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Biomedical subjects

Christoph B Ostertag

Publications and source records attributed to Christoph B Ostertag.

7 recordsLinked to original sources

Capillary physiology of human medulloblastoma: impact on chemotherapy.

BACKGROUND: Advances in the treatment of medulloblastoma have largely been attributed to the introduction of chemotherapy, although Phase III trials have shown advantages for chemotherapy only in subgroups. Because the efficacy of chemotherapy depends on tumor vascularization, the vascular physiology of human medulloblastomas was evaluated. METHODS: Seven patients with histologically proven medulloblastomas underwent measurements of capillary permeability and vascular plasma volume using contrast-enhanced dynamic computer tomography. Regional blood flow was measured in 5 patients using xenon computed tomography (CT). RESULTS: The capillary permeability-surface product for water-soluble compounds ranged from 1.7 +/- 5.5 to 17.6 +/- 12.3 muL/g/min with a mean of 10.5 +/- 6.3 microL/g/min. The vascular plasma volume ranged from 0.02 +/- 0.021 to 0.045 +/- 0.049 mL/g with a mean of 0.03 +/- 0.01 mL/g. The efflux rate ranged from 0.012 +/- 0.007 to 0.065 +/- 0.064 1/min with a mean of 0.039 +/- 0.020 1/min. Regional tumoral blood flow showed a mean of 19.86 +/- 6.8 mL/100g/min as compared with normal cerebellum with 45.4 +/- 12.03 mL/100g/min (P < .005). CONCLUSIONS: The current study demonstrated a low capillary permeability and blood flow in medulloblastomas that could explain the limited response rates of partially resected tumors even after aggressive high-dose chemotherapy, as recently reported.

Antineoplastic Combined Chemotherapy Protocols↗

Interstitial 125I radiosurgery of supratentorial de novo WHO Grade 2 astrocytoma and oligoastrocytoma in adults: long-term results and prognostic factors.

BACKGROUND: Detailed long-term outcome data are not available for adult patients with World Health Organization (WHO) Grade 2 astrocytoma or oligoastrocytoma. METHODS: A previously published short-term data set of 239 adult patients with circumscribed de novo supratentorial astrocytoma (187 patients) and oligoastrocytoma (52 patients) treated with interstitial iodine-125 ((125)I) radiosurgery as primary treatment (1979-1992) was revisited. Survival, progression-free survival, functionally independent survival, postrecurrence survival, and time to malignant transformation were estimated with the Kaplan-Meier method. Prognostic factors were obtained from the Cox multivariate proportional hazards model. RESULTS: Five-, 10-, and 15-year survival was 56%, 37%, and 26%, respectively (median follow-up, 10.3 yrs). Progression-free survival was 45%, 21%, and 14%, respectively. The corresponding malignant transformation rates were 33%, 54%, and 67%. No leveling off of the Kaplan-Meier curves could be observed for any of the chosen endpoints. Age > 50 years, a tumor volume > 20 mL, and/or a Karnofsky score < or = 80 were associated with decreased survival or progression-free survival. Age > 35 years and/or a tumor volume > 20 mL increased risk of malignant transformation. Prognostic factors determined subsets of patients with 10-year survival ranging from as low as 6% to as high as 55% and progression-free survival ranging 1-31%. CONCLUSIONS: Long-term tumor stabilization is rare. As outcome is mainly determined by treatment-independent factors, minimization of any treatment-related risk must be considered essential.

Adolescent↗

Capillary physiology and drug delivery in central nervous system lymphomas.

To evaluate whether the chemosensitivity of primary central nervous system lymphomas to water-soluble drugs could result from improved drug delivery, we quantitatively assessed pharmacokinetic factors in seven patients. The capillary permeability surface product was found to be significantly increased in central nervous system lymphomas compared with glioblastoma multiforme, medulloblastomas, and metastases. Tumoral blood flow was significantly greater than in normal white matter. Our results suggest favorable pharmacokinetics to water- and lipid-soluble drugs in primary central nervous system lymphomas.

Adult↗

Long term course of WHO grade II astrocytomas of the Insula of Reil after I-125 interstitial irradiation.

OBJECTIVE: To present long-term results after interstitial iodine-125 irradiation of adult patients with de-novo World Health Organization (WHO) Grade II astrocytomas and oligoastrocytomas of the insula of Reil with special respect to the treatment-related risk. METHODS: 55 consecutively treated patients (from 1979 to 1992) with circumscribed tumors with a diameter < 5 cm (astrocytomas: 46 patients, oligoastrocytomas: 9 patients) were included. The reference dose-calculated to the outer boundary of the tumor-was in the range of 60-100 Gy and the dose rate was low (< 10 cGy/h). Progression-free survival, risk of malignant transformation, survival, and the incidence of radiogenic complications were estimated by the Kaplan-Meier method. Prognostic factors were obtained from the Cox-model. RESULTS: Median follow up for the survivors was > 10 years. 5-year (10-year) progression-free survival was 40.7 % (20.2 %), and 5-year (10-year) survival 54.6 % (28.4 %). Malignant transformation occurred in 42.4 % after 5 years. Neither of the Kaplan-Meier curves showed a leveling off over time. Transient (progressive) radiogenic complications were observed in 13 [4] patients (one-year overall complication rate: 18%), and were significantly associated with a tumor diameter >3.5 cm (p<0.001). No long term side-effects were detected and delayed external beam irradiation (in case of tumor progression) did not enhance the risk. Tumor enhancement on CT was the only unfavorable predictor for survival. CONCLUSION: A limited overall prognosis for adult patients with insular WHO grade II astrocytomas and oligoastrocytomas was detected. Interstitial I-125 irradiation offers a minimal-invasive and low-risk treatment option for circumscribed tumors with a diameter < 3.5 cm. Larger tumors require further evaluation for optimal treatment.

Adult↗

Deep brain stimulation of the nucleus ventralis intermedius for Holmes (rubral) tremor and associated dystonia caused by upper brainstem lesions. Report of two cases.

Holmes tremor is caused by structural lesions in the perirubral area of the midbrain. Patients often present with associated symptoms such as dystonia and paresis, which are usually refractory to medical therapy. Here, the authors describe two patients in whom both tremor and associated dystonia improved markedly following unilateral stimulation of the thalamic nucleus ventralis intermedius.

Ataxia↗

Radiosurgery followed by planned observation in patients with one to three brain metastases.

OBJECTIVE: To analyze the role of radiosurgery alone in patients with brain metastases. There were three specific study goals: 1) to determine whether survival of patients selected for this treatment approach can be predicted successfully by use of the recursive partitioning analysis classification defined by the Radiation Therapy Oncology Group; 2) to evaluate local control; and 3) to identify risk factors of cerebral failure. METHODS: A total of 101 patients with Karnofsky Performance Scale scores of at least 50 and up to three brain metastases, each 3 cm or less in maximum diameter, were treated with radiosurgery alone. Survival, local control, distant brain freedom from progression (FFP), and overall brain FFP were evaluated according the method of Kaplan and Meier. Risk factors for survival and overall brain FFP were analyzed using the Cox model. RESULTS: Median survival was 13.4 months, 9.3 months, and 1.5 months for patients in recursive partitioning analysis Classes 1, 2, and 3, respectively (P < 0.0001). At 1 year, local control, distant brain FFP, and overall brain FFP were 91, 53, and 51%, respectively. An interval greater than 2 years between diagnosis of the primary tumor and diagnosis of brain metastases and the presence of a single brain metastasis were associated with significantly higher overall brain FFP. CONCLUSION: Recursive partitioning analysis classification successfully predicted survival. Radiosurgery alone yielded high local control. Overall brain FFP was highest in patients with an interval greater than 2 years between primary diagnosis and diagnosis of a single brain metastasis.

Adult↗