Multicentric Glioblastoma Research Articles

Multicentric glioblastoma multiforme. Report of 3 cases, clinical and pathological study and literature review

Multicentric gliomas are uncommon lesions of the central nervous system. Their management remains controversial, but histopathologic diagnosis after complete or partial resection must be performed to differentiate these tumors from other multiple cerebral lesions. Three cases of multicentric glioma are presented, one of which had supra- and infratentorial lesions. Histological specimens were obtained from removal of at least one of the lesions. Neuropathological examinations confirmed the diagnosis of grade IV malignant glioma (glioblastoma). All 3 patients died soon after symptom onset. However, one patient, with metachronous glioblastomas, had a comparatively long survival. We discuss the pathogenetic hypotheses and the diagnostic problems, especially the differential diagnosis from other multifocal diseases of the central nervous system.

Multiple craniotomies in the management of multifocal and multicentric glioblastoma

Multiple craniotomies have been performed for resection of multiple brain metastases in the same surgical session with satisfactory outcomes, but the role of this procedure in the management of multifocal and multicentric glioblastomas is undetermined, although it is not the standard approach at most centers. The authors performed a retrospective analysis of data prospectively collected between 1993 and 2008 in 20 patients with multifocal or multicentric glioblastomas (Group A) who underwent resection of all lesions via multiple craniotomies during a single surgical session. Twenty patients who underwent resection of solitary glioblastoma (Group B) were selected to match Group A with respect to the preoperative Karnofsky Performance Scale (KPS) score, tumor functional grade, extent of resection, age at time of surgery, and year of surgery. Clinical and neurosurgical outcomes were evaluated. In Group A, the median age was 52 years (range 32-78 years); 70% of patients were male; the median preoperative KPS score was 80 (range 50-100); and 9 patients had multicentric glioblastomas and 11 had multifocal glioblastomas. Aggressive resection of all lesions in Group A was achieved via multiple craniotomies in the same session, with a median extent of resection of 100%. Groups A and B were comparable with respect to all the matching variables as well as the amount of tumor necrosis, number of cysts, and the use of intraoperative navigation. The overall median survival duration was 9.7 months in Group A and 10.5 months in Group B (p = 0.34). Group A and Group B (single craniotomy) had complication rates of 30% and 35% and 30-day mortality rates of 5% (1 patient) and 0%, respectively. Aggressive resection of all lesions in selected patients with multifocal or multicentric glioblastomas resulted in a survival duration comparable with that of patients undergoing surgery for a single lesion, without an associated increase in postoperative morbidity. This finding may indicate that conventional wisdom of a minimal role for surgical treatment in glioblastoma should at least be questioned.

Heterogeneity of response to bevacizumab in multifocal and multicentric glioblastomas.

2019 Background: Bevacizumab (BEV) is approved for treatment of recurrent glioblastoma (GBM). However, whether the subset of pts with multifocal (MF) or multicentric (MC) GBM respond favorably to BEV has not been described. Hypothesizing that MF/MC lesions may represent an initially more invasive and biologically heterogeneous phenotype in GBM which may exhibit varied responses to BEV, we examined their patterns of radiologic response and correlation with clinical outcome. Methods: Clinical and MRI data from pts with recurrent GBM who received BEV were reviewed to identify those with MC or MF disease who had adequate baseline and follow-up MRI. Enhancing and nonenhancing (FLAIR) disease were analyzed for response to BEV and categorized in each pt as homogeneous (similar changes in all lesions) or heterogeneous (varied across lesions) in response or progression. Progression-free survival (PFS) and overall survival (OS) were analyzed by the Kaplan Meier method and log rank test. Results: Of the 179 evaluable pts, 31 (17.3%) had multiple lesions (16 pts - MF, 15 pts - MC) prior to BEV treatment. Patients with MC/MF lesions had a significantly worse outcome than those with unifocal lesions in both PFS (Median 19 wks vs. 24.4 wks, p = 0.0124, HR 1.84, CI [1.14, 2.9]) and OS (Median 31 wks vs. 45.9 wks, p = 0.0011, HR 2.42, CI [1.42, 4.12]). Unlike previous reports of BEV response in recurrent GBM pts, MRI responders (homogenous or heterogeneous) among pts with MC/MF lesions did not have a better OS compared with nonresponders. In addition, no significant difference was seen in PFS or OS between patients with homogenous versus heterogeneous progression. There was no significant difference in median PFS (median 17.6 wks vs. 18.4 wks) or median OS (median 27.7 wks vs. 32.3 wks) between pts with MC versus MF GBM. Conclusions: The subset of GBM pts with MF/MC lesions had a worse outcome to BEV treatment compared with those with unifocal disease. Although a homogenous radiological response of all lesions to BEV was the commonest pattern on MRI, neither radiologic response nor pattern of radiologic progression correlated with improved PFS or OS. Our data also suggests that outcome of pts MC/MF GBM may need to be analyzed separately in studies with BEV containing regimens. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration IMEDEX Celgene, Lilly, MGI Pharma, Pfizer

A rare case of multicentric synchronous bi-frontal glioma in a young female. Diagnostic and therapeutic problems: a case report

Multicentric glioblastoma is a uncommon brain malignant tumour.We report the case of a 43-years-old woman, born in Ukraine and living in Italy, who manifested an initial isolated epileptic seizure and subsequent atypical psychiatric symptoms. Clinical neurological examination, Brain Computed Tomography and standard EEG examinations were negative at the moment of admission. A month later, she presented apathy, apraxia, psychomotor slowdown and expressive aphasia. A Magnetic Resonance Imaging examination showed a bi-frontal lesion. The patient underwent to two neurosurgical removals of the lesions: histological examination demonstrated the presence of a grade IV glioblastoma.Clinical onset, diagnostic and therapeutic problems are discussed.In case of atypical psychiatric presentation, it should be taken into consideration neoplastic, inflammatory or infective causes. Despite the absence of focal neurological signs and basal CT scan and EEG alterations, complementary imaging examinations, such as MRI and contrast enhancement CT, are necessary, especially when the conditions become quickly worse

Concomitant (without Adjuvant) Temozolomide and Radiation to Treat Glioblastoma: a Retrospective Study

Between November 2004 and August 2006 we treated 35 patients with concomitant temozolomide (TMZ) and radiotherapy. Twelve patients had very large or multicentric glioblastoma multiforme with a poor performance status and received TMZ plus radiation doses of 45–50.4 Gy. The median survival of these patients was only 3.8 months. Twenty-three patients would have been eligible for randomisation in the European Organisation for Research and Treatment of Cancer/National Cancer Institute of Canada (EORTC/NCIC) trial comparing combined and adjuvant TMZ plus radiation against radiotherapy alone. This group of patients received 60 Gy in 30 fractions plus concomitant TMZ (75 mg/m 2) but no adjuvant chemotherapy. At a median follow-up of 26 months, five of 23 patients are alive. The median survival time was 17 months (1.43 years; 95% confidence interval 0.96–1.55). Eighteen per cent were alive at 2 years. Toxicity from TMZ was infrequent. This series adds to indirect evidence that the concomitant rather than the adjuvant is the more efficacious part of the EORTC/NCIC schedule for this type of patient. Further trials should include a concomitant chemoradiotherapy regimen as well as concomitant plus adjuvant chemotherapy.

FDG-PET to predict different patterns of progression in multicentric glioblastoma: a case report

True multicentric glioblastoma multiforme (GBM) is rare and consists of separate distinct tumors in different cerebral lobes or hemispheres without any apparent route of dissemination. Few data are available describing its imaging using positron emission tomography (PET) with [18F]-fluoro-2-deoxy-D: -glucose (FDG). In this paper, we report on the case of a man with bifocal tumor in the right frontal and temporal lobes who underwent FDG-PET imaging. Visual and semiquantitative analysis showed two different metabolic patterns with much more intense uptake in the smaller temporal lesion. Subtotal surgical removal of the main frontal lesion allowed satisfactory control in the operative site, whereas the temporal lesion was rapidly progressive with occurrence of necrosis, which led to a second neurosurgery. The diagnosis of glioblastoma was confirmed by neuropathological examination in both cases but with much higher immunohistochemical expression of O(6)-methylguanine-DNA-methyltransferase (MGMT) in the temporal lesion. This report illustrates the potential interest of FDG-PET in multicentric GBMs to identify different metabolic patterns, in accordance with clinical, morphological, and molecular aggressiveness.

2518 POSTER Prolonged maintenance chemotherapy with Temozolomide (TMZ) after concomitant treatment in newly diagnosed GBM: safety profile

Between November 2004 and August 2006 we treated 35 patients with concomitant temozolomide (TMZ) and radiotherapy. Twelve patients had very large or multicentric glioblastoma multiforme with a poor performance status and received TMZ plus radiation doses of 45–50.4 Gy. The median survival of these patients was only 3.8 months. Twenty-three patients would have been eligible for randomisation in the European Organisation for Research and Treatment of Cancer/National Cancer Institute of Canada (EORTC/NCIC) trial comparing combined and adjuvant TMZ plus radiation against radiotherapy alone. This group of patients received 60 Gy in 30 fractions plus concomitant TMZ (75 mg/m2) but no adjuvant chemotherapy. At a median follow-up of 26 months, five of 23 patients are alive. The median survival time was 17 months (1.43 years; 95% confidence interval 0.96–1.55). Eighteen per cent were alive at 2 years. Toxicity from TMZ was infrequent. This series adds to indirect evidence that the concomitant rather than the adjuvant is the more efficacious part of the EORTC/NCIC schedule for this type of patient. Further trials should include a concomitant chemoradiotherapy regimen as well as concomitant plus adjuvant chemotherapy.

Multicentric Glioblastoma Multiforme in a Patient with BRCA-1 Invasive Breast Cancer

Breast cancer is the most common cancer in women. Germline mutations in BRCA-1 and BRCA-2 significantly increase the risk of developing breast and ovarian cancers, and are also associated with an increased incidence of primary cancers at other sites. We report the case of a 46-year-old woman previously treated for ductal adenocarcinoma of the breast with BRCA-1 who subsequently was diagnosed with multicentric glioblastoma multiforme (GBM) in the right temporal and right occipital lobes. We briefly discuss the incidence of BRCA-1 mutations in breast cancer as well as other primary neoplasms and consider potential mechanisms shared in the pathogenesis of breast and glial tumors.

Chemoradiotherapy in multicentric glioblastoma multiforme—A clinical study

11525 Background: Glioblastoma multiforme constitutes 40% of primary brain tumors. Multicentric Glioblastoma multiforme is rare about 3%.No definite guidelines is available in literature for management of these tumors. Methods: All Multicentric Glioblastoma multiforme were analyzed retrospectively from Jan 2003 to July 2005 for clinical behavior and response to chemoradiotharpy. Either Temozolamide or Carboplatin or Paclitaxel is used concurrently with radiation. Radiation dose 60 Gy/30 fractions over 6 weeks by bilateral parallel opposed fields was delivered using Cobalt-60 machine. Results: 27 cases were found, Male: Female 24:3, KPS 60 [40–70], Majority of them are symptomatic for 4 months, main symptoms were seizures, headache, vomiting, neurological deficite. 89% of them underwent one form of other surgical intervention. 11% were diagnosed on basis of radiological findings. 85% were supratentorial, 15% were both supra and infratentorial, one of which had spinal cord lesion. 6 [22%] patients did not receive any treatment. Among 21 patients 4 were treated only with radiotherapy, 17 with concurrent Chemoradiotherapy [Paclitaxel-8, Temozolamide-7 and Carboplatin-2]. 5 patients did not complete treatment. Among 16 patients only 6 came for first follow up, 5 of were concurrent Chemoradiotherapy [Temozolamide-4, Paclitaxel-l and RT alone 1]. At the end of 3 months only 2 patients with Temozolamide were alive. Conclusions: Multicentric Glioblastoma multiforme is an aggressive disease. Concurrent Chemoradiotherapy with Temozolamide has better role. No significant financial relationships to disclose.

Multicentric glioblastoma multiforme determined by positron emission tomography: a case report

The actual incidence of true multicentric glioblastoma multiforme (GBM) varies between 2.4 and 4.9% of all GBMs. True multicentric tumors are described as widespread lesions in different lobes or hemispheres, which cannot be explained by spreading along the cerebrospinal fluid or blood pathways. We present here a case of multicentric GBM identified with positron emission tomography. Case report: A 73-year-old woman with sudden onset headaches, balance problems, and one episode of syncope was diagnosed as having an irregular, contrast-enhancing, space-occupying lesion in the left-temporal–parietal region on magnetic resonance imaging (MRI). The tissue diagnosis was confirmed as GBM, and she received stereotactic radiosurgery using the Leksell Gamma Knife® (Elekta Instruments, Atlanta, GA). A 3-month, follow-up, MRI scan showed a remarkable decrease in the size of the contrast-enhancing area that was targeted during radiosurgery. A suspicious area of enhancement was detected on the right side, although no surrounding edema was evident. Fluorodeoxyglucose (FDG)-PET scanning revealed a large irregular neoplasm extending from the inferior left-temporal lobe into the deep parietal lobe with extremely intense FDG uptake, suggesting a very aggressive tumor. A smaller lesion was also discovered in the deep right-frontal lobe, representing a second neoplastic focus. The patient refused any further treatment. Conclusion: PET scans, in conjunction with MRI scans, allow for the best possible and most comprehensive diagnosis and treatment plans.

Glioblastoma multiforme in three family members, including a case of true multicentricity.

Three cases of glioblastoma multiforme are described, occurring in two brothers and the sister of their father. One of the cases was found at autopsy to represent true multicentric glioblastoma, with five widely separated lesions affecting both hemispheres. It is postulated that there may be an association between factors responsible for multiple foci of transformation and a familial tendency to develop glioma.

Multicentric glioma as a cause of multiple cerebral lesions

Two new cases of multicentric glioblastoma are presented to re-emphasize the needs (a) to consider this diagnosis in patients with multiple intracerebral lesions suggesting metastases or abscesses and (b) to consider prompt biopsy of accessible lesions in these patients. (Neurosurgery 13:170-175, 1983)

CT findings in multicentric glioblastoma: Diagnostic-pathologic correlation

Computerized cranial tomography (CCT)and angiographic findings in three cases of multicentric glioblastoma are reported. Differentiation of multicentric glioblasroma from diffure metastatic deposits or multiple abscesses can be difficult with CCT. Apart from demonstrating a mass effect in one case and tumor neovascularity in the second case, angiography did not provide additional helpful information. The pathological diagnoses of these lesions were confirmed by biopsy and subsequent autopsy. Pathological differentiation of the multifocal or multicentric nature of the glioblastoma can be made only at autopsy.

Multicentric glioblastomas. Methods of diagnosis and treatment

Although multicentric glioblastomas are relatively rare, their occurrence is not an extreme rarity. A multicentric lesion should always be thought of when the symptoms cannot be related to a single focus and when the special investigations do not confirm a single lesion. In our opinion the brain scintigram and the computer tomogram offer the best diagnostic possibilities at present. If the preoperative diagnosis has been made, then an indication for operation can be justified only if multiple tumours can be removed through one approach and, what is even more important, at one sitting. The cases demonstrated prove that this procedure can be successful. If, on the other hand, only one of several tumours is excised, then a fatal outcome is almost certain.

Multicentric and isolated multifocal glioblastoma multiforme simulating metastatic disease

Single case reports of multicentric glioblastoma multiforme and multifocal glioblastoma multiforme tumours are presented. Multicentric glioblastoma multiforme tumours are those which have no macroscopic or microscopic connection. Multifocal gliomatous tumours, on the other hand, are those with either gross or microsopic continuity or evidence of cerebral spinal fluid spread and/or local metastases. The cerebral scintigram findings, cerebral angiogram studies and pathological description of these entities are presented. These lesions may be mistaken for metastases. In patients with multiple cerebral lesions multiple primary malignancies of brain should be considered when there is no clinical or radiographical evidence for extracranial primary neoplasms.