Surgery For Recurrent Glioblastoma Research Articles

P17.14.B Strategy of the recurrent Glioblastoma treatment. Three neuro-oncology centers study

Abstract Background The prognosis for patients with Glioblastoma (GBM) remains dismal. The most aggressive multimodal therapy (maximally radical and safe tumor resection, followed by the Stupp protocol oncotherapy) has yielded the best treatment outcomes. Notwithstanding the slowly prolonged patient′s overall survival, this tumor inevitable recurs. An optimal therapy of the recurrent GBM is still a controversial theme.The aim of our study is to evaluate our treatment strategy of recurrent GBM. Material and Methods For this study, we retrospectively selected a group of resected recurrent GBM patients in a period from June 1, 2009 to December 31, 2019, which were treated in tree Czech neuro-oncologic centers. All patients underwent early post-surgical MRI (within 72 h) to determine resection radicality. Following resection, patients received periodic checkups with MRI every 3 months until death. Patients with psedoprogession were excluded. Information about all surgeries, oncotherapies, patient clinical condition, MRI, PET/CT, and results of histological, immunohistochemical, molecular genetic, and cytogenetic investigations was gathered.We consider surgery for recurrent GBM in case, if: 1.The tumor volume increasing > 20-30% or tumor rediscovery after radiologic disappearing. 2.Clinic condition - Karnofsky score (KS) ≥ 70% and Performance status (PS) WHO ≤ gr. 2. 3.Localized tumor, without multilfocality. 4.Assumed the least tumor volume reduction > 80%. Results We gathered 122 patients with recurrent GBM, 98,9% of tumors was determined as wild-type, age median was 53,36 years. All patients underwent Stupp protocol oncotherapy after prime surgery. Median of OS from prime surgery was 21 months (15.8, 29.6). The best results proved a surgery of GBM recurrency proceeding more than 6 months after diagnosis. OS2 (from redo up to the death) was 7.4 months (6.41, 11.3). 43.3% of patients recalled temozolomide chemotherapy. We confirmed positive link between OS and resection radicality, negative relations between OS and a postoperative neurologic deficits. Only limited relation was presented between OS and repeated oncotherapy. Relation to the further histologic, imunohistochemic, cytogenetic and molecular markers will be discussed. Conclusion Due to the common unfavorable outcomes of GBM therapy, out of despair, we often decided for repeated surgery. The aim of our study was avoid ineffective surgical overtreatment. The best results of surgery yield right selected recurrent GBMs. Surgery of GBM regrown during initial oncotherapy (6 months after prime surgery) presented unsatisfactory effects. Positive effect of the surgical radicality and clinic status were confirmed. Again, necessity of second-line oncotherapy has been emerged. Supported by Ministry of Health of the Czech Republic, grant nr. NV19- 04-00281 and grant nr. NU21-03-00195

PO-1169 Impact of Recurrence Pattern in Patients Undergoing a Second Surgery for Recurrent Glioblastoma

PO-1169 Impact of Recurrence Pattern in Patients Undergoing a Second Surgery for Recurrent Glioblastoma

Age-adjusted Charlson comorbidity index in recurrent glioblastoma: a new prognostic factor?

BackgroundFor recurrent glioblastoma (GB) patients, several therapy options have been established over the last years such as more aggressive surgery, re-irradiation or chemotherapy. Age and the Karnofsky Performance Status Scale (KPSS) are used to make decisions for these patients as these are established as prognostic factors in the initial diagnosis of GB. This study’s aim was to evaluate preoperative patient comorbidities by using the age-adjusted Charlson Comorbidity Index (ACCI) as a prognostic factor for recurrent GB patients.MethodsIn this retrospective analysis we could include 123 patients with surgery for primary recurrence of GB from January 2007 until December 2016 (43 females, 80 males, mean age 57 years (range 21–80 years)). Preoperative age, sex, ACCI, KPSS and adjuvant treatment regimes were recorded for each patient. Extent of resection (EOR) was recorded as a complete/incomplete resection of the contrast-enhancing tumor part.ResultsMedian overall survival (OS) was 9.0 months (95% CI 7.1–10.9 months) after first re-resection. Preoperative KPSS > 80% (P < 0.001) and EOR (P = 0.013) were associated with significantly improved survival in univariate analysis. Including these factors in multivariate analysis, preoperative KPSS < 80 (HR 2.002 [95% CI: 1.246–3.216], P = 0.004) and EOR are the only significant prognostic factor (HR 1.611 [95% CI: 1.036–2.505], P = 0.034). ACCI was not shown as a prognostic factor in univariate and multivariate analyses.ConclusionFor patients with surgery for recurrent glioblastoma, the ACCI does not add further information about patient’s prognosis besides the well-established KPSS and extent of resection.

Impact of recurrence pattern in patients undergoing a second surgery for recurrent glioblastoma

The impact of different patterns of glioblastoma (GBM) recurrence has not yet been fully established in patients suitable for a second surgery. Through the present observational study carried out at Pisa University Hospital, we aimed to investigate how different patterns of GBM failure influence second surgery outcomes. Overall survival (OS) and post-recurrence survival (PRS) were assessed according to clinical characteristics, including pattern of recurrence, in a prospective cohort of recurrent GBM patients. Survival curves were calculated using the Kaplan-Meier method and the log-rank test was applied to evaluatethe differences between curves. Patients with local recurrence had better OS than patients with non-local one, 24.1 versus 18.2months, respectively [P = 0.015, HR = 1.856 (1.130-3.050)]. The second surgery conferred an advantage in OS respect to non-operated patients, however, this advantage was more evident in patients with local recurrence [P = 0.002 with HR 0.212 (95% CI 0.081-0.552) and P = 0.029 with HR = 0.522 (95% CI 0.291-0.936), respectively]. The recurrence pattern can influence the outcome of patients with recurrent GBM suitable for a second surgery.

Impact of surgery versus other treatment options in recurrent glioblastoma. Analysis of the Spanish Group of Neurooncology Research (GEINO) RETSINE database.

e14047 Background: Glioblastoma (GBM) is the most common brain primary tumor. Almost all patients have recurrent disease after initial treatment with surgery, radiotherapy and chemotherapy. After disease recurrence, there is no standardized treatment and reoperation is common but there is no proven benefit in randomized trials. Here we retrospectively review the Spanish national database to identify the frequency of reoperations in recurrent GBM and to analyze the impact of surgery on survival in this setting. Methods: We retrospectively reviewed relapsed GBM patients from the Spanish national database RETSINE (Registro Nacional Español de Tumores del Sistema Nervioso Central) supported by the GEINO group. Kaplan-Meier curves and log rank test were used to compare survival. Results: The number of patients with recurrent GBM analyzed was 538, 40% were women and 60% were men. The MGMT status was: methylated 30.9%, unmethylated 33.8%, unknown 35.3%. A total of 89.9% of the patients received radiotherapy and 88.7% received chemotherapy after initial surgery. The median progression-free survival until first recurrence was 7.63 months (IC95% 6.97-8.29). Median overall survival (OS) from GBM diagnosis was 11.96 months (IC95% 10.69- 23.23). At the time of the first progression, surgery was performed in 75 patients, (13.9%), 18 cases were treated with a second radiotherapy (3.3%), second line CT was administered in 268 patients (49.6%), 221 cases received only chemotherapy (40.9%), 47 cases were treated with both surgery and chemotherapy (8.7%); 28 were treated with surgery without chemotherapy (5.2%), 19 cases had a surgery procedure but we have no data about CT, 223 cases did nor receive CT nor surgery (41%). Median overall survival after relapse was 4.06 months (IC95% 3.25-4.87). For those patients without surgery, median OS after relapse was 3.1 m (IC95% 2.84-3.71) and for patients reoperated, median OS was 12.2 m (IC95% 10.8-13.52) p=0.00 Median overall survival after relapse was 1.7 months (IC95% (IC 1.31-2.08) for patients that did not had CT and 7.03 for those with CT(IC95%5.9-8.16) p=0.00 We also compared the results from different treatment options: median OS was 1.6 m (IC95% 1.11-2.08), for patients without treatment; 6.33 m (IC95% 5.34-7.32) for patients treated with chemotherapy; 12.2 m (IC95%11.05-13.34) for patients treated with surgery and CT;12.1 m(IC95% 4.64-19.55) for patients with surgery. Conclusions: Recurrent glioblastoma is a very aggressive disease. In this retrospective study, patients treated with surgery and surgery and CT could have a clinical benefit in terms of survivalin comparison with those not treated with reoperation. Randomized prospective trials are needed to clarify the role of surgery in recurrent GBM.

Reoperation does not provide a survival advantage in patients with recurrent Glioblastoma treated with irinotecan/bevacizumab treatment.

Treatment options for recurrent glioblastoma (GBM) have limited efficacy. Although reoperation is useful for both the confirmation of the diagnosis of recurring disease and the relief of the symptoms, its effect on survival is unknown. The aim of this study was to evaulate the impact of second surgery in recurrent GBM. Patients with GBM followed in our center between January 2015 and April 2018 were analyzed retrospectively based on the treatment options. 25 patients diagnosed with recurrent GBM were analyzed. Ten patients (40%) were treated with chemotherapy following reoperation, and 15 patients (60%) were treated with only chemotherapy. No benefits of reoperation were observed in the univariate analysis. The second surgery in recurrent GBM has limited effect in clinical course.

Diffusion Magnetic Resonance Imaging Phenotypes Predict Overall Survival Benefit From Bevacizumab or Surgery in Recurrent Glioblastoma With Large Tumor Burden.

Diffusion magnetic resonance (MR) characteristics are a predictive imaging biomarker for survival benefit in recurrent glioblastoma treated with anti-vascular endothelial growth factor (VEGF) therapy; however, its use in large volume recurrence has not been evaluated. To determine if diffusion MR characteristics can predict survival outcomes in patients with large volume recurrent glioblastoma treated with bevacizumab or repeat resection. A total of 32 patients with large volume (>20 cc or > 3.4 cm diameter) recurrent glioblastoma treated with bevacizumab and 35 patients treated with repeat surgery were included. Pretreatment tumor volume and apparent diffusion coefficient (ADC) histogram analysis were used to phenotype patients as having high (>1.24 μm2/ms) or low (<1.24 μm2/ms) ADCL, the mean value of the lower peak in a double Gaussian model of the ADC histogram within the contrast enhancing tumor. In bevacizumab and surgical cohorts, volume was correlated with overall survival (Bevacizumab: P=.009, HR=1.02; Surgical: P=.006, HR=0.96). ADCL was an independent predictor of survival in the bevacizumab cohort (P=.049, HR=0.44), but not the surgical cohort (P=.273, HR=0.67). There was a survival advantage of surgery over bevacizumab in patients with low ADCL (P=.036, HR=0.43) but not in patients with high ADCL (P=.284, HR=0.69). Pretreatment diffusion MR imaging is an independent predictive biomarker for overall survival in recurrent glioblastoma with a large tumor burden. Large tumors with low ADCL have a survival benefit when treated with surgical resection, whereas large tumors with high ADCL may be best managed with bevacizumab.

Primary versus recurrent surgery for glioblastoma\u2014a prospective cohort study

BackgroundThere is currently limited evidence for surgery in recurrent glioblastoma (GBM). Our aim was to compare primary and recurrent surgeries, regarding changes in perioperative, generic health-related quality of life (HRQoL), complications, extents of resection and survival.MethodsBetween 2007 and 2018, 65 recurrent and 160 primary GBM resections were prospectively enrolled. HRQoL was recorded with EQ-5D 3L preoperatively and at 1 month postoperatively. Median perioperative change in HRQoL and change greater than the minimal clinically important difference (MCID) were assessed. Tumour volume and extent of resection were obtained from pre- and postoperative MRI scans. Survival was assessed from date of surgery.ResultsComparing recurrent surgeries and primary resections, most variables were balanced at baseline, but median age (59 vs. 62, p = 0.005) and median preoperative tumour volume (14.9 vs. 25.3 ml, p = 0.001) were lower in recurrent surgeries. There were no statistically significant differences regarding complication rates, neurological deficits, extents of resection or EQ-5D 3L index values at baseline and at follow-up. Twenty (36.4%) recurrent resections vs. 39 (27.5%) primary resections reported clinically significant deterioration in HRQoL at follow-up. Stratified by clinically significant change in EQ-5D 3L, the survival distributions were not statistically significantly different in either group. Survival was associated with extent of resection (p = 0.015) in recurrent surgeries only.ConclusionsOutcomes after primary and recurrent surgeries were quite similar in our practice. As surgery may prolong life in patients where gross total resection is obtainable with reasonable risk, the indication for surgery in GBM should perhaps not differ that much in primary and recurrent resections.

P.049 Repeat surgery in recurrent glioblastoma: a systematic review and meta-analysis

Background: Recurrent glioblastoma portends a poor prognosis and the role of repeat surgery in improving survival remains uncertain. Our systematic review and meta-analysis aims to address whether re-resection provides a meaningful survival benefit and to what degree. Methods: Articles were collected from Pubmed, -CINAHL, EMBASE, Medline and Cochrane from January 1990 to 2018. Studies in the temozolomide era with both single surgery and re-resection cohorts were included. Primary outcomes were odds ratio for survival at 6, 12, and 24 months following re-resection and initial surgery. Results: Fourteen articles were included for analysis (3048 patients). Meta-analysis showed improved overall survival following re-resection at 6- (OR 1.73, 95% CI 1.23-2.45, p&lt;0.05), 12- (OR 1.71, 95% CI 1.20-2.45, p&lt;0.05), and 24-months (OR 2.24, 95% CI 1.01-4.95, p&lt;0.05). Overall survival from diagnosis or first surgery was also improved in patients who underwent re-resection at -recurrence, similarly at 6- (OR 8.22, 95% CI 5.23-12.93, p&lt;0.01), 12- (OR 4.16, 95% CI 3.25-5.36, p&lt;0.01), and 24- (2.35, 95% CI 1.77-3.11, p&lt;0.05) months. Subgroup analyses were done for patients stratified by age, performance status, and number of re-resections. Conclusions: Repeat surgery for recurrent glioblastoma is associated with a significant survival advantage independent of other salvage therapies that include chemotherapy, radiation, and other antineoplastic regimens.

The effect of an adenosine A2A agonist on intra-tumoral concentrations of temozolomide in patients with recurrent glioblastoma

BackgroundThe blood–brain barrier (BBB) severely limits the entry of systemically administered drugs including chemotherapy to the brain. In rodents, regadenoson activation of adenosine A2A receptors causes transient BBB disruption and increased drug concentrations in normal brain. This study was conducted to evaluate if activation of A2A receptors would increase intra-tumoral temozolomide concentrations in patients with glioblastoma.MethodsPatients scheduled for a clinically indicated surgery for recurrent glioblastoma were eligible. Microdialysis catheters (MDC) were placed intraoperatively, and the positions were documented radiographically. On post-operative day #1, patients received oral temozolomide (150 mg/m2). On day #2, 60 min after oral temozolomide, patients received one intravenous dose of regadenoson (0.4 mg). Blood and MDC samples were collected to determine temozolomide concentrations.ResultsSix patients were enrolled. Five patients had no complications from the MDC placement or regadenoson and had successful collection of blood and dialysate samples. The mean plasma AUC was 16.4 ± 1.4 h µg/ml for temozolomide alone and 16.6 ± 2.87 h µg/ml with addition of regadenoson. The mean dialysate AUC was 2.9 ± 1.2 h µg/ml with temozolomide alone and 3.0 ± 1.7 h µg/ml with regadenoson. The mean brain:plasma AUC ratio was 18.0 ± 7.8 and 19.1 ± 10.7% for temozolomide alone and with regadenoson respectively. Peak concentration and Tmax in brain were not significantly different.ConclusionsAlthough previously shown to be efficacious in rodents to increase varied size agents to cross the BBB, our data suggest that regadenoson does not increase temozolomide concentrations in brain. Further studies exploring alternative doses and schedules are needed; as transiently disrupting the BBB to facilitate drug entry is of critical importance in neuro-oncology.

Outcomes after second surgery for recurrent glioblastoma: a retrospective case-control study.

Studies looking at the benefit of surgery at first relapse (second surgery) for recurrent glioblastoma were confounded by including patients with varying grades of glioma, performance status and extent of resection. This case-controlled study aims to remove these confounders to assess the survival impact of second surgery in recurrent glioblastoma. Retrospective data on patients with glioblastoma recurrence at two tertiary Australian hospitals from July 2009 to April 2015 was reviewed. Patients who had surgery at recurrence were matched with those who did not undergo surgery at recurrence, based on the extent of their initial resection and age. Overall survival (OS1 assessed from initial diagnosis and OS2 from the date of recurrence) as well as functional outcomes after resection were analysed. There were 120 patients (60 in each institution); median age at diagnosis was 56years. Median OS1 was 14months (95% CI 11.5-15.7) versus 22months (95% CI 18-25) in patients who did not undergo second surgery and those with surgery at recurrence. OS2 was improved by second surgery (4.7 vs 9.6, HR 0.52, 95% CI 0.38-0.72, P < 0.001), and by chemotherapy, given at recurrence, (HR 0.47, 95% CI 0.24-0.92, P = 0.03). After second surgery, 80% did not require rehabilitation and 61% were independently mobile. Second surgery for recurrent glioblastoma was associated with a survival advantage. Chemotherapy independent of surgery, also improved survival. Functional outcomes were encouraging. More research is required in the era of improved surgical techniques and new antineoplastic therapies.

Hypofractionated Re-irradiation after Maximal Surgical Resection for Recurrent Glioblastoma: Therapeutic Adequacy and Its Prognosticators of Survival.

PurposeTo evaluate the adequacy of retreatment, including hypofractionated re-irradiation (HFReRT), after surgery for recurrent glioblastoma (GBM) and related prognosticators of outcomes.Materials and MethodsFrom 2011 to 2014, 25 consecutive patients with recurrent (n=17) or secondary (n=7) disease underwent maximal surgery and subsequent HFReRT after meeting the following conditions: 1) confirmation of recurrent or secondary GBM after salvage surgery; 2) Karnofsky performance score (KPS) ≥60; and 3) interval of ≥12 months between initial radiotherapy and HFReRT. HFReRT was delivered using a simultaneous integrated boost technique, with total dose of 45 Gy in 15 fractions to the gross tumor volume (GTV) and 37.5 Gy in 15 fractions to the clinical target volume.ResultsDuring a median follow-up of 13 months, the median progression-free and overall survival (OS) were 13 and 16 months, respectively. A better KPS (p=0.026), no involvement of the eloquent area at recurrence (p=0.030), and a smaller GTV (p=0.005) were associated with better OS. Additionally, OS differed significantly between risk groups stratified by the National Institutes of Health Recurrent GBM Scale (low-risk vs. high-risk, p=0.025). Radiologically suspected radiation necrosis (RN) was observed in 16 patients (64%) at a median of 9 months after HFReRT, and 8 patients developed grade 3 RN requiring hospitalization.ConclusionHFReRT after maximal surgery prolonged survival in selected patients with recurrent GBM, especially those with small-sized recurrences in non-eloquent areas and good performance.

Phase I study of AZD1775 with radiation therapy (RT) and temozolomide (TMZ) in patients with newly diagnosed glioblastoma (GBM) and evaluation of intratumoral drug distribution (IDD) in patients with recurrent GBM.

2005 Background: The standard of care treatment for newly diagnosed GBM is maximal safe surgical resection followed by two DNA damaging agents, RT and TMZ. Cellular response to DNA damage involves checkpoints that halt the cell cycle to allow DNA repair. AZD1775 is an oral small molecular inhibitor of a nuclear tyrosine kinase Wee1, a key regulator of the G2/M checkpoint. Abrogation of the G2/M checkpoint prevents repair and pushes cells into mitosis with unrepaired DNA damage. AZD1775 was shown to enhance TMZ and RT effects in preclinical models. Methods: The Adult Brain Tumor Consortium 1202 trial (NCT01849146) is a phase I, open label, multicenter dose-finding study of AZD1775 in combination with standard RT and TMZ followed by an IDD study for patients undergoing surgery for recurrent GBM. The dose finding portion is comprised of two arms, one with AZD1775 given Monday through Friday during concurrent RT/TMZ and a second arm given with adjuvant TMZ qd x 5d/28d cycle. Each arm had standard 3+3 design. A combination cohort with both concurrent and adjuvant AZD1775 at MTD and analysis of PK/PD and IDD at MTD in patients undergoing surgery for recurrent GBM followed. Results: 51 patients enrolled in the dose finding arms. For the concurrent arm, the MTD was 200 mg. At 275 mg one patient had grade 3 fatigue and another had grade 4 thrombocytopenia and neutropenia. Two of 6 total patients enrolled at 200 mg experienced DLTs (grade 4 neutropenia and grade 3 ALT elevation). The MTD for the adjuvant arm was 425 mg as 1 of 6 patients had DLT (grade 4 decrease in ANC). At 500 mg, 2 of 3 patients experienced intolerable diarrhea despite prophylaxis. Enrollment in the combination cohort is completed and evaluation of safety is underway. The drug concentration in contrast enhancing and non-enhancing brain tumor was 4-8 x and 0.5-2.6 x greater than plasma, respectively for patients on IDD portion. Conclusions: The MTD for AZD1775 in combination with RT/TMZ is 200 mg qd M-F with concurrent RT/TMZ and 425 mg qd x 5d/28d cycle in combination with adjuvant TMZ. IDD and PK/PD analysis is ongoing to inform the decision to proceed to phase II testing. Clinical trial information: NCT01849146.

Expression of CD133 and CD44 in glioblastoma stem cells correlates with cell proliferation, phenotype stability and intra-tumor heterogeneity.

Glioblastoma (GBM) is a heterogeneous tumor of the brain with a poor prognosis due to recurrence and drug resistance following therapy. Genome-wide profiling has revealed the existence of distinct GBM molecular subtypes that respond differently to aggressive therapies. Despite this, molecular subtype does not predict recurrence or drug resistance and overall survival is similar across subtypes. One of the key features contributing to tumor recurrence and resistance to therapy is proposed to be an underlying subpopulation of resistant glioma stem cells (GSC). CD133 expression has been used as a marker of GSCs, however recent evidence suggests the relationship between CD133 expression, GSCs and molecular subtype is more complex than initially proposed. The expression of CD133, Olig2 and CD44 was investigated using patient derived glioma stem-like cells (PDGCs) in vitro and in vivo. Different PDGCs exhibited a characteristic equilibrium of distinct CD133+ and CD44+ subpopulations and the influence of environmental factors on the intra-tumor equilibrium of CD133+ and CD44+ cells in PDGCs was also investigated, with hypoxia inducing a CD44+ to CD133+ shift and chemo-radiotherapy inducing a CD133+ to CD44+ shift. These data suggest that surveillance and modulation of intra-tumor heterogeneity using molecular markers at initial surgery and surgery for recurrent GBM may be important for more effective management of GBM.

Patient outcomes following second surgery for recurrent glioblastoma.

The most appropriate management of recurrent glioblastoma is still controversial. In particular, the role of surgery at recurrence remains uncertain. From our Institutional data warehouse we analyzed 270 consecutive patients who received second surgery for recurrent glioblastoma, to assess survival after second surgery, and to evaluate prognostic factors. Complete resection was found in 128 (47.4%) and partial resection in 142 patients (52.6%). Median survival from second surgery was 11.4 months (95% CI: 10.0-12.7). Multivariate analysis showed that age (p = 0.001), MGMT methylation (p = 0.021) and extent of surgery (p < 0.001) are associated with better survival. A complete resection should be the goal for second resection and younger age and MGMT methylation status might be considered in the selection of patients.

Complete resection of contrast-enhancing tumor volume is associated with improved survival in recurrent glioblastoma-results from the DIRECTOR trial.

The role of reoperation for recurrent glioblastoma (GBM) remains unclear. Prospective studies are lacking. Here, we studied the association of clinical outcome with extent of resection upon surgery for recurrent GBM in the patient cohort of DIRECTOR, a prospective randomized multicenter trial comparing 2 dose-intensified temozolomide regimens at recurrence of GBM. We analyzed prospectively collected clinical and imaging data from the DIRECTOR cohort (N = 105). Volumetric analysis was performed on gadolinium contrast-enhanced MRI as well as fluid attenuated inversion recovery/T2 MRI and correlated with PFS after initial progression (PFS2) and post-recurrence survival (PRS). Quality of life was monitored by the EORTC QLQ-C30 and QLQ-BN20 questionnaires at 8-week intervals. Seventy-one patients received surgery at first recurrence. Prognostic factors, including age, MGMT promoter methylation, and Karnofsky performance score, were balanced between patients with and without reoperation. Outcome in patients with versus without surgery at recurrence was similar for PFS2 (2.0 mo vs 1.9 mo, P = .360) and PRS (11.4 mo vs 9.8 mo, P = .633). Among reoperated patients, post-surgery imaging was available in 59 cases. In these patients, complete resection of contrast-enhancing tumor (N = 40) versus residual detection of contrast enhancement (N = 19) was associated with improved PRS (12.9 mo [95% CI: 11.5-18.2] vs 6.5 mo [95% CI: 3.6-9.9], P < .001) and better quality of life. Incomplete tumor resection was associated with inferior PRS compared with patients who did not undergo surgery (6.5 vs 9.8 mo, P = .052). Quality of life was similar in these 2 groups. Surgery at first recurrence of GBM improves outcome if complete resection of contrast-enhancing tumor is achieved.

Does extent of resection matter in recurrent glioblastoma? Lessons from the DIRECTOR trial.

2041 Background: The role of surgery for recurrent glioblastoma is under debate. Tumor volume at recurrence was prognostic in single-institution retrospective studies, but no data from prospective ...

Histopathological correlates with survival in reoperated glioblastomas

The addition of concomitant and adjuvant chemotherapy to radiation therapy after surgical resection has increased significantly the survival of patients with glioblastoma (GB). In conjunction, there has been an increasing fraction of patients who present with new enlarged areas of contrast enhancement and edema on post-treatment imaging that improve without further treatment. It remains to be established how this phenomenon, commonly termed pseudoprogression, can be distinguished from true tumor recurrence defined as the histological presence of active high-grade tumor, as well as its prognostic significance. Data for over 500 patients undergoing surgery for recurrent GB were reviewed. Pathological specimens were categorized as those that contained active high-grade glioma in any amount, and those that did not. Patient survival was compared between these two groups, and independent associations were assessed using Cox proportionate hazards regression analysis. 59 patients met the study criteria including complete pathological and follow-up data. Mean age was 53 ± 11 years. Median survival from suspected recurrence and initial diagnosis were 8 [5-14] and 20 [12-30] months. Seventeen patients (29 %) had no evidence of active high-grade tumor and 42 (71 %) had at least focal active high-grade glioma. Pathologic pseudoprogression at re-operation (p = 0.03) and gross total resection (p = 0.01) were independently associated with survival. The histopathological features defined here and used to assess the tumor at reoperation were independently associated with survival. These findings may be important in designing treatment strategies and clinical trial endpoints for patients with GB.

Second surgery for recurrent glioblastoma: advantages and pitfalls

Deciding upon the therapeutic approach for patients with recurrent glioblastoma is a challenge. Although second surgery may provide effective palliation, it has yet to be established whether it prolongs survival and/or improves quality of life; nor have data been reported in literature to demonstrate that repeat surgery is indicated for patients with recurrence. The few studies investigating this issue are retrospective and have been conducted on small series, and their data sets are not homogeneous. The aim of the present study was, therefore, to analyze predictors of outcome in patients with recurrent glioblastoma and to make a critical of review of data in literature with a view to comparing the effect on outcome of second surgery against well-known prognostic determinants.

Impact of bevacizumab chemotherapy on craniotomy wound healing

The FDA approval of bevacizumab for recurrent glioblastoma has resulted in its increased use in this patient population. Phase II trials reported 4%-6% impaired wound healing for bevacizumab initiated postoperatively. The effect of preoperative bevacizumab on subsequent craniotomy healing has not been addressed. The authors retrospectively reviewed the cases of patients who underwent craniotomy for recurrent glioblastoma between 2005 and 2009, evaluating bevacizumab therapy/duration and healing complications (dehiscence, pseudomeningocele, CSF leak, and wound/bone infection). The Wilcoxon rank-sum test and Kruskal-Wallis test were used to compare continuous variables between groups. The Fisher exact test was used to assess for an association between categorical variables, including the comparison of wound-healing complication rates. Logistic regression models were used to estimate odds ratios of wound-healing complications while adjusting for baseline variables. Two hundred nine patients underwent a second craniotomy (161 patients) or third craniotomy (48 patients) for recurrent glioblastoma. Twenty-six individuals (12%) developed wound-healing complications. One hundred sixty-eight patients received no bevacizumab, 23 received preoperative bevacizumab, and 18 received postoperative bevacizumab. Significantly more patients receiving preoperative bevacizumab developed healing complications (35%) than non-bevacizumab-treated patients (10.0%, p = 0.004). Postoperative bevacizumab was associated with 6% impaired healing, not significantly different from non-bevacizumab-treated controls (p = 1.0). Preoperative bevacizumab treatment duration (weeks) did not influence healing (OR 0.98, p = 0.55). More healing complications occurred in patients receiving preoperative bevacizumab than in non-bevacizumab-treated controls before the third craniotomy (44% vs 9%, p = 0.03). Although subject to the limitations of a retrospective study, we demonstrate that preoperative bevacizumab treatment resulted in impaired healing after a second and third craniotomy, compared with minimal effect of postoperative bevacizumab. This effect is more striking for the third craniotomy and for a shorter delay between bevacizumab and surgery. These complications should be acknowledged as increased bevacizumab use results in more post-bevacizumab-treated patients in whom surgery for recurrent glioblastoma is considered. Based on these results, the authors recommend performing repeated craniotomy more than 28 days after last administered dose of bevacizumab whenever possible.