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T L Phillips

Publications and source records attributed to T L Phillips.

At least 55 records · Page 3Linked to original sources
PubMed1994

Patterns of recurrence of glioblastoma multiforme after external irradiation followed by implant boost.

PURPOSE: To study patterns of recurrence in patients with focal primary glioblastoma treated on Northern California Oncology Group protocol 6G-82-2 including surgery, focal external beam radiotherapy (59.4-60 Gy) with oral hydroxyurea followed by temporary brain implant with high-activity iodine-125 sources (50 Gy), and six cycles of chemotherapy with procarbazine, lomustine, and vincristine. METHODS AND MATERIALS: Serial brain imaging scans were available for review in 25 of 34 patients with glioblastoma who underwent brain implant boost. Of 381 scans performed between the date of diagnosis and the date of death or last follow-up, 362 (95%) were re-reviewed. Disease progression was scored as local (within 2 cm of the implant site), separate within the brain parenchyma (> or = 2 cm from the implant site), subependymal, or systemic. Both initial and subsequent failures were scored. RESULTS: Three patients are 5-year survivors, without evidence of disease, at 267, 292, and 308 weeks. Of the 22 initial sites of failure, 17 (77%) were local, three (14%) were separate brain lesions (one of which was due in retrospect to multicentric disease at diagnosis), one (5%) subependymal, and one (5%) systemic. Five patients with local failure later had other sites of failure, including a separate brain lesion in 1, subependymal spread in 3, and both in 1. One patient with separate brain failure later had local progression and then subependymal spread. CONCLUSION: Although there was a significant risk of separate brain lesions or subependymal spread over time, local tumor progression was the predominant pattern of failure.

Adult↗
PubMed1994

Liposomes and hyperthermia in mice: increased tumor uptake and therapeutic efficacy of doxorubicin in sterically stabilized liposomes.

We have shown that sterically stabilized (Stealth) liposomes (SL), can accumulate in the extracellular space within tumors, and may improve pharmacokinetics and therapeutic efficacy of encapsulated doxorubicin (SL-DOX). When SL-DOX were incubated in vitro at different temperatures with 50% bovine serum, approximately 20% of the encapsulated DOX was released at 42 degrees C within 1 min, compared with less than 1% DOX released at 37 degrees C. In vivo, mice were implanted s.c. with C-26 colon carcinoma in both flanks to produce matched tumors 6-10 mm in diameter. Topical hyperthermia treatment consisting of 42 degrees C minimum tumor temperature for 30 min was applied with a microwave device to the tumor on one side only at 1 h after i.v. injection of SL-DOX or free DOX. Tumor DOX concentration in the group which was given injections of SL-DOX and sacrificed 2 h after drug injection was 1.5-fold higher compared with the nonheated tumor in mice given injections of SL-DOX. At 24 h after injection the thermal enhancement ratio for DOX accumulation in tumor remained at 1.5. In addition, there was a 15-fold higher concentration of DOX in tumor from the group given injections of SL-DOX compared to mice given injections of free doxorubicin. To assess therapeutic efficacy, we treated mice with hyperthermia for 15 min either at 1, or at 24 h or at both time points after injection of SL-DOX. We have found that the life span of the group of mice treated with SL-DOX and two 15-min hyperthermia treatments increased 51% compared with control groups receiving the same dosage of SL-DOX but without hyperthermia, and 59% compared to those receiving two hyperthermia treatments but with free DOX. A single hyperthermia treatment either at 1 or 24 h was less effective in increasing life span compared with two treatments, but all groups treated with SL-DOX and single hyperthermia were still superior to the control groups, showing a 27-38% increase in life span.

Animals↗
PubMed1994

HSP 70 synthesis in clinical hyperthermia patients: preliminary results of a new technique.

PURPOSE: Although thermotolerance may be an important variable in clinical hyperthermia, few means have been described to measure its effect or duration in the clinical setting. This study was undertaken to determine if heat shock protein 70 could be used as an assay to predict the presence of retained thermotolerance in human tumors. METHODS AND MATERIALS: Tissue samples were obtained from patients undergoing hyperthermia and assayed for heat shock protein 70 synthesis. Eight patients having advanced, persistent, or recurrent malignant tumors had open-ended thermometry catheters placed into the lesion being heated. Through these catheters, tissue samples were obtained using a fine needle aspiration technique. Attempts were made to obtain samples before and after the first three heat treatments. Some samples were labeled immediately with radioactive methionine (35S) at 37 degrees C for 4-8 hr, others were given a test heat dose in vitro and then labeled. Protein synthesis profiles were analyzed by gel electrophoresis and autoradiography. RESULTS: Preliminary results show that it is possible to obtain tissue from hyperthermia patients in a safe and practical manner, that the rate of heat shock protein 70 synthesis can be measured in a variety of tumors, and that the persistence of thermotolerance in the clinical setting can be shown by the inability to reinduce heat shock protein 70 synthesis. CONCLUSION: The measurement of heat shock protein 70 using the described technique may provide an assay for retained thermotolerance in clinical hyperthermia. Technical difficulties which need to be addressed include obtaining sufficient tissue in all patients, confirming the presence of tumor in the obtained tissue, and obtaining tissue at more frequent intervals to best determine the kinetics of thermotolerance.

Aged↗
PubMed1994

Helium charged particle radiotherapy for meningioma: experience at UCLBL. University of California Lawrence Berkeley Laboratory.

PURPOSE: Evaluate the use of helium charged particle radiotherapy in the treatment of residual or unresectable meningioma adjacent to critical structures. METHODS AND MATERIALS: Twenty-nine patients with meningioma of the skull base or spine were irradiated with helium charged particle radiotherapy at the University of California Lawrence Berkeley Laboratory (UCLBL) during the period 1981-1992. Twenty-six patients were treated for intracranial and three for spinal tumors. Total doses of 53.0-80.4 Gray equivalent (GyE) with a mean of 63 GyE were delivered using the helium ion beam. RESULTS: Ten-year local control and survival rates calculated by the Kaplan-Meier product limit method were 84% and 80% respectively. Doses of 60.0 GyE were delivered with a low rate of complications. The only failures were in massive, recurrent tumors. CONCLUSION: High doses using helium charged particle radiotherapy can be safely and effectively delivered to large residual or unresectable meningioma near radiosensitive structures.

Adult↗
PubMed1994

Defining treatment margins for six field conformal irradiation of localized prostate cancer.

PURPOSE: To define the "ideal margins" to be used for the delivery of six-field conformal radiotherapy for localized prostate cancer. METHODS AND MATERIALS: For a typical patient, 3-D based 6-field conformal treatment plans were generated using uniform margins ranging from 0.5-2.5 cm (in 0.25 cm increments). In a step-wise fashion the minimum margins required to encompass the gross tumor volume within the 90% isodose shell were identified. Additional margins were then added to account for extracapsular penetration, setup and patients movement error as well as for organ movement. Assumptions about the relative tolerance of surrounding normal tissues were also incorporated into the final decisions regarding margins. RESULTS: For the various areas of interface, between the prostate and surrounding normal tissues "ideal margins" varied from 0.75-2.25 cm. CONCLUSION: The use of nonuniform "ideal margins" appears to insure adequate coverage of the tumor, while minimizing the volume of surrounding dose limiting normal tissues irradiated. This approach should in theory improve the tumor control and complication probabilities compared to using conventional treatment techniques and to using a 6-field conformal technique with uniform margins.

Humans↗
PubMed1994

Optimization of the oblique angles in the treatment of prostate cancer during six-field conformal radiotherapy.

Historically, four perpendicular treatment fields or bilateral arcs have been used in the treatment of prostate cancer. As new techniques challenge the four-field box technique for their superiority of tumor coverage and adjacent critical structure sparing, oblique beam angles (in addition to right and left laterals) have been introduced as an alternative to anterior (AP) and posterior (PA) beams. Among the most popular of these alternative approaches is a six-field technique. Traditionally 45 degrees angles have been used with this technique. In this study, opposed coplanar oblique beams angled 20, 25, 30, 35, 40, and 45 degrees off the lateral beam position, were compared for their ability to minimize adjacent critical structure doses, while maintaining maximum clinical target volume (CTV) coverage. This analysis compared rectum, bladder, and femoral head dose volume histograms (DVH) for each of these varying oblique gantry angles. As the angle of the posterior oblique beams became more horizontal, it is more difficult to encompass the apex of the prostate in the 95% isodose value. On inferior CT slices near the apex of the prostate, the density of the pelvic bones in the path of the posterior oblique fields causes the beam to be slightly attenuated, thereby underdosing the CTV. The oblique angles most affected by this bone heterogeneity are beams angled from 20 to 30 degrees off the lateral beam position. As the angles approach the vertical direction, rectal and bladder doses increase, while femoral head doses decrease. Oblique gantry angles approaching the horizontal direction result in a decrease in rectal and bladder doses, while femoral head doses increase. Of the oblique angles studied, 35 degrees off the lateral position provides lower rectum and bladder doses than 30, 40, and 45 degrees; lower femoral head doses than 20, 25, and 30 degrees, and the maximum CTV coverage on all CT slices studied.

Adenocarcinoma↗
PubMed1994

Carcinoma of the extrahepatic bile ducts. The University of California at San Francisco experience.

OBJECTIVE: The authors investigated the combined experience of a single institution in treating bile duct carcinoma during the modern era. SUMMARY BACKGROUND DATA: Bile duct carcinomas are notoriously difficult to cure, with locoregional recurrence the rule, even after radical resection. Adjuvant efforts have included various radiation modalities, with limited success. Recently, charged-particle radiotherapy has also been used in these patients. METHODS: The authors performed a retrospective chart analysis of 129 patients with bile duct adenocarcinomas treated between 1977 and 1987 through the University of California at San Francisco, including 22 patients treated at Lawrence Berkeley Laboratory with the charged particles helium and neon. The minimum follow-up was 5 years. Survival, outcome, and complication results were analyzed. RESULTS: Sixty-two patients were treated with surgery alone (S), 45 patients received conventional adjuvant x-ray radiotherapy (S + X), and 22 were treated with charged particles (S + CP). The median survival times were 6.5, 11, and 14 months, respectively, for the entire group, and 16, 16, and 23 months in patients treated with curative intent. There was a survival difference in patients undergoing total resection compared with debulking (p = 0.05) and minor resections (p = 0.0001). Patients with microscopic residual disease had increased median survival times when they were treated with adjuvant irradiation, most markedly after CP (p = 0.0005) but also with conventional X (p = 0.0109). Patients with gross residual disease had a less marked but still statistically significant extended survival (p = 0.05 for S + X and p = 0.0423 for S + CP) after irradiatio CONCLUSIONS: The mainstay of bile duct carcinoma management was maximal surgical resection in these patients. Postoperative radiotherapy gave patients with positive microscopic margins a significant survival advantage and may be of value in selected patients with gross disease.

Adenocarcinoma↗
PubMed1994

Practical induction heating coil designs for clinical hyperthermia with ferromagnetic implants.

Interstitial techniques for hyperthermia therapy of cancer continue to evolve in response to requirements for better localization and control over heating of deep seated tissues. Magnetic induction heating of ferromagnetic implants is one of several available techniques for producing interstitial hyperthermia, using thermal conduction to redistribute heat within an array of controlled temperature "hot sources." This report describes seven induction heating coil designs that can be used for producing strong magnetic fields around ferromagnetic seed implants located in different sites in the body. The effect of coil design on the extent and uniformity of the magnetic field is characterized, and appropriate electrostatic shield designs for minimizing electric field coupling to the patient are described. Advantages and disadvantages of each coil type are discussed in terms of the radiated fields, coil efficiency, and ease of use, and appropriate applications are given for each design. This armamentarium of induction coils provides the ability to customize magnetic field distributions for improved coupling of energy into ferromagnetic implant arrays located at any depth or orientation in the body. Proper selection of heating coil configuration should simplify patient setup, improve the safety of patient treatments, and pave the way for future applications of interstitial heating in sites that were previously untreatable.

Equipment Design↗
PubMed1993

Carcinoma of the cervix: predictive value of clinical and magnetic resonance (MR) imaging assessment of prognostic factors.

PURPOSE: This retrospective study assesses the predictive value of magnetic resonance imaging (MRI) to identify high risk cervical cancer patients. METHODS AND MATERIALS: The MRI evaluation of morphologic risk factors in patients with invasive cervical carcinoma treated with definitive radiation therapy were correlated with clinical factors and with complete tumor regression (CTR) at 6 months, tumor local control (TLC), and patient outcome at 12 months after irradiation. Sixty-six patients, median age 44.5 years, with bulky Stage I or greater disease were included in the study. RESULTS: In univariate analysis, clinical International Federation of Gynecology and Obstetrics (FIGO) stage had significant correlation with patient outcome, but it correlated poorly with complete tumor regression and tumor local control. In contrast, MRI stage showed significant correlation with complete tumor regression, tumor local control, and disease-free survival at 12 months. When each stage was analyzed separately, the greatest difference was demonstrated between clinical and MRI assignment of stage Ib disease. MRI Stage Ib disease significantly correlated with all three categories analyzed, while clinical Stage Ib did not. Superiority of MRI assessment of low stage disease was also evident in the detection of lymph node metastasis. Significant risk for nodal metastasis was related to tumor size greater than 4 cm, invasion of the parametria and urinary bladder, and stage of the disease. CONCLUSION: The multivariate analysis demonstrated that the most related variables in order of significance were the presence of juxta-regional and paraaortic lymph nodes, patient age, tumor size, and MRI tumor stage. This study demonstrates the value of MR imaging as an adjunct to clinical assessment of bulky invasive cervical cancer, rendering more complete assessment of morphologic risk factors important in patient prognosis.

Adult↗
PubMed1993

Definitive postoperative irradiation of bile duct carcinoma with charged particles and/or photons.

PURPOSE: To determine the rates of survival and local control in patients with bile duct adenocarcinomas treated with post-operative photons and/or charged particles. METHODS AND MATERIALS: A retrospective study was performed analyzing all patients with bile duct adenocarcinomas who received radiotherapy through the University of California San Francisco and at Lawrence Berkeley Laboratory between 1977 and 1987, a total of 62 patients. University of California San Francisco patients received photon therapy (median dose 5400 cGy), and Lawrence Berkeley Laboratory patients were treated with the charged particles helium and/or neon (median dose 6000 cGyE). Forty-eight patients were treated post-operatively with curative intent, 30 with photons and 18 with particles. Thirty-six patients in the study had gross residual disease; none had microscopically negative margins. RESULTS: The overall two-year actuarial survival was 28%: 44% for particle-treated patients and 18% for patients treated with photons (p = .048). Median actuarial survival was 23 months in particle patients and 12 months in photon patients. Local control was also improved, though less significantly, in patients treated with particles (median disease-free survival 20 months vs. 4.5 months, p = .054). A univariate and multivariate analysis was performed and revealed that only extent of residual disease predicted local failure and overall survival; no other prognostic factors were identified. CONCLUSION: Compared to conventional photon radiotherapy, treatment with post-operative charged particle irradiation at Lawrence Berkeley Laboratory appeared to offer a survival advantage in this non-randomized series. Additional investigation into protection of surrounding normal tissue with better dose localization through the use of charged particles is planned.

Adenocarcinoma↗
PubMed1993

Interstitial thermoradiotherapy with ferromagnetic implants for locally advanced and recurrent neoplasms.

PURPOSE: The University of Arizona, University of California at San Francisco, City of Hope Medical Center, and University of Wisconsin participated in a Phase I/II protocol to assess the heating ability and the toxicity of interstitial thermoradiotherapy using ferromagnetic implantation. METHODS AND MATERIALS: Forty-four patients with advanced primary or recurrent extra-cranial solid malignancies were enrolled in this study. Fourteen gauge catheters were implanted into tumors and, once in the department of Radiation Oncology, loaded with ferromagnetic seeds to deliver a 60 min hyperthermia treatment. Multi-point thermometry was continuously used throughout the heating sessions for all patients, sampling the periphery as well as the core of the tumor. After 192Iridium brachytherapy, 18 patients then had an additional treatment. The mean radiation dose while on protocol was 50.0 Gy, with total doses (including prior radiotherapy) ranging from 20.3-151.8 Gy (median = 88.7 Gy). Response and toxicity were assessed by inspection, palpation, and/or radiologic studies. Forty-one patients were evaluable for response, and there were 55 analyzable hyperthermia treatment sessions. RESULTS: The complete response rate was 61% (25/41). The partial response rate was 31.7% and only 7.3% failed to respond. Median duration of local control has not yet been reached. The mean maximum, minimum, and mean time-averaged temperatures for all in-tissue sensors were 43.7 degrees C, 38.7 degrees C, and 41.0 degrees C, respectively. Tumor size was the only factor significantly correlated with temperatures or with complete response rate; larger tumors attained higher temperatures but smaller tumors had a higher response probability. Nineteen patients (43%) experienced toxicities, however there was only a 7% (3/44) rate of serious complications (Grade 3 or 4). Prior treatment with hyperthermia was the only factor significantly correlated with serious toxicity. CONCLUSION: These results, a 93% total response with only 7% serious toxicity, are encouraging especially in the context of the patient population treated. Phase II/III studies involving ferromagnetic implantation are warranted.

Adult↗
PubMed1993

High intensity 125-iodine (125I) plaque treatment of uveal melanoma.

PURPOSE: Episcleral 125I plaque therapy of uveal melanoma is an important treatment modality to control tumor, salvage the globe, and potentially preserve vision. We retrospectively analyzed our experience in 239 patients to assess treatment outcome with this technique. METHODS AND MATERIALS: Between 1983 and 1990, 239 uveal melanoma patients were treated with 125I plaques at the University of California, San Francisco. High intensity 125I seeds in the range of 3-20 mCi were used to give a minimum tumor dose of 70 Gy in 4 days. Initial mean tumor size was 10.9 mm x 9.2 mm x 5.5 mm with a range in tumor diameter from 4 to 18 mm and tumor height from 1.9 to 11.1 mm. Best corrected pre-treatment visual acuity was 20/200 or better in 92% of patients. RESULTS: Local tumor control was maintained in 91.7% of patients with a mean follow-up of 35.9 months; 19 patients had local tumor progression; mean time to progression was 27.3 mo (1.8 to 60.1 mo). Actuarial local control is 82% at 5 years. Multivariate analysis demonstrates significant correlation of local failure with larger maximum tumor diameter (p = 0.0008), closer proximity to the fovea (p = 0.0001), lower radiation dose (p = 0.0437), and smaller ultrasound height (p = 0.0034). The actuarial incidence of distant metastases is 12% at 5 years with multivariate analysis showing significant correlation only with maximum tumor diameter (p = 0.0064). Visual outcome is 20/200 or better in 58% of patients. CONCLUSION: While the tumor control rates appear favorable, ocular morbidity is significant. A current randomized trial comparing 125I plaque with Helium ion therapy is in progress with specific comparison of tumor control, survival, and visual outcome.

Adult↗
PubMed1993

Charged particle irradiation of sacral chordomas.

PURPOSE: The purpose of this report is determine the impact of charged particle irradiation at Lawrence Berkeley Laboratory (LBL) in treating patients with sacral chordomas. Overall survival, local control, complications, and predictive parameters are analyzed. METHODS AND MATERIALS: Fourteen patients with sacral chordomas were treated with the charged particles helium and neon between 1977 and 1989. The median dose was 7565 cGyE and the median follow up is 5 years. All patients were treated post-operatively; ten had gross residual disease. RESULTS: Kaplan-Meier survival at 5 years is 85%. Overall 5-year local control is 55%. A trend to improved local control at 5 years was seen in patients treated with neon when compared to patients treated with helium (62% vs 34%), in patients following complete resection versus patients with gross residual tumor (75% vs 40%), and in patients who had treatment courses under 73 days (61% vs 21%). Distant metastases were seen in two patients (14%). No patient developed neurologic sequelae or pain syndromes. One previously irradiated patient required colostomy, one patient had delayed wound healing following a negative post-radiation biopsy, and one patient developed a second malignancy. There were no genitourinary complications. CONCLUSION: Our experience indicates that post-operative charged particle irradiation of sacral chordomas appears to result in reasonable local control and survival with acceptable risk, and that additional evaluation on the use of heavy charged particles is warranted.

Adult↗
PubMed1993

Lipid peroxidation does not appear to be a factor in late radiation injury of the cervical spinal cord of rats.

PURPOSE: We tested the role of lipid peroxidation in the demyelination and white matter necrosis associated with radiation injury of the central nervous system. METHODS AND MATERIALS: We irradiated the cervical spinal cords of female F344 rats (23 Gy) and assayed for the accumulation of the peroxidation byproducts malondialdehyde and hydroxyeicosatetraenoic acids, and for the consumption of the endogenous free radical scavengers vitamins E and C. We further tested the role of lipid peroxidation in radiation injury of the central nervous system by determining the sensitivity of the cervical spinal cord to radiation in rats on diets containing deficient, normal, and supplemental levels of the antioxidant vitamin E. Rats were placed on these diets at 4 weeks of age and irradiated (18.5-21.5 Gy) 16 weeks later. RESULTS: During the 5 months between irradiation and the onset of paralysis, no accumulation of peroxidation byproducts or consumption of endogenous scavengers was seen in the cervical spinal cords of the irradiated rats. The cervical spinal cords of some of the rats placed on the diets with deficient, normal, and supplemental levels of vitamin E were analyzed at the time of irradiation and contained 197 +/- 57, 501 +/- 19, and 717 +/- 35 pmol vitamin E/mg protein, respectively. Despite the statistical differences in these levels, the radiation sensitivity of the cervical spinal cord (ED50 for white matter necrosis) in rats receiving the three diets was not different (20.4, 20.7, and 20.6 Gy). CONCLUSION: These data do not support a role for free radical-induced lipid peroxidation in the white matter damage seen in radiation injury of the central nervous system.

Animals↗
PubMed1993

Survival comparison of radiosurgery-eligible and -ineligible malignant glioma patients treated with hyperfractionated radiation therapy and carmustine: a report of Radiation Therapy Oncology Group 83-02.

PURPOSE: The purpose is twofold: (1) to identify the malignant glioma patients treated in a trial of hyperfractionated radiotherapy (RT) and carmustine (BCNU) who may have been eligible for a stereotactic radiosurgery (SRS) boost; and (2) to compare survival of such patients with that of those considered SRS-ineligible. PATIENTS AND METHODS: From January 1983 to July 1989, 778 malignant glioma patients were enrolled on Radiation Therapy Oncology Group (RTOG) 83-02, a randomized phase I/II hyperfractionated RT dose-escalation trial with BCNU chemotherapy. The SRS criteria used in a single-institution trial were applied to these patients; they are: Karnofsky performance status (KPS) of greater than 60; well-circumscribed tumor less than 4.0 cm; no subependymal spread; and a location not adjacent to brainstem or optic chiasm. RESULTS: Eighty-nine patients (11.9%) were identified as potentially SRS-eligible. The median survival times (MST) and 18-month survival rates of the 89 eligible and 643 ineligible patients were 14.4 versus 11.7 months and 40% versus 27%, respectively (P = .047). The MST and 18-month survival rate of the 544 SRS-ineligible patients with KPS greater than 60 were 12.1 months and 29%, respectively, and were not statistically inferior to the survival of the SRS-eligible group (P = .21). Multivariate analysis revealed age, KPS, and histopathology to be strongly predictive of survival, and SRS eligibility was also significantly predictive (P = .047). CONCLUSION: SRS-eligible patients enrolled on RTOG 83-02 had survival superior to that of the SRS-ineligible group, and this advantage is mainly due to the selection of a subgroup with a high minimum KPS.

Carmustine↗