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Biomedical subjects

T L Phillips

Publications and source records attributed to T L Phillips.

287 records · Page 16Linked to original sources
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Catamnesis.

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Follow-Up Studies↗
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Initial pharmacology and toxicology of intravenous desmethylmisonidazole.

Since January 1981, 52 patients have entered the Radiation Therapy Oncology Group Phase I trial with intravenous (i.v.) desmethylmisonidazole (DMM). DMM is less lipophilic than misonidazole (MISO) and theoretically will be less neurotoxic due to lower penetration into neural tissue and more rapid elimination. The drug is administered intravenously to achieve the maximum drug concentration in tumor for a given dose. The protocol slowly escalates the total dose of drug administered. At this time the planned dose on the three week schedule is 1g/m2 five times per week to a total of 15g/m2, and on the seven week schedule is 1.25g/m2 twice weekly to a total dose of 17.5g/m2. The preliminary plasma pharmacokinetic data demonstrates high peak plasma levels within five minutes of the end of the drug infusion. Compared to MISO the percent of DMM excreted in the urine is increased, 63% vs 10%, and the elimination half-life is decreased: DMM, i.v. 5.3h; MISO, i.v. 9.3h; MISO, oral 10 to 13h. Neurotoxicity has been observed in approximately 30% of patients given a cumulative dose of greater than 11g/m2. This is in comparison to a 50% incidence in the RTOG Phase I study with oral MISO at doses of 12g/m2. There is not sufficient data to evaluate the relationship between neurotoxicity and drug exposure. Further patient accrual on this study is required to better define the properties of DMM.

Adult↗
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Comparative thermal dosimetry of interstitial microwave and radiofrequency-LCF hyperthermia.

Steady-state temperature distributions induced by commercial radiofrequency localized current field (RF-LCF) and microwave (MW) interstitial heating systems were compared in dog thigh muscle in vivo using repeated 15-min heating experiments in the same implant site. Control experiments consisting of up to nine successive, identical heat trials with either modality verified that induced temperature distributions could be duplicated reliably. For all comparative dosimetry experiments a square array of parallel heat sources and thermometry probes was inserted percutaneously through a 5 mm grid Plexiglas template to a depth of 7.0-8.0 cm. Metal trocar electrodes were left at the corners of square arrays for two or three successive RF-LCF heat trials. After the metal trocars were removed, two or three more heat trials were performed using dipole microwave antennas in Teflon catheters at the same four positions. The three-dimensional temperature distributions within the array boundaries were characterized by mapping up to 11 fibre optic temperature probes in 1 cm increments during the steady-state plateau of each trial. The distributions were analysed quantitatively in terms of the percentage of measured points which achieved at least 50 per cent of the maximum array temperature increase above baseline (delta Tmax). Results showed that the RF-LCF technique heated more uniformly with depth along the bare metal electrodes and more consistently within the array boundaries than the microwave dipole antennas. For all array spacings studied (1.0-3.5 cm), the RF electrodes heated approximately 10-20 per cent more of the array volume to greater than 50 per cent of delta Tmax.

Animals↗
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Heating patterns of the Helios ultrasound hyperthermia system.

Thermal dosimetry studies of the Helios ultrasound system were performed in a tissue-equivalent phantom and in porcine tissues in vivo. SAR distributions in the phantom demonstrate the adjustability of the power deposition pattern from the 50 cm diameter annular array of 30 transducers. Examples are given of well-localized SAR patterns (< 3 cm diameter) in the phantom, and of peripherally enhanced (doughnut-shaped) SAR patterns up to 10 cm in diameter at the focal plane. In vivo trials in porcine thigh muscle demonstrate the ability of the Helios system to produce regions of therapeutic heating (42-45 degrees C) as small as 20 cm3 and as large as 200 cm3 at depths of greater than 10 cm at a frequency of 0.5 MHz.

Animals↗
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Direct-coupled interstitial ultrasound applicators for simultaneous thermobrachytherapy: a feasibility study.

This study presents the design and performance evaluation of interstitial ultrasound applicators designed specifically for thermal therapy with simultaneous brachytherapy. The applicator consists of a multielement array of piezoceramic tubular radiators, each with separate power control, surrounded by thin layers of electrically-insulating and biocompatible coatings (< 2.6 mm OD). A catheter which is compatible with remote afterloaders and standard brachytherapy technology forms the inner lumen. These 'direct-coupled interstitial ultrasound applicators' (DCIUA's) are placed within the tumour or target region, with the coated transducer surface forming the outer wall of the implant catheter. Thermocouple sensors embedded in the coating over each transducer can be used for continuous monitoring of the tissue/applicator interface temperatures for feedback control of power to each transducer segment. Theoretical acoustic power deposition and corresponding temperature distributions from thermal simulations have demonstrated that the radius of effective heating is highly dependent upon the acoustic efficiency of the piezoceramic transducers, with effective heating extending > 1 - 1.5 cm radially for typical DCIUA applicators that are 60-65% efficient. This exceeds the effective heating radius of both thermal conduction and RF heating technologies. Measurements with prototype multielement ultrasound applicators have demonstrated acoustic efficiencies between 60 and 65% and beam distributions which are fairly uniform and collimated to the transducer axial length. Thermal dosimetry measurements within in vivo tissues have demonstrated controllable therapeutic temperature rises at 1 - 1.5 cm radial depth from the applicators, which were in agreement with the simulations. This study demonstrates that direct-coupled ultrasound applicators, designed without an active cooling mechanism in order to accommodate the insertion of radiation sources, are practicable for simultaneous thermobrachytherapy and promises to give more adjustable heating patterns than current alternative techniques.

Animals↗
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Therapy for hepatocellular cancer with intrahepatic arterial adriamycin and 5-fluorouracil combined with whole-liver irradiation: a Northern California Oncology Group Study.

Thirteen patients with hepatocellular cancer were treated with intrahepatic arterial Adriamycin and 5-fluorouracil combined with whole-liver irradiation. Six patients (46%) had an objective regression and five (38%) had stable disease. Symptomatic improvement was noted in 81% of the patients. The minimum median survival time was 5.0 months for those patients who responded. Toxicity was acceptable. This is an effective combination for the treatment of this especially aggressive and intractable form of cancer.

Adult↗
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A productivity system for a hospital education department.

The development of productivity systems for hospital education departments is reported. A time-based and value-based approach to documenting productivity is discussed, and the design and implementation process of a specific productivity tool is detailed.

Education Department, Hospital↗
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Combined radiotherapy and bleomycin for advanced head and neck cancers: results of a phase I pilot study.

Forty-two patients with inoperable stage III or IV head and neck epithelial tumors were entered in a phase I pilot study to evaluate the toxicity and efficacy of combined radiotherapy and bleomycin for advanced head and neck cancers. Twenty-three patients (52%) achieved complete remissions and 18 patients (42%) had greater than 50% regression. Most patients tolerated bleomycin at a dose of 5 units twice a week, with a full course of radiotherapy delivered at 1809 rads/day, 5 days/week. Although the complete remission rate appears to be higher than with radiotherapy alone and 13 of the 23 complete remissions (57%) lasted greater than 1 year, methods of prolonging the duration of remission need to be developed.

Bleomycin↗
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Gamma knife radiosurgery for malignant melanoma brain metastases.

PURPOSE: To evaluate the efficacy and toxicity of gamma knife radiosurgery in the treatment of melanoma metastases to the brain. PATIENTS AND METHODS: We retrospectively reviewed 55 patients with single or multiple intracranial melanoma metastases treated at the University of California, San Francisco, with gamma knife radiosurgery from 1991 through 1995. Sixteen patients were treated with gamma knife radiosurgery for recurrence following previous radiation therapy, 11 received radiosurgery as a boost to whole-brain radiation therapy, and 28 had radiosurgery alone for initial management of brain metastases. The median minimum radiosurgery tumor dose for 140 treated lesions was 19 Gy (range, 10-22 Gy) prescribed at the 35% to 90% isodose contour (median, 50%). The median total target volume per patient was 6.1 cc (range, 0.25-28.3 cc). RESULTS: With a median follow-up of 75 weeks in living patients, the median survival times were 35 weeks overall: 35 weeks for patients with solitary metastases versus 33 weeks for those with multiple metastases. A factor that was significant in univariate analysis of survival was total target volume treated. This parameter remained significant on multivariate analysis. The actuarial median freedom from progression analyzed by lesion for 113 lesions in 46 patients with imaging follow-up was 89 weeks with 6-month and 1-year actuarial freedom from progression rates of 89% (95% confidence interval, 80%-95%) and 77% (95% confidence interval, 62%-87%). In univariate analysis, improved freedom from progression was associated with smaller target volume treated, smaller maximum diameter, or higher prescribed dose. Four patients (7%) developed acute Radiation Therapy Oncology Group grade > or = 2 morbidity, and five patients (9%) developed late grade > or = 2 morbidity. DISCUSSION: Median survival and freedom from progression in patients treated with radiosurgery for melanoma metastatic to the brain are comparable to results in published radiosurgery series of grouped histologies. For melanoma patients, total intracranial tumor volume appears to be of greater prognostic significance than the absolute number of metastases treated. We conclude that gamma knife radiosurgery is effective and should be considered among various management strategies.

Adolescent↗
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Identification of a high-risk clinically localized prostate cancer subgroup receiving maximum benefit from whole-pelvic irradiation.

PURPOSE: We recently identified a progression-free survival advantage for clinically localized high-risk prostate cancer patients receiving whole-pelvic irradiation. We now seek to identify a subgroup most likely to benefit from whole-pelvic irradiation. METHODS: Between October 1987 and December 1995, 506 clinically localized prostate cancer patients were treated with definitive radiotherapy consisting of whole-pelvic irradiation followed by a prostate-only boost, or prostate-only treatment (median follow-up, 35 months vs 30 months). Prostate-specific antigen (PSA) failure was defined as (1) a PSA value > or = 1 ng/mL or (2) a PSA value that rose > or = 0.5 ng/mL in < or = 1 year posttreatment on two consecutive measurements, with the first rise defined as the time of failure. The calculated risk of lymph node positivity (%rLN+) was defined as 2/3 (initial PSA) + 10(Gleason score - 6), with intermediate risk defined as 15% < or = %rLN+ < 35% and highest risk defined as %rLN+ > or = 35%. Univariate and multivariate analyses were performed. RESULTS: Intermediate-risk patients receiving whole-pelvic irradiation had significantly improved freedom from PSA failure compared with those receiving prostatic irradiation only (median progression-free survival 39.5 months vs 22.5 months; P < 0.0001); highest-risk patients did not (median progression-free survival 27.2 months vs 20.8 months, P = NS). Multivariate analysis revealed type of radiation treatment to be the most significant independent predictor of outcome (P < 0.0001). DISCUSSIONS: Whole-pelvic radiotherapy most significantly improves the PSA failure-free survival in patients with an intermediate calculated risk of lymph node positivity, suggesting that highest-risk patients may present with distant micrometastases.

Chi-Square Distribution↗