Analytical HDR prostate brachytherapy planning with automatic catheter and isotope selection.

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.

High-dose-rate skin brachytherapy with interstitial, surface, or a combination of interstitial and surface mold technique.

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.

High-Dose Rate Interstitial Spine Brachytherapy Using an Intraoperative Mobile Computed Tomography-Guided Surgical Navigation System.

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.

Extracellular Vesicles From KSHV-Infected Cells Stimulate Antiviral Immune Response Through Mitochondrial DNA.

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.

Lipopolysaccharide-Preconditioned Periodontal Ligament Stem Cells Induce M1 Polarization of Macrophages through Extracellular Vesicles.

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.

The effect of storage temperature on the biological activity of extracellular vesicles for the complement system.

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.

Activation of the complement system in an osteosarcoma cell line promotes angiogenesis through enhanced production of growth factors.

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.

Head and neck cancer reirradiation with interstitial high-dose-rate brachytherapy.

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.

Comparison of patient-reported acute urinary and sexual toxicity scores in a 6- versus 2-fraction course of high-dose-rate prostate brachytherapy monotherapy.

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.

Clinical outcomes using image-guided interstitial brachytherapy for definitive cervical cancer patients with high-risk clinical target volumes greater than 30 cc.

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 D90 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 D90 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.

American Brachytherapy Society recurrent carcinoma of the endometrium task force patterns of care and review of the literature.

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.

Pretreatment 3T multiparametric MRI staging predicts for biochemical failure in high-risk prostate cancer treated with combination high-dose-rate brachytherapy and external beam radiotherapy.

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.

High-dose-rate brachytherapy monotherapy without androgen deprivation therapy for intermediate-risk prostate cancer.

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 BED1.5 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.

Time-driven activity-based costing of low-dose-rate and high-dose-rate brachytherapy for low-risk prostate cancer.

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.

A consensus-based, process commissioning template for high-dose-rate gynecologic treatments.

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.

High-Dose-Rate Monotherapy for Localized Prostate Cancer: 10-Year Results.

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.

Image-guided high-dose-rate brachytherapy: preliminary outcomes and toxicity of a joint interventional radiology and radiation oncology technique for achieving local control in challenging cases.

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.

Early clinical outcomes of ultrasound-guided CT-planned high-dose-rate interstitial brachytherapy for primary locally advanced cervical cancer.

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.

Dosimetric comparison of brachyablation and stereotactic ablative body radiotherapy in the treatment of liver metastasis.

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.