Viola Chen

Six-Dimensional Correction of Intra-Fractional Prostate Motion with CyberKnife Stereotactic Body Radiation Therapy

Large fraction radiation therapy offers a shorter course of treatment and radiobiological advantages for prostate cancer treatment. The CyberKnife is an attractive technology for delivering large fraction doses based on the ability to deliver highly conformal radiation therapy to moving targets. In addition to intra-fractional translational motion (left–right, superior–inferior, and anterior–posterior), prostate rotation (pitch, roll, and yaw) can increase geographical miss risk. We describe our experience with six-dimensional (6D) intra-fraction prostate motion correction using CyberKnife stereotactic body radiation therapy (SBRT). Eighty-eight patients were treated by SBRT alone or with supplemental external radiation therapy. Trans-perineal placement of four gold fiducials within the prostate accommodated X-ray guided prostate localization and beam adjustment. Fiducial separation and non-overlapping positioning permitted the orthogonal imaging required for 6D tracking. Fiducial placement accuracy was assessed using the CyberKnife fiducial extraction algorithm. Acute toxicities were assessed using Common Toxicity Criteria v3. There were no Grade 3, or higher, complications and acute morbidity was minimal. Ninety-eight percent of patients completed treatment employing 6D prostate motion tracking with intra-fractional beam correction. Suboptimal fiducial placement limited treatment to 3D tracking in two patients. Our experience may guide others in performing 6D correction of prostate motion with CyberKnife SBRT.

Hypofractionated stereotactic body radiation therapy as monotherapy for intermediate-risk prostate cancer

BackgroundHypofractionated stereotactic body radiation therapy (SBRT) has been advanced as monotherapy for low-risk prostate cancer. We examined the dose distributions and early clinical outcomes using this modality for the treatment of intermediate-risk prostate cancer.MethodsForty-one sequential hormone-naïve intermediate-risk prostate cancer patients received 35–36.25 Gy of CyberKnife-delivered SBRT in 5 fractions. Radiation dose distributions were analyzed for coverage of potential microscopic ECE by measuring the distance from the prostatic capsule to the 33 Gy isodose line. PSA levels, toxicities, and quality of life (QOL) measures were assessed at baseline and follow-up.ResultsAll patients completed treatment with a mean coverage by the 33 Gy isodose line extending >5 mm beyond the prostatic capsule in all directions except posteriorly. Clinical responses were documented by a mean PSA decrease from 7.67 ng/mL pretreatment to 0.64 ng/mL at the median follow-up of 21 months. Forty patients remain free from biochemical progression. No Grade 3 or 4 toxicities were observed. Mean EPIC urinary irritation/obstruction and bowel QOL scores exhibited a transient decline post-treatment with a subsequent return to baseline. No significant change in sexual QOL was observed.ConclusionsIn this intermediate-risk patient population, an adequate radiation dose was delivered to areas of expected microscopic ECE in the majority of patients. Although prospective studies are needed to confirm long-term tumor control and toxicity, the short-term PSA response, biochemical relapse-free survival rate, and QOL in this interim analysis are comparable to results reported for prostate brachytherapy or external beam radiotherapy.Trial registrationThe Georgetown Institutional Review Board has approved this retrospective study (IRB 2009–510).

Low incidence of new biochemical and clinical hypogonadism following hypofractionated stereotactic body radiation therapy (SBRT) monotherapy for low- to intermediate-risk prostate cancer

BackgroundThe CyberKnife is an appealing delivery system for hypofractionated stereotactic body radiation therapy (SBRT) because of its ability to deliver highly conformal radiation therapy to moving targets. This conformity is achieved via 100s of non-coplanar radiation beams, which could potentially increase transitory testicular irradiation and result in post-therapy hypogonadism. We report on our early experience with CyberKnife SBRT for low- to intermediate-risk prostate cancer patients and assess the rate of inducing biochemical and clinical hypogonadism.MethodsTwenty-six patients were treated with hypofractionated SBRT to a dose of 36.25 Gy in 5 fractions. All patients had histologically confirmed low- to intermediate-risk prostate adenocarcinoma (clinical stage ≤ T2b, Gleason score ≤ 7, PSA ≤ 20 ng/ml). PSA and total testosterone levels were obtained pre-treatment, 1 month post-treatment and every 3 months thereafter, for 1 year. Biochemical hypogonadism was defined as a total serum testosterone level below 8 nmol/L. Urinary and gastrointestinal toxicity was assessed using Common Toxicity Criteria v3; quality of life was assessed using the American Urological Association Symptom Score, Sexual Health Inventory for Men and Expanded Prostate Cancer Index Composite questionnaires.ResultsAll 26 patients completed the treatment with a median 15 months (range, 13-19 months) follow-up. Median pre-treatment PSA was 5.75 ng/ml (range, 2.3-10.3 ng/ml), and a decrease to a median of 0.7 ng/ml (range, 0.2-1.8 ng/ml) was observed by one year post-treatment. The median pre-treatment total serum testosterone level was 13.81 nmol/L (range, 5.55 - 39.87 nmol/L). Post-treatment testosterone levels slowly decreased with the median value at one year follow-up of 10.53 nmol/L, significantly lower than the pre-treatment value (p < 0.013). The median absolute fall was 3.28 nmol/L and the median percent fall was 23.75%. There was no increase in biochemical hypogonadism at one year post-treatment. Average EPIC sexual and hormonal scores were not significantly changed by one year post-treatment.ConclusionsHypofractionated SBRT offers the radiobiological benefit of a large fraction size and is well-tolerated by men with low- to intermediate-risk prostate cancer. Early results are encouraging with an excellent biochemical response. The rate of new biochemical and clinical hypogonadism was low one year after treatment.

CyberKnife with Tumor Tracking: An Effective Treatment for High-Risk Surgical Patients with Stage I Non-Small Cell Lung Cancer.

Published data suggests that wedge resection for stage I non-small cell lung cancer (NSCLC) is associated with improved overall survival compared to stereotactic body radiation therapy. We report CyberKnife outcomes for high-risk surgical patients with biopsy-proven stage I NSCLC. PET/CT imaging was completed for staging. Three-to-five gold fiducial markers were implanted in or near tumors to serve as targeting references. Gross tumor volumes (GTVs) were contoured using lung windows; the margins were expanded by 5 mm to establish the planning treatment volume (PTV). Treatment plans were designed using a mean of 156 pencil beams. Doses delivered to the PTV ranged from 42 to 60 Gy in three fractions. The 30 Gy isodose contour extended at least 1 cm from the GTV to eradicate microscopic disease. Treatments were delivered using the CyberKnife system with tumor tracking. Examination and PET/CT imaging occurred at 3 month follow-up intervals. Forty patients (median age 76) with a median maximum tumor diameter of 2.6 cm (range, 1.4–5.0 cm) and a mean post-bronchodilator percent predicted forced expiratory volume in 1 s (FEV1) of 57% (range, 21–111%) were treated. A median dose of 48 Gy was delivered to the PTV over 3–13 days (median, 7 days). The 30 Gy isodose contour extended a mean 1.9 cm from the GTV. At a median 44 months (range, 12–72 months) follow-up, the 3 year Kaplan–Meier locoregional control and overall survival estimates compare favorably with contemporary wedge resection outcomes at 91 and 75%, respectively. CyberKnife is an effective treatment approach for stage I NSCLC that is similar to wedge resection, eradicating tumors with 1–2 cm margins in order to preserve lung function. Prospective randomized trials comparing CyberKnife with wedge resection are necessary to confirm equivalence.

A prospective, randomized, double‐blind study comparing the efficacy of topical anesthetics in nasal endoscopy

Transnasal endoscopy is commonly performed in an outpatient otolaryngology setting. Patients are typically administered a topical anesthetic and decongestant prior to this procedure to alleviate discomfort and improve visualization. There is no consensus on which topical anesthetic is most effective in optimizing patient experience during the procedure.

Five Fraction Image-Guided Radiosurgery for Primary and Recurrent Meningiomas

Purpose: Benign tumors that arise from the meninges can be difficult to treat due to their potentially large size and proximity to critical structures such as cranial nerves and sinuses. Single fraction radiosurgery may increase the risk of symptomatic peritumoral edema. In this study, we report our results on the efficacy and safety of five fraction image-guided radiosurgery for benign meningiomas. Materials/Methods: Clinical and radiographic data from 38 patients treated with five fraction radiosurgery were reviewed retrospectively. Mean tumor volume was 3.83 mm3 (range, 1.08–20.79 mm3). Radiation was delivered using the CyberKnife, a frameless robotic image-guided radiosurgery system with a median total dose of 25 Gy (range, 25–35 Gy). Results: The median follow-up was 20 months. Acute toxicity was minimal with eight patients (21%) requiring a short course of steroids for headache at the end of treatment. Pre-treatment neurological symptoms were present in 24 patients (63.2%). Post treatment, neurological symptoms resolved completely in 14 patients (58.3%), and were persistent in eight patients (33.3%). There were no local failures, 24 tumors remained stable (64%) and 14 regressed (36%). Pre-treatment peritumoral edema was observed in five patients (13.2%). Post-treatment asymptomatic peritumoral edema developed in five additional patients (13.2%). On multivariate analysis, pre-treatment peritumoral edema and location adjacent to a large vein were significant risk factors for radiographic post-treatment edema (p = 0.001 and p = 0.026 respectively). Conclusion: These results suggest that five fraction image-guided radiosurgery is well tolerated with a response rate for neurologic symptoms that is similar to other standard treatment options. Rates of peritumoral edema and new cranial nerve deficits following five fraction radiosurgery were low. Longer follow-up is required to validate the safety and long-term effectiveness of this treatment approach.

CyberKnife with Tumor Tracking: An Effective Treatment for High-Risk Surgical Patients with Single Peripheral Lung Metastases

Standard treatment for operable patients with single peripheral lung metastases is metastasectomy. We report mature CyberKnife outcomes for high-risk surgical patients with biopsy proven single peripheral lung metastases. Twenty-four patients (median age 73 years) with a mean maximum tumor diameter of 2.5 cm (range, 0.8–4.5 cm) were treated over a 6-year period extending from September 2004 to September 2010 and followed for a minimum of 1 year or until death. A mean dose of 52 Gy (range, 45–60 Gy) was delivered to the prescription isodose line in three fractions over a 3–11 day period (mean, 7 days). At a median follow-up of 20 months, the 2-year Kaplan–Meier local control and overall survival rates were 87 and 50%, respectively. CyberKnife with fiducial tracking is an effective treatment for high-risk surgical patients with single small peripheral lung metastases. Trials comparing CyberKnife with metastasectomy for operable patients are necessary to confirm equivalence.

Histopathologic effects of hypofractionated robotic radiation therapy on malignant and benign prostate tissue.

We describe the first histopathologic analysis of prostatic tissue following hypofractionated robotic radiation therapy. A 66 year-old man presented with stage II, low risk adenocarcinoma of the prostate and underwent elective conformal hypofractionated radiation therapy. His pretreatment evaluation revealed T1c adenocarcinoma, Gleasons grade 3 + 3 = 6 and a prostate specific antigen (PSA) level of 4.87 ng/ml. Hypofractionated radiation therapy (37.5 Gy in five daily fractions of 7.5 Gy) was completed on an Internal Review Board approved protocol. One year later, he developed progressive urinary retention. Transurethral prostatic resection was performed to alleviate obstructive symptoms. Bilobar hypertrophy was observed without evidence of stricture. Histolopathologic analyses of resected prostate tissues revealed changes consistent with radiation treatment, including cellular changes, inflammation, glandular atrophy and hyperplasia. There was no evidence of residual cancer, fibrosis or necrosis. The patients postoperative course was uneventful with post-treatment PSA of 0.5 ng/ml and residual grade 1 stress incontinence.

A multicenter retrospective study of frameless robotic radiosurgery for intracranial arteriovenous malformation.

Introduction: CT-guided, frameless radiosurgery is an alternative treatment to traditional catheter-angiography targeted, frame-based methods for intracranial arteriovenous malformations (AVMs). Despite the widespread use of frameless radiosurgery for treating intracranial tumors, its use for treating AVM is not-well described. Methods: Patients who completed a course of single fraction radiosurgery at The University of North Carolina or Georgetown University between 4/1/2005–4/1/2011 with single fraction radiosurgery and received at least one follow-up imaging study were included. All patients received pre-treatment planning with CTA ± MRA and were treated on the CyberKnife (Accuray) radiosurgery system. Patients were evaluated for changes in clinical symptoms and radiographic changes evaluated with MRI/MRA and catheter-angiography. Results: Twenty-six patients, 15 male and 11 female, were included in the present study at a median age of 41 years old. The Spetzler-Martin grades of the AVMs included seven Grade I, 12 Grade II, six Grade III, and one Grade IV with 14 (54%) of the patients having a pre-treatment hemorrhage. Median AVM nidal volume was 1.62 cm3 (0.57–8.26 cm3) and was treated with a median dose of 1900 cGy to the 80% isodose line. At median follow-up of 25 months, 15 patients had a complete closure of their AVM, 6 patients had a partial closure, and 5 patients were stable. Time since treatment was a significant predictor of response, with patients experience complete closure having on average 11 months more follow-up than patients with partial or no closure (p = 0.03). One patient experienced a post-treatment hemorrhage at 22 months. Conclusion: Frameless radiosurgery can be targeted with non-invasive MRI/MRA and CTA imaging. Despite the difficulty of treating AVM without catheter angiography, early results with frameless, CT-guided radiosurgery suggest that it can achieve similar results to frame-based methods at these time points.

Clinical characteristics and management of late symptom flare following stereotactic body radiation therapy for clinically localized prostate cancer.

194 Background: Stereotactic body radiation therapy (SBRT) is increasingly utilized as primary treatment for clinically localized prostate cancer. While acute urinary symptoms are well recognized, late toxicities of SBRT have not been fully described. Here, we characterize the clinical features of late symptom flare and describe symptom management approaches. Methods: Two hudred sixteen patients with clinically localized prostate cancer were treated with SBRT between February 2008 and January 2011 at Georgetown University Hospital. Twenty-nine patients who experienced late-symptom flare were included in this retrospective analysis. Treatment was delivered using the CyberKnife (35 Gy to 36.25 Gy in five fractions). Prevalence of urinary toxicities was determined using CTCAE v.4. Patient-reported urinary symptoms were assessed using the American Urological Association Symptom Score (AUA) and the Expanded Prostate Cancer Index Composite (EPIC) short form. Results: Median age was 66 with 55% being of African ...