A review of nonstandardized applicators digitization in Nucletron™ HDR procedures.

The major errors in HDR procedures were failures to enter the correct treatment distance, which could be caused by either entering wrong transmission lengths or imprecisely digitizing the dwelling positions. Most of those errors were not easily avoidable by enhancing the HDR management level because they were caused by implementations of nonstandardized applicators utilizing transmission tubes of different lengths in standard HDR procedures. We performed this comprehensive study to include all possible situations with different nonstandardized applicators that frequently occurred in HDR procedures, provide corresponding situations with standard applicator as comparisons, list all possible errors and in planning, clarify the confusions in offsets setting, and provide mathematical and quantitative solutions for each given scenarios. Training on HDR procedures with nonstandardized applicators are normally not included in most residential program for medical physics, thus this study could be meaningful in both clinical and educational purpose. At precision of 1 mm, our study could be used as the essential and practical reference for finding the correct treatment length as well as locating the accurate dwelling positions in any HDR procedure with nonstandardized applicators.

Practical Considerations During Brachytherapy Applicator Placement for Locally Advanced Cervical Cancer.

Brachytherapy is an integral part of the definitive treatment for locally advanced cervical cancer following external beam radiation therapy. Placement of brachytherapy applicators is an important skill for radiation oncologists and care must be taken to place applicators appropriately to limit complications associated with the procedure and ensure that the radiation dose sufficiently covers the target while sparing the surrounding organs at risk. Using example cases, we discuss strategies for the placement of brachytherapy applicators in patients with anatomical considerations such as large obstructing uterine fibroids and the retroverted uterus. We also discuss the management of uterine perforation during applicator placement and approaches to patients with a poor response to external beam radiation therapy before brachytherapy delivery. We draw upon the available literature and our clinical experience to suggest approaches to these challenging scenarios.

Primary Versus Secondary Radiotherapy for Heterotopic Ossification Prevention About the Elbow.

OBJECTIVES: To examine the efficacy and safety of radiotherapy for the prevention of heterotopic ossification (HO) about the elbow. DESIGN: Retrospective chart review. SETTING: Level 1 trauma center. PATIENTS/PARTICIPANTS: Two hundred and twenty-nine patients who received prophylactic radiotherapy (XRT) over a 15-year period were identified. Patients were included if they received XRT to the elbow joint and had at least 12 weeks of follow-up after XRT. Fifty-four patients were ultimately included. INTERVENTION: All patients were treated with a single dose of 7 Gy. Ninety-eight percentage of patients received XRT within 24 hours after surgery, and all patients received XRT within 72 hours after surgery. MAIN OUTCOMES MEASUREMENTS: The primary study measures evaluated were the presence or absence of clinically symptomatic HO and the presence of radiographic HO after XRT to the elbow joint. RESULTS: Eighteen patients were treated with XRT after a traumatic injury requiring surgery (primary prophylaxis), and 36 were treated with XRT after excision surgery to remove HO which had already formed (secondary prophylaxis). In the primary cohort, 16.7% developed symptomatic HO after XRT and 11.1% required surgery to resect the heterotopic bone. In the secondary cohort, 11.1% developed symptomatic HO after surgery and XRT and 5.5% required resection surgery. No secondary malignancies were identified. CONCLUSIONS: Our findings suggest that XRT for elbow HO may be safe and effective for both primary and secondary HO. XRT for HO was not shown to be associated with radiation-induced sarcoma in this series, at least in the short term. Further study in a large patient population with extended follow-up is required to better characterize populations at high risk for development of HO and secondary malignancy. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Dosimetric effects of the Smit sleeve on high-dose-rate brachytherapy tandem and ovoids plans for patients with locally advanced cervical cancer.

PURPOSE: Smit sleeves are used to facilitate insertion of the intrauterine tandem during brachytherapy for cervical cancer. When a tandem and ovoids system is used the base of the Smit sleeve displaces the ovoids distally. The dosimetric impact of this displacement is not known. Herein we performed a dosimetric analysis to quantify this impact on the integral dose and dose delivered to the organs at risk (OARs). MATERIAL AND METHODS: Eleven high-dose-rate brachytherapy plans in which a Smit sleeve was used with a tandem and ovoids were reviewed. A second set of plans was generated modifying the position of the ovoids to simulate absence of the Smit sleeve. The high-risk clinical tumor volume (HR-CTV) dose coverage was maintained the same for both sets of plans by appropriately rescaling the dwell times of the simulated plan. The mean integral dose, D2cc to the OARs (bladder, bowel, sigmoid and rectum) and the ICRU rectum point dose were compared between the original and modified plans using a paired two-sample t-test. RESULTS: Simulating removal of the Smit sleeve was associated with an average reduction in the mean integral dose of 6.1% (p < 0.001) and an average reduction of 10.9% (p = 0.004) to the rectal D2cc. Doses to the remaining OARs decreased to a lesser magnitude with only that of the sigmoid being statistically significant. CONCLUSIONS: The use of a Smit sleeve with a tandem and ovoids system could lead to the delivery of a higher mean integral dose to achieve similar HR-CTV coverage. In addition, it could increase the dose to surrounding OARs, primarily the rectum. The clinical significance of these findings is unknown, but the potential dosimetric impact of using a Smit sleeve should be taken into consideration during the planning when this device is used.

Lung metastases treated by CyberKnife image-guided robotic stereotactic radiosurgery at 41 months.

OBJECTIVES: Based on the reported success of stereotactic body radiotherapy in treating extracranial tumors, we used CyberKnife (Accuray Incorporated, Sunnyvale, CA) to treat patients with metastatic lung cancer. METHODS: This is a retrospective report of treatment details and outcomes of 35 patients, ranging in age from 33 to 91 years, with 69 histologically proven pulmonary metastases, treated by image-guided robotic stereotactic radiosurgery at the CyberKnife Center of Miami, between March 2004 and August 2007. Tumor volumes ranged from 0.7 mL to 152 mL. Total doses ranged from 5 to 60 Gy delivered in one to four fractions with an equivalent dose range from 6 to 110 Gy NTD delivered in 2-Gy fractions assuming an alpha/beta of 20 Gy. RESULTS: All patients tolerated radiosurgery well with fatigue as the main side effect. Grade 3 and grade 4 pulmonary toxic reactions were observed in one patient who had undergone a repeat treatment. Of the 35 treated patients, 27 (77%) were still alive at a median 18-month (range 2-41 mo) follow-up. Local control was 71% with 25 tumors showing a complete response, 16 a partial response, and 7 stable with disease. Eight had progressive disease. CONCLUSIONS: The delivery of precisely targeted radiation doses to lung tumors in a hypofractionated fashion is feasible and safe. Image-guided robotic stereotactic radiosurgery of pulmonary metastases with the CyberKnife achieves good rates of local disease control with limited toxicity to surrounding tissues and in many cases may be beneficial for patients for whom surgery is not an option.

CyberKnife radiosurgery for stage I lung cancer: results at 36 months.

PURPOSE: The aims of this study were to determine if image-guided robotic stereotactic radiosurgery by CyberKnife Radiosurgery System using ablative radiation doses achieves acceptable local control in medically inoperable patients with early non-small-cell lung cancer (NSCLC) and to evaluate disease-free survival, toxicity, and failure. CyberKnife can deliver the prescribed dose by using many different angles converging on the target, with real-time target tracking through a combined orthogonal radiograph imaging and optic motion tracking system (Synchrony). MATERIALS AND METHODS: A review of treatment details and outcomes for 59 patients, ranging in age from 51 years to 96 years, with 61 tumors with histologically proven cancers treated by image-guided robotic stereotactic radiosurgery at the CyberKnife Center of Miami between March 2004 and March 2007 is presented. Target localization and respiratory movement compensation were accomplished using a single fiducial marker placed within the tumor, and the X-Sight and Synchrony systems. Total doses ranged from 15 Gy to 67.5 Gy delivered in 1-5 fractions with an equivalent dose range of 24-110 Gy normalized treatment dose in 2 Gy fractions (alpha/beta = 20 Gy). RESULTS: Four patients with stage 1A NSCLC and 2 patients with stage 1B NSCLC had persistent or recurrent disease. All patients tolerated the radiosurgery well, fatigue being the main side effect. Of the 59 patients treated, 51 (86%) were still alive at 1-33-month follow-up. Eight patients have died, 2 of diseases other than cancer progression. CONCLUSION: The results indicate that the delivery of precisely targeted ablative radiation doses with surgical precision to limited treatment volumes of lung tumors in a hypofractionated fashion is feasible and safe. Image-guided robotic stereotactic radiosurgery of lung tumors with CyberKnife(R) achieves excellent rates of local disease control with limited toxicity to surrounding tissues and, in many cases, might be curative for patients for whom surgery is not an option.

Early results of CyberKnife image-guided robotic stereotactic radiosurgery for treatment of lung tumors.

OBJECTIVE: To determine if image-guided robotic stereotactic radiosurgery (IGR-SRS) by CyberKnife achieves acceptable local control in resectable but medically inoperable patients with non-small cell lung cancer (NSCLC) or pulmonary metastasis, and to evaluate control rates and toxicity. METHODS: Treatment details and outcomes were reviewed for 95 patients (age range 33-96 years) with 136 histologically proven cancers treated by IGR-SRS at the CyberKnife Center of Miami between March 2004 and March 2007. Tumor volumes ranged from 1.2 cc to 338 cc. Targeting was accomplished using combined skeletal alignment and real-time tracking via fiducials placed within the tumor. Total doses ranged from 15 to 67.5 Gy delivered in 1 to 5 fractions. RESULTS: Of the 95 patients treated, 78 (82%) are still alive at 1 to 36 months post-treatment. Nineteen patients have died, four from disease other than cancer progression. All patients but one achieved at least partial response to treatment and tolerated radiosurgery well. For the majority of our patients, fatigue had been the main side effect. CONCLUSIONS: The delivery of precisely targeted high radiation doses with surgical precision to lung tumors in a hypo-fractionated fashion is feasible and safe. Image-guided robotic stereotactic radiosurgery (IGR-SRS) of lung tumors with the CyberKnife achieves excellent rates of local disease control with limited toxicity to surrounding tissues, and in many cases may be curative for patients for whom surgery is not an option.

Treatment of early non-small cell lung cancer, stage IA, by image-guided robotic stereotactic radioablation--CyberKnife.

OBJECTIVE: To evaluate the efficacy of using image-guided robotic stereotactic radioablation as an alternative treatment modality for patients with surgically resectable, but medically inoperable, T1 N0 M0, stage IA non-small cell lung cancer. METHODS: Between January 2004 and May 2006, 19 patients, 11 women and 8 men ranging in age from 52 to 88 years, with stage IA non-small cell lung cancer were treated. Tumor volume ranged from 1.7 to 13 mL. Total doses ranged from 24 to 60 Gy delivered in 3 fractions. Eleven patients received 60 Gy. Real-time target localization was accomplished by radiographic detection of fiducial marker(s) implanted within the tumor combined with respiratory motion tracking. RESULTS: All patients tolerated radioablation well with fatigue as the main side effect. Fourteen patients are alive from 1 to 25 months posttreatment. Four patients died: 2 of comorbid disease and 2 of cancer progression (status post 60 and 55.5 Gy). Three patients developed grade I radiation pneumonitis. Two patients have stable disease. In 3 patients, cancer recurred in the planning treatment volume: in 2 patients after treatment with 60 Gy and in 1 patient after treatment with 55.5 Gy. One patient had local control in the target volume but developed metastasis to the ipsilateral hilum. Nine patients had a complete response and show no evidence of disease. CONCLUSIONS: In our early experience, stereotactic radioablation using the CyberKnife system appears to be a safe, minimally invasive, and effective modality for treating early stage lung cancer in patients with medically inoperable disease. Dose escalation and/or increasing the treatment volumes, with the aid of the high conformality of this technique, may help to achieve further improvements in these promising results.

GENIS: gene expression of sodium iodide symporter for noninvasive imaging of gene therapy vectors and quantification of gene expression in vivo.

With the goal of optimizing adenovirus-mediated suicide gene therapy for prostate cancer, we have developed a method based on the human sodium iodide symporter (hNIS) that allows for noninvasive monitoring of adenoviral vectors and quantification of gene expression magnitude and volume within the prostate. A replication-competent adenovirus (Ad5-yCD/mutTK(SR39)rep-hNIS) coexpressing a therapeutic yeast cytosine deaminase (yCD)/mutant herpes simplex virus thymidine kinase (mutTK(SR39)) fusion gene and the hNIS gene was developed. Ad5-yCD/mutTK(SR39)rep-hNIS and a replication-defective hNIS adenovirus (rAd-CMV-FLhNIS) were injected into contralateral lobes of the dog prostate and hNIS activity was monitored in live animals following administration of Na(99m)TcO(4) using gamma camera scintigraphy. Despite the close proximity of the urinary bladder, (99m)TcO(4)(-) uptake was readily detected in the prostate using viral dose levels (10(10) to 10(12) viral particles) that have been safely administered to humans. Due to its rapid clearance and short physical half-life (6 h), it was possible to obtain daily measurements of (99m)TcO(4)(-) uptake in vivo, allowing for dynamic monitoring of reporter gene expression within the prostate as well as biodistribution throughout the body. High-resolution autoradiography of prostate sections coupled with 3D reconstruction of gene expression demonstrated that the magnitude and volume of gene expression could be quantified with submillimeter resolution. Implementation of the GENIS (gene expression of Na/I symporter) technology in the clinic will facilitate optimization of future human gene therapy trials.