April 2020 and July 2020, patients without influenza-like illness symptoms at four radiation oncology departments (two academic university hospitals and two community hospitals) underwent polymerase chain reaction testing for SARS-CoV-2 before the initiation of treatment. Patients were tested either before radiation therapy simulation or after simulation but before treatment initiation. Patients tested for indications of influenza-like illness symptoms were excluded from this analysis. Management of SARS-CoV-2-positive patients was individualized based on disease site and acuity. RESULTS: Over a 3-month period, a total of 385 tests were performed in 336 asymptomatic patients either before simulation (n = 75), post-simulation, before treatment (n = 230), or on-treatment (n = 49). A total of five patients tested positive for SARS-CoV-2, for a pretreatment prevalence of 1.3% (2.6% in north/central New Jersey and 0.4% in southern New Jersey/southeast Pennsylvania). The median age of positive patients was 58 years (range, 38-78 years). All positive patients were white and were relatively equally distributed with regard to sex (2 male, 3 female) and ethnicity (2 Hispanic and 3 non-Hispanic). The median Charlson comorbidity score among positive patients was five. All five patients were treated for different primary tumor sites, the large majority had advanced disease (80%), and all were treated for curative intent. The majority of positive patients were being treated with either sequential or concurrent immunosuppressive systemic therapy (80%). Initiation of treatment was delayed for 14 days with the addition of retesting for four patients, and one patient was treated without delay but with additional infectious-disease precautions. CONCLUSIONS: Broad-based pretreatment asymptomatic testing of radiation oncology patients for SARS-CoV-2 is of limited value, even in a high-incidence region. Future strategies may include focused risk-stratified asymptomatic testing.

Dosimetric comparison of inverse and forward planning for Gamma Knife stereotactic radiosurgery of brain metastases.

The Leksell GammaPlan (LGP) with an inverse planning (IP) tool has been upgraded to version 11.1 since its launch in 2010. We evaluated its IP planning performance by re-planning 16 targets that had been planned using forward planning (FP). The FP and IP plans were compared. A planning guideline for IP process was developed aiming for an unbiased comparison. Sixteen brain metastases (BMs) without nearby critical structures were included in the study (size > 1 cm for all targets). All prior FP were re-planned in the LGP using IP and maintaining the same beam-on time and coverage. The dose to all the targets was scaled to 20 Gy in a single fraction at 50% isodose line (IDL) for FP and IP comparison purpose. The coverage and beam-on time were nearly the same for both the FP and IP plans. For all the IP plans, the mean selectivity was 0.85 ± 0.04 (vs 0.83 ± 0.04 in FP plans, p = 0.02), the mean GI was 2.92 ± 0.21 (vs 3.18 ± 0.60 in FP plans, p = 0.047), the mean V12Gy was 8.18 ± 8.57 cc (vs 9.09 ± 9.08 cc in FP plans, p = 0.001), the mean V8Gy was 14.63 ± 15.14 cc (vs 16.34 ± 16.17 cc in FP plans, p = 0.001), and the mean V5Gy was 29.01 ± 28.77 cc (vs 32.77 ± 31.41 cc in FP plans, p = 0.001). The number of shots was higher in IP plans (means of 16.69 ± 8.11 vs 10.81 ± 6.87 in FP plans, p = 0.001). We retrospectively re-planned 16 FP plans using the IP tool while meeting the quality limiting factors for the FP plans. The dosimetry parameters from the IP plans outperformed the treated FP plans and the IP tool should be preferred for tumors with size > 1 cm.

Tuning-Target-Guided Inverse Planning of Brain Tumors With Abutting Organs at Risk During Gamma Knife Stereotactic Radiosurgery.

Purpose We proposed a planning strategy that utilized tuning targets to guide GammaKnife (GK) Inverse Planning (IP) to deliver higher dose to the tumor, while keeping acceptable dose to the abutting organ at risk (OAR). Methods Ten patients with a large portion of brain tumor abutting the OAR previously treated with GK stereotactic radiosurgery (SRS) were selected. For each patient, multiple tuning targets were created by cropping the target contour from three-dimensional (3D) expansions of the OAR. The number of the tuning targets depended on the complexity of the planning process. To demonstrate dose sparing effect, an IP plan was generated for each tuning target after one round of optimization without shot fine-tuning. In the dose enhancement study, a more aggressive target dose was prescribed to the tuning target with a larger margin and one to two shots were filled in the region with missing dose. The resulting plans were compared to the previously approved clinical plans. Results For all 10 patients, a dose sparing effect was observed, i.e. both target coverage and dose to the OARs decreased when the margins of 3D expansion increased. For one patient, a margin of 6 mm was needed to decrease the maximum dose to the optical chiasm and optical nerve by 44.3% and 28.4%, respectively. For the other nine patients, the mean dropping rate of V12Gyto brain stem were 28.2% and 59.5% for tuning targets of 1 and 2 mm margins, respectively. In the dose enhancement study, the tuning-target-guided plans were hotter than the approved treatment plans, while keeping similar dose to the OARs. The mean of the treatment and enhancement dose was 15.6 ± 2.2 Gy and 18.5 ± 3.2 Gy, respectively. The mean coverage of the target by prescription dose was slightly higher in the enhancement plans (96.9 ± 2.6% vs 96.3 ± 3.6%), whereas the mean coverage of the enhancement dose was 20.1% higher in the enhancement plans (89.6 ± 9.0% vs 74.6 ± 19.9%). Conclusions We demonstrated that an inverse planning strategy could facilitate target dose enhancement for challenging GK cases while keeping acceptable OAR dose.

Improved Dose Conformity for Adjacent Targets: A Novel Planning Technique for Gamma Knife Stereotactic Radiosurgery.

Purpose In the current Gamma Knife (GK) planning system (GammaPlan, version 10.2, Elekta AB, Stockholm, Sweden), multiple adjacent brain metastasis (BMs) had to be planned sequentially if BMs were drawn separately, leading to less conformal target dose in the composite plan due to inter-target dose contribution and fine-tuning of the shots being quite tedious. We proposed a method to improve target dose conformality and planning efficiency for such cases. Methods and Materials Fifteen patients with multiple BMs treated on the Leksell GK Perfexion system were retrospectively replanned in the Institutional Review Board (IRB) approved study. The recruitment criterion was all the BMs should be entirely encompassed within the maximum dose grid allowed in the GammaPlan. The BMs were first planned sequentially as routine clinic cases. The contours of the BMs were then exported to the VelocityAI (Varian, CA, USA) to generate a composite contour after a union operation, and all the BMs were planned again simultaneously using this composite contour in the GammaPlan. The inverse planning (IP) was employed in both methods with the same treatment time allowed for a fair plan comparison. Dose evaluation was performed in the VelocityAI with all planning magnetic resonance (MR) images, structure set and dose were exported to the VelocityAI. The dosimetery parameters, including conformality index (CI), V20Gy, V16Gy, V12Gy, and V5Gy, were compared between the two methods. Results The planning results from both methods were reviewed qualitatively and quantitatively. The proposed method exhibited superior CI, except for an outlier case with very tiny BMs. The mean and standard deviation (std.) of the Paddick CI for all patients were 0.76±0.11 for the proposed method, comparing to 0.69±0.13 for the sequential method. The V20Gy, V16Gy, V12Gy, and V5Gy for the proposed method were 10.9±0.9%, 9.5±10.2%, 6.2±16.4% and 3.3±21.8%, all lower than those from the sequential method. Conclusions The proposed method showed improved target dose conformality for all cases except for very tiny BMs. Planning efficiency is considerably better with the combined target technique. The improved dose conformality will be beneficial to patients in long term with lowered risk of radiation necrosis after GK stereotactic radiosurgery (SRS).

Diagnostic Medical Imaging in Pediatric Patients and Subsequent Cancer Risk.

The use of diagnostic medical imaging is becoming increasingly more commonplace in the pediatric setting. However, many medical imaging modalities expose pediatric patients to ionizing radiation, which has been shown to increase the risk of cancer development in later life. This review article provides a comprehensive overview of the available data regarding the risk of cancer development following exposure to ionizing radiation from diagnostic medical imaging. Attention is paid to modalities such as computed tomography scans and fluoroscopic procedures that can expose children to radiation doses orders of magnitude higher than standard diagnostic x-rays. Ongoing studies that seek to more precisely determine the relationship of diagnostic medical radiation in children and subsequent cancer development are discussed, as well as modern strategies to better quantify this risk. Finally, as cardiovascular imaging and intervention contribute substantially to medical radiation exposure, we discuss strategies to enhance radiation safety in these areas.

Defining the role of adjuvant therapy: ampullary and duodenal adenocarcinoma.

Adenocarcinomas of the ampulla of Vater and duodenum are more rare than pancreatic cancer and have a better prognosis. However, studies conducted on the management of these cancers, such as adjuvant chemotherapy and radiation therapy, are limited by small sample sizes and series that are retrospective. This review evaluates ampullary and duodenal adenocarcinomas with regard to incidence, anatomy, prognostic features, patterns of failure, and the available literature studying adjuvant therapy.

Involved-nodal radiation therapy leads to lower doses to critical organs-at-risk compared to involved-field radiation therapy.

BACKGROUND: Involved field radiotherapy (IFRT) after cytotoxic chemotherapy has become the standard of care in treating pediatric patients with Hodgkin lymphoma. However, recent interest in shrinking the treatment volume to involved node radiotherapy (INRT) may allow lower doses to critical organ structures. We dosimetrically compared IFRT and INRT treatment approaches. METHODS: INRT treatment plans were retrospectively constructed from 17 consecutively treated pediatric patients identified with Hodgkin lymphoma who had been previously treated with conventional IFRT. The radiation doses delivered to organs-at-risk (OARs) with virtual INRT treatment plans based on INRT field design were then compared to the original IFRT treatment plans. Metrics for comparison included mean doses to organs and volumes of organ receiving at least 50% of the original prescription dose (V50%). A one-tailed, paired t-test was then performed to verify statistical significance at an alpha level of 0.05. RESULTS: All organs at risk compared in this investigation (kidneys, heart, thyroid, parotids, and lungs) had significantly lower doses of radiation with INRT when compared to IFRT (p<0.05). Furthermore, the volume of the breast receiving at least 50% of the initial prescription dose was statistically lower in the INRT plans. CONCLUSIONS: Utilizing the concept of INRT results in a reduction of radiation dose to critical organ structures in pediatric patients with Hodgkin lymphoma when compared to the more traditional method of IFRT.

Effect of CAT or AGG interruptions and CpG methylation on nucleosome assembly upon trinucleotide repeats on spinocerebellar ataxia, type 1 and fragile X syndrome.

Nucleosome packaging regulates many aspects of DNA metabolism and is thought to mediate genetic instability and transcription of expanded trinucleotide repeats. Both instability and transcription are sensitive to repeat length, tract purity, and CpG methylation. CAT or AGG interruptions within the (CAG)n or (CGG)n tracts of spinocerebellar ataxia, type 1 or fragile X syndrome, respectively, confer increased genetic stability to the repeats. We report the formation of nucleosomes on sequences containing pure and interrupted (CAG)n and (CGG)n repeats having lengths above and below the genetic stability thresholds. Increased lengths of pure repeats led to increased and decreased propensities for nucleosome assembly on the (CAG)n and (CGG)n repeats, respectively. CpG methylation of the CGG repeat further reduced assembly. CAT interruptions in (CAG)n tracts decreased nucleosome assembly. In contrast, AGG interruptions in (CGG)n tracts did not affect assembly by hypoacetylated histones. The latter observation was unaltered by CpG methylation of the repeats. However, nucleosome assembly by hyperacetylated histones on interrupted CGG tracts was increased relative to pure tracts and this effect was abolished by CpG methylation. Thus, CAT or AGG interruptions can modulate the ability of (CAG)n and (CGG) tracts to assemble into chromatin and the effect of the AGG interruptions is dependent upon both the methylation status of the DNA and the acetylation status of the histones. Compared with the genetically unstable pure repeats, both interruptions permit a propensity of nucleosome assembly closer to that of random (genetically stable) sequences, suggesting an association of nucleosome assembly of trinucleotide repeats and genetic instability.

Two breakpoint clusters at fragile site FRA3B form phased nucleosomes.

Fragile sites are gaps and breaks in metaphase chromosomes generated by specific culture conditions. Fragile site FRA3B is the most unstable site and is directly involved in the breakpoints of deletion and translocation in a wide spectrum of cancers. To learn about the general characteristics of common fragile sites, we investigated the chromatin structure of the FRA3B site. Because FRA3B spans several hundred kilobases, we focused our study on two breakpoint clusters found in FRA3B. Using various nucleases, we demonstrated that these two regions contain phased nucleosomes, regardless of treatment with aphidicolin. Because these regions are located in intron 4 of the FHIT gene, it is very interesting to observe phased nucleosomes over these regions, which are several hundred kilobases downstream from the promoter. Further, by using nucleosome assembly assays, we demonstrate that these two regions do not contain strong nucleosome positioning elements. These results suggest that other factors appear to cooperate with the DNA sequence of these regions to impart nucleosome phasing. This study provides the first information on the chromatin structure of breakpoint regions in a common fragile site. The observation of phased nucleosomes over these breakpoint regions could offer a foundation to understand the expression of fragile sites.

CAG nucleotide repeat profiles in persons with schizophrenia or schizoaffective disorders with and without tardive dyskinesia: pilot study.

Tardive dyskinesia (TD) is a drug-induced syndrome of involuntary movements often associated with neuroleptic treatment of psychiatric conditions. Huntington's disease (HD) and other neurological conditions are caused by CAG nucleotide repeat expansions in specific genes. We, therefore, explore the hypothesis that TD may be related to CAG repeat expansion by using the repeat expansion detection (RED) method as a measure of CAG content without knowledge of the location of the responsible gene. The number of CAG repeats ([CAG](n)) from persons with schizophrenia or schizoaffective disorders with (n = 10) and without (n = 9) TD are determined. A comparison of [CAG](n) in persons with (56.90 +/- 23.45 repeats) and without (57.00 +/- 19.35 repeats) TD was not statistically different. The total [CAG](n) was determined by combining [CAG](n) for both groups. The median of 45 repeats was used to divide the total into two groups (SG1 and SG2 with smaller and larger [CAG](n) fragments, respectively) and a means analysis of the two subgroups based on [CAG](n) demonstrated that SG1 (n = 10 samples at 45 repeats per sample, mean [CAG](n) = 45.00 +/- 0.00) was significantly smaller than SG2 (n = 9, ranging from 48 to 120 repeats, mean = 70.22 +/- 24.83; P < 0.005). Thus, this lends support to the idea of CAG repeat expansions in the study population. Results are encouraging that a larger population and a more structured subject selection process may yield more meaningful information about the relationship between CAG repeat expansion and TD.