Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines Update on the Role of Cytotoxic Chemotherapy and Other Cytotoxic Therapies in the Management of Progressive Glioblastoma in Adults

Abstract Target populationThese recommendations apply to adult patients diagnosed with progressive glioblastoma (pGBM).Question (Q1):In adult patients with pGBM does the use of temozolomide (TMZ) with alternative dosing or the use of TMZ in combination with other cytotoxic treatments result in increased overall survival compared to other chemotherapy?Recommendation:Level III: Adult patients with pGBM might derive benefit in treatment with TMZ especially those who progress after more than 5 months of TMZ-treatment free interval. Level III: Combination of TMZ with other cytotoxic agents such as nitrosourea, cisplatin, electrohypothermia, or tamoxifen is not suggested in adult patients with pGBM as a stand-alone therapy.There is insufficient data to make a recommendation about which alternative TMZ dosing provides the best benefits.Question (Q2):In adult patients with pGBM does the use of systemic or in situ nitrosourea result in increased overall survival compared to other chemotherapy?Recommendation:Level III: In the setting of pGBM, fotemustine is suggested in elderly patients with methylated MGMT promoter status. There is insufficient evidence to compare fotemustine to other nitrosoureas. There is insufficient evidence to make a suggestion about the use of in situ nitrosourea in patients with pGBM who underwent the Stupp regimen.Question (Q3):In adult patients with pGBM does the use of platinum compounds and topoisomerase result in increased survival compared to other chemotherapy?Recommendation:Level III: Other chemotherapy including platinum compounds and topoisomerase inhibitors are not suggested to be used in adult patients with pGBM.Level III: Other cytotoxic therapies like perillyl acohol and ketogenic diet are not suggested for use in adult patients with pGBM as a stand-alone therapy.Question (Q4):In adult patients with pGBM does the use of tumor treating field (TTF) result in increased overall survival compared to chemotherapy?Recommendation:Level III: The use of TTF with other chemotherapy may be considered when treating adult patients with pGBM.There is insufficient evidence to recommend TTF to increase overall survival in adult patients with pGBM.Question (Q5):In adult patients with pGBM does the use of oncolytic virotherapy result in increased survival compared to chemotherapy?Recommendation:Level III: Oncolytic virotherapy is not suggested in patients with pGBM.

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Congress of Neurological Surgeons Systematic Review and Evidence-based Guidelines Update on the Role of Targeted Therapies and Immunotherapies in the Management of Progressive Glioblastomaoncolo

10.21203/rs.3.rs-842786/v1 ◽

2021 ◽

Author(s):

Evan Winograd ◽

Isabelle Germano ◽

Patrick Wen ◽

Jeffrey J. Olson ◽

David Ryan Ormond

Keyword(s):

Overall Survival ◽

Combination Therapy ◽

Progression Free Survival ◽

Cytotoxic Chemotherapy ◽

Cytotoxic Agents ◽

Defined Benefit ◽

Targeted Agents ◽

Insufficient Evidence ◽

Free Survival ◽

Cytotoxic Therapies

Abstract The following questions and recommendations are pertinent to the following:Target PopulationThese recommendations apply to adults with progressive GBM who have undergone standard primary treatment with surgery and/or chemoradiation.Question 1In adults with progressive glioblastoma is the use of bevacizumab as monotherapy superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival?RecommendationLevel III: Treatment with bevacizumab is suggested in the treatment of progressive GBM, as it provides improved disease control compared to historical controls as measured by best imaging response and progression free survival at 6 months, while not providing evidence for improvement in overall survival. Question 2In adults with progressive glioblastoma is the use of bevacizumab as combination therapy with cytotoxic agents superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival?RecommendationLevel III: There is insufficient evidence to show benefit or harm of bevacizumab in combination with cytotoxic therapies in progressive glioblastoma due to a lack of evidence supporting a clearly defined benefit without significant toxicity.Question 3In adults with progressive glioblastoma is the use of bevacizumab as a combination therapy with targeted agents superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival?Recommendation There is insufficient evidence to support a recommendation regarding this question.Question 4In adults with progressive glioblastoma is the use of targeted agents as monotherapy superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival?RecommendationThere is insufficient evidence to support a recommendation regarding this question.Question 5In adults with progressive glioblastoma is the use of targeted agents in combination with cytotoxic therapies superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival?Recommendation There is insufficient evidence to support a recommendation regarding this question.Question 6In adults with progressive glioblastoma is the use of immunotherapy monotherapy superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival?RecommendationThere is insufficient evidence to support a recommendation regarding this question.Question 7In adults with progressive glioblastoma is the use of immunotherapy in combination with targeted agents superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival?Recommendation There is insufficient evidence to support a recommendation regarding this question.Question 8In adults with progressive glioblastoma is the use of immunotherapy in combination with bevacizumab superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival?RecommendationThere is insufficient evidence to support a recommendation regarding this question.

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Identification of research gaps from evidence-based guidelines: A pilot study in cystic fibrosis

International Journal of Technology Assessment in Health Care ◽

10.1017/s0266462311000225 ◽

2011 ◽

Vol 27 (3) ◽

pp. 247-252 ◽

Cited By ~ 8

Author(s):

Karen A. Robinson ◽

Ian J. Saldanha ◽

Naomi A. McKoy

Keyword(s):

Cystic Fibrosis ◽

Target Population ◽

The United States ◽

Future Research ◽

Evidence Based ◽

Insufficient Evidence ◽

Research Gaps ◽

Consensus Recommendations ◽

Cystic Fibrosis Population ◽

Evidence Based Guidelines

Objectives: Evidence-based guideline committees are multidisciplinary and explicitly consider the existing evidence. They are thus in an ideal position to identify research gaps. However, gaps have not been systematically identified through guidelines. We pilot tested a method to systematically identify and classify gaps from evidence-based guidelines.Methods: We reviewed all evidence-based guidelines published by the Cystic Fibrosis Foundation. We identified research gaps as topics for which there was insufficient evidence (recommendations were not made or consensus recommendations were made) and topics specified as needing further research. We characterized gaps using a standard framework and classified them by type of management issue, specificity of target population, and age of target population.Results: We identified sixty-two research gaps in five guidelines (mean = 12.4/guidelines document). While thirteen gaps were topics specified as needing further research, most (n = 49) were topics with insufficient evidence. Of these forty-nine, recommendations were not made for twenty-two topics while consensus recommendations were made for twenty-seven topics. Most gaps were issues of comparative effectiveness (44/62), addressed the general cystic fibrosis population (40/62), and were specific to infants (33/62). Relevant comparisons and outcomes were explicitly stated for only 7 percent and 16 percent of gaps respectively.Conclusions: Almost 80 percent of the gaps were not topics identified as future research needs in the guidelines documents but rather were topics with insufficient evidence for making recommendations. Although we used cystic fibrosis in the United States as an example, the method we developed could be applied in other settings, including other countries and for different diseases.

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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

10.21203/rs.3.rs-835385/v1 ◽

2021 ◽

Author(s):

Hayes H. Patrick ◽

Jonathan H Sherman ◽

Bradley Elder ◽

Jeffrey Olson

Keyword(s):

Overall Survival ◽

Cytoreductive Surgery ◽

Progression Free Survival ◽

Target Population ◽

Free Survival ◽

Alternative Interventions ◽

Level Ii ◽

Neoplastic Process ◽

Evidence Based Guidelines

Abstract 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.

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AML1/RUNX1 mutations in 470 adult patients with de novo acute myeloid leukemia: prognostic implication and interaction with other gene alterations

Blood ◽

10.1182/blood-2009-05-223784 ◽

2009 ◽

Vol 114 (26) ◽

pp. 5352-5361 ◽

Cited By ~ 211

Author(s):

Jih-Luh Tang ◽

Hsin-An Hou ◽

Chien-Yuan Chen ◽

Chieh-Yu Liu ◽

Wen-Chien Chou ◽

...

Keyword(s):

Overall Survival ◽

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

De Novo ◽

Remission Rate ◽

Adult Patients ◽

Poor Prognostic Factor ◽

The Impact ◽

Runx1 Mutation ◽

Acute Myeloid

AbstractSomatic mutation of the AML1/RUNX1(RUNX1) gene is seen in acute myeloid leukemia (AML) M0 subtype and in AML transformed from myelodysplastic syndrome, but the impact of this gene mutation on survival in AML patients remains unclear. In this study, we sought to determine the clinical implications of RUNX1 mutations in 470 adult patients with de novo non-M3 AML. Sixty-three distinct RUNX1 mutations were identified in 62 persons (13.2%); 32 were in N-terminal and 31, C-terminal. The RUNX1 mutation was closely associated with male sex, older age, lower lactic dehydrogenase value, French-American-British M0/M1 subtypes, and expression of HLA-DR and CD34, but inversely correlated with CD33, CD15, CD19, and CD56 expression. Furthermore, the mutation was positively associated with MLL/PTD but negatively associated with CEBPA and NPM1 mutations. AML patients with RUNX1 mutations had a significantly lower complete remission rate and shorter disease-free and overall survival than those without the mutation. Multivariate analysis demonstrated that RUNX1 mutation was an independent poor prognostic factor for overall survival. Sequential analysis in 133 patients revealed that none acquired novel RUNX1 mutations during clinical courses. Our findings provide evidence that RUNX1 mutations are associated with distinct biologic and clinical characteristics and poor prognosis in patients with de novo AML.

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Somatic Mutation Profiling in the Liquid Biopsy and Clinical Analysis of Hereditary and Familial Pancreatic Cancer Cases Reveals KRAS Negativity and a Longer Overall Survival

Cancers ◽

10.3390/cancers13071612 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1612

Author(s):

Julie Earl ◽

Emma Barreto ◽

María E. Castillo ◽

Raquel Fuentes ◽

Mercedes Rodríguez-Garrote ◽

...

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Somatic Mutation ◽

Disease Status ◽

Clinical Analysis ◽

Cytotoxic Agents ◽

Disease Stage ◽

Ductal Adenocarcinoma ◽

Familial Pancreatic Cancer ◽

Circulating Free Dna

Pancreatic ductal adenocarcinoma (PDAC) presents many challenges in the clinic and there are many areas for improvement in diagnostics and patient management. The five-year survival rate is around 7.2% as the majority of patients present with advanced disease at diagnosis that is treatment resistant. Approximately 10–15% of PDAC cases have a hereditary basis or Familial Pancreatic Cancer (FPC). Here we demonstrate the use of circulating free DNA (cfDNA) in plasma as a prognostic biomarker in PDAC. The levels of cfDNA correlated with disease status, disease stage, and overall survival. Furthermore, we show for the first time via BEAMing that the majority of hereditary or familial PDAC cases (around 84%) are negative for a KRAS somatic mutation. In addition, KRAS mutation negative cases harbor somatic mutations in potentially druggable genes such as KIT, PDGFR, MET, BRAF, and PIK3CA that could be exploited in the clinic. Finally, familial or hereditary cases have a longer overall survival compared to sporadic cases (10.2 vs. 21.7 months, respectively). Currently, all patients are treated the same in the clinic with cytotoxic agents, although here we demonstrate that there are different subtypes of tumors at the genetic level that could pave the way to personalized treatment.

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RADT-29. EFFECT OF RADIATION THERAPY ON OVERALL SURVIVAL FOLLOWING SUBTOTAL RESECTION OF ADULT PILOCYTIC ASTROCYTOMA

Neuro-Oncology ◽

10.1093/neuonc/noaa215.782 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii187-ii188

Author(s):

Adham Khalafallah ◽

Adrian Jimenez ◽

Henry Brem ◽

Debraj Mukherjee

Keyword(s):

Overall Survival ◽

Radiation Therapy ◽

Pilocytic Astrocytoma ◽

Radiation Treatment ◽

Cox Proportional Hazards Model ◽

Adult Patients ◽

Subtotal Resection ◽

Adjuvant Radiation ◽

Low Grade ◽

Risk Of Death

Abstract BACKGROUND Pilocytic astrocytoma (PCA) is a low-grade glioma common in children but also rarely diagnosed in adults. The role of adjuvant radiation therapy (RT) in treating these tumors remains unclear. OBJECTIVE We investigated the effect of RT on overall survival, specifically among adult patients who had undergone subtotal PCA resection. METHODS Information on adult patients (age 18 years old) who had undergone subtotal PCA resection between 2004 and 2016 was collected from the National Cancer Database (NCDB). A multivariate Cox proportional hazards model was utilized to determine factors independently associated with overall survival. RESULTS A total of 451 patients were identified. The mean age of our patient cohort was 36.8 years old, and the majority of patients (83.4%) did not receive radiation treatment following subtotal PCA resection. Overall median survival was 93.8 months. Survival was longer (p < 0.001) in the patients who did not receive post-surgical RT (median: 98.3 months) compared to patients who did (median: 54.8 months). Patients who had older age at diagnosis (hazard ratio [HR]=1.05, 95% confidence interval [CI]=1.03-1.07, p < 0.01), were Black or African American (HR=2.76, CI=1.12-6.46, p=0.019), received radiation during their initial treatment (HR=4.53, CI=2.08-9.89, p < 0.01), or had a Charlson/Deyo score of > 1 (HR=3.68, CI=1.55, p=0.003) had a significantly higher risk of death following subtotal PCA resection. CONCLUSION Postoperative RT is independently associated with a significantly higher risk of death among adults who underwent subtotal PCA resection. Our findings provide a rationale for further investigation into the efficacy and safety of RT within this patient population.

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In situ modification of the Mitrofanoff principle in adult patients

Urinary Diversion ◽

10.3109/9780203341025-36 ◽

1995 ◽

pp. 507-525

Keyword(s):

Adult Patients ◽

In Situ Modification

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Functional status as a determinant prognostic factor for overall survival in adult patients with medulloblastoma treated with chemotherapy and radiotherapy

Annals of Oncology ◽

10.1093/annonc/mdz419.005 ◽

2019 ◽

Vol 30 ◽

pp. ix21

Author(s):

J.C. Ayala Alvarez ◽

R.R. Trejo Rosales ◽

R. Riera Salas ◽

M.F. Chilaca Rosas ◽

S. Rivera Rivera ◽

...

Keyword(s):

Overall Survival ◽

Prognostic Factor ◽

Functional Status ◽

Adult Patients

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Characterization of a Myeloid Activation Signature That Correlates with Survival in Melanoma Patients

Cancers ◽

10.3390/cancers12061431 ◽

2020 ◽

Vol 12 (6) ◽

pp. 1431

Author(s):

Mirela Kremenovic ◽

Nives Rombini ◽

Alfred A. Chan ◽

Thomas Gruber ◽

Lukas Bäriswyl ◽

...

Keyword(s):

Overall Survival ◽

Checkpoint Inhibitors ◽

Myeloid Cells ◽

Poly I:C ◽

Cellular Interactions ◽

Therapeutic Modalities ◽

Signature Genes ◽

Melanoma Model ◽

Melanoma Patients

Understanding the cellular interactions within the tumor microenvironment (TME) of melanoma paved the way for novel therapeutic modalities, such as T cell-targeted immune checkpoint inhibitors (ICI). However, only a limited fraction of patients benefits from such therapeutic modalities, highlighting the need for novel predictive and prognostic biomarkers. As myeloid cells orchestrate the tumor-specific immune response and influence the efficacy of ICI, assessing their activation state within the TME is of clinical relevance. Here, we characterized a myeloid activation (MA) signature, comprising the three genes Cxcl11, Gbp1, and Ido1, from gene expression data of human myeloid cells stimulated with poly(I:C) or cGAMP. This MA signature positively correlated to overall survival in melanoma. In addition, increased expression of the MA signature was observed in melanoma patients responding to ICI (anti-PD-1), as compared to non-responders. Furthermore, the MA signature was validated in the murine B16F10 melanoma model where it was induced and associated with decreased tumor growth upon intratumoral administration of poly(I:C) and cGAMP. Finally, we were able to visualize co-expression of the MA signature genes in myeloid cells of human melanoma tissues using RNAscope in situ hybridization. In conclusion, the MA signature indicates the activation state of myeloid cells and represents a prognostic biomarker for the overall survival in melanoma patients.

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Role of allogeneic stem cell transplantation in adult patients with Ph-negative acute lymphoblastic leukemia

Blood ◽

10.1182/blood-2014-09-599894 ◽

2015 ◽

Vol 125 (16) ◽

pp. 2486-2496 ◽

Cited By ~ 134

Author(s):

Nathalie Dhédin ◽

Anne Huynh ◽

Sébastien Maury ◽

Reza Tabrizi ◽

Kheira Beldjord ◽

...

Keyword(s):

Overall Survival ◽

Stem Cell ◽

Acute Lymphoblastic Leukemia ◽

High Risk ◽

Complete Remission ◽

Lymphoblastic Leukemia ◽

Adult Patients ◽

Key Points ◽

First Complete Remission

Key Points SCT in first complete remission is associated with 69.5% 3-year overall survival in high-risk ALL adult patients treated with intensified pediatric-like protocol. Poor early MRD response is a powerful tool to select patients who may benefit from SCT in first complete remission.

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