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Biomedical subjects

K E Wallner

Publications and source records attributed to K E Wallner.

29 records · Page 2Linked to original sources

Treatment of oligodendrogliomas with or without postoperative irradiation.

The authors have reviewed the treatment results in 42 patients with intracranial oligodendroglioma treated from 1940 through 1983 at the University of California, San Francisco. Two patients who died postoperatively were excluded from analysis. Eleven patients had mixed tumors, with a minor astrocytic component. The overall survival rates for the 29 patients with pure oligodendroglioma were 61% and 33% at 5 and 10 years, respectively; these rates for the 11 patients with mixed tumors were 57% and 38% at 5 and 10 years, respectively. The 10-year survival rate for 14 patients with pure oligodendroglioma who received greater than 45 Gy irradiation was 56% versus 18% for 11 patients who did not receive postoperative irradiation (p = 0.09). Nine patients with mixed tumor who received more than 45 Gy postoperatively had survival rates similar to those for the 14 patients with pure tumors irradiated with more than 45 Gy (p = 0.89). All patients who died of their tumor had evidence of intracranial recurrence. One patient, who did not receive initial postoperative irradiation, also had clinical and myelographic evidence of spinal seeding. All five patients examined postmortem had tumor recurrence at the primary site; one patient also had intraventricular seeding. Six of the 10 patients with pure oligodendroglioma who had a repeat biopsy at the time of tumor recurrence or at postmortem examination showed histological progression to an anaplastic astrocytoma or glioblastoma multiforme. Based on this study, adult patients with pure or mixed oligodendroglioma currently are treated with partial-brain irradiation to a dose of about 60 Gy. In general, children are treated with partial-brain irradiation to about 50 Gy.

Adolescent↗

Treatment results of juvenile pilocytic astrocytoma.

Treatment results for 36 patients with juvenile pilocytic astrocytoma treated from 1942 through 1985 at the University of California, San Francisco, were reviewed. Twenty-two tumors were located in the posterior fossa, 10 were in the hypothalamic region, and four were in the cerebral hemispheres. Twenty-eight patients were less than 18 years of age. The overall survival rate was 83% and 70% at 10 and 20 years, respectively. All 12 patients who had total tumor resection remain disease-free; only two of the 12 received postoperative irradiation. The 10- and 20-year freedom-from-progression for the 19 patients who had incomplete resection and received at least 40 Gy of postoperative irradiation was 74% and 41%, respectively. All patients who failed treatment had local recurrence. One patient developed diffuse meningeal seeding, after four local recurrences in the posterior fossa over a 23-year period. Six patients failed treatment and had a repeat biopsy at the time of recurrence or at postmortem examination, and three showed histological progression of the tumor to an anaplastic astrocytoma. Based on this study and others in the literature, a protocol has been adopted whereby patients who have total tumor resection are not treated with postoperative irradiation. Patients who have incomplete tumor resection and are older than 3 years of age are currently treated with postoperative partial-brain irradiation, to a dose of 45 to 60 Gy. In general, young children with incomplete resection are followed closely with computerized tomography or magnetic resonance imaging and are treated with chemotherapy or irradiation if tumor progression is documented.

Adolescent↗

Hyperthermic enhancement of cell killing by mitomycin C in mitomycin C-resistant Chinese hamster ovary cells.

The interaction of hyperthermia and mitomycin C (MMC) was studied in wild-type Chinese hamster ovary cells and in Chinese hamster ovary cells selected for resistance to MMC. Hyperthermic potentiation of MMC activity was maximal if heating was done simultaneously, or up to 3 h following MMC exposure. Heat enhanced the effect of MMC in both drug-sensitive and -resistant cells. Dose enhancement ratios increased from 1.3-2.0 at 42 degrees C to 2.6-3.8 at 43.5 degrees C and were similar for all cell lines. Cellular uptake of MMC was determined by high pressure liquid chromatography. MMC uptake was similar in the drug-sensitive and -resistant cell lines at 37 degrees C. Hyperthermia (43.5 degrees C) increased cellular uptake of MMC by 78 and 27% in MMC-sensitive and -resistant cell lines. MMC-resistant cells were more sensitive to heat alone at 42, 43, and 44 degrees C. The results suggest that tumor cells that have developed resistance to MMC might be treated effectively with MMC combined with heat to augment the response to MMC. Resistance to MMC may also render tumor cells more sensitive to hyperthermia.

Animals↗

Effect of drug exposure duration and sequencing on hyperthermic potentiation of mitomycin-C and cisplatin.

The effects of drug exposure duration and of heat and drug sequencing on hyperthermic potentiation of mitomycin-C (MMC) and cisplatin (DDP) were studied. Heating for 1 h at 42 degrees C was combined with drug exposure times of 1, 2, 4, or 8 h. For both DDP and MMC, hyperthermic potentiation was greatest when heating was done during drug exposure. Dose enhancement ratios for both drugs at 1% survival were highest with the shortest drug exposure times and decreased as the drug exposure time increased from 1 to 8 h. For DDP, the dose enhancement ratio decreased from 1.9 with a 1-h drug exposure to 1.2 with an 8-h drug exposure. For MMC, the dose enhancement ratio decreased from 1.8 to 1.5 as the drug exposure duration was increased from 1 to 8 h. Our results suggest that thermochemotherapy in vivo is likely to be most effective with rapid infusions of DDP or MMC.

Animals↗

Effect of cisplatin resistance on cellular radiation response.

Cisplatin-resistant tumors of the head and neck are generally resistant to irradiation. To determine whether the association between cisplatin (DDP) resistance and radiation resistance is a cellular phenomenon, we developed DDP-resistant Chinese hamster fibroblasts and studied their response to radiation. DDP resistance did not confer cross resistance to radiation. DDP-resistant cells did not demonstrate altered ability to repair sublethal or potentially lethal radiation damage. However, an isodose concentration of DDP did not inhibit repair of radiation damage in drug-resistant cells as readily as it did in drug-sensitive cells. The results suggest that cross resistance of tumors between DDP and radiation may be a result of the tumor microenvironment, rather than being a cellular phenomenon. Additionally, DDP may not inhibit the repair of radiation damage in DDP-resistant tumors.

Animals↗

Efficacy of irradiation for incompletely excised acoustic neurilemomas.

The records of 124 patients treated for acoustic neurilemoma at the University of California, San Francisco, from 1945 through 1983 were reviewed. Patients were classified by the extent of surgical resection: total, nearly total (90% to 99% resection), subtotal (less than 90% resection), or biopsy. Thirty-one patients received irradiation as part of their primary treatment. Total resection of tumor, without irradiation, was associated with a 3% chance of local recurrence. One of 15 patients who had nearly total resection of their tumor and did not receive postoperative irradiation suffered a recurrence, compared with neither of the two patients who received postoperative irradiation (greater than 45 Gy) following nearly total resection. Postoperative irradiation (greater than 45 Gy) decreased the recurrence rate after subtotal resection from 46% (six of 13 cases without irradiation) to 6% (one of 17 cases: p = 0.01). All three patients treated by biopsy alone received postoperative irradiation (greater than 45 Gy), and none had a recurrence. Six patients were treated with preoperative irradiation because of excessive tumor vascularity; four are without evidence of disease 12 to 23 years later. Only three of seven patients treated with irradiation for tumor recurrence after surgical resection survived. It is concluded that postoperative irradiation significantly decreased the chance for local tumor progression following subtotal resection of acoustic neurilemoma, and that postoperative irradiation may be effective therapy following treatment by biopsy. Patients with total or nearly total resection appeared not to benefit from postoperative irradiation.

Adolescent↗

Retreatment of pediatric brain tumors with radiation and misonidazole. Results of a CCSG/RTOG phase I/II study.

Twenty-nine patients with recurrent pediatric brain tumors after full-dose treatment with radiation were retreated with misonidazole (9 gm/m2) and whole-brain irradiation (300 rad X 10). Seventeen of 29 patients (59%) experienced nausea and vomiting with misonidazole administration and 6 patients (21%) developed peripheral neuropathy. Serum levels of misonidazole were similar to those reported for adults. One patient died of trauma shortly after retreatment. For the remaining 28 patients, the median time-to-progression was 5.5 months. Median survival was 13 months. Six patients (21%) developed radiation toxicity, two of whom died from the toxicity. Whereas the results on this study are similar to reported series of patients receiving salvage chemotherapy for recurrent pediatric brain tumors, more effective treatment clearly is needed.

Adolescent↗

Intracranial ependymomas: results of treatment with partial or whole brain irradiation without spinal irradiation.

Twenty patients with intracranial ependymoma (16) or anaplastic ependymoma (4) received post-operative radiation therapy at the University of California, San Francisco from 1959 through 1981. No patient received prophylactic spinal irradiation. The actuarial survival at 5, 10, and 15 years for 15 patients with ependymoma who received greater than 45 Gy was 67, 57, and 46%, respectively. Only one patient (7%) developed clinically recognized spinal metastases; this patient was eventually shown to have tumor at the primary site, within the irradiated volume. Six of 11 patients treated with partial brain irradiation had an intracranial recurrence, versus 1 of 4 patients treated with whole brain irradiation. Three patients were autopsied after failing partial brain irradiation for an ependymoma and the site of failure was within the irradiated volume of each patient. Partial brain irradiation was used to treat 4 patients with anaplastic ependymoma. One developed a local recurrence within the irradiated volume. The other three survived longer than 10 years. At UCSF, most patients with low grade ependymomas are presently treated with partial brain irradiation, but whole brain plus spinal irradiation is used for anaplastic tumors.

Adolescent↗

Hyperthermic potentiation of cis-diamminedichloroplatinum(II) cytotoxicity in Chinese hamster ovary cells resistant to the drug.

The cytotoxic and pharmacological properties of hyperthermia and cis-diamminedichloroplatinum(II) (DDP) were studied in DDP-sensitive and DDP-resistant Chinese hamster ovary cells in vitro. Cytotoxicity was measured by cell survival using colony formation assay and cellular platinum levels were determined by atomic absorption spectrophotometry. Hyperthermia potentiated DDP cytotoxicity in both DDP-sensitive and DDP-resistant Chinese hamster ovary cells. Dose enhancement ratios increased from 1.4 to 6.5 over the temperature range of 39-43 degrees C. Cellular accumulation of platinum at 37 degrees C in the sensitive cells was 2.3- to 3.3-fold greater than that in the drug-resistant cells. Cellular accumulation of DDP was increased by factors of 1.5 and 2.2 at elevated temperature. DDP resistance did not confer cross-resistance to heat alone. The results suggest that hyperthermia could be used to circumvent DDP resistance.

Animals↗

Squamous cell carcinoma of the head and neck after radiation therapy for Hodgkin's disease. A report of two cases and a review of the literature.

Squamous cell carcinoma (SCC) of the head and neck developed in two patients 12 and 22 years, respectively, after radiation treatment for Hodgkin's disease (HD). Both tumors arose in previously irradiated fields. Sixteen reported cases of SCC of the head and neck occurring after treatment for HD are summarized. Details of treatment were lacking in most instances. The authors suspect that cases similar to the two reported here will be seen more frequently with longer follow-up of patients cured of HD.

Adult↗