-
Journal of the Egyptian National Cancer... May 2024Nivolumab (Nivo) and ipilimumab (Ipi) have revolutionized cancer treatment by targeting different pathways. Their combination shows promising results in various cancers,... (Comparative Study)
Comparative Study Meta-Analysis
Evaluating the efficacy and safety of nivolumab and ipilimumab combination therapy compared to nivolumab monotherapy in advanced cancers (excluding melanoma): a systemic review and meta-analysis.
BACKGROUND
Nivolumab (Nivo) and ipilimumab (Ipi) have revolutionized cancer treatment by targeting different pathways. Their combination shows promising results in various cancers, including melanoma, but not all studies have demonstrated significant benefits. A meta-analysis was performed to assess the effectiveness and safety of Nivo-Ipi compared to Nivo alone in advanced cancer types (excluding melanoma).
METHODS
Following PRISMA guidelines, we conducted a meta-analysis up to September 30, 2023, searching databases for randomized controlled trials (RCTs). We focused on advanced solid malignancies (excluding melanoma) with specific Nivo and Ipi dosing. Primary outcomes were overall survival (OS), progression-free survival (PFS), grades 3-4 adverse events (AEs), and treatment-related discontinuations. Secondary outcomes included specific adverse events. Statistical analysis in Review Manager included hazard ratio (HR) and risk ratio (RR), assessing heterogeneity (Higgins I).
RESULTS
Nine RCTs, involving 2152 patients covering various malignancies, were analyzed. The Nivo plus Ipi group exhibited a median OS of 12.3 months and a median PFS of 3.73 months, compared to monotherapy with 11.67 months and 3.98 months, respectively. OS showed no significant difference between Nivo and Ipi combination and Nivo alone (HR = 0.97, 95% CI: 0.88 to 1.08, p = 0.61). PFS had a slight improvement with combination therapy (HR = 0.91, 95% CI: 0.82 to 1.00, p = 0.04). Treatment-related cumulative grades 3-4 adverse events were higher with Nivo and Ipi (RR = 1.52, 95% CI: 1.30 to 1.78, p < 0.00001), as were treatment-related discontinuations (RR = 1.99, 95% CI: 1.46 to 2.70, p < 0.0001). Hepatotoxicity (RR = 2.42, 95% CI: 1.39 to 4.24, p = 0.002), GI toxicity (RR = 2.84, 95% CI: 1.44 to 5.59, p = 0.002), pneumonitis (RR = 2.29, 95% CI: 1.24 to 2.23, p = 0.008), dermatitis (RR = 2.96, 95% CI: 1.08 to 8.14, p = 0.04), and endocrine dysfunction (RR = 6.22, 95% CI: 2.31 to 16.71, p = 0.0003) were more frequent with Nivo and Ipi.
CONCLUSIONS
Combining nivolumab and ipilimumab did not significantly improve overall survival compared to nivolumab alone in advanced cancers (except melanoma). However, it did show slightly better PFS at the cost of increased toxicity, particularly grades 3-4 adverse events. Specific AEs occurred more frequently in the combination group. Further trials are needed to fully assess this combination in treating advanced cancers.
Topics: Humans; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Immune Checkpoint Inhibitors; Ipilimumab; Neoplasms; Nivolumab; Progression-Free Survival; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 38705953
DOI: 10.1186/s43046-024-00218-2 -
Medicine May 2024Benign thyroid nodules (BTNs) represent a prevalent clinical challenge globally, with various ultrasound-guided ablation techniques developed for their management.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Benign thyroid nodules (BTNs) represent a prevalent clinical challenge globally, with various ultrasound-guided ablation techniques developed for their management. Despite the availability of these methods, a comprehensive evaluation to identify the most effective technique remains absent. This study endeavors to bridge this knowledge gap through a network meta-analysis (NMA), aiming to enhance the understanding of the comparative effectiveness of different ultrasound-guided ablation methods in treating BTNs.
METHODS
We comprehensively searched PubMed, Embase, Cochrane, Web of Science, Ovid, SCOPUS, and ProQuest for studies involving 16 ablation methods, control groups, and head-to-head trials. NMA was utilized to evaluate methods based on the percentage change in nodule volume, symptom score, and cosmetic score. This study is registered in INPLASY (registration number 202260061).
RESULTS
Among 35 eligible studies involving 5655 patients, NMA indicated that RFA2 (radiofrequency ablation, 2 sessions) exhibited the best outcomes at 6 months for percentage change in BTN volume (SUCRA value 74.6), closely followed by RFA (SUCRA value 73.7). At 12 months, RFA was identified as the most effective (SUCRA value 81.3). Subgroup analysis showed RFA2 as the most effective for solid nodule volume reduction at 6 months (SUCRA value 75.6), and polidocanol ablation for cystic nodules (SUCRA value 66.5).
CONCLUSION
Various ablation methods are effective in treating BTNs, with RFA showing notable advantages. RFA with 2 sessions is particularly optimal for solid BTNs, while polidocanol ablation stands out for cystic nodules.
Topics: Humans; Thyroid Nodule; Network Meta-Analysis; Ultrasonography, Interventional; Radiofrequency Ablation; Treatment Outcome; Ablation Techniques
PubMed: 38701262
DOI: 10.1097/MD.0000000000038014 -
International Immunopharmacology May 2024Complete pathological response (pCR) and major pathological response (MPR) have been proven to have a close association with improved event-free survival (EFS) and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Complete pathological response (pCR) and major pathological response (MPR) have been proven to have a close association with improved event-free survival (EFS) and overall survival (OS) for patients accepting chemotherapy or chemoradiotherapy. However, further study focusing on neoadjuvant immunotherapy is limited. Here we provided an updated and comprehensive evaluation of the association between pathological response and long-term survival outcomes at patient level and trial level for neoadjuvant immunotherapy.
METHODS
We systematically searched and assessed studies in PubMed, Embase, the Cochrane Library and relevant conference abstracts from inception to June 1, 2023. Studies reported EFS/OS results by pCR/MPR status were eligible.
RESULTS
Forty-three studies comprising a total of 4100 patients were eligible for the analysis, which included 39 studies for the patient-level analysis and 5 randomized controlled trials for the trial-level analysis. Our results highlighted that pCR was associated with improved EFS (HR, 0.48 [95 % CI, 0.39-0.60]) and OS (HR, 0.55 [95 % CI, 0.41-0.74]). The magnitude of HRs by MPR status were similar to the results by pCR status (EFS HR, 0.31 [95 % CI, 0.18-0.53]) and OS HR, 0.43 [95 % CI, 0.19-0.96]). However, no association between pCR and EFS at trial level was found (P = 0.8, R = 0).
CONCLUSION
Our meta-analysis demonstrates a strong association between pathological response and long-term survival outcomes at patient level across studies applying neoadjuvant immunotherapy in most solid tumors but we fail to validate the relationship at trial level. Therefore, an accepted surrogate endpoint applied to both patient and trial levels are waited for further search.
Topics: Humans; Neoadjuvant Therapy; Immunotherapy; Neoplasms; Treatment Outcome; Randomized Controlled Trials as Topic
PubMed: 38685176
DOI: 10.1016/j.intimp.2024.112078 -
Annals of Internal Medicine Jun 2024Many patients participate in cancer trials to access new therapies. The extent to which new treatments produce clinical benefit for trial participants is unclear. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Many patients participate in cancer trials to access new therapies. The extent to which new treatments produce clinical benefit for trial participants is unclear.
PURPOSE
To estimate the progression-free survival (PFS) and overall survival (OS) advantage of assignment to experimental groups in randomized trials for 6 solid tumors.
DATA SOURCES
ClinicalTrials.gov was searched for trials of investigational drugs with results posted between 2017 and 2021.
STUDY SELECTION
Investigational drugs were defined as those not yet having full approval from the U.S. Food and Drug Administration for the study indication. Trials were included if they were randomized and tested drugs or biologics.
DATA EXTRACTION
Data extraction was completed by 2 independent reviewers. Data were pooled using a random-effects model.
DATA SYNTHESIS
The sample included 128 trials comprising 141 comparisons of a new drug and a comparator. These comparisons included 47 050 patients. The pooled hazard ratio for PFS was 0.80 (95% CI, 0.75 to 0.85), indicating statistically significant benefit for patients in experimental groups. This corresponded to a median PFS advantage of 1.25 months (CI, 0.80 to 1.68 months). The pooled hazard ratio for OS was 0.92 (CI, 0.88 to 0.95), corresponding to a survival gain of 1.18 months (CI, 0.72 to 1.71 months). The absolute risk for a serious adverse event for comparator group patients was 29.56% (CI, 26.64% to 32.65%), with an increase in risk of 7.40% (CI, 5.66% to 9.14%) for patients in experimental groups.
LIMITATIONS
Trials in this sample were heterogeneous. Comparator group interventions were assumed to reflect standard of care.
CONCLUSION
Assignment to experimental groups produces statistically significant survival gains. However, the absolute survival gain is small, and toxicity is statistically significantly greater. The findings of this review provide reassuring evidence that patients are not meaningfully disadvantaged by assignment to comparator groups.
PRIMARY FUNDING SOURCE
Canadian Institutes of Health Research.
Topics: Humans; Neoplasms; Randomized Controlled Trials as Topic; Drugs, Investigational; Antineoplastic Agents; Progression-Free Survival; Risk Assessment
PubMed: 38684102
DOI: 10.7326/M23-2515 -
BMC Cancer Apr 2024Although numerous studies have reported the prognostic value of the lung immune prognostic index (LIPI) in non-small cell lung cancer (NSCLC) patients treated with... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Although numerous studies have reported the prognostic value of the lung immune prognostic index (LIPI) in non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs), the prognostic value of the LIPI in a pancancer setting remains unclear.
METHODS
A comprehensive search was conducted until July 2023 across the PubMed, Embase, Web of Science, and Cochrane Library databases to identify relevant studies evaluating the prognostic value of the LIPI in cancer patients treated with ICIs. The outcomes were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). We described and compared the pooled outcomes by stratifying the patients based on different groupings of LIPI (good vs. intermediate [0 vs. 1], good vs. poor [0 vs. 2], and good vs. intermediate / poor [0 vs. 1 + 2]).
RESULTS
A total of 9959 patients in 35 studies were included. A higher score of LIPI was associated with impaired OS. The pooled HRs were 1.69 (95% CI: 1.55-1.85, p < 0.001; 0 vs. 1), 3.03 (95% CI: 2.53-3.63, p < 0.001; 0 vs. 2), and 2.38 (95% CI: 1.97-2.88, p < 0.001; 0 vs. 1 + 2). A higher LIPI score was associated with shorter PFS. The pooled HRs were 1.41 (95% CI: 1.31-1.52, p < 0.001; 0 vs. 1), 2.23 (95% CI: 1.87-2.66, p < 0.001; 0 vs. 2), and 1.65 (95% CI: 1.46-1.86, p < 0.001; 0 vs. 1 + 2). Similarly, a higher LIPI score was associated with a lower ORR. The pooled ORs were 0.63 (95% CI: 0.54-0.75, p < 0.001; 0 vs. 1) and 0.38 (95% CI: 0.29-0.50, p < 0.001; 0 vs. 2). A higher LIPI score was associated with a lower DCR. The pooled ORs were 0.47 (95% CI: 0.35-0.61, p < 0.001; 0 vs. 1) and 0.19 (95% CI: 0.12-0.30, p < 0.001; 0 vs. 2).
CONCLUSION
In patients with NSCLC or other solid tumours, the lung immune prognostic index could robustly stratify the clinical outcomes into three groups among the patients who receive ICIs. LIPI is a low-cost, simple, accessible, and accurate prognostic tool in a pancancer setting and it may contribute to the evaluation of risk stratification in patients treated with ICIs.
Topics: Humans; Immune Checkpoint Inhibitors; Prognosis; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Progression-Free Survival
PubMed: 38664760
DOI: 10.1186/s12885-024-12271-0 -
BMC Oral Health Apr 2024Oral leukoplakia (OLK) is a prevalent precancerous lesion with limited non-pharmacological treatment options. Surgery and various lasers are the mainstay of treatment;... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Oral leukoplakia (OLK) is a prevalent precancerous lesion with limited non-pharmacological treatment options. Surgery and various lasers are the mainstay of treatment; however, their relative efficacy and optimal choice remain unclear. This first network meta-analysis compared the effects of different lasers and surgical excision on post-treatment recurrence and comfort in OLK patients.
METHODS
We searched four databases for relevant randomized controlled trials (RCTs) up to April 2023. The primary outcome was post-treatment recurrence, and secondary outcomes included intraoperative hemorrhage and postoperative pain scores. The Cochrane Risk of Bias tool was used to assess the study quality. Meta-analysis and network meta-analysis were employed to determine efficacy and identify the optimal intervention.
RESULTS
A total of 11 RCTs including 917 patients and 1138 lesions were included. Er,Cr:YSGG laser treatment showed significantly lower recurrence rates compared to CO laser (OR: 0.04; 95% CI: 0.01-0.18), CO laser with margin extension (OR: 0.06; 95% CI: 0.01-0.60), Er:YAG laser (OR: 0.10; 95% CI: 0.03-0.37), electrocautery (OR: 0.03; 95% CI: 0.00-0.18), and standard care (OR: 0.08; 95% CI: 0.02-0.33). Er,Cr:YSGG laser also ranked the best for reducing recurrence, followed by standard care and CO laser combined with photodynamic therapy (PDT). Er:YAG and Er:Cr:YSGG lasers minimized bleeding and pain, respectively. None of the interventions caused severe adverse effects.
CONCLUSION
For non-homogeneous OLK, Er:YAG, Er:Cr:YSGG, and CO laser combined with PDT offer promising alternatives to surgical excision, potentially reducing recurrence and improving patient comfort. Further high-quality RCTs are necessary to confirm these findings and determine the optimal laser-PDT combination for OLK treatment.
Topics: Humans; Network Meta-Analysis; Carbon Dioxide; Patient Comfort; Laser Therapy; Leukoplakia, Oral; Lasers, Solid-State
PubMed: 38632580
DOI: 10.1186/s12903-024-04179-9 -
BMC Cancer Apr 2024This article examines the potential of using liquid biopsy with piRNAs to study cancer survival outcomes. While previous studies have explored the relationship between... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
This article examines the potential of using liquid biopsy with piRNAs to study cancer survival outcomes. While previous studies have explored the relationship between piRNA expression and cancer patient outcomes, a comprehensive investigation is still lacking. To address this gap, we conducted a systematic review and meta-analysis of existing literature.
METHODS
We searched major online databases up to February 2024 to identify articles reporting on the role of piRNA in cancer patient survival outcomes. Our meta-analysis used a random-effects model to pool hazard ratios with 95% confidence intervals (CI) and assess the prognostic value of deregulated piRNA-823. For survival analysis, the Kaplan-Meier method and COX analysis were used.
RESULTS
Out of 6104 articles screened, 20 met our inclusion criteria. Our analysis revealed that dysregulated piRNA expression is associated with cancer patient survival outcomes. Specifically, our meta-analysis found that overexpression of piR-823 is significantly linked with poorer overall survival in patients with colorectal cancer and renal cell cancer (HR: 3.82, 95% CI = [1.81, 8.04], I = 70%).
CONCLUSION
Our findings suggest that various piRNAs may play a role in cancer survival outcomes and that piRNA-823 in particular holds promise as a prognostic biomarker for multiple human cancers.
IMPLICATIONS FOR CANCER SURVIVORS
Our systematic review and meta-analysis of piRNA-823 has important implications for cancer survivors. Our findings suggest that piRNA-823 can be used as a prognostic biomarker for predicting cancer recurrence and survival rates. This information can help clinicians develop personalized treatment plans for cancer survivors, which can improve their quality of life and reduce the risk of recurrence.
Topics: Humans; Piwi-Interacting RNA; RNA, Small Interfering; Quality of Life; Neoplasm Recurrence, Local; Biomarkers
PubMed: 38627675
DOI: 10.1186/s12885-024-12180-2 -
Immunopharmacology and Immunotoxicology Jun 2024The purpose of this study was to investigate the efficacy and safety of lenvatinib in various types of solid tumors. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The purpose of this study was to investigate the efficacy and safety of lenvatinib in various types of solid tumors.
METHOD
By searching PubMed, Web of Science, Cochrane, CNKI, Wanfang and other databases, all the literatures about the comparison of clinical efficacy of lenvatinib in the treatment of various solid tumors. According to the criteria of inclusion and exclusion of literature, two participants screened the literature, collated the data and evaluated the literature. RevMan 5.4 software was used for meta-analysis of the included literatures.
RESULTS
A total of 12 studies were included, including 5213 patients. Meta-analysis showed that, in terms of efficacy, the risk (HR) of prolonging PFS in the treatment of various solid tumors in the lenvatinib group was 1.91 times that in the control group (HR = 1.91, 95% CI: 1.58-2.31, < 0.00001), and the risk (HR) of prolonging OS was 1.27 times that in the single targeted drug group (HR = 1.27, 95% CI: 1.15-1.40, < 0.00001). In terms of safety, the risk of adverse events in the treatment of various solid tumors in the lenvatinib group was higher than that in the control group, especially in Endocrine Toxicities, Renal/Urinary Toxicities, Vascular Toxicities, Musculoskeletal/a Connective Tissue Toxicities and Metabolism/Nutrition Toxicities.
CONCLUSIONS
Lenvatinib in various solid tumors can prolong OS and disease PFS of patients, improve the clinical benefit rate and improve the quality of life of patients. At the same time, there is a certain incidence of adverse events, and symptomatic intervention should be given in clinical medication.
Topics: Humans; Antineoplastic Agents; Neoplasms; Phenylurea Compounds; Protein Kinase Inhibitors; Quinolines; Treatment Outcome
PubMed: 38627024
DOI: 10.1080/08923973.2024.2344153 -
Risk of childhood neoplasms related to neonatal phototherapy- a systematic review and meta-analysis.Pediatric Research Apr 2024Observational studies have shown conflicting results as to whether exposure to neonatal phototherapy is associated with increased rates of childhood cancer.
CONTEXT
Observational studies have shown conflicting results as to whether exposure to neonatal phototherapy is associated with increased rates of childhood cancer.
OBJECTIVE
To describe the rates of childhood neoplasms and cancer after neonatal phototherapy.
DATA SOURCES
The CENTRAL, PubMed, Scopus, and Web of Science databases.
STUDY SELECTION
Observational studies regardless of design were included.
DATA EXTRACTION
The data were extracted by one author and validated by another. The risk-of-bias assessment was performed using the ROBINS-E and Joanna Briggs Institute critical appraisal tools.
RESULTS
Six cohort and 10 case-control studies were included. The overall risk of bias was high in seven and low in nine studies. In cohort studies, the odds ratio (OR) was increased for hematopoietic cancer (1.44; confidence interval [CI]: 1.16-1.80) and solid tumors (OR: 1.18; CI: 1.00-1.40). In case-control studies, the OR was 1.63 (CI: 0.99-2.67) for hematopoietic cancers and 1.18 (CI: 1.04-1.34) for solid tumors.
CONCLUSIONS
Children with a history of neonatal phototherapy had increased risk of hematopoietic cancer and solid tumors. The evidence quality was limited due to the high risk of bias and potential residual confounding.
IMPACT STATEMENT
Exposure to neonatal phototherapy increased later risk of hematopoietic cancer and solid tumors. This is the most comprehensive study on the association between phototherapy and cancer, but the evidence quality was limited due risk of bias and residual confounding. Future large scale well conducted studies are still needed to better estimate the association and.
PubMed: 38615073
DOI: 10.1038/s41390-024-03191-7 -
Journal of Clinical Medicine Mar 2024The optimal management of duodenal neuroendocrine neoplasms (dNENs) sized 10-20 mm remains controversial and although endoscopic resection is increasingly performed... (Review)
Review
The optimal management of duodenal neuroendocrine neoplasms (dNENs) sized 10-20 mm remains controversial and although endoscopic resection is increasingly performed instead of surgery, the therapeutic approach in this setting is not fully standardized. We performed a systematic review of the literature and a meta-analysis to clarify the outcomes of endoscopic resection for 10-20 mm dNENs in terms of efficacy (i.e., recurrence rate) and safety. A computerized literature search was performed using relevant keywords to identify pertinent articles published until January 2023. Seven retrospective studies were included in this systematic review. The overall recurrence rate was 14.6% (95%CI 5.4-27.4) in 65 patients analyzed, without significant heterogeneity. When considering studies specifically focused on endoscopic mucosal resection, the recurrence rate was 20.5% (95%CI 10.7-32.4), without significant heterogeneity. The ability to obtain the free margin after endoscopic resection ranged between 36% and 100%. No complications were observed in the four studies reporting this information. Endoscopic resection could be the first treatment option in patients with dNENs sized 10-20 mm and without evidence of metastatic disease. Further studies are needed to draw more solid conclusions, particularly in terms of superiority among the available endoscopic techniques.
PubMed: 38592317
DOI: 10.3390/jcm13051466