scholarly journals Retrospective and Randomized Analysis of Influence and Correlation of Clinical and Molecular Prognostic Factors in a Mono-Operative Series of 122 Patients with Glioblastoma Treated with STR or GTR

2020 ◽  
Vol 10 (2) ◽  
pp. 91
Author(s):  
Maurizio Salvati ◽  
Placido Bruzzaniti ◽  
Michela Relucenti ◽  
Mariagrazia Nizzola ◽  
Pietro Familiari ◽  
...  

Glioblastoma is a solid, infiltrating, and the most frequent highly malignant primary brain tumor. Our aim was to find the correlation between sex, age, preoperative Karnofsky performance status (KPS), presenting with seizures, and extent of resection (EOR) with overall survival (OS), progression-free survival (PFS), and postoperative KPS, along with the prognostic value of IDH1, MGMT, ATRX, EGFR, and TP53 genes mutations and of Ki67 through the analysis of a single-operator series in order to avoid the biases of a multi-operator series, such as the lack of homogeneity in surgical and adjuvant nonsurgical treatments. A randomized retrospective analysis of 122 patients treated by a single first operator at Sapienza University of Rome was carried out. After surgery, patients followed standard Stupp protocol treatment. Exclusion criteria were: (1) patients with primary brainstem and spinal cord gliomas and (2) patients who underwent partial resections (resection < 90%) or a biopsy exclusively for diagnostic purposes. Statistical analysis with a simultaneous regression model was carried out through the use of SPSS 25® (IBM). Results showed statistically significant survival increase in four groups: (1) patients treated with gross total resection (GTR) (p < 0.030); (2) patients with mutation of IDH1 (p < 0.0161); (3) patients with methylated MGMT promoter (p < 0.005); (4) patients without EGFR amplification or EGFRvIII mutation (p < 0.035). Higher but not statistically significant survival rates were also observed in: patients <75 years, patients presenting with seizures at diagnosis, patients affected by lesions in noneloquent areas, as well as in patients with ATRX gene mutation and Ki-67 < 10%.

Author(s):  
Maurizio Salvati ◽  
Placido Bruzzaniti ◽  
Michela Rilucenti ◽  
Mariagrazia Nizzola ◽  
Pietro Familiari ◽  
...  

Glioblastoma is a solid, infiltrating and the most frequent highly malignant primary brain tumor. Our aim was to find the prognostic value of mutations of IDH1, MGMT, EGFR, p53, ATRX, Ki67 genes and the correlation between sex, age, presenting with seizures, number of interventions, extent of resection with Overall Survival (OS), Progression Free Survival (PFS) and Karnofsky performance status (KPS) score. A randomized retrospective analysis of 122 patients treated by a single operator at Sapienza University of Rome, was carried out. After surgery patients followed standard treatment Stupp protocol [6]. Exclusion criteria were: patients with primitive brainstem and spinal cord gliomas and patients who underwent partial resections (resection &lt; 90%) and cases of brain biopsy exclusively for diagnostic purposes. Statistical analysis with a simultaneous regression model was carried on by SPSS 25 &reg; (IBM) program. Results showed statistically significant survival increase in four groups: 1) patients treated with gross total resection (p&lt; 0.03); 2) patients with methylated MGMT promoter (p&lt;0.005); 3) patients with non EGFR amplification or EGFRvIII mutation (p&lt;0.035); 4) mutated IDH1/IDH2 (p&lt;0.0161). Higher survival rates (but not statistically significant) were observed also in patients with: age &lt; 75 years, Ki 67 &lt;10%, lesions in non eloquent areas, ATRX gene mutation and presentation with seizures.


2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Helena C. W. Wahner ◽  
Malte Träger ◽  
Katja Bender ◽  
Leonille Schweizer ◽  
Julia Onken ◽  
...  

Abstract Background Current guidelines for the treatment of anaplastic astrocytoma (AA) recommend maximal safe resection followed by radiotherapy and chemotherapy. Despite this multimodal treatment approach, patients have a limited life expectancy. In the present study, we identified variables associated with overall survival (OS) and constructed a model score to predict the OS of patients with AA at the time of their primary diagnosis. Methods We retrospectively evaluated 108 patients with newly diagnosed AA. The patient and tumor characteristics were analyzed for their impact on OS. Variables significantly associated with OS on multivariable analysis were included in our score. The final algorithm was based on the 36-month survival rates corresponding to each characteristic. Results On univariate analysis, age, Karnofsky performance status, isocitrate dehydrogenase status, and extent of resection were significantly associated with OS. On multivariable analysis all four variables remained significant and were consequently incorporated in the score. The total score ranges from 20 to 33 points. We designated three prognostic groups: A (20–25), B (26–29), and C (30–33 points) with 36-month OS rates of 23%, 71%, and 100%, respectively. The OS rate at 5 years was 8% in group A, 61% in group B and 88% in group C. Conclusions Our model score predicts the OS of patients newly diagnosed with AA and distinguishes patients with a poor survival prognosis from those with a greater life expectancy. Independent and prospective validation is needed. The upcoming changes of the WHO classification of brain tumors as well as the practice changing results from the CATNON trial will most likely require adaption of the score.


2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 178-178 ◽  
Author(s):  
David Goldstein ◽  
Robert Hassan El Maraghi ◽  
Pascal Hammel ◽  
Volker Heinemann ◽  
Volker Kunzmann ◽  
...  

178^ Background: In the phase III MPACT trial, nab-paclitaxel (nab-P) + gemcitabine (G) was tolerable and demonstrated superiority to G alone for all efficacy endpoints in pts with metastatic pancreatic cancer (MPC). nab-P + G vs G alone met the study’s primary endpoint by demonstrating a significant improvement in overall survival (OS; median 8.5 vs 6.7 months; HR 0.72; 95% CI, 0.617 - 0.835; P < 0.001) and the secondary endpoints of progression-free survival (PFS; median 5.5 vs 3.7 months; HR 0.69; 95% CI, 0.581 - 0.821; P < 0.001) and overall response rate (ORR; 23% vs 7%; P < 0.001). The 1-year survival rates for nab-P + G vs G alone were 35% vs 22%. The OS data reported above were based on a database cutoff of September 17, 2012, at which time 80% of pts had died. Here, we report an updated OS analysis (post hoc) from MPACT. Methods: 861 pts with MPC and a Karnofsky performance status (KPS) ≥ 70 were randomized at 151 community and academic centers 1:1 to receive nab-P 125 mg/m2 + G 1000 mg/m2 on days 1, 8, and 15 of a 28-day cycle or G alone 1000 mg/m2weekly for 7 weeks followed by 1 week of rest (cycle 1) and then days 1, 8, and 15 of a 28-day cycle (cycle ≥ 2). The data for this survival analysis were collected through April 1, 2013. Results: As of the updated data cutoff, 380/431 (88%) pts in the nab-P + G arm and 394/430 (92%) pts in the G alone arm had died. OS was superior for nab-P + G vs G alone in the intent-to-treat population, and the longer follow-up allowed an estimate of the 3-year survival rates (Table). The treatment effect was consistent across all pt subgroups examined. Conclusions: This updated survival analysis revealed a sustained difference in OS over time between the 2 arms. MPACT is the first phase III study in MPC to report 3-year survival rates. These data confirm and extend the previous report of the primary endpoint and support the superior efficacy of nab-P + G over G alone. These results may encourage efforts to build upon this well tolerated backbone to further extend survival. Clinical trial information: NCT00844649. [Table: see text]


2020 ◽  
Vol 9 (10) ◽  
pp. 3231
Author(s):  
Teresa Augustin ◽  
Dmytro Oliinyk ◽  
Viktoria Florentine Koehler ◽  
Josefine Rauch ◽  
Claus Belka ◽  
...  

Background: The present study aims to evaluate the outcomes and toxicity of elderly anaplastic thyroid cancer (ATC) patients receiving (chemo)radiotherapy, as well as to identify prognostic factors. Patients and methods: A systematic review using the MEDLINE/PubMed and Cochrane databases was performed. Individual data from all eligible studies were extracted, and a pooled analysis (n = 186) was conducted to examine patient characteristics and treatment. All consecutive ATC patients (≥65 years) treated between 2009 and 2019 at our institution were evaluated for outcomes concerning progression-free survival (PFS), overall survival (OS) probabilities and treatment-related toxicity. Results: The systematic review and pooled analysis identified age as a prognostic factor. The median OS of our patient cohort (n = 26) was three months (range = 0–125). The 6-, 12- and 24-month survival rates were 35%, 22% and 11%, respectively. In the univariate analysis, a Karnofsky performance status of >70%, the Union for International Cancer Control Tumor–Node–Metastasis classification, multimodal therapy and an EQD2 of >49 Gy were correlated with longer OS and PFS. The acute grade 3 toxicity of dysphagia, dyspnea, dermatitis, mucositis and dysphonia was found in 23%, 15%, 12%, 12% and 8% of patients. Conclusion: Age appears to be a prognostic factor in ATC. Elderly ATC patients can tolerate multimodal treatment and achieve a promising outcome. Prospective studies need to confirm our findings.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2054-2054
Author(s):  
Kristoph Jahnke ◽  
Uwe Pleyer ◽  
Martina Herwig ◽  
Rainer Guthoff ◽  
Matthias Lueke ◽  
...  

2054 Background: Primary intraocular lymphoma (PIOL) is a very rare disorder, and the optimal treatment is yet to be defined. Here, we report clinical characteristics and outcome of patients with PIOL enrolled in the prospective German PIOL registry (PIOL-R). Methods: Patient data in this prospective, non-interventional multicenter study were compiled by standardized questionnaires sent to Ophthalmology and Hematology/Oncology centers in Germany. All histologically or cytologically confirmed immunocompetent PIOL patients were eligible. Results: Fifteen patients (8 female, median age 66 years, median Karnofsky performance status 90%) from 4 centers were included between August 2008 and January 2012. Median follow-up was 7 months. Median time from first occurrence of symptoms to PIOL diagnosis was 5 (range, 1-11) months. All PIOL were of diffuse large B-cell histology. Eight patients had concomitant (n=3), prior (n=2) and/or subsequent (n=4) parenchymal brain involvement. First-line treatment included methotrexate (MTX)-, rituximab- and/or ifosfamide-based systemic chemotherapy in 12 (including high-dose chemotherapy [HDCT] with autologous stem cell transplantation [ASCT] in 2), intraocular (i.o.) chemotherapy with MTX (n=2) and/or rituximab (n=6) in 7, and ocular radiation in one patient(s). Two patients received prophylactic intrathecal (i.th.) treatment with MTX and none had whole-brain irradiation. The PIOL remission rate was 100% (complete remission in 11/14 evaluable patients and partial remission in 3 patients). Four patients relapsed in the brain after 5, 6, 21 and 23 months and received salvage treatment with MTX and/or ifosfamide (n=3) and HDCT with ASCT (n=1). No ocular or systemic relapses were observed. Median progression-free survival was 23 (95% confidence interval, 19-26) months. All patients are alive. Conclusions: Although the awareness of PIOL and diagnostic possibilities have improved over the past 2 decades, time from symptom presentation to diagnosis seems to remain at previously reported levels. There appears to be a shift from local ocular treatments and radiation to systemic therapy as compared to anecdotal data with promising response and survival rates.


2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi118-vi118
Author(s):  
Diana Shi ◽  
Mary Jane Lim-Fat ◽  
Amin Nassar ◽  
Jared Woods ◽  
Gilbert Youssef ◽  
...  

Abstract BACKGROUND We evaluated sex-based differences in clinical outcomes and tumor genomics in patients with newly-diagnosed GBM. METHODS We reviewed 665 IDH-wild type GBM patients with Karnofsky Performance Status (KPS) ≥60 treated at our institution from 2010-2019 including; 585 patients with targeted exome sequencing of 447 cancer associated genes (OncoPanel). Deleterious mutations were defined as homozygous deletions or loss of function mutations of known tumor suppressors (as reported in TCGA, ≥ 3 times in the COSMIC database, or predicted as “damaging” in SIFT and/or “probably damaging” in Polyphen 2) or known oncogenic mutations in proto-oncogenes (reported in TCGA or ≥ 3 times in COSMIC). RESULTS There were 384 (57.7%) males and 281 (42.3%) females. Median OS was 22.5 months for females and 19.3 months for males (hazard ratio [HR] 0.81, 95% CI 1.03-1.48, p = 0.02). On multivariable analysis adjusted for age, KPS ≥90, extent of resection, and MGMT methylation status, female sex (adjusted hazard ratio 0.78, 95% CI [0.64-0.95], p = 0.015) was associated with improved OS. Superior OS in females was observed in MGMT-unmethylated patients (HR 0.69, 95% CI [0.54-0.90], p = 0.005) but not MGMT-methylated patients. Thirteen genes were deleteriously altered in ≥5% of our cohort: CDK4 (12.1% male vs. 7.8% female), CDKN2A (46.5% vs. 45.7%), CDKN2B (41.8% vs. 43.3%), EGFR (34.7% vs. 40.0%, MTAP (18.2% vs. 18.8%), NF1 (11.5% vs. 9.4%), PTEN (28.2% vs. 29.8%), TP53 (28.2% vs. 30.2%), RB1 (5.6% vs. 6.5%), MDM4 (6.2% vs. 5.7%), ATM (5.9% vs. 3.7%), MDM2 (7.4% vs. 4.1%), PIK3R1 (6.2% vs. 4.1%). There were no differences in frequency of mutations in these individual genes between males and females (χ 2 [1, N=585] = 0.05-2.86, p = 0.09-0.86). CONCLUSIONS Female sex is associated with improved survival. We did not identify sex-based differences in deleterious genomic alterations amongst commonly altered genes in GBM.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2024-2024
Author(s):  
Scott Randall Plotkin ◽  
Priya Kumthekar ◽  
Patrick Y. Wen ◽  
Frederick G. Barker ◽  
Anat Stemmer-Rachamimov ◽  
...  

2024 Background: Grade II/III meningiomas represent about 20% of tumors and have increased rates of recurrence with no approved medical therapies. Historically, the progression-free survival at 6 months (PFS-6) for these tumors is 25%. The Response Assessment in Neuro-Oncology (RANO) group identified a PFS-6 rate of > 35% to be of interest for trials of grade II/III meningioma. Methods : NF2 gene inactivation occurs in the majority of meningiomas and is associated with mTORC1 activation. Human studies of everolimus for neurofibromatosis 2 patients documented growth arrest in only a minority of tumors. Based on our studies showing mTORC2/SGK1 pathway activation in NF2-deficient meningiomas and the known paradoxical activation of the mTORC2/AKT pathway in meningiomas, we hypothesized that dual inhibition of mTORC1/2 would be superior in meningiomas. Treatment of primary meningioma cells with vistusertib led to decreased cell proliferation and showed greater efficacy than rapamycin, regardless of NF2 expression. We studied the effect of vistusertib in patients with progressive or recurrent grade II/III meningiomas (NCT03071874). Vistusertib was administered orally at 125mg twice daily on two consecutive days each week. MRIs were obtained every 2 cycles (1 cycle = 28 days). Tumor size was defined as the largest cross-sectional area. Progression was defined as ≥25% increase in the sum of products of all measurable lesions over smallest sum observed. The primary endpoint was PFS-6. Secondary endpoints included toxicity, radiographic response, and correlative studies including immunohistochemistry for mTORC1/2 pathway activation and genetic biomarkers. Results: Twenty-eight patients (13 female), with a median age of 58 years (range, 32 to 77 years), were enrolled in this multicenter study. The median Karnofsky performance status was 80. Twenty-five patients have been followed to six months or to tumor progression. The median duration of treatment was 6.5 month (range, 1-18 months). Four patients chose to discontinue treatment, 1 withdrew to intercurrent illness, and 1 was withdrawn due to non-compliance. PFS-6 is 51.5% (CI, 29.3% - 70.0%). Adverse events at least possibly related to vistusertib with frequency > 10% include nausea (54%); fatigue (36%); hypophosphatemia (29%); diarrhea, anorexia, dry mouth, and hypertriglyceridemia (all 14%); hypertension, vomiting, increased ALT, constipation, and weight loss (all 11%). Conclusions: Vistusertib treatment was associated with a PFS-6 rate that exceeds the RANO target of 35% for recurrent high-grade meningioma. The follow-up data continue to mature. Adverse events were tolerable in this patient population. Correlative studies to identify biological factors that correlate with response are under way. These data support the initiation of larger randomized studies of vistusertib in this setting. Clinical trial information: NCT03071874.


2019 ◽  
Vol 80 (04) ◽  
pp. 262-268 ◽  
Author(s):  
Yahya Ahmadipour ◽  
Monika Kaur ◽  
Daniela Pierscianek ◽  
Oliver Gembruch ◽  
Marvin Darkwah Oppong ◽  
...  

Objective Extent of resection (EOR) and Karnofsky Performance Status (KPS) are at odds in glioblastoma (GBM) surgery, that is, the anticipated postoperative disability limits the EOR. This study analyzes the correlation of different surgical modalities with the resulting physical status and survival of patients with GBM. Methods A total of 565 patients with primary GBM were operated on in a single institution between 2006 and 2014. Possible surgical modalities comprised supratotal resection (SLR), gross total resection (GTR; ≥ 95% by volume), tumor debulking (TDB; ≤ 95% by volume), and stereotactic biopsy (SB). Pre- and postoperative KPS before and up to 4 weeks after surgery as well as overall survival (OS) rate were determined retrospectively. Hazard ratio (HR) and 95% confidence intervals were calculated using a Cox proportional hazards model. Results Median postoperative KPS was ≥ 70, irrespective of surgical modality. Mean OS was 12.5 months. Multivariate analysis revealed age ≥ 70 years (HR: 1.93), preoperative KPS < 70 (HR: 2.15), and unmethylation in MGMT promoter (HR: 1.27) as independent factors for worse OS. Regarding surgical modality, SB was associated with the worst survival (HR: 2.3) followed by TDB (HR: 1.36). SLR was inferior to GTR (HR: 1.27). Conclusion Higher EOR in patients with GBM does not seem inevitably correlated with increasing functional impairment, but better survival, provided there is a balanced preoperative indication. Nevertheless, SLR does not seem to be superior to GTR. Whenever possible, maximal safe resection should be considered in patients with GBM, even if an EOR ≥ 95% is not possible.


Neurology ◽  
2020 ◽  
Vol 94 (10) ◽  
pp. e1027-e1039 ◽  
Author(s):  
Caroline Houillier ◽  
Carole Soussain ◽  
Hervé Ghesquières ◽  
Pierre Soubeyran ◽  
Olivier Chinot ◽  
...  

ObjectiveReal-life studies on patients with primary CNS lymphoma (PCNSL) are scarce. Our objective was to analyze, in a nationwide population-based study, the current medical practice in the management of PCNSL.MethodsThe French oculo-cerebral lymphoma network (LOC) database prospectively records all newly diagnosed PCNSL cases from 32 French centers. Data of patients diagnosed between 2011 and 2016 were retrospectively analyzed.ResultsWe identified 1,002 immunocompetent patients (43% aged >70 years, median Karnofsky Performance Status [KPS] 60). First-line treatment was high-dose methotrexate-based chemotherapy in 92% of cases, with an increasing use of rituximab over time (66%). Patients <60 years of age received consolidation treatment in 77% of cases, consisting of whole-brain radiotherapy (WBRT) (54%) or high-dose chemotherapy with autologous stem cell transplantation (HCT-ASCT) (23%). Among patients >60 years of age, WBRT and HCT-ASCT consolidation were administered in only 9% and 2%, respectively. The complete response rate to initial chemotherapy was 50%. Median progression-free survival was 10.5 months. For relapse, second-line chemotherapy, HCT-ASCT, WBRT, and palliative care were offered to 55%, 17%, 10%, and 18% of patients, respectively. The median, 2-year, and 5-year overall survival was 25.3 months, 51%, and 38%, respectively (<60 years: not reached [NR], 70%, and 61%; >60 years: 15.4 months, 44%, and 28%). Age, KPS, sex, and response to induction CT were independent prognostic factors in multivariate analysis.ConclusionsOur study confirms the increasing proportion of elderly within the PCNSL population and shows comparable outcome in this population-based study with those reported by clinical trials, reflecting a notable application of recent PCNSL advances in treatment.


2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Makoto Ohno ◽  
Yasuji Miyakita ◽  
Masamichi Takahashi ◽  
Hiroshi Igaki ◽  
Yuko Matsushita ◽  
...  

Abstract Background and purpose The purpose of this study was to evaluate the outcomes of elderly patients (aged ≥75 years) with newly diagnosed glioblastoma (GBM), who were treated with hypofractionated radiotherapy comprising 45 Gy in 15 fractions combined with temozolomide (TMZ) or TMZ and bevacizumab (TMZ/Bev). Materials and methods Between October 2007 and August 2018, 30 patients with GBM aged ≥75 years were treated with hypofractionated radiotherapy consisting of 45 Gy in 15 fractions. Twenty patients received TMZ and 10 received TMZ/Bev as upfront chemotherapy. O-6-methylguanine DNA methyltransferase (MGMT) promoter methylation status was analyzed by pyrosequencing. The cutoff value of the mean level of methylation at the 16 CpG sites was 16%. Results Median overall survival (OS) and progression-free survival (PFS) were 12.9 months and 9.9 months, respectively. The 1-year OS and PFS rates were 64.7 and 34.7%, respectively. Median OS and PFS did not differ significantly between patients with MGMT promoter hypermethylation (N = 11) and those with hypomethylation (N = 16) (17.4 vs. 11.8 months, p = 0.32; and 13.1 vs. 7.3 months, p = 0.11, respectively). The median OS and PFS were not significantly different between TMZ (N = 20) and TMZ/Bev (N = 10) chemotherapy (median OS: TMZ 12.9 months vs. TMZ/Bev 14.6 months, p = 0.93, median PFS: TMZ 8.5 months vs TMZ/Bev 10.0 months, p = 0.64, respectively). The median time until Karnofsky performance status (KPS) score decreasing below 60 points was 7.9 months. The best radiological responses included 11 patients with a partial response (36.7%). Grade 3/4 toxicities included leukopenia in 15 patients (50%), anorexia in 4 (13.3%), and hyponatremia during concomitant chemotherapy in 3 (10%). Conclusion Our hypofractionated radiotherapy regimen combined with TMZ or TMZ/Bev showed benefits in terms of OS, PFS, and KPS maintenance with acceptable toxicities in elderly patients with GBM aged ≥75 years.


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