Factors influencing survival after gamma knife radiosurgery for patients with single and multiple brain metastases

BACKGROUND: Significant changes are restructurng the U.S. health care delivery system. National health reform is now extending itself into the public sector. Increased health and medical costs by federal and state governments are forcing a reevaluation of major entitlement programs, especially Medicaid. METHODS/RESULTS: Because Medicaid is the single largest item in many state budgets, states are now enrolling Medicaid patients into managed and coordinated care arrangements as a means to control costs and increase access to care. HMOs are not only competing for private patients but also actively seeking the Medicaid population. Nationally, almost one-fourth of all Medicaid patients are now enrolled in managed care plans. Various models and approaches have been developed by individual states. CONCLUSIONS: Because managed care enrollment in the Medicaid program has increased substantially in recent years, selected services including vision care are no longer rendered by any practitioner willing to accept Medicaid fees. Freedom of choice is now restricted to pre-selected and panel practitioners participating with the managed care program. The rules, regulations, billing procedures, fees, and program requisites will differ under managed care programs. Private optometric practitioners must consider entering economic and organizational relationships and linkages that make them attractive to managed care organizations.     

Early effects of gamma knife radiosurgery on brain metastases: assessment by 201TlCl SPECT and 99mTc-DTPA-human serum albumin SPECT

Thallium-201 chloride (201TlCl) single photon emission computed tomography (SPECT) was used to determine tumor viability, and the early and delayed images of technetium-99m-diethylenetriaminepenta-acetic acid-human serum albumin (99mTc-HSA-D) SPECT were used to assess tumor vascularity and permeability, respectively, in 17 patients with 18 brain metastases. SPECT was performed before, 1 week after, and 1 month after radiosurgery. The ratios of 201Tl and 99mTc-HSA-D uptake in a tumor were expressed as a ratio to uptake in the corresponding normal contralateral areas (uptake index). Magnetic resonance imaging with gadolinium was used to determine tumor volume. 201Tl index decreased significantly 1 week (p < 0.05) and 1 month (p < 0.005) after radiosurgery. In contrast, 99mTc-HSA-D indices of early and delayed images obtained at 1 week after radiosurgery were not significantly different from the pretreatment values. However, both were significantly low (p < 0.05) 1 month after radiosurgery. No change in tumor volume was detected 1 week following radiosurgery, but there was a significant decrease (p < 0.005) after 1 month. The reduction in tumor viability that occurs before the appearance of evidence of tumor shrinkage represents the early effect of radiosurgery on brain metastases. Reduction in tumor size, vascularity, and permeability occur subsequently.     

Gamma-knife radiosurgery for metastatic brain tumors from primary lung cancer

INTRODUCTION: Improvements of the results of combined chemoradiotherapy (CRT) in esophageal cancer has led several groups to adopt a non surgical attitude specially in case of complete response (endoscopy +/- biopsy). Few information are available about the follow-up of these patients. We studied long-term results of 35 patients who underwent resection after complete response to preoperative chemoradiotherapy. PATIENTS AND METHODS: 161 patients with resecable carcinoma of the thoracic esophagus have received the same protocol of CRT (cisplatin 80 mg/m2, radiation therapy split course: 37.5 Gy) all patients were followed every for 4 months (no lost of view). RESULTS: Complete response (endoscopy and biopsy) was obtained for 35 patients (21.7%), 19 of them (54%) had pathologic complete response (PCR) (no tumor in the specimen), 16 have microscopic foci of residual tumor (46%). The overall 5-year survival rate was 49.8% for the whole group (median survival 64 months), 70% for the group without tumor in the specimen, 48% for the group with microscopic foci of residual tumor (NS). CONCLUSIONS: One half of the complete response (endoscopy + biopsy) have not a pathologic complete response (microscopic foci of residual tumor in the specimen). The 49.8% of five year survival suggests a benefit from esophagectomy for complete response after combined chemoradiotherapy.     

Profile of ambulatory radiosurgery with the gamma knife system. 1: Method and multicenter irradiation concept]

Radiosurgery represents a minimally invasive radiologic method for the treatment of intracranial tumours and arteriovenous malformations. In 1994 the radiosurgical device 'Leksell Gamma Knife' (LGK) was installed in a dedicated logistic environment for outpatient treatments. High quality requirements have to be met for radiosurgery. The target point accuracy taking into account the whole system was shown to be reliably below 0.5 mm whereas the spatial therapeutic resolution was 0.035 cm3. Quality parameters of the dose plan were evaluated for the first 500 consecutive treatments. These values and examples of dose plans were used to emphasize the advantages of the treatment principle with multiple isocenters. An analysis of data in the literature revealed that there is no uniform standard of treatment available in radiosurgery. A highly significant correlation between a risk prediction model for the stereotactic linear accelerator on the one hand and a different model for the LGK on the other could be shown. This result could be helpful in order to proceed towards a more uniform treatment standard in radiosurgery and to improve overall treatment results.     

Gamma knife radiosurgery and albendazole for cerebral alveolar hydatid disease

We measured pharyngeal mucosal pressures at six different locations on the laryngeal mask airway (LMA) and tested the hypothesis that the efficacy of the seal is not related to pharyngeal mucosal pressure. Twenty anesthetized, paralyzed adult patients were studied. Microchip sensors were attached to the size 5 LMA at locations corresponding to the lateral and posterior pharynx, the hypopharynx, the pyriform fossa, the base of tongue, and the oropharynx. Mucosal pressures and airway sealing pressures were recorded during inflation of the cuff from 0 to 40 mL in 10-mL increments. The highest mean mucosal pressure was in the oropharynx (26 cm H2O), and the lowest was in the posterior pharynx (2 cm H2O). Mucosal pressures increased with increasing intracuff pressure and cuff volume, but the rate of increase varied among locations. Airway sealing pressure increased with increasing intracuff volume from 0 to 10 mL (P < 0.0001) and 10 to 20 mL (P = 0.0001), was unchanged from 20 to 30 mL, and decreased from 30 to 40 mL (P = 0.005). The airway sealing pressure was higher than pharyngeal mucosal pressure until the intracuff volume was > or =30 mL. There was no correlation between mucosal pressures and airway sealing pressure at any location. We conclude that the efficacy of the seal is not related to pharyngeal mucosal pressure. Pharyngeal mucosal pressures are generally lower than those considered safe for the tracheal mucosa during prolonged intubation. IMPLICATIONS: We measured pharyngeal mucosal pressures at six different locations on the laryngeal mask airway and showed that the efficacy of the seal is not related to pharyngeal mucosal pressure. Pharyngeal mucosal pressures are generally lower than those considered safe for the tracheal mucosa during prolonged intubation.     

Radiosurgical lesions in the normal human brain 17 years after gamma knife capsulotomy

OBJECTIVE: To our knowledge, this is the first long-term follow-up study of high-dose single-session irradiation to the human brain and provides new data concerning late tissue reactions after irradiation to small target volumes. The long-term lesional brain changes in 14 patients subjected to bilateral gamma knife capsulotomy for otherwise intractable anxiety disorders were retrospectively analyzed by magnetic resonance imaging. METHODS: The prototype gamma unit was used for the radiosurgical procedure, and the collimators provided rectangular cross-sectional fields with an anteroposterior diameter of 3 mm and a transverse diameter of 5 or 11 mm. Maximum target doses were 120 to 180 Gy. Magnetic resonance imaging was performed 15 to 18 years (mean, 17 yr) after treatment, and dose-volume histograms were calculated for the dose distributions. RESULTS: One patient had been irradiated twice on one side. In all but one of the remaining 27 targets, lesions with a volume of less than 100 mm3 were revealed by magnetic resonance imaging. The volumes of the lesions were confined within the volume corresponding to a minimum dose of approximately 110 Gy, with one exception. In one of three targets receiving a maximum dose of 120 Gy, no lesion was detected. There were no late radiation effects such as cyst formations, telangiectasias, hemorrhagic infarctions, or neoplasms. CONCLUSION: This investigation indicates that a minimum dose of 110 Gy, with the currently used 4-mm collimator, to the edge of the target volume is required to create a lesion. The results prove that gamma knife surgery can be used in functional neurosurgery for producing small permanent lesions in the normal human brain.     

Prognosis of brain tumors: epidemiology, survival time and clinical course

The purpose of this study is to investigate the thermophysiological significance of hydrophilic and hydrophobic properties of underwear materials under the influences of profuse sweating produced during severe exercise in the cold. Two kinds of underwear were used: two layers of cotton underwear with two-piece long-sleeved shirt and full-trousers (C), and two layers of polypropylene underwear with two-piece long-sleeved shirt and full-trousers (P). In addition, the subject put on a two-piece ski suit of 100% polyester including 100% polyester padding. Eight adult females volunteered as subjects in this study. The test was performed in a climatic chamber at an ambient air temperature of 2 degrees C and an air velocity of 0.26 m.s-1. The subject exercised on a cycle ergometer at an intensity of 65% maximal oxygen uptake for 30 min and followed by 60 min recovery. The major findings are summarized as follows: 1) The fall of rectal temperature tended to be greater in P during the recovery. 2) The absolute humidity of innermost layer and middle layer was significantly higher in C than in P during the recovery, but the absolute humidity of middle layer and outermost layer was significantly higher in P than in C during the exercise. 3) Clothing microclimate temperature of innermost at back was significantly higher in C during the exercise and recovery. 4) Metabolic heat production for last 30 min during recovery was significantly higher in P. 5) The degree of skin wettedness sensation and sweating sensation for whole body was significantly higher in P during the exercise. It was concluded that the slower evaporation behavior by absorbing of underwear material in the clothing system has a beneficial influence on thermophysiological responses during severe exercise and its recovery in the cold, although the differences were very small.     

Stereotactic radiosurgery for brain metastasis from renal cell carcinoma

The PRESAGE database is a collaborative resource for structural genomics. It provides a database of proteins to which researchers add annotations indicating current experimental status, structural predictions and suggestions. The database is intended to enhance communication among structural genomics researchers and aid dissemination of their results. The PRESAGE database may be accessed at http://presage.stanford.edu/     

The costs of radiosurgical treatment: comparison between gamma knife and linear accelerator

Radiosurgical treatment can be carried out by means of a Gamma Knife or a Linear Accelerator. The Linear Accelerator may be either a single-purpose appliance, exclusively employed in radiosurgery, or an adapted appliance, which is used primarily for fractioned radiotherapy, and only additionally for radiosurgical purposes. The first alternative will be referred to briefly as a "dedicated Linac", the latter as an "adapted Linac". Cost accounting data for these alternatives will be discussed under three main categories: investment costs, operating costs, and finally staffing costs. Costs are only considered to the extent that this is necessary to facilitate a comprehensive cost comparison. Factors for which the costs remain the same or at least broadly the same will from the outset not be taken into consideration. These include, for instance, the costs of general or special administration, diagnosis, and image processing. The results and conclusions of this study therefore cannot be employed immediately in the evaluation of cost reimbursement schemes of the type carried out by agencies responsible for social insurance. Here, appropriate complete cost analyses especially for this purpose are required. The final comprehensive cost comparison reveals that the adapted Linac is the most favourable alternative with small annual quantities of patients. With larger numbers of patients the Gamma Knife represents the most favourable from a cost accounting angle. The dedicated Linac accordingly does not have a cost advantage for any of the examined numbers of patients. Clearly the lowest treatment costs per patient can be achieved by employing a Gamma Knife and using it to capacity.     

Angiogenesis in brain tumors; pathobiological and clinical aspects

Angiogenesis is the outgrowth of new blood vessels from the preexistent vasculature. In 1971, Folkman hypothesized that solid tumors are dependent on angiogenesis for sustained growth and that anti-angiogenic treatment is a potential antineoplastic therapy. Because glioblastoma multiforma (GBM) frequently shows florid microvascular proliferation (MVP), this tumor has been considered since then as a suitable candidate for such treatment that attempts to eradicate or control a neoplasm by interfering with its blood supply. Indeed, in animal models the growth of glioma xenografts can be inhibited by targeting the angiogenic process. However, unlike many glioma xenografts, human infiltrating gliomas such as GBMs have a diffuse infiltrative growth pattern, and preexistent vessels may suffice to provide many tumor cells with much of their blood supply, particularly in the critical peripheral infiltrative margins. Thus, while attractive in concept, anti-angiogenic therapy of GBM must address the anatomic vascular realities of this neoplasm. Even if anti-angiogenic therapy ultimately has a role in infiltrative neoplasms, there are a host of other intracranial neoplasms whose discrete architecture might make them attractive candidates for anti-angiogenic therapy. This review summarizes the angiogenic process in GBM and suggests other types of tumors for which the efficacy of anti-angiogenic therapy might be studied.     

Chemotherapy for pediatric brain tumors

Advances have recently been made in the use of chemotherapy for pediatric brain tumors. Chemotherapy increases disease-free survival in high-risk primitive neuroectodermal tumor/medulloblastoma patients and enables the reduction of radiation therapy in standard-risk patients. Radiation can be significantly delayed and neurotoxicity ameliorated in many infants using chemotherapy. Chemotherapy can cause reduction in size of low-grade glioma, optic glioma, and oligodendroglioma. High-grade glioma and ependymoma are relatively chemoresistant. Physicians caring for children with brain tumors are encouraged to participate in controlled studies, so that objective information can be gathered and the role of chemotherapy in these tumors can be better defined.     

Interstitial brachytherapy procedures for brain tumors

This report characterizes the immunological host response to a syngeneic murine mammary carcinoma along with variants genetically modified to express B7-1 or secrete GM-CSF and interleukin-12 (IL-12). MT-901 is a subline of a mammary adenocarcinoma that was chemically induced in the Balb/c host. It was found to be weakly immunogenic by immunization/ challenge experiments, and it induced tumor-specific T-cell responses in lymph nodes (LN) draining progressive subcutaneous tumors. Tumor clones expressing B7-1 or secreting GM-CSF exhibited reduced tumorigenicity without completely abrogating tumor growth, whereas IL-12 elaboration lead to complete tumor growth inhibition. In vivo subcutaneous inoculation of a transgenic cell clone secreting GM-CSF (240 ng/10(6) cells/24 hours) resulted in significantly enhanced T-cell reactivity of tumor-draining lymph node (TDLN) cells as compared to wild-type TDLN cells. This finding was obtained from observations assessed by several different methods, including: 1) in vitro cytotoxicity, 2) in vitro interferon-gamma release, and 3) adoptive transfer in mice with established tumor. Moreover, the transfer of activated LN cells derived from mice inoculated with GM-CSF-secreting tumor cells resulted in the prolonged survival of animals with macroscopic metastatic disease, which was not evident utilizing LN cells from mice inoculated with wild-type tumor. By contrast, clones that expressed B7-1 or IL-12 (4 ng/10(6) cells/24 hours) did not elicit enhanced tumor-reactive TDLN cells compared with wild-type tumor when assessed in the adoptive transfer model. The autocrine secretion of GM-CSF by transduced tumor cells was found to serve as an effective immune adjuvant in the host response to this weakly immunogenic tumor.     

Reoperation for recurrent metastatic brain tumors

Results of reoperation in 48 patients who developed recurrent brain metastases between January 1984 and April 1993 are presented. Median time from first craniotomy to diagnosis of recurrence (time to recurrence) was 6.7 months. Median Karnofsky performance scale (KPS) score prior to reoperation was 80. Recurrence was local in 30 patients, distant in 16 patients, and both local and distant in two patients. Median survival time after reoperation was 11.5 months. There were no operative mortalities. Multivariate analysis revealed that presence of systemic disease (p = 0.008), KPS scores less than or equal to 70 (p = 0.008), time to recurrence of less than 4 months (p = 0.008), age greater than or equal to 40 years (p = 0.51), and primary tumor type of breast or melanoma (p = 0.028) negatively affected patient survival time. These five factors were used to develop a grading system (Grades I-IV). Patients categorized in Grade I had a 5-year survival rate of 57%, whereas the median survival time of patients in Grades II, III, and IV was 13.4, 6.8, and 3.4 months, respectively (p < 0.0001). Overall, 26 patients developed a second recurrence after reoperation. Seventeen patients underwent a second reoperation, whereas nine did not. Patients undergoing a second reoperation survived a median of 8.6 additional months versus 2.8 months for those who did not (p < 0.0001). This study concludes that reoperation for recurrent brain metastasis can prolong survival and improve quality of life. A second reoperation can also increase survival. Five factors influence survival: status of systemic disease, KPS score, time to recurrence, age, and type of primary tumor. The grading system using these five factors correlates with survival time. Reoperation should be approached with caution in Grade IV patients because of their poor prognosis.     

The use of Taguchi's methods for the evaluation of industrial knife design

Knives are used in industry, and particularly on meat packaging assembly lines, where a premium is placed on the speed of cutting. One consequence of this is that knife design and selection has been based on the speed of cutting as the most significant measure of a knife. In industry the cuts that knives make vary in difficulty with many factors such as thickness, contour, and temperature of the material being cut. These factors may change the speed with which these cuts are made. According to Taguchi's methods, a robust design is one that maintains high performance while remaining insensitive to changes in its environment. This means that a robust knife design would enable an employee to cut not only with as much speed as possible in one particular cutting scenario, but also with a consistently high speed in as many cutting scenarios as possible. An experiment with various knife designs was evaluated with Taguchi's method. Ten subjects cut outlined clay patterns in 15 min with each one of nine different knives. The nine different designs were generated from the following combinations; three grip sizes (44.4, 50.8 and 63.5 mm), three coupling angles between the grip and the blade (0, 45 and 90 degrees), three blade heights measured from the middle of the blade (10, 13 and 15 mm), and three blade lengths (85, 125 and 155 mm). Eight conditions of cutting material were used to generate 'noise'. They are combinations of temperature of the clay to be cut (from temperature (R) approximately 25 degrees C, frozen for 1 h (F) approximately 5 degrees C), thickness of the clay to be cut (15 and 25 mm), and orientation of the work surface (0 and 30 degrees). The result shows that the knife design of 63.5 mm grip size, 0 degree coupling angle, 13 mm blade height, and 85 mm blade length provides the highest number of cuts, the knife design of 50.8 mm grip size, 45 degrees coupling angle, 15 mm blade height, and 85 mm blade length gives the highest signal to noise ratio. The shorter blade (85 mm) is suggested by both designs, but the two designs are different in the other three variables. Further analysis of the noise variables shows that lowering clay temperature significantly reduces cutting speed. Although there is more than one design that can resolve changes in clay thickness and clay orientation, a 15 mm blade height is the only design insensitive to the clay temperature change.     

The use of SPECT with 201Tl in the evaluation of brain tumors

There is increasing interest in the literature regarding the use of SPECT (single photon emission computed tomography) with 201Tl in the evaluation of cerebral tumours. Thallium (201Tl) is one of the isotopes most commonly used in studies of the myocardium and in the diagnosis of various tumours. Normal brain takes up very little 201Tl, but in viable tumour tissue the 201Tl becomes intracellular and is rapidly cleared from the blood stream. Such cerebral tumour uptake is related to changes in the permeability of the blood-brain barrier, regional blood flow and transport by means of the Na(+)-K+ adenosine triphosphate pump. Once the SPECT images have been obtained following administration of the radioisotope, one can calculate the indices of early and of late uptake together with the retention index. The usefulness of SPECT in the preoperative detection of malignant expansive pathology, choice of tumour region during stereotaxic biopsy, control of tumour reproduction and their differentiation from post-radiotherapy necrotic tissue, and evaluation of chemotherapy in treatment of cerebral tumours are analyzed. Finally the application of SPECT in metastatic conditions and the differential diagnosis of expansive lesions is considered.     

2 years' experience with treatment of uveal melanoma using the Leksell gamma knife

In the last years, the therapy of ocular melanoma with Leksell's gamma-knife was indicated at several clinics in Prague. It referred to bulky tumors and to unfavourably localized tumors so that only enucleation of the eyeball was the only alternative in our conditions. The results of the treatment of 11 patients have been evaluated in this article. Some other patients treated with this method have not been included in this sample for various reasons (short-term follow-up, combination of radiotherapy with gamma-knife with other therapeutic modality etc.) Gradual decrease in tumor size developed in 10 patients during follow-up. The decrease in tumor size has been observed on repeated ultrasound examinations and magnetic resonance imaging. The growth of tumor was reappeared in one patient, which led to the necessity of enucleation of the eyeball. The complications in other patients were numerous but not serious to such extent that would lead to enucleation. Marked deterioration in visual acuity connected with the treatment occurred in 6 patients. The results achieved by this method are comparable with those achieved by other therapeutic modalities and with the results from other clinics employing gamma-knife for the treatment of uveal melanoma. The results lead to the conclusion that this is an effective method of treatment of uveal melanoma and that this method is able to go through further development, especially in combination with other therapeutic modalities.