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Meic H. Schmidt, Mitchel S. Berger, Kathleen R. Lamborn, Ken Aldape, Michael W. McDermott, Michael D. Prados, and Susan M. Chang

Object. Progression of infiltrative low-grade gliomas (LGGs) has been reported previously. The limitations of such studies include diverse histological grading systems, intervening therapy, and the lack of histological confirmation of malignant tumor progression. The aim of this study was to determine tumor progression in adult patients with an initial diagnosis of infiltrative LGG who subsequently underwent a repeated operation, but no other intervening therapy. The authors examined factors that may be associated with tumor progression.

Methods. The authors retrospectively reviewed a database of 300 patients with the initial diagnosis of LGG and who had been treated at their institution between 1990 and 2000. One hundred four of these patients had undergone a second surgery. Patients with infiltrative LGGs who had undergone two surgical procedures at least 3 months apart without intervening therapy were selected; the authors identified 40 patients who fit these criteria. Clinical, neuroimaging, and pathological data were centrally reviewed.

There were 29 men and 11 women in the study, whose median age was 35.5 years (range 23–48 years). At the time of the second surgery, 50% of patients had experienced tumor progression. Patients whose tumors had progressed had a longer median time to repeated operation (49 compared with 22.5 months). Patients who had undergone gross-total resection, as demonstrated on postoperative magnetic resonance images, had a median time to repeated operation of 49 compared with 25 and 24 months in patients who underwent subtotal resection and biopsy, respectively (p = 0.02). The extent of resection did not influence the likelihood of tumor progression (p > 0.3).

Conclusions. Fifty percent of patients with initially diagnosed infiltrative LGGs had tumor progression at the time of a repeated operation. A gross-total resection was associated with an increased time to repeated surgery. There was no statistically significant effect of gross-total resection as a predictor of tumor progression.

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Andrew T. Parsa, Scott Wachhorst, Kathleen R. Lamborn, Michael D. Prados, Michael W. McDermott, Mitchel S. Berger, and Susan M. Chang

Object. The clinical outcome and treatment of adult patients with disseminated intracranial glioblastoma multiforme (GBM) is unclear. The objective in the present study was to assess the prognostic significance of disseminated intracranial GBM in adults at presentation and at the time of tumor progression.

Methods. Clinical data from 1491 patients older than 17 years and harboring a GBM that had been diagnosed between 1988 and 1998 at the University of California at San Francisco neurooncology clinic were retrospectively reviewed. Dissemination of the GBM (126 patients) was determined based on Gd-enhanced magnetic resonance images. Classification of dissemination was as follows: Type I, single lesion with subependymal or subarachnoid spread; Type II, multifocal lesions without subependymal or subarachnoid spread; and Type III, multifocal lesions with subependymal or subarachnoid spread. Subgroups of patients were compared using Kaplan—Meier curves that depicted survival probability.

The median postprogression survival (PPS), defined according to neuroimaging demonstrated dissemination, was 37 weeks for Type I (23 patients), 25 weeks for Type II (50 patients), and 10 weeks for Type III spread (19 patients). Patients with dissemination at first tumor progression (52 patients) overall had a shorter PPS than those in a control group with local progression, after adjusting for age, Karnofsky Performance Scale score, and time from tumor diagnosis to its progression (311 patients). When analyzed according to tumor dissemination type, PPS was significantly shorter in patients with Type II (33 patients, p < 0.01) and Type III spread (11 patients, p < 0.01) but not in those with Type I spread (eight patients, p = 0.18).

Conclusions. Apparently, the presence of intracranial tumor dissemination on initial diagnosis does not in itself preclude aggressive treatment if a patient is otherwise well. A single focus of GBM that later demonstrates Type I dissemination on progression does not have a worse prognosis than a lesion that exhibits only local recurrence.

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Aaron J. Clark, Nicholas A. Butowski, Susan M. Chang, Michael D. Prados, Jennifer Clarke, Mei-Yin C. Polley, Michael E. Sughrue, Michael W. McDermott, Andrew T. Parsa, Mitchel S. Berger, and Manish K. Aghi

Object

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.

Methods

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.

Results

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).

Conclusions

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.

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Fred G. Barker II, Michael D. Prados, Susan M. Chang, Philip H. Gutin, Kathleen R. Lamborn, David A. Larson, Mary K. Malec, Michael W. McDermott, Penny K. Sneed, William M. Wara, and Charles B. Wilson

✓ To determine the value of radiographically assessed response to radiation therapy as a predictor of survival in patients with glioblastoma multiforme (GBM), the authors studied a cohort of 301 patients who were initially treated according to uniform clinical protocols. All patients had newly diagnosed supratentorial GBM and underwent the maximum safe resection followed by external-beam radiation treatment (60 Gy in standard daily fractions or 70.4 Gy in twice-daily fractions of 160 cGy). The radiation response and survival rates were assessable in 222 patients. The extent of resection and the immediate response to radiation therapy were highly correlated with survival, both in a univariate analysis and after correction for age and Karnofsky performance scale (KPS) score in a multivariate Cox model (p < 0.001 for radiation response and p = 0.04 for extent of resection). A subgroup analysis suggested that neuroimaging obtained within 3 days after surgery served as a better baseline for assessment of radiation response than images obtained later. Imaging obtained within 3 days after completion of a course of radiation therapy also provided valid radiation response scores. The impact of the radiographically assessed radiation response on survival time was comparable to that of age or KPS score. This information is easily obtained early in the course of the disease, may be of value for individual patients, and may also have implications for the design and analysis of trials of adjuvant therapy for GBM, including volume-dependent therapies such as radiosurgery or brachytherapy.

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Oral Presentations

2010 AANS Annual Meeting Philadelphia, Pennsylvania May 1–5, 2010