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Cancer Medicine Feb 2021A combination of programmed cell death protein-1 (PD-1)/programmed cell death ligand-1 (PD-L1) inhibitors and radiotherapy (RT) is increasingly being used to treat... (Meta-Analysis)
Meta-Analysis
BACKGROUND
A combination of programmed cell death protein-1 (PD-1)/programmed cell death ligand-1 (PD-L1) inhibitors and radiotherapy (RT) is increasingly being used to treat non-small-cell lung cancer (NSCLC). However, the safety and efficacy of this approach remains controversial. We performed a systematic review and meta-analysis to summarize the related research.
METHODS
We searched the China Biology Medicine, EMBASE, Cochrane Library, and PubMed databases for all the relevant studies. The Stata software, version 12.0 was used for the meta-analysis.
RESULTS
The study included 20 clinical trials that enrolled 2027 patients with NSCLC. Compared with non-combination therapy, combination therapy using PD-1/PD-L1 inhibitors and RT was associated with prolonged overall survival (OS) (1-year OS: odds ratio [OR] 1.77, 95% confidence interval [CI] 1.35-2.33, p = 0.000; 2-year OS: OR 1.77, 95% CI 1.35-2.33, p = 0.000) and progression-free survival (PFS) (0.5-year PFS: OR 1.83, 95% CI 1.13-2.98, p = 0.014; 1-year PFS: OR 2.09, 95% CI 1.29-3.38, p = 0.003; 2-year PFS: OR 2.47, 95% CI 1.13-5.37, p = 0.023). Combination therapy also improved the objective response rate (OR 2.76, 95% CI 1.06-7.19, p = 0.038) and disease control rate (OR 1.80, 95% CI 1.21-2.68, p = 0.004). This meta-analysis showed that compared with non-combination therapy, combination therapy using PD-1/PD-L1 inhibitors and RT did not increase the serious adverse event rates (≥grade 3); however, this approach increased the rate of grade 1-2 immune-related or radiation pneumonitis. Subgroup analyses revealed that the sequence of PD-1/PD-L1 inhibitors followed RT outperformed in which concurrent PD-1/PD-L1 inhibitor and RT followed PD-1/PD-L1 inhibitor. Combination of stereotactic body RT or stereotactic radiosurgery with PD-1/PD-L1 inhibitors may be more effective than a combination of conventional RT with PD-1/PD-L1 inhibitors in patients with advanced NSCLC.
CONCLUSION
Combination therapy using PD-1/PD-L1 inhibitors and RT may improve OS, PFS, and tumor response rates without an increase in serious adverse events in patients with advanced NSCLC. However, combination therapy was shown to increase the incidence of mild pneumonitis.
Topics: B7-H1 Antigen; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Combined Modality Therapy; Humans; Immune Checkpoint Inhibitors; Immunotherapy; Lung Neoplasms; Programmed Cell Death 1 Receptor; Radiosurgery; Randomized Controlled Trials as Topic; Survival Rate
PubMed: 33465302
DOI: 10.1002/cam4.3718 -
World Neurosurgery Jul 2019Frame-based stereotaxy has generally been considered the reference standard for brain biopsies. However, frameless stereotaxy might expedite the efficiency of the... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Frame-based stereotaxy has generally been considered the reference standard for brain biopsies. However, frameless stereotaxy might expedite the efficiency of the clinical work flow. Conflicting findings have been reported regarding the relative efficacy and safety of frame-based and frameless needle biopsy of brain lesions. We performed a meta-analysis of the reported data to compare the relative efficacy, safety, and time efficiency of frame-based and frameless stereotactic needle biopsy.
METHODS
The PubMed database was searched for studies comparing frame-based and frameless biopsy. Of the 5248 reports found, 15 were included in the present meta-analysis.
RESULTS
The 15 studies included in the present meta-analysis included 2400 patients. Our analysis found no statistically significant differences between frame-based and frameless biopsy in the diagnostic yield (odds ratio [OR], 1.01; 95% confidence interval [CI], 0.71-1.41), morbidity (OR, 1.13; 95% CI, 0.76-1.66), mortality (OR, 0.94; 95% CI, 0.40-2.17), postbiopsy hemorrhage (OR, 1.16; 95% CI, 0.68-1.96), and postbiopsy neurological deficit (OR, 1.01; 95% CI, 0.62-1.65). The results from our integrated analysis indicated that frameless biopsies are associated with a shorter procedural time relative to frame-based biopsy (standard difference in the mean, 0.64; 95% CI, 0.24-1.04; P = 0.002; I [Higgins inconsistency index] = 86.66%).
CONCLUSIONS
The results from our meta-analysis suggest no significant differences exist between frame-based and frameless biopsy in diagnostic yield, morbidity, and mortality. Frameless biopsy is associated with shorter procedural times relative to frame-based biopsy. We have also discussed the relative merits of frame-based and frameless biopsies.
Topics: Biopsy; Brain; Epidemiologic Methods; Female; Humans; Male; Middle Aged; Neuronavigation; Operative Time; Publication Bias; Surgical Instruments; Treatment Outcome
PubMed: 30974279
DOI: 10.1016/j.wneu.2019.04.016 -
Neurosurgical Review Jun 2019Over the last years, fluorescence-based technology has begun an emergent intraoperative method for diagnostic confirmation of brain tumor tissue in stereotactic needle...
Over the last years, fluorescence-based technology has begun an emergent intraoperative method for diagnostic confirmation of brain tumor tissue in stereotactic needle biopsy. However, the actual level of evidence is quite low, especially about fluorescein sodium (FL) application. This method needs to be further validated and better analyzed about its impact in clinical practice. Retrospective analysis of 11 cases with contrast-enhancing brain tumors, underwent awake stereotactic needle biopsy with intraoperative FL assistance (group 1), was verified under the operative microscope filter. This group was matched with a control group of 18 patients (group 2). In addition, a systematic literature review was performed in PubMed/Medline database according to PRISMA statement. All studies concerning FL or 5-ALA application in stereotactic biopsy as intraoperative confirmation of brain tumor tissue were included. The primary endpoint was the evaluation of diagnostic accuracy. In group 1, all fluorescent specimens were diagnostic. The number of samplings was the useful minimum and non-use of intraoperative neuropathological examination allowed to significantly reduce procedure time (42.09 vs 69.72 min of group 2). No complications occurred, and the average hospitalization time after procedure was 1.09 days (vs 2.33 of group 2). Literature analysis supports the usefulness of photodiagnosis and its high diagnostic yield especially at the core of high-grade/contrast-enhancing tumors. FL assistance during stereotactic biopsy of contrast-enhancing brain tumors may give a real-time confirmation of tumor tissue, maximizing the diagnostic yield, and reducing time of procedure, morbidity, and hospitalization.
Topics: Adult; Aged; Aminolevulinic Acid; Biopsy, Needle; Brain; Brain Neoplasms; Female; Fluorescein; Fluorescence; Fluorescent Dyes; Humans; Intraoperative Period; Male; Microscopy; Middle Aged; Retrospective Studies; Stereotaxic Techniques
PubMed: 29383601
DOI: 10.1007/s10143-018-0947-z -
Neurosurgery Jun 2013The feasibility and safety of stereotactic biopsy for brainstem tumors (BSTs) are controversial. Although magnetic resonance imaging (MRI) has been reported as the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The feasibility and safety of stereotactic biopsy for brainstem tumors (BSTs) are controversial. Although magnetic resonance imaging (MRI) has been reported as the preferred diagnostic tool, histopathological analysis is frequently necessary to establish a definitive diagnosis. Recent advances in molecular characterization of brainstem gliomas-accounting for the majority of BSTs-have revealed several potential targets for molecular-based therapies. Hence, a molecular stereotactic biopsy that combines histopathological diagnosis with molecular-genetic analysis will become increasingly important for patients with BSTs.
OBJECTIVE
We conducted a systemic review and meta-analysis to determine the risks and benefits of stereotactic biopsy for BSTs.
METHODS
A systematic search in PubMed, Embase, and the Web of Science yielded 3766 potentially eligible abstracts. Meta-analysis was conducted on 38 studies describing 1480 biopsy procedures for BSTs. Primary outcome measures were diagnostic success and procedure-related complications. Data were analyzed according to standard meta-analytic techniques.
RESULTS
The weighted average proportions across the analyzed studies were: 96.2% (95% confidence interval [CI]: 94.5%-97.6%) for diagnostic success, 7.8% (95% CI: 5.6%-10.2%) for overall morbidity, 1.7% (95% CI: 0.9%-2.7%) for permanent morbidity, and 0.9% (95% CI: 0.5%-1.4%) for mortality. Meta-regression revealed a significant correlation between diagnostic success rates and the number of biopsy procedures performed annually in each center (P = .011). Other factors did not affect the outcome measures.
CONCLUSION
Stereotactic biopsy of BSTs is safe. It allows exact histopathological diagnosis as a prerequisite for adequate treatment and opens new perspectives for the molecular characterization of these tumors as a crucial first step toward more individualized treatment concepts.
ABBREVIATIONS
: BST, brainstem tumorCI, confidence intervalD-BSG, diffuse brainstem gliomaHGG, high-grade gliomaLGG, low-grade gliomasTC, transcerebellarTF, transfrontal.
Topics: Biopsy; Brain Stem Neoplasms; Humans; Stereotaxic Techniques
PubMed: 23426149
DOI: 10.1227/NEU.0b013e31828bf445 -
Neurosurgical Review Feb 2021Stereotactic frame-based brain biopsy is one of the most used procedures to obtain brain tissue. This procedure is usually considered as mini-invasive, quick, efficient,...
Stereotactic frame-based brain biopsy is one of the most used procedures to obtain brain tissue. This procedure is usually considered as mini-invasive, quick, efficient, and safe even if results of the different studies are widely heterogenous. The objective of this review of the literature is to describe and analyze the complications of stereotactic frame-based brain biopsy. About 132 articles were found after a research in the Medline database. We only considered English references published between 1994 and June 2019. Additional studies were found by using the references from articles identified in the original search. This systematic review was conducted according to PRISMA guidelines. After applying exclusion criteria, we eventually considered 25 relevant studies. The mortality rate varies from 0.7 to 4%. Overall morbidity ranges from 3 to 13%. Most of the complications are revealed by the following symptoms: neurological impairment (transient or permanent), seizure, and unconsciousness. Symptomatic hemorrhage range varies from 0.9 to 8.6%, whereas considering asymptomatic bleeding, the range may be up to 59.8%. Complications were clinically evident within minutes to a few hours after the biopsy. Corrective surgeries are very rare (< 1%). Complications occurring after a frame-based stereotactic brain biopsy are rare but with serious side effects. It rarely leads to death or to permanent neurological impairment. Description and classification of complications are often heterogeneous in the literature. The use of a grading scale could help comparisons between series from around the world. Future studies should establish a score that allows neurosurgeon to predict post-biopsy complications.
Topics: Biopsy; Brain; Brain Neoplasms; Cerebral Hemorrhage; Female; Humans; Male; Postoperative Complications; Stereotaxic Techniques
PubMed: 31900737
DOI: 10.1007/s10143-019-01234-w -
World Neurosurgery Feb 2017To evaluate the diagnostic value and safety of stereotactic biopsy in acquired immune deficiency syndrome (AIDS) patients with intracranial lesions via meta-analysis. (Review)
Review
OBJECTIVE
To evaluate the diagnostic value and safety of stereotactic biopsy in acquired immune deficiency syndrome (AIDS) patients with intracranial lesions via meta-analysis.
METHODS
Relevant cohort studies were identified through a literature search in PubMed, Embase, and Ovid from 1985 to October 1, 2016. Appropriate studies were identified per search criteria. Systematic review and meta-analysis were used to assess the diagnostic success rate, changed management rate, clinical improvement rate, mortality rate, morbidity rate, hemorrhage rate, hemorrhage in morbidity rate, and final histologic diagnosis results. Study-specific outcomes were combined per a random effects model. Outcomes were compared between the pre-highly active antiretroviral therapy (HAART) and post-HAART groups. Correlations between outcomes were assessed via meta-regression analysis.
RESULTS
A total of 19 cohort studies with 820 patients were included in this meta-analysis. The weighted proportions per the random effects model were 92.2% (95% confidence interval [CI; 89.3%-94.5%]) for diagnostic success rate, 5.1% (95% CI [2.5%-8.3%]) for morbidity, and 0.7% (95% CI [0%-1.9%]) for mortality. The most common procedure-related morbidity was hemorrhage at 3.3% (95% CI [1.1%-6.3%]). Hemorrhage in morbidity was 78.0% (95% CI [51.4%-97.4%]). Management changed and clinical improvement were 60.4% (95% CI [49.4%-71.0%]) and 34.0% (95% CI [22.2%-46.8%]), respectively. The 4 most common diagnoses were primary central nervous system lymphoma (27.8%; 95% CI [20.2%-36.1%]), progressive multifocal leukoencephalopathy (PML) (21.0%; 95% CI [14.3%-28.4%]), toxoplasma encephalitis (TE) (20.3%; 95% CI [14.3%-27.0%]), and human immunodeficiency virus (HIV) encephalitis (4.1%; 95% CI [1.4%-7.6%]). Multiple diagnoses rate was 1.2% (95% CI [0.0%-3.6%]). HIV encephalitis rate was significantly higher in the post-HAART group than the pre-HAART group (17.9% vs. 3.2%, respectively; P = 0.0024).
CONCLUSIONS
Stereotactic biopsy is a safe and effective way of diagnosing intracranial lesions in patients with AIDS. It is helpful for the differential diagnosis and for choosing a suitable therapy. The 4 most common intracranial lesions in patients with AIDS are lymphoma, PML, TE, and HIV encephalitis.
Topics: AIDS Dementia Complex; AIDS-Related Opportunistic Infections; Antiretroviral Therapy, Highly Active; Biopsy; Brain; Female; Humans; Leukoencephalopathy, Progressive Multifocal; Male; Patient Safety; Stereotaxic Techniques; Tomography, X-Ray Computed; Toxoplasmosis, Cerebral
PubMed: 27965075
DOI: 10.1016/j.wneu.2016.11.151 -
Journal of Neurosurgery. Pediatrics Sep 2017OBJECTIVE Recent studies have shed light on the molecular makeup of diffuse intrinsic pontine gliomas and led to the identification of potential treatment targets for... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE Recent studies have shed light on the molecular makeup of diffuse intrinsic pontine gliomas and led to the identification of potential treatment targets for these lesions, which account for the majority of pediatric brainstem tumors (pedBSTs). Therefore, stereotactic biopsy-driven molecular characterization of pedBSTs may become an important prerequisite for the management of these fatal brain tumors. The authors conducted a systemic review and meta-analysis to precisely determine the safety and diagnostic success of stereotactic biopsy of pedBSTs. METHODS A systematic search of PubMed, EMBASE, and the Web of Science yielded 944 potentially eligible abstracts. Meta-analysis was conducted on 18 studies (including the authors' own institutional series), describing a total of 735 biopsy procedures for pedBSTs. The primary outcome measures were diagnostic success and procedure-related complications. Pooled estimates were calculated based on the Freeman-Tukey double-arcsine transformation and DerSimonian-Laird random-effects model. Heterogeneity, sensitivity, and meta-regression analyses were also conducted. RESULTS The weighted average proportions across the analyzed studies were 96.1% (95% CI 93.5%-98.1%) for diagnostic success, 6.7% (95% CI 4.2%-9.6%) for overall morbidity, 0.6% (95% CI 0.2%-1.4%) for permanent morbidity, and 0.6% (95% CI 0.2%-1.3%) for mortality. Subgroup analyses at the study level identified no significant correlation between the outcome measures and the distribution of the chosen biopsy trajectories (transfrontal vs transcerebellar), age, year of publication, or the number of biopsy procedures annually performed in each center. CONCLUSION Stereotactic biopsy of pedBSTs is safe and allows successful tissue sampling as a prerequisite for the molecular characterization and the identification of potentially druggable targets toward more individualized treatment concepts to improve the outcome for children harboring such lesions.
Topics: Biopsy; Brain Stem Neoplasms; Child; Humans; Stereotaxic Techniques
PubMed: 28621573
DOI: 10.3171/2017.2.PEDS1665 -
BMC Cancer Oct 2023Brain metastases are the most common intracranial tumours. Variation exists in the use of stereotactic radiosurgery for patients with 10 or more brain metastases.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Brain metastases are the most common intracranial tumours. Variation exists in the use of stereotactic radiosurgery for patients with 10 or more brain metastases. Concerns include an increasing number of brain metastases being associated with poor survival, the lack of prospective, randomised data and an increased risk of toxicity.
METHODS
We performed a systematic review and meta-analysis to assess overall survival of patients with ten or more brain metastases treated with stereotactic radiosurgery as primary therapy. The search strings were applied to MEDLINE, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL). Log hazard ratios and standard errors were estimated from each included study. A random-effects meta-analysis using the DerSimonian and Laird method was applied using the derived log hazard ratios and standard errors on studies which included a control group.
RESULTS
15 studies were included for systematic review. 12 studies were used for pooled analysis for overall survival at set time points, with a predicted 12 month survival of 20-40%. The random-effects meta-analysis in five studies of overall survival comparing ten or greater metastases against control showed statistically worse overall survival in the 10 + metastases group (1.10, 95% confidence interval 1.03-1.18, p-value = < 0.01, I = 6%). A funnel plot showed no evidence of bias. There was insufficient information for a meta-analysis of toxicity.
DISCUSSION
Overall survival outcomes of patients with ten or more brain metastases treated with SRS is acceptable and should not be a deterrent for its use. There is a lack of prospective data and insufficient real-world data to draw conclusions on toxicity.
PROSPERO ID
CRD42021246115.
Topics: Humans; Radiosurgery; Cranial Irradiation; Brain Neoplasms; Combined Modality Therapy; Proportional Hazards Models; Retrospective Studies
PubMed: 37858075
DOI: 10.1186/s12885-023-11452-7 -
Surgical Neurology International 2021Stereotactic brain biopsy techniques have been a focus of rapid technological innovation. The recent advent of frameless stereotaxy has invited the question of whether...
BACKGROUND
Stereotactic brain biopsy techniques have been a focus of rapid technological innovation. The recent advent of frameless stereotaxy has invited the question of whether it can provide the same diagnostic yield as frame-based techniques, without increasing risk of harm to patients. The goal of this meta-analysis was to compare each of these techniques in terms of yield and safety.
METHODS
We independently searched four databases for English studies comparing frameless and frame-based stereotactic brain biopsies. Our primary outcome was biopsy diagnostic yield. Our secondary outcomes included mortality, morbidity (e.g., symptomatic postbiopsy intracranial hemorrhage, asymptomatic postbiopsy intracranial hemorrhage, new postbiopsy neurological deficit, and postbiopsy seizure), and frequency of repeat biopsy. We calculated pooled estimates and relative risks for dichotomous outcomes using Review Manager 5.3, with corresponding 95% confidence intervals.
RESULTS
A total of 3256 stereotactic brain biopsies (2050 frame based and 1206 frameless), from 20 studies, were included in our final analysis. The results did not demonstrate any significant difference between the two stereotactic systems in terms of diagnostic yield (risk ratio [RR] 1.00, 95% confidence interval [CI] 0.99-1.02, = 0.64, I = 0%). The only significant difference was the increased frequency of asymptomatic hemorrhages in the frameless group (RR 1.37, 95% CI 1.06-1.75, = 0.01, I = 0%). Application of Grading of Recommendations Assessment, Development, and Evaluation to the results yielded very low quality of all outcomes.
CONCLUSION
Based on very low-quality evidence, both frame-based and frameless stereotaxy are safe and effective for biopsy of intracranial tumors. Further study of patient preference and cost comparing analysis is required to identify if either modality should be preferred.
PubMed: 33654555
DOI: 10.25259/SNI_824_2020 -
Neurosurgical Review Mar 2023The role of radiotherapy (RT) and stereotactic radiosurgery (SRS) as adjuvant or salvage treatment in high-grade meningiomas (HGM) is still debated. Despite advances in... (Meta-Analysis)
Meta-Analysis Review
Efficacy of radiotherapy and stereotactic radiosurgery as adjuvant or salvage treatment in atypical and anaplastic (WHO grade II and III) meningiomas: a systematic review and meta-analysis.
The role of radiotherapy (RT) and stereotactic radiosurgery (SRS) as adjuvant or salvage treatment in high-grade meningiomas (HGM) is still debated. Despite advances in modern neuro-oncology, HGM (WHO grade II and III) remains refractory to multimodal therapies. Published reports present aggregated data and are extremely varied in population size, exclusion criteria, selection bias, and inclusion of mixed histologic grades, making it extremely difficult to draw conclusions when taken individually. This current work aims to gather the existing evidence on RT and SRS as adjuvants following surgery or salvage treatment at recurrence after multimodality therapy failure and to conduct a systematic comparison between these two modalities. An extensive systematic literature review and meta-analysis were performed. A total of 42 papers were eligible for final analysis (RT n = 27; SRS n = 15) after searching MEDLINE via PubMed, Web-of-science, Cochrane Wiley, and Embase databases. Adjuvant regimens were addressed in 37 papers (RT n = 26; SRS n = 11); salvage regimens were described in 5 articles (RT n = 1; SRS n = 4). The primary outcomes of the study were the overall recurrence rate and mortality. Other actuarial rates (local and distant control, OS, PFS, and complications) were retrieved and analyzed as secondary outcomes. A total of 2853 patients harboring 3077 HGM were included. The majority were grade II (87%) with a mean pre-radiation volume of 8.7 cc. Adjuvant regimen: 2742 patients (76.4% RT; 23.6% SRS) with an overall grade II/III rate of 6.6/1. Lesions treated adjSRS were more frequently grade III (17 vs 12%, p < 0.001), and received subtotal resection (57 vs 27%, p = 0.001) compared to the RT cohort. AdjSRS cohort had a significantly shorter mean follow-up than adjRT (36.7 vs 50.3 months, p = 0.01). The overall recurrence rate was 38% in adjRT vs 25% in adjSRS (p = 0.01), while mortality did not differ between the groups (20% vs 23%, respectively; p = 0.80). The median time to recurrence was 1.5 times longer in the RT group (p = 0.30). Five-year local control was 55% in adjRT and 26% in adjSRS (p = 0.01), while 5-year OS was 73% and 78% (p = 0.62), and 5-year PFS was 62% and 40% in adjRT and adjSRS (p = 0.008). No difference in the incidence of complications (24% vs 14%, p = 0.53). Salvage regimen: 110 patients (37.3% RT; 62.7% SRS) with a grade II/III rate of 8.6/1. The recurrence rate was 46% in salRT vs 24% in salSRS (p = 0.39), time to recurrence was 1.8 times longer in the salRT group (35 vs 18.5 months, p = 0.74). Mortality was slightly yet not significantly higher in salRT (34% vs 12%, p = 0.54). Data on local and distant control were only available for salSRS. The 5-year OS was 49% and 83% (p = 0.90), and the 5-year PFS was 39% and 50% in salRT and salSRS (p = 0.66), respectively. High-grade meningiomas (WHO grade II and III) receiving adjuvant RT showed a higher overall recurrence rate than meningiomas receiving adjuvant SRS. The adjRT cohort, however, achieved higher 5-year LC and PFS rates, thus suggesting a potentially longer time to recurrence compared to adjSRS patients, who, meanwhile, experienced a significantly shorter follow-up. This result must also consider the higher number of grade III lesions and the smaller extent of resection achieved in the adjSRS group. Overall mortality did not differ between the two groups. No differences in outcome measures were observed in salvage regimens.
Topics: Humans; Meningioma; Radiosurgery; Treatment Outcome; Salvage Therapy; Retrospective Studies; Meningeal Neoplasms; World Health Organization; Neoplasm Recurrence, Local; Follow-Up Studies
PubMed: 36928326
DOI: 10.1007/s10143-023-01969-7