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Biomedical subjects

G G Grabenbauer

Publications and source records attributed to G G Grabenbauer.

At least 37 records · Page 2Linked to original sources

Accelerated radiotherapy with concomitant ACNU/Ara-C for the treatment of malignant glioma.

PURPOSE: To evaluate activity and toxicity of simultaneous ACNU and Ara-C with concurrent accelerated hyperfractionated radiotherapy in the treatment of high-grade glioma. PATIENTS AND METHODS: Thirty patients aged 23-71 years (median 47.5), 16 patients with glioblastoma multiforme (GBM) and 14 patients with grade-III glioma, received 93 courses of ACNU/Ara-C (median 4 courses) at following dose levels (ACNU/Ara-C in mg/m2/day): 70/90 (11 courses), 75/100 (36 courses) and 90/120 (46 courses). ACNU was administered IV on day 1 of each cycle, Ara-C as a 2 h-intravenous infusion on days 1-3. Patients received concomitant radiation therapy with 2 daily fractions of 1.75 Gy up to 57 Gy (median). RESULTS: Median survival of all patients was 13 months, 11 months for GBM and > 28 months for grade-III glioma; 31% (9 patients) survived longer than 24 months. The percentage of grade IV hematological toxicity was dose-dependent: 33% at the 70/90 dose level, 40% at 75/100 and 58% at 90/120. Six patients required platelet transfusion, 1 patient red blood cells; no febrile neutropenia occurred. Among 18 patients evaluable for response, 3 (17%) showed PR, 8 (44%) NC and 7 (39%) PD at completion of chemoradiation. No acute or late neurological toxicity occurred in this study. Younger age (p = 0.0001) and grade-III histology (p = 0.0009) were important prognostic factors for prolonged survival. CONCLUSION: This chemoradiation regimen is active in malignant gliomas and can be safely recommended at a dose level using 70 mg/m2 ACNU together with 90 mg/m2 Ara-C.

Adult↗

Primary spinal germinoma in a patient with concomitant Klinefelter's syndrome.

It is known that patients with Klinefelter's syndrome are inclined to develop concomitant malignant tumours, as well as extragonadal germ cell tumours. The association of a primary spinal germinoma in a patient with Klinefelter's syndrome is reported for the first time, and the coincidence of elevated gonadotropin levels and oncogenesis is discussed.

Adult↗

Gonadotrophin-independent puberty in a boy with a beta-HCG-secreting brain tumour.

We report on a short-statured boy in whom therapy with recombinant human growth hormone was initiated at the age of 9.7 years for assumed idiopathic growth hormone deficiency. On recombinant human growth hormone, height improved from -1.9 (standard deviation score) to -0.9 within 1 year, and the patient entered puberty spontaneously at 10.7 years. At 11.6 years he showed low morning cortisol and thyroxine levels, but was otherwise well. He showed an inconspicuous growth, and puberty progressed adequately until the age of 13.4 years, when he developed signs of an increased intracranial pressure, and a suprasellar choriocarcinoma was diagnosed. This case confirms the fact that beta chorionic gonadotrophin secreting tumours will not be diagnosed by the characteristic clinical manifestation of gonadotrophin-independent puberty if they occur at a time when normal puberty is expected. Particularly, it raises the question of how often the CNS should be re-evaluated by magnetic resonance imaging in children with growth hormone deficiency and normal initial neuroradiological imaging, when they develop additional hormonal deficiencies but no other clinical symptoms of an intracranial process.

Adolescent↗

[Neoadjuvant radiochemotherapy in soft tissue sarcomas. Optimization of local functional tumor control].

BACKGROUND: Adequate local control rates > 90% and acceptable functional results are the paramount goals in the treatment of soft-tissue sarcoma. Purpose of this paper is to evaluate response, long-term control, functional outcome and toxicity following neoadjuvant radiochemotherapy (RCT) in advanced and recurrent soft tissue sarcoma. PATIENTS AND METHODS: Between 1992 and 1998, a total of 23 patients in whom primary curative limb and function sparing surgery seemed impossible entered the study. Sixteen patients had primary and 7 patients recurrent sarcoma. The stages according to AJCC/UICC 1997 were as follows: rIA (2), rIIA (5) IIA (4), IIB (2), III (7), IV (3). RCT consisted of an accelerated split-course radiation (1.5 to 1.6 Gy twice daily, median total dose 60 Gy, range 60 to 64 Gy, break of 1 week after 30 Gy) with concomitant chemotherapy using adriamycin (50 mg/m2/d on days 2 and 30) and ifosfamide (1.5 g/m2/d on days 1 to 5, 29 to 33). Median follow-up was 26 months (range 2 to 92 months). RESULTS: Twenty-two patients underwent surgery with a curative (R0) resection being achieved in 20/22 (91%) patients and gross residual (R2) tumor or unclear tumor margins (RX) in 1 patient, respectively. Effective tumor-downstaging was documented in 4/22 (18%) patients (ypT0: 3 patients, ypT1: 1 patient). Long-term local tumor control after R0/RX resection remained 100%. Without prognostic impact on tumor response and local control have been the variables primary vs. recurrent tumor, grading, stage and gender. Delayed wound healing was only noted in 1/22 (5%) patients. Four patients developed distant metastases. Overall-, NED- and distant-metastases-free survival rates were 83%, 64% and 68%, respectively, at 3 years. Grade 3/4 neutropenia (WHO) was seen after 21/46 (46%) cycles of chemotherapy with 1 patient dying of septicemia. The functional results were good to excellent in 18/22 (82%) patients. CONCLUSION: Accelerated split-course radiation with 60 to 64 Gy and concurrent chemotherapy using adriamycin/ifosfamide is a safe and effective treatment for soft tissue sarcoma. This regimen may be considered in all cases with recurrent and advanced disease not amenable to primary curative or limb sparing surgery.

Adult↗

[Nasopharyngeal carcinoma: only irradiation or simultaneous radiochemotherapy?].

BACKGROUND: Between 1979 and 1997, a total of 92 patients with primary nasopharyngeal carcinoma were treated at the Hospitals of the University of Erlangen. Until 1988, radiotherapy alone was the treatment of choice and simultaneous radiochemotherapy was consistently applied thereafter. This retrospective analysis was performed to evaluate the influence of concurrent radiochemotherapy on survival and to identify possible prognostic factors on cause-specific survival-, locoregional tumor control- and distant-metastases-free survival rates. PATIENTS AND METHODS: Fifty-three patients (58%) received treatment by radiotherapy alone and 39 (42%) underwent primary radiochemotherapy with 2 courses of 5-FU and cisplatin. Median total dose to the bilateral neck region was 60 Gy (range, 50 to 62 Gy), and 74 Gy (range, 56 to 88 Gy) to the primary tumor. Median follow-up of the surviving patients was 8 years. RESULTS: Following radiochemotherapy and radiotherapy alone, the 5-year-survival rates were 67% and 48%, respectively (p = 0.06). Female patients had a survival advantage as compared to male patients (5-year-survival rate 77% vs 44%, p = 0.01). Patients with and without cranial nerve palsy at presentation had survival rates of 0% and 61%, respectively, at 5 years (p = 0.01). Distant-metastases-free survival was influenced by the following factors: lymph-node involvement (NO: 82% vs N1 to N3: 68%, p = 0.04), gender (female: 88% vs male: 64%, p = 0.01), type of treatment (radiochemotherapy: 86% vs radiotherapy: 63%, p = 0.02) and cranial nerve involvement (76% without and 42% with involvement, p = 0.04). CONCLUSIONS: In primary nasopharyngeal carcinoma simultaneous radiochemotherapy can significantly reduce distant metastases and improve survival as compared to radiotherapy alone. Since late toxicity rates were similar in both treatment groups and the slightly increased acute side effects following radiochemotherapy were effectively compensated by standard supportive care, patients with advanced nasopharyngeal carcinoma may benefit from simultaneous radiochemotherapy.

Adolescent↗

Effects of puberty on bone age maturation in a girl after medulloblastoma therapy.

BACKGROUND: Craniospinal radiotherapy for malignant brain tumors can result in a variety of neuroendocrine disturbances, among which are the development of growth hormone deficiency and early puberty, which can markedly reduce adult height. METHODS: The authors report the case of a girl who received craniospinal radiotherapy for a medulloblastoma at the age of 3.4 years. At 9.1 years, growth hormone therapy was started, and spontaneous onset of puberty (Tanner stage B2) occurred at age 10.3 years. Interval until menarche was short, at only 0.9 years. RESULTS: Although chronologic age at appearance of Tanner stages was within the normal range, the patient showed a rapid acceleration in skeletal maturation, resulting in adult short stature. CONCLUSION: Bone age seems to be a more precise parameter for biologic maturation in some patients after craniospinal irradiation than is clinical assessment of pubertal stages. Thus, if progression of bone age and decreasing final height predictions are noted, puberty should be stopped with gonadotropin-releasing hormone analogs, even if pubertal development seems to be adequate for chronologic age, because this increases the remaining time for growth hormone treatment.

Age Determination by Skeleton↗

Regression of a large solid papillary craniopharyngioma following fractionated external radiotherapy.

We present a patient harboring a large squamous papillary craniopharyngioma. The diagnosis was confirmed by a stereotactic biopsy. Because of vegetative symptoms indicating hypothalamic derangement, we were reluctant to perform surgical resection. Following fractionated megavoltage radiotherapy, MR imaging and CT demonstrated complete regression of the craniopharyngioma and the patient recovered from endocrine deficiency, chiasmal syndrome and vegetative hypothalamic symptoms.

Brain Neoplasms↗

Sphincter preservation with chemoradiation in anal canal carcinoma: abdominoperineal resection in selected cases?

PURPOSE: This study contained herein assessed long-term results, toxicity, and prognostic variables following combined modality therapy of patients with International Union Against (Cancer Classification T1-4, N0-3, M0 squamous-cell carcinoma of the anal canal. PATIENTS AND METHODS: Between 1985 and 1996, 62 patients completed treatment with combined modality therapy. A median total dose of 50 Gy was given to the primary, perirectal, presacral, and inguinal nodes followed by a local boost in selected cases. 5-Fluorouracil was scheduled as a continuous infusion of 1,000 mg/m2 per 24 hours on days 1 to 5 and 29 to 33 and mitomycin C as a bolus of 10 mg/m2 on days 1 and 29. Routinely processed paraffin-embedded sections were stained using monoclonal antibodies for detection of proliferating cell nuclear antigen and MIB1 (Ki-67) antigen to determine the labeling index. In addition, DNA ploidy was assessed after Feulgen staining. RESULTS: Actuarial cancer-related survival, no evidence of disease survival, and colostomy-free survival rates at five years were 81, 76, and 86 percent, respectively. In univariate analysis, T category (T1/2 vs. T3/4) was predictive for no evidence of disease survival (87 vs. 59 percent; P = 0.03) and colostomy-free survival (94 vs. 73 percent; P = 0.05). N category (N0 vs. N1-3) influenced actuarial cancer-related survival (85 vs. 58 percent; P = 0.002) and no evidence of disease survival (80 vs. 53 percent; P = 0.02). A higher proliferative potential as measured by the MIB1 labeling index was associated with a better colostomy-free survival (90 vs. 50 percent; P = 0.04). In multivariate analysis, actuarial cancer-related survival was only influenced by the N category (P = 0.03) and no evidence of disease survival by N category (P = 0.03) and mitomycin C dose (P = 0.04). Salvage abdominoperineal resection achieved long-term control in only four of seven patients with local failures. CONCLUSION: Treatment with a combination of radiotherapy and chemotherapy is safe and effective for patients with anal canal carcinoma. Abdominoperineal resection is indicated as a salvage procedure in nonresponding and recurrent lesions and may be of benefit in a small subgroup of patients with poor prognostic factors.

Adult↗

Nodal CT density and total tumor volume as prognostic factors after radiation therapy of stage III/IV head and neck cancer.

PURPOSE: To determine whether the immunohistochemical expression of proliferation-associated antigens (proliferating cell nuclear antigen, MIB1) and the nuclear p53 reactivity in addition to total tumor volume, nodal CT density and T and N category are predictive for overall survival and locoregional tumor control in patients with squamous cell carcinoma of the head and neck region. MATERIALS AND METHODS: Between October 1989 and September 1993, 87 patients with biopsy proven head and neck cancer were randomly allocated to receive radiation alone or simultaneous radiation and chemotherapy as part of a multicenter trial with a total of 298 randomized patients. There were only inoperable lesions in UICC (1992) stage III (8%) and IV (92%). Radiotherapy was delivered with 180 cGy twice daily up to a total dose of 7020 cGy in 51 days. Three cycles of 2340 cGy each were separated by a rest period of 11 days. Chemotherapy consisted of cis-DDP, 5-fluorouracil and leucovorin and was repeated on days 22 and 44. Routinely-processed paraffin-embedded sections were stained using monoclonal antibodies for detection of proliferation-associated antigens (MIB1 and PCNA) and p53 oncoprotein to determine the labeling index (LI). In addition, the total tumor volume and the percentage of necrosis were measured using CT data. The median follow-up was 3.9 years (range 1.9-5.0 years). RESULTS: The overall survival and locoregional control for all 87 patients were 34 and 39% at 3 years, respectively. The addition of chemotherapy resulted in a better overall survival (27 versus 47%, P = 0.03) but did not influence locoregional control (31 versus 47%, P = 0.08). In univariate analysis, nodal CT density (P < 0.0001), total tumor volume (P < 0.0001), age (P = 0.001) and the MIB1-LI (P = 0.04) had a significant impact on overall survival. However, in the final Cox model only the nodal CT density (P = 0.0003) and age (P = 0.05) were independent prognostic factors for survival and only the nodal CT density (P = 0.0006) was an independent prognostic factor for locoregional control. The expression of the p53 oncoprotein was not found to have a clear predictive value. CONCLUSION: Nodal CT density, total tumor volume and age will remain the relevant prognostic factors in stage III/IV head and neck cancer.

Antineoplastic Combined Chemotherapy Protocols↗

Simultaneous radiochemotherapy versus radiotherapy alone in advanced head and neck cancer: a randomized multicenter study.

PURPOSE: A prospective randomized multicenter trial was performed to evaluate the contribution of simultaneously administered chemotherapy (CT) and radiotherapy (RT) in previously untreated patients with unresectable stage III/IV head and neck cancer. PATIENTS AND METHODS: Patients with locoregionally advanced head and neck cancer were treated either with RT alone (arm A) or simultaneous RT plus CT (RCT; arm B). RT was identical in both arms and administered in three courses with 13 fractions of 1.8 Gy each twice daily. During one course, from day 3 to 11, 23.4 Gy was delivered. In arm B, cisplatin (CDDP) 60 mg/m2, fluorouracil (5-FU) 350 mg/m2 by intravenous (i.v.) bolus, and leucovorin (LV) 50 mg/m2 by i.v. bolus were given on day 2, and 5-FU 350 mg/m2/24 hour by continuous infusion and LV 100 mg/m2/24 hours by continuous infusion were given from day 2 to 5. Treatment was repeated on days 22 and 44; a total RT dose of 70.2 Gy was administered. Treatment breaks were scheduled from days 12 to 21 and days 34 to 43. RESULTS: From 1989 to 1993, 298 patients were enrolled and 270 patients were assessable. Acute mucositis grade 3 or 4 was more frequent in arm B (38%) than in arm A (16%) (P < .001). Total treatment time was significantly longer in arm B than in arm A (P < .001) due to prolonged breaks. According to hematologic toxicity, scheduled drug doses were given in 74% of patients for the second course and 46% for the third course. The 3-year overall survival rate was 24% in arm A and 48% in arm B (P < .0003). The 3-year locoregional control rate was 17% in arm A and 36% in arm B (P < .004). Both arms showed similar distant failure patterns (arm A, 13 of 140; arm B, 12 of 130). Serious late side effects were not significantly different between treatment arms (arm A, 6.4%; arm B, 10%; not significant). CONCLUSION: Concomitant CT offered improved disease control and survival in advanced head and neck cancer patients. Due to increased acute toxicity, more supportive care is demanded when CT is given simultaneously. Increased total treatment time does not exert a negative impact on outcome in this combined modality regimen.

Adult↗

[The acute toxicity of the simultaneous radiochemotherapy of rectal carcinoma].

AIM: We retrospectively examined the acute toxicity of (neo-)adjuvant combined treatment for rectal cancer in an attempt to evaluate potential factors that influence the severity of toxic side effects. PATIENTS AND METHOD: Between 1987 and 1995, 120 patients with rectal cancer (73 patients with primary tumor, 47 with recurrent disease) received chemoradiation for rectal cancer. Fifty-six patients received preoperative chemoradiation, 64 patients were treated postoperatively. Radiation was given by 4-field box technique with 6 to 10 MV-photons. Daily fraction size was 1.8 Gy, total dose 50.4 Gy (range: 41.4 to 56 Gy) +/- 5.4 Gy (range: 3.6 to 19.8 Gy) local boost in selected cases, specified to the ICRU reference point. During the first and fifth week of radiation 5-FU at a dose of 1000 m2/d for 120 hours was administered by continuous infusion. Toxicity was recorded following (modified) WHO-criteria. RESULTS: Acute grade 3 toxicity occurred mainly as diarrhea (33%), perineal skin reaction (37%), and leukopenia (10%). Extension of the treatment volume including paraaortic lymph nodes (L3) led to a significant increase of grade 3-diarrhea (68% vs. 25%, p = 0.0003) and grade 3-leukopenia (18% vs. 8%, p = 0.03). After abdominoperineal resection less patients suffered from grade 3-diarrhea (8% vs. 47% after sphincter preserving procedures, p = 0.0006), whereas severe perineal erythema occurred more frequently (56% vs. 29%, p = 0.02). Women had significantly more toxic side effects (grade 3-diarrhea: 39% vs. 16% in men, p = 0.04; grade 2 to 3-nausea/emesis: 21% vs. 8% in men, p = 0.018; grade 2 to 3-leukopenia 53% vs. 31% in men, p = 0.02). After preoperative chemoradiation a significant reduction of grade 3-diarrhea (11% vs 29%, p = 0.03) and grade 3-erythema (16% vs. 41%, p = 0.04) was noted. CONCLUSION: Treatment volume, type of surgery, sex and sequence of treatment modalities are the most important factors that influence the severity of toxic side effects. Individual adjustment of 5-FU dosage by monitoring its systemic clearance (which is lower in women) could help to avoid toxic side effects. The reduced acute toxicity of the preoperative approach provides a further argument in favor of the neoadjuvant chemoradiation for rectal cancer.

Acute Disease↗