Biomedical subjects

M D Prados

Publications and source records attributed to M D Prados.

At least 73 records · Page 4Linked to original sources

PubMed1995

The treatment of brain stem and thalamic gliomas with 78 Gy of hyperfractionated radiation therapy.

PURPOSE: To see whether increasing the dose of hyperfractionated radiation therapy from 72 to 78 Gy would increase survival time in patients with gliomas, particularly those with brain stem or thalamic tumors. METHODS: Seventy-eight patients with a clinical and radiographic diagnosis of a brain stem or thalamic glioma were enrolled in a trial to receive 78 Gy (1.0 Gy twice a day). Six patients with disease in other sites were also treated. The initial response to therapy was determined by comparing pretreatment magnetic resonance images and neurological examinations with those obtained within 2 weeks of completing therapy; subsequent responses were determined from bimonthly follow-up images. Time-to-tumor progression was measured from the date radiation therapy began until the date of documented radiographic or clinical progression. Survival time was measured from the date radiation therapy began until the date of death. Cox proportional hazards analysis was used to estimate the effects of specific variables on survival. RESULTS: Of 81 evaluable patients, 68 received > or = 76 Gy, 10 received between 70 and 75 Gy, and 3 received between 60 and 68 Gy. The overall response or stabilization rate was 70.4%. Tumor size decreased in 30.8% of patients; 39.5% had stable disease, and 29.6% had immediate progression. The median survival time was 12.7 months (16.1 months for adults and 10.8 months for children). The median time to tumor progression was 9.0 months (11.4 months for adults and 8.4 months for children). A duration of symptoms < or = 2 months and a diffuse lesion were each associated with shorter survival and progression times. CONCLUSIONS: For patients with brain stem or thalamic gliomas, increasing the dose of radiation therapy from 72 to 78 Gy did not significantly improve survival. Different treatment strategies are clearly needed.

Adolescent↗

PubMed1995

Carboplatin hypersensitivity in children. A report of five patients with brain tumors.

BACKGROUND: Carboplatin, which is used in the treatment of several childhood tumors, increasingly has been reported to cause hypersensitivity reactions, the majority reported in adults. Five cases of children with primary brain tumors who were treated with carboplatin and developed acute allergic reactions are presented. METHODS: The clinical history of each patient is described, as is the schedule, cumulative dose, and number of infusions of carboplatin, type of reaction, and retreatment. RESULTS: Four of the five patients had histologically proven low grade astrocytic tumors; three had juvenile pilocytic astrocytomas, and one had a mixed oligoastrocytoma. One patient with neurofibromatosis type I had radiographically-defined bilateral optic nerve gliomas. Three patients had prior chemotherapy, one with cisplatin. All five patients developed hypersensitivity reactions such as urticaria, facial erythema, and facial swelling after multiple infusions of carboplatin. Two were retreated with carboplatin after receiving antihistamines, but still developed a reaction. Carboplatin therapy was discontinued in all patients. CONCLUSION: The purpose of this report is to heighten awareness of this potentially serious complication of carboplatin in children so that potentially dangerous retreatment is avoided. As use of a weekly schedule of carboplatin in children with low grade gliomas increases, with planned therapy extending for more than 50 weeks, more hypersensitivity reactions are anticipated.

Adolescent↗

PubMed1995

Chemotherapy for gliomas.

Despite advances in surgical and radiation therapy techniques, the prognosis of patients with malignant gliomas remains poor. Few agents have been developed specifically for brain tumors, and the nitrosoureas remain the most active antitumor agents available. In this paper we review the chemotherapeutic and chemoradiation protocols currently being used to treat primary and recurrent gliomas in adults.

Adult↗

PubMed1995

Sarcomas subsequent to cranial irradiation.

The development of sarcoma subsequent to cranial irradiation is a rare but serious and potentially fatal event. We describe seven patients who had undergone cranial irradiation (range, 1600-6000 cGy) to treat their primary disease and who developed sarcomas within the irradiated field. The median time from radiation therapy to the development of a sarcoma was 8 years (range, 4 to 15 yr). Fibrosarcomas developed in four patients, and malignant fibrous histiocytomas developed in three. Despite aggressive treatment, the prognosis was poor; the median survival from the diagnosis of sarcoma was 19 months. Sarcoma should be considered in the differential diagnosis of a new lesion or a lesion that progresses several years after radiation therapy.

Adolescent↗

PubMed1995

Large effect of age on the survival of patients with glioblastoma treated with radiotherapy and brachytherapy boost.

A retrospective review was undertaken to study the influence of age on the survival of patients undergoing brachytherapy boost for glioblastoma multiforme. From February 1981 through December 1992, 159 adults with primary glioblastoma multiforme underwent high-activity iodine-125 brain implant boost after external beam radiotherapy. There were 98 men and 61 women, ranging in age from 18 to 73 years (median, 52 yr). Karnofsky performance scores ranged from 70 to 100 (median, 90). Surgery before radiotherapy consisted of biopsy in 7% of patients, subtotal resection in 66%, and gross total resection in 27%. External beam radiotherapy doses ranged from 39.6 to 76.8 Gy, with 91% of patients receiving 59.4 to 61.2 Gy. Brachytherapy doses ranged from 35.7 to 66.5 Gy (median, 55.0 Gy) at 0.30 to 0.70 Gy per hour (median, 0.43 Gy/h). Reoperations were performed in 81 patients (51%). Information on quality of life was available for 13 of the 14 living 3-year survivors; 10 patients were steroid independent, and mean Karnofsky performance scores had decreased from 92 at the time of brachytherapy to 75 at the last follow-up. Univariate and multivariate analyses showed that age was the most important parameter influencing survival (P < 0.0005). The nine patients 18 to 29.9 years old had a 3-year survival probability of 78 +/- 14% (median survival was not yet reached at the time of this report), with a follow-up of 145 to 511 weeks in living patients (median, 322 wk).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1995

Pineoblastoma in adults.

This is the first report of a series of adults (> 16 years of age) with pineoblastomas who had their entire neuraxis staged at the time of diagnosis. Between 1975 and 1992, seven men and four women with histologically proven pineoblastomas were evaluated at the University of California, San Francisco. The median age at diagnosis was 36 years (range, 17-59 yr). All patients presented with symptomatic hydrocephalus. One patient had a complete surgical resection, eight had subtotal resections, and two had biopsies only. One patient refused any treatment or follow-up review and died 6 months after diagnosis. The five patients with positively staged disease had progression either focally or in the spine 8 to 49 months (median, 10 mo) after initial diagnosis and died 1 to 20 months after recurrence; the median overall survival time from the date of surgery was 30 months. In contrast, all five patients with negatively staged disease were alive without disease progression after a median of 26 months of follow-up. Our retrospective review shows that the extent of disease at diagnosis seems to be an important prognostic factor for pineoblastomas, as is true for medulloblastomas and other primitive neuroectodermal tumors. Initial staging should include examination of the cerebrospinal fluid and magnetic resonance imaging of the spine. Although patients with pineoblastomas are often treated with adjuvant systemic chemotherapy after craniospinal irradiation, the benefits of this approach are unclear.

Adolescent↗

PubMed1995

Infiltrative astrocytomas of the thalamus.

Clinical characteristics and outcome in 57 patients with infiltrative thalamic astrocytomas were analyzed retrospectively. The median patient age was 22 years (range 1 to 69 years). Fourteen patients had no surgery, 37 had biopsy, and six had subtotal resection. The histological diagnosis was astrocytoma in 14 patients, anaplastic astrocytoma in 25, and glioblastoma multiforme in two; two specimens were nondiagnostic. The initial treatment was conventional radiation therapy (RT) in 20 patients (one also received interstitial brachytherapy), RT followed by chemotherapy in 18, hyperfractionated RT in 17 (one also received chemotherapy), and chemotherapy alone in two. The median time to tumor progression was 47 weeks (range 5 to 388 weeks); median survival was 73 weeks (range 11 to 502 weeks). Actuarial 1-, 2-, 3-, and 5-year survival rates were 67%, 35%, 24%, and 20%, respectively. Tumor progression was usually treated with chemotherapy. The assessed treatment failure was within 2 months after RT in 12 patients in whom the findings of the neurological and radiological examinations did not correspond. This assessment showed false-negative diagnosis of radiation-induced changes in five patients (42%); false-positive diagnosis of tumor progression could not be ascertained. In univariate Cox proportional-hazards analysis, histological diagnosis of astrocytoma, age under 18 years, and open biopsy were prognostically favorable features; in multivariate analysis, only open biopsy was favorable. Infiltrative astrocytomas of the thalamus carry a dismal prognosis, regardless of the type of treatment. Hyperfractionated RT does not increase toxicity but its benefit over conventional RT remains unproven.

Adolescent↗

PubMed1995

Surgery for low-grade glioma: rationale for early intervention.

We feel that early surgical intervention is appropriate in the patient who presents with a clinical picture suggesting a low-grade glioma. Neuroimaging is not adequate to make an accurate diagnosis of the underlying pathology. Tumor tissue sampling allows a more specific diagnosis and testing for biologic factors such as the proliferative potential of the lesion. Surgical diagnosis allows a disease-specific therapy to be more appropriately prescribed to the patient, including the option for no further treatment, radiotherapy, and/or chemotherapy. There is compelling early data that suggest that the extent of surgery and the postoperative tumor volume will be predictive of outcome in at least some tumor types. We encourage participation of physician and patients in well-designed clinical trails that will ultimately answer the many questions that remain about these unique diseases.

Brain Neoplasms↗

PubMed1994

Pattern of recurrence of medulloblastoma after low-dose craniospinal radiotherapy.

PURPOSE: We retrospectively evaluated relapse of medulloblastoma after low- or high-dose craniospinal radiotherapy, and after conventional or hyperfractionated posterior fossa irradiation. METHODS AND MATERIALS: Ninety-two pediatric patients were treated postoperatively since 1970 at the University of California, San Francisco. Until 1989, we employed conventional fractionation with low (< or = 30 Gy) or high-dose craniospinal fields and low-dose (< or = 56 Gy) posterior fossa boosts. Recently, hyperfractionation delivered low- or high-dose to the craniospinal axis and high-dose to the posterior fossa. Most patients treated after 1979 received chemotherapy. RESULTS: Median follow-up was 70 months. Five-year disease-free survival was 36% (22% for poor-risk vs. 59% for good-risk patients). Five-year overall survival was 52% (43% for poor vs. 68% for good-risk). Neither the dose to the posterior fossa nor the craniospinal axis was statistically related to recurrence. Failure in the posterior fossa occurred despite boosts greater than 56 Gy. Females, over the age of 6 years, had significantly better relapse-free survival than males of the same age. Six of the 54 patients who relapsed were long-term survivors. CONCLUSIONS: Low-dose craniospinal radiotherapy, where the majority of patients received chemotherapy, was not associated with increased failure. High-dose posterior fossa hyperfractionation did not improve control. Long-term survival was noted in a number of patients after relapse. We recommend 60 Gy or greater with conventional fractions to the primary area, and continued study of low-dose craniospinal irradiation with adjuvant chemotherapy.

Adolescent↗

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

Hyperfractionated craniospinal radiation therapy for primitive neuroectodermal tumors: early results of a pilot study.

PURPOSE: To report the early results of hyperfractionated craniospinal radiation therapy with and without adjuvant chemotherapy for primitive neuroectodermal brain tumors (PNETs). METHODS AND MATERIALS: Thirty-nine patients with PNETs were classified as good-risk (23) or poor-risk (16), based on postoperative magnetic resonance imaging and a cytological examination of cerebrospinal fluid. All patients received hyperfractionated craniospinal radiation therapy; poor-risk patients subsequently received adjuvant chemotherapy with cisplatin, lomustine, and vincristine. The first six patients received 72 Gy to the primary tumor site and 24 Gy to the rest of the craniospinal axis. Subsequent patients received 30 Gy to the craniospinal axis. RESULTS: During a median of 1.9 years of follow-up (range 4 months to 3.5 years), there have been ten treatment failures in 39 patients, five in the good-risk group and five in the poor-risk group. Three failures occurred in the primary tumor site in areas that received 72 Gy; two were in poor-risk patients with residual disease after surgery; one was in a good-risk patient who had a gross total resection. Three failures occurred in the spine and craniospinal fluid of patients treated with 24 Gy. Four occurred in areas treated to 30 Gy; two of these were in areas thought to be undertreated because of treatment planning errors. Adjuvant chemotherapy was difficult to give to poor-risk patients because of poor bone marrow recovery, even with relatively low doses of lomustine (75 mg/m2). CONCLUSION: We think a dose of 24 Gy to the craniospinal axis is inappropriate because three of the six patients who received it had treatment failures outside the primary site. Whether 30 Gy is an appropriate dose for good-risk patients is still unclear. Even after a dose of 30 Gy, chemotherapy was difficult to give; this potentially limits the impact of adjuvant chemotherapy in poor-risk patients. Further follow-up is necessary to evaluate the use of hyperfractionated radiation therapy alone or with chemotherapy in patients with PNETs.

Adolescent↗

PubMed1994

Proliferative potential and prognostic evaluation of low-grade astrocytomas.

Despite their histological similarity, low-grade astrocytomas vary widely in their clinical behavior. To elucidate this variable behavior, we measured the proliferative potential of 69 primary and 18 recurrent low-grade astrocytomas and correlated the results with the clinical characteristics and outcome. Each patient received an intravenous infusion of bromodeoxyuridine (BUdR); BUdR-labeled nuclei in excised tumor specimens were identified by immunoperoxidase staining. The BUdR labeling index (LI), or S-phase fraction, ranged from < 1 to 9.3%; the LI was < 1% in 64 (74%) patients and > or = 1% in 23 patients (26%). The LI did not appear to be associated with age, sex, tumor location, or whether the tumor was primary or recurrent. A Cox proportional-hazards analysis of the influence of the LI and other variables (age, sex, tumor location, extent of surgery, primary versus recurrent tumor) on survival showed that the LI and extent of surgery (total resection, subtotal resection, biopsy) were significant in predicting both survival and progression-free survival for all patients and for patients with primary tumors. The LI was also significant in predicting progression-free survival for patients with recurrent tumors. The correlation between the BUdR LI and both survival and time to recurrence suggests that the outcome of low-grade astrocytomas varies according to the proliferative potential. The growth rate of these histologically similar tumors should be assessed individually in order to select specific treatment.

Adolescent↗

PubMed1994

A phase II study of intravenous carboplatin for the treatment of recurrent gliomas.

Thirty-two patients with recurrent glioma who had previously received radiation therapy and chemotherapy with nitrosoureas were treated with intravenous carboplatin every 3 weeks, starting at a dose of 350 mg/m2, with a dose escalation of 25 mg/m2 every 6 weeks until a level 4 hematologic toxicity was reached. Of the 28 patients who could be evaluated for a response, 50% demonstrated a response or had stabilization of their disease after two infusions of carboplatin. Their median time to tumor progression and median duration of survival were 19 weeks and 38 weeks. Thrombocytopenia was the major toxicity and was severe in one-third of the patients. No neurologic or renal toxicities were noted. Carboplatin has demonstrated activity against recurrent gliomas in patients who have already had extensive chemotherapy. Increasing the dose of carboplatin may improve the rate of response and the duration of progression-free survival in patients with recurrent glioma.

Adult↗

PubMed1994

The prognostic implications of histologic classification and bromodeoxyuridine labeling index of mixed gliomas.

To clarify the biological and clinical behavior and prognosis of mixed gliomas, 47 patients underwent intraoperative bromodeoxyuridine (BrdU) labeling studies. The mean age was 27.8 years at symptom onset and 31.8 years at labeling (median, 36 years). Forty-five tumors were supratentorial, 30 were frontal, and two were cerebellar; 16 were recurrent at labeling. The median labeling index (LI) was 1% (range, < 1 to 15.1%). Forty-six tumors has oligodendroglial and astrocytic elements, and one had astrocytic and ependymal elements. The median LI was 4.4% in recurrent tumors and < 1% in primary tumors. A higher BrdU LI correlated with an increased risk of recurrence and a shorter time to recurrence. During a median follow-up of 16 months, four patients died; each had a BrdU LI > or = 4.4%. The median time to recurrence was 4.5 months for tumors with BrdU LI's > 5% but was not reached for tumors with LI's < 5% (p < 0.003). The histologic grade of the oligodendroglial component correlated with the median time to recurrence (8 months for Smith Grade C tumors, not reached for Smith Grade B tumors; p < 0.05); there were too few cases to evaluate the median times to recurrence of Smith Grade A and Grade D tumors. The median time to recurrence was not reached for any astrocytic grade, and there were no significant differences in the Kaplan-Meier survival curves. These findings suggest that the BrdU LI and the grade of the oligodendroglial component of mixed gliomas have prognostic significance.

Adolescent↗

PubMed1994

Treatment options and prognosis for multicentric juvenile pilocytic astrocytoma.

Little is known about the risk of developing multicentric disease in patients with juvenile pilocytic astrocytoma (JPA), and even less about its prognosis. Only five cases have been reported. Between 1986 and 1992, the authors treated 90 patients with either primary or recurrent JPA, 11 of whom developed multicentric spread. Ten patients had primary tumors in the hypothalamic region, eight were under 4 years of age at initial diagnosis, all had initially undergone a subtotal resection or biopsy, and 10 received postoperative multiagent chemotherapy or irradiation for residual disease. Multicentric spread was discovered immediately to 108 months after initial diagnosis; nine patients were asymptomatic at the time. Most patients received chemotherapy for the multicentric disease, which was found throughout the craniospinal axis. During 21 to 148 months of follow-up monitoring, seven patients had stabilization or regression of multicentric disease and four died. Patients with hypothalamic region tumors were 23 times more likely to develop multicentric spread than were those with primary tumors located elsewhere (p < 0.001). Based on this review, it is concluded that multicentric spread of JPA occurs more frequently than was previously recognized. In patients with subtotally resected JPA and several years of follow-up review via magnetic resonance imaging, the incidence of recurrence in a site different from the original was 12%. Patients with subtotally resected JPA in the hypothalamic region should be considered to be at high risk for developing multicentric spread. Chemotherapy appears useful in stabilizing multicentric disease. Earlier detection and intervention may result in longer disease-free survival in patients with multicentric spread of JPA.

Adult↗

PubMed1994

Identical twins with Ollier's disease and intracranial gliomas: case report.

Sarcomatous transformation of the enchondromas is a well-known complication of Ollier's disease, and nonsarcomatous malignancies have usually been associated with Maffucci's syndrome. Only 13 cases of multiple enchondromatosis associated with intracranial gliomas have been described, 5 of which were in patients with Ollier's disease. We describe three patients, including identical twins, who had both Ollier's disease and primary brain tumors. This is the first report of Ollier's disease in identical twins. These three cases support the theory that Ollier's disease and Maffucci's syndrome may represent a spectrum of the same disease process rather than two distinct diseases.

Adult↗

PubMed1993

Prognostic significance of the proliferative potential of intracranial gliomas measured by bromodeoxyuridine labeling.

The growth potential of 174 intracranial gliomas was estimated by calculating the bromodeoxyuridine labeling index (BUdR LI). Each patient received a 30-min infusion of BUdR, 200 mg/m2, before tumor removal. Excised tumor specimens were stained immunohistochemically to determine the BUdR LI, or percentage of S-phase cells. A Cox proportional-hazards stepwise model was used to determine the correlation between the BUdR LI and survival. Among patients with glioblastomas, the BUdR LI did not improve the prediction once age was entered in the model. Among patients with malignant or low-grade astrocytomas, the BUdR LI was the best single predictor of survival. The relative predictive abilities of BUdR LI and histopathology were determined by analyzing malignant astrocytoma and glioblastomas together. Distinguishing between malignant astrocytomas and glioblastomas did not significantly improve the prediction of survival once the BUdR LI and age were entered into the model. Equations derived from the model indicate that the probability of survival is a function of age and BUdR LI in patients with glioblastoma or malignant astrocytoma, but is a function of BUdR LI alone in patients with low-grade astrocytoma. The equations also show a substantial difference in the impact of increased BUdR LI on survival among patients with glioblastoma or malignant astrocytoma and those with low-grade astrocytoma. Without highly effective treatments for specific tumor phenotypes, the survival of a patient with an intracranial glioma appears to depend strongly on the proliferative potential of the tumor. Thus, accurate estimates of the proliferative potential are important in predicting the survival of individual patients with gliomas as well as in evaluating the effectiveness of various types of treatment.

Age Factors↗

PubMed1993

Intracranial myxopapillary ependymoma: case report.

The authors report an unusual case of a myxopapillary ependymoma arising from the lateral ventricle. The patient, a 37-year-old woman, developed recurrent symptoms including scotomata, disorientation, and headache during two successive pregnancies before the definitive diagnosis. The causes of this ependymoma variant and its relationship to pregnancy are discussed.

Adult↗