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Blood Reviews Nov 2023Despite recent advancements, treatment of cytopenia due to bone marrow failures (BMF) and myeloid neoplasms remains challenging. Androgens promote renewal and maturation... (Review)
Review
Despite recent advancements, treatment of cytopenia due to bone marrow failures (BMF) and myeloid neoplasms remains challenging. Androgens promote renewal and maturation of blood cells and may be beneficial in these forms. Here we report a systematic review of androgens use as single agent in hematologic conditions. Forty-six studies, mainly retrospective with various androgen types and doses, were included: 12 on acquired aplastic anemia (AA), 11 on inherited BMF, 17 on myelodysplastic syndromes (MDS), and 7 on myelofibrosis. Responses ranged from 50 to 70% in inherited BMF, 40-50% in acquired AA and MDS, while very limited evidence emerged for myelofibrosis. In acquired AA, response was associated with presence of non-severe disease; in MDS androgens were more effective on thrombocytopenia or mild to moderate anemia, whilst limited benefit was observed for transfusion dependent anemia. Toxicity profile mainly consisted of virilization and liver enzyme elevation, whilst the risk of leukemic evolution remains controversial.
Topics: Humans; Androgens; Primary Myelofibrosis; Retrospective Studies; Neoplasms; Anemia, Aplastic; Myelodysplastic Syndromes; Bone Marrow Failure Disorders; Pancytopenia; Myeloproliferative Disorders; Thrombocytopenia
PubMed: 37709654
DOI: 10.1016/j.blre.2023.101132 -
JAMA Network Open Feb 2024Conventional external beam radiotherapy (cEBRT) and stereotactic body radiotherapy (SBRT) are commonly used treatment options for relieving metastatic bone pain. The... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Conventional external beam radiotherapy (cEBRT) and stereotactic body radiotherapy (SBRT) are commonly used treatment options for relieving metastatic bone pain. The effectiveness of SBRT compared with cEBRT in pain relief has been a subject of debate, and conflicting results have been reported.
OBJECTIVE
To compare the effectiveness associated with SBRT vs cEBRT for relieving metastatic bone pain.
DATA SOURCES
A structured search was performed in the PubMed, Embase, and Cochrane databases on June 5, 2023. Additionally, results were added from a new randomized clinical trial (RCT) and additional unpublished data from an already published RCT.
STUDY SELECTION
Comparative studies reporting pain response after SBRT vs cEBRT in patients with painful bone metastases.
DATA EXTRACTION AND SYNTHESIS
Two independent reviewers extracted data from eligible studies. Data were extracted for the intention-to-treat (ITT) and per-protocol (PP) populations. The study is reported following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline.
MAIN OUTCOMES AND MEASURES
Overall and complete pain response at 1, 3, and 6 months after radiotherapy, according to the study's definition. Relative risk ratios (RRs) with 95% CIs were calculated for each study. A random-effects model using a restricted maximum likelihood estimator was applied for meta-analysis.
RESULTS
There were 18 studies with 1685 patients included in the systematic review and 8 RCTs with 1090 patients were included in the meta-analysis. In 7 RCTs, overall pain response was defined according to the International Consensus on Palliative Radiotherapy Endpoints in clinical trials (ICPRE). The complete pain response was reported in 6 RCTs, all defined according to the ICPRE. The ITT meta-analyses showed that the overall pain response rates did not differ between cEBRT and SBRT at 1 (RR, 1.14; 95% CI, 0.99-1.30), 3 (RR, 1.19; 95% CI, 0.96-1.47), or 6 (RR, 1.22; 95% CI, 0.96-1.54) months. However, SBRT was associated with a higher complete pain response at 1 (RR, 1.43; 95% CI, 1.02-2.01), 3 (RR, 1.80; 95% CI, 1.16-2.78), and 6 (RR, 2.47; 95% CI, 1.24-4.91) months after radiotherapy. The PP meta-analyses showed comparable results.
CONCLUSIONS AND RELEVANCE
In this systematic review and meta-analysis, patients with painful bone metastases experienced similar overall pain response after SBRT compared with cEBRT. More patients had complete pain alleviation after SBRT, suggesting that selected subgroups will benefit from SBRT.
Topics: Humans; Bone Neoplasms; Pain; Radiosurgery; Cancer Pain; Pain Management; Pathologic Complete Response; Randomized Controlled Trials as Topic
PubMed: 38345820
DOI: 10.1001/jamanetworkopen.2023.55409 -
Orthopaedics & Traumatology, Surgery &... Jun 2022Benign and pseudo-neoplastic bone lesions are usually treated by curettage and filling of the cavity. This filling is usually achieved with the use of autologous bone... (Review)
Review
BACKGROUND
Benign and pseudo-neoplastic bone lesions are usually treated by curettage and filling of the cavity. This filling is usually achieved with the use of autologous bone grafts, bone cement, allografts, xenografts, or synthetic bone substitutes. Recently, some authors have suggested that these defects do not require filling for consolidation but the respective rate of complications of each method is not well defined. Therefore, we did a systematic review aiming to answer: (1) Not filling bone cavities after benign bone tumour curettage may increase the rate of fractures? (2) Can the volume of the bone defect in itself be a specific or reliable predictor of fracture? (3) Does the mean functional outcome, recurrence, non-weight bearing time, other postoperative complications or bone consolidation time vary between the methods of filling?
PATIENTS AND METHODS
The PubMed (2407 articles) and Latin American and Caribbean Health Sciences Literature (LILACS) (50 articles) databases were reviewed, without restriction considering publication date. After exclusion criteria, 62 articles were selected for data collection. Filling or not filling (UN), methods of filling, fracture rate, bone defect size, mean functional outcome, recurrence, non-weight bearing time, other postoperative complications, consolidation time were the data of interest.
RESULTS
The number of patients was 2555 distributed among the different filling methods. Unfilled cavities were associated with higher fracture rate [20/302 (6.62%)] versus 4/189 (2.12%) for allografts, 14/343 (4.08%) for cement filling, 4/247 for autograft (1.62%), and 12/580 (2.07%) for bone substitute. The volume of the bone defect alone is not a specific or reliable predictor of fracture. All filling methods were similar regarding the mean functional outcome, recurrence rate and consolidation time. The bone cement allowed early weight bearing time (mean of weeks): UN: 9.67; autologous bone grafts: 9.8; bone cement: 0.5; allografts: 9.0; synthetic bone substitutes: 9.96.
CONCLUSION
Not filling the bone cavity after benign bone tumour curettage is an alternative, but can increase fracture rate, even in small volume bone defects. The use of prophylactic fixation drastically reduces the fracture rate. Filling with cement reduces weight bearing time. There are little differences between the methods used to fill, even compared to not filling the cavity.
LEVEL OF EVIDENCE
III; systematic review.
Topics: Bone Cements; Bone Neoplasms; Bone Substitutes; Bone Transplantation; Curettage; Humans; Postoperative Complications; Retrospective Studies
PubMed: 34033919
DOI: 10.1016/j.otsr.2021.102966 -
Frontiers in Immunology 2023Various immunosuppressive regimens have been developed for the treatment of lupus nephritis (LN). This study aimed to compare the efficacy and safety of... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Various immunosuppressive regimens have been developed for the treatment of lupus nephritis (LN). This study aimed to compare the efficacy and safety of immunosuppressive regimens in adults with LN.
METHODS
We systematically searched the PubMed, Embase, and Cochrane Central Register of Controlled Trials databases, including conference proceedings, trial registries, and reference lists, from inception until July 10, 2022. The effects of treatment were compared and ranked using the surface under the cumulative ranking curve (SUCRA). The primary endpoint was total remission. The secondary endpoints were complete remission, systemic lupus erythematosus disease activity index (SLEDAI), relapse, all-cause mortality, end-stage renal disease (ESRD), infection, herpes zoster, ovarian failure, myelosuppression, and cancer.
RESULTS
Sixty-two trials reported in 172 studies involving 6,936 patients were included in the network meta-analysis. The combination of tacrolimus (TAC), mycophenolate mofetil (MMF), and glucocorticoid (GC) provided the best result for the total remission rate (SUCRA, 86.63%) and SLEDAI (SUCRA, 91.00%), while the combination of voclosporin (VCS) , MMF and GC gave the best improvement in the complete remission rate (SUCRA, 90.71%). The combination of cyclophosphamide (CYC), MMF and GC was associated with the lowest risk of relapse (SUCRA, 85.57%) and cancer (SUCRA, 85.14%), while the combination of obinutuzumab (OTB), MMF and GC was associated with the lowest risk of all-cause mortality (SUCRA, 84.07%). Rituximab (RTX) plus MMF plus GC was associated with the lowest risk of ESRD (SUCRA, 83.11%), while the risk of infection was lowest in patients treated with azathioprine (AZA) plus CYC plus GC (SUCRA, 68.59%). TAC plus GC was associated with the lowest risk of herpes zoster (SUCRA, 87.67%) and ovarian failure (SUCRA, 73.60%). Cyclosporine (CsA) plus GC was associated with the lowest risk of myelosuppression (SUCRA, 79.50%), while AZA plus GC was associated with the highest risk of myelosuppression (SUCRA, 16.25%).
DISCUSSION
This study showed that a combination of TAC, MMF and GC was the best regimen for improving the total remission rate. The optimal regimen for specific outcomes should be highlighted for high-risk patients.
Topics: Humans; Adult; Immunosuppressive Agents; Lupus Nephritis; Network Meta-Analysis; Treatment Outcome; Cyclophosphamide; Tacrolimus; Azathioprine; Mycophenolic Acid; Glucocorticoids; Bone Marrow Diseases; Kidney Failure, Chronic; Recurrence; Herpes Zoster; Neoplasms
PubMed: 37901212
DOI: 10.3389/fimmu.2023.1232244 -
Neurosurgical Review Sep 2023Endoscopic transsphenoidal surgery is a novel surgical technique requiring specific training. Different models and simulators have been recently suggested for it, but no... (Review)
Review
Endoscopic transsphenoidal surgery is a novel surgical technique requiring specific training. Different models and simulators have been recently suggested for it, but no systematic review is available. To provide a systematic and critical literature review and up-to-date description of the training models or simulators dedicated to endoscopic transsphenoidal surgery. A search was performed on PubMed and Scopus databases for articles published until February 2023; Google was also searched to document commercially available. For each model, the following features were recorded: training performed, tumor/arachnoid reproduction, assessment and validation, and cost. Of the 1199 retrieved articles, 101 were included in the final analysis. The described models can be subdivided into 5 major categories: (1) enhanced cadaveric heads; (2) animal models; (3) training artificial solutions, with increasing complexity (from "box-trainers" to multi-material, ct-based models); (4) training simulators, based on virtual or augmented reality; (5) Pre-operative planning models and simulators. Each available training model has specific advantages and limitations. Costs are high for cadaver-based solutions and vary significantly for the other solutions. Cheaper solutions seem useful only for the first stages of training. Most models do not provide a simulation of the sellar tumor, and a realistic simulation of the suprasellar arachnoid. Most artificial models do not provide a realistic and cost-efficient simulation of the most delicate and relatively common phase of surgery, i.e., tumor removal with arachnoid preservation; current research should optimize this to train future neurosurgical generations efficiently and safely.
Topics: Humans; Animals; Endoscopy; Cadaver; Computer Simulation; Databases, Factual; Skull Base Neoplasms
PubMed: 37725193
DOI: 10.1007/s10143-023-02149-3 -
Radiotherapy and Oncology : Journal of... Jan 2024Advances in characterizing cancer biology and the growing availability of novel targeted agents and immune therapeutics have significantly changed the prognosis of many... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND PURPOSE
Advances in characterizing cancer biology and the growing availability of novel targeted agents and immune therapeutics have significantly changed the prognosis of many patients with metastatic disease. Palliative radiotherapy needs to adapt to these developments. In this study, we summarize the available evidence for stereotactic body radiotherapy (SBRT) in the treatment of spinal metastases.
MATERIALS AND METHODS
A systematic review and meta-analysis was performed using PRISMA methodology, including publications from January 2005 to September 2021, with the exception of the randomized phase III trial RTOG-0631 which was added in April 2023. Re-irradiation was excluded. For meta-analysis, a random-effects model was used to pool the data. Heterogeneity was assessed with the I-test, assuming substantial and considerable as I > 50 % and I > 75 %, respectively. A p-value < 0.05 was considered statistically significant.
RESULTS
A total of 69 studies assessing the outcomes of 7236 metastases in 5736 patients were analyzed. SBRT for spine metastases showed high efficacy, with a pooled overall pain response rate of 83 % (95 % confidence interval [CI] 68 %-94 %), pooled complete pain response of 36 % (95 % CI: 20 %-53 %), and 1-year local control rate of 94 % (95 % CI: 86 %-99 %), although with high levels of heterogeneity among studies (I = 93 %, I = 86 %, and 86 %, respectively). Furthermore, SBRT was safe, with a pooled vertebral fracture rate of 9 % (95 % CI: 4 %-16 %), pooled radiation induced myelopathy rate of 0 % (95 % CI 0-2 %), and pooled pain flare rate of 6 % (95 % CI: 3 %-17 %), although with mixed levels of heterogeneity among the studies (I = 92 %, I = 0 %, and 95 %, respectively). Only 1.7 % of vertebral fractures required surgical stabilization.
CONCLUSION
Spine SBRT is characterized by a favorable efficacy and safety profile, providing durable results for pain control and disease control, which is particularly relevant for oligometastatic patients.
Topics: Humans; Radiosurgery; Spinal Neoplasms; Prognosis; Spine; Spinal Fractures; Pain; Clinical Trials, Phase III as Topic; Randomized Controlled Trials as Topic
PubMed: 37922993
DOI: 10.1016/j.radonc.2023.109969 -
Cancer Treatment Reviews Apr 2023The anti-tumor activity of WEE1 inhibitors (WEE1i) in gynecological malignancies has recently been demonstrated in clinical trials and its rationale is based on... (Review)
Review
INTRODUCTION
The anti-tumor activity of WEE1 inhibitors (WEE1i) in gynecological malignancies has recently been demonstrated in clinical trials and its rationale is based on biological/molecular features of gynecological cancers. With this systematic review, we aim to outline the clinical development and current evidence regarding the efficacy and safety of these targeted agents in in this patient group.
METHODS
Systematic literature review of trials including patients with gynecological cancers treated with a WEE1i. The primary objective was to summarize the efficacy of WEE1i in gynecological malignancies regarding objective response rate (ORR), clinical benefit rate (CBR), overall survival (OS) and progression-free survival (PFS). Secondary objectives included toxicity profile, Maximum Tolerated Dose (MTD), pharmacokinetics, drug-drug interactions and exploratory objectives such as biomarkers for response.
RESULTS
26 records were included for data extraction. Almost all trials used the first-in-class WEE1i adavosertib; one conference abstract reported about Zn-c3. The majority of the trials included diverse solid tumors (n = 16). Six records reported efficacy results of WEE1i in gynecological malignancies (n = 6). Objective response rates of adavosertib monotherapy or in combination with chemotherapy ranged between 23% and 43% in these trials. Median PFS ranged from 3.0 to 9.9 months. The most common adverse events were bone marrow suppression, gastrointestinal toxicities and fatigue. Mainly alterations in cell cycle regulator genes TP53 and CCNE1 were potential predictors of response.
CONCLUSION
This report summarizes encouraging clinical development of WEE1i in gynecological cancers and considers its application in future studies. Biomarker-driven patient selection might be essential to increase the response rates.
Topics: Female; Humans; Genital Neoplasms, Female; Antineoplastic Agents; Protein-Tyrosine Kinases; Cell Cycle Proteins
PubMed: 36893690
DOI: 10.1016/j.ctrv.2023.102531 -
Radiation Oncology (London, England) Oct 2022This study aimed to systematically evaluate and conduct a meta-analysis of the efficacy and safety of carbon ion radiotherapy for bone sarcomas. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This study aimed to systematically evaluate and conduct a meta-analysis of the efficacy and safety of carbon ion radiotherapy for bone sarcomas.
METHODS
We searched for articles using the PubMed, Embase, Cochrane Library, and the Web of Science databases from their inception to January 12, 2022. Two researchers independently screened the literature and extracted data based on the inclusion and exclusion criteria. Statistical analyses were performed using STATA version 14.0.
RESULTS
We searched for 4378 candidate articles, of which 12 studies were included in our study according to the inclusion and exclusion criteria. Of the 897 BSs patients who received carbon ion radiotherapy in the studies, 526 patients had chordoma, 255 patients had chondrosarcoma, 112 patients had osteosarcoma, and 4 patients had other sarcomas. The local control rate at 1, 2, 3, 4, 5, and 10 years in these studies were 98.5% (95% confidence interval [CI] = 0.961-1.009, I = 0%), 85.8% (95% CI = 0.687-1.030, I = 91%), 86% (95% CI = 0.763-0.957, I = 85.3%), 91.1% (95% CI = 0.849-0.974), 74.3% (95% CI = 0.666-0.820, I = 85.2%), and 64.7% (95% CI = 0.451-0.843, I = 95.3%), respectively. The overall survival rate at 1, 2, 3, 4, 5, and 10 years in these studies were 99.9% (95% CI = 0.995-1.004, I = 0%), 89.6% (95% CI = 0.811-0.980, I = 96.6%), 85% (95% CI = 0.750-0.950, I = 89.4%), 92.4% (95% CI = 0.866-0.982), 72.7% (95% CI = 0.609-0.844, I = 95.3%), and 72.1% (95% CI = 0.661-0.781, I = 46.5%), respectively. Across all studies, the incidence of acute and late toxicities was mainly grade 1 to grade 2, and grade 1 to grade 3, respectively.
CONCLUSION
As an advanced radiotherapy, carbon ion radiotherapy is promising for patients with bone sarcomas that are unresectable or residual after incomplete surgery. The data indicated that carbon ion radiotherapy was safe and effective for bone sarcomas, showing promising results for local control, overall survival, and lower acute and late toxicity.
PROSPERO REGISTRATION NUMBER
CRD42021258480.
Topics: Humans; Heavy Ion Radiotherapy; Osteosarcoma; Chondrosarcoma; Sarcoma; Bone Neoplasms
PubMed: 36284346
DOI: 10.1186/s13014-022-02089-0 -
Journal of Orthopaedic Surgery and... Oct 2021Osteosarcoma is the most prevalent malignant osseous sarcoma in children and adolescents, whose prognosis is still relatively poor nowadays. Recent studies have shown... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Osteosarcoma is the most prevalent malignant osseous sarcoma in children and adolescents, whose prognosis is still relatively poor nowadays. Recent studies have shown the critical function and potential clinical applications of circular RNAs (circRNAs) in osteosarcoma. Our review aimed to perform an updated meta-analysis to explore their clinicopathologic significance and prognostic value.
METHODS
The structured literature was conducted via eight electronic databases and four gray literature sources until 20 Feb 2021 to identify eligible studies. The data was extracted directly from the articles or reconstructed based on Kaplan-Meier curves. The Newcastle-Ottawa Scale (NOS) tool was used to assess study quality. The clinicopathologic significance of circRNAs was measured through odds ratios (ORs) and their 95% confidence intervals (CIs), while the prognostic value was evaluated through hazard ratios (HRs) and their 95% CIs of overall survival (OS) and disease-free survival (DFS). Heterogeneity and publication bias were assessed. Sensitivity analyses were conducted. Subgroup analyses were performed according to study characteristics. An additional analysis was performed to investigate the relation between circ_0002052 and osteosarcoma.
RESULTS
Fifty-two studies were identified, in which 38 on clinicopathologic features and 36 on survival prognosis were included in quantitative analysis. The overall study quality was moderate with a median NOS score of 5.5 stars (range 3 to 8). For clinicopathologic features, dysregulated circRNAs were related to larger tumor size (OR 2.122, 95%CI 1.418-3.175), advanced clinical stage (OR 2.847, 95%CI 2.059-3.935), and present of metastasis (OR 2.630, 95%CI 1.583-4.371). For chemotherapy, dysregulated circRNAs suggest a better response (OR 0.443, 95%CI 0.231-0.849), but a higher probability of resistance (OR 9.343, 95%CI 5.352-16.309). For survival prognosis, dysregulated circRNAs were significantly correlated with poor OS (HR 2.437, 95%CI 2.224-2.670) and DFS (HR 2.125, 95%CI 1.621-2.786). The results did not show differences among subgroups. Higher circ_0002052 expression showed a relation with poor OS (HR 3.197, 95%CI 2.054-4.976).
CONCLUSIONS
Our review demonstrated that abnormally expressed circRNAs have a relation with advanced clinicopathologic features and better response, but a higher probability of resistance and poor survival prognosis in osteosarcoma patients. However, more studies are encouraged to provide more robust evidence to translate circRNAs into clinical practice.
TRIAL REGISTRATION
PROSPERO ID: CRD42021235031.
Topics: Adolescent; Biomarkers, Tumor; Bone Neoplasms; Humans; Osteosarcoma; Prognosis; RNA, Circular
PubMed: 34620208
DOI: 10.1186/s13018-021-02568-2 -
Frontiers in Public Health 2023Appropriately selected complementary therapies, such as virtual reality (VR) and active video games (AVG), provide support to young patients during the process of cancer... (Meta-Analysis)
Meta-Analysis
Virtual reality in chemotherapy support for the treatment of physical functions, fear, and quality of life in pediatric cancer patients: A systematic review and meta-analysis.
BACKGROUND
Appropriately selected complementary therapies, such as virtual reality (VR) and active video games (AVG), provide support to young patients during the process of cancer treatment. Therefore, this systematic review with meta-analysis aimed to analyze the effects of VR and AVG on fear, physical functions, and quality of life.
METHODS
A systematic search was performed independently in Scopus, PubMed, Embase, Web of Science and Cochrane Library electronic databases for relevant randomized controlled and crossover studies. From a total of 5,963 records, 11 met the inclusion criteria. After full-text screening two publications were excluded, yet six studies were included in the quantitative analysis because three studies had a large discrepancy in their measured outcomes. For methodological quality assessments, the RoB2 software program was used, while RevMan 5.4.1 was used for statistical analysis and meta-analysis. Standard Mean Difference (SMD) outcome measures were used for the analysis. Statistical heterogeneity was assessed using the I2 statistic with a cut-off value of 50% considering intervention and outcome measures.
RESULTS
Our systematic review includes six randomized controlled studies and three randomized crossover studies. The participants represented both sexes and were children and adolescents (<18 years old) with a diagnosis of cancer. The analysis of the results allows for a careful conclusion that VR has the potential to become an accessory tool in rehabilitation and oncologic treatment. All of the included studies noted a significant advantage of this intervention.
CONCLUSION
VR has the potential to be an effective and important tool in the oncologic treatment of children. VR immerses the patient, and as a result, produces a distraction that effectively reduces pain associated with standard oncologic care procedures in children. However, this systematic review and meta-analysis highlights the need for more research into the use of VR as support for pediatric oncologic care.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO database (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=319000), CRD42022319000.
Topics: Child; Male; Adolescent; Female; Humans; Quality of Life; Fear; Outcome Assessment, Health Care; Pain; Virtual Reality; Neoplasms
PubMed: 37124795
DOI: 10.3389/fpubh.2023.1039720