Paclitaxel and simultaneous radiation in locally advanced stage IIIA/B non-small cell lung cancer: a clinical phase I study.

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is one of the most active single agents for the treatment of non-small cell lung cancer, with response rates of 21% to 24%. We present a phase I study with paclitaxel and simultaneous radiation in previously untreated, locally advanced, inoperable, stage IIIA/B non-small cell lung cancer. The aims of the study were to determine the maximum tolerated dose, define the safety and toxicity, and obtain preliminary data about the activity of the combined modality. Patients received a fixed dose of radiotherapy (1.8 Gy/d, 5 days a week for 6.5 weeks, for a total dose of 59.4 Gy) and concomitant chemotherapy with paclitaxel 45 mg/m2 days 1, 8, and 15 in level 1; days 1, 8, 15, 22, and 29 in level 2; and days 1, 8, 15, 22, 29, 36, and 43 in level 3. The paclitaxel dosage was increased to 55 mg/m2 on days 1, 8, 15, 22, 29, 36, and 43 in level 4. Paclitaxel was administered as a 3-hour continuous intravenous infusion. Dexamethasone, clemastine, and ranitidine were given for hypersensitivity prophylaxis. Twenty-two patients (18 men and four women) entered the study; their median age was 66.5 years (age range, 38 to 74 years). Disease stage was IIIA in six of 22 patients and stage IIIB in 16. Six patients were treated at level 1, five at level 2, five at level 3, and six at level 4. There were 18 patients evaluable for toxicity and response. Side effects generally were moderate during the treatment period. One patient withdrew by request after the first course, one patient died of tumor bleeding after five courses, one patient died of progressive disease (lymphangiosis carcinomatosa of both lungs) after the sixth course, and one patient is too early for evaluation. Among the 18 patients evaluable for response, there were one complete and 10 partial remissions; seven patients reached a minor response. It is concluded that the therapy was well tolerated in these patients. Importantly, no severe adverse events were observed that could be associated with paclitaxel or radiotherapy. This combined modality appears to be a practicable and effective treatment of non-small cell lung cancer. The maximum tolerated dose has not yet been reached, and dose escalation is planned.

Considerations on recombination losses in ionization chambers using pulsed electron beams with beam scanning.

Based on Boag's theory, referring to saturation effects in ionization chambers with pulsed electron beams, we developed a simple method of determining recombination losses. The correction factors for chamber readings result from slope and intercept of a regression line M1/3 = f(M/V) obtained with at least two different chamber voltages, V, and chamber readings, M. The deviation of these correction factors, compared with those of Boag's precise theory, does not exceed +/- 0.5%.

Cerebral radiation surgery using moving field irradiation at a linear accelerator facility.

A modified irradiation technique at a linear accelerator facility for radiation surgery within the brain is described consisting of several moving field irradiations in non-coplanar planes. Using collimated narrow beams, a localization system and special computer programs for precise patient positioning, a high concentration of dose within small, well circumscribed volumes is obtained. Resulting dose distributions were studied experimentally and by calculations. A simple algorithm for treatment planning was developed and based on CT images. Radiation surgery within the brain is now technically feasible at our linear accelerator. Seventeen patients have now been treated.

Stereotactic percutaneous single dose irradiation of brain metastases with a linear accelerator.

The effectivity of stereotactic percutaneous single dose irradiations in the treatment of solitary brain metastases has been assessed in a series of 12 consecutive patients. Only radioresistant deeply localized metastases have been treated. Photon-irradiation was carried out with the convergent beam technique using stereotactic localization methods, in a linear accelerator facility. In 11 of the 12 patients no side effects occurred. The first 7 patients, who could be observed 3 months or longer, have been studied in detail. In each of these cases single dose irradiation with 20-30 Gy yielded arrest of tumor growth. In one case a marked decrease in contrast enhancement and in four cases shrinkage of the metastasis as well as a marked decrease of the edema occurred. In every patient a marked, sometimes dramatic improvement of the clinical condition was achieved, beginning a few days after irradiation. Stereotactic radiosurgery is a valuable tool in the treatment of inoperable, radioresistant brain metastases, the major advantage being high efficacy and smoothness of the procedure, as well as extremely short hospitalization times (2-3 days).

Comparison of calibration procedures for 192Ir high-dose-rate brachytherapy sources.

PURPOSE: To compare the efficacy of different calibration procedures for 192Ir high-dose-rate (HDR) brachytherapy sources and to determine their suitability in clinical practice. In addition the manufacturer's calibration is compared with our experimental measurements so that the accuracy of the source strength on the manufacturer certificate which is supplied with each new 192Ir source can be accessed. METHODS AND MATERIALS: We compared three types of calibration system: well-type chambers (HDR-1000 and SDS), cylindrical phantom, and plate phantom. The total number of measurements we obtained was 365. The number of sources used for the calibration procedure comparison was 20 and the number used for comparison with the manufacturer's calibration was 46. This study was made during the period 1989-1997. Also, Physikalisch-Technische Bundesanstalt (PTB) calibrated one of our sources using their PTB protocol so that the results could be compared with our own. RESULTS: The sensitivity of each system on scattering from the room walls was studied. It was found that different minimum lateral distances from the walls were required for the different systems tested: 15 cm and 25 cm for the well-type chambers, 75 cm for the cylindrical phantom, and 13 cm for the plate phantom. The minimum thickness required to reach phantom scattering saturation for the plate phantom setup is 24 cm. The influence of the applicator material used in the calibration setup was found to be 1.7% for the stainless steel dosimetry applicator compared to the plastic 5F applicator. The accuracy of source positioning within the applicator can lead to dosimetric errors of +/-1.2% for the radial distance of 8.0 cm used with both solid phantoms. The change in the response for both well-type chambers was only 0.1% for changes in the source position within +/-7.5 mm around the response peak. Good agreement was found between all dosimetry systems included in our study. Taking the HDR-1000 well-type chamber results as a reference, we observed percentage root mean square (RMS) values of 0.11% for the SDS well-type chamber, 0.44% for the cylindrical, and 0.60% for the plate phantom setup. A comparison of our results using the cylindrical phantom with those of the manufacturer showed a percentage RMS value of 3.3% with a percentage fractional error range of -13.0% to +6.0%. The comparison of our calibration results with those of PTB gave deviations less than 0.4% for all systems. CONCLUSIONS: Our results have shown that with careful use of all calibration system protocols an accurate determination of source strength can be obtained. However, the manufacturer's calibration is not accurate enough on its own, and it should be mandatory for clinics to always measure the source strength of newly delivered 192Ir brachytherapy sources. The influence of the applicator material, metal or plastic, should always be taken into account.

Dosimetry of rotational partial-skin electron irradiation.

BACKGROUND AND PURPOSE: Often, the most appropriate treatment for superficially and extensively spreading tumors of the skin is to use electron irradiation at enlarged distances. Rotational skin electron irradiation is a proven method for the treatment of the entire skin surface. We here report modifications of this technique in the set-up of partial-skin electron irradiation and the results of dosimetric examinations with regard to optimal shielding, dose profiles and depth dose curves under various irradiation conditions. MATERIALS AND METHODS: Irradiation was performed using electron beams with nominal energies of 6 MeV from a linear accelerator. The phantom was located on a rotating platform at a source-surface distance SSD=300 cm. A horizontal slit aperture (height: 32 cm) within a 2 cm thick polymethylmethacrylate (PMMA) shielding plate near the phantom was used to define the size of the irradiated region. Influences on dose distributions due to scattering processes on the PMMA edges were investigated using a flat ionization chamber and films. Absolute dose measurements and film calibration were made with the flat chamber. The quality of bremsstrahlung radiation behind the shielding was determined with a thimble ionization chamber in the phantom. RESULTS AND CONCLUSIONS: The results of rotational partial-skin electron irradiation reveal some of the investigated shielding geometries to be optimal. Depth dose distributions and dose rates correspond to the results obtained in total skin electron rotational irradiation. It is possible to apply the dose superficially in the first millimeters of the skin; the dose maximum is located at a depth of 0-2 mm, the 80% isodose at 9 mm. The amount of bremsstrahlung contamination is 2.5%. The local amount of absorbed dose per monitor unit depends strongly on patient/phantom cross-section geometry. At our institute, rotational partial-skin electron irradiation was implemented into clinical routine in 1997.

A simple and reliable method to simulate multileaf-plans.

To combine conformity of the irradiation with time effectiveness during treatment, the use of multileaf collimators has become more and more common. However, the simulation of the leaf positions is rather difficult compared with metal blocks. We developed a new method, utilizing an acrylic template in which the contour produced by the leaves is machined in the form of a 1 mm groove by a computerized numerically controlled milling machine. This template is then inserted into a mount attached to the simulator. The main advantages are the errorfree, direct communication from the therapy planning system to the milling machine via a network, the possibility to transfer the contour to the skin, and the documentation on the simulation film. The use of templates is reliable and, e.g. the costs of the materials are lower than for block simulation.

Effects of local irradiation and i.v. methotrexate on brain morphology in rabbits: early changes.

Brain damage following cranial radiation therapy can be crippling or even life-threatening and has been studied in both patients and animals. An additional toxic effect of chemotherapy has been found in children, who died following brain irradiation and systemic chemotherapy for the treatment of acute lymphoblastic leukemia. To study the interaction of radiation and drugs on brain tissue, we treated rabbits with brain irradiation and/or i.v. methotrexate. For a period of up to 3 months following radiation therapy, brain morphology was compared in seven treatment groups. Weekly doses of methotrexate administered i.v. produced no brain damage. Histological examination showed myelin swelling and beading 14 weeks after fractionated brain irradiation with 24 Gy. Combination of brain irradiation and methotrexate produced additional hypertrophy of microglia and pyknosis of adventitial cells. In none of these groups, even after doses of 48 Gy brain irradiation, was calcification or brain necrosis observed during the first 14 weeks following irradiation.

[Dosimetry in computerized tomography]. / Dosimetrie in der Computertomographie.

During CT, the surface dose increases towards the centre of the axis of rotation. Measurements on 35 patients and theoretical considerations indicate a hyperbolic relationship between the axis of rotation and the surface dose.

["Cold lesions" in bone scintigraphy (author's transl)]. / "Cold lesions" in der Knochenszintigraphie.

Frequency and location of "cold lesions" has been analysed in 1000 consecutive bone scans. Among the 554 abnormal cases there were 18 (1,8% of the total) with localized diminished activity due to metastatic lesions and 5 (0,5%) secondary to radiation osteitis. 10 of the 18 patients with metastatic disease had pure defects while 8 showed a reactive margin. It is pointed out that the quality of the examination is crucial for the demonstration of such defects and that single scans of the different regions of the skeleton are superior to a whole body scan. The survey of the literature shows that "cold lesions" are predominant in malignant bone diseases, however no relation exists to a definite histology.

[Intra-arterial dynamic computed tomography in characterizing liver metastases of colorectal cancer]. / Intraarterielle dynamische Computertomographie in der Charakterisierung von Lebermetastasen kolorektaler Karzinome.

Locoregional chemotherapy of liver metastases from colorectal tumours is a promising new approach. The results of CT in fifteen patients after intravenous and intra-arterial contrast injection are compared. The liver metastases are supplied mainly by the arterial route and this permits a means of assessing therapy. Contrast injections through a hepatic catheter may result in flow phenomena which limits the value of this investigation. It is unknown whether such flow phenomena may influence the result of intra-arterial chemotherapy. Although the margins of the metastases were more clearly defined, diagnostic accuracy was not increased, as compared with intravenous CT enhancement.

[Angio-CT: an improvement in the diagnosis of malignant liver diseases]. / Angio-CT: Eine Erweiterung der Diagnostik maligner Leberprozesse.

Dynamic contrast studies of the liver make it possible to evaluate the vascularity of liver metastases. Up to the present, the examination has only been carried out in single planes, whereas studies of the whole of the liver during one examination have not yet been published. This can be obtained by performing sequential CT (angio-CT), using special software. A clinical study of the value of the procedure has been undertaken on 64 patients with suspected liver metastases. In addition to the plain scans, the examination was repeated during the early phase of a bolus injection and subsequently ten minutes after injection (enhancement). The various structures which can be seen are described and the changes in density patterns have been interpreted according to contrast kinetics derived from nephrographic examinations. The advantages of angio-CT as compared with plain films and with scans after normal contrast infusions are described. The improved sensitivity and specificity obtained by using the three modes of examination, as compared with a single examination, is stressed.

[Nuclear magnetic resonance tomographic staging of tumors of the oral cavity, oro- and hypopharynx and the larynx. A comparison with computed tomography and sonography]. / Kernspintomographisches Staging von Tumoren der Mundhöhle, des Oro- und Hypopharynx sowie des Larynx. Vergleich mit Computertomographie und Somographie.

Thirty-six patients with tumours of the mouth, the oropharynx and hypopharynx and the larynx were examined by nuclear resonance tomography. The results were compared with the clinical findings of inspection and palpation and with CT and sonography, with respect to T and N classification. In seven patients the classification could be confirmed at operation. NMR provides very good anatomical detail and marked contrast between tumour and the surrounding tissues, particularly on T2 weighted images. NMR showed the best correlation with the clinical findings as regards the T classification and was the most accurate method, as confirmed by surgery. It is superior to CT and sonography for diseases in the oropharynx and hypopharynx. For the examination of the cervical lymphatics, sonography remains the recommended method.

[Functional heterogeneity of liver metastases in 3-phase computerized tomograms]. / Funktionelle Heterogenität von Lebermetastasen im Dreiphasen-Computertomogramm.

Ninety patients with liver metastases (68 colorectal carcinomas, 22 breast carcinomas) were examined by triphasic angio-CT. This included demonstration of the entire liver after a bolus-like injection of contrast. Originally, the metastases were hypodense, but showed four patterns of contrast enhancement. Quantitative evaluation of the mammary carcinomas showed a marked increase in density during the bolus phase, with similar contrast values in the liver and at the centre and edge of the metastasis at ten minutes after the injection. Colorectal carcinomas showed only slight increase in density after contrast injection. The difference in density between the centre and the periphery of the metastasis was still present on later images. This finding indicates that there are differences in the vascularisation of these metastases.

Microwave fidelity studies by varying antenna coupling.

The fidelity decay in a microwave billiard is considered, where the coupling to an attached antenna is varied. The resulting quantity, coupling fidelity, is experimentally studied for three different terminators of the varied antenna: a hard-wall reflection, an open wall reflection, and a 50 Ω load, corresponding to a totally open channel. The model description in terms of an effective Hamiltonian with a complex coupling constant is given. Quantitative agreement is found with the theory obtained from a modified VWZ approach [J. J. M. Verbaarschot, Phys. Rep. 129, 367 (1985)].