Tag: survival

Posted on

A proposed classification system that projects outcomes based on preoperative variables for adult patients with glioblastoma multiforme

J Neurosurg 112:997–1004, 2010. DOI: 10.3171/2009.9.JNS09805

Glioblastoma multiforme (GBM) is the most common and aggressive type of primary brain tumor in adults. Although the average survival is ~ 12 months, individual survival is heterogeneous. The ability to predict short- and long-term survivors is limited. Therefore, the aims of this study were to ascertain preoperative risk factors associated with survival, develop a preoperative prognostic grading system, and evaluate the utility of this grading system in predicting survival for patients undergoing resection of a primary intracranial GBM.

Methods. Cases involving adult patients who underwent surgery for an intracranial primary (de novo) GBM between 1997 and 2007 at The Johns Hopkins Hospital, an academic tertiary-care institution, were retrospectively reviewed. Multivariate proportional hazards regression analysis was used to identify preoperative factors associated with survival, after controlling for extent of resection and adjuvant therapies. The identified associations with survival were then used to develop a grading system based on preoperative variables. Survival as a function of time was plotted using the Kaplan-Meier method, and survival rates were compared using Log-rank analysis. Associations with p < 0.05 were considered statistically significant.

Results. Of the 393 patients in this study, 310 (79%) had died as of most recent follow-up (median time from surgery to death 11.9 months). The preoperative factors, independent of extent of resection and adjuvant therapies (carmustine wafers, temozolomide, and radiation), found to be negatively associated with survival were: age > 60 years (p < 0.0001), Karnofsky performance status score ≤ 80 (p < 0.0001), motor deficit (p = 0.02), language deficit (p = 0.001), and periventricular tumor location (p = 0.04). Patients possessing 0–1, 2, 3, and 4–5 of these variables were assigned a preoperative grade of 1, 2, 3, and 4, respectively. Patients with a preoperative grade of 1, 2, 3, and 4 had a median survival of 16.6, 10.2, 6.8, and 6.1 months, respectively.

Conclusions. The present study found that older age, poor performance status, motor deficit, language deficit, and periventricular tumor location independently predicted poorer survival in patients undergoing GBM resection. A grading system based on these factors was able to identify 4 distinct groups of patients with different survival rates. This grading system, based only on preoperative variables, may provide patients and physicians with prognostic information that may guide medical and surgical therapy before any intervention is pursued

Posted on

Integrated Genomic Analysis Identifies Clinically Relevant Subtypes of Glioblastoma Characterized by Abnormalities in PDGFRA, IDH1, EGFR, and NF1

Cancer Cell 17, 98–110, January 19, 2010

The Cancer Genome Atlas Network recently cataloged recurrent genomic abnormalities in glioblastoma multiforme (GBM). We describe a robust gene expression-based molecular classification of GBM into Proneural, Neural, Classical, and Mesenchymal subtypes and integrate multidimensional genomic data to establish patterns of somatic mutations and DNA copy number. Aberrations and gene expression of EGFR, NF1, and PDGFRA/IDH1 each define the Classical, Mesenchymal, and Proneural subtypes, respectively. Gene signatures of normal brain cell types show a strong relationship between subtypes and different neural lineages. Additionally, response to aggressive therapy differs by subtype, with the greatest benefit in the Classical subtype and no benefit in the Proneural subtype. We provide a framework that unifies transcriptomic and genomic dimensions for GBM molecular stratification with important implications for future studies.

This work expands on previous glioblastoma classification studies by associating known subtypes with specific alterations in NF1 and PDGFRA/IDH1 and by identifying two additional subtypes, one of which is characterized by EGFR abnormalities and wild-type p53. In addition, the subtypes have specific differentiation characteristics that, combined with data from recent mouse studies, suggest a link to alternative cells of origin. Together, these data provide a framework for investigation of targeted therapies. Temozolomide and radiation, a common treatment for glioblastoma, has demonstrated a significant increase in survival. Our analysis illustrates that a survival advantage in heavily treated patients varies by subtype, with Classical or Mesenchymal subtypes having significantly delayed mortality that was not observed in the Proneural subtype


Posted on

Long-term outcome and survival of surgically treated supratentorial low-grade glioma in adult patients

Acta Neurochir (2009) 151:1359–1365. DOI 10.1007/s00701-009-0435-x

The appropriate management of low-grade gliomas is still a matter of debate. So far, there are no randomized studies that analyze the impact of surgical

resection on patient outcome. The value of the data obtained from the few retrospective reports available is often limited.

Patients and methods In the present study, we performed an analysis on data of 130 adult low-grade glioma patients. Extent of the resection was evaluated in correlation to the overall survival (OS) and progression-free survival (PFS) using Cox regression multivariate analysis.

Results Extended surgery was shown to prolong OS and PFS significantly. Re-surgery in the case of a tumor relapse has a significant impact on OS and PFS, too.

Conclusions In summary, we could retrospectively evaluate a large case series of well-defined low-grade gliomas patients with a long follow-up period showing that

extended surgery would be the most effective therapy for low-grade glioma patients even in recurrent diseases

Posted on

Craniotomy for resection of meningioma in the elderly: a multicenter, prospective analysis from the National Surgical Quality Improvement Program

J Neurol Psychiatry. DOI:10.1136/jnnp.2009.185074

Whether there is an increased surgical risk in elderly patients who undergo craniotomy for meningioma resection, remains a point of controversy. Utilizing multicenter, prospective data from the National Surgical Quality Improvement Program, the present study sought to address this controversy.

All patients who underwent a craniotomy for resection of intracranial meningioma between 1997 and 2006 at 123 VA hospitals around the country were included. After controlling for preoperative factors such as ASA class, race, diabetes mellitus, disseminated cancer, tobacco use, tumor location, and functional health status in a multivariate logistic regression model, the effect of elderly age (age greater than 70 years) on 30-day mortality was determined.

Our study included 1,281 patients who underwent surgical resection of an intracranial meningioma. The elderly cohort, represented 21.2% (n=258) of our total study population. Elderly patients had a higher 30-day mortality (12.0%) than younger subjects (4.6%) (P < 0.0001). Similarly, elderly patients were more likely to have one or more complications (29.8% vs. 13.1%, P < 0.0001). Multivariate logistic regression identified age, functional status, preoperative disseminated cancer, and tumor location as important predictors of 30-day mortality. After controlling for preoperative comorbidities and risk factors, the odds of perioperative mortality in elderly patients were 3 times that of younger patients (95% CI = 1.7 – 5.3, P = 0.0102).

After carefully controlling for various patient characteristics, ASA class and functional status, elderly patients have poorer outcome after surgical resection of intracranial meningioma than younger subjects.

Posted on

Bevacizumab Alone and in Combination With Irinotecan in Recurrent Glioblastoma

Journal of Clinical Oncology. DOI:10.1200/JCO.2008.19.8721

Purpose

We evaluated the efficacy of bevacizumab (Avastin TM), alone and in combination with irinotecan, in patients with recurrent glioblastoma in a phase II, multicenter, open-label, noncomparative trial.

Patients and Methods

One hundred sixty-seven patients were randomly assigned to receive bevacizumab 10 mg/kg alone or in combination with irinotecan 340 mg/m2 or 125 mg/m2 (with or without concomitant enzyme-inducing antiepileptic drugs, respectively) once every 2 weeks. Primary end points were 6-month progression-free survival and objective response rate, as determined by independent radiology review. Secondary end points included safety and overall survival.

Results

In the bevacizumab-alone and the bevacizumab-plus-irinotecan groups, estimated 6-month progression-free survival rates were 42.6% and 50.3%, respectively; objective response rates were 28.2% and 37.8%, respectively; and median overall survival times were 9.2 months and 8.7 months, respectively. There was a trend for patients who were taking corticosteroids at baseline to take stable or decreasing doses over time. Of the patients treated with bevacizumab alone or bevacizumab plus irinotecan, 46.4% and 65.8%, respectively, experienced grade  3 adverse events, the most common of which were hypertension (8.3%) and convulsion (6.0%) in the bevacizumab-alone group and convulsion (13.9%), neutropenia (8.9%), and fatigue (8.9%) in the bevacizumab-plus-irinotecan group. Intracranial hemorrhage was noted in two patients (2.4%) in the bevacizumab-alone group (grade 1) and in three patients (3.8%) patients in the bevacizumabplus-irinotecan group (grades 1, 2, and 4, respectively).

Conclusion

Bevacizumab, alone or in combination with irinotecan, was well tolerated and active in recurrent glioblastoma.

Posted on

Prognostic factors in intramedullary astrocytomas

Eur Spine J (2009) 18:1397–1422 DOI 10.1007/s00586-009-1076-8

Astrocytomas affect a significant portion of patients with intramedullary tumors. These infiltratively growing tumors are treated by a variety of methods—biopsy and decompressive surgery, maximal safe resection, adju- vant oncological therapy. Also, numerous prognostic factors are reported in the literature. Better understanding of factors that influence prognosis may help in treatment planning with the goal of prolonging survival. We have thus undertaken an extensive literature review in order to define factors affecting prognosis. A total of 38 articles were studied. Only tumor grade was consistently reported as the major factor affecting prognosis. The influence of other clinical factors (age, gender, history length, functional status, tumor location or extent, syrinx or cyst presence) can be speculated upon, but cannot be assessed adequately from the available literature. For both low- and high-grade (HG) astrocytomas, maximal safe tumor resection should be the primary treatment objective but is often not feasible in contrast to other intramedullary and spinal neoplasms. Since the biological nature of spinal cord HG glioma is identical to that of the brain, the same treatment algorithm of maximal safe resection followed by concomitant radio and chemotherapy would be sensible to implement.

Posted on

Do children and adults differ in survival from medulloblastoma? A study from the SEER registry

J Neurooncol (2009) 95:81–85 DOI 10.1007/s11060-009-9894-4

Studies investigating whether adults have diminished survival from medulloblastoma (MB) compared with children have yielded conflicting results. We sought to determine in a population-based registry whether adults and children with MB differ in survival, and to examine whether dissimilar use of chemotherapy might contribute to any disparity.

1,226 MB subjects were identified using the Surveillance Epidemiology and End Results (SEER-9) registry (1973–2002) and survival analysis performed. MB was defined strictly to exclude non-cerebellar primitive neuro- ectodermal tumors. Patients were stratified by age at diagnosis: <3 years (infants), 3–17 years (children) and >18 years (adults). Because the SEER-9 registry lacks treatment data, a subset of 142 patients were identified using the San Francisco-Oakland SEER registry (1988–2003) and additional analyses performed.

There was no significant difference in survival between children and adults with MB in either the SEER-9 (P = 0.17) or SFO (P = 0.89) cohorts but infants fared worse compared to both children (P < 0.01) and adults (P < 0.01). In the SFO sample, children and adults who received chemotherapy plus radiation therapy (XRT) did not differ in survival. Among patients treated with XRT alone, children showed increased survival (P = 0.04) compared with adults. Children and adults with MB do not differ with respect to overall survival, yet infants fare significantly worse.

For children and adults with MB treated with both XRT and chemotherapy, we could not demonstrate a survival difference. Similar outcomes between adult and childhood MB may justify inclusion of adults in pediatric cooperative trials for MB.

Proudly powered by WordPress