Carmustine Wafer Implantation Research Articles

Extent of resection and Carmustine wafer implantation safely improve survival in patients with a newly diagnosed glioblastoma: a single center experience of the current practice.

For newly diagnosed glioblastomas treated with resection in association with the standard combined chemoradiotherapy, the impact of Carmustine wafer implantation remains debated regarding postoperative infections, quality of life, and feasibility of adjuvant oncological treatments. To assess together safety, tolerance and efficacy of Carmustine wafer implantation and of extent of resection for glioblastoma patients in real-life experience. Observational retrospective monocentric study including 340 consecutive adult patients with a newly diagnosed supratentorial glioblastoma who underwent surgical resection with (n = 123) or without (n = 217) Carmustine wafer implantation as first-line oncological treatment. Carmustine wafer implantation and extent of resection did not significantly increase postoperative complications, including postoperative infections (p = 0.269, and p = 0.446, respectively). Carmustine wafer implantation and extent of resection did not significantly increase adverse events during adjuvant oncological therapies (p = 0.968, and p = 0.571, respectively). Carmustine wafer implantation did not significantly alter the early postoperative Karnofsky performance status (p = 0.402) or the Karnofsky performance status after oncological treatment (p = 0.636) but a subtotal or total surgical resection significantly improved those scores (p < 0.001, and p < 0.001, respectively). Carmustine wafer implantation, subtotal and total resection, and standard combined chemoradiotherapy were independently associated with longer event-free survival (adjusted Hazard Ratio (aHR), 0.74 [95% CI 0.55-0.99], p = 0.043; aHR, 0.70 [95% CI 0.54-0.91], p = 0.009; aHR, 0.40 [95% CI 0.29-0.55], p < 0.001, respectively) and with longer overall survival (aHR, 0.69 [95% CI 0.49-0.96], p = 0.029; aHR, 0.52 [95% CI 0.38-0.70], p < 0.001; aHR, 0.58 [95% CI 0.42-0.81], p = 0.002, respectively). Carmustine wafer implantation in combination with maximal resection, followed by standard combined chemoradiotherapy is safe, efficient, and well-tolerated in newly diagnosed supratentorial glioblastomas in adults.

Opening the ventricle during surgery diminishes survival among patients with newly diagnosed glioblastoma treated with carmustine wafers: a multi-center retrospective study.

Carmustine wafers (CW) were approved in Japan for newly diagnosed and recurrent malignant gliomas during 2013. The ventricle is often opened during surgery to achieve maximum resection. While not generally recommended in such situations, CW might be safely achieved by occluding an opened ventricle using gelform or collagen sheets. However, whether CW implantation actually confers a survival benefit for patients who undergo surgery with an open ventricle to treat glioblastoma remains unclear. Clinical, imaging, and survival data were collected in this multicenter retrospective study of 122 consecutive patients with newly diagnosed glioblastoma to determine adverse events and efficacy. Overall, 54 adverse events of all grades developed in 35 (28.6%) patients, with the most common being new seizures (16%). Adverse events did not significantly differ between patients with opened and closed ventricles during surgery. The 10- and 21.7-month, median, progression-free (PFS) and overall survival (OS), respectively did not significantly differ according to resection rates. However, median PFS and OS were significantly longer among patients with closed, than open ventricles (12.8 vs. 7.4 months; p = 0.0039 and 26.9 vs. 18.6 months; p = 0.011, respectively). Implanting CW into the resection cavity during concomitant radiochemotherapy with temozolomide seems to yield better survival rates without increased adverse events. Occlusion of the ventricular opening during surgery might be safe for CW implantation, but less so for treating patients with newly diagnosed glioblastoma.

Importance of biomarkers in glioblastomas patients receiving local BCNU wafer chemotherapy

BackgroundTo assess the influence of molecular markers with potential prognostic value to groups of patients with newly diagnosed glioblastoma patients were examined: group A with 36 patients (surgical resection plus standard combined chemoradiotherapy) and group B with 36 patients (surgical resection, standard combined chemoradiotherapy plus carmustine wafer implantation).Our aim was to determine chromosomal alterations, methylation status of MGMT, p15, and p16 (CDKN2A) in order to analyse the influence on patient survival time as well as radio- and chemotherapy responses. Promoter hypermethylation of MGMT, p16, and p15 genes were determined by MS-PCR. Comparative genomic hybridisation (CGH) analyses were performed with isolated, labelled DNA of each tumor to detect genetic alterations.ResultsAge of onset of the disease showed a significant effect on overall survival (OS) (p < 0.0001). Additional treatment with carmustine wafer (group B) compared to the control group (group A) did not result in improved OS (p = 0.562). Patients with a methylated MGMT promotor showed a significant longer OS compared to those patients with unmethylated MGMT promotor (p = 0.041). Subgroup analyses revealed that patients with methylated p15 showed a significant shorter OS when administered to group B rather than in group A (p = 0.0332). In patients additionally treated with carmustine wafer an amplification of 4q12 showed a significant impact on a reduced OS (p = 0.00835). In group B, a loss of 13q was significantly associated with a longer OS (p = 0.0364). If a loss of chromosome 10 occurred, patients in group B showed a significantly longer OS (p = 0.0123).ConclusionA clinical benefit for the widespread use of additional carmustine wafer implantation could not be found. However, carmustine wafer implantation shows a significantly improved overall survival if parts of chromosome 10 or chromosome 13 are deleted. In cases of 4q12 amplification and in cases of a methylated p15 promotor, the use of carmustine wafers is especially not recommended.The MGMT promoter methylation is a strong prognostic Biomarker for benefit from temozolomide and BCNU chemotherapy.

Prognostic effects of O6-Methylguanine DNA methyltransferase promoter hypermethylation in high-grade glioma patients with carmustine wafer implants

Background: Local chemotherapy with carmustine (BCNU) wafer implantation has survival benefits for malignant glioma patients. However, available data regarding its association with O6-methylguanine-DNA-methyltransferase (MGMT) are scant. Purpose: To evaluate whether MGMT hypermethylation has prognostic effects in malignant glioma patients with interstitial BCNU wafer implants. Methods: From September 2004 to August 2007, 32 patients with malignant gliomas underwent surgical resection plus interstitial BCNU wafer implantation at our hospital. Results and Conclusion: BCNU wafer implantation was performed in 18 patients with newly diagnosed gliomas and in 14 with recurrent gliomas. All patients had a Karnofsky performance status of ≥70. The median age was 51 years. At a median follow-up of 31 months, the 1- and 2-year overall survival (OS) rate was 43% and 22%, respectively. OS rates did not significantly differ between the newly diagnosed and recurrent patients. Gross total tumor resection was achieved in 19 (59%) patients, and MGMT hypermethylation was noted in 13 (41%) tumor specimens. Multivariate analysis demonstrated that patients with MGMT hypermethylation in their tumors and gross total tumor removal have more favorable survival rates (P = 0.03).

The influence of carmustine wafer implantation on tumor bed cysts and peritumoral brain edema

The development of perifocal edema and tumor bed cyst has been reported after implantation of biodegradable carmustine wafers for the treatment of malignant gliomas. We retrospectively evaluated these changes in a series of patients; 19 consecutive patients with malignant glioma who received carmustine wafer implantation at our hospital from January 2013 through July 2013, and 28 patients who underwent surgery prior to our institution’s initiation of carmustine wafer implantation, as historical controls. The volume of the tumor bed cyst and perifocal edema was calculated on MRI acquired at four time points: ⩽72hours after surgery for baseline, and at 1–4, 5–8, and 9–12weeks after surgery. The volume of the tumor bed cyst in the wafer group increased significantly relative to the control group at all time points (p=0.04). Opening of the ventricle was inversely correlated with enlargement of the tumor bed cyst in the wafer group (p=0.04). The change in the volume of perifocal edema in the wafer group was not significantly different (p=0.48), but exhibited a considerable increase in patients with anaplastic oligodendroglioma relative to glioblastoma patients in the wafer group (p=0.01). We demonstrated significant enlargement of the tumor bed cyst volume after carmustine wafer implantation, as well as the development of marked perifocal edema in patients with anaplastic oligodendroglioma.

Rapid regression of glioblastoma following carmustine wafer implantation: A case report.

Carmustine wafers, which are locally delivered chemotherapy in the form of biodegradable implants, confer a survival benefit to patients with glioblastoma (GB) following surgical resection. While the adverse events of this method, including gas retention and perifocal edema, have been extensively investigated, the immediate efficacy of the implant has rarely been reported. To the best of our knowledge, this is the first reported case of GB in which the tumor rapidly regressed after partial surgical removal followed by implantation of carmustine wafers. A 77-year-old woman presented with motor aphasia and right hemiparesis. Neuroimaging revealed a tumor located in the left frontal lobe of the brain. The tumor was partially removed under 5-aminolevulinic acid fluorescence guidance and 8 carmustine wafers were implanted in the resection cavity. The histopathological findings suggested the diagnosis of GB. Genetic and immunohistochemical analyses revealed O6-methylguanine-DNA methyltransferase (MGMT) gene promoter methylation and low MGMT protein expression, respectively, in the tumor cells. One month after the operation, when adjuvant temozolomide chemotherapy was planned, computed tomography and magnetic resonance imaging revealed a marked regression of the residual tumor and perifocal edema. The patient's symptoms and signs had improved. As adjuvant temozolomide without radiation was therapeutically beneficial, the tumor gradually regressed and the patient has remained progression-free for >12 months after the operation. Therefore, adjuvant local chemotherapy with carmustine wafer implants was able to induce rapid regression of GB.

Delaying standard combined chemoradiotherapy after surgical resection does not impact survival in newly diagnosed glioblastoma patients

BackgroundTo assess the influence of the time interval between surgical resection and standard combined chemoradiotherapy on survival in newly diagnosed and homogeneously treated (surgical resection plus standard combined chemoradiotherapy) glioblastoma patients; while controlling confounding factors (extent of resection, carmustine wafer implantation, functional status, neurological deficit, and postoperative complications). MethodsFrom 2005 to 2011, 692 adult patients (434 men; mean of 57.5±10.8years) with a newly diagnosed glioblastoma were enrolled in this retrospective multicentric study. All patients were treated by surgical resection (65.5% total/subtotal resection, 34.5% partial resection; 36.7% carmustine wafer implantation) followed by standard combined chemoradiotherapy (radiotherapy at a median dose of 60Gy, with daily concomitant and adjuvant temozolomide). Time interval to standard combined chemoradiotherapy was analyzed as a continuous variable and as a dichotomized variable using median and quartiles thresholds. Multivariate analyses using Cox modeling were conducted. ResultsThe median progression-free survival was 10.3months (95% CI, 10.0–11.0). The median overall survival was 19.7months (95% CI, 18.5–21.0). The median time to initiation of combined chemoradiotherapy was 1.5months (25% quartile, 1.0; 75% quartile, 2.2; range, 0.1–9.0). On univariate and multivariate analyses, OS and PFS were not significantly influenced by time intervals to adjuvant treatments. On multivariate analysis, female gender, total/subtotal resection and RTOG-RPA classes 3 and 4 were significant independent predictors of improved OS. ConclusionsDelaying standard combined chemoradiotherapy following surgical resection of newly diagnosed glioblastoma in adult patients does not impact survival.

Evaluation of serial changes on computed tomography and magnetic resonance imaging after implantation of carmustine wafers in patients with malignant gliomas for differential diagnosis of tumor recurrence.

Carmustine wafers are approved for localized treatment of malignant glioma. In this study, overall changes in computed tomography (CT) and magnetic resonance (MR) images of malignant glioma patients treated with carmustine wafer implantation were evaluated. The subjects were 25 patients undergoing craniotomy for malignant glioma resection and carmustine wafer implantation. Changes in the appearance of wafers, the resection cavity, and the adjacent parenchyma on CT and MR imaging were evaluated retrospectively. On CT, the wafers changed from an initially high-dense to an iso-dense appearance. All MR studies showed a low-intense wafer within 2 days. The wafers changed to a high- or iso-intense appearance on fluid attenuated inversion recovery and T1-weighted imaging, whereas they changed to an iso- to low-intense appearance on T2-weighted imaging. Gas in the cavity increased gradually after surgery, achieved a peak at 1 week postoperatively, and then disappeared in 1-3 months. Increased volume of the resection cavity was observed in 48% of patients. Regarding changes in the adjacent parenchyma, obvious contrast enhancement at the wall of the resection cavity was seen in 91% of cases at 1 month, but this disappeared gradually. Edema around the resection cavity was increased in 7 patients (28%), of whom only two experienced symptoms due to edema. We conclude that these radiological changes after carmustine wafer implantation should be carefully followed up, because these changes can easily be mistaken for infectious disease or recurrent tumors.

Risk of surgical site infection in 401 consecutive patients with glioblastoma with and without carmustine wafer implantation

Objectives:Patients with glioblastoma (GBM) have an inherently shortened survival because of their disease. It has been recently shown that carmustine wafers in addition to other therapies (surgery, temozolomide, and radiation) can further extend survival. There is concern, however, that these therapies may increase infection risk. The goals of this study were to calculate the incidence of postoperative infection, evaluate if carmustine wafers changes the risk of infection and identify factors independently associated with an infection following GBM surgery.Methods:All patients who underwent non-biopsy, surgical resection of an intracranial GBM from 2007 to 2011 at a single institution were retrospectively reviewed. Stepwise multivariate proportional hazards regression analysis was used to identify factors associated with infection, including the use of carmustine wafers. Variables with P < 0.05 were considered statistically significant.Results:Four hundred and one patients underwent resection of an intracranial GBM during the reviewed period, and 21 (5%) patients developed an infection at a median time of 40 [28–286] days following surgery. The incidence of infection was not higher in patients who had carmustine wafers, and this remained true in multivariate analyses to account for differences in treatment cohorts. The factors that remained significantly associated with an increased risk of infection were prior surgery [RR (95% CI); 2.026 (1.473–4.428), P = 0.01], diabetes mellitus [RR (95% CI); 6.090 (1.380–9.354)], P = 0.02], and increasing duration of hospital stay [RR (95% CI); 1.048 (1.006–1.078); P = 0.02], where the greatest risk occurred with hospital stays >5 days [RR (95% CI); 3.904 (1.003–11.620), P = 0.05].Discussion:These findings may help guide treatment regimens aimed at minimizing infection for patients with GBM.

Combining intraoperative carmustine wafers and Stupp regimen in multimodal first-line treatment of primary glioblastomas

Background. The study investigated if intraoperative use of carmustine wafers, particularly in combination with Stupp regimen, is a viable and safe first-line treatment option of glioblastomas. Methods. Eighty-three consecutive adult patients (50 men; mean age 60 years) with newly diagnosed supratentorial primary glioblastomas that underwent surgical resection with intraoperative carmustine wafers implantation (n = 7.1 ± 1.7) were retrospectively studied. Results. The median overall survival (OS) was 15.8 months with 56 patients dying over the course of the study. There was no significant association between the number of implanted carmustine wafers and complication rates (four surgical site infections, one death). The OS was significantly longer in Stupp regimen patients (19.5 months) as compared with patients with other postoperative treatments (13 months; p = 0.002). In addition patients with eight or more implanted carmustine wafers survived longer (24.5 months) than patients with seven or less implanted wafers (13 months; p = 0.021). Finally, regardless of the number of carmustine wafers, median OS was significantly longer in patients with a subtotal or total resection (21.5 months) than in patients with a partial resection (13 months; p = 0.011). Conclusions. The intraoperative use of carmustine wafers in combination with Stupp regimen is a viable first-line treatment option of glioblastomas. The prognostic value of this treatment association should be evaluated in a multicenter trial, ideally in a randomized and placebo-controlled one.

Long-term results of carmustine wafers implantation for newly-diagnosed glioblastomas in France: Controlled propensity matched multicenter cohort study

Introduction Analyse de l’efficacite et de la tolerance des implants de carmustine (Gliadel ® ) deposes lors d’une exerese en association avec le protocole Stupp pour le traitement de premiere intention des glioblastomes supratentoriels de l’adulte nouvellement diagnostiques.’ Materiel/methode Etude cas-temoin et etude appariee en score de propension chez 787 glioblastomes avec (groupe Implantation) et sans (groupe Standard) implantation de Gliadel ® en association avec le protocole Stupp. Resultats La survie sans progression mediane etait de 12,0 mois (95 % CI 10,7–12,6) dans le groupe implantation et de 10,0 mois (95 % CI : 9,0–10,0) dans le groupe standard. Le hazard ratio de progression tumorale dans le groupe implantation en comparaison du groupe standard etait de 0,81 (95 % CI 0,69–0,94 ; p = 0,004) dans l’etude cas-temoin et de 0,78 (95 % CI 0,63–0,95 ; p = 0,016) dans l’etude appariee. La survie globable mediane etait de 21,0 mois (95 % CI 19,7–23,4) chez les patients ayant eu du Gliadel ® au cours de l’evolution de la maladie (en premiere intention et/ou en recidive) et de 17,6 mois (95 % CI 16,0–19,0) chez les patients n’en ayant jamais eu. Le hazard ratio de deces dans le groupe ayant eu du Gliadel ® au cours de l’evolution de leur maladie en comparaison du groupe n’en ayant jamais etait de 0,76 (95 % CI 0,65–0,90 ; p = 0,001) dans l’etude cas-temoin et de 0,73 (95 % CI 0,62–0,86 ; p p Conclusion L’implantation peroperatoire de Gliadel ® au cours d’une chirurgie de resection large associee au protocole Stupp pour le traitement de premiere intention des glioblastomes offre un gain de survie significatif avec une tolerance acceptable.

Delayed post-operative haemorrhage after carmustine wafer implantation: A case series from two UK centres

Object. Significant haemorrhage following intracranial tumour resection may occur in 1–2% of cases and the majority occur within the first few hours post-operatively. Implantation of carmustine wafers has been associated with increased operative site complications in some series, but post-operative haematoma is not routinely reported. We analyzed the characteristics of post-operative haemorrhage after carmustine wafer insertion. Methods. We performed a retrospective audit of surgical site haematoma after tumour resection and insertion of carmustine wafers in two neurosurgical units in the UK (University Hospital of North Staffordshire, Stoke-on-Trent, March 2003 – July 2012; Wessex Neurological Centre, Southampton, October 2005 – January 2013). Results. During the specified time periods, carmustine wafers were inserted in 181 operations in 177 patients. We identified acute operative site haematomas after carmustine wafer insertion in 8 (4.4%) patients. All presented in a delayed fashion on or after Day 2 post-operatively. In contrast, acute operative site haematoma was present in 4/491 (0.81%) of patients who underwent resection without gliadel wafer insertion. Conclusions. In contrast to the expected timing of bleeding following intracranial tumour resection, all carmustine wafer patients who experienced haemorrhage presented in a delayed fashion on or after Day 2 post-operatively. The causative factors for universally delayed post-operative haematoma after carmustine wafer insertion are unclear and further studies are required to characterize this phenomenon.

Bevacizumab for the treatment of glioblastoma

Glioblastoma (GB) is the most common adult malignant primary brain tumor that arises from glial precursor cells. Survival in GB is variable ranging from 6 to 20 months notwithstanding current standard of care (SOC) treatment. Therapy has improved, but nonetheless GB is still invariably recurrent and incurable. Treatment options at recurrence include re-operation with or without carmustine (BCNU) wafer implantation (Gliadel), re-irradiation and standard/experimental chemo- or targeted therapy. Recurrent GB radiographic response rates to cytotoxic chemotherapy are less than 10% and median 6-month progression-free survival (PFS6) is 15%. With the recognition of the importance of tumor angiogenesis and the development of targeted therapy based on angiogenic inhibition, two pivotal trials of the VEGF-directed monoclonal antibody, bevacizumab (BEV, Avastin), were conducted in recurrent GB. Based upon the results of these two prospective US trials (median radiographic response rate: 25%; PFS6: 40%), BEV as a single agent was granted accelerated approval in the USA for recurrent GB. This review is a summary of current literature and clinical trials research in the role of BEV for the treatment of newly diagnosed and recurrent GB and potential future use of anti-angiogenic therapies in the management of GB.

MGMT promoter methylation status and prognosis of patients with primary or recurrent glioblastoma treated with carmustine wafers

The prognostic role of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation in glioblastoma patients treated with carmustine (BCNU) wafer implantation is unclear. Here, we report on a retrospective study of 47 patients with either newly diagnosed (30 patients) or recurrent (17 patients) glioblastoma (WHO grade IV) treated with BCNU (bis-chloroethylnitrosourea) wafers. Thirteen of the newly diagnosed patients received local BCNU and irradiation only (first-line BCNU), while 17 patients additionally received concomitant and adjuvant temozolomide (TMZ) radiochemotherapy (first-line BCNU + TMZ). Of the 17 patients treated for recurrent glioblastoma (second-line BCNU), 16 had received radiotherapy with concomitant and adjuvant TMZ as an initial treatment. Median overall survival (OS) did not significantly differ between 19 patients with MGMT promoter methylated tumors when compared to 28 patients with unmethylated tumors (18.9 vs 15.0 months; p = 0.1054). In the first-line BCNU + TMZ group, MGMT promoter methylation was associated with longer OS (21.0 vs 11.1 months, p = 0.0127), while no significant survival differences were detected in the other two subgroups. Progression-free survival did not significantly differ between patients with and without MGMT promoter methylated tumors in the entire patient cohort or any of the three subgroups. The first-line BCNU + TMZ group showed no significant difference in OS when compared to the first-line BCNU group (18.9 vs 14.7 months), but tended to have more therapy-related adverse effects (53% vs 24%, p = 0.105). In summary, MGMT promoter methylation showed a non-significant trend toward longer survival in our patient cohort. The combination of TMZ radiochemotherapy with local delivery of BCNU did not provide a significant survival benefit compared to local BCNU alone, but was associated with a higher rate of adverse effects. Owing to the small number of patients investigated, however, these findings would need to be corroborated in larger patient cohorts.

The effects of the NICE Technology Appraisal 121 (Gliadel and Temozolomide) on survival in high-grade glioma

Objective. The prognosis of high-grade glioma (HGG) is poor with a median survival of about 1 year for glioblastoma. In 2007, NICE published a technology appraisal (TA121) recommending the use of carmustine wafers (Gliadel) and systemic therapy with temozolomide for selected patients with HGG. Outcomes for HGG surgery in the United Kingdom with these combined treatments have not been published. Design. Retrospective audit of consecutive patients in a single unit with carmustine wafer implantation. Subjects. Fifty-nine patients had carmustine wafers implanted at primary surgery, between October 2005 and October 2010 at Wessex Neurological Centre, Southampton, UK. Methods. Patients were given chemotherapeutic treatments strictly according to NICE TA121. Survival was calculated using Kaplan-Meier method. Results. Fifty-five patients had WHO grade IV tumours and four had grade III. Median age was 61 years. At follow-up, 39 patients had died. Median survival was 15.3 months. Eight patients (13.5%) experienced post-operative complications (including five infections) for which four had the carmustine wafers removed. Forty-seven (80%) patients were treated with radical radiotherapy (55–60 Gy) and six (10%) patients received palliative radiotherapy (30 Gy). Thirty-seven patients (63%) received concomitant temozolomide chemotherapy. In the subset of 37 patients receiving multimodal treatment with radical radiotherapy and concomitant temozolomide, median survival was 15.8 months compared with 7.4 months in those not receiving multimodal treatment. Discussion. Carmustine wafers for primary HGG surgery in accordance with the NICE TA121 were associated with a median survival of 15.3 months; this is improved compared with previously reported randomised trials. Multimodal treatment with carmustine wafers, radical radiotherapy and concomitant temozolomide was associated with improved survival. Increased incidence of infections was observed in cases receiving carmustine wafers.

Comment on the Letter to the editor: Bock et al. Occlusion of surgical opening of the ventricular system with fibrinogen-coated collagen fleece: a case collection study. Acta Neurochir (2011) 153:533–539

Thank you for your interesting comments outlining the sufficiency of collagen-fleece sealing for ventricular defects after carmustine wafer implantation. The use of fibrinogencoated collagen fleeces for sealing and reconstructive procedures of ventricular defects in neurosurgery has not yet been analysed by randomised clinical trials, but their use for neurosurgical indication as a local hemostatic agent with potent prevention of cerebrospinal fluid fistula has been reported in the literature, e.g. Nistor et al. (Skull Base Surg 7:23-30, 1997). We used the fleece for several complex hemostatic and dural-reconstructive indications, including cerebral as well as spinal operative procedures. The sponge-like consistency allows comfortable and accurate modelling, with a fast adhesive effect after direct fluid contact. We share the opinion of the authors that welldesigned studies are needed to analyse the potential benefit of using this agent for different neurosurgical indications compared with other biomaterials for reconstructive and watertight sealing strategies.

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

<title/>Objective: Peak incidence of glioblastoma multiforme (GBM) occurs in individuals aged 65 years and older. The goal was to evaluate the efficacy of carmustine wafers in prolonging survival for older GBM patients.Methods: One hundred and thirty-three consecutive patients aged 65 years and older who underwent surgery for an intracranial primary (de novo) GBM from 1997-2007 were retrospectively reviewed. Among these 133 patients, 45 patients with carmustine wafer implantation were matched with 45 patients without implantation. These groups were matched for factors consistently shown to be associated with survival (age, Karnofsky performance scale, extent of resection, radiation therapy, and temozolomide). Survival was expressed as estimated Kaplan-Meier plots, and log-rank analysis was used to compare survival curves. Variables with P<0·05 were considered statistically significant.Results: The mean (±standard deviation) age of the cohort was 73±5 years, and the median survival of the entire cohort was 5·9 months. Among patients with and without carmustine wafers, there were no significant differences in pre- and peri-operative variables. However, patients with carmustine wafers demonstrated prolonged survival as compared to patients without wafers. The median survival for patients with carmustine wafers was 8·7 months, while median survival for patients without wafers was 5·5 months (P = 0·007). Likewise, in subgroup analysis, patients older than 70 years (P = 0·0003) and 75 years (P = 0·04) who had carmustine wafers had significantly longer survival than matched patients without wafers.Discussion: Older patients with GBM may benefit from carmustine wafers. The survival for older patients who received carmustine wafers is significantly longer than matched patients who did not receive carmustine wafers.

Adverse Events in Multimodal Treatment Therapies for High-Grade Gliomas

T reatment for malignant glioma continues to evolve, and with each new advance in treatment modality there is a slight increase in overall and progression-free survival. armustine wafer treatment and systemic temozolomide plus adiotherapy have both been shown to increase patient survivorhip (8, 9). However, it is important to analyze the adverse events nd potential complications that may occur with combined treatent modalities. Initial placebo-controlled trials with carmustine afers reported numerous adverse events, the most frequent eing new onset seizures, cerebral edema, wound healing abormalities, and intracranial infection (7). Many studies are now sing carmustine wafer implantation in combination with radiaion therapy and adjuvant temozolomide chemotherapy, although vidence that this triple combination is effective is still anecdotal. n addition, the full extent of the adverse events associated with uch a combination has not been explored. In this issue, Della uppa et al. (2) in their article, “Carmustine Wafers Implantation hen Surgical Cavity Is Communicating With Cerebral Ventriles: Technical Considerations on a Clinical Series,” explore one f the lesser mentioned adverse events associated with carmusine wafers, hydrocephalus.

Surgical outcomes for older patients with glioblastoma multiforme: preoperative factors associated with decreased survival

As the population ages, the incidence of glioblastoma multiforme (GBM) among older patients (age > 65 years) will increase. Older patients, unlike their younger counterparts, are not often offered aggressive surgery because of their age, comorbidities, and potential inability to tolerate surgery. The goal of this study was to identify preoperative factors associated with decreased survival for older patients who underwent resection of a GBM. The identification of these factors may provide insight into which patients would benefit most from aggressive surgery. All patients older than 65 years who underwent nonbiopsy resection of an intracranial GBM at a single institution between 1997 and 2007 were retrospectively reviewed. Factors associated with overall survival were assessed using multivariate proportional hazards regression analysis after controlling for peri- and postoperative factors known to be associated with outcome (extent of resection, carmustine wafer implantation, temozolomide chemotherapy, and radiation therapy). Variables with p < 0.05 were considered statistically significant. A total of 129 patients with an average age of 73 ± 5 years met the inclusion/exclusion criteria. At last follow-up, all 129 patients had died, with a median survival of 7.9 months. The preoperative factors that were independently associated with decreased survival were Karnofsky Performance Scale (KPS) score less than 80 (p = 0.001), chronic obstructive pulmonary disease (p = 0.01), motor deficit (p = 0.01), language deficit (p = 0.005), cognitive deficit (p = 0.02), and tumor size larger than 4 cm (p = 0.002). Patients with 0-1 (Group 1), 2-3 (Group 2), and 4-6 (Group 3) of these factors had statistically different survival times, where the median survival was 9.2, 5.5, and 4.4 months, respectively. In log-rank analysis, the median survival for Group 1 was significantly longer than that for Group 2 (p = 0.004) and Group 3 (p < 0.0001), while Group 2 had longer survival than Group 3 (p = 0.02). Older patients with an increasing number of these factors may not benefit as much from aggressive surgery as patients with fewer factors. This may provide insight into identifying which patients older than 65 years of age may benefit from aggressive surgery.

Cerebrospinal Fluid Leak During Treatment With Bevacizumab and Irinotecan After Carmustine-Impregnated Wafers Placement in Patients With Grade 2 Oligodendroglioma and Glioblastoma Multiforme: Report of Two Cases and Review of Literature

ABSTRACTPlacement of carmustine-impregnated wafers has become a common practice after surgical resection of malignant gliomas. Bevacizumab is used as a second-line agent for the treatment of malignant gliomas and is sometimes used in patients who have had recent wafer implantation. We describe two cases of fatal cerebrospinal fluid (CSF) leak in patients treated with bevacizumab and irinotecan after 4 weeks of carmustine wafer implantation. Possible mechanisms for the CSF leak in these patients are discussed. We recommend waiting for a longer period of time before starting bevacizumab in patients who had implantation of carmustine wafers.