scholarly journals Case-Based Review: newly diagnosed glioblastoma

2015 ◽  
Vol 2 (3) ◽  
pp. 106-121 ◽  
Author(s):  
Derek R. Johnson ◽  
Shannon E. Fogh ◽  
Caterina Giannini ◽  
Timothy J. Kaufmann ◽  
Aditya Raghunathan ◽  
...  
Keyword(s):  
Treatment Options ◽  
Standard Of Care ◽  
Primary Brain Tumor ◽  
Newly Diagnosed ◽  
Therapeutic Approaches ◽  
Who Grade ◽  
Current Therapies ◽  
Newly Diagnosed Glioblastoma ◽  
New Treatments ◽  
Active Investigation

Abstract Glioblastoma (WHO grade IV astrocytoma) is the most common and most aggressive primary brain tumor in adults. Optimal treatment of a patient with glioblastoma requires collaborative care across numerous specialties. The diagnosis of glioblastoma may be suggested by the symptomatic presentation and imaging, but it must be pathologically confirmed via surgery, which can have dual diagnostic and therapeutic roles. Standard of care postsurgical treatment for newly diagnosed patients involves radiation therapy and oral temozolomide chemotherapy. Despite numerous recent trials of novel therapeutic approaches, this standard of care has not changed in over a decade. Treatment options under active investigation include molecularly targeted therapies, immunotherapeutic approaches, and the use of alternating electrical field to disrupt tumor cell division. These trials may be aided by new insights into glioblastoma heterogeneity, allowing for focused evaluation of new treatments in the patient subpopulations most likely to benefit from them. Because glioblastoma is incurable by current therapies, frequent clinical and radiographic assessment is needed after initial treatment to allow for early intervention upon progressive tumor when it occurs.

scholarly journals NK Cell-Based Immunotherapy and Therapeutic Perspective in Gliomas

2021 ◽  
Vol 11 ◽  
Author(s):  
Changqing Pan ◽  
You Zhai ◽  
Guanzhang Li ◽  
Tao Jiang ◽  
Wei Zhang
Keyword(s):  
Nk Cells ◽  
Nk Cell ◽  
Primary Brain Tumor ◽  
Therapeutic Approaches ◽  
Independent Manner ◽  
Clinical Prognosis ◽  
Cell Based Therapy ◽  
Current Therapies ◽  
Immunosuppressive Microenvironment ◽  
Therapeutic Perspective

Glioma is the most common malignant primary brain tumor diagnosed in adults. Current therapies are unable to improve its clinical prognosis, imposing the need for innovative therapeutic approaches. The main reason for the poor prognosis is the great cell heterogeneity of the tumor and its immunosuppressive microenvironment. Development of new therapies that avoid this immune evasion could improve the response to the current treatments. Natural killer (NK) cells are an intriguing candidate for the next wave of therapies because of several unique features that they possess. For example, NK cell-based immunotherapy causes minimal graft-versus-host disease. Cytokine release syndrome is less likely to occur during chimeric antigen receptor (CAR)-NK therapy, and CAR-NK cells can kill targets in a CAR-independent manner. However, NK cell-based therapy in treating glioma faces several difficulties. For example, CAR molecules are not sufficiently well designed so that they will thoroughly release functioning NK cells. Compared to hematological malignancies, the application of many potential NK cell-based therapies in glioma lags far behind. Here, we review several issues of NK cells and propose several strategies that will improve the efficacy of NK cell-based cancer immunotherapy in the treatment of glioma.

scholarly journals HOUT-02. TREATMENT PATTERNS AND OUTCOMES FOR PATIENTS WITH NEWLY-DIAGNOSED GLIOBLASTOMA MULTIFORME IN A US COMMUNITY ONCOLOGY SETTING

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi112-vi112
Author(s):  
Alex Fu ◽  
Nicholas Robert ◽  
Trang Pham ◽  
Alexander Marshall ◽  
Srinivas Annavarapu
Keyword(s):  
Glioblastoma Multiforme ◽  
Clinical Outcomes ◽  
Dna Methyltransferase ◽  
Treatment Options ◽  
Methylation Status ◽  
Treatment Patterns ◽  
Newly Diagnosed ◽  
Mgmt Methylation ◽  
The Us ◽  
Newly Diagnosed Glioblastoma

Abstract BACKGROUND This study aims to describe real world characteristics and outcomes of newly-diagnosed glioblastoma multiforme (GBM) patients in relationship to O6-methylguanine DNA methyltransferase promoter (MGMT) testing and methylation status, in the US. METHODS Patients receiving care for GBM were identified in the US Oncology Network database from 1/1/2013 to 6/30/2018 and followed up to 9/30/2018. Structured data and chart reviews were used to assess demographic and clinical characteristics, treatment patterns, type of surgery, MGMT methylation, and clinical outcomes. RESULTS Of 600 patient charts planned for review, 195 have been randomly selected and reviewed thus far. Of these, 165 (84.6%) had surgical resection and 30 (15.4%) had biopsy only. Eighty-eight (45.1%) patients were tested for MGMT status and 107 (54.9%) were not. Of those tested, 33 (37.5%) were methylated, and 45 (51.1%) unmethylated. Median ages in the overall (including tested and untested), methylated and unmethylated cohorts were 63.7, 58.8, and 66.7 years, respectively. Most common first-line (1L) treatment in overall, methylated, and unmethylated cohorts was radiation concurrent with temozolomide received by 86.2%, 93.9%, and 91.1%, respectively. Median duration of 1L treatment in the overall cohort was 15.1 weeks (95% confidence interval [CI]: 11.9, 21.6) and higher in the methylated vs. unmethylated cohort (25.9 [18.1, 34.6] vs. 15.1 [9.3, 23.4] weeks, p=0.0375). Unadjusted median overall survival and progression-free survival in the overall cohort were 11.4 [9.4, 14.0] months and 5.2 [3.9, 5.8] months, and higher in the methylated vs. unmethylated cohort (20.5 [14.9, not realized] vs. 12.2 [7.1, 17.0] months, p=0.0052, and 9.4 [5.6, 14.0] vs. 5.5 [3.3, 6.8], p=0.0092, respectively). CONCLUSIONS Fewer than half of GBM patients were tested for MGMT methylation in the US community. Clinical outcomes, while better among patients with methylated MGMT, remain poor and current treatment options are limited.

scholarly journals Therapy for Diffuse Astrocytic and Oligodendroglial Tumors in Adults: ASCO-SNO Guideline

2021 ◽  
Author(s):  
Nimish A. Mohile ◽  
Hans Messersmith ◽  
Na Tosha Gatson ◽  
Andreas F. Hottinger ◽  
Andrew Lassman ◽  
...  
Keyword(s):  
Performance Status ◽  
Treatment Options ◽  
Poor Performance ◽  
Best Supportive Care ◽  
Poor Performance Status ◽  
Newly Diagnosed ◽  
Who Grade ◽  
Oligodendroglial Tumors ◽  
Mgmt Promoter ◽  
Grade 3

PURPOSE To provide guidance to clinicians regarding therapy for diffuse astrocytic and oligodendroglial tumors in adults. METHODS ASCO and the Society for Neuro-Oncology convened an Expert Panel and conducted a systematic review of the literature. RESULTS Fifty-nine randomized trials focusing on therapeutic management were identified. RECOMMENDATIONS Adults with newly diagnosed oligodendroglioma, isocitrate dehydrogenase (IDH)–mutant, 1p19q codeleted CNS WHO grade 2 and 3 should be offered radiation therapy (RT) and procarbazine, lomustine, and vincristine (PCV). Temozolomide (TMZ) is a reasonable alternative for patients who may not tolerate PCV, but no high-level evidence supports upfront TMZ in this setting. People with newly diagnosed astrocytoma, IDH-mutant, 1p19q non-codeleted CNS WHO grade 2 should be offered RT with adjuvant chemotherapy (TMZ or PCV). People with astrocytoma, IDH-mutant, 1p19q non-codeleted CNS WHO grade 3 should be offered RT and adjuvant TMZ. People with astrocytoma, IDH-mutant, CNS WHO grade 4 may follow recommendations for either astrocytoma, IDH-mutant, 1p19q non-codeleted CNS WHO grade 3 or glioblastoma, IDH-wildtype, CNS WHO grade 4. Concurrent TMZ and RT should be offered to patients with newly diagnosed glioblastoma, IDH-wildtype, CNS WHO grade 4 followed by 6 months of adjuvant TMZ. Alternating electric field therapy, approved by the US Food and Drug Administration, should be considered for these patients. Bevacizumab is not recommended. In situations in which the benefits of 6-week RT plus TMZ may not outweigh the harms, hypofractionated RT plus TMZ is reasonable. In patients age ≥ 60 to ≥ 70 years, with poor performance status or for whom toxicity or prognosis are concerns, best supportive care alone, RT alone (for MGMT promoter unmethylated tumors), or TMZ alone (for MGMT promoter methylated tumors) are reasonable treatment options. Additional information is available at www.asco.org/neurooncology-guidelines .

scholarly journals A Review of Newly Diagnosed Glioblastoma

2021 ◽  
Vol 10 ◽  
Author(s):  
Bryan Oronsky ◽  
Tony R. Reid ◽  
Arnold Oronsky ◽  
Navjot Sandhu ◽  
Susan J. Knox
Keyword(s):  
Brain Tumor ◽  
Surgical Resection ◽  
Standard Of Care ◽  
Newly Diagnosed ◽  
Current Standard ◽  
Genetic Characteristics ◽  
Dismal Prognosis ◽  
Newly Diagnosed Glioblastoma ◽  
Temozolomide Chemotherapy

Glioblastoma is an aggressive and inevitably recurrent primary intra-axial brain tumor with a dismal prognosis. The current mainstay of treatment involves maximally safe surgical resection followed by radiotherapy over a 6-week period with concomitant temozolomide chemotherapy followed by temozolomide maintenance. This review provides a summary of the epidemiological, clinical, histologic and genetic characteristics of newly diagnosed disease as well as the current standard of care and potential future therapeutic prospects.

Therapy for Diffuse Astrocytic and Oligodendroglial Tumors in Adults: ASCO-SNO Guideline

2021 ◽  
Author(s):  
Nimish A Mohile ◽  
Hans Messersmith ◽  
Na Tosha N Gatson ◽  
Andreas F Hottinger ◽  
Andrew B Lassman ◽  
...  
Keyword(s):  
Performance Status ◽  
Treatment Options ◽  
Poor Performance ◽  
Best Supportive Care ◽  
Poor Performance Status ◽  
Newly Diagnosed ◽  
Who Grade ◽  
Additional Information ◽  
Oligodendroglial Tumors ◽  
Grade 3

Abstract Purpose To provide guidance to clinicians regarding therapy for diffuse astrocytic and oligodendroglial tumors in adults. Methods ASCO and the Society for Neuro-Oncology convened an Expert Panel and conducted a systematic review of the literature. Results Fifty-nine randomized trials focusing on therapeutic management were identified. Recommendations Adults with newly diagnosed oligodendroglioma, isocitrate dehydrogenase (IDH)–mutant, 1p19q codeleted CNS WHO grade 2 and 3 should be offered radiation therapy (RT) and procarbazine, lomustine, and vincristine (PCV). Temozolomide (TMZ) is a reasonable alternative for patients who may not tolerate PCV, but no high-level evidence supports upfront TMZ in this setting. People with newly diagnosed astrocytoma, IDH-mutant, 1p19q non-codeleted CNS WHO grade 2 should be offered RT with adjuvant chemotherapy (TMZ or PCV). People with astrocytoma, IDH-mutant, 1p19q non-codeleted CNS WHO grade 3 should be offered RT and adjuvant TMZ. People with astrocytoma, IDH-mutant, CNS WHO grade 4 may follow recommendations for either astrocytoma, IDH-mutant, 1p19q non-codeleted CNS WHO grade 3 or glioblastoma, IDH-wildtype, CNS WHO grade 4. Concurrent TMZ and RT should be offered to patients with newly diagnosed glioblastoma, IDH-wildtype, CNS WHO grade 4 followed by 6 months of adjuvant TMZ. Alternating electric field therapy, approved by the US Food and Drug Administration, should be considered for these patients. Bevacizumab is not recommended. In situations in which the benefits of 6-week RT plus TMZ may not outweigh the harms, hypofractionated RT plus TMZ is reasonable. In patients age ≥ 60 to ≥ 70 years, with poor performance status or for whom toxicity or prognosis are concerns, best supportive care alone, RT alone (for MGMTpromoter unmethylated tumors), or TMZ alone (for MGMT promoter methylated tumors) are reasonable treatment options. Additional information is available at www.asco.org/neurooncology-guidelines.

scholarly journals Very low mutation burden is a feature of inflamed recurrent glioblastomas responsive to cancer immunotherapy

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Matthias Gromeier ◽  
Michael C. Brown ◽  
Gao Zhang ◽  
Xiang Lin ◽  
Yeqing Chen ◽  
...  
Keyword(s):  
Genomic Analysis ◽  
Immune Checkpoint Blockade ◽  
Recurrent Glioblastoma ◽  
Newly Diagnosed ◽  
Who Grade ◽  
Term Survival ◽  
Tumor Mutation Burden ◽  
Mutation Burden ◽  
Newly Diagnosed Glioblastoma

AbstractSeveral immunotherapy clinical trials in recurrent glioblastoma have reported long-term survival benefits in 10–20% of patients. Here we perform genomic analysis of tumor tissue from recurrent WHO grade IV glioblastoma patients acquired prior to immunotherapy intervention. We report that very low tumor mutation burden is associated with longer survival after recombinant polio virotherapy or after immune checkpoint blockade in recurrent glioblastoma patients. A relationship between tumor mutation burden and survival is not observed in cohorts of immunotherapy naïve newly diagnosed or recurrent glioblastoma patients. Transcriptomic analyses reveal an inverse relationship between tumor mutation burden and enrichment of inflammatory gene signatures in cohorts of recurrent, but not newly diagnosed glioblastoma tumors, implying that a relationship between tumor mutation burden and tumor-intrinsic inflammation evolves upon recurrence.

Progress in the Treatment of Metastatic Pancreatic Cancer and the Search for Next Opportunities

2015 ◽  
Vol 33 (16) ◽  
pp. 1779-1786 ◽  
Author(s):  
Andrew H. Ko
Keyword(s):  
Pancreatic Cancer ◽  
Standard Of Care ◽  
Phase Iii ◽  
Metastatic Pancreatic Cancer ◽  
Therapeutic Approaches ◽  
Cytotoxic Therapy ◽  
Phase Iii Clinical Trials ◽  
Signal Transduction Inhibitors ◽  
Positive Results ◽  
Active Investigation

A growing number of therapeutic options are now available for patients with metastatic pancreatic cancer, informed by positive results from recently completed phase III clinical trials. These have led to modest, if not necessarily transformative, improvements in clinical outcomes. Although the standard of care for metastatic disease remains cytotoxic therapy, a variety of novel therapeutic approaches are currently under active investigation, several of which have already demonstrated encouraging results in phase I/II studies. The following three broad categories (with significant overlap among them) are highlighted here: stromal-depleting agents, immunotherapies, and signal transduction inhibitors. The mechanistic rationale, limitations, and promise of each of these strategies specific to pancreatic cancer are discussed, as are the aspects of this disease and this patient population that pose ongoing challenges in terms of both therapeutic management and biomarker-driven trial design.

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