[Long-term results of pituitary irradiation in Cushing's disease].
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Biomedical subjects
Publications and source records attributed to G G Grabenbauer.
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Between 1975 and 1991, 40 patients with newly diagnosed medulloblastoma of the posterior fossa were treated at the authors' institutions. After aggressive surgical resection 39/40 patients (98%) received craniospinal radiation therapy (RT), including a local boost. A group of 29 patients was treated with adjuvant chemotherapy. The estimated overall 5-year survival and 5-year relapse-free survival (RFS) probabilities were 75% and 65%, respectively. The 5-year survival was significantly prolonged for patients treated after 1981 as compared to those treated between 1975 and 1980 (80% vs 64%, p = .02). However, multivariate analysis identified the adequate coverage of the target volume by external RT as the only significant variable (p = .0031). The extent of resection, stage according to Chang, radiation dose to the posterior fossa (< 55 Gy vs > or = 55 Gy) and the use of chemotherapy did not significantly influence survival and RFS. The initial site of recurrence was the posterior fossa with or without disseminated central nervous system (CNS) disease in 5 patients, the CNS without posterior fossa in 4 patients, and the bone marrow in 2 patients. An isolated frontal relapse occurred in 1 patient. We conclude that quality control of RT plays a decisive role in the long-term outcome of patients with medulloblastoma.
PURPOSE: External radiation therapy for non functioning pituitary adenomas is clearly indicated in inoperable patients, after incomplete transsphenoidal microsurgery and in case of tumor progression. This retrospective analysis gives results and toxicity following surgery and postoperative radiotherapy of non-functioning pituitary adenomas. PATIENTS AND METHODS: Between 1983 and 1990, 50 patients with non-functioning pituitary adenomas received combined treatment at our institutions. Surgical approaches were transsphenoidal (61%), transcranial (24%) or a combination of both (15%) in short intervals. All 50 patients received a full-dose radiotherapy with single fractions between 1.9 and 2.1 Gy (median 1.9 Gy) and total doses between 46 and 63 Gy (median 48 Gy). Field sizes ranged between 20 and 72 cm2 (median 30 cm2). Endpoints of this study were: progression-free survival, late effects of brain, optic nerve and intracranial vessels, visual impairment and hypothalamic-pituitary dysfunction. Median follow-up was 54 months. RESULTS: Forty-seven of the 50 patients remained progression-free. Patients over age 60 years progressed more frequently (3/17) as compared to younger patients (0/33, p = 0.034). Following radiotherapy vision improved in 8 patients (16%), 14 patients (28%) experienced a visual impairment between 10% and 60% (according to the grading system of the German Ophthalmologic Society). In multivariate analysis no influence of age (p = 0.097) or biologically effective dose (BED) (p = 0.11) was seen on visual impairment. Three patients (6%) experienced late effects with optic neuropathy in 2 cases and temporal lobe necrosis in 1 case. Only the BED had a significant impact on late effects (p = 0.0094). Adrenal, thyroid and gonadal function abnormalities were present in 58%, 66% and 96% of the patients at last follow-up, respectively. CONCLUSIONS: Radiotherapy after incomplete transsphenoidal or transcranial surgery of non-functioning pituitary adenoma is an effective treatment. Future perspectives must include the better defining of high-risk patients and the reduction of late morbidity.
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PURPOSE: Evaluation of prognostic variables, results and toxicity after chemo-radiation (CRT) of anal canal carcinoma (ACC). MATERIAL AND METHODS: Between 1982 and 1992, 139 patients with epidermoid carcinoma of the anal canal were treated by radiation and chemotherapy with 5-fluorouracil (5-Fu) and mitomycin C (MMC). 99 patients belonged to a prospectively designed trial (50 Gy, 2 courses of chemotherapy) and 40 to a historical control group (40 Gy, 1 course of chemotherapy). The female/male ratio was 116/23. Median age was 62 years. Staging (UICC 1987): T1: 16.5%; T2: 49%; T3: 23%; T4: 9.4%; unknown: 2.1%. Abnormal regional nodes were present in 15% of the patients. HISTOLOGY: Squamous cell carcinoma: 68%; cloacogenic carcinoma: 31%; unknown: 1%. External beam radiation (ERT) was given to the primary tumour including perirectal, inguinal and iliac nodes by a 3 to 4 field box technique (50 patients) or parallel opposed fields (89 patients). Median single fraction and total dose were 1.8 Gy and 50 Gy. An additional boost to the involved sites was delivered by ERT (32 cases; median dose 16 Gy) or interstitial brachytherapy (BT) in 28 cases with a median dose 14 Gy. 84 patients (60%) received 2 or more cycles, 50 patients (36%) 1 cycle, 5 patients (4%) no chemotherapy. RESULTS: The survival rate, NED-survival rate and local tumour control rate were 78%, 64% and 69% at 5 years. Anorectal function was retained in 94 of 139 patients (68%). Multivariate analysis indicated that T-stage (p = 0.037) and belonging to the historical control group (p = 0.003) were significant variables for local tumour control. T-stage was a marginally significant factor (p = 0.09) for NED-survival. Acute toxicity of grade 3 and 4 (WHO) was observed in 36%, severe late toxicity (grade 3 Eschwege) in 3% of the patients. CONCLUSIONS: CRT with 2 courses 5-FU, MMC and ERT to a total dose of 45 to 50 Gy is a safe and effective treatment for ACC. Intensification of treatment is recommended in advanced stages T3/4.
PURPOSE: The records of 52 patients with inoperable but localized squamous cell carcinomas of the esophagus were reviewed to determine the influence of different treatment modalities on survival, dysphagia and sites of recurrence. PATIENTS AND METHODS: 22 patients were treated by concurrent radio-chemotherapy with cis-platin/5-FU or carboplatin/5-FU; 19 patients by radiotherapy alone; six patients by chemotherapy followed by irradiation and five patients by concurrent radio-chemotherapy with various drugs. External beam radiotherapy consisted of treating the primary lesion (mean dose 53 Gy) and the lymphatic areas (mean dose 31 +/- 26 Gy) at the rate of 2 Gy/day for five days/week. Additional intraluminal high-dose-rate radiotherapy was performed in 13 patients with single fractions of 6 Gy as a boost. Minimum follow-up was twelve months, median follow-up 4.3 years. RESULTS: For the whole population a remission rate of 65% (34/52 patients) was achieved (complete remission 18/52 patients = 35%; partial remission 16/52 patients = 31%). Relief of dysphagia accompanied tumor regression. Median survival was eleven months; three-year survival rate 23%; five-year survival rate 7.6%. The analysis of recurrence revealed a high rate of local failures (26/52 patients = 50%) and distant metastases (9/52 patients = 18%). Comparing the different modalities the best results were achieved by concurrent radio-chemotherapy with cis-platin/5-FU or carboplatin/5-FU: Complete remission could be determined in 46% and median survival was 14.9 months. Additional intracavitary radiotherapy resulted in a slightly better local control rate (54% vs. 46%) and three-year-survival rate (30% vs. 20%) compared to external beam irradiation alone. CONCLUSIONS: Concurrent radio-chemotherapy with cis-platin/5-FU is superior to other treatment modalities in inoperable carcinoma of the esophagus. Additional intraluminal radiotherapy may increase local control rate.
AIM: To evaluate the radiocurability of esthesioneuroblastoma, we have retrospectively analyzed the results of radiation therapy in this tumor in our clinic. PATIENTS AND METHODS: From 1985 through 1990, twelve patients with esthesioneuroblastoma have been treated at the Department of Radiotherapy at the University of Erlangen. Two had Kadish stage A, one stage B, and nine stage C. There were seven males and five females with a mean age of 43 years. Eleven patients had combined transcranial-transbasal surgery prior to radiotherapy (five R0-, four R1-, and two patients R2-resections) and one received radiotherapy only. The dose was 12 to 60 Gy (mean 54 Gy) in 1.8 Gy to 2 Gy per fraction. RESULTS: 8/12 patients (67%) were locally controlled. One had progressive disease during radiotherapy after partial resection and died. Three had local recurrences, one in-field and two marginal. One patient with a local recurrence developed cervical lymph node metastases, and one locally controlled patient developed bone metastases but is alive eight years after chemotherapy plus radiotherapy for metastatic disease. The five-year-overall and recurrence-free survival was 72% and 55%, respectively. CONCLUSIONS: Sophisticated surgery plus radiotherapy may cure a reasonable number of patients with esthesioneuroblastoma.
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From June 1985 to September 1991, 44 patients with epidermoid carcinoma of the anal canal were treated prospectively by a protocol of combined radiation and chemotherapy (RCT) with 5-fluorouracil (5-FU) and mitomycin C (MTC). External radiation was delivered with 10 MV photons and single daily fractions between 1.8 and 2 Gy in an uninterrupted course up to a median total dose of 50 Gy. 5-FU was given by a continuous intravenous infusion (1 g/m2/day) for 96 h on days 1-4 and 29-32, MTC by a single bolus intravenous injection of 10 mg/m2 on days 1 and 29. The actuarial survival rate, no evidence of disease (NED) survival rate and local tumour control rate were 84%, 71% and 83% at 5 years. Anorectal function was retained in 33 of 41 patients (80%). Severe acute toxicity including three fatal outcomes was observed and there was an acceptable late morbidity. The only marginally significant prognostic factor (p = 0.06) for local tumour control was T-stage. RCT can provide good local control and preserve anal function with acceptable morbidity.
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Between 1975 and 1991, 40 patients with newly diagnosed medulloblastoma were treated at the authors' institutions. After aggressive surgical resection 39/40 (98%) received craniospinal radiation therapy with a local boost to the posterior fossa and other macroscopically involved areas. A group of 29 patients was treated with adjuvant chemotherapy. The five-year actuarial survival and event-free survival were 75% and 65%, respectively. Survival was significantly better for patients treated after 1981 as compared to those treated between 1975 and 1980 (p = .02). Younger age (two to four years) was associated with a better prognosis (p = .02). The extend of resection, Chang-stage, radiation dose to posterior fossa and the use of chemotherapy did not significantly impact on survival and relapse-free survival.
Between 1985 and 1992, 46 patients with epidermoid carcinoma of the anal canal were treated prospectively by a protocol of combined radiation and chemotherapy with 5-Fluorouracil and Mitomycin C. The survival rate, NED-survival rate and local tumour control rate were 84%, 71% and 83% at 5 years. Anorectal function was retained in 33 of 41 patients (80%). We observed severe acute toxicity including three deaths, but very little late morbidity. The only marginally significant prognostic factor (P = 0.06) for local tumour control was T-stage. NED-survival was significantly affected (P = 0.02) by reduction of chemotherapy during the second course.
Between 1978 and 1991, 31 patients with primary (n = 28) and recurrent (n = 3) ependymoma received external radiation after initial surgery. There were 26 cases of intracranial and five cases of spinal ependymoma. Histological grading revealed low-grade in 23 and high-grade tumors in eight patients. Craniospinal irradiation was given to 13 of 28 patients, whole cranial radiation with boost to posterior fossa in three and local treatment to twelve patients. Six of 28 patients received chemotherapy. Dose to the primary, tumor localisation, grading and extend of surgery did not significantly impact on survival and relapse-free survival. Age was a marginally significant prognostic factor for survival. In patients with intracranial ependymoma (n = 24) survival and relapse-free survival at five years were 54% and 42%, respectively. Patterns of recurrence showed a local recurrence alone in eight, a CNS-relapse with local recurrence in four and local recurrence with distant metastases in one case. Spinal seeding occurred in two of 13 after craniospinal irradiation and two of twelve patients after local treatment. The main problem in the treatment of ependymoma remains local control, the use of spinal irradiation does not seem to improve treatment results.
Between 1.1. 1987 and 31.12. 1988 47 patients with locally advanced head- and neck tumours (UICC-stage II: one patient, stage III: 16 patients, stage IV: 30 patients) were treated with simultaneous radio-chemotherapy. Localisations were hypopharynx (23 = 49%), oropharynx (16 = 34%) and other sites (8 = 17%). Radiation therapy consisted of 60 Gy (primary region, N+) or 50 Gy (N0) in daily fractions of 2 Gy each over six weeks. During week 1 and 5 of radiotherapy two courses of chemotherapy with 5-FU (600 mg/m2/day, i.v. continuous infusion for five days) and cis-platin (25 mg/m2/day i.v. bolus for five days) were administered. 43/47 patients (91%) responded to therapy. 34/47 (72%) patients achieved a complete remission, 9/47 (19%) a partial remission, and 4/47 (9%) no change. With a minimum follow-up of 26 months 17/47 patients (36%) are alive and NED, 4/47 (9%) are alive with tumour. 18 patients (38%) died of cancer, eight patients (17%) died of second tumours, intercurrent diseases and of unknown reasons. Actuarial four-year survival is 45% (stage III: 56%, stage IV: 42%), four-year NED survival is 35% (stage III: 68%, stage IV: 18%). There were no loco-regional recurrences after additional surgical treatment of the primary and the neck following complete remission. In contrast after RCT alone and complete remission local recurrences in 6/21 patients (29%) and regional recurrences in 5/24 patients (21%) occurred. We conclude that simultaneous RCT is a new very effective treatment modality of locally advanced head and neck tumours producing superior loco-regional control compared to conventional management.
External radiation in stage I (Royal Marsden system) seminoma is given to para-aortic lymphnodes with total doses between 26 and 30 Gy. In stage IIa/IIb additional treatment of ipsilateral iliac nodes up to 30 Gy (stage IIa) and 36 Gy (stage IIb) is recommended. In patients with bulky abdominal disease (stage IIc) whole abdominal irradiation with doses between 25 and 30 Gy followed by a small field to encompass residual masses (15-20 Gy) can be offered as primary treatment. Prophylactic supradiaphragmatic irradiation is not advocated.
From 1.1. 1986 to 31.12. 1990 50 patients with epidermoid carcinoma of the floor of the mouth and the mobile tongue (stage T1 18, stage T2 20, stage T3 eight and stage T4 four patients) were treated by surgery, 192-iridium implantation using the plastic tube technique and percutaneous irradiation. Surgery was performed as enoral resection (35 patients) or en bloc tumour resection with part of the mandible and flap reconstruction (15 patients). Interstitial therapy was considered as a boost to primary tumour region, the dose given ranged between 16 and 33 Gy. 50 to 60 Gy were applied with external beam radiotherapy. Management of the neck consisted of elective or radical neck dissection followed by external beam radiotherapy (50 to 60 Gy). At 2/1991 median follow-up was 17 (three to 53) months. 35 patients are alive and tumour-free, one patient lives with tumour. 14 patients died, eight patients tumour-related, four patients of intercurrent disease and two patients because of a second primary. Primary local control was 18/18 patients for stage T1, 19/20 patients for stage T2, 7/8 patients T3, 3/4 patients for stage T4. Three patients suffered from nodal recurrences, four patients from distant metastases. Complication rate was acceptable. Soft tissue necrosis occurred in 4/18 patients (T1); 5/20 patients (T2); 3/8 patients (T3) and 1/4 patients (T4). Three patients developed osteoradionecrosis. Our results show that combined modality treatment for tumours of the oral cavity yields high local control with acceptable complication rate.
Between 1979 and 1989 a total of 113 women underwent treatment for Hodgkin's disease at the Department of Radiation Oncology of the University of Erlangen-Nürnberg. Only 17 female patients of child bearing age received total lymphoid irradiation including pelvic and inguinal nodes. 15/17 patients underwent prophylactic bilateral oophoropexy during staging laparotomy: ten had lateral, five had midline ovarian transposition. Reproductive and ovarian function was investigated in 13 patients--all in complete remission after a minimum follow-up of three years--by menstrual history and serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), testosterone, dehydroepiandrosteronsulfate (DHEAS), androstendion, estradiol, progesterone, 17-OH progesterone, sexual hormone binding globulin (SHBG), free androgen index (FAI). Thyroid function was assessed by measuring thyroxine (T4), triiodothyronine (T3), thyroxine stimulating hormone (TSH) and thyroxine binding globulin (TBG). Normal cyclic ovarian activity was found in seven out of nine patients following lateral oophoropexy (including one pregnancy), but only in one out of four cases after midline fixation. Median calculated dose was 325 cGy (range 260 to 500 cGy) to the laterally fixed ovaries and 490 cGy (range 390 to 500 cGy) for midline transposition. We conclude, if ovarian protection is required prior to pelvic radiation, lateral oophoropexy should be preferred.