Role of neo-adjuvant chemotherapy followed by surgery in cervical cancer: a review

Incidence of cervical cancer is predominantly found in developing countries. In Indian set up, it is most commonly found in rural locations in younger population. Chemotherapy was initially introduced for the treatment of recurrent/metastatic cervix cancer and has subsequently been explored in primary treatment either as neo-adjuvant prior to radiation or surgery in an attempt to reduce the incidence of loco-regional recurrence. The review study tries to evaluate the role of neoadjuvant chemotherapy (NACT) followed by surgery in cervical cancer management. Randomized trials and meta-analysis were analysed. Most of them used short course chemotherapy course of 4-6 weeks followed by surgery. patients with high risk pathological features received postoperative RT. The results of trials indicated significant reduction in the risk of death with NACT, but there were few differences between the trials. NACT followed by surgery is found to be associated with an improved response rate and progression-free survival. However, the impact on overall survival remains to be confirmed.

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The Effect of Anakinra in Hospitalized Patients with COVID-19: An Updated Systematic Review and Meta-Analysis

Journal of Clinical Medicine ◽

10.3390/jcm10194462 ◽

2021 ◽

Vol 10 (19) ◽

pp. 4462

Author(s):

Konstantinos G. Kyriakoulis ◽

Anastasios Kollias ◽

Garyphallia Poulakou ◽

Ioannis G. Kyriakoulis ◽

Ioannis P. Trontzas ◽

...

Keyword(s):

Systematic Review ◽

Meta Analysis ◽

Interleukin 1 ◽

Severe Pneumonia ◽

Hospitalized Patients ◽

Current Evidence ◽

Adjusted Risk ◽

Risk Of Death ◽

The Impact

The role of immunomodulatory agents in the treatment of hospitalized patients with COVID-19 has been of increasing interest. Anakinra, an interleukin-1 inhibitor, has been shown to offer significant clinical benefits in patients with COVID-19 and hyperinflammation. An updated systematic review and meta-analysis regarding the impact of anakinra on the outcomes of hospitalized patients with COVID-19 was conducted. Studies, randomized or non-randomized with adjustment for confounders, reporting on the adjusted risk of death in patients treated with anakinra versus those not treated with anakinra were deemed eligible. A search was performed in PubMed/EMBASE databases, as well as in relevant websites, until 1 August 2021. The meta-analysis of six studies that fulfilled the inclusion criteria (n = 1553 patients with moderate to severe pneumonia, weighted age 64 years, men 66%, treated with anakinra 50%, intubated 3%) showed a pooled hazard ratio for death in patients treated with anakinra at 0.47 (95% confidence intervals 0.34, 0.65). A meta-regression analysis did not reveal any significant associations between the mean age, percentage of males, mean baseline C-reactive protein levels, mean time of administration since symptoms onset among the included studies and the hazard ratios for death. All studies were considered as low risk of bias. The current evidence, although derived mainly from observational studies, supports a beneficial role of anakinra in the treatment of selected patients with COVID-19.

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Combination therapy of Tocilizumab and steroid for COVID-19 patients: A meta-analysis

10.21203/rs.3.rs-553068/v1 ◽

2021 ◽

Author(s):

Mahmood moosazadeh ◽

Tahoora Mousavi

Keyword(s):

Combination Therapy ◽

Meta Analysis ◽

Control Group ◽

Mechanical Ventilators ◽

Risk Of Death ◽

And Control ◽

The Impact ◽

Pro Inflammatory Cytokines

Abstract BackgroundThe coagulation markers, pro-inflammatory cytokines (such as IL-2R, IL-6, IL-10, and TNF-a) and Lymphopenia are associated with the severity of COVID-19 disease. The use of anti-inflammatory agents such as corticosteroids (CS) or Tosilizumab (TCZ) has been suggested for the treatment of advanced stage of COVID-19 and reduction of mechanical ventilators and mortality. The aim of this meta-analysis is to determine the role of combination therapy with Tocilizumab and steroid in COVID-19 patient. Material and methodsRelevant studies were found using online international databases and suitable studies were selected and assessed by two independent researchers. The quality of all papers were determined by a checklist. Heterogeneity assay among the primary studies was evaluated by Cochran's Q test and I2 index. The statistical analyses were done using Stata ver. 14 package (StataCorp, College Station, TX, USA) software. Publication bias was estimated through the Egger's test and the impact of each study on the overall estimate was assessed by sensitivity analysis.Result 6 studies were entered into this meta-analysis. The results of these studies showed that the risk of death for COVID-19 patients treated with the combination of corticosteroids and Tocilizumab compared to Tocilizumab or [C1] control group was 0.74 (95% CI: 0.36-1.50) and 0.48(95% CI: 0.31-0.74) respectively. ConclusionThis meta-analysis showed that the risk of death in COVID-19 patients who treated with Corticosteroids and Tocilizumab was lower than Tocilizumab and control group (26% and 52% respectively).

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Polymorphisms in the dopamine (DA) signaling to predict outcome in patients (pts) with metastatic colorectal cancer (mCRC): Data from TRIBE, MAVERICC, and FIRE-3 phase III trials.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.3048 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 3048-3048

Author(s):

Francesca Battaglin ◽

Shu Cao ◽

Fotios Loupakis ◽

Sebastian Stintzing ◽

Aparna Raj Parikh ◽

...

Keyword(s):

Multiple Testing ◽

Meta Analysis ◽

Critical Role ◽

Progression Free Survival ◽

Phase Iii ◽

P Value ◽

Nucleotide Polymorphisms ◽

First Line ◽

The Impact

3048 Background: Strong evidence supports the critical role of the gut-brain axis in modulating gastrointestinal function and homeostasis. Available data suggest an involvement of the dopaminergic pathway in CRC dynamics. DA could inhibit proliferation and migration of tumor endothelial cells and enhanced 5-fluorouracil efficacy in CRC preclinical models. Hence, we hypothesized that genetic variants in DA signaling may predict treatment outcomes in mCRC pts. Methods: The impact on outcome of 22 selected single nucleotide polymorphisms (SNPs) in 9 genes of the DA signaling pathway ( DRD1, DRD2, DRD3, DRD4, DRD5, TAAR1, SLC6A3, SLC18A2, PPP1R1B) was analyzed on a total of 884 pts enrolled in three independent randomized first-line trials: TRIBE (n = 324), MAVERICC (n = 324), and FIRE-3 (n = 236). Genomic DNA from blood samples of pts was genotyped through the OncoArray, a custom array manufactured by Illumina. A meta-analysis approach using the METASOFT software was used to quantify SNPs prognostic effects and heterogeneities across treatment arms. P values were adjusted for multiple testing using the false discovery rate (FDR) method. Results: Overall, DRD3 rs3732790, rs9817063 and rs2134655 showed a significant nominal p value ( P) in association with tumor response (TR) across trials ( P= 0.032, P= 0.021, P= 0.027, respectively). TAAR1 rs8192620 showed an association with both progression free survival (PFS) ( P= 0.01) and overall survival (OS) ( P= 0.033), similar to DA transporter SLC6A3 rs6347 ( P= 0.016 and P= 0.002, respectively). SLC6A3 rs6347 association with OS remained significant after FDR ( PFDR= 0.045). Subgroup analyses showed a significant association with PFS for DRD1 rs267410 and SLC6A3 rs2652510 in females ( PFDR= 0.056), and between SLC6A3 rs6347 and OS ( PFDR= 0.041) and SLC6A3 rs6876890 and TR ( PFDR= 0.05) in KRAS wild type. Conclusions: Our results suggest that SNPs in DA signaling may have a prognostic value in mCRC pts receiving first-line treatment. Upon validation, these findings may provide novel insight on the role of DA signaling in CRC and possibly contribute to open novel therapeutic perspectives.

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Evaluating Contemporary Radiotherapy Approaches in the Primary Treatment of Cervical Cancer

International Journal of Gynecological Cancer ◽

10.1111/igc.0b013e3181e0ef81 ◽

2010 ◽

Vol 20 (6) ◽

pp. 1087-1091 ◽

Cited By ~ 4

Author(s):

Rajiv Samant ◽

Sofya Kobeleva ◽

Choan E ◽

Khalid Balaraj ◽

Tien Le ◽

...

Keyword(s):

Cervical Cancer ◽

Statistical Significance ◽

Progression Free Survival ◽

Primary Treatment ◽

Rank Test ◽

Curative Intent ◽

The Difference ◽

Group 2 ◽

The Impact ◽

Group 1

Purpose:Radiotherapy with concurrent cisplatinum-based chemotherapy became a standard recommendation for the management of advanced cervical cancer in 1999. We reviewed our experience with this approach to determine the impact on patient outcomes.Methods:A retrospective review of all cervical cancer patients treated with curative intent using radical radiotherapy ± chemotherapy from 1992 to 2005 was performed. Survival and relapse rates were analyzed using the Kaplan-Meier method and were compared using the log-rank test.Results:During this period, 224 treated patients were identified: 153 (68%) were treated between 1992 and 1999 (group 1) and 71 (32%) were treated after 1999 (group 2). The median age was 53 and 55 years with a median follow-up of 49 and 34 months for groups 1 and 2, respectively. Stage classification and histological diagnosis were similar for both groups. Treatment usually consisted of external beam pelvic radiotherapy (40-45 Gy in 20-25 fractions) followed by low-dose rate brachytherapy (35-40 Gy to point A). Chemotherapy consisted of weekly intravenous cisplatinum (40 mg/m2) given concurrently with pelvic radiation. The proportion of patients receiving chemotherapy increased significantly after 1999, 12% in group 1 compared with 79% in group 2 (P < 0.01). The 5-year overall survival (OS) and progression-free survival (PFS) rates were 53% and 54% for group 1 and 64% and 67% for group 2. The improvement in PFS for group 2 approached statistical significance (P = 0.06), but the difference in OS did not.Conclusions:There has been a significant increase in the use of concurrent chemoradiation for cervical cancer treatment after 1999, and this seems to have led to higher rates of PFS and OS, although these have yet to achieve statistical significance.

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Effect of Adjuvant Chemotherapy in Stage III Cervical Cancer Patients Treated With Concurrent Chemoradiation: A Multicenter Study

Oncology Research and Treatment ◽

10.1159/000521980 ◽

2022 ◽

Author(s):

Muhammed Mustafa Atci ◽

Baran Akagunduz ◽

Metin Demir ◽

Binnur Dönmez Yılmaz ◽

Tugba Akin Telli ◽

...

Keyword(s):

Cervical Cancer ◽

Adjuvant Chemotherapy ◽

Locally Advanced ◽

Significant Proportion ◽

Progression Free Survival ◽

Figo Stage ◽

Stage Iii ◽

Free Survival ◽

The Impact

Introduction: A significant proportion of cervical cancer (CC) patients are diagnosed at a locally advanced stage. Concurrent chemoradiotherapy (CCRT) is the cornerstone of treatment for patients with locally advanced CC. However, the role of adjuvant chemotherapy (AC) after CCRT is controversial. In this study, we analyzed the efficacy of AC after CCRT in stage III CC patients. Methods: We performed a multicenter, retrospective analysis of 139 FIGO stage III CC patients treated with CCRT of whom 45.3% received AC. Our goal was to determine the impact of AC on survival in these patients. Results: Five-year progression-free survival was 37.5% and 16% in patients receiving CCRT with and without AC, respectively (p=0.008). Median PFS was 30.9 months (CI 95 %14.8-46.9) and 16.6 months (CI 95% 9.3-23.9) in patients receiving CCRT with and without AC, respectively. Five-year overall survival was 78.2% and 28.4% in patients receiving CCRT with and without AC, respectively (p<0.001). Median OS was 132.2 months (CI 95, %66.5-197.8) and 34.9 months (CI 95% 23.1-46.7) in patients receiving CCRT with and in without AC, respectively. Conclusion: Our study suggests that AC provides OS and PFS benefit in stage III CC patients. Larger studies are needed to identify subgroups of patients who would benefit from AC.

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Impact of brachytherapy technique (2D versus 3D) on outcomes of cervical cancer: A Systematic Review and Meta-analysis

10.21203/rs.3.rs-16273/v1 ◽

2020 ◽

Author(s):

Yeon Joo Kim ◽

Hyun-Cheol Kang ◽

Young Seok Kim

Keyword(s):

Systematic Review ◽

Cervical Cancer ◽

Meta Analysis ◽

Three Dimensional ◽

Progression Free Survival ◽

Severe Toxicity ◽

Free Survival ◽

Standard Management ◽

Quantitative Synthesis ◽

The Impact

Abstract Background: To perform a systematic review and meta-analysis of the impact of brachytherapy (BT) technique (two-dimensional [2D] or three-dimensional image-guided [3D]) on outcomes of cervical cancer patients.Methods: PubMed and Embase databases were searched up to April 16, 2019, for studies which evaluated the effect of 3D-BT compared to 2D-BT in cervical cancer, and endpoints included cumulative incidence of severe toxicity, locoregional recurrence-free survival (LRRFS), progression-free survival (PFS), and overall survival (OS). Hazard ratios (HRs) were pooled in the meta-analysis using the random-effects model.Results: Six studies of 8 cohorts were included in the quantitative synthesis. The pooled hazard ratio (HR) regarding toxicity was evaluated in 5 cohorts in 3 studies, and the HR of 3D-BT compared to 2D-BT was 0.54 (95% confidence interval [CI], 0.37-0.77). All 6 studies were included for the synthesis for LRRFS, and the pooled HR favors 3D-BT (0.61 [95% CI, 0.40-0.93]). For PFS, 3 studies were included for analysis and 3D-BT was superior to 2D-BT (HR = 0.75 [95% CI, 0.0.59–0.96]). Five studies were included for the pooled HR regarding OS, and pooled HR of 3D-BT compared to 2D-BT was 0.65 (95% CI, 0.40–1.06).Conclusions: 3D-BT might reduce severe toxicity and improve LRRFS, and PFS in patients with cervical cancer. 3D-BT should be considered for standard management of cervical cancer, and efforts for adopting this procedure in Korea should be pursued.

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Why Do Firms Participate in Voluntary Environmental Programs? A Meta-Analysis of the Role of Institutions, Resources, and Program Stringency

Organization & Environment ◽

10.1177/1086026621990063 ◽

2021 ◽

pp. 108602662199006

Author(s):

Peter Tashman ◽

Svetlana Flankova ◽

Marc van Essen ◽

Valentina Marano

Keyword(s):

Quality Management ◽

Prior Experience ◽

Meta Analysis ◽

Institutional Pressures ◽

Environmental Programs ◽

Voluntary Environmental Programs ◽

Management Standards ◽

Trade Offs ◽

The Impact

We meta-analyze research on why firms join voluntary environmental programs (VEPs) to assess the impact of program stringency, or the extent to which they have rigorous, enforceable standards on these decisions. Stringency creates trade-offs for firms by affecting programs’ effectiveness, legitimacy, and adoption costs. Most research considers singular programs and lacks cross program variation needed to analyze program stringency’s impact. Our meta-analysis addresses this by sampling 127 studies and 23 VEPs. We begin by identifying common institutional and resource-based drivers of participation in the literature, and then analyze how program stringency moderates their impacts. Our results suggest that strictly governed VEPs encourage participation among highly visible and profitable firms, and discourage it when informal institutional pressures are higher, and firms have prior experience with other VEPs or quality management standards. We demonstrate that VEP stringency has nuanced effects on firm participation based on the institutional and resource-based factors facing them.

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Treatment with Antiangiogenic Drugs in Multiple Lines in Patients with Metastatic Colorectal Cancer: Meta-Analysis of Randomized Trials

Gastroenterology Research and Practice ◽

10.1155/2016/9189483 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 5

Author(s):

R.-D. Hofheinz ◽

U. Ronellenfitsch ◽

S. Kubicka ◽

A. Falcone ◽

I. Burkholder ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Kinase Inhibitors ◽

Meta Analysis ◽

Progression Free Survival ◽

Optimal Sequence ◽

Primary Endpoints ◽

Disease Stabilization ◽

Antiangiogenic Drugs ◽

The Impact

Background. In metastatic colorectal cancer (mCRC), continuing antiangiogenic drugs beyond progression might provide clinical benefit. We synthesized the available evidence in a meta-analysis.Patients and Methods. We conducted a meta-analysis of studies investigating the use of antiangiogenic drugs beyond progression. Eligible studies were randomized phase II/III trials. Primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoints were the impact of continuing antiangiogenic drugs (i) in subgroups, (ii) in different types of compounds targeting the VEGF-axis (monoclonal antibodies versus tyrosine kinase inhibitors), and (iii) on remission rates and prevention of progression.Results. Eight studies (3,668 patients) were included. Continuing antiangiogenic treatment beyond progression significantly improved PFS (HR 0.64; 95%-CI, 0.55–0.75) and OS (HR 0.83; 95%-CI, 0.76–0.89). PFS was significantly improved in all subgroups with comparable HR. OS was improved in all subgroups stratified by age, gender, and ECOG status. The rate of patients achieving at least stable disease was improved with an OR of 2.25 (95%-CI, 1.41–3.58).Conclusions. This analysis shows a significant PFS and OS benefit as well as a benefit regarding disease stabilization when using antiangiogenic drugs beyond progression in mCRC. Future studies should focus on the optimal sequence of administering antiangiogenic drugs.

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