Neurosurgery Blog

Neurosurgery 67:446-458, 2010 DOI: 10.1227/01.NEU.0000371990.86656.E8

OBJECTIVE: To investigate the pattern of care and outcomes for newly diagnosed glioblastoma in Italy and compare our results with the previous Italian Patterns of Care study to determine whether significant changes occurred in clinical practice during the past 10 years.

METHODS: Clinical, pathological, therapeutic, and survival data regarding 1059 patients treated in 18 radiotherapy centers between 2002 and 2007 were collected and retrospectively reviewed.

RESULTS:Most patients underwent both computed tomography and magnetic resonance imaging either preoperatively (62.7%) or postoperatively (35.5%). Only 123 patients (11.6%) underwent a biopsy. Radiochemotherapy with temozolomide was the most frequent adjuvant treatment (70.7%). Most patients (88.2%) received 3-dimensional conformal radiotherapy. Median survival was 9.5 months. Two- and 5-year survival rates were 24.8% and 3.9%, respectively. Multivariate analysis showed the statistical significance of age, postoperative Karnofsky Performance Status scale score, surgical extent, use of 3-dimensional conformal radiotherapy, and use of chemotherapy. Use of a more aggressive approach was associated with longer survival in elderly patients. Comparing our results with those of the subgroup of patients included in our previous study who were treated between 1997 and 2001, relevant differences were found: more frequent use of magnetic resonance imaging, surgical removal more common than biopsy, and widespread use of 3-dimensional conformal radiotherapy + temozolomide. Furthermore, a significant improvement in terms of survival was noted (P < .001).

CONCLUSION: Changes in the care of glioblastoma over the past few years are documented. Prognosis of glioblastoma patients has slightly but significantly improved with a small but noteworthy number of relatively long-term survivors.

J Neurooncol (2009) 95:301–305 DOI 10.1007/s11060-009-9946-9

Extended survival of 3 or more years is rare in patients with glioblastoma (GBM) but is becoming more common. Clinical outcome has not been well studied. We reviewed GBM patients at Memorial Sloan-Kettering Cancer Center between 2001 and 2003 who were seen for two or more visits. Patient characteristics and long-term clinical outcomes were reviewed for patients who had survived 3 or more years following diagnosis. Thirty-nine (11%) of 352 GBM patients were identified as long-term survivors. Median survival was 9.15 years (range: 3–18 years). Median age was 47 years (range: 16–69); 13% were 65 years or older. Median KPS was 90 (range: 50–100). One long-term survivor underwent biopsy alone; 19 patients each had either complete or subtotal resection. All received focal radiotherapy (RT) with a median dose of 5940 cGy; 18% received concurrent temozolomide. Adjuvant chemotherapy was administered to 35 (90%). Twelve patients (31%) remained in continuous remission. Twenty-seven had tumor progression a median of 29.2 months after diagnosis (range: 1.2–167 months); 18 had multiple relapses. Median KPS at last follow-up was 70 (range: 40–100); 85% of long-term survivors had at least one significant neurologic deficit. Eleven (28%) had clinically significant RT-induced leukoencephalopathy, 9 (23%) developed RT necrosis and 9 (23%) treatment-related strokes. Treatment-related complications occurred a median of 2.7 years from diagnosis (range: 0.9–11.5 years).

Long-term survivors remain rare, but are found across all age groups despite multiple recurrences; clinically significant delayed complications of treatment are common.

Acta Neurochir (2009) 151:1349–1358. DOI 10.1007/s00701-009-0387-1

Glioblastoma is a highly lethal neoplasm with a median survival of 12–14 months; only 2–5% of patients survive >3 years.

Methods At our institute, patients with glioblastoma are initially treated with maximum tumor resection followed by radiation and the intravenous injection of nimustine hydrochloride (ACNU).

Results Using this strategy, 18 of 123 (14.6%) patients treated at our hospital survived >3 years; 7 manifested no recurrence, and the other 11 had early recurrence and received additional therapies. To identify factors associated with prolonged survival, we compared these patients with 21 short-term (<1.5 years) glioblastoma survivors. In the long-term survivors, the MGMT promoter methylation was significantly more frequent. The rate of p53 mutation was lower, and the rate of PTEN mutations and the proliferation index were slightly higher in short-term survivors.

Conclusion By multivariate analysis,  we found that a younger age and MGMT promoter methylation were significant favorable factors in patients with glioblastoma.

J Neurooncol (2009) 95:151–163 DOI 10.1007/s11060-009-9916-2

Glioblastoma is the most common and aggressive form of primary brain tumor. The prognosis for patients diagnosed with glioblastoma is poor, with a median survival of 12–14 months and a 5-year survival rate of <5%. The upfront standard treatment for patients with newly diagnosed glioblastoma, consisting of surgery followed by chemotherapy combined with radiotherapy, provides only short-term survival benefits. Recurrent glioblastoma is an extremely challenging therapeutic setting because of the aggressive and resistant nature of the tumor. A set of key molecular targets in oncology is the Src family of non-receptor protein kinases. Dysregulated signaling via the Src kinases has been shown to underlie glioma-related proliferation, angiogenesis, migration, and survival. Here we review the biologic role of Src in malignant glioma and discuss key preclinical studies demonstrating the potential utility of inhibiting Src in glioma. Proof of clinical benefit is forthcoming from the first clinical studies involving the newest generation of small molecule Src inhibitors currently in clinical trials for recurrent glioblastoma. Blocking Src alone will likely not translate into a significant clinical benefit; thus, strategies for combining Src inhibitors with potential synergistic therapeutic modalities will be discussed. This review focus on dasatinib, the most advanced Src inhibitor being tested in glioblastoma, which is currently in phase I/II trials in this setting.