Daniel A. Bassano

Anti-epidermal growth factor receptor monoclonal antibody cetuximab augments radiation effects in glioblastoma multiforme in vitro and in vivo

OBJECTIVE:Previously, we demonstrated that the anti-epidermal growth factor receptor (EGFR) antibody cetuximab alone was effective against EGFR-amplified glioblastoma multiforme (GBM) cells in vivo and in vitro. The purpose of the present work was to study further the effectiveness of cetuximab as a monotherapy as well as combining it with radiation therapy or chemotherapy. METHODS:EGFR-amplified GBM cells were implanted either in the flanks of nude mice to determine the effectiveness of cetuximab on larger tumor burden or intracranially to assess the ability of cetuximab to cross the blood-brain barrier. Cells were also exposed to cetuximab in combination with radiation in vivo or chemotherapeutic agents in vitro. RESULTS:Increasing tumor burden in the flanks of mice decreased the amount of tumor growth inhibition. For the first two intracranial models using cetuximab for 5 weeks, the treated mice had a significant increase in median survival compared with controls. When cetuximab was given indefinitely, the results were encouraging, with an increase in median survival for the treated group not yet reached but at least 900%. Mice with flank GBM exposed to cetuximab and radiation had a larger increase in median survival than those with either treatment alone. Preliminary in vitro experiments using cetuximab and chemotherapeutic agents showed increased cytotoxicity. CONCLUSION:These results were encouraging, demonstrating the effectiveness of cetuximab against EGFR-amplified GBM. Surprisingly, cetuximab was effective when administered systemically in an intracranial model. Radiation augmented the effect of cetuximab on GBM in vitro and in vivo. In vitro analysis demonstrated additive effects for chemotherapeutic agents as well. These results confirm EGFR blockade with cetuximab as a potential treatment against human GBM.

Computed tomography of the lung.

Preliminary work has shown that normal lungs have predictable CT patterns and density ranges. In emphysema, there are irregular zones of extremely low density as well as an overall low mean density. CT appears to have considerable potential for early detection of pulmonary emphysema and characterization of the degree of involvement. CT can also be useful in the study of physiological phenomena such as regional blood flow.

Gamma Knife surgery in the management of radioresistant brain metastases in high-risk patients with melanoma, renal cell carcinoma, and sarcoma

OBJECT The purpose of this study was to examine the results of using Gamma Knife surgery (GKS) for brain metastases from classically radioresistant malignancies. METHODS The authors retrospectively reviewed the records of 76 patients with melanoma (50 patients), renal cell carcinoma (RCC; 23 patients), or sarcoma (3 patients) who underwent GKS between August 1998 and July 2007. Overall patient survival, intracranial progression, and local progression of individual lesions were analyzed. RESULTS The median age of the patients was 57 years (range 18-85 years) and median Karnofsky Performance Scale (KPS) score was 80 (range 20-100). Sixty-two patients (81.6%) had uncontrolled extracranial disease. A total of 303 intracranial lesions (average 3.97 per patient, range 1-27 lesions) were treated using GKS. More than 3 lesions were treated in 30 patients (39.5%). Median GKS tumor margin dose was 18 Gy (range 8-30 Gy). Thirty-seven patients (48.7%) underwent whole brain radiation therapy. The actuarial 12-month rate for freedom from local progression for individual lesions was 77.7% and was significantly higher for RCC compared with melanoma (93.6 vs 63.0%; p = 0.001). The percentage of coverage of the prescribed dose to target volume was the only treatment-related variable associated with local control: 12-month actuarial rate of freedom from local progression was 71.4% for lesions receiving >or= 90% coverage versus 0.0% for lesions receiving < 90% (p = 0.00048). Median overall survival was 5.1 months after GKS and 8.4 months after the discovery of brain metastases. Univariate analysis revealed that KPS score (p = 0.000004), recursive partitioning analysis class (p = 0.00043), and single metastases (p = 0.028), but not more than 3 metastases, to be prognostic factors of overall survival. The KPS score remained significant after multivariate analysis. Overall survival for patients with a KPS score >or= 70 was 7.1 months compared with 1.3 months for a KPS score <or= 60 (p = 0.013). CONCLUSIONS Gamma Knife surgery is an effective treatment option for patients with radioresistant brain metastases. In this setting, KPS score appeared to be a more important factor in predicting survival than having > 3 metastases. Higher rates of local tumor control were achieved for RCC in comparison with melanoma, and this may have an effect on survival in some patients. Although outcomes generally remained poor in this study population, these results suggest that GKS can be considered as a treatment option for many patients with radioresistant brain metastases, even if these patients have multiple lesions.

The linear-quadratic model and fractionated stereotactic radiotherapy

PURPOSE To determine the dose per fraction that could be used when gamma knife or linear accelerator-based stereotactic treatments are delivered in 2 or more fractions. METHODS AND MATERIALS The linear-quadratic (LQ) model was used to calculate the dose per fraction for a multiple-fraction regimen which is biologically equivalent to a given single-fraction treatment. The results are summarized in lookup tables. RESULTS AND CONCLUSION The tables can be used by practicing clinicians as a guide in planning fractionated treatment. For the large doses used in typical stereotactic treatments and for small fraction numbers, the model is not very sensitive to the value of the alpha/beta ratio in the LQ model. A simple rule of thumb is found that for two-fraction and three-fraction treatments the dose per fraction is roughly two-thirds and one-half of the single-fraction treatment dose, respectively.

A dwell position verification method for high dose rate brachytherapy.

Misplacement of dwell positions is a potential source of misadministration in high dose rate (HDR) brachytherapy. In this work, we present a dwell position verification method using fluoroscopic images. A mobile C‐arm fluoroscopic machine is used to take a snapshot of the treatment machines check cable as it reaches the most distal dwell position. This fluoroscopic image is displayed side‐by‐side with a treatment planning image on a dual monitor relay station at the HDR treatment console. Any discrepancy between the check cables position on the verification image and the intended dwell position on the planning image can be identified, immediately, thus avoiding the possibility of treating the wrong target volume. PACS numbers: 87.53.Jw, 87.53.Xd, 87.59.Ci

Physical, Performance, and Dosimetric Characteristics of the Δ-Scan 50 Whole-Body/Brain Scanner

The Δ-Scan 50 computed tomographic (CT) scanner has the ability to determine x-ray attenuation coefficients with a precision ranging from 0.3 to 2.6% depending upon such factors as patient size and scan diameter. Resolution is 20–80% greater than the pixel width, with values ranging from 1.2 to 2.1 mm. The collimating system determines certain characteristics of the image and affects the dose to the patient: doses for typical procedures are on the order of 1 rad, and gonadal doses are in the millirad range. Potential improvements are discussed.

Determination of 137Cs dosimetry parameters according to the AAPM TG-43 formalism

Traditional treatment planning systems calculate dose distributions around 137Cs intracavitary sources by interpolating stored dose rate tables or by Sievert-type integrals. Some of the recently introduced planning systems, such as the Varian BrachyVision and Eclipse (Varian Medical Systems, Palo Alto, CA), have discontinued the use of tables and have implemented instead the AAPM TG-43 formalism as a brachytherapy dosimetry calculation algorithm. In this work we present the dosimetry parameters for 137Cs intracavitary sources as determined according to the TG-43 formalism. With the availability of the TG-43 parameters, the commissioning of a 137Cs source in any current brachytherapy planning system is a straightforward task for a clinical physicist.

Lung density effect on 125I dose distribution

Perturbations in 125I implant dose distribution due to lung tissue variations have been investigated. Dose correction factors for a point source, a planar, and a volume implant have been calculated using a model which accounts for the changes in primary photon attenuation and in buildup factor when the medium is lung rather than water. Results of our calculation show that the change in dose is about 9% and 20% in the core and the periphery, respectively, of a representative implanted volume whose density is 0.25 relative to water.

Dosimetry of computerized tomography in the evaluation of hip dysplasia

The usefulness of computerized tomography (CT) in the assessment of hip dysplasia has recently been given attention in the literature and concern regarding radiation dose has been raised. This study was undertaken to measure the radiation dose, both in and out of plaster, for plain films, arthrography, tomography, and CT. A method is suggested to reduce dosage by 80% without compromising diagnostic information. Our experience with 25 scans of patients aged 4 months to 39 years is presented.

Relative Doses to Skin and Superficial Nodes from 10 MV Photons as a Function of Field Size and Distance from Shadow Tray

Although low entrance dosea are desirable for cosmetic and tolerance reasons, they may leave the superficial nodes underdosed. Surface dose dependence on area and distance from the shadow tray for 10 MV photons was studied and comparisons made with 60Co and 4 MV energies. The use of 10 MV photons would leave superficial nodes underdosed unless a bolus or supplementary treatment, such as electrons, is used. Treatment planning implications for a mantle field are discussed.