Evaluation of time, attendance of medical staff, and resources during interstitial brachytherapy for prostate cancer : DEGRO-QUIRO trial.

INTRODUCTION: The German Society of Radiation Oncology initiated a multicenter trial to evaluate core processes and subprocesses of radiotherapy by prospective evaluation of all important procedures in the most frequent malignancies treated by radiation therapy. The aim of this analysis was to assess the required resources for interstitial high-dose-rate (HDR) and low-dose-rate (LDR) prostate brachytherapy (BRT) based on actual time measurements regarding allocation of personnel and room occupation needed for specific procedures. PATIENTS AND METHODS: Two radiotherapy centers (community hospital of Offenbach am Main and community hospital of Eschweiler) participated in this prospective study. Working time of the different occupational groups and room occupancies for the workflow of prostate BRT were recorded and methodically assessed during a 3-month period. RESULTS: For HDR and LDR BRT, a total of 560 and 92 measurements, respectively, were documented. The time needed for treatment preplanning was median 24 min for HDR (n = 112 measurements) and 6 min for LDR BRT (n = 21). Catheter implantation with intraoperative HDR real-time planning (n = 112), postimplantation HDR treatment planning (n = 112), and remotely controlled HDR afterloading irradiation (n = 112) required median 25, 39, and 50 min, respectively. For LDR real-time planning (n = 39) and LDR treatment postplanning (n = 32), the assessed median duration was 91 and 11 min, respectively. Room occupancy and overall mean medical staff times were 194 and 910 min respectively, for HDR, and 113 and 371 min, respectively, for LDR BRT. CONCLUSION: In this prospective analysis, the resource requirements for the application of HDR and LDR BRT of prostate cancer were assessed methodically and are presented for first time.

Time management in radiation oncology: evaluation of time, attendance of medical staff, and resources during radiotherapy for prostate cancer: the DEGRO-QUIRO trial.

PURPOSE: In order to evaluate resource requirements, the German Society of Radiation Oncology (DEGRO) recorded the times needed for core procedures in the radio-oncological treatment of various cancer types within the scope of its QUIRO trial. The present study investigated the personnel and infrastructural resources required in radiotherapy of prostate cancer. METHODS: The investigation was carried out in the setting of definitive radiotherapy of prostate cancer patients between July and October 2008 at two radiotherapy centers, both with well-trained staff and modern technical facilities at their disposal. Personnel attendance times and room occupancy times required for core procedures (modules) were each measured prospectively by two independently trained observers using time measurements differentiated on the basis of professional group (physician, physicist, and technician), 3D conformal (3D-cRT), and intensity-modulated radiotherapy (IMRT). RESULTS: Total time requirements of 983 min for 3D-cRT and 1485 min for step-and-shoot IMRT were measured for the technician (in terms of professional group) in all modules recorded and over the entire course of radiotherapy for prostate cancer (72-76 Gy). Times needed for the medical specialist/physician were 255 min (3D-cRT) and 271 min (IMRT), times of the physicist were 181 min (3D-cRT) and 213 min (IMRT). The difference in time was significant, although variations in time spans occurred primarily as a result of various problems during patient treatment. CONCLUSION: This investigation has permitted, for the first time, a realistic estimation of average personnel and infrastructural requirements for core procedures in quality-assured definitive radiotherapy of prostate cancer. The increased time needed for IMRT applies to the step-and-shoot procedure with verification measurements for each irradiation planning.

Time management in radiation oncology: development and evaluation of a modular system based on the example of rectal cancer treatment. The DEGRO-QUIRO trial.

PURPOSE: The goal was to develop and evaluate a modular system for measurement of the work times required by the various professional groups involved in radiation oncology before, during, and after serial radiation treatment (long-term irradiation with 25-28 fractions of 1.8 Gy) based on the example of rectal cancer treatment. MATERIALS AND METHODS: A panel of experts divided the work associated with providing radiation oncology treatment into modules (from the preparation of radiotherapy, RT planning and administration to the final examination and follow-up). The time required for completion of each module was measured by independent observers at four centers (Rostock, Bamberg, Düsseldorf, and Offenbach, Germany). RESULTS: A total of 1,769 data sets were collected from 63 patients with 10-489 data sets per module. Some modules (informed consent procedure, routine treatments, CT planning) exhibited little deviation between centers, whereas others (especially medical and physical irradiation planning) exhibited a wide range of variation (e.g., 1 h 49 min to 6 h 56 min for physical irradiation planning). The mean work time per patient was 12 h 11 min for technicians, 2 h 59 min for physicists, and 7 h 6 min for physicians. CONCLUSION: The modular system of time measurement proved to be reliable and produced comparable data at the different centers. Therefore, the German Society of Radiation Oncology (DEGRO) decided that it can be extended to other types of cancer (head and neck, prostate, and breast cancer) with appropriate modifications.

On the use of HDR 60Co source with the MammoSite radiation therapy system.

This work summarizes Monte Carlo results in order to evaluate the potential of using HDR 60Co sources in accelerated partial breast irradiation (APBI) with the MammoSite applicator. Simulations have been performed using the MCNP5 Monte Carlo Code, in simple geometries comprised of two concentric spheres; the internal consisting of selected concentrations, C, of a radiographic contrast solution in water (Omnipaque 300) to simulate the MammoSite balloon and the external consisting of water to simulate surrounding tissue. The magnitude of the perturbation of delivered dose due to the radiographic contrast medium used in the MammoSite applicator is calculated. At the very close vicinity of the balloon surface, a dose build-up region is observed, which leads to a dose overestimation by the treatment planning system (TPS) which depends on Omnipaque 300 solution concentration (and is in order of 2.3%, 3.0%, and 4.5%, respectively, at 1 mm away from the balloon - water interface, for C=10%, 15%, and 20%). However, dose overestimation by the TPS is minimal for points lying at the prescription distance (d=1 cm) or beyond, for all simulated concentrations and radii of MammoSite balloon. An analytical estimation of the integral dose outside the CTV in the simple geometries simulated shows that dose to the breast for MammoSite applications is expected to be comparable using HDR 60Co and 192Ir sources, and higher than that for 169Yb. The higher enegies of 60Co sources result to approximately twice radiation protection requirements as compared to 169Ir sources. However, they allow for more accurate dosimetry calculation with currently used treatment planning algorithms for 60Co sources, compared to 169Ir.

High Dose Rate Brachytherapy as Monotherapy for Localised Prostate Cancer: Review of the Current Status.

The aim of this article is to review and present the published data on high dose rate (HDR) brachytherapy as monotherapy in the treatment of localised prostate cancer. A search and review of the literature was carried out on PubMed and MedLine using the medical subject headings 'high-dose-rate, brachytherapy, prostate cancer, monotherapy' as search terms. The search yielded more than 100 articles and abstracts published between 2000 and 2016. Only original clinical data on HDR monotherapy reporting oncological outcomes were included. When more than one series from the same institution were identified, the most recent one encompassing the largest patient number was considered for analysis. For citation crosscheck, the ISI web of science database was used employing the same search terms. Data tables were generated and summary descriptions created. The main outcome parameters used were biochemical control and toxicity scores. Fifteen articles comprising 3546 patients reported clinical outcome and toxicity, with follow-up ranging from median 1.4 to 8.0 years. A variety of dose and fractionation schedules were described, including 19.0 Gy as a single fraction to 54.0 Gy in nine fractions. Biochemical control rates ranged from 66 to 100% in low-risk, 63 to 98% in intermediate-risk and 81-93% in high-risk patients. Late grade 3 genitourinary and gastrointestinal toxicity was 0-16% and 0-2%, respectively. The reported potency preservation rates ranged from 60 to 90%. In conclusion, high biochemical control and low complication rates are reported with HDR monotherapy. It is a safe and effective local treatment modality for organ-confined prostate cancer with reproducible high-quality dosimetry.

Simultaneous paclitaxel and radiotherapy: initial clinical experience in lung cancer and other malignancies.

This report summarizes results from a series of pilot trials using combined-modality chemoradiotherapy with paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) as a radiosensitizing agent in patients with cancers of the lung, cervix, and bladder. In a phase I study of paclitaxel/radiotherapy in patients with locally advanced non-small cell lung cancer, five paclitaxel dose levels were evaluated in conjunction with simultaneous radiation (total dose, 59.4 Gy). A minimum of five patients were treated at each dose level; paclitaxel doses ranged from 45 mg/m2 over 3 weeks (level 1) to 65 mg/m2 for 7 weeks. Of 34 enrolled patients, 25 are evaluable for toxicity and response. Side effects were generally moderate for this combined-modality therapy, although two patients at level 5 developed dose-limiting toxicities (grade 4 esophagitis and grade 3 pneumonitis). Among 25 evaluable patients, complete and partial response rates were 4% (one patient) and 64% (16 patients), respectively; eight patients had a minor response. Median survival was 6 months (range, 1 to 20 months). Therapy was well tolerated, suggesting that the combined modalities offer a practical, effective therapy for patients with non-small cell disease. A paclitaxel dose of 55 mg/m2 is recommended for further study of combined-modality chemoradiotherapy in this clinical setting. In another trial, 33 women with inoperable, locally advanced cervical cancer received carboplatin 50 mg/m2 via intravenous infusion simultaneously with external-beam radiation therapy and vaginal brachytherapy, to define the regimen's toxicity and safety. Among the 33 women, 78% achieved a complete response to therapy. The investigators next conducted a trial of paclitaxel 50 mg/m2 given weekly over 3 hours with the previous carboplatin/radiotherapy regimen in four women and documented two partial responses, one near-complete response, and one minor response, with moderate, manageable toxicity. In a final case report on a patient with recurrent bladder cancer, simultaneous radiotherapy and weekly paclitaxel 50 mg/m2 intravenously over 3 hours yielded a partial remission, prompting the investigators to plan a phase I study to confirm the regimen's efficacy and safety. Additional planned studies include a phase I trial of simultaneous chemoradiotherapy in patients with cancer of the head and neck.

Carboplatin and radiotherapy in the treatment of head and neck cancer: six years' experience.

Between 1987 and 1991, 103 patients with advanced head and neck carcinoma were treated with radiochemotherapy plus carboplatin. Tumors were located in the oral cavity in 33 patients, the oropharynx in eight, and the hypopharynx in seven. Four patients had a tumor of the epipharynx and three, tumor of the larynx. In 48 patients tumor involvement included two or more compartments. Radiotherapy was performed with cobalt-60 rays or 8-MeV photons in a fractionation of 5 x 2 Gy/wk to a dose of 50 Gy. Carboplatin 60 to 70 mg/m2/d was administered days 1 through 5 and 29 through 33. For inoperable patients radiotherapy was continued to a dose of 70 to 74 Gy. To date, 103 patients have entered the study and 100 have completed treatment; three patients died during the treatment period. Actuarial 1- and 2-year survival rates are 77% and 53%, respectively, for all patients; comparable figures for patients with interposed surgery are 93% and 69%, and for the patients treated with radiotherapy alone, 71% and 47%. In a pilot study conducted between 1990 and 1991, 15 patients with advanced head and neck carcinomas underwent hyperfractionated accelerated radiotherapy (2 x 1.6 Gy/d 5 days per week; total dose, 64 to 67.2 Gy) and simultaneous intravenous carboplatin (60 mg/m2, days 1 through 5 and 29 through 33). Eleven patients had T4 and four had T3 tumors. At the end of the treatment period, 12 patients had achieved a complete tumor remission and all others attained a partial tumor involution. Although acute side effects were more pronounced compared with conventional irradiation, this treatment regimen is feasible and the initial complete remission rate of 80% is encouraging. As a result of the encouraging results achieved with hyperfractionated accelerated radiotherapy, we initiated a multicenter randomized study in November 1991. Patients with advanced head and neck carcinomas are either randomized for conventional radiotherapy plus carboplatin or hyperfractionated accelerated irradiation plus carboplatin. As of July 1994, 178 patients have been entered in the study. Results will be evaluated after the study is completed.

Simultaneous radiochemotherapy with paclitaxel in 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 available for the treatment of non-small cell lung cancer (NSCLC), with reported response rates of 21% to 24%. Its observed radiosensitizing effect is attributed to its interruption of cell development at the G2/M phase of the cell cycle, when cells are most sensitive to the killing effects of ionizing radiation. This phase I study of paclitaxel and simultaneous radiation therapy in patients with previously untreated, locally advanced inoperable stage IIIA/B NSCLC was designed to determine the maximum tolerated paclitaxel dose, to define the safety and toxicity of this combined modality, and to obtain preliminary data on its activity. Patients received a fixed dose of radiotherapy (1.8 Gy/d, 5 days a week, in shrinking-field technique, for a total dose of 59.4 Gy) and concomitant chemotherapy with a 3-hour infusion of paclitaxel once weekly on day 1, initially at a dose of 45 mg/m2, for 3 weeks. This dose remained constant during study levels 1 to 3, with the number of weeks of treatment increasing to 5 and 7 at levels 2 and 3, respectively. At dose level 4, the paclitaxel dose was increased to 55 mg/m2 over 7 weeks. Of 22 NSCLC patients who entered the study, 18 are evaluable for toxicity and response. Responses included one complete and 10 partial remissions; the other seven patients had minimal improvement. The therapy was well tolerated; no severe adverse events were associated with paclitaxel or radiotherapy. This combined modality appears to be a practicable and effective treatment for NSCLC. The maximum tolerated paclitaxel dose has not yet been reached, and dose escalation is planned.

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.

In vivo thermoluminescence dosimetry dose verification of transperineal 192Ir high-dose-rate brachytherapy using CT-based planning for the treatment of prostate cancer.

PURPOSE: To evaluate the potential of in vivo thermoluminescence dosimetry to estimate the accuracy of dose delivery in conformal high-dose-rate brachytherapy of prostate cancer. METHODS AND MATERIALS: A total of 50 LiF, TLD-100 cylindrical rods were calibrated in the dose range of interest and used as a batch for all fractions. Fourteen dosimeters for every treatment fraction were loaded in a plastic 4F catheter that was fixed in either one of the 6F needles implanted for treatment purposes or in an extra needle implanted after consulting with the patient. The 6F needles were placed either close to the urethra or in the vicinity of the median posterior wall of the prostate. Initial results are presented for 18 treatment fractions in 5 patients and compared to corresponding data calculated using the commercial treatment planning system used for the planning of the treatments based on CT images acquired postimplantation. RESULTS: The maximum observed mean difference between planned and delivered dose within a single treatment fraction was 8.57% +/- 2.61% (root mean square [RMS] errors from 4.03% to 9.73%). Corresponding values obtained after averaging results over all fractions of a patient were 6.88% +/- 4.93% (RMS errors from 4.82% to 7.32%). Experimental results of each fraction corresponding to the same patient point were found to agree within experimental uncertainties. CONCLUSIONS: Experimental results indicate that the proposed method is feasible for dose verification purposes and suggest that dose delivery in transperineal high-dose-rate brachytherapy after CT-based planning can be of acceptable accuracy.

A conformal index (COIN) to evaluate implant quality and dose specification in brachytherapy.

PURPOSE: To propose a new index (COIN) that can be easily understood and computed to assess high dose rate (HDR) brachytherapy interstitial implant quality and dose specification and is an improvement on existing indexes. METHODS AND MATERIALS: The COIN index is based on an extension of dose-volume histograms and employs an analogous concept to that of cost-benefit analysis, which has already been applied to quality-of-life assessments for two alternative treatment protocols. The COIN index calculation methodology is shown for two cases: with and without critical structures. An analysis is given of dose distributions for two planning treatment volumes (PTV) of simple geometrical shape, applying both the rules of the Paris system and that of the "Offenbach" system. 40 patients who have received interstitial implants form the clinical material. With current HDR brachytherapy technology both for dose delivery, using remote afterloaders, and for three-dimensional (3D) treatment planning, it is now possible to relatively easily plan conformal brachytherapy treatments that would have been impossible with manual afterloading techniques and two-dimensional (2D) treatment planning. RESULTS: Examples of the use of the COIN index are presented for experimental and clinical data. CONCLUSIONS: The results show that COIN is a useful and practical index to improve the quality of treatment of interstitial brachytherapy implants. Further work will be undertaken with a larger population of implanted cancer patients and a subdivision of the results by treatment site.

Effect of recombinant human granulocyte colony stimulating factor (R-metHuG-CSF) as an adjunct to large-field radiotherapy: a phase I study.

PURPOSE: To test the feasibility of recombinant human granulocyte colony stimulating factor application during large-field radiotherapy. METHODS AND MATERIALS: Fifteen patients with clinically and histologically proven malignancy who received large-field radiotherapy entered this study. Administration of recombinant granulocyte colony stimulating factor (G-CSF) at a dose of 300 microgram subcutaneously was started on Friday and was continued on Saturday and Sunday after the first radiotherapy treatment, which began on the Monday before. In this way four courses of G-CSF were applied every Friday, Saturday, and Sunday during the radiotherapy period. Absolute neutrophil cell (ANC) and blood counts were monitored twice a week and compared to a second group of 15 patients who received large-field radiotherapy without G-CSF. Before and at the end of every cycle of G-CSF, ANC, blood counts, and biochemistry were measured. We compared the myelotoxicity of the patients treated with G-CSF with 15 patients without G-CSF treated at the same period with large-field radiotherapy, in match pair technique. RESULTS: G-CSF increased the ANC throughout the period of irradiation, and the treatment time needed for competing radiotherapy was shorter in the group who received G-CSF. Fourteen of 15 patients who received G-CSF treatment completed large-field radiotherapy without pause. Only 1 of 15 patients not receiving G-CSF was able to receive radiation treatment on schedule. Patients receiving G-CSF completed treatment with the mantle-field technique in 24 days and those with the abdominal bath technique in 26.5 days. Conversely, patients treated without G-CSF completed treatment with the mantle-field technique in 30.5 days and those with the abdominal bath technique in 36 days. The most frequent side effect was musculoskeletal pain. CONCLUSION: The prophylactic application of G-CSF during large-field radiotherapy before the onset of neutropenia was feasible in this schedule. Whether or not this shortening of treatment duration will translate into an improvement in efficacy is not clear.

Reconstruction and navigation system for intraoperative brachytherapy using the flab technique for colorectal tumor bed irradiation.

PURPOSE: To present the development of a new navigation and reconstruction system based on an electromagnetic free-hand tracker and on CT imaging for treatment planning of intraoperative high-dose-rate brachytherapy (IORT-HDRB) in the sacral region. Our aim is to improve accuracy and to enable individualized treatment planning and dose documentation to be performed for IORT-HDRB using a flab technique. METHODS AND MATERIALS: The material consists of an electromagnetic 3D tracker system, a PC workstation with Microsoft Windows NT 4.0 operating system, and a recognition program for continuous speech. In addition, we designed an external reference system constructed of titanium and Perspex, which is positioned in the pelvis, and a special digitizer pen for reconstruction of the flab geometry. The flab design incorporates a series of silicon 10-mm-diameter spherical pellets. Measurements were made with a pelvic phantom in order to study the accuracy of the system. The reconstruction results are stored and can be exported via network or floppy to our different treatment planning systems. RESULTS: Our results for the reconstruction of a flab with six catheters and a total of 100 spherical pellets give mean errors in the range (2.5 +/- 0.6) mm to (3.5 +/- 0.8) mm depending on the positions of the pelvic phantom and transmitter relative to the operation table. These errors are calculated by comparing the reconstruction results of our system with those using a CT-based reconstruction of the flab geometry. For the accuracy of the navigation system for the pelvic phantom, we obtained mean errors in the range (2.2 +/- 0.7) mm to (3. 1 +/- 1.0) mm. CONCLUSIONS: The new system we have developed enables navigation and reconstruction within the surgical environment with a clinically acceptable level of accuracy. It offers the possibility of individualized treatment planning and effective documentation of the 3D dose distribution in IORT-HDRB using a flab technique.

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.

A fast screening method for histochemical localization of carbonic anhydrase. Application to kidney, skeletal muscle, and thrombocytes.

A simple method for histochemical localization of carbonic anhydrase using 5-dimethyl-amino-naphthalene-1-sulfonamide (DNSA) is described. Cryosections of tissues, or cell smears, are incubated in 3 to 10 X 10(-5) M DNSA and viewed in a fluorescence microscope. Upon excitation with ultraviolet light, sites of carbonic anhydrase localization can be identified by an intense blue fluorescence, which is due to the emission of blue light (lambda max = 470 nm) by carbonic anhydrase-DNSA complexes. This fluorescence can be largely suppressed by simultaneous incubation with 1 X 10(-4) to 2 X 10(-3) M concentrations of nonfluorescent carbonic anhydrase inhibitors, displacing DNSA from its binding site on the enzyme. Application of the method to kidney, skeletal muscle, and thrombocytes yields patterns of carbonic anhydrase localization that are in good agreement with results that have been obtained with a variety of other techniques.

Navigation system for interstitial brachytherapy.

PURPOSE: To develop a computed tomography (CT) based electromagnetic navigation system for interstitial brachytherapy. This is especially designed for situations when needles have to be positioned adjacent to or within critical anatomical structures. In such instances interactive 3D visualisation of the needle positions is essential. METHODS AND MATERIALS: The material consisted of a Polhemus electromagnetic 3D digitizer, a Pentium 200 MHz laptop and a voice recognition for continuous speech. In addition, we developed an external reference system constructed of Perspex which could be positioned above the tumour region and attached to the patient using a non-invasive fixation method. A specially designed needle holder and patient bed were also developed. Measurements were made on a series of phantoms in order to study the efficacy and accuracy of the navigation system. RESULTS: The mean navigation accuracy of positioning the 20.0 cm length metallic needles within the phantoms was in the range 2.0-4.1 mm with a maximum of 5.4 mm. This is an improvement on the accuracy of a CT-guided technique which was in the range 6.1-11.3 mm with a maximum of 19.4 mm. The mean reconstruction accuracy of the implant geometry was 3.2 mm within a non-ferromagnetic environment. We found that although the needles were metallic this did not have a significant influence. We also found for our experimental setups that the CT table and operation table non-ferromagnetic parts had no significant influence on the navigation accuracy. CONCLUSIONS: This navigation system will be a very useful clinical tool for interstitial brachytherapy applications, particularly when critical structures have to be avoided. It also should provide a significant improvement on our existing technique.

New interstitial HDR brachytherapy technique for prostate cancer: CT based 3D planning after transrectal implantation.

We have developed a new interstitial HDR brachytherapy technique for the treatment of prostate cancer using CT based 3D planning after transrectal implantation of four non-parallel needles. CT based needle reconstruction, target definition, evaluation and documentation, including DVHs and 3D imaging, is a feasible, safe and well tolerated treatment concept.

Predictive factors in radiotherapy for non-small cell lung cancer: present status.

PURPOSE: To evaluate the predictive factors for radiation response in non-small cell lung cancer (NSCLC) and the role of such factors in guiding high dose radiation therapy. METHODS: The first International Workshop on Prognostic and Predictive Factors in Lung Cancer was organized by the Hellenic Cooperative Oncology Group and held in Athens, Greece under the auspices of the International Association for the Study of Lung Cancer. Presentations at this meeting provided the outline of this report, which has also been supplemented with available data from the current literature. RESULTS: The predictive factors for both the natural history and the therapy outcome of NSCLC are grouped as follows: (1) tumor related factors (anatomic factors); the extent of tumor (tumor stage) is one of most important prognostic factors affecting the therapy outcome. Tumor size (T stage), anatomical structures involved (T4 vs. T3 lesion), and the presence of regional lymph node metastasis have a significant impact on both prognosis and response to appropriate therapy; (2) host-related factors (clinical factors) that are important in therapy response include performance status, weight loss of more than 10% of body weight in the previous 6 months, and associated co-morbidities, i.e. pulmonary and cardiac diseases; (3) technical factors of radiation therapy which play a decisive role in successful outcome. The target volume should be defined accurately using modern imaging studies. The radiation dose fractionation schedule, in terms of the dose intensity and total dose, should be high enough to provide local tumor control in the majority of patients. Three-dimensional (3-D) conformal planning is an essential tool in dose escalation studies to determine the maximum tolerated dose of radiation; (4) biological/radiobiological/metabolic factors. Biologic markers resulting from genetic lesions in lung cancer are grouped as follows: (a) oncogene amplification and overexpression (aberrant gene expression) and mutated tumor suppressor genes -- ras gene, myc gene, HER-2/neu and survivin gene, p53 and mutated beta-tubulin gene; (b) tumor biologic/radiobiologic factors -- tumor cell proliferation kinetics, hypoxia, intrinsic cellular radiosensitivity, gamma factor, and DNA content; (c) enzymes and hormones: neuron-specific enolase, serum lactate dehydrogenase, and enhanced glucose metabolic rate supported by increased glucose transporter protein. The surviving fraction of tumor cells at 2.0 Gy of radiation (SF2) as a measure of intrinsic tumor cell radiosensitivity, potential doubling time (T(Pot)) as a measure of the rate of tumor cell proliferation and gamma factor representing the slope of the survival curve at 50% survival rate are being investigated as potential predictors for therapy response. Enhanced glucose utilization, a hallmark of malignant transformation, is being studied as a potential monitor for therapy response by using PET-FDG. CONCLUSION: Current data indicate that there is a dose-response relationship between radiation dose and local tumor control, and also between local tumor control and survival in stage III NSCLC. Therapeutic factors, i.e. total radiation dose, fractionation schedule and dose intensity, and use of 3-D conformal radiation to secure the optimum therapeutic ratio are important for improved local tumor control and survival. Future research should be directed towards radiation dose escalation using 3-D conformal therapy to determine the maximum tolerated dose (MTD) of radiation in chemo-radiotherapy, and the use of this MTD for improved local tumor control and survival. Radiobiological, molecular, and metabolic markers may have potential for monitoring tumor response and optimizing radiation therapy.

Anatomy-based three-dimensional dose optimization in brachytherapy using multiobjective genetic algorithms.

In conventional dose optimization algorithms, in brachytherapy, multiple objectives are expressed in terms of an aggregating function which combines individual objective values into a single utility value, making the problem single objective, prior to optimization. A multiobjective genetic algorithm (MOGA) was developed for dose optimization based on an a posteriori approach, leaving the decision-making process to a planner and offering a representative trade-off surface of the various objectives. The MOGA provides a flexible search engine which provides the maximum of information for a decision maker. Tests performed with various treatment plans in brachytherapy have shown that MOGA gives solutions which are superior to those of traditional dose optimization algorithms. Objectives were proposed in terms of the COIN distribution and differential volume histograms, taking into account patient anatomy in the optimization process.

Dose-volume histograms computation comparisons using conventional methods and optimized fast Fourier transforms algorithms for brachytherapy.

In anatomy based optimization procedures for large volume implants the calculation of dose-volume histograms (DVH) accounts for the major part of the time involved and can be as long as a few hours. This time is proportional to the number of seeds or source dwell positions required for the implant. A procedure for the calculation of brachytherapy seed dose distribution calculation employing fast Fourier transforms (FFT) and the convolution theorem has been described by others and was supposed to significantly improve the speed of the dose distribution computation. Using new significantly improved FFT algorithms and various other optimization techniques we have compared the calculated differential and integral DVHs in high dose rate (HDR) brachytherapy with a single stepping source using actual clinical implants. This is so that we could assess the efficiency and accuracy of the FFT method with that of conventional methods. Our results showed that the FFT based method of calculating DVHs in brachytherapy is comparable in speed with conventional dose calculation methods, but only for implants with more than 287 sources. It is therefore of limited practical use even for large implants. This result is in direct opposition to the claim by other authors.