Treatment patterns and outcomes for patients with newly diagnosed glioblastoma multiforme: a retrospective cohort study

Annavarapu, Srinivas; Gogate, Anagha; Pham, Thuy Thi Thu; Davies, Kalatu; Singh, Prianka; Robert, Nicholas J.

doi:10.2217/cns-2021-0007

Cited by 9 publications

(3 citation statements)

References 24 publications

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“…However, we note that all patients included in the Girvan cohort received at least two LOTs, whereas only 67.1% of patients in our cohort received 2L therapy. Another cohort of 750 patients with GBM assembled by Annavarapu et al 23 showed that the majority of patients received 1L radiation concurrent with temozolomide (90.1%), bevacizumab was the most common 2L therapy (73.4% of patients receiving 2L therapy), and the median 1L duration was 135.1 days. That study defined treatment duration as the interval between the date of LOT initiation and the date of last administration, which does not account for the date of initiation for the subsequent LOT.…”

Section: Discussionmentioning

confidence: 99%

Extraction of Unstructured Electronic Health Records to Evaluate Glioblastoma Treatment Patterns

Swaminathan,

Ren,

et al. 2024

JCO Clin Cancer Inform

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PURPOSE Data on lines of therapy (LOTs) for cancer treatment are important for clinical oncology research, but LOTs are not explicitly recorded in electronic health records (EHRs). We present an efficient approach for clinical data abstraction and a flexible algorithm to derive LOTs from EHR-based medication data on patients with glioblastoma multiforme (GBM). METHODS Nonclinicians were trained to abstract the diagnosis of GBM from EHRs, and their accuracy was compared with abstraction performed by clinicians. The resulting data were used to build a cohort of patients with confirmed GBM diagnosis. An algorithm was developed to derive LOTs using structured medication data, accounting for the addition and discontinuation of therapies and drug class. Descriptive statistics were calculated and time-to-next-treatment (TTNT) analysis was performed using the Kaplan-Meier method. RESULTS Treating clinicians as the gold standard, nonclinicians abstracted GBM diagnosis with a sensitivity of 0.98, specificity 1.00, positive predictive value 1.00, and negative predictive value 0.90, suggesting that nonclinician abstraction of GBM diagnosis was comparable with clinician abstraction. Of 693 patients with a confirmed diagnosis of GBM, 246 patients contained structured information about the types of medications received. Of them, 165 (67.1%) received a first-line therapy (1L) of temozolomide, and the median TTNT from the start of 1L was 179 days. CONCLUSION We described a workflow for extracting diagnosis of GBM and LOT from EHR data that combines nonclinician abstraction with algorithmic processing, demonstrating comparable accuracy with clinician abstraction and highlighting the potential for scalable and efficient EHR-based oncology research.

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Section: Discussionmentioning

confidence: 99%

Extraction of Unstructured Electronic Health Records to Evaluate Glioblastoma Treatment Patterns

Swaminathan,

Ren,

et al. 2024

JCO Clin Cancer Inform

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“…Consequently, promoter methylation of the MGMT gene is associated with a favourable prognosis and a better response to TMZ treatment [32]. Several studies confirmed this association and reported a higher overall survival and better response to treatment compared to patients without methylation of the MGMT gene [61][62][63][64][65]. For patients in this situation, O 6 -benzylguanine (O 6 -BG) can be used for MGMT inactivation.…”

Section: Mgmt Promoter Methylationmentioning

confidence: 99%

Principles in the Management of Glioblastoma

Roda,

Veiga,

Melo

et al. 2024

Genes

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Glioblastoma, the most aggressive and common malignant primary brain tumour, is characterized by infiltrative growth, abundant vascularization, and aggressive clinical evolution. Patients with glioblastoma often face poor prognoses, with a median survival of approximately 15 months. Technological progress and the subsequent improvement in understanding the pathophysiology of these tumours have not translated into significant achievements in therapies or survival outcomes for patients. Progress in molecular profiling has yielded new omics data for a more refined classification of glioblastoma. Several typical genetic and epigenetic alterations in glioblastoma include mutations in genes regulating receptor tyrosine kinase (RTK)/rat sarcoma (RAS)/phosphoinositide 3-kinase (PI3K), p53, and retinoblastoma protein (RB) signalling, as well as mutation of isocitrate dehydrogenase (IDH), methylation of O6-methylguanine-DNA methyltransferase (MGMT), amplification of epidermal growth factor receptor vIII, and codeletion of 1p/19q. Certain microRNAs, such as miR-10b and miR-21, have also been identified as prognostic biomarkers. Effective treatment options for glioblastoma are limited. Surgery, radiotherapy, and alkylating agent chemotherapy remain the primary pillars of treatment. Only promoter methylation of the gene MGMT predicts the benefit from alkylating chemotherapy with temozolomide and it guides the choice of first-line treatment in elderly patients. Several targeted strategies based on tumour-intrinsic dominant signalling pathways and antigenic tumour profiles are under investigation in clinical trials. This review explores the potential genetic and epigenetic biomarkers that could be deployed as analytical tools in the diagnosis and prognostication of glioblastoma. Recent clinical advancements in treating glioblastoma are also discussed, along with the potential of liquid biopsies to advance personalized medicine in the field of glioblastoma, highlighting the challenges and promises for the future.

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“…MGMT, a cellular DNA repair enzyme that neutralizes the cytotoxic effects of alkylating drugs like TMZ, is another important biological component related to clinical response in GB patients ( 165 ). It has been demonstrated that MGMT promoter methylation is a mechanism of MGMT regulation in gliomas, which is a favorable predictor of progression-free survival and overall survival in TMZ-treated patients ( 166 ). In this respect, Weathers et al.…”

Section: Cmv-specific Adoptive T Cell Therapymentioning

confidence: 99%

The Basis and Advances in Clinical Application of Cytomegalovirus-Specific Cytotoxic T Cell Immunotherapy for Glioblastoma Multiforme

et al. 2022

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A high percentage of malignant gliomas are infected by human cytomegalovirus (HCMV), and the endogenous expression of HCMV genes and their products are found in these tumors. HCMV antigen expression and its implications in gliomagenesis have emerged as a promising target for adoptive cellular immunotherapy (ACT) strategies in glioblastoma multiforme (GB) patients. Since antigen-specific T cells in the tumor microenvironments lack efficient anti-tumor immune response due to the immunosuppressive nature of glioblastoma, CMV-specific ACT relies on in vitro expansion of CMV-specific CD8+ T cells employing immunodominant HCMV antigens. Given the fact that several hurdles remain to be conquered, recent clinical trials have outlined the feasibility of CMV-specific ACT prior to tumor recurrence with minimal adverse effects and a substantial improvement in median overall survival and progression-free survival. This review discusses the role of HCMV in gliomagenesis, disease prognosis, and recent breakthroughs in harnessing HCMV-induced immunogenicity in the GB tumor microenvironment to develop effective CMV-specific ACT.

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Treatment patterns and outcomes for patients with newly diagnosed glioblastoma multiforme: a retrospective cohort study

Cited by 9 publications

References 24 publications

Extraction of Unstructured Electronic Health Records to Evaluate Glioblastoma Treatment Patterns

Extraction of Unstructured Electronic Health Records to Evaluate Glioblastoma Treatment Patterns

Principles in the Management of Glioblastoma

The Basis and Advances in Clinical Application of Cytomegalovirus-Specific Cytotoxic T Cell Immunotherapy for Glioblastoma Multiforme

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