Neurosurg Rev DOI 10.1007/s10143-010-0280-7
Randomized phase III trials have shown significant improvement of survival 1, 2, and 3 years after implantation of 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) wafers for patients with newly diagnosed malignant glioma. But these studies and subsequent non-phase III studies have also shown risks associated with local chemotherapy within the central nervous system. The introduction of concomitant radiochemotherapy with temozolomide (TMZ) has later demonstrated a survival benefit in a phase III trial and has become the current treatment standard for newly diagnosed malignant glioma patients. Lately, this has resulted in clinical protocols combining local chemotherapy with BCNU wafers and concomitant radiochemotherapy with TMZ although this may carry the risk of increased toxicity. We have compiled the treatment experience of seven neurosurgical centers using implantation of carmustine wafers at primary surgery followed by 6 weeks of radiation therapy (59–60 Gy) and 75 mg/m2/day TMZ in patients with newly diagnosed glioblastoma followed by TMZ monochemotherapy. We have retrospectively analyzed the postoperative clinical course, occurrence and severity of adverse events, progression-free interval, and overall survival in 44 patients with newly diagnosed glioblastoma multiforme. All patients received multimodal treatment including tumor resection, BCNU wafer implantation, and concomitant radiochemotherapy. Of 44 patients (mean age 59±10.8 years) with glioblastoma who received Gliadel wafer at primary surgery, 28 patients (64%) had died, 16 patients (36%) were alive, and 15 patients showed no evidence of clinical or radiographic progression after a median follow-up of 15.6 months. At time of analysis of adverse events in this patient population, the median overall survival was 12.7 months and median progression-free survival was 7.0 months. Surgical, neurological, and medical adverse events were analyzed. Twenty-three patients (52%) experienced adverse events of any kind including complications that did not require treatment. Nineteen patients (43%) experienced grade 3 or grade 4 adverse events. Surgical complications included cerebral edema, healing abnormalities, cerebral spinal fluid leakage, meningitis, intracranial abscess, and hydrocephalus. Neurological adverse events included newly diagnosed seizures, alteration of mental status, and new neurological deficits. Medical complications were thromboembolic events (thrombosis, pulmonary embolism) and hematotoxicity. Combination of both treatment strategies, local chemotherapy with BCNU wafer and concomitant radiochemotherapy, appears attractive in aggressive multimodal treatment schedules and may utilize the sensitizing effect of TMZ and carmustine on MGMT and AGT on their respective drug resistance genes. Our data demonstrate that combination of local chemotherapy and concomitant radiochemotherapy carries a significant risk of toxicity that currently appears underestimated. Adverse events observed in this study appear similar to complication rates published in the phase III trials for BCNU wafer implantation followed by radiation therapy alone, but further add the toxicity of concomitant radiochemotherapy with systemic TMZ. Save use of a combined approach will require specific prevention strategies for multimodal treatments.
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 Neurosurg Spine 12:144–153, 2010. (DOI: 10.3171/2009.6.SPINE08910)
The goal in this study was to review a series of patients who underwent surgical removal of intramedul- lary high-grade gliomas, focusing on the functional outcome, recurrence rates, and technical problems continually debated in neurosurgical practice.
Methods. Between December 1976 and December 2006, 22 patients underwent removal of intramedullary high- grade gliomas. Lesions were located in the cervical spinal cord in 12 patients, and in the thoracic cord in 10.
Results. Histological examinations showed 10 Grade III astrocytomas and 12 glioblastomas. Only 2 of the 22 high-grade astrocytomas could be completely removed. The clinical postoperative status worsened in 14 patients (63.6%), was unchanged in 7 patients (31.8%), and there was 1 case of intraoperative death (4.5%). None of the 22 patients showed improvement in their neurological status postoperatively. In this series, excluding the 1 intraopera- tive death, all patients died of progression of the malignancy.
Conclusions. Surgical treatment did not ameliorate the postoperative neurological status; instead, in the majority of cases, it prompted a worsening of the deficit. Radiotherapy and chemotherapy have a little influence on the length of survival. In this series, multimodality treatment of intramedullary high-grade astrocytomas has been shown to increase length of survival without improving the neurological status.
J Neurooncol. DOI 10.1007/s11060-009-0032-0
This retrospective series explores temozolomide monotherapy in elderly patients with primary CNS lymphoma (PCNSL) and severe comorbidities. In 17 patients (62–90 years old), the complete response rate was 47%, median progression-free survival was 5 months, and median overall survival was 21 months. Five of 17 patients (29.4%) had prolonged responses for at least 12 months and survived for more than 24 months. Three of these patients had a methylated O6-methylguanine-DNA methyltransferase (MGMT) promoter, while the MGMT status was not assessable in the remaining two patients.
Temozolomide monotherapy appears to be effective in a subgroup of elderly PCNSL patients and deserves further evaluation.
J Neurooncol (2009) 95:81–85 DOI 10.1007/s11060-009-9894-4
Studies investigating whether adults have diminished survival from medulloblastoma (MB) compared with children have yielded conflicting results. We sought to determine in a population-based registry whether adults and children with MB differ in survival, and to examine whether dissimilar use of chemotherapy might contribute to any disparity.
1,226 MB subjects were identified using the Surveillance Epidemiology and End Results (SEER-9) registry (1973–2002) and survival analysis performed. MB was defined strictly to exclude non-cerebellar primitive neuro- ectodermal tumors. Patients were stratified by age at diagnosis: <3 years (infants), 3–17 years (children) and >18 years (adults). Because the SEER-9 registry lacks treatment data, a subset of 142 patients were identified using the San Francisco-Oakland SEER registry (1988–2003) and additional analyses performed.
There was no significant difference in survival between children and adults with MB in either the SEER-9 (P = 0.17) or SFO (P = 0.89) cohorts but infants fared worse compared to both children (P < 0.01) and adults (P < 0.01). In the SFO sample, children and adults who received chemotherapy plus radiation therapy (XRT) did not differ in survival. Among patients treated with XRT alone, children showed increased survival (P = 0.04) compared with adults. Children and adults with MB do not differ with respect to overall survival, yet infants fare significantly worse.
For children and adults with MB treated with both XRT and chemotherapy, we could not demonstrate a survival difference. Similar outcomes between adult and childhood MB may justify inclusion of adults in pediatric cooperative trials for MB.
