Biomedical subjects

J R Castro

Publications and source records attributed to J R Castro.

At least 19 recordsLinked to original sources

PubMed2000

Expression of growth hormone receptor in the human brain.

This study was designed to investigate the presence of growth hormone receptor (GHR) expression in the human brain tissue, both normal and tumoral, as well as in the human glioblastoma cell line U87MG. Reverse transcription-polymerase chain reaction revealed the presence of GHR mRNA in all brain samples investigated and in U87MG cells. GHR immunoreactivity was also detected in this cell line using both immunocytochemistry and western blotting. All together, our data demonstrate the existence of GHR expression within the central nervous system (CNS), thus supporting a possible role for GH in the CNS physiology.

Blotting, Western↗

PubMed1997

15 years experience with helium ion radiotherapy for uveal melanoma.

PURPOSE: To review the long-term experience of helium ion therapy as a therapeutic alternative to enucleation for uveal melanoma, particularly with respect to survival, local control, and morbidity. METHODS AND MATERIALS: 347 patients with uveal melanoma were treated with helium ion RT from 1978-1992. A nonrandomized dose-searching study was undertaken, with doses progressively reduced from 80 GyE in five fractions to 48 GyE in four fractions, given in 3-15 days, mean of 7 days. RESULTS: Local control was achieved in 96% of patients, with no difference in the rate of local control being seen at 80, 70, 60, or 50 GyE in five fractions. At the lowest dose level of 48 GyE in four fractions, the local control rate fell to 87%. Fifteen of 347 patients (4%) had local regrowth in the eye requiring enucleation (12 patients), laser (1 patient) or reirradiation (2 patients). The time of appearance of local regrowth ranged from 4 months to 5 years posttreatment, with 85% occurring within 3 years. Of the 347 patients, 208 are alive as of May 1, 1997. The median follow up of all patients is 8.5 years, range 1-17 years. Kaplan-Maier (K-M) survival is 80% at 5 years, 76% at 10 years, and 72% at 15 years posttreatment. Patients with tumors not involving the ciliary body have a 15-year K-M survival of 80%. The results for patients whose tumors involved the ciliary body are poor, with a 15-year K-M survival of 43%. Seventy-five percent of patients with tumors at least 3.0 mm from the fovea and optic nerve, and initial ultrasound height less than 6.0 mm, retained vision of 20/200 or better posttreatment. Patients with tumors larger than 6 mm in thickness, or with tumors lying close to the optic nerve or fovea, have a reduced chance of retaining useful vision. The enucleation rate is 19%, 3% for local failure and 16% because of complications of the helium RT, particularly neovascular glaucoma, which occurred in 35% of patients. CONCLUSIONS: Local control and retention of the eye are excellent. Complications of therapy reduce vision and eye preservation. Twenty-four percent of patients manifested distant metastases 6 to 146 months posttreatment, mean of 43 months, median of 36 months. Late-appearing distant metastases do not appear to be caused by persistent tumor in the eye. The risk of metastases is high for patients with tumors greater than 7 mm in initial ultrasound height (37%), anterior tumors involving the ciliary body (47%), and in those with local failure (53%). Patients with tumors not involving the ciliary body and initial dimensions less than 10 mm had only an 8% chance of death from melanoma. A search for effective adjuvant therapy is needed for patients at high risk of metastases (large tumors, ciliary body involved, local regrowth in eye).

Ciliary Body↗

PubMed1997

Anterior segment sparing to reduce charged particle radiotherapy complications in uveal melanoma.

PURPOSE: The purpose of this investigation is to delineate the risk factors in the development of neovascular glaucoma (NVG) after helium-ion irradiation of uveal melanoma patients and to propose treatment technique that may reduce this risk. METHODS AND MATERIALS: 347 uveal melanoma patients were treated with helium-ions using a single-port treatment technique. Using univariate and multivariate statistics, the NVG complication rate was analyzed according to the percent of anterior chamber in the radiation field, tumor size, tumor location, sex, age, dose, and other risk factors. Several University of California San Francisco-Lawrence Berkeley National Laboratory (LBNL) patients in each size category (medium, large, and extralarge) were retrospectively replanned using two ports instead of a single port. By using appropriate polar and azimuthal gaze angles or by treating patients with two ports, the maximum dose to the anterior segment of the eye can often be reduced. Although a larger volume of anterior chamber may receive a lower dose by using two ports than a single port treatment. We hypothesize that this could reduce the level of complications that result from the irradiation of the anterior chamber of the eye. Dose-volume histograms were calculated for the lens, and compared for the single and two-port techniques. RESULTS: NVG developed in 121 (35%) patients. The risk of NVG peaked between 1 and 2.5 years posttreatment. By univariate and multivariate analysis, the percent of lens in the field was strongly correlated with the development of NVG. Other contributing factors were tumor height, history of diabetes, and vitreous hemorrhage. Dose-volume histogram analysis of single-port vs. two-port techniques demonstrate that for some patients in the medium and large category tumor groups, a significant decrease in dose to the structures in the anterior segment of the eye could have been achieved with the use of two ports. CONCLUSION: The development of NVG after helium-ion irradiation is correlated to the amount of lens, anterior chamber in the treatment field, tumor height, proximity to the fovea, history of diabetes, and the development of vitreous hemorrhage. Although the influence of the higher LET deposition of helium-ions is unclear, this study suggests that by reducing the dose to the anterior segment of the eye may reduce the NVG complications. Based on this retrospective analysis of LBNL patients, we have implemented techniques to reduce the amount of the anterior segment receiving a high dose in our new series of patients treated with protons using the cyclotron at the UC Davis Crocker Nuclear Laboratory (CNL).

Adolescent↗

PubMed1997

Neon heavy charged particle radiotherapy of glioblastoma of the brain.

PURPOSE: High-linear energy transfer (LET) radiation beams have potential applications in the treatment of glioblastoma, but have not yet demonstrated significant improvement in results. However, some patients have had local control of glioblastoma with high-LET irradiations such as neutrons and heavy charged particles. METHODS AND MATERIALS: In this collaborative study, 15 patients were entered into a randomized protocol comparing two dose levels of 20 and 25 Gy in 4 weeks of neon ion irradiation. This trial was intended to determine the optimal neon dose in terms of survival and effects of radiation. RESULTS: Fourteen patients were evaluable with no significant differences in median survival (13 and 14 months; p = NS) or median time to failure (7 and 9 months; p = NS) between the two dose arms. Three patients died of nontumor-related causes, of whom one (who died 19 months posttreatment) had autopsy confirmation of no tumor on pathological exam. The other two patients had stable magnetic resonance imaging scans at 6 and 22 months posttreatment. CONCLUSION: Although the results did not demonstrate the optimal high-LET dose level, there is an intriguing effect in that two patients had control of glioblastoma until death at 19 and 22 months. This suggests that better conformation of the high-LET dose to the tumor with neutron capture therapy or dynamic conformal heavy charged particle therapy might control glioblastoma while minimizing brain damage from radiation.

Adult↗

PubMed1995

Results of heavy ion radiotherapy.

The potential of heavy ion therapy for clinical use in cancer therapy stems from the biological parameters of heavy charged particles and their precise dose localization. Biologically, carbon, neon, and other heavy ion beams (up to about silicon) are clinically useful in overcoming the radioresistance of hypoxic tumors, thus increasing the biological effectiveness relative to low linear energy transfer x-ray or electron beams. Cells irradiated by heavy ions show less variation in cell-cycle-related radiosensitivity and decreased repair of radiation injury. The physical parameters of these heavy charged particles allow precise delivery of high doses to tumors while minimizing irradiation of normal tissues. Clinical use requires a close interaction between radiation oncologists, medical physicists, accelerator physicists, engineers, computer scientists, and radiation biologists.

Bile Duct Neoplasms↗

PubMed1995

[Dentists in 1810].

Buenos Aires way of life at the ending of 18th and beginning of 19th centuries, when this city was the so called "Gran Aldea" (big small village), is here depicted and so its costumes are, as well as beginnings of the activities of organization and regulation for people dedicates to practise professions related to Health Sciences. The First dentists who acted in this environment are also recalled.

Argentina↗

PubMed1994

Experience in charged particle irradiation of tumors of the skull base: 1977-1992.

PURPOSE: To review the experience at University of California Lawrence Berkeley Laboratory in using charged particles to irradiate primary neoplasms of the skull base and those extending to the skull base from the nasopharynx and paranasal sinuses. METHODS AND MATERIALS: During the period from 1977 to 1992, 223 patients were irradiated with charged particles at the Lawrence Berkeley Laboratory for tumors either arising in or extending to the skull base, of whom 48 (22%) had recurrent lesions, either post previous surgery or radiotherapy. One hundred twenty-six patients had lesions arising in the cranial base, mostly chordoma (53), chondrosarcoma (27), paraclival meningioma (27) with 19 patients having other histologies such as osteosarcoma or neurofibrosarcoma. There were also 31 patients with primary or recurrent squamous carcinoma of the nasopharynx extending to the skull base, 44 patients with major or minor salivary gland tumors, mostly adenocarcinoma, and 22 patients with squamous carcinoma of the paranasal sinuses, all with cranial base extension. RESULTS: Local control and survival appeared improved in tumors arising in the skull base, following the ability with charged particles to deliver high doses (mean of 65 Gy-equivalent) with relative sparing of the adjacent normal tissues. The Kaplan-Meier 5-year local control was 85% for meningioma, 78% for chondrosarcoma, 63% for chordoma and 58% for other sarcoma. Follow-up ranged from 4-191 months with a median of 51 months. CONCLUSION: Charged particle radiotherapy is highly effective in controlling cranial base lesions which have have been partially resected. Better tumor localization with CT and MRI, improved 3-D treatment planning and beam delivery techniques have continued to reduce the level of serious complications and increase local control and survival.

Female↗

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

Anterior segment complications after helium ion radiation therapy for uveal melanoma. Radiation cataract.

OBJECTIVE: To delineate the factors in the development of visually significant cataract after helium ion irradiation of eyes with uveal melanomas. DESIGN: Retrospective analysis with multivariate analysis using life tables and Cox proportional hazard models in addition to other nonparametric techniques. PATIENTS: All patients with a noncataractous other eye and adequate dosimetry data who were treated with helium ion irradiation. RESULTS: Significant cataracts (grade 3+ or 4+ on a 0 to 4+ scale) developed in 129 patients (44%). The risk of cataract development peaked at 3 years (25% per person-year) and then declined to a sustained level of 7% to 9% per year after 7 years. In multivariate analysis, the percentage of lens included in the treatment port was the predominant predictive correlate with time to significant cataract (relative risk of 2.97 for a 25% increase in the percentage of lens in the treatment port). Patient age, preexisting cortical opacity, and ultrasound tumor height were also significant; ciliary body involvement and tumor dose had smaller effects. Kaplan-Meier analysis demonstrated an increased rate of cataractogenesis with each increment of the percentage of lens in the treatment port; when more than half of the lens was in the beam, the risk of cataract exceeded 90% within 7 years. CONCLUSIONS: Cataract development after helium ion irradiation is a function of the amount of the lens in the beam. Unlike neovascular glaucoma that develops mainly in the first few years after treatment, cataract continues to develop during the entire length of follow-up.

Adult↗

PubMed1994

Helium-ion-induced human cataractogenesis.

Retrospective and ongoing analyses of clinical records from 347 primary intraocular melanoma patients treated with helium ions at LBL will allow examination of the exposure-response data for human cataract; which is a complication of the therapy from incidental exposure of the lens. Direct particle beam traversal of at least a portion of the lens usually is unavoidable in treatment of posterior intraocular tumors. The precise treatment planned for each patient permits quantitative assessment of the lenticular dose and its radiation quality. We are reporting our preliminary results on the development of helium-ion-induced lens opacifications and cataracts in 54 of these patients who had 10% or less of their lens in the treatment field. We believe these studies will be relevant to estimating the human risk for cataract in space flight.

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

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

Helium ions versus iodine 125 brachytherapy in the management of uveal melanoma. A prospective, randomized, dynamically balanced trial.

PURPOSE: Optimal radiation therapy for uveal melanoma is uncertain, and the relative efficacies of radioactive plaques and charged particles are unclear. METHODS: The authors prospectively studied helium-ion irradiation and iodine 125 (125I) brachytherapy in a randomized, dynamically balanced trial. Of the 184 patients who met the eligibility criteria, 86 were treated with helium ions and 98 with 125I brachytherapy. RESULTS: No patients with uveal melanoma had a history of systemic malignancy. Tumors were less than 15 mm in maximum diameter and less than 10 mm in thickness. A minimum tumor dose of 70 GyE was delivered to the tumor apex. There was a significantly higher local recurrence rate after 125I brachytherapy than after helium-ion irradiation. Enucleations occurred more frequently after brachytherapy (relative risk = 1.99; 95% confidence interval, 0.78-5.78). More anterior segment complications occurred after helium-ion irradiation. To date, there has been no measurable impact on survival. CONCLUSIONS: Most uveal melanomas can be managed with radiation with retention of the eye. There was better tumor control with helium-ion irradiation; however, there were more anterior segment complications.

Adult↗

PubMed1992

Clinical gain from improved beam delivery systems.

The feasibility of dynamic conformal heavy charged particle radiotherapy has been investigated at UCLBL, and shows high promise of: 1. an improved therapeutic ratio and 2. reduction in the number of treatment portals required for efficient treatment delivery. Assessment of dose to tumor and critical structures for several anatomical sites have been carried out using a normal tissue complication algorithm developed at LBL. For high-LET charged particle treatment delivery, dynamic conformal therapy using a raster scanned beam with variable modulation and multileaf collimator appears to be the optimal technique for treatment delivery.

Energy Transfer↗

PubMed1992

Charged particle radiotherapy of paraspinal tumors.

Between 1976 and 1987, 52 patients with tumors adjacent to and/or involving the cervical, thoracic, or lumbar spinal cord were treated with charged particles at the University of California Lawrence Berkeley Laboratory. The histologies included chordoma and chondrosarcoma (24 pts), other bone and soft tissue sarcoma (14 pts), and metastatic or unusual histology tumors (14 pts). Radiation doses ranged from 29 to 80 Gray-equivalent (GyE), with a median dose of 70 GyE. Twenty-one patients received a portion of their treatment with photons. Median followup was 28 months. For 36 previously untreated patients, local control was achieved in 21/36 patients and the 3-year actuarial survival was 61%. Of 16 patients treated for recurrent disease, 7/16 were locally controlled and the 3-year actuarial survival was 51%. For patients treated for chordoma and chondrosarcoma, probability of local control was influenced by tumor volume (less than 100 cc or greater than 150 cc) and whether disease was recurrent or previously untreated. Complications occurred in 6/52 patients, including one spinal cord injury, one cauda equina and one brachial plexus injury, and three instances of skin or subcutaneous fibrosis. Charged particle radiotherapy can safely deliver high tumor doses to paraspinal tumors with good local control.

Adolescent↗

PubMed1992

Recurrent locally advanced nasopharyngeal carcinoma treated with heavy charged particle irradiation.

Between June 1981 and May 1990, 11 patients with recurrent locally advanced nasopharyngeal carcinoma were treated with heavy charged particle radiation at Lawrence Berkeley Laboratory. All patients had previously undergone full course radiotherapy to a median dose of 70.2 Gy [range 61-81 Gy]. Median time to recurrence was 18.2 months. At the time of heavy charged particle radiotherapy treatment, all had evidence of invasion of the base of skull and 7 of 11 had cranial nerve deficits. None of the patients were candidates for brachytherapy because of tumor extent or poor geometry. The tumor histology was squamous cell carcinoma in 10 patients and lymphoepithelioma in one patient. Ten of the 11 patients had received chemotherapy prior to re-irradiation. The heavy charged particle tumor dose delivered ranged from 31.80 GyE to 62.30 GyE (average 50.25 GyE, median 50 GyE). Local control was achieved in 45%. Median survival was 42 months. Actuarial survival was 59% at 3 years and 31% at 5 years (Kaplan-Meier). There were no fatal complications. The results in treating locally advanced recurrent nasopharyngeal carcinoma with heavy charged particles appear superior to those reported by others using photon therapy.

Carcinoma, Squamous Cell↗

PubMed1992

Preliminary results in heavy charged particle irradiation of bone sarcoma.

Between 1979 and 1989, 17 patients with unfavorable bone sarcoma were treated wholly or in part with heavy charged particle irradiation (helium and/or neon ions) at the University of California Lawrence Berkeley Laboratory. The majority of tumors were located near critical structures such as the spinal cord or brain. Gross tumor was present in all but two patients at the time of irradiation. Six patients were treated for recurrent disease. Histologies included osteosarcoma, Ewing's sarcoma, and recurrent osteoblastoma. Four of the osteosarcomata were believed to have been induced by previous therapeutic irradiation for various tumors. Follow-up time since initiation of radiation ranged from 7 to 118 months (median 40 months). The 5-year Kaplan-Maier local control rate was 48%; the corresponding survival rate was 41%. Over half the patients succumbed to distant metastases despite the majority of patients receiving chemotherapy. In this preliminary study, we have shown that heavy charged particle irradiation can be effectively used for control of bone sarcoma. A Phase II trial is warranted to determine optimal treatment for unresectable or gross residual disease.

Antineoplastic Combined Chemotherapy Protocols↗