The efficacy of carmustine wafers for older patients with glioblastoma multiforme: prolonging survival

Chaichana, Kaisorn L.; Zaidi, Hasan A.; Pendleton, Courtney; McGirt, Matthew J.; Grossman, Rachel; Weingart, Jon; Olivi, Alessandro; Quiñones‐Hinojosa, Alfredo; Brem, Henry

doi:10.1179/1743132811y.0000000006

Cited by 54 publications

(31 citation statements)

References 27 publications

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“…The multivariate proportional hazards regression analysis was used to identify an association between resection number and survival. This analysis was conducted after controlling for preoperative (age, KPS score, and periventricular tumor location), 4,8,22,23 intraoperative (extent of resection), 6,20,22,25,31 and postoperative factors (carmustine wafer implantation, 3,9,27,36 temozolomide chemotherapy, 16,34 and radiation therapy 14 ) known to be associated with survival. In addition, to evaluate the role of resection number and survival, a case-control study was performed.…”

Section: Methodsmentioning

confidence: 99%

Multiple resections for patients with glioblastoma: prolonging survival

Chaichana¹,

Zadnik²,

Weingart³

et al. 2013

JNS

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168

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Object Glioblastoma is the most common and aggressive type of primary brain tumor in adults. These tumors recur regardless of intervention. This propensity to recur despite aggressive therapies has made many perceive that repeated resections have little utility. The goal of this study was to evaluate if patients who underwent repeat resections experienced improved survival as compared with patients with fewer numbers of resections, and whether the number of resections was an independent predictor of prolonged survival. Methods The records of adult patients who underwent surgery for an intracranial primary glioblastoma at an academic tertiary-care institution between 1997 and 2007 were retrospectively reviewed. Multivariate proportional-hazards regression analysis was used to identify an association between glioblastoma resection number and survival after controlling for factors known to be associated with survival, such as age, functional status, periventricular location, extent of resection, and adjuvant therapy. Survival as a function of time was plotted using the Kaplan-Meier method, and survival rates were compared using log-rank analysis. Results Five hundred seventy-eight patients with primary glioblastoma met the inclusion/exclusion criteria. At last follow-up, 354, 168, 41, and 15 patients underwent 1, 2, 3, or 4 resections, respectively. The median survival for patients who underwent 1, 2, 3, and 4 resections was 6.8, 15.5, 22.4, and 26.6 months (p < 0.05), respectively. In multivariate analysis, patients who underwent only 1 resection experienced shortened survival (relative risk [RR] 3.400, 95% CI 2.423–4.774; p < 0.0001) as compared with patients who underwent 2 (RR 0.688, 95% CI 0.525–0.898; p = 0.0006), 3 (RR 0.614, 95% CI 0.388–0.929; p = 0.02), or 4 (RR 0.600, 95% CI 0.238–0.853; p = 0.01) resections. These results were verified in a case-control evaluation, controlling for age, neurological function, periventricular tumor location, extent of resection, and adjuvant therapy. Patients who underwent 1, 2, or 3 resections had a median survival of 4.5, 16.2, and 24.4 months, respectively (p < 0.05). Additionally, the risk of infections or iatrogenic deficits did not increase with repeated resections in this patient population (p > 0.05). Conclusions Patients with glioblastoma will inevitably experience tumor recurrence. The present study shows that patients with recurrent glioblastoma can have improved survival with repeated resections. The findings of this study, however, may be limited by an intrinsic bias associated with patient selection. The authors attempted to minimize these biases by using strict inclusion criteria, multivariate analyses, and case-control evaluation.

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Section: Methodsmentioning

confidence: 99%

Multiple resections for patients with glioblastoma: prolonging survival

Chaichana¹,

Zadnik²,

Weingart³

et al. 2013

JNS

Self Cite

168

125

View full text Add to dashboard Cite

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“…Second, formal volumetric analysis using manual tumor tracing was performed using manual segmentation with region of interest analysis to measure tumor volume (in cm 3 ) on the basis of contrast enhancement, as previously described. 5,20 …”

Section: Extent Of Resection Analysismentioning

confidence: 99%

Comparison of outcomes between a less experienced surgeon using a fully endoscopic technique and a very experienced surgeon using a microscopic transsphenoidal technique for pituitary adenoma

Zaidi

Awad

Bohl

et al. 2016

JNS

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abbreviatioNs CSF = cerebrospinal fluid; EOR = extent of tumor resection; GTR = gross-total resection; QOL = quality of life; STR = subtotal resection; TNTS = transnasal transsphenoidal. obJective The comparative efficacy of microscopic and fully endoscopic transsphenoidal surgery for pituitary adenomas has not been well studied despite the adoption of fully endoscopic surgery by many pituitary centers. The influence of surgeon experience has also not been examined in this setting. The authors therefore compared the extent of tumor resection (EOR) and the endocrine outcomes of 1 very experienced surgeon performing a microscopic transsphenoidal surgery technique with those of a less experienced surgeon using a fully endoscopic transsphenoidal surgery technique for resection of nonfunctioning pituitary adenomas in a concurrent series of patients. methods Post hoc analysis was conducted of a cohort of adult patients prospectively enrolled in a pituitary adenoma quality-of-life study between October 2011 and June 2014. Patients were followed up for 6 months after surgery. Patients were treated either by a less experienced surgeon (100 independent cases) who practices fully endoscopic surgery exclusively or by a very experienced surgeon (1800 independent cases) who practices microscopic surgery exclusively. Patient demographic characteristics, tumor characteristics, hypopituitarism, complications, and length of hospital stay were analyzed. Tumor volumes and EOR were determined by formal volumetric analysis involving manual segmentation of MR images performed before surgery and within 6 months after surgery. Logistic regression analysis was used to determine predictors of EOR. results Fifty-five patients underwent fully endoscopic transsphenoidal surgery, and 80 patients underwent fully microscopic transsphenoidal surgery. The baseline characteristics of the 2 treatment groups were well matched. EOR was similar between the endoscopic and microscopic groups, respectively, as estimated by gross-total resection rate (78.2% vs 81.3%, p = 0.67), percentage of tumor resected (99.2% vs 98.7%, p = 0.42), and volume of residual tumor (0.12 cm 3 vs 0.20 cm 3 , p = 0.41). Multivariate modeling suggested that preoperative tumor volume was the most important predictor of EOR (p = 0.001). No difference was found in the development of anterior gland dysfunction (p > 0.14), but there was a higher incidence of permanent posterior gland dysfunction in the microscopic group (p = 0.04). Combined rates of major complications and unplanned readmissions were lower in the endoscopic group (p = 0.02), but individual complications were not significantly different. coNclusioNs A less experienced surgeon using a fully endoscopic technique was able to achieve outcomes similar to those of a very experienced surgeon using a microscopic technique in a cohort of patients with nonfunctioning tumors smaller than 60 cm 3 . The study raises the provocative notion that certain advantages afforded by the fully endoscopic technique may impact the learning c...

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“…These drugs are being used as second-line therapeutics for malignant brain tumors, notably glioblastoma multiforme, metastizing melanoma, Hodgkin lymphoma and brain metastases of different origin. [2][3][4][5][6][7][8][9] The main molecular target of these agents is the DNA inducing, upon generation of nucleophilic chloroethylenium ions, a broad spectrum of DNA adducts. 10 From these adducts, it has been suggested that O 6 -chloroethylguanine is the main killing lesion.…”

Section: Introductionmentioning

confidence: 99%

Chloroethylnitrosourea-induced cell death and genotoxicity: Cell cycle dependence and the role of DNA double-strand breaks, HR and NHEJ

et al. 2012

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C hloroethylnitrosureas (CNUs) are powerful DNA-reactive alkylating agents used in cancer therapy. Here, we analyzed cyto-and genotoxicity of nimustine (ACNU), a representative of CNUs, in synchronized cells and in cells deficient in repair proteins involved in homologous recombination (HR) or nonhomologous end-joining (NHEJ). We show that HR mutants are extremely sensitive to ACNU, as measured by colony formation, induction of apoptosis and chromosomal aberrations. The NHEJ mutants differed in their sensitivity, with Ku80 mutants being moderately sensitive and DNA-PKcs mutated cells being resistant. HR mutated cells displayed a sustained high level of γH2AX foci , which co-stained with Rad51 and 53BP1, indicating DNA double-strand breaks (DSB) to be formed. Using synchronized cells, we analyzed whether DSB formation after ACNU treatment was replication-dependent. We show that γH2AX foci were not induced in G 1 but increased significantly in S phase and remained at a high level in G 2 , where a fraction of cells became arrested and underwent, with a delay of > 12 h, cell death by apoptosis and necrosis. Rad51, ATM, MDC-1 and RPA-2 foci were also formed and shown to co-localize with γH2AX foci induced in S phase, indicating that the DNA damage response was activated. All effects observed were abrogated by MGMT, which repairs O 6 -chloroethylguanine that is converted into DNA cross-links. We deduce that the major genotoxic and killing lesion induced by CNUs are O 6 -chloroethylguanine-triggered

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The efficacy of carmustine wafers for older patients with glioblastoma multiforme: prolonging survival

Cited by 54 publications

References 27 publications

Multiple resections for patients with glioblastoma: prolonging survival

Multiple resections for patients with glioblastoma: prolonging survival

Comparison of outcomes between a less experienced surgeon using a fully endoscopic technique and a very experienced surgeon using a microscopic transsphenoidal technique for pituitary adenoma

Chloroethylnitrosourea-induced cell death and genotoxicity: Cell cycle dependence and the role of DNA double-strand breaks, HR and NHEJ

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