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Biomedical subjects

T L Phillips

Publications and source records attributed to T L Phillips.

At least 109 records · Page 6Linked to original sources
PubMed1989

Correlation of exposure time, concentration and incorporation of IdUrd in V-79 cells with radiation response.

These experiments were designed to find the minimum concentration at which incorporation of and sensitization by IdUrd (Iododeoxyuridine) would occur and the effect of concentrations from .1 to 100 microM for exposures of 8 to 96 hr in cultured V-79 cells exposed to 137Cs gamma rays at 2 Gy per minute. At 0.1 microM thymidine replacement averaged 1% and the SER ranged from 1.1 to 1.28, significant at the 95% level. The maximum thymidine replacement was 49% after 48 hr exposure to 30 microM yielding an SER of 2.7. SER generally peaked after 72 hr of exposure. This cell line has an 8 hr cycle time in our hands and thus optimal sensitization would occur after 9 cell cycles. These ranges need testing in human cells in culture and in Phase I clinical trials.

Animals↗
PubMed1989

Modification of SR 2508 sensitization in hypoxic V79 cells by manipulation of glutathione levels.

This series of experiments employed the hypoxic cell sensitizer SR 2508 in concentrations ranging from 0.1 to 10 mM and V-79 cells irradiated in air or made hypoxic in glass syringes, then irradiated with 15 MV X rays. Using a series of survival curves measured at the various concentrations, K curves relating sensitizer enhancement ratio (SER) to SR 2508 concentration were calculated with normal GSH levels or with depletion of GSH to 0% using 1 mM buthionine sulfoximine (BSO) or elevation to 200% of normal using 1 mM oxothiazolidine carboxylate (OTZ). Survival curves were fitted by computer, allowing calculation of standard errors for the SER values. The depletion of GSH by BSO sensitized hypoxic and aerated cells significantly and caused more than additive enhancement of SR 2508 sensitization in hypoxic cells. Elevation of GSH with OTZ protects cells irradiated in air or hypoxia and reduces the SER obtained with SR 2508. The results further support the importance of GSH levels in influencing sensitization by nitroimidazoles.

Animals↗
PubMed1989

Computer assisted treatment planning for 125I ophthalmic plaque radiotherapy.

This paper describes a computer program for planning the treatment of ocular tumors with 125I plaques. The program permits the input of the tumor configuration into a model eye and facilitates the viewing of the relative geometry of the tumor and various eye structures in different perspectives. Custom-designed 125I plaques can be localized onto the globe, and dose distributions can be calculated and superimposed on the eye structures in any plane or on the inner eye surface. The program allows efficient evaluation of the plaque design in terms of radiation dose distribution relative to the tumor and critical structures.

Brachytherapy↗
PubMed1989

Identification of an optimal subgroup for treatment evaluation of patients with brain metastases using RTOG study 7916.

The overall poor prognosis of brain metastases patients has complicated the evaluation of treatment effectiveness in previous clinical trials involving radiation therapy. Therapy has not been seen to alter survival, which is generally short in these patients. Possible benefits of the treatments tested may be better assessed using a favorable group of patients who are at lower risk of dying quickly from cancer. The determination of a patient subgroup having prolonged survival allows for improvement in the design and analysis of subsequent clinical trials. An optimal patient group was identified in an RTOG study (7916) that evaluated two fractionation schedules (30 Gy/10 fractions/2 weeks and 20 Gy/6 fractions/3 weeks) with or without the administration of misonidazole (MISO) in the treatment of brain metastases. A Cox regression model was used to identify the pretreatment characteristics associated with a favorable prognosis for survival: Karnofsky Performance Status (KPS) of 70-100, an absent/controlled primary tumor, age less than 60 years, and metastatic spread limited to the brain. A logistic model confirmed that the odds of surviving at least 200 days depend on these pretreatment characteristics. Patients with all four favorable characteristics constitute 11% of the evaluable study population and have a predicted 200 day survival of 52%. Prognostically favorable subgroups have been identified as patients having at least three of these four favorable characteristics. These patients have predicted probabilities of 200 day survival between 33 and 52%. Conversely, unfavorable subgroups are defined as patients having two or less favorable characteristics. Subsequent verification of these results by a second data set is warranted. The prognostically favorable characteristics have been used to define the patient population in a current RTOG study evaluating accelerated radiation therapy in patients with brain metastases.

Brain Neoplasms↗
PubMed1989

Radiation therapy alone or combined with misonidazole in the treatment of locally advanced non-oat cell lung cancer: report of an RTOG prospective randomized trial.

From September 1979 to February 1983, 268 patients with unresectable, locally advanced (RTOG Stage III), non-small cell lung cancer were randomized to receive radiation therapy alone (RT) (50 Gy large field and 10 Gy boost), or combined with misonidazole (400 mg/m2 2-4 hr prior to RT daily for 5-6 weeks to a maximum dose of 12 g/m2 or until tumor progression). One hundred twenty-three patients who received irradiation alone and 116 given RT + misonidazole were evaluable for toxicity, time to tumor progression, and survival as of April 1987. The distribution of patient characteristics was similar in both treatment groups; 59% of the patients had a Karnofsky score of 90 or better, 53% had adenocarcinoma or large cell tumors, and 47% had Stage T3 tumors. Complete tumor regression was reported for 33 (27%) patients treated with radiation therapy alone and 24 (21%) who received misonidazole + RT. Median survival was 8 months with RT alone and 7.4 months with misonidazole + RT. Ninety-five percent of the patients have died. Seventy percent of the patients treated with radiation alone and 77% of those treated with misonidazole + RT died of progressive disease. Three patients treated with radiation alone and two with RT + misonidazole died subsequent to radiotherapy-related pneumonitis or pulmonary fibrosis. There was no significant improvement in response rates, local control, or survival for patients who received daily misonidazole along with irradiation compared with patients treated by irradiation alone.

Adenocarcinoma↗
PubMed1989

Cholinergic responsiveness of goblet cells during intestinal maturation.

In adult rat intestine, cholinergic stimulation accelerates discharge of mucus from crypt, but not villus, goblet cells. It was not known whether goblet cells in fetal or suckling rats are cholinergically sensitive. Rat pups (20 days of gestation to 30 postnatal days) were given subcutaneous injections of carbachol and the intestines were fixed 5 min later. Accelerated mucus secretion was assessed by light microscopy of semithin plastic sections. Goblet cells in ileal and colonic crypts did not show an adult-like response until 20-25 days after birth. Ileal and colonic mucosal explants in vitro showed age-dependent responses identical to those observed in vivo. The onset of cholinergic sensitivity occurred well after the formation of crypts and was always limited to crypt goblet cells.

Aging↗
PubMed1989

Uveal melanoma radiation. 125I brachytherapy versus helium ion irradiation.

The optimum radiation therapy for uveal melanoma is uncertain. Both helium ion irradiation and 125I brachytherapy have been used to treat this neoplasm. This investigation analyzed the control and complication rates of uveal melanomas treated with helium ions of 125I plaques. In both a retrospective and a prospective dynamically balanced study, the control rates appeared to be similar. There were more posterior segment complications after 125I plaques and more anterior segment complications, including neovascular glaucoma, after helium ion irradiation. The follow-up period is too short to draw definitive conclusions on the radiation complications. Overall, approximately 89% of eyes were retained and less than 4% of treated eyes were removed because of failure to control the tumor.

Adult↗
PubMed1988

Failure of preenucleation radiation to decrease uveal melanoma mortality.

We analyzed uveal melanoma metastases in a group of 41 patients who received 20 Gy of preenucleation radiation in a Northern California Oncology Group preliminary phase I/II study, and compared their survival rates with a retrospective control group of 31 patients with characteristics matching the entrance criteria but treated with enucleation alone. Using the Cox proportional hazards model, we found that increased tumor diameter, mixed or epithelioid cell type, and radiation adversely affected survival. In vivo studies of cell cycling indicated that 20 Gy of preenucleation radiation appeared to diminish the reproductive integrity of the tumor cells. It is most likely that the failure of preenucleation irradiation to prolong patient survival was because of micrometastases that occurred before treatment.

Adult↗
PubMed1988

Radiation dose response of normal brain.

Dose response relationships were determined after hemibrain x-irradiation of normal beagle dogs. Radiation doses of 11.5, 13.5, 14.3, and 17 Gy were delivered in a single dose and results were compared to previous studies using doses of 15 and 30 Gy. Brain injury was quantified using computed tomography (CT), with serial studies obtained monthly up to 1 year following irradiation. Quantitative endpoints included low density volume and contrast enhancement. Doses above 14.3 Gy resulted in high lethality 5-8 months following irradiation, and an LD50 of 14.9 Gy was calculated. At these lethal doses, low density volume representing edema, demyelination, and necrosis had a similar response with an ED50 of 14.6 Gy. Radiation-induced decreases in white matter density appeared 5-6 months after sublethal doses (less than or equal to 14.3 Gy) and the volume of tissue characterized by this low density increased with time and dose. This sublethal low density change had an ED50 of 12.8 Gy, and may reflect a loss or generalized atrophy of glial cells and/or myelin. These results show that: (a) the dose response curves obtained after hemibrain x-irradiation are extremely steep; and (b) at least two processes may be involved in the development of late radiation damage, one that is rapid upon onset (a "delayed acute" reaction) and the other which is a slower and more degenerative process.

Animals↗
PubMed1988

Charged particle irradiation of chordoma and chondrosarcoma of the base of skull and cervical spine: the Lawrence Berkeley Laboratory experience.

Forty-five consecutive patients with chordoma or chondrosarcoma at the base of skull or cervical spine were treated at the University of California Lawrence Berkeley Laboratory (UCLBL) and University of California School of Medicine, San Francisco (UCSF) between November 1977 and October 1986. All patients had undergone a subtotal surgical resection. Twenty-three patients were treated definitively with charged particles, 13 patients were treated with photons and particles, and 9 patients were treated for recurrent disease. Total doses ranged from 36 to 80 Gray equivalent (GyE). Thirty-three patients are alive with a minimum followup of 1 year. The actuarial survival and local control for all patients at 5 years is 62% and 59%, respectively. Patients treated for primary disease had a 78% actuarial local control rate at 2 years, whereas the rate for patients with recurrent disease was 33%. Patients with smaller visible tumor volumes (less than 20 cc) had a significantly better local control rate than patients with larger tumor volumes (80% vs 33% actuarial rate at 5 years). Patients with chondrosarcoma had the highest local control rate, as did patients treated with particles alone. Complications included 3 patients with unilateral visual loss, two patients who became blind, and 4 patients with radiation injury to the brainstem.

Actuarial Analysis↗
PubMed1988

Radiosensitization produced by iododeoxyuridine with high linear energy transfer heavy ion beams.

Little is known about radiosensitization produced by iododeoxyuridine (IUDR) with high linear energy transfer radiation. Likewise, the effect of IUDR on repair of sublethal or potentially lethal damage is unclear. A series of in vitro experiments was performed examining these aspects of IUDR radiosensitization. Human T1 cells were grown in the presence of 3.0 micromolar IUDR for 72 hours (approximately three doubling times), an exposure which resulted in minimal cytotoxicity to unirradiated cells. As the cells entered plateau phase they were exposed to X rays and a variety of heavy ion beams. Sensitization was found to decrease as linear energy transfer (LET) increased. No sensitization took place in an extremely high LET Lanthanum ion beam (1000 keV/micrometer). However, IUDR produced significant sensitization in the Neon ion beam currently used to treat cancer patients at Lawrence Berkeley Laboratory. Sensitization enhancement ratios at the 40% cell survival level were found to be 1.8 for X rays, 1.5 for the proximal Bragg peak of the clinical Neon beam, and 1.3 for the distal peak of the clinical Neon beam. Cell survival curves fitted to the linear-quadratic model showed IUDR significantly increased the value of the linear component (alpha) in beams with LETs below 40 keV/micron. The value of the quadratic component (beta) was unaffected by IUDR, regardless of LET. Split-dose experiments with both X rays and proximal peak Neon ions revealed IUDR did not affect sublethal damage repair. Similarly, delayed-plating experiments showed IUDR did not affect repair of potentially lethal damage. In contrast to cells unexposed to IUDR, IUDR-treated cells showed near-equal levels of cell killing throughout the extended Bragg peak of the clinical Neon beam. These findings suggest that the addition of IUDR to Neon ion radiotherapy could enhance the therapeutic ratio of the clinical Neon beam.

Cell Survival↗
PubMed1988

Final report on phase I trial of WR-2721 before protracted fractionated radiation therapy.

This is the final report of the Phase I Protocol for the initial clinical study of Multiple Dose WR-2721 with radiotherapy (RTOG 80-02). The essential object of the study was to determine the highest dose of WR-2721 that could be given daily for the greatest number of weeks 15 to 30 minutes before conventional radiation treatment schedules. Eighty-four patients were entered into various dose levels. The major and dose-limiting toxicities were emesis, hypotension and malaise. The latter symptom was characterized by increasing weakness, fatigability, and ill-feeling. The maximum tolerated dose (MTD) established by this study is 340 mg/m2 given 4 days a week (excepting Wednesday) for 5 weeks. The drug is delivered intravenously in 7 minutes. There were no long-term blood chemistry changes. There were no deaths due to the administration of the radioprotector.

Adolescent↗
PubMed1988

Vision following helium ion radiotherapy of uveal melanoma: a Northern California Oncology Group study.

One hundred eighty-six uveal melanoma patients were treated with helium ion radiotherapy at Lawrence Berkeley Laboratory and followed for at least 6 months. (Follow-up times ranged from 6 to 90 months; median 26.4 months.) At last examination, 92 of 186 patients (49%) had visual acuity of 20/200 or better in the treated eye. Univariate statistical analysis revealed that post-treatment vision correlated with tumor size, distance between tumor and optic disc, distance between tumor and fovea, pretreatment visual acuity, dose delivered to the optic disc, and dose delivered to the fovea (p less than .05). Neither the maximum tumor dose nor site of tumor origin (ciliary body vs. choroid) correlated with post-treatment vision on a univariate basis. However, multivariate statistical analysis revealed that the strongest independent risk factors influencing vision outcome (p less than .05) were tumor size, pretreatment visual acuity, tumor-fovea distance, and maximum tumor dose. Neither the fovea dose nor the dose to optic disc appeared to significantly affect vision outcome when other variables were taken into account. These results suggest that post-treatment visual acuity of 20/200 or better can be achieved in one-half of uveal melanoma patients treated using helium ion irradiation. Several independent risk factors affecting vision outcome have been identified.

Helium↗
PubMed1988

Comparison of helium-ion radiation therapy and split-course megavoltage irradiation for unresectable adenocarcinoma of the pancreas. Final report of a Northern California Oncology Group randomized prospective clinical trial.

Forty-nine patients with locally advanced carcinoma of the pancreas were treated in a randomized, prospective study comparing definitive helium ion radiation therapy with conventional split-course megavoltage photon irradiation. Patients in each treatment arm underwent exploratory staging laparotomy followed by concurrent radiation therapy and 5-fluorouracil chemotherapy. Patients treated with photons received 6,000 cGy over a period of 10 weeks; patients treated with helium irradiation received a 6,000-7,000-cGy-equivalent dose over a period of 8-9 weeks. There was no significant difference in overall survival between patients in the two treatment arms (P = .29). Patients treated with helium ions had a slightly longer median survival (7.8 months) than the photon-treated patients (6.5 months). Local control rates were slightly higher in the helium-treated patients (10% vs 5%). Complications included one chemotherapy-related death. Four of the five helium-treated patients who survived longer than 18 months died of local failure without distant metastases. These results suggest that more aggressive local therapy could result in improved survival in helium-treated patients.

Adenocarcinoma↗