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Frontiers in Immunology 2023The incidence and risk factors of acute kidney injury (AKI) in patients with malignancies receiving immune checkpoint inhibitors (ICIs) are being extensively reported... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The incidence and risk factors of acute kidney injury (AKI) in patients with malignancies receiving immune checkpoint inhibitors (ICIs) are being extensively reported with their widespread application.
OBJECTIVE
This study aimed to quantify the incidence and identify risk factors of AKI in cancer patients treated with ICIs.
METHODS
We searched the electronic databases of PubMed/Medline, Web of Science, Cochrane and Embase before 1 February 2023 on the incidence and risk factors of AKI in patients receiving ICIs and registered the protocol in PROSPERO (CRD42023391939). A random-effect meta-analysis was performed to quantify the pooled incidence estimate of AKI, identify risk factors with pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) and investigate the median latency period of ICI-AKI in patients treated with ICIs. Assessment of study quality, meta-regression, and sensitivity and publication bias analyses were conducted.
RESULTS
In total, 27 studies consisting of 24048 participants were included in this systematic review and meta-analysis. The overall pooled incidence of AKI secondary to ICIs was 5.7% (95% CI: 3.7%-8.2%). Significant risk factors were older age (OR: 1.01, 95% CI: 1.00-1.03), preexisting chronic kidney disease (CKD) (OR: 2.90, 95% CI: 1.65-5.11), ipilimumab (OR: 2.66, 95% CI: 1.42-4.98), combination of ICIs (OR: 2.45, 95% CI: 1.40-4.31), extrarenal immune-related adverse events (irAEs) (OR: 2.34, 95% CI: 1.53-3.59), and proton pump inhibitor (PPI) (OR: 2.23, 95% CI: 1.88-2.64), nonsteroidal anti-inflammatory drug (NSAID) (OR: 2.61, 95% CI: 1.90-3.57), fluindione (OR: 6.48, 95% CI: 2.72-15.46), diuretic (OR: 1.78, 95% CI: 1.32-2.40) and angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin-receptor blockers (ARBs) (pooled OR: 1.76, 95% CI: 1.15-2.68) use. Median time from ICIs initiation to AKI was 108.07 days. Sensitivity and publication bias analyses indicated robust results for this study.
CONCLUSION
The occurrence of AKI following ICIs was not uncommon, with an incidence of 5.7% and a median time interval of 108.07 days after ICIs initiation. Older age, preexisting chronic kidney disease (CKD), ipilimumab, combined use of ICIs, extrarenal irAEs, and PPI, NSAID, fluindione, diuretics and ACEI/ARB use are risk factors for AKI in patients receiving ICIs.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42023391939.
Topics: Humans; Immune Checkpoint Inhibitors; Ipilimumab; Angiotensin Receptor Antagonists; Incidence; Angiotensin-Converting Enzyme Inhibitors; Neoplasms; Acute Kidney Injury; Anti-Inflammatory Agents, Non-Steroidal
PubMed: 37313406
DOI: 10.3389/fimmu.2023.1173952 -
Radiation Oncology (London, England) May 2023Particle therapy, mainly including carbon-ion radiotherapy (CIRT) and proton beam therapy (PBT), has dose distribution advantages compared to photon radiotherapy. It has... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND PURPOSE
Particle therapy, mainly including carbon-ion radiotherapy (CIRT) and proton beam therapy (PBT), has dose distribution advantages compared to photon radiotherapy. It has been widely reported as a promising treatment method for early non-small cell lung cancer (NSCLC). However, its application in locally advanced non-small cell lung cancer (LA-NSCLC) is relatively rare, and its efficacy and safety are inconclusive. This study aimed to provide systematic evidence for evaluating the efficacy and safety of particle therapy for inoperable LA-NSCLC.
METHODS
To retrieve published literature, a systematic search was conducted in PubMed, Web of Science, Embase, and Cochrane Library until September 4, 2022. The primary endpoints were local control (LC) rate, overall survival (OS) rate, and progression-free survival (PFS) rate at 2 and 5 years. The secondary endpoint was treatment-related toxicity. The pooled clinical outcomes and 95% confidence intervals (CIs) were calculated by using STATA 15.1.
RESULTS
Nineteen eligible studies with a total sample size of 851 patients were included. The pooled data demonstrated that the OS, PFS, and LC rates at 2 years of LA-NSCLC treated by particle therapy were 61.3% (95% CI = 54.7-68.7%), 37.9% (95% CI = 33.8-42.6%) and 82.2% (95% CI = 78.7-85.9%), respectively. The pooled 5-year OS, PFS, and LC rates were 41.3% (95% CI = 27.1-63.1%), 25.3% (95% CI = 16.3-39.4%), and 61.5% (95% CI = 50.7-74.6%), respectively. Subgroup analysis stratified by treatment type showed that the concurrent chemoradiotherapy (CCRT, PBT combined with concurrent chemotherapy) group had better survival benefits than the PBT and CIRT groups. The incidence rates of grade 3/4 esophagitis, dermatitis, and pneumonia in LA-NSCLC patients after particle therapy were 2.6% (95% CI = 0.4-6.0%), 2.6% (95% CI = 0.5-5.7%) and 3.4% (95% CI = 1.4-6.0%), respectively.
CONCLUSIONS
Particle therapy demonstrated promising efficacy and acceptable toxicity in LA-NSCLC patients.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Progression-Free Survival; Proton Therapy; Chemoradiotherapy
PubMed: 37217970
DOI: 10.1186/s13014-023-02264-x -
Cancers Apr 2023Complex anatomy surrounding the oropharynx makes proton therapy (PT), especially intensity-modulated PT (IMPT), a potentially attractive option due to its ability to... (Review)
Review
BACKGROUND
Complex anatomy surrounding the oropharynx makes proton therapy (PT), especially intensity-modulated PT (IMPT), a potentially attractive option due to its ability to reduce the volume of irradiated healthy tissues. Dosimetric improvement may not translate to clinically relevant benefits. As outcome data are emerging, we aimed to evaluate the evidence of the quality of life (QOL) and patient-reported outcomes (PROs) following PT for oropharyngeal carcinoma (OC).
MATERIALS AND METHODS
We searched PubMed and Scopus electronic databases (date: 15 February 2023) to identify original studies on QOL and PROs following PT for OC. We employed a fluid strategy in the search strategy by tracking citations of the initially selected studies. Reports were extracted for information on demographics, main results, and clinical and dose factor correlates. Quality assessment was performed using the NIH's Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. The PRISMA guidelines were followed in the preparation of this report.
RESULTS
Seven reports were selected, including one from a recently published paper captured from citation tracking. Five compared PT and photon-based therapy, although none were randomized controlled trials. Most endpoints with significant differences favored PT, including xerostomia, cough, need for nutritional supplements, dysgeusia, food taste, appetite, and general symptoms. However, some endpoints favored photon-based therapy (sexual symptoms) or showed no significant difference (e.g., fatigue, pain, sleep, mouth sores). The PROs and QOL improve following PT but do not appear to return to baseline.
CONCLUSION
Evidence suggests that PT causes less QOL and PRO deterioration than photon-based therapy. Biases due to the non-randomized study design remain obstacles to a firm conclusion. Whether or not PT is cost-effective should be the subject of further investigation.
PubMed: 37190180
DOI: 10.3390/cancers15082252 -
Journal of Radiation Research Jun 2023To assess the safety and efficacy of proton beam therapy (PBT) for muscle-invasive bladder cancer (MIBC), we examined the outcomes of 36 patients with MIBC (cT2-4aN0M0)...
To assess the safety and efficacy of proton beam therapy (PBT) for muscle-invasive bladder cancer (MIBC), we examined the outcomes of 36 patients with MIBC (cT2-4aN0M0) who were enrolled in the Proton-Net prospective registry study and received PBT with concurrent chemotherapy from May 2016 to June 2018. PBT was also compared with X-ray chemoradiotherapy in a systematic review (X-ray (photon) radiotherapy). The radiotherapy consisted of 40-41.4 Gy (relative biological effectiveness (RBE) delivered in 20-23 fractions to the pelvic cavity or the entire bladder using X-rays or proton beams, followed by a boost of 19.8-36.3 Gy (RBE) delivered in 10-14 fractions to all tumor sites in the bladder. Concurrently, radiotherapy was given with intra-arterial or systemic chemotherapy of cisplatin alone or in combination with methotrexate or gemcitabine. Overall survival (OS), progression-free survival (PFS) and local control (LC) rates were 90.8, 71.4 and 84.6%, respectively, after 3 years. Only one case (2.8%) experienced a treatment-related late adverse event of Grade 3 urinary tract obstruction, and no severe gastrointestinal adverse events occurred. According to the findings of the systematic review, the 3-year outcomes of XRT were 57-84.8% in OS, 39-78% in PFS and 51-68% in LC. The weighted mean frequency of adverse events of Grade 3 or higher in the gastrointestinal and genitourinary systems was 6.2 and 2.2%, respectively. More data from long-term follow-up will provide us with the appropriate use of PBT and validate its efficacy for MIBC.
Topics: Humans; Protons; Proton Therapy; Urinary Bladder Neoplasms; Registries; Muscles; Multicenter Studies as Topic
PubMed: 37185773
DOI: 10.1093/jrr/rrad027 -
Physical and Engineering Sciences in... Jun 2023Particle therapies are becoming increasingly available clinically due to their beneficial energy deposition profile, sparing healthy tissues. This may be further...
Particle therapies are becoming increasingly available clinically due to their beneficial energy deposition profile, sparing healthy tissues. This may be further promoted with ultra-high dose rates, termed FLASH. This review comprehensively summarises current knowledge based on studies relevant to proton- and carbon-FLASH therapy. As electron-FLASH literature presents important radiobiological findings that form the basis of proton and carbon-based FLASH studies, a summary of key electron-FLASH papers is also included. Preclinical data suggest three key mechanisms by which proton and carbon-FLASH are able to reduce normal tissue toxicities compared to conventional dose rates, with equipotent, or enhanced, tumour kill efficacy. However, a degree of caution is needed in clinically translating these findings as: most studies use transmission and do not conform the Bragg peak to tumour volume; mechanistic understanding is still in its infancy; stringent verification of dosimetry is rarely provided; biological assays are prone to limitations which need greater acknowledgement.
Topics: Protons; Biological Assay; Carbon; Electrons; Health Status
PubMed: 37160539
DOI: 10.1007/s13246-023-01266-z -
World Journal of Pediatrics : WJP Aug 2023Advances in cancer treatments, particularly the development of radiation therapy, have led to improvements in survival outcomes in children with brain tumors. However,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Advances in cancer treatments, particularly the development of radiation therapy, have led to improvements in survival outcomes in children with brain tumors. However, radiation therapy is associated with significant long-term neurocognitive morbidity. The present systematic review and meta-analysis aimed to compare the neurocognitive outcomes of children and adolescents with brain tumors treated with photon radiation (XRT) or proton therapy (PBRT).
METHODS
A systematic search was conducted (PubMed, Embase, Cochrane, and Web of Science from inception until 02/01/2022) for studies comparing the neurocognitive outcomes of children and adolescents with brain tumors treated with XRT vs. PBRT. The pooled mean differences (expressed as Z scores) were calculated using a random effects method for those endpoints analyzed by a minimum of three studies.
RESULTS
Totally 10 studies (n = 630 patients, average age range: 1-20 years) met the inclusion criteria. Patients who had received PBRT achieved significantly higher scores (difference in Z scores ranging from 0.29-0.75, all P < 0.05 and significant in sensitivity analyses) after treatment than those who had received XRT for most analyzed neurocognitive outcomes (i.e., intelligence quotient, verbal comprehension and perceptual reasoning indices, visual motor integration, and verbal memory). No robust significant differences (P > 0.05 in main analyses or sensitivity analyses) were found for nonverbal memory, verbal working memory and working memory index, processing speed index, or focused attention.
CONCLUSIONS
Pediatric brain tumor patients who receive PBRT achieve significantly higher scores on most neurocognitive outcomes than those who receive XRT. Larger studies with long-term follow-ups are needed to confirm these results.
Topics: Child; Adolescent; Humans; Infant; Child, Preschool; Young Adult; Adult; Protons; Brain Neoplasms; Proton Therapy
PubMed: 37154861
DOI: 10.1007/s12519-023-00726-6 -
Journal of Ethnopharmacology Sep 2023Functional dyspepsia (FD), a chronic upper gastrointestinal syndrome, seriously affects the quality of life of patients and poses a significant economic burden. Since... (Meta-Analysis)
Meta-Analysis Review
ETHNOPHARMACOLOGICAL RELEVANCE
Functional dyspepsia (FD), a chronic upper gastrointestinal syndrome, seriously affects the quality of life of patients and poses a significant economic burden. Since the pathological mechanisms of FD have not been fully elucidated, conventional therapies such as prokinetics, proton pump inhibitors, and antidepressants have some limitations. Siho-sogan-san (SHS) is commonly used as a therapeutic alternative in traditional medicine; however, scientific and clinical evidence supporting its application in FD remains insufficient.
AIM OF THE STUDY
This review aimed to assess the safety and effectiveness of SHS and in combined with Western medicine (WM) for the treatment of FD.
METHODS
Eleven databases, including EMBASE, Medline, and Cochrane Library, were searched for randomized controlled trials (RCTs) on FD published before December 31, 2022. After two independent reveiwers sceened and selected studies according to the inclusion and exclusion criteria, clinical data was pooled and synthesized via Review Manager software. The outcome parameters included total clinical effectiveness rate (TCE), time for symptom improvement, levels of motilin and corticotropin-releasing hormone (CRH), and adverse events. Cochrane's risk of bias tool was used for quality assessment.
RESULTS
A total of 12 studies that included 867 participants comparing WM with SHS or combination therapy (SHS plus WM) were identified. Through a meta-analysis of five studies including 363 patients, SHS compared with WM showed a positive result in safely increasing TCE [risk ratio = 1.36, 95% confidence interval (CI) 1.22 to 1.51, P < 0.00001]. The time for symptom improvement, including abdominal pain, belching, nausea, vomiting, and abdominal distension, was significantly more shortened in the combination therapy than WM group. Furthermore, combination therapy resulted in greater secretion of motilin than WM alone [mean difference = 67.95, 95% CI 39.52 to 96.39, P < 0.00001]. No remarkable difference was observed in CRH levels between the combination therapy and WM groups. For a subgroup analysis, the administration of SHS based on the type of pattern identification (PI) showed larger effect size than in the group that do not consider PI.
CONCLUSIONS
These results suggest that SHS and combination therapy can be considered effective and safe options for the treatment of FD. However, owing to the low quality of the included studies, more well-designed investigational studies and RCTs with longer treatment and follow-up period are needed.
Topics: Humans; Dyspepsia; Motilin; Drugs, Chinese Herbal; Phytotherapy; Plants, Medicinal; Medicine, Traditional
PubMed: 37127143
DOI: 10.1016/j.jep.2023.116518 -
Journal of Radiation Research Jun 2023The aim of this study was to investigate the efficacy and safety of particle beam therapy (PBT) with proton or carbon ion beam for pelvic recurrence of colorectal cancer... (Meta-Analysis)
Meta-Analysis
The aim of this study was to investigate the efficacy and safety of particle beam therapy (PBT) with proton or carbon ion beam for pelvic recurrence of colorectal cancer (PRCC) by comparing the clinical outcomes of a dataset of prospectively enrolled patients for PBT with those from the literature, which were collected by a systematic review of external X-ray radiotherapy (XRT) and PBT. Patients with PRCC treated at 14 domestic facilities between May 2016 and June 2019 and entered the database for prospective observational follow-up were analyzed. The registry data analyzed included 159 PRCC patients treated with PBT of whom 126 (79%) were treated with carbon ion radiation therapy (CIRT). The 3-year overall survival and local control rate were 81.8 and 76.4%, respectively. Among these PRCC patients, 5.7% had Grade 3 or higher toxicity. Systematic search of PubMed and Cochrane databases published from January 2000 to September 2020 resulted in 409 abstracts for the primary selection. Twelve studies fulfilled the inclusion criteria. With one additional publication, 13 studies were selected for qualitative analysis, including 9 on XRT and 4 on PBT. There were nine XRT studies, which included six on 3D conformal radiotherapy and three on stereotactic body radiation therapy, and four PBT studies included three on CIRT and one on proton therapy. A pilot meta-analysis using literatures with median survival time extractable over a 20-month observation period suggested that PBT, especially CIRT, may be a promising treatment option for PRCC not amenable to curative resection.
Topics: Humans; Japan; Proton Therapy; Heavy Ion Radiotherapy; Colorectal Neoplasms; Registries; Observational Studies as Topic
PubMed: 37117038
DOI: 10.1093/jrr/rrad024 -
BMC Nephrology Apr 2023Several risk factors of immune checkpoint inhibitors (ICIs)-associated acute kidney injury (AKI) have been reported sporadically. To identify the risk factors of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Several risk factors of immune checkpoint inhibitors (ICIs)-associated acute kidney injury (AKI) have been reported sporadically. To identify the risk factors of ICIs-associated AKI in a large-scale population, therefore we conducted a systematic review and a real-world retrospective study.
METHODS
We search literature concerning risk factors of ICIs-associated AKI in ClinicalTrials.gov and electronic databases (PubMed, Cochrane Library, Embase) up to January 2022. Meta-analysis was performed by using odds ratios (ORs) with 95%CIs. In a separate retrospective pharmacovigilance study by extracting data from US FDA Adverse Event Reporting System (FAERS) database, disproportionality was analyzed using the reporting odds ratio (ROR).
RESULTS
A total of 9 studies (5927 patients) were included in the meta-analysis. The following factors were associated with increased risk of ICIs-associated AKI, including proton pump inhibitors(PPIs) (OR = 2.07, 95%CI 1.78-2.42), angiotensin-converting enzyme inhibitors (ACEIs)/ angiotensin receptor blockers (ARBs) (OR = 1.56, 95%CI 1.24-1.95), nonsteroidal anti-inflammatory drugs (NSAIDs) (OR = 1.29, 95%CI 1.01-1.65), diuretics (OR = 2.00, 95%CI 1.38-2.89), diabetes mellitus (OR = 1.28, 95%CI 1.04-1.57), genitourinary cancer (OR = 1.46, 95%CI 1.15-1.85), combination therapy of ICIs (OR = 1.93, 95%CI 1.25-2.97) and extrarenal immune-related adverse events(irAEs) (OR = 2.51, 95%CI 1.96-3.20). Furthermore, analysis from FAERS database verified that concurrent exposures of PPIs (ROR = 2.10, 95%CI 1.91-2.31), ACEIs/ARBs (ROR = 3.25, 95%CI 2.95-3.57), NSAIDs (ROR = 3.06, 95%CI 2.81-3.32) or diuretics (ROR = 2.82, 95%CI 2.50-3.19) were observed significant signals associated with AKI in ICIs-treated patients.
CONCLUSIONS
Concurrent exposures of PPIs, ACEIs/ARBs, NSAIDs or diuretics, diabetes mellitus, genitourinary cancer, combination therapy, and extrarenal irAEs seem to increase the risk of AKI in ICIs-treated patients.
Topics: Humans; Retrospective Studies; Immune Checkpoint Inhibitors; Pharmacovigilance; Angiotensin-Converting Enzyme Inhibitors; Angiotensin Receptor Antagonists; Risk Factors; Acute Kidney Injury; Diuretics; Anti-Inflammatory Agents, Non-Steroidal
PubMed: 37087434
DOI: 10.1186/s12882-023-03171-9 -
Journal of Radiation Research Jun 2023Japanese national oncological experts convened to evaluate the efficacy and safety of particle beam therapy (PT) for pulmonary, liver and lymph node oligometastases...
Comprehensive analysis of Japanese nationwide cohort data of particle beam therapy for pulmonary, liver and lymph node oligometastases: particle beam therapy versus high-precision X-ray radiotherapy.
Japanese national oncological experts convened to evaluate the efficacy and safety of particle beam therapy (PT) for pulmonary, liver and lymph node oligometastases (P-OM, L-OM and LN-OM, respectively) and to conduct a statistically comparative analysis of the local control (LC) rate and overall survival (OS) rate of PT versus those of X-ray stereotactic body radiotherapy (X-SBRT) and X-ray intensity-modulated radiotherapy (X-IMRT). They conducted [1] an analysis of the efficacy and safety of metastasis-directed therapy with PT for P-OM, L-OM and LN-OM using a Japanese nationwide multi-institutional cohort study data set; [2] a systematic review of X-ray high-precision radiotherapy (i.e. X-SBRT/X-IMRT) and PT for P-OM, L-OM and LN-OM; and [3] a statistical comparison between LC and OS of the cohort data set in PT and that of the extracted historical data set in X-SBRT/X-IMRT from the preceding systematic review. Safety was evaluated as the incidence of grade ≥ 3 adverse events, while statistical comparisons of LC and OS were conducted by estimating the incidence rate ratios (IRR) for local progression and mortality, respectively. This study demonstrated that PT provided durable LC (3-year LC rate: 72.8-83.2%) with acceptable OS (3-year OS rate: 38.5-68.1%) and risk of severe toxicity incidence of 0.8-3.5% in radical metastasis-directed therapy for P-OM, L-OM and LN-OM. Compared to LC with X-SBRT or X-IMRT, LC with PT was potentially superior for P-OM; superior for L-OM; and equivalent for LN-OM. In particular, this study demonstrated that PT may be a new treatment option for L-OM tumors measuring > 5 cm.
Topics: Humans; Cohort Studies; East Asian People; Liver; Radiosurgery; Retrospective Studies; Treatment Outcome; X-Rays; Neoplasm Metastasis
PubMed: 37053162
DOI: 10.1093/jrr/rrad004