Parental occupation and childhood astrocytoma: results of a case-control study.

Parental occupations were investigated as possible risk factors for astrocytoma, the most frequently occurring brain tumor in children. A case-control study of 163 pairs was performed. Cases under 15 years of age at diagnosis in 1980-1986 were identified through the tumor registries of eight hospitals in Pennsylvania, New Jersey, and Delaware. Controls were selected by random-digit dialing and were matched to cases on age, race, and telephone area code. Occupations before the child's conception, during the pregnancy, and after the child's birth were studied separately. We did not observe any strong associations. Significantly more fathers of cases were electrical or electronic repairmen, a subgroup of an occupational category previously associated with increased risk. An excess of case mothers employed as nurses was observed, which was significant for mothers of children diagnosed before 5 years of age. Elevated although not significant odds ratios were observed for some white collar and professional occupations in case parents; for paternal exposure to paint and paternal occupation in the paper and pulp mill industry, both in the period after the child's birth; and for maternal occupation as a hairdresser. The lack of strong associations may have resulted from low statistical power for some job groupings. Our study, unlike previous studies, focused on a single type of brain tumor: childhood astrocytoma. Thus our results suggest that some parental occupations associated with childhood brain tumors in previous studies may not be risk factors for childhood astrocytoma.     

Gestational and familial risk factors for childhood astrocytoma: results of a case-control study

Gestational and familial risk factors were investigated for their association with astrocytoma, the most frequently occurring brain tumor in children. A case-control study of 163 matched pairs was performed. Cases under 15 years of age at diagnosis in 1980-1986 were identified through the tumor registries of 8 hospitals in Pennsylvania, New Jersey, and Delaware. Controls were selected by random digit dialing and were matched to cases for age, race, and telephone area code and exchange. Maternal antinausea medications increased the risk of childhood astrocytoma [OR (odds ratio) = 2.0, P = 0.04]. Cured meat consumption during pregnancy was more common among cases (OR = 1.9, P = 0.07), and a significant trend with increasing frequency of consumption was observed (P = 0.04). Results for gestational exposure to marijuana (OR = 2.8, P = 0.07) were of borderline significance. Gestational exposure to neurally active medications, alcohol, and tobacco were not risk factors. There was a significant trend for cases to be of higher birth weight (P = 0.03). Mental retardation (OR = 3.0, P = 0.04) and cancer (OR = 1.7, P = 0.02) in a relative of the child significantly increased the risk of astrocytoma. Significantly increased risks were observed for brain tumors in relatives of children 0-4 years of age at diagnosis (OR = 6/0, P = 0.04). A significant protective effect was observed for maternal history of miscarriage or stillbirth (OR = 0.5, P = 0.01). The results of this study suggest that some gestational and familial factors may increase the risk of childhood astrocytoma.     

Radiotherapy and L-triiodothyronine in the treatment of high-grade astrocytoma

From January 1983 to March 1984, eight patients with high-grade astrocytoma received postoperative irradiation concomitantly with triiodothyronine at the Radiation Therapy Department of the I. González Martínez Oncologic Hospital in San Juan, Puerto Rico. There were no complications related to treatment. One patient is alive without evidence of disease at 39 months and seven patients died with disease, one of whom lived for 3 yr. The survival curve for these patients is similar to the survival curve of 18 patients treated at the University of Chicago by surgery, radiation, and triiodothyronine. The value of triiodothyronine as an adjuvant in the treatment of high grade astrocytoma should be further investigated.     

Radical proposal for the treatment of malignant astrocytoma.

The traditional treatment for anaplastic astrocytoma (AAF) and glioblastoma multiforme (GBM) leads to local relapse. The recurring element is assumed to be previously radioresistant, reorganizing hypoxic cells that require up to three times the traditional photon irradiation dose for inactivation. We are proposing to coagulate the original lesion with high-dose precision brachytherapy, immediately followed by resection to save the patient from secondary effects of the necrotic region. The treatment then continues with adjuvant external beam radiation therapy to the local surrounding brain and concomitant chemotherapy. The approach inverts the traditional regimen. It has the virtue of being precise, avoiding secondary effects of the necrotic tumor, and satisfying accepted radiobiological principles.     

Superfractionation radiation therapy in the treatment of malignant astrocytoma

Superfractionation (SF) radiation therapy is the administration of three fractions per day. We have assessed the effect of SF in a prospective randomized clinical study of malignant astrocytomas from July 1978 to December 1980. Thirty-five patients were randomized to SF (4000 rad in 45 fractions in 3 weeks whole brain and 1000 rad in five fractions in one week local boost). Thirty-four patients were randomized to conventional fractions (3400 rad in 17 fractions whole brain in 3.5 weeks and 1600 rad in eight fractions in 1.5 weeks local boost). Both treatment arms received chemotherapy with CCNU. The 1- and 2-year actuarial survival rate is 54% and 21% for SF group and 32% and 10% for CF group. The other advantages of SF include shorter mean duration of steroid administration and improved performance status following radiation therapy.     

Pion therapy at TRIUMF. Treatment results for astrocytoma grades 3 and 4: a pilot study

At TRIUMF, (located on the University of B.C. Campus), 53 patients with supratentorial astrocytoma grades 3 and 4 were treated with pions between 1982 and 1985. A 3-dimensional spot-scanning treatment technique has proven to be practical. The accuracy of the beam alignment system used for treatment was reproducible daily within 2 mm. Low pion flux has hindered optimal beam shaping but this will soon be remedied as flux improves. The overall median survival observed (53 patients) is 262 days from date of first radiation treatment. Younger (less than 49 years) patients have significantly better survival than older (greater than 50 years) patients (p = 0.001). From a base line dose of 40 Gy photons whole brain and 17.5 Gy pion boost, doses were escalated to 33 Gy pions localised to the primary tumour and the median survival improved from 198 to 436 days. Survival curves for patients treated with localised pion techniques to doses above 30 Gy are significantly better than for those treated with schedules of pions mixed with photons (p = 0.04). It appears that optimal pion dose for brain tumours is 33 Gy minimum with a possible maximum of 36 Gy and doses delivered in 15 fractions in 3 weeks. Requirements for future trials are discussed.     

Ependymomas: results of radiation treatment

Between 1958 and 1980, 102 patients with the diagnosis of ependymoma were seen at the Princess Margaret Hospital. Eleven patients had recurrent disease or were treated elsewhere and 91 patients received radiation therapy following their primary surgical procedure. Fifty patients had cranial tumors and 41 had spinal tumors. The overall survival at five years was 60% and at 10 years was 54%. Those patients with spinal tumours did significantly better with a five year survival of 83% versus 43% for the group with cranial tumors. The other prognostic factors included tumor grade, functional status, age of the patient and interval from surgery to radiation. The most common site of relapse was at the original tumor location, but five patients did show spread through the craniospinal axis. An analysis of dose and the volume treated is made and recommendations for therapy given.     

Spinal cord astrocytoma: multidisciplinary experience

Background  

Astrocytomas of the spinal cord have rarely been reported. We examined our experience, treatment and outcome of patients treated during the last four years.     

Hemorrhagic onset of pilocytic astrocytoma and pilomyxoid astrocytoma

The incidence of hemorrhagic onset in pilocytic astrocytoma and pilomyxoid astrocytoma, and the clinical and histological characteristics, were compared to other types of neuroepithelial tumors or nonhemorrhagic pilocytic astrocytoma by retrospective review of 445 consecutive neuroepithelial tumors treated at our institute. Hemorrhagic onset was observed in 4 of 35 (11.4%) patients with pilocytic astrocytoma and pilomyxoid astrocytoma, with higher incidence than in glioblastoma (3.9%), anaplastic oligodendroglioma (7.7%), and anaplastic ependymoma (7.1%). The hemorrhagic onset occurred in 2 patients with sporadic pilocytic astrocytoma, 1 with pilocytic astrocytoma associated with neurofibromatosis type 1, and 1 with pilomyxoid astrocytoma. There was no correlation between hemorrhagic onset and clinical features, including age, sex, tumor location, proliferative activity, or microvascular proliferation. Hemorrhagic onset of pilocytic astrocytoma and pilomyxoid astrocytoma is not as uncommon as was previously thought, so pilocytic astrocytoma or pilomyxoid astrocytoma should be considered in the differential diagnosis of patients with brain tumors manifesting as hemorrhagic onset.     

Inhibition of furin-mediated processing results in suppression of astrocytoma cell growth and invasiveness.

PURPOSE: Astrocytoma arises in the central nervous system as a tumor of great lethality, in part because of the invasive potential of the neoplastic cells that are able to release extracellular matrix-degrading enzymes. Furin convertase activates several precursor matrix metalloproteases involved in the breakdown of the extracellular matrix. In the present study inhibition of furin was achieved by gene transfer of alpha(1)-antitrypsin Portland (PDX) cDNA. EXPERIMENTAL DESIGN: This furin inhibitor was transfected into two tumorigenic astrocytoma cell lines. The inhibitory effect was evaluated using in vivo tumorigenicity, invasion, and proliferation assays, as well as by investigating impairment of furin substrate processing. RESULTS: Expression of PDX prevented the s.c. growth of the transfected cells. Invasion assays demonstrated that PDX-transfected cells exhibited a reduced invasive ability in vitro and in vivo. Furthermore, s.c. growth of PDX transfectant xenotransplants showed a significant reduction in size that coincided with a significant decrease of the in vitro doubling time and of the in vivo cell proliferation ability. Additional studies showed that the furin substrates insulin-like growth factor IR, transforming growth factor beta and membrane type 1-matrix metalloprotease were not activated in PDX-expressing astrocytoma cells. CONCLUSIONS: PDX expression in astrocytoma cells demonstrated a direct mechanistic link between furin inhibition, and decreased astrocytoma proliferation and invasive ability. Because furin inhibition inhibits both invasiveness and cell growth in astrocytoma, furin should be considered a promising target for glioblastoma therapy.     

Carcinoma of the esophagus: treatment results

Of the 172 patients with carcinoma of the esophagus or the gastro-esophageal junction seen between January 1978 and January 1981, 69 patients had combined treatment, radiotherapy and resection, and 38 had curative radiotherapy. The remaining 65 were treated palliatively. The 4-year actuarial survival of the first two treatment groups was respectively 40% and 4%. The resectability rate of the operated patients was 84% with a post-operative mortality of 20%. The tumor size and sex were two important prognostic factors. Patients with combined treatment and a tumor size of less than two corresponding underlying vertebrae, had a 4-year actuarial survival of 60%.     

Conservative surgery and radiotherapy in the treatment of spinal cord astrocytoma

Spinal cord astrocytomas are rare neoplasms, and optimaltreatment guidelines are undefined. 23 patients with spinalcord astrocytomas were treated between 1984 and 1993with conservative surgery and postoperative radiotherapy. The meanage was 31 years. Twelve patients were maleand eleven female. All patients presented with neurologicdeficits. Cervical cord was involved in five patients,cervicothoracic in four, thoracic in eight and thoracolumbarin six. Five patients had intramedullary cysts. Fifteenpatients had low grade tumors and six highgrade. Surgery was near total excision in threepatients, partial excision in ten and biopsy inten patients. All patients received postoperative radiotherapy toa median dose of 45 Gy in 25fractions over 5 weeks. The median followup was51 months (range 7–143 months). At 6 monthspost radiotherapy, twelve patients had improvement of neurologicstatus, nine had stable status, and two deteriorated.The actuarial overall survival was 55% at 5years and 39% at 10 years. The actuarialprogression free survival probability was 75% at 5years and 55% at 10 years. Five patientshad local failure and two failed at distantsites. Twelve patients died, six due to progressivedisease, five due to complications of paraplegia andone patient of unrelated causes. Tumor grade wasa significant prognostic factor for overall survival. 5year overall survival was 79% for low gradetumors. No patient with high grade tumor survivedmore than 2 years and the median survivalwas 10 months. Low grade, female sex andpresence of intramedullary cysts were associated with significantlyimproved progression free survival. Conservative surgery followed byradiotherapy appears to have a role in achievingtumor control and neurologic recovery in patients withlow grade astrocytomas of the spinal cord. Treatmentresults of high grade tumors remain poor andnew therapeutic strategies need to be studied.     

Importance of histologic condition and treatment of pediatric cerebellar astrocytoma.

Histologic classification and treatment of pediatric cerebellar astrocytomas is an area of controversy. At the Medical College of Wisconsin, 34 patients less than 15 years of age (median, 7.3 years of age) with cerebellar astrocytomas were seen from 1965 to 1988. Effect of histologic condition and treatment on overall survival (OS) and progression-free survival (PFS) was analyzed. Progression was defined as radiographic evidence of an enlarging mass and/or signs and symptoms indicative of advancing disease. Histologic material was reviewed and classified by the system of Winston and Gilles. Twenty-eight patients had glioma A tumors, and six patients had glioma B tumors. For patients with glioma A (n = 28), 5-year actuarial OS rate was 100%. For patients with glioma B (n = 6), 5-year actuarial OS rate was 41%. PFS rate was 66% and 0% for patients with glioma A and glioma B, respectively. The poorer PFS for patients with B histologic tumors was statistically significant (P less than 0.001). The median time to progression was 36 months and 23 months for patients with glioma A and B, respectively. Patients were retrospectively divided into total resection and observation, total resection and irradiation, subtotal resection and observation, and subtotal resection and irradiation groups, which were composed of 12, 2, 3, and 17 patients, respectively. Five-year actuarial OS rates were 100%, 50%, 50%, and 100%, respectively. PFS rates were 60%, 50%, 33% and 58%, respectively. These data support the Gilles classification as a prognostic tool because patients with B tumors had a higher incidence of disease progression and accounted for all deaths. Postoperative irradiation after subtotal resection seems to be beneficial, but additional investigation, ideally with a prospective randomized trial, will be necessary to firmly establish this.     

Patterns of failure following treatment for glioblastoma multiforme and anaplastic astrocytoma

Recurrence patterns of glioblastoma multiforme (25) and anaplastic astrocytoma (9) were studied using CT scans of 34 patients who received all or a portion of their surgical treatment at Memorial Sloan-Kettering Cancer Center from January 1983 through February 1987. Thirty-two patients presented with unifocal tumors and two with multifocal tumors. All patients received radiation therapy following initial surgery. Eighteen patients who underwent re-operation following CT evidence of recurrence had histologic verification of recurrent tumor; sixteen patients had radiographic evidence of recurrence only. Seventy-eight percent (25/32) of unifocal tumors recurred within 2.0 cm of the pre-surgical, initial tumor margin, defined as the enhancing edge of the tumor on CT scan. Fifty-six percent (18/32) of tumors recurred within 1.0 cm of the initial tumor margin. Tumors for which a gross total resection was accomplished tended to recur closer to the initial tumor margin than did subtotally resected tumors (p greater than 0.1). Extensive pre-operative edema was associated with a decreased distance between initial and recurrent tumor margins. Large tumors were generally not more likely to recur further from the initial tumor margin than were smaller tumors. No unifocal tumor recurred as a multifocal tumor. Only one tumor (initially near the midline) recurred in the contralateral hemisphere. The findings support the use of partial brain irradiation for post-operative treatment of glioblastoma multiforme and anaplastic astrocytomas, and may help to determine the most appropriate treatment volume for interstitial irradiation.     

Bilateral thalamic astrocytoma

We present a 68-year-old woman who presented with symptoms of frontotemporal dementia. Brain MRI revealed tumor mass in both thalami and according to WHO classification, the tumor corresponded to diffuse fibrillary astrocytoma grade II. This case points to the role of neuroimaging in patients presenting with classical symptoms of dementia.     

Pineal region tumors: Analysis of treatment results

This article represents a review of 32 patients with pineal region tumors seen and treated at the University of Michigan Medical Center from January 1950 to December 1980. All patients presented with manifestations of increased intracranial pressure: limitation of the upward gaze (Parinaud's syndrome), hydrocephalus and a mass in the posterior aspect of the third ventricle. The tumor was demonstrated by pneumoencephalography, ventric ulography, angiography or CT scans. Ventricular decompression was performed in all patients. Eighteen of the 32 patients (56%) had a histological diagnosis of germinoma, one patient had a diagnosis of hamartoma; no histological diagnosis was obtained in the remainder of the patients. Twenty-seven patients received post-operative irradiation. Irradiation dosage ranged between 30 and 55 Gy. The overall 10 year survival for evaluable patients was $\text{16}\text{24}$ (67%). The low incidence of spinal cord metastasis in these patients does not justify routine use of spinal irradiation.