The impact of the time factor on the outcome of a combined treatment of patients with laryngeal cancer

PurposeTo investigate the impact of the time factor on the locoregional control in combined treatment (surgery and postoperative radiotherapy) in patients with advanced laryngeal cancer.Materials and MethodsBetween January 1993 and December 1996, 254 patients with pT3 or pT4 and pN0-pN2 laryngeal cancer were treated by surgery and postoperative radiotherapy (RT). The median age of patients was 56.3 years (range: 30–70 years). The analyzed group consisted of 236 males (92%) and 18 females (8%). In all cases total laryngectomy was performed. 196 out of 254 patients underwent homolateral neck dissection and 58 out of 254 bilateral neck dissection. RT began 45 days postoperatively (range: 22 to 78 days) and continued for 47 days (range: 40–74 days). The primary tumour bed was irradiated to the median total dose of 61.2 Gy (range: 57 – 64 Gy) and all regional lymph nodes were treated in all patients to a dose of 50 Gy. Postoperative RT was indicated in case of close postoperative margins at the tumour site or pathological status of lymph nodes described as pN1 or pN2. Univariate and multivariate analyses were used to determine the predictors for locoregional failure. The following factors were studied for their prognostic importance of locoregional outcome: the overall treatment time (OTT), radiotherapy treatment time (RTT), the interval between surgery and the beginning of radiotherapy, age, sex, pT and pN categories.Results: The actuarial 5-year overall survival rate was 49%, the actuarial loco regional control rate was 70%. The univariate analysis, using a log-rank test indicated that prolongation of the overall treatment time (OTT), the time of radiotherapy (RTT), the interval time between surgery and radiotherapy, and the pN status were predicted for the loco regional control of postoperative radiotherapy. The multivariate analysis using Cox proportional hazard model indicated that only RTT, OTT, and the pathological status of lymph nodes were independent prognostic factors for the loco regional control.Conclusions: The analysis showed that the prolongation of the overall treatment time of the combined modality (OTT) and the time of radiotherapy course (RTT) were independent prognostic time factors correlated with lower loco regional control.     

Effects of prolactin and bromocriptine in Discoglossus pictus (anuran amphibian. Otth) tadpoles

1. The results obtained by ovine prolactin administration during the larval development of Discoglossus pictus (OTT) suggests that prolactin-like hormone is the "larval factor" necessary for growth and for maintaining the larval aquatic features. 2. Bromocriptine treatment during the larval development of D. pictus has contrary effect on growth and larval structures. 3. Prolactin administration does not inhibit but delays metamorphosis. 4. When bromocriptine is added at late stages of the development, metamorphosis is accelerated.     

The Impact of the Overall Radiotherapy Time on Clinical Outcome of Patients with Nasopharyngeal Carcinoma; A Retrospective Study

Purpose

In Yogyakarta, nasopharyngeal carcinoma (NPC) shows a poor response to radiotherapy treatment. Previous study showed a prolonged overall treatment time (OTT), due to interruptions during treatment. This study explores the association between clinical outcome and OTT. Secondary, the relation between clinical outcome and disease stage, waiting time to radiation (WT) and chemotherapy schedule was explored.

Methods

In this retrospective cohort, 142 patients who started curative intent radiotherapy for NPC between March 2009 and May 2014, with or without chemotherapy, were included. The median follow up time was 1.9 years. Data was collected on WT, OTT, disease stage, and chemotherapy schedule. Time factors were log-transformed. Clinical outcome was defined as therapy response, loco-regional control (LRC), disease free survival (DFS) and overall survival (OS).

Results

The median WT was 117 days (range 12–581) and OTT was 58 days (43–142). OTT and disease stage were not associated to any of the clinical outcome parameters. The log- WT was associated to poor therapy outcome (HR 1.68; 95% ci: 1.09–2.61), LRC (HR 1.66; 95% ci: 1.15–2.39), and DFS (HR 1.4; 95% ci: 1.09–1.81). In the multivariable analysis, significant hazard risk for poor therapy response, LRC, DFS and OS were seen for patients who didn’t received concurrent chemotherapy.

Conclusion

Not receiving concurrent chemotherapy showed the strongest risk for poor outcome. Since the choice of chemotherapy is related to a variety of factors, like the WT and patient’s physical condition when radiation can start, careful interpretation is needed. Reason for not finding a relation between OTT and clinical outcome might be the low number of patients who finished radiotherapy within 7 weeks, or by a stronger detrimental effect of other factors.     

Establishment of a novel factor-dependent myeloid cell line from primary cultures of mouse bone marrow

We describe here a novel myelomonocytic cell line (OTT1) obtained from primary cultures of mouse bone marrow cells infected with a retroviral vector carrying the mouse interleukin (IL)-1 alpha gene. OTT1 cells are dependent for their survival and proliferation on IL-3, granulocyte-macrophage colony-stimulating factor (GM-CSF) or, unexpectedly, IL-5. Despite their IL-5 dependency, OTT1 cells form colonies showing predominantly monocyte maturation when plated in methylcellulose. It is suggested that constitutive expression of the exogenous IL-1 alpha gene may predispose to a monocytic phenotype. OTT1 cells should be a useful experimental model to investigate the molecular mechanisms of IL-5 signal transduction and the possible interrelationships between this signal pathway and those utilized by IL-3 and GM-CSF.     

Survival Impact of Delaying Postoperative Radiotherapy in Patients with Esophageal Cancer

The purpose of the current study was to retrospectively assess the effect of postoperative radiotherapy (RT) delay on survival for patients with esophageal cancer. From 2008 to 2011, patients with esophageal cancer who had undergone postoperative RT in five different hospitals in China were reviewed. Clinical data, including time interval between surgery to RT, were prospectively collected. Kaplan-Meier method was conducted to estimate the effect of each variable on progression-free survival (PFS) and overall survival (OS), with differences assessed by log-rank test. Univariate Cox proportional-hazards models were performed for both PFS and OS for all assumed predictor variables. Statistically significant predictor variables (P < .05) on univariate analysis were then included in multivariate Cox proportional-hazards models, which were performed to compare the effects of RT delay on PFS and OS. A total of 316 patients were finally enrolled in this prospectively multicentric study. Time to RT after surgery varied from 12 days to over 60 days (median, 26 days). Multivariate analysis showed that delay to RT longer than the median does not appear to be a survival cost. There was also no statistically difference in PFS (P = .513) or OS (P = .236) between patients stratified by quartiles (≤21 days vs ≧35 days). However, patients with particularly long delays (≧42 days) demonstrated a detrimental impact on OS (P = .021) but not PFS (P = .580). Delaying postoperative RT of esophageal cancer does not impact PFS, but results in a significant reduction on OS if delaying longer than 6 weeks.     

A Prospective Study: Current Problems in Radiotherapy for Nasopharyngeal Carcinoma in Yogyakarta,Indonesia

Introduction

Nasopharyngeal carcinoma (NPC) has a high incidence in Indonesia. Previous study in Yogyakarta revealed a complete response of 29% and a median overall survival of less than 2 years. These poor treatment outcome are influenced by the long diagnose-to-treatment interval to radiotherapy (DTI) and the extended overall treatment time of radiotherapy (OTT). This study reveals insight why the OTT and DTI are prolonged.

Method

All patients treated with curative intent radiotherapy for NPC between July 2011 until October 2012 were included. During radiotherapy a daily diary was kept, containing information on DTI, missed radiotherapy days, the reason for missing and length of OTT.

Results

Sixty-eight patients were included. The median DTI was 106 days (95% CI: 98−170). Fifty-nine patients (87%) finished the treatment. The median OTT for radiotherapy was 57 days (95% CI: 57–65). The main reason for missing days was an inoperative radiotherapy machine (36%). Other reasons were patient’s poor condition (21%), public holidays (14%), adjustment of the radiation field (7%), power blackout (3%), inoperative treatment planning system (2%) and patient related reasons (9%). Patient’s insurance type was correlated to DTI in disadvantage for poor people.

Conclusion

Yogyakarta has a lack of sufficient radiotherapy units which causes a delay of 3–4 months, besides the OTT is extended by 10–12 days. This influences treatment outcome to a great extend. The best solution would be creating sufficient radiotherapy units and better management in health care for poor patients. The growing economy in Indonesia will expectantly in time enable these solutions, but in the meantime solutions are needed. Solutions can consist of radiation outside office hours, better maintenance of the facilities and more effort from patient, doctor and nurse to finish treatment in time. These results are valuable when improving cancer care in low and middle income countries.     

Tumor-associated carbonic anhydrase 9 spatially coordinates intracellular pH in three-dimensional multicellular growths

CA9 is a membrane-tethered, carbonic anhydrase (CA) enzyme, expressed mainly at the external surface of cells, that catalyzes reversible CO(2) hydration. Expression is greatly enhanced in many tumors, particularly in aggressive carcinomas. The functional role of CA9 in tumors is not well established. Here we show that CA9, when expressed heterologously in cultured spheroids (0.5-mm diameter, ~25,000 cells) of RT112 cells (derived from bladder carcinoma), induces a near-uniform intracellular pH (pH(i)) throughout the structure. Dynamic pH(i) changes during displacements of superfusate CO(2) concentration are also spatially coincident (within 2 s). In contrast, spheroids of wild-type RT112 cells lacking CA9 exhibit an acidic core (~0.25 pH(i) reduction) and significant time delays (~9 s) for pH(i) changes in core versus peripheral regions. pH(i) non-uniformity also occurs in CA9-expressing spheroids after selective pharmacological inhibition of the enzyme. In isolated RT112 cells, pH(i) regulation is unaffected by CA9 expression. The influence of CA9 on pH(i) is thus only evident in multicellular tissue. Diffusion-reaction modeling indicates that CA9 coordinates pH(i) spatially by facilitating CO(2) diffusion in the unstirred extracellular space of the spheroid. We suggest that pH(i) coordination may favor survival and growth of a tumor. By disrupting spatial pH(i) control, inhibition of CA9 activity may offer a novel strategy for the clinical treatment of CA9-associated tumors.     

肝转移癌放射治疗进展

过去的几十年,在肝转移癌的治疗方面,放疗已经越来越多的应用于临床。对于局部肝转移癌,临床上往往采取加大剂量已提高局部控制率,以期提高患者生产期。但是,对于有症状的广泛性肝转移患者则给以全肝低剂量照射。放疗已成为不适合手术或化疗等方式的肝转移癌患者的有效治疗手段。放疗靶区勾画及放疗技术进步更好的保护了高剂量靶区周围的正常肝脏组织,使得提高靶区放疗剂量的手段很好的应用于临床。关于肝转移癌的适形与立体定向放疗治疗的提高局控率及生存期的临床研究不断出现。本文就局部肝转移的根治放疗与全肝的姑息放疗临床数据做相关综述,认为放疗在肝转移癌的治疗中是安全,有效的。但是,肝转移癌的临床随机试验研究仍较匮乏。     

Theranostic Gold Nanoparticles Modified for Durable Systemic Circulation Effectively and Safely Enhance the Radiation Therapy of Human Sarcoma Cells and Tumors

Radiation therapy (RT) is an integral component of the treatment of many sarcomas and relies on accurate targeting of tumor tissue. Despite conventional treatment planning and RT, local failure rates of 10% to 28% at 5 years have been reported for locally advanced, unresectable sarcomas, due in part to limitations in the cumulative RT dose that may be safely delivered. We describe studies of the potential usefulness of gold nanoparticles modified for durable systemic circulation (through polyethylene glycosylation; hereinafter “P-GNPs”) as adjuvants for RT of sarcomas. In studies of two human sarcoma-derived cell lines, P-GNP in conjunction with RT caused increased unrepaired DNA damage, reflected by approximately 1.61-fold increase in γ-H2AX (histone phosphorylated on Ser¹³⁹) foci density compared with RT alone. The combined RT and P-GNP also led to significantly reduced clonogenic survival of tumor cells, compared to RT alone, with dose-enhancement ratios of 1.08 to 1.16. In mice engrafted with human sarcoma tumor cells, the P-GNP selectively accumulated in the tumor and enabled durable imaging, potentially aiding radiosensitization as well as treatment planning. Mice pretreated with P-GNP before targeted RT of their tumors exhibited significantly improved tumor regression and overall survival, with long-term survival in one third of mice in this treatment group compared to none with RT only. Interestingly, prior RT of sarcoma tumors increased subsequent extravasation and in-tumor deposition of P-GNP. These results together suggest P-GNP may be integrated into the RT of sarcomas, potentially improving target imaging and radiosensitization of tumor while minimizing dose to normal tissues.     

Protective and therapeutic effects of molsidomine on radiation induced neural injury in rats

We investigated the protective and therapeutic effects of molsidomine (MOL) in a rat model of whole brain radiotherapy (RT). Forty female rats were divided into five groups of eight: group 1, control; group 2, 15 Gy single dose RT (RT); group 3, 4 mg/kg MOL treated for 5 days (MOL); group 4, 4 mg/kg MOL for 5 days, 10 days after RT treatment (RT + MOL); group 5, 4 mg/kg MOL treatment for 5 days before RT treatment and for 5 days after RT treatment (MOL + RT). All rats were sacrificed on day 16. Neurodegenerative changes in the brain and tissue levels of oxidants and antioxidants were evaluated. The oxidative parameters were increased and antioxidant status was decreased in group RT compared to groups MOL + RT and RT + MOL. Histopathological examination showed that treatment with MOL after RT application and treatment with MOL before RT treatment decreased neuronal degeneration. No difference in neuronal appearance was found between groups RT + MOL and MOL + RT. MOL treatment protected the nervous system of rats and may be a treatment option for preventing RT induced neural injury.     

A mathematical model of brain tumour response to radiotherapy and chemotherapy considering radiobiological aspects

Glioblastoma is the most frequent and malignant brain tumour. For many years, the conventional treatment has been maximal surgical resection followed by radiotherapy (RT), with a median survival time of less than 10 months. Previously, the use of adjuvant chemotherapy (given after RT) has failed to demonstrate a statistically significant survival advantage. Recently, a randomized phase III trial has confirmed the benefit of temozolomide (TMZ) and has defined a new standard of care for the treatment of patients with high-grade brain tumours. The results showed an increase of 2.5 months in median survival, and 16.1% in 2 year survival, for patients receiving RT with TMZ compared with RT alone. It is not clear whether the major benefit of TMZ comes from either concomitant administration of TMZ with RT, or from six cycles of adjuvant TMZ, or both.The objectives were to develop our original model, which addressed survival after RT, to construct a new module to assess the potential role of TMZ from clinical data, and to explore its synergistic contribution in addition to radiation. The model has been extended to include radiobiological parameters. The addition of the linear quadratic equation to describe cellular response to treatment has enabled us to quantify the effects of radiation and TMZ in radiobiological terms.The results indicate that the model achieves an excellent fit to the clinical data, with the assumption that TMZ given concomitantly with RT synergistically increases radiosensitivity. The alternative, that the effect of TMZ is due only to direct cell killing, does not fit the clinical data so well. The addition of concomitant TMZ appears to change the radiobiological parameters. This aspect of our results suggests possible treatment developments.Our observations need further evaluations in real clinical trials, may suggest treatment strategies for new trials, and inform their design.     

Impact of hospital volume on mortality for brain metastases treated with radiation

BackgroundThe impact of hospital volume on cancer patient survival has been demonstrated in the surgical literature, but sparsely for patients receiving radiation therapy (RT). This analysis addresses the impact of hospital volume on patients receiving RT for the most common central nervous system tumor: brain metastases.Materials and methodsAnalysis was conducted using the National Cancer Database (NCDB) from 2010–2015 for patients with metastatic brain disease from lung cancer, breast cancer, and colorectal cancer requiring RT. Hospital volume was stratified as high-volume (≥ 12 brain RT/year), moderate (5–11 RT/year), and low (< 5 RT/year). The effect of hospital volume on overall survival was assessed using a multivariable Cox regression model.ResultsA total of 18,841 patients [9479 (50.3%) men, 9362 (49.7%) women; median age 64 years] met the inclusion criteria. 16.7% were treated at high-volume hospitals, 36.5% at moderate-volume, and the remaining 46.8% at low-volume centers. Multivariable analysis revealed that mortality was significantly improved in high-volume centers (HR: 0.95, p = 0.039) compared with low-volume centers after accounting for multiple demographics including age, sex, race, insurance status, income, facility type, Charlson-Deyo score and receipt of palliative care.ConclusionHospitals performing 12 or more brain RT procedures per year have significantly improved survival in brain metastases patients receiving radiation as compared to lower volume hospitals. This finding, independent of additional demographics, indicates that the increased experience associated with increased volume may improve survival in this patient population.     

Radiation Therapy-Induced Tumor Invasiveness Is Associated with SDF-1-Regulated Macrophage Mobilization and Vasculogenesis

Radiation therapy (RT) remains the front-line treatment for high-grade gliomas; however, tumor recurrence remains the main obstacle for the clinical success of RT. Using a murine astrocytoma tumor cell line, ALTS1C1, the present study demonstrates that whole brain irradiation prolonged the survival of tumor-bearing mice, although the mice eventually died associated with increased tumor infiltration. Immunohistochemical (IHC) analysis indicated that RT decreased the microvascular density (MVD) of the primary tumor core, but increased the MVD of the tumor invasion front. RT also increased the number of tumor-associated macrophages (TAMs) and the expression of stromal cell-derived factor-1 (SDF-1) and hypoxia-inducible factor-1 (HIF-1) at the tumor invasion front. SDF-1 expression suppressed by siRNA (SDFkd tumors) showed a decrease in RT-enhanced tumor invasiveness, leading to prolonged survival of mice bearing these tumors. The invasion front in SDFkd tumors showed a lower MVD and TAM density than that in the islands of the control or irradiated ALTS1C1 tumors. Our results indicate that tumor-secreted SDF-1 is one key factor in RT-induced tumor invasiveness, and that it exerts its effect likely through macrophage mobilization and tumor revascularization.     

Brain Radiotherapy plus Concurrent Temozolomide versus Radiotherapy Alone for Patients with Brain Metastases: A Meta-Analysis

Objective

We performed a meta-analysis of randomized clinical trials to compare the efficacy of brain radiotherapy (RT) combined with temozolomide (TMZ) versus RT alone as first-line treatment for brain metastases (BM).

Methods

Medline, Embase, and Pubmed were used to search for relevant randomized controlled trials (RCTs). Two investigators reviewed the abstracts and independently rated the quality of trials and relevant data. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), and adverse events.

Results

Seven studies were selected from the literature search. RT plus TMZ produced significant improvement in ORR with odds ratio (OR) of 2.27 (95% CI, 1.29 to 4.00; P = 0.005) compared with RT alone. OS and PFS were not significantly different between the two arms (OS: HR, 1.00; P = 0.959; PFS: HR, 0.73; P = 0.232). However, the RT plus TMZ arm was associated with significantly more grade 3 to 4 nausea and thrombocytopenia.

Conclusion

Concomitant RT and TMZ, compared to RT alone, significantly increases ORR in patients with BM, but yields increased toxicity and fails to demonstrate a survival advantage.     

Thrombolysis in Acute Ischemic Stroke: A Simulation Study to Improve Pre- and in-Hospital Delays in Community Hospitals

Background

Various studies demonstrate better patient outcome and higher thrombolysis rates achieved by centralized stroke care compared to decentralized care, i.e. community hospitals. It remains largely unclear how to improve thrombolysis rate in decentralized care. The aim of this simulation study was to assess the impact of previously identified success factors in a central model on thrombolysis rates and patient outcome when implemented for a decentral model.

Methods

Based on a prospectively collected dataset of 1084 ischemic stroke patients, simulation was used to replicate current practice and estimate the effect of re-organizing decentralized stroke care to resemble a centralized model. Factors simulated included symptom onset call to help, emergency medical services transportation, and in-hospital diagnostic workup delays. Primary outcome was proportion of patients treated with thrombolysis; secondary endpoints were good functional outcome at 90 days, Onset-Treatment-Time (OTT), and OTT intervals, respectively.

Results

Combining all factors might increase thrombolysis rate by 7.9%, of which 6.6% ascribed to pre-hospital and 1.3% to in-hospital factors. Good functional outcome increased by 11.4%, 8.7% ascribed to pre-hospital and 2.7% to in-hospital factors. The OTT decreased 17 minutes, 7 minutes ascribed to pre-hospital and 10 minutes to in-hospital factors. An increase was observed in the proportion thrombolyzed within 1.5 hours; increasing by 14.1%, of which 5.6% ascribed to pre-hospital and 8.5% to in-hospital factors.

Conclusions

Simulation technique may target opportunities for improving thrombolysis rates in acute stroke. Pre-hospital factors proved to be the most promising for improving thrombolysis rates in an implementation study.     

Comparative Effectiveness of Cognitive Therapies Delivered Face-to-Face or over the Telephone: An Observational Study Using Propensity Methods

Objectives

To compare the clinical and cost-effectiveness of face-to-face (FTF) with over-the-telephone (OTT) delivery of low intensity cognitive behavioural therapy.

Design

Observational study following SROBE guidelines. Selection effects were controlled using propensity scores. Non-inferiority comparisons assessed effectiveness.

Setting

IAPT (improving access to psychological therapies) services in the East of England.

Participants

39,227 adults referred to IAPT services. Propensity score strata included 4,106 individuals; 147 pairs participated in 1∶1 matching.

Intervention

Two or more sessions of computerised cognitive behavioural therapy (CBT).

Main outcome measures

Patient-reported outcomes: Patient Health Questionnaire (PHQ-9) for depression; Generalised Anxiety Disorder questionnaire (GAD-7); Work and Social Adjustment Scale (WSAS). Differences between groups were summarised as standardised effect sizes (ES), adjusted mean differences and minimally important difference for PHQ-9. Cost per session for OTT was compared with FTF.

Results

Analysis of covariance controlling for number of assessments, provider site, and baseline PHQ-9, GAD-7 and WSAS indicated statistically significantly greater reductions in scores for OTT treatment with moderate (PHQ-9: ES: 0.14; GAD-7: ES: 0.10) or small (WSAS: ES: 0.03) effect sizes. Non-inferiority in favour of OTT treatment for symptom severity persisted as small to moderate effects for all but individuals with the highest symptom severity. In the most stringent comparison, the one-to-one propensity matching, adjusted mean differences in treatment outcomes indicated non-inferiority between OTT versus FTF treatments for PHQ-9 and GAD-7, whereas the evidence was moderate for WSAS. The per-session cost for OTT was 36.2% lower than FTF.

Conclusions

The clinical effectiveness of low intensity CBT-based interventions delivered OTT was not inferior to those delivered FTF except for people with more severe illness where FTF was superior. This provides evidence for better targeting of therapy, efficiencies for patients, cost savings for services and greater access to psychological therapies for people with common mental disorders.     

The Response,Outcome and Toxicity of Aggressive Palliative Thoracic Radiotherapy for Metastatic Non-Small Cell Lung Cancer Patients with Controlled Extrathoracic Diseases

Background and Purpose

For metastatic non-small cell lung cancer (NSCLC) patients with controlled extrathoracic disease after systemic treatment, stable or progressive primary lung lesions may cause respiratory symptoms and increase comorbidities. In the present study, we sought to investigate whether aggressive palliative thoracic radiotherapy (RT) can enhance local control and improve the survival for this subgroup of patients.

Materials and Methods

Between March 2006 and December 2014, 56 patients with metastatic NSCLC who had responsive or stable extrathoracic diseases after chemotherapy and/or molecular targets, and received thoracic RT for stable and progressive primary lung lesions were included. RT with a median dose of 55 Gy (range, 40–62 Gy) was administered in 1.8–2.5 Gy fractions to primary lung tumor and regional mediastinal lymph nodes using modern RT technique. Overall survival (OS) from diagnosis, and locoregional progression-free survival (LRPFS), and survival calculated from radiotherapy (OS-RT) were estimated using the Kaplan-Meier method.

Results

There were 37 men and 19 women with a median age of 60 years at diagnosis. The median interval from the diagnosis of metastatic disease to thoracic RT was 8 months. Following thoracic RT, 26 patients (46%) achieved complete or partial response (overall response rate, ORR). Patients with squamous cell carcinoma or poorly-differentiated carcinoma had a higher ORR than those with adenocarcinoma (63% vs. 34%, P = 0.034). EGFR mutations was closely associated with a better ORR (45% vs. 29%, P = 0.284). At a median follow-up time of 44 months, the median OS, LRPFS after RT, and OS-RT were 50 months, 15 months, and 18 months.

Conclusion

Radical palliative throractic RT is safe and might be beneficial for primary lung lesions of metastatic NSCLC patients with controlled extrathoracic diseases.     

Factors determining survival of patients with malignant gliomas diagnosed by stereotactic biopsy

We analyzed the prognostic significance of tumor histology, location, treatment, and selected clinical features at presentation in 91 consecutive patients with malignant gliomas diagnosed by stereotactic biopsy. In 64 patients with glioblastoma multiforme (GBM) the following factors were associated with longer survival: lobar tumor location, adequate radiation therapy (RT) tumor dose 5,000-6,000 cGy, Karnofsky performance rating (KPR) at presentation greater than or equal to 70, and a normal level of consciousness before biopsy. In 27 patients with anaplastic astrocytoma, factors associated with longer survival were lobar tumor location, adequate RT, age less than 40 years at presentation, and a history of seizures. Delayed cytoreductive surgery in lobar GBM extended median survival but did not improve long-term survival. For patients with deep or midline malignant gliomas and for selected patients with lobar tumors, stereotactic biopsy followed by RT may be the most reasonable initial treatment strategy.