H. Kucera

Benefit of external irradiation in pathologic stage I endometrial carcinoma: A prospective clinical trial of 605 patients who received postoperative vaginal irradiation and additional pelvic irradiation in the presence of unfavorable prognostic factors

Six hundred and five cases of endometrial carcinoma, pathologic stage I, without definable extrauterine disease were initially treated with total abdominal hysterectomy and bilateral salpingo-oophorectomy, followed by high-dose-rate iridium-192 irradiation of the vagina. External irradiation of the pelvis was performed only for patients with poor prognostic factors. Five-year survival was calculated by the product-limit method of Kaplan and Meier. Three hundred and forty-eight patients with tumor invasion of the inner third, of any tumor grade, received postoperative vaginal irradiation only. Twenty-eight patients with grade 1 tumor invasion of the middle third received vaginal irradiation only. One hundred and six patients with grade 2 or 3 tumor and infiltration of the middle third received vaginal and external irradiation of the pelvis. One hundred and twenty-three patients with deep muscle invasion of the external third of the myometrium received vaginal and pelvic irradiation. Differences in survival figures were not significant. Survival of the treatment group with good prognosis who received vaginal irradiation alone (91%) was similar to that of the group with poor prognosis who received additional pelvic irradiation (87.7%). Despite the unfavorable situation of patients with poor prognostic factors, treatment results after additional external irradiation were relatively equal to the results for patients with good prognostic factors who had not received external irradiation. Therefore, the benefit of external irradiation in patients with stage I endometrial carcinoma with unfavorable prognostic factors seems evident.

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.

Radiation management of primary carcinoma of the vagina: Clinical and histopathological variables associated with survival

Data are presented on 434 patients treated at the Gynecologic Radiotherapy Department of the University of Vienna for invasive primary carcinoma of the vagina between 1952 and 1984; data on 110 patients treated in the last few years are more detailed. In stage I, 5-year survival was 76.7%; in stage II, 44.5%; in stage III, 31%; and in stage IV, 18.2%. The overall uncorrected 5-year survival rate was 39.9%. The disease is primarily one of the elderly as 78% were found to be older than 60 years of age. Younger patients had a 5-year survival of 50%; patients between 61 and 75 years of age, 41.2%; and those 76 years of age or older, 34.3%. Patients with presenting symptoms had a cure rate of 36.9%, whereas 61.1% of asymptomatic cases survived. Best results (60%) were obtained when the lesion was in the upper third of the vagina; only 37% of patients with lesions of the middle third and lower third survived more than 5 years. Well-differentiated tumors were associated with a 5-year survival of 62.5%; and poorly differentiated tumors, with a rate of 34.9%. Our results indicate that stage of disease is the most significant prognostic factor, but age of the patient, location of lesion in the vagina, and differentiation of the tumor influence outcome too. The majority of patients were managed by a combination of external pelvic irradiation and local application of radium. In stage I and II patients treated with radium alone, good results were obtained, but no patient with stage III or IV disease survived 5 years when external irradiation was not performed.

The influence of nicotine abuse and diabetes mellitus on the results of primary irradiation in the treatment of carcinoma of the cervix

References in the literature to the frequent occurrence of cervix carcinoma accompanied by nicotine abuse led us to investigate the effects of cigarette smoking on the results of treatment in primary irradiation of cervix carcinoma. As not only nicotine abuse but also diabetes mellitus can lead to angiopathy, we also investigated the influence of diabetes mellitus on the results of treatment. Of 410 nonsmokers with carcinoma of the cervix in Stages I and II, 260 (63.4%) reached the 5‐year limit, but only 62 of 115 smokers survived (53.9%). In Stages III and IV there were significantly less favorable rates of cure in patients with nicotine abuse. Of 626 nonsmokers with cervix carcinoma in Stages III and IV, 212 survived (33.9%); but of 153 smokers, only 31 (20.1%) could be cured (P < 0.01). The frequency of side effects of primary irradiation was distinctly higher in smokers than in nonsmokers. Reversible complications occurred in 17.5% of the smokers and 15.5% of the nonsmokers. Severe irreversible changes occurred in 28% of the smokers versus 15.2% of the comparative group of nonsmokers (P < 0.01). The injuries caused by smoking not only reduce the biologic effectiveness of ionizing radiation but also increase the rate of side effects due to the deficient capacity for regeneration of the tissue surrounding the tumor. With diabetes as a complication, however, no significant changes in frequency of side effects were noted. Five‐year survival in diabetic patients was affected in Stage I and II, but not in the advanced stages.

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.

Radiation therapy in the treatment of endometrial stromal sarcoma.

Abstract 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.

High-dose-rate (HDR) brachytherapy with or without external beam radiotherapy in the treatment of primary vaginal carcinoma: Long-term results and side effects

PURPOSE To report toxicity, prognostic factors, and outcome of HDR brachytherapy in the primary management of vaginal carcinoma. METHODS AND MATERIALS A total of 86 patients receiving radiotherapy for primary vaginal carcinoma were analyzed. FIGO stages 0-IV were found in 6, 17, 38, 20, and 5 patients, respectively. Early stages of disease (Stages 0-II) were treated with intravaginal HDR brachytherapy alone (n = 26/86), whereas locally advanced diseases (Stages II-IV) received HDR brachytherapy combined with external beam therapy (n = 55/86). Teletherapy only was used in 5 of 86 cases, all of which were treated with palliative intent (i.e., advanced stage, poor general status). Recurrence-free intervals as well as overall- and disease-specific survival rates were determined for all patients. Frequencies of side effects and the influence of prognostic factors and treatment modalities on outcome were analyzed. RESULTS Five-year overall survival rates for Stages 0-IV diseases were 83%, 41%, 43%, 37%, and 0%, respectively. Corresponding 5-year disease-specific survival rates were 100%, 92%, 57%, 59%, and 0%. Regarding 5-year recurrence-free intervals, values of 100%, 77%, 50%, 23%, and 0% (Stages 0-IV) were found, respectively. Tumor stage was the most significant prognostic factor. Chronic side effects G 1-4 were observed in <or=2% (bladder, rectum) and 1%-6% (vagina). CONCLUSION In the treatment of primary vaginal carcinoma, HDR brachytherapy appeared to be well-tolerated and as effective as LDR brachytherapy techniques.

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.

Radiation therapy for primary carcinoma of the female urethra: a survey over 25 years

Sixty-two patients with primary carcinoma of the female urethra were treated with a combined radiation therapy (high-dose intracavitary vaginal radium and external beam). Treatment was strictly individualized, but an administered tumor dose of 5500-7000 rad (55-70 Gy) was always attempted. Forty-two patients (67.7%) had tumors of the anterior urethra, and in 20 women (32.3%) the posterior urethra was involved. In 19 patients (30.6%) the clinical diagnosis of lymph node involvement was made. The overall 5-year-survival rate was 64.5%. Patients with anterior urethral carcinoma had a higher 5-year-survival rate (71.4%) than patients with posterior carcinoma (50.0%). The favorable results underline the substantial role of radiation therapy for this malignancy.

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.