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Biomedical subjects

V Levin

Publications and source records attributed to V Levin.

At least 19 recordsLinked to original sources

The treatment of recurrent unresectable and malignant meningiomas with interferon alpha-2B.

OBJECTIVE: Recurrent malignant meningiomas and unresectable meningiomas represent a great therapeutic challenge after the failure of radiation therapy. No effective chemotherapy has been found. We report the preliminary results of the treatment of patients with recurrent unresectable or malignant meningiomas with recombinant interferon alpha-2B (IFN-alpha-2B). METHOD: Each of six patients with either a recurrent malignant meningioma or an unresectable meningioma was treated with IFN-alpha, administered subcutaneously at a dosage of 4 mU/m2 per day, 5 days per week. Two of the six meningiomas were regular, one was atypical, and three were malignant. RESULTS: Five of six patients exhibited positive response to treatment; with stabilization of the size of the tumor in four patients and slight regression in one. The responses observed lasted from 6 to 14 months. The toxicity associated with prolonged use of IFN-alpha was mild and well tolerated. CONCLUSION: These results suggest that IFN-alpha is effective in the treatment of recurrent malignant meningiomas.

Adult

Morphologic alterations in esophageal squamous cell carcinoma after preoperative high dose rate intraluminal brachytherapy.

BACKGROUND: Total esophagectomy specimens from 4 patients given preoperative high dose rate intraluminal brachytherapy (HDRILBT) of 20 Gray (GY) in 2 fractions of 10 Gy each week were reviewed for radiation changes. METHODS: In all patients, preoperative biopsy specimens showed moderate to poorly differentiated squamous cell carcinoma with minimal to negligible keratin production. The esophagectomy specimens were sampled at the resection margins, the edge of irradiated length, 1 cm from the proximal and distal edge of visible tumor, the center of the tumor, and the lymph nodes. RESULTS: Radiation change in the form of fibrosis was limited to the submucosa at the resection margins, the circular muscle layer at the edge of irradiated length, and full thickness at 1 cm from the edge of the visible tumor and the center of the tumor. Surface epithelium did not show any changes at the resection margins but did show basal cell hyperplasia at the edge of the irradiated length and ulceration at 1 cm from the edge of the visible tumor and the center of the tumor. Endarteritis obliterans was seen only 1 cm from the edge of the visible tumor and the center of the tumor. Necrosis, intense keratin formation, and giant cell reaction were observed at the center of the tumor. When compared with the preradiotherapy biopsies, the amount of keratin in the postradiotherapy specimens was extensive. HDRILBT may cause induction of the keratin gene in the irradiated cells to stimulate differentiation toward better differentiated cells. CONCLUSIONS: HDRILBT may cause the keratin gene in the irradiated cells to induce differentiation toward better differentiated cells. Preoperative high dose rate intraluminal brachytherapy may have a role in improving the prognosis of patients with early esophageal cancer treated with a combination of radiotherapy and surgery.

Adult

Toxicity in patients with testicular seminoma treated with radiotherapy. Different dose levels and treatment fields.

The aim of this study was to evaluate the acute and late effects of irradiation in 56 patients with stage I and II testicular seminomas. A retrospective study of patients' records was performed paying attention to the acute and late toxicity of radiation in relation to treatment fields and radiation doses. Treatment groups were compared using the chi squared-test. Mild to moderate nausea and/or vomiting was seen in 66% of patients and occurred equally independent of the treatment volume or radiation dose. Increased bowel frequency was seen in 59% and was more common when a larger treatment volume was used. Skin reactions increased with increase in treatment volume and dose (p = 0.046). Severe late complications were recorded in two patients (myocardial damage-1/4 at risk, duodenal ulcer-1/56 at risk). These could not be attributed solely to the irradiation as other contributing factors might play a role. Overall the data suggest that the risk of major posttreatment morbidity is minimal for patients with testicular seminoma treated with postoperative radiotherapy.

Acute Disease

Initial experience with telebrachytherapy treatment in palliation of advanced oesophageal cancer.

Ten patients with advanced metastatic squamous cell carcinoma of the middle third of the oesophagus were treated with palliative external radiotherapy and intraluminal brachytherapy. All patients had long lesions, 8-15 cm in length, and narrow lumens that did not allow the passage of a guidewire for dilatation. Improvement in dysphagia by more than 2 grades was seen in 9 of 10 patients. This finding was correlated with an increase in the size of the oesophageal lumen at the end of 6 weeks following treatment by barium swallow. No complications of treatment were noted in any patient. Low doses of external beam radiotherapy and high-dose-rate intraluminal brachytherapy can provide quick and effective palliation in advanced metastatic oesophageal carcinoma.

Adult

Fertility in patients treated with radiotherapy following orchidectomy for testicular seminoma.

This study evaluated the effect of paraaortic and ipsilateral pelvic node irradiation on the fertility of a group of 50 patients with Stage I and II testicular seminoma. Eleven patients were infertile before the start of treatment, and another 23 were unable or unwilling to father a child after radiotherapy. From the remaining 16 patients, 11 pregnancies resulted. It has been shown that fertility can be preserved if the dose to the remaining testis can be reduced to less than 2 Gy. No genetic abnormalities were seen in the offspring of any patient.

Adult

Radiotherapy of aggressive fibromatosis.

The long term results of 24 patients treated with postoperative irradiation for aggressive fibromatosis are presented. Tumour sites were the pelvis (8), chest wall (5), shoulder (5), extremities (4) and head and neck (2). Macroscopic complete resection (R1) was performed in 3 cases. 17 patients presented postoperatively with gross disease (R2), 8 of which were recurrent tumours. 4 patients with inoperable disease had biopsies only. Radiation doses ranged from 28 to 64 Gy at a fractionation of 5 x 2 or 4 x 2.5 Gy/week. 4 patients had external irradiation in combination with 192Ir implants, 2 were irradiated with implants alone. In the combined treatment group, external doses ranged from 28 to 52 Gy and additional interstitial doses from 35 to 50 Gy. 192Ir treatment alone was given with 45 and 57 Gy to the contour of the target volume. The 10 year recurrence free survival rate is 75%. A dose response relationship has been established in the dose range of 30-60 Gy revealing an expected 80% persistent tumour control rate at 60 Gy. A dose volume relationship however, could not be derived from our data. Moderate fibrosis without functional impairment developed in 5 patients (21%). These data support a policy of postoperative radiotherapy with 60 Gy in patients with incompletely excised or gross residual tumour following surgery.

Adolescent

The role of neutrons in the treatment of soft tissue sarcomas.

Two-hundred twenty-one patients with soft tissue sarcoma were treated from 1978 to 1983. Treatment was nonrandomized and consisted of neutron irradiation in 94 cases with gross tumor. Treatment was nonrandomized and consisted of neutron boost irradiation after photon-irradiation or electron-irradiation in 127 cases with no gross tumor after surgery. Patient distribution according to UICC (1978) criteria was 15, 100, and 106 of T1, T2, and T3 respectively. Distribution by pathologic grade was 54, 107, and 60 for Grade 1, Grade 2, and Grade 3 tumors. Distribution by tumor residuum after surgery was 23 cases without microscopic disease (R0), 104 with microscopic disease (R1), and 94 with gross residuum (R2) or nonoperative disease. Five-year follow-up reveals a significant difference (P = 0.024) in disease-free survival (DFS) for T1 (60%), T2 (71%), and T3 (29%, P = 0.016) tumors. Similarly, there are significant DFS differences among G 1 (74%), G 2 (48%, P = 0.035), and G 3 lesions (22%, P = 0.024). The impact of tumor bulk or residuum on DFS after operation is significant when comparing R0 (87%) and R1 (65%) disease (P = 0.042). The 5-year survival of patients who had gross residuum (R2) after surgery was significantly worse (26%, P = 0.003). Ninety percent of patients failed treatment locally and distally within 2 years. The late morbidity rate was 27% for neutron and 7% for neutron-boost irradiation. In our series and reported photon data, local control rates for tumors 5 to 10 cm with neutrons were 76% and 53%, respectively. Low energy (d(14) + Be) neutrons are considered beneficial in the postoperative treatment of well-differentiated soft tissue sarcomas where gross tumor remains. Neutron-boost irradiation is of potential benefit in the treatment after operation of T2-3, and G 1-2 tumors if there is microscopic residual tumor.

Adult

Treatment of recurrent gliomas with 1,3-bis(2-chloroethyl)-1-nitrosourea and alpha-difluoromethylornithine.

Thirty-eight patients with primary recurrent anaplastic gliomas and glioblastomas, were treated with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and the polyamine inhibitor alpha-difluoromethylornithine (DFMO). There were 5 brain stem, 1 cerebellar, and 32 supratentorial glioma tumors. All had been treated with surgery (except in the case of 4 brain stem tumors for which biopsies were not obtained) and radiotherapy. Eight patients had received prior chemotherapy. Of the 21 patients with evaluable supratentorial anaplastic gliomas, 2 (9.5%) had a partial response and 10 (47.6%) had stable disease. The median time to tumor progression for the anaplastic gliomas has not been attained yet. However, median survival for these 12 patients was 119 weeks measured from the initiation of chemotherapy. Median survival for the entire anaplastic glioma group of 21 was 56 weeks. Minimal activity was seen against glioblastoma multiforme. The median time to tumor progression was 8 weeks with median survival of 21 weeks. Of the 5 patients with brain stem tumors, 3 are alive with stable disease at 77, 93, and 220 weeks. The combination was well tolerated with dose-limiting toxicity being myelosuppression and hearing loss. Further trials are warranted to compare the combination of BCNU and DFMO against BCNU alone in a prospective randomized trial.

Antineoplastic Combined Chemotherapy Protocols

Neuronal cell differentiation of human neuroblastoma cells by retinoic acid plus herbimycin A.

We investigated the effect of retinoic acid (RA) and herbimycin A (herb-A) on cell growth, cell differentiation, and colony formation of human neuroblastoma cell lines. The neuroblastoma line SK-N-SH expressed both neuroblast and nonneuronal phenotypes, whereas its subclone SH-SY5Y and the Kelly cell line were predominantly neuroblastic. Both herb-A and RA, given alone, moderately reduced cell growth and colony formation of the neuroblastic cell lines. Growth curve analyses with SK-N-SH suggested that herb-A greatly reduced the number of initially growing cells, whereas RA slightly enhanced initial cell growth. Morphological changes were determined with the use of rhodaminephalloidin staining of actin. Retinoic acid caused an increase in the fraction of neuroblast cell in SK-N-SH, and conversely of nonneuronal cells in SH-SY5Y and Kelly cell lines. Both drugs also caused partial differentiation towards a neuronal phenotype, and herb-A induced selective lysis of nonneuronal cells of SK-N-SH. Because of their discrepant effects, RA (10 microM) and herb-A (236 nM) were tested in combination at a concentration that had only moderate effects when given alone. The combination further reduced cell growth and colony formation and dramatically enhanced differentiation towards a neuronal morphology. The Kelly cell line with amplified N-myc genome, which correlates with clinical progression of neuroblastoma, was also sensitive to RA plus herb-A. These results recommend the combination of RA and herb-A for differentiation therapy of neuroblastoma.

Anti-Bacterial Agents

Treatment of recurrent brain stem gliomas and other central nervous system tumors with 5-fluorouracil, CCNU, hydroxyurea, and 6-mercaptopurine.

Twenty-one patients with recurrent malignant central nervous system gliomas were treated with a combination of 5-fluorouracil, CCNU, hydroxyurea, and 6-mercaptopurine. Thirteen patients had brain stem gliomas, 3 patients had spinal cord gliomas, 3 patients had thalamic gliomas, and 2 patients had cerebellar astrocytomas. All patients had received radiation therapy, and 4 brain stem patients had also been treated with chemotherapy. Sixteen patients (76%) responded to treatment with either stabilization of disease or improvement. Nine of the 13 patients with brain stem gliomas (71%) had response or stabilization of disease. The median time to tumor progression (TTP) for the brain stem patients who responded or had stabilization of disease was 25 weeks. The median survival from recurrence for the brain stem glioma patients was 27 weeks. Patients with cerebellar, thalamic, and spinal cord tumors did very well, with an 87% response or stabilization of disease and a median TTP of 122 weeks.

Adolescent

Malignant supratentorial gliomas in childhood.

In this review, we try to review concisely the incidence, genetic predilections, classification, and diagnosis of supratentorial gliomas (astrocytomas, oligodendrogliomas, and mixed gliomas) in children. While surgery and irradiation present the most commonly used and valuable modes of treatment, chemotherapy is a valuable adjunctive therapy. Used either with surgery and radiation in primary untreated patients or at recurrence (progression), chemotherapy can increase useful life. The late effects of treatment are primarily endocrine deficiencies and intellectual impairment; nevertheless, they are not of a degree to preclude aggressive therapy. In order to improve therapy, and because of the small number of patients with supratentorial tumors, collaborative multi-institutional trials should be encouraged.

Adolescent