Optimization of the interface between radiology, surgery, radiotherapy, and pathology in head and neck tumor surgery: a navigation-assisted multidisciplinary network.

A navigation-assisted multidisciplinary network to improve the interface between radiology, surgery, radiotherapy, and pathology in the field of head and neck cancer is described. All implicated fields are integrated by a common server platform and have remote data access in a ready-to-use format. The margins of resection and exact locations of biopsies are mapped intraoperatively. The pathologist uses the numerical coordinates of these samples to precisely trace each specimen in the anatomical field. Subsequently, map-guided radiotherapy is planned. In addition to the benefits of image-guided resection, this model enables radiotherapy planning according to the specific coordinates of the resection defect plus any residually affected sites identified by the pathologist. Irradiation of adjacent healthy structures is thereby minimized. In summary, the navigation-assisted network described grants timely multidisciplinary feedback between all fields involved, attains meticulous pathological definition, and permits optimized coordinate-directed radiotherapy.

Long-term effects on the intelligence of children treated for acute lymphoblastic leukemia.

The purpose of this study was to investigate whether the intelligence quotient (IQ) in children treated for leukemia decreases in the years following whole brain irradiation. Twenty-seven leukemic children were assessed following a mean time lapse between radiotherapy and IQ measurement of 9 years. The IQ test used was the Hamburg Weschsler Intelligence Test for Adults. The IQ results did not differ significantly, p > 0.05, from the IQs of the general population. It was found that age and dose were not predictors of a decrease in IQ. The only predictor was time lapse between irradiation and IQ measurement, which we found to be indicative of an IQ decrease even after 9 years. Time lapse between irradiation is a useful predictor of IQ.

Role of interstitial brachytherapy in the treatment of malignant disease.

Interstitial brachytherapy was first applied using radium needles, with minimum protection of physicians and nurses. Modern techniques involve the use of radionuclide (192)Ir as the source used in computer-controlled remote afterloading machines, which can deliver a high dose rate (HDR). Treatment planning is also undertaken with the use of computers and anatomical cross-section images using CT, ultrasound and MRI. This review presents these modern techniques for tumors of a series of body sites: prostate, head and neck, breast, bladder, brain, and for soft-tissue sarcomas. Low dose rate (LDR) interstitial brachytherapy techniques are also included in this review since in some body sites there is a choice between HDR and LDR.

[Intraoperative radiotherapy--progress with a CT-assisted navigation system]. / Intraoperative Strahlentherapie--Fortschritt durch ein CT-gestütztes Navigationssystem.

INTRODUCTION: The fact that conventional intraoperative radiotherapy (IORT) does not give the opportunity for exact documentation of the applied radiation volume and dose distribution has been criticised. We would like to introduce a system for surgical navigation and documentation of the flab positioning for intraoperative brachytherapy in afterloading flab technique. METHODS: Our system consists of an electromagnetic 3D digitizer and a PC workstation. Preoperatively taken spiral CT scans of the tumour region are used for navigation and documentation of the flab positioning, analogous to the procedure in neuronavigation. Registration is done via an external reference system attached to the iliac bone of the patient. RESULTS: The mean accuracy of digitalization of the 100 spheres in a pelvis model is about 2.6 +/- 0.5-3.7 +/- 0.9 mm. Mean navigation accuracy is 2.4 +/- 0.8-3.3 +/- 0.8 mm. These figures correspond to the clinical experience of our surgeons. CONCLUSIONS: The optimization of the flab positioning by CT-guided navigation and the more accurate documentation of the dose volume and distribution in the patient is an important step towards improving the quality of individual radiotherapy. We are of the opinion that surgical navigation in the pelvic region should be subject to additional investigation in order to optimize the procedure.

CT-based navigation systems for intraoperative radiotherapy using the afterloading-flab technique.

INTRODUCTION: The fact that conventional intraoperative radiotherapy does not give the opportunity to exactly document the radiation volume applied and the dose distribution has been criticized in many ways. We would like to introduce a system for surgical navigation and documentation of flap positioning in intraoperative brachytherapy using the afterloading flap technique. METHODS: Our system consists of an electromagnetic 3D-digitizer and a PC workstation. Spiral CT scans of the tumor region taken preoperatively are used for navigation and documentation of flap positioning, analogous to the procedure in neuronavigation. Registration is done via an external reference system which is attached to the iliac bone of the patient. RESULTS: The mean accuracy of digitalization of the 100 spheres in a pelvis model is about 2.6 +/- 0.5 to 3.7 +/- 9.9 mm. The mean navigation accuracy is 2.4 +/- 0.8 to 3.3 +/- 0.8 mm. These figures correspond to the clinical experience of our surgeons. DISCUSSION: The optimization of flab positioning by CT-guided navigation and the more accurate documentation of the dose volume and distribution in the patient is an important step on the way to improving the quality of individual radiation therapy. We are of the opinion that surgical navigation in the pelvic region should be subject to additional investigation in order to optimize the procedure.

Autoactivation of source dwell positions for HDR brachytherapy treatment planning.

The most accurate classical dose optimization algorithms in HDR brachytherapy strongly depend on an appropriate selection of source dwell positions which fulfill user-defined geometrical boundary conditions which are relative to patient anatomy. Most anatomical situations, such as for prostate and head and neck tumors, are complex and can require geometries with 5-15 catheters with 48 possible dwell positions per catheter depending on the tumor volume. The manual selection of dwell positions using visual checks by trial and error is very time consuming. This can only be improved by the use of a technique which automatically recognizes and selects the optimum dwell positions for each catheter. We have developed an algorithm, termed an autoactivation algorithm, which improves implant planning by providing a facility for the necessary automatic recognition of HDR source dwell positions.

3D interstitial HDR brachytherapy combined with 3D external beam radiotherapy and androgen deprivation for prostate cancer. Preliminary results.

BACKGROUND: Evaluation of feasibility, tolerance and efficiency for a new 3D interstitial HDR brachytherapy technique combined with 3D external beam radiotherapy and androgen deprivation for prostate cancer. PATIENTS AND METHODS: Between January 1997 and August 1998 we treated 35 patients with stage cT1-3 N0 M0 prostate cancer. Thirty-two patients with a follow-up of 12 to 28 months (median: 18 months) were evaluated. After ultrasound-guided transrectal implantation of 4 non-parallel needles, CT based 3D brachytherapy treatment planning ("Offenbach system") was performed. All patients received 4 fractions brachytherapy using a fractional dose of 5 or 7 Gy. Time between each fraction was 14 days. After brachytherapy 3D external irradiation followed up to 39.6 or 45.0 Gy. All patients received androgen deprivation, starting 2 to 19 months before brachytherapy, ending 3 months after 3D external radiotherapy. RESULTS: Posttreatment PSA levels dropped to < 1.5 ng/ml in 29/32 patients (91%). In 25 patients PSA levels were < 0.5 ng/ml, in 4 patients 0.5 to 1.5 ng/ml. In 2 patients we noted biochemical relapse. Transrectal implantation was very well tolerated. Grade 3 acute urinary toxicity occurred in 1 patient. We noted no Grade 2 or higher acute gastrointestinal toxicity. One patient developed a Grade 3 late urinary toxicity. No patient showed late gastrointestinal side effects. All 140 dose-volume histograms for 3D HDR brachytherapy were analyzed. CONCLUSIONS: The new 3D HDR brachytherapy technique, combined with 3D external irradiation and androgen deprivation, is a feasible, so far well-tolerated and effective treatment in the short-time follow-up of median 18 months.

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.

Catheter autoreconstruction in computed tomography based brachytherapy treatment planning.

The aim of this study is to develop an automatic reconstruction of brachytherapy catheters using CT (computed tomography) data. Previously no such automatic facility has existed in any treatment planning software. To achieve this facility we have developed tools for the automatic reconstruction (which we term autoreconstruction) of plastic and metallic catheters. These algorithms overcome a number of difficulties which arise when a large number of catheters are present. These include situations with intersecting catheters and with loop techniques. The time required for the catheter reconstruction process using our autoreconstruction method is significantly reduced. The accuracy of our autoreconstruction is at least as high as the classical manual slice-by-slice method.

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.

Clinical relevance of tumor ploidy and micronucleus formation for oral cavity cancer.

AIMS AND BACKGROUND: To study the clinical relevance of tumor ploidy and micronucleus formation as prognostic factors. METHODS AND STUDY DESIGN: Twenty-eight patients with squamous cell carcinoma of the oral cavity were treated with primary radiochemotherapy consisting of irradiation up to 70 Gy in combination with cisplatin. Cell cycle distribution, micronucleus formation and ploidy were evaluated by flow cytometry of biopsies taken before treatment and after irradiation to 10 Gy (5x2 Gy). Sexteen out of 28 patients relapsed after a minimum follow-up period of two years. RESULTS: Flow cytometry of the recurrence biopsy showed hyperpentaploid (5c exceeding) cells in 13/16 (81%) of the relapsed patients. In 7 patients the hyperploid clone was not present in the flow cytometry of the primary tumors. Ploidy could retrospectively be determined also by image cytometry in archival tumor material of the pretreatment specimens. Patients with a level below 100 5c cells per 10,000 cell nuclei were shown to have a significantly better prognosis than patients with more than 100 hyperpentaploid tumor cells. The micronucleus formation was 2-5 times higher in tumors showing a good response to treatment than in carcinomas relapsing within two years. CONCLUSIONS: The 5c-exceeding ratio measured by image cytometry and micronucleus formation proved to be good prognostic parameters for the clinical outcome of patients with locally advanced head and neck carcinomas.

CT-Based interstitial HDR brachytherapy.

PURPOSE: Development, application and evaluation of a CT-guided implantation technique and a fully CT-based treatment planning procedure for brachytherapy. METHODS AND MATERIALS: A brachytherapy procedure based on CT-guided implantation technique and CT-based treatment planning has been developed and clinical evaluated. For this purpose a software system (PROMETHEUS) for the 3D reconstruction of brachytherapy catheters and patient anatomy using only CT scans has been developed. An interface for the Nucletron PLATO BPS treatment planning system for optimization and calculation of dose distribution has been devised. The planning target volume(s) are defined as sets of points using contouring tools and are used for optimization of the 3D dose distribution. Dose-volume histogram based analysis of the dose distribution (COIN analysis) enables a clinically realistic evaluation of the brachytherapy application to be made. The CT-guided implantation of catheters and the CT-based treatment planning procedure has been performed for interstitial brachytherapy and for different tumor sites in 197 patients between 1996 and 1997. RESULTS: The accuracy of the CT reconstruction was tested using first a quality assurance phantom and second, a simulated interstitial implant of 12 needles. These were compared with the results of reconstruction using radiographs. Both methods gave comparable results with regard to accuracy, but the CT based reconstruction was faster. Clinical feasibility was proved in pre-irradiated recurrences of brain tumors, in pretreated recurrences or metastatic disease, and in breast carcinomas. The tumor volumes treated were in the range 5.1 to 2,741 cm3. Analysis of implant quality showed a slightly significant lower COIN value for the bone implants, but no differences with respect to the planning target volume. CONCLUSIONS: The Offenbach system, incorporating the PROMETHEUS software for interstitial HDR brachytherapy has proved to be extremely valuable in routine clinical practice for many tumor sites. Our CT-guided implantation technique together with a fully CT-based planning system has enabled conformal brachytherapy treatment to become routine.

Colorectales Carcinom--Behandlungsalternative durch intraoperative Radiotherapie mittels Afterloading-flab-Technik?

Intraoperative radiotherapy (IORT) is a new concept in the treatment of recurrent and primary advanced colorectal tumors. Between October 1994 and December 1997 27 patients (primary tumor: 8, first recurrent tumor: 12, second recurrent tumor: 7) received IORT (32 applications). Chemotherapy and percutaneous radiotherapy had already been given to all patients with advanced and recurrent colorectal tumors. The intraoperative irradiation was performed through HDR iridium afterloading. A flexible flab--individually adapted to the "tumor bed"--was used as applicator. The contact dose ranged from 10 to 15 Gy. The mean operation time (rectum resection: 5, rectum amputation: 14, debulking: 8) increased by 30 min on average. Eight patients had postoperative complications: perianal wound infections (3), sacrovesical fistulas (3), leakage of anastomosis (1) and neural ureter dysfunction (1). To date--on average 17.1 months (range: 3-33) after operation--13 patients are free of tumor recurrence or show stable disease. Ten patients--all of them had macroscopic residual tumor--have local tumor progression combined with good quality of life. Only 4 patients died (acute kidney failure, stroke, marasmus, systemic progression). The afterloading flab technique represents a technically simple, minimally harmful procedure in the therapy of colorectal tumor. Even when IORT with electrons is not feasible or the patients have already been irradiated, a higher radiation dose is possible. Given the demonstrated rate of local tumor recurrence, the afterloading flab technique seems to be a valuable treatment alternative to extended, high-risk resections. Long-term follow-ups will be necessary.

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.

CT guided interstitial high dose rate brachytherapy for recurrent malignant gliomas.

This paper describes the technique and preliminary results of high dose rate (HDR) interstitial brachytherapy for recurrent grade III and grade IV gliomas. Although in the initial treatment of malignant gliomas brachytherapy has been shown to give better results than external beam therapy, this has previously always been with low dose rate (LDR) brachytherapy. Stereotactic frames are used for interstitial LDR brachytherapy but a CT image-guided technique does not require such a frame. The survival rates for our initial 53 patients do not significantly differ from LDR results. However, using HDR there are several advantages, including a much shorter treatment time with HDR than LDR and better patient comfort. HDR also allows better individualized optimization of the treatment than LDR.

Application of the Monte Carlo integration (MCI) method for calculation of the anisotropy of 192Ir brachytherapy sources.

Source anisotropy is a very important factor in the brachytherapy quality assurance of high-dose rate (HDR) 192Ir afterloading stepping sources. If anisotropy is not taken into account then doses received by a brachytherapy patient in certain directions can be in error by a clinically significant amount. Experimental measurements of anisotropy are very labour intensive. We have shown that within acceptable limits of accuracy, Monte Carlo integration (MCI) of a modified Sievert integral (3D generalization) can provide the necessary data within a much shorter time scale than can experiments. Hence MCI can be used for routine quality assurance schedules whenever a new design of HDR or PDR 192Ir is used for brachytherapy afterloading. Our MCI calculation results are compared with published experimental data and Monte Carlo simulation data for microSelectron and VariSource 192Ir sources. We have shown not only that MCI offers advantages over alternative numerical integration methods, but also that treating filtration coefficients as radial distance-dependent functions improves Sievert integral accuracy at low energies. This paper also provides anisotropy data for three new 192Ir sources, one for the microSelectron-HDR and two for the microSelectron-PDR, for which data are currently not available. The information we have obtained in this study can be incorporated into clinical practice.

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.

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.