Clinical signs of neurofibromatosis impact on the outcome of malignant peripheral nerve sheath tumors.

OBJECTIVE: Malignant peripheral nerve sheath tumors (MPNST) are a rare subtype of sarcoma, with a poor outcome. MPNST are regarded as being sporadic or associated with neurofibromatosis type 1 (NF1). Few comparative overall-survival (OS) data in these 2 subsets of MPNST patients exist. The aim of this retrospective study was to assess OS in sporadic and NF1-associated MPNST patients. METHODS: Fourteen consecutive patients with initial localized as well as initial metastatic MPNST were diagnosed and treated in our department. Patients with sporadic MPNST were assigned to group A and those with NF1-associated MPNST to group B. RESULTS: Eight versus 6 patients were allocated to groups A and B. Primary tumors were located on the extremities in all but 1 patient. Two patients in group A and 4 patients in group B experienced a relapse. Four patients died in each of the 2 groups. Median follow-up was 66.2 and 57.2 months in group A and group B, respectively. Median OS in group A was 46.9 months versus 12.7 months in group B. CONCLUSIONS: In this small, single-center study, sporadic-MPNST patients had a longer median OS than those with NF1-associated MPNST.

Preoperative short-term radiation therapy (25 Gy, 2.5 Gy twice daily) for primary resectable rectal cancer (phase II).

To evaluate the feasibility, effectiveness, and long-term bowel function of preoperative hyperfractionated accelerated radiotherapy in primary resectable rectal cancer. A total of 184 consecutive patients (median age 65 years, male : female=2 : 1) with clinical T3Nx rectal adenocarcinoma received preoperative pelvic radiation therapy with single fractions of 2.5 Gy twice daily (interval 6 h between fractions) to a total dose of 25 Gy within 1 week. Surgery was conducted the following week. Postoperative histology revealed UICC stage I in 33%, stage II in 26%, stage III in 34%, and stage IV in 7% of the patients. Median follow-up was 43 months (53 months for surviving patients). The actuarial 4-year-local-recurrence rate was 2.1%, overall recurrence 23%. Disease-specific and disease-free survivals at 4 years (excluding stage IV) were 82 and 69%, respectively. Overall survival for 4 years was 68%. Postoperative mortality was 0.5% (one patient), early anastomotic leakage occurred in 11.4%, and anastomotic stenosis requiring treatment in 6%, of 132 patients with primary anastomosis. Seven of 184 patients (3.8%) died of abdominal complications, all within the first year. Bowel function was satisfactory after more than 5 years. Local control in primarily resectable rectal cancer after 10 x 2.5 Gy is excellent, warranting further evaluation of this treatment.

Hyperfractionated accelerated radiochemotherapy (HFA-RCT) with mitomycin C for advanced head and neck cancer.

To investigate efficacy and feasibility of hyperfractionated accelerated radiotherapy combined with mitomycin C, patients with locally advanced unresectable squamous cell carcinomas of the head and neck region were administered 64-66 Gy in four weeks and mitomycin C (20 mg/m(2)) on day five. Twenty-one consecutive patients were included between November 1997 and June 1999 (median age: 57 years). All tumours were stage T3-4 and 18/21 were N2-3. Eighteen patients experienced grade 3 and three patients grade 2 mucosal toxicity. With median follow up for surviving patients of 42 months, loco-regional control was 55% at three years, overall survival was 33% at three years. This treatment is at the edge of local tolerability, but there is a good curative chance even for very advanced localised tumours, provided a complete remission is induced at primary treatment.

Endovascular brachytherapy in peripheral arteries.

Increasing knowledge about the pathophysiology of the process leading to restenosis has given the rationale to investigate the potential role of radiation in the prevention of restenosis. Compared to the rapidly increasing experience in the coronary circulation, there is until now only a limited number of studies concerning the use of brachytherapy (BT) in the peripheral circulation. The-Vienna 2-Trial was the first randomized study to demonstrate the efficacy of endovascular BT for prophylaxis of restenosis after femoropopliteal percutaneous transluminal angioplasty. The cumulative patency rates at 12 months of follow-up were 63.6% in the PTA + BT-group and 35.3% in the PTA-group (p < 0.005), and the significant improvement in patency was also maintained after two years. The results of two ongoing randomized, double-blinded multicenter trials (PARIS; Vienna 3) have to be awaited before definitive recommendations can be given. The rather high incidence of late thrombotic occlusion after long-segment femoropopliteal stenting and endovascular BT requires optimization of the antithrombotic regimen.

Endovascular brachytherapy for prophylaxis against restenosis after long-segment femoropopliteal placement of stents: initial results.

PURPOSE: To evaluate the feasibility, safety, and effectiveness of endovascular brachytherapy for the prevention of restenosis after long-segment femoropopliteal percutaneous transluminal angioplasty (PTA) and stent implantation. MATERIALS AND METHODS: Thirty-three patients (23 men, 10 women; mean age, 66 years) with femoropopliteal lesions (mean treated length, 17 cm; range, 4-30 cm) underwent PTA and stent implantation followed by brachytherapy with a centering catheter. A dose of 14 Gy was delivered to the adventitia by using an iridium 192 source. Long-term pharmacotherapy with acetylsalicylic acid was combined with clopidogrel for 1 month. Follow-up examinations included measurement of the ankle-brachial index, color-coded duplex ultrasonography, and angiography. RESULTS: The overall 6-month recurrence rate was 30% (10 of 33 arteries). Seven patients developed sudden late thrombotic occlusion of the segment with the stent 3.5-6 months after stent implantation. Considering the overall results after successful local thrombolysis in six of these seven patients, only four (12%) of 33 arteries with a stent had in-stent restenosis caused by neointimal hyperplasia. CONCLUSION: The study results are promising concerning the possibility of reducing in-stent restenosis by means of brachytherapy after long-segment femoropopliteal placement of stents. The high incidence of late thrombotic occlusion requires optimization of the antithrombotic regimen.

Dose-volume histograms based on serial intravascular ultrasound: a calculation model for radioactive stents.

BACKGROUND AND PURPOSE: Radioactive stents are under investigation for reduction of coronary restenosis. However, the actual dose delivered to specific parts of the coronary artery wall based on the individual vessel anatomy has not been determined so far. Dose-volume histograms (DVHs) permit an estimation of the actual dose absorbed by the target volume. We present a method to calculate DVHs based on intravascular ultrasound (IVUS) measurements to determine the dose distribution within the vessel wall. MATERIALS AND METHODS: Ten patients were studied by intravascular ultrasound after radioactive stenting (BX Stent, P-32, 15-mm length) to obtain tomographic cross-sections of the treated segments. We developed a computer algorithm using the actual dose distribution of the stent to calculate differential and cumulative DVHs. The minimal target dose, the mean target dose, the minimal doses delivered to 10 and 90% of the adventitia (DV10, DV90), and the percentage of volume receiving a reference dose at 0.5 mm from the stent surface cumulated over 28 days were derived from the DVH plots. Results were expressed as mean+/-SD. RESULTS: The mean activity of the stents was 438+/-140 kBq at implantation. The mean reference dose was 111+/-35 Gy, whereas the calculated mean target dose within the adventitia along the stent was 68+/-20 Gy. On average, DV90 and DV10 were 33+/-9 Gy and 117+/-41 Gy, respectively. Expanding the target volume to include 2.5-mm-long segments at the proximal and distal ends of the stent, the calculated mean target dose decreased to 55+/-17 Gy, and DV 90 and DV 10 were 6.4+/-2.4 Gy and 107+/-36 Gy, respectively. CONCLUSIONS: The assessment of DVHs seems in principle to be a valuable tool for both prospective and retrospective analysis of dose-distribution of radioactive stents. It may provide the basis to adapt treatment planning in coronary brachytherapy to the common standards of radiotherapy.

Prescribing, recording, and reporting in endovascular brachytherapy. Quality assurance, equipment, personnel and education.

Endovascular brachytherapy is a new, rapidly growing field of interest in radiotherapy for the prevention of neointimal hyperplasia after angioplasty in both coronary and peripheral arteries. Many physics aspects of these treatments have already been addressed in the report of the American Association of Physicists in Medicine task group on 'Intravascular brachytherapy', but up to now there are no generally accepted recommendations for recording and reporting radiation doses and volumes. The terminology to be used by all individuals involved in such treatments (radiation oncologists, physicists, and interventionalists) is not clearly defined. The Endovascular Groupe Européen de Curiethérapie/European Society for Therapeutic Radiology and Oncology Working Group in this document presents recommendations for a common language for general use in endovascular brachytherapy. This proposal addresses general terms and concepts for target and dose specification as well as detailed recommendations for dose prescription, recording and reporting in endovascular brachytherapy for both peripheral and coronary arteries. Additionally, quality assurance and radiation safety aspects are briefly addressed, as are aspects related to equipment, personnel, and training and education related to endovascular brachytherapy.

[MRI-assisted brachytherapy of nonresectable liver metastases. Preliminary technical and clinical experiences]. / MR-gestützte Brachytherapie nichtresektabler Lebermetastasen. Vorläufige technische und klinische Erfahrungen.

PURPOSE: To evaluate the feasibility and efficacy of MR-guided interstitial brachytherapy of non-resectable liver metastasis. METHODS: Liver metastases (0.8-5.2 cm in diameter) were treated during a prospective phase I/II study using an open 0.2 Tesla MR system (Magnetom Open Viva, Siemens, Erlangen). MR-compatible brachytherapy applicators were placed percutaneously under MR-guidance in an open 0.2 Tesla MR system (Magnetom Open Viva, Siemens, Erlangen) using fast T1-weighted sequences. Pretreatment and follow-up studies were performed using a 1.5 Tesla MR system. RESULTS: Preliminary results of an unpublished prospective study are discussed exemplary on 2 selected patients. The median procedure time was 4.9 h. No major complications were observed and late effects were acceptable. In large symptomatic metastases only a temporary relief of pain was achieved. In smaller metastases (DM 3 cm) a tumor control was observed. CONCLUSION: MR-guided brachytherapy is feasible and has the potential to ablate liver metastases with diameter of less than 3 cm. Further developments are necessary.

Intraluminal 192Ir brachytherapy following transjugular intrahepatic portosystemic shunt revision: long-term results and radiotherapy parameters.

PURPOSE: The stenosis or occlusion of transjugular intrahepatic portosystemic shunt (TIPS) occurs in up to 75% of patients within 12 months after treatment. The aim of our investigation was to evaluate the feasibility, safety and efficacy of intraluminal high-dose rate brachytherapy (HDRBT) with Iridium-192 following TIPS revision to prevent restenosis due to pseudointimal hyperplasia. MATERIALS AND METHODS: Between September and November 1996, intraluminal BT was performed in five patients after TIPS revision. The indications for initial TIPS were a Budd-Chiari syndrome in two female patients and recurrent variceal bleeding by alcoholic liver cirrhosis in three male patients. TIPS was created with Wallstents (10 mm diameter in four patients) and Palmaz stent (10 mm diameter in one patient). The re-dilatation was done in all five patients 6 months after first stenting because of restenosis (>50% stent lumen reduction) or occlusion of the stent. A 5-French closed-tip, noncentered BT delivery catheter was used for subsequent radiotherapy. The whole length of the stent and performed dilatation (interventional length - IL) was taken as clinical target length (CTL). A 10-mm safety margin was added proximal and distal to the CTL due to uncertainties of BT source positioning, so forming the planning target length (PTL). To ensure that prescribed dose covers the whole PTL, the active source length (ASL) was 5 mm longer proximal and distal than PTL, so forming the reference isodose length (RIL). A dose of 12 Gy was prescribed in 3 mm distance from the source axis in the mid-plane of the applicator for three patients and in 5 mm distance for two patients. RESULTS: A normal patency (<50% lumen reduction) of the stent was achieved at 44 months follow-up (duplex sonography+portography) in all three patients with liver cirrhosis, whereas further revisions were necessary in two patients with Budd-Chiari syndrome (after 5.5 and 18 months). No acute, subacute or late brachytherapy (BT)-related side effects were seen until now. CONCLUSIONS: HDRBT following TIPS revision was safe and feasible in all patients. The exact impact of BT on the TIPS patency should be evaluated in larger clinical trials. Moderate dose escalation and use of today's commercially available centering radiation catheters seem to be necessary.

Intraarterial (192)Ir high-dose-rate brachytherapy for prophylaxis of restenosis after femoropopliteal percutaneous transluminal angioplasty: the prospective randomized Vienna-2-trial radiotherapy parameters and risk factors analysis.

PURPOSE: The aim of the Vienna-2-trial was to compare the restenosis rate of femoropopliteal arteries after percutaneous transluminal angioplasty (PTA) with or without intraarterial high-dose-rate (HDR) brachytherapy (BT) using an (192)Ir source. MATERIALS AND METHODS: A prospective, randomized trial was conducted from 11/96 to 8/98. A total of 113 patients (63 men, 50 women), with a mean age of 71 years (range, 43-89 years) were included. Inclusion criteria were (1) claudication or critical limb ischemia, (2) de-novo stenosis of 5 cm or more, (3) restenosis after former PTA of any length, and (4) no stent implantation. Patients were randomized after successful PTA for BT vs. no further treatment. A well-balanced patient distribution was achieved for the criteria used for stratification, as there were "de-novo stenosis vs. restenosis after former PTA," "stenosis vs. occlusion," "claudication vs. critical limb ischemia" and above these for "diabetes vs. nondiabetes." PTA length was not well balanced between the treatment arms: a PTA length of 4-10 cm was seen in 19 patients in the PTA alone group and in 11 patients in the PTA+BT group, whereas a PTA length of greater than 10 cm was seen in 35 patients and 42 patients, respectively. A dose of 12 Gy was prescribed in 3-mm distance from the source axis. According to AAPM recommendations, the dose was 6.8 Gy in 5-mm distance (vessel radius + 2 mm). Primary endpoint of the study was femoropopliteal patency after 6 months. RESULTS: PTA and additional BT were feasible and well tolerated by all 57 pts in this treatment arm. No acute, subacute, and late adverse side effects related to BT were seen after a mean follow up of 12 months (6-24 months) in 107 patients (PTA n = 54; PTA+ BT n = 53). Crude restenosis rate at 6 months was in the PTA arm 54% vs. 28% in the PTA + BT arm (chi(2) test; p < 0.013). Actuarial estimate of the patency rate was at 6 months 45% vs. 72% (p < 0.004). Comparison of restenosis rates for the different subgroups with risk factors (restenosis after former PTA, occlusion and PTA length >10 cm) showed significant decrease of the restenosis rate, if BT was added. Significant reduction was not achieved in diabetes patients. CONCLUSION: BT after femoropopliteal PTA is feasible and a safe therapeutic option. No BT related morbidity was observed. A significant reduction of the restenosis rate was obtained in the PTA+BT arm. Subgroup analysis showed significant decrease of restenosis rate in the subgroups with restenosis after former PTA, occlusion and PTA length of greater than 10 cm. With dose escalation and reduction of dose variation by a centering device a further significant decrease of restenosis rate can be expected.

Endovascular brachytherapy for prophylaxis of restenosis after femoropopliteal angioplasty : results of a prospective randomized study.

BACKGROUND: Inasmuch as endovascular brachytherapy (BT) has gained recent interest because of its inhibitory effect on mechanisms leading to restenosis after percutaneous transluminal angioplasty (PTA), we performed this randomized study to determine its efficacy for prophylaxis of restenosis after femoropopliteal PTA. METHODS AND RESULTS: One hundred thirteen patients (63 men, 50 women; mean age 71 years) with de novo or recurrent femoropopliteal lesions were included in this randomized trial comparing the restenosis rate after PTA plus BT (57 patients, PTA+BT group) versus PTA (56 patients, PTA group) without stent implantation. The mean treated length was 16.7 cm (PTA+BT group) versus 14.8 cm (PTA group). In patients randomized to PTA plus BT, a dose of 12 Gy was applied by an (192)Ir source 3 mm from the source axis. Follow-up examinations included measurement of the ankle-brachial index, color-flow duplex sonography, and angiography. The primary end point of the study was patency after 6 months. The overall recurrence rate after 6 months was 15 (28.3%) of 53 in the PTA+BT group versus 29 (53.7%) of 54 in the PTA group (chi(2) test, P<0.05). The cumulative patency rates at 12 months of follow-up were 63.6% in the PTA+BT group and 35.3% in the PTA group (log-rank test, P<0.005). CONCLUSIONS: This is the first randomized study to demonstrate the efficacy of endovascular BT for prophylaxis of restenosis after femoropopliteal PTA. The value of this approach should now be improved by modification of the BT procedure and by combination with stent implantation.

Results of primary and adjuvant radiotherapy in the treatment of mixed Müllerian tumors of the corpus uteri.

OBJECTIVE: The benefit of primary or adjuvant irradiation in the treatment of mixed Müllerian tumors is still not clear. METHODS: During 1981-1997 63 patients were referred for primary (n = 13) or postoperative (n = 50) radiotherapy. Analysis of outcome of primarily and postoperatively irradiated patients was performed separately because of different staging systems. Of 50 patients treated after surgery 29 presented in histopathologic stage I, 4 in stage II, 14 in stage III, and 3 in stage IV. Clinical stage distribution for primary treatment was stage I: n = 9, stage II: n = 1, stage III: n = 3. Forty-four patients in the postoperatively treated group and 6 in the primarily treated group received radiotherapy with a curative intent; external beam therapy was given up to 56 Gy to the pelvis combined with intravaginal or intracavitary brachytherapy. RESULTS: Five-year actuarial overall survival, disease-specific survival, local control, and distant control for 50 patients receiving adjuvant irradiation was 52.9, 57. 5, 83.4, and 70.8%, in stage I: 68.4, 76.1, 95.2, and 81.7%, in stage II: 50.0, 50.0, 75.0, and 66.7%, and in stage III: 31.3, 34.1%, 70.4, and 47.6%, respectively. Four of 13 patients treated with primary irradiation achieved long-term local control. CONCLUSION: These data suggest that adjuvant radiotherapy improves local control and disease specific survival in the treatment of mixed Müllerian tumors compared to data in the literature concerning treatment by surgery alone.

[A comparison of CT-supported 3D planning with simulator planning in the pelvic irradiation of primary cervical carcinoma]. / Vergleich der CT-gestützten 3D-Planung mit der Simulatorplanung bei der Beckenbestrahlung des primären Zervixkarzinoms.

BACKGROUND: Using standardized simulator planning guided by bony landmarks for pelvic irradiation of primary cervical carcinoma with some patients a geographical miss regarding tumor or potential tumor spread can happen because of insufficient knowledge of the individual anatomical situation. The question arises whether for patients with this indication the higher effort in terms of time and personnel for 3D treatment planning is justified. PATIENTS AND METHOD: In a prospective study on 20 subsequent patients with primary cervical carcinoma in Stages I to III simulator planning of a 4-field box-technique was performed. After defining the planning target volume (PTV) in the 3D planning system the field configuration of the simulator planning was transmitted. The resulting plan was compared to a second one based on the defined PTV and evaluated regarding a possible geographical miss and encompassment of the PTV by the treated volume (ICRU). Volumes of open and shaped portals were calculated for both techniques. RESULTS: Planning by simulation resulted in 1 geographical miss and in 10 more cases the encompassment of the PTV by the treated volume was inadequate. For a PTV of mean 1,729 cm3 the mean volume defined by simulation was 3,120 cm3 for the open portals and 2,702 cm3 for the shaped portals (Figure 1). The volume reduction by blocks was 13.4% (mean). With CT-based 3D treatment planning the volume of the open portals was 3.3% (mean) enlarged to 3,224 cm3 (Figure 2). The resulting mean volume of the shaped portals was 2,458 ccm. The reduction compared to the open portals was 23.8% (mean). The treated volumes were 244 cm3 or 9% (mean) smaller compared to simulator planning. The "treated volume/planning target volume ratio" was decreased from 1.59 to 1.42. CONCLUSION: The introduction of 3D treatment planning for pelvic irradiation of cervical carcinoma is to be recommended for reasons of quality assurance. Reduction of the treated volume is possible but further research has to be done to determine whether the rate of complications can be decreased as well.

Results of postoperative radiotherapy in the treatment of sarcoma of the corpus uteri.

BACKGROUND: The role of radiotherapy in the treatment of uterine sarcoma still is not clear. Data from the literature advocating adjuvant radiotherapy most often are based on very small patient groups, whereas larger epidemiologic studies, which appear to show no benefit for the additional radiotherapy, lack information regarding clinical data influencing the choice for adjuvant irradiation. METHODS: During 1981-1992, 72 patients were referred for postoperative radiotherapy. Histologic diagnoses were leiomyosarcoma (LMS) in 30 patients, endometrial stromal sarcoma (ESS) in 11 patients, mixed müllerian tumors (MMT) in 28 patients, and other sarcoma types in 3 patients. The 1988 International Federation of Gynecology and Obstetrics classification for endometrial carcinoma was applied retrospectively. Forty patients presented with Stage I disease, 9 with Stage II, 17 with Stage III, and 6 with Stage IV. External beam therapy was given with a cobalt-60 unit using a rotation technique with 2 separate arcs in daily fractions of 2 gray (Gy), up to a total dose of 56 Gy to the pelvis. Brachytherapy was given to the vaginal vault either with 2 radium applications (median: 1600 milligram-hours to the applicator surface) or, in the majority of cases, with 3 fractions of high dose rate afterloading applications (iridium-192, 10-Curie source) with 7 Gy each to an isodose 7.5 mm from the applicator surface. RESULTS: The 5-year actuarial overall survival, disease specific survival, and local control rates for 72 patients were 52.3%, 58.5%, and 77.9%, respectively; in Stage I patients they were 74.8%, 84.6%, and 94.4%, respectively; in Stage II patients they were 53.3%, 53.3%, and 88.9%, respectively; in Stage III patients they were 15.7%, 17.9%, and 55.5%, respectively; and in Stage IV patients they were 0%, 0%, and 0%, respectively. For LMS, the 5-year actuarial overall survival, disease specific survival, and local control rates were 49.4%, 52.0%, and 76.0%, respectively; for ESS they were 81.8%, 81.8%, and 90.9%, respectively; and for MMT they were 42.3%, 54.9%, and 72.4%, respectively. CONCLUSIONS: These data suggest that adjuvant radiotherapy is an effective treatment for uterine sarcoma with regard to disease specific survival in patients with early stage disease and increases local control, even in patients with advanced stage disease.

Brachytherapy for prophylaxis of restenosis after long-segment femoropopliteal angioplasty: pilot study.

PURPOSE: To evaluate in a pilot study the feasibility and efficacy of endovascular brachytherapy for prophylaxis of restenosis after femoropopliteal percutaneous transluminal angioplasty (PTA) without stent implantation in a group of patients with a high risk of restenosis. MATERIALS AND METHODS: Ten patients (six women, four men; mean age, 68 years) with long-segment (mean length, 16 cm; range, 9-22 cm) restenosis underwent PTA followed by endovascular irradiation with high-dose-rate afterloading of an iridium-192 rod. A dose of 12 Gy was targeted to the inner intimal layer of the vessel. Follow-up examinations until 12 months after PTA included measurement of the ankle-brachial index, color duplex ultrasonography (US) with calculation of the peak velocity ratio, and intraarterial angiography when recurrence was suspected. RESULTS: Irradiation was technically feasible in all patients without complications. In six patients, the dilated and irradiated segment remained widely patent at color US, with corresponding excellent hemodynamic and clinical results after 12 months. In four patients, clinical and laboratory findings indicated recurrence and arteriography demonstrated restenosis with a diameter reduction of 60%, 70%, 80%, or 90%. CONCLUSION: Considering the negative selection of patients with a high risk of restenosis, the results of our pilot study are promising concerning the possibility of reduction of restenosis by means of endovascular brachytherapy after long-segment femoropopliteal PTA without stent implantation. The value of this approach should now be determined definitively in randomized trials.

Tumor marker determinations.

A combination of 2 or 3 tumor markers was determined in the serum of 478 patients with malignant tumors. In 195 out of 213 patients with differentiated thyroid cancer and without relapse or metastases, the Tg concentration has undetectable. In 9 patients with nonfunctioning thyroid metastases the Tg level was correlated with the progress of the disease or the success of the treatment. In 114 patients with gastrointestinal cancer CA 19-9, TPA and IAP were measured simultaneously. The highest discrepancies between patients with relapse or metastases (increased values in 1/2 of patients) and patients without relapse or metastases (increased values in 1/4 of patients) were given by CA 19-9. In the serum of 90 patients with breast cancer increased CA 15-3 values were found in 2/3 of patients with relapse or metastases and in 1/4 of patients without signs of tumor. A combination of universal tumor markers TPA and IAP had no value in monitoring 26 patients with melanoma.