zifeng-ai/TrialReviewBench huggingface dataset:
Title: Efficacy and Safety of CAR-T Therapy for ...
Topic: Immunotherapy

ABSTRACT
Background: Multiple myeloma (MM) is incurable in spite of recent treatment improvements, highlighting the development of new therapies. Chimeric antigen receptor (CAR) T-cell therapy has dramatically changed the therapeutic effectiveness in high-risk B-cell malignancies. For relapsed/refractory multiple myeloma (RRMM), preclinical evaluations of CAR-T therapy have shown promising efficacy, thus various active clinical trials are under way. Herein, we conducted this review to summarize efficacy and safety of CAR-T therapy and provide more evidence to guide clinical treatments.

Method: We systematically searched literature based on databases (PubMed, EMBASE, Cochrane Central Register of Controlled Trials), and conference abstracts reported from American Society of Hematology (ASH), European Hematology Association (EHA) and American Society of Clinical Oncology (ASCO), in addition to other sources (www.clinicaltrials.gov, article citations). Data assessed efficacy and safety of CAR-T therapy in patients with RRMM were extracted and evaluated, and then systematically analyzed by Comprehensive Meta-analysis 3.0 (CMA 3.0).

Results: A total of 23 studies including 350 participants from different countries, diagnosed as RRMM and treated with CAR-T therapy (containing 7 antigens targeted by CARs) were combined. In summary, we discovered the pooled overall response rate (77%), complete response rate (37%) and minimal residual disease (MRD) negativity rate within responders (78%). Furthermore, the pooled relapse rate of responders was 38% and median progression-free survival was 8 months. The pooled survival rate was 87% at last follow-up (median, 12 months). In addition, the pooled grade 3-4 rates of cytokine release syndrome (CRS) and neurologic toxicities (NT) were 14% and 13%, respectively.

Conclusion: Our study suggests that CAR-T therapy has demonstrated efficacy and safety in RRMM patients. BCMA-targeted CAR-T and anti-BCMA contained regimen have shown better efficacy.

Keywords: RRMM, CARs, CAR-T therapy, antigens, BCMA, co-stimulatory domain, systematic review, meta-analysis

PICO:
P: Patients with relapsed/refractory multiple myeloma (RRMM)
I: CAR-T therapy
C: N/A
O: Efficacy outcomes such as overall response rate, complete response rate, minimal residual disease (MRD) negativity rate, relapse rate, and median progression-free survival; Safety outcomes such as rates of grade 3-4 cytokine release syndrome (CRS) and neurologic toxicities (NT)
Title: Is PEGylated G-CSF superior to G-CSF in patients with breast cancer receiving chemotherapy? A systematic review and meta-analysis
Topic: Immunotherapy

Background: PEGylated granulocyte colony-stimulating factor (G-CSF) is a safe alternative to G-CSF to improve chemotherapy-induced neutropenia (CIN). This superiority has resulted in its increased use by physicians; however, the superiority of PEGylated G-CSF for CIN in breast cancer has not been conclusively determined.

Objectives: To assess the superiority of PEGylated G-CSF for CIN in breast cancer in terms of effectiveness and safety via a systematic review and meta-analysis.

Methods: A literature search in PubMed, Embase, Cochrane Library, and Web of Science was performed for eligible studies published from database inception to December 2019. All studies comparing PEGylated G-CSF and G-CSF for CIN of breast cancer were reviewed. After literature selection, data extraction and quality assessment were performed by two reviewers independently. Meta-analysis was conducted using Revman, version 5.2.

Results: Nine randomized controlled trials were finally identified. The publication bias of these studies was acceptable. For the endpoint of effectiveness, analysis of the incidence/duration of grade ≥ 3 neutropenia, the duration of grade 4 neutropenia, the incidence of febrile neutropenia (FN), and the time to absolute neutrophil count recovery showed no advantage of PEGylated G-CSF over G-CSF for CIN of breast cancer (P > 0.05), with the premise of a sufficient dose of G-CSF according to the guidelines. No significant differences in grade 4 adverse events were observed between the groups (P = 0.29), and PEGylated G-CSF did not increase the incidence of skeletal and/or muscle pain compared with G-CSF (P = 0.32).

Conclusion: PEGylated G-CSF was as effective and safe as G-CSF to reduce CIN in breast cancer but did not show an obvious superiority. However, in clinical practice, PEGylated G-CSF has an obvious advantage in terms of convenience, which could improve patient's quality of life.

Keywords: Breast cancer; Chemotherapy; G-CSF; PEGylated G-CSF.


PICO:
P: breast cancer receiving chemotherapy
I: 1. PEGylated granulocyte colony-stimulating factor (G-CSF); 2. G-CSF
O: 1. risk ratios (RRs) of grade >= 3 / 4 neutropenia; 2. RRs of febrile neutropenia (FN); 3. time to absolute neutrophil count recovery; 4. grade 4 AEs; 5. RRs of skeletal and/or muscle pain
Title: Comparison of allogeneic hematopoietic stem cell transplantation and TKI combined with chemotherapy for adult philadelphia chromosome positive acute lymphoblastic leukemia: a systematic review and meta-analysis
Topic: Immunotherapy

Objective: This study seeks to clarify whether allogeneic hematopoietic stem cell transplantation (allo-HSCT) is necessary for adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) in post-remission based on a comparison with tyrosine kinase inhibitor (TKI) combined with chemotherapy. Methods: We searched the Pubmed, Embase, and Web of Science databases and limited the date range for the studies from January 2010 to August 2020. A hazard ratio (HR) with a 95% confidence interval (CI) was employed to assess overall survival (OS) and relapse-free survival (RFS), and an odds ratio (OR) with a 95% CI was used to evaluate the ratio of non-relapsed mortality (NRM) and non-relapsed survival (NRS). All analyses were conducted with Stata software 16.0 and Revman 5.3. Results: Fifteen studies, totaling 959 patients, were included in our analysis. Among those patients, 473 underwent allo-HSCT, and 486 received TKI plus chemotherapy. The pooled results showed no difference in OS between outcomes for patients receiving TKI plus chemotherapy and those treated with allo-HSCT (HR = 0.76, 95% CI [0.51-1.12], p = 0.16). Patients undergoing allo-HSCT did better than those receiving TKI plus chemotherapy regarding RFS (HR = 0.48, 95% CI [0.37-0.63], p = 0.00), and NRS (OR = 2.64, 95% CI [1.25-5.57], p = 0.00). The NRM rate of the TKI plus chemotherapy group was significantly lower than the allo-HSCT group (OR = 2.33, 95% CI [1.51-3.59], p = 0.00). Conclusion: TKI combined with chemotherapy can be considered a post-remission treatment option for adult Ph+ ALL patients who are ineligible for allo-HSCT. However, more prospective studies with large sample sizes should be carried out in the future. Keywords: Philadelphia chromosome positive acute lymphoblastic leukemia; allogeneic hematopoietic stem cell transplantation; meta-analysis; tyrosine kinase inhibitor.

PICO:
P: Adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) in post-remission
I: Allogeneic hematopoietic stem cell transplantation (allo-HSCT)
C: Tyrosine kinase inhibitor (TKI) combined with chemotherapy
O: Overall survival (OS), relapse-free survival (RFS), non-relapsed mortality (NRM), and non-relapsed survival (NRS)
Title: Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): An update on 107 randomized trials and 19,805 patients, on behalf of MACH-NC Group
Topic: Radiation/Chemotherapy

Abstract
Background and purpose: The Meta-Analysis of Chemotherapy in squamous cell Head and Neck Cancer (MACH-NC) demonstrated that concomitant chemotherapy (CT) improved overall survival (OS) in patients without distant metastasis. We report the updated results.

Materials and methods: Published or unpublished randomized trials including patients with non-metastatic carcinoma randomized between 1965 and 2016 and comparing curative loco-regional treatment (LRT) to LRT + CT or adding another timing of CT to LRT + CT (main question), or comparing induction CT + radiotherapy to radiotherapy + concomitant (or alternating) CT (secondary question) were eligible. Individual patient data were collected and combined using a fixed-effect model. OS was the main endpoint.

Results: For the main question, 101 trials (18951 patients, median follow-up of 6.5 years) were analyzed. For both questions, there were 16 new (2767 patients) and 11 updated trials. Around 90% of the patients had stage III or IV disease. Interaction between treatment effect on OS and the timing of CT was significant (p < 0.0001), the benefit being limited to concomitant CT (HR: 0.83, 95%CI [0.79; 0.86]; 5(10)-year absolute benefit of 6.5% (3.6%)). Efficacy decreased as patients age increased (p_trend = 0.03). OS was not increased by the addition of induction (HR = 0.96 [0.90; 1.01]) or adjuvant CT (1.02 [0.92; 1.13]). Efficacy of induction CT decreased with poorer performance status (p_trend = 0.03). For the secondary question, eight trials (1214 patients) confirmed the superiority of concomitant CT on OS (HR = 0.84 [0.74; 0.95], p = 0.005).

Conclusion: The update of MACH-NC confirms the benefit and superiority of the addition of concomitant CT for non-metastatic head and neck cancer.

Keywords: Chemotherapy; Head and Neck Cancer; Individual Patient Data; Meta-analysis; Radiotherapy; Randomised Clinical Trials.

PICO:
P: Patients with non-metastatic squamous cell carcinoma of the head and neck
I: Concomitant chemotherapy (CT) with loco-regional treatment (LRT)
C: Loco-regional treatment alone, or loco-regional treatment with induction or adjuvant chemotherapy, or different timing of chemotherapy (e.g., induction CT + radiotherapy vs. radiotherapy + concomitant or alternating CT)
O: Overall survival (OS)
Title: Adjuvant endocrine therapy in HER2-positive breast cancer patients: systematic review and meta-analysis
Topic: Hormone Therapy

Background: Approximately 50% of human epidermal growth factor receptor 2 (HER2)-positive breast cancer lesions express hormone receptors. These tumors present a unique therapeutic challenge, and the optimal endocrine therapeutic approach remains controversial. We aimed to study the optimal adjuvant endocrine therapy in this setting, to better establish the basis for clinical recommendations in HER2-positive disease.

Methods: We conducted a literature search up to May 2020, in which we identified randomized controlled trials (RCTs) that investigated the efficacy of various adjuvant hormonal therapies among premenopausal and postmenopausal patients with hormone receptor (HR)-positive, HER2-positive early breast cancer. Disease-free survival (DFS) was calculated with the random effect model and hazard ratios (HRs) with 95% confidence intervals (CI).

Results: Six RCTs (N = 5390 patients) were included in the final analysis. There was no significant difference in DFS between adjuvant treatment with aromatase inhibitors and tamoxifen (HR 0.99, 95% CI 0.68-1.44, P = 0.96). Furthermore, after omitting the ALTTO trial, as it did not randomize patients to hormonal therapy, no significant difference was observed between the two protocols (HR 1.06, 95% CI 0.65-1.73, P = 0.81).

Conclusion: Our study demonstrates similar DFS with tamoxifen and aromatase inhibitors as adjuvant endocrine treatment in HER2-positive HR-positive early-stage breast cancer patients. Future larger prospective studies focusing on the various contemporary endocrine regimens are warranted to validate our findings.

Keywords: HER2-positive; adjuvant treatment; breast cancer; endocrine therapy.

PICO:
P: HR-positive/HER2-positive early-stage breast cancer
I: 1. adjuvant endocrine therapy (tamoxifen); 2. aromatase inhibitors
O: disease-free survival
Title: Point-A vs. volume-based brachytherapy for the treatment of cervix cancer: A meta-analysis
Topic: Radiation/Chemotherapy

Background & purpose: To report disease-free survival (DFS) for volume-based and point-A based brachytherapy (BT) in locally advanced cervical cancer.

Materials & methods: We conducted a meta-analysis of studies assessing the effects of point-A and volume-based brachytherapy on 3-year DFS. Studies including stage I-IVA cervical cancer patients were included if standard treatment of concomitant chemo-radiotherapy and high-dose- or pulsed dose rate BT was delivered. The primary outcome was 3-year DFS, and secondary outcomes were 3-year local control (LC), 3-year overall survival (OS) and late toxicity. A random-effects subgroup meta-analysis was done.

Results: In total, 5499 studies were screened, of which 24 studies with 5488 patients were eligible. There was significant heterogeneity among point-A studies (1538 patients) (I2 = 82%, p < 0.05) relative to volume-based studies (3950 patients) (I2 = 58, p = 0.01). The 3-year DFS for point-A and volume-based studies were 67% (95% CI 60%-73%) and 79% (95% CI 76%-82%) respectively (p = 0.001). Three-year LC for point-A and volume-based studies were 86% (95% CI 81%-90%) and 92% (91%-94%) respectively (p = 0.01). The difference in 3-year OS (72% vs. 79%, p = 0.12) was not statistically significant. The proportion of prospectively enrolled patients was 23% for point-A studies and 33% for volume-based studies. There was no difference in late grade 3 or higher gastrointestinal (3% vs. 4%, p = 0.76) genitourinary toxicities (3% vs. 3% p = 0.45) between the two groups.

Conclusion: Volume-based BT results in superior 3-year DFS and 3-year LC. In the absence of randomized trials, this meta-analysis provides the best evidence regarding transition to 3D planning.

Keywords: Brachytherapy; Disease-free survival; Image-guided radiation therapy; Uterine cervical neoplasms.

PICO:
P: Patients with locally advanced cervical cancer
I: Volume-based brachytherapy (BT)
C: Point-A based brachytherapy (BT)
O: 3-year disease-free survival (DFS), 3-year local control (LC), 3-year overall survival (OS), and late toxicity
Title: Survival outcomes of neoadjuvant versus adjuvant chemotherapy in triple-negative breast cancer: a meta-analysis of 36,480 cases
Topic: Radiation/Chemotherapy

Background: The survival outcomes of neoadjuvant chemotherapy (NACT) versus adjuvant chemotherapy (ACT) for patients with triple-negative breast cancer (TNBC) remain unclear. Therefore, in this study, a meta-analysis was conducted to analyze current evidence on the survival outcomes of NACT versus ACT in TNBC.

Methods: A systematic search was performed on the PubMed and Embase databases to identify relevant articles investigating the survival outcomes of NACT versus ACT in TNBC.

Results: A total of nine studies involving 36,480 patients met the selection criteria. Among them, 10,728 (29.41%) received NACT, and 25,752 (70.59%) received ACT. The pathological complete response (pCR) rate was 35% (95% CI = 0.23-0.48). Compared with ACT, the overall survival (OS) of NACT was poor (HR = 1.59; 95% CI = 1.25-2.02; P = 0.0001), and there was no significant difference in disease-free survival (DFS) between the two treatments (HR = 0.85; 95% CI = 0.54-1.34; P = 0.49). NACT with pCR significantly improved the OS (HR = 0.53; 95% CI = 0.29-0.98; P = 0.04) and DFS (HR = 0.52; 95% CI = 0.29-0.94; P = 0.03), while the OS (HR = 1.18; 95% CI = 1.09-1.28; P < 0.0001) and DFS (HR = 2.36; 95% CI = 1.42-3.89; P = 0.0008) of patients with residual disease (RD) following NACT were worse compared to those receiving ACT.

Conclusion: These findings suggest that, for TNBC, NACT with pCR is superior to ACT in improving OS and DFS, and it turns to be opposite when patients are receiving NACT with RD.

Keywords: Adjuvant chemotherapy; Meta-analysis; Neoadjuvant; Survival outcomes; Triple-negative breast cancer.

PICO:
P: triple-negative breast cancer (TNBC)
I: 1. neoadjuvant chemotherapy (NACT); 2. adjuvant chemotherapy (ACT)
O: 1. overall survival; 2. disease-free survival (DFS)
Title: Outcomes with chimeric antigen receptor t-cell therapy in relapsed or refractory acute myeloid leukemia: a systematic review and meta-analysis
Topic: Immunotherapy

Background: We conducted a systematic review and meta-analysis to evaluate outcomes following chimeric antigen receptor T cell (CAR-T) therapy in relapsed/refractory acute myeloid leukemia (RR-AML). Methods: We performed a literature search on PubMed, Cochrane Library, and Clinicaltrials.gov. After screening 677 manuscripts, 13 studies were included. Data was extracted following PRISMA guidelines. Pooled analysis was done using the meta-package by Schwarzer et al. Proportions with 95% confidence intervals (CI) were computed. Results: We analyzed 57 patients from 10 clinical trials and 3 case reports. The pooled complete and overall response rates were 49.5% (95% CI 0.18-0.81, I2 =65%) and 65.2% (95% CI 0.36-0.91, I2 =57%). The pooled incidence of cytokine release syndrome, immune-effector cell associated neurotoxicity syndrome, and graft-versus-host disease was estimated as 54.4% (95% CI 0.17-0.90, I2 =77%), 3.9% (95% CI 0.00-0.19, I2 =22%), and 1.6% (95%CI 0.00-0.21, I2 =33%), respectively. Conclusion: CAR-T therapy has demonstrated modest efficacy in RR-AML. Major challenges include heterogeneous disease biology, lack of a unique targetable antigen, and immune exhaustion.

PICO:
P: Patients with relapsed/refractory acute myeloid leukemia (RR-AML)
I: Chimeric antigen receptor T cell (CAR-T) therapy
C: N/A
O: Outcomes following CAR-T therapy in RR-AML such as complete and overall response rates, and the incidence of cytokine release syndrome, immune-effector cell associated neurotoxicity syndrome, and graft-versus-host disease
Title: Microwave ablation compared with radiofrequency ablation for the treatment of liver cancer: a systematic review and meta-analysis
Topic: Hyperthermia

Background: Guidelines have reported that although microwave ablation (MWA) has potential advantages over radiofrequency ablation (RFA), superiority in efficacy and safety remain unclear. Aim of the study is to compare MWA with RFA in the treatment of liver cancer.

Methods: Meta-analysis was conducted according to the PRISMA guidelines for studies published from 2010 onwards. A random-effects model was used for the meta-analyses. Complete ablation (CA), local tumor progression (LTP), intrahepatic distant recurrence (IDR), and complications were analyzed.

Results: Four randomized trials and 11 observational studies with a total of 2,169 patients met the inclusion criteria. Although overall analysis showed no significant difference in LTP between MWA and RFA, subgroup analysis including randomized trials for patients with hepatocellular cancer (HCC) demonstrated statistically decreased rates of LTP in favor of MWA (OR, 0.40; 95% CI, 0.18-0.92; p = 0.03). No significant differences were found between the two procedures in CA, IDR, complications, and tumor diameter less or larger than 3 cm.

Conclusions: MWA showed promising results and demonstrated better oncological outcomes in terms of LTP compared to RFA in patients with HCC. MWA can be utilized as the ablation method of choice in patients with HCC.

Keywords: carcinoma hepatocellular; liver; liver neoplasms; microwaves; radiofrequency ablation.

PICO:
P: liver cancer
I: 1. microwave ablation; 2. radiofrequency ablation
O: 1. complete ablation (CA); 2. local tumor prgression (LTP); 3. intrahepatic distant (IDR); 4. complications
Title: Comparison of chronic gastrointestinal and genitourinary toxicities between brachytherapy and external beam radiotherapy for patients with prostate cancer: A systematic review and meta-analysis
Topic: Radiation/Chemotherapy

Background: 125I BT is an effective radiotherapy for prostate cancer. However, comparison data of GI and GU toxicities between BT, BT + EBRT, and EBRT-alone patient groups is limited.

Objective: To define the GI and GU toxicities in prostate cancer to prevent adverse events after treatment.

Methods: We searched published studies in PubMed, Cochrane, and Embase databases up to December 31, 2022. The endpoints were the RRs of GI and GU toxicities. Pooled data were assessed using a random-effects model.

Results: Fifteen eligible studies were included into this analysis. LDR-BT had significantly lower RRs than LDR-BT + EBRT for acute GI (2.13; 95% CI, 1.22-3.69; P= 0.007) and late GI toxicities (3.96; 95% CI, 1.23-12.70; P= 0.02). Moreover, EBRT had significantly higher RRs than LDR-BT for acute GU (2.32; 95% CI, 1.29-4.15; P= 0.005) and late GU toxicities (2.38; 95% CI, 1.27-4.44; P= 0.007). HDR-BT had significantly higher RRs for acute GU toxicities than LDR-BT alone (0.30; 95% CI, 0.23-0.40; P< 0.00001).

Conclusion: The results implied that BT with and without EBRT can result in both GI and GU toxicities in patients with prostate cancer, with LDR-BT leading to a poorer urinary function than EBRT.

Keywords: Prostate cancer; brachytherapy; external beam radiotherapy; gastrointestinal;

PICO:
P: Patients with prostate cancer
I: Brachytherapy (BT), specifically 125I BT, Low Dose Rate Brachytherapy (LDR-BT), and High Dose Rate Brachytherapy (HDR-BT)
C: External Beam Radiotherapy (EBRT) alone, and the combination of Brachytherapy (BT) + External Beam Radiotherapy (EBRT)
O: Chronic gastrointestinal (GI) and genitourinary (GU) toxicities
Title: Adjuvant Chemotherapy for Muscle-invasive Bladder Cancer: A Systematic Review and Meta-analysis of Individual Participant Data from Randomised Controlled Trials
Topic: Radiation/Chemotherapy

Context: Our prior systematic review and meta-analysis of individual participant data (IPD) suggesting a benefit of adjuvant chemotherapy for muscle-invasive bladder cancer was limited by the number and size of included randomised trials. We have updated results to include additional trials, providing the most up-to-date and reliable evidence of the effects of this treatment.

Objective: To investigate the role of adjuvant cisplatin-based chemotherapy in the treatment of muscle-invasive bladder cancer.

Evidence acquisition: Published and unpublished trials were sought via searches of bibliographic databases, trials registers, conference proceedings, and hand searching. Updated IPD were centrally collected, checked, and analysed. Results from individual randomised controlled trials (RCTs) were combined using a two-stage fixed-effect model. Prespecified analyses explored any variation in effect by trial and participant characteristics.

Evidence synthesis: Analyses of ten RCTs (1183 participants) demonstrated a benefit of cisplatin-based adjuvant chemotherapy on overall survival (hazard ratio [HR] = 0.82, 95% confidence interval [CI] = 0.70-0.96, p = 0.02). This represents an absolute improvement in survival of 6% at 5 yr, from 50% to 56%, and a 9% absolute benefit when adjusted for age, sex, pT stage, and pN category (HR = 0.77, 95% CI = 0.65-0.92, p = 0.004). There was no clear evidence that the effect varied by trial or participant characteristics. Adjuvant chemotherapy was also shown to improve recurrence-free survival (HR = 0.71, 95% CI = 0.60-0.83, p < 0.001), locoregional recurrence-free survival (HR = 0.68, 95% CI = 0.55-0.85, p < 0.001), and metastasis-free survival (HR = 0.79, 95% CI = 0.65-0.95, p = 0.01), with absolute benefits of 11%, 11%, and 8%, respectively.

Conclusions: This systematic review and meta-analysis demonstrates that cisplatin-based adjuvant chemotherapy is a valid option for improving outcomes for muscle-invasive bladder cancer.

Patient summary: We looked at the effect of cisplatin-based chemotherapy on outcomes in participants with muscle-invasive bladder cancer. We gathered this information from eligible randomised controlled trials. We demonstrated that cisplatin-based chemotherapy is a valid option for improving outcomes of muscle-invasive bladder cancer.

Keywords: Bladder cancer; Chemotherapy; Individual participant data; Meta-analysis; Systematic review.

PICO:
P: Patients with muscle-invasive bladder cancer
I: Cisplatin-based adjuvant chemotherapy
O: Overall survival, recurrence-free survival, locoregional recurrence-free survival, and metastasis-free survival