Radiotherapy alone for invasive vaginal cancer: outcome with intracavitary high dose rate brachytherapy versus conventional low dose rate brachytherapy.

PURPOSE: Our aim was to compare the role of remote afterloaded high-dose-rate brachytherapy (HDRB) with traditional low-dose-rate brachytherapy (LDRB) for patients with invasive primary vaginal carcinoma. METHODS: The study group comprised 190 patients with invasive carcinoma of the vagina. The patients were staged according to the International Federation of Gynecology and Obstetrics (FIGO) staging system. Eighty patients were treated with intracavitary high-dose rate iridium 192 brachytherapy with or without external beam therapy. These patients are compared with a historical group of 110 patients treated with intracavitary low-dose-rate radium 226 or cesium 137 brachytherapy with or without external beam therapy. RESULTS: No significant differences were found for stages, tumor grade or location between the two groups. Crude 5-year survival for all patients was 41% in the former LDRB group, 81% in stage I and 43% in stage II. Overall actuarial 3-year survival and disease-specific survival rates for all patients in the HDRB series were 51% and 66%, respectively. Disease-specific 3-year survival attained 83% in stage I and 66% in stage II. There were no significant differences in local and distant recurrences between the treatment modalities. The comparison of treatments with or without external beam radiation and of complications showed no significant differences between the HDRB and LDRB series. CONCLUSION: With HDRB and its advantages of decreased radiation exposure and patient immobilization and precise positioning, treatment results to be obtained are at least similar to traditional LDRB for primary vaginal cancer.

High-dose versus low-dose rate brachytherapy in definitive radiotherapy of cervical cancer.

BACKGROUND: To retrospectively compare the clinical outcome in cervical cancer patients treated by external irradiation and intracavitary high-dose rate (HDR) brachytherapy with iridium 192 versus low-dose rate (LDR) brachytherapy with radium 226 or caesium 139. METHODS: 450 LDR patients were treated from 1982 to 1986 and compared with 189 HDR patients treated from 1993 to 1999. Cobalt (CO) 60 treatment was replaced in the HDR group by modern megavoltage photon radiotherapy (Linac 25 MV). Brachytherapy was given in either 2 or 3 LDR radium 226 implants for the earlier patient cohort, and 3-6 HDR iridium 192 implants for the latter cohort. The primary endpoint assessed was the 3-year overall survival. RESULTS: The median duration of follow-up was 70 months (range, 2-108 months) in the LDR group and 34 months (range, 4-69 months) in the HDR group. Actuarial overall 3-year survival after conventional LDR brachytherapy was 51.3%, versus 58.2% after HDR brachytherapy. No difference in 3-year survivors was seen in the small groups of stage I (68.3% vs. 84.6%) and stage IV (23.1% vs. 37.5%) patients. In stage II and III and in the overall group there were statistically significantly more 3-year survivors in the HDR group (58.1% vs. 78.9%, p < 0.001 in stage II; 37.3% vs. 53.8%, p < 0.01 in stage III; and 46.7% vs. 67.2%, p < 0.001 in the total group). Retrospectively assessed complication rates in the former LDR group were 3.8% for irreversible side effects, and 13.3% for chronic radiation damage. In the HDR group the actuarial late complication rates for grades 3 and 4 were 2.9% for the bladder, 4.0% for the bowel, and 6.1% for the rectum. CONCLUSION: In our preliminary experience, HDR brachytherapy combined with external beam radiation produced similar and even better survival rates compared with the LDR series. HDR brachytherapy combined with external beam radiation is an efficient method for the treatment of cervical cancer and adverse side effects are comparable.

Radiation therapy in the treatment of endometrial stromal sarcoma.

OBJECTIVE: The efficacy of radiation therapy in the treatment of endometrial stromal sarcoma (ESS) is still not clear. We report our results over an 18-year period in comparison to data from literature concerning adjuvant radiation therapy and other treatment modalities. PATIENTS AND METHODS: During 1981-1998, 21 patients with ESS were treated at General Hospital Vienna. The age of the patients ranged between 44-76 years (median: 65 yr). The 1989 FIGO classification for endometrial carcinoma was used in this study retrospectively. Eleven patients presented in Stage I, 1 in Stage II and 5 in Stage III. Four patients had Stage IV tumors or recurrences. The majority of patients (66.7%) had a Grade 3 tumor. Seventeen patients were treated in a curative intent. Fifteen patients were referred for postoperative radiotherapy after hysterectomy. Thirteen of them received a combined radiotherapy. Two patients were referred for primary radiotherapy. They received a combined radiotherapy. Four patients were referred for radiotherapy with a palliative intent. Twenty patients received external beam therapy (EBT) in daily fractions of 1.6-2.0 Gy up to a total dose of 27-57 Gy to the pelvis. Seventeen patients received brachytherapy. RESULTS: Follow-up was 8 to 170 months (mean: 70.3 months, median: 64 months). Eleven patients are still alive, 10 without tumor and 1 with tumor. Ten patients are dead, 6 due to ESS, 1 due to breast cancer, and 3 due to intercurrent diseases. After adjuvant radiotherapy, 3 patients had tumor recurrences. All had distant metastases, and 1 had local failure additionally. Two patients with primary treatment died due to intercurrent disease without tumor. The overall actuarial survival and the disease-specific survival rates were 63.4% and 80.9% after 5 years and 52.8% and 80.9% after 10 years. The overall local control rate was 93.8% after 5 years. Four patients treated with a palliative intent showed partial response. Three patients died rapidly due to tumor. One patient with a Grade 1 tumor is still alive 12 months after treatment. CONCLUSION: In our experience, surgery and adjuvant radiation therapy are most effective treatments for patients with ESS due to the excellent local control in all stages and the good disease-specific survival in early stages.

Comparison of radiography- and computed tomography-based treatment planning in cervix cancer in brachytherapy with specific attention to some quality assurance aspects.

INTRODUCTION: A modern approach in treatment planning for cervix carcinoma is based on a series of computed tomography (CT) sections and 3D dose computation. When these techniques were not yet available, dose evaluation was based on orthogonal radiographs. The CT based planning provides information on target and organ volumes and dose-volume histograms. The radiography based planning provides only dimensions and doses at selected points. The aim of the presented study is to correlate the information obtained with the two approaches for high dose-rate (HDR) brachytherapy of cervix carcinoma. METHODS: For the study 28 patients with 35 applications receiving HDR treatment with Ir-192 were investigated. The planning system PLATO (Nucletron) was used. The different aspects of available data, results and inaccuracies regarding quality assurance were looked at. RESULTS: From the CT based planning, the volume, location and dose-volume histograms were calculated for the CTV, rectum and bladder. From the radiography-based planning, the dose to point A (prescription), point B, rectum and bladder ICRU reference points [14], points related to the bony structures could be evaluated as well as volumes receiving different dose levels. These two sets of information were compared and following mean values derived. For a dose prescription of 7 Gy at point A, as an average, 83% (44 cm(3)) of the clinical target volume (CTV) receives at least 7 Gy. The mean dose at the rectum ICRU reference point is 4.3 Gy, and 12% (9 cm(3)) of the rectum is encompassed by the 4.3 Gy isodose. The mean dose at the bladder ICRU reference point is 5.8 Gy, and 8% (16 cm(3)) of the bladder is encompassed by the 5.8 Gy isodose. The maximum dose to the rectum is 1.5 times higher than the dose at the ICRU reference point, and for the bladder 1.4 times higher. Uncertainties caused by the reconstruction of the applicator and merging of isodoses could be evaluated. DISCUSSION: The subdivision of different approaches and the transfer from point doses to volumes in treatment planning is possible and practical for the treatment of cervix carcinoma in brachytherapy.

Definitive radiotherapy based on HDR brachytherapy with iridium 192 in uterine cervix carcinoma: report on the Vienna University Hospital findings (1993-1997) compared to the preceding period in the context of ICRU 38 recommendations.

UNLABELLED: According to the reports described in the literature, fractionated HDR brachytherapy seems to represent one option for the primary treatment of cervical carcinoma. In order to render such treatment transparent and comparable for those interested in the field, we have attempted to report our recent experience obtained in Vienna from 1993-1997 using the terminology proposed by the ICRU report 38, focusing in particular on dose and volume reporting and a linear-quadratic model. Based on these parameters, a comparison with the preceding period in Vienna (LDR/HDR) has been made, with an attempt to correlate different methods and parameters with outcome. MATERIAL AND METHODS: One hundred and eighty-nine patients (mean age 67 years) were treated with curative intent (stage Ia: 2, Ib: 11, IIa: 11, IIb: 79, IIIa: 19, IIIb: 59, IVa: 5, IVb: 3 patients) using a combination of intracervical high-dose rate (HDR) brachytherapy (ring-tandem applicator) and a box technique for external-beam therapy (EBT: 48.6-50 Gy, linac 25 MV). Small tumors were treated with 5-6 fractions of 7 Gy at point A and 50 Gy EBT (25 Gy in the brachytherapy reference volume) which is isoeffective to 76-86 Gy at point A. Large tumors received 3-4 fractions of 7 Gy after 50 Gy EBT with open fields, which is isoeffective to 82-92 Gy at point A. TRAK varied from mean 1.4 cGy (3 fractions) to 2.8 cGy (6 fractions) at one meter. 3-D treatment planning for brachytherapy was based on conventional X-rays and in 181/189 patients on computed tomography (CT) with the applicator in place. Computer-calculated volumes of the brachytherapy reference isodose (7 Gy/fraction) ranged from 46-155 ccm (mean 87 ccm); the respective mean hwt-volume (height x width x thickness) was 180 ccm. The 60 Gy HWT volumes (25 Gy from EBT) for the irradiation of small tumors ranged from 240 to 407 ccm (mean 337 ccm) and for larger tumors (50 Gy for EBT) from 452 to 785 ccm (mean 607 ccm). The mean dose for brachytherapy was 16.2 Gy (6.2-37.8 Gy) at the ICRU rectum reference point and 14.4 Gy (4.6-35.7 Gy) at the ICRU bladder point. Taking into account the dose for EBT, the mean isoeffective dose at the ICRU rectum reference point was 69.9 Gy (28.4-98.7 Gy). Overall treatment time was six weeks for small tumors and eight weeks for large tumors. RESULTS: After a mean follow-up of 34 months, actuarial pelvic control and disease-specific survival rates at three years were 77.6/68.6% for all patients, 100/77.1% for stage Ib, 100/100% stage IIa, 87.0/78.0% stage IIb, 52.7/52.1% stage IIIa, 69.1/58.6% stage IIIb and 60/53.3% stage IVa. According to the LENT/SOMA score which had been prospectively introduced, the actuarial late complication rate for grades 3 and 4 was 2.9% for the bladder, 4.0% for the bowel, 6.1% for the rectum and 30.6% for the vagina (shortening and obliteration); in total for all grades 23.6, 18.4, 24.2, and 67.6%, respectively. CONCLUSION: In our experience, HDR brachytherapy combined with EBT is an efficient method if sufficient radiation doses and volumes are applied, both with regard to tumor control and adverse side effects. In future, the therapeutic window will be increased by systematic integration of magnetic resonance imaging (MRI) into treatment planning, thus allowing for a highly individualized approach with further adaptation of radiation dose and volume both to the target and to the individual topography of organs at risk.

Portal imaging based definition of the planning target volume during pelvic irradiation for gynecological malignancies.

PURPOSE: Geometrical accuracy in patient positioning can vary substantially during external radiotherapy. This study estimated the set-up accuracy during pelvic irradiation for gynecological malignancies for determination of safety margins (planning target volume, PTV). METHODS AND MATERIALS: Based on electronic portal imaging devices (EPID), 25 patients undergoing 4-field pelvic irradiation for gynecological malignancies were analyzed with regard to set-up accuracy during the treatment course. Regularly performed EPID images were used in order to systematically assess the systematic and random component of set-up displacements. Anatomical matching of verification and simulation images was followed by measuring corresponding distances between the central axis and anatomical features. Data analysis of set-up errors referred to the x-, y-,and z-axes. Additionally, cumulative frequencies were evaluated. RESULTS: A total of 50 simulation films and 313 verification images were analyzed. For the anterior-posterior (AP) beam direction mean deviations along the x- and z-axes were 1.5 mm and -1.9 mm, respectively. Moreover, random errors of 4.8 mm (x-axis) and 3.0 mm (z-axis) were determined. Concerning the latero-lateral treatment fields, the systematic errors along the two axes were calculated to 2.9 mm (y-axis) and -2.0 mm (z-axis) and random errors of 3.8 mm and 3.5 mm were found, respectively. The cumulative frequency of misalignments < or =5 mm showed values of 75% (AP fields) and 72% (latero-lateral fields). With regard to cumulative frequencies < or =10 mm quantification revealed values of 97% for both beam directions. CONCLUSION: During external pelvic irradiation therapy for gynecological malignancies, EPID images on a regular basis revealed acceptable set-up inaccuracies. Safety margins (PTV) of 1 cm appear to be sufficient, accounting for more than 95% of all deviations.

The benefit of Beam's eye view based 3D treatment planning for cervical cancer.

PURPOSE: The aim of this study was to evaluate the possibility of Beam's eye view (BEV) based three dimensional (3D) treatment planning, to reduce portions of organs at risk included in the treated volume without increasing the risk of geographical miss in external beam therapy of cervical cancer. MATERIALS AND METHODS: Three dimensional dose distribution of BEV based 3D treatment plans was compared to the 3D dose distribution derived from a four-field-box-technique using standard portals. A total of 20 patients with cervical cancer stage FIGO IIB and FIGO IIIB was included. Dose distribution in the target volumes and in the organs at risk of BEV based treatment planning, was compared to the dose distribution of the standard field technique using dose-volume-histograms. RESULTS: In 4/20 patients (20%) a geographical miss at the cervix uteri was observed for the standard field technique. The BEV based treatment planning resulted in an adequate coverage of target volume and additionally in a reduction of portions of bladder and bowel volume included in the treated volume (-13.5, -10%). In contrast the BEV based technique resulted in an increase of portions of the rectum volume included in the treated volume compared to standard portals due to a shift of the rectum by the enlarged cervix uteri from its posterior to a lateral position. An overall 7% reduction of treated volume was observed, although the maximum width of lateral fields increased for the BEV technique. Moreover, we have found a remarkable impact of bladder fillings on the amount of bowel and bladder volume included in the treated volume. CONCLUSION: BEV based 3D treatment planning for external beam therapy of cervical cancer offers a possibility to avoid geographical miss of part of the CTV with reduced portions of bladder and bowel volume included in the treated volume.

External audit on the clinical practice and medical decision-making at the departments of radiotherapy in Budapest and Vienna.

PURPOSE: To present an example of how to study and analyze the clinical practice and the quality of medical decision-making under daily routine working conditions in a radiotherapy department, with the aims of detecting deficiencies and improving the quality of patient care. METHODS: Two departments, each with a divisional organization structure and an established internal audit system, the University Clinic of Radiotherapy and Radiobiology in Vienna (Austria), and the Department of Radiotherapy at the National Institute of Oncology in Budapest (Hungary), conducted common external audits. The descriptive parameters of the external audit provided information on the auditing (auditor and serial number of the audit), the cohorts (diagnosis, referring institution, serial number and intention of radiotherapy) and the staff responsible for the treatment (division and physician). During the ongoing external audits, the qualifying parameters were (1) the sound foundation of the indication of radiotherapy, (2) conformity to the institution protocol (3), the adequacy of the choice of radiation equipment, (4) the appropriateness of the treatment plan, and the correspondence of the latter with (5) the simulation and (6) verification films. Various degrees of deviation from the treatment principles were defined and scored on the basis of the concept of Horiot et al. (Horiot JC, Schueren van der E. Johansson KA, Bernier J, Bartelink H. The program of quality assurance of the EORTC radiotherapy group. A historical overview. Radiother. Oncol. 1993,29:81-84), with some modifications. The action was regarded as adequate (score 1) in the event of no deviation or only a small deviation with presumably no alteration of the desired end-result of the treatment. A deviation adversely influencing the result of the therapy was considered a major deviation (score 3). Cases involving a minor deviation (score 2) were those only slightly affecting the therapeutic end-results, with effects between those of cases with scores 1 and 3. Non-performance of the necessary radiotherapeutic procedures was penalized by the highest score of 4. Statistical evaluation was performed with the BMDP software package, using variance analysis. RESULTS: Bimonthly audits (six with a duration of 4-6 h in each institution) were carried out by three auditors from the evaluating departments; they reviewed a total of 452 cases in Department A, and 265 cases in Department B. Despite the comparable staffing and instrumental conditions, a markedly higher number (1.5 times) of new cases were treated in Department A, but with a lower quality of radiotherapy, as adequate values of qualifying parameters (1-6) were more frequent for the cases treated in Department B (85.3%, 94%, 83.4%, 28.3%, 41.9% and 81.1%) than for those in Department A (67%, 83.4%, 87.8%, 26.1%, 33.2% and 17.7%). The responsible division (including staff and instrumentation), the responsible physician and the type of the disease each exerted a highly significant effect on the quality level of the treatment. Statistical analysis revealed a positive influence of the curative (relative to the palliative/symptomatic) intention of the treatment on the level of quality, but the effect of the first radiotherapy (relative to the second or further one) was statistically significant in only one department. At the same time, the quality parameters did not vary with the referring institution, the auditing person or the serial number of the audit. CONCLUSION: The external audit relating to the provision of radiotherapeutic care proved feasible with the basic conformity and compliance of the staff and resulted in valuable information to take correction measures.

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.

[Evaluation of the effectiveness of radiotherapy in an Austrian-Hungarian collaboration]. / A sugárterápiás tevékenység eredményességének külsö minöségi felülvizsgálata osztrák-magyar együttmüködésben.

To present an example of how to study and analyse the clinical practice and the quality of medical decision-making under daily routine working conditions in a radiotherapy department, with the aims of detecting deficiencies and improving the quality of patient care. Bimonthly audits (6 with a duration of 4-6 hours in each institution) were carried out by 3 auditors from the evaluating departments; they reviewed a total of 452 cases in Department A, and 265 cases in Department B. During the ongoing external audits, the qualifying parameters were (1) the sound foundation of the indication of radiotherapy, (2) the conformity to the institution protocol (3), the adequacy of the choice of radiation equipment, (4) the appropriateness of the treatment plan, and the correspondence of the latter with (5) the simulation and (6) verification films. Various degrees of deviation from the treatment principles were defined and scored on the basis of the concept of Horiot et al. (10), with some modifications. The action was regarded as adequate (score 1) in the event of no deviation or only a small deviation with presumably no alteration of the desired end-result of the treatment. A deviation adversely influencing the result of the therapy was considered a major deviation (score 3). Cases involving a minor deviation (score 2) were those only slightly affecting the therapeutic end-results, with effects between those of cases with scores 1 and 3. Non-performance of the necessary radiotherapeutic procedures was penalized by the highest score of 4. Statistical evaluation was performed with the BMDP software package, using variance analysis. Despite the comparable staffing and instrumental conditions, a markedly higher number (1.5 times) of new cases were treated in Department A, but with a lower quality of radiotherapy, as adequate values of qualifying parameters (1)-(6) were more frequent for the cases treated in Department B (85, 94%, 83%, 28%, 42% and 81%) than for those in Department A (67%, 83%, 88%, 26%, 33% and 18%). The responsible division (including staff and instrumentation), the responsible physician and the type of the disease each exerted a highly significant effect on the quality level of the treatment. Statistical analysis revealed a positive influence of the curative (relative to the palliative/symptomatic) intention of the treatment on the level of quality, but the effect of the first radiotherapy (relative to the second or further one) was statistically significant in only one department. The external audit related to the provision of radiotherapeutic care proved feasible with real valuation of the staff's activity.

[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.

Intratumoral pO2-measurements as predictive assay in the treatment of carcinoma of the uterine cervix.

BACKGROUND: Several studies have shown that pretreatment oxygenation status of cervical tumors measured with a polarographic oxygen electrode could be a predictive factor for radiation response and survival. The purpose of this study was to evaluate the impact of intratumoral pO2 levels and hypoxic fractions on local control and disease free survival employing a standardized measuring procedure under routine conditions. MATERIALS AND METHODS: Between April 1994 and December 1997 pO2 measurements were performed prior to radiotherapy with an Eppendorf histograph in 51 evaluable patients with primary cervical carcinoma. All patients were treated with curative intent by combined external beam therapy (median total dose 49.6 Gy) and 3-6 applications of high dose rate- (7 Gy/fr. at point 'A') or pulse dose rate brachytherapy (20-25 h pulses, 1 Gy/pulse at point 'A'). Oxygenation data are given as median pO2 of pooled readings and percentage of readings below 5 mm Hg (HF 5). RESULTS: Median pO2 values ranged from 0 to 60 mm Hg (median 10). HF5 ranged from 0 to 95% (median 22%). Median follow-up was 26 months (range 9-54 months). Actuarial overall and disease-free survival rates (OS/DFS) at 3 years were 53%/50%. Comparing patients with median pO2 < or = 10 mm Hg (n = 26) to patients with higher median pO2 levels (n = 25) calculated DFS was 34 and 69%, respectively (P < 0.02). Corresponding data for local control were 47 and 84% (P = 0.053). Comparing patients with HF5 below and above the median calculated DFS was 36 and 66%, respectively (P < 0.02). Patients who had median pO2 < 10 mm Hg and HF5 > 20% had the worst prognosis (3-year DFS: 28%). Besides oxygenation status, stage and initial hemoglobin concentration were statistically significant for treatment outcome. CONCLUSIONS: This study confirms earlier data that the presence of hypoxia is associated with poor local control and survival in patients with carcinoma of the uterine cervix. Polarographic pO2 measurements are feasible under routine conditions and can be regarded as a reproducible predictive assay.

Ropivacaine and bupivacaine for long-term epidural infusion in a small child.

Ropivacaine is assumed to be less toxic than bupivacaine but there are no reports concerning its long-term use in paediatric anaesthesia. We report the use of ropivacaine for long-term epidural anaesthesia in a 21-month-old girl. In two consecutive periods of 3 days each, 0.5% bupivacaine and 0.5% or 0.75% ropivacaine were administered to facilitate painful vaginal brachytherapy. The mean dose of bupivacaine increased from 1.05 to 1.32 mg kg-1 h-1 and that of ropivacaine increased from 1.40 to 3.86 mg kg-1 h-1. No toxic side effects were observed. We conclude that both epidural ropivacaine and bupivacaine were effective and safe during long-term epidural anaesthesia in this particular case. However, the doses were potentially toxic and should therefore be used with extreme caution.

Treatment of endometrial carcinoma with high-dose-rate brachytherapy alone in medically inoperable stage I patients.

PURPOSE: To review the results of treatment with high-dose-rate brachytherapy alone in 228 patients with stage I endometrial carcinoma who are unfit for surgery. METHODS: All patients received an exclusive radiation therapy by means of high-dose-rate Iridium 192 intracavitary brachytherapy without additional external beam radiation. RESULTS: At 5 years, the overall survival rate was 59.7% and disease specific survival 85.4% at 10 years 30.2% and 75.1%. In clinical stage Ia disease specific survival was 88.6% at 5 years and 82.7% at 10 years, in stage Ib 80.2% and 63.4%, respectively (p<0.02). Disease specific survival was not affected by tumor grade or age. The rates of local control are related to the size of the uterus but not to the tumor grading. Intrauterine recurrence occurred in 17.5% but extrauterine pelvic relapse in only 0.4% of patients. The calculated probability of severe complications was 4.6% at 5 years. CONCLUSION: HDR brachytherapy alone achieves excellent disease specific survival rates in patients with medically inoperable stage I endometrial carcinoma.

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.

Primary treatment of endometrial carcinoma with high-dose-rate brachytherapy: results of 12 years of experience with 280 patients.

PURPOSE: This study aimed to evaluate the efficacy of high-dose-rate brachytherapy (HDRB) in the primary treatment of endometrial carcinoma. The results of 12 years of experience (1981-1992) covering 280 patients (mean age 72 years) and their follow-up over 10 years (mean 55 months) are reported. METHODS AND MATERIALS: Staging was based on clinical examination and fractionated curettage. There were 116 patients in clinical Stage Ia, 119 in Stage Ib, 37 in Stage II, and 8 in Stage III. HDRB was performed four to five times (8.5 Gy) with a one-channel intracavitary applicator and one to two times (7 Gy) with an intravaginal cylinder applicator. Overall and disease-specific survival, local control according to stage and histology, and late side effects were analyzed retrospectively (actuarial method). RESULTS: At 5 years, overall survival, disease-specific survival, and local control were 52.7%, 76.6%, and 75.4% (Stage Ia: 63.9%, 84.9%, and 86.0%; Stage Ib: 47.3%, 73.3%, and 68.8%; and Stage II: 40.2%, 68.6%, and 60.5%) according to histopathologic Grade 1: 65.1%, 83.5%, and 77.7%; for Grade 2: 44.7 %, 75.4%, and 75.8%; and for Grade 3: 37.7%, 63.9%, and 74.1%. Eight patients showed progressive disease, 64 developed recurrence after a median of 13 months (45 of whom had a local recurrence only, and 6 of whom had a local recurrence with distant metastases), 6 developed a lymph node recurrence only, and 7 developed distant metastases only. The calculated probability for developing a Grade III late side effect was 5.2% at 5 years. CONCLUSION: At Stages Ia, Ib, and II in endometrial carcinoma, HDRB is a very effective treatment modality with acceptable local control rates and disease-specific survival for patients who are not fit for surgery. During the time frame of 12 years and in 280 patients the method has proven to have a low risk of acute complications and an acceptable risk of long-term side effects.

Brachytherapy in the combined modality treatment of pediatric malignancies. Principles and preliminary experience with treatment of soft tissue sarcoma (recurrence) and Ewing's sarcoma.

Radiotherapy is an integral part in the treatment of soft tissue and Ewing's sarcoma in children. By brachytherapy a high dose can be delivered in a restricted volume with sparing of normal tissues surrounding the target. Taking into account this principle potential benefit brachytherapy may play some role in the local treatment especially in children. However, only limited experience with pediatric brachytherapy has been reported apart from a few centers, which have gained their experience with Low-Dose-Rate (LDR)-brachytherapy. Since 1991 - 12 patients with soft tissue sarcoma and 6 patients with Ewing's sarcoma were treated with High-Dose-Rate (HDR) and Pulse-Dose-Rate (PDR)-brachytherapy at the departments of radiotherapy in Münster, Kiel and Vienna. The combined modality treatment was performed according to the CWS-86/91, EICESS-92 and CESS/CWS-REZ-91 protocols. In 8 patients with soft tissue sarcoma brachytherapy was part of the recurrence treatment regime, in 4 patients brachytherapy was part of the primary treatment alone or in combination with external beam therapy. In HDR-treatment a dose of 15 to 43 Gy was delivered in 3 to 16 fractions, in PDR-treatment 13 to 36 Gy in fractions of 1 Gy/hour. Follow-up is 3-39 months (median 14 months). 7 patients show no evidence of disease, 9 patients are locally controlled and 3 patients progressed locoregionally. In 6 patients with Ewing's sarcoma brachytherapy was performed intraoperatively as a boost treatment after external beam therapy (50-55 Gy), if no wide resection could be achieved within first line-treatment. A dose of 10-12 Gy was applied in one fraction in a limited volume (20-50 ccm) at the time of surgery. Follow-up is 13-26 months (median 21 months). There is no evidence of disease in all patients, perioperative and subacute morbidity was not increased. These encouraging preliminary results with HDR/PDR-brachytherapy must be further evaluated prospectively and systematically within an interdisciplinary approach by some specialized collaborating centers, which not only have the equipment (HDR/PDR/(LDR)-brachytherapy) but also can meet the complex demands to accumulate the necessary experience.

[The results of primary HDR-afterloading brachytherapy in corpus carcinoma]. / Ergebnisse der primären HDR-Afterloading-Brachytherapie beim Korpuskarzinom.

PURPOSE: In general the results of radiotherapy are regarded to be inferior compared to those of surgery, when it comes to the treatment of endometrial carcinoma, but some patients are elderly and have multiple medical problems, which make them inoperable. The risk of intracavitary radium therapy, caused by immobilisation, can be reduced by the use of fractionated high-dose-rate afterloading brachytherapy. With this method there are only very few results reported. PATIENTS AND METHODS: Treatment results of HDR brachytherapy (4 to 5 times 8.5 Gy, one-channel applicator, intracavitary and 1 to 2 times 7 Gy intravaginal) at the University Hospital Vienna were analysed retrospectively (actuarial method [Kaplan-Meier]) regarding overall survival and recurrence-free interval according to stage and histology. Over a period from April 1981 until December 1992 325 patients were treated by this technique alone or combined with external beam therapy. Two hundred and eighty patients could be evaluated. Staging based on clinical examination and fractionated curettage. RESULTS: Five-year overall survival was 58.1%, in stage Ia 68.5%, stage Ib 49.9%, stage II 48.7%, according to histopathologic grading 1 68.5%, grade 2 53.2%, grade 3 37.5%. 64 patients developed a recurrence after a median of 13 months, 45 of those a local recurrence only, 6 a local recurrence with distant metastases, 6 a lymph node recurrence only and 7 patients distant metastases only. CONCLUSION: These results are at least comparable to those of intracavitary radium therapy and low-dose-rate afterloading techniques. Better local control rates should be obtained by the Heyman packing method using Norman-Simon applicators based on individualised brachytherapy treatment planning, which optimises dose distribution according to the target volume based on computerised imaging.