Preliminary results from a Phase II trail of conformal radiation therapy for pediatric patients with localised low-grade astrocytoma and ependymoma

PURPOSE: To estimate the local control and patterns of failure for pediatric patients with low-grade astroglial tumors (LGA) and ependymoma (EP) treated with three-dimensional conformal radiation therapy (CRT) using an anatomically defined clinical target volume (CTV). METHODS AND MATERIALS: From an ongoing, prospective Phase II trial initiated in July 1997, 102 pediatric patients with LGA (n = 38) and EP (n = 64) have been treated with CRT using an anatomically defined CTV extending 1.0 cm beyond the gross tumor volume and a 0.5-cm margin (planning target volume) extending outside of the CTV. The prescribed dose was 54 Gy (LGA) and 59.4 Gy (EP). RESULTS: Patients with EP have been followed for a median of 17 months (range 3--43 months), and six failures have occurred. Patients with LGA have been followed for a median of 17 months (3--44 months), and four failures have occurred. Three-dimensional magnetic resonance (MR) studies performed to document treatment failure were registered with the MR and computed tomography (CT) data used in the treatment planning process. Failure occurred within the CTV for 5 patients with EP, including 3 with concurrent subarachnoid dissemination. One patient with EP developed metastatic disease with no evidence of local failure. Three patients with LGA failed within the CTV and one failed immediately outside of the CTV. CONCLUSIONS: Treatment of an anatomically defined CTV, encompassing 1.0 cm of non-involved brain beyond the margin of resection or neuroimaging-defined tumor, appears to be safe for pediatric patients with LGA and EP based on these preliminary data. Normal tissue sparing through the use of advanced radiation therapy treatment planning and delivery techniques should be beneficial to pediatric patients if the rate and patterns of failure are similar to conventional techniques and toxicity reduction can be objectively documented.     

Preirradiation endocrinopathies in pediatric brain tumor patients determined by dynamic tests of endocrine function

PURPOSE: To prospectively evaluate pediatric patients with localized primary brain tumors for evidence of endocrinopathy before radiotherapy (RT). METHODS AND MATERIALS: Seventy-five pediatric patients were evaluated with the arginine tolerance test and L-dopa test for growth hormone secretory capacity and activity; thyroid-stimulating hormone surge and thyrotropin-releasing hormone stimulation test for the hypothalamic-thyroid axis; the 1-microg adrenocorticotropin hormone (ACTH) and metyrapone test for ACTH reserve; and, depending on age, a gonadotropin-releasing hormone stimulation test to determine gonadotropin response. The study included 38 male and 37 female patients, age 1-21 years with ependymoma (n = 35), World Health Organization (WHO) Grade I-II astrocytoma (n = 18), WHO Grade III-IV astrocytoma (n = 10), craniopharyngioma (n = 7), optic pathway tumor (n = 4), and germinoma (n = 1). Seven patients receiving dexamethasone at the time of the evaluation were excluded from the final analysis. RESULTS: Of 68 assessable patient, 45 (66%) had evidence of endocrinopathy before RT, including 15 of 32 patients (47%) with posterior fossa tumors. Of the 45 patients, 38% had growth hormone deficiency, 43% had thyroid-stimulating hormone secretion abnormality, 22% had an abnormality in ACTH reserve, and 13% had an abnormality in age-dependent gonadotropin secretion. CONCLUSION: The incidence of pre-RT endocrinopathy in pediatric brain tumor patients is high, including patients with tumors not adjacent to the hypothalamic-pituitary unit. These data suggest an overestimation in the incidence of radiation-induced endocrinopathy. Baseline endocrine function should be determined for brain tumor patients before therapy. The potential for radiation-induced endocrinopathy alone cannot be used as an argument for alternatives to RT for most patients. Pre-RT endocrinopathy may be an early indicator of central nervous system damage that will influence the functional outcome unrelated to RT.     

Complications of total hip arthroplasty: MR imaging-initial experience

PURPOSE: To investigate the use of standard magnetic resonance (MR) imaging sequences with simple parameter modifications for the detection and characterization of total hip arthroplasty (THA) complications. MATERIALS AND METHODS: An initial phantom study was performed with cobalt-chrome and titanium prostheses to establish the imaging parameters for a subsequent clinical study. In the clinical study, coronal and transverse MR imaging of 14 THA prostheses was performed before and after intravenous contrast material administration in 12 patients who were being considered for revision arthroplasty. The images were reviewed for evidence of juxtaarticular or periprosthetic abnormalities, patterns of contrast enhancement, and quality of periprosthetic tissue depiction. RESULTS: Phantom study results showed improved periprosthetic tissue depiction with use of thin sections, increased frequency-encoding gradient strength, and fast spin-echo sequences. The clinical study results demonstrated periprosthetic abnormalities in 11 cases: mechanical loosening in two cases (including one case with an associated periprosthetic fracture); granulomatosis, eight; and infection, one. In 100% of cases, tissue depiction around the femoral component was judged to be of "diagnostic quality." Tissue depiction around the acetabular component was of diagnostic quality in five (36%) cases. In all seven surgically confirmed cases, a correct diagnosis was made preoperatively with MR imaging. CONCLUSION: By using simple modifications to standard MR imaging sequences, diagnostic-quality MR imaging of THA complications can be performed, particularly around the femoral prosthetic stem.     

Phase I clinical and pharmacokinetic study of NSC 655649, a rebeccamycin analogue, given in both single-dose and multiple-dose formats.

PURPOSE: NSC 655649 was given in both single- and multiple-dose formats, to characterize maximum tolerated dose (MTD), toxicity, and pharmacokinetic profile. Experimental Design: Patients with advanced malignancies were treated with escalating doses of NSC 655649 in either a single-dose format (step 1) or a multiple-dose format (step 2). In step 1, NSC 655649 was given as a 30-60 min infusion. In step 2, the NSC 655649 dose was divided into three consecutive daily doses. Plasma and urine were sampled to assess the pharmacokinetic and excretory characteristics of NSC 655649. A total of 12 patients were enrolled at the MTD for the purpose of gender equity. RESULTS: Forty-three patients were treated with NSC 655649 for a total of 108 cycles in step 1, and 26 patients were treated for a total of 41 cycles in step 2. The MTD for both steps 1 and 2 was determined to be 572 mg/m(2). Myelosuppression was the dose-limiting toxicity. Local venous irritation was generally grade 1-2 in severity but could only be adequately prevented by administration of study drug through central i.v. access. One patient with adenocarcinoma of unknown primary experienced a partial response on step 1. Four patients experienced stable disease of >100 days duration. CONCLUSIONS: NSC 655649 may be safely given at an MTD of 572 mg/m(2) in both single-dose and multiple-dose formats. Optimally, this drug should be administered through central i.v. access.     

Giant bronchial carcinoid tumors: a multidisciplinary approach

BACKGROUND: Bronchial carcinoid tumors account for approximately 2% of all lung tumors. Although they were considered benign lesions, they are now categorized malignant, occasionally with poor prognosis. The clinical symptoms can be highly variable and are often present for many years before diagnosis. Whereas some carcinoids are entirely asymptomatic, others are accompanied by carcinoid or paraneoplastic syndromes. METHODS: We describe the multidisciplinary management of a 34-year-old female patient with a massive actively secreting bronchial carcinoid tumor of the right lung. Furthermore, we provide a review of the literature regarding the operative treatment and the perioperative management of pulmonary carcinoid tumors with respect to surgical, anesthetic, radiologic, and pathologic considerations. RESULTS: In the reported case, the first symptoms were chronic watery diarrhea, skin flushing, progressive shortness of breath, and increasing right shoulder pain. When the patient initially presented at our institution, the tumor had already reached an enormous size and it involved the right and left atrium as well as the atrial septum. Using an evidence-based, multidisciplinary approach the patient was treated successfully with extended surgical resection. CONCLUSIONS: Carcinoid tumors are potentially curable even if they reach a significant size and thus an aggressive strategy is warranted. The management of such cases requires careful investigation, planning, and treatment with collaborative expertise provided by a multidisciplinary team. We demonstrated that this approach can lead to a favorable outcome in what first appeared to be a formidable and unresectable tumor.     

Absolute configuration of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol formed metabolically from 4-(methylnitrosamino)-1-(3-pyridyl)-1- butanone

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) is an important metabolite of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1- (3-pyridyl)-1-butanone (NNK). Using the chiral derivatizing agent, (R)- (+)-alpha-methylbenzyl isocyanate [(R)-(+)-MBIC], previous work has shown that the enantiomeric ratio of metabolically formed NNAL and its glucuronide derivative may be species dependent. However, the absolute configuration of such NNAL has not been previously reported. Synthetically prepared racemic NNAL was converted to diastereomeric esters by reaction with (R)-(+)- and (S)-(-)-alpha-methoxy-alpha- (trifluoromethyl)phenylacetic acid (MTPA) chloride (Mosher's reagent) and the products were characterized by 1H-NMR. Based on chemical shift data, the absolute configuration of NNAL in each diastereomeric ester was assigned. Hydrolysis of (R)-NNAL-(R)-MTPA gave (R)-NNAL. This was converted to the corresponding carbamate by reaction with (R)-(+)-alpha- MBIC and the absolute configurations of the diastereomeric carbamates formed by reaction of (R)- and (S)-NNAL with (R)-(+)-MBIC were thereby assigned. Conversion of metabolically produced NNAL to the same carbamates allowed us to assign the NNAL formed from NNK by rat liver microsomes as (R)-NNAL. The major and minor NNAL-glucuronide diastereomers found in the urine of patas monkeys and humans exposed to NNK were similarly assigned; they were formed from (R)-NNAL and (S)- NNAL, respectively.      

Thoracic empyema: a study of 56 patients

Fifty seven children with thoracic empyema (37 boys and 20 girls) aged less than 12 years were seen at the University of Port Harcourt Teaching Hospital between January 1989 and December 1991. Staphylococcus aureus was the most common organism isolated from the pus of these patients (36 (63%) patients). Pseudomonas aeruginosa, the next most common organism, was isolated in 10 (18%) patients. The most common symptoms at presentation were acute illness with fever and cough (51 (89%) patients). All the patients were treated with closed intercostal tube drainage and appropriate antibiotics. Decortication was resorted to in only one patient. There were two deaths and the overall survival rate was 97%.