Biomedical subjects

P Gutin

Publications and source records attributed to P Gutin.

16 recordsLinked to original sources

PubMed1999

A phase 3 randomized study of radiotherapy plus procarbazine, CCNU, and vincristine (PCV) with or without BUdR for the treatment of anaplastic astrocytoma: a preliminary report of RTOG 9404.

PURPOSE: This study was an open label, randomized Phase 3 trial in newly diagnosed patients with anaplastic glioma comparing radiotherapy plus adjuvant procarbazine, CCNU, and vincristine (PCV) chemotherapy with or without bromodeoxyuridine (BUdR) given as a 96-hour infusion each week of radiotherapy. METHODS AND MATERIALS: Only patients 18 years or older with newly diagnosed anaplastic glioma were eligible; central pathology review was accomplished, but was not mandated prior to registration. The study had initially opened as a Northern California Oncology Group (NCOG) trial in 1991, becoming an Intergroup RTOG, SWOG, and NCCTG study in July 1994. Total accrual of 293 patients was planned as the sample size, using survival and time to tumor progression as the primary endpoints. The experiment arm (RT/BUdR plus PCV) was to be compared to the control arm (RT plus PCV) using an alpha = 0.05, one-tailed, with a power of 85% for detecting an increase in median survival from 160 to 240 weeks, assuming a 3-year follow-up after completion of enrollment. RESULTS: As of July 1996, 281 patients had been randomized; 53 (20%) were ineligible, primarily based upon central pathology review, and another 39 cases were canceled. In total, 30% of cases were excluded from analysis. The treatment arms were well balanced despite this rate of exclusion. The RTOG Data Monitoring Committee recommended suspension of enrollment in July 1996 based upon a stochastic curtailment analysis which strongly suggested that the addition of BUdR would not be associated with increased survival. In February 1997, the study was closed prior to full enrollment. At that time, the 1-year survival estimates were 82% versus 68% for RT plus PCV and RT/BUdR plus PCV respectively (one-sided, p = 0.96). The conditional power analysis indicated that even with an additional 12 months of additional accrual and follow-up the probability of detecting the prespecified difference was less than 0.01%. The differences in the two arms seem to be due to early deaths in the BUdR arm, not related to toxicity of the treatment. CONCLUSIONS: Despite encouraging Phase 2 results with BUdR, it is unlikely that a survival benefit will be seen. A final study analysis will not be done for at least 3 more years.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1999

Five year results of LINAC radiosurgery for arteriovenous malformations: outcome for large AVMS.

PURPOSE: For radiosurgery of large arteriovenous malformations (AVMs), the optimal relationship of dose and volume to obliteration, complications, and hemorrhage is not well defined. Multivariate analysis was performed to assess the relationship of multiple AVM and treatment factors to the outcome of AVMs significantly larger than previously reported in the literature. METHODS AND MATERIALS: 73 patients with intracranial AVMs underwent LINAC radiosurgery. Over 50% of the AVMs were larger than 3 cm in diameter and the median and mean treatment volumes were 8.4 cc and 15.3 cc, respectively (range 0.4-143.4 cc). Minimum AVM treatment doses varied between 1000-2200 cGy (median: 1600 cGy). RESULTS: The obliteration rates for treatment volumes < 4 cc, 4-13.9 cc, and > or = 14 cc were 67%, 58%, and 23%, respectively. AVM obliteration was significantly associated with higher minimum treatment dose and negatively associated with a history of prior embolization with particulate materials. No AVM receiving < 1400 cGy was obliterated. The incidence of post-radiosurgical imaging abnormalities and clinical complications rose with increasing treatment volume. For treatment volumes > 14 cc receiving > or = 1600 cGy, the incidence of post-radiosurgical MRI T2 abnormalities was 72% and the incidence of radiation necrosis requiring resection was 22%. The rate of post-radiosurgical hemorrhage was 2.7% per person-year for AVMs with treatment volumes < 14 cc and 7.5% per person-year for AVMs > or = 14 cc. CONCLUSION: As AVM size increases, the dose-volume range for the optimal balance between successful obliteration and the risk of complications and post-radiosurgical hemorrhage narrows.

Adolescent↗

PubMed1999

A distinctive glioneuronal tumor of the adult cerebrum with neuropil-like (including "rosetted") islands: report of 4 cases.

Four examples of a novel glioneuronal neoplasm are presented. All tumors affected adults (including two males and two females aged 25-40 years) as supratentorial, cerebral hemispheric masses with associated seizure activity and, in one case, symptoms of raised intracranial pressure and progressive hemiparesis. CT scans in two cases revealed hypodense masses without calcification. MRI scans at presentation demonstrated, in all cases, solid T1-hypointense and T2-hyperintense tumors with mass effect in one instance but no edema or contrast enhancement. Only one was relatively circumscribed on neuroradiologic study. All were infiltrative in their histologic growth pattern and predominantly glial in appearance, being composed mainly of fibrillary, gemistocytic, or protoplasmic astroglial elements of WHO grade II to III. Their distinguishing feature was their content of sharply delimited, neuropil-like islands of intense synaptophysin reactivity inhabited and rimmed in rosetted fashion by cells demonstrating strong nuclear immunolabeling for the neuronal antigens NeuN and Hu. These cells included small, oligodendrocyte-like ("neurocytic") elements as well as larger, more pleomorphic forms. Two cases contained, in addition, well-differentiated neurons of medium to ganglion-cell size. Proliferative activity was observed principally within the glial compartment; two cases contained mitotic figures and exhibited relatively elevated MIB-1 indices (6.8% and 8.2%). One of the latter progressed and proved fatal at 30 months following subtotal resection and radiotherapy. The three other patients are alive at intervals of 14 to 83 months, two tumor-free and one with extensive disease associated with the appearance of enhancement on MRI. This glioneuronal tumor variant may pursue an unfavorable clinical course.

Adult↗

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

Cavernous malformations: results of image-guided resection.

With increased use of magnetic resonance imaging (MRI), diagnosis of cavernous malformations (CMs) has become straightforward. Surgical excision is the treatment of choice for these lesions. These malformations, though, are often small and can be difficult to localize during surgery. In these cases, stereotactic resection with a frame-based system is recommended to aid in localization of the malformation. However, use of these frame-based systems can be time consuming for the surgeon and onerous for the patient. With the advent of frameless stereotactic systems, these problems can be circumvented. Therefore, stereotactic resection of 17 CMs was performed for 15 patients over the course of 2 years at our institution during an investigative trial of a frameless stereotactic device. Eight patients presented with seizures, five patients with hemorrhage, and two patients with progressive headaches. Twelve of fifteen patients had normal neurological examination results on presentation, whereas three patients had deficits resulting from intracranial hemorrhages. All patients underwent diagnostic MRI preoperatively. Fourteen lesions were found to be cortical and subcortical; the other three lesions were in the basal ganglia, lateral ventricle, and pons. Following resection, 11 of 15 patients improved. Two patients developed postoperative deficits shortly after resection. One patient with a preoperative neurological deficit remained unchanged, and one patient had a recurrence of a deficit several months following resection. Image-guided stereotactic resection provides for easy localization of small malformations without requiring the use of a stereotactic frame or retractor and is well suited for resection of cavernous malformations.

Adolescent↗

PubMed1995

Stereotactic radiosurgery in children.

The role of stereotactic radiosurgery in the treatment of pediatric patients is still being explored. We report the Gamma Knife treatment of 33 patients under the age of 21, at the University of California, San Francisco, between the years 1991 and 1993. Treatment-related toxicity has been low. 10/14 patients treated for arteriovenous malformation (AVM) with follow-up > 1 month have shown partial or complete AVM obliteration. No patient has had a new hemorrhage after AVM treatment. In children with malignant tumors, treatment was well tolerated, although most patients, ultimately, had progressive disease. Stereotactic radiosurgery is logistically possible in the pediatric population. Its use in selected patients with AVMs seems appropriate, although its role in the treatment of malignant brain tumors remains to be defined.

Adolescent↗

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↗

PubMed1990

A CT-based computerized treatment planning system for I-125 stereotactic brain implants.

A computer program has been developed at the University of California, San Francisco, as an aid in planning and evaluating stereotactic brain implants made with 125I seeds. The program allows images of seeds and catheters to be positioned in the target volume revealed by CT. It then generates and displays the resulting isodose distributions. Catheters may be changed interactively until an optimum implant is achieved. From the geometry of a stereotactic implant frame as measured by CT, the program calculates the approach angles of the catheters in the frame coordinate system. After the seeds are implanted, films made with a fiducial marker box can be used to generate true seed positions and hence true isodoses. This paper describes mathematically the geometrical transformations used by the program, and also outlines its many features and options. In its first 2 years of use the program has proved to be a valuable contributor to improved patient care.

Brachytherapy↗

PubMed1989

Interstitial brachytherapy for metastatic brain tumors.

Since December 1979, 14 patients with progressive metastatic brain lesions have been treated with temporary implantation of high-activity iodine 125 sources using stereotaxic techniques. Four patients had prior surgical resections, and 13 had been treated with external whole-brain radiotherapy. Nine patients had brachytherapy performed at recurrence 4 to 16 months after conventional radiation therapy; the other four had implants as an adjuvant "boost" to the tumor area from 2 to 4 weeks after external radiation. Six patients have since died: two with stable brain lesions at 4 and 22 weeks, respectively; three with progressive systemic and CNS tumors at 23, 24, and 29 weeks, respectively; and one with progressive CNS disease 116 weeks postimplant. The remaining eight patients are alive with a median follow-up of 63 weeks (range, 52-239+ weeks). Median survival for the entire group is 80 weeks. Brain tumor brachytherapy may be useful for palliation and possible long-term survival in selected patients with solitary metastatic disease.

Adult↗

PubMed1989

Charged particle radiotherapy for lesions encircling the brain stem or spinal cord.

Since 1981, a specialized technique has been under development at the University of California Lawrence Berkeley Laboratory for charged particle irradiation of tumors partially or completely encircling the brain stem or spinal cord. By dividing the target volume into two or more portions and using a combination of beams, a reasonably homogeneous irradiation of the target volume can be obtained which protects critical CNS structures from over-irradiation. This technique requires knowledge of the physical and biological effects of charged particles, precise, reproducible patient immobilization, careful treatment planning based upon Metrizamide contrast CT and/or MRI scanning, compensation for tissue inhomogeneities, and accurate, verifiable radiation delivery. Uncertainties in the dose distribution must be taken into account when prescribing treatment. We have used this technique in 47 patients with a variety of tumors abutting the brain stem and spinal cord, including chordoma, chondrosarcoma, meningioma, osteosarcoma and metastatic tumors. The results have shown a significant local control rate (62%) and the incidence of serious complications has been acceptable (13%). The median follow-up is 20 months with a range of 6-90 months. We conclude that charged particles can be safely and effectively used to irradiate lesions encircling the brain stem or spinal cord to doses higher than can be achieved with low-LET irradiation.

Brain Neoplasms↗

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↗

PubMed1987

[Heavy particle radiotherapy at the University of California Lawrence Berkeley Laboratory. Clinical studies by the Northern California Oncology Group].

At the university of California Lawrence Berkeley Laboratory, patients have been irradiated for 10 years with heavy ions (He, C, Ne, Si). Due to the biologic efficacy of this type of radiation as well as the possibility of a precise dose application, the tumors can be irradiated with very high doses without exposing the surrounding tissues. The experience gained in the treatment of more than 800 patients is presented. It shows that this radiation can be used to localize tumors situated near to particularly radiosensitive organs such as skull base, paraspinal region, and the eye.

Humans↗

PubMed1985

Precision, high dose radiotherapy. II. Helium ion treatment of tumors adjacent to critical central nervous system structures.

In this paper we present a technique for treating relatively small, low grade tumors located very close to critical, radiation sensitive central nervous system structures such as the spinal cord and the brain stem. A beam of helium ions is used to irradiate the tumor. The nearby normal tissues are protected by exploiting the superb dose localization properties of this beam, particularly its well defined and controllable range in tissue, the increased dose deposited near the end of this range (i.e., the Bragg peak), the sharp decrease in dose beyond the Bragg peak, and the sharp penumbra of the beam. To execute this type of treatment, extreme care must be taken in localization of the tumor and normal tissues, as well as in treatment planning and dosimetry, patient immobilization, and verification of treatment delivery. To illustrate the technique, we present a group of 19 patients treated for chordomas, meningiomas and low grade chondrosarcomas in the base of the skull or spinal column. We have been able to deliver high, uniform doses to the target volumes (doses equivalent to 60 to 80 Gy of cobalt-60) while keeping the doses to the nearby critical tissues below the threshold for radiation damage. Follow-up on this group of patients is short, averaging 22 months (2 to 75 months). Currently, 15 patients have local control of their tumor. Two major complications, a spinal cord transection and optic tract damage, are discussed in detail. Our treatment policies have been modified to minimize the risk of these complications in the future, and we are continuing to use this method to treat such patients. We are enthusiastic about this technique, since we believe there is no other potentially curative treatment for these patients.

Aged↗

PubMed1985

Helium-ion radiation therapy at the Lawrence Berkeley Laboratory: recent results of a Northern California Oncology Group Clinical Trial.

We report on the first decade of the helium-ion radiotherapy clinical trial being carried out at the Lawrence Berkeley Laboratory. Over 500 patients have now been treated. We have had very good results to date in treating patients with small tumors critically located near a radiation-sensitive organ which would preclude delivering a curative dose with conventional radiotherapy. On the other hand, patients with larger tumors where the tumor dose cannot be increased more than 10% over conventional radiotherapy have not responded well to helium ion radiotherapy. This is illustrated by discussing selected patient groups in detail, namely those with uveal melanoma, small, low-grade tumors near the central nervous system, carcinoma of the pancreas, and carcinoma of the esophagus.

Adenocarcinoma↗

PubMed1977

Multifocal leukoencephalopathy in adult leukemia: histologic features and etiologic considerations.

A number of structural alteration in brains of leukemic children have been attributed to intrathecal administration of methotrexate and radiation therapy. We report an instance of asymptomatic encephalopathy in an adult who received thio-TEPA (by subarachnoid injection) as treatment for leukemic meningitis. The lesions were microscopic, confined to cerebral white matter and included: vacuolation, myelin destruction, axonal swelling, gliosis, deposition of mineral salts and aggregates of large foamy cells. The etiology of this condition remains undetermined.

Adult↗

PubMed1976

Single-agent chemotherapy of brain tumors. A five-year review.

Identification of effective single chemotherapeutic agents for brain tumors must precede the rational use of multiple drug combinations. In phase 2 trials beginning in 1968, 158 patients with intrinsic brain tumors (mostly recurrent malignant astrocytomas) were considered evaluable. The larger trials with more effective drugs produced these results: carmustine (BCNU) response rate, 47%, with median duration of nine months; lomustine (CCNU), 44%, with median duration of six months; procarbazine hydrochloride, 52%, with median duration six months; carmustine and vincristine sulfate combined, 44%, with median duration of only four months; and BIC (5-[3,3-bis(2-chloroethyl)-1-triazeno]imidazole-4-carboxamide), 38%, with median duration of five months. Administration of glucocorticoids was not found to bias the frequency of response. Forty-seven patients, 26 of whom had responded to the initial drug, received a second drug. Among 26 patients who were evaluable, only four responded to the second drug.

Astrocytoma↗