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.

Investigations of dose response of BANG polymer-gels to carbon ion irradiation.

In this presentation BANG polymer-gel dosimetry using magnetic resonance imaging (MRI) is applied to densely ionizing radiation such as carbon ion beams. BANG polymer-gels were irradiated with monoenergetic 12C ions at an energy of 205 MeVu(-1). The irradiation of the gels with doses up to 100 Gy were performed at the radiotherapy facility of the GSI, Darmstadt, Germany. For comparison with sparsely ionizing radiation data were obtained for 6 MV photon radiation, too. It was the object to examine the saturation effect for densely ionizing radiation that occurs at high values of linear energy transfer (LET). Up to now the dose response is unknown for mixed radiation fields of primary carbon ions. Therefore, to facilitate such conversions of measured MR signals into dose model calculations are proposed. This model relies only on heavy ion track structure and the experimentally determined photon response.

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.

Experimentally determined three-dimensional dose distributions in small complex targets.

OBJECT: The purpose of the paper is to describe a workable three-dimensional dosimetry system for use in quality assurance programs of departments in which radiosurgery is performed. METHODS: A system was developed on the basis of radiochromatic films. The experimental findings of the measured dose distributions for small complex-shaped targets, within a specially designed phantom, are described and compared with the same parameters calculated from the corresponding dose plan. The following parameters were determined for 83 patients with irregularly shaped targets who underwent gamma knife radiosurgery (GKS): target volume; dose-volume histograms of the target; 12-Gy, 15-Gy, and 18-Gy volumes; dose plan conformity; dose fall profiles in all dimensions to 50% of the prescription dose; and a quality factor (QF) to evaluate the adequacy of a GKS plan or treatment. The precise function and accuracy of the developed measuring device is shown and it demonstrated the expected steep dose falloff outside the irregularly shaped targets in all directions. The dose falloff was of the order of > 3 Gy/mm and the values of the QF were in the range between 0.5 and 0.9. CONCLUSIONS: A comparison with data from the literature shows that at least for small targets (< 2 cm3 and < 2.5 cm3) simulated within a head phantom, the dose gradient is significantly steeper in all directions than when using alternative treatment devices in radiosurgery and the overall QF is superior in most of the cases.

Tartrate-resistant acid phosphatase 5b as serum marker of bone metabolism in cancer patients.

BACKGROUND: The serum marker tartrate-resistant acid phosphatase isoform 5b (TRACP 5b) is considered a specific parameter of osteoclast activity and a useful marker of bone resorption. Regarding the utility of TRACP 5b in bone metastases, this review aims to draw clinically relevant conclusions. MATERIALS AND METHODS: The available literature data regarding the laboratory methods, the characteristics of TRACP 5b and the clinical data, as well as our own results about TRACP 5b in cancer patients has been reviewed. RESULTS: In contrast to enzymatic assays, two new assays based on a monoclonal antibody and on heparin-induced inhibition of TRACP 5a, respectively, demonstrated low biological and analytical variabilities in healthy subjects as well as in patients with osteoporosis. Up to now, only a few studies have evaluated the utility of TRACP 5b in cancer patients with bone metastases. In these studies, the sensitivity of TRACP 5b was higher compared to other markers. Furthermore, TRACP 5b activity correlates with the response to the treatment of bone metastases. CONCLUSION: Although the clinical data available are promising, the results are still preliminary. In addition to further evaluation of the analytical method, more studies in cancer patients are needed to establish TRACP 5b in the diagnostic procedure and in the therapy monitoring of bone metastases.

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.

Selenium levels during the course of radiotherapy. No influence of irradiation on blood selenium concentration.

PURPOSE: To evaluate the influence of tumor characteristics and irradiation on blood selenium concentrations and their course during radiotherapy. MATERIAL AND METHODS: Selenium Levels were determined at various times during radiotherapy (I: beginning, II: mid, III: end, IV: 6 weeks after) by atomic absorption spectrometry in whole blood. The values were correlated with patient-, tumor- and irradiation-related parameters. RESULTS: A total of 690 samples were analyzed in 224 patients. The mean selenium value was 75.64 microg/l at the beginning of radiotherapy. 170 patients (77%) had reduced selenium Levels < 89 microg/l. Twelve patients (5.4%), mostly with head-and-neck cancer, had critically low values which need to be controlled and monitored. Three patients (1.3%) with breast cancer had critically increased values. Female patients showed higher seLenium concentrations than male patients (p = 0.0404). Patients diagnosed for head-and-neck cancer had significantly lower seLenium values than breast cancer patients (p = 0.016). Previous treatment by surgery and/or chemotherapy was correlated with lower selenium concentrations compared with irradiation as primary treatment (p = 0.039). According to analysis of variance, there was no significant change of the selenium concentration during the course of radiotherapy (p > 0.05). CONCLUSION: A preexisting selenium deficiency could be diagnosed in the broad majority of cancer patients undergoing radiotherapy. In contrast to the widely held opinion, it was not further aggravated by standard radiotherapy protocols.

In vivo dosimetry with semiconducting diodes for dose verification in total-body irradiation. A 10-year experience.

BACKGROUND AND PURPOSE: For total-body irradiation (TBI) using the translation method, dose distribution cannot be computed with computer-assisted three-dimensional planning systems. Therefore, dose distribution has to be primarily estimated based on CT scans (beam-zone method) which is followed by in vivo measurements to ascertain a homogeneous dose delivery. The aim of this study was to clinically establish semiconductor probes as a simple and fast method to obtain an online verification of the dose at relevant points. PATIENTS AND METHODS: In 110 consecutively irradiated TBI patients (12.6 Gy, 2 x 1.8 Gy/day), six semiconductor probes were attached to the body surface at dose-relevant points (eye/head, neck, lung, navel). The mid-body point of the abdomen was defined as dose reference point. The speed of translation was optimized to definitively reach the prescribed dose in this point. Based on the entrance and exit doses, the mid-body doses at the other points were computed. The dose homogeneity in the entire target volume was determined comparing all measured data with the dose at the reference point. RESULTS: After calibration of the semiconductor probes under treatment conditions the dose in selected points and the dose homogeneity in the target volume could be quantitatively specified. In the TBI patients, conformity of calculated and measured doses in the given points was achieved with small deviations of adequate accuracy. The data of 80% of the patients are within an uncertainty of +/- 5%. CONCLUSION: During TBI using the translation method, dose distribution and dose homogeneity can be easily controlled in selected points by means of semiconductor probes. Semiconductor probes are recommended for further use in the physical evaluation of TBI.

Results of postoperative (90)Sr radiotherapy of keloids in view of patients' subjective assessment.

BACKGROUND AND PURPOSE: As treatment of keloids is mainly a cosmetic indication, the authors investigated, beyond the recurrence rate, the patients' satisfaction with the result and its correlation with objective medical findings. PATIENTS AND METHODS: 83 keloids of 66 patients had been irradiated after excision by a uniform protocol with 4 x 5 Gy (strontium- 90 [(90)Sr] surface applicator). A questionnaire was developed and sent out in which, above all, the satisfaction with the therapeutic and cosmetic outcome was obtained. These results were correlated with objective parameters and medical findings which were ascertained during an extra follow-up examination. RESULTS: Among 18 of the 41 patients (44%), who had answered the questionnaire, 19 of the 53 keloids treated (36%) had relapsed. 61% of the patients were extremely or mainly satisfied with the therapeutic outcome, 51% extremely or mainly satisfied with the cosmetic outcome. The relief from former keloid-caused symptoms (therapeutic outcome: p = 0.0005; cosmetic outcome: p = 0.0011), the ear as keloid localization (p = 0.0008 and p = 0.0197), and male gender (therapeutic outcome: p = 0.0423) were significantly associated with higher satisfaction. The recurrence rate as well as the extent of radiation side effects had no significant influence on patients' assessment. CONCLUSION: Cosmetic aspects like the dermal side effects and the patients' satisfaction should be taken into account when evaluating the results of radiotherapy in keloids.

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.

[Quality assurance in stereotactic space. Determination of the accuracy of aim and dose in single dose radiosurgery]. / Qualitätssicherung im stereotaktischen RaumBestimmung der Genauigkeit von Ort und Dosis bei Ein-Zeit-Bestrahlungen.

BACKGROUND: Single dose irradiation techniques require methods of quality assurance of high precision. The complete operational sequence of a treatment from imaging over irradiation planning up to the patient irradiation has to be controlled and verified in a phantom (Figure 2). These demands receive special topicality by the E-DIN 6875-1 [38], which will appear soon. MATERIAL AND METHODS: A quality assurance package was developed to meet the requirements of the E-DIN 6875-1 [38]. It consists of versatile usable precision phantom (Figure 1), a dose measuring system for the tissue equivalent radiochromic film GAFCHROMIC trade mark type MD 55 II using a high-quality scanner, and a software for standardized test routines (Figures 2 to 4). Correction routines for film fog, darkening, temperature effect as well as for film inhomogeneities (double exposure technology) are implemented. RESULTS: The measuring system permits routine dosimetry with inaccuracies typically < 5%, for the double exposure procedure typically < 3% with local dissolutions of approx. 1/100 mm in film plane, perpendicularly to it the film stack density and the film thickness (0.3 mm) are determining. The measuring system is designed to simulate the complete three-dimensional treatment of a patient (Figure 4). CONCLUSIONS: The procedure achieves a high quality standard for all steps in radiosurgery. The simple handling permits the employment for the daily routine (according to E-DIN 6875-1 [38]), in addition, for the modelling of complicated 3-d of scattering conditions, e. g. close to risk structures.