TY - JOUR AB - Glioblastoma multiforme (GBM) is one of the most malignant types of central nervous system tumors. Despite advances in treatment modalities it remains largely incurable. The objective of our review is to provide a holistic picture of GBM epidemiology, etiology, pathogenesis, clinical findings and treatment. A literature search was conducted for GBM at PubMed and Google Scholar, with relevant key words like glioblastoma multiforme, pathogenesis, signs and symptoms, treatment etc., and papers published until 2015 were reviewed. It was found that radiation and certain genetic syndromes are the only risk factors identified to date for GBM. Depending on the tumor site patients may present to the clinic with varying symptoms. To confirm the presence and the extent of tumor, various invasive and non-invasive imaging techniques require employment. The literature survey revealed the pathogenesis to involve aberrations of multiple signaling pathways through multiple genetic mutations and altered gene expression. Although several treatment options are available, including surgery, along with adjuvant chemo- and radio-therapy, the disease has a poor prognosis and patients generally succumb within 14 months of diagnosis. AU - Hanif, Farina AU - Muzaffar, Kanza AU - Perveen, Kahkashan AU - Malhi, Saima M. AU - Simjee, Shabana U. DO - 10.22034/APJCP.2017.18.1.3 IS - 1 KW - Epidemiology KW - Glioblastoma multiforme KW - MRI scan KW - Mutations KW - Temozolomide PY - 2017 SP - 3 EP - 9 TI - Glioblastoma multiforme: A review of its epidemiology and pathogenesis through clinical presentation and treatment T2 - Asian Pacific Journal of Cancer Prevention VL - 18 ER - TY - JOUR AB - Glioblastoma multiforme (GBM) is the most common and aggressive primary central nervous system malignancy with a median survival of 15 months. The average incidence rate of GBM is 3.19/100,000 population, and the median age of diagnosis is 64 years. Incidence is higher in men and individuals of white race and non-Hispanic ethnicity. Many genetic and environmental factors have been studied in GBM, but the majority are sporadic, and no risk factor accounting for a large proportion of GBMs has been identified. However, several favorable clinical prognostic factors are identified, including younger age at diagnosis, cerebellar location, high performance status, and maximal tumor resection. GBMs comprise of primary and secondary subtypes, which evolve through different genetic pathways, affect patients at different ages, and have differences in outcomes. We report the current epidemiology of GBM with new data from the Central Brain Tumor Registry of the United States 2006 to 2010 as well as demonstrate and discuss trends in incidence and survival. We also provide a concise review on molecular markers in GBM that have helped distinguish biologically similar subtypes of GBM and have prognostic and predictive value. AU - Thakkar, Jigisha P. AU - Dolecek, Therese A. AU - Horbinski, Craig AU - Ostrom, Quinn T. AU - Lightner, Donita D. AU - Barnholtz-Sloan, Jill S. AU - Villano, John L. DA - 2014/10// DO - 10.1158/1055-9965.EPI-14-0275 IS - 10 PB - American Association for Cancer Research Inc. PY - 2014 SP - 1985 EP - 1996 TI - Epidemiologic and molecular prognostic review of glioblastoma T2 - Cancer Epidemiology Biomarkers and Prevention VL - 23 ER - TY - JOUR AB - Glioblastoma multiforme (GBM) is one of the most frequently occurring tumors in the central nervous system and the most malignant tumor among gliomas. Despite aggressive treatment including surgery, adjuvant TMZ-based chemotherapy, and radiotherapy, GBM still has a dismal prognosis: the median survival is 14.6 months from diagnosis. To date, many studies report several determinants of resistance to this aggressive therapy: (1) O 6- methylguanine-DNA methyltransferase (MGMT), (2) the complexity of several altered signaling pathways in GBM, (3) the existence of glioma stem-like cells (GSCs), and (4) the blood-brain barrier. Many studies aim to overcome these determinants of resistance to conventional therapy by using various approaches to improve the dismal prognosis of GBM such as modifying TMZ administration and combining TMZ with other agents, developing novel molecular-targeting agents, and novel strategies targeting GSCs. In this paper, we review up-to-date clinical trials of GBM treatments in order to overcome these 4 hurdles and to aim at more therapeutical effect than conventional therapies that are ongoing or are about to launch in clinical settings and discuss future perspectives. © 2012 Fumiharu Ohka et al. AU - Ohka, Fumiharu AU - Natsume, Atsushi AU - Wakabayashi, Toshihiko DO - 10.1155/2012/878425 PY - 2012 TI - Current trends in targeted therapies for glioblastoma multiforme T2 - Neurology Research International VL - 2012 ER - TY - JOUR AB - Objective: Glioblastoma multiforme (GBM) accounts for up to 60% of all malignant primary brain tumours in adults, occurring in 2-3 cases per 100 000 in Europe and North America. In 2005, a Phase III clinical trial demonstrated a significant improvement in survival over 2, and subsequently 5, years with the addition of concurrent and adjuvant temozolomide (TMZ) to radical radiotherapy (RT). The aim of this study was to investigate if the demonstrated improved survival in the literature translated to clinical practice. Methods: This was a retrospective study including all patients with histologically proven GBM diagnosed from 1999 to 2008 and treated with adjuvant RT at our institution. A total of 273 patients were identified. Statistical analysis was carried out using SPSS® v.18 (SPSS, Chicago, IL). Results: The median survival for the whole group ( n=273) over the 10-year period was 7.6 months (95% confidence interval 6.7-8.4 months). Overall, the cumulative probability of survival at 1 and 2 years was 31.5% and 9.4%, respectively. In total, 146 patients received radical RT. 103 patients were treated with radical RT and TMZ and 43 patients received radical RT alone. The median survival for patients receiving radical RT with TMZ was 13.4 months (95% CI 10.9-15.8 months) vs 8.8 months for radical RT alone (95% CI 6.9-10.7 months, p=0.006). 2-year survival figures were 21.2% vs 4.7%, respectively. On multivariate analysis, independent predictors of survival included Karnofsky Performance Status, RT dose, TMZ and extent of surgery. The strongest predictors of poorer outcome based on the hazard ratio were palliative RT, followed by not receiving TMZ chemotherapy, then KPS <90 and a biopsy only surgical approach. Conclusion: This paper demonstrates improved survival outcomes consistent with those published in the literature for the addition of concurrent and adjuvant TMZ to radical RT for the treatment of GBM. Although 63% of patients seen in the clinic were suitable for a combined modality approach, the prognosis for the lower Radiation Therapy Oncology Group classes still remains poor. © 2012 The British Institute of Radiology. AU - Rock, Kathy AU - Mcardle, O AU - Forde, P. AU - Dunne, M. AU - Fitzpatrick, D. AU - O'Neill, B. AU - Faul, C. DA - 2012/9// DO - 10.1259/bjr/83796755 IS - 1017 PY - 2012 SP - e729 EP - e733 TI - A clinical review of treatment outcomes in glioblastoma multiforme—the validation in a non-trial population of the results of a randomised Phase III clinical trial: has a more radical approach improved survival? T2 - The British Journal of Radiology UR - http://www.birpublications.org/doi/10.1259/bjr/83796755 VL - 85 ER - TY - JOUR AU - Ostrom, Quinn T. AU - Gittleman, Haley AU - Truitt, Gabrielle AU - Boscia, Alexander AU - Kruchko, Carol AU - Barnholtz-Sloan, Jill S. DA - 2018/10// DO - 10.1093/neuonc/noy131 IS - suppl_4 PY - 2018 SP - iv1 EP - iv86 TI - CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2011–2015 T2 - Neuro-Oncology UR - https://academic.oup.com/neuro-oncology/article/20/suppl_4/iv1/5090960 VL - 20 ER - TY - JOUR AB - Gliomas of astrocytic, oligodendroglial and ependymal origin account for more than 70% of all brain tumors. The most frequent (65%) and most malignant histological type is the glioblastoma. Since the introduction of computerized tomography and magnetic resonance imaging, the incidence rates of brain tumors have been rather stable, with a tendency of higher rates in highly developed, industrialized countries. Some reports indicate that Caucasians have higher incidence than black or Asian populations, but to some extent, this may reflect socio-economic differences and under-ascertainment in some regions, rather than a significant difference in genetic susceptibility. With the exception of pilocytic astrocytomas, the prognosis of glioma patients is still poor. Less than 3% of glioblastoma patients are still alive at 5 years after diagnosis, higher age being the most significant predictor of poor outcome. Brain tumors are a component of several inherited tumor syndromes, but the prevalence of these syndromes is very low. Several occupations, environmental carcinogens, and diet (N-nitroso compounds) have been reported to be associated with an elevated glioma risk, but the only environmental factor unequivocally associated with an increased risk of brain tumors, including gliomas, is therapeutic X-irradiation. In particular, children treated with X-irradiation for acute lymphoblastic leukemia show a significantly elevated risk of developing gliomas and primitive neuroectodermal tumor (PNET), often within 10 years after therapy.TP53 mutations are frequent in low-grade gliomas and secondary glioblastomas derived therefrom. Approximately 60% of mutations are located in the hot spot codons 248 and 273, and the majority of these are G:C→A:T transitions at CpG sites.TP53 mutations are significantly more frequent in low-grade astrocytomas with promoter methylation of the O6-methylguanine-DNA methyltransferase repair gene, suggesting that, in addition to deamination of 5-methylcytosine, exogenous or endogenous alkylation in the O6 position of guanine may contribute to the formation of these mutations. © Springer-Verlag 2005. AU - Ohgaki, Hiroko AU - Kleihues, Paul DA - 2005/1// DO - 10.1007/s00401-005-0991-y IS - 1 KW - Glioma KW - Incidence KW - N-Nitroso compounds KW - Occupation KW - Survival PY - 2005 SP - 93 EP - 108 TI - Epidemiology and etiology of gliomas T2 - Acta Neuropathologica UR - http://www.ncbi.nlm.nih.gov/pubmed/15685439 UR - http://link.springer.com/10.1007/s00401-005-0991-y VL - 109 ER - TY - JOUR AB - Objective: The role of repeat resection for recurrent glioblastoma multiforme (rGBM) is unclear. This large comparative cohort study assessed overall survival (OS), survival since recurrence (SSR), quality of life, and complications in reoperated versus non-reoperated patients for rGBM. Patients and methods: All patients with rGBM between 2005 and 2015, who were discussed by our institution's multi-disciplinary team, and who either did or did not undergo reoperation, were prospectively followed up with data collected and compared. Survival and prognostic factors were analysed using Kaplan–Meier and Cox regression methods. Results: 312 patients (reoperated, n = 145; non-reoperated, n = 167) were analysed. Median SSR was 10.8 months and 6.9 months in the reoperated and non-reoperated groups respectively (Log-rank test: p = 0.02). Median OS was 24.1 months and 20.4 months in the reoperated and non-reoperated groups, respectively (Log-rank test: p = 0.04). Quality of life as measured by Short Form 36 scores were 59 versus 54 at baseline and 62 versus 51 at four-month follow-up for re-operated and non-reoperated groups, respectively (p < 0.05). Age < 60 years, Karnofsky Performance Status (KPS) ≥ 80, recurrence ≥ 9 months from initial diagnosis, methylguanine methyltransferase (MGMT) promoter methylation, and extent of resection (EOR) > 80 %, each were significant predictors of SSR and OS. Complication rates were 5.5 % and 6.2 % following repeat resection and primary resection, respectively (p > 0.05). Conclusion: This is the first large prospective comparative cohort study of rGBM and demonstrates that repeat resection confers a small but significant benefit in survival and quality of life over non-operative treatment. Best prognosis is associated with: younger age, KPS ≥ 80, late recurrence, MGMT promoter methylation and EOR > 80 %. AU - Mukherjee, Soumya AU - Wood, Joseph AU - Liaquat, Imran AU - Stapleton, Simon R. AU - Martin, Andrew J. DA - 2020/1// DO - 10.1016/j.clineuro.2019.105568 KW - Complications KW - Glioblastoma KW - Recurrence KW - Repeat resection KW - Survival PB - Elsevier B.V. PY - 2020 TI - Craniotomy for recurrent glioblastoma: Is it justified? A comparative cohort study with outcomes over 10 years T2 - Clinical Neurology and Neurosurgery VL - 188 ER - TY - BOOK AB - Glioblastoma (GBM) is the most aggressive malignant primary brain tumor. With an incidence rate of 3.19 per 100,000 persons in the United States and a median age of 64 years, it is uncommon in children. The incidence is 1.6 times higher in males compared to females and 2.0 times higher in Caucasians compared to Africans and Afro-Americans, with lower incidence in Asians and American Indians. GBM is commonly located in the supratentorial region (frontal, temporal, parietal, and occipital lobes) and is rarely located in cerebellum. Genetic and environmental factors have been investigated in GBM. Risk factors include prior radiotherapy, decreased susceptibility to allergy, immune factors and immune genes, as well as some single nucleotide polymorphisms detected by genomic analysis. Use of anti-inflammatory medication has been found to be protective against GBM. Survival from GBM is poor; only few patients survive 2.5 years and less than 5% of patients survive 5 years following diagnosis. Survival rates for patients with GBM have shown no notable improvement in population statistics in the last three decades. Molecular epidemiology integrates molecular technology into epidemiological studies and outcomes. The future of the epidemiology of GBM will depend on multicenter studies generating large clinical data sets of genomic data potentially leading to further understanding of the roles of genes and environment in the development of this devastating disease. AU - Tamimi, Ahmad Faleh AU - Juweid, Malik DA - 2017/9// DO - 10.15586/codon.glioblastoma.2017.ch8 KW - Brain tumors KW - Epidemiology KW - Glioblastoma KW - Outcome PB - Codon Publications PY - 2017 SN - 9780994438126 SP - 143 EP - 153 TI - Epidemiology and Outcome of Glioblastoma T2 - Glioblastoma UR - http://www.ncbi.nlm.nih.gov/pubmed/29251870 ER - TY - GEN AB - Glioblastoma is the most frequent and malignant brain tumor. The vast majority of glioblastomas (∼90%) develop rapidly de novo in elderly patients, without clinical or histologic evidence of a less malignant precursor lesion (primary glioblastomas). Secondary glioblastomas progress from low-grade diffuse astrocytoma or anaplastic astrocytoma. They manifest in younger patients, have a lesser degree of necrosis, are preferentially located in the frontal lobe, and carry a significantly better prognosis. Histologically, primary and secondary glioblastomas are largely indistinguishable, but they differ in their genetic and epigenetic profiles. Decisive genetic signposts of secondary glioblastoma are IDH1 mutations, which are absent in primary glioblastomas and which are associated with a hypermethylation phenotype. IDH1 mutations are the earliest detectable genetic alteration in precursor low-grade diffuse astrocytomas and in oligodendrogliomas, indicating that these tumors are derived from neural precursor cells that differ from those of primary glioblastomas. In this review, we summarize epidemiologic, clinical, histopathologic, genetic, and expression features of primary and secondary glioblastomas and the biologic consequences of IDH1 mutations. We conclude that this genetic alteration is a definitive diagnostic molecular marker of secondary glioblastomas and more reliable and objective than clinical criteria. Despite a similar histologic appearance, primary and secondary glioblastomas are distinct tumor entities that originate from different precursor cells and may require different therapeutic approaches. Copyright © 2013 American Association for Cancer Research. AU - Ohgaki, Hiroko AU - Kleihues, Paul DA - 2013/2// DO - 10.1158/1078-0432.CCR-12-3002 IS - 4 PY - 2013 SP - 764 EP - 772 TI - The definition of primary and secondary glioblastoma T2 - Clinical Cancer Research UR - http://www.ncbi.nlm.nih.gov/pubmed/23209033 VL - 19 ER - TY - CHAP AB - Glioblastoma (GBM) is a disease that strikes without warning, often manifested by a single seizure or a few days of progressive headaches, yet evaluation with magnetic resonance imaging reveals a large mass that was likely present for months. Its stealth-like behavior belies the hallmark feature of this deadly cancer; it infiltrates normal brain diffusely, early in the disease course and over long distances, making it impossible to detect early or to cure surgically. The median survival time is 15 months with approximately 25% of patients alive at 2 years. The mainstay of treatment is external beam radiation in combination with the oral alkylating agent, temozolomide. The glioblastoma genome has been well characterized, yet no molecular targeted therapies have yet proven effective in the clinic. Improvements in outcome for this devastating disease will require a better understanding of the pathophysiology and the development of robust preclinical models for testing new therapies. AU - Maher, Elizabeth A. AU - Bachoo, Robert M. DO - 10.1016/B978-0-12-410529-4.00078-4 KW - Glioblastoma KW - IDH KW - Infiltration KW - Metabolism KW - Mouse models PB - Elsevier PY - 2015 SN - 9780124105294 SP - 909 EP - 917 TI - Glioblastoma T2 - Rosenberg's Molecular and Genetic Basis of Neurological and Psychiatric Disease UR - https://linkinghub.elsevier.com/retrieve/pii/B9780124105294000784 ER - TY - JOUR AB - Background: Most patients with glioblastoma are older than 60 years, but treatment guidelines are based on trials in patients aged only up to 70 years. We did a randomised trial to assess the optimum palliative treatment in patients aged 60 years and older with glioblastoma. Methods: Patients with newly diagnosed glioblastoma were recruited from Austria, Denmark, France, Norway, Sweden, Switzerland, and Turkey. They were assigned by a computer-generated randomisation schedule, stratified by centre, to receive temozolomide (200 mg/m 2 on days 1-5 of every 28 days for up to six cycles), hypofractionated radiotherapy (34·0 Gy administered in 3·4 Gy fractions over 2 weeks), or standard radiotherapy (60·0 Gy administered in 2·0 Gy fractions over 6 weeks). Patients and study staff were aware of treatment assignment. The primary endpoint was overall survival. Analyses were done by intention to treat. This trial is registered, number ISRCTN81470623. Findings: 342 patients were enrolled, of whom 291 were randomised across three treatment groups (temozolomide n=93, hypofractionated radiotherapy n=98, standard radiotherapy n=100) and 51 of whom were randomised across only two groups (temozolomide n=26, hypofractionated radiotherapy n=25). In the three-group randomisation, in comparison with standard radiotherapy, median overall survival was significantly longer with temozolomide (8·3 months [95% CI 7·1-9·5; n=93] vs 6·0 months [95% CI 5·1-6·8; n=100], hazard ratio [HR] 0·70; 95% CI 0·52-0·93, p=0·01), but not with hypofractionated radiotherapy (7·5 months [6·5-8·6; n=98], HR 0·85 [0·64-1·12], p=0·24). For all patients who received temozolomide or hypofractionated radiotherapy (n=242) overall survival was similar (8·4 months [7·3-9·4; n=119] vs 7·4 months [6·4-8·4; n=123]; HR 0·82, 95% CI 0·63-1·06; p=0·12). For age older than 70 years, survival was better with temozolomide and with hypofractionated radiotherapy than with standard radiotherapy (HR for temozolomide vs standard radiotherapy 0·35 [0·21-0·56], p<0·0001; HR for hypofractionated vs standard radiotherapy 0·59 [95% CI 0·37-0·93], p=0·02). Patients treated with temozolomide who had tumour MGMT promoter methylation had significantly longer survival than those without MGMT promoter methylation (9·7 months [95% CI 8·0-11·4] vs 6·8 months [5·9-7·7]; HR 0·56 [95% CI 0·34-0·93], p=0·02), but no difference was noted between those with methylated and unmethylated MGMT promoter treated with radiotherapy (HR 0·97 [95% CI 0·69-1·38]; p=0·81). As expected, the most common grade 3-4 adverse events in the temozolomide group were neutropenia (n=12) and thrombocytopenia (n=18). Grade 3-5 infections in all randomisation groups were reported in 18 patients. Two patients had fatal infections (one in the temozolomide group and one in the standard radiotherapy group) and one in the temozolomide group with grade 2 thrombocytopenia died from complications after surgery for a gastrointestinal bleed. Interpretation: Standard radiotherapy was associated with poor outcomes, especially in patients older than 70 years. Both temozolomide and hypofractionated radiotherapy should be considered as standard treatment options in elderly patients with glioblastoma. MGMT promoter methylation status might be a useful predictive marker for benefit from temozolomide. Funding: Merck, Lion's Cancer Research Foundation, University of Umeå, and the Swedish Cancer Society. © 2012 Elsevier Ltd. AU - Malmström, Annika AU - Grønberg, Bjørn Henning AU - Marosi, Christine AU - Stupp, Roger AU - Frappaz, Didier AU - Schultz, Henrik AU - Abacioglu, Ufuk AU - Tavelin, Björn AU - Lhermitte, Benoit AU - Hegi, Monika E. AU - Rosell, Johan AU - Henriksson, Roger DA - 2012/9// DO - 10.1016/S1470-2045(12)70265-6 IS - 9 PY - 2012 SP - 916 EP - 926 TI - Temozolomide versus standard 6-week radiotherapy versus hypofractionated radiotherapy in patients older than 60 years with glioblastoma: The Nordic randomised, phase 3 trial T2 - The Lancet Oncology UR - http://www.ncbi.nlm.nih.gov/pubmed/22877848 VL - 13 ER - TY - JOUR AB - The influence of the degree of resection on survival in patients with glioblastoma multiforme is still under discussion. The highly controlled 5-aminolevulinic acid study provided a unique platform for addressing this question as a result of the high frequency of “complete” resections, as revealed by postoperative magnetic resonance imaging scans achieved by fluorescence-guided resection and homogeneous patient characteristics.Two hundred forty-three patients with glioblastoma multiforme per protocol from the 5-aminolevulinic acid study were analyzed. Patients with complete and incomplete resections as revealed by early magnetic resonance imaging scans were compared. Prognostic factors that might cause bias regarding resection and influence survival (e.g., tumor size, edema, midline shift, location, age, Karnofsky Performance Scale score, National Institutes of Health Stroke Scale score) were used for analysis of overall survival. Time to reintervention (chemotherapy, reoperation) was analyzed further to exclude bias regarding second-line therapies.Treatment bias was identified in patients with complete (n = 122) compared with incomplete resection (n = 121), i.e., younger age and less frequent eloquent tumor location. Other factors, foremost preoperative tumor size, were identical. Patients without residual tumor survived longer (16.7 versus 11.8 mo, P < 0.0001). In multivariate analysis, only residual tumor, age, and Karnofsky Performance Scale score were significantly prognostic. To account for distribution bias, patients were stratified for age (>60 or ≤60 yr) and eloquent location. Survival advantages from complete resection remained significant within subgroups, and age/eloquent location were no longer unevenly distributed. Reinterventions occurred marginally earlier in patients with residual tumor (6.7 versus 9.5 mo, P = 0.0582).Treatment bias was demonstrated regarding resection and second-line therapies. However, bias and imbalances were controllable in the cohorts available from the 5-aminolevulinic acid study so that the present data now provide Level 2b evidence (Oxford Centre for Evidence-based Medicine) that survival depends on complete resection of enhancing tumor in glioblastoma multiforme. AU - Stummer, Walter AU - Reulen, Hanns-Jürgen AU - Meinel, Thomas AU - Pichlmeier, Uwe AU - Schumacher, Wiebke AU - Tonn, Jörg-Christian AU - Rohde, Veit AU - Oppel, Falk AU - Turowski, Bernd AU - Woiciechowsky, Christian AU - Franz, Kea AU - Pietsch, Torsten DA - 2008/3// DO - 10.1227/01.neu.0000317304.31579.17 IS - 3 PY - 2008 SP - 564 EP - 576 TI - EXTENT OF RESECTION AND SURVIVAL IN GLIOBLASTOMA MULTIFORME T2 - Neurosurgery UR - https://doi.org/10.1227/01.neu.0000317304.31579.17 UR - https://academic.oup.com/neurosurgery/article/62/3/564/2558483 VL - 62 ER - TY - JOUR AB - BACKGROUND Glioblastoma, the most common primary brain tumor in adults, is usually rapidly fatal. The current standard of care for newly diagnosed glioblastoma is surgical resection to the extent feasible, followed by adjuvant radiotherapy. In this trial we compared radiotherapy alone with radiotherapy plus temozolomide, given concomitantly with and after radiotherapy, in terms of efficacy and safety. METHODS Patients with newly diagnosed, histologically confirmed glioblastoma were randomly assigned to receive radiotherapy alone (fractionated focal irradiation in daily fractions of 2 Gy given 5 days per week for 6 weeks, for a total of 60 Gy) or radiotherapy plus continuous daily temozolomide (75 mg per square meter of body-surface area per day, 7 days per week from the first to the last day of radiotherapy), followed by six cycles of adjuvant temozolomide (150 to 200 mg per square meter for 5 days during each 28-day cycle). The primary end point was overall survival. RESULTS A total of 573 patients from 85 centers underwent randomization. The median age was 56 years, and 84 percent of patients had undergone debulking surgery. At a median follow-up of 28 months, the median survival was 14.6 months with radiotherapy plus temozolomide and 12.1 months with radiotherapy alone. The unadjusted hazard ratio for death in the radiotherapy-plus-temozolomide group was 0.63 (95 percent confidence interval, 0.52 to 0.75; P<0.001 by the log-rank test). The two-year survival rate was 26.5 percent with radiotherapy plus temozolomide and 10.4 percent with radiotherapy alone. Concomitant treatment with radiotherapy plus temozolomide resulted in grade 3 or 4 hematologic toxic effects in 7 percent of patients. CONCLUSIONS The addition of temozolomide to radiotherapy for newly diagnosed glioblastoma resulted in a clinically meaningful and statistically significant survival benefit with minimal additional toxicity. AU - Stupp, Roger AU - Mason, Warren P. AU - van den Bent, Martin J AU - Weller, Michael AU - Fisher, Barbara AU - Taphoorn, Martin J.B. AU - Belanger, Karl AU - Brandes, Alba A. AU - Marosi, Christine AU - Bogdahn, Ulrich AU - Curschmann, Jürgen AU - Janzer, Robert C. AU - Ludwin, Samuel K. AU - Gorlia, Thierry AU - Allgeier, Anouk AU - Lacombe, Denis AU - Cairncross, J. Gregory AU - Eisenhauer, Elizabeth AU - Mirimanoff, René O. DA - 2005/3// DO - 10.1056/NEJMoa043330 IS - 10 PY - 2005 SP - 987 EP - 996 TI - Radiotherapy plus Concomitant and Adjuvant Temozolomide for Glioblastoma T2 - New England Journal of Medicine UR - http://www.ncbi.nlm.nih.gov/pubmed/15758009 UR - http://www.nejm.org/doi/abs/10.1056/NEJMoa043330 VL - 352 ER - TY - RPRT TI - (No Title) ER - TY - CHAP AB - Cerebral cavernous malformations (CCM) are vascular abnormalities of the central nervous system with an incidence of 0.4–0.5% and an annual rate of hemorrhage ranging from 0.7% to 1%. Most lesions are located in the cerebral hemisphere but some occur in deeper locations such as the basal ganglia and pons. The most common symptoms during presentation are headache, seizures, and focal neurologic deficits. Surgery remains the most effective treatment modality for symptomatic CCM, while the management of incidental CCM remains controversial. Factors associated with increased risk of hemorrhage include being female and less than 40 years old. This finding, however, is not consistent in all natural history studies evaluated. During follow-up, the most important and consistent risk factor for rebleed was a prior hemorrhage. Here, we provide an indepth but concise review of the literature regarding the natural history of CCMs. AU - Ene, Chibawanye AU - Kaul, Anand AU - Kim, Louis DA - 2017/1// DO - 10.1016/B978-0-444-63640-9.00021-7 KW - brainstem KW - cavernous malformations KW - familial cavernoma KW - hemorrhage KW - microsurgery KW - natural history KW - pediatric KW - radiation therapy KW - rebleed KW - seizure PB - Elsevier B.V. PY - 2017 SP - 227 EP - 232 TI - Natural history of cerebral cavernous malformations T2 - Handbook of Clinical Neurology UR - https://linkinghub.elsevier.com/retrieve/pii/B9780444636409000217 VL - 143 ER - TY - JOUR AB - Glioblastoma multiforme (GBM) universally recurs with dismal prognosis. We evaluated the efficacy of standard treatment strategies for patients with recurrent GBM (rGBM). From two centers in the Netherlands, 299 patients with rGBM after first-line treatment, diagnosed between 2005 and 2014, were retrospectively evaluated. Four different treatment strategies were defined: systemic treatment (SYST), re-irradiation (RT), re-resection followed by adjuvant treatment (SURG) and best supportive care (BSC). Median OS for all patients was 6.5 months, and median PFS (excluding patients receiving BSC) was 5.5 months. Older age, multifocal lesions and steroid use were significantly associated with a shorter survival. After correction for confounders, patients receiving SYST (34.8%) and SURG (18.7%) had a significantly longer survival than patients receiving BSC (39.5%), 7.3 and 11.0 versus 3.1 months, respectively [HR 0.46 (p < 0.001) and 0.36 (p < 0.001)]. Median survival for patients receiving RT (7.0%) was 9.2 months, but this was not significantly different from patients receiving BSC (p = 0.068). Patients receiving SURG compared to SYST had a longer PFS (9.0 vs. 4.3 months, respectively; p < 0.001), but no difference in OS was observed. After adjustments for confounders, patients with rGBM selected for treatment with SURG or SYST do survive significantly longer than patients who are selected for BSC based on clinical parameters. The value of reoperation versus systemic treatment strategies needs further investigation. AU - van Linde, Myra E. AU - Brahm, Cyrillo G. AU - de Witt Hamer, Philip C. AU - Reijneveld, Jaap C. AU - Bruynzeel, Anna M E AU - Vandertop, W. Peter AU - van de Ven, Peter M. AU - Wagemakers, Michiel AU - van der Weide, Hiske L. AU - Enting, Roelien H. AU - Walenkamp, Annemiek M E AU - Verheul, Henk M W DA - 2017/10// DO - 10.1007/s11060-017-2564-z IS - 1 KW - Recurrent glioblastoma multiforme KW - Survival outcome KW - Treatment effectiveness KW - Treatment strategies PB - Springer US PY - 2017 SN - 0123456789 SP - 183 EP - 192 TI - Treatment outcome of patients with recurrent glioblastoma multiforme: a retrospective multicenter analysis. T2 - Journal of neuro-oncology UR - http://www.ncbi.nlm.nih.gov/pubmed/28730289 UR - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC5658463 VL - 135 ER - TY - JOUR AB - PURPOSE OF REVIEW Recurrent glioblastoma (rGBM) has no standard treatment. Despite a better molecular knowledge, few therapies have brought changes in clinical practice so far. Here we will review the current data evaluating the re-radiation, re-resection, bevacizumab, and cytotoxic chemotherapy agents in this setting. We will also discuss the advances of immunotherapy and the possible benefit of this treatment for patients with rGBM. RECENT FINDINGS Next-generation sequencing is increasingly utilized in the clinical practice of neuro-oncologists, bringing gene mutations as targets for therapies. As in other solid tumors, immunotherapy has been also extensively studied in rGBM, with interesting results in phase I and II trials. The most promising therapies in the horizon are combinations including immune checkpoint inhibitors, virotherapy, vaccines, and monoclonal antibodies. Although re-radiation, re-resection, bevacizumab, and chemotherapy are still the most widely used therapies for treating rGBM, the clinical benefit from these treatments is still not well established. Preliminary results of studies with immune checkpoint inhibitors were disappointing, but virotherapy emerges as more promising immunotherapy in rGBM, especially in combination with other strategies. In addition to the gain in overall survival, the improvement in the quality of life of these patients is also expected. AU - Chaul-Barbosa, Caroline AU - Marques, Daniel Fernandes DO - 10.1007/s11912-019-0834-y IS - 10 KW - Immunotherapy in gliomas KW - Re-irradiation KW - Recurrent glioblastoma KW - Virotherapy PB - Current Oncology Reports PY - 2019 SP - 94 EP - 94 TI - How We Treat Recurrent Glioblastoma Today and Current Evidence. T2 - Current oncology reports UR - http://dx.doi.org/10.1007/s11912-019-0834-y UR - http://www.ncbi.nlm.nih.gov/pubmed/31606796 VL - 21 ER - TY - JOUR AB - Background: Glioblastoma (GBM) is a dismal disease managed in the first instance by surgical resection, temozolomide, and radiation. The role of repeat surgery at recurrence remains ill defined. This study aims to quantify the effect of repeat surgery in recurrent GBM on overall survival and determine if a trend in reported effect over time exists. Methods: Searches of 7 electronic databases from inception to January 2018 were conducted following PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines. There were 2692 articles identified for screening. Prognostic hazard ratios (HRs) derived from multivariate regression analysis were extracted and analyzed using meta-analysis of proportions and linear regression. Results: Eight observational studies reporting prognostic HRs in 10 cohorts were included. They described 1906 recurrent GBM diagnoses, managed by surgery at primary diagnosis, with 709 (37%) undergoing further repeat surgery at recurrence. Repeat surgery was shown to confer a statistically significant survival advantage compared with no surgery at recurrence in the pooled cohort (HR, 0.722; P < 0.001). Newer studies trended toward a more superior prognostic advantage of repeat surgery compared with earlier studies (effect coefficient, 0.856; P = 0.012). Conclusions: This meta-analysis of contemporary literature suggests that repeat surgery at GBM recurrence in select patients confers a significant, prognostic overall survival advantage independent of other prognostic factors. Furthermore, newer studies are significantly more likely to suggest greater benefit than are older studies. The main limitation is the selection bias inherent in the cohorts pooled for analysis. Larger prospective randomized controlled studies are needed to validate the findings of this study and provide stratification for such benefit justified by quality of life metrics. AU - Lu, Victor M. AU - Jue, Toni R. AU - McDonald, Kerrie L. AU - Rovin, Richard A. DO - 10.1016/j.wneu.2018.04.016 KW - Glioblastoma KW - Meta-analysis KW - Recurrence KW - Repeat surgery KW - Systematic review PB - Elsevier Inc PY - 2018 SP - 453 EP - 459.e3 TI - The Survival Effect of Repeat Surgery at Glioblastoma Recurrence and its Trend: A Systematic Review and Meta-Analysis T2 - World Neurosurgery UR - https://doi.org/10.1016/j.wneu.2018.04.016 VL - 115 ER - TY - JOUR AB - The role of reoperation for glioblastoma multiforme (GBM) recurrence is currently unknown. However, multiple studies have indicated that survival and quality of life are improved with a repeat operation at the time of disease recurrence. Prognosis is likely interdependent on several factors, including age, functional status, initial resection status, disease location, and surgical efficacy. However, there are significant data indicating no survival benefit for reoperation. This comprehensive literature review considering the controversial question of whether to operate for progressive or recurrent GBM seeks to evaluate the current available evidence and report on its conclusions. AU - Robin, Adam M. AU - Lee, Ian AU - Kalkanis, Steven N. DA - 2017/7// DO - 10.1016/j.nec.2017.02.007 IS - 3 KW - Extent of resection KW - Glioblastoma multiforme KW - Recurrence KW - Reoperation KW - Resection KW - Survival PB - Elsevier Inc PY - 2017 SP - 407 EP - 428 TI - Reoperation for Recurrent Glioblastoma Multiforme T2 - Neurosurgery Clinics of North America UR - http://dx.doi.org/10.1016/j.nec.2017.02.007 UR - https://linkinghub.elsevier.com/retrieve/pii/S1042368017300190 VL - 28 ER - TY - GEN AB - Question: In patients with previously diagnosed glioblastoma who are suspected of experiencing progression, does repeat cytoreductive surgery improve progression free survival or overall survival compared to alternative interventions? Target population: These recommendations apply to adults with previously diagnosed glioblastoma who are suspected of experiencing progression of the neoplastic process and are amenable to surgical resection. Recommendation: Level II: Repeat cytoreductive surgery is recommended in progressive glioblastoma patients to improve overall survival. AU - Patrick, Hayes H. AU - Sherman, Jonathan H. AU - Elder, J. Bradley AU - Olson, Jeffrey J. DA - 2022/6// DO - 10.1007/s11060-021-03881-w IS - 2 KW - Cytoreductive surgery KW - Glioblastoma KW - Recurrent PB - Springer PY - 2022 SP - 167 EP - 177 TI - Congress of neurological surgeons systematic review and evidence-based guidelines update on the role of cytoreductive surgery in the management of progressive glioblastoma in adults T2 - Journal of Neuro-Oncology VL - 158 ER - TY - JOUR AB - Purpose: Glioblastoma multiforme (GBM) is the most common malignant brain tumor. Moreover, GBM recurs in nearly all patients. Although a standard STUPP protocol has been widely used for newly diagnosed GBM, no standard regimen has been established for recurrent patients. Here we evaluated the clinical value of recurrent GBM reoperation by comparing overall survival and quality of life (QoL) in patients with recurrent GBM undergoing repeat surgery or conservative treatment. Methods: This was a prospective study of 165 patients with GBM receiving first operations for their disease between 2011 and 2013 at two tertiary neurosurgery centers in Poland. Thirty-five eligible patients were re-operated for recurrence (the study group), and 35 patients were selected as the control group using propensity score matching. A model was created to determine advantageous prognostic factors for longer survival of patients qualifying for reoperation using stepwise linear regression. Results: The mean overall survival of patients undergoing repeat surgery was 528 days compared to 297 days in patients who did not undergo repeat surgery. Reoperation did not result in a significant deterioration in performance status as measured by the Karnofsky Performance Scale. Older age, the presence of symptoms of increased intracranial pressure, and a shorter period between initial operation and reoperation were independent predictors of a worse outcome. Conclusion: In selected patients, reoperation for recurrent GBM prolongs survival with no significant deteriorations in performance status. AU - Furtak, Jacek AU - Kwiatkowski, Artur AU - Śledzińska, Paulina AU - Bebyn, Marek AU - Krajewski, Stanisław AU - Szylberg, Tadeusz AU - Birski, Marcin AU - Druszcz, Adam AU - Krystkiewicz, Kamil AU - Gasiński, Piotr AU - Harat, Marek DA - 2022/6// DO - 10.1016/j.suronc.2022.101771 IS - March 2022 KW - Glioblastoma KW - Predictors of survival KW - Reoperation KW - Survival time PY - 2022 SP - 101771 EP - 101771 TI - Survival after reoperation for recurrent glioblastoma multiforme: A prospective study T2 - Surgical Oncology UR - https://linkinghub.elsevier.com/retrieve/pii/S0960740422000640 VL - 42 ER - TY - JOUR AU - Robin, Adam M AU - Lee, Ian AU - Kalkanis, Steven N DO - https://doi.org/10.1016/j.nec.2017.02.007 IS - 3 KW - Extent of resection KW - Glioblastoma multiforme KW - Recurrence KW - Reoperation KW - Resection KW - Survival PY - 2017 SP - 407 EP - 428 TI - Reoperation for Recurrent Glioblastoma Multiforme T2 - Neurosurgery Clinics of North America UR - https://www.sciencedirect.com/science/article/pii/S1042368017300190 VL - 28 ER - TY - JOUR AB - The role of reoperation for glioblastoma multiforme (GBM) recurrence is currently unknown. However, multiple studies have indicated that survival and quality of life are improved with a repeat operation at the time of disease recurrence. Prognosis is likely interdependent on several factors, including age, functional status, initial resection status, disease location, and surgical efficacy. However, there are significant data indicating no survival benefit for reoperation. This comprehensive literature review considering the controversial question of whether to operate for progressive or recurrent GBM seeks to evaluate the current available evidence and report on its conclusions. AU - Robin, Adam M. AU - Lee, Ian AU - Kalkanis, Steven N. DA - 2017/7// DO - 10.1016/j.nec.2017.02.007 IS - 3 KW - Extent of resection KW - Glioblastoma multiforme KW - Recurrence KW - Reoperation KW - Resection KW - Survival PB - Elsevier Inc PY - 2017 SP - 407 EP - 428 TI - Reoperation for Recurrent Glioblastoma Multiforme T2 - Neurosurgery Clinics of North America UR - http://dx.doi.org/10.1016/j.nec.2017.02.007 UR - https://linkinghub.elsevier.com/retrieve/pii/S1042368017300190 VL - 28 ER - TY - JOUR AB - Surgical resection represents the standard of care in diffuse glioma, and more extensive tumour resection appears to be associated with favourable outcome. Up to now, terminology to describe extent of resection has been inconsistently applied across clinical trials which hampers comparative analysis of cohorts between different studies. Based on a comprehensive literature review, we developed evidence-based expert recommendations on categories for extent of resection. Recommendations are formulated for the categories ‘biopsy’, ‘partial resection’, ‘subtotal resection’, ‘near total resection’, ‘complete resection’ and ‘supramaximal resection’. Definitions rest on reduction of contrast- and non–contrast-enhancing tumour in glioblastoma, and on reduction of T2/FLAIR-hyperintense tumour in gliomas WHO grade 2 or 3. Both relative reduction of tumour volume (in percentage) as a measurement of surgical efficacy and absolute residual tumour volume (in cm3) as a measurement of remaining tumour burden are incorporated into the categories for extent of resection. Class of evidence for the proposed categories ranges from class IIB to IV. Limitations of the suggested categories are discussed. The proposed categories on extent of resection offer a framework to standardize nomenclature based on previous studies, and will need to be evaluated in prospective, molecularly well-defined cohorts. Our categories may eventually help as a stratification factor for future clinical trials. AU - Karschnia, Philipp AU - Vogelbaum, Michael A. AU - van den Bent, Martin AU - Cahill, Daniel P. AU - Bello, Lorenzo AU - Narita, Yoshitaka AU - Berger, Mitchel S. AU - Weller, Michael AU - Tonn, Joerg-Christian DA - 2021/5// DO - 10.1016/j.ejca.2021.03.002 KW - Diffuse glioma KW - Extent of resection KW - Glioblastoma KW - MRI KW - Nomenclature KW - Surgical resection PB - Elsevier Ltd PY - 2021 SP - 23 EP - 33 TI - Evidence-based recommendations on categories for extent of resection in diffuse glioma T2 - European Journal of Cancer UR - https://doi.org/10.1016/j.ejca.2021.03.002 UR - https://linkinghub.elsevier.com/retrieve/pii/S0959804921001490 VL - 149 ER - TY - JOUR AB - Glioblastoma is a disease with a poor prognosis. Multiple efforts have been made to improve the long-term outcome, but the 5-year survival rate is still 5–10%. Recurrence of the disease is the usual way of progression. In this situation, there is no standard treatment. Different treatment options can be considered. Among them would be reoperation or reirradiation. There are different studies that have assessed the impact on survival and the selection of patients who may benefit most from these strategies. Chemotherapy treatments have also been considered in several studies, mainly with alkylating agents, with data mostly from phase II studies. On the other hand, multiple studies have been carried out with target-directed treatments. Bevacizumab, a monoclonal antibody with anti-angiogenic activity, has demonstrated activity in several studies, and the FDA has approved it for this indication. Several other TKI drugs have been evaluated in this setting, but no clear benefit has been demonstrated. Immunotherapy treatments have been shown to be effective in other types of tumors, and several studies have evaluated their efficacy in this disease, both immune checkpoint inhibitors, oncolytic viruses, and vaccines. This paper reviews data from different studies that have evaluated the efficacy of different forms of relapsed glioblastoma. AU - Vaz-Salgado, Maria Angeles AU - Villamayor, María AU - Albarrán, Víctor AU - Alía, Víctor AU - Sotoca, Pilar AU - Chamorro, Jesús AU - Rosero, Diana AU - Barrill, Ana M. AU - Martín, Mercedes AU - Fernandez, Eva AU - Gutierrez, José Antonio AU - Rojas-Medina, Luis Mariano AU - Ley, Luis DA - 2023/8// DO - 10.3390/cancers15174279 IS - 17 KW - brain tumor KW - glioblastoma KW - glioblastoma chemotherapy KW - glioblastoma radiotherapy KW - glioblastoma surg KW - immunotherapy KW - recurrent glioblastoma PY - 2023 SP - 4279 EP - 4279 TI - Recurrent Glioblastoma: A Review of the Treatment Options T2 - Cancers UR - https://www.mdpi.com/2072-6694/15/17/4279 VL - 15 ER - TY - JOUR AB - OBJECTIVE: To determine the selection factors for and results of second resections performed to treat recurrent glioblastoma multiforme (GM), we studied 301 patients with GM who were treated from the time of diagnosis using two prospective clinical protocols. METHODS: The patients were prospectively followed from the time of diagnosis, using clinical and radiographic criteria after maximal surgical resection and external beam radiotherapy with or without adjuvant chemotherapy. Resection of recurrent GM was performed at the recommendation of the treating clinicians. The results of the second resections were retrospectively reviewed and analyzed using multivariate logistic regression, Kaplan-Meier-Turnbull survival analysis, Cox regression, and propensity score stratification. RESULTS: Forty-six patients underwent second resections during the study period. The actuarial rate of the second resections was 15% of the patients 1 year after diagnosis and 31% 2 years after diagnosis. Younger age (P = 0.01) and more extensive initial resection (P = 0.02), but not Karnofsky Performance Scale (KPS) score at the time of diagnosis or recurrence, predicted a higher chance of selection for reoperation after initial tumor recurrence. Twenty-eight percent of the patients had improved KPS scores after undergoing reoperation, 49% were stable, and 23% had declines in KPS scores of 10 to 30 points. There was no operative mortality. After reoperation, 85% of the patients received chemotherapy, 11% received brachytherapy or underwent stereotactic radiosurgery, and 17% underwent third resections. The median survival period after reoperation was 36 weeks. Higher preoperative KPS scores predicted longer survival periods after reoperation (P = 0.03). Age and interval since diagnosis were not significant prognostic factors. The median high-quality survival period (KPS score, > or =70) was 18 weeks. The median survival period after first tumor progression was 23 weeks for 130 patients treated using the same protocols who did not undergo reoperations. Patients who did undergo reoperations experienced clinically and statistically significantly longer survival periods. However, this was determined to be partially because of selection bias. CONCLUSION: Survival after resection of recurrent GM remains poor despite advances in imaging, operative technique, and adjuvant therapies. High-quality survival after resection of recurrence to treat GM seems to have increased significantly since an earlier report from our institution. AU - Barker, Fred G. AU - Chang, Susan M AU - Gutin, Philip H AU - Malec, Mary K AU - McDermott, Michael W AU - Prados, Michael D AU - Wilson, Charles B DA - 1998/4// DO - 10.1097/00006123-199804000-00013 IS - 4 KW - Adolescent KW - Adult KW - Aged KW - Brain Neoplasms KW - Cohort Studies KW - Combined Modality Therapy KW - Female KW - Glioblastoma KW - Humans KW - Local KW - Male KW - Middle Aged KW - Neoplasm Recurrence KW - Postoperative Period KW - Prognosis KW - Prospective Studies KW - Reoperation KW - Statistics as Topic KW - Survival Analysis KW - physiopathology KW - radiotherapy KW - surgery PY - 1998 SP - 709 EP - 719 TI - Survival and Functional Status after Resection of Recurrent Glioblastoma Multiforme T2 - Neurosurgery UR - http://journals.lww.com/00006123-199804000-00013 VL - 42 ER - TY - JOUR AB - BACKGROUND: While standards for the treatment of newly diagnosed glioblastomas exist, therapeutic regimens for tumor recurrence remain mostly individualized. The role of a surgical resection of recurrent glioblastomas remains largely unclear at present. This study aimed to assess the effect of repeated resection of recurrent glioblastomas on patient survival. METHODS: In a multicenter retrospective-design study, patients with primary glioblastomas undergoing repeat resections for recurrent tumors were evaluated for factors affecting survival. Age, Karnofsky performance status (KPS), extent of resection (EOR), tumor location, and complications were assessed. RESULTS: Five hundred and three patients (initially diagnosed between 2006 and 2010) undergoing resections for recurrent glioblastoma at 20 institutions were included in the study. The patients' median overall survival after initial diagnosis was 25.0 months and 11.9 months after first re-resection. The following parameters were found to influence survival significantly after first re-resection: preoperative and postoperative KPS, EOR of first re-resection, and chemotherapy after first re-resection. The rate of permanent new deficits after first re-resection was 8%. CONCLUSION: The present study supports the view that surgical resections of recurrent glioblastomas may help to prolong patient survival at an acceptable complication rate. AU - Ringel, Florian AU - Pape, Haiko AU - Sabel, Michael AU - Krex, Dietmar AU - Bock, Hans Christoph AU - Misch, Martin AU - Weyerbrock, Astrid AU - Westermaier, Thomas AU - Senft, Christian AU - Schucht, Philippe AU - Meyer, Bernhard AU - Simon, Matthias DA - 2016/1// DO - 10.1093/neuonc/nov145 IS - 1 KW - 80 and over KW - Adolescent KW - Adult KW - Aged KW - Brain Neoplasms KW - Female KW - Glioblastoma KW - Humans KW - Kaplan-Meier Estimate KW - Karnofsky Performance Status KW - Male KW - Middle Aged KW - Neurosurgical Procedures KW - Prognosis KW - Reoperation KW - Retrospective Studies KW - Treatment Outcome KW - Young Adult KW - methods KW - surgery PY - 2016 SP - 96 EP - 104 TI - Clinical benefit from resection of recurrent glioblastomas: results of a multicenter study including 503 patients with recurrent glioblastomas undergoing surgical resection T2 - Neuro-Oncology UR - https://academic.oup.com/neuro-oncology/article-lookup/doi/10.1093/neuonc/nov145 VL - 18 ER - TY - JOUR AB - Glioblastoma multiforme (GBM) universally recurs with dismal prognosis. We evaluated the efficacy of standard treatment strategies for patients with recurrent GBM (rGBM). From two centers in the Netherlands, 299 patients with rGBM after first-line treatment, diagnosed between 2005 and 2014, were retrospectively evaluated. Four different treatment strategies were defined: systemic treatment (SYST), re-irradiation (RT), re-resection followed by adjuvant treatment (SURG) and best supportive care (BSC). Median OS for all patients was 6.5 months, and median PFS (excluding patients receiving BSC) was 5.5 months. Older age, multifocal lesions and steroid use were significantly associated with a shorter survival. After correction for confounders, patients receiving SYST (34.8%) and SURG (18.7%) had a significantly longer survival than patients receiving BSC (39.5%), 7.3 and 11.0 versus 3.1 months, respectively [HR 0.46 (p < 0.001) and 0.36 (p < 0.001)]. Median survival for patients receiving RT (7.0%) was 9.2 months, but this was not significantly different from patients receiving BSC (p = 0.068). Patients receiving SURG compared to SYST had a longer PFS (9.0 vs. 4.3 months, respectively; p < 0.001), but no difference in OS was observed. After adjustments for confounders, patients with rGBM selected for treatment with SURG or SYST do survive significantly longer than patients who are selected for BSC based on clinical parameters. The value of reoperation versus systemic treatment strategies needs further investigation. AU - van Linde, Myra E AU - Brahm, Cyrillo G AU - de Witt Hamer, Philip C AU - Reijneveld, Jaap C AU - Bruynzeel, Anna M E AU - Vandertop, W Peter AU - van de Ven, Peter M AU - Wagemakers, Michiel AU - van der Weide, Hiske L AU - Enting, Roelien H AU - Walenkamp, Annemiek M E AU - Verheul, Henk M W DA - 2017/10// DO - 10.1007/s11060-017-2564-z IS - 1 KW - 80 and over KW - Adult KW - Aged KW - Brain Neoplasms KW - Female KW - Follow-Up Studies KW - Glioblastoma KW - Humans KW - Local KW - Male KW - Middle Aged KW - Neoplasm Recurrence KW - Netherlands KW - Retrospective Studies KW - Survival Analysis KW - Treatment Outcome KW - Young Adult KW - therapy PY - 2017 SP - 183 EP - 192 TI - Treatment outcome of patients with recurrent glioblastoma multiforme: a retrospective multicenter analysis T2 - Journal of Neuro-Oncology UR - http://link.springer.com/10.1007/s11060-017-2564-z VL - 135 ER - TY - JOUR AB - Glioblastoma inevitably recurs, but no standard regimen has been established for treating this recurrent disease. Several reports claim that reoperative surgery can improve survival, but the effects of reoperation timing on survival have rarely been investigated. We, therefore, evaluated the relationship between reoperation timing and survival in recurrent GBM. A consecutive cohort of unselected patients (real-world data) from three neuro-oncology cancer centers was analyzed (a total of 109 patients). All patients underwent initial maximal safe resection followed by treatment according to the Stupp protocol. Those meeting the following criteria during progression were indicated for reoperation and were further analyzed in this study: (1) The tumor volume increased by >20–30% or a tumor was rediscovered after radiological disappearance; (2) The patient’s clinical status was satisfactory (KS ≥ 70% and PS WHO ≤ gr. 2); (3) The tumor was localized without multifocality; (4) The minimum expected tumor volume reduction was above 80%. A univariate Cox regression analysis of postsurgical survival (PSS) revealed a statistically significant effect of reoperation on PSS from a threshold of 16 months after the first surgery. Cox regression models that stratified the Karnofsky score with age adjustment confirmed a statistically significant improvement in PSS for time-to-progression (TTP) thresholds of 22 and 24 months. The patient groups exhibiting the first recurrence at 22 and 24 months had better survival rates than those exhibiting earlier recurrences. For the 22-month group, the HR was 0.5 with a 95% CI of (0.27, 0.96) and a p-value of 0.036. For the 24-month group, the HR was 0.5 with a 95% CI of (0.25, 0.96) and a p-value of 0.039. Patients with the longest survival were also the best candidates for repeated surgery. Later recurrence of glioblastoma was associated with higher survival rates after reoperation. AU - Kalita, Ondrej AU - Kazda, Tomas AU - Reguli, Stefan AU - Jancalek, Radim AU - Fadrus, Pavel AU - Slachta, Marek AU - Pospisil, Petr AU - Krska, Lukas AU - Vrbkova, Jana AU - Hrabalek, Lumir AU - Smrcka, Martin AU - Lipina, Radim DA - 2023/4// DO - 10.3390/cancers15092530 IS - 9 KW - glioblastoma KW - reoperation timing KW - treatment strategy PY - 2023 SP - 2530 EP - 2530 TI - Effects of Reoperation Timing on Survival among Recurrent Glioblastoma Patients: A Retrospective Multicentric Descriptive Study T2 - Cancers UR - https://www.mdpi.com/2072-6694/15/9/2530 VL - 15 ER -