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J S Loeffler

Publications and source records attributed to J S Loeffler.

At least 19 recordsLinked to original sources
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↗
PubMed1991

Variables associated with the development of complications from radiosurgery of intracranial tumors.

Between 5/21/86 and 11/1/89, we treated 64 recurrent or inoperable intracranial tumors in 60 patients (40 primary, 24 metastatic) with stereotactic radiosurgery using a modified 6 MeV linear accelerator at the Joint Center for Radiation Therapy. Patients were followed until death or 1/1/90. The median follow-up was 8 months (2-43 months). Fourteen patients experienced complications from 12 hours to 7 months (median 3 months, but only two patients more than 4 months) following radiosurgery. To determine variables related to complication, we calculated integral dose-volume histograms for 61/64 lesions and the surrounding CT-defined normal tissue. We excluded 16 lesions in 15 patients for follow-up less than 4 months (12 patients) or insufficient treatment information (3 patients). The variables for which higher values were associated with significantly more toxicity in a univariate score test were: a) tumor dose inhomogeneity (p less than 0.00001), b) maximum tumor dose (p = 0.00002), c) number of isocenters (p = 0.00002), d) maximum normal tissue dose (p = 0.00005) and e) tumor volume (p = 0.0001). These variables were all highly correlated with tumor dose inhomogeneity (coefficients of rank correlation 0.75-0.81). Tumor dose inhomogeneity had a much higher loglikelihood in a logistic model than any other single variable and a higher loglikelihood than any other two variables combined. None of the 21 patients with metastatic lesions experienced a complication. When we excluded the metastatic lesions, the above five variables remained significant in univariate tests. The mean tumor dose, number of treatment arcs, total degrees of arc, tumor location, previous radiotherapy, tumor geometry, pretreatment performance status, collimator size, and age were not significantly associated with toxicity. We conclude that radiosurgery of intracranial tumors is associated with a low risk of complications for lesions less than 10cc treated with a single isocenter to maximum tumor doses less than 25 Gy with tumor dose inhomogeneity less than 10 Gy, but that treatment of larger lesions will require new treatment strategies which reduce the tumor dose inhomogeneity associated with multiple isocenter treatments.

Brain Neoplasms↗
PubMed1991

Treatment planning for stereotactic radiosurgery of intra-cranial lesions.

Stereotactic radiosurgery of intra-cranial lesions is a treatment modality where a well defined target volume receives a high radiation dose in a single treatment. Our technique delivers this dose using a set of non-coplanar arcs and small circular collimators. We use a standard linear accelerator in our treatments, and the adjustable treatment parameters are: isocenter location, gantry arc rotation interval, couch angle, collimator field size, and dose. The treatment planning phase of the treatment determines these parameters such that the target volume is sufficiently irradiated, and dose to surrounding healthy tissue and critical, dose-limiting structures is minimized. The attachment of a BRW localizing frame to the patient's cranium combined with CT imaging (and optionally MRI or angiography) provides the required accuracy for localizing individual structures in the treatment volume. The treatment is fundamentally 3-dimensional and requires a volumetric assessment of the treatment plan. The selection of treatment arcs relies primarily on geometric constraints and the beam's eye view concept to avoid irradiating critical structures. The assessment of a treatment plan involves isodose distributions throughout the volume and integral dose-volume histograms. We present the essential concepts of our treatment planning approach, and illustrate these in three clinical cases.

Adolescent↗
PubMed1991

Quality assurance in stereotactic radiosurgery using a standard linear accelerator.

Methods have recently been developed for using standard linear accelerators to perform stereotactic radiosurgery. The accuracy necessary to perform this procedure requires an intensive quality assurance program to encompass all aspects of dose calibration and mechanical integrity of the treatment unit, the treatment planning process, and treatment delivery. The programs developed at the Joint Center for Radiation Therapy (JCRT) include testing of the linear accelerator and the stereotactic system, cross checking of the treatment planning process, and a quality assurance check list of the treatment delivery procedure. This report outlines in detail the quality assurance program currently in use at the JCRT.

Humans↗
PubMed1991

Extracranial metastatic glioblastoma: appearance on thallium-201-chloride/technetium-99m-HMPAO SPECT images.

Sequential thallium-201-chloride and technetium-99m-hexamethylpropyleneamine oxime single-photon emission computed tomography (SPECT) images were obtained in a patient with extracranial metastatic glioblastoma multiforme. Thallium-201 uptake was high (three times the scalp background) in all pathologically confirmed extracranial metastases and moderate (1.6 times scalp background) intracranially, where most biopsy specimens showed gliosis with scattered atypical astrocytes. Technetium-99m-HMPAO uptake was decreased intracranially in the right frontal and parietal lobes which had been irradiated. It was also decreased in one well-encapsulated scalp lesion and high in another scalp mass with less defined borders. Possible mechanisms of tumor uptake of these agents are reviewed.

Adult↗
PubMed1991

Computer-assisted superimposition of magnetic resonance and high-resolution technetium-99m-HMPAO and thallium-201 SPECT images of the brain.

A method for registering three-dimensional CT, MR, and PET data sets that require no special patient immobilization or other precise positioning measures was adapted to high-resolution SPECT and MRI and was applied in 14 subjects (five normal volunteers, four patients with dementia (Alzheimer's disease), two patients with recurrent glioblastoma, and three patients with focal lesions (stroke, arachnoid cyst and head trauma]. T2-weighted axial magnetic resonance images and transaxial 99mTc-HMPAO and 201Tl images acquired with an annular gamma camera were merged using an objective registration (translation, rotation and rescaling) program. In the normal subjects and patients with dementia and focal lesions, focal areas of high uptake corresponded to gray matter structures. Focal lesions observed on MRI corresponded to perfusion defects on SPECT. In the patients who had undergone surgical resection of glioblastoma followed by interstitial brachytherapy, increased 201Tl corresponding to recurrent tumor could be localized from the superimposed images. The method was evaluated by measuring the residuals in all subjects and translational errors due to superimposition of deep structures in the 12 subjects with normal thalamic anatomy and 99mTc-HMPAO uptake. This method for superimposing magnetic resonance and high-resolution SPECT images of the brain is a useful technique for correlating regional function with brain anatomy.

Alzheimer Disease↗
PubMed1990

Results of stereotactic brachytherapy used in the initial management of patients with glioblastoma.

Recent studies have shown a survival benefit for patients with recurrent glioblastomas treated with stereotactic brachytherapy. On the basis of these encouraging results, we began a prospective study in 1987 to evaluate the use of brachytherapy in patients with newly diagnosed glioblastoma. Patients were considered eligible for this study if they met the following criteria: Karnofsky performance status 70% or greater; tumor size not greater than 5 cm in any dimension; a radiographically well delineated, supratentorial lesion not involving the ependymal surfaces; and pathologically confirmed glioblastoma. We treated 35 such patients between 1987 and 1990 with stereotactic brachytherapy as part of their initial therapy. The treatment protocol involved surgery, partial brain external-beam radiotherapy (59.4 Gy in 33 fractions), and stereotactic brachytherapy with temporary high-activity iodine 125 sources giving an additional 50 Gy to the tumor bed. Chemotherapy was not used in the initial management of these 35 patients. To compare our results with those obtained in a matched control group, we identified 40 patients with glioblastoma treated with surgery and external radiotherapy, with or without chemotherapy, between 1977 and 1986 at our institution. These patients had clinical and radiographic characteristics that would have made them eligible for the brachytherapy protocol. Survival rates at 1 and 2 years after diagnosis were 87% and 57%, respectively, for patients receiving brachytherapy versus 40% and 12.5%, respectively, for the controls (P less than .001). We conclude that stereotactic brachytherapy improves the survival of patients with glioblastoma when it can be incorporated into the initial treatment approach. Unfortunately, only about one in four patients with glioblastoma are suitable candidates for brachytherapy at the time of initial presentation.

Adolescent↗
PubMed1990

Definitive radiation therapy in the management of symptomatic patients with optic glioma. Survival and long-term effects.

We reviewed 24 children who had symptomatic gliomas that involved the optic chiasm and were treated with definitive radiation therapy from 1971 to 1986. In eight patients (33%), histologic confirmation of low-grade astrocytoma was obtained. Patients had radiation therapy only if there was evidence of visual deterioration or other clinical or radiographic evidence of disease progression. Radiation doses ranged from 4500 to 5660 cGy (median, 5400 cGy) with up to a 17-year follow-up period (median, 6 years). The 6-year actuarial freedom from disease progression and overall 6-year survival are 88% and 100%, respectively. Visual improvement or stabilization was seen in 21 (91%) patients after radiation. A high incidence of endocrine abnormalities is reported, with 15 of the 18 patients evaluated after treatment showing growth hormone deficiency. We conclude that definitive radiation therapy is associated with tumor control in most of the patients with progressive optic chiasm gliomas. However, neuropsychiatric and endocrine abnormalities are significant problems that need additional evaluation in these children.

Adolescent↗