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The Lancet. Oncology Jul 2024Systematic evaluations of cancer risk in people living with HIV or AIDS (PLHIV) and solid organ transplant recipients provide unique insights into the role of the immune... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Systematic evaluations of cancer risk in people living with HIV or AIDS (PLHIV) and solid organ transplant recipients provide unique insights into the role of the immune system in cancer development. In this systematic review and meta-analysis, we expand previous analyses of cancer risk for these two immunocompromised populations.
METHODS
We considered studies published in English and listed on PubMed or Embase up to July 1, 2022. Studies were eligible for inclusion if they used population-based registries and compared cancer incidence in PLHIV or solid organ transplant recipients with the general population in the same geographical area. We extracted the number of observed site-specific cancers and expected cases and calculated meta-standardised incidence ratios for cancer within PLHIV and solid organ transplant recipients. In solid organ transplant recipients meta-standardised incidence ratios were compared by organ type. This project is registered on PROSPERO, CRD42022366679.
FINDINGS
46 studies in PLHIV and 67 in solid organ transplant recipients were included in the analysis. Meta-standardised incidence ratios for cancers associated with human papillomavirus were increased in both populations; the highest meta-standardised incidence ratio in PLHIV was anal cancer (37·28 [95% CI 23·65-58·75], I=97·4%), and in solid organ transplant recipients was cutaneous squamous cell carcinoma (45·87 [31·70-66·38], I=99·0%). Meta-standardised incidence ratios were significantly increased for most non-HPV viral-infection-related cancers in both populations; the highest standard incidence ratios were for Kaposi sarcoma (PLHIV: 801·52 [95% CI 200·25-3208·13], I=100·0%; solid organ transplant recipients: 47·31 [23·09-96·95], I=87·7%) and non-Hodgkin lymphoma (32·53 [19·64-53·87], I=99·8%; 10·24 [8·48-12·35], I=94·9%). Eight types of cancer with no known viral cause showed an increased risk in solid organ transplant recipients only; no cancer type showed increased risk in PLHIV only.
INTERPRETATION
Cancer risk was increased for a range of infection-related cancers in both PLHIV and solid organ transplant recipients, but divergent results in these and other cancers have emerged. The cancer risk patterns probably reflect variances in the degree of impaired immunity, exposure to carcinogenic viruses, and perhaps exposure to carcinogenic immunosuppressive agents.
FUNDING
US National Cancer Institute, National Institutes of Health.
Topics: Humans; Organ Transplantation; HIV Infections; Neoplasms; Incidence; Transplant Recipients; Immunocompromised Host; Risk Factors; Risk Assessment; Female; Male
PubMed: 38936380
DOI: 10.1016/S1470-2045(24)00189-X -
Pediatric Blood & Cancer Jul 2023Numerous studies have demonstrated a variety of social inequalities within pediatric and young adult patients with solid tumors. This systematic review examines and... (Review)
Review
BACKGROUND
Numerous studies have demonstrated a variety of social inequalities within pediatric and young adult patients with solid tumors. This systematic review examines and consolidates the existing literature regarding disparities in pediatric and young adult solid tumor oncology.
PROCEDURE
A MeSH search was performed on the following databases: MEDLINE, PubMed, OvidSP Cochrane, Central, Embase, Cinhal, and Scopus. The systematic review was performed using Rayyan QCRI.
RESULTS
Total 387 articles were found on the initial search, and 34 articles were included in final review. Twenty-seven studies addressed racial and ethnic disparities; 23 addressed socioeconomic disparities. Patients with Hispanic ethnicity, Black race, and lower socioeconomic status were more likely to present at later stages, have differences in treatments and higher mortality rates.
CONCLUSION
This qualitative systematic review identified both racial and socioeconomic disparities in pediatric cancer patients across a variety of solid tumor types. Patients with Hispanic ethnicity, Black race, and lower socioeconomic status are associated with disparities in stage at presentation, treatment, and outcome. Characterization of existing disparities provides the evidence necessary to support changes at a systemic level.
Topics: Child; Humans; Adolescent; Young Adult; Ethnicity; Social Class; Socioeconomic Factors; Racial Groups; Neoplasms
PubMed: 37066595
DOI: 10.1002/pbc.30355 -
Journal of Cachexia, Sarcopenia and... Oct 2021Sarcopenia, which is characterized by a decrease in muscle quantity or quality, is commonly observed in patients with cancer. Recent research has reported contradictory... (Meta-Analysis)
Meta-Analysis Review
Sarcopenia, which is characterized by a decrease in muscle quantity or quality, is commonly observed in patients with cancer. Recent research has reported contradictory results on the association between sarcopenia and the efficacy of immune checkpoint inhibitors (ICIs). We conducted a systematic review and meta-analysis to investigate this discrepancy. We systematically searched three electronic databases to identify articles reporting on the association between sarcopenia and treatment outcomes in patients with solid cancers who received ICIs. The outcomes assessed were hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and odds ratios (ORs) for objective response rate (ORR), disease control rate (DCR), and toxicity. Pooled estimates and their 95% confidence intervals (CIs) were calculated. A total of 2501 patients from 26 studies were analysed. Sarcopenia was observed in 44.7% (95% CI: 38.2-51.3) of the patients and was significantly associated with poor survival (HR = 1.55, 95% CI = 1.32-1.82 for OS and HR = 1.61, 95% CI = 1.35 to 1.93 for PFS). The HRs (95% CIs) for OS according to the diagnostic measures used were 1.97 (0.88-4.41) for psoas muscle index (PMI), 1.41 (0.87-2.28) for skeletal muscle density (SMD), and 1.43 (1.23-1.67) for skeletal mass index (SMI). The HRs (95% CIs) for PFS were 1.86 (1.08-3.21) for PMI, 1.27 (0.94-1.71) for SMD, and 1.38 (1.11-1.71) for SMI. Poor radiological response to ICI therapy was observed in patients with sarcopenia (OR = 0.52, 95% CI = 0.34-0.80 for ORR and OR = 0.45, 95% CI = 0.30-0.67 for DCR). The ORs for ORR (95% CIs) were 0.56 (0.15-2.05) for PMI and 0.78 (0.56-1.09) for SMI. The oncologic outcomes associated with melanoma and non-small cell lung cancer (NSCLC) were comparable with those observed overall (HR for OS = 2.02, 95% CI = 1.26-3.24 for melanoma and HR for OS = 1.61, 95% CI = 1.19-2.18 for NSCLC). In contrast, the occurrence of severe toxicity was not associated with sarcopenia (OR = 1.13, 95% CI = 0.51-2.52). Poor survival and poor response in patients with sarcopenia indicate a negative association between sarcopenia and efficacy of ICIs. Sarcopenia's predictive ability is consistent across various tumour types. For the selection of patients who may respond to ICIs pre-therapeutically, the presence of sarcopenia should be assessed in clinical practice.
Topics: Carcinoma, Non-Small-Cell Lung; Humans; Immune Checkpoint Inhibitors; Lung Neoplasms; Progression-Free Survival; Sarcopenia
PubMed: 34337889
DOI: 10.1002/jcsm.12755 -
Frontiers in Immunology 2023Identification of modulators of the immune response with inhibitory properties that could be susceptible for therapeutic intervention is a key goal in cancer research.... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Identification of modulators of the immune response with inhibitory properties that could be susceptible for therapeutic intervention is a key goal in cancer research. An example is the human leukocyte antigen G (HLA-G), a nonclassical major histocompatibility complex (MHC) class I molecule, involved in cancer progression.
METHODS
In this article we performed a systematic review and meta-analysis on the association between HLA-G expression and outcome in solid tumors. This study was performed in accordance with PRISMA guidelines and registered in PROSPERO.
RESULTS
A total of 25 studies met the inclusion criteria. These studies comprised data from 4871 patients reporting overall survival (OS), and 961 patients, reporting disease free survival (DFS). HLA-G expression was associated with worse OS (HR 2.09, 95% CI = 1.67 to 2.63; P < .001), that was higher in gastric (HR = 3.40; 95% CI = 1.64 to 7.03), pancreatic (HR = 1.72; 95% CI = 0.79 to 3.74) and colorectal (HR = 1.55; 95% CI = 1.16 to 2.07) cancer. No significant differences were observed between the most commonly utilized antibody (4H84) and other methods of detection. HLA-G expression was associated with DFS which approached but did not meet statistical significance.
DISCUSSION
In summary, we describe the first meta-analysis associating HLA-G expression and worse survival in a variety of solid tumors.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022311973.
Topics: Humans; Disease-Free Survival; HLA-G Antigens; Neoplasms; Prognosis; Progression-Free Survival
PubMed: 37275862
DOI: 10.3389/fimmu.2023.1165813 -
BMC Cancer Dec 2023The clinical relevance of circulating tumor cell-white blood cell (CTC-WBC) clusters in cancer prognosis is a subject of ongoing debate. This study aims to unravel their... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The clinical relevance of circulating tumor cell-white blood cell (CTC-WBC) clusters in cancer prognosis is a subject of ongoing debate. This study aims to unravel their contentious predictive value for patient outcomes.
METHODS
We conducted a comprehensive literature search of PubMed, Embase, and Cochrane Library up to December 2022. Eligible studies that reported survival outcomes and examined the presence of CTC-WBC clusters in solid tumor patients were included. Hazard ratios (HR) were pooled to assess the association between CTC-WBC clusters and overall survival (OS), as well as progression-free survival (PFS)/disease-free survival (DFS)/metastasis-free survival (MFS)/recurrence-free survival (RFS). Subgroup analyses were performed based on sampling time, treatment method, detection method, detection system, and cancer type.
RESULTS
A total of 1471 patients from 10 studies were included in this meta-analysis. The presence of CTC-WBCs was assessed as a prognostic factor for overall survival and PFS/DFS/MFS/RFS. The pooled analysis demonstrated that the presence of CTC-WBC clusters was significantly associated with worse OS (HR = 2.44, 95% CI: 1.74-3.40, P < 0.001) and PFS/DFS/MFS/RFS (HR = 1.83, 95% CI: 1.49-2.24, P < 0.001). Subgroup analyses based on sampling time, treatment method, detection method, detection system, cancer type, and study type consistently supported these findings. Further analyses indicated that CTC-WBC clusters were associated with larger tumor size (OR = 2.65, 95% CI: 1.58-4.44, P < 0.001) and higher alpha-fetoprotein levels (OR = 2.52, 95% CI: 1.50-4.22, P < 0.001) in hepatocellular carcinoma. However, no significant association was found between CTC-WBC clusters and TNM stage, depth of tumor invasion, or lymph node metastasis in the overall analysis.
CONCLUSIONS
CTC-WBC clusters are negative predictors for OS and PFS/DFS/MFS/RFS in patients with solid tumors. Monitoring CTC-WBC levels may provide valuable information for predicting disease progression and guiding treatment decisions.
Topics: Humans; Prognosis; Neoplastic Cells, Circulating; Disease-Free Survival; Progression-Free Survival; Liver Neoplasms
PubMed: 38087278
DOI: 10.1186/s12885-023-11711-7 -
Pharmacological Research Feb 2024To assess the efficacy and safety of FDA-approved KRAS inhibitors in patients with KRAS-mutated solid tumors. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To assess the efficacy and safety of FDA-approved KRAS inhibitors in patients with KRAS-mutated solid tumors.
METHODS
We searched PubMed, EMBASE, Cochrane Library, and major international conferences for clinical trials published in English up to March 6, 2023. Clinical trials investigating sotorasib or adagrasib and reporting the clinical outcomes of the objective response rate (ORR), disease control rate (DCR), or incidence rate of grade ≥ 3 adverse events (AEs) were eligible. The primary endpoint was the ORR. Secondary endpoints included the DCR, incidence rate of grade ≥ 3 AEs, and odds ratio (OR) of the ORR between patients with or without co-mutation. The Random-effects model was applied for the outcomes of interest.
RESULTS
18 studies with 1224 patients were included in this meta-analysis. The pooled ORR, DCR, and incidence rate of grade ≥ 3 AEs were 31 % (95 % CI, 25-37 %), 86 % (95 % CI, 82-89 %), and 29 % (95 % CI, 23-36 %), respectively. KRAS-mutated NSCLC patients with a co-mutation of KEAP1 exhibited a worse ORR than those with wild-type KEAP1 (OR: 0.35, 95 % CI: 0.16-0.77).
CONCLUSIONS
This study provided a comprehensive understanding of the efficacy and safety of KRAS inhibitors in treating solid tumors and identified KEAP1 mutation as a potential predictive biomarker of inferior response in patients treated with KRAS inhibitors. These findings may assist in the design of future clinical trials for identifying populations that may benefit from KRAS inhibitor treatment.
Topics: Humans; Kelch-Like ECH-Associated Protein 1; Proto-Oncogene Proteins p21(ras); NF-E2-Related Factor 2; Carcinoma, Non-Small-Cell Lung; Mutation; Lung Neoplasms
PubMed: 38185210
DOI: 10.1016/j.phrs.2024.107060 -
Diagnostic and Interventional Imaging 2020The purpose of this study was to perform a systematic review of current literature describing the efficacy and technical outcomes of transarterial liver therapies using... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
The purpose of this study was to perform a systematic review of current literature describing the efficacy and technical outcomes of transarterial liver therapies using automated feeder detection (AFD) software.
MATERIALS AND METHODS
This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. A structured search was performed in the PubMed, SCOPUS, and Embase databases of patients undergoing locoregional therapy of liver tumors utilizing AFD software. Demographic data, procedure data (including radiometrics) and tumor response rate were recorded. Where available, performance of AFD was compared to conventional digital subtraction angiography (DSA) and cone-beam CT (CBCT) without AFD.
RESULTS
A total of 14 full-text manuscripts met inclusion criteria, comprising 1042 tumors in 604 patients (305 men, 156 women; mean age, 68.6±6.0 [SD] years), including 537 patients with hepatocellular carcinoma, 8 with metastases from neuroendocrine tumors, and 59 patients without reported etiology. Reported sensitivity of AFD ranged between 86% and 98.5%, compared to DSA alone (38% - 64%) or DSA in combination with CBCT (69% - 81%). Three studies reported tumor response by modified response evaluation criteria in solid tumors (mRECIST) guidelines, with complete response in the range of 60% - 69%.
CONCLUSION
AFD is a promising new technology for the identification of intrahepatic and extrahepatic tumor-feeding arteries and should be considered a useful adjunct to conventional DSA and CBCT in the treatment of liver tumors.
Topics: Aged; Angiography, Digital Subtraction; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Cone-Beam Computed Tomography; Female; Humans; Liver Neoplasms; Male; Middle Aged; Software
PubMed: 32035822
DOI: 10.1016/j.diii.2020.01.011 -
Journal of Oral Pathology & Medicine :... Feb 2023In this systematic review, we aimed to evaluate the clinicopathological and prognosis data of patients with salivary gland myoepithelial carcinoma. (Review)
Review
OBJECTIVES
In this systematic review, we aimed to evaluate the clinicopathological and prognosis data of patients with salivary gland myoepithelial carcinoma.
MATERIALS AND METHODS
MEDLINE/PubMed, Scopus, and Embase search was performed with the keywords "myoepithelial carcinoma" "malignant myoepithelioma," and "salivary glands." Primary salivary glands myoepithelial carcinoma that fulfilled the World Health Organization diagnostic criteria were included. The Joanna Briggs Institute tool was used to assess the risk of bias.
RESULTS
Forty-three studies (71 patients) met the inclusion criteria. The patients showed a mean age of 56.4 ± 19.6 years with no sex predilection. The parotid was the most affected gland (49.3%). The tumor presented as an asymptomatic (65.1%) mass (84%). The most common histological findings were the presence of clear tumor cells (39.7%) and multinodular growth patterns (60.7%). Multivariate analysis showed plasmacytoid cell type (p = 0.010) and solid growth pattern (p = 0.003) were related to decreased disease-free survival. Surgery alone was the most used treatment (53.5%). Patients with a combination of treatments showed a longer disease-free survival (p = 0.049). The 2-year and 5-year overall survival rates were 67.5% and 46.1%, respectively.
CONCLUSION
Salivary gland myoepithelial carcinoma showed no sex predilection, with a higher incidence in the parotid gland. Cell type, growth pattern, and treatment type may be related to a lower disease-free survival. Overall, salivary gland myoepithelial carcinoma presented low recurrence and metastasis rates. Registration and protocol: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 checklist and registered in the International Prospective Register of Systematic Reviews (PROSPERO) database (CRD42022311512).
Topics: Humans; Adult; Middle Aged; Aged; Myoepithelioma; Salivary Gland Neoplasms; Salivary Glands; Disease-Free Survival; Carcinoma
PubMed: 36504414
DOI: 10.1111/jop.13395 -
European Journal of Cancer (Oxford,... May 2021Poly (ADP-ribose) polymerase-inhibitors (PARPis) showed antitumour activity in BRCA1/2-mutated cancers, with more heterogeneous outcomes in tumours harbouring... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Poly (ADP-ribose) polymerase-inhibitors (PARPis) showed antitumour activity in BRCA1/2-mutated cancers, with more heterogeneous outcomes in tumours harbouring mutations that impair other genes involved in the DNA homologous recombination repair (HRR) or wild-type (wt).
METHODS
We conducted a systematic review and meta-analysis to better assess the role of PARPis in the treatment of metastatic solid tumours, with and without BRCA1/2 mutations. The primary end-point was progression-free survival (PFS). The secondary end-points were overall response rate (ORR) and overall survival (OS). A random-effects model was applied.
RESULTS
Twenty-nine studies (8,839 patients) were included. PFS was significantly improved (hazard ratio [HR]: 0.59, 95% confidence interval [CI]: 0.51-0.68, p < 0.001), without being affected by BRCA mutational status (p = 0.65). Significant subgroup differences were observed with regard to the tumour site (p = 0.001), line of therapy (p = 0.002), control arm (p < 0.001), type of PARPi (p < 0.001) and trials' phase (p = 0.006). PARPis were associated with ORR (relative risk: 1.35, 95% CI: 1.16-1.56, p < 0.001), with significant subgroup differences observed with regard to treatment line (p = 0.03), control arm (p = 0.04) and PARPis (p < 0.001) and independent of mutational status (p = 0.44), tumour site (p = 0.86) and trials' phase (p = 0.09). OS was significantly improved by PARPis (HR: 0.86, 95% CI: 0.80-0.92, p < 0.001), regardless of mutational status (p = 0.57), tumour site (p = 0.82), treatment line (p = 0.22), control arm (p = 0.21), PARPis (p = 0.30) and trials' phase (p = 0.26). Finally, an exploratory subgroup analysis showed a significant PFS improvement (HR: 0.51, 95% CI: 0.43-0.60, p < 0.001) with PARPis in BRCA-wt/HRR-deficient tumours.
CONCLUSION
Our results confirm the efficacy of already approved PARPi-based treatments in BRCA1/2-mutant solid tumours, support their role also in BRCA-independent HRR-deficient tumours and suggest a potentially broader efficacy in some wt tumours, perhaps with appropriate therapeutic partners. Prospective studies are warranted.
Topics: BRCA1 Protein; BRCA2 Protein; Humans; Mutation; Neoplasms; Poly(ADP-ribose) Polymerase Inhibitors; Progression-Free Survival; Recombinational DNA Repair; Risk Factors; Time Factors
PubMed: 33862496
DOI: 10.1016/j.ejca.2021.02.035 -
The Lancet. Haematology Dec 2022Lenalidomide has been standard therapy for multiple myeloma and other haematological malignancies for more than a decade. Previous meta-analyses identified an... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Lenalidomide has been standard therapy for multiple myeloma and other haematological malignancies for more than a decade. Previous meta-analyses identified an association between lenalidomide and second primary malignancies (SPM) in patients with multiple myeloma. However, newer randomised controlled trials using lenalidomide for other indications have not reported an increased incidence of SPM. The aim of this study was to investigate the risk of developing SPM with lenalidomide use in all disease settings.
METHODS
We did a systematic review of randomised controlled trials that reported SPM in patients treated with lenalidomide. PubMed, Embase, CENTRAL, Europe PubMed Central, and ClinicalTrials.gov were searched from Jan 1, 2004, to March 18, 2022. Randomised controlled trials with at least one lenalidomide group and one non-lenalidomide group were selected, regardless of the disease setting. Studies with a median follow-up of less than 12 months were excluded. Summary data were extracted by two reviewers (KS and KL) independently and verified by a third reviewer (JF). We then conducted a meta-analysis to assess the risk ratio (RR) of SPM with lenalidomide use across various disease subtypes using a random-effects model. We chose random effects for the primary analysis because of anticipated heterogeneity between different diseases, but we used fixed effects for stratified meta-analysis of multiple myeloma studies. Risk of bias was assessed with the PROTECT tool. The study was registered with PROSPERO, CRD42021257508.
FINDINGS
Our search yielded 9078 studies, and 38 trials that included 14 058 patients were eligible for meta-analysis after screening, 18 of which were in multiple myeloma. The RR across all malignancies was 1·16 (95% CI 0·96-1·39). However, there was heterogeneity across indications (p=0·020). The RR when lenalidomide was used for multiple myeloma was 1·42 (1·09-1·84). There was no increase in SPM in lymphoma or chronic lymphocytic leukaemia (0·90 [0·76-1·08]) and myelodysplastic syndrome (0·96 [0·23-3·97]) trials. In the setting of multiple myeloma, lenalidomide increased both solid and haematological SPM, both in the no-transplantation and post-transplantation settings. From the 38 trials, 21 (55%) had low risk of bias, 12 (32%) had unclear risk of bias, and five (13%) had high risk of bias.
INTERPRETATION
Based on the current data, lenalidomide-induced SPM seem to occur exclusively in patients with multiple myeloma. Thus, lenalidomide can be used for other indications without the major concern of a therapy-related neoplasm. In the multiple myeloma setting, lenalidomide is an effective drug, but patients should be monitored both for haematological and solid tumour SPM. This monitoring includes patients that have not received autologous haematopoietic stem-cell transplantation. Further investigations are needed to improve understanding on why lenalidomide only promotes SPM in patients with multiple myeloma.
FUNDING
None.
Topics: Humans; Lenalidomide; Multiple Myeloma; Neoplasms, Second Primary; Transplantation, Autologous; Hematologic Neoplasms
PubMed: 36354020
DOI: 10.1016/S2352-3026(22)00289-7