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Therapeutic Advances in Medical Oncology 2024Immunotherapy is an emerging antitumor therapy that can improve the survival of patients with advanced non-small-cell lung cancer (NSCLC). However, only about 20% of... (Review)
Review
BACKGROUND
Immunotherapy is an emerging antitumor therapy that can improve the survival of patients with advanced non-small-cell lung cancer (NSCLC). However, only about 20% of NSCLC patients can benefit from this treatment. At present, whether patients with driving gene-positive NSCLC can benefit from immunotherapy is one of the hot issues. Therefore, we conducted a meta-analysis to evaluate the efficacy of immunotherapy in patients with oncogene-driven NSCLC and concluded the efficacy of altered subtypes.
METHODS
A literature search was performed using PubMed, Web of Science, and Cochrane databases. The primary endpoints included the objective response rate (ORR), median progression-free survival (mPFS), and median overall survival (mOS) in patients with oncogene-driven NSCLC.
RESULTS
In all, 86 studies involving 4524 patients with oncogene-driven NSCLC were included in this meta-analysis. The pooled ORRs in clinical trials treated with monoimmunotherapy of EGFR, ALK, and KRAS alteration were 6%, 0%, and 23%, respectively. In retrospective studies, the pooled ORRs of EGFR, ALK, KRAS, BRAF, MET, HER2, RET, and ROS1 alteration were 8%, 3%, 28%, 24%, 23%, 14%, 7%, and 8%, respectively. Among them, the pooled ORRs of KRAS non-G12C mutation, KRAS G12C mutation, BRAF V600E mutation, BRAF non-V600E mutation, MET-exon 14 skipping, and MET-amplification were 33% 40%, 20%, 34%, 17%, and 60%, respectively. In addition, the pooled mPFS rates of EGFR, KRAS, MET, HER2, and RET alteration were 2.77, 3.24, 2.48, 2.31, and 2.68 months, while the pooled mOS rates of EGFR and KRAS alteration were 9.98 and 12.29 months, respectively. In prospective data concerning EGFR mutation, the pooled ORR and mPFS treated with chemo-immunotherapy (IC) reached 38% and 6.20 months, while 58% and 8.48 months with chemo-immunotherapy plus anti-angiogenesis therapy (ICA). Moreover, the pooled mPFS and mOS of monoimmunotherapy was 2.33 months and 12.43 months.
CONCLUSIONS
, and -altered NSCLC patients have poor reactivity to monoimmunotherapy but the efficacy of immune-based combined therapy is significantly improved. G12C mutation, non-V600E mutation, and amplification have better responses to immunotherapy, and more prospective studies are needed for further research.
PubMed: 38420602
DOI: 10.1177/17588359231225036 -
European Respiratory Review : An... Jan 2024Molecular pathways found to be important in pulmonary fibrosis are also involved in cancer pathogenesis, suggesting common pathways in the development of pulmonary... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Molecular pathways found to be important in pulmonary fibrosis are also involved in cancer pathogenesis, suggesting common pathways in the development of pulmonary fibrosis and lung cancer.
RESEARCH QUESTION
Is pulmonary fibrosis from exposure to occupational carcinogens an independent risk factor for lung cancer?
STUDY DESIGN AND METHODS
A comprehensive search of PubMed, Embase, Web of Science and Cochrane databases with over 100 search terms regarding occupational hazards causing pulmonary fibrosis was conducted. After screening and extraction, quality of evidence and eligibility criteria for meta-analysis were assessed. Meta-analysis was performed using a random-effects model.
RESULTS
52 studies were identified for systematic review. Meta-analysis of subgroups identified silicosis as a risk factor for lung cancer when investigating odds ratios for silicosis in autopsy studies (OR 1.47, 95% CI 1.13-1.90) and for lung cancer mortality in patients with silicosis (OR 3.21, 95% CI 2.67-3.87). Only considering studies with an adjustment for smoking as a confounder identified a significant increase in lung cancer risk (OR 1.58, 95% CI 1.34-1.87). However, due to a lack of studies including cumulative exposure, no adjustments could be included. In a qualitative review, no definitive conclusion could be reached for asbestosis and silicosis as independent risk factors for lung cancer, partly because the studies did not take cumulative exposure into account.
INTERPRETATION
This systematic review confirms the current knowledge regarding asbestosis and silicosis, indicating a higher risk of lung cancer in exposed individuals compared to exposed workers without fibrosis. These individuals should be monitored for lung cancer, especially when asbestosis or silicosis is present.
Topics: Humans; Silicon Dioxide; Lung Neoplasms; Pulmonary Fibrosis; Asbestosis; Silicosis; Occupational Exposure
PubMed: 38355151
DOI: 10.1183/16000617.0224-2023 -
BMC Cancer Feb 2024There is limited evidence of comparative results among different treatments regarding impacts of Health-Related Quality of Life (HRQoL) for patients with metastatic... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
There is limited evidence of comparative results among different treatments regarding impacts of Health-Related Quality of Life (HRQoL) for patients with metastatic colorectal cancer (mCRC). We aimed to compare efficacy of systemic treatments on HRQoL among patients with mCRC.
METHODS
We collected randomized controlled trials (RCTs) reported in English up until July 2023, from databases including PubMed, Embase, Cochrane Library, ClinicalTrials.gov, and prominent conference databases, for this Bayesian network meta-analysis. Phase 2 or 3 trials that evaluated at least two therapeutic regimens were included. Primary outcomes were short-term and long-term mean changes in EORTC QLQ-C30 global health status/quality of life (GHS/QoL) scores. Secondary outcome was mean change in EQ-5D health utility scores. Mean differences (MDs) with 95% confidence intervals (CIs) were used as effect size. Subgroup analysis was performed based on whether patients received systemic treatments before. We conducted various sensitivity analyses, including differentiating between chemotherapy types, and analyzed patient cohorts with non-specified gene expression levels as well as those with target KRAS expression statuses. The current systematic review protocol was registered on PROSPERO (CRD42023453315 and CRD42023420498).
RESULTS
Immunotherapy and targeted therapy significantly improved HRQoL over chemotherapy, with MDs of 9.27 (95% CI: 3.96 to 14.6) and 4.04 (95% CI: 0.11 to 7.94), respectively. Monotherapy significantly outperformed both combination therapy (MD 5.71, 95%CI 0.78 to 10.63) and no active treatment (MD 3.7, 95%CI 1.41 to 6.01) regarding GHS/QoL in the short-term. Combining targeted therapy with chemotherapy did not improve HRQoL. Focusing on HRQoL, cetuximab excelled when gene expression baselines were unspecified. Subgroup and sensitivity analyses upheld these robust findings, unaffected by model or patient baseline characteristics. Evidence from clinical trials without specific gene level data suggested that monotherapies, especially targeted therapies such as cetuximab, demonstrated superiority in HRQoL. For KRAS wild-type patients, no significant HRQoL differences emerged between chemotherapy, targeted therapy, or their combination..
CONCLUSIONS
Targeted therapies and immunotherapy demonstrate superior HRQoL benefits, monotherapy such as cetuximab is associated with significant improvements as compared to combination therapy. However, tailoring these results to individual gene expression profiles requires more evidence.
Topics: Humans; Cetuximab; Colorectal Neoplasms; Network Meta-Analysis; Proto-Oncogene Proteins p21(ras); Quality of Life; Systematic Reviews as Topic
PubMed: 38336718
DOI: 10.1186/s12885-024-11937-z -
European Archives of... Jul 2024Sinonasal nuclear protein in testis carcinoma (SNUTC) is a rare, aggressive malignancy caused by genetic rearrangements in the NUTM1 gene. The prognosis of SNUTC ranks...
PURPOSE
Sinonasal nuclear protein in testis carcinoma (SNUTC) is a rare, aggressive malignancy caused by genetic rearrangements in the NUTM1 gene. The prognosis of SNUTC ranks among the most unfavorable within the naso-sinusal district, with an overall survival of 9.7 months. This systematic review aimed to determine the best therapeutic strategy for SNUTC.
METHODS
We reviewed eligible articles for patient demographics, TNM and stage at presentation, best response after primary treatment, disease-free survival and overall survival (OS) times, other following therapy lines, and final outcomes.
RESULTS
Among 472 unique citations, 17 studies were considered eligible, with reported treatment data for 25 patients. Most studies (n = 12) were case reports. The most frequently administered treatment regimen was surgery as primary treatment and combined radiochemotherapy as second-line or adjuvant treatment. Four patients were alive at follow-up.
CONCLUSION
Basing on the existing literature, a standardized line in the treatment of SNUTC is not yet well delineated. A self-personalized strategy of therapy should be drawn on each patient affected by SNUTC.
Topics: Humans; Carcinoma; Combined Modality Therapy; Neoplasm Proteins; Neoplasm Staging; Nuclear Proteins; Oncogene Proteins; Paranasal Sinus Neoplasms
PubMed: 38329527
DOI: 10.1007/s00405-024-08489-0 -
PloS One 2024Although milk and dairy products are almost complete food, they can contain toxic heavy elements with potential hazards for consumers. This review aims to provide a...
OBJECTIVE
Although milk and dairy products are almost complete food, they can contain toxic heavy elements with potential hazards for consumers. This review aims to provide a comprehensive report on the occurrence, concentration, and health risks of selected heavy metals in pasteurized and sterilized milk recorded worldwide.
METHODS
The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) was used to develop this systematic review. Databases included the Web of Knowledge, Scopus, Scientific Information Database, Google Scholar, and PubMed from inception until January 2023. Keywords related to the terms "Heavy metals", "Arsenic" and "Pasteurized and sterilized milk" and "Risk Assessment" were used. The potential health risks to human health from milk daily consumption were estimated using extracted data on heavy metals concentration based on metal estimated daily intake, target hazard quotient, and carcinogenic risk.
RESULTS
A total of 48 potentially relevant articles with data on 981 milk samples were included in the systematic review. Atomic Absorption Spectroscopy, atomic absorption spectroscopy, inductively coupled plasma-mass spectrometry, and inductively coupled plasma-optical emission spectrometry were the most common valid methods to measure heavy metals in milk samples. Following the initial evaluation, Cu, Cd, Zn, and Pb were the most contaminants, which exceeded the maximum permissible criteria in 94%, 67%, 62%, and 46% of the milk samples tested. Relying on target hazard quotient and carcinogenic risk results, milk consumers in 33(68.75%) and 7 (14.5%) studies were exposed to moderate to high levels of carcinogenic and non-carcinogenic risk, respectively. The highest level of risk is due to the consumption of pasteurized and sterilized milk detected in Pakistan, Brazil, Egypt, Slovakia, and Turkey.
CONCLUSION
The elevated levels of heavy metals in milk samples, especially Pb and Cd is a public health concern; therefore, maximum control and strict regulations must be adopted to decrease heavy metals contaminants in the dairy industry. Further studies are required to develop safe milk processing and handling methods for the decontamination of heavy metals in milk and its products.
Topics: Humans; Animals; Milk; Cadmium; Lead; Metals, Heavy; Risk Assessment; Carcinogens; Environmental Monitoring
PubMed: 38315713
DOI: 10.1371/journal.pone.0296649 -
Frontiers in Oncology 2023Dysregulation of the long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been linked to some oncogenic pathways that induce cancer...
BACKGROUND
Dysregulation of the long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been linked to some oncogenic pathways that induce cancer initiation and progression. This meta-analysis was conducted to specifically summarize the most recent research on MALAT1 function in human gastric cancer (GC).
METHODS
The eligible studies were first identified by searching HowNet, Web of Science, PubMed, The Cochrane Library, Embase, and databases for studies published as of April 1, 2023. The meta-analysis included 14 studies assessing MALAT1 expression and presenting clinical parameters and survival outcomes.
RESULTS
The results illustrated that high MALAT1 expression is predictive of lymph node metastasis (pooled odds ratio [OR] = 2.99, 95% confidence interval [CI] = 1.97-4.54, P < 0.001) and distant metastasis in GC (OR = 3.11, 95% CI = 1.68-5.75, P < 0.001). In addition, MALAT1 was associated with GC tumor invasion (T/T vs. T/T: OR = 2.90, 95% CI = 1.90- 4.41, P <0.001) and TNM stage (III/IV vs I/II: OR = 2.93, 95% CI: 1.80-4.77, P <0.001). Additionally, higher MALAT-1 expression predicted poorer overall survival in patients with GC (hazard ratio = 1.64, 95% CI = 1.20-2.09, P < 0.001).
CONCLUSIONS
The current findings suggest that the high MALAT1 expression is an adverse biomarker for prognostic outcomes, lymph node metastasis, TNM stage, and distant metastasis in GC and MALAT1 could be a prognostic biomarker for GC.
PubMed: 38239645
DOI: 10.3389/fonc.2023.1257120 -
BMC Public Health Jan 2024This scoping review examines controllable predisposing factors attributable to cancer in the Middle East and North Africa (MENA) region's adult population, highlighting...
PURPOSE
This scoping review examines controllable predisposing factors attributable to cancer in the Middle East and North Africa (MENA) region's adult population, highlighting opportunities to enhance cancer prevention programs.
DESIGN
We systematically searched the PubMed, Science Direct, and CINAHL, EMBASE, and Cochrane Library databases from 1997 to 2022 for articles reporting on the impact of modifiable risk factors on adult patients with cancer in the MENA region.
RESULTS
The review identified 42 relevant articles, revealing that tobacco consumption, obesity, physical inactivity, and diet are significant modifiable risk factors for cancer in the region. Tobacco smoking is a leading cause of lung, bladder, squamous cell carcinoma, and colorectal cancer. A shift towards a westernized, calorie-dense diet has been observed, with some evidence suggesting that a Mediterranean diet may be protective against cancer. Obesity is a known risk factor for cancer, particularly breast malignancy, but further research is needed to determine its impact in the MENA region. Physical inactivity has been linked to colorectal cancer, but more studies are required to establish this relationship conclusively. Alcohol consumption, infections, and exposure to environmental carcinogens are additional risk factors, although the literature on these topics is limited.
CONCLUSION
The review emphasizes the need for further research and the development of targeted cancer prevention strategies in the MENA region.
Topics: Adult; Humans; Risk Factors; Africa, Northern; Middle East; Obesity; Colorectal Neoplasms
PubMed: 38238708
DOI: 10.1186/s12889-024-17787-5 -
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 -
Ecotoxicology and Environmental Safety Jan 2024Disinfection by-products (DBPs), including trihalomethanes (THMs) and haloacetic acids (HAAs), have attracted attention due to their carcinogenic properties, leading to... (Meta-Analysis)
Meta-Analysis Review
Disinfection by-products (DBPs), including trihalomethanes (THMs) and haloacetic acids (HAAs), have attracted attention due to their carcinogenic properties, leading to varying conclusions. This meta-analysis aimed to evaluate the dose-response relationship and the dose-dependent effect of DBPs on cancer risk. We performed a selective search in PubMed, Web of Science, and Embase databases for articles published up to September 15th, 2023. Our meta-analysis eventually included 25 articles, encompassing 8 cohort studies with 6038,525 participants and 10,668 cases, and 17 case-control studies with 10,847 cases and 20,702 controls. We observed a positive correlation between increased cancer risk and higher concentrations of total trihalomethanes (TTHM) in water, longer exposure durations, and higher cumulative TTHM intake. These associations showed a linear trend, with relative risks (RRs) and 95 % confidence intervals (CIs) being 1.02 (1.01-1.03), 1.04 (1.02-1.06), and 1.02 (1.00-1.03), respectively. Gender-specific analyses revealed slightly U-shaped relationships in both males and females, with males exhibiting higher risks. The threshold dose for TTHM in relation to cancer risk was determined to be 55 µg/L for females and 40 µg/L for males. A linear association was also identified between bladder cancer risk and TTHM exposure, with an RR and 95 % CI of 1.08 (1.05-1.11). Positive linear associations were observed between cancer risk and exposure to chloroform, bromodichloromethane (BDCM), and HAA5, with RRs and 95 % CIs of 1.02 (1.01-1.03), 1.33 (1.18-1.50), and 1.07 (1.03-1.12), respectively. Positive dose-dependent effects were noted for brominated THMs above 35 µg/L and chloroform above 75 µg/L. While heterogeneity was observed in the studies for quantitative synthesis, no publication bias was detected. Exposure to TTHM, chloroform, BDCM, or HAA5 may contribute to carcinogenesis, and the risk of cancer appears to be dose-dependent on DBP exposure levels. A cumulative effect is suggested by the positive correlation between TTHM exposure and cancer risk. Bladder cancer and endocrine-related cancers show dose-dependent and positive associations with TTHM exposure. Males may be more susceptible to TTHM compared to females.
Topics: Male; Female; Humans; Disinfection; Chloroform; Trihalomethanes; Urinary Bladder Neoplasms; Water Pollutants, Chemical; Disinfectants
PubMed: 38183752
DOI: 10.1016/j.ecoenv.2023.115925 -
Journal of Immunotherapy (Hagerstown,... May 2024The therapeutic landscape for patients with advanced or metastatic non-small cell lung cancer (NSCLC) is rapidly evolving due to advances in molecular testing and the...
Clinical Outcomes of PD-1/PD-L1 Inhibitors Among Patients With Advanced or Metastatic Non-Small Cell Lung Cancer With BRAF, ERBB2/HER2, MET , or RET Alterations: A Systematic Literature Review.
The therapeutic landscape for patients with advanced or metastatic non-small cell lung cancer (NSCLC) is rapidly evolving due to advances in molecular testing and the development of new targeted therapies and immunotherapies. However, the efficacy of programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors in advanced or metastatic patients with NSCLC whose tumors harbor BRAF V600E mutation, HER2/ERBB2 alteration, MET exon 14 skipping mutation, or RET rearrangement is not completely understood. A systematic literature review was performed to summarize evidence from clinical trials and observational studies on objective response rate, progression-free survival, and overall survival in patients whose tumors express these biomarkers and who were treated with PD-1/PD-L1 inhibitors. Searches of Embase, MEDLINE, conference abstracts, and a clinical trial registry identified a total of 12 unique studies: 4 studies included patients with BRAF V600E mutation, 6 studies included patients with HER2/ERBB2 alteration, 7 studies included patients with MET exon 14 skipping mutation, and 5 studies included patients with RET rearrangement. Across studies, there was heterogeneity in treatment and patient characteristics and a lack of reporting on many important predictive and prognostic factors, including treatment regimens, patients' line of therapy, and tumor PD-L1 expression, which may explain the wide variation in objective response rate, progression-free survival, and overall survival across studies. Therefore, additional studies prospectively evaluating clinical outcomes of PD-1/PD-L1 inhibitors among patients with advanced or metastatic NSCLC whose tumors harbor emerging predictive or prognostic biomarkers are needed to determine whether this class of immunotherapy can provide additional survival benefits for these patients.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Immune Checkpoint Inhibitors; Proto-Oncogene Proteins B-raf; B7-H1 Antigen; Programmed Cell Death 1 Receptor; Proto-Oncogene Proteins c-ret; Receptor, ErbB-2
PubMed: 38112201
DOI: 10.1097/CJI.0000000000000500