TLD array for precise dose measurements in stereotactic radiation techniques

We developed a new TLD array for precise dose measurement and verification of the spatial dose distribution in small radiation targets. It consists of a hemicylindrical, tissue-equivalent rod made of polystyrene with 17 parallel moulds for an exact positioning of each TLD. The spatial resolution of the TLD array was evaluated using the Leskell spherical phantom. Dose planning was performed with KULA 4.4 under stereotactic conditions on axial CT images. In the Leksell gamma unit the TLD array was irradiated with a maximal dose of 10 Gy with an unplugged 14 mm collimator. The doses delivered to the TLDs were rechecked by diode detector and film dosimetry and compared to the computer-generated dose profile. We found excellent agreement of our measured values, even at the critical penumbra decline. For the 14 mm and 18 mm collimator and for the 11 mm collimator combination we compared the measured and calculated data at full width at half maximum. This TLD array may be useful for phantom or tissue model studies on the spatial dose distribution in confined radiation targets as used in stereotactic radiotherapy.     

Combining cyclosporin with chemotherapy controls intraocular retinoblastoma without requiring radiation

Chemotherapy without radiation has not controlled most intraocular retinoblastoma, perhaps because of the common high expression of multidrug resistance P-glycoprotein that we found in retinoblastoma. Cyclosporin blocks P-glycoprotein-induced efflux of vincristine and teniposide in vitro, and possibly modulates responses to carboplatin. To avoid eye irradiation in bilateral retinoblastoma patients with RB1 germline mutations, which incurs a high second malignancy rate, we added cyclosporin A to a vincristine-teniposide-carboplatin protocol and consolidated chemotherapy responses with focal therapy. We scored patients requiring irradiation, enucleation, or focal ablation of central vision as failures. In 21 study patients, the overall relapse-free rate at a median follow-up of 3.3 years was 76%, with a rate of 92% for newly diagnosed and 50% for previously treated, relapsed retinoblastoma. Our results for the most unfavorable tumors with vitreous seeds (86% at 3.5 years) are better than published success rates of irradiation for similar tumors, or irradiation with the same chemotherapy without cyclosporin (45% at 2. 6 years). These results also exceeded our historic success rate with similar chemotherapy without cyclosporin, focal therapy, and/or radiation in 19 equivalently poor-risk patients (relapse-free rate 37% at a median follow-up of 5.6 years, P = 0.032), 16 of whom were previously untreated (relapse-free rate also 37%, P = 0.012). A better outcome occurred with higher cyclosporin blood levels and projected tissue exposure. Cyclosporin did not enhance the usual chemotoxicity. This clinical study suggests that cyclosporin improves the long-term response of retinoblastoma to chemotherapy, possibly by more than one mechanism.     

Comparison of ciliary sulcus fixation techniques for posterior chamber intraocular lenses

OBJECTIVE: To anatomically and histologically evaluate suturing techniques for sulcus fixation of posterior chamber intraocular lenses. SETTING: Kitano Hospital, Osaka, Japan. METHODS: The reproducibility of three suturing techniques (perpendicular to the eye wall; parallel to the iris; midway between perpendicular to the eye wall and parallel to the iris) were evaluated in a postmortem eye. Histologic sections of another eye and ultrasound biomicroscopy (UBM) images of 21 normal eyes were evaluated to determine the safety zone for the needle to avoid damaging adjacent structures. RESULTS: The ciliary sulcus was completely penetrated in the three techniques in 100, 40, and 70% of cases, respectively. The histologic sections and the UBM images showed that when sutures were placed perpendicular to the eye wall, there was the possibility of postoperative angle closure and suturing parallel to the iris might damage adjacent structures because of a narrow safety zone. CONCLUSIONS: The needle should penetrate obliquely, as in the technique in which the suturing is midway between perpendicular to the eye wall and parallel to the iris. This technique provides better reproducibility and causes less damage to adjacent tissue.     

Magnetic resonance imaging changes after stereotactic radiation therapy for childhood low grade astrocytoma

BACKGROUND: Stereotactic radiotherapy (SRT) is fractionated radiotherapy delivered under stereotactic guidance to produce highly focal and precise therapy. We studied the incidence of imaging changes that can mimic tumor progression after completion of SRT for childhood low grade astrocytoma. METHODS: Between June 1992 and September 1994, we prospectively treated 28 children with low grade astrocytomas with SRT. The patients ranged in age from 2 to 22 years (median: 10 yrs) and none had received prior radiation therapy or radiosurgery. Routine fractionation was employed (180-200 centigray[cGy]) to a total dose of 5220-6000 cGy over 5 to 6 weeks. All of the patients underwent initial and follow-up magnetic resonance imaging (MRI) according to protocol. RESULTS: Median clinical follow-up for the 28 patients was 24 months (range, 5-32 mos) with a median radiographic follow-up of 15 months (range, 3-26 mos). Fifteen patients had reduction in tumor size, one patient had stable disease. Twelve patients (43%) developed increased size of the lesion, increased signal intensity or enhancement, cysts or cavitations, and an increase in edema or mass effect on follow-up MRI. Most of these changes occurred between 9 and 12 months after the start of SRT and resolved or decreased by 15 to 21 months. All but one patient had normal or stable neurologic examinations. CONCLUSIONS: Treatment-related MRI changes are common after conventionally fractionated schedules using stereotactic radiation techniques for patients with low grade astrocytomas. These changes can be distinguished from tumor progression by their transient nature as well as the general absence of clinical symptoms.     

A stereotactic radiation therapy device for retinoblastoma using a noncircular collimator and intensity filter

The proximity of the lens to the retina makes the treatment of retinoblastoma a challenge for external beam radiation therapy. The approximately 1 mm separation between the posterior edge of the lens and the anterior region of the retina causes a trade-off between coverage of the entire retina and excessive dose to the lens. A stereotactic, LINAC based, lens sparing technique for treating retinoblastoma is presented. The technique uses noncoplanar arcs with the lens at isocenter. A special noncircular collimator blocks the lens but it also causes the dose distribution to vary across the retina. A fluence modulation filter is used to reduce the dose inhomogeneity across the target. The resulting dose distribution is roughly hemispheric, providing both anterior coverage of the retina and lens blocking unlike conventional techniques. The method used to develop the collimator and filter assembly is presented. Dosimetry of the assembly was carried out using radiochromic film, and the results were entered in a treatment planning system. The dose distribution as measured in a phantom is provided and compared to calculations.     

Fluconazole prophylaxis in patients with head and neck tumours undergoing radiation and radiochemotherapy

The aim of the present study was to investigate the incidence of Candida stomatitis and resulting interruptions in radiation and radiochemotherapy in 50 patients suffering from squamous cell carcinomas of the head and neck region receiving fluconazole (100 mg d-1) in comparison with a historical control group (n = 50) without specific prophylaxis. Twenty of the control patients (40%) demonstrated Candida stomatitis, with seven of them (14%) requiring interruptions in anticancer therapy. In contrast, none of the patients with fluconazole had evidence of Candida stomatitis (P = 0.0000051) and subsequent interruption of anti-cancer therapy (P = 0.0061). Laboratory monitoring for the presence of Candida species was performed in 30 patients before and after therapy with fluconazole. Candida albicans was identified less frequently after therapy when compared with the pretreatment status. However, C. glabrata and C. krusei were isolated in some of the patients, probably because of drug resistance of these subspecies. The results demonstrate the clinical usefulness of prophylactic fluconazole applications in patients suffering from head and neck tumours with the aim of reducing Candida stomatitis and the resulting interruptions in radiation and radiochemotherapy.     

Thyroid radiation doses during radioimmunotherapy of CEA-expressing tumours with 131I-labelled monoclonal antibodies

A number of radioimmunotherapy (RAIT) trials with iodinated antibodies have shown a high variability in the radiation doses to the thyroid. Therefore, the aim of this study was to evaluate which factors influence these thyroid doses during RAIT with 131iodinated monoclonal anti-carcinoembryonic antigen (CEA) antibodies. Data from 36 patients with CEA-expressing tumours were analysed. The patients underwent RAIT with the 131I-labelled IgG1 anti-CEA antibody, MN-14 (Ka = 10(9) l mol-1) or its F(ab')2 fragment (activity range 45.8-220.0 mCi). The thyroid was blocked with 120 mg iodine (lugol's orSSKI solution) and 400 mg perchlorate per day, starting 1 day prior to the first study. Blood clearance and molecular composition of labelled plasma compounds were determined by blood sampling and size-exclusion high-performance liquid chromatography analysis. The cumulated activities of tissues were determined from daily imaging and blood clearance data. Doses were derived from the MIRD scheme. Thyroid radiation doses showed a high variability, between 1.2 and 37.7 cGy mCi-1 (mean +/- S.D.: 11.1 +/- 8.3 cGy mCi-1), corresponding to absolute doses between 2.5 and 43.6 Gy. However, the maximal iodine uptake in the thyroid was 2.4 +/- 1.9 microCi mCi-1 (range 0.2-10.0 microCi mCi-1), which was less than 1% of the injected activity, indicating that more than 99% of the thyroid was blocked in all cases. No correlation was found between these thyroid doses and conditions leading to an enhanced exposure to free radioiodine, such as unbound I- in the mAb preparation, rapid metabolic breakdown of the labelled antibody due to human anti-mouse antibodies (HAMA), or immune complex formation with circulating antigen. However, a relationship between the thyroid doses and the patients' compliance in taking their Lugol's and perchlorate blocking medications, as well as to a relatively high variability in the biological half-life of the iodine in the thyroid (range from 31.1 h to virtual infinity), is indicated. No rising TSH titres or other signs of (latent) hypothyroidism were seen in these patients during a 2 year follow-up period. Longer follow-up was not possible because of the terminal condition of most of the patients. These data show that thyroid doses in an appropriately blocked individual given a standard, non-myeloablative dose of RAIT, are generally lower than those assumed to be required to cause late hypothyroidism. Even if higher activities are used, potential hypothyroidism may be overcome easily by hormone replacement. Thyroid doses are independent of parameters leading to an enhanced exposure of the thyroid to free radioiodine, suggesting that patient compliance in taking their blocking medication may be the most crucial factor for reducing thyroid doses in RAIT with 131I-labelled antibodies.     

Bartonella serology for patients with intraocular inflammatory disease

AIMS: Five cases of primary gastrointestinal (GI) lymphoma (three in the stomach, one in the ileum (IPSID) and one in the colon) associated with localized AL amyloidosis were studied to identify morphological or immunohistochemical features which could explain the amyloid deposition. METHODS AND RESULTS: All the cases were low-grade marginal zone B-cell lymphomas; one case of gastric lymphoma and the IPSID also had a high-grade component. The lymphomas had a monoclonal plasma cell population, with different light and heavy-chain type expression in the five cases. Plasma cell differentiation was closely associated with the amyloid deposits. The latter were an incidental microscopic finding in one case, but produced tumoral masses in the other. CONCLUSIONS: The presence of amyloid in primary GI lymphoma is rare, but can have diagnostic value. In the present study, neither particular features of the lymphomatous proliferation nor specific agents are identified. Therefore, the factors predisposing to amyloid deposition require elucidation.     

Preoperative cortical localization with functional MRI for use in stereotactic radiosurgery

Accurate localization of the lesion with respect to functionally significant brain is essential to safe stereotactic radiosurgical dose planning. We report the use of functional MR imaging in 3 patients to identify critical areas of surrounding brain and to provide assistance with dose planning, especially with regard to shaping the peripheral isodose around the lesion. We used a functional MRI system employing a conventional 1.5-tesla MRI unit that can detect decreases in deoxyhemoglobin concentration occurring with performance of specific tasks. Two of the patients had supratentorial arteriovenous malformations and 1 patient had a recurrent parasagittal meningioma. Functional MRI provided information on the location of speech, motor, and sensory cortex in these patients. Radiosurgical dose plans were constructed that kept these cortical areas outside of the 30% isodose curves. We believe that the safety of supratentorial parenchymal radiosurgery will be enhanced by the localization of critical brain regions around the target.     

Dose characteristics of in-house-built collimators for stereotactic radiotherapy with a linear accelerator

Dose characteristics of a stereotactic radiotherapy unit based on a standard Varian Clinac 4/100 4 MV linear accelerator, in-house-built Lipowitz collimators and the SMART stereotactic radiotherapy treatment planning software have been determined. Beam collimation is constituted from the standard collimators of the linear accelerator and a tertiary collimation consisting of a replaceable divergent Lipowitz collimator. Four collimators with isocentre diameters of 15, 25, 35 and 45 mm, respectively, were constructed. Beam characteristics were measured in air, acrylic or water with ionization chamber, photon diode, electron diode, diamond detector and film. Monte Carlo simulation was also applied. The radiation leakage under the collimators was less than 1% at 50 mm depth in water. Specific beam characteristics for each collimator were imported to SMART and dose planning with five non-coplanar converging 140 degrees arcs separated by 36 degrees angles was performed for treatment of a RANDO phantom. Dose verification was made with TLD and radiochromic film. The in-house-built collimators were found to be suitable for stereotactic radiotherapy and patient treatments with this system are in progress.     

Evaluation of stereotactic thalamotomies for pain relief with reference to pulvinar intervention

Stereotactic thalamotomies were carried out in 51 cases of malignant and 9 cases of other painful conditions. The patients were divided into two groups--those with a relatively small lesion created in the basal part of the CM nucleus and those with a larger lesion extending into the pulvinar. In total, 50% of the cases showed complete pain relief, 20% partial relief and 30% no effect. The group with pulvinar intervention showed better results, especially those with malignancies.     

In vitro studies on the potential use of 5-aminolaevulinic acid-mediated photodynamic therapy for gynaecological tumours

Results are reported on the sensitivity of various gynaecological tumour cell lines to 5-aminolaevulinic acid-induced protoporphyrin IX-sensitised photodynamic therapy (ALA-PDT) in vitro. All cell lines tested accumulated ALA-induced protoporphyrin IX (PpIX) and demonstrated good sensitivity to ALA-PDT. Localisation of PpIX in the mitochondria was demonstrated by fluorescence microscopy. Subcellular damage following ALA-PDT was observed using transmission electron microscopy. This damage was localised initially to the mitochondria, with damage to membranes and the nucleus and complete loss of intracytoplasmic organisation being observed subsequently. There was no apparent difference in ALA-PDT response between a multidrug-resistant ovarian carcinoma cell line and its parent line. These results indicate that ALA-PDT has potential for application to therapy of gynaecological malignancies.     

Development of telemetric techniques for use in studies of the electrical activity of the brain

A telemetry system has been designed to transmit two channels of wideband activity (0.2 Hz-2.5 KHz) recorded from high-impedance microelectrodes in the brains of free-moving cats. Thus, both unit activity and slow-wave field activity are accessible without disruption of the animals' behavior. In addition, circuitry is described that conditions the receiver signals, that dicriminates valid subcarrier signals from receiver noise and that automatically aborts data output in the absence of discriminable subcarrier. This receiver signal processing circuitry thus assures the fidelity of the decoded subcarrier, greatly facilitates further machine processing of the data and frees the experimenter from having to continuously monitor the receiver signals to subjectively edit out noisy data.     

Nested polymerase chain reaction for detection of Theileria annulata and comparison with conventional diagnostic techniques: its use in epidemiology studies

In this work we studied the ability of a nested polymerase chain reaction (PCR) to detect Theileria annulata, the causative agent of Mediterranean theileriosis, in blood samples obtained from cattle on farms in different Spanish regions and its possible use in epidemiology studies. Of the 214 samples analyzed, 78.04%, 69.86%, and 62.26% were found to be positive by nested PCR, indirect immunofluorescent antibody test, and optical microscopy of Giemsa-stained smears, respectively. The three techniques were in agreement in 68.6% of the results. The observation that the prevalence of Mediterranean theileriosis estimated using nested PCR alone (70.3%) and that obtained using all three diagnostic techniques together (80.4%) did not significantly differ verifies the utility of this technique in epidemiology studies.     

Analytical techniques for cell fractions. XXIII. A stable thermal gradient device for heat denaturation studies on proteins

The ISO-DALT two-dimensional electrophoretic system (1,2), based on the method of O'Farrell (3), is capable of performing large numbers of analysis on complex mixtures of proteins. However, both separations employed are carried out under dissociating or denaturing conditions and no enzyme activities are readily observable in the analyzed proteins. In order to identify the spots corresponding to particular enzymes, it is therefore necessary to employ some nondestructive resolving technique first and as a second step to perform both enzyme and two-dimensional electrophoretic analyses on the fractions generated. By correlating enzyme activity with intensity of various spots on the two-dimensional gels throughout the series of initial fractions, identifications, can be made. This approach, unlike the more direct immunoprecipitation methods (4), requires the running of large numbers of enzyme analyses and two-dimensional gels and some convenient initial resolving procedure. Convenient and rapid techniques for the analyses (5,6) and gels (1,2) have been described previously in this series and elsewhere. This paper deals with the use of selective denaturation in a temperature gradient as an initial resolving procedure and describes a simple thermal gradient device for generating such a gradient.