Search

Purpose: High-dose-rate brachytherapy (HDR-BT) is now becoming more common than low-dose-rate and pulsed-dose-rate BT in the treatment of lip cancer. However, due to the limited history of HDR-BT, relatively few studies have been published. Two institutions (in Ukraine and the USA) reviewed their clinical outcomes of lip cancer patients treated with HDR-BT as monotherapy or in combination with external beam radiotherapy (EBRT)., Methods and Materials: An interstitial (IS), surface custom mold (SC), or a combination of IS and SC (IS+SC) was used for treatments based on the depth of tumor invasion. Prescription doses were 24 Gy in 6 BID fractions when combined with 46-50 Gy of EBRT, 45-55 Gy in 9-10 BID fractions for IS and IS+SC monotherapy or 3 Gy × 16 daily fractions for SC monotherapy., Results: A total of 33 cases of lip cancer were treated from 2015 to 2021. By using TNM staging classification, there were 14 stage I (42.4%), 15 stage II (45.5%), and 4 stage III (12.1%) lip cancers. Thirty-one patients (93.9%) had a complete response to the treatment. Only 2 patients (6.1%) displayed local recurrence. Grade 1, 2, and 3 acute toxicities were observed in 30.3%, 51.5%, and 18.2% of patients, respectively. Grade 1, 2, and 3 late toxicities were observed in 39.4%, 21.2%, and 0.0% of cases. Cosmetic results were excellent in 21.2%, good in 54.5%, fair in 18.2%, and poor in 6.1% of patients., Conclusions: HDR-BT is an effective and safe treatment for lip carcinomas with excellent local control, functional, and cosmetic outcomes and should be considered as a standard treatment., (Copyright © 2024 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Bayesian analysis of variance (BANOVA), implemented through R packages, offers a Bayesian approach to analyzing experimental data. A tutorial in Psychological Methods extensively documents BANOVA. This note critically examines a method for evaluating mediation using partial eta-squared as an effect size measure within the BANOVA framework. We first identify an error in the formula for partial eta-squared and propose a corrected version. Subsequently, we discuss limitations in the interpretability of this effect size measure, drawing on previous research, and argue for its potential unsuitability in assessing indirect effects in mediation analysis. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Background: High dose rate (HDR) brachytherapy is commonly used to treat prostate cancer. Existing HDR planning systems solve the dwell time problem for predetermined catheters and a single energy source., Purpose: Additional degrees of freedom can be obtained by relaxing the catheters' pre-designation and introducing more source types, and may have a dosimetric benefit, particularly in improving conformality to spare the urethra. This study presents a novel analytical approach to solving the corresponding HDR planning problem., Methods: The catheter and dual-energy source selection problem was formulated as a constrained optimization problem with a non-convex group sparsity regularization. The optimization problem was solved using the fast-iterative shrinkage-thresholding algorithm (FISTA). Two isotopes were considered. The dose rates for the HDR 4140 Ytterbium (Yb-169) source and the Elekta Iridium (Ir-192) HDR Flexisource were modeled according to the TG-43U1 formalism and benchmarked accordingly. Twenty-two retrospective HDR prostate brachytherapy patients treated with Ir-192 were considered. An Ir-192 only (IRO), Yb-169 only (YBO), and dual-source (DS) plan with optimized catheter location was created for each patient with N catheters, where N is the number of catheters used in the clinically delivered plans. The DS plans jointly optimized Yb-169 and Ir-192 dwell times. All plans and the clinical plans were normalized to deliver a 15 Gy prescription (Rx) dose to 95% of the clinical treatment volume (CTV) and evaluated for the CTV D90%, V150%, and V200%, urethra D0.1cc and D1cc, bladder V75%, and rectum V75%. Dose-volume histograms (DVHs) were generated for each structure., Results: The DS plans ubiquitously selected Ir-192 as the only treatment source. IRO outperformed YBO in organ at risk (OARs) OAR sparing, reducing the urethra D0.1cc and D1cc by 0.98% ( p = 2.22 ∗ 10 - 9 $p\ = \ 2.22*{10^{ - 9}}$ ) and 1.09% ( p = 1.22 ∗ 10 - 10 $p\ = \ 1.22*{10^{ - 10}}$ ) of the Rx dose, respectively, and reducing the bladder and rectum V75% by 0.09 ( p = 0.0023 $p\ = \ 0.0023$ ) and 0.13 cubic centimeters (cc) ( p = 0.033 $p\ = \ 0.033$ ), respectively. The YBO plans delivered a more homogenous dose to the CTV, with a smaller V150% and V200% by 3.20 ( p = 4.67 ∗ 10 - 10 $p\ = \ 4.67*{10^{ - 10}}$ ) and 1.91 cc ( p = 5.79 ∗ 10 - 10 $p\ = \ 5.79*{10^{ - 10}}$ ), respectively, and a lower CTV D90% by 0.49% ( p = 0.0056 $p\ = \ 0.0056$ ) of the prescription dose. The IRO plans reduce the urethral D1cc by 2.82% ( p = 1.38 ∗ 10 - 4 $p\ = \ 1.38*{10^{ - 4}}$ ) of the Rx dose compared to the clinical plans, at the cost of increased bladder and rectal V75% by 0.57 ( p = 0.0022 $p\ = \ 0.0022$ ) and 0.21 cc ( p = 0.019 $p\ = \ 0.019$ ), respectively, and increased CTV V150% by a mean of 1.46 cc ( p = 0.010 $p\ = \ 0.010$ ) and CTV D90% by an average of 1.40% of the Rx dose ( p = 8.80 ∗ 10 - 8 $p\ = \ 8.80*{10^{ - 8}}$ ). While these differences are statistically significant, the clinical differences between the plans are minimal., Conclusions: The proposed analytical HDR planning algorithm integrates catheter and isotope selection with dwell time optimization for varying clinical goals, including urethra sparing. The planning method can guide HDR implants and identify promising isotopes for specific HDR clinical goals, such as target conformality or OAR sparing., (© 2023 American Association of Physicists in Medicine.)

Purpose: In order to demonstrate capabilities of brachytherapy in skin cancer treatment, we reviewed clinical outcomes of patients with non-melanoma skin cancer (NMSC) treated with high-dose-rate brachytherapy (HDR-BT) at a single-institution., Material and Methods: A surface custom mold (SC), interstitial (IS), or a combination of IS and SC applicator (IS + SC) was used for treatment based on depth of tumor invasion. Contoured growth tumor volume plus a 0.5 cm margin for basal cell carcinomas (BCC) and a 1-1.5 cm margin for squamous cell carcinomas (SCC) was considered a target. A prescription dose of 41.6 Gy in 8 fractions was delivered to BCC, and 46.8 Gy in 9 fractions to SCC., Results: From 2013 to 2018, a total of 751 NMSC patients (534 BCCs and 217 SCCs) were treated with HDR-BT (518 with IS, 225 with SC, and 8 with IS + SC technique). Thirty patients (4%) partially responded to treatment, and 721 patients (96%) had complete responses. Only 3 patients (0.4%) displayed local recurrences. Grade 1, 2, and 3 acute toxicities were observed in 28.0%, 46.7%, and 1.2% of patients, respectively. Grade 1, 2, and 3 late toxicities were observed in 3.3%, 1.3%, and 0.1% of cases. Cosmetic results were excellent in 79.9%, good in 17.8%, fair in 1.7%, and poor in 0.5% of patients., Conclusions: HDR-BT using SC, IS, or IS + SC is an effective treatment for NMSC with good outcomes and cosmetic results in both BCC and SCC., Competing Interests: The authors report no conflict of interest., (Copyright © 2022 Termedia.)

Background: Up to 15% of previously irradiated metastatic spine tumors will progress. Re-irradiation of these tumors poses a significant risk of exceeding the radiation tolerance to the spinal cord. High-dose rate (HDR) brachytherapy is a treatment alternative., Objective: To develop a novel HDR spine brachytherapy technique using an intraoperative computed tomography-guided navigation (iCT navigation)., Methods: Patients with progressive metastatic spine tumors were included in the study. HDR brachytherapy catheters were placed under iCT navigation. CT-based planning with magnetic resonance imaging fusion was performed to ensure conformal dose delivery to the target while sparing normal tissue, including the spinal cord. Patients received single fraction radiation treatment., Results: Five patients with thoracolumbar tumors were treated with HDR brachytherapy. Four patients previously received radiotherapy to the same spinal level. Preimplant plans demonstrated median clinical target volume (CTV) D90 of 116.5% (110.8%-147.7%), V100 of 95.7% (95.5%-99.6%), and Dmax of 8.08 Gy (7.65-9.8 Gy) to the spinal cord/cauda equina. Postimplant plans provided median CTV D90 of 113.8% (93.6%-120.1%), V100 of 95.9% (87%-99%), and Dmax of 9.48 Gy (6.5-10.3 Gy) to cord/cauda equina. Patients who presented with back pain (n = 3) noted symptomatic improvement at a median follow-up of 22 d after treatment. Four patients demonstrated local tumor control of spinal metastatic tumor at a median follow-up of 92 d after treatment. One patient demonstrated radiographic evidence of local tumor progression 2.7 mo after treatment., Conclusion: HDR spine brachytherapy with iCT navigation is a promising treatment alternative to induce local tumor control and reduce pain symptoms associated with metastatic spine disease., (© Congress of Neurological Surgeons 2021.)

Kaposi's Sarcoma-associated herpesvirus (KSHV) is the etiologic agent of Kaposi's sarcoma, which is the most common cancer in acquired immune deficiency syndrome patients. KSHV contains a variety of immunoregulatory proteins. There have been many studies on the modulation of antiviral response by these immunoregulatory proteins of KSHV. However, the antiviral effects of extracellular vesicles (EVs) during de novo KSHV infection have not been investigated to our best knowledge. In this study, we showed that KSHV-infected cells induce interferon-stimulated genes (ISGs) response but not type I interferon in uninfected bystander cells using EVs. mRNA microarray analysis showed that ISGs and IRF-activating genes were prominently activated in EVs from KSHV-infected cells (KSHV EVs)-treated human endothelial cells, which were validated by RT-qPCR and western blot analysis. We also found that this response was not associated with cell death or apoptosis by virus infection. Mechanistically, the cGAS-STING pathway was linked with these KSHV EVs-mediated ISGs expressions, and mitochondrial DNA on the surface of KSHV EVs was one of the causative factors. Besides, KSHV EVs-treated cells showed lower infectivity for KSHV and viral replication activity than mock EVs-treated cells. Our results indicate that EVs from KSHV-infected cells could be an initiating factor for the innate immune response against viral infection, which may be critical to understanding the microenvironment of virus-infected cells.

Periodontitis is a common disease characterized by chronic inflammation and tissue destruction of gums. Human periodontal ligament stem cells (PDLSCs), derived from the periodontium, have stem cell properties similar to those of mesenchymal stem cells. PDLSCs possess not only the potential to differentiate into other tissues, but also immunomodulatory abilities. Macrophages play a critical role in periodontal disease, but little is known regarding the role of PDLSCs in macrophage modulation during inflammation. In this study, we investigated the effect of PDLSCs on the macrophage cell line. While the conditioned media from PDLSCs under normal culture conditions did not affect macrophage polarization, the lipopolysaccharide (LPS)-preconditioned PDLSCs induced significant changes in M1 polarization. Extracellular vesicles (EVs) isolated from the conditioned media of LPS-preconditioned PDLSCs induced strong M1 polarization of macrophages. Additionally, the M1 polarization was abolished by DNase I treatment of EVs. Therefore, the LPS-stimulated PDLSCs induce M1 polarization of macrophages through EVs, suggesting that the EVs from PDLSCs might be a potential therapeutic target for inflammation in the periodontium.

Background: As high-dose-rate (HDR) brachytherapy can preferentially spare normal anatomic structures surrounding the radiation target, we report on our experience using this technique in head and neck cancer reirradiation., Methods: Twenty patients received HDR brachytherapy reirradiation with curative or palliative intent from 2010-2015. Clinical and toxicity outcomes were recorded. Actuarial outcomes were calculated using Kaplan-Meier analysis., Results: For curative treatment, actuarial 2-year rates of local control and overall survival (OS) were 73% and 56%, respectively. Palliatively, a 6-month local control rate of 65% was seen. Age >70 years was associated with poorer OS (P = .042). Prior salvage resection showed a trend toward improved local control and OS (P = .069 and P = .063, respectively). Thirty-three percent had grade 3 to 4 late toxicities., Conclusion: Curative-intent HDR brachytherapy reirradiation can provide excellent local control and encouraging OS. Given the late toxicity rates, patient selection is essential, with particular utility for younger patients or those treated with salvage resection., (© 2018 Wiley Periodicals, Inc.)

Extracellular vesicles (EVs) are mediators of intercellular communication by transporting cargo containing proteins, lipids, mRNA, and miRNA. There is increasing evidence that EVs have various roles in regulating migration, invasion, stemness, survival, and immune functions. Previously, we have found that EVs from Kaposi's sarcoma-associated herpesvirus (KSHV)-infected human endothelial cells have the potential to activate the complement system. Although many studies have shown that the physical properties of EVs can be changed by their storage condition, there have been few studies for the stability of biological activity of EVs in various storage conditions. In this study, we investigated various conditions to identify the best conditions to store EVs with functional stability for 25 d. Furthermore, the correlation between the function and other characteristics of EVs, including the expression of EV markers, size distribution, and particle number, were also analyzed. Our results demonstrated that storage temperature is an important factor to maintain the activity of EVs and would be useful information for basic research and clinical application using EVs.

There is increasing evidence that the complement system is activated in various cancer tissues. Besides being involved in innate immunity against pathogens, the complement system also participates in inflammation and the modulation of tumor microenvironment. Recent studies suggest that complement activation promotes tumor progression in various ways. Among some cancer cell lines, we found that human bone osteosarcoma epithelial cells (U2-OS) can activate the alternative pathway of the complement system by pooled normal human serum. Interestingly, U2-OS cells showed less expression of complement regulatory proteins, compared to other cancer cell lines. Furthermore, the activated complement system enhanced the production of growth factors, which promoted angiogenesis of human endothelial cells. Our results demonstrated a direct linkage between the complement system and angiogenesis using the in vitro model, which suggest the complement system and related mechanisms might be potential targets for cancer treatment.

Purpose: Given the limited data using an interstitial approach with 3D-based planning for definitive cervical cancer utilizing the GEC-ESTRO defined high-risk clinical target volume (HR-CTV), we reviewed our institutional experience of cervical cancer patients with HR-CTVs ≥ 30 cc to determine whether our clinical and toxicity outcomes are acceptable., Methods: A retrospective review of 37 cervical cancer patients with high-risk clinical target volumes (HR-CTVs) ≥30 cc treated with interstitial image-guided brachytherapy (IS IGBT) was performed. All patients received external beam radiotherapy to a median dose of 45 Gy, followed by IS IGBT delivered in a single implant to a median dose of 6 Gy × 5 fractions. Median HR-CTV was 59 cc. A median HR-CTV D 90 of 87.44 Gy was achieved. Kaplan-Meier method was used to evaluate local control (LC), distant control, and overall survival (OS), with stratification by overall treatment time (OTT) ≤ 7 or >7 weeks., Results: Median followup was 17 months. The estimated 2-year LC, distant control, and OS were 77.6% (confidence interval [CI]: 63.8-94.5%), 56.8% (CI: 41.3-78.1%), and 54.4% (CI: 39.4-75%), respectively. The 2-year LC for OTT ≤7 weeks and >7 weeks were 100% and 58.3%, respectively (p = 0.026). The 2-year OS for OTT ≤7 weeks and >7 weeks were 77.8% and 38%, respectively (p = 0.021)., Discussions: IS IGBT can achieve a high D 90 to the HR-CTV even in the setting of large-volume disease and results in a favorable LC and toxicity profile. OTT > 7 weeks is associated with significant decrease in LC and OS., Conclusions: Efforts should be made to complete whole treatment within 7 weeks as this is associated with improved clinical outcomes., (Copyright © 2017 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Introduction: To identify differences in acute urinary and sexual toxicity between a 6-fraction and 2-fraction high-dose-rate brachytherapy monotherapy regimen and correlate dosimetric constraints to short-term toxicity., Methods: A single institution retrospective study of 116 men with prostate cancer treated with HDR monotherapy from 2010 to 2015 was conducted. Eighty-one men had 7.25 Gy × 6-fractions and 35 men had 13.5 Gy × 2-fractions. Patients had two CT-planned implants spaced 1-2 weeks apart. Patient baseline characteristics, International Prostate Symptom Scores (IPSS) and Sexual Health Inventory for Men (SHIM) scores were collected pre-treatment and 3, 6 and 12 months post-implantation. Mixed effect modelling was undertaken to compare baseline, 1-6 month and 7-12 month scores between groups. Poisson regression analysis was performed to correlate dosimetric constraints with acute toxicity., Results: There was no difference between baseline and post-implantation IPSS scores between 6-fraction and 2-fraction groups. SHIM scores for men treated with 6-fractions had a steeper decline at 1-6 months, but resolved at 7-12 months. Pre-treatment alpha-blocker use correlated with worse short-term acute urinary toxicity. Worsened SHIM score correlated with increasing age, diabetes mellitus and androgen-deprivation therapy. In a dosimetric analysis of outcomes, prostate V150 dose and bladder wall (D01.cc, D1cc, D2cc) dose correlated with increased IPSS score., Conclusion: No increased acute genitourinary or sexual dysfunction has been observed in men when transitioning from 6-fraction to 2-fraction HDR monotherapy. A dosimetric correlation was found between the V150 and bladder wall doses for acute urinary toxicity. Future research should continue to standardize and validate dose constraints for prostate HDR monotherapy patients., (© 2017 The Royal Australian and New Zealand College of Radiologists.)

Purpose: The purpose of this American Brachytherapy Society task force is to present a literature review and patterns of care by a panel of experts for the management of vaginal recurrence of endometrial cancer., Methods and Materials: In 2016, the American Brachytherapy Society Board selected a panel of experts in gynecologic brachytherapy to update our current state of knowledge for managing vaginal recurrence of endometrial cancer. Practice patterns were evaluated via an online survey and clinical updates occurred through a combination of literature review and clinical experience and/or expertise., Results: There are various retrospective series of patients treated with radiation for vaginal recurrence of endometrial cancer, which include a varied group of patients, multiple treatment techniques, and a range of total doses and demonstrate a wide scope of local control and overall survival outcomes. In the era of image-guided brachytherapy, high local control rates with low significant late-term morbidities can be achieved. Lower rates of local control and higher late-term toxicity are reported in the retreatment setting. In patients with no previous history of radiation treatment, external beam radiation therapy followed by brachytherapy boost should be used. There are varying practices with regard to the definition and appropriate doses of both the high-risk clinical target volume and the intermediate-risk clinical target volume in the setting of vaginal recurrence of endometrial cancer. There are limited data to provide appropriate dose constraints for some organs at risk with the majority of guidance taken from the definitive cervical cancer literature., Conclusions: A summary of literature and expert practice patterns for patient selection, dose recommendations, and constraints are provided as guidance for practitioners., (Copyright © 2017 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine whether pretreatment 3T multiparametric MRI (mpMRI) staging impacts biochemical recurrence-free survival (BRFS) or distant metastasis-free survival (DMFS) for men with high-risk prostate cancer treated with combination high-dose-rate (HDR) brachytherapy and external beam radiation therapy (EBRT)., Materials and Methods: This institutional review board-approved retrospective study included a cohort of 37 men with high-risk prostate cancer treated with HDR brachytherapy and EBRT after 3T mpMRI. Kaplan-Meier analysis was used to evaluate whether mpMRI evidence of extracapsular extension or seminal vesicle invasion (SVI) resulted in differences in BRFS or DMFS. Pretreatment and treatment-related variables were evaluated for association with biochemical failure (Phoenix definition) and distant metastatic failure using univariate Cox regression analysis., Results: The median prostate-specific antigen at diagnosis was 9 ng/mL (range 2-100). Biopsy Gleason score (bGS) was ≤8 in 38% and nine in 62%. Clinical T-category was T1-T2 in 89%, T3a in 8%, and T3b in 3%. With a median followup of 30.6 months, actuarial 3-year BRFS and DMFS were 76% and 86%, respectively. Kaplan-Meier analysis revealed that mpMRI evidence of extracapsular extension or SVI resulted in significantly higher rates of both biochemical recurrence and distant failure. Using Cox regression analysis, only mpMRI evidence of SVI vs. no SVI predicted for biochemical failure (hazard ratio 13.98, p = 0.0055)., Conclusions: For high-risk prostate cancer treated with combination HDR brachytherapy and EBRT, mpMRI evidence of SVI predicted for biochemical failure, whereas traditional pretreatment variables did not. Therefore, pretreatment 3T mpMRI appears useful for identifying men who may benefit from treatment intensification., (Copyright © 2017 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: Outcomes using high-dose-rate (HDR) brachytherapy monotherapy (without androgen deprivation therapy or external beam radiation therapy) for National Comprehensive Cancer Network-defined intermediate-risk (IR) patients are limited. We report our long-term data using HDR monotherapy for this patient population., Methods and Materials: One-hundred ninety IR prostate cancer patients were treated 1996-2013 with HDR monotherapy. Biochemical prostate-specific antigen (PSA) failure was per the Phoenix definition. Acute and late genitourinary and gastrointestinal toxicities were graded according to Common Toxicity Criteria of Adverse Events, version 4. Kaplan-Meier (KM) biochemical progression-free survival (BPFS), cause-specific survival, and overall survival rates were calculated. Univariate analyses were performed to determine relationships with BPFS. The median patient age was 66 years (43-90), and the median initial PSA was 7.4 ng/mL. The Gleason score was ≤6 in 26%, 3 + 4 in 62%, and 4 + 3 in 12%. The median treatment BED 1.5 was 254 Gy; 83% of patients were treated with a dose of 7.25 Gy × six fractions delivered in two separate implants., Results: With a median follow-up of 6.2 years, KM BPFS at 5/8 years was 97%/90%, cause-specific survival at 8 years was 100%, and overall survival at 5/8 years was 93%/88%. Late genitourinary toxicities were 36.3% Grade 1, 18.9% Grade 2, and 3.7% Grade 3. Late gastrointestinal toxicities were 6.3% Grade 1, 1.1% Grade 2, and no Grade ≥3. Of the patients with no sexual dysfunction before treatment, 68% maintained potency. Age, initial PSA, T stage, Gleason score, prostate volume, and percent positive cores did not correlate with BPFS. Stratifying by favorable vs. unfavorable IR groups did not affect BPFS., Conclusions: HDR brachytherapy monotherapy represents a safe and highly effective treatment for IR prostate cancer patients with long-term follow-up., (Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: Cost estimates through traditional hospital accounting systems are often arbitrary and ambiguous. We used time-driven activity-based costing (TDABC) to determine the true cost of low-dose-rate (LDR) and high-dose-rate (HDR) brachytherapy for prostate cancer and demonstrate opportunities for cost containment at an academic referral center., Methods and Materials: We implemented TDABC for patients treated with I-125, preplanned LDR and computed tomography based HDR brachytherapy with two implants from initial consultation through 12-month followup. We constructed detailed process maps for provision of both HDR and LDR. Personnel, space, equipment, and material costs of each step were identified and used to derive capacity cost rates, defined as price per minute. Each capacity cost rate was then multiplied by the relevant process time and products were summed to determine total cost of care., Results: The calculated cost to deliver HDR was greater than LDR by $2,668.86 ($9,538 vs. $6,869). The first and second HDR treatment day cost $3,999.67 and $3,955.67, whereas LDR was delivered on one treatment day and cost $3,887.55. The greatest overall cost driver for both LDR and HDR was personnel at 65.6% ($4,506.82) and 67.0% ($6,387.27) of the total cost. After personnel costs, disposable materials contributed the second most for LDR ($1,920.66, 28.0%) and for HDR ($2,295.94, 24.0%)., Conclusions: With TDABC, the true costs to deliver LDR and HDR from the health system perspective were derived. Analysis by physicians and hospital administrators regarding the cost of care afforded redesign opportunities including delivering HDR as one implant. Our work underscores the need to assess clinical outcomes to understand the true difference in value between these modalities., (Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: There is a lack of prescriptive, practical information for those doing the work of commissioning high-dose-rate (HDR) gynecologic (GYN) treatment equipment. The purpose of this work is to develop a vendor-neutral, consensus-based, commissioning template to improve standardization of the commissioning process., Methods and Materials: A series of commissioning procedures and tests specific to HDR GYN treatments were compiled within one institution. The list of procedures and tests was then sent to five external reviewers at clinics engaged in HDR GYN treatments. External reviewers were asked to (1) suggest deletions, additions, and improvements/modifications to descriptions, (2) link the procedures and tests to common, severe failure modes based on their effectiveness at mitigating those failure modes, and (3) rank the procedures and tests based on perceived level of importance., Results: External reviewers suggested the addition of 14 procedures and tests. The final template consists of 67 procedures and tests. "Treatment process" and "staff training" sections were identified as mitigating the highest number of commonly reported failure modes. The mean perceived importance for all procedures and tests was 4.4 of 5, and the mean for each section ranged from 3.6 to 4.8. Sections of the template that were identified as mitigating the highest number of commonly reported failure modes were not assigned the highest perceived importance., Conclusion: The commissioning template developed here provides a standardized approach to process and equipment commissioning. The discord between perceived importance and mitigation of the highest number of failure modes suggests that increased focus should be placed on procedures and tests in "treatment process" and "staff training" sections., (Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: High-dose-rate (HDR) brachytherapy was originally used with external beam radiation therapy (EBRT) to increase the dose to the prostate without injuring the bladder or rectum. Numerous studies have reported HDR brachytherapy is safe and effective. We adapted it for use without EBRT for cases not requiring lymph node treatment., Patients and Methods: We entered the patient demographics, disease characteristics, and treatment parameters into a prospective registry and serially added follow-up data for 448 men with low-risk (n=288) and intermediate-risk (n=160) prostate cancer treated from 1996 to 2009. Their median age was 64 years (range 42-90). The median prostate-specific antigen (PSA) level was 6.0 ng/mL (range 0.2-18.2). The Gleason score was ≤6 in 76% and 7 in 24%. The median dose was 43.5 Gy in 6 fractions. The clinical and biochemical disease control and survival rates were calculated. Adverse events were graded according to the Common Toxicity Criteria of Adverse Events., Results: The median follow-up period was 6.5 years (range 0.3-15.3). The actuarial 6- and 10-year PSA progression-free survival was 98.6% (95% confidence interval [CI] 96.9%-99.4%) and 97.8% (95% CI 95.5%-98.9%). Overall survival at 10 years was 76.7% (95% CI 69.9%-82.2%). The local control, distant metastasis-free survival, and cause-specific survival were 99.7% (95% CI 97.9%-99.9%), 98.9% (95% CI 96.3%-99.7%), and 99.1% (95% CI 95.8%-99.8%). T stage, initial PSA level, Gleason score, National Comprehensive Cancer Network risk group, patient age, and androgen deprivation therapy did not significantly correlate with disease control or survival. No late grade 3 to 4 rectal toxicities developed. Late grade 3 to 4 genitourinary toxicity occurred in 4.9% (grade 3 in 4.7%)., Conclusions: HDR monotherapy is a safe and highly effective treatment of low- and intermediate-risk prostate cancer., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: To determine the ability of image-guided high-dose-rate brachytherapy (IG-HDR) to provide local control (LC) of lesions in non-traditional locations for patients with heavily pre-treated malignancies., Material and Methods: This retrospective series included 18 patients treated between 2012 and 2014 with IG-HDR, either in combination with external beam radiotherapy (EBRT; n = 9) or as monotherapy (n = 9). Lesions were located in the pelvis (n = 5), extremity (n = 2), abdomen/retroperitoneum (n = 9), and head/neck (n = 2). All cases were performed in conjunction between interventional radiology and radiation oncology. Toxicity was graded based on CTCAE v4.0 and local failure was determined by RECIST criteria. Kaplan-Meier analysis was performed for LC and overall survival., Results: The median follow-up was 11.9 months. Two patients had localized disease at presentation; the remainder had recurrent and/or metastatic disease. Seven patients had prior EBRT, with a median equivalent dose in 2 Gy fractions (EQD2) of 47.0 Gy. The median total EQD2s were 34 Gy and 60.9 Gy for patients treated with monotherapy or combination therapy, respectively. Image-guided high-dose rate brachytherapy was delivered in one to six fractions. Six patients had local failures at a median interval of 5.27 months with a one-year LC rate of 59.3% and a one-year overall survival of 40.7%. Six patients died from their disease at a median interval of 6.85 months from the end of treatment. There were no grade ≥ 3 acute toxicities but two patients had serious long term toxicities., Conclusions: We demonstrate a good one year LC rate of nearly 60%, and a favorable toxicity profile when utilizing IG-HDR to deliver high doses of radiation with high precision into targets not readily accessible by other forms of local therapy. These preliminary results suggest that further studies utilizing this approach may be considered for patients with difficult to access lesions that require LC.

Purpose: To report early clinical outcomes of high-dose-rate interstitial image-guided brachytherapy (BT) in the definitive management of locally advanced cervical cancer., Methods: We retrospectively analyzed 31 locally advanced cervical cancer patients treated at our institution between January 2010 and April 2013. About 88% had advanced disease based on the International Federation of Gynecology and Obstetrics guidelines, and 87% received concurrent chemotherapy. All patients were treated with external beam radiation therapy to a median dose of 45 Gy (range, 39.6-58 Gy) before receiving BT. High-dose-rate BT was delivered in a single implant to a median dose of 6 Gy × five fractions to a CT-defined volume. Median total equivalent 2-Gy dose, dose covered by 90% of the high-risk clinical target volume (HR-CTV D90), and HR-CTV were 84, 87.4, and 49.9 cc, respectively. Kaplan-Meier method was used for actuarial survival analysis, and toxicity was graded using Common Terminology Criteria for Adverse Events, version 4.0., Results: Median followup was 19.3 months. Two-year actuarial local control, regional control, and distant metastasis (DM) were 90%, 93%, and 23.6%, respectively. Two-year disease-free survival was 55%. Genitourinary, gastrointestinal, or gynecologic Grade 3 toxicity was seen in 5 patients (3 T4a and 2 T3b) for crude rates of 13%, 7%, and 3%, respectively. Stratifying HR-CTV by <30 and >30 cc and then by HR-CTV D90 of <85, 85-90, and >90 Gy showed that 100% of the local failures, regional failures, DM, and G3 toxicity occurred in >30 cc group. The rate of DM was also significantly higher in the >30 cc group (p = 0.036)., Conclusions: An interstitial approach can achieve excellent outcomes in cases where intracavitary and/or hybrid approaches are either not suitable or not available., (Copyright © 2015 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: We compared the dosimetry of brachyablation (BA) and stereotactic ablative radiotherapy (SABR) in the treatment of liver metastases., Methods and Materials: Treatment plans for 10 consecutive liver metastasis patients, treated with SABR, were replanned for BA. BA treatment was planned using five 12 Gy fractions to the same planning target volume (PTV) used for SABR. Dosimetric parameters were compared using a Student's paired t test., Results and Conclusions: BA and SABR plans had similar mean volume receiving 100% of the prescribed dose (94.1% vs. 93.9% of PTV, p = 0.8). Mean volume receiving 150% of the prescribed dose for BA was 63.6%, whereas for SABR it was 0. The minimum dose to the PTV was 65.8% for BA, whereas for SABR it was 87.4% (p = 0.0002). Liver volume receiving ≥15 Gy was similar for BA and SABR (278 vs. 256 cc, p = 0.3). Small bowel mean dose, as percent prescription dose, was higher for BA (10.8% vs. 7.1%, p = 0.006). Stomach mean dose was similar (4.9% vs. 4.8% of prescription dose, p = 0.98). Right kidney mean dose was greater for BA (6.7% vs. 4.2%, p = 0.07). BA leads to a higher target dose, similar dose to organs at risk, but potentially with lower target coverage compared with SABR. Further work is needed to determine ideal suitability for mono vs. combination therapy with this approach., (Copyright © 2015 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: To assess the magnitude of dosimetric reductions of a focal and ultra-focal high-dose-rate (HDR) prostate brachytherapy treatment strategy relative to standard whole gland (WG) treatment., Methods and Materials: HDR brachytherapy plans for five patients treated with WG HDR monotherapy were optimized to assess different treatment strategies. Plans were generated to treat the hemigland (HG), one-third gland (1/3G), and one-sixth gland (1/6G), as well as to assess treating the WG with a boost to one of those sub-volumes (WG + HG, WG + 1/3G, WG + 1/6G). Dosimetric parameters analyzed included Target D90%, V100%, V150%, Bladder (B), Rectal (R), Urethral (U) D0.1, 1 and 2cc, Urethral V75%, and the V50% to the contralateral HG. Two-tailed t tests were used for comparison of means, and p-values less than 0.05 were considered statistically significant., Results: Target objectives (D90 > 100% and V100 > 97%) were met in all cases. Significant organs at risk dose reductions were achieved for all approaches compared with WG plans. 1/6G vs WG plans resulted in the greatest reduction in dose with a mean bladder D2cc 24.7 vs 64.8%, rectal D2cc 32.8 vs 65.3%, urethral D1cc 52.1 vs 103.8%, and V75 14.5 vs 75% (p < 0.05 for all comparisons)., Conclusion: Significant dose reductions to organs at risk can be achieved using HDR focal brachytherapy. The magnitude of the reductions achievable with treating progressively smaller sub-volumes suggests the potential to reduce morbidity, but the clinical impact on morbidity and tumor control remain to be investigated., (Copyright © 2015 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine the utility of ureteral stents in interstitial gynecological brachytherapy., Methods and Materials: We reviewed 289 patients with cervix cancer treated with high-dose-rate interstitial brachytherapy who did not have pretreatment hydronephrosis to determine the relative incidence of benign ureteral strictures after treatment. We also did comparative dosimetry analysis in five cases of high-dose-rate brachytherapy. Bilateral ureteral stents were placed during the procedure. Three dosimetry plans were created to determine the impact of modifying clinical target volume (CTV) and applying ureteral dose constraints. In Plan 1, the ureters were contoured and excluded from the CTV and 120% dose constraints were applied. In Plan 2, the ureters were contoured and excluded, but no dose constraints were applied to the ureter. In Plan 3, the CTV was created as if the location of the ureters was unknown and then ureteral dose was determined., Results: There were 11 ureteral strictures observed in 255 nonstented cases and 0 ureteral strictures in 34 stented cases. Plan 1 reduced the ureter dose (D(0.1cc)) by a median 22% (7.0-53.8%) compared with Plan 2 and by a median of 30.9% (12.3-65%). compared with Plan 3., Conclusions: Placement of stents and ureteral dose constraints facilitates dosimetry and reduces the dose to ureters. Temporary ureteral stents prevent obstruction during interstitial gynecologic brachytherapy and allows the ureters to be addressed as an organ at risk., (Copyright © 2015. Published by Elsevier Inc.)

Purpose: High-dose-rate (HDR) prostate brachytherapy delivers a heterogeneous dose distribution throughout the prostate gland. There is however limited information regarding the spatial distribution of this dose heterogeneity. To this end, we analyzed the magnitude and location of intraprostatic dose heterogeneity in HDR prostate brachytherapy., Methods and Materials: Five consecutive prostate cancer patients treated with HDR were analyzed. Based on CT-simulation images, each prostate was divided into three sections (apex, base, and mid-gland). These were further subdivided into eight symmetrical sections to give a total of 24 sections. Dose-volume histograms were analyzed from V100-V200% for these 24 sections comparing the means of individual regions, left vs right, apex vs base vs mid-gland, lateral vs medial, and anterior vs posterior. A separate analysis on dose as a function of individual region volume was also performed., Results: Analyses comparing the 24 regions showed a maximum 62% difference (range, 21.9-83.9%) at V130% and 19.9% (1.9-20.8%) at V200%. Seven regions were significantly decreased and one significantly elevated from V130-V180% when compared with the mean. The means for lateral sections were 1.57-fold higher than medial sections from V110-V200% (p < 0.0001). The dose at the base was significantly higher than the rest of the gland from V120-V200 (V150, 35.6 ± 16.2% vs 20.9 ± 13.1%, p < 0.0001)., Conclusions: There is significant intra-prostatic dose heterogeneity in prostate HDR brachytherapy. This is most notable in the increased dose to base and lateral portions of the gland. Further studies are needed to determine the impact of heterogeneity on clinical outcomes., (Copyright © 2015 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

The present review has been focused largely on the sex type differences in beef quality among heifers, cows, steers and bulls in various feeding environments. Genetic groups, feeding systems and gender are the major factors that change carcass characteristics and fatty acid profiles of cattle. Studies identified that heifer beef has super characteristics in eating quality and a better healthy composition in fatty acids than steer, cow and bull. Diet influences the variation of fatty acid profile; particularly the level of polyunsaturated fatty acids (PUFA) interacts with breed and sex. Animals finished in pasture systems were reported to show better ratios of PUFA/ saturated fatty acids and n-6/n-3. Carcasses of roughage-fed beef are lighter and have less marbling and lower quality grades but have higher cutability than carcasses of grain-fed bulls. Heifers and cows are reported to deposit more fat than steers and bulls. Among males, lower production of testosterone by steers favors more fat thickness compared with bulls. Marbling greatly varies among cattle belonging to different sexes, and particularly, females have genetic makeup that efficiently controls deposition. The current review identified that heifers can be a premium beef brand, while steer beef currently take a large part of market share across the world., (© 2014 Japanese Society of Animal Science.)

Purpose: To study the dosimetric differences of various channel combinations of the Capri vaginal applicator., Methods and Materials: The Capri consists of a single central channel (R1), an inner array of 6 channels (R2), and an outer array of 6 channels (R3). Three-dimensional plans were simulated for 6 channel arrangements (R1, R2, R12, R13, R23, and R123). Treatment plans were optimized to the applicator surface or 5-mm depth while minimizing dose to organs at risk (OARs: bladder, rectum, sigmoid, and urethra). The clinical target volume (CTV) was defined as a 5-mm circumferential shell extending 4 cm in length around the applicator. Clinical target volume coverage (Dmean, D90, V100, and V150) and OAR doses (D0.1 cm3, D1 cm3, D2 cm3, and Dmean) were compared. A comparison between the Capri (R123) and a conventional single-channel applicator was also done. Statistical significance (P value<.05) was evaluated with a 2-tailed t test., Results: When prescribing to 5-mm depth, CTV coverage using all 13 channels (R123) versus a single channel (R1) was similar; however, when prescribing to the surface there were differences (P<.0001) in all CTV metrics except for the V150. The R1 plans had higher doses to all OARs compared with R123 plans (P<.007). Doses to OARs were not significantly different between R23 and R123 plans (P=.05-.95), and CTV coverage differences were on the order of 1%. Capri R123 plans provided slightly lower CTV D90 and Dmean but equivalent OAR doses with smaller standard deviations compared with conventional cylinder plans for both prescriptions., Conclusions: The Capri multichannel applicator provides equivalent target coverage at 5-mm depth, with significantly reduced dose to OARs relative to using a single channel. Optimal plans can be achieved using R12 (lowest V150) or R123 or R23 (lowest OAR doses)., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: To determine the utility of focal high-dose-rate brachytherapy for localized prostate cancer, we investigated the impact on target coverage and dose to organs at risk (OARs) with hemigland (HG) compared with whole-gland (WG) treatment., Methods and Materials: A total of 10 WG implants were used to generate 10 WG and 20 HG (left and right) treatment plans optimized with the inverse planning simulation annealing algorithm using Oncentra MasterPlan (Nucletron B.V., Veenendaal, The Netherlands). The standard distribution of 17-18 catheters designed for WG was used to generate HG plans. The same OARs namely bladder, rectum, and urethra contours and dose constraints were applied for HG and WG plans. The HG contour was a modification of the WG contour whereby the urethra divided the prostate into HGs. The prescription dose was 7.25 Gy×6. Evaluated dose parameters were target dose D90, V100, and V150 and D0.1 cc, D1 cc, and D2 cc to OARs., Results: The HG plans had a D90, V100, and V150 to the HG target of 112%, 97.6%, and 33.8%, respectively. The WG plans had a D90, V100, and V150 to the WG target of 108%, 98.8%, and 26.5%, respectively. The OAR D2 cc doses were significantly lower in HG vs. WG plans: rectum (53.1% vs. 64.1%, p<0.0001), bladder (55.9% vs. 67.5%, p<0.0001), and urethra (69.3% vs. 95.2%, p<0.0001)., Conclusions: In the present model, HG plans yielded a statistically significant decreased radiation dose to OARs and provided complete target coverage with a catheter array designed for WG coverage. The good dosimetry results obtained in this study support the feasibility of HG brachytherapy by using a subset of the WG catheter array. Catheter distribution and dosimetry refinements tailored to subtotal prostate brachytherapy should be explored to see if further improvements in dosimetry can be achieved., (Copyright © 2013 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: A new platform for brachytherapy called electronic brachytherapy (EBT) has been developed, which uses a miniature X-ray source to generate low-energy radiation. A retrospective study of adverse events and clinical outcomes in patients treated with EBT to the vaginal cuff, either as monotherapy or in combination with external beam radiation therapy (EBRT), was conducted., Methods and Materials: Medical records were reviewed from 16 patients treated with postoperative EBT for endometrial (n=13) or cervical cancer (n=3) between February 2009 and November 2010. Patients received either intracavitary vaginal EBT alone or EBT in combination with EBRT. The radiobiologic effectiveness of EBT was assumed to be one., Results: Median follow-up was 20.5 months (range, 7-36 months). When EBT was used alone (n=5), the median dose per fraction, number of fractions, and total dose delivered were: 6Gy (range, 5.5-6.2Gy), 5 fractions (range, 5-6), and 30Gy (range, 30-34Gy), respectively. When EBT was combined with EBRT, the EBT component median dose per fraction, number of fractions, and total dose delivered were: 5Gy (range, 4.5-7Gy), 2 fractions (range, 2-4), and 14Gy (range, 9-20Gy), respectively. The median EBRT dose was 45Gy (range, 45-49.2Gy). Our local control rate, locoregional (pelvic) control rate, and overall survival rate were 94%, 94%, and 88%, respectively. Of the 16 patients, 4 patients reported Grade 2 or greater toxicity (25%); however, there were no Grade 4-5 adverse events. Gynecologic, genitourinary, and gastrointestinal adverse events accounted for 57% (n=4), 43% (n=3), and 0% (n=0) of all Grade 2 or greater side effects. No Grade 2 or higher toxicities were noted in patients treated with EBT alone., Conclusion: EBT is an acceptable means of delivering postoperative vaginal brachytherapy and appears comparable with other methods; as the sole method of treatment, the toxicity rates of EBT are low., (Copyright © 2013 American Brachytherapy Society. All rights reserved.)

Purpose: We performed a dosimetry analysis to determine how well the goals for clinical target volume coverage, dose homogeneity, and normal tissue dose constraints were achieved with high-dose-rate (HDR) prostate brachytherapy., Methods and Materials: Cumulative dose-volume histograms for 208 consecutively treated HDR prostate brachytherapy implants were analyzed. Planning was based on ultrasound-guided catheter insertion and postoperative CT imaging; the contoured clinical target volume (CTV) was the prostate, a small margin, and the proximal seminal vesicles. Dosimetric parameters analyzed for the CTV were D90, V90, V100, V150, and V200. Dose to the urethra, bladder, bladder balloon, and rectum were evaluated by the dose to 0.1 cm(3), 1 cm(3), and 2 cm(3) of each organ, expressed as a percentage of the prescribed dose. Analysis was stratified according to prostate size., Results: The mean prostate ultrasound volume was 38.7 ± 13.4 cm(3) (range: 11.7-108.6 cm(3)). The mean CTV was 75.1 ± 20.6 cm(3) (range: 33.4-156.5 cm(3)). The mean D90 was 109.2% ± 2.6% (range: 102.3%-118.4%). Ninety-three percent of observed D90 values were between 105 and 115%. The mean V90, V100, V150, and V200 were 99.9% ± 0.05%, 99.5% ± 0.8%, 25.4% ± 4.2%, and 7.8% ± 1.4%. The mean dose to 0.1 cm(3), 1 cm(3), and 2 cm(3) for organs at risk were: Urethra: 107.3% ± 3.0%, 101.1% ± 14.6%, and 47.9% ± 34.8%; bladder wall: 79.5% ± 5.1%, 69.8% ± 4.9%, and 64.3% ± 5.0%; bladder balloon: 70.3% ± 6.8%, 59.1% ± 6.6%, and 52.3% ± 6.2%; rectum: 76.3% ± 2.5%, 70.2% ± 3.3%, and 66.3% ± 3.8%. There was no significant difference between D90 and V100 when stratified by prostate size., Conclusions: HDR brachytherapy allows the physician to consistently achieve complete prostate target coverage and maintain normal tissue dose constraints for organs at risk over a wide range of target volumes., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose/objectives: To facilitate catheter spacing, implant stability, and patient comfort during multicatheter interstitial brachytherapy., Methods and Materials: Uniform and consistent spacing of multiple interstitial implant catheters can be difficult because individual catheters may become displaced during the course of treatment. The authors have developed a brachytherapy catheter fixation method using Jackson-Pratt (JP) drains that can be used within wounds to maintain catheter spacing or on the skin surface for applicator fixation. JP drains are threaded over the implant needles to space and stabilize the implant geometry. The needles are then replaced with the usual brachytherapy catheters., Results: Surgically directed ("open") placement of implant catheters is less prone to displacement when a drain connects and spaces the catheters in the wound. Fixation on the skin surface can also be achieved with the JP drains, which make the friction buttons optional. The soft drain material helps avoid discomfort and pressure injury sometimes associated with hard plastic buttons. Small (10 French) round JP drains are suitable for breast, and head and neck sites and larger 7×10-mm flat JP drains for extremity sarcomas, abdominal, or thoracic tumors., Conclusions: The complex brachytherapy devices fashioned from widely available surgical drains effectively guide and maintain geometry for multicatheter interstitial implants. Stable implant geometry leads to more reliable implementation of brachytherapy dosimetry. Patient comfort is improved and soft tissue injury from hard-edged buttons is avoided., (Copyright © 2012 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

For PET/CT, fast CT acquisition time can lead to errors in attenuation correction, particularly at the lung/diaphragm interface. Gated 4D PET can reduce motion artifacts, though residual artifacts may persist depending on the CT dataset used for attenuation correction. We performed phantom studies to evaluate 4D PET images of targets near a density interface using three different methods for attenuation correction: a single 3D CT (3D CTAC), an averaged 4D CT (CINE CTAC), and a fully phase matched 4D CT (4D CTAC). A phantom was designed with two density regions corresponding to diaphragm and lung. An 8 mL sphere phantom loaded with 18F-FDG was used to represent a lung tumor and background FDG included at an 8:1 ratio. Motion patterns of sin(x) and sin4(x) were used for dynamic studies. Image data was acquired using a GE Discovery DVCT-PET/CT scanner. Attenuation correction methods were compared based on normalized recovery coefficient (NRC), as well as a novel quantity "fixed activity volume" (FAV) introduced in our report. Image metrics were compared to those determined from a 3D PET scan with no motion present (3D STATIC). Values of FAV and NRC showed significant variation over the motion cycle when corrected by 3D CTAC images. 4D CTAC- and CINE CTAC-corrected PET images reduced these motion artifacts. The amount of artifact reduction is greater when the target is surrounded by lower density material and when motion was based on sin4(x). 4D CTAC reduced artifacts more than CINE CTAC for most scenarios. For a target surrounded by water equivalent material, there was no advantage to 4D CTAC over CINE CTAC when using the sin(x) motion pattern. Attenuation correction using both 4D CTAC or CINE CTAC can reduce motion artifacts in regions that include a tissue interface such as the lung/diaphragm border. 4D CTAC is more effective than CINE CTAC at reducing artifacts in some, but not all, scenarios.

The purpose of this study is to investigate the effect that image-guided adaptation of the gating window during treatment could have on the residual tumor motion, by simulating different gated radiotherapy techniques. There are three separate components of this simulation: (1) the 'Hokkaido Data', which are previously measured 3D data of lung tumor motion tracks and the corresponding 1D respiratory signals obtained during the entire ungated radiotherapy treatments of eight patients, (2) the respiratory gating protocol at our institution and the imaging performed under that protocol and (3) the actual simulation in which the Hokkaido Data are used to select tumor position information that could have been collected based on the imaging performed under our gating protocol. We simulated treatments with a fixed gating window and a gating window that is updated during treatment. The patient data were divided into different fractions, each with continuous acquisitions longer than 2 min. In accordance to the imaging performed under our gating protocol, we assume that we have tumor position information for the first 15 s of treatment, obtained from kV fluoroscopy, and for the rest of the fractions the tumor position is only available during the beam-on time from MV imaging. The gating window was set according to the information obtained from the first 15 s such that the residual motion was less than 3 mm. For the fixed gating window technique the gate remained the same for the entire treatment, while for the adaptive technique the range of the tumor motion during beam-on time was measured and used to adapt the gating window to keep the residual motion below 3 mm. The algorithm used to adapt the gating window is described. The residual tumor motion inside the gating window was reduced on average by 24% for the patients with regular breathing patterns and the difference was statistically significant (p-value = 0.01). The magnitude of the residual tumor motion depended on the regularity of the breathing pattern suggesting that image-guided adaptive gating should be combined with breath coaching. The adaptive gating window technique was able to track the exhale position of the breathing cycle quite successfully. Out of a total of 53 fractions the duty cycle was greater than 20% for 42 fractions for the fixed gating window technique and for 39 fractions for the adaptive gating window technique. The results of this study suggest that real-time updating of the gating window can result in reliably low residual tumor motion and therefore can facilitate safe margin reduction.

In previous studies, an electronic portal imaging device (EPID) in cine mode was used for validating respiratory gating and stereotactic body radiation therapy (SBRT) by tracking implanted fiducials. The manual marker tracking methods that were used were time and labor intensive, limiting the utility of the validation. The authors have developed an automatic algorithm to quickly and accurately extract the markers in EPID images and reconstruct their 3D positions. Studies have been performed with gold fiducials placed in solid water and dynamic thorax phantoms. In addition, the authors have examined the cases of five patients being treated under an SBRT protocol for hepatic metastases. For each case, a sequence of images was created by collecting the exit radiation using the EPID. The markers were detected and recognized using an image processing algorithm based on the Laplacian of Gaussian function. To reduce false marker detection, a marker registration technique was applied using image intensity as well as the geometric spatial transformations between the reference marker positions produced from the projection of 3D CT images and the estimated marker positions. An average marker position in 3D was reconstructed by backprojecting, towards the source, the position of each marker on the 2D image plane. From the static phantom study, spatial accuracies of <1 mm were achieved in both 2D and 3D marker locations. From the dynamic phantom study, using only the Laplacian of the Gaussian algorithm, the marker detection success rate was 88.8%. However, adding a marker registration technique which utilizes prior CT information, the detection success rate was increased to 100%. From the SBRT patient study, intrafractional tumor motion (3.1-11.3 mm) in the SI direction was measured using the 2D images. The interfractional patient setup errors (0.1-12.7 mm) in the SI, AP, and LR directions were obtained from the average marker locations reconstructed in 3D and compared to the reference planning CT image. The authors have developed an automatic algorithm to extract marker locations from MV images and have evaluated its performance. The measured intrafractional tumor motion and the interfractional daily patient setup error can be used for off-line retrospective verification of SBRT.

Gated (4D) PET/CT has the potential to greatly improve the accuracy of radiotherapy at treatment sites where internal organ motion is significant. However, the best methodology for applying 4D-PET/CT to target definition is not currently well established. With the goal of better understanding how to best apply 4D information to radiotherapy, initial studies were performed to investigate the effect of target size, respiratory motion and target-to-background activity concentration ratio (TBR) on 3D (ungated) and 4D PET images. Using a PET/CT scanner with 4D or gating capability, a full 3D-PET scan corrected with a 3D attenuation map from 3D-CT scan and a respiratory gated (4D) PET scan corrected with corresponding attenuation maps from 4D-CT were performed by imaging spherical targets (0.5-26.5 mL) filled with (18)F-FDG in a dynamic thorax phantom and NEMA IEC body phantom at different TBRs (infinite, 8 and 4). To simulate respiratory motion, the phantoms were driven sinusoidally in the superior-inferior direction with amplitudes of 0, 1 and 2 cm and a period of 4.5 s. Recovery coefficients were determined on PET images. In addition, gating methods using different numbers of gating bins (1-20 bins) were evaluated with image noise and temporal resolution. For evaluation, volume recovery coefficient, signal-to-noise ratio and contrast-to-noise ratio were calculated as a function of the number of gating bins. Moreover, the optimum thresholds which give accurate moving target volumes were obtained for 3D and 4D images. The partial volume effect and signal loss in the 3D-PET images due to the limited PET resolution and the respiratory motion, respectively were measured. The results show that signal loss depends on both the amplitude and pattern of respiratory motion. However, the 4D-PET successfully recovers most of the loss induced by the respiratory motion. The 5-bin gating method gives the best temporal resolution with acceptable image noise. The results based on the 4D scan protocols can be used to improve the accuracy of determining the gross tumor volume for tumors in the lung and abdomen.

Stereotactic body radiation therapy is predicated on a high degree of targeting accuracy. However, inaccurate patient setup as well as intra-fractional motion can hinder the delivery of high doses preferentially to the target. To ensure that the coverage delivered to the patient is as planned, an image-guided verification system has been created to estimate the delivered dose retrospectively. This will not only aid the assessment of treatment techniques, but will also allow for more accurate dose response analysis. Patients with limited hepatic metastases from solid tumors were treated with SBRT. Implanted gold markers were used as target surrogates and a body frame and compression plate provided stereotactic localization and target immobilization, respectively. During treatment, an electronic portal imaging device (EPID), operating in cine mode, collected the exit dose. The sequences of images for each field were processed off-line using in-house software for registration and seed localization. The beam's-eye-view seed positions in the treatment images were compared to those in the DRR's to determine the target shifts in the imaging plane. These target shifts were then imported into the treatment planning software. Each original field was multiplied by the number of images taken during treatment. The calculated shift from each image was then applied to each of the new subfields. Summing all of these subfields together gives the dose distribution that was actually delivered to the patient. The dose-volume histograms for the planned and delivered distributions for four patients' complete treatments are shown. For two of the patients, underdosing due to a setup error or intra-fractional drift was not wholly resolved by subsequent fractions. For one of these patients two alternative corrective strategies have been applied, retrospectively, and the prescribed target coverage recovered for both. The delivered dose can be estimated using the information contained in cine EPID images acquired during irradiation. Calculating the dose actually delivered to the target will allow us to assess treatment procedures as well as more accurately report clinical results.

A small animal positron emission tomography (PET) instrument using a high-resolution solid-state detector insert in a conventional PET system was investigated for its potential to achieve sub-millimeter spatial resolution for mouse imaging. Monte Carlo simulations were used to estimate the effect of detector configurations (thickness, length and radius) on sensitivity. From this initial study, a PET system having an inner cylindrical silicon detector (4 cm ID, 4 cm length and 1.6 cm thickness composed of 16 layers of 300 microm x 300 microm x 1 mm pads), for scattering, surrounded by an outer cylindrical BGO scintillation detector (17.6 cm ID, 16 cm length and 2 cm thickness segmented into 3 mm x 3 mm x 20 mm crystals), for capture was evaluated in detail. In order to evaluate spatial resolution, sensitivity and image quality of the PET system, 2D images of multiple point and cylinder sources were reconstructed with the simulation data including blurring from positron range and annihilation photon acollinearity using filtered backprojection (FBP). Simulation results for (18)F demonstrate 340 microm FWHM at the center of the field of view with 1.0% sensitivity from the coincidence of single scattering events in both silicon detectors and 1.0 mm FWHM with 9.0% sensitivity from the coincidence of single scattering in the silicon and full energy absorption of the second photon in the BGO detector.

A very high resolution positron emission tomography (PET) scanner for small animal imaging based on the idea of inserting a ring of high-granularity solid-state detectors into a conventional PET scanner is under investigation. A particularly interesting configuration of this concept, which takes the form of a degenerate Compton camera, is shown capable of providing sub-millimeter resolution with good sensitivity. We present a Compton PET system and estimate its performance using a proof-of-concept prototype. A prototype single-slice imaging instrument was constructed with two silicon detectors 1 mm thick, each having 512 1.4 mm x 1.4 mm pads arranged in a 32 x 16 array. The silicon detectors were located edgewise on opposite sides and flanked by two non-position sensitive BGO detectors. The scanner performance was measured for its sensitivity, energy, timing, spatial resolution and resolution uniformity. Using the experimental scanner, energy resolution for the silicon detectors is 1%. However, system energy resolution is dominated by the 23% FWHM BGO resolution. Timing resolution for silicon is 82.1 ns FWHM due to time-walk in trigger devices. Using the scattered photons, time resolution between the BGO detectors is 19.4 ns FWHM. Image resolution of 980 microm FWHM at the center of the field-of-view (FOV) is obtained from a 1D profile of a 0.254 mm diameter (18)F line source image reconstructed using the conventional 2D filtered back-projection (FBP). The 0.4 mm gap between two line sources is resolved in the image reconstructed with both FBP and the maximum likelihood expectation maximization (ML-EM) algorithm. The experimental instrument demonstrates sub-millimeter resolution. A prototype having sensitivity high enough for initial small animal images can be used for in vivo studies of small animal models of metabolism, molecular mechanism and the development of new radiotracers.

A very high resolution small animal positron emission tomograph (PET) which can achieve sub-millimeter spatial resolution is being developed using silicon pad detectors. The prototype PET for a single slice instrument consists of two 1 mm thick silicon pad detectors, each containing a 32 x 16 array of 1.4 mm x 1.4 mm pads read out with four VATAGP3 chips which have 128 channels low-noise self triggering ASIC in each chip, coincidence units, a source turntable and tungsten slice collimator. The silicon detectors were located edgewise on opposite sides of a 4 cm field-of-view to maximize efficiency. Energy resolution is dominated by electronic noise, which is 0.98% (1.38 keV) FWHM at 140.5 keV. Coincidence timing resolution is 82.1 ns FWHM and coincidence efficiency was measured to be 1.04 x 10(-3) % from two silicon detectors with annihilation photons of (18)F source Image data were acquired and reconstructed using conventional 2-D filtered-back projection (FBP) and a maximum likelihood expectation maximization (ML-EM) method. Image resolution of approximately 1.45 mm FWHM is obtained from 1-D profile of 1.1 mm diameter (18)F line source image. Even better resolution can be obtained with smaller detector element sizes. While many challenges remain in scaling up the instrument to useful efficiency including densely packed detectors and significantly improved timing resolution, performance of the test setup in terms of easily achieving submillimeter resolution is compelling.