scholarly journals Assessment of Prognostic Value of Cystic Features in Glioblastoma Relative to Sex and Treatment with Standard-of-Care

2019 ◽  
Author(s):  
Lee Curtin ◽  
Paula Whitmire ◽  
Cassandra R. Rickertsen ◽  
Gina L. Mazza ◽  
Peter Canoll ◽  
...  
Keyword(s):  
Survival Benefit ◽  
Standard Of Care ◽  
Primary Brain Tumor ◽  
Prognostic Impact ◽  
Current Standard ◽  
Significant Survival Benefit ◽  
Significant Survival ◽  
Cystic Component ◽  
Potential Link ◽  
Magnetic Resonance Imaging Mri

AbstractGlioblastoma (GBM) is the most aggressive primary brain tumor and can have cystic components, identifiable through magnetic resonance imaging (MRI). Previous studies suggest that cysts occur in 7-23% of GBMs and report mixed results regarding their prognostic impact. Using our retrospective cohort of 493 patients with first-diagnosis GBM, we carried out an exploratory analysis on this potential link between cystic GBM and survival. Using pretreatment MRIs, we manually identified 88 patients with GBM that had a significant cystic component at presentation and 405 patients that did not. Patients with cystic GBM had significantly longer overall survival and were significantly younger at presentation. Within patients who received the current standard of care (SOC) (N=184, 40 cystic), we did not observe a survival benefit of cystic GBM. Unexpectedly, we did not observe a significant survival benefit between this SOC cystic cohort and patients with cystic GBM diagnosed before the standard was established (N=40 with SOC, N=19 without SOC); this significant SOC benefit was clearly observed in patients with noncystic GBM (N=144 with SOC, N=111 without SOC). When stratified by sex, this significant survival benefit was only preserved in male patients (N=303, 47 cystic). We report differences in the absolute and relative sizes of imaging abnormalities on MRI and the prognostic implication of cysts based on sex. We discuss hypotheses for these differences, including the possibility that the presence of a cyst could indicate a less aggressive tumor.

scholarly journals RARE-09. CYSTIC GLIOBLASTOMA PRESENTATION AS A BENEFICIAL PROGNOSTIC INDICATOR FOR OVERALL SURVIVAL

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi223-vi223
Author(s):  
Lee Curtin ◽  
Paula Whitmire ◽  
Cassandra Rickertsen ◽  
Peter D Canoll ◽  
Maciej Mrugala ◽  
...  
Keyword(s):  
Overall Survival ◽  
Survival Benefit ◽  
Standard Of Care ◽  
Prognostic Impact ◽  
Current Standard ◽  
Significant Survival Benefit ◽  
Care Treatment ◽  
Significant Survival ◽  
Cystic Component ◽  
Standard Of Care Treatment

Abstract Glioblastoma (GBM) is the most aggressive primary brain tumor with a median overall survival of 15 months with standard-of-care treatment. GBM patients sometimes present with a cystic component, which can be identified through magnetic resonance imaging (MRI). Previous studies suggest that cysts occur in 7–22% of GBM patients and have reported mixed results regarding whether cystic GBM have a survival benefit compared to noncystic GBM. Using our large retrospective cohort of 493 first-diagnosis GBM patients, we aim to elucidate this link between cystic GBM and survival. Within this cohort, 88 patients had a significant cystic component at presentation as identified on MRI. Compared to noncystic GBM (n=405), cystic GBM patients had significantly better overall survival (15 vs 22 months median, log-rank, p=0.001) and were significantly younger at the time of presentation (t-test, p=0.002). However, within patients that received current standard-of-care treatment (n=184), cystic GBM (n=40) was not as beneficial for outcome (22 vs 25 months, log-rank, p=0.3). We also did not observe a significant survival benefit when comparing this standard-of-care cystic cohort to cystic GBM patients diagnosed before the standard was established (n=19, 25 vs 23 months, log-rank, p=0.3), but the analogous result for noncystic GBM patients gives a sizeable benefit, as expected (n=144, n=111, respectively, 22 vs 12 months, log-rank p < 0.0001). Together, these results on current standard-of-care may explain later studies that note no significant survival benefit for cystic GBM patients receiving current standard-of-care. We also report differences in the absolute and relative sizes of imaging abnormalities on MRI and in prognostic impact of cysts based on sex. We discuss current hypotheses for these observed differences, including the possibility that the presence of a cyst could be indicative of a less aggressive tumor.

MSCs Successfully Deliver Oncolytic Virotherapy to Diffuse Intrinsic Pontine Glioma

2020 ◽  
Author(s):  
Michael Chastkofsky ◽  
Katarzyna C. Pituch ◽  
Hiroaki Katagi ◽  
Liliana Ilut ◽  
Ting Xiao ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Survival Benefit ◽  
Standard Of Care ◽  
Pediatric Brain Tumors ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Surface Proteins ◽  
Oncolytic Virotherapy ◽  
Pontine Glioma ◽  
Significant Survival Benefit ◽  
Significant Survival

AbstractDiffuse intrinsic pontine glioma (DIPG) is among the deadliest of pediatric brain tumors. Radiation therapy is the standard of care treatment for DIPG, but offers only transient relief of symptoms for DIPG patients without providing significant survival benefit. Oncolytic virotherapy (OV) is an anticancer treatment that has been investigated for treating various types of brain tumors. Here, we have explored the use of mesenchymal stem cells (MSC) for OV delivery and evaluated treatment efficacy using preclinical models of DIPG. Our results show that DIPG cells and tumors exhibit robust expression of cell surface proteins that are important for OV entry, and that MSCs loaded with OV disseminate within and release OV throughout the tumor in mice bearing DIPG brainstem xenografts. When combining administration of OV-loaded MSCs with radiotherapy, mice bearing brainstem DIPG xenografts experience a significant survival benefit, relative to that conferred by either therapy alone (p<0.0001). Our results support further preclinical investigation of cell-based OV therapy with radiation for potential translation in treating DIPG patients.

scholarly journals P14.56 Recurrent Glioblastomas: Should we operate a second and even a third time

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii80-iii80
Author(s):  
M Yahia-Cherif ◽  
O De Witte ◽  
C Mélot ◽  
F Lefranc
Keyword(s):  
Overall Survival ◽  
Survival Benefit ◽  
Standard Of Care ◽  
Recurrent Glioblastoma ◽  
Kaplan Meier ◽  
Significant Survival ◽  
Significant Difference ◽  
Second Surgery ◽  
Second Resection ◽  
Initial Resection

Abstract BACKGROUND The aim of this study was i) to analyse the effect of repeat surgeries on the survival of patients with focally recurrent glioblastoma who have benefited from temozolomide treatment and ii) to identify potential prognostic factors for survival. MATERIAL AND METHODS Cases from 2005 to 2014 in the glioblastoma database of our department were retrospectively reviewed. The Kaplan-Meier method was used to estimate overall survival (OS) as a function of time after one, two and three surgical resections. All patients received the standard of care after the first surgery (temozolomide during and after radiotherapy) and adjuvant treatment after repeat surgeries. RESULTS One hundred-thirty-two glioblastoma patients (median age: 57 years) were included in the study. Among them, 68, 53 and 11 patients underwent one, two and three surgical resections, respectively. The median OS was 11, 16 and 18 months, respectively, for patients who underwent one, two and three surgical resections. Patients who underwent two (p<0.001) or three (p<0.01) surgeries survived significantly longer than patients who underwent only one. No significant difference was observed between patients who underwent two versus three surgeries (p=0.76). A second resection performed more than 6 months after the initial resection was the only factor associated with prolonged survival (p=0.008). CONCLUSION Glioblastoma patients who benefited from temozolomide treatment and underwent surgery for recurrent glioblastoma exhibited a significant increase in survival compared with patients who did not undergo a second surgery. By contrast, a third surgery for a second recurrence did not contribute to any significant survival benefit.

scholarly journals Radiotherapy of glioblastoma 15 years after the landmark Stupp’s trial: more controversies than standards?

2018 ◽  
Vol 52 (2) ◽  
pp. 121-128 ◽  
Author(s):  
Tomas Kazda ◽  
Adam Dziacky ◽  
Petr Burkon ◽  
Petr Pospisil ◽  
Marek Slavik ◽  
...  
Keyword(s):  
Concurrent Chemoradiotherapy ◽  
Standard Of Care ◽  
Primary Brain Tumor ◽  
Current Standard ◽  
Tumor Treating Fields ◽  
Integrated Boost ◽  
Hippocampal Sparing ◽  
New Treatment ◽  
Personalized Approach

Abstract Background The current standard of care of glioblastoma, the most common primary brain tumor in adults, has remained unchanged for over a decade. Nevertheless, some improvements in patient outcomes have occurred as a consequence of modern surgery, improved radiotherapy and up-to-date management of toxicity. Patients from control arms (receiving standard concurrent chemoradiotherapy and adjuvant chemotherapy with temozolomide) of recent clinical trials achieve better outcomes compared to the median survival of 14.6 months reported in Stupp’s landmark clinical trial in 2005. The approach to radiotherapy that emerged from Stupp’s trial, which continues to be a basis for the current standard of care, is no longer applicable and there is a need to develop updated guidelines for radiotherapy within the daily clinical practice that address or at least acknowledge existing controversies in the planning of radiotherapy. The goal of this review is to provoke critical thinking about potentially controversial aspects in the radiotherapy of glioblastoma, including among others the issue of target definitions, simultaneously integrated boost technique, and hippocampal sparing. Conclusions In conjunction with new treatment approaches such as tumor-treating fields (TTF) and immunotherapy, the role of adjuvant radiotherapy will be further defined. The personalized approach in daily radiotherapy practice is enabled with modern radiotherapy systems.

A randomized phase III trial of active symptom control (ASC) with or without chemotherapy in the treatment of patients with malignant pleural mesothelioma: First results of the Medical Research Council (MRC) / British Thoracic Society (BTS) MS01 trial

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. LBA7525-LBA7525 ◽  
Author(s):  
M. Muers ◽  
P. Fisher ◽  
M. Snee ◽  
E. Lowry ◽  
M. O'Brien ◽  
...  
Keyword(s):  
Randomized Trial ◽  
Median Survival ◽  
Malignant Pleural Mesothelioma ◽  
Survival Benefit ◽  
Phase Iii ◽  
Pleural Mesothelioma ◽  
Significant Survival Benefit ◽  
Significant Survival ◽  
Symptom Palliation ◽  
Weekly Cycles

LBA7525 Background: Although chemotherapy is widely used in the treatment of mesothelioma it has never been compared in a randomized trial with ASC alone. Two chemotherapy regimens that had shown good symptom palliation in phase II studies were chosen for investigation. Methods: Patients with malignant pleural mesothelioma were randomized to ASC alone (regular follow-up in a specialist clinic, and treatment could include steroids, analgesics, bronchodilators, palliative radiotherapy, etc), ASC+MVP (4 × 3-weekly cycles of mitomycin 6g/m2, vinblastine 6mg/m2, and cisplatin 50mg/m2), or ASC+N (12 weekly injections of vinorelbine 30mg/m2). 420 patients were required to detect a 3-month improvement in median survival with ASC+CT (both chemotherapy arms combined). Quality of Life (QL) was assessed using the EORTC QLQ-C30. Results: 409 patients were accrued (136 ASC, 137 ASC+MVP, 136 ASC+N). Median age: 65 years, male: 91%, Performance status 0: 23%, Epithelial histology: 73%, Stage III: 33%, Stage IV: 48%. In the ASC+MVP group 61% received all 4 cycles, and in the ASC+N group 49% received at least 10 weekly cycles. Good symptom palliation (defined as prevention, control or improvement) was achieved in all 3 groups, and no between-group differences were observed in 4 pre-defined QL subscales (physical functioning, dyspnoea, pain and global QL). A small (not conventionally significant) survival benefit was seen for ASC+CT (349 deaths, HR 0.89, 95%CI 0.72, 1.12, p=0.32). Median survival: ASC: 7.6 months, ASC+CT: 8.5 months. Exploratory analyses suggested a survival advantage for vinorelbine compared to ASC alone (HR 0.81, 95%CI 0.63, 1.05, p=0.11), with a median survival of 9.4 months, but no evidence of a benefit with MVP (HR 0.98, 95%CI 0.76, 1.28), p=0.91). Conclusions: This is the 2nd largest ever randomized trial in mesothelioma and the first to compare ASC with or without chemotherapy. Although the addition of chemotherapy to ASC did not result in a conventionally significant survival benefit, there was an indication that vinorelbine should be investigated further, and that MVP probably has no role in this disease. [Table: see text]

scholarly journals 51 Timing of adjuvant treatments on glioblastoma survival: A retrospective cohort analysis based on the national cancer database

2018 ◽  
Vol 45 (S3) ◽  
pp. S11-S12
Author(s):  
Ping Zhu ◽  
Xianglin L. Du ◽  
Yoshua Esquenazi ◽  
Jay-Jiguang Zhu
Keyword(s):  
Adjuvant Treatment ◽  
Survival Benefit ◽  
Cohort Analysis ◽  
Cox Proportional Hazards ◽  
High Dose ◽  
National Cancer Database ◽  
Risk Of Death ◽  
Significant Survival Benefit ◽  
Significant Survival ◽  
The Impact

Few studies investigated the associations between intervention modalities, timing, and survival in glioblastoma (GBM) patients. A total of 20511 eligible GBM patients underwent biopsy and craniotomy surgeries followed by adjuvant treatments (2005-2014) were derived from the National Cancer Database (NCDB). The time intervals (days) from the date of diagnosis to the initiation date of adjuvant treatment [radiation therapy only (RT), chemotherapy only, concurrent chemoradiation (CRT), or non-concurrent RT and chemotherapy] were categorized into quartiles (Q1-Q4). Kaplan-Meier method and Cox proportional hazards regression were applied for survival analysis. Multivariate logistic regression was performed to compare differences in treatment timing, intervention modalities, and secondary outcomes. The patients underwent biopsy obtained significant survival benefit by having delayed adjuvant treatment [comparing to Q1, Q2: HR (hazard ratio), 0.88, Q3: HR, 0.86]. For patients underwent resection, the prolonged waiting time of adjuvant treatment had 5-6% reduced risk of death [comparing to Q1, Q2: HR, 0.95; Q3: HR, 0.94]. Patients received more RT fractions [comparing to 10-29 fractions, 30-33 fractions: HR: 0.62 (biopsy), 0.62 (resection); ≥34 fractions: HR: 0.53 (biopsy), 0.62 (resection)] and high-dose RT [comparing to 34-46 Gy, 50-60 Gy: HR: 0.91 (biopsy), 0.95 (resection); ≥ 60 Gy: HR: 0.77 (biopsy), 0.88 (resection)] experienced significantly superior survival in both biopsy and resection groups. The impact of timing to adjuvant treatment on GBM survival varied by surgery procedures. Having adjuvant treatment initiated within 21 days for both biopsy and craniotomy groups may not guarantee a significant survival benefit. More RT fractions and high-dose RT are associated with better GBM survival.

scholarly journals Characterizing Cell Stress and GRP78 in Glioma to Enhance Tumor Treatment

2020 ◽  
Vol 10 ◽  
Author(s):  
Kristie Liu ◽  
Kathleen Tsung ◽  
Frank J. Attenello
Keyword(s):  
Radiation Therapy ◽  
Patient Outcomes ◽  
Cellular Proliferation ◽  
Standard Of Care ◽  
Tumor Grade ◽  
Primary Brain Tumor ◽  
Current Standard ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response

Glioblastoma (GBM) is the most common primary brain tumor, carrying a very poor prognosis, with median overall survival at about 12 to 15 months despite surgical resection, chemotherapy with temozolomide (TMZ), and radiation therapy. GBM recurs in the vast majority of patients, with recurrent tumors commonly displaying increase in resistance to standard of care chemotherapy, TMZ, as well as radiotherapy. One of the most commonly cited mechanisms of chemotherapeutic and radio-resistance occurs via the glucose-regulated protein 78 (GRP78), a well-studied mediator of the unfolded protein response (UPR), that has also demonstrated potential as a biomarker in GBM. Overexpression of GRP78 has been directly correlated with malignant tumor characteristics, including higher tumor grade, cellular proliferation, migration, invasion, poorer responses to TMZ and radiation therapy, and poorer patient outcomes. GRP78 expression is also higher in GBM tumor cells upon recurrence. Meanwhile, knockdown or suppression of GRP78 has been shown to sensitize cells to TMZ and radiation therapy. In light of these findings, various novel developing therapies are targeting GRP78 as monotherapies, combination therapies that enhance the effects of TMZ and radiation therapy, and as treatment delivery modalities. In this review, we delineate the mechanisms by which GRP78 has been noted to specifically modulate glioblastoma behavior and discuss current developing therapies involving GRP78 in GBM. While further research is necessary to translate these developing therapies into clinical settings, GRP78-based therapies hold promise in improving current standard-of-care GBM therapy and may ultimately lead to improved patient outcomes.

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