scholarly journals O-OGC09 PD-1 inhibitors in Oesophageal Cancer: A systematic review of the oncological outcomes associated with PD-1 blockade and the evolving therapeutic landscape

2021 ◽  
Vol 108 (Supplement_9) ◽  
Author(s):  
Jack Whooley ◽  
Muhammed Al Azzawi ◽  
Noel Donlon ◽  
Jarlath Bolger ◽  
William Robb
Keyword(s):  
Systematic Review ◽  
Survival Data ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Adjuvant Setting ◽  
Standard Regimen ◽  
Clinical Prognosis ◽  
Therapeutic Landscape ◽  
Clinically Significant ◽  
Meta Analyses

Abstract Background Patients with oesophageal or gastro-oesophageal junction (GOJ) cancer that fail to respond to chemoradiotherapy have a poor clinical prognosis. Recent clinical trials have investigated the use of immune checkpoint inhibitors in these patients. The use of programmed cell death protein 1 (PD-1) inhibitors have emerged as exciting therapeutic options in other solid tumors, such as non-small cell lung cancer, renal cell carcinoma and melanoma. We assessed the efficacy and safety of PD-1 inhibitors in oesophageal and GOJ cancers. Methods This systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive electronic literature search from the EMBASE, Pubmed, Scopus, MEDLINE and Google Scholar databases was conducted up to April 1st 2021. Results This review identified nine eligible studies reporting outcomes of 2149 patients treated with PD-1 blockade compared with 1244 patients treated with either a placebo or the standard regimen of chemotherapy for oesophageal and GOJ cancer. Clinically significant improvements in median overall survival have been demonstrated in advanced and metastatic oesophageal and GOJ cancer while maintaining acceptable safety profiles. Promising survival data has also recently emerged from PD-1 blockade in the adjuvant setting. Conclusions PD-1 blockade in oesophageal and GOJ cancer has delivered impressive survival benefit whilst remaining well tolerated. Its use in the adjuvant setting may further advance our treatment options for this difficult-to-treat tumour, and more advancements in the immunotherapy landscape are highly anticipated. However, further characterization of the PD-1/PD-L1 pathway is required to optimise patient selection.

PD-1 inhibitors in esophageal cancer: a systematic review of the oncological outcomes associated with PD-1 blockade and the evolving therapeutic paradigm

2021 ◽  
Author(s):  
J Whooley ◽  
M Alazzawi ◽  
N E Donlon ◽  
J C Bolger ◽  
W B Robb
Keyword(s):  
Systematic Review ◽  
Survival Data ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Gastroesophageal Junction ◽  
Adjuvant Setting ◽  
Standard Regimen ◽  
Clinical Prognosis ◽  
Programmed Death ◽  
Clinically Significant

Abstract Patients with esophageal or gastroesophageal junction (GEJ) cancer who fail to respond to chemoradiotherapy have a poor clinical prognosis. Recent clinical trials have investigated the use of immune checkpoint inhibitors in these patients. The use of programmed cell death protein 1 (PD-1) inhibitors has emerged as exciting therapeutic options in the curative and palliative setting of other solid tumors. We assessed the efficacy and safety of PD-1 inhibitors in esophageal and GEJ cancers. This systematic review was performed in accordance with the PRISMA guidelines. A comprehensive electronic literature search from the EMBASE, Pubmed, Scopus, MEDLINE, and Google Scholar databases was conducted up to 25 July 2021. This review identified 11 eligible studies reporting outcomes of 3451 patients treated with PD-1 blockade compared with 2286 patients treated with either a placebo or the standard regimen of chemotherapy. Clinically significant improvements in median overall survival have been demonstrated in advanced and metastatic esophageal and GEJ cancer while maintaining acceptable safety profiles. Promising survival data have also recently emerged from PD-1 blockade in the adjuvant setting. PD-1 blockade in esophageal and GEJ cancer has delivered impressive survival benefit while remaining well tolerated. Its use in the adjuvant setting will further advance treatment options, and more advancements in this area of therapy are highly anticipated. However, further characterization of the PD-1/programmed death ligand-1 pathway and elucidation of biomarkers to predict response are required to optimize patient selection.

scholarly journals Indications and outcomes of enterovesical and colovesical fistulas: systematic review of the literature and meta-analysis of prevalence

BMC Surgery ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Stefano Granieri ◽  
Francesco Sessa ◽  
Alessandro Bonomi ◽  
Sissi Paleino ◽  
Federica Bruno ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Symptoms ◽  
Rare Complication ◽  
Meta Analysis ◽  
Treatment Options ◽  
Palliative Surgery ◽  
Review Of The Literature ◽  
Colovesical Fistula ◽  
Level Of Evidence ◽  
Meta Analyses

Abstract Background Entero-colovesical fistula is a rare complication of various benign and malignant diseases. The diagnosis is prominently based on clinical symptoms; imaging studies are necessary not only to confirm the presence of the fistula, but more importantly to demonstrate the extent and the nature of the fistula. There is still a lack of consensus regarding the if, when and how to repair the fistula. The aim of the study is to review the different surgical treatment options, focus on surgical indications, and explore cumulative recurrence, morbidity, and mortality rates of entero-vesical and colo-vesical fistula patients. Methods A systematic review of the literature was conducted according to PRISMA guidelines. Random effects meta-analyses of proportions were developed to assess primary and secondary endpoints. I2 statistic and Cochran’s Q test were computed to assess inter-studies’ heterogeneity. Results Twenty-two studies were included in the analysis with a total of 861 patients. Meta-analyses of proportions pointed out 5, 22.2, and 4.9% rates for recurrence, complications, and mortality respectively. A single-stage procedure was performed in 75.5% of the cases, whereas a multi-stage operation in 15.5% of patients. Palliative surgery was performed in 6.2% of the cases. In 2.3% of the cases, the surgical procedure was not specified. Simple and advanced repair of the bladder was performed in 84.3% and 15.6% of the cases respectively. Conclusions Although burdened by a non-negligible rate of complications, surgical repair of entero-colovesical fistula leads to excellent results in terms of primary healing. Our review offers opportunities for significant further research in this field. Level of Evidence Level III according to ELIS (SR/MA with up to two negative criteria).

scholarly journals A systematic review and meta-analyses of pregnancy and fetal outcomes in women with multiple sclerosis: a contribution from the IMI2 ConcePTION project

2020 ◽  
Vol 267 (9) ◽  
pp. 2721-2731 ◽  
Author(s):  
Sandra Lopez-Leon ◽  
Yvonne Geissbühler ◽  
Meritxell Sabidó ◽  
Moise Turkson ◽  
Charlotte Wahlich ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Systematic Review ◽  
Congenital Malformations ◽  
Treatment Options ◽  
Preterm Births ◽  
Disease Modifying Drugs ◽  
Pregnancy And Birth Outcomes ◽  
Major Congenital Malformations ◽  
Meta Analyses ◽  
Pregnancy And Birth

Abstract Neurologists managing women with Multiple Sclerosis (MS) need information about the safety of disease modifying drugs (DMDs) during pregnancy. However, this knowledge is limited. The present study aims to summarize previous studies by performing a systematic review and meta-analyses. The terms “multiple sclerosis” combined with DMDs of interest and a broad profile for pregnancy terms were used to search Embase and Medline databases to identify relevant studies published from January 2000 to July 2019.1260 studies were identified and ten studies met our inclusion criteria. Pooled risk ratios (RR) of pregnancy and birth outcomes in pregnancies exposed to DMDs compared to those not exposed were calculated using a random effects model. For spontaneous abortion RR = 1.14, 95% CI 0.99–1.32, for preterm births RR = 0.93, 95% CI 0.72–1.21 and for major congenital malformations RR = 0.86, 95% CI 0.47–1.56. The most common major congenital malformations reported in MS patients exposed to MS drugs were atrial septal defect (ASD) (N = 4), polydactyly (N = 4) and club foot (N = 3), which are among the most prevalent birth defects observed in the general population. In conclusion, interferons, glatiramer acetate or natalizumab, do not appear to increase the risk for spontaneous abortions, pre-term birth or major congenital malformations. There were very few patients included that were exposed to fingolimod, azathioprine and rituximab; therefore, these results cannot be generalized across drugs. Future studies including internal comparators are needed to enable treating physicians and their patients to decide on the best treatment options.

scholarly journals The therapeutic landscape of advanced melanoma

2020 ◽  
Vol 13 (3) ◽  
pp. 306-308 ◽  
Author(s):  
Erika Richtig
Keyword(s):  
Metastatic Melanoma ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Short Review ◽  
Advanced Melanoma ◽  
Oncolytic Viruses ◽  
Therapeutic Landscape ◽  
The World ◽  
Melanoma Treatment ◽  
Tumor Entities

Summary The therapeutic landscape of advanced and metastatic melanoma has changed dramatically in the last ten years. Targeted therapies as well as checkpoint inhibitors and oncolytic viruses have launched a broad revolution within this field. First presented at ASCO 2011, changes in melanoma treatment giving “light at the end of the tunnel” have also changed the treatment of many other tumor entities. So oncologists all over the world can offer their patients these treatment options with higher efficacy than we ever had. But despite all optimism we are still losing about half of our patients with metastatic melanoma along the way. In this short review the therapeutic landscape of advanced melanoma is described.

The effectiveness of ocriplasmin versus surgery for the treatment of macular holes: A systematic review and meta-analysis

2020 ◽  
pp. 112067212094692
Author(s):  
Brian Edward Yu ◽  
Tom Sheidow ◽  
Raman-Deep Singh Sambhi ◽  
Phil Hooper ◽  
Monali S. Malvankar-Mehta
Keyword(s):  
Systematic Review ◽  
Visual Acuity ◽  
Meta Analysis ◽  
Treatment Options ◽  
Closure Rate ◽  
Randomized Controlled ◽  
Macular Holes ◽  
Pars Plana ◽  
Meta Analyses ◽  
Hole Closure

Objective: To conduct a systematic review looking at the effects of ocriplasmin compared to pars plana vitrectomy on macular holes to assess the effectiveness of the treatment options. Methods: Literature was searched through MEDLINE, EMBASE, CINAHL, Clinical Trials.gov, and ProQuest Dissertations and Theses until June 12, 2018. Conferences held through Association for Research in Vision and Ophthalmology, Canadian Society of Ophthalmology, and American Academy of Ophthalmology were searched until June 18, 2018. A total of 208 records were screened leaving 26. One author independently reviewed them for quality and extracted data. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines were followed. The adverse events, MH closure rate, change in MH size, and the extent to which the patients’ visual acuity is restored by each treatment option; ocriplasmin and vitrectomy. Results: Twenty-six articles were included for qualitative and quantitative analysis. Meta-analysis results showed a 34% closure of macular holes after ocriplasmin treatment compared to 92% after vitrectomy. A significant improvement in visual acuity was seen after vitrectomy (SMD = −1.42; CI: [−1.98, −0.86]) as well as the ocriplasmin treatment (SMD = −0.73; CI: [−0.98, −0.48]). Conclusions: Results suggested 92% macular hole closure after vitrectomy compared to 34% after ocriplasmin. A significant improvement in visual acuity of patients was seen after both treatments. More good quality randomized controlled trials are required to make strong conclusions.

Antiemetics: ASCO Guideline Update

2020 ◽  
Vol 38 (24) ◽  
pp. 2782-2797 ◽  
Author(s):  
Paul J. Hesketh ◽  
Mark G. Kris ◽  
Ethan Basch ◽  
Kari Bohlke ◽  
Sally Y. Barbour ◽  
...  
Keyword(s):  
Systematic Review ◽  
Anticancer Agents ◽  
Checkpoint Inhibitors ◽  
Phase Iii ◽  
Two Phase ◽  
Hematopoietic Stem ◽  
Lung Cancers ◽  
Additional Information ◽  
Phase Iii Trials ◽  
Meta Analyses

PURPOSE To update the guideline to include new anticancer agents, antiemetics, and antiemetic regimens and to provide recommendations on the use of dexamethasone as a prophylactic antiemetic in patients receiving checkpoint inhibitors (CPIs). METHODS ASCO convened an Expert Panel and updated the systematic review to include randomized controlled trials (RCTs) and meta-analyses of RCTs published between June 1, 2016, and January 24, 2020. To address the dexamethasone and CPI question, we conducted a systematic review of RCTs that evaluated the addition of a CPI to chemotherapy. RESULTS The systematic reviews included 3 publications from the updated search and 10 publications on CPIs. Two phase III trials in adult patients with non–small-cell lung cancers evaluating a platinum-based doublet with or without the programmed death 1 (PD-1) inhibitor pembrolizumab recommended that all patients receive dexamethasone as a component of the prophylactic antiemetic regimen. In both studies, superior outcomes were noted in the PD-1 inhibitor–containing arms. Other important findings address olanzapine in adults and fosaprepitant in pediatric patients. RECOMMENDATIONS Recommendations for adults are unchanged with the exception of the option of adding olanzapine in the setting of hematopoietic stem cell transplantation. Dosing information now includes the option of a 5-mg dose of olanzapine in adults and intravenous formulations of aprepitant and netupitant-palonosetron. The option of fosaprepitant is added to pediatric recommendations. There is no clinical evidence to warrant omission of dexamethasone from guideline-compliant prophylactic antiemetic regimens when CPIs are administered to adults in combination with chemotherapy. CPIs administered alone or in combination with another CPI do not require the routine use of a prophylactic antiemetic. Additional information is available at www.asco.org/supportive-care-guidelines .

scholarly journals Effect of tetracyclines on pulpal and periodontal healing after tooth replantation: a systematic review of human and animal studies

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Mingmei Meng ◽  
Yandi Chen ◽  
Huidi Ren ◽  
Qiong Zhang ◽  
Song Chen ◽  
...  
Keyword(s):  
Systematic Review ◽  
Normal Saline ◽  
Animal Studies ◽  
Human Study ◽  
Permanent Teeth ◽  
Tooth Replantation ◽  
Clinically Significant ◽  
Meta Analyses ◽  
Periodontal Healing ◽  
Systemic Application

Abstract Background Pulpal and periodontal healing are two main concerns of delayed replantation of avulsed teeth. The objective of this review was to evaluate the effectiveness of topical and systemic application of tetracyclines on pulpal and periodontal healing after tooth replantation. Methods A comprehensive electronic search was conducted in six databases. This systematic review was carried out according to Cochrane Handbook and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Results After exclusion of 246 irrelevant papers, 14 animal studies and one human study were included in this review. The human study showed that avulsed permanent teeth treated with doxycycline did not show a better clinical outcome for pulp and periodontal healing compared with treatment with normal saline. As for animal studies, significant more pulpal healing was observed in immature teeth treated with topical doxycycline in two researches, while another one study showed that there is no difference between teeth treated with normal saline and teeth treated with doxycycline. Systemic doxycycline exerted no significant effect on pulpal revascularization illustrated by one research. Only one out of four articles illustrated the positive effect of systemic tetracyclines on periodontal healing. One paper reported that intracanal application of demeclocycline promoted favorable periodontal healing. Two articles showed topical doxycycline contributed to favorable periodontal healing, while five studies showed no significant effect of topical tetracyclines on periodontal healing. Conclusions As a result of data heterogeneity and limitations of the studies, the effect of topical or systemic application of tetracyclines on pulpal and periodontal healing is inconclusive. More studies are required to get more clinically significant conclusions.

The effectiveness of serious games in alleviating anxiety: A systematic review and meta-analysis (Preprint)

2021 ◽  
Author(s):  
Alaa Abd-alrazaq ◽  
Mohannad Alajlani ◽  
Dari Alhuwail ◽  
Jens Schneider ◽  
Laila Akhu-Zaheya ◽  
...  
Keyword(s):  
Systematic Review ◽  
Serious Games ◽  
Behavioral Therapy ◽  
Risk Of Bias ◽  
Anxiety Level ◽  
Reference List ◽  
Clinically Significant ◽  
Meta Analyses ◽  
Quality Evidence

BACKGROUND Anxiety is one of the mental disorders characterized by apprehension, tension, uneasiness, and other related behavioral disturbances. One of the non-pharmacological treatments used for reducing anxiety is serious games, which are games that have a purpose other than entertainment. The effectiveness of serious games in alleviating anxiety was investigated by several systematic reviews, however, they are limited by design and methodological weaknesses. OBJECTIVE This study aims to assess the effectiveness of serious games in alleviating anxiety through summarizing the results of previous studies and providing an up-to-date review. METHODS We carried out a systematic review of randomized controlled trials (RCTs). We searched 7 databases: MEDLINE, CINAHL, PsycINFO, ACM Digital Library IEEE Xplore, Scopus, and Google Scholar. We also conducted backward and forward reference list checking of the included studies and relevant reviews. Two reviewers independently carried out the study selection, data extraction, risk of bias assessment, and quality of evidence appraisal. We used a narrative and statistical approach, as appropriate, to synthesize results of the included studies. RESULTS Out of 935 citations retrieved, 33 studies were included in this review. Of those, 22 RCTs were eventually included in meta-analyses. Very low quality evidence from 9 RCTs and 5 RCTs showed no statistically significant effect of exergames (games entailing physical exercises) on the anxiety level as compared to conventional exercises (P=0.70) and no intervention (P=0.27), respectively. While 6 RCTs demonstrated a statistically and clinically significant effect of computerized cognitive behavioral therapy (CBT) games on the anxiety level when compared with no intervention (P=0.01), the quality of the evidence reported was low. Likewise, low quality evidence from 3 RCTs showed a statistically and clinically significant effect of biofeedback games on the anxiety level when compared with conventional video games (P=0.03). CONCLUSIONS This review shows that serious games have the potential in alleviating anxiety levels. However, our findings remain inconclusive mainly due to the high risk of bias in the individual studies included, the low quality of meta-analyzed evidence, few studies included in some meta-analyses, patients without anxiety recruited in most studies, and using purpose-shifted serious games in most studies. Therefore, serious games should be deemed as complementary to existing interventions. To have adequate and robust evidence, researchers should use serious games that are designed specifically to alleviate depression and deliver other therapeutic modalities, recruit a diverse population of patients with anxiety, and minimize the risk of bias by following the recommended guidelines for conducting and reporting RCTs.

scholarly journals Risk factors for adverse events induced by immune checkpoint inhibitors in patients with non-small-cell lung cancer: a systematic review and meta-analysis

2021 ◽  
Author(s):  
E. Suazo-Zepeda ◽  
M. Bokern ◽  
P. C. Vinke ◽  
T. J. N. Hiltermann ◽  
G. H. de Bock ◽  
...  
Keyword(s):  
Risk Factors ◽  
Lung Cancer ◽  
Systematic Review ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Small Cell Lung ◽  
Meta Analyses

Abstract Background Immune checkpoint inhibitors (ICIs) can cause serious immune-related adverse events (irAEs). This study aimed to identify risk factors for all types of irAEs induced by ICIs in patients with non-small-cell lung cancer (NSCLC), by systematic review and meta-analyses. Methods A systematic search was performed in Pubmed, Embase and Web of Science by two independent reviewers. Studies were selected that included patients with NSCLC and evaluated characteristics of patients with and without irAEs induced by ICIs. Quality and risk of bias of the selected studies were assessed. Random effects meta-analyses were conducted to estimate pooled odds ratios (ORs) for risk factors of developing all type of irAEs, and separately for pneumonitis, interstitial lung disease and severe irAEs. With the objective of exploring sources of heterogeneity, stratified analyses were performed by quality and region. Results 25 studies met the inclusion criteria. In total, the data of 6696 patients were pooled. 33 different risk factors for irAEs were reported. irAEs of interest were reported for 1653 (25%) of the patients. Risk factors related to the development of irAEs were: C-reactive protein, neutrophil lymphocyte ratio (NLR), use of PD-1 inhibitor, high PD-L1 expression, an active or former smoking status, ground glass attenuation, and a better treatment response. Conclusion The identified risk factors for the development of these irAEs are mostly related to the alteration of the immune system, proinflammatory states and loss of immunological self-tolerance. Patients identified as having a higher risk for irAEs should be monitored more closely.

scholarly journals Treatments for subacute cough in primary care: systematic review and meta-analyses of randomised clinical trials

2018 ◽  
Vol 68 (675) ◽  
pp. e694-e702 ◽  
Author(s):  
Benjamin Speich ◽  
Anja Thomer ◽  
Soheila Aghlmandi ◽  
Hannah Ewald ◽  
Andreas Zeller ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Treatment Options ◽  
Combined Treatment ◽  
Randomised Clinical Trials ◽  
Cochrane Central Register ◽  
Central Register ◽  
Severity Scores ◽  
Drug Treatments ◽  
Meta Analyses

BackgroundSubacute cough following a non-specific viral infection lasting 3–8 weeks is common. However, despite many treatment options there are no systematic reviews evaluating these.AimTo provide a systematic overview of treatment options and outcomes evaluated in randomised clinical trials (RCTs).Design and settingSystematic review and meta-analyses assessing the overall effects of any treatment for subacute cough.MethodThe authors systematically searched PubMed/MEDLINE and the Cochrane Central Register of Controlled Trials (last search March 2017) for RCTs in adult patients with subacute cough. The authors considered trials evaluating any outcome of any drug or non-drug treatments, apart from traditional Chinese and Asian medicines. They combined treatment effects on cough-related outcomes in random effects meta-analyses.ResultsSix eligible RCTs including 724 patients were identified. These assessed montelukast, salbutamol plus ipratropium bromide, gelatine, fluticasone propionate, budesonide, and nociception opioid 1 receptor agonist and codeine. Five studies reported effects on various cough severity scores at various timepoints. No treatment option was associated with a clear benefit on cough recovery or other patient-relevant outcomes in any of the studies or in meta-analyses for cough outcomes at 14 days and 28 days. Reported adverse events were rather mild and reported for 14% of patients across all treatments.ConclusionEvidence on treatment options for subacute cough is weak. There is no treatment showing clear patient-relevant benefits in clinical trials.

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