Simulation of different applicator positions for treatment of a presacral tumour.

INTRODUCTION: Proximally located presacral recurrences of rectal carcinomas are known to be difficult to heat due to the complex anatomy of the pelvis, which reflect, shield and diffract the power. This study is to clarify whether a change of position of the Sigma-Eye applicator in this region can improve the heating. MATERIAL AND METHODS: Finite element (FE) planning calculations were made for a phantom model with a proximal presacral tumour using a fixed 100 MHz radiofrequency radiation. Shifts of the applicator were simulated in 1 cm steps in x-(lateral), y-(posterior) and z-(longitudinal) direction. Computations also considered the network effects of the Sigma-Eye applicator. Optimisation of the phases and amplitudes for all positions were performed after solving the bioheat-transfer-equation. The parameters T90, T50, sensitivity, hot spot volume and total deposited power have been sampled for every applicator position with optimised plans and a standard plan. RESULTS: The ability to heat a presacral tumour clearly depends on the applicator position, for standard antenna adjustment and also for optimised steering of the Sigma-Eye applicator. The gamma-direction (anterior-posterior) is very sensitive. Using optimised steering for each position, in z-direction (longitudinal), we found an unexpected additional optimum at 8 cm cranial from the middle position of the phantom. The x-direction (lateral) is in a clinical setting less important and shows only smaller changes of T90 with an expected optimum in the central position. A positioning of the applicator in the axial and anterior position of the mid-pubic symphysis should be avoided for treatment of the presacral region, regardless of the used adjustment. Use of amplitude and phase optimisation yields better T90 values than plans optimised only by phases, but they are much more sensitive for small variations of phases and amplitudes during a treatment, and the total power of the Sigma-Eye applicator can be restricted by the treatment software. CONCLUSIONS: Complex geometry of the human pelvis seems to be the reason for the difficulties to warm up the proximal presacral region. The assumption that every position can be balanced by a proper phase adaption, is true only in a small range. A centring of the applicator on the mid-pubic symphysis to heat this region should be avoided. From the practical point of view improved warming should be performed by optimisation of phases only.

Intracranial thermotherapy using magnetic nanoparticles combined with external beam radiotherapy: results of a feasibility study on patients with glioblastoma multiforme.

We aimed to evaluate the feasibility and tolerability of the newly developed thermotherapy using magnetic nanoparticles on recurrent glioblastoma multiforme. Fourteen patients received 3-dimensional image guided intratumoral injection of aminosilane coated iron oxide nanoparticles. The patients were then exposed to an alternating magnetic field to induce particle heating. The amount of fluid and the spatial distribution of the depots were planned in advance by means of a specially developed treatment planning software following magnetic resonance imaging (MRI). The actually achieved magnetic fluid distribution was measured by computed tomography (CT), which after matching to pre-operative MRI data enables the calculation of the expected heat distribution within the tumor in dependence of the magnetic field strength. Patients received 4-10 (median: 6) thermotherapy treatments following instillation of 0.1-0.7 ml (median: 0.2) of magnetic fluid per ml tumor volume and single fractions (2 Gy) of a radiotherapy series of 16-70 Gy (median: 30). Thermotherapy using magnetic nanoparticles was tolerated well by all patients with minor or no side effects. Median maximum intratumoral temperatures of 44.6 degrees C (42.4-49.5 degrees C) were measured and signs of local tumor control were observed. In conclusion, deep cranial thermotherapy using magnetic nanoparticles can be safely applied on glioblastoma multiforme patients.

Radiochemotherapy combined with regional pelvic hyperthermia induces high response and resectability rates in patients with nonresectable cervical cancer > or =FIGO IIB "bulky".

PURPOSE: To evaluate preoperative radiochemotherapy combined with regional pelvic hyperthermia in patients with nonresectable cervical cancer >/= International Federation of Gynecology and Obstetrics (FIGO) IIB "bulky" in a Phase II study. METHODS AND MATERIALS: Thirty-two patients with nonresectable FIGO IIB-IVA cervical cancer confined to the pelvis were treated with radiochemotherapy (5 x 1.8 Gy/wk, 45-50.4 Gy; cisplatin, 40 mg/m2/wk) and weekly regional pelvic hyperthermia (SIGMA-60 applicator, system BSD-2000; BSD Medical Corp., Salt Lake City, UT). Responders underwent hysterectomy if possible, whereas patients still unresectable received definitive hyperthermic radiochemotherapy. Feasibility, toxicity, as well as response and resectability, local progression free- and overall survival rates, were evaluated. RESULTS: Thirty of 32 patients completed treatment. Grade III/IV toxicities (National Cancer Institute-Common Toxicity Criteria) were diarrhea (n = 5), weight loss >10 kg (n = 4), and nausea (n = 2). Twenty-four of 32 patients (75%) achieved a partial remission after 45-50 Gy, and 20 patients underwent hysterectomy (18 patients, R0; 8 patients pCR). Three-year overall survival was 60%, with moderate (13%) rates of severe late toxicity. R0-resected patients had a favorable chronic toxicity profile and an excellent prognosis (3-year survival rate: 93%). Response depended on thermal parameters (vaginal reference point), whereas response, R0-resection, and FIGO stage are significant prognostic factors for survival. CONCLUSION: Preoperative hyperthermic radiochemotherapy (45-50 Gy) induces high response rates and enables curative surgery in a high proportion of patients with nonresectable cervical cancer. Therefore, the use of hyperthermia in conjunction with standard chemo-/radiotherapy +/- surgery may allow for more effective tumor treatment while decreasing the risk of complications in patients with locally advanced cervical cancer.

Noninvasive magnetic resonance thermography of soft tissue sarcomas during regional hyperthermia: correlation with response and direct thermometry.

BACKGROUND: The objective of this study was to evaluate noninvasive magnetic resonance (MR) thermography for the monitoring of regional hyperthermia (RHT) in patients with soft tissue sarcomas of the lower extremities and pelvis. METHODS: Noninvasive MR monitoring during RHT was performed in 9 patients who had high-risk soft tissue sarcomas of the lower extremities or pelvis during neoadjuvant chemotherapy plus RHT in the scope of the European Organization for Research and Treatment of Cancer 62961/European Society for Hyperthermic Oncology RHT-95 study. Anatomic and temperature-sensitive data sets were acquired every 10 minutes before and during RHT (using gradient-echo-sequences with variable echo times). MR temperature distributions were derived from the phase differences by using the proton-resonance frequency shift method. A phase convolution setting phase shifts to zero in the fat tissue was performed as a drift correction. The mean MR temperatures in the tumor and muscles and the index temperatures (e.g., T90, which covers 90% of the target volume) and thermal doses were determined and compared with pathohistologic responses and direct temperature measurements if available. RESULTS: Thirty of 72 MR-thermography data sets (>40% of heat sessions) were evaluable. A significant correlation was observed between pathohistologic response (defined as a necrosis rate >or=90%) and standardized thermal parameters, such as thermal dose cumulative equivalent minutes at 43 degrees C to 90% of the target volume (T90) (P = .050), mean T90 (P = .048), or T50 (P = .050). The correlation of 13 conventional temperature measurements performed in selected patients and sessions invasively in the tumor or noninvasively in rectum and bladder revealed an excellent correlation with MR temperatures (R2 = .96). CONCLUSIONS: Noninvasive MR thermography of soft tissue sarcoma was feasible and suitable for validating the quality of heating during RHT.

18F-FET PET for planning of thermotherapy using magnetic nanoparticles in recurrent glioblastoma.

PURPOSE: Thermotherapy using magnetic nanoparticles (nano cancer therapy) is a new concept of local tumour therapy, which is based on controlled heating of intra-tumoural injected magnetic nanoparticles. The aim of this study was to evaluate the usefulness of PET with a recently introduced amino acid tracer O-(2-[18F]fluoroethyl)-]L-tyrosine (FET) for targeting the nanoparticles implantation. MATERIALS AND METHODS: Eleven patients with glioblastoma recurrences underwent MR and FET-PET imaging for planning of the nano cancer therapy. Thereafter, the gross tumour volumes (GTV) were defined, taking into consideration the results of both imaging tools. RESULTS: The MRI-based mean GTV was 24.3 cm3 (range 2.5-59.7) and the PET-based mean GTV 31.9 cm3 (range 5.2-77.9). On the average the MRI identified an additional 8.9 +/- 4.7 cm3 and the FET-PET scan-an additional 16.5 +/- 15.2 cm3 outside of the common GTV (15.4 +/- 11.0 cm3). The mean final GTV accounted to 33.8 cm3 (range, 5.2-77.9). The additional information of FET-PET led to an increase in GTV by 22-286% in eight patients and to a decrease of 23% and 26%, respectively, in two patients. In one patient, the final GTV was defined on the basis of MRI data only. CONCLUSIONS: FET-PET adds important information on the actual tumour volume in recurrent glioblastomas and is highly valuable for defining the target volume for the nano cancer therapy.

Diagnostic value of 123I-IMT SPECT in the follow-up of head and neck cancer.

BACKGROUND: Nuclear medicine imaging is increasingly used in the evaluation of tumors of the head and neck. In the current study, we assess the value of single-photon emission tomography (SPECT) using the amino acid tracer L-3-[123I]iodine-alpha-methyl-tyrosine (IMT) for the detection of recurrent head and neck cancer. PATIENTS AND METHODS: 45 consecutive patients with suspected recurrence of previously treated head and neck cancer were examined by IMT-SPECT using a dual head system with integrated low-dose computed tomography (CT). The accuracy of the IMT-SPECT was evaluated by correlating the findings with results of histology or clinical and CT/MRI (magnetic resonance imaging) follow-up examinations. RESULTS: The sensitivity, specificity and accuracy of IMT-SPECT in the detection of recurrent/persistent tumors were 83, 89 and 84.5%, respectively. The positive and negative predictive value amounted to 96.5 and 60%, respectively. CONCLUSION: IMT-SPECT using integrated low-dose CT appears to be a helpful complementary imaging tool for the detection of local recurrences and lymph node metastases of head and neck cancer and their differentiation from treatment-induced changes. The advantage of the method is the high positive predictive value in the diagnosis of relapsed tumors. However, a negative IMT-SPECT result does not exclude a recurrence.

Adjuvant chemotherapy with folinic acid and 5-fluorouracil in patients with locally advanced rectal cancer previously treated by preoperative radiochemotherapy and curative tumor resection.

BACKGROUND AND AIMS: The role of postoperative adjuvant chemotherapy in patients with rectal cancer pretreated by preoperative radiochemotherapy (RCT) and curative surgery is still poorly investigated. PATIENTS AND METHODS: We pooled data from both arms of a phase III trial in which patients with locally advanced (T3/4) rectal cancer were randomized to preoperative RCT alone or combined with pelvic radio-frequency hyperthermia. After surgery, R0-resected patients were scheduled to adjuvant chemotherapy with four monthly courses of 50 mg folinic acid (FA) and gradually escalated 5-fluorouracil (5-FU, 350-500 mg/m2, days 1-5). Reasons preventing initiation of chemotherapy and treatment-related toxicities were evaluated. Patients' characteristics and survival parameters were compared between the treated and untreated patient groups. RESULTS: Out of 93 patients, 73 (79%) started adjuvant chemotherapy, whereas 19 (21%) did not, mostly due to perioperative complications and refusal. Chemotherapy-related toxicities were mild to moderate in most cases, but--together with protracted postoperative complications--prevented the intended dose escalation of 5-FU in 71% of patients. Distant-failure-free (p=0.03) and overall survival (p=0.03) were improved in the chemotherapy group, although there was a negative selection of patients with unfavourable characteristics into the untreated patient group. INTERPRETATION/CONCLUSION: Adjuvant chemotherapy using FA and 5-FU can be safely applied to the majority of patients with rectal cancer pretreated by RCT and surgery. Survival data are not suitable to allow far-reaching conclusions, but are in line with suggestions of a favourable effect of adjuvant chemotherapy in these patients.

The effect of thermotherapy using magnetic nanoparticles on rat malignant glioma.

Thermotherapy using magnetic nanoparticles is a new technique for interstitial hyperthermia and thermoablation based on magnetic field-induced excitation of biocompatible superparamagnetic nanoparticles. To evaluate the potential of this technique for minimally invasive treatment, we carried out a systematic analysis of its effects on experimental glioblastoma multiforme in a rat tumor model. Tumors were induced by implantation of RG-2-cells into the brains of 120 male Fisher rats. Animals were randomly allocated to 10 groups of 12 rats each, including controls. Animals received two thermotherapy treatments following a single intratumoral injection of two different magnetic fluids (dextran- or aminosilane-coated iron-oxide nanoparticles). Treatment was carried out on days four and six after tumor induction using an alternating magnetic field applicator system operating at a frequency of 100 kHz and variable field strength of 0-18 kA/m. The effectiveness of treatment was determined by the survival time of the animals and histopathological examinations of the brain and the tumor.Thermotherapy with aminosilane-coated nanoparticles led up to 4.5-fold prolongation of survival over controls, while the dextran-coated particles did not indicate any advantage. Intratumoral deposition of the aminosilane-coated particles was found to be stable, allowing for serial thermotherapy treatments without repeated injection. Histological and immunohistochemical examinations after treatment revealed large necrotic areas close to particle deposits, a decreased proliferation rate and a reactive astrogliosis adjacent to the tumor.Thus, localized interstitial thermotherapy with magnetic nanoparticles has an antitumoral effect on malignant brain tumors. This method is suitable for clinical use and may be a novel strategy for treating malignant glioma, which cannot be treated successfully today. The optimal treatment schedules and potential combinations with other therapies need to be defined in further studies.

Magnetic nanoparticles for interstitial thermotherapy--feasibility, tolerance and achieved temperatures.

BACKGROUND: The concept of magnetic fluid hyperthermia is clinically evaluated after development of the whole body magnetic field applicator MFH 300F and the magnetofluid MFL 082AS. This new system for localized thermotherapy is suitable either for hyperthermia or thermoablation. The magnetic fluid, composed of iron oxide nanoparticles dispersed in water, must be distributed in the tumour and is subsequently heated by exposing to an alternating magnetic field in the applicator. We performed a feasibility study with 22 patients suffering from heavily pretreated recurrences of different tumour entities, where hyperthermia in conjunction with irradiation and/or chemotherapy was an option. The potential to estimate (by post-implantation analyses) and to achieve (by improving the technique) a satisfactory temperature distribution was evaluated in dependency on the implantation technique. MATERIAL AND METHODS: Three implantation methods were established: Infiltration under CT fluoroscopy (group A), TRUS (transrectal ultrasound)--guided implantation with X-fluoroscopy (group B) and intra-operative infiltration under visual control (group C). In group A and B the distribution of the nanoparticles can be planned prior to implantation on the basis of three-dimensional image datasets. The specific absorption rates (SAR in W/kg) can be derived from the particle distribution imaged via CT together with the actual H-field strength (in kA/m). The temperature distribution in the tumour region is calculated using the bioheat-transfer equation assessing a mean perfusion value, which is determined by matching calculated temperatures to direct (invasive or endoluminal) temperature measurements in reference points in or near the target region. RESULTS: Instillation of the magnetic fluid and the thermotherapy treatments were tolerated without or with only moderate side effects, respectively. Using tolerable H-field-strengths of 3.0-6.0 kA/m in the pelvis, up to 7.5 kA/m in the thoracic and neck region and >10.0 kA/m for the head, we achieved SAR of 60-380 W/kg in the target leading to a 40 degrees C heat-coverage of 86%. However, the coverage with > or =42 degrees C is unsatisfactory at present (30% of the target volume in group A and only 0.2% in group B). CONCLUSION: Further improvement of the temperature distribution is required by refining the implantation techniques or simply by increasing the amount of nanofluid or elevation of the magnetic field strength. From the actual nanoparticle distribution and derived temperatures we can extrapolate, that already a moderate increase of the H-field by only 2 kA/m would significantly improve the 42 degrees C coverage towards 100% (98%). This illustrates the great potential of the nanofluid-based heating technology.

Noninvasive magnetic resonance thermography of recurrent rectal carcinoma in a 1.5 Tesla hybrid system.

To implement noninvasive thermometry, we installed a hybrid system consisting of a radiofrequency multiantenna applicator (SIGMA-Eye) for deep hyperthermia (BSD-2000/3D) integrated into the gantry of a 1.5 Tesla magnetic resonance (MR) tomograph Symphony. This system can record MR data during radiofrequency heating and is suitable for application and evaluation of methods for MR thermography. In 15 patients with preirradiated pelvic rectal recurrences, we acquired phase data sets (25 slices) every 10 to 15 minutes over the treatment time (60-90 minutes) using gradient echo sequences (echo time = 20 ms), transformed the phase differences to MR temperatures, and fused the color-coded MR-temperature distributions with anatomic T1-weighted MR data sets. We could generate one complete series of MR data sets per patient with satisfactory quality for further analysis. In fat, muscle, water bolus, prostate, bladder, and tumor, we delineated regions of interest (ROI), used the fat ROI for drift correction by transforming these regions to a phase shift zero, and evaluated the MR-temperature frequency distributions. Mean MR temperatures (T(MR)), maximum T(MR), full width half maximum (FWHM), and other descriptors of tumors and normal tissues were noninvasively derived and their dependencies outlined. In 8 of 15 patients, direct temperature measurements in reference points were available. We correlated the tumor MR temperatures with direct measurements, clinical response, and tumor features (volume and location), and found reasonable trends and correlations. Therefore, the mean T(MR) of the tumor might be useful as a variable to evaluate the quality and effectivity of heat treatments, and consequently as optimization variable. Feasibility of noninvasive MR thermography for regional hyperthermia has been shown and should be further investigated.

A clinical water-coated antenna applicator for MR-controlled deep-body hyperthermia: a comparison of calculated and measured 3-D temperature data sets.

A magnetic resonance (MR)-compatible three-dimensional (3-D) hyperthermia applicator was developed and evaluated in the magnetic resonance (MR) tomograph Siemens MAGNETOM Symphony 1.5 T. Radiating elements of this applicator are 12 so-called water coated antenna (WACOA) modules, which are designed as specially shaped and adjustable dipole structures in hermetically closed cassettes that are filled by deionized water. The WACOA modules are arranged in the applicator frame in two transversal antenna subarrays, six antennas per subarray. As a standard load for the applicator an inhomogeneous phantom was fabricated. Details of applicator's realization are presented and a 3-D comparison of calculated and measured temperature data sets is made. A fair agreement is achieved that demonstrates the numerically supported applicator's ability of phase-defined 3-D pattern steering. Further refinement of numerical models and measuring methods is necessary. The applicator's design and the E-field calculations were performed using the finite-difference time-domain (FDTD) method. The calculation and optimization of temperature patterns was obtained using the finite element method (FEM). For MR temperature measurements the proton resonance frequency (PRF) method was used.

Regional hyperthermia in conjunction with definitive radiotherapy against recurrent or locally advanced prostate cancer T3 pN0 M0.

BACKGROUND AND PURPOSE: Since long-term results of the standard treatment of locally advanced or recurrent prostatic carcinoma are unsatisfactory, the role for additional regional hyperthermia was evaluated in a phase I/II study. PATIENTS AND METHODS: From 08/1996 to 03/2000, 22 patients were treated by a standard irradiation regimen (68.4 Gy) in combination with regional hyperthermia (weekly, five to six times), and five of 22 patients received short-term (neoadjuvant) hormonal treatment. Of these, 15 patients had primary prostatic carcinoma T3 pN0 M0 and seven a histologically confirmed local recurrence after radical prostatectomy. Feasibility of hyperthermia, and acute/late toxicity as well as long-term follow-up (prostate- specific antigen [PSA] control, overall survival) were analyzed. Clinical endpoints were correlated with thermal parameters. RESULTS: Mean maximum temperatures along the urethra of 41.4 degrees C (41.0 degrees C for the recurrences), and mean T(90) values of 40.7 degrees C could be achieved. Severe acute toxicity of grade 3 occurred at the rectum in three, at the urethra in four, at the intestine in one, and a burn induced by hyperthermia in one of 22 patients. Late toxicity was only observed rectally in one patient (grade 3) and at the urethra in two patients (grade 2). There was no correlation between thermal parameters and any toxicity. The survival curves showed a PSA control for primary prostatic carcinoma > 50% after 6 years, but no long-term PSA control for the recurrences. Overall survival after 6 years was 95% for primary carcinoma, and 60% for the recurrences. There was a clear correlation between higher temperatures or thermal doses with long-term PSA control. CONCLUSION: Regional hyperthermia might be a low-toxicity approach to increase PSA control of common treatment schedules. Further evaluation, in particular employing improved hyperthermia technology, is worthwhile.

Value of 123I-IMT SPECT for diagnosis of recurrent non-astrocytic intracranial tumours.

The value of single-photon emission tomography (SPECT) using iodine-123-alpha-methyl-tyrosine (IMT) for the diagnosis of recurrent or residual gliomas is well established. In the current study we investigated whether IMT-SPECT could also be useful in the follow-up of brain metastases and other intracranial tumours of non-astrocytic origin. The study included 22 patients with suspected recurrent intracranial tumours of non-astrocytic origin (12 brain metastases, one supratentorial primitive neuroendocrine tumour (PNET), one rhabdoid tumour, two clivus chordomas, three ependymomas, two pituitary tumours, one anaplastic meningioma) who had previously been treated by surgery and/or radio/chemotherapy. SPECT results were correlated with clinical and MRI follow-up data. The study was true positive in 13 patients, true negative in five, false positive in one and false negative in three patients. Notably, all false negative findings were <13 mm. The resulting sensitivity of the IMT-SPECT was 81%. We concluded that the IMT-SPECT is a promising complementary imaging tool for the detection of recurrences of non-astrocytic intracranial tumours and their distinguishing from treatment-induced changes. The limitation of the IMT-SPECT is its low sensitivity for the detection of small lesions.

A practical approach to thermography in a hyperthermia/magnetic resonance hybrid system: validation in a heterogeneous phantom.

PURPOSE: This study investigates the feasibility and accuracy of noninvasive magnetic resonance (MR) monitoring for a system that includes a multiantenna applicator for part-body hyperthermia (SIGMA-Eye applicator, BSD-2000/3D) and a 1.5 Tesla MR tomograph (Siemens Magnetom Symphony). METHODS: A careful electrical decoupling enabled simultaneous operation of both systems, the hyperthermia system (100 MHz, up to 1600 W) and the MR tomograph (63.9 MHz). We used the phase data sets of a gradient echo sequence (long echo time TE = 20 ms) according to the proton frequency shift (PFS) method to determine MR temperature changes. Data postprocessing and visualization was conducted in the software platform AMIRA-HyperPlan. Heating was evaluated in an elliptical Lucite cylinder of 50 cm length filled with tissue-equivalent agarose and a skeleton made from low-dielectric material to simulate the heterogeneity of a real patient. Multiple catheters were included longitudinally for direct thermometry (using Bowman high-impedance thermistors). The phantom was positioned in the 24-antenna applicator SIGMA-Eye employing the integrated water bolus (filled with deionized water) both for coupling the radiated power into the lossy medium and to enable a correction procedure based on direct temperature measurements. RESULTS: In eight phantom experiments we monitored the heating in the applicator not only by repetitive acquisition of three-dimensional MR datasets, but also by measuring temperature-time curves directly at selected spatial positions. For the correction, we specified regions in the bolus. Direct bolus temperatures at fixed positions were taken to aim at best possible agreement between MR temperatures and these direct temperature-time curves. Then we compared additional direct temperature-position scans (thermal maps) for each experiment with the MR temperatures along these probes, which agreed satisfactorily (averaged accuracy of +/- 0.4-0.5 degrees C). The deviations decreased with decreasing observation time, temperature increase, and thermal load to the surroundings (corresponding to bolus heating)-estimating a resolution of, at best, +/- 0.2-0.3 degrees C. The acquired MR temperature distributions give also insight into limitations and control possibilities of regional hyperthermia (annular phased array technology) for various tumor sites. CONCLUSIONS: On-line MR monitoring of regional hyperthermia by using the PFS method is feasible in a phantom setup and can be further developed for clinical applications.

Liver malignancies: CT-guided interstitial brachytherapy in patients with unfavorable lesions for thermal ablation.

PURPOSE: To evaluate computed tomography (CT)-guided brachytherapy in patients with very large liver malignancies or with liver tumors located adjacent to the liver hilum. MATERIALS AND METHODS: In this prospective nonrandomized phase II trial, we treated 20 patients (19 liver metastases and one cholangiocarcinoma) with CT-guided high-dose-rate (HDR) brachytherapy using a (192) Iridium source. All patients demonstrated no functional liver degradation prior to irradiation. Entry criteria were liver tumors > 5 cm (group A, n = 11, no upper limit) or liver tumors < or = 5 cm adjacent to the liver hilum (group B, n = 9). Dose planning for brachytherapy was performed with three dimensional (3D) CT data acquired after percutaneous applicator positioning. Magnetic resonance (MR) imaging follow-up was performed 6 weeks and every 3 months post intervention. Primary endpoints were complications, local tumor control (absence of tumor growth after treatment followed by shrinkage of the lesion starting at 6 months) and progression-free survival. RESULTS: The mean tumor diameter was 7.7 cm (range, 5.5-10.8 cm) in group A, 3.6 cm (range, 2.2-4.9 cm) in group B. On average, a minimal dose of 17 Gy in the target volume was applied (range, 12-25 Gy). Severe side effects were recorded in two patients (10%). One patient demonstrated an obstructive jaundice caused by tumor edema after irradiation of a metastasis adjacent to the bile duct bifurcation. One patient developed intra-abdominal hemorrhage that was treated by a single blood transfusion and has ceased. We frequently encountered moderate increases of liver enzymes (70% of patients) and bilirubin (50% of patients) without clinical symptoms and thus considered to be insignificant. The median follow-up was 13 months. In group A (tumors > 5 cm), primary local tumor control after 6 and 12 months was 74% and 40%, respectively; in group B, it was 100% and 71%, respectively. All but one local recurrence (in a patient with diffuse tumor progression) were successfully treated during another CT-guided brachytherapy leading to a primary assisted local control of 93% after 12 months. CONCLUSION: CT-guided brachytherapy based on individual dose plans and 3D CT data sets generated encouraging results in large liver malignancies as well as in tumors located adjacent to the liver hilum.

Clinical and physical determinants for toxicity of 125-I seed prostate brachytherapy.

BACKGROUND AND PURPOSE: To assess acute as well as long-term toxicity after permanent prostate seed implantation. To find predictive clinical or dosimetric factors for side effects in order to work out strategies for improvement. PATIENTS AND METHODS: A group of 174 patients with localised prostate cancer was treated with permanent seed implantation between 1999 and 2001, either alone (140 patients) or in combination with external radiotherapy (34 patients). For the majority (114/174, i.e. 66%) a CT was performed four weeks after implantation and analysed in the planning system VariSeed. In the postimplant analysis, dosimetric descriptors (doses, volumes) were determined for the prostate and rectum and compared with the intraoperative values. In addition, a questionnaire was sent to all patients to assess and quantify acute and chronic toxicity (urinary, rectal, sexual) and the impact on subjective acceptance and quality of life (return rate of questionnaires 83%). The derived score changes were correlated with clinical and dosimetric factors. RESULTS: In the mono-brachytherapy group 14% (16/140) required a bladder catheter, of them 8% (9/140) with a manifest urinary obstruction. Long-term rectal toxicity (<5%) and impairment of potency (<30%) are moderate and obviously below other treatment options. Urinary toxicity is dominant with an overall long-term dysuria up to 30% (at a mean observation interval of ten months), and a significant trend to decline with follow-up time. Conversely, the erectile function tends to deteriorate with follow-up time. Nevertheless, quality of life is not significantly reduced and acceptance is high. Our analysis suggests that the main factor for urinary toxicity and impaired erectile function is the dose load to larger portions of the prostate (D(50)>240 Gy), which appears to be attributed to unnecessarily high numbers of seeds (for a fixed activity per seed) and needles. The rectal toxicity is correlated with the high dose regions in the rectum (>/=145 Gy). Urinary toxicity is lower for combined-brachytherapy, while rectal toxicity and impairment of potency are slightly higher. CONCLUSIONS: Toxicity spectrum and quality of life after permanent seed implantation for early prostate cancer are acceptable for nearly all patients (98%). To further improve tolerance we should attempt to achieve a better dose homogeneity, i.e. by reducing D(50). Therefore, special attention should be given to D(50) during the real-time planning process. The necessity of more homogeneous dose distributions might imply a reduction of the activity per seed, e.g. from 0.7 mCi down to 0.6 mCi.

Hepatic arterial port systems for treatment of liver metastases: factors affecting patency and adverse events.

PURPOSE: To assess the outcome of interventional hepatic arterial port placement in a prospective phase II trial. MATERIALS AND METHODS: One-hundred five consecutive patients were included in this study. Primary endpoint was port patency; secondary endpoints were complications, toxicity, response, and progression free and overall survival. Seventy-eight patients presented with liver metastasis only, 6 patients had additional minor extrahepatic disease, and 21 patients had no evidence of disease after liver resection, laser-induced thermotherapy, or computed tomography (CT)-guided interstitial brachytherapy of liver metastasis. Exclusive access route was the femoral artery. Subgroup analysis compared either 4-F catheters (n = 58) to 2.2-F (n = 33) and 2.7-F (n = 20) microcatheters or different strategies in anatomic variants of the celiac branch: neglect (n = 10) or embolization of minor hepatic feeders (n = 11), splenic arterial port (n = 8), double port (n = 7). RESULTS: Technical success was 99%. Assisted port patency after 6 months was 93%. Complications demanding port revisions were significantly lower in patients receiving 4-F versus 2.2-F and 2.7-F systems (P <.001), with disconnection as the major problem with use of microcatheters. Hepatic artery thrombosis occurred in 10 patients (9%), with successful lysis in two patients. With use of 4-F and 2.2-F catheters, there was no difference with respect to catheter occlusion or hepatic thrombosis. No differences were noted in complications or outcome applying four different strategies in celiac branch variants. In a subgroup of patients receiving folinic acid/5-fluorouracil (170 mg/600 mg; 10% dose escalation per cycle) for 5 days every 4 weeks only 15% experienced Grade 3 toxicity. Patients with liver metastasis and salvage therapy demonstrated progression-free survival of 63% after 6 months and a median survival of 16 months. CONCLUSION: Interventional placement of hepatic arterial port systems may overcome frequent hepatic arterial chemotherapy failures as encountered in all published major trials on hepatic arterial infusion.

Repetitive transarterial chemoembolization (rTACE) of hepatocellular carcinoma: comparisons between an arterial port system and conventional angiographic technique.

PURPOSE: To compare the cost and radiation exposure of repetitive transarterial chemoembolization (rTACE) using percutaneously implantable port system with rTACE using conventional catheterization technique. MATERIALS AND METHODS: In five patients with unresectable hepatocellular carcinoma, three cycles of TACE were performed using conventional technique and six cycles using port. The cumulative cost of material and contrast agent and dose area product (DAP) were compared with the cost and DAP that would be expected if the rTACE was performed conventionally. RESULTS: The cost of material and contrast agent was 1002.6 Euro after three cycles of TACE using conventional technique and six cycles using port, but would be 1111.8 Euro if the nine cycles were performed using conventional technique alone. The rTACE with three cycles using conventional technique and six cycles using port led to approximately 63% of the cumulative DAP that would be expected in rTACE using conventional technique alone. CONCLUSION: In rTACE, the use of percutaneously implantable port system might enable a reduction of cost and radiation exposure.

[CT-Guided brachytherapy. A novel percutaneous technique for interstitial ablation of liver metastases]. / CT-gesteuerte Brachytherapie. Eine neue perkutane Technik zur interstitiellen Ablation von Lebermetastasen.

PURPOSE: To assess safety and efficacy of CT-guided brachytherapy of liver malignancies. PATIENTS AND METHODS: 21 patients with 21 liver malignancies (19 metastases, two primary liver tumors) were treated with interstitial CT-guided brachytherapy applying a (192)Ir source. In all patients, the use of image-guided thermal tumor ablation such as by radiofrequency or laser-induced thermotherapy (LITT) was impeded either by tumor size > or = 5 cm in seven, adjacent portal or hepatic vein in ten, or adjacent bile duct bifurcation in four patients. Dosimetry was performed using three-dimensional CT data sets acquired after CT-guided positioning of the brachytherapy catheters. RESULTS: The mean tumor diameter was 4.6 cm (2.5-11 cm). The mean minimal tumor dose inside the tumor margin amounted to 17 Gy (12-20 Gy). The proportion of the liver parenchyma exposed to > 5 Gy was 18% (5-39%) of total liver parenchyma minus tumor volume. Nausea and vomiting were observed in six patients after brachytherapy (28%). One patient demonstrated obstructive jaundice due to tumor edema after irradiation of a metastasis adjacent to the bile duct bifurcation. We commonly encountered asymptomatic increases of liver enzymes. Local control rates after 6 and 12 months were 87% and 70%, respectively. CONCLUSION: CT-guided brachytherapy is safe and effective. This technique displays broader indications compared to image-guided thermal ablation by radiofrequency or LITT with respect to tumor size or localization.

CT-guided interstitial brachytherapy of liver malignancies alone or in combination with thermal ablation: phase I-II results of a novel technique.

PURPOSE: To assess the safety and efficacy of CT-guided brachytherapy alone or in combination with laser-induced thermotherapy (LITT) in patients with liver malignancies. METHODS AND MATERIALS: Thirty-seven patients presented with 36 liver metastases and two primary liver carcinomas. Twenty-one patients were treated with CT-guided high-dose-rate brachytherapy alone using a 192Ir source. Sixteen patients received brachytherapy directly after MRI-guided LITT. The indications for brachytherapy alone were a tumor size >5 cm, adjacent central bile duct or adjacent major vessels causing unfavorable cooling effects for thermal ablation, and technical failures of LITT. The dosimetry for brachytherapy was performed using three-dimensional CT data acquired after percutaneous applicator positioning. On average, a minimal dose of 17 Gy inside the tumor margin was applied (range, 10-20 Gy). RESULTS: The mean tumor size was 4.6 cm (range, 2.5-11 cm). The mean liver volume receiving > or =5 Gy was 16% (range, 2-40%) of the total liver. Severe complications were recorded in 2 patients (5%). One patient developed acute liver failure possibly related to accidental continuation of oral capecitabine treatment. Another patient demonstrated obstructive jaundice owing to tumor edema after irradiation of a metastasis adjacent to the bile duct bifurcation. A commonly encountered moderate increase of liver enzymes was greatest in patients with combined treatment. The local control rate after 6 months was 73% and 87% for combined treatment and brachytherapy alone, respectively. CONCLUSION: CT-guided brachytherapy using three-dimensional CT data for dosimetry is safe and effective alone or in combination with LITT. Brachytherapy as a stand-alone treatment displayed genuine advantages over thermal tumor ablation.