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Pharmacological Research Sep 2021Glioblastoma multiforme (GBM) is a WHO grade IV glioma and the most common malignant, primary brain tumor with a 5-year survival of 7.2%. Its highly infiltrative nature,...
Glioblastoma multiforme (GBM) is a WHO grade IV glioma and the most common malignant, primary brain tumor with a 5-year survival of 7.2%. Its highly infiltrative nature, genetic heterogeneity, and protection by the blood brain barrier (BBB) have posed great treatment challenges. The standard treatment for GBMs is surgical resection followed by chemoradiotherapy. The robust DNA repair and self-renewing capabilities of glioblastoma cells and glioma initiating cells (GICs), respectively, promote resistance against all current treatment modalities. Thus, durable GBM management will require the invention of innovative treatment strategies. In this review, we will describe biological and molecular targets for GBM therapy, the current status of pharmacologic therapy, prominent mechanisms of resistance, and new treatment approaches. To date, medical imaging is primarily used to determine the location, size and macroscopic morphology of GBM before, during, and after therapy. In the future, molecular and cellular imaging approaches will more dynamically monitor the expression of molecular targets and/or immune responses in the tumor, thereby enabling more immediate adaptation of tumor-tailored, targeted therapies.
Topics: Animals; Antineoplastic Agents; Brain Neoplasms; Drug Resistance, Neoplasm; Glioblastoma; Humans
PubMed: 34302977
DOI: 10.1016/j.phrs.2021.105780 -
Journal of Veterinary Internal Medicine 2015Intracranial neoplasia is commonly diagnosed in dogs and can be treated by a variety of methods, but formal comparisons of treatment efficacy are currently unavailable.... (Review)
Review
Intracranial neoplasia is commonly diagnosed in dogs and can be treated by a variety of methods, but formal comparisons of treatment efficacy are currently unavailable. This review was undertaken to summarize the current state of knowledge regarding outcome after the treatment of intracranial masses in dogs, with the aim of defining optimal recommendations for owners. This review summarizes data from 794 cases in 22 previously published reports and follows PRISMA guidelines for systematic review. A Pubmed search was used to identify suitable articles. These then were analyzed for quality and interstudy variability of inclusion and exclusion criteria and the outcome data extracted for summary in graphs and tables. There was a high degree of heterogeneity among studies with respect to inclusion and exclusion criteria, definition of survival periods, and cases lost to follow-up making comparisons among modalities troublesome. There is a need for standardized design and reporting of outcomes of treatment for brain tumors in dogs. The available data do not support lomustine as an effective treatment, but also do not show a clear difference in outcome between radiotherapy and surgery for those cases in which the choice is available.
Topics: Animals; Antineoplastic Agents; Brain Neoplasms; Dog Diseases; Dogs; Radiotherapy
PubMed: 26375164
DOI: 10.1111/jvim.13617 -
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 -
Journal of Thoracic Oncology : Official... Dec 2023Brain metastases (BMs) in patients with advanced and metastatic NSCLC are linked to poor prognosis. Identifying genomic alterations associated with BM development could... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Brain metastases (BMs) in patients with advanced and metastatic NSCLC are linked to poor prognosis. Identifying genomic alterations associated with BM development could influence screening and determine targeted treatment. We aimed to establish prevalence and incidence in these groups, stratified by genomic alterations.
METHODS
A systematic review and meta-analysis compliant with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses were conducted (PROSPERO identification CRD42022315915). Articles published in MEDLINE, EMBASE, and Cochrane Library between January 2000 and May 2022 were included. Prevalence at diagnosis and incidence of new BM per year were obtained, including patients with EGFR, ALK, KRAS, and other alterations. Pooled incidence rates were calculated using random effects models.
RESULTS
A total of 64 unique articles were included (24,784 patients with NSCLC with prevalence data from 45 studies and 9058 patients with NSCLC having incidence data from 40 studies). Pooled BM prevalence at diagnosis was 28.6% (45 studies, 95% confidence interval [CI]: 26.1-31.0), and highest in patients that are ALK-positive (34.9%) or with RET-translocations (32.2%). With a median follow-up of 24 months, the per-year incidence of new BM was 0.13 in the wild-type group (14 studies, 95% CI: 0.11-0.16). Incidence was 0.16 in the EGFR group (16 studies, 95% CI: 0.11-0.21), 0.17 in the ALK group (five studies, 95% CI: 0.10-0.27), 0.10 in the KRAS group (four studies, 95% CI: 0.06-0.17), 0.13 in the ROS1 group (three studies, 95% CI: 0.06-0.28), and 0.12 in the RET group (two studies, 95% CI: 0.08-0.17).
CONCLUSIONS
Comprehensive meta-analysis indicates a higher prevalence and incidence of BM in patients with certain targetable genomic alterations. This supports brain imaging at staging and follow-up, and the need for targeted therapies with brain penetrance.
Topics: Humans; Lung Neoplasms; Incidence; Protein-Tyrosine Kinases; Proto-Oncogene Proteins p21(ras); Proto-Oncogene Proteins; Carcinoma, Non-Small-Cell Lung; Genomics; Brain Neoplasms; Receptor Protein-Tyrosine Kinases; ErbB Receptors
PubMed: 37392903
DOI: 10.1016/j.jtho.2023.06.017 -
The Cochrane Database of Systematic... May 2021Glioblastoma (GBM) is a highly malignant brain tumour that almost inevitably progresses or recurs after first line standard of care. There is no consensus regarding the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Glioblastoma (GBM) is a highly malignant brain tumour that almost inevitably progresses or recurs after first line standard of care. There is no consensus regarding the best treatment/s to offer people upon disease progression or recurrence. For the purposes of this review, progression and recurrence are considered as one entity.
OBJECTIVES
To evaluate the effectiveness of further treatment/s for first and subsequent progression or recurrence of glioblastoma (GBM) among people who have received the standard of care (Stupp protocol) for primary treatment of the disease; and to prepare a brief economic commentary on the available evidence.
SEARCH METHODS
We searched MEDLINE and Embase electronic databases from 2005 to December 2019 and the Cochrane Central Register of Controlled Trials (CENTRAL, in the Cochrane Library; Issue 12, 2019). Economic searches included the National Health Service Economic Evaluation Database (NHS EED) up to 2015 (database closure) and MEDLINE and Embase from 2015 to December 2019.
SELECTION CRITERIA
Randomised controlled trials (RCTs) and comparative non-randomised studies (NRSs) evaluating effectiveness of treatments for progressive/recurrent GBM. Eligible studies included people with progressive or recurrent GBM who had received first line radiotherapy with concomitant and adjuvant temozolomide (TMZ).
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies and extracted data to a pre-designed data extraction form. We conducted network meta-analyses (NMA) and ranked treatments according to effectiveness for each outcome using the random-effects model and Stata software (version 15). We rated the certainty of evidence using the GRADE approach.
MAIN RESULTS
We included 42 studies: these comprised 34 randomised controlled trials (RCTs) and 8 non-randomised studies (NRSs) involving 5236 participants. We judged most RCTs to be at a low risk of bias and NRSs at high risk of bias. Interventions included chemotherapy, re-operation, re-irradiation and novel therapies either used alone or in combination. For first recurrence, we included 11 interventions in the network meta-analysis (NMA) for overall survival (OS), and eight in the NMA for progression-free survival (PFS). Lomustine (LOM; also known as CCNU) was the most common comparator and was used as the reference treatment. No studies in the NMA evaluated surgery, re-irradiation, PCV (procarbazine, lomustine, vincristine), TMZ re-challenge or best supportive care. We could not perform NMA for second or later recurrence due to insufficient data. Quality-of-life data were sparse. First recurrence (NMA findings) Median OS across included studies in the NMA ranged from 5.5 to 12.6 months and median progression-free survival (PFS) ranged from 1.5 months to 4.2 months. We found no high-certainty evidence that any treatments tested were better than lomustine. These treatments included the following. Bevacizumab plus lomustine: Evidence suggested probably little or no difference in OS between bevacizumab (BEV) combined with lomustine (LOM) and LOM monotherapy (hazard ratio (HR) 0.91, 0.75 to 1.10; moderate-certainty evidence), although BEV + LOM may improve PFS (HR 0.57, 95% confidence interval (CI) 0.44 to 0.74; low-certainty evidence). Bevacizumab monotherapy: Low-certainty evidence suggested there may be little or no difference in OS (HR 1.22, 95% CI 0.84 to 1.76) and PFS (HR 0.90, 95% CI 0.58 to 1.38; low-certainty evidence) between BEV and LOM monotherapies; more evidence on BEV is needed. Regorafenib (REG): REG may improve OS compared with LOM (HR 0.50, 95% CI 0.33 to 0.76; low-certainty evidence). Evidence on PFS was very low certainty and more evidence on REG is needed. Temozolomide (TMZ) plus Depatux-M (ABT414): For OS, low-certainty evidence suggested that TMZ plus ABT414 may be more effective than LOM (HR 0.66, 95% CI 0.47 to 0.92) and may be more effective than BEV (HR 0.54, 95% CI 0.33 to 0.89; low-certainty evidence). This may be due to the TMZ component only and more evidence is needed. Fotemustine (FOM): FOM and LOM may have similar effects on OS (HR 0.89, 95% CI 0.51 to 1.57, low-certainty evidence). Bevacizumab and irinotecan (IRI): Evidence on BEV + irinotecan (IRI) versus LOM for both OS and PFS is very uncertain and there is probably little or no difference between BEV + IRI versus BEV monotherapy (OS: HR 0.95, 95% CI 0.70 to 1.30; moderate-certainty evidence). When treatments were ranked for OS, FOM ranked first, BEV + LOM second, LOM third, BEV + IRI fourth, and BEV fifth. Ranking does not take into account the certainty of the evidence, which also suggests there may be little or no difference between FOM and LOM. Other treatments Three studies evaluated re-operation versus no re-operation, with or without re-irradiation and chemotherapy, and these suggested possible survival advantages with re-operation within the context of being able to select suitable candidates for re-operation. A cannabinoid treatment in the early stages of evaluation, in combination with TMZ, merits further evaluation. Second or later recurrence Limited evidence from three heterogeneous studies suggested that radiotherapy with or without BEV may have a beneficial effect on survival but more evidence is needed. Evidence was insufficient to draw conclusions about the best radiotherapy dosage. Other evidence suggested that there may be little difference in survival with tumour-treating fields compared with physician's best choice of treatment. We found no reliable evidence on best supportive care. Severe adverse events (SAEs) The BEV+LOM combination was associated with significantly greater risk of SAEs than LOM monotherapy (RR 2.51, 95% CI 1.72 to 3.66, high-certainty evidence), and ranked joint worst with cediranib + LOM (RR 2.51, 95% CI 1.29 to 4.90; high-certainty evidence). LOM ranked best and REG ranked second best. Adding novel treatments to BEV was generally associated with a higher risk of severe adverse events compared with BEV alone.
AUTHORS' CONCLUSIONS
For treatment of first recurrence of GBM, among people previously treated with surgery and standard chemoradiotherapy, the combination treatments evaluated did not improve overall survival compared with LOM monotherapy and were often associated with a higher risk of severe adverse events. Limited evidence suggested that re-operation with or without re-irradiation and chemotherapy may be suitable for selected candidates. Evidence on second recurrence is sparse. Re-irradiation with or without bevacizumab may be of value in selected individuals, but more evidence is needed.
Topics: Brain Neoplasms; Glioblastoma; Humans; Lomustine; Neoplasm Recurrence, Local; Network Meta-Analysis
PubMed: 34559423
DOI: 10.1002/14651858.CD013579.pub2 -
Neuro-oncology Jun 2021Patients with metastatic breast cancer (MBC) are living longer, but the development of brain metastases often limits their survival. We conducted a systematic review and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Patients with metastatic breast cancer (MBC) are living longer, but the development of brain metastases often limits their survival. We conducted a systematic review and meta-analysis to determine the incidence of brain metastases in this patient population.
METHODS
Articles published from January 2000 to January 2020 were compiled from four databases using search terms related to breast cancer, brain metastasis, and incidence. The overall and per patient-year incidence of brain metastases were extracted from studies including patients with human epidermal growth factor receptor-2 positive (HER2+), triple negative, and hormone receptor (HR)+/hormone receptor negative (HER2-) MBC; pooled overall estimates for incidence were calculated using random effects models.
RESULTS
937 articles were compiled, and 25 were included in the meta-analysis. Incidence of brain metastases in patients with HER2+ MBC, triple negative MBC, and HR+/HER2- MBC was reported in 17, 6, and 4 studies, respectively. The pooled cumulative incidence of brain metastases was 31% for the HER2+ subgroup (median follow-up: 30.7 months, IQR: 24.0-34.0), 32% for the triple negative subgroup (median follow-up: 32.8 months, IQR: 18.5-40.6), and 15% among patients with HR+/HER2- MBC (median follow-up: 33.0 months, IQR: 31.9-36.2). The corresponding incidences per patient-year were 0.13 (95% CI: 0.10-0.16) for the HER2+ subgroup, 0.13 (95%CI: 0.09-0.20) for the triple negative subgroup, and only 0.05 (95%CI: 0.03-0.08) for patients with HR+/HER2- MBC.
CONCLUSION
There is a high incidence of brain metastases among patients with HER2+ and triple negative MBC. The utility of a brain metastases screening program warrants investigation in these populations.
Topics: Brain Neoplasms; Breast Neoplasms; Female; Humans; Incidence; Receptor, ErbB-2; Triple Negative Breast Neoplasms
PubMed: 33367836
DOI: 10.1093/neuonc/noaa285 -
JAMA Oncology Nov 2016Glioblastoma multiforme (GBM) remains almost invariably fatal despite optimal surgical and medical therapy. The association between the extent of tumor resection (EOR)... (Meta-Analysis)
Meta-Analysis Review
IMPORTANCE
Glioblastoma multiforme (GBM) remains almost invariably fatal despite optimal surgical and medical therapy. The association between the extent of tumor resection (EOR) and outcome remains undefined, notwithstanding many relevant studies.
OBJECTIVE
To determine whether greater EOR is associated with improved 1- and 2-year overall survival and 6-month and 1-year progression-free survival in patients with GBM.
DATA SOURCES
Pubmed, CINAHL, and Web of Science (January 1, 1966, to December 1, 2015) were systematically reviewed with librarian guidance. Additional articles were included after consultation with experts and evaluation of bibliographies. Articles were collected from January 15 to December 1, 2015.
STUDY SELECTION
Studies of adult patients with newly diagnosed supratentorial GBM comparing various EOR and presenting objective overall or progression-free survival data were included. Pediatric studies were excluded.
DATA EXTRACTION AND SYNTHESIS
Data were extracted from the text of articles or the Kaplan-Meier curves independently by investigators who were blinded to each other's results. Data were analyzed to assess mortality after gross total resection (GTR), subtotal resection (STR), and biopsy. The body of evidence was evaluated according to Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria and PRISMA guidelines.
MAIN OUTCOME AND MEASURES
Relative risk (RR) for mortality at 1 and 2 years and progression at 6 months and 1 year.
RESULTS
The search produced 37 studies suitable for inclusion (41 117 unique patients). The meta-analysis revealed decreased mortality for GTR compared with STR at 1 year (RR, 0.62; 95% CI, 0.56-0.69; P < .001; number needed to treat [NNT], 9) and 2 years (RR, 0.84; 95% CI, 0.79-0.89; P < .001; NNT, 17). The 1-year risk for mortality for STR compared with biopsy was reduced significantly (RR, 0.85; 95% CI, 0.80-0.91; P < .001). The risk for mortality was similarly decreased for any resection compared with biopsy at 1 year (RR, 0.77; 95% CI, 0.71-0.84; P < .001; NNT, 21) and 2 years (RR, 0.94; 95% CI, 0.89-1.00; P = .04; NNT, 593). The likelihood of disease progression was decreased with GTR compared with STR at 6 months (RR, 0.72; 95% CI, 0.48-1.09; P = .12; NNT, 14) and 1 year (RR, 0.66; 95% CI, 0.43-0.99; P < .001; NNT, 26). The quality of the body of evidence by the GRADE criteria was moderate to low.
CONCLUSION AND RELEVANCE
This analysis represents the largest systematic review and only quantitative systematic review to date performed on this subject. Compared with STR, GTR substantially improves overall and progression-free survival, but the quality of the supporting evidence is moderate to low.
Topics: Brain; Brain Neoplasms; Disease-Free Survival; Glioblastoma; Humans; Risk; Treatment Outcome
PubMed: 27310651
DOI: 10.1001/jamaoncol.2016.1373 -
Frontiers in Immunology 2022Although immunotherapy has been widely used, there is currently no research comparing immunotherapy for non-small cell lung cancer (NSCLC) patients with brain metastases... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Although immunotherapy has been widely used, there is currently no research comparing immunotherapy for non-small cell lung cancer (NSCLC) patients with brain metastases (BMs). This meta-analysis addresses a gap in the comparison of immunotherapy efficacy, including immune checkpoint inhibitors (ICIs), chemotherapy (CT), radiotherapy (RT), and ICI combined CT or RT.
METHODS
A search of Pubmed, Cochrane, EMBASE, and ClinicalTrial.gov was conducted to identify studies which enrolled NSCLC patients with BM treated with ICIs. The outcomes consisted of intracerebral overall response rate (iORR), intracerebral disease control rate (iDCR), extracranial overall response rate (EORR), distant brain failure (DBF), local control (LC), progression-free survival (PFS), and overall survival (OS).
RESULTS
A total of 3160 participants from 46 trials were included in the final analysis. Patients treated with immunotherapy were associated with a longer PFS (0.48, 95%CI: 0.41-0.56), and a longer OS (0.64, 95%CI: 0.60-0.69) compared with immunotherapy-naive patients. In prospective studies, dual ICI combined CT and ICI combined CT achieved a better OS. The hazard ratio (HR) of dual ICI combined CT versus dual ICI was 0.61, and the HR of ICI combined CT versus ICI monotherapy was 0.58. Moreover, no statistical difference in PFS, OS, EORR, iORR, iDCR, and EDCR was found between patients with ICI monotherapy and ICI combined cranial radiotherapy. Concurrent ICI combined RT was shown to decrease the rate of DBF (OR = 0.15, 95% CI: 0.03-0.73) compared with RT after ICI. Patients treated with WBRT might have an inferior efficacy than those with SRS because the iORR of SRS was 0.75 (0.70, 0.80) and WBRT was 0. Furthermore, no obvious difference in PFS and OS was observed among the three different types of ICI, which targets PD-1, PD-L1, and CTLA-4, respectively.
CONCLUSIONS
Patients treated with ICI got superior efficacy to those without ICI. Furthermore, dual ICI combined CT and ICI combined CT seemed to be optimal for NSCLC patients with BM. In terms of response and survival, concurrent administration of SRS and ICI led to better outcomes for patients with BMs than non-concurrent or non-SRS.
IMPORTANCE OF THE STUDY
In the new era of immunotherapy, our meta-analysis validated the importance of immunotherapy for non-small cell lung cancer (NSCLC) patients with brain metastases (BMs). By comparing the long-term and short-term impacts of various regimens, all immunotherapy treatments had superior efficacy to immunotherapy-naive. At the same time, through pairwise comparison in immunotherapy, our findings can help clinicians to make treatment decisions for NSCLC patients with BMs.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=269621, identifier CRD42021269621.
Topics: Brain Neoplasms; Carcinoma, Non-Small-Cell Lung; Humans; Immunotherapy; Lung Neoplasms; Prospective Studies
PubMed: 35693805
DOI: 10.3389/fimmu.2022.875488 -
International Journal of Molecular... Oct 2023Glioblastoma (GBM) is characterized by aggressive growth and high rates of recurrence. Despite the advancements in conventional therapies, the prognosis for GBM patients... (Review)
Review
Glioblastoma (GBM) is characterized by aggressive growth and high rates of recurrence. Despite the advancements in conventional therapies, the prognosis for GBM patients remains poor. Immunotherapy has recently emerged as a potential treatment option. The aim of this systematic review is to assess the current strategies and future perspectives of the GBM immunotherapy strategies. A systematic search was conducted across major medical databases (PubMed, Embase, and Cochrane Library) up to 3 September 2023. The search strategy utilized relevant Medical Subject Heading (MeSH) terms and keywords related to "glioblastomas," "immunotherapies," and "treatment." The studies included in this review consist of randomized controlled trials, non-randomized controlled trials, and cohort studies reporting on the use of immunotherapies for the treatment of gliomas in human subjects. A total of 1588 papers are initially identified. Eligibility is confirmed for 752 articles, while 655 are excluded for various reasons, including irrelevance to the research topic (627), insufficient method and results details (12), and being case-series or cohort studies (22), systematic literature reviews, or meta-analyses (3). All the studies within the systematic review were clinical trials spanning from 1995 to 2023, involving 6383 patients. Neuro-oncology published the most glioma immunotherapy-related clinical trials (15/97, 16%). Most studies were released between 2018 and 2022, averaging nine publications annually during this period. Adoptive cellular transfer chimeric antigen receptor (CAR) T cells were the primary focus in 11% of the studies, with immune checkpoint inhibitors (ICIs), oncolytic viruses (OVs), and cancer vaccines (CVs) comprising 26%, 12%, and 51%, respectively. Phase-I trials constituted the majority at 51%, while phase-III trials were only 7% of the total. Among these trials, 60% were single arm, 39% double arm, and one multi-arm. Immunotherapies were predominantly employed for recurrent GBM (55%). The review also revealed ongoing clinical trials, including 9 on ICIs, 7 on CVs, 10 on OVs, and 8 on CAR T cells, totaling 34 trials, with phase-I trials representing the majority at 53%, and only one in phase III. Overcoming immunotolerance, stimulating robust tumor antigen responses, and countering immunosuppressive microenvironment mechanisms are critical for curative GBM immunotherapy. Immune checkpoint inhibitors, such as PD-1 and CTLA-4 inhibitors, show promise, with the ongoing research aiming to enhance their effectiveness. Personalized cancer vaccines, especially targeting neoantigens, offer substantial potential. Oncolytic viruses exhibited dual mechanisms and a breakthrough status in the clinical trials. CAR T-cell therapy, engineered for specific antigen targeting, yields encouraging results, particularly against IL13 Rα2 and EGFRvIII. The development of second-generation CAR T cells with improved specificity exemplifies their adaptability.
Topics: Humans; Glioblastoma; Immune Checkpoint Inhibitors; Cancer Vaccines; Neoplasm Recurrence, Local; Glioma; Immunotherapy; Immunotherapy, Adoptive; Brain Neoplasms; Tumor Microenvironment
PubMed: 37894718
DOI: 10.3390/ijms242015037 -
International Journal of Radiation... Jan 2024Radiation necrosis (RN) secondary to stereotactic radiosurgery is a significant cause of morbidity. The optimal management of corticosteroid-refractory brain RN remains... (Review)
Review
A Systematic Review Informing the Management of Symptomatic Brain Radiation Necrosis After Stereotactic Radiosurgery and International Stereotactic Radiosurgery Society Recommendations.
Radiation necrosis (RN) secondary to stereotactic radiosurgery is a significant cause of morbidity. The optimal management of corticosteroid-refractory brain RN remains unclear. Our objective was to summarize the literature specific to efficacy and toxicity of treatment paradigms for patients with symptomatic corticosteroid-refractory RN and to provide consensus guidelines for grading and management of RN on behalf of the International Stereotactic Radiosurgery Society. A systematic review of articles pertaining to treatment of RN with bevacizumab, laser interstitial thermal therapy (LITT), surgical resection, or hyperbaric oxygen therapy was performed. The primary composite outcome was clinical and/or radiologic stability/improvement (ie, proportion of patients achieving improvement or stability with the given intervention). Proportions of patients achieving the primary outcome were pooled using random weighted-effects analysis but not directly compared between interventions. Twenty-one articles were included, of which only 2 were prospective studies. Thirteen reports were relevant for bevacizumab, 5 for LITT, 5 for surgical resection and 1 for hyperbaric oxygen therapy. Weighted effects analysis revealed that bevacizumab had a pooled symptom improvement/stability rate of 86% (95% CI 77%-92%), pooled T2 imaging improvement/stability rate of 93% (95% CI 87%-98%), and pooled T1 postcontrast improvement/stability rate of 94% (95% CI 87%-98%). Subgroup analysis showed a statistically significant improvement favoring treatment with low-dose (below median, ≤7.5 mg/kg every 3 weeks) versus high-dose bevacizumab with regards to symptom improvement/stability rate (P = .02) but not for radiologic T1 or T2 changes. The pooled T1 postcontrast improvement/stability rate for LITT was 88% (95% CI 82%-93%), and pooled symptom improvement/stability rate for surgery was 89% (95% CI 81%-96%). Toxicity was inconsistently reported but was generally low for all treatment paradigms. Corticosteroid-refractory RN that does not require urgent surgical intervention, with sufficient noninvasive diagnostic testing that favors RN, can be treated medically with bevacizumab in carefully selected patients as a strong recommendation. The role of LITT is evolving as a less invasive image guided surgical modality; however, the overall evidence for each modality is of low quality. Prospective head-to-head comparisons are needed to evaluate the relative efficacy and toxicity profile among treatment approaches.
Topics: Humans; Radiosurgery; Bevacizumab; Prospective Studies; Brain Neoplasms; Brain; Radiation Injuries; Necrosis; Adrenal Cortex Hormones; Retrospective Studies
PubMed: 37482137
DOI: 10.1016/j.ijrobp.2023.07.015