Biomedical subjects
A B Levin
Publications and source records attributed to A B Levin.
A multiinstitutional outcome and prognostic factor analysis of radiosurgery for resectable single brain metastasis.
PURPOSE: Recent randomized trials of selected patients with single brain metastasis comparing resection followed by whole-brain radiotherapy (WBRT) to WBRT alone have shown a statistically significant survival advantage for surgery and WBRT. A multiinstitutional retrospective study was performed, which identified comparable patients who were treated with stereotactic radiosurgery (RS) and WBRT. METHODS AND MATERIALS: The RS databases of four institutions were reviewed to identify patients who met the following criteria: single-brain metastasis; no prior cranial surgery or WBRT; age > 18 years; surgically resectable lesion; Karnofsky Performance Status (KPS) > or = 70 at time of RS; nonradiosensitive histology. One hundred twenty-two patients were identified who met these criteria. Patients were categorized by: (a) status of the primary, (b) status of non-CNS metastasis, (c) age, (d) baseline KPS (from 70-100), (e) histology, (f) time from diagnosis of primary to the detection of the brain metastasis, (g) gender, and (h) tumor volume. RS was performed with a linear accelerator based technique (peripheral dose range was 10-27 Gy, median was 17 Gy). WBRT was performed in all but five patients who refused WBRT (dose range was 25-40 Gy, median was 37.5 Gy). RESULTS: The median follow-up for all patients was 123 weeks. The overall local control rate (defined as lack of progression in the RS volume) was 86%. Intracranial recurrence outside of the RS volume was seen in 27 patients (22%). The actuarial median survival from date of RS is 56 weeks, and the 1-year and 2-year actuarial survival rates are 53% and 30%. The median duration of functional independence (sustained KPS > or = 70) is 44 weeks. Nineteen of 77 deaths were attributed to CNS progression (25% of all deaths). Multivariate analysis revealed the following factors to be statistically significant predictors of survival: baseline KPS (p < .0001) and absence of other sites of metastasis (p = 0.008). CONCLUSION: The RS in conjunction with WBRT for single brain metastasis can produce substantial functional survival, especially in patients with good performance status and without extracranial metastasis. These results are comparable to recent randomized trials of resection and WBRT. The advantages of RS over surgery in terms of cost, hospitalization, morbidity, and wider applicability strongly suggest that a randomized trial to compare RS with surgery is warranted.
Radiosurgery in the initial management of malignant gliomas: survival comparison with the RTOG recursive partitioning analysis. Radiation Therapy Oncology Group.
PURPOSE: To evaluate the impact of stereotactic radiosurgery on the survival of patients treated with malignant gliomas. METHODS AND MATERIALS: A total of 115 patients from three institutions (75 from the Joint Center for Radiation Therapy, 30 from the University of Wisconsin, and 10 from the University of Florida) were treated with a combination of surgery, external beam radiation therapy, and linac-based radiosurgery as part of similar institutional protocols from March 1988 through July 1993. Patients were stratified into six prognostic classes (classes 1-6) based on the recursive partitioning analysis of multiple prognostic factors previously reported by the Radiation Therapy Oncology Group. RESULTS: The actuarial 2-year and median survival for all patients analyzed was 45% and 96 weeks, respectively. In comparison to the results from a previously published analysis of 1578 patients entered on three Radiation Therapy Oncology Group external beam radiotherapy protocols from 1974 to 1989, those patients treated with radiosurgery had a significantly improved 2-year and median survival (p = 0.01) corresponding with a standardized mortality risk ratio of 0.51 [95% confidence interval (CI): 0.31, 0.85]. This improvement in survival was seen predominantly for the worse prognostic classes (classes 3-6). The 2-year survival for the radiosurgical patients compared with the previously reported patients was 81% vs. 76% for classes 1/2, 75% vs. 35% for class 3, 34% vs. 15% for class 4, and 21% vs. 6% for classes 5/6, respectively. Although Karnofsky performance status and prognostic class were significant on univariate analysis, only the Karnofsky score was a significant predictor of outcome on multivariate analysis. Median and 2-year survival for patients with a Karnofsky score > or = 70 was 106 weeks and 51%, respectively, as compared to 38 weeks and 0% for patients with a Karnofsky score < 70% (p = 0.001). CONCLUSIONS: The addition of radiosurgery to conventional treatment (surgery and external beam radiotherapy) of malignant gliomas appears to improve survival when compared to historical reports. These results should be interpreted with caution because the recursive partitioning model does not completely predict the prognosis of the patients treated in the present study. Although this study suggests that radiosurgery may prolong survival in patients with malignant gliomas, the role of radiosurgery in the management of these patients remains to be defined by a prospective randomized trial.
Complications associated with infusion pumps implanted for spasticity.
Implanted infusion pumps are an effective method for delivering medications into the intrathecal space to reduce spasticity. Complications can occur with the surgical aspect of implantation, as well as with the hardware. We describe an 8-year experience with the implantation of 34 infusion pumps in 30 patients in whom either morphine or baclofen was used to control spasticity. The overall incidence of total complications was 62%; 24% in the Infusaid pumps, and 167% in the Medtronic pumps. The incidence and types of complications are important in informed consent as well as in the selection of pumps and connectors.
Stereotactic radiosurgery for glioblastoma: a final report of 31 patients.
From February 1989 to December 1992, 31 patients who presented with an initial pathological diagnosis of glioblastoma multiforme underwent tumor debulking or biopsy, stereotactic radiosurgery, and standard radiation therapy as part of their primary treatment. Presenting characteristics in the 22 men and nine women included a median age of 57 years, Karnofsky Performance Scale score median of 80, and median tumor volume of 16.4 cm3. Stereotactic radiosurgery delivered a central dose of 15 to 35 Gy with the isocenter location, collimator size, and beam paths individualized by means of three-dimensional software developed at the University of Wisconsin. The peripheral isodose line varied from 40% to 90% with a median of 72.5% and a mode of 80%. The mean follow-up period was 12.84 months with a median of 9.5 months. Statistical analysis was performed using Kaplan-Meier analysis and log-rank comparison of risk factor groups. The parameters of age, initial Karnofsky Performance Scale score, and biopsy were significantly different in patient survival from debulking; but no difference was noted between single and multiple isocenters and patterns of steroid requirement. Radiographic recurrences were divided by location into the following categories: central (within central stereotactic radiosurgery dose), 0; peripheral (within 2 cm of central dose), 19; and distant (> 2 cm), 4. There is no evidence of recurrence in five surviving patients. Actuarial 12-month survival was 37%, with a median survival of 9.5 months. These values are similar to previous results for surgery and standard radiotherapy alone. The results suggest that the curative value of radiosurgery is significantly limited by peripheral recurrences.
Stereotactic radiosurgery for glioblastoma multiforme.
From February 1989 to August 1992, 26 patients who presented with an initial pathological diagnosis of glioblastoma multiforme underwent tumor debulking (17) or biopsy (9), stereotactic radiosurgery (SR) and standard radiation therapy (dose range 50-66 Gy) as part of their primary tumor therapy. Presenting characteristics included median age of 55 years (range 20-79), Karnofsky Performance Score (KPS) median 82.5 (20-100), and median tumor volume 18.6 cm3 (2.2-59.7). SR collimator size ranged from 2.25 to 4 cm with a central dose of 15-35 Gy. Isocenter location, collimator size and beam paths were individualized using three-dimensional software such that the maximum possible solid angle was subtended without exceeding a 20% tumor dose gradient. The mean follow-up was 10.9 months (6-19.5) with a median of 9.5 months. Statistical analysis was performed using Kaplan-Meier actuarial analysis developing predicted 12-month survival rates. There were no significant differences noted in patient survival for the parameters of biopsy versus debulking, single versus multiple isocenters, age, initial KPS, and patterns of steroid requirement. Radiographic recurrences were divided by location into central (within central SR dose) = 0, peripheral (within 1 cm of central dose) = 16, and distant (< 1 cm) = 4. Predicted 12-month survival was 24%, with a median survival of 9.5 months. These values are similar to previous results for surgery and standard radiotherapy alone [1]. The results suggest that radiosurgery, when used as a mode of primary therapy, offers little or no benefit in quality of life or survival as recurrences occur immediately outside or distant to the central SR field.
Defining the role of radiosurgery in the management of brain metastases.
The role of stereotactic radiosurgery in the management of recurrent and newly diagnosed brain metastases was evaluated prospectively. From December 1988 to March 1991, 58 lesions in 40 patients were treated with accelerator-based stereotactic radiosurgery. All patients were followed for a minimum of 6 months or to death. The primary purpose was to determine the impact of radiosurgery on local control and its subsequent effects on quality of life. An overall tumor control rate of 82% with a complete response rate of 43% were achieved. As anticipated, the response rate for smaller tumors was substantially better than that for larger tumors (78% for lesions < 2 cm3; 50% for lesions > or = 10 cm3). Although the overall in-field progression rate was 18.5%, only 1/23 (4%) complete responders subsequently recurred. The in-field failure rate is highly comparable with recently published surgical data. Progression outside the brain was noted in two-thirds of patients. One quarter of the deaths were neurologic. The median survival for this minimally selected patient population was 6.5 months. Stereotactic radiosurgery was also associated with improved quality of life as measured by Karnofsky score, neurologic function, and steroid dependence. Long-term steroid dependence was encountered in only four patients. We conclude that stereotactic radiosurgery can be used effectively in patients with brain metastases. In this series, a high tumor response rate was achieved which was associated with improved quality of life.
Early changes in tumor metabolism after treatment: the effects of stereotactic radiotherapy.
Four patients with intracranial neoplasms, two with malignant gliomas and two with brain metastases, were treated with stereotactic radiotherapy. Patients received between 15 and 27.5 Gray of photon irradiation to the central tumor target point; the 80% isodose line covered the periphery of the tumor as determined by contrast enhanced computed tomography. Patients underwent a sequence of three Positron Emission Tomographic scans using [18F]-fluorodeoxyglucose (PET-FDG)--a baseline scan the day before treatment, and follow-up scans 1 and 7 days after treatment. Ratios between the maximal tumor regional cerebral metabolic rate for glucose (rCMRGlu) (T*) and the contralateral remote white matter rCMRGlu (RW), that is, the glucose uptake ratio (T*/RW), were calculated. The percent change in ratios relative to each patient's baseline scan were calculated. Ratios increased 25% to 42% 1 day post-radiotherapy, then decreased to between 10% above and 12% below the baseline value 7 days post-radiotherapy. The T*/RW increased acutely after stereotactic radiotherapy in a fashion similar to that previously described following chemotherapy with a complex multi-drug regimen. A common metabolic pathway may underlie the increase in T*/RW after these different treatments.
Anterior plating of unstable cervical spine fractures.
Medical records and radiographs of 16 patients who had anterior decompression, bone grafting, and plating of grade III and IV (Allen 1982) unstable cervical spine injuries were reviewed. Surgery was performed within 15 days of injury, reductions were achieved and maintained at follow-up, and fusion occurred in all cases. Neurologic function stabilised or improved in all cases. However, 3 patients (19%) had complications that necessitated additional surgery: one patient with undiagnosed non-contiguous posterior instability, and 2 patients for broken plates. These complications, in retrospect, could have been avoided.
[Streptococcus pneumoniae serotypes in children with acute pneumonia and pleurisy].
The study of pneumococci of different serotypes, isolated from patients with acute pneumonia and pleuritis and from healthy children was carried out. Among the pneumococcal serotypes causing pneumonia and pleuritis in children serotypes 1, 6, 19, 14 and 3 were most widely spread and constituted 62.3% of all isolated pneumococci. In young children cases of acute pneumonia and pleuritis were more often induced by serotypes 6 and 14 and in older children, by serotypes 1 and 3. In patients with uncomplicated pneumonia and pleuritis differences in the detected serotypes of pneumococci were observed, and the disease course differed in severity. Serotypes 14, 3 and 3 induced destructive processes in the lungs more often than other serotypes. Monitoring of the sensitivity of pneumococci to antibiotics showed that most of the strains retained high sensitivity to penicillin and ampicillin. In most cases the detected resistant pneumococcal strains belonged to serogroup 19.
"Eight-drugs-in-one-day" chemotherapy administered before and after radiotherapy to adult patients with malignant gliomas.
Thirty-one adult patients with malignant glioma (23 with glioblastoma multiforme, six with anaplastic astrocytoma, and two with brainstem glioma) were treated with up to ten cycles of "eight-drugs-in-one-day" chemotherapy (methylprednisolone 300 mg/m2, vincristine 1.5 mg/m2 [maximum of 2 mg/cycle], CCNU 75 mg/m2, procarbazine 75 mg/m2, hydroxyurea 3000 mg/m2, cisplatin 90 mg/m2, cytosine arabinoside 300 mg/m2, and imidazole carboxamide 150 mg/m2). Chemotherapy was planned as two cycles before and eight cycles after 60 Gy of involved brain irradiation. A total of 117 cycles of chemotherapy was administered. There was one treatment-related death. Myelosuppression was the most frequent toxic effect (leucopenia was less than 1000/mm3 in 9% of cycles and 1000-2500/mm3 in 25%; thrombocytopenia was less than 100,000/mm3 in 33% of cycles). Sixteen patients developed infections requiring treatment, two of which were life-threatening. Five patients suffered ototoxicity. Nausea and vomiting were observed in 35% of patients. A reversible rise in creatinine was observed in five patients. One patient developed a severe motor neuropathy, and three patients developed mild peripheral neuropathies. Three patients had episodes of atrial fibrillation. One new bundle branch block with supraventricular tachycardia was observed in a patient with pulmonary embolus. Five patients developed thrombophlebitis, three of whom had pulmonary emboli. Two patients suffered strokes in areas anatomically separate from their tumor. Eleven patients declined to continue therapy after receiving an average of three cycles. Two had complete, and five had partial responses. The median survival time was 47 weeks. The responses and survival times observed are comparable to less toxic treatment protocols for adults with malignant gliomas.
Eight-drugs-in-one-day chemotherapy in postirradiated adult patients with malignant gliomas.
Fifteen patients, 12 with glioblastoma multiforme and 3 with anaplastic astrocytoma, were treated with "eight-drugs-in-one-day" chemotherapy [methylprednisolone 300 mg/m2, vincristine 1.5 mg/m2 (maximum of 2 mg/cycle), CCNU 75 mg/m2, procarbazine 75 mg/m2, hydroxyurea 3,000 mg/m2, cisplatin 90 mg/m2, cytosine arabinoside 300 mg/m2, and imidazole carboxamide 150 mg/m2]. All patients had prior brain irradiation but none had previous chemotherapy. The population included 10 patients with progressive disease after irradiation and 5 who presented within 2 months of completing radiation. Patients received an average of 5 monthly cycles of chemotherapy. Three patients achieved a complete and 2 a partial response (CR + PRrate was 33%). The median survival time was 46 weeks. Myelosuppression was the dose-limiting toxicity. Leucocyte counts between 2.0-4.5 x 10(3)/mm3 were observed in 40% of patients, between 1.0- less than 2.0 x 10(3)/mm3 in 33%, and less than 1.0 x 10(3)/mm3 in 7%. Platelet counts between 50-130 x 10(3)/mm3 were observed in 27% of patients, and less than 50 x 10(3)/mm3 in 33%. Six patients suffered infections, 4 had reversible renal toxicity, 2 developed paresthesias, and one a debilitating myopathy related to treatment with dexamethasone. Ototoxicity was seen in 3 patients. Two patients developed pulmonary emboli. Nine patients had nausea and vomiting, in one case associated with Candida esophagitis. One long-term survivor developed necrosis of the corpus callosum and dementia. Four patients discontinued treatment after an average of 3.5 cycles because of toxicity. Although extremely toxic, this regimen has modest activity in previously irradiated adult patients with malignant glioma.
Role of corticosteroids in the development of pneumonia in mechanically ventilated head-trauma victims.
The development of pneumonia was monitored in head-trauma patients requiring mechanical ventilation. Of the 66 patients studied, 15 (23%) developed pneumonia within 14 days after ICU admission. In each case the diagnosis was based on x-ray evidence and at least two of the following: increased white blood cell count, increased fever, and/or increased sputum production with a predominant organism on the sputum stain. Coagulase-positive Staphylococcus aureus was the most common etiologic agent. There was no difference in the occurrence of pneumonia between patients treated with no steroids or with low, moderate, or high steroid doses. Although there was an association between thiopental use and the development of pneumonia, dexamethasone treatment was not a significant risk factor in the development of pneumonia in this patient population.
[Fucidin in the surgical treatment of acute suppurative destruction of the lungs in children].
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[Acute suppurative destructive pneumonias in children].
Their experience with the observation of 1112 children with acute purulent destructive pneumonias allowed the authors to considerably improve the method of complex curative-diagnostic measures which resulted in lower lethality among this critical contingent of patients and better remote results of their treatment.
Experience in the first 100 patients undergoing computerized tomography-guided stereotactic procedures utilizing the Brown-Roberts-Wells guidance system.
A series of 100 patients undergoing CT-guided stereotactic procedures for biopsy and/or drainage (n = 87), deep brain electrode placement (n = 9), endoscopy (n = 1), and functional lesioning (n = 3) was reviewed. Only 1 patient required general anesthesia. There were 4 procedural related hematomas, only 1 of which was symptomatic. No other complications were encountered.
A new approach in epidural intracranial pressure monitoring.
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Pain relief after hypophysectomy.
Thirteen series of patients who underwent surgical or chemical hypophysectomy for the relief of pain associated with cancer were reviewed. In 10 series, involving 334 patients with breast or prostate cancer, surgical hypophysectomy produced pain relief in 70% of the patients afflicted with either tumor, including some with no evidence of hormone dependence. These results were then compared with the results of chemical hypophysectomy. This procedure was performed in 3 series involving 533 patients, of whom 24% had cancer other than breast or prostate. Chemical hypophysectomy produced pain relief in over 75% of the patients, regardless of tumor type or hormonal dependence. The possible role of the pituitary, the hypothalamus, and endogenous opiates in mediating the pain relief associated with hypophysectomy was examined. The mechanism by which pain relief is achieved remains unclear, but there is significant evidence that this relief is not related directly to the expected fall in the levels of known pituitary hormones. Evidence is provided that pain relief is the result of a hypothalamic pain-suppressing capability triggered by hypophysectomy. On the basis of both clinical data and the mechanism of action, we conclude that surgical and chemical hypophysectomy are fundamentally similar procedures.