Results of a randomized clinical trial of external beam radiation to prevent restenosis after superficial femoral artery stenting.

OBJECTIVE: The objective of this study was to evaluate the safety and efficacy of external beam radiation (EBR) in preventing restenosis after superficial femoral artery (SFA) stenting in comparison with a control group treated with SFA stenting only. METHODS: In this Institutional Review Board-approved study, patients who provided written informed consent were randomly assigned to 0 Gy or 14 Gy of EBR to the stent site 24 hours after SFA stenting. The primary end point was the angiographic binary restenosis rate 2 years after stenting. Categorical and continuous end points were respectively analyzed using logistic regression models and Wilcoxon tests. End points expressed as time to event were analyzed using a log-rank test. RESULTS: The study included 155 patients, 46 women and 109 men (mean age, 66 years; range, 45-85 years). In the 0 and 14 Gy groups, binary restenosis was present, respectively, in 44% (34/77) and 68% (52/76; P = .003) 2 years after stenting. Stent thrombosis occurred in 13% (10/78) of the 0 Gy group and in 33% (25/77) of the 14 Gy group (P = .003). Target lesion revascularization at 2 years was 26% (25/78) in the 0 Gy group and 30% (23/77) in the 14 Gy group (P = .56). There were no significant differences in total walking distances change from baseline to 2 years (46 ± 100 and 26 ± 79 m, respectively, in the 0 Gy and 14 Gy group; P = .25). There were no procedure-related deaths and no major amputations. CONCLUSIONS: A single 14 Gy dose of EBR to the SFA stenting site did not prevent in-stent restenosis.

Risk factors for PSA bounce following radiotherapy: outcomes from a multi-modal therapy analysis.

INTRODUCTION: To identify risk factors for PSA bounce (PSAb) and compare characteristics of prostate cancer patients treated with brachytherapy and external beam radiotherapy (EBRT). MATERIALS AND METHODS: We identified 362 patients treated for low risk prostate adenocarcinoma (D'Amico criteria) with a follow up time of at least 36 months. Patients received either: 1) EBRT 76 Gy in 38 fractions (n = 58); 2) hypofractionated EBRT, 45 Gy in 9 once-weekly fractions (n = 74); 3) seed brachytherapy (n = 230). PSAb was defined as a rise >= 0.2 ng/mL with subsequent return to baseline within the first 3 years after treatment. Univariate and multivariate logistic regression models were estimated to assess the association between clinical factors and occurrence of PSAb. RESULTS: There was no significant difference between treatment groups (p = 0.349), with an overall PSAb rate of 28.5%. Upon univariate analysis, the following were predictive of a lower PSAb rate: older age (OR = 0.96), higher PSA at diagnosis (OR = 0.87), more positive biopsy cores (OR = 0.98), and a higher Cancer of the Prostate Risk Assessment (CAPRA) score (CAPRA of 3 versus 1: OR = 0.33). Multivariate analysis confirmed the significance of fewer positive biopsy cores (OR = 0.99) and a lower CAPRA score (CAPRA 3 versus 1: OR = 0.34). These factors also predicted a shorter time to first PSAb. CONCLUSIONS: We found comparable rates of PSAb after different regimens of radiotherapy. We hypothesize that it results from late damage to healthy prostatic tissue. This idea is supported by the fact that we found that clinical factors indicative of a lower tumor burden were predictive of a PSAb.

Feasibility and safety of endoscopic ultrasound-guided diffusing alpha emitter radiation therapy for advanced pancreatic cancer: Preliminary data.

Background and study aims Pancreatic cancer is a devastating disease with limited locoregional treatment options. Diffusing alpha-emitter radiation therapy (Alpha DaRT), a novel cancer treatment using alpha-particle interstitial radiotherapy, may help address this challenge. The aim of this study was to evaluate the feasibility and safety of endoscopic ultrasound (EUS)-guided Alpha DaRT for advanced pancreatic cancer. Patients and methods Patients with inoperable locally advanced or metastatic pancreatic adenocarcinoma were treated with EUS-guided Alpha DaRT insertion. The Alpha DaRT sources were delivered into pancreatic tumors using a standard EUS needle with a novel proprietary applicator. Adverse events (AEs) were assessed based on the Common Terminology Criteria for Adverse Events version 5.0. Tumor response was evaluated by imaging 4 to 6 weeks post treatment. Results The first five patients were treated between March and September 2023. The procedure was technically successful in all cases, with Alpha DaRT sources inserted into the target tumor. Estimated gross tumor volume coverage ranged from 8% to 44%. Fourteen AEs were reported among three patients. Four were serious AEs, none of which was associated with the treatment, but rather, with disease progression or medical assistance in dying. Only two AEs (mild) were deemed possibly related to the study device. At the 35-day visit, two patients had progressive disease and three had stable disease, with one of the latter showing partial response 2 months post procedure. Conclusions Preliminary results from this first-in-human trial indicate that EUS-guided Alpha DaRT treatment for unresectable pancreatic cancer is feasible and safe, with no device-associated serious AEs. Further investigation of this promising novel modality is underway.

Deferred permanent prostate seed brachytherapy does not affect PSA outcome: results from a large retrospective cohort.

INTRODUCTION: To examine the outcome of deferred permanent seed brachytherapy (BT) for localized low or intermediate risk prostate cancer in order to identify predictors of delayed therapy (DT). MATERIALS AND METHODS: We studied 714 patients treated with BT with or without external radiotherapy. DT was defined as no treatment for > 350 days after the first biopsy with cancer. Factors influencing DT were analyzed. PSA outcome was assessed only in patients with a follow up ≥ 24 months. Patients with DT were compared to patients treated < 350 days using non-parametric tests. Multivariate analysis was performed using linear-regression analysis. RESULTS: BT was deferred in 125 patients (17.5%) for a median of 607 days (IQR 445-926). Patients with DT were older (71 years versus 69 years, p = 0.04) and had significantly less aggressive disease (percentage of positive biopsies, T1 disease, Gleason 6) on univariate analysis. On multivariate analysis, age (p = 0.01) and Gleason score (p = 0.05) were predictive for DT. Median (range) PSA follow up for DT patients was 36 months (24-78). The rate of patients with DT attaining a PSA at last follow up of < 0.2 ng/mL, < 0.5 ng/mL and ≤ 1 ng/mL was 53%, 73 % and 95%, respectively; only one patient (1.6 %) had biochemical failure (p = 0.61 compared to immediate BT). Multivariate analysis showed that age was predictive (p = 0.02) for a nadir of < 0.5 ng/mL and < 0.2 ng/mL (p = 0.017) and T-stage for a PSA < 0.2 ng/mL (p = 0.04). CONCLUSIONS: This is the largest analysis of the effects of deferred BT showing a promising rate of early PSA response.

Prognostic Assessment of Interim F18-Fluorodeoxyglucose Positron Emission Tomography in Esophageal Cancer Treated With Chemoradiation With or Without Surgery.

Purpose This study aimed to evaluate if the F18-fluorodeoxyglucose positron emission tomography (F18-FDG PET) response after two weeks of chemoradiation for locoregionally advanced esophageal cancer (staged Tumor (T) 3 and/or Nodes (N)+ Metastases (M) 0) was linked to the pathologic response for patients undergoing surgery, to disease-free survival (DFS) or overall survival (OS). Materials and Methods Between March 2006 and September 2017, 40 patients were prospectively enrolled in our study, gave written consent, and had PET scans performed before treatment and after two weeks of chemoradiation. One patient did not undergo his two-week PET without informing study coordinators and was excluded from analyses. Results The median age at diagnosis was 62 years. Seventy-two percent of patients had N+ disease. Median OS for the entire group was 24 months. Five-year overall survival was 17%. Survival curves for patients with no PET response, minor PET response, or good PET response overlapped and were not statistically different. For the 25 patients who underwent surgery, the positive predictive value (PPV) of the PET response relative to the pathologic response was 75% and the negative predictive value (NPV) was 62%. In study patients, the crude recurrence rate was 68% and there was no correlation between PET response and DFS. Conclusion In our study, interim PET response after two weeks of chemoradiation for locoregionally advanced esophageal cancer was not predictive of outcome or pathologic response. Based on our data and current literature, interim PET should not be used to alter treatment (whether to escalate neo-adjuvant treatment or omit surgery).

Association between erectile function and lower urinary tract symptoms in patients treated with permanent seed prostate brachytherapy.

PURPOSE: Among men who underwent permanent seed prostate brachytherapy, we aimed to: 1) investigate: whether development of lower urinary tract symptoms (LUTS) after permanent seed prostate brachytherapy was associated with suboptimal erectile function before brachytherapy, and 2) identify factors that are associated with normal erectile function before brachytherapy. METHODS AND MATERIALS: We analyzed data from 215 consecutive patients with low- or intermediate-risk prostate cancer who received permanent seed brachytherapy at our center. Erectile function at baseline (prior to brachytherapy) was assessed using the Mount Sinai Erectile Function Score (MSEFS). Urinary symptoms at baseline and at 1 month and 4 months after brachytherapy were measured using the International Prostate Symptom Score (IPSS) questionnaire. Multiple linear regression, and a multivariable mixed linear model were used to analyze differences in IPSS from baseline to 1 month and 4 months after brachytherapy. Multiple logistic regression was used to investigate factors associated with normal erectile function at baseline. RESULTS: A total of 124 patients had data available for baseline, and 1 month and 4 months after brachytherapy. Having normal erectile function (MSEFS of 3) versus suboptimal erectile function (MSEFS 0 to 2) was not associated with increases in IPSS from baseline to 1 month or 4 months after brachytherapy. Larger increases in IPSS were found in subjects who had smaller prostates (regression coefficient = -0.36) or higher seed radioactivity (regression coefficient = 0.33). Patients with higher baseline IPSS were less likely to have normal erectile function (MSEFS = 3) before brachytherapy (odds ratio = 0.88). CONCLUSION: Normal erectile function prior to brachytherapy was not associated with worse IPSS after brachytherapy. However, patients with a higher IPSS before brachytherapy also had worse erectile function before brachytherapy, which may point to a common pathway.

Clinical implementation of a digital tomosynthesis-based seed reconstruction algorithm for intraoperative postimplant dose evaluation in low dose rate prostate brachytherapy.

PURPOSE: The low dose rate brachytherapy procedure would benefit from an intraoperative postimplant dosimetry verification technique to identify possible suboptimal dose coverage and suggest a potential reimplantation. The main objective of this project is to develop an efficient, operator-free, intraoperative seed detection technique using the imaging modalities available in a low dose rate brachytherapy treatment room. METHODS: This intraoperative detection allows a complete dosimetry calculation that can be performed right after an I-125 prostate seed implantation, while the patient is still under anesthesia. To accomplish this, a digital tomosynthesis-based algorithm was developed. This automatic filtered reconstruction of the 3D volume requires seven projections acquired over a total angle of 60 degrees with an isocentric imaging system. RESULTS: A phantom study was performed to validate the technique that was used in a retrospective clinical study involving 23 patients. In the patient study, the automatic tomosynthesis-based reconstruction yielded seed detection rates of 96.7% and 2.6% false positives. The seed localization error obtained with a phantom study is 0.4 +/- 0.4 mm. The average time needed for reconstruction is below 1 min. The reconstruction algorithm also provides the seed orientation with an uncertainty of 10 degrees +/- 8 degrees. The seed detection algorithm presented here is reliable and was efficiently used in the clinic. CONCLUSIONS: When combined with an appropriate coregistration technique to identify the organs in the seed coordinate system, this algorithm will offer new possibilities for a next generation of clinical brachytherapy systems.

Poor predictive value of intraoperative real-time dosimetry for prostate seed brachytherapy.

PURPOSE: To identify dosimetric parameters predictive of a good prostate seed I(125) quality implant. We analyzed preimplant and postimplant realtime dosimetry in patients treated with intraoperative (IO) inverse planning. METHODS AND MATERIALS: We analyzed 127 consecutively treated patients with primarily low-risk prostate carcinoma who underwent prostate permanent seed I(125) brachytherapy using an IO planning approach. The implant was done using the three-dimensional transrectal ultrasound (PRE-TRUS)-guided IO interactive inverse preplanning system. The TRUS was repeated in the operating room after the implant procedure was complete (POST-TRUS). The prostate was recontoured and postimplant dosimetry was calculated. Each patient underwent computed tomography scan on Day 28 (CT-D28) to evaluate implant quality. Area under the receiver operating characteristic curves (AUROC) was evaluated for models predictive of a V100 of > or =90% and a D90 of > or =140 Gy on the basis of CT-D28 values. RESULTS: On CT-D28, 72.4% of patients had a V100 of > or =90% and 74.8% had a D90 of > or =140 Gy. AUROC for a V100 of > or =90% was 0.665 (p = 0.004) on PRE-TRUS and 0.619 (p = 0.039) on POST-TRUS. AUROC for D90 of > or =140 Gy was 0.602 (p = 0.086) on PRE-TRUS and 0.614 (p = 0.054) on POST-TRUS. Using PRE-TRUS V100 cutoff of >97% gives sensitivity of 88% and a false-positive rate of 63%. A POST-TRUS D90 cutoff of >170 Gy resulted in a sensitivity of 62% and a false-positive rate of 34%. CONCLUSIONS: Because of unacceptably high false-positive rates, IO preimplant and postimplant TRUS-based dosimetry are not accurate tools to predict for postimplant computed tomography-based dosimetry.

Factors influencing treatment decisions in patients with low risk prostate cancer referred to a brachytherapy clinic.

OBJECTIVE: The present study aimed to analyze factors influencing treatment decisions in patients diagnosed with low risk prostate cancer who were referred to a brachytherapy clinic and had to choose from four treatment options: expectant management (watchful waiting), radical prostatectomy, external beam radiation therapy, and permanent seed brachytherapy. METHODS: We analyzed factors that influenced the treatment decisions of 110 consecutive patients with low risk prostate cancer who were referred to a brachytherapy clinic in a hospital in Montreal, Canada. These factors included patient age, marital status, and profession, as well as referral source (a urologist or a radiation oncologist), and distance and driving time from the patient's home to the medical center. Cost was not a factor as the procedure is covered under the Canadian healthcare system. RESULTS: Of the 110 patients, 53 patients (48.2%) chose permanent seed brachytherapy, 33 patients (31.8%) chose expectant management, 12 patients (10.9%) chose external beam radiation therapy, and 10 patients (9.1%) chose radical prostatectomy. Patients who chose brachytherapy were significantly younger than those who chose external beam radiation therapy (p = 0.011). Patients living further away from the hospital than the median distance of 19.85 miles were more likely to choose brachytherapy than expectant management (p = 0.017).

Fusion of Intraoperative Transrectal Ultrasound Images with Post-implant Computed Tomography and Magnetic Resonance Imaging.

Purpose To compare the impact of the fusion of intraoperative transrectal ultrasound (TRUS) images with day 30 computed tomography (CT) and magnetic resonance imaging (MRI) on prostate volume and dosimetry. Methods and materials Seventy-five consecutive patients with CT and MRI obtained on day 30 with a Fast Spin Echo T2-weighted magnetic resonance (MR) sequence were analyzed. A rigid manual registration was performed between the intraoperative TRUS and day-30 CT based on the prostate volume. A second manual rigid registration was performed between the intraoperative TRUS and the day-30 MRI. The prostate contours were manually modified on CT and MRI. The difference in prostate volume and dosimetry between CT and MRI were compared. Results Prostate volume was on average 8% (standard deviation (SD) ± 16%) larger on intraoperative TRUS than on CT and 6% (18%) larger than on MRI. In 48% of the cases, the difference in volume on CT was > 10% compared to MRI. The difference in prostate volume between CT and MRI was inversely correlated to the difference in D90 (minimum dose that covers 90% of the prostate volume) between CT and MRI (r = -0.58, P < .001). A D90 < 90% was found in 5% (n = 4) on MRI and in 10% (n = 7) on CT (Fisher exact test one-sided P = .59), but in no patient was the D90 < 90% on both MRI and CT. Conclusions When fusing TRUS images with CT and MRI, the differences in prostate volume between those modalities remain clinically important in nearly half of the patients, and this has a direct influence on how implant quality is evaluated.

Stereotactic body radiotherapy (SBRT) for patients with locally advanced pancreatic cancer: A single center experience.

INTRODUCTION: Despite advances in treatment, notably in systemic therapy, the prognosis of pancreatic adenocarcinoma (PADC) remains dismal. Stereotactic body radiotherapy (SBRT) is an emerging tool in the complex management of PADC. We review outcomes of SBRT for PADC at our institution. METHODS: We reviewed patients treated with SBRT for either unresectable PADC or locally recurrent PADC after surgery. Treatment was delivered using a robotic radiosurgery system with respiratory tracking. The median prescribed dose was 30 Gy (30-35 Gy), delivered in 5-6 fractions. Toxicities were reported as per CTCAE v4.0. Survival was estimated using the Kaplan-Meier method. RESULTS: Between October 2010 and March 2016, 21 patients were treated at our institution. The median follow-up was 7 months (range: 1-28). The 1-year local control rate was 57%. The 1-year overall survival was 25% for locally advanced patients and 67% for those with local recurrences (p = 0.27). Eighty percent of cancer related deaths were due to metastatic progression. Five patients (24%) had Grade I-II gastrointestinal acute toxicity; one patient had fatal gastrointestinal bleeding 6 months after SBRT. CONCLUSION: In PADC, fractionated SBRT dose schedules near 30 Gy may strike the best balance of local control and bowel toxicity. More work is required to integrate pancreatic SBRT with modern systemic therapy.

Is intraoperative real-time dosimetry in prostate seed brachytherapy predictive of biochemical outcome?

PURPOSE: To analyze intraoperative (IO) dosimetry using transrectal ultrasound (TRUS), performed before and after prostate low-dose-rate brachytherapy (LDR-BT), and compare it to dosimetry performed 30 days following the LDR-BT implant (Day 30). MATERIAL AND METHODS: A total of 236 patients underwent prostate LDR-BT using 125I that was performed with a three-dimensional TRUS-guided interactive inverse preplanning system (preimplant dosimetry). After the implant procedure, the TRUS was repeated in the operating room, and the dosimetry was recalculated (postimplant dosimetry) and compared to dosimetry on Day 30 computed tomography (CT) scans. Area under curve (AUC) statistics was used for models predictive of dosimetric parameters at Day 30. RESULTS: The median follow-up for patients without BF was 96 months, the 5-year and 8-year biochemical recurrence (BR)-free rate was 96% and 90%, respectively. The postimplant median D90 was 3.8 Gy lower (interquartile range [IQR], 12.4-0.9), and the V100 only 1% less (IQR, 2.9-0.2%) than the preimplant dosimetry. When comparing the postimplant and the Day 30 dosimetries, the postimplant median D90 was 9.6 Gy higher (IQR [-] 9.5-30.3 Gy), and the V100 was 3.2% greater (0.2-8.9%) than Day 30 postimplant dosimetry. The variables that best predicted the D90 of Day 30 was the postimplant D90 (AUC = 0.62, p = 0.038). None of the analyzed values for IO or Day 30 dosimetry showed any predictive value for BR. CONCLUSIONS: Although improving the IO preimplant and postimplant dosimetry improved dosimetry on Day 30, the BR-free rate was not dependent on any dosimetric parameter. Unpredictable factors such as intraprostatic seed migration and IO factors, prevented the accurate prediction of Day 30 dosimetry.

External beam radiation to prevent restenosis after superficial femoral artery balloon angioplasty.

BACKGROUND: Femoropopliteal percutaneous transluminal angioplasty (PTA) remains limited by restenosis. Although vascular brachytherapy may be effective in reducing restenosis, external beam radiation would be more practical to administer after PTA. METHODS AND RESULTS: After femoropopliteal PTA without stent placement, 99 patients were randomly assigned to 0 Gy (placebo; n=24), 7 Gy (n=24), 10.5 Gy (n=26), or 14 Gy (n=25) of external beam radiation of the PTA site (with a 3-cm margin at both extremities) in 1 session 24 hours after PTA. The primary end point was minimum lumen diameter on quantitative angiography 1 year after PTA. One year after PTA, the mean minimum lumen diameter was 1.92, 1.64, 1.92, and 2.91 mm, respectively, for the 0-, 7-, 10.5-, and 14-Gy groups (P=0.0072 for 0 versus 14 Gy). Mean luminal loss was 1.14, 1.27, 1.08, and 0.14 mm, respectively, for the 4 groups (P=0.0072 for 0 versus 14 Gy). Restenosis >50% was present in 50%, 65%, 48%, and 25% of patients, respectively, for the 0-, 7-, 10.5-, and 14-Gy groups (P=0.072). At 18 months, repeated revascularizations were required in 25% of patients in the 0-Gy group versus 12% of patients in the 14-Gy group (P=0.24). CONCLUSIONS: A single session of external beam radiation of 14 Gy of the femoropopliteal angioplasty site significantly reduces restenosis at 1 year.

A Study of Pseudoprogression After Spine Stereotactic Body Radiation Therapy.

PURPOSE: To determine the incidence of pseudoprogression (PP) after spine stereotactic body radiation therapy based on a detailed and quantitative assessment of magnetic resonance imaging (MRI) morphologic tumor alterations, and to identify predictive factors distinguishing PP from local recurrence (LR). METHODS AND MATERIALS: A retrospective analysis of 35 patients with 49 spinal segments treated with spine stereotactic body radiation therapy, from 2009 to 2014, was conducted. The median number of follow-up MRI studies was 4 (range, 2-7). The gross tumor volumes (GTVs) within each of the 49 spinal segments were contoured on the pretreatment and each subsequent follow-up T1- and T2-weighted MRI sagittal sequence. T2 signal intensity was reported as the mean intensity of voxels constituting each volume. LR was defined as persistent GTV enlargement on ≥2 serial MRI studies for ≥6 months or on pathologic confirmation. PP was defined as a GTV enlargement followed by stability or regression on subsequent imaging within 6 months. Kaplan-Meier analysis was used for estimation of actuarial local control, disease-free survival, and overall survival. RESULTS: The median follow-up was 23 months (range, 1-39 months). PP was identified in 18% of treated segments (9 of 49) and LR in 29% (14 of 49). Earlier volume enlargement (5 months for PP vs 15 months for LR, P=.005), greater GTV to reference nonirradiated vertebral body T2 intensity ratio (+30% for PP vs -10% for LR, P=.005), and growth confined to 80% of the prescription isodose line (80% IDL) (8 of 9 PP cases vs 1 of 14 LR cases, P=.002) were associated with PP on univariate analysis. Multivariate analysis confirmed an earlier time to volume enlargement and growth within the 80% IDL as significant predictors of PP. LR involved the epidural space in all but 1 lesion, whereas PP was confined to the vertebral body in 7 of 9 cases. CONCLUSIONS: PP was observed in 18% of treated spinal segments. Tumor growth confined to the 80% IDL and earlier time to tumor enlargement were predictive for PP.

Stereotactic Body Radiotherapy for Inoperable Liver Tumors: Results of a Single Institutional Experience.

OBJECTIVES: Stereotactic body radiation therapy (SBRT) is an emerging treatment option for liver tumors unsuitable for ablation or surgery. We report our experience with SBRT in the treatment of liver tumors. MATERIALS AND METHODS: Patients with primary or secondary liver cancer were identified in our local SBRT database. Patients were included irrespective of prior liver-directed therapies. The primary endpoint of our review was in-field local control (LC). Secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity. RESULTS: From 2009 to 2015, a total of 71 liver lesions in 68 patients were treated with SBRT (three patients had two liver lesions treated). The median age was 71 years (27-89 years). Hepatocellular carcinoma (HCC) was the diagnosis in 23 patients (34%), with the grade of Child-Pugh A (52%), B (39%), or C (nine percent) cirrhosis. Six patients (nine percent) had intrahepatic cholangiocarcinoma (IHC). The remaining 39 patients (57%) had metastatic liver lesions. Colorectal adenocarcinoma was the most common primary tumor type (81%). The median size for HCC, IHC, and metastatic lesions was 5 cm (2-9 cm), 3.6 cm (2-4.9 cm), and 4 cm (1-8 cm), respectively. The median prescribed dose was 45 Gy (16-50 Gy). Median follow-up was 11.5 months (1-45 months). Actuarial one-year in-field LC for HCC and metastatic lesions was 85% and 64% respectively (p= 0.66). At one year, the actuarial rate of new liver lesions was 40% and 26%, respectively, (p=0.58) for HCC and metastases. Only six patients with IHC were treated with SBRT in this study - in these patients, one-year LC was 78% with new liver lesions in 53%. The SBRT treatments were well tolerated. The side effects included common criteria for adverse events (CTCAE) v4 grade 1 acute gastrointestinal toxicity in three patients, grade 3 nausea in one patient, and grade 3 acute dermatitis in another patient. Two patients had grade 5 toxicity. Radiation pneumonitis was observed in one patient two months post-SBRT treatment, and another patient was suspected to have had radio-induced liver disease (RILD) two months after SBRT. No late toxicity was seen. CONCLUSION: SBRT is a well-tolerated and effective alternative treatment option for selected patients with primary and metastatic liver tumors.

Refining prostate seed brachytherapy: Comparing high-, intermediate-, and low-activity seeds for I-125 permanent seed prostate brachytherapy.

PURPOSE: To analyze the difference in prostate coverage and dose to the rectum in men with prostate carcinoma treated with permanent seed brachytherapy with different seed activities. METHODS: Forty-nine patients treated with iodine-125 permanent seed prostate brachytherapy with low-activity seeds of 0.30-0.37 mCi were identified. For each of these patients, 2 patients with similar prostate volume (±2 cc) were paired: one treated with intermediate seed activity (0.44-0.46 mCi) and one with high seed activity (0.60-0.66 mCi). The doses to prostate and rectum were compared using CT on Day 30. RESULTS: A total of 147 patients divided into the three seed activity groups were analyzed. Mean prostate volume was 35.7 cc (standard deviation [SD], 11.70). Compared with low-activity seeds, implants with high-activity seeds consisted of an average of 22 seeds and 4.7 needles less. The dose to the prostate (prostate volume receiving 100% of the prescribed dose [V100], prostate volume receiving 150% of the prescribed dose, and minimal dose covering 90% of the prostate volume expressed in Gy) was not higher on Day 30 (p = 0.58-0.97). The mean volume (in cubic centimeters) of rectal wall receiving 100% of the prescribed dose (V100) increased with activity: low activity, 0.34 cc (SD, 0.49), intermediate activity, 0.47 cc (SD, 0.48), and high activity, 0.72 cc (SD, 0.79) (p = 0.009). There was a trend (p = 0.073) toward a higher frequency of clinically unfavorable rectal dosimetry (V100 > 1.3 cc) in patients with high-activity seeds (16.7%) compared with low-activity (6.3%) or intermediate-activity (4.2%) seeds. CONCLUSION: High-activity seeds do not result in a higher dose to the prostate but in a higher dose to the rectum.

Intracoronary brachytherapy for the prevention of restenosis after percutaneous coronary revascularization.

PURPOSE: The purpose of this article is to review the current literature pertaining to intracoronary brachytherapy for the prevention of restenosis after percutaneous coronary revascularization (PCR). METHODS: English-language articles were identified through a MEDLINE search (January 1984 to January 2003) using the keywords brachytherapy, radioactive stents, and coronary arteries. In addition, pertinent reference citations from relevant articles were reviewed. RESULTS: Restenosis after PCR is a complex process, thought to be due to a combination of vessel wall remodeling and neointimal proliferation. To date, catheter-based delivery of intracoronary brachytherapy has been found to prevent vessel wall remodeling and causes a reduction in the proliferation of the neointima. Neointimal proliferation, as measured by mean neointimal area, was reduced in all animal studies (range 26%-91%). In contrast, animal studies examining radioactive stents demonstrated an increase in neointimal proliferation, suggesting that they may not be helpful at preventing post-PCR restenosis. All human studies using catheter-based intracoronary brachytherapy for in-stent restenosis have employed either beta (beta) or gamma (gamma) radiation sources with variable doses of radiation (range 7-56 Grays [Gy]). Restenosis occurred in 12% to 40% of patients in nonrandomized studies, and clinical events occurred in 13% to 50% of patients. To date, there have been 7 published randomized trials in humans comparing catheter-based intracoronary brachytherapy to placebo, with a total of 1047 patients. The dose of radiation in the trials ranged from 14 Gy to 30 Gy. During follow-up, 8% to 33% of patients who received brachytherapy had restenosis versus 39% to 64% of patients receiving placebo. Clinical events occurred in 19% to 50% among patients who received brachytherapy versus 29% to 79% among patients receiving placebo. The majority of human studies examining radioactive stents do not demonstrate a reduction in restenosis in patients post-PCR. There are no randomized trials examining radioactive stents in humans. CONCLUSION: Nonrandomized studies of radioactive stents suggest they are not effective at preventing in-stent restenosis. In contrast, data from animal and human studies suggest that catheter-based intracoronary brachytherapy can prevent in-stent restenosis and reduce clinical events post-PCR.

Preoperative intensity modulated radiation therapy for retroperitoneal sarcoma.

The use of intensity modulated radiation therapy (IMRT) has allowed for the administration of high doses to retroperitoneal sarcomas (RSTS) while limiting toxicity to adjacent organs. The purpose of our study is to assess the outcome and toxicities of patients with RSTS treated with neo-adjuvant external beam radiation (EBRT) therapy using IMRT. This is a retrospective study of 21 patients treated with preoperative IMRT for primary or recurrent RSTS between 2005 and 2011. Overall survival (OS) and local recurrence free survival (LRFS) were computed using the Kaplan-Meier method (log-rank test). Acute and chronic toxicities were assessed using the CTCAE v. 3 criteria. The actuarial 2 and 3-year OS was 66% for both and the 5-year OS was 51%. As for LRFS it was 57% at 2 and 3-year and 51% for the 5-year LRFS. Factors predictive for local control were microscopically negative margins (p = 0.022), a median tumor diameter <15 cm (p = 0.007) and pathology of liposarcoma (p = 0.021). Furthermore, patients treated for recurrent disease fared worse (p = 0.04) in local control than patients treated for primary disease. As for OS, patients treated for Grade 1 histology had a better outcome (p 5 0.05). EBRT was generally well tolerated. Acute gastrointestinal (GI) Grade 1 or 2 toxicities occurred in 33% of patients and one patient had unexplained post-radiation Grade 2 fever that resolved after tumor resection. As for chronic toxicities 24% of our patients presented Grade 1 GI toxicity and one patient presented Grade 3 small bowel stenosis not clearly due to radiation toxicity. Despite the location and volume of the tumors treated, preoperative IMRT was very well tolerated in our patients with retroperitoneal sarcoma. Unfortunately local recurrences remain common and dose escalation is to be considered.

Unusually high prostate-specific antigen bounce after prostate brachytherapy: Searching for etiologic factors.

PURPOSE: Determine whether fat distribution, body mass index, or clinical and dosimetric factors are associated with prostate specific antigen (PSA) bounce (PSAb) of ≥1.6 ng/mL in patients treated with permanent seed (125)I prostate brachytherapy (PB). METHODS AND MATERIALS: We identified 23 patients with a PSAb of ≥1.6 ng/mL. For each patient with a bounce, at least one control with similar age (age ± 2 years, n=31) was identified. Control patients had to have no bounce (≤0.2 ng/mL) and a most recent PSA of <1 ng/mL. CT at Day 30 after PB was used to determine the volume of subcutaneous adipose tissue, visceral adipose tissue, and peri-prostatic fat. Univariate and multivariate logistic models were used to assess the association between PSAb and adipose tissue distribution and clinical and dosimetric factors. RESULTS: Mean patient age was 62.3 ± 5.3 years. Mean PSAb height was 2.7 ± 0.8 ng/mL, and mean time to bounce was 9.6 ± 4 months. More than 90% of the patients reached a PSA nadir before PSAb within 12 months post-PB. Patients showing PSAb were more likely to have a T1c disease vs. T2a (odds ratio = 18.87; 95% confidence interval: 2.32-454.55; p=0.019) and a lower seed activity per cc of prostate volume (odds ratio=0.02; 95% confidence interval=0.42-2.22; p=0.026). Neither fat distribution nor body mass index was associated with PSAb (p=0.11-0.597). CONCLUSIONS: Clinical and dosimetric factors play a role in PSAb of ≥1.6 ng/mL. Fat distribution is not associated with a PSAb. There is presently no satisfactory theory to explain the etiology of PSAb.