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Biomedical subjects

J S Loeffler

Publications and source records attributed to J S Loeffler.

At least 19 recordsLinked to original sources
PubMed1995

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.

Brain Neoplasms↗
PubMed1995

Stereotactic radiosurgery for the definitive, noninvasive treatment of brain metastases.

BACKGROUND: The spread of systemic cancer to the brain is a common complication for cancer patients. Conventional radiotherapy offers modest palliation, and surgery is helpful only for the patient with a single metastasis in an accessible location. Stereotactic radiosurgery, a technique that permits the precise delivery of a high dose of radiation to a small intracranial target while sparing the surrounding normal brain, has been used as an alternative treatment for brain metastases. PURPOSE: Our medical center's 7-year experience with radiosurgery for metastases was reviewed to establish the effectiveness of the treatment and to understand the prognoses in patients so treated. METHODS: Retrospective analysis of hospital records, from 248 consecutive patients (421 lesions) that were treated with radiosurgery between May 1986 and May 1993, was performed. Patients were only excluded for a Karnofsky performance score of less than 70, evidence of acute neurologic deterioration, or tumor diameter more than 4 cm. Median follow-up was 26.2 months. Seventy-six percent of patients had recurrent disease, 69% had evidence of systemic disease, 69% had a single metastasis. Treatment was performed using a 6-MeV linear accelerator. The median tumor volume was 3 cm3. The median treatment dose was 1500 cGy. Whole brain radiotherapy was given to all newly diagnosed patients. Patients were followed by neurological examination and neuroimaging at regular intervals. Local control of disease was defined as a lack of progression of solid-contrast enhancement on computed tomography scan or magnetic resonance imaging. RESULTS: Median overall survival from radiosurgery was 9.4 months. The absence of active systemic disease, younger than 60 years of age, two or fewer lesions, and female sex were significantly associated with increased survival (two-sided P < .05). Actuarial local control rates were approximately 85% at 1 year and 65% at 2 years. Factors associated with a significantly decreased local control rate were location below the tentorium, recurrent tumor, and larger tumor volume (two-sided P < .05). Radioresponsive and radioresistant tumor types had similar control rates. The median drop in Karnofsky performance score at 1 year was 10%. CONCLUSIONS: The results of this retrospective analysis show that radiosurgery is an effective, minimally invasive outpatient treatment option for small intracranial metastases. Results of this study also indicate that radiosurgery not only provides local control rates equivalent to those from surgical series but is also effective in treating patients with surgically inaccessible lesions, with multiple lesions, or with tumor types that are resistant to conventional treatment.

Adolescent↗
PubMed1995

Results of radiosurgery in the management of recurrent and residual medulloblastoma.

Between June 1989 and January 1994, 14 patients with recurrent (n = 11) or posttreatment residual (n = 3) medulloblastoma were enrolled in a program to evaluate the efficacy and toxicity of stereotactic radiosurgery (SR). Initial treatment consisted of subtotal surgical resection in 12 patients and complete surgical resection in 2. Thirteen patients received systemic chemotherapy, and all had craniospinal irradiation prior to SR. SR was used as a technique for boosting sites of posttreatment residual disease in 3 patients (3 tumors) and as salvage therapy in 11 patients (14 tumors) with radiographically well-defined, discrete recurrent tumors. Patients underwent SR 1-97 (median 20) months after completing craniospinal irradiation. The median minimum peripheral tumor dose was 12 Gy. The median tumor volume at the time of SR was 6.9 cm3. With a median follow-up period from diagnosis of 27 (range 8-39) months, all patients treated with SR as a boost to sites of residual disease are alive without evidence of disease. In contrast, 6 of 11 patients who underwent SR for treatment of recurrent disease have died of progressive medulloblastoma. The median survival from the time of SR for patients treated for recurrent disease was 10 (range 5-59+) months. The predominant site of failure after SR was distant within the central nervous system, with 6 patients (43%) failing outside the posterior fossa. No patient failed locally within the radiosurgical target volume. Two patients (14%) developed marginal recurrences.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Magnetic resonance image-directed stereotactic neurosurgery: use of image fusion with computerized tomography to enhance spatial accuracy.

Distortions of the magnetic field, such as those caused by susceptibility artifacts and peripheral magnetic field warping, can limit geometric precision in the use of magnetic resonance (MR) imaging in stereotactic procedures. The authors have routinely found systematic error in MR stereotactic coordinates with a median of 4 mm compared to computerized tomography (CT) coordinates. This error may place critical neural structures in jeopardy in sme procedures. A description is given of an image fusion technique that uses a chamfer matching algorithm; the advantages of MR imaging in anatomical definition are combined with the geometric precision of CT, while eliminating most of the anatomical spatial distortion of stereotactic MR imaging. A stereotactic radiosurgical case is presented in which the use of MR localization alone would have led to both irradiation of vital neural structures outside the desired target volume and underdose of the intended target volume. The image fusion approach allows for the use of MR imaging, combined with stereotactic CT, as a reliable localizing technique for stereotactic neurosurgery and radiosurgery.

Algorithms↗
PubMed1995

Advances in the diagnosis and management of pituitary tumors.

The diagnosis of pituitary tumors has improved with advances in magnetic resonance and radionuclide and hormonal testing. The widespread availability of neuroimaging has significantly increased the number of incidental pituitary tumors coming to medical attention. Conventional therapy with transsphenoidal surgery, external-beam radiotherapy, and bromocriptine has enabled the majority of patients with pituitary tumors to be effectively treated. These therapies have been complemented by advances in stereotactic radiosurgery, stereotactic fractionated radiotherapy, and the development of pharmacologic agents with greater specificities or longer duration of actions such as quinagolide, octreotide, lanreotide, and depot preparations of bromocriptine. These newer treatments have improved the control of pituitary tumors refractory to conventional therapy.

Humans↗
PubMed1992

Development of Lhermitte's sign after bone marrow transplantation.

The authors observed Lhermitte's sign in four patients after bone marrow transplantation (BMT) for hematologic malignancies. Three patients had acute myelogenous leukemia (AML), and one had chronic myelogenous leukemia. Before BMT, the patients with AML received daunorubicin, cytosine arabinoside and etoposide, whereas the patient with chronic myelogenous leukemia received hydroxyurea. One patient with AML received MY-9 antibody-depleted autologous BMT. The other patients received human lymphocyte antigen-identical, allogeneic BMT. Preparative therapy for BMT was cytosine arabinoside, cyclophosphamide, and total body exposure to radiation for two patients, and busulfan, cyclophosphamide, and no exposure to radiation in two other patients. Lhermitte's sign appeared 4 to 8 months after BMT and resolved spontaneously after 2 to 5 months. Neurologic sequelae had developed in none of the patients 16 to 34 months after BMT. No unifying etiologic factor could be identified in these patients. The development of Lhermitte's sign after BMT appears to be a benign, self-limited phenomenon that requires no specific treatment.

Adult↗
PubMed1992

Distribution of etanidazole into human brain tumors: implications for treating high grade gliomas.

Etanidazole was developed as an oxygen-mimetic radiosensitizer less lipophilic than misonidazole. Sensitization depends on an adequate concentration of drug in the tumor at the time of irradiation. Therefore, due to the presence of the blood-brain barrier, brain tumors may theoretically be difficult to radiosensitize due to the hydrophilic characteristics of etanidazole. Based on previous reports of loss of BBB integrity in brain tumors, we investigated the ability of etanidazole to penetrate into malignant gliomas of patients receiving etanidazole as part of a Phase I continuous infusion protocol. The patients had completed previous external beam irradiation. Twenty-two patients were studied and their etanidazole plasma and biopsy data were compared to the 2-compartment model derived from a second group of 19 patients with bolus etanidazole. Etanidazole concentration in brain tumor biopsies varied widely and appeared to be clustered into a higher and a lower pharmacokinetic group having mean tumor to well-perfused second compartment ratios of 1 and 0.25, respectively. Both high and low etanidazole concentrations were evident in different biopsies obtained from the same patient. Correlations between histology and tissue concentrations suggested that the higher level correspond to malignant tissue. These data indicate that the blood brain barrier is disrupted to varying degrees by the brain tumor and/or prior irradiation and that etanidazole penetrates into brain tumors.

Brain Neoplasms↗
PubMed1992

Final report of the phase I trial of continuous infusion etanidazole (SR 2508): a Radiation Therapy Oncology Group study.

Seventy-eight patients have been treated on a Phase I trial using continuous infusion etanidazole while undergoing brachytherapy for locally advanced tumors. There were two sequential schemata, the first treated 63 patients with doses ranging from 8-23 g/m2 over 48 hr and the second treated 15 patients with doses ranging from 20-23 g/m2 over 96 hr. The tumor sites were: brain (n = 42), cervix (n = 22), and breast (n = 14). Patients received a loading dose of etanidazole of 2 g/m2 followed by a continuous infusion for a total of 48 or 96 hr while radioactive implants were in place. Of the 63 patients in the 48-hr study, 52 were entered at doses of less than or equal to 21 g/m2 and there were no definite neuropathies but two patients with the cramping/arthralgia syndrome. Of the 11 patients entered at 22-23 g/m2, 1 patient had symptoms of peripheral neuropathy (Grade II) and 6 had the cramping/arthralgia syndrome. This is a new syndrome, distinct from the peripheral neuropathy, characterized by transient alterations in sensations consisting of cramping, arthralgias, or tingling that resolved completely at intervals varying from a few hours to about 1 week post-treatment. The cramping/arthralgia syndrome limited dose escalation; therefore, the maximum tolerated dose over 48 hr was determined to be 20-21 g/m2. The 96-hr infusion was limited to patients with recurrent gliomas undergoing stereotactic implantation. To date, 15 patients have been treated with doses of 20-23 g/m2. No toxicity was encountered at doses less than or equal to 22 g/m2. At 23 g/m2, one patient developed Grade III neuropathy and three patients had mild cramping/arthralgia syndrome, for whom the drug was discontinued. Therefore, it appears the maximum tolerated dose at 96 hr will be approximately 23 g/m2, which is 10-15% higher than for the 48-hr infusion.

Brachytherapy↗
PubMed1992

Radiosurgery as part of the initial management of patients with malignant gliomas.

PURPOSE: Between May 1988 and May 1991, 41 patients with malignant gliomas were enrolled onto a prospective study designed to evaluate the role of radiosurgery as a component of initial management. PATIENTS AND METHODS: Thirty-seven patients underwent radiosurgery according to the protocol and were assessable for survival and complications of treatment. Diagnoses included glioblastoma multiforme (GBM) in 23 (62%) cases and anaplastic astrocytoma in 14 (38%) cases. In 20 (54%) cases, surgical resection was attempted initially, whereas 17 (46%) patients underwent biopsy only. Patients in the study group received external-beam radiotherapy that consisted of 5,940 cGy given in 33 fractions to partial brain fields that encompassed the primary tumor with a 3 to 4 cm margin. Radiosurgery, used as a technique for boosting the dose to any residual contrast-enhancing mass lesion, was given 2 to 4 weeks after the completion of conventional radiotherapy. Minimum radiosurgical doses ranged from 1,000 to 2,000 cGy (median, 1,200 cGy), whereas maximum doses ranged from 1,250 to 2,500 cGy (median, 1,500 cGy). The median tumor volume at the time of radiosurgery was 4.8 cm3 (range, 1.2 to 72 cm3). Adjuvant chemotherapy was not given. RESULTS: After a median follow-up of 19 months, only nine of 37 (24%) patients have died. Six patients (all glioblastoma multiforme) died of recurrent tumor, whereas death was attributable to complications of treatment in two cases and intercurrent disease in one case. Four patients with recurrent tumor failed at the margins of the radiosurgical treatment volume, whereas two patients progressed locally. One patient is alive with local and marginal failure. Seven (19%) patients underwent reoperation at a median time of 5 months (range, 1 to 14 months) after radiosurgery. CONCLUSION: We conclude that radiosurgery is a useful adjunct to other modalities in the initial management of patients with small, radiographically well-defined malignant gliomas.

Actuarial Analysis↗
PubMed1992

Detection of recurrent gliomas with quantitative thallium-201/technetium-99m HMPAO single-photon emission computerized tomography.

Deteriorating clinical status after high-dose radiation therapy for high-grade gliomas may be due to radiation changes or may signal recurrent or residual tumor mass. The two conditions cannot be distinguished reliably by computerized tomography (CT) or magnetic resonance (MR) imaging. The authors assessed the ability of sequential thallium-201 chloride (201Tl) and technetium-99m hexamethylpropylene amine oxime (99mTc HMPAO) single-photon emission CT (SPECT) to distinguish tumor recurrence from radiation changes after high-dose (greater than or equal to 600 cGy) radiation therapy for malignant gliomas. Preoperative tumor/nontumor uptake ratios were analyzed in 32 patients and correlated with the presence of gross tumor at the time of reoperation. In 12 of 13 patients with 201Tl tumor/scalp ratios of 3.5 or greater, recurrent tumor was present. The authors found 99mTc HMPAO SPECT to be useful for identifying the absence of solid tumor recurrence in patients with low to moderate 201Tl uptake (ratio 1.1 to 3.4) and low perfusion to that site. In 11 of 12 patients with 99mTc HMPAO tumor/cerebellum ratios of 0.50 or less, no recurrent tumor mass was present. Three of seven patients with 201Tl ratios of 3.4 or less and 99mTc HMPAO ratios of 0.51 or more had recurrent tumor found at surgery; thus the test was not predictive in this group. It is concluded that the use of sequential 201Tl and 99mTc HMPAO SPECT accurately identifies the presence of tumor recurrence versus radiation changes in most patients with high-grade astrocytomas who have undergone tumor resection and high-dose radiation therapy.

Adult↗
PubMed1992

Radiosurgery using a modified linear accelerator.

Stereotactic radiosurgery using modified LINACs is a powerful new technique that offers a versatile method for administering high-dose radiation in a single session. Treatment-planning techniques currently in use enable individual isocenter field shaping, three-dimensional optimization of isocenter placement (including the use of multiple isocenters), and real-time analysis of isodose distribution in three dimensions relative to specifically defined anatomic structures from MR imaging or CT data. Modified linear accelerators offer successful control of both arteriovenous malformations and benign tumors (acoustic neuromas, craniopharyngiomas, and meningiomas), with results equal to the best series reported by users of the gamma knife or heavy-particle systems. More recent work indicates that radiosurgery may play an important role in controlling recurrent pediatric malignant tumors, metastatic cerebral lesions, and even malignant astrocytomas in some patients. Improved correlation of isodose distributions with imaging data allows for sophisticated analysis of results and specific complications, ultimately enabling improved patient care using this exciting new technique.

Adolescent↗
PubMed1991

The change in patterns of relapse in medulloblastoma.

The authors reviewed 89 patients treated for cerebellar medulloblastoma between 1970 and 1989 to determine the impact of changing treatment (high-dose posterior fossa radiation therapy and chemotherapy) on the pattern of failure in medulloblastoma. Between 1970 and 1983, 50 patients (median follow-up, 110 months) were treated with surgery and postoperative craniospinal irradiation (CSI). Nineteen of the 50 (38%) recurred in the central nervous system (CNS). Isolated systemic (bone) metastases occurred in six. The median time to the development of bone metastases was 12 months. Since 1984, 39 patients (median follow-up, 27 months) were treated with preradiation chemotherapy consisting of cisplatin and vincristine for 9 weeks before initiation of CSI. Nine of the 39 (23%) patients recurred in the CNS. There were no systemic failures in this cohort. The actuarial 5-year disease-free survival was 55 +/- 7% for the earlier cohort and 72 +/- 8% for the later cohort (P equals 0.3). Posterior fossa recurrence was associated with radiation therapy to this area. The cumulative incidence of posterior fossa relapse was 50 +/- 13% in patients who received less than 5300 cGy and 18 +/- 7% in those who received 5300 cGy or more (P equals 0.005). All six bone relapses were in patients treated with CSI alone and 5300 cGy or more to the posterior fossa for a 5-year cumulative incidence of bone metastases of 18 +/- 7% compared with 0% for patients treated with 5300 cGy or more and chemotherapy (P equals 0.03). The authors concluded that high-dose radiation therapy has altered the pattern of relapse with an increase in systemic recurrence after radiation therapy alone that is now equivalent to the risk of recurrence in the posterior fossa. Chemotherapy may be indicated in an attempt to decrease this high risk of systemic metastases.

Adolescent↗
PubMed1991

The therapy of primary brain lymphoma.

Recommendations regarding the current therapy of primary brain lymphoma (NHL-CNS) take into account the occurrence of this tumor in immunocompetent and immunosuppressed hosts. Immunohistochemical evaluation of biopsy material or spinal fluid provides the diagnosis in 90% of patients. For the immunocompetent, pre-irradiation intra-venous or intra-arterial chemotherapy with Methotrexate alone or in combination with other agents is provided to treat tumor within multiple brain sites. Subarachnoid deposits are treated with Methotrexate by intrathecal administration. Radiation is provided after chemotherapy and for the treatment of vitreal/retinal deposits or symptomatic lesions within the spinal axis. The therapy of recurrent NHL-CNS makes use of intravenous Methotrexate or high dose Cytosine Arabinoside. Immunosuppressed patients respond to reduction of immunosuppressive medication. The therapy of NHL-CNS in the AIDS patient makes use of corticosteroids followed by cranial irradiation. A discussion of emerging trends in the therapy of NHL-CNS in the AIDS and non-AIDS population is provided.

Acquired Immunodeficiency Syndrome↗