Bernard F. Schneider

Loss of chromosomes 22 and 14 in the malignant progression of meningiomas: A comparative study of fluorescence in situ hybridization (FISH) and standard cytogenetic analysis☆

The majority of meningiomas are classified as typical and have a relatively benign course. However, approximately 10% are diagnosed as atypical, anaplastic, or malignant and have a worse prognosis. The genetic differences between the typical and higher grade meningiomas are not well characterized, although there appear to be increasingly complex karyotypic changes associated with the higher grade tumors. Because higher grade meningiomas are not common tumors, and because of the inherent problems associated with the culturing of tumors, the use of interphase cytogenetic techniques with paraffin-embedded archival material is desirable for studying these neoplasms. To determine its accuracy in detecting aneuploidy, we performed fluorescence in situ hybridization (FISH) on 2-micron paraffin sections of nine previously karyotyped meningiomas using an alpha-satellite probe for chromosomes 14 and 22. Sections of normal tissue from six patients without malignancy were used as controls. FISH analysis detected all of the chromosome losses in the meningioma cases that had been characterized cytogenetically. In five cases, cell lines not detected by standard cytogenetics were identified by FISH. These results indicate that FISH is a reliable method for detecting chromosomal loss and may be more sensitive than standard cytogenetics alone. Furthermore, the results of this study support the concept that loss of chromosome 14 is associated with malignant progression in meningiomas.

Occult carcinoma discovered after simple hysterectomy treated with postoperative radiotherapy

PURPOSE Treatment of patients with occult carcinoma of the cervix discovered after simple hysterectomy is controversial. The purpose of this review is to examine our results with postoperative radiotherapy and to compare them to similar reports and to reports of treatment with radical parametrectomy. METHODS AND MATERIALS Between November 1979 and April:, 18 patients were treated with radiotherapy at the University of Virginia for invasive carcinoma of the cervix discovered after simple hysterectomy. Simple hysterectomy was performed in all 18 patients for a variety of indications. After surgery gross residual carcinoma remained in four patients; and microscopic disease was present at the surgical margins in two patients. The remaining patients had no evidence of residual disease. All 18 patients had postoperative radiotherapy with or without brachytherapy. The endpoints for this study were local control, survival, and treatment-related toxicity. Actuarial rates were calculated using the Life Table method. RESULTS Median follow-up for all 18 patients was 42 months (range 2-202 months). Both the 5 and the 10-year actuarial local control rates were 88%. Five and 10-year actuarial overall survival rates were both 93%. Two patients had both local and distant cancer recurrences. There were no recurrences among the six patients treated with external beam alone. The remaining patients are all alive without evidence of disease, including two patients who had gross residual disease after surgery, and one patient with both microscopic positive margin and a positive lymph node (the only patient to undergo lymph node sampling). There was no severe acute morbidity and only one patient had severe late morbidity. CONCLUSIONS Invasive carcinoma found after simple hysterectomy may be treated safely and effectively with postoperative radiotherapy. Patients with known residual disease following surgery do poorly with either radiotherapy or reoperation, but treatment with radiotherapy alone may be less morbid. Also, for the treatment of minimal disease external beam radiation to the pelvis appears to be as effective and possibly less morbid than radical reoperation.

A method to compare supra-pubic ultrasound and CT images of the prostate: Technique and early clinical results

We describe a unique method that allows the comparison of spatially registered ultrasound (SRUS) images and computed tomography-derived contours (CTDCs) that were acquired with a minimal time lapse. As such, we have a tool that will provide validation of the spatial accuracy of the US system and that will allow comparison of anatomical boundaries derived via the two different imaging modalities. We describe the method by which the commercial US system is mechanically registered to a CT simulator and a unique data processing procedure. This data processing procedure circumvents the standard data acquisition and manual contouring sequence, thus reducing the time lapse from CT to US image acquisition to 10 minutes on average. Verification using a phantom demonstrated the method to be spatially accurate to within +/- 1 mm in the anterior-posterior (AP) and lateral directions and +/- 3 mm in the inferior-superior (IS) direction. Early clinical results gathered on 8 patients demonstrated alignment between the US and the CTDCs to be 0 mm in the AP and lateral directions and 2 mm in the IS direction, on average. The technique was used to compare the appearance of the prostate using US and CT imaging. The lateral dimension of the prostate indicated by the CTDCs was larger than that indicated by US imaging in all cases and on average by 0.9 cm. The height of the prostate in the AP direction was larger on average by 0.3 cm using CTDCs than US, and was larger by 5 mm or more in 3 out of 7 cases. The role of uncertainties in the determination of the CTDCs is examined as a possible cause and implications for treatment planning are described.

3D DOSE VERIFICATION USING TOMOTHERAPY CT DETECTOR ARRAY

PURPOSE To evaluate a three-dimensional dose verification method based on the exit dose using the onboard detector of tomotherapy. METHODS AND MATERIALS The study included 347 treatment fractions from 24 patients, including 10 prostate, 5 head and neck (HN), and 9 spinal stereotactic body radiation therapy (SBRT) cases. Detector sonograms were retrieved and back-projected to calculate entrance fluence, which was then forward-projected on the CT images to calculate the verification dose, which was compared with ion chamber and film measurement in the QA plans and with the planning dose in patient plans. RESULTS Root mean square (RMS) errors of 2.0%, 2.2%, and 2.0% were observed comparing the dose verification (DV) and the ion chamber measured point dose in the phantom plans for HN, prostate, and spinal SBRT patients, respectively. When cumulative dose in the entire treatment is considered, for HN patients, the error of the mean dose to the planning target volume (PTV) varied from 1.47% to 5.62% with a RMS error of 3.55%. For prostate patients, the error of the mean dose to the prostate target volume varied from -5.11% to 3.29%, with a RMS error of 2.49%. The RMS error of maximum doses to the bladder and the rectum were 2.34% (-4.17% to 2.61%) and 2.64% (-4.54% to 3.94%), respectively. For the nine spinal SBRT patients, the RMS error of the minimum dose to the PTV was 2.43% (-5.39% to 2.48%). The RMS error of maximum dose to the spinal cord was 1.05% (-2.86% to 0.89%). CONCLUSIONS An excellent agreement was observed between the measurement and the verification dose. In the patient treatments, the agreement in doses to the majority of PTVs and organs at risk is within 5% for the cumulative treatment course doses. The dosimetric error strongly depends on the error in multileaf collimator leaf opening time with a sensitivity correlating to the gantry rotation period.

Cytogenetic Abnormalities in Primary Bronchopulmonary Leiomyosarcoma of Childhood

Primary bronchopulmonary leiomyosarcoma (PBLMS) is a rare malignant neoplasm in all age groups and only 10 pediatric cases of PBLMS have been reported. This report presents cytogenetic findings of a PBLMS from an 8-year-old boy. Tumor diagnosis was established by using routine histopathology, immunohistochemistry, and electron microscopy. The karyotype was highly complex, demonstrating consistent structural abnormalities of chromosomes 1, 5, 6, and 7, relative gain of chromosomes 2 and 11, and relative loss of chromosomes 9, 19, 20, and 22, along with the presence of multiple marker chromosomes. Cytogenetic results of previously reported leiomyosarcomas are reviewed and compared with the present case.

Non-surgical treatment of primary female urethral cancer

Primary carcinomas of the female urethra are extremely rare, with an annual incidence of less than ten in one million. Currently, there is no consensus regarding management of this malignancy. However, there have been several case reports demonstrating the efficacy of chemoradiation in the treatment of female urethral cancer. In this report we present two cases of female primary urethral adenocarcinoma that were treated by concomitant chemotherapy and external beam radiotherapy, followed by interstitial brachytherapy.

SU‐E‐T‐427: Effect of Contrast in Radiadyne Alatus Balloon Packing System on Bladder and Rectal Doses in Gynecological Brachytherapy

PURPOSE Vaginal packing for gynecological brachytherapy is used to immobilize the applicator and reduce doses to the bladder and rectum by increasing the separation from the applicator. With the introduction of theRadiadyne Alatus™ balloon packing system, we evaluate further reductions in dose to these structures by increasing the concentration of contrast in the balloon, increasing its attenuation. This evaluation has been performed using the Acuros™ dose calculation algorithm. METHODS A patient with cervical cancer was treated with HDR Ir-192 by insertion of a tandem and ovoid applicator, with the Alatus™ balloon system used for vaginal packing instead of wet gauze. The balloons were filled with distilled water containing 10% Omnipaque contrast. Retrospectively, the balloons were contoured in the BrachyVision™ planning system, and the CT number of the structure set was adjusted to determine the effect of the concentration of the contrast in the balloons on bladder and rectal doses after heterogeneity correction using the Acuros™ algorithm. RESULTS Use of 10% Omnipaque solution reduced the bladder and rectal point doses by 6% and 9.5%, respectively, with similar reductions in the D2cc and D1cc for each structure. Overriding the density of the balloon showed that a 50% solution would reduce the doses by 8% and 30%, respectively, due to the positions of the balloons with respect to the applicator dwell positions. CONCLUSIONS Use of the Alatus™ balloon packing system allows reduction of the bladder and rectal doses both by increasing the distance between the bladder and rectum and the applicators and by increased attenuation of the dose by the use of contrast solution. Optimal dilution of the contrast should take into account both the positive protective effect of the solution as well as any negative artifact that the solution causes in the CT scan, which might obscure the patients anatomy patient.

Prostate Seed Brachytherapy - Methods to Improve Implant Characteristics

Prostate cancer is diagnosed in over 230,000 men each year in the United States (Jemel, et al, 2006), and with the use of screening prostate specific antigen (PSA) the majority is diagnosed with locally confined prostate cancer. Many of these patients are good candidates for prostate brachytherapy. With the development of transperineal implantation using trans-rectal ultrasound guidance the number of patients undergoing permanent radioactive seed implants for prostate cancer has increased significantly over the past ten years. (Cooperberg, et al, 2004).