Donald A. McRae

TREATMENT OF SPINAL TUMORS USING CYBERKNIFE FRACTIONATED STEREOTACTIC RADIOSURGERY: PAIN AND QUALITY-OF-LIFE ASSESSMENT AFTER TREATMENT IN 200 PATIENTS

OBJECTIVEBenign and malignant tumors of the spine significantly impair the function and quality of life of many patients. Standard treatment options, including conventional radiotherapy and surgery, are often limited by anatomic constraints and previous treatment. Image-guided stereotactic radiosurgery using the CyberKnife system (Accuray, Inc., Sunnyvale, CA) is a novel approach in the multidisciplinary management of spinal tumors. The aim of this study was to evaluate the effects of CyberKnife stereotactic radiosurgery on pain and quality-of-life outcomes of patients with spinal tumors. METHODSWe conducted a prospective study of 200 patients with benign or malignant spinal tumors treated at Georgetown University Hospital between March 2002 and September 2006. Patients were treated by means of multisession stereotactic radiosurgery using the CyberKnife as initial treatment, postoperative treatment, or retreatment. Pain scores were assessed by the Visual Analog Scale, quality of life was assessed by the SF-12 survey, and neurological examinations were conducted after treatment. RESULTSMean pain scores decreased significantly from 40.1 to 28.6 after treatment (P < 0.001) and continued to decrease over the entire 4-year follow-up period (P < 0.05). SF-12 Physical Component scores demonstrated no significant change throughout the follow-up period. Mental Component scores were significantly higher after treatment (P < 0.01), representing a quality-of-life improvement. Early side effects of radiosurgery were mild and self-limited, and no late radiation toxicity was observed. CONCLUSIONCyberKnife stereotactic radiosurgery is a safe and effective modality in the treatment of patients with spinal tumors. CyberKnife offers durable pain relief and maintenance of quality of life with a very favorable side effect profile.

CyberKnife® radiosurgery in the treatment of complex skull base tumors: analysis of treatment planning parameters

BackgroundTumors of the skull base pose unique challenges to radiosurgical treatment because of their irregular shapes, proximity to critical structures and variable tumor volumes. In this study, we investigate whether acceptable treatment plans with excellent conformity and homogeneity can be generated for complex skull base tumors using the Cyberknife® radiosurgical system.MethodsAt Georgetown University Hospital from March 2002 through May 2005, the CyberKnife® was used to treat 80 patients with 82 base of skull lesions. Tumors were classified as simple or complex based on their proximity to adjacent critical structures. All planning and treatments were performed by the same radiosurgery team with the goal of minimizing dosage to adjacent critical structures and maximizing target coverage. Treatments were fractionated to allow for safer delivery of radiation to both large tumors and tumors in close proximity to critical structures.ResultsThe CyberKnife® treatment planning system was capable of generating highly conformal and homogeneous plans for complex skull base tumors. The treatment planning parameters did not significantly vary between spherical and non-spherical target volumes. The treatment parameters obtained from the plans of the complex base of skull group, including new conformity index, homogeneity index and percentage tumor coverage, were not significantly different from those of the simple group.ConclusionOur data indicate that CyberKnife® treatment plans with excellent homogeneity, conformity and percent target coverage can be obtained for complex skull base tumors. Longer follow-up will be required to determine the safety and efficacy of fractionated treatment of these lesions with this radiosurgical system.

Non-invasive, in-vivo electrical impedance of EMT-6 tumours during hyperthermia: Correlation with morphology and tumour-growth-delay

The electrical impedance at frequencies from 100 Hz to 40 MHz of EMT-6 tumours was measured non-invasively, in vivo, during hyperthermia using an apparatus constructed for this purpose. Histology and morphometry were performed on tumours harvested periodically during the heating. A ratio of conductivities at two frequencies (sigma (10MHz)/sigma (10kHz)), which minimizes the tissues temperature-coefficient effects, was used to correlate impedance changes with the histopathological changes. The bulk of the cell population followed a necrotic cell death sequence during heating. Initial increase of the sigma-ratio correlated with cell swelling, and a reversal of the rate of this increase correlated with the appearance of small membrane breaks and evidence of mitochondrial damage. A continued, slowing sigma-ratio increase to a maximum correlated with continued cell swelling accompanied by increasing membrane disruption. The subsequent decrease in sigma-ratio correlated with continued general cell lysing. Between the appearance of the first membrane breaks (sigma-ratio peak) and the evidence of general lysing (sigma-ratio peak), the tumour-growth-delay increased non-linearly. Because the sigma-ratio consistently discerned these events, these measurements were able to predict the fate of this cell population when subjected to hyperthermia. Knowledge of temperature or time of heating was not required.

Percutaneous placement of fiducial markers for thoracic malignancies

Image-guided placement of fiducial markers is in some ways an extension of percutaneous procedures such as needle biopsy of lung pathology, which are native to most interventional radiology practices. To that extent, learning the procedure is not difficult for those who are familiar with the basic principles of image-guided lung nodule biopsy. However, there are significant modifications in the procedure that are necessary in order to ensure appropriate placement and distribution of the fiducial markers. Proper positioning of fiducial markers in specific geometric configurations is essential for accurate targeting of the nodule. This chapter focuses on the principles of CT-guided percutaneous placement of fiducial markers. For the most part, this procedure is performed on a consultative basis by interventional radiologists, physicians who specialize in minimally invasive image-guided therapy. Special considerations for patient selection, pre-procedural preparation, techniques, and post-procedural care are explained.

CyberKnife frameless Image-Guided high-dose fractionated stereotactic radiosurgery with the synchrony motion tracking module in the treatment of single small peripheral lung tumors

Curative surgery is not an option for many patients with clinical stage I non-small-cell lung carcinoma (NSCLC) because of associated comorbidities. Stereotactic radiosurgery with the CyberKnife® (Accuray Incorporated, Sunnyvale, CA) tumor tracking system may be an option for many of these medically inoperable patients. Here we provide a concise overview of the standard treatment options for stage I lung cancer and a practical summary of the Georgetown University Hospital stereotactic radiosurgery treatment protocol. We review preliminary outcomes for single small peripheral lung tumors uniformly treated with the CyberKnife using the Synchrony® (Accuray Incorporated, Sunnyvale, CA) motion tracking module.

Cumulative volumetric analysis as a key criterion for the treatment of brain metastases

BACKGROUND Recent studies have demonstrated diminished cognitive function, worse quality of life, and no overall survival benefit from the addition of adjuvant whole brain radiation therapy (WBRT) to stereotactic radiosurgery (SRS) in the management of brain metastases. This study analyzes the treatment outcome of SRS, specifically CyberKnife Radiosurgery, based on the total tumor volume compared to the absolute number of lesions. METHODS A retrospective analysis of hospital records at Virginia Hospital Center for patients with brain metastases who underwent CyberKnife Radiosurgery between June 2008 and June 2014 was performed. Previous treatment history, metastatic tumor dimensions, and outcomes were recorded. Predictors of neurological defects, local tumor progression, and overall survival were assessed with univariate and multivariate analysis. RESULTS We identified 130 adult patients with a median age of 61.5years and a median follow-up of 7.1months. Unfavorable outcomes such as death, tumor progression, or neurological defect showed correlation with cumulative tumor volume greater than the median volume of 7cc (p<0.05). Worsening neurological defects showed an association with an increased number of lesions (p<0.02) and age (p<0.05). For local tumor progression, patients who have received WBRT were less likely to progress (.74, 95% CI, .48, 1.10), while those who received chemotherapy (1.48 95% CI, .98, 2.26), or surgery (1.56 95%, CI .98, 2.47) without WBRT were more likely to progress. CONCLUSIONS Our data suggest that a cumulative tumor volume greater than 7cc correlates with worse outcomes following CyberKnife Radiosurgery. In addition, WBRT appears to have a role in improved survival for patients with increased tumor burden. A prospective study is warranted to validate these findings.

Use of a target complexity index in radiosurgical plan evaluation

There is a great need for reliable tools for radiosurgery plan evaluation. With the increasing sophistication of radiosurgical treatment planning systems, the radiosurgeon finds a more challenging treatment environment and feels the need to utilize more sophisticated methods of plan evaluation. Ultimately, these methods carry the promise of assisting treatment decisions, or even replacing some of them with consistent, reliable, and verifiable measures of probable treatment success. Among the most common are indices of homogeneity, dose uniformity across the target area, and conformity, the shaping of the radiation dose to the target area. These can often be expressed as simple ratios of treatment target and normal tissue volumes receiving certain radiation doses, although more complicated forms exist. The importance of these tools lies in their rendering of complex concepts into simple values, allowing either more sophisticated additions to multiple clinical treatment parameters, or more simplification of a limited treatment parameter set to a limited metric.

Monitoring temperature and tissue-dependent changes via electrical impedance trajectories during therapy

The low frequency (<EQ 10 MHz) electrical impedance of a volume of tissue is sensitive to its temperature and its response to heating and other stresses. Major tissue changes, such as those accompanying higher hyperthermic temperatures or prolonged ischemia, and not necessarily reversible unless detected in time to alleviate the stress. Thus, it is imperative to assess the temperature and/or tissue changes in real-time if adequate monitoring of thermal treatments is to be accomplished. To this end, we focus on the use of electrical impedance measurements of a volume of tissue at temperatures in the hyperthermia region (<EQ 47 degree(s)C) where tissue responses occur at a rate which is controllable. First, using well controlled freshly excised tissue data, we examine the prototypical impedance changes associated with the early and later stages of necrosis within a tissue subjected to heating and ischemia. Then, impedance measurements made non-invasively, in vivo, in HT29 tumors are used to demonstrate the differences caused by different thermal treatments and from differences in the ischemic condition of the tissues. The electrical impedance signature of the tumors were indicative of certain cellular-level changes occurring within the tumors. The histological findings corroborate the ability of the electrical impedance to report these cellular changes. The changes are consistent with the cells proceeding along the path of necrosis. Initial cell swelling appears to be largely due to ischemia, and the cell lysing and tumor response to the defined period of heating.