Fractionated stereotactic radiosurgery and preservation of hearing in patients with vestibular schwannoma: a preliminary report.

OBJECTIVE: Microsurgery and stereotactic radiosurgery (SRS) for vestibular schwannomas are associated with a relatively high incidence of sensorineural hearing loss. A prospective trial of fractionated SRS was undertaken in an attempt to preserve hearing and minimize incidental cranial nerve injury. METHODS: Thirty-three patients with vestibular schwannomas were treated with 2100 cGy in three fractions during a 24-hour period using conventional frame-based linear accelerator radiosurgery. The median tumor diameter was 20 mm (range, 7-42 mm). Baseline and follow-up evaluations included audiometry and contrast-enhanced magnetic resonance imaging. End points were tumor progression, preservation of serviceable hearing, and treatment-related complications. RESULTS: Thirty-one patients (32 tumors) were assessable for tumor progression and treatment-related complications and 21 patients for preservation of serviceable hearing, with a median follow-up interval of 2 years (range, 0.5-4.0 yr). Tumor regression or stabilization was documented in 30 patients (97%) and tumor progression in 1 (3%). The patient with tumor progression remains asymptomatic and has not required surgical intervention. Five patients (16%) developed trigeminal nerve injury at a median of 6 months (range, 4-12 mo) after SRS; two of these patients had preexisting trigeminal neuropathy. One patient (3%) developed facial nerve injury (House-Brackmann Class 3) 7 months after SRS. Preservation of useful hearing (Gardner-Robertson Class 1-2) was 77% at 2 years. All patients with pretreatment Gardner-Robertson Class 1 to 2 hearing maintained serviceable (Class 1-3) hearing as of their last follow-up examination. CONCLUSION: Three-fraction SRS with a conventional stereotactic frame is feasible and well tolerated in the treatment of acoustic neuroma. This study demonstrates a high rate of hearing preservation and few treatment-related complications among a relatively high-risk patient cohort (tumors >15 mm or neurofibromatosis Type 2). Longer follow-up will be required to assess the durability of tumor control.

Total skin electron beam therapy with or without adjuvant topical nitrogen mustard or nitrogen mustard alone as initial treatment of T2 and T3 mycosis fungoides.

PURPOSE: To compare the efficacy of total skin electron beam therapy (TSEBT) with or without adjuvant topical nitrogen mustard (+/- HN2) with topical nitrogen mustard (HN2) alone as initial management of T2 and T3 mycosis fungoides (MF). METHODS AND MATERIALS: A retrospective analysis of 148 patients presenting to Stanford from January, 1970 through January, 1995 within 4 months of pathologic diagnosis of MF. Fifty-five patients with T2 and 27 with T3 disease received TSEBT +/- HN2. Fifty-four patients with T2 and 12 with T3 disease received HN2 alone. Boosts with radiotherapy were usually administered to cutaneous tumors of patients with T3 disease. RESULTS: TSEBT +/- HN2 yielded significantly higher complete response (CR) rates than did HN2 alone in patients with T2 and T3 disease (76% vs 39%, p = 0.03 for T2, and 44% vs 8%, p < 0.05 for T3, respectively). In T2 disease, treatment with adjuvant HN2 was associated with a longer freedom from relapse following TSEBT when compared to observation following a CR to TSEBT (p = 0.068). However, no significant differences in survival were observed for different management programs for T2 or T3 disease. In T2 disease, both TSEBT and HN2 were as effective as salvage therapy as when utilized as initial therapy. However, salvage therapy in T3 disease was rarely effective. Limited tumor involvement in T3 disease did not correlate with improved survival compared to more generalized tumorous disease. MF contributed to 27% and 68% of deaths in patients with T2 and T3 disease, respectively. CONCLUSION: Because of high response rates, management of significantly symptomatic or extensive T2 MF should include TSEBT, and adjuvant HN2 should be administered after a CR to TSEBT. Patients with T2 disease who fail TSEBT or HN2 can be salvaged with the other modality. TSEBT is also an effective treatment for T3 disease. The small subset of patients with limited T3 disease may also be treated with HN2 and local radiotherapy to the tumors. Further investigations are necessary to improve the overall outcome for T3 mycosis fungoides.

A pilot survey of sexual function and quality of life following 3D conformal radiotherapy for clinically localized prostate cancer.

PURPOSE: To assess the impact of high dose three-dimensional conformal radiotherapy (3D CRT) for prostate cancer on the sexual function-related quality of life of patients and their partners. METHODS AND MATERIALS: Sixty of 124 consecutive patients (median age 72.3 years) treated with 3D CRT for localized prostate cancer were surveyed and reported being potent prior to treatment. The answers to survey questions assessing the impact of quality of life related to sexual function from these 60 patients and their partners forms the basis for this retrospective analysis. RESULTS: Following 3D CRT, 37 of 60 patients (62%) retained sexual function sufficient for intercourse. Intercourse at least once per month was reduced from 71 to 40%, whereas intercourse less than once per year increased from 12 to 35%. Following treatment, 25% of patients reported that the change in sexual dysfunction negatively affected their relationship or resulted in poor self-esteem. This outcome was associated with impotence following treatment (p < 0.01). Patients who had partners and satisfactory sexual function appeared to be at a higher risk of having a negatively affected relationship or losing self-esteem if they become impotent (p < 0.05). Partners of patients who reported a negatively affected relationship or loss of self-esteem appear to be less likely to return the survey instrument used (p = 0.02). CONCLUSIONS: More work is needed to evaluate the impact of radiotherapy and other treatments on the quality of life of patients and their partners to allow adequate informed consent to be given.

Potency following high-dose three-dimensional conformal radiotherapy and the impact of prior major urologic surgical procedures in patients treated for prostate cancer.

PURPOSE: To assess the impact of high-dose three-dimensional conformal radiotherapy (3DCRT) on potency in patients treated for clinically localized prostate cancer and to identify factors that might predict the outcome of sexual function following treatment. METHODS AND MATERIALS: One hundred twenty-four consecutive patients treated with 3DCRT for localized prostate cancer at UCSF between 1991-1993 were included in this retrospective analysis. Patient responses were obtained from a mailed questionnaire, telephone interviews, or departmental records. Medial follow-up was 21 months. RESULTS: Sixty patients reported having sexual function prior to 3DCRT, including 47 who were fully potent and 13 who were marginally potent. Of the remaining 64 patients, 45 were impotent, 7 were on hormones, 1 was status-postorchiectomy, and 11 were not evaluable. Following 3DCRT, 37 of 60 patients (62%) retained sexual function sufficient for intercourse. Of those with sexual function before irradiation, 33 of 47 (70%) of patients fully potent and 4 of 13 (31%) of patients marginally potent maintained function sufficient for intercourse (p < 0.01). Potency was retained in 6 of 15 (40%) patients with a history of a major urologic surgical procedure (MUSP) and in 31 of 45 (69%) with no history of a MUSP (p < 0.04). Transurethral resection of the prostate was the MUSP in eight of these patients, with four (50%) maintaining sexual function. CONCLUSIONS: Patients who receive definitive 3DCRT for localized prostate cancer appear to maintain potency similar to patients treated with conventional radiotherapy. However, patients who are marginally potent at presentation or who have a history of a MUSP appear to be at increased risk of impotence following 3DCRT.

Analysis of naltrexone and 6-beta-naltrexol in plasma and urine by gas chromatography/negative ion chemical ionization mass spectrometry.

A procedure for the analysis of naltrexone and 6-beta-naltrexol in plasma and urine samples is described. The method takes advantage of the specificity of negative ion chemical ionization mass spectrometry and the resolving power of capillary column chromatography to achieve a limit of quantitation of 0.1 ng/mL. The trideuterated analogs of naltrexone and 6-beta-naltrexol are used as internal standards. Samples are first made basic with K2HPO4 buffer (50% w/v), and then extracted twice with n-butyl chloride-acetonitrile (4:1). After back extraction into 0.2 N H2SO4, the samples are again extracted with n-butyl chloride-acetonitrile. The extracts are derivatized with 2% methoxyamine in pyridine and pentafluoropropionic anhydride to form the methoxime bis-(pentafluoropropionyl) derivative of naltrexone and the tris-(pentafluoropropionyl) derivative of 6-beta-naltrexol. The derivatized extracts are analyzed by selected ion monitoring of prominent ions formed by electron-capture negative ion chemical ionization.

Drugs and driving: a systematic analytical approach.

To collect useful epidemiological data about drug involvement in highway safety, it is essential that sensitive and specific analytical procedures be used to establish the presence of and to determine the concentrations of drugs and metabolites in samples collected from drivers. This paper describes a comprehensive and systematic screening procedure requiring 6 mL of blood, which has been used for the analysis of samples collected from injured and fatally injured drivers. The procedure uses radioimmunoassay, gas chromatography with selective detectors, and high performance liquid chromatography. Drugs and metabolites presumptively identified are then confirmed primarily using gas chromatography--chemical ionization mass spectrometry.

Quantitative measurement of delta 9-tetrahydrocannabinol and two major metabolites in physiological specimens using capillary column gas chromatography negative ion chemical ionization mass spectrometry.

delta 9-Tetrahydrocannabinol and two of its metabolites, 11-hydroxy-delta 9-tetrahydrocannabinol and 11-nor-9-carboxy-delta 9-tetrahydrocannabinol, can be measured in a single 1-ml sample of blood, plasma, or urine by a new assay which combines a relatively rapid extraction procedure with capillary column gas chromatography and negative ion chemical ionization mass spectrometry. Deuterium-labeled analogs of each cannabinoid are added to the physiological specimen as internal standards. Two extracts are obtained from each sample: a neutral fraction containing delta 9-tetrahydrocannabinol and 11-hydroxy-delta 9-tetrahydrocannabinol, and an acid fraction containing 11-nor-9-carboxy-delta 9-tetrahydrocannabinol. The neutral fraction is derivatized by treatment with trifluoroacetic anhydride; the acid fraction is first treated with BF3-methanol followed by reaction with trifluoroacetic anhydride. Under electron-capture chemical ionization conditions the derivatized delta 9-tetrahydrocannabinol and 11-nor-9-carboxy-delta 9-tetrahydrocannabinol give abundant molecular anions ideally suited for selected ion monitoring. The negative ion chemical ionization spectrum of the HO-THC-trifluoroacetate shows no molecular anion. Consequently, quantitation of the hydroxy metabolite is achieved by monitoring a fragment ion formed by loss of CF3CO2 from its molecular anion. The limits of reliable measurement are judged to be 0.1 ng ml-1 for 11-nor-9-carboxy-delta 9-tetrahydrocannabinol, 0.2 ng ml-1 for delta 9-tetrahydrocannabinol and 0.5 ng ml-1 for 11-hydroxy-delta 9-tetrahydrocannabinol. Four examples are given of the application of the assay to the analysis of specimens of medico-legal importance.

Plasma and urine disposition of 1-alpha-acetylmethadol and its principal metabolites in man.

The disposition of 1-alpha-acetylmethadol (LAAM) in plasma and urine was monitored by GC/CIMS following oral administration of 10 doses (0.73-1.5 mg/kg) over 42 days, to twelve human subjects. Plasma concentration-time course profiles fitted a two-compartment, first order kinetic model. Mean plasma t1/2 alpha for LAAM was 2.4 hours; t1/2 beta was 37.5 hours for the first dose and 46.8 hours for the last dose. The mean terminal half-life for nor-LAAM was 38.2 hours for first and 64.6 for last dose; for dinor-LAAM t1/2 beta was 168 hours, last dose. Drug accumulation occurred in some subjects, but within the study range, dosage was not related to maximum plasma levels nor to accumulation. In urine, the sum of LAAM, nor-LAAM, and dinor-LAAM represented 25% of the dose, and unconjugated methadol metabolites, 1.6-1.7%.

Quantitative analysis for tricyclic antidepressant drugs in plasma or serum by gas chromatography-chemical-ionization mass spectrometry.

We describe a gas chromatographic-chemical-ionization mass spectrometric procedure for determining concentrations of the tricyclic antidepressant drugs and their demethylated metabolites in plasma. The procedure requires 2.0 mL of plasma or serum and involves internal standard addition, extraction with a mixed organic solvent, and separation on a column packed with 0.5% potassium hydroxide and 2% Carbowax 20M. Between-assay and within-assay (n = 10) CVs were less than 11.0%. The procedure has been applied to several interesting cases, three of which are summarized.

Gas chromatography-chemical ionization mass spectrometry of cocaine and its metabolites in biological fluids.

A gas chromatographic-chemical ionization mass spectrometric (GC-CIMS) method is described for the determination of cocaine, benzoylecgonine, and norcocaine. The procedure uses stable isotopes as internal standards and a mixture of methane-ammonia as chemical ionization reagent gas. Run-to-run and within-run coefficients of variation (%) are less than 10% and the method has a sensitivity of less than 5 ng/mL from 1 mL or 1 gram of sample. The procedure has been applied to a number of cases involving cocaine intoxication and analytical data from these are described.

The quantitative analysis of 1-alpha-acetylmethadol and its principal metabolites in biological specimens by gas chromatography-chemical ionization-multiple ion monitoring mass spectrometry.

1-alpha-acetylmethadol (LAAM) is a new drug under development for the treatment of heroin dependence. A new analytical method applicable to the accurate biodispositional study of the drug and its metabolities is described and critically discussed in this report. The procedure involves sample preparation and direct organic solvent extraction using eta-butyl chloride, amide derivatization by molecular rearrangement, and gas chromatography-chemical ionization mass spectrometry-selected ion monitoring, with methane as the carrier and ammonia as reagent gases. Deuterated (d3 stable isotopes of LAAM and its metabolites are used as internal standards. The method is free from qualitative interferences and has quantitative sensitivity to 5 ng/ml for 2.0 ml samples with 10-15% accuracy and precision in the range 5-100 ng/ml; and 2-5% at concentrations up to 750 ng/ml. Specimens of plasma, whole blood, urine, bile, brain, liver, and other visceral samples have been successfully analyzed, as well as in vitro preparations such as hepatic microsomes. By appropriate data processing, the method lends itself to routine analysis and high volume work; even manually the method is capable of at least 50 samples per week. A simplified procedure for the analysis of LAAM and its metabolites in urine only is also presented and discuet up and use the methods.

Simultaneous determination of cocaine and benzoyl ecgonine in urine by gas chromatography with on-column alkylation.

A gas chromatographic procedure has been developed for the simultaneous determination of cocaine and benzoyl ecgonine in urine specimens. The two drugs are extracted by isopropanol/chloroform from urine samples saturated with a bisalt buffer. The organic extract is evaporated to dryness, and an aliquot of the residue is injected onto the gas chromatograph to determine the presence of cocaine and the location of any extraneous peaks. Benzoyl ecgonine is then analyzed as its particular alkyl ester subject to the least interference from extraneous peaks as observed in an initial underivatized injection. The reconstituted residue is co-injected with the appropriate dimethylformamide dialkyl acetal for on-column alkylation. The use of two columns or more than one benzoyl ecgonine alkyl ester gives positive identification, and the use of isopropyl benzoyl ecgonine as an internal standard allows accurate quantification.