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Cancers Nov 2022: Posterior fossa tumors (PFTs) are a morbid group of central nervous system tumors that most often present in childhood. While early diagnosis is critical to drive... (Review)
Review
: Posterior fossa tumors (PFTs) are a morbid group of central nervous system tumors that most often present in childhood. While early diagnosis is critical to drive appropriate treatment, definitive diagnosis is currently only achievable through invasive tissue collection and histopathological analyses. Machine learning has been investigated as an alternative means of diagnosis. In this systematic review and meta-analysis, we evaluated the primary literature to identify all machine learning algorithms developed to classify and diagnose pediatric PFTs using imaging or molecular data. : Of the 433 primary papers identified in PubMed, EMBASE, and Web of Science, 25 ultimately met the inclusion criteria. The included papers were extracted for algorithm architecture, study parameters, performance, strengths, and limitations. : The algorithms exhibited variable performance based on sample size, classifier(s) used, and individual tumor types being investigated. Ependymoma, medulloblastoma, and pilocytic astrocytoma were the most studied tumors with algorithm accuracies ranging from 37.5% to 94.5%. A minority of studies compared the developed algorithm to a trained neuroradiologist, with three imaging-based algorithms yielding superior performance. Common algorithm and study limitations included small sample sizes, uneven representation of individual tumor types, inconsistent performance reporting, and a lack of application in the clinical environment. : Artificial intelligence has the potential to improve the speed and accuracy of diagnosis in this field if the right algorithm is applied to the right scenario. Work is needed to standardize outcome reporting and facilitate additional trials to allow for clinical uptake.
PubMed: 36428701
DOI: 10.3390/cancers14225608 -
Radiation Oncology (London, England) Nov 2022This systematic review aims to synthesise the outcomes of different strategies of incorporating functional biological markers in the radiation therapy plans of patients... (Review)
Review
RATIONALE
This systematic review aims to synthesise the outcomes of different strategies of incorporating functional biological markers in the radiation therapy plans of patients with glioblastoma to support clinicians and further research.
METHODS
The systematic review protocol was registered on PROSPERO (CRD42021221021). A structured search for publications was performed following PRISMA guidelines. Quality assessment was performed using the Newcastle-Ottawa Scale. Study characteristics, intervention methodology and outcomes were extracted using Covidence. Data analysis focused on radiation therapy target volumes, toxicity, dose distributions, recurrence and survival mapped to functional image-guided radiotherapy interventions.
RESULTS
There were 5733 citations screened, with 53 citations (n = 32 studies) meeting review criteria. Studies compared standard radiation therapy planning volumes with functional image-derived volumes (n = 20 studies), treated radiation therapy volumes with recurrences (n = 15 studies), the impact on current standard target delineations (n = 9 studies), treated functional volumes and survival (n = 8 studies), functionally guided dose escalation (n = 8 studies), radiomics (n = 4 studies) and optimal organ at risk sparing (n = 3 studies). The approaches to target outlining and dose escalation were heterogeneous. The analysis indicated an improvement in median overall survival of over two months compared with a historical control group. Simultaneous-integrated-boost dose escalation of 72-76 Gy in 30 fractions appeared to have an acceptable toxicity profile when delivered with inverse planning to a volume smaller than 100 cm[Formula: see text].
CONCLUSION
There was significant heterogeneity between the approaches taken by different study groups when implementing functional image-guided radiotherapy. It is recommended that functional imaging data be incorporated into the gross tumour volume with appropriate technology-specific margins used to create the clinical target volume when designing radiation therapy plans for patients with glioblastoma.
Topics: Humans; Glioblastoma; Radiotherapy Dosage; Radiotherapy, Intensity-Modulated; Radiotherapy Planning, Computer-Assisted; Functional Neuroimaging
PubMed: 36371225
DOI: 10.1186/s13014-022-02146-8 -
Journal of Neuro-oncology Nov 2022Shorter hypofractionated radiation therapy (HF-RT) schedules may have radiobiological, patient convenience and healthcare resource advantages over conventionally... (Meta-Analysis)
Meta-Analysis
Moderately hypofractionated versus conventionally fractionated radiation therapy with temozolomide for young and fit patients with glioblastoma: an institutional experience and meta-analysis of literature.
PURPOSE
Shorter hypofractionated radiation therapy (HF-RT) schedules may have radiobiological, patient convenience and healthcare resource advantages over conventionally fractionated radiation therapy (CF-RT) in glioblastoma (GBM). We report outcomes of young, fit GBM patients treated with HF-RT and CF-RT during the COVID-19 pandemic, and a meta-analysis of HF-RT literature in this patient subgroup.
METHODS
Hospital records of patients with IDH-wildtype GBM treated with HF-RT (50 Gy/20 fractions) and CF-RT (60 Gy/30 fractions) between January 2020 and September 2021 were reviewed. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. Univariable analysis was performed using Cox regression analysis. A systematic search and meta-analysis of studies from January 2000 to January 2022 was performed.
RESULTS
41 patients were treated (HF-RT:15, CF-RT:26). For both HF-RT and CF-RT groups, median age was 58 years and 80-90% were ECOG 0-1. There were more methylated tumours in the HF-RT group. All patients received concurrent/adjuvant temozolomide. At 19.2 months median follow-up, median OS was 19.8 months and not-reached for HF-RT and CF-RT (p = 0.5), and median PFS was 7.7 and 5.8 months, respectively (p = 0.8). HF-RT or CF-RT did not influence OS/PFS on univariable analysis. Grade 3 radionecrosis rate was 6.7% and 7.7%, respectively. 15 of 1135 studies screened from a systematic search were eligible for meta-analysis. For studies involving temozolomide, pooled median OS and PFS with HF-RT were 17.5 and 9.9 months (927 and 862 patients). Studies using shortened HF-RT schedules reported 0-2% Grade 3 radionecrosis rates.
CONCLUSION
HF-RT may offer equivalent outcomes and reduce treatment burden compared to CF-RT in young, fit GBM patients.
Topics: Humans; Middle Aged; Antineoplastic Agents, Alkylating; Brain Neoplasms; COVID-19; Glioblastoma; Pandemics; Temozolomide
PubMed: 36355260
DOI: 10.1007/s11060-022-04151-z -
Neurology India 2022Different variant of GBM has been reported viz. Epithelioid Glioblastoma (GBM-E), Rhabdoid GBM (GBM-R), Small cell GBM (GBM-SC), Giant cell GBM (GBM-GC), GBM with neuro...
OBJECTIVES
Different variant of GBM has been reported viz. Epithelioid Glioblastoma (GBM-E), Rhabdoid GBM (GBM-R), Small cell GBM (GBM-SC), Giant cell GBM (GBM-GC), GBM with neuro ectodermal differentiation (GBM-PNET) with unknown behavior.
MATERIALS
We conducted a systematic review and individual patient data analysis of these rare GBM variants. We searched PubMed, google search, and Cochrane library for eligible studies till July 1 2016 published in English language and collected data regarding age, sex, subtype and treatment received, Progression Free Survival (PFS), Overall Survival (OS). Statistical Package for social sciences (SPSS) v16 software was used for all statistical analysis.
RESULTS
We retrieved data of 196 patients with rare GBM subtypes. Among these GBM-GC is commonest (51%), followed by GBM-R (19%), GBM-PNET (13%), GBM-SC (9%) and GBM-E (8%). Median age at diagnosis was 38, 40, 43.5, 69.5 and 18 years, respectively. Male: female ratio was 2:1 for GBM-E, and 1:3 for GBM-SC. Maximal safe resection followed by adjuvant local radiation was used for most of the patients. However, 6 patients with GBM-PNET, 3 each of GBM-E, GBM-SC received adjuvant craniospinal radiation. Out of 88 patients who received chemotherapy, 64 received Temozolomide alone or combination chemotherapy containing Temozolomide. Median PFS and OS for the entire cohort were 9 and 16 months. In univariate analysis, patient with a Gross Total Resection had significantly better PFS and OS compared to those with a Sub Total Resection [23 vs. 13 months (p-0.01)]. Median OS for GBM PNET, GBM-GC, GBM-SC, GBM-R and GBM-E were 32, 18.3, 11, 12 and 7.7 months, respectively (P = 0.001). Interestingly, 31.3%, 37.8% of patients with GBM-E, GBM-R had CSF dissemination.
CONCLUSION
Overall cohort of rarer GBM variant has equivalent survival compared to GBM not otherwise specified. However, epithelioid and Rhabdoid GBM has worst survival and one third shows CSF dissemination.
Topics: Humans; Male; Female; Glioblastoma; Temozolomide; Data Analysis; Brain Neoplasms; Retrospective Studies; Neuroectodermal Tumors, Primitive; Antineoplastic Agents, Alkylating
PubMed: 36352613
DOI: 10.4103/0028-3886.359222 -
Frontiers in Surgery 2022Survival amongst posterior fossa tumour (PFT) patients is improving. Clinical endpoints such as overall survival fail to depict QoL. There is yet to be a review of... (Review)
Review
INTRODUCTION
Survival amongst posterior fossa tumour (PFT) patients is improving. Clinical endpoints such as overall survival fail to depict QoL. There is yet to be a review of current QoL instruments used for adult PFTs. Aim of this review is to outline the QoL reporting in the management of PFTs and measure participation level.
METHODS
This systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis. A search strategy to identify adult patients with PFTs who took part in QoL metrics was conducted. Observational and experimental studies published from 1990 to date were included. Studies with a sample size less than 10 and performance measures such as Karnofsky Performance Status were not considered.
RESULTS
A total of 116 studies were included in the final analysis. Vestibular schwannomas were the most common tumour pathology ( = 23,886, 92.6%) followed by pilocytic astrocytomas ( = 657, 2.5%) and meningiomas ( = 437, 1.7%) Twenty-five different QoL measures were used in the study pool. SF-36 was the most common ( = 55, 17 47.4%) QoL metric in the whole study pool, followed by the Penn Acoustic Neuroma QoL scale ( = 24, 20.7%) and Dizziness Handicap Inventory ( = 16, 13.8%). Seventy-two studies reported less-than 100% participation in QoL evaluation. The commonest reason for non-participation was a lack of response ( = 1,718, 60.8%), incomplete questionnaires ( = 268, 9.4%) and cognitive dysfunction ( = 258, 9.1%).
CONCLUSION
Informed clinical decision-making in PFT patients requires the development of specific QoL outcomes. Core outcome sets, and minimal clinically important differences (MCID) are essential for these metrics to show clinically significant improvements in patient QoL.
PubMed: 36303860
DOI: 10.3389/fsurg.2022.970889 -
Current Issues in Molecular Biology Oct 2022Both (isocitrate dehydrogenase 1) and (isocitrate dehydrogenase 2) mutations play a vital role in the development of gliomas through disruption of normal cellular...
Both (isocitrate dehydrogenase 1) and (isocitrate dehydrogenase 2) mutations play a vital role in the development of gliomas through disruption of normal cellular metabolic processes. Here we describe a case of a patient with an IDH-mutant astrocytoma, in which both and mutations were detected within the same tumour. The patient remains disease-free, nine and a half years after her initial diagnosis. Interrogation of cancer genomic databases and a systematic review was undertaken, demonstrating the rarity of the co-occurrence of and mutations in a variety of cancer types, and in glioma specifically. Due to the favourable outcome observed in this patient, the potential effect of concurrent and mutations on survival was also investigated.
PubMed: 36286062
DOI: 10.3390/cimb44100348 -
Brain & Spine 2022Pediatric Brain Tumors (PBT) are a common cause of cancer-related mortality globally. Contrary to high-income countries (HIC), survival rates in low-and-middle income... (Review)
Review
BACKGROUND
Pediatric Brain Tumors (PBT) are a common cause of cancer-related mortality globally. Contrary to high-income countries (HIC), survival rates in low-and-middle income countries (LMIC) remains low despite advances in neurosurgical care and diagnostics over the past decades. The aim of this systematic review was to investigate the surgical outcomes for PBT in Sub-Saharan Africa, and the distribution of PBT types.
METHODS
A systematic review was conducted on PubMed, for all available literature on the surgical outcomes of PBT in Sub-Saharan Africa, published before May 3, 2022. Two reviewers performed abstract, full text screening and data collection independently, resolving any conflicts by consensus.
RESULTS
The search yielded 256 studies, of which 22 met the inclusion criteria, amounting to a total of 243 patients. Nigeria was the country with most data. Only subgroups of patients could be extracted from 12 studies, and variables of interest in 6 studies had inconsistent sample sizes. The age centered around 9 years, and there were approximately equal number of girls and boys. The most common tumor was medulloblastoma, followed by craniopharyngioma and astrocytoma. There was large heterogeneity in the reporting of outcomes, and a trend was difficult to discern, considering the large number of different tumor types and different extents of resection.
DISCUSSION AND CONCLUSION
Data is insufficient and inconsistent, precluding statistical conclusions. There is a need for more studies in the field.
PubMed: 36248098
DOI: 10.1016/j.bas.2022.100912 -
European Journal of Cancer (Oxford,... Nov 2022Grading and classification of IDH-mutant astrocytomas has shifted from solely histology towards histology combined with molecular diagnostics. In this systematic review,... (Review)
Review
BACKGROUND
Grading and classification of IDH-mutant astrocytomas has shifted from solely histology towards histology combined with molecular diagnostics. In this systematic review, we give an overview of all currently known clinically relevant molecular markers within IDH-mutant astrocytomas grade 2 to 4.
METHODS
A literature search was performed in five electronic databases for English original papers on patient outcome with respect to a molecular marker as determined by DNA/RNA sequencing, micro-arrays, or DNA methylation profiling in IDH-mutant astrocytomas grade 2 to 4. Papers were included if molecular diagnostics were performed on tumour tissue of at least 15 IDH-mutant astrocytoma patients, and if the investigated molecular markers were not limited to the diagnostic markers MGMT, ATRX, TERT, and/or TP53.
RESULTS
The literature search identified 4508 unique articles, published between August 2012 and December 2021, of which ultimately 44 articles were included. Numerous molecular markers from these papers were significantly correlated to patient outcome. The associations between patient outcome and non-canonical IDH mutations, PI3K mutations, high expression of MSH2, high expression of RAD18, homozygous deletion of CDKN2A/B, amplification of PDGFRA, copy number neutral loss of chromosomal arm 17p, loss of chromosomal arm 19q, the G-CIMP-low DNA methylation cluster, high total CNV, and high tumour mutation burden were confirmed in multiple studies.
CONCLUSIONS
Multiple genetic and epigenetic markers are associated with survival in IDH-mutant astrocytoma patients. Commonly affected are the RB signalling pathway, the RTK-PI3K-mTOR signalling pathway, genomic stability markers, and (epigenetic) gene regulation.
Topics: Astrocytoma; Biomarkers, Tumor; Brain Neoplasms; DNA; DNA-Binding Proteins; Homozygote; Humans; Isocitrate Dehydrogenase; Lymphoma, Follicular; MutS Homolog 2 Protein; Mutation; Phosphatidylinositol 3-Kinases; Sequence Deletion; TOR Serine-Threonine Kinases; Ubiquitin-Protein Ligases
PubMed: 36152406
DOI: 10.1016/j.ejca.2022.08.016 -
Chinese Clinical Oncology Aug 2022Glioma is the most common intracranial primary malignant tumor, and half of it is glioblastoma. Despite receiving the standard treatment, the prognosis of glioblastoma...
BACKGROUND AND OBJECTIVE
Glioma is the most common intracranial primary malignant tumor, and half of it is glioblastoma. Despite receiving the standard treatment, the prognosis of glioblastoma is still poor and its 5-year survival rate in China is only 9%. In addition, new targeted and immunotherapy therapy and tumor treating fields also have certain curative effects on glioblastoma. To help clinicians and patients make appropriate treatment based on current evidences, we summarize the Chinese guidelines on the management of glioma and review the recent management of glioblastoma.
METHODS
We systematically searched PubMed, China National Knowledge Infrastructure (CNKI) and Wanfang databases to retrieve guidelines on glioma in China published from the establishment of the database to 24 January 2022. We performed a narrative review of current clinical study related to the management of glioblastoma, especially in the surgical, targeted and immunotherapy therapy and tumor treating fields.
KEY CONTENT AND FINDINGS
In this review, 19 guidelines were included, including 8 subclassified as the guideline, 8 subclassified as the consensus and 3 subclassified as the standard. Two guidelines reported the contents of the system search, 4 guidelines are updated, and 9 guidelines reported the source of funding. At present, most clinical trials on the immune and targeted therapy of glioblastoma are ongoing in China.
CONCLUSIONS
China's guidelines still need to be improved in terms of preciseness, applicability and editorial independence. In addition, the cooperation in clinical research of glioblastoma in multiple centers needs to be strengthened in China.
Topics: Brain Neoplasms; China; Databases, Factual; Glioblastoma; Glioma; Humans
PubMed: 36098100
DOI: 10.21037/cco-22-18 -
International Journal of Molecular... Aug 2022Background: Glioblastoma (GBM) is a highly aggressive cancer with poor prognosis that needs better treatment modalities. Moreover, there is a lack of reliable biomarkers... (Meta-Analysis)
Meta-Analysis Review
Background: Glioblastoma (GBM) is a highly aggressive cancer with poor prognosis that needs better treatment modalities. Moreover, there is a lack of reliable biomarkers to predict the response and outcome of current or newly designed therapies. While several molecular markers have been proposed as potential biomarkers for GBM, their uptake into clinical settings is slow and impeded by marker heterogeneity. Detailed assessment of prognostic and predictive value for biomarkers in well-defined clinical trial settings, if available, is scattered throughout the literature. Here we conducted a systematic review and meta-analysis to evaluate the prognostic and predictive significance of clinically relevant molecular biomarkers in GBM patients. Material and methods: A comprehensive literature search was conducted to retrieve publications from 3 databases (Pubmed, Cochrane and Embase) from January 2010 to December 2021, using specific terms. The combined hazard ratios (HR) and confidence intervals (95% CI) were used to evaluate the association of biomarkers with overall survival (OS) in GBM patients. Results: Twenty-six out of 1831 screened articles were included in this review. Nineteen articles were included in the meta-analyses, and 7 articles were quantitatively summarised. Fourteen studies with 1231 GBM patients showed a significant association of MGMT methylation with better OS with the pooled HR of 1.66 (95% CI 1.32−2.09, p < 0.0001, random effect). Five studies including 541 GBM patients analysed for the prognostic significance of IDH1 mutation showed significantly better OS in patients with IDH1 mutation with a pooled HR of 2.37 (95% CI 1.81−3.12; p < 0.00001]. Meta-analysis performed on 5 studies including 575 GBM patients presenting with either amplification or high expression of EGFR gene did not reveal any prognostic significance with a pooled HR of 1.31 (95% CI 0.96−1.79; p = 0.08). Conclusions: MGMT promoter methylation and IDH1 mutation are significantly associated with better OS in GBM patients. No significant associations were found between EGFR amplification or overexpression with OS.
Topics: Biomarkers; Biomarkers, Tumor; Brain Neoplasms; DNA Methylation; DNA Modification Methylases; DNA Repair Enzymes; Glioblastoma; Humans; Tumor Suppressor Proteins
PubMed: 36012105
DOI: 10.3390/ijms23168835