Retrospective analysis of the superior vena cava syndrome in irradiated cancer patients.

BACKGROUND: A carcinoma is the underlying cause of superior vena cava syndrome (SVCS) in 95-97% of patients. The aim of our study is to retrospectively analyse the outcome of patients after local radiotherapy compared to literature data. PATIENTS AND METHODS: In 35 consecutively registered patients, irradiated because of SVCS, different primary carcinomas (lung, breast, head-and-neck, Non-Hodgkin's lymphoma) were ascertained. Distant metastases had already been diagnosed in 33 patients. Chemotherapy had previously been given in seven patients. RESULTS: In 30 patients, radiotherapy obtained a reduction of symptoms within 5-9 days. However, in seven patients, radiotherapy had to be stopped early because of local progress and tumor induced complications. Local recurrences were observed in six patients. The 1-year overall survival rate was 15.6%. Survival rate depended significantly on the performance status (p < 0.004). CONCLUSION: Based on literature data our results are comparable regarding the incidence, the radio-oncological procedure and the response to treatment. These data confirm that radiotherapy is the standard treatment in most patients suffering from SVCS. However, it should be determined if endovascular stenting, which is more frequently considered in the last few years in patients with a tumor induced SVCS, may be a useful option as a simultaneous or sequentially given treatment to optimize the palliative effect.

Analyzing 3-tesla magnetic resonance imaging units for implementation in radiosurgery.

OBJECT: The limiting factor affecting accuracy during gamma knife surgery is image quality. The new generation of magnetic resonance (MR) imaging units with field strength up to 3 teslas promise superior image quality for anatomical resolution and contrast. There are, however, questions about chemical shifts or susceptibility effects, which are the subject of this paper. METHODS: The 3-tesla MR imaging unit (Siemens Trio) was analyzed and compared with a 1-tesla unit (Siemens Magnetom Expert) and to a 1.5-tesla unit (Philips Gyroscan). Evaluation of the magnitude of error was performed within transverse slices in two orientations (axial/coronal) by using a cylindrical phantom with an embedded grid. Deviations were determined for 21 targets in a slab phantom with known geometrical positions within the stereotactic frame. Distortions caused by chemical shift and/or susceptibility effects were analyzed in a head phantom. Inhouse software was used for data analyses. The mean deviation was less than 0.3 mm in axial and less than 0.4 mm in coronal orientations. For the known targets the maximum deviation was 1.16 mm. By optimizing these parameters in the protocol these inaccuracies could be reduced to less than 1.1 mm. Due to inhomogeneities a shift in the z direction of up to 1.5 mm was observed for a dataset, which was shown to be compressed by 1.2 mm. CONCLUSIONS: The 3-tesla imaging unit showed superior anatomical contrast and resolution in comparison with the established 1-tesla and 1.5-tesla units; however, due to the high field strength the field within the head coil is very sensitive to inhomogeneities and therefore 3-tesla imaging data will have be handled with care.

High precision film dosimetry with GAFCHROMIC films for quality assurance especially when using small fields.

Treatment units for radiosurgery, brachytherapy, implementation of seeds, and IMRT generate small high dose regions together with steep dose gradients of up to 30%-50% per mm. Such devices are used to treat small complex-shaped lesions, often located close to critical structures, by superimposing several single high dose regions. In order to test and verify these treatment techniques, to perform quality assurance tasks and to simulate treatment conditions as well as to collect input data for treatment planning, a GAFCHROMIC film based dosimetry system for measuring two-dimensional (2-D) and three-dimensional (3-D) dose distributions was developed. The nearly tissue-equivalent radiochromic GAFCHROMIC film was used to measure dose distributions. A drum scanner was investigated and modified. The spectral emission of the light source and the filters together with the efficiency of the CCD filters for the red color were matched and balanced with the absorption spectra of the film. Models based on refined studies have been developed to characterize theoretically the physics of film exposure and to calibrate the film. Mathematical descriptions are given to calculate optical densities from spectral data. The effect of darkening has been investigated and is described with a mathematical model. The influence of the scan temperature has been observed and described. In order to cope with the problem of individual film inhomogeneities, a double irradiation technique is introduced and implemented that yields dose accuracies as good as 2%-3%. Special software routines have been implemented for evaluating and handling the film data.

Radiation enhancement by gemcitabine-mediated cell cycle modulations.

The purpose of this study was to investigate the exact dose dependency and time dependency of the radiation-enhancing effect of gemcitabine (2',2'difluoro desoxycytidine [dFdC]) in in vitro experiments (HeLa cells: cancer of the uterine cervix, #4197 cells: oropharyngeal squamous cell carcinoma), and to correlate this effect with the underlying changes in cell cycle distribution. Cell viability was determined fluorometrically after exposure to dFdC (0-20.0 micro mol/l), irradiation (0-37.5 Gy), and both modalities. Combining both therapies, cells were exposed to dFdC (0-10.0 micro mol/l) for 24 hours before further treatment and irradiated (0-30 Gy) immediately afterwards with or without removal of dFdC. For cell cycle analysis by flow cytometry, cells were irradiated (0-40 Gy) or treated with dFdC (0.012-1.0 micro mol/l, 24-48 hours). Additionally, cells were exposed to dFdC (2.0 micro mol/l, 0-4 hours). Cell cycle kinetics were evaluated using bromodeoxyuridine (BrdU) (10 micro mol/l) S-phase labeling, given either 30 minutes before or in the last hour of dFdC treatment (2.0 micro mol/l, 0-6 hours). The fluorometric assay revealed that dFdC enhances radiation-induced cytotoxicity at marginally toxic or nontoxic concentrations (<37 nmol/l). Radiation resulted in the anticipated G2/M arrest already at 2 Gy. DFdC induced concentration and exposure time-dependent cell cycle changes that were better resolved using BrdU, demonstrating a pronounced S-phase arrest already at 12 nmol/l. BrdU-pulse labeling revealed that the cell cycle block occurred at the G1/S boundary. Our data reconfirm the already known radiation enhancement, the S-phase specific activities of dFdC, and the relevance of the synchronized progression of cells through the S-phase with regard to the radiosensitizing properties of low-dose dFdC. However, we could demonstrate that before progressing in the S-phase, cells were blocked and partially synchronized at the more radiosensitive G1/S boundary. Furthermore, cells progressing past the block might accumulate proapoptotic signals caused by both radiation and dFdC, which will also results in cell death.

Multimodality treatment including postoperative radiation and concurrent chemotherapy with weekly docetaxel is feasible and effective in patients with oral and oropharyngeal cancer.

BACKGROUND: To examine the feasibility and efficacy of weekly docetaxel with concurrent radiation as postoperative treatment in a multimodality approach to oral and oropharyngeal cancer. PATIENTS AND METHODS: 94 patients (Table 1) with primary resectable squamous cell carcinoma of the oral cavity and oropharynx (UICC stage I 14%, II 15%, III 18%, IV 53%; Table 2) were treated with a multimodality therapy program consisting of neoadjuvant intra-arterial high-dose chemotherapy (cisplatin 150 mg/m(2) with parallel systemic sodium thiosulfate 9 g/m(2) for neutralization), followed by surgery of the primary and neck, and postoperative concurrent radiation and chemotherapy with weekly docetaxel (20-30 mg/m(2); Table 3). Chronic toxicities were followed over a period of 5 years. RESULTS: At a median follow-up of 4 years, the 5-year survival rate for all 94 patients was 80%, and disease-free survival was 73% (Figures 1 and 2). Among patients with advanced disease (stage III and IV), survival was 83 and 59%, respectively (Figure 4). Grade 3 and 4 mucositis was the main acute toxicity necessitating supportive care. Long-term toxicity appears to be moderate (Table 4). The maximum tolerated dose of weekly docetaxel was 25 mg/m(2). CONCLUSIONS: Concurrent radiation and chemotherapy with weekly docetaxel is a feasible postoperative treatment in a multimodality approach to oral and oropharyngeal cancer, resulting in high overall and disease-free survival. This approach warrants further evaluation in prospective randomized trials.

[Combined radiotherapy and gemcitabine. Evaluation of clinical data based on experimental knowledge]. / Kombination von Radiotherapie und Gemcitabine. Bewertung der klinischen Daten auf der Basis experimenteller Erkenntnisse.

BACKGROUND: In experimental studies the nucleoside analog Gemcitabine (2',2' difluorodesoxycytidine) clearly demonstrates radiation enhancing properties. After describing the pharmacological Gemcitabine-related data and the clinical studies regarding combined radiochemotherapy and taking under consideration the in-vitro data and the results provided by animal models, this overview is aimed to draw clinically relevant conclusions, resulting in the improvement of treatment approaches. MATERIALS AND METHODS: The available literature data regarding the metabolism and the mechanism of action, the evaluation of possible schedules of administration, and combined radiochemotherapy including Gemcitabine has been reviewed. Publications reporting experimental data in vitro and in vivo as well as our own experimental results have been incorporated. RESULTS: In clinical phase I and II studies, the favorable tumor response is accompanied by a high incidence of grade III-IV toxicities whereby the maximum-tolerated dose (MTD) of the various schedules of administration used is always lower compared to the MTD of single-agent treatment. In in-vitro and in-vivo data addressing the description and the evaluation of the radiation enhancing mechanism (especially influence on cell cycle, depletion of the dATP pool, induction of apoptosis, inhibition of DNA synthesis, reduction of DNA repair) this effect is already observed with non and moderately toxic Gemcitabine concentrations and depends on drug concentration and exposure time. Independent of the fractionation effect of radiotherapy, the radiation enhancement is persistent for at most 72 hours after the end of drug exposure. Taking under consideration the single dose per day and the target volume, a prolonged infusion and/or a twice-weekly administration of Gemcitabine at low concentration each and simultaneous radiotherapy are presumably considered to resemble the experimental data. CONCLUSION: It is without doubt that data provided by clinical studies are of highest relevance for the evaluation of an optimized radiochemotherapy with Gemcitabine. However, although it is often difficult to transfer experimental data into the clinical situation, these data offer the possibility to develop an improved schedule of administration in patient treatment based on rational evidence in tumor biology.