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International Journal of Radiation... Feb 2024This systematic review and meta-analysis reports on outcomes and hepatic toxicity rates after stereotactic body radiation therapy (SBRT) for liver-confined... (Meta-Analysis)
Meta-Analysis Review
This systematic review and meta-analysis reports on outcomes and hepatic toxicity rates after stereotactic body radiation therapy (SBRT) for liver-confined hepatocellular carcinoma (HCC) and presents consensus guidelines regarding appropriate patient management. Using the Preferred Reporting Items for Systemic Review and Meta-Analyses guidelines, a systematic review was performed from articles reporting outcomes at ≥5 years published before October 2022 from the Embase, MEDLINE, Cochrane, and Scopus databases with the following search terms: ("stereotactic body radiotherapy" OR "SBRT" OR "SABR" OR "stereotactic ablative radiotherapy") AND ("hepatocellular carcinoma" OR "HCC"). An aggregated data meta-analysis was conducted to assess overall survival (OS) and local control (LC) using weighted random effects models. In addition, individual patient data analyses incorporating data from 6 institutions were conducted as their own subgroup analyses. Seventeen observational studies, comprising 1889 patients with HCC treated with ≤9 SBRT fractions, between 2003 and 2019, were included in the aggregated data meta-analysis. The 3- and 5-year OS rates after SBRT were 57% (95% confidence interval [CI], 47%-66%) and 40% (95% CI, 29%-51%), respectively. The 3- and 5-year LC rates after SBRT were 84% (95% CI, 77%-90%) and 82% (95% CI, 74%-88%), respectively. Tumor size was the only prognostic factor for LC. Tumor size and region were significantly associated with OS. Five-year LC and OS rates of 79% (95% CI, 0.74-0.84) and 25% (95% CI, 0.20-0.30), respectively, were observed in the individual patient data analyses. Factors prognostic for improved OS were tumor size <3 cm, Eastern region, Child-Pugh score ≤B7, and the Barcelona Clinic Liver Cancer stage of 0 and A. The incidence of severe hepatic toxicity varied according to the criteria applied. SBRT is an effective treatment modality for patients with HCC with mature follow-up. Clinical practice guidelines were developed on behalf of the International Stereotactic Radiosurgery Society (ISRS).
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Radiosurgery; Treatment Outcome; Retrospective Studies
PubMed: 37597757
DOI: 10.1016/j.ijrobp.2023.08.015 -
Clinical Lung Cancer Sep 2023MET exon 14 (METex14) skipping is a rare oncogenic driver in non-small-cell lung cancer (NSCLC) for which targeted therapy with MET tyrosine kinase inhibitors (TKIs) was... (Review)
Review
INTRODUCTION
MET exon 14 (METex14) skipping is a rare oncogenic driver in non-small-cell lung cancer (NSCLC) for which targeted therapy with MET tyrosine kinase inhibitors (TKIs) was recently approved. Given the heterogeneity in published data of METex14 skipping NSCLC, we conducted a systematic literature review to evaluate its frequency, patient characteristics, and outcomes.
METHODS
On June 13, 2022 we conducted a systematic literature review of publications and conference abstracts reporting frequency, patient characteristics, or outcomes of patients with METex14 skipping NSCLC.
RESULTS
We included 139 studies reporting frequency or patient characteristics (350,997 patients), and 39 studies reporting clinical outcomes (3989 patients). Median METex14 skipping frequency was 2.0% in unselected patients with NSCLC, with minimal geographic variation. Median frequency was 2.4% in adenocarcinoma or nonsquamous subgroups, 12.0% in sarcomatoid, and 1.3% in squamous histology. Patients with METex14 skipping NSCLC were more likely to be elderly, have adenocarcinoma histology; there was no marked sex or smoking status distribution. In first line of treatment, median objective response rate ranged from 50.7% to 68.8% with targeted therapies (both values correspond to MET TKIs), was 33.3% with immunotherapy, and ranged from 23.1% to 27.0% with chemotherapy.
CONCLUSIONS
Patients with METex14 skipping are more likely to have certain characteristics, but no patient subgroup can be ruled out; thus, it is crucial to test all patients with NSCLC to identify suitable candidates for MET inhibitor therapy. MET TKIs appeared to result in higher efficacy outcomes, although no direct comparison with chemotherapy or immunotherapy regimens was found.
Topics: Aged; Humans; Adenocarcinoma; Carcinoma, Non-Small-Cell Lung; Exons; Lung Neoplasms; Mutation; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-met
PubMed: 37451931
DOI: 10.1016/j.cllc.2023.06.008 -
JAMA Network Open Jan 2024The NAPOLI 3 trial showed the superiority of fluorouracil, leucovorin, liposomal irinotecan, and oxaliplatin (NALIRIFOX) over the combination of gemcitabine and... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
The NAPOLI 3 trial showed the superiority of fluorouracil, leucovorin, liposomal irinotecan, and oxaliplatin (NALIRIFOX) over the combination of gemcitabine and nab-paclitaxel (GEM-NABP) as first-line treatment of metastatic pancreatic ductal adenocarcinoma (PDAC). Analyses comparing NALIRIFOX and GEM-NABP with fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) have not yet been reported.
OBJECTIVE
To derive survival, response, and toxic effects data from phase 3 clinical trials and compare NALIRIFOX, FOLFIRINOX, and GEM-NABP.
DATA SOURCES
After a systematic search of PubMed, Scopus, Embase, and American Society of Clinical Oncology and European Society for Medical Oncology meetings' libraries, Kaplan-Meier curves were extracted from phase 3 clinical trials conducted from January 1, 2011, until September 12, 2023.
STUDY SELECTION
Phase 3 clinical trials that tested NALIRIFOX, FOLFIRINOX, or GEM-NABP as first-line treatment of metastatic PDAC and reported overall survival (OS) and progression-free survival (PFS) curves were selected. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses of Individual Participant Data reporting guidelines.
DATA EXTRACTION AND SYNTHESIS
Individual patient OS and PFS data were extracted from Kaplan-Meier plots of original trials via a graphic reconstructive algorithm. Overall response rates (ORRs) and grade 3 or higher toxic effects rates were also collected. A pooled analysis was conducted, and results were validated via a network meta-analysis.
MAIN OUTCOMES AND MEASURES
The primary end point was OS. Secondary outcomes included PFS, ORR, and toxic effects rates.
RESULTS
A total of 7 trials with data on 2581 patients were analyzed, including 383 patients treated with NALIRIFOX, 433 patients treated with FOLFIRINOX, and 1756 patients treated with GEM-NABP. Median PFS was longer in patients treated with NALIRIFOX (7.4 [95% CI, 6.1-7.7] months) or FOLFIRINOX (7.3 [95% CI, 6.5-7.9] months; [HR], 1.21 [95% CI, 0.86-1.70]; P = .28) compared with patients treated with GEM-NABP (5.7 [95% CI, 5.6-6.1] months; HR vs NALIRIFOX, 1.45 [95% CI, 1.22-1.73]; P < .001). Similarly, GEM-NABP was associated with poorer OS (10.4 [95% CI, 9.8-10.8]; months) compared with NALIRIFOX (HR, 1.18 [95% CI, 1.00-1.39]; P = .05], while no difference was observed between FOLFIRINOX (11.7 [95% CI, 10.4-13.0] months) and NALIRIFOX (11.1 [95% CI, 10.1-12.3] months; HR, 1.06 [95% CI, 0.81-1.39]; P = .65). There were no statistically significant differences in ORR among NALIRIFOX (41.8%), FOLFIRINOX (31.6%), and GEM-NABP (35.0%). NALIRIFOX was associated with lower incidence of grade 3 or higher hematological toxic effects (eg, platelet count decreased 1.6% vs 11.8% with FOLFIRINOX and 10.8% with GEM-NABP), but higher rates of severe diarrhea compared with GEM-NABP (20.3% vs 15.7%).
CONCLUSIONS AND RELEVANCE
In this systematic review and meta-analysis, NALIRIFOX and FOLFIRINOX were associated with similar PFS and OS as first-line treatment of advanced PDAC, although NALIRIFOX was associated with a different toxicity profile. Careful patient selection, financial toxic effects consideration, and direct comparison between FOLFIRINOX and NALIRIFOX are warranted.
Topics: Humans; Pancreatic Neoplasms; Irinotecan; Antineoplastic Combined Chemotherapy Protocols; Leucovorin; Oxaliplatin; Gemcitabine; Fluorouracil; Adenocarcinoma
PubMed: 38190183
DOI: 10.1001/jamanetworkopen.2023.50756 -
Frontiers in Endocrinology 2023Differentiated thyroid cancer (DTC) is rare in childhood and adolescence although it represents the most frequent endocrine malignancy in this population. DTC includes... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Differentiated thyroid cancer (DTC) is rare in childhood and adolescence although it represents the most frequent endocrine malignancy in this population. DTC includes both papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC). Most pediatric DTCs are PTCs, while FTCs are rare. To date, no systematic reviews on the global epidemiology of pediatric and adolescent DTC have been published. This systematic review and meta-analysis aims to estimate the overall incidence and prevalence of DTCs in patients aged 0-19 years.
METHODS
The systematic research was conducted from January 2000 to December 2021 through MEDLINE via PubMed, Cochrane Library, and Embase databases. Two separate meta-analyses were performed for PTC and FTC.
RESULTS
After the selection phase, a total of 15 studies (3,332 screened) met the inclusion criteria and are reported in the present systematic review. Five studies were conducted in Europe, five in North America, two in South America, one in Asia, one reported data for 49 countries and territories across the five continents, and one from both the USA and Africa. Most of the studies ( = 14) reported data obtained from national registries, and only one provided information collected from hospital medical records. Beyond the actual trend over time, our study reported a pooled global incidence rate (IR) of PTC and FTC in the pediatric age of 0.46 (95% CI: 0.33-0.59) and 0.07 (95% CI: 0.02-0.12) per 100,000 person-years, respectively. The highest IRs were recorded among Caucasian girls, and the lowest in black or other races/ethnicities.
CONCLUSION
Our data confirm that DTC in the pediatric population is a rare condition. The pooled IRs of the studies included in this meta-analysis are ~0.5 for PTC, which is the most common histological type when both genders and all age groups are considered. The implementation of a prospective international registry on pediatric DTC, as part of the wider European Registries for Rare Endocrine Conditions, has been recently proposed. In addition to providing relevant information on the clinical behavior of this rare disease, standardization of data collection will be pivotal to fill current gaps and allow an accurate estimation of the real incidence and risk factors of DTC.
Topics: Adolescent; Humans; Child; Male; Female; Incidence; Prevalence; Prospective Studies; Carcinoma, Papillary; Thyroid Neoplasms; Adenocarcinoma, Follicular; Thyroid Cancer, Papillary
PubMed: 37795368
DOI: 10.3389/fendo.2023.1270518 -
Pathology, Research and Practice Sep 2023Cholangiocarcinoma (CCA) is a common primary liver malignancy with a poor prognosis. Many studies have demonstrated the involvement of circular RNAs (circRNAs) in... (Review)
Review
BACKGROUND
Cholangiocarcinoma (CCA) is a common primary liver malignancy with a poor prognosis. Many studies have demonstrated the involvement of circular RNAs (circRNAs) in tumorigenesis and progression.
METHODS
Four online databases (PubMed, Web of Science, Embase, and Scopus) were searched on May 04, 2023, for original papers regarding CCA and circRNAs. Bibliometric analysis of included studies was performed on R Studio and GraphPad Prism.
RESULTS
Thirty studies were included in the systematic review and bibliometric analysis. The systematic review showed that circRNAs were involved in CCA proliferation, invasion, metastasis, chemotherapy resistance, and other biological processes and were related to the prognosis of patients and many clinicopathological features. Exosomal circRNAs provide a new idea for the early diagnosis of CCA. The bibliometric analysis showed a significant upward trend in the number of studies on CCA and circRNAs. The 30 included papers had 201 authors and were published in 22 English journals. The first paper was published in 2018, and the second paper was the most cited (148 citations).
CONCLUSION
This systematic review and bibliometric analysis demonstrates that circRNAs in CCA have not been studied enough. CircRNAs play an important role in the occurrence and progression of CCA. They may become new targets for the diagnosis, treatment, and prognostic monitoring of CCA.
Topics: Humans; RNA, Circular; Bibliometrics; Cholangiocarcinoma; Bile Duct Neoplasms; Bile Ducts, Intrahepatic
PubMed: 37651837
DOI: 10.1016/j.prp.2023.154755 -
Cureus Oct 2023Pancreatic cancer is a malignant tumor with one of the worst prognosis. Its incidence has been on the rise in recent years. First-line and second-line treatments as well... (Review)
Review
Pancreatic cancer is a malignant tumor with one of the worst prognosis. Its incidence has been on the rise in recent years. First-line and second-line treatments as well as adjuvant therapies have been employed in clinical trials for pancreatic cancer along with traditional chemotherapy and radiotherapy that has been enhanced. The prognosis of pancreatic ductal adenocarcinoma (PDAC) is still quite bad despite recent improvements in diagnostic and treatment methods. Since most patients are not candidates for treatment with a curative purpose, effective palliative care is crucial. For this systematic review, between December 25, 2022, and January 5, 2023, we searched PubMed, Medline, Cochrane, and Science Direct and discovered 225 relevant articles. The appropriateness of the literature abstracts for the pooled analysis was evaluated using different combinations of keywords such as pancreatic cancer, first- and second-line chemotherapy, palliative chemotherapy, gemcitabine and nab-paclitaxel (GnP), FOLFIRINOX (FFX), and fluorouracil. Eight research studies with a total of 15,236 people, including systematic reviews, meta-analyses, and randomized controlled trials (RCTs), were included. The only treatment of choice for patients without metastatic disease who have clinical staging that suggests resectable or borderline resectable pancreatic cancer (BRPC) should be resection. This research examined how first- and second-line chemotherapeutic regimens (using different drug combinations) affected patients with locally advanced pancreatic cancer (LAPC) or BRPC and how they responded in terms of overall survival (OS), tumor resectability, and progression-free interval. The review concludes by highlighting the results of these therapies. Notably, a growing body of research indicates that the two most popular first-line medication combinations GnP and FFX have similar results in RCTs and in real-world populations. Results of second-line therapy after first-line regime failure are still dismal, and there is still a great deal of doubt regarding the best course of action. More RCTs and real-world evidence studies that address current and innovative regimens, as well as the best order in which to administer them, are required, with a greater emphasis on targeted therapy with fewer side effects.
PubMed: 37937003
DOI: 10.7759/cureus.46630 -
Clinics (Sao Paulo, Brazil) 2024The oral cavity is a link between of external environment with gastrointestinal tract. Studies are controversial on the presence of Periodontal Disease (PD) and its... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The oral cavity is a link between of external environment with gastrointestinal tract. Studies are controversial on the presence of Periodontal Disease (PD) and its association with Gastric Adenocarcinoma (GAC).
METHODS
The authors performed a systematic review and meta-analysis to verify the association between PD and GAC. Six electronic databases were evaluated between 1961 and 2022. Titles and abstracts were reviewed independently according to the eligibility criteria, assessing full texts of selected studies. The quality of the included research was verified using the Newcastle-Ottawa Scale for case-control and cohort studies. Statistical analyses were performed based on fixed and/or random effects models to calculate the summarized Relative Risk (RR) and its 95 % Confidence Interval (95 % CI).
RESULTS
There were 639 studies, of which nine articles were included (3 case-controls and 6 cohorts). Overall, the authors identified 1,253 cases of GAC 2,501 controls in case-control studies, and 1,631 patients with GAC enrolled in cohort studies. Patients presenting PD increased the risk of developing GAC by 17 % (RR=1.17; 95 % CI 1.03‒1.32), which remained regardless of the diagnostic method for PD, i.e., clinical examination (RR = 1.19; 95 % CI 1.14‒1.24) and self-report (RR = 1.34; 95 % CI 1.06‒1.69). Moreover, Asian patients (RR=1.17; 95 % CI 1.00‒1.36) with PD had a higher risk of having GAC than American and European patients (RR = 1.18; 95 % CI 0.84‒1.66).
CONCLUSIONS
The presence of PD the risk of GAC suggesting that its infectious-inflammatory process of PD may be related to GAC development. Further investigations on the oral-gastric microbiota and its role in the carcinogenesis of gastric cancer should be carried out, and the screening of patients with potential risk for GAC should be considered in the clinical practice of dentists.
Topics: Humans; Stomach Neoplasms; Periodontal Diseases; Adenocarcinoma; Cohort Studies; Case-Control Studies
PubMed: 38301538
DOI: 10.1016/j.clinsp.2023.100321 -
Current Oncology (Toronto, Ont.) Jul 2023Pancreatic cancer is the seventh leading cause of cancer deaths worldwide, accounting for 4.7% of all cancer deaths, and is expected to climb significantly over the next... (Review)
Review
Pancreatic cancer is the seventh leading cause of cancer deaths worldwide, accounting for 4.7% of all cancer deaths, and is expected to climb significantly over the next decade. The purpose of this systematic review and guidance document was to synthesize the evidence surrounding the role of adjuvant treatment (chemotherapy and chemoradiation therapy [CRT], and stereotactic body radiation therapy [SBRT]) in resected pancreatic ductal adenocarcinoma (PDAC). Systematic literature searches of MEDLINE, EMBASE, and 11 guideline databases were conducted. Both direct and indirect comparisons indicate adjuvant chemotherapy offers a survival advantage over surgery alone. The optimal regimens recommended are mFOLFIRINOX with alternative options of gemcitabine plus capecitabine, gemcitabine alone, or S-1 (which is not available in North America). Trials comparing a CRT strategy to modern chemotherapy regimens are lacking. However, current evidence demonstrates that the addition of CRT to chemotherapy does not result in a survival advantage over chemotherapy alone and is therefore not recommended. Trials evaluating SBRT in PDAC are also lacking. SBRT should only be used within a clinical trial or multi-institutional registry.
Topics: Humans; Deoxycytidine; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Pancreatic Ductal; Pancreatic Neoplasms; Chemotherapy, Adjuvant
PubMed: 37504342
DOI: 10.3390/curroncol30070482 -
EBioMedicine Jul 2023Various studies have reported cell-free RNAs (cfRNAs) as noninvasive biomarkers for detecting hepatocellular carcinoma (HCC). However, they have not been independently...
BACKGROUND
Various studies have reported cell-free RNAs (cfRNAs) as noninvasive biomarkers for detecting hepatocellular carcinoma (HCC). However, they have not been independently validated, and some results are contradictory. We provided a comprehensive evaluation of various types of cfRNA biomarkers and a full mining of the biomarker potential of new features of cfRNA.
METHODS
We first systematically reviewed reported cfRNA biomarkers and calculated dysregulated post-transcriptional events and cfRNA fragments. In 3 independent multicentre cohorts, we further selected 6 cfRNAs using RT-qPCR, built a panel called HCCMDP with AFP using machine learning, and internally and externally validated HCCMDP's performance.
FINDINGS
We identified 23 cfRNA biomarker candidates from a systematic review and analysis of 5 cfRNA-seq datasets. Notably, we defined the cfRNA domain to describe cfRNA fragments systematically. In the verification cohort (n = 183), cfRNA fragments were more likely to be verified, while circRNA and chimeric RNA candidates were neither abundant nor stable as qPCR-based biomarkers. In the algorithm development cohort (n = 287), we build and test the panel HCCMDP with 6 cfRNA markers and AFP. In the independent validation cohort (n = 171), HCCMDP can distinguish HCC patients from control groups (all: AUC = 0.925; CHB: AUC = 0.909; LC: AUC = 0.916), and performs well in distinguishing early-stage HCC patients (all: AUC = 0.936; CHB: AUC = 0.917; LC: AUC = 0.928).
INTERPRETATION
This study comprehensively evaluated full-spectrum cfRNA biomarker types for HCC detection, highlighted the cfRNA fragment as a promising biomarker type in HCC detection, and provided a panel HCCMDP.
FUNDING
National Natural Science Foundation of China, and The National Key Basic Research Program (973 program).
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; alpha-Fetoproteins; Cell-Free Nucleic Acids; Biomarkers, Tumor; ROC Curve; MicroRNAs
PubMed: 37315449
DOI: 10.1016/j.ebiom.2023.104645 -
Nutrients Sep 2023Available results on the association between the Mediterranean diet (MD) and gastric cancer (GC) incidence are controversial. The present study aimed to determine the... (Meta-Analysis)
Meta-Analysis Review
Available results on the association between the Mediterranean diet (MD) and gastric cancer (GC) incidence are controversial. The present study aimed to determine the correlation between different subtypes of GC and MD adherence. This meta-analysis was registered on PROSPERO (CRD42021284432). We searched Embase, PubMed, Cochrane Library, and Web of Science from inception through 22 April 2023 to retrieve relevant studies. A random-effects model was used to pool odds ratios (ORs) with 95% confidence intervals (CIs). Eleven studies were included in the meta-analysis. Pooled analyses revealed that adherence to the MD was inversely associated with GC risk (OR, 0.43; 95% CI, 0.29 to 0.63; OR, 0.84; 95% CI, 0.77 to 0.92). Higher MD adherence was significantly associated with a reduced GC risk in male (OR, 0.78; 95% CI, 0.65 to 0.93; OR, 0.81; 95% CI, 0.65 to 1.01), but not in female (OR, 0.83; 95% CI, 0.68 to 1.01; OR, 1.04; 95% CI, 0.82 to 1.31). Furthermore, adherence to the MD possibly decreased the risk of gastric cardia adenocarcinoma (GCA) (OR, 0.64; 95% CI, 0.49 to 0.83; OR, 0.88; 95% CI, 0.76 to 1.02) and gastric non-cardia adenocarcinoma (GNCA) (OR, 0.68; 95% CI, 0.59 to 0.79; OR, 0.85; 95% CI, 0.78 to 0.94). Our results indicate that adherence to the MD reduces the risk of GC and its subtypes.
Topics: Female; Male; Humans; Stomach Neoplasms; Diet, Mediterranean; Adenocarcinoma; Odds Ratio; PubMed
PubMed: 37686858
DOI: 10.3390/nu15173826