Maternal group B Streptococcus-related stillbirth: a systematic review.

BACKGROUND: Limited epidemiological data on the association between maternal rectovaginal group B Streptococcus (GBS) colonisation and stillbirth makes assessment of antenatal interventions for GBS stillbirth difficult. OBJECTIVES: To systematically review the existing literature and evaluate the incidence of GBS-related stillbirth by region up to March 2015. SEARCH STRATEGY: A systematic review of the published literature was completed using PubMed/MEDLINE, EMBASE, LILACS, and Cochrane Library, with Medical Subject Headings (MeSH) and search terms based upon the Centers for Disease Control and Prevention's (CDC) Active Bacterial Core Surveillance (ABCs) GBS-related stillbirth definition and chorioamnionitis. SELECTION CRITERIA: Studies reporting original data on GBS-related stillbirth occurring ≥20 weeks of gestation, with GBS confirmed by autopsy or by culture from the placenta, amniotic fluid, or other normally sterile site samples from the stillborn. DATA COLLECTION AND ANALYSIS: Descriptive analyses were performed with the absolute GBS-related stillbirth rates and proportion of stillbirths attributed to GBS calculated per study where possible. Differences in stillbirth definitions did not allow for pooled estimates to be calculated. MAIN RESULTS: Seventeen studies reported GBS-related stillbirth rates varying from 0.04 to 0.9 per 1000 births, with the proportion of stillbirths associated with GBS ranging from 0 to 12.1%. Most studies reported data from before the year 2000 and from high-income countries. CONCLUSIONS: The sparsely available epidemiological evidence was not reported consistently, emphasising the importance of standardised stillbirth definitions and diagnostic methods to optimally assess the effectiveness of any future antenatal interventions. Timing of stillbirth, GBS serotype, and global diversity were gaps in the current evidence. TWEETABLE ABSTRACT: Systematic review finds Group B Streptococcus causes up to 12.1% of stillbirths, but more research is needed.

Prognostic role for diffusion-weighted imaging of pediatric optic pathway glioma.

Optic pathway glioma (OPG) has an unpredictable course, with poor correlation between conventional imaging features and tumor progression. We investigated whether diffusion-weighted MRI (DWI) predicts the clinical behavior of these tumors. Twelve children with OPG (median age 2.7 years; range 0.4-6.2 years) were followed for a median 4.4 years with DWI. Progression-free survival (time to requiring therapy) was compared between tumors stratified by apparent diffusion coefficient (ADC) from initial pre-treatment scans. Tumors with baseline ADC greater than 1,400 × 10(-6) mm(2)/s required treatment earlier than those with lower ADC (log-rank p = 0.002). In some cases, ADC increased leading up to treatment, and declined following treatment with surgery, chemotherapy, or radiation. Baseline ADC was higher in tumors that eventually required treatment (1,562 ± 192 × 10(-6) mm(2)/s), compared with those conservatively managed (1,123 ± 114 × 10(-6) mm(2)/s) (Kruskal-Wallis test p = 0.013). Higher ADC predicted earlier tumor progression in this cohort and in some cases declined after therapy. Evaluation of OPG with DWI may therefore be useful for predicting tumor behavior and assessing treatment response.

A systematic review of treatment guidelines for metastatic colorectal cancer.

AIM: A systematic review of treatment guidelines for metastatic colorectal cancer (mCRC) was performed to assess recommendations for monoclonal antibody therapy in these guidelines. METHOD: Relevant papers were identified through electronic searches of MEDLINE, MEDLINE In Process, EMBASE and the Cochrane Library; through manual searches of reference lists; and by searching the Internet. RESULTS: A total of 57 relevant guidelines were identified, 32 through electronic database searches and 25 through the website searches. The majority of guidelines were published between 2004 and 2010. The country publishing the most guidelines was the USA (12), followed by the UK (10), Canada (eight), France (eight), Germany (three), Australia (two), Spain (two) and Italy (one). In addition, eight European and three international guidelines were identified. As monoclonal antibody therapy for mCRC was not introduced until 2004, no firm recommendations for monoclonal antibody therapy were made in guidelines published between 2004 and 2006. Recommendations for monoclonal antibody therapy first appeared in 2007 and evolved as more data became available. The most recent international, European and US guidelines recommend combination chemotherapy with the addition of a monoclonal antibody for the first-line treatment of mCRC. Second-line treatment depends on the first-line regimen used. For chemoresistant mCRC, cetuximab or panitumumab are recommended as monotherapy in patients with wild-type KRAS tumours. CONCLUSION: The study indicates that recent treatment guidelines have recognized the role of monoclonal antibodies in the management of mCRC, and that treatment guidelines should be updated in a timely manner to reflect the most recently available data.

The role of specific antibody in alternative complement pathway-mediated opsonophagocytosis of type III, group B Streptococcus.

The native capsular polysaccharide antigen of type III, group B Streptococcus contains a terminal sialic acid residue on each repeating unit that masks all end-group galactopyranose residues and prevents alternative pathway complement activation by adult human sera in the absence of type-specific antibody. The critical role of the sialic acid residues in allowing the organism to evade activating the alternative complement pathway was shown when neuraminidase treatment of the organism converted the bacteria to activators of the alternative pathway as assessed in agammaglobulinemic serum. The requirement for specific antibody in permitting alternative pathway activation by the fully sialated bacteria was shown when sera that contained low levels of specific antibody failed to activate this pathway, and when prior absorption of serum that contained higher type-specific antibody levels with the capsular antigen failed to activate this pathway. The use of C2-deficient sera showed that the calssical pathway was not required for antibody-dependent alternative pathway activation. The use of isotonic, pH 7.5, veronal-NaCl buffer that contained 1% gelatin and that was supplemented to 4 mM Mg++ and 16 mM EGTA and adjusted to pH 7.5 (MgEGTA) ruled out the participation of the C1-bypass pathway. The presence of sialic acid on the bacterial surface is one means of evading an important mechanism of natural immunity, namely activation of complement by the alternative pathway. Only specific antibody, i.e., acquired immunity, can overcome this virulence factor.

Deep Learning for Pediatric Posterior Fossa Tumor Detection and Classification: A Multi-Institutional Study.

BACKGROUND AND PURPOSE: Posterior fossa tumors are the most common pediatric brain tumors. MR imaging is key to tumor detection, diagnosis, and therapy guidance. We sought to develop an MR imaging-based deep learning model for posterior fossa tumor detection and tumor pathology classification. MATERIALS AND METHODS: The study cohort comprised 617 children (median age, 92 months; 56% males) from 5 pediatric institutions with posterior fossa tumors: diffuse midline glioma of the pons (n = 122), medulloblastoma (n = 272), pilocytic astrocytoma (n = 135), and ependymoma (n = 88). There were 199 controls. Tumor histology served as ground truth except for diffuse midline glioma of the pons, which was primarily diagnosed by MR imaging. A modified ResNeXt-50-32x4d architecture served as the backbone for a multitask classifier model, using T2-weighted MRIs as input to detect the presence of tumor and predict tumor class. Deep learning model performance was compared against that of 4 radiologists. RESULTS: Model tumor detection accuracy exceeded an AUROC of 0.99 and was similar to that of 4 radiologists. Model tumor classification accuracy was 92% with an F1 score of 0.80. The model was most accurate at predicting diffuse midline glioma of the pons, followed by pilocytic astrocytoma and medulloblastoma. Ependymoma prediction was the least accurate. Tumor type classification accuracy and F1 score were higher than those of 2 of the 4 radiologists. CONCLUSIONS: We present a multi-institutional deep learning model for pediatric posterior fossa tumor detection and classification with the potential to augment and improve the accuracy of radiologic diagnosis.

Revascularization for atherosclerotic renal artery stenosis: the treatment of choice?

Atherosclerotic renal artery stenosis (ARAS) is an important cause of renal dysfunction and secondary hypertension, and is associated with adverse cardiovascular events and increased mortality. The natural history of ARAS is characterized by anatomic disease progression and/or renal dysfunction in only a minority of patients. Medical therapy for ARAS is directed primarily toward blood pressure control and cardiovascular risk factor reduction. Renal artery revascularization is an additional treatment option for ARAS associated with ischemic nephropathy or severe, poorly controlled hypertension despite aggressive medical therapy. Unfortunately, the benefits associated with revascularization versus medical therapy alone remain unproven. Renal artery revascularization may be accomplished through open surgical revascularization or angioplasty and stenting. Although surgical renal revascularization is associated with more durable results and relatively lower risk for postoperative renal function decline, the increased risk of death or major complications associated with this management approach limit its use in patients with significant comorbidities. Renal artery angioplasty and stenting is being utilized with increasing frequency but is of uncertain benefit and is associated with rates of post-intervention renal function improvement and deterioration that are approximately equal. Renal function outcomes associated with angioplasty and stenting may be improved through a selective treatment approach and utilization of distal embolic protection. Renal artery revascularization represents the only treatment alternative for patients unresponsive to medical management, and is therefore the ''treatment of choice'' in this select group. Results of ongoing randomized trials are eagerly anticipated and may provide useful guidance for future management of ARAS.

Immunogenicity of polysaccharides from type III, group B Streptococcus.

The immunogenicity and safety of two polysaccharides isolated from type III, group B Streptococcus, were tested in adults selected for existing low concentrations of natural antibody to the capsular polysaccharide of this organism. Both vaccine preparations (trichloroacetic acid and EDTA) were found to lack pyrogenicity and toxicity for experimental animals. A single 50-microgram subcutaneous injection of either polysaccharide in human subjects elicited significant increase in antibody concentration in immunized compared with control individuals receiving phosphate-buffered saline. Antibody responses were maximal by 2 wk and remained at 21 wk after immunization. Vaccine-induced antibody was primarily of the IgG class. Of the two vaccines, the larger molecular size polysaccharide was significantly more immunogenic. Although no systemic reactions were recorded, mild transient local reactions occurred in 45% of vaccinees.

Antibody-independent classical pathway-mediated opsonophagocytosis of type Ia, group B streptococcus.

The opsonophagocytic requirements of human sera containing endogenous complement for a variety of type Ia, and group B streptococcal strains were defined. Significant reduction (>==90%) in colony-forming units was noted after a 40-min incubation for the highly encapsulated, mouse-passed prototype strain 090 by sera containing moderate to high concentrations of antibody to type Ia polysaccharide (mean, 16.5 mug/ml), whereas bacterial growth occurred in 25 sera with low levels of specific antibody (mean, 2.1 mug/ml). This absolute requirement for a critical amount of specific antibody in promoting opsonophagocytic killing of strain 090 was not found when 18 fresh clinical type Ia isolates were tested. In antibody-deficient and agammaglobulinemic sera, respectively, mean reductions in colony-forming units of 94 and 95% were seen for fresh clinical isolates, whereas strain 090 was not killed by polymorphonuclear leukocytes in the presence of these sera. All strains required a considerable amount of specific antibody for alternative pathway-mediated opsonophagocytosis. That opsonophagocytic killing of clinical type Ia isolates was mediated by the classical pathway in a nonantibody-dependent fashion was shown when MgEGTA chelation of agammaglobulinemic serum or use of serum deficient in C2 resulted in bacterial growth. The addition of C2 to C2-deficient serum restored bactericidal activity of this serum. These experiments indicate that substances other than the exposed surface of the type Ia capsular polysaccharide initiate classical pathway-mediated opsonophagocytosis of clinical isolates of type Ia, group B streptococci by human sera in the absence of immunoglobulin. Perhaps, a deficiency in classical complement pathway function is critical to the susceptibility of neonates to type Ia, group B streptococcal disease.

Is embolic protection during renal artery intervention really necessary?

Atherosclerotic renovascular disease is an increasingly recognized cause of both renal function impairment and hypertension, and its presence is associated with increased cardiovascular mortality and dialysis dependence. Although surgical renal revascularization is associated with the most favorable reported renal function outcomes, the significant perioperative mortality and complication rates have resulted in a shift to renal artery percutaneous transluminal angioplasty and stenting (RA-PTAS) as the most frequently performed method of revascularization. Renal function outcomes following RA-PTAS are less favorable, with patients experiencing functional improvement and deterioration with approximately equal frequency in reported series. Distal atheroembolization is thought to occur during RA-PTAS and has been suggested as a potential cause of the disparate renal function outcomes. Distal embolic protection devices primarily used and evaluated in the coronary and cerebrovascular circulations have also been successfully employed during RA-PTAS. Initial clinical results following RA-PTAS with distal embolic protection have been promising, with high rates of technical success, renal function outcomes that approximate those reported with open surgical revascularization, and maintenance of relatively low death and complication rates. Further investigation with controlled comparison groups is warranted before routine use of distal embolic protection can be uniformly endorsed.

Predictive value of cerebrospinal fluid polyamines in medulloblastoma.

Seventy-five cerebrospinal fluid polyamine determinations were evaluated in 16 patients with medulloblastoma. Parameters utilized in evaluating patient status for correlation with the polyamine concentrations were neurological examination, computerized tomography, radionuclide scan, myelography, and cerebrospinal fluid cytology. Fifteen of the 16 patients showed absolute correlation with the eventual clinical picture. One determination on one patient resulted in a false negative. No false positives have been observed to date.

Distribution of leukemia, lymphoma, and allied disease in parts of Great Britain: analysis by administrative districts and simulations of adjacencies. Leukaemia Research Fund 1984 Data Collection Group.

An analysis is presented of the distribution of cases of leukemia and allied disorders occurring in 151 administrative districts from England, Wales, and Scotland during 1984. The age-adjusted rates for certain conditions present an unusual pattern highlighting excessively high and low rates in parts of the country, some of which share contiguous boundaries. In particular, high rates for non-Hodgkin's lymphoma are found in rural Yorkshire districts, whereas leukemias and primary polycythemias are much more common in the Midland districts.

Idiopathic hypothalamic diabetes insipidus, pituitary stalk thickening, and the occult intracranial germinoma in children and adolescents.

We report nine consecutive children and adolescents [five females and four males; aged 2 yr 8 months (m) to 18 yr 1 m] studied over the last 5 yr with idiopathic central diabetes insipidus. In addition to vasopressin deficiency, anterior pituitary hormone deficiencies were detected, either on evaluation at presentation or during follow-up studies over the following 3 yr. Four patients had an increased concentration of plasma PRL. One patient had multiple pituitary hormone deficiencies at diagnosis, and two others developed the same by 21 m of follow-up. Brain magnestic resonance imaging scans, performed at presentation, were originally interpreted as normal in four of nine patients, except for absence of the bright posterior pituitary signal; after retrospective review, two of nine were considered normal. All of the brain magnetic resonance imaging (MRI) scans showed positive findings by 14 m of follow-up. The first abnormal finding in all patients was isolated pituitary stalk thickening. Evaluation of cerebrospinal fluid (CSF) for hCG was positive in three of eight evaluated patients; the three positive CSF values were found at presentation and 3 and 9 m after presentation. All eight patients assessed were negative for CSF alpha-fetoprotein and cytology, and no patient had serum tumor markers. Transsphenoidal biopsy of the lesion in seven of nine patients showed a germinoma in six patients and inflammatory cells in one. The six patients with documented germinoma comprise 31% of the intracranial germinomas diagnosed in this age group at the University of California-San Francisco during the last 5 yr. The patient with mononuclear inflammatory cells on biopsy along with one other patient have had spontaneous resolution of their stalk thickening. So-called "idiopathic" central diabetes insipidus warrants close follow-up to determine the etiology, especially if anterior pituitary hormone deficiencies are detected. Normal brain MRI scans or scans that show isolated pituitary stalk thickening merit follow-up with serial contrast enhanced brain MRI for the early detection of an evolving occult hypothalamic-stalk lesion. CSF evaluation is recommended at presentation because elevated CSF hCG may precede MRI abnormalities.

Evaluation of SR-2508 induced neurotoxicity and myotoxicity in rats using brainstem auditory evoked potentials and the posterior auricular muscle response.

Brainstem auditory evoked potential (BAEPs) and a middle latency component attributed to the posterior auricular muscle response (PAMR) to an intense auditory stimulus were used to measure the onset of neurotoxic and myotoxic effects in rats after chronic exposure to the radiosensitizer SR-2508. The rats received intraperitoneal injections of SR-2508, 500 mg/kg, 5 days/week for 6 weeks. BAEP and PAMR were measured after 10, 20, and 30 injections and 4 weeks after the drug treatment was stopped. A significant neurotoxic effect was observed: After 10 injections of SR-2508, latency of the fourth positive (P4) component of the BAEP, which is thought to represent activity from the superior olivary nuclei, increased from baseline levels, and a further increase was measured after 30 injections. Four weeks after drug treatment was stopped, P4 latency had not returned to baseline levels, indicating permanent injury. PAMR latency was also increased after 10 injections of SR-2508, but increased no further during the drug treatment period. Four weeks after the last injection, PAMR latencies had returned to pretreatment levels, indicating that the myotoxic effects of SR-2508 were reversible.

Evaluation of desmethylmisonidazole-induced neurotoxicity in the rat using brainstem auditory evoked potentials.

Brainstem auditory evoked responses (BAEPs) and a scale that evaluates clinical signs of neurotoxicity were used to measure the onset of neurotoxic effects seen in rats after chronic injection of 400 mg/kg/day of the radiosensitizer desmethylmisonidazole (DMM) for 5 days/week for 7 weeks. A significant neurotoxic effect was indicated by increases in the latencies of peaks 4 and 5 of the BAEP after the 24th injection of DMM; clinical signs of neurotoxicity were observed after the 30th injection. Histologic examination of brainstems from rats sacrificed after selected number of injections during treatment showed that the onset of lesions in the brainstem was gradual but not extensive. Pentobarbital used as an anesthetic agent had no effect on the induction of neurotoxicity.

Hyperfractionated irradiation for adults with brainstem gliomas.

Hyperfractionated irradiation appears to have improved survival for pediatric patients with brainstem gliomas. However, the efficacy and safety of this technique are less well established for adults with brainstem tumors. In 1984 the UCSF Department of Radiation Oncology began treating adults with brainstem gliomas using 100 cGy fractions given twice daily to total doses ranging between 6600-7800 cGy (median dose 7200 cGy). By the end of 1989, a total of 14 patients had been irradiated with follow-up times for surviving patients ranging between 4-69 months (median follow-up 33 months). Tumor histologies included five moderately anaplastic astrocytomas, one highly anaplastic astrocytoma, and eight which were unbiopsied. At the time of this analysis, six patients had failed locally, with five dying as a result of recurrent tumor. There were no deaths caused by complications or intercurrent illness. The 3-year actuarial survival rate was 59%, with a corresponding 3-year actuarial local control rate of 48%. The projected median survival was in excess of 5 years, whereas the actuarial median time to progression was 31 months (134 weeks). The treatments were well tolerated: the mean pretreatment Karnofsky Performance Status was 74% (range 60-90%); at the end of treatment the mean KPS was 78% (range 60-100%). In terms of neurologic status, six patients improved by the end of treatment, seven were stable, and one experienced only minor deterioration without change in KPS. There were no significant long-term complications (specifically, no instances of either radiation brain necrosis or myelitis). Seven patients required prolonged steroid administration after completing radiotherapy; six of these eventually recurred locally. These results appear to be substantially better than those achieved using conventional radiotherapy regimens, and suggest that this technique merits further investigation.

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.

Evaluation of misonidazole peripheral neurotoxicity in rats by analysis of nerve trains evoked response.

The clinical use of misonidazole and other nitroimidazole radiosensitizing agents is limited by the peripheral and central neurotoxicity that is produced in animals and humans. In a blinded study, rats treated with misonidazole at either 100 mg/kg or 300 mg/kg, 5 days/week for 3 weeks, were evaluated for peripheral neurotoxicity using nerve trains evoked responses. Only one rat treated at a dose of 100 mg/kg developed symptoms and signs of neurotoxicity, while all rats treated at 300 mg/kg developed these signs and symptoms. Nerve trains analysis made possible a diagnosis of neurotoxicity before overt clinical signs appeared. This test is non-invasive and may be useful for evaluating patients receiving nitroimidazole radiosensitizers as part of a radiation therapy regimen.

Radiotherapy of primary intracranial germinomas: the case against routine craniospinal irradiation.

A retrospective study was performed on all patients with biopsy-proven intracranial germinomas and unbiopsied suprasellar or pineal region tumors treated during the past 30 years in the Department of Radiation Oncology, University of California, San Francisco. A total of 33 patients were treated: 13 with biopsy-proven germinomas, and 20 others who were unbiopsied. All patients were treated with megavoltage equipment; total dose varied between 40-55 Gy. Only two patients were treated with prophylactic spinal irradiation. No patient received initial or adjuvant chemotherapy. Follow-up times for biopsy-proven patients ranged from 0.5 to 16.7 years with a median 5.3 years. No biopsy-proven patient had a recurrence of the tumor or died; thus, actuarial relapse-free and determinate survivals at 5 years were 100%. Although only one patient in this group received prophylactic spinal irradiation, no patient failed in the spinal axis. The 20 unbiopsied patients had follow-up times ranging from 0.1 to 27.5 years with a median of 5.5 years. Six unbiopsied patients died: two from recurrent disease at the primary site, one from distant peritoneal metastases, two from complications of treatment, and one from intercurrent disease. For this group, actuarial relapse-free survival at 5 years was 72%; the corresponding determinate survival was 73%. Nineteen unbiopsied patients were treated without craniospinal irradiation. Only one developed spinal metastases. The results from this and other series indicate that the risk of spinal metastases from intracranial germinoma is too low to warrant routine prophylactic spinal irradiation. However, patients with gross tumor spill causing contamination of the CSF, malignant CSF cytology, or documented subependymal or subarachnoid metastases presumably are at higher risk for leptomeningeal failure. Craniospinal irradiation is recommended for these patients.

Low-dose craniospinal radiation therapy for medulloblastoma.

At the University of California, San Francisco, 65 children with medulloblastoma of the posterior fossa were treated postoperatively with craniospinal irradiation; the dose to the posterior fossa was 54 Gy. The 26 children initially treated had only radiation therapy, receiving 30 to 40 Gy to the spine and 40 to 50 Gy to the brain. Subsequently, 39 children were treated with low-dose craniospinal irradiation and chemotherapy; 24 to 30 Gy was directed to the whole brain and 24 to 26 Gy to the spinal axis. Chemotherapy generally consisted of procarbazine just before, and hydroxyurea during, radiation therapy. Poor-risk and good-risk patients (defined by tumor resection less than 75% or greater than 75%, positive or negative myelogram, positive or negative cerebrospinal fluid analysis, age less than or greater than 2 years, respectively) were evenly distributed between the low-dose and high-dose craniospinal radiation therapy groups. Median follow-up was 51 months (range, 24 to 228 months). Kaplan-Meier actuarial survival for all patients was 73% at 5 years, 70% at 10 years. Freedom from disease progression was 68% at 5 years, 65% at 10 years. Whereas poor-risk patients treated with low-dose craniospinal irradiation and chemotherapy had a 5-year survival of 58% and a 5-year freedom from disease progression of 39%, those figures in the comparable good-risk patients were 83% and 77%, respectively. For both good-risk and poor-risk patients, the posterior fossa was the primary site of recurrence. Tumors recurred in the frontal region, probably under blocks, in three patients receiving low-dose irradiation and in two receiving the higher dose. Reducing the dose of whole-brain and spinal irradiation and giving chemotherapy did not result in a higher rate of recurrence in the brain or spinal cord. Intellectual and social function appeared better in patients receiving the lower dose. We did not study whether chemotherapy benefitted good-risk patients. Craniospinal axis irradiation at a lower dose than conventionally used does not compromise local control or survival in patients with medulloblastoma, and may reduce toxicity.

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.