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International Journal of Surgery... Nov 2023Hepatocellular carcinoma (HCC) is the third-most lethal malignant tumor worldwide. The rapid development of immunotherapy utilizing immune checkpoint inhibitors for... (Meta-Analysis)
Meta-Analysis
Clinico-characteristics of patients which correlated with preferable treatment outcomes in immunotherapy for advanced hepatocellular carcinoma: a systematic review and meta-analysis.
BACKGROUND AND AIMS
Hepatocellular carcinoma (HCC) is the third-most lethal malignant tumor worldwide. The rapid development of immunotherapy utilizing immune checkpoint inhibitors for advanced HCC patients has been witnessed in recent years, along with numerous randomized clinical trials demonstrating the survival benefits for these individuals. This systematic review and meta-analysis aimed to identify specific clinico-pathological characteristics of advanced HCC patients that may lead to preferable responses to immunotherapy in terms of overall survival (OS), progression-free survival (PFS), and objective response rate (ORR).
METHODS
The included clinical trials were retrieved from PubMed, Embase, the Cochrane library, and the Web of Science databases published in English between 1 January 2002 and 20 October 2022. A systematic review and meta-analysis for first-line and second-line phase II/III studies were conducted on immunotherapy for patients with advanced HCC by using OS as the primary outcome measure, and PFS and ORR as the secondary outcome measures to obtain clinico-pathological characteristics of patients which might be preferable responses to programmed death-1 (PD-1) and programmed cell death-Ligand 1 (PD-L1) inhibitors. Toxicity and specific treatment-related adverse events (TRAEs) were also determined.
RESULTS
After screening 1392 relevant studies, 12 studies were included in this systematic review and meta-analysis to include 5948 patients. Based on the analysis of interaction, the difference in OS after first-line immunotherapy between the subgroups of viral hepatitis [hazard ratio (HR)=0.73 vs 0.87, P for interaction=0.02] and macrovascular invasion and/or extrahepatic spread (HR=0.73 vs 0.89, P for interaction=0.02) were significant. The difference in PFS between the subgroups of viral hepatitis was highly significant (pooled HR=0.55 vs 0.81, P for interaction=0.007). After second-line immunotherapy, the difference in ORR between the subgroups of Barcelona Clinic Liver Cancer was significant (pooled ES=0.12 vs 0.23, P for interaction=0.04). Compared with PD-L1 inhibitors, PD-1 inhibitors may have a higher probability to cause TRAEs. Diarrhea, increased aspartate aminotransferase, and hypertension were the top three TRAEs.
CONCLUSIONS
This systematic review and meta-analysis represents the first pilot study aimed at identifying crucial clinico-pathological characteristics of patients with advanced HCC that may predict favorable treatment outcomes in terms of OS, PFS, and ORR to immunotherapy. Findings suggest that patients with viral hepatitis positivity (especially hepatitis B virus) and macrovascular invasion and/or extrahepatic spread may benefit more in OS when treated with PD-1/PD-L1 immune checkpoint inhibitors.
Topics: Humans; Carcinoma, Hepatocellular; B7-H1 Antigen; Immune Checkpoint Inhibitors; Pilot Projects; Programmed Cell Death 1 Receptor; Liver Neoplasms; Treatment Outcome; Immunotherapy; Hepatitis, Viral, Human; Lung Neoplasms
PubMed: 37598406
DOI: 10.1097/JS9.0000000000000652 -
Clinics (Sao Paulo, Brazil) 2022The increase in the incidence of pancreatic and biliary cancers has attracted the search for methods of early detection of diseases and biomarkers. The authors propose... (Review)
Review
INTRODUCTION
The increase in the incidence of pancreatic and biliary cancers has attracted the search for methods of early detection of diseases and biomarkers. The authors propose to analyze new findings on the association between microbiota and Pancreatic Ductal Adenocarcinoma (PDAC) or Cholangiocarcinoma (CCA).
METHODS
This systematic review was carried out according to the items of Preferred Reports for Systematic Reviews and Protocol Meta-Analysis (PRISMA-P). This study was registered by the Prospective Register of Systematic Reviews (PROSPERO), identification code CRD42020192748 before the review was carried out. Articles were selected from the PUBMED, EMBASE, and Cochrane databases.
RESULTS
Most studies (86.67%) used 16s rRNA as a sequencing method. The main comorbidities found were diabetes mellitus, systemic arterial hypertension, and dyslipidemia. Many studies were limited by the small number of participants, but the biases were mostly low. There was very little concordance about the composition of the microbiome of different sites, for both case and control groups when compared to other studies' results. Bile sample analysis was the one with a greater agreement between studies, as three out of four studies found Escherichia in cases of CCA.
CONCLUSION
There was great disagreement in the characterization of both the microbiota of cases and control groups. Studies are still scarce, making it difficult to adequately assess the data in this regard. It was not possible to specify any marker or to associate any genus of microbiota bacteria with PDAC or CCA.
Topics: Carcinoma, Pancreatic Ductal; Humans; Microbiota; Pancreatic Neoplasms; RNA, Ribosomal, 16S; Syndrome
PubMed: 36122499
DOI: 10.1016/j.clinsp.2022.100101 -
ESMO Open Feb 2023Neoadjuvant chemotherapy may improve overall survival (OS) in 'borderline' resectable pancreatic cancer (RPC). Whether the results are the same in upfront RPC is unknown. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Neoadjuvant chemotherapy may improve overall survival (OS) in 'borderline' resectable pancreatic cancer (RPC). Whether the results are the same in upfront RPC is unknown.
MATERIALS AND METHODS
To evaluate the association of neoadjuvant treatment and survival outcomes in RPC, a systematic literature review was carried out including prospective randomized trials of neoadjuvant treatment versus upfront surgery. Articles indexed in PubMed, Embase and Scopus were evaluated. Data regarding systemic treatment regimens, R0 resection rates, disease-free survival (DFS) and OS were extracted. The outcomes were compared using a random-effects model. The index I and the graphs of funnel plot were used for the interpretation of the data.
RESULTS
Of 3229 abstracts, 6 randomized controlled trials were considered eligible with a combined sample size of 805 RPC patients. Among the trials, PACT-15, PREP-02/JSAP-05 and updated long-term results from PREOPANC and NEONAX trials were included. Combining the studies with meta-analysis, we could see that neoadjuvant treatment in RPC does not improve DFS [hazard ratio (HR) 0.71 (0.46-1.09)] or OS [HR 0.76 (0.52-1.11)], without significant heterogeneity. Interestingly, R0 rates improved ∼20% with the neoadjuvant approach [HR 1.2 (1.04-1.37)]. It is important to note that most studies evaluated gemcitabine-based regimens in the neoadjuvant setting.
CONCLUSIONS
Neoadjuvant chemotherapy or chemoradiation does not improve DFS or OS in RPC compared to upfront surgery followed by adjuvant treatment. Neoadjuvant treatment improves R0 rates by ∼20%. Randomized ongoing trials are eagerly awaited with more active combined regimens including modified FOLFIRINOX.
Topics: Humans; Pancreatic Neoplasms; Neoadjuvant Therapy; Antineoplastic Combined Chemotherapy Protocols; Prospective Studies; Randomized Controlled Trials as Topic
PubMed: 36638709
DOI: 10.1016/j.esmoop.2022.100771 -
The Cochrane Database of Systematic... Nov 2021Several available therapies for neuroendocrine tumours (NETs) have demonstrated efficacy in randomised controlled trials. However, translation of these results into... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Several available therapies for neuroendocrine tumours (NETs) have demonstrated efficacy in randomised controlled trials. However, translation of these results into improved care faces several challenges, as a direct comparison of the most pertinent therapies is incomplete.
OBJECTIVES
To evaluate the safety and efficacy of therapies for NETs, to guide clinical decision-making, and to provide estimates of relative efficiency of the different treatment options (including placebo) and rank the treatments according to their efficiency based on a network meta-analysis.
SEARCH METHODS
We identified studies through systematic searches of the following bibliographic databases: the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library; MEDLINE (Ovid); and Embase from January 1947 to December 2020. In addition, we checked trial registries for ongoing or unpublished eligible trials and manually searched for abstracts from scientific and clinical meetings.
SELECTION CRITERIA
We evaluated randomised controlled trials (RCTs) comparing two or more therapies in people with NETs (primarily gastrointestinal and pancreatic).
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies and extracted data to a pre-designed data extraction form. Multi-arm studies were included in the network meta-analysis using the R-package netmeta. We separately analysed two different outcomes (disease control and progression-free survival) and two types of NET (gastrointestinal and pancreatic NET) in four network meta-analyses. A frequentist approach was used to compare the efficacy of therapies.
MAIN RESULTS
We identified 55 studies in 90 records in the qualitative analysis, reporting 39 primary RCTs and 16 subgroup analyses. We included 22 RCTs, with 4299 participants, that reported disease control and/or progression-free survival in the network meta-analysis. Precision-of-treatment estimates and estimated heterogeneity were limited, although the risk of bias was predominantly low. The network meta-analysis of progression-free survival found nine therapies for pancreatic NETs: everolimus (hazard ratio [HR], 0.36 [95% CI, 0.28 to 0.46]), interferon plus somatostatin analogue (HR, 0.34 [95% CI, 0.14 to 0.80]), everolimus plus somatostatin analogue (HR, 0.38 [95% CI, 0.26 to 0.57]), bevacizumab plus somatostatin analogue (HR, 0.36 [95% CI, 0.15 to 0.89]), interferon (HR, 0.41 [95% CI, 0.18 to 0.94]), sunitinib (HR, 0.42 [95% CI, 0.26 to 0.67]), everolimus plus bevacizumab plus somatostatin analogue (HR, 0.48 [95% CI, 0.28 to 0.83]), surufatinib (HR, 0.49 [95% CI, 0.32 to 0.76]), and somatostatin analogue (HR, 0.51 [95% CI, 0.34 to 0.77]); and six therapies for gastrointestinal NETs: 177-Lu-DOTATATE plus somatostatin analogue (HR, 0.07 [95% CI, 0.02 to 0.26]), everolimus plus somatostatin analogue (HR, 0.12 [95%CI, 0.03 to 0.54]), bevacizumab plus somatostatin analogue (HR, 0.18 [95% CI, 0.04 to 0.94]), interferon plus somatostatin analogue (HR, 0.23 [95% CI, 0.06 to 0.93]), surufatinib (HR, 0.33 [95%CI, 0.12 to 0.88]), and somatostatin analogue (HR, 0.34 [95% CI, 0.16 to 0.76]), with higher efficacy than placebo. Besides everolimus for pancreatic NETs, the results suggested an overall superiority of combination therapies, including somatostatin analogues. The results indicate that NET therapies have a broad range of risk for adverse events and effects on quality of life, but these were reported inconsistently. Evidence from this network meta-analysis (and underlying RCTs) does not support any particular therapy (or combinations of therapies) with respect to patient-centred outcomes (e.g. overall survival and quality of life).
AUTHORS' CONCLUSIONS
The findings from this study suggest that a range of efficient therapies with different safety profiles is available for people with NETs.
Topics: Humans; Indoles; Network Meta-Analysis; Pancreatic Neoplasms; Positron-Emission Tomography; Pyrimidines; Radionuclide Imaging; Sulfonamides
PubMed: 34822169
DOI: 10.1002/14651858.CD013700.pub2 -
HPB : the Official Journal of the... Jun 2023Minimally Invasive Pancreatic Enucleation, either laparoscopic or robot-assisted, is rarely performed. The aim of this study was to offer the current available evidence... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Minimally Invasive Pancreatic Enucleation, either laparoscopic or robot-assisted, is rarely performed. The aim of this study was to offer the current available evidence about the outcomes of minimally invasive pancreatic enucleations and explore the possible advantage of this approach over traditional surgery.
METHODS
PubMed (MEDLINE), Cochrane Library and Embase (ELSEVIER) medical databases were searched for articles published from January 1990 to March 2022. Studies which included more than 10 cases of minimally-invasive pancreatic enucleation were included. Data on the outcomes were synthetized and meta-analyzed when appropriate.
RESULTS
Twenty studies published between 2009 and 2022 with a total of 552 patients were included in the systematic review: three hundred fifty-one patients (63.5%) had a laparoscopic intervention, two hundred and one (36.5%) robot-assisted with a cumulative incidence of conversion rate of 5%. Minimally-invasive surgery was performed in 63% of cases on the body/tail of the Pancreas and in 37% of the cases on the head/uncinate process of the Pancreas. The cumulative post-operative 30 days - mortality rate was 0.2% and the major postoperative morbidity (Clavien-Dindo III-IV-V) 35%. Clinically relevant pancreatic fistula was observed in 17% of the patients. Compared with the standardized open approach (n: 366 patients), mean length of hospital stay was significantly reduced in patients undergoing minimally invasive pancreatic enucleation (2.45 days, p = 0.003) with a favorable trend for post-operative major morbidity (Clavien-Dindo III-IV) (- 24% RR, p: 0.13). Operative time, blood loss and clinically relevant pancreatic fistula rate were comparable between the two groups. One hundred and fourteen robot-assisted enucleations entered in a subgroup analysis with comparable results to open surgery.
CONCLUSION
Minimally-Invasive approach for pancreatic enucleation is safe, feasible and offers short-term clinical outcomes comparable with open surgery. The potential benefit of robotic surgery will need to be verified in further studies.
Topics: Humans; Pancreatectomy; Pancreatic Neoplasms; Pancreatic Fistula; Laparoscopy; Minimally Invasive Surgical Procedures; Pancreas; Postoperative Complications
PubMed: 36958987
DOI: 10.1016/j.hpb.2023.02.014 -
Cancers Mar 2021Highly proliferative (G3) neuroendocrine neoplasms are divided into well differentiated tumors (NETs) and poorly differentiated carcinomas (NECs), based on the... (Review)
Review
BACKGROUND
Highly proliferative (G3) neuroendocrine neoplasms are divided into well differentiated tumors (NETs) and poorly differentiated carcinomas (NECs), based on the morphological appearance. This systematic review aims to evaluate the clinicopathological features and the treatment response of the NEC subgroup with a Ki67 labeling index (LI) < 55%.
METHODS
A literature search was performed using MEDLINE, Cochrane Library, and Scopus between December 2019 and April 2020, last update in October 2020. We included studies reporting data on the clinicopathological characteristics, survival, and/or therapy efficacy of patients with NECs, in which the Ki67 LI was specified.
RESULTS
8 papers were included, on a total of 268 NEC affected patients. NECs with a Ki67 LI < 55% have been reported in patients of both sexes, mainly of sixth decade, pancreatic origin, and large-cell morphology. The prevalent treatment choice was chemotherapy, followed by surgery and, in only one study, peptide receptor radionuclide therapy. The subgroup of patients with NEC with a Ki67 LI < 55% showed longer overall survival and progression free survival and higher response rates than the subgroup of patients with a tumor with higher Ki67 LI (≥55%).
CONCLUSIONS
NECs are heterogeneous tumors. The subgroup with a Ki67 LI < 55% has a better prognosis and should be treated and monitored differently from NECs with a Ki67 LI ≥ 55%.
PubMed: 33809007
DOI: 10.3390/cancers13061247 -
Medicina (Kaunas, Lithuania) Feb 2023: Metformin has been found to potentially reduce the risk and improve the prognosis of a variety of tumors, but these findings remain controversial in biliary tract... (Meta-Analysis)
Meta-Analysis Review
: Metformin has been found to potentially reduce the risk and improve the prognosis of a variety of tumors, but these findings remain controversial in biliary tract cancer (BTC). Therefore, this systematic review and meta-analysis was conducted to investigate the association between metformin and BTC. : Two independent researchers comprehensively searched PubMed, Embase, the Cochrane Library, and Web of Science for eligible studies published from their inception to 31 March 2022. Comparisons of risk, overall survival (OS), and disease-free survival (DFS) for patients with BTC were selected as the endpoints of interest and pooled by random or fixed-effects models. : Eleven studies with a total of 24,788,738 participants were eligible for this analysis. The overall pooled effects showed no significant differences in biliary tract cancer risk (hazard ratio (HR) = 0.82, 95% confidence interval (CI): 0.50-1.35, = 0.436), OS (HR = 0.88, 95% CI: 0.74-1.04, = 0.135), or DFS (HR = 1.03, 95% CI: 0.79-1.34, = 0.829) between metformin users and non-users. When restricting participants to those with diabetes, a similar negative result was found, demonstrating that metformin use was not significantly associated with a lower risk of developing BTC compared with a lack of metformin use (HR = 0.65, 95% CI: 0.39-1.07, = 0.089); notably, the included studies exhibited significant heterogeneity in the selection of participants and the definition of metformin users. : Metformin may not be able to reduce the risk of BTC and improve prognosis in certain populations. Based on the limited quantity and quality of the included studies, the present results should be interpreted within their limitations, and further studies are warranted to determine the optimal timing, dose, duration, and scenario of metformin administration.
Topics: Humans; Metformin; Hypoglycemic Agents; Prognosis; Diabetes Mellitus; Biliary Tract Neoplasms
PubMed: 36837499
DOI: 10.3390/medicina59020298 -
BMC Cancer Jan 2022Interleukin (IL)-17 family is a group of six cytokines that plays a central role in inflammatory processes and participates in cancer progression. Interleukin-17A has...
BACKGROUND
Interleukin (IL)-17 family is a group of six cytokines that plays a central role in inflammatory processes and participates in cancer progression. Interleukin-17A has been shown to have mainly a protumorigenic role, but the other members of the IL-17 family, including IL-17F, have received less attention.
METHODS
We applied systematic review guidelines to study the role of IL-17F, protein and mRNA expression, polymorphisms, and functions, in cancer. We carried out a systematic search in PubMed, Ovid Medline, Scopus, and Cochrane libraries, yielding 79 articles that met the inclusion criteria.
RESULTS
The findings indicated that IL-17F has both anti- and protumorigenic roles, which depend on cancer type and the molecular form and location of IL-17F. As an example, the presence of IL-17F protein in tumor tissue and patient serum has a protective role in oral and pancreatic cancers, whereas it is protumorigenic in prostate and bladder cancers. These effects are proposed to be based on multiple mechanisms, such as inhibition of angiogenesis, vasculogenic mimicry and cancer cell proliferation, migration and invasion, and aggravating the inflammatory process. No solid evidence emerged for the correlation between IL-17F polymorphisms and cancer incidence or patients' prognosis.
CONCLUSION
IL-17F is a multifaceted cytokine. There is a clear demand for more well-designed studies of IL-17F to elucidate its molecular mechanisms in different types of cancer. The studies presented in this article examined a variety of different designs, study populations and primary/secondary outcomes, which unfortunately reduces the value of direct interstudy comparisons.
Topics: Animals; Biomarkers, Tumor; Carcinogenesis; Cell Line, Tumor; Humans; Interleukin-17; Lymphocytes; Mice; Neoplasms; Polymorphism, Single Nucleotide; Prognosis
PubMed: 35012470
DOI: 10.1186/s12885-021-08969-0 -
Cancer Treatment Reviews Feb 2023The aim of this review was to characterize the second- and later-line (≥2L) treatment landscape for patients with metastatic pancreatic ductal adenocarcinoma (mPDAC). (Review)
Review
INTRODUCTION
The aim of this review was to characterize the second- and later-line (≥2L) treatment landscape for patients with metastatic pancreatic ductal adenocarcinoma (mPDAC).
METHODS
This systematic literature review (PROSPERO: CRD42021279753) involved searches of MEDLINE® and Embase to identify results from prospective studies of ≥2L treatment options for metastatic pancreatic cancer published from 2016 to 2021. Publications were screened according to predetermined eligibility criteria; population-level data were extracted using standardized data fields. Publication quality was assessed according to Grading of Recommendations Assessment, Development and Evaluation (GRADE). The data were analyzed descriptively, grouped by drug class.
RESULTS
Sixty publications were identified, including 23 relating to comparative trials. GRADE assessment found that, of these 23 trials, 83% reported high or moderate-quality evidence. Of the publications relating to comparative trials, nine (three trials) reported favorable results: the pivotal phase 3 NAPOLI-1 trial for liposomal irinotecan; a phase 3 trial of non-liposomal irinotecan within the FOLFIRINOX regimen; and a phase 2 trial of eryaspase plus chemotherapy.
CONCLUSIONS
The level of unmet need for ≥2L treatment options for mPDAC remains high. Irinotecan-based regimens currently offer the greatest promise. Investigations into paradigm-changing agents and combination approaches continue.
Topics: Humans; Pancreatic Neoplasms; Irinotecan; Fluorouracil; Antineoplastic Combined Chemotherapy Protocols; Prospective Studies; Leucovorin; Adenocarcinoma; Carcinoma, Pancreatic Ductal
PubMed: 36641880
DOI: 10.1016/j.ctrv.2022.102502 -
American Journal of Cancer Research 2022Pancreatic cancer (PC) has a dismal prognosis, with identified disparities in survival outcomes based on demographic characteristics. These disparities may be... (Review)
Review
INTRODUCTION
Pancreatic cancer (PC) has a dismal prognosis, with identified disparities in survival outcomes based on demographic characteristics. These disparities may be ameliorated by equitable access to treatments and health services. This systematic review identifies patient and service-level characteristics associated with PC health service utilisation (HSU).
METHODS
Medline, Embase, CINAHL, PsycINFO and Scopus were systematically searched between 1 January, 2010 and 17 May, 2021 for population-based, PC studies which conducted univariable and/or multivariable regression analyses to identify patient and/or service-level characteristics associated with use of a treatment or health service. Direction of effect sizes were reported in an aggregate manner.
RESULTS
Sixty-two eligible studies were identified. Most (48/62) explored the predictors of surgery (n=25) and chemotherapy (n=23), and in populations predominantly based in the United States of America (n=50). Decreased HSU was observed among people belonging to older age groups, non-Caucasian ethnicities, lower socioeconomic status (SES) and lower education status. Non-metropolitan location of residence predicted decreased use of certain treatments, and was associated with reduced hospitalisations. People with comorbidities were less likely to use treatments and services, including specialist consultations and palliative care but were more likely to be hospitalised. A more recent year of diagnosis/year of death was generally associated with increased HSU. Academically affiliated and high-volume centres predicted increased treatment use and hospital readmissions.
CONCLUSION
Findings of this review may assist identification of vulnerable patient groups experiencing disparities in accessing and using treatments and therapies.
PubMed: 35261792
DOI: No ID Found