Initially localized synovial sarcoma in adults: a retrospective single-center analysis of 26 patients registered at the Department of Oncology, University of Vienna between 2004 and 2013.

BACKGROUND: Synovial sarcoma is a rare subgroup of all soft-tissue sarcomas. The aim of this retrospective single-center analysis was to investigate the outcome of patients with initially localized disease. PATIENTS AND METHODS: Twenty-six patients were enrolled in this retrospective single-center analysis. Baseline characteristics, treatment and outcome were evaluated. RESULTS: In 13 patients (50%), the tumor was located in the lower extremity and in 4 patients (15%) in the upper extremity. Surgical resection was done in all but 2 patients (92%). Re-resection was done in 7 patients (27%). Fourteen patients (54%) received adjuvant chemotherapy. After a median follow-up of 23.3 months (range: 2.6-150.3), median disease-free survival was not reached at the time of analysis. Eight patients (31%) relapsed after initial therapy. Surgery was done in 2 patients, amputation in 1 patient, palliative chemotherapy was administered in 3 and radiation therapy in 2 patients. Median overall survival (OS) for all patients was not reached at the time of analysis. The estimated 5-year OS rate was 62%. CONCLUSION: Patients with initially localized synovial sarcoma who were included in this retrospective single-center analysis have an estimated 5-year OS rate of 62%.

Randomized comparison between intracoronary beta-radiation brachytherapy and implantation of paclitaxel-eluting stents for the treatment of diffuse in-stent restenosis.

BACKGROUND AND PURPOSE: Intracoronary brachytherapy was the primary therapeutic option for the treatment of in-stent restenosis (ISR) during the last years. Especially for the treatment of diffuse ISR (lesions >10mm), beta-source brachytherapy was significantly superior to singular balloon angioplasty. Despite lacking clinical database, the implantation of drug eluting stents recently became a common procedure for the treatment of ISR. This randomized trial aimed to compare the efficacy of beta-brachytherapy with beta-radioisotopes (90)Sr/(90)Y and paclitaxel-eluting stent implantation for the treatment of diffuse ISR. MATERIAL AND METHODS: Thirty-seven patients with diffuse ISR were randomly assigned to beta-brachytherapy after balloon angioplasty (Beta-Cath in 17 patients) or paclitaxel-eluting stent implantation (Taxus-Express2 in 20 patients). Six-month clinical follow-up was obtained for all patients, while angiographic follow-up was available for 30 patients. RESULTS: Binary ISR (restenosis >50%) within target segment was observed in three patients treated with Beta-Cath, of which one needed target segment revascularisation for recurrent ISR, whereas no significant restenosis occurred in the patients treated with Taxus-Express2 (P=0.037). No further major adverse cardiac (target segment revascularisation, myocardial infarction, death) was found in either group (P=NS). Stent implantation was the more time-saving (31+/-11 min versus 60+/-23 min, P<0.001) procedure. CONCLUSIONS: Although this trial revealed a significant reduction of binary restenosis in the Taxus-Express2 arm, we found no difference in clinical outcome after implantation of paclitaxel-eluting stents for the treatment of diffuse ISR when compared to beta-brachytherapy.

Randomized blinded clinical trial of intracoronary brachytherapy with 90Sr/Y beta-radiation for the prevention of restenosis after stent implantation in native coronary arteries in diabetic patients.

BACKGROUND: We report a double-blind, randomized clinical trial of intracoronary beta-radiation for prevention of restenosis after stent implantation in native coronary de novo lesions in diabetic patients. METHODS: After successful stent implantation in native coronary de novo lesions, 106 lesions in 89 diabetic patients were randomly allocated to treatment with beta-radiation with 18 Gy at 1 mm vessel depth (n = 53) or placebo treatment (n = 53). RESULTS: Angiographic analysis at 9 month follow-up revealed a late lumen loss of 0.7+/-0.9 mm in the radiotherapy group versus 1.2+/-0.8 mm in the control group at the injured segment (P = 0.006), 0.9+/-1.0 versus 1.3+/-0.7 mm at the radiated segment (P = 0.02), and 0.9+/-1.0 versus 1.3+/-0.7 mm at the target segment (P = 0.04) (defined as active source length plus 5mm on proximal and distal sites). Binary restenosis rates were significantly lower in the radiation group in all subsegments (injured segment: 10.9 versus 37.3%, P = 0.003; radiated segment: 21.7 versus 49.0%, P = 0.005; target segment: 23.9 versus 49.0%, P = 0.01). Target lesion revascularization for restenosis was required in nine lesions (17.6%) in the radiotherapy group versus 18 (34.0%) in the placebo group (P = 0.05). Late thrombosis occurred in four radiated patients (after premature discontinuation of antiplatelet therapy in all), resulting in a major adverse clinical event rate of 37.2% in the brachytherapy group versus 38.6% in the placebo group (P = ns). CONCLUSIONS: In diabetic patients with de novo coronary lesions, intracoronary radiation after stent implantation significantly reduced restenosis. However, this clinical benefit was reduced by the frequent occurrence of late thrombosis.

Induction chemotherapy with the TIP regimen (paclitaxel/ifosfamide/cisplatin) in stage III non-small cell lung cancer.

Induction chemotherapy may improve clinical outcome of locally advanced non-small cell lung cancer (NSCLC). To further pursue this, the Austrian Association for the Study of Lung Cancer (AASLC) performed a multi-center phase II trial with TIP induction chemotherapy (Taxol 175 mg/m2 over 3h on day 1, ifosfamide 1000 mg/m2 daily on days 1-3, cisplatin 60 mg/m2 on day 1, and prophylactic filgrastim 5 microg/kg daily on days 4-13). Treatment cycles were repeated every 3 weeks for 3 cycles. Then patients were re-staged and selected for local treatment. Forty-seven patients (33 male, 14 female; median age 58 years, range 36-78; 22 cIIIA, 25 cIIIB; 26 adenocarcinomas, 14 squamous cell carcinomas, 4 large cell carcinomas, 3 undifferentiated carcinomas) were included in this trial. Forty-five patients were evaluable for response and toxicity. An overall response rate of 43% (complete remission 4.5% and partial remission 38%) was achieved. Stable disease and progressive disease were seen in 38 and 15% of the patients, respectively. Down-staging occurred in 36% of the patients. The toxicities of the chemotherapy were mild and, in particular, no severe hematotoxicity was observed. Surgery was performed in 24 (51%) patients and resulted in complete tumor resection in 19 patients. Twenty-four patients received thoracic radiotherapy, 10 patients after surgery. Median survival was 10.3 months for the total population, 13.5 months for patients with cIIIA and 10 months for patients with clinical cIIIB. Survival was longer for patients with down-staging as compared to those without (median not reached versus 10 months, p=0.005) and for patients with complete tumor resection as compared to the remaining patients (27 months versus 10 months, p=0.05). In conclusion, the TIP regimen shows activity and good tolerance as induction chemotherapy in patients with locally advanced NSCLC.

Vascular morphometric changes after radioactive stent implantation: a dose-response analysis.

OBJECTIVES: The goal of this study was to evaluate the dose-dependency of morphometric changes in the coronary arterial wall after radioactive stenting. BACKGROUND: Radioactive stents have been found to reduce intrastent intimal hyperplasia (IIH) but lead to a characteristic type of restenosis occurring predominantly at the stent edges. METHODS: Fifteen patients underwent intravascular ultrasound (IVUS) examination after implantation of a P-32 radioactive stent and at the six-month follow-up. The post-stent IVUS measurements on seven predefined locations of each lesion were subjected to a computer algorithm for the development of dose-volume histograms (DVH). Thus, we derived the radiation doses delivered to at least 10% and 90% of the adventitia (DV10, DV90). The IIH and vascular remodeling at follow-up were correlated with the doses in each segment. RESULTS: The IIH was most pronounced at the stent edges and lowest in the stent-body, whereas we detected a significant expansive remodeling within the stent body. The delivered doses correlated with a decreased IIH (r = 0.52, p < 0.001 for DV10 and r = 0.62, p < 0.001 for DV90) and with expansive remodeling (r = 0.48, p = 0.009 for DV10 and r = 0.50, p = 0.006 for DV90). A DV10 >90 Gy or a DV90 >15 Gy reduced IIH and induced expansive remodeling. Plaque growth was not reduced by radioactive stents. CONCLUSIONS: The DVH analysis reveals a dose-dependent increase of external elastic lamina area behind radioactive stents, whereas plaque growth is not reduced but inverted into an outward direction from the stent. A DV10 >90 Gy or a DV90 >15 Gy results in a beneficial long-term outcome after radioactive stenting.

Geographical miss during intracoronary irradiation: impact on restenosis and determination of required safety margin length.

OBJECTIVE: The goal of this study was to evaluate the incidence and effects of underdosage of injured segments during intracoronary irradiation and to define the minimal length of safety margin required to avoid mismatched source placement. BACKGROUND: Underdosage of injured segments due to misplacement of active source has been suggested as the underlying mechanism for the occurrence of edge restenosis. METHODS: Baseline angiograms of 112 vessels in 109 patients with in-stent restenosis undergoing coronary reintervention followed by intracoronary irradiation ((192)Ir: Checkmate, Cordis, Miami, Florida; (32)P: Gallileo, Guidant, Houston, Texas; (90)Sr/Y: Beta-Cath, Novoste, Norcross, Georgia) were analyzed. The distances between the outermost injury and outermost end of "reference isodose length" (RIL), defined as a segment with >/=90% of reference dose at 1 mm vessel wall depth, were measured. "Safety margin" was defined as the distance between the outermost injury and outermost end of the RIL, "geographical miss" (GM) as a complete injured segment not being covered by the RIL, and "restenosis" as the percent diameter stenosis >50%. RESULTS: Baseline angiographic analysis was performed for 224 edges in 112 vessels. Geographical miss was found in 46 (20.6%) edges. The incidence of target lesion restenosis within the 78 vessels with available follow-up was 43.3% for patients with GM versus 14.9% for patients with no GM (p = 0.005). Analysis of various injured segments exposed highest restenosis rates in injured segments with negligible irradiation (27.8%) in comparison with injured segments with dose fall-off (16.7%) or injured segments with full-dose irradiation (7.7%) (p = 0.006). Receiver operating curve analysis revealed a safety margin of 10 mm required per vessel (i.e., 5-mm safety margin/edge) to achieve 95% specificity of GM. CONCLUSIONS: Geographical miss is associated with a higher incidence of restenosis at the corresponding edges. Restenosis was more pronounced in injured segments with negligible irradiation than in injured segments at the dose fall-off zones. We recommend a safety margin of 10 mm per vessel to minimize GM.

Endovascular brachytherapy prevents restenosis after femoropopliteal angioplasty: results of the Vienna-3 randomised multicenter study.

BACKGROUND AND PURPOSE: The aim of the trial was to investigate the effect of Iridium-192 gamma endovascular brachytherapy on reduction of restenosis after femoropopliteal angioplasty. PATIENTS AND METHODS: Between Oct, 1998 and Jul, 2001 a total of 134 patients have been randomized after successful angioplasty to brachytherapy or sham irradiation in a prospective, randomized, multicenter, double blind controlled trial. Patients with de novo lesion of at least 5 cm or recurrent lesion of any length after prior angioplasty have been enrolled. Brachytherapy was performed with 7F centering catheter. Mean lesion length was 9.1cm (1.5-25 cm) and mean intervention length 13.6 cm (4-27.5 cm) in brachytherapy cohort. RESULTS: In placebo cohort mean lesion length was 10.3 cm (2-25 cm) and mean intervention length 14.1 cm (2-29 cm). A dose of 18 Gy was prescribed 2 mm from the surface of centering balloons. Analyzed (based on angiography) on intention to treat basis the binary restenosis rate at 12 months was 41.7% (28/67) in brachytherapy cohort and 67.1% (45/67) in placebo cohort (chi2 test, P<0.05). Corresponding data for as treated analysis (A total of 38 patients was excluded from analysis due to lack of follow-up, early recurrence within 30 days and >30% residual stenosis after angioplasty) have been 23.4% in the brachytherapy and 53.3% in the placebo group (P<0.05), respectively. The cumulative patency rates after 24 months on intention to treat analysis were 54% in the brachytherapy and 27% in the placebo group (P<0.005). Corresponding data for as treated analysis were 77% in the brachytherapy and 39% in the placebo group (P<0.001). Late thrombosis was not seen. CONCLUSIONS: Significant reduction of restenosis rate was obtained with endovascular gamma brachytherapy after femoropopliteal angioplasty.

3D-conformal radiotherapy for prevention of carotid recurrent in-stent restenosis. Initial experience.

OBJECTIVE: To investigate 3D-conformal external beam radiotherapy for prevention of recurrent instent restenosis after carotid artery angioplasty. PATIENTS AND METHODS: Between Oct 2000 and Sep 2001 five patients with recurrent carotid artery in-stent restenosis of more than 50% lumen loss diagnosed with duplex sonography were enrolled. After successful revascularization, radiotherapy treatment planning was performed, which was based on the angioplasty protocol and all images documenting the intervention. A single dose of 5 Gy was prescribed to the 100% isodose. The treatment started on day one after angioplasty. In total, 4 fractions were given within 3 days. RESULTS: All patients tolerated the treatment well. No acute radiotherapy associated side effects were observed. Two patients developed recurrence within four months after therapy. In both cases, late total occlusion of the stent was noticed. One patient died and one developed a severe stroke. The other three patients remained asymptomatic with evidence of less than 50% restenosis. CONCLUSION: 3D-conformal radiotherapy is a feasible treatment option for highly selected patients with carotid artery in-stent restenosis. These preliminary results from a very small group of patients do show some potential for radiotherapy to prevent restenosis. However, due to the risk of late stent thrombosis, radiotherapy for the prevention of recurrent carotid artery in-stent restenosis is not recommended.

Treatment parameters for beta and gamma devices in peripheral endovascular brachytherapy.

PURPOSE: To determine dosimetric parameters, such as radial and longitudinal dose profiles, for beta and gamma devices in peripheral endovascular brachytherapy. METHODS AND MATERIALS: An (192)Ir high-dose rate stepping source, a (90)Sr source train, and a (32)P-coated radiation balloon were investigated. The treatment-planning software PLATO, Monte Carlo code EGSnrc, and GafChromic film dosimetry were used to analyze the dose distribution of these devices. RESULTS: For a 5-mm-diameter vessel, the ratio between the dose at 2 mm depth and the dose at the lumen surface was 1.8, 3.4, and 16.2 for the (192)Ir, (90)Sr, and (32)P devices, respectively. The dose variation at the reference depth of 2 mm into the vessel wall was 7-18 Gy, for different analyzed dose prescriptions. The reference lumen dose was different by a factor >8. For all three devices, the reference isodose length was not <5 mm on the proximal and distal edge of the active source length. CONCLUSIONS: A complete set of dose parameters for beta and gamma sources has to be considered for appropriate treatment planning and performance, including reporting of reference depth dose, reference lumen dose, and reference isodose length.

Clinical quality assurance for endovascular brachytherapy devices.

BACKGROUND AND PURPOSE: Endovascular brachytherapy is still an important therapy modality with a high number of treated patients per year. Quality assurance of devices used has been addressed already in several publications (AAPM, DGMP, ESTRO, NCS). However, there are no clear recommendations given on test procedures and related equipment. Our experience with four different devices containing beta- ((32)P, (90)Sr/Y) and gamma-sources ((192)Ir), which were used in clinical routine during the last 3 years is described. PATIENTS AND METHODS: The incoming check includes leakage radiation, missing catheter interlock, positioning test, timer check, interrupt button check, power-off test and verification of the manual retraction facility. Dose profiles are measured using GafChromic film. Source strength verification is performed using well type chambers or air-kerma measurements. In addition, the proposed reference absorbed dose rate at 2 mm distance from the source centre is measured with a dedicated film dosimetry technique where two additional films are exposed to two known doses in a (60)Co field for calibration. RESULTS: Dosimetrical parameters (dose profiles, source strength) are found to be within +/-10% of the manufacturers specifications. The reference dose rate measured with film is on average +3.1% for 13 (90)Sr seed trains, +8.1% for three (32)P wire sources and -3.7% for one (192)Ir seed ribbon compared to the source certificate. The activity of 30 individual (32)P wire sources measured by using a calibrated well type chamber showed a deviation of mean -0.3%, the activity of 16 (192)Ir seed ribbons determined with air kerma measurements a deviation of mean 2.8%. CONCLUSIONS: The QA programme introduced in our department provides methods to verify all relevant parameters proposed by international recommendations. Film dosimetry can be used as independent verification of the reference dose rate within a 10% limit.

Possible impact of iridium-192 source centering on restenosis rate after femoro-popliteal angioplasty and endovascular brachytherapy in Vienna-2 study.

PURPOSE: Endovascular brachytherapy (EVBT) has been proven to significantly reduce restenosis after percutaneous transluminal angioplasty (PTA). The object of this analysis was to assess the possible correlation between iridium-192 source non-centering and angiographic-determined restenosis. MATERIALS AND METHODS: A total of 113 patients with long-segment lesions of the superficial femoro-popliteal artery (SFA) were randomized to receive either PTA alone or PTA followed by EVBT in the Vienna-2 study. This analysis was performed on a subgroup of 34 out of 57 patients, who received PTA+EVBT. Angiographic restenosis was defined as lumen reduction of more than 50%. Angiograms taken immediately after PTA (34 patients) and at follow-up (25 patients) were analyzed. The distance between the vessel wall and the actual position of the source at the time of EVBT was measured (in mm) and correlated with the follow-up vessel lumen diameter. Measurements were performed at points at a distance of 10 mm from each other. The dose was determined at the luminal surface and at the reference depth of 2 mm into the vessel wall for different distances from the source. RESULTS: Among the 622 measured points, 62 (10.0%) were within restenotic areas; 560 (90.0%) were in arterial segments without proven angiographic restenosis. As far as source centering is concerned, 7.9% of restenotic points were observed when the maximum distance to the arterial wall was <3 mm and 9.6% for 4 mm, respectively. The percentage of restenotic points increased up to 15.9% when the maximum distance to the arterial wall was 5 mm and reached 22.2% when it was >5 mm. CONCLUSIONS: The proportion of restenotic points significantly increased with source non-centering. This observation was interpreted as being related to a decrease in dose at the target. When the maximum distance between the source and the vessel surface was >5 mm, the dose at the reference depth (2 mm into the vessel wall) decreased to values lower than 5 Gy.

Determination and application of the reference isodose length (RIL) for commercial endovascular brachytherapy devices.

BACKGROUND AND PURPOSE: During the last years endovascular brachytherapy has been established as a new field in radiotherapy. In a recent recommendation of the EndoVAscular, Groupe Européen de Curiethérapie, European Society for Therapeutic Radiation Oncology, Working Group the reference isodose length (RIL) has been introduced as a central parameter for treatment planning. It is defined as the vessel length at the reference depth enclosed by the 90% isodose. The dose is normalized to 100% at the reference depth (i.e. lumen radius plus 1 mm into the vessel wall) at the central plane. In order to avoid a geographic miss the clinical target length has to be encompassed by the RIL. MATERIAL AND METHODS: RILs are determined by Monte Carlo calculations and GafChromic film dosimetry for three endovascular brachytherapy devices currently in clinical use (192Ir seed ribbon, 32P wire source, 90Sr seed train). For all measurements, phantoms and devices the sensitive layer of GafChromic film is located in a plane at 2+/-0.1 mm parallel to the axis of the source delivery catheter. The EGSnrc code system is applied to calculate the dose profile at 2 and 3 mm distance from the source axis. RESULTS: For the ten seed 192Ir source calculated RIL at 2 mm radial distance is 30.2 mm whereas the measured RIL is 33.5 mm. In case of a 20 mm 32P wire source with two steps the calculated RIL of 36.6 mm shows excellent agreement compared with the measured value of 36.2 mm. The calculated RIL of a 40 mm 90Sr seed train was 35.8 mm compared to a measured value of 34.8 mm. CONCLUSION: As a compromise between calculated and measured RIL values at 2 and 3 mm radial distances we propose to use a RIL of 30 mm for the 192Ir ten seed ribbon, 36 mm for the32P wire source with two steps and 35 mm for the 40 mm 90Sr seed train. These parameter values can be used to define the maximum intervention length for endovascular sources.

Quality assurance in intracoronary brachytherapy. Recommendations for determining the planning target length to avoid geographic miss.

BACKGROUND AND PURPOSE: A new method of assessing geographic miss (GM) in endovascular brachytherapy (EVBT) is applied to evaluate the quality of intracoronary brachytherapy treatments, retrospectively. Based on the Vienna experience, recommendations for adequate safety margins are derived to avoid GM. PATIENTS AND METHODS: Evaluation is done on 136 vessels of 128 consecutive patients treated between October 1999 and July 2001. The quality of EVBT is assessed using the concept and terminology of the EVA GEC ESTRO task group. Evaluation of GM and/or safety margin is performed by comparing the outermost interventions with the reference isodose length (RIL) of the applied delivering devices on recorded compact disk (CD) angiograms. The RIL is defined as the length of the vessel segment, which receives at least 90% of the reference dose at the reference depth (=1 mm within the vessel). GM is defined as injured vessel segments, which receive a dose lower than 90% of reference dose. Measurements of intervention length (IL) and active source length (ASL) are performed with respect to anatomical landmarks within the vessel in the region of interest (e.g. stent edges), and by using the nominal length of the devices (balloons, sources) as a reference scale. The edges of RIL are determined by subtracting the length of the dose-fall-off zone (specific to the applied delivery devices: (192)Ir 4.5 mm, (90)Sr 2.5 mm, (32)P 2.0 mm) from the edges of ASL. RESULTS: The described method to assess GM is applicable to 128 vessels (94%). GM is found in 23% of proximal edges and 20% of distal edges. 95% of all GM are observed if the total margin (proximal+distal margin) between RIL and IL is shorter than 10.5 mm. CONCLUSIONS: GM in intracoronary brachytherapy can be widely avoided by adding an appropriate safety margin to the IL (5-6 mm each edge in this study) in order to determine the necessary RIL for a treatment.

Recommendations for implementation of high dose rate 192Ir brachytherapy in developing countries by the Advisory Group of International Atomic Energy Agency.

PURPOSE: To provide recommendations for the implementation of high dose rate (HDR) 192Ir brachytherapy technology in developing countries. METHODS: An Advisory Group Meeting of the International Atomic Energy Agency (IAEA) met to address the implementation of HDR 192Ir brachytherapy technology in developing countries. These recommendations reflect only the personal opinions of the authors and do not necessarily represent the opinion of the IAEA. RESULTS: An HDR treatment system should be purchased as a complete unit that includes the 192Ir radioactive source, source loading unit, applicators, treatment planning system, and control console. Infrastructure support may require additional or improved buildings and procurement of or access to new imaging facilities. A supportive budget is needed for quarterly source replacement and the annual maintenance necessary to keep the system operational. The radiation oncologist, medical physicist, and technologist should be specially trained before HDR can be introduced. Training for the oncologist and medical physicist is an ongoing process as new techniques or sites of treatment are introduced. Procedures for quality assurance (QA) of patient treatment, and the planning system must be introduced. Emergency procedures with adequate training of all associated personnel must be in place. CONCLUSIONS: The decision to select HDR in preference to alternate methods of brachytherapy is influenced by the ability of the machine to treat a wide variety of clinical sites. In departments with personnel and budgetary resources to support this equipment appropriately, economic advantage becomes evident only if large numbers of patients are treated. Intangible benefits of source safety, personnel safety, and easy adaptation to fluctuating demand for treatments also require consideration when evaluating the need to introduce this treatment system.

Intracoronary brachytherapy with beta-radiation for the treatment of long diffuse in-stent restenosis.

OBJECTIVE: To assess the efficacy of intracoronary brachytherapy with beta-radiation (Sr/Y) for the treatment of long diffuse in-stent restenosis (ISR). METHODS: As recurrent ISR depends on intimal injury after coronary angioplasty, long in-stent restenotic lesions were defined as lesions with a treatment length >26 mm (lesion length >20 mm plus a treatment margin of 3 mm at each end). Seventy-eight patients with long ISR were treated at our institution with beta-brachytherapy after coronary angioplasty. Patients were irradiated with either an approximate dose of 12 Gy at 1 mm vessel wall depth or with 18 Gy at 1 mm vessel wall depth. Clinical follow-up was available for 69 patients and angiographic follow-up for 65 patients. Late lumen loss (LLL), binary restenosis (stenosis >50%), target lesion revascularization (TLR) and major adverse cardiac events (MACE) were assessed for a follow-up time of 6.6+/-2.2 months. RESULTS: Mean interventional treatment length was 46+/-18 mm. TLR was performed in all 23 patients with binary restenosis (33%). Death of cardiac cause was reported for two patients, one of whom did not undergo TLR. Thus, overall MACE rate was 35%. Recurrent ISR was significantly more frequent in patients with geographic miss. Comparison of the different radiation dose regimens revealed significantly lower LLL in patients irradiated with the higher dose (0.20+/-0.68 mm compared with 0.65+/-0.96 mm, P=0.03). CONCLUSION: Intracoronary brachytherapy with beta-radiation (Sr/Y) is a safe and effective therapeutic option for the reduction of recurrent ISR in long diffuse lesions. We recommend a high-dose irradiation with 18 Gy at 1 mm vessel wall depth.

Basic treatment planning parameters for a 90Sr / 90Y source train used in endovascular brachytherapy.

Working groups of the AAPM, DGMP, and ESTRO have published recommendations for endovascular brachytherapy, introducing concepts of relevant parameters for dose specification and treatment planning. However, the procedures for this treatment remain often mainly based on trial protocols and manufacturer instructions. Treatment planning requires the essential knowledge of the radial and longitudinal dose distribution, as well as information about geometrical uncertainties. The present study includes a whole data set for daily clinical practice using a commercially available device for endovascular brachytherapy (Novoste Betacath). The dose distribution around the 90Sr seed train was calculated with Monte-Carlo algorithms and verified by film dosimetry. The radial dose profile was determined starting from the surface of the delivery catheter Calculated dose profiles were in good agreement to measured values. The geometrical uncertainties were estimated with a retrospective analysis of 51 patient treatments. This shows the importance of using a safety margin of at least 10 mm between Intervention Length and Reference Isodose Length. Based on the longitudinal dose profile and the necessary safety margins, the maximum treatable intervention length is 25 mm and 45 mm for a 40 mm and 60 mm source train, respectively.

Estimation of doses to personnel and patients during endovascular brachytherapy applications.

In the last few years coronary endovascular brachytherapy using gamma- and beta-emitting radionuclides has been established as a standard treatment procedure to prevent restenosis after percutaneous coronary interventions. Direct measurements and calculations were made to determine personnel doses and organ doses of patients due to gamma rays of 192Ir and beta rays of 90Sr/90Y and 32P sources. In general, our results show that the dose levels are low compared with the X-ray exposure from angiography. The dose rate from bremsstrahlung at 1 m distance from a device containing a 90Sr/90Y source of 2.3 GBq is 4 micro Sv h(-1). The skin dose from beta rays during source transfer into and from the patient was estimated with the directional dose equivalent H'(0.07) of 10 micro Sv at 1 m distance from the catheter. By maintaining safe distances, the dose levels can be kept well within annual dose limits.

Intensified adjuvant IFADIC chemotherapy in combination with radiotherapy versus radiotherapy alone for soft tissue sarcoma: long-term follow-up of a prospective randomized feasibility trial.

Adjuvant chemotherapy for grade 2 and 3 soft tissue sarcoma (STS) patients still has to be considered experimental. Fifty-nine patients underwent primary surgery by wide or marginal excision and were subsequently randomized to receive radiotherapy alone or in combination with six courses of chemotherapy consisting of ifosfamide, DTIC, and doxorubicin administered in 14-day intervals supported by G-CSF on days 5-13. Twenty-eight patients received radiotherapy (control group) and 31 patients were treated with additional chemotherapy. After a median observation period of 97 months (range: 13-158 months), 58 patients were followed up to assess long-term relapse-free survival (RFS), time to local failure (TLF), time to distant failure (TDF), and overall survival (OS). Fifteen patients (56%) in the control group vs. 19 patients (61%) in the chemotherapy group were free of disease. Within the control group, tumor relapses occurred in 12 patients (44%) vs. 12 patients (39%) in the chemotherapy group. RFS (P = 0.87), TLF (P = 0.58), TDF (P = 0.60) as well as OS (P = 0.99) did not differ significantly between the two groups. Adjuvant chemotherapy was not translated into a significant benefit concerning RFS, TLF, TDF, and OS for STS patients.

Treatment of vascular soft tissue sarcomas with razoxane, vindesine, and radiation.

PURPOSE: In previous studies, razoxane and vindesine together with radiotherapy was proved to be effective in soft tissue sarcomas (STS). Because razoxane leads to a redifferentiation of pathological tumor blood vessels, it was of particular interest to study the influence of this drug combination in vascular soft tissue sarcomas. METHODS AND MATERIALS: This open multicenter Phase II study was performed by the Austrian Society of Radiooncology. Among 13 evaluable patients (10 angiosarcomas and 3 hemangio-pericytomas), 9 had unresectable measurable disease, 3 showed microscopic residuals, and 1 had a resection with clear margins. They received a basic treatment with razoxane and vindesine supported by radiation therapy. Outcome measures were objective response rates, survival time, and the incidence of distant metastases. RESULTS: In nine patients with measurable vascular soft tissue sarcomas (eight angiosarcomas and one hemangiopericytoma), 6 complete remissions, 2 partial remissions, and 1 minor remission were achieved, corresponding to a major response rate of 89%. A maintenance therapy with razoxane and vindesine of 1 year or longer led to a suppression of distant metastases. The median survival time from the start of the treatment is 23+ months (range, 3-120+) for 12 patients with macroscopic and microscopic residual disease. The progression-free survival at 6 months was 75%. The combined treatment was associated with a low general toxicity, but attention must be given to increased normal tissue reactions. CONCLUSIONS: This trimodal treatment leads to excellent response rates, and it suppresses distant metastases when given as maintenance therapy.

Beta endovascular brachytherapy using CO2-filled centering catheter for treatment of recurrent superficial femoropopliteal artery disease.

BACKGROUND: Recurrent disease (restenosis) after endovascular treatment of the superficial femoral artery (SFA) remains a major problem. We evaluated the efficacy of beta-endovascular brachytherapy using the CORONA centering catheter in patients with SFA restenosis in a single-arm Phase II trial. METHODS AND RESULTS: A total of 28 patients (mean age 70 years; 16 female, 12 male) with recurrent SFA stenosis were treated, and in-stent restenosis was present in 17 patients (61%). Brachytherapy was performed with strontium-90 beta source using a 7-French CO(2)-filled one-segment centering catheter. New stents had to be applied in two cases. Mean interventional length was 129 mm (range 20-240 mm). A dose of 14 Gy in vessel radius (postinterventional) plus 2 mm was applied in 24 patients and 18.4 Gy in four patients. Treatment time was 7 min 32 s per radiation segment. No major adverse events occurred. Patients were followed by ankle-brachial index and duplex sonography for a median of 42 months. Cumulative restenosis rates at 1, 2, and 3 years were 9%, 28%, and 40%, respectively. Target vessel revascularization was performed in seven cases (25%). CONCLUSIONS: In comparison to literature data, the treatment of SFA restenosis with beta brachytherapy may improve long-term patency.