zifeng-ai/TrialReviewBench huggingface dataset:
Title: Efficacy and activity of PD-1 blockade in patients with advanced esophageal squamous cell carcinoma: a systematic review and meta-analysis with focus on the value of PD-L1 combined positive score
Topic: Immunotherapy

Background: Recently, several randomized controlled trials (RCTs) investigated immunotherapy-based regimens versus chemotherapy alone in patients with advanced esophageal squamous cell carcinoma (ESCC). Here we conducted a systematic review and meta-analysis on the efficacy and activity of programmed cell death protein 1 blockade in these patients, with focus on the value of programmed death-ligand 1 combined positive score (CPS) for selecting patients who may benefit the most.

Methods: RCTs investigating treatment with or without immune checkpoint inhibitors for advanced ESCC were selected. The hazard ratio (HR) and the odds ratio were used to compare the treatment effect on survival outcomes and tumor response, respectively, for immunotherapy-based regimens compared with standard chemotherapy, overall and according to geographic region or treatment line. We carried out a subgroup analysis comparing patients with CPS ≥10 or <10 and the evidence for treatment effect was evaluated by interaction test.

Results: A total of 5257 patients and 10 RCTs were included. Overall, the HR for overall survival benefit with immunotherapy-based regimens was 0.71 [95% confidence interval (CI) 0.66-0.76] compared with chemotherapy alone; such effect was independent from geographical region (Asia versus rest of the world) and treatment line (upfront versus second/further lines). The HR for progression-free survival benefit and the odds ratio for overall response rate increase were 0.78 (95% CI 0.66-0.93) and 1.50 (95% CI 1.22-1.83), respectively. The HR for overall survival benefit with immunotherapy-based treatment was 0.60 (95% CI 0.51-0.70) for CPS ≥10 subgroup versus 0.83 (95% CI 0.69-1.00) for CPS <10 (P for interaction 0.009).

Conclusions: Immune checkpoint inhibitors have a consistent benefit in reducing the risk of death for ESCC patients which is dependent on programmed death-ligand 1 CPS status. Further investigations of biomarkers for immunotherapy in the subgroup of patients with CPS <10 are needed.

Keywords: combined positive score; esophageal squamous cell carcinoma; immune checkpoint inhibitors; meta-analysis.

PICO:
P: Patients with advanced esophageal squamous cell carcinoma (ESCC)
I: Immunotherapy-based regimens (PD-1 blockade)
C: Standard chemotherapy alone
O: Survival outcomes (overall survival benefit, progression-free survival benefit, and overall response rate), with a particular focus on comparing these outcomes based on differences in the programmed death-ligand 1 combined positive score (CPS)
Title: Nephrotoxicity in patients with solid tumors treated with anti-PD-1/PD-L1 monoclonal antibodies: a systematic review and meta-analysis
Topic: Immunotherapy

Background Programmed death-1 (PD-1) and programmed death ligand 1 (PD-L1) have dramatically improved cancer therapy for many patients. Adverse kidney effects have been found to be an important complication but have unclear mechanisms. Methods We searched Embase, PubMed, and the Cochrane Library to identify potential eligible studies. All included studies were randomized controlled trials (RCTs) examining patients with solid tumors treated with anti-PD-1/PD-L1 monoclonal antibodies (mAbs) and/or chemotherapy. The relative risk (RR) was used to assess the risk of nephrotoxic events. Results We included 27 clinical trials (15,063 patients). Compared with chemotherapy, the RR of all-grade nephritis was significantly increased with anti-PD-1/PD-L1 mAbs (RR = 2.77, 95% CI: 1.09-6.99, P = 0.03). Furthermore, anti-PD-1/PD-L1 mAbs plus chemotherapy can significantly increase the RR of all-grade nephritis (RR = 2.99, 95% CI: 1.07-8.35, P = 0.04). There was also a significant increase in the RRs of all-grade increased blood creatinine (RR = 1.88, 95% CI: 1.24-2.86, P = 0.003) and acute kidney injury (AKI) (RR =3.35, 95% CI: 1.48-7.60, P = 0.004). Conclusions Anti-PD-1/PD-L1 mAbs can significantly increase nephrotoxicity in patients with solid tumors, especially when combined with chemotherapy. During the application of these drugs, we should remain aware of nephrotoxicity for better efficacy. Trial registration number and date of registration Not applicable.

PICO:
P: Patients with solid tumors
I: Treatment with anti-PD-1/PD-L1 monoclonal antibodies
C: Chemotherapy
O: Risk of nephrotoxic events including all-grade nephritis, increased blood creatinine, and acute kidney injury (AKI)
Title: Neoadjuvant hormone therapy for patients with high-risk prostate cancer: a systematic review and meta-analysis
Topic: Hormone Therapy

This study aimed to identify the pathological outcomes and survival benefits of neoadjuvant hormone therapy (NHT) combined with radical prostatectomy (RP) and radiotherapy (RT) administered to patients with high-risk prostate cancer (HRPCa). We searched PubMed, Embase, and the Cochrane Library for studies comparing NHT plus RP or RT with RP or RT alone, administered to patients with HRPCa. We used a random-effects model to compute risk estimates with 95% confidence intervals (CIs) and quantified heterogeneity using the I "2" statistic. Subgroup and sensitivity analyses were performed to identify potential sources of heterogeneity. We selected 16 studies. NHT before RP significantly decreased lymph node involvement (risk ratio [RR] = 0.69, 95% CI: 0.56-0.87) and increased the rates of pathological downstaging (RR = 2.62, 95% CI: 1.22-5.61) and organ-confinement (RR = 2.24, 95% CI: 1.54-3.25), but did not improve overall survival and biochemical progression-free survival (bPFS). The administration of NHT before RT to patients with HRPCa was associated with significant benefits for cancer-specific survival (hazard ratio [HR] = 0.51, 95% CI: 0.39-0.68), disease-free survival (HR = 0.51, 95% CI: 0.44-0.60), and bPFS (HR = 0.54, 95% CI: 0.46-0.64). Short-term NHT combined with RT administered to patients with HRPCa conferred significant improvements. Although the advantage of local control was observed when NHT was administered before RP, there was no significant survival benefit associated with HRPCa. Therefore, short-term NHT combined with RT is recommended for implementation in standard clinical practice but not for patients who undergo RP.

Keywords: high-risk diseases; meta-analysis; neoadjuvant hormone therapy; prostate cancer; prostatectomy; radiotherapy.

PICO:
P: high-risk prostate cancer (HRPCa)
I: 1. neoadjuvant hormone therapy (NHT) with radical prostatectomy (RP); 2. RP alone
O: 1. overall survival; 2. biochemical progression-free survival; 3. cancer-specific survival; 4. disease-free survival; 5. risk rates (RRs) of lymph node involvement; 6. RRs of pathological downstaging; 7. RRs of organ-confinement; 8. RRs of positive surgical margins; 9. RRs of seminal vesicle invasion
Title: Meta-analysis of immune-related adverse events of immune checkpoint inhibitor therapy in cancer patients
Topic: Immunotherapy

Abstract
Background: Immune checkpoint inhibitors (ICIs) have significant clinical efficacy in the treatment of non-small cell lung cancer (NSCLC); however, the incidence of immune-related adverse events (irAEs) of up to 50% has prevented their widespread use. With the increase in the use of ICIs alone or as combination therapy, clinicians are required to have a better understanding of irAEs and be able to manage them systematically. In this study, we aimed to assess the incidence of irAEs associated with ICIs.

Methods: We searched PubMed, Embase, and the Web of Science databases, and also included relevant literature references to widen our search. The relevant data with inclusion criteria were performed using RevMan 3.6.0 for meta-analysis. We undertook a systematic literature search which included published data up to December 2019.

Results: Overall, 147 articles and 23 761 cancer patients with 11 different ICI treatment-related (grade 1-5 and 3-5) irAEs were included in the study. There were 46 articles on pembrolizumab (6598 patients), 27 on nivolumab (3576 patients), 13 on atezolizumab (2787 patients), 12 on avelumab (3213 patients), 10 on durvalumab (1780 patients), 22 on ipilimumab (4067 patients), eight on tremelimumab (1158 patients), three on JS001 (223 patients), four on camrelizumab (SHR-1210) (178 patients), one on sintilimab (96 patients), and one on cemiplimab (85 patients). Grade 1-5 irAEs were: cytotoxic T lymphocyte antigen 4 (CTLA-4) (82.87%), programmed cell death 1 (PD-1) (71.89%), and programmed cell death ligand-1 (PD-L1) (58.95%). Subgroup analysis was: Avelumab (44.53%), durvalumab (66.63%), pembrolizumab (67.25%), atezolizumab (68.77%), nivolumab (76.25%), Ipilimumab (82.18%), and tremelimumab (86.78%). Grade 3-5 irAEs were: CTLA-4 (27.22%), PD-1(17.29%), and PD-L1(17.29%). Subgroup analysis was: Avelumab (5.86%), durvalumab (13.43%), atezolizumab (14.45%), nivolumab (15.72%), pembrolizumab (16.58%), tremelimumab (22.04%), and ipilimumab (28.27%).

Conclusions: This meta-analysis confirmed that anti-PD-1 and anti-PD-L1 inhibitors had a lower incidence of irAEs compared with anti-CTLA-4 inhibitors.

Keywords: Cancer; immune checkpoint inhibitor (ICI); immune-related adverse events (irAEs).

PICO:
P: Cancer patients receiving immune checkpoint inhibitor therapy
I: Immune checkpoint inhibitor (ICI) therapy
C: Different types of ICI therapies, including pembrolizumab, nivolumab, atezolizumab, avelumab, durvalumab, ipilimumab, tremelimumab, JS001 (toripalimab), camrelizumab (SHR-1210), sintilimab, and cemiplimab
O: Incidence of immune-related adverse events (irAEs)
Title: Active Immunotherapy for Glioblastoma Treatment: A Systematic Review and Meta-Analysis
Topic: Immunotherapy

Introduction: Glioblastoma multiforme (GBM) makes 60-70% of gliomas and 15% of primary brain tumors. Despite the availability of standard multimodal therapy, 2 years, 3 years, and 5 years survival rate of GBM are still low. Active immunotherapy is a relatively new treatment option for GBM that seems promising.

Methods: An electronic database search on PubMed, Cochrane, Scopus, and clinicaltrials.gov was performed to include all relevant studies. This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). Reported parameters are OS, PFS, AEs, post treatment KPS, and 2 year mortality.

Results: Active immunotherapy provided better OS (HR = .85; 95% CI = .71-1.01; P = .06) and PFS (HS = .83; 95% CI= .66 - 1.03; P = .11) side albeit not statistically significant. Active immunotherapy reduces the risk of 2 year mortality as much as 2.5% compared to control group (NNT and RRR was 56.7078 and 0,0258, respectively).

Conclusion: Active immunotherapy might be beneficial in terms of survival rate in patients with GBM although not statistically significant. It could be a treatment option for GBM in the future.

Keywords: active immunotherapy; glioblastoma; glioblastoma multiforme; high-grade glioma; vaccine.

PICO:
P: Patients with Glioblastoma multiforme (GBM)
I: Active immunotherapy
O: Overall Survival (OS), Progression-Free Survival (PFS), Adverse Events (AEs), post treatment Karnofsky Performance Scale (KPS), and 2 year mortality
Title: Progression-Free Survival and Overall Survival of CDK 4/6 Inhibitors Plus Endocrine Therapy in Metastatic Breast Cancer: A Systematic Review and Meta-Analysis
Topic: Hormone Therapy

Abstract The introduction of CDK4/6 inhibitors in combination with endocrine therapy (ET) represents the most relevant advance in the management of hormone receptor (HR) positive, HER2-negative metastatic breast cancer over the last few years. This meta-analysis of randomized controlled trials (RCTs) is aimed to better characterize the efficacy of CDK4/6 inhibitors in some relevant subgroups and to test heterogeneity between different compounds with a particular focus on their ability to improve overall survival (OS). Pooled estimates of hazard ratios (HRs) were computed for progression-free survival (PFS), OS, and objective response rate (ORR) analysis in predefined subgroups to better understand treatment effect concerning specific patients' characteristics. To estimate the absolute benefit in terms of PFS, pooled survival curves were generated by pooling the data of all trials. A total of eight RCTs were included. Adding a CDK4/6 inhibitor to ET is beneficial in terms of PFS, irrespective of the presence or not of visceral metastases, the number of metastatic sites, and the length of the treatment-free interval (TFI). The addition of CDK4/6 inhibitors produces a significant OS improvement, both in aromatase inhibitor (AI)-sensitive (HR 0.75, 95% CI) and AI-resistant patients (HR 0.77, 95% CI [0.67-0.89]). Pooled data from each single drug show that palbociclib remains the only class member not showing a statistically significant HR for OS (HR 0.83, 95% CI [0.68-1.02]).

PICO:
P: patients with HR-positive/HER2-negative advanced or metastatic breast cancer
I: 1. CDK4/6 inhibitors with endocrine therapy (ET); 2. ET only
O: 1. progression-free survival; 2. overall survival; 3. objective response rate (ORR)
Title: Efficacy of targeted therapy in patients with HER2-positive non-small cell lung cancer: A systematic review and meta-analysis
Topic: Immunotherapy

Anti-human epidermal growth factor receptor 2 (HER2) therapy is an effective treatment for HER2-positive gastric and breast malignancies. However, the efficacy of HER2-targeted therapy in non-small cell lung cancer (NSCLC) patients with HER2 alterations remains controversial. We searched studies on HER2-targeted therapy in NSCLC patients that reported objective response rate (ORR), disease control rate (DCR) and progressionfree survival (PFS) published from database inception to 30 May 2021. A total of 32 trials involving 958 patients were included. The ORRs of HER2-TKIs targeted therapy, humanised monoclonal antibody, trastuzumab-based treatment and antibody-drug conjugate (ADC) (T-DM1) were 22% (95% CI 11-31), 23% (95% CI 20-65), 26% (95% CI 14-39) and 16% (95% CI _6-37), while that of ADC (DS-8201) was 60% (95% CI 35-85). The DCRs of these groups were 59% (95% CI 49-69), 39% (95% CI _9-88), 63% (95% CI 37-89), 31% (95% CI 4-58) and 87% (95% CI 62-112), respectively. In the subgroup analysis, numerically higher ORRs and DCRs were observed in the poziotinib (38%; 75%) and pyrotinib (35%; 83%) groups. The median PFSs of these groups were 5.51 months, 3.09 months, 4.61 months, 2.65 months and 12.04 months, respectively. HER2-targeted therapy can be considered an acceptable treatment strategy for NSCLC patients with HER2 alterations. In particular, ADC (DS-8201), pyrotinib and poziotinib demonstrated promising anti-tumour activity in HER2-positive NSCLC.

PICO:
P: Patients with HER2-positive non-small cell lung cancer
I: HER2-targeted therapy (Including HER2-TKIs, humanised monoclonal antibody, trastuzumab-based treatment, antibody-drug conjugate (ADC) (T-DM1), and ADC (DS-8201))
O: Objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS)
Title: Comparison of Thermal Ablation and Surgery for Low-Risk Papillary Thyroid Microcarcinoma: A Systematic Review and Meta-Analysis
Topic: Hyperthermia

Objective: Although thermal ablation is effective in treating low-risk papillary thyroid microcarcinomas (PTMCs), comparison of treatment outcomes between thermal ablation and surgery has not yet been systematically evaluated. This study aimed to compare the efficacy and safety of thermal ablation and surgery for the treatment of low-risk PTMCs.

Materials and methods: Ovid-MEDLINE and EMBASE databases were searched for studies reporting comparisons of treatment results between thermal ablation and surgery for patients with low-risk PTMC published up to April 6, 2020. The analysis evaluated the efficacy (local tumor recurrence, occurrence of new tumor, metastasis, and rescue surgery) and safety (complication rate) of thermal ablation and surgery.

Results: This systematic review included four studies with a total of 339 PTMCs in 339 patients who underwent thermal ablation and 320 PTMCs in 314 patients who underwent surgery. There was no local tumor recurrence or distant metastasis in either group. There was no significant difference in the pooled proportion of lymph node metastasis (2.6% with thermal ablation vs. 3.3% with surgery, p = 0.65), occurrence of new tumors (1.4% with thermal ablation vs. 1.3% with surgery, p = 0.85), or rescue surgery (2.6% with thermal ablation vs. 1.6% with surgery, p = 0.62). However, the pooled complication rate was significantly higher in the surgery group than in the ablation group (3.3% with thermal ablation vs. 7.8% with surgery, p = 0.03).

Conclusion: Both thermal ablation and surgery are effective and safe options for the management of low-risk PTMCs, with thermal ablation achieving a lower complication rate. Therefore, thermal ablation may be considered as an alternative treatment option for low-risk PTMC in patients who refuse surgery and active surveillance or are ineligible for surgery.

Keywords: Meta-analysis; Papillary thyroid microcarcinoma; Radiofrequency ablation; Thermal ablation; Thyroid gland.

PICO:
P: low-risk papillary thyroid microcarcinomas (PTMCs)
I: 1. thermal ablation; 2. surgery
O: 1. new tumor after treatment; 2. lymph node metastasis; 3. complication
Title: Safety and efficacy of ultrasound-guided thermal ablation in treating T1aN0M0 and T1bN0M0 papillary thyroid carcinoma: A meta-analysis
Topic: Hyperthermia

Background: Papillary thyroid cancer (PTC) is the most common thyroid tumor, and early diagnosis and treatment can effectively improve prognosis. Many controversies surround the treatment method of T1N0M0 PTC. Recently, thermal ablation (TA) has shown some benefits in the treatment of PTC patients, but the safety and efficacy of its treatment remain controversial. This article performs a meta-analysis of TA in patients with T1aN0M0 and T1bN0M0 PTC.

Methods: The PubMed, Embase, Web of Science, and Cochrane Library databases were systematically searched for retrospective or prospective studies of TA for treating patients with T1N0M0 PTC from the database establishment to May 1, 2022. Data on volume reduction rate (VRR), disease progress, and complication rate were collected. In addition, a meta-analysis was performed using the Stata 12.0 and Review Manager 5.3.

Results: A total of 9 eligible studies were included. Our study demonstrated the effectiveness of VRR and disease progress. The VRR was reduced after 3 months (-75.90%; 95% CI [-118.46-33.34%]), 6 months (34.33%; 95% CI [15.01-53.65%]), 12 months (78.69%; 95% CI [71.69-85.68%]), and 24 months (89.97%; 95% CI [84.00-95.94%]). The disease progress was 1.9% (95% CI [1.1-3.0]). Safety is justified by the complication rate, which was 6.5% (95% CI [3.5-10.2]). Pain and hoarseness were the most common complications, and no life-threatening complications were reported. Egger's test demonstrated that publication bias was acceptable.

Conclusions: TA is an effective and safe method for managing T1aN0M0 and T1bN0M0 papillary thyroid nodules.

Keywords: laser ablation; meta‐analysis; microwave ablation; papillary thyroid carcinoma; radiofrequency ablation; thermal ablation; thyroid nodule.

PICO:
P: T1aN0M0 and T1bN0M0 papillary thyroid carcinoma
I: ultrasound-guided thermal ablation (LA, RFA, or MWA)
O: 1. volume reduction rate; 2. overall diseasee progress rate; 3. complication rate
Title: Are immune-related adverse events associated with the efficacy of immune checkpoint inhibitors in patients with cancer? A systematic review and meta-analysis
Topic: Immunotherapy

Background: A number of studies have reported an association between the occurrence of immune-related adverse events (irAEs) and clinical efficacy in patients undergoing treatment with immune checkpoint inhibitors (ICIs), but the results remain controversial.

Methods: Under the guidance of a predefined protocol and Preferred Reporting Items for Systematic Reviews and Meta-analyses statement, this meta-analysis included cohort studies investigating the association of irAEs and efficacy of ICIs in patients with cancer. The primary outcome was overall survival (OS), and the secondary outcome was progression-free survival (PFS). Subgroup analyses involving the cancer type, class of ICIs, combination therapy, sample size, model, landmark analysis, and approach used to extract the data were performed. Specific analyses of the type and grade of irAEs were also performed.

Results: This meta-analysis included 30 studies including 4971 individuals. Patients with cancer who developed irAEs experienced both an OS benefit and a PFS benefit from ICI therapy compared to patients who did not develop irAEs (OS: hazard ratio (HR), 0.54, 95% confidence interval (CI), 0.45-0.65; p < 0.001; PFS: HR, 0.52, 95% CI, 0.44-0.61, p < 0.001). Subgroup analyses of the study quality characteristics and cancer types recapitulated these findings. Specific analyses of endocrine irAEs (OS: HR, 0.52, 95% CI, 0.44-0.62, p < 0.001), dermatological irAEs (OS: HR, 0.45, 95% CI, 0.35-0.59, p < 0.001), and low-grade irAEs (OS: HR, 0.57, 95% CI, 0.43-0.75; p < 0.001) yielded similar results. The association between irAE development and a favorable benefit on survival was significant in patients with cancer who were undergoing treatment with programmed cell death-1 inhibitors (OS: HR, 0.51, 95% CI, 0.42-0.62; p < 0.001), but not cytotoxic T-lymphocyte antigen-4 inhibitors (OS: HR, 0.89, 95% CI, 0.49-1.61; p = 0.706). Additionally, the association was significant in patients with cancer who were treated with ICIs as a monotherapy (OS: HR, 0.53, 95% CI, 0.43-0.65; p < 0.001), but not as a combination therapy (OS: HR, 0.62, 95% CI, 0.36-1.05; p = 0.073).

Conclusions: The occurrence of irAEs was significantly associated with a better ICI efficacy in patients with cancer, particularly endocrine, dermatological, and low-grade irAEs. Further large-scale prospective studies are warranted to validate our findings.

Systematic review registration: PROSPERO CRD42019129310.

Keywords: Cancer; Efficacy; Immune checkpoint inhibitors; Immune-related adverse events.

PICO:
P: Patients with cancer undergoing treatment with immune checkpoint inhibitors (ICIs)
I: The occurrence of immune-related adverse events (irAEs)
C: Patients who did not develop irAEs
O: Overall survival (OS) and progression-free survival (PFS)