scholarly journals Immunotherapy in Pediatric Solid Tumors—A Systematic Review

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 2022 ◽  
Author(s):  
Raoud Marayati ◽  
Colin H. Quinn ◽  
Elizabeth A. Beierle
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Solid Tumors ◽  
Recurrent Disease ◽  
Treatment Options ◽  
Pediatric Solid Tumors ◽  
Course Of Action ◽  
Dismal Prognosis ◽  
High Risk Disease ◽  
Intensified Chemotherapy

Despite advances in the treatment of many pediatric solid tumors, children with aggressive and high-risk disease continue to have a dismal prognosis. For those presenting with metastatic or recurrent disease, multiple rounds of intensified chemotherapy and radiation are the typical course of action, but more often than not, this fails to control the progression of the disease. Thus, new therapeutics are desperately needed to improve the outcomes for these children. Recent advances in our understanding of both the immune system’s biology and its interaction with tumors have led to the development of novel immunotherapeutics as alternative treatment options for these aggressive malignancies. Immunotherapeutic approaches have shown promising results for pediatric solid tumors in early clinical trials, but challenges remain concerning safety and anti-tumor efficacy. In this review, we aim to discuss and summarize the main classes of immunotherapeutics used to treat pediatric solid tumors.

scholarly journals Approaches to Enhance Natural Killer Cell-Based Immunotherapy for Pediatric Solid Tumors

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2796
Author(s):  
Aicha E. Quamine ◽  
Mallery R. Olsen ◽  
Monica M. Cho ◽  
Christian M. Capitini
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Solid Tumors ◽  
Nk Cell ◽  
Therapeutic Option ◽  
Treatment Options ◽  
Intensive Therapy ◽  
Killer Cell ◽  
Cell Therapies ◽  
Pediatric Solid Tumors

Treatment of metastatic pediatric solid tumors remain a significant challenge, particularly in relapsed and refractory settings. Standard treatment has included surgical resection, radiation, chemotherapy, and, in the case of neuroblastoma, immunotherapy. Despite such intensive therapy, cancer recurrence is common, and most tumors become refractory to prior therapy, leaving patients with few conventional treatment options. Natural killer (NK) cells are non-major histocompatibility complex (MHC)-restricted lymphocytes that boast several complex killing mechanisms but at an added advantage of not causing graft-versus-host disease, making use of allogeneic NK cells a potential therapeutic option. On top of their killing capacity, NK cells also produce several cytokines and growth factors that act as key regulators of the adaptive immune system, positioning themselves as ideal effector cells for stimulating heavily pretreated immune systems. Despite this promise, clinical efficacy of adoptive NK cell therapy to date has been inconsistent, prompting a detailed understanding of the biological pathways within NK cells that can be leveraged to develop “next generation” NK cell therapies. Here, we review advances in current approaches to optimizing the NK cell antitumor response including combination with other immunotherapies, cytokines, checkpoint inhibition, and engineering NK cells with chimeric antigen receptors (CARs) for the treatment of pediatric solid tumors.

scholarly journals P10 Reporting of offspring data in diabetes, HIV infection and hypertension trials during pregnancy: a systematic review

2019 ◽  
Vol 104 (6) ◽  
pp. e21.1-e21
Author(s):  
B Aurich ◽  
T Martin-Montoya ◽  
D Zhang ◽  
E Jacqz-Aigrain
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Hiv Infection ◽  
Pregnant Women ◽  
Health Care Professionals ◽  
Full Text ◽  
Treatment Options ◽  
Safety Data ◽  
Chronic Medication ◽  
Neonatal Deaths

BackgroundAccording to international guidelines clinical trials are conducted during pregnancy to evaluate benefits and risks of medicines for both the mother and her offspring. Consolidated Standards of Reporting Trials (CONSORT) reporting criteria apply to these trials and should include safety data on the offspring. The safety of maternal treatments is a key issue for health care professionals and parents. Diabetes, human immunodeficiency virus (HIV) infection and hypertension are among the most frequent chronic diseases worldwide in women of child bearing potential. The objective of this systematic review was to analyse offspring data reported in clinical trials conducted in pregnant women receiving chronic drug treatment for one of these conditions.MethodsPubmed and Embase (01/01/1997–31/12/2017) were searched for drug trials in pregnant women with diabetes, HIV infection or hypertension. Titles and abstracts were screened, followed by a full text review of eligible articles. Inclusion criteria were interventional clinical trials in pregnant women treated with chronic medication and full text in English. Trial characteristics, maternal and offspring data were extracted. Data was summarised by disease and study. Twelve key items were considered for the offspring. The protocol was registered on PROSPERO (CRD42017057024).ResultsOverall, 196 articles reporting 132 clinical trials (diabetes n=55; HIV n=59; hypertension n=18) were included. The number of births were frequently not reported (diabetes 40%; HIV 24%; hypertension 56%). Congenital malformations were infrequently reported with sufficient detail (diabetes 27%; HIV 34%; hypertension 6%). Similar observations were made for other key items (e.g. foetal losses, neonatal deaths, birth weight corrected for gestational age).ConclusionsUnderreporting of key data for the offspring was frequent in publications of clinical trials in pregnant women with diabetes, HIV infection or hypertension making the assessment of the benefit-risk ratio of treatment options during pregnancy difficult.Disclosure(s)Nothing to disclose

Management of carcinoid syndrome (CS): A systematic review of systemic treatment options.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 516-516
Author(s):  
Edward M. Wolin ◽  
Al Bowen Benson
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Systemic Treatment ◽  
Treatment Options ◽  
Symptom Relief ◽  
Safety Data ◽  
Significant Heterogeneity ◽  
Carcinoid Heart Disease ◽  
Systemic Treatments ◽  
Symptom Response

516 Background: CS is a major cause of symptom burden (diarrhea/flushing) in patients (pts) with neuroendocrine tumors and is associated with shortened survival and severe complications such as carcinoid heart disease. We performed a systematic review of clinical evidence for CS systemic treatments. Methods: PubMed, Embase, and Cochrane databases were searched. Large ( > 60 pt) prospective clinical trials investigating the efficacy/safety of systemic treatment options for pts with CS were eligible for inclusion. Data extracted included study design, pt population, interventions, prior treatments, permitted concomitant medications, study endpoints/statistical analyses, and efficacy/safety outcomes. Results: Six large prospective clinical trials (total 953 pts) were identified from 144 search results. Significant heterogeneity existed in pt populations, control groups (placebo vs active comparator), duration of therapy, study endpoints, and efficacy/safety data reporting. Interventions assessed were long-acting and subcutaneous octreotide (OCT & OCT SC), lanreotide (LAN), telotristat ethyl (TE)+somatostatin analogues (SSA), pasireotide (PAS), and everolimus (EVE)+OCT. Symptom response was variably assessed by the frequency of diarrhea/flushing and/or receipt of rescue short-acting SSA in 5/6 studies; a significant improvement in at least one of these measures occurred in 4 studies (OCT and OCT SC; LAN; TE+SSA). Failure to meet symptom response criteria ranged from 29-82% in the studies. Reported reductions in CgA and/or 5-HIAA reached statistical significance in 3 studies (LAN; EVE+OCT; TE+SSA). Interventions were generally well tolerated. Two phase 3 trials focused specifically on management of CS symptoms refractory to SSA; strategies included switching to PAS or an increased dose of OCT (40 mg q28d) for refractory diarrhea/flushing, or receipt of TE with continued SSA for refractory diarrhea. Conclusions: SSA provide substantial symptom relief for pts with CS. For refractory symptoms, TE can be added, SSA dose increased, and metastasis debulking can be used (with surgery, hepatic artery embolization, ablation, and PRRT). The addition of biologic agents to SSA can further improve CS management.

scholarly journals The efficacy of topical, oral and surgical interventions for the treatment of tungiasis: A systematic review of the literature

2021 ◽  
Vol 15 (8) ◽  
pp. e0009722
Author(s):  
Ana Carolina Tardin Martins ◽  
Amanda Ramos de Brito ◽  
Patrícia Shu Kurizky ◽  
Rodrigo Gurgel Gonçalves ◽  
Yago Ranniere Teixeira Santana ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Observational Studies ◽  
Treatment Options ◽  
Sufficient Evidence ◽  
Tissue Destruction ◽  
Adequate Treatment ◽  
Surgical Interventions ◽  
Surgical Extraction ◽  
Quantitative Descriptive

Background Tungiasis is a neglected disease caused by Tunga penetrans that can be complicated by secondary infections and local tissue destruction. Adequate treatment is important, especially in vulnerable populations; potential treatment options proposed range from surgical extraction to the use of oral and topical medications. We aimed to perform a systematic review to assess the efficacy of topical, oral and surgical interventions for the treatment of tungiasis. Methodology/Principal findings The present review is registered in PROSPERO (CRD42021234741). On September 1, 2020, we searched PubMed, EMBASE, Scopus, Web of Science, Science Direct, Scielo and LILACS BVS. We included clinical trials and longitudinal observational studies that evaluated any topical, systemic or mechanical treatment for tungiasis. We used the Revised Cochrane Risk of Bias (RoB) Tool for Randomized Trials for clinical trial analysis. Qualitative and quantitative descriptive syntheses were performed. Our search strategy resulted in 3376 references. Subsequently, 2568 titles/abstracts and 114 full texts were screened. We finally included 19 articles; 9 were classified as clinical trials. Two and 3 articles presented low and some RoB, respectively, according to the tool. Only two articles tested the efficacy of oral medications (niridazole, ivermectin), with discouraging results. Six clinical trials evaluated topical products for the treatment of tungiasis; 2 evaluated dimeticone-based compounds and reported positive results in lesion reduction and cure. None reported significant adverse reactions. Surgical extraction was evaluated only in observational studies. Conclusions/Significance We conclude that, although surgical extraction is the most commonly used treatment, there is sufficient evidence supporting the use of occlusive agents, especially manufactured dimeticone-based products.

scholarly journals Systematic Review of Patient-Derived Xenograft Models for Preclinical Studies of Anti-Cancer Drugs in Solid Tumors

Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 418 ◽  
Author(s):  
Yoshikatsu Koga ◽  
Atsushi Ochiai
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Solid Tumors ◽  
Cancer Biology ◽  
Drug Efficacy ◽  
Cancer Drugs ◽  
Personalized Care ◽  
Patient Derived Xenograft ◽  
Anti Cancer ◽  
Pdx Models

Patient-derived xenograft (PDX) models are used as powerful tools for understanding cancer biology in PDX clinical trials and co-clinical trials. In this systematic review, we focus on PDX clinical trials or co-clinical trials for drug development in solid tumors and summarize the utility of PDX models in the development of anti-cancer drugs, as well as the challenges involved in this approach, following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Recently, the assessment of drug efficacy by PDX clinical and co-clinical trials has become an important method. PDX clinical trials can be used for the development of anti-cancer drugs before clinical trials, with their efficacy assessed by the modified response evaluation criteria in solid tumors (mRECIST). A few dozen cases of PDX models have completed enrollment, and the efficacy of the drugs is assessed by 1 × 1 × 1 or 3 × 1 × 1 approaches in the PDX clinical trials. Furthermore, co-clinical trials can be used for personalized care or precision medicine with the evaluation of a new drug or a novel combination. Several PDX models from patients in clinical trials have been used to assess the efficacy of individual drugs or drug combinations in co-clinical trials.

scholarly journals Deficiency in the Treatment Description of mTOR Inhibitor Resistance in Medulloblastoma, a Systematic Review

2021 ◽  
Vol 23 (1) ◽  
pp. 464
Author(s):  
Hajar Alammar ◽  
Rayan Nassani ◽  
Mana M. Alshehri ◽  
Alaa A. Aljohani ◽  
Bahauddeen M. Alrfaei
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
First Generation ◽  
Treatment Options ◽  
Pediatric Brain Tumor ◽  
Mtor Inhibitors ◽  
Malignant Cell ◽  
Phase I Clinical Trials ◽  
Inhibitor Resistance ◽  
Pediatric Brain

Medulloblastoma is a common fatal pediatric brain tumor. More treatment options are required to prolong survival and decrease disability. mTOR proteins play an essential role in the disease pathogenesis, and are an essential target for therapy. Three generations of mTOR inhibitors have been developed and are clinically used for immunosuppression and chemotherapy for multiple cancers. Only a few mTOR inhibitors have been investigated for the treatment of medulloblastoma and other pediatric tumors. The first-generation mTOR, sirolimus, temsirolimus, and everolimus, went through phase I clinical trials. The second-generation mTOR, AZD8055 and sapanisertib, suppressed medulloblastoma cell growth; however, limited studies have investigated possible resistance pathways. No clinical trials have been found to treat medulloblastoma using third-generation mTOR inhibitors. This systematic review highlights the mechanisms of resistance of mTOR inhibitors in medulloblastoma and includes IDO1, T cells, Mnk2, and eIF4E, as they prolong malignant cell survival. The findings promote the importance of combination therapy in medulloblastoma due to its highly resistant nature.

Toxicity profile of approved anti-PD1 monoclonal antibodies in solid tumors: A systematic review and meta-analysis of randomized clinical trials.

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. 3064-3064 ◽  
Author(s):  
Ricardo Lima Barros Costa ◽  
Benedito A. Carneiro ◽  
Alfred Rademaker ◽  
Mark Agulnik ◽  
Victoria Meucci Villaflor ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Monoclonal Antibodies ◽  
Solid Tumors ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Toxicity Profile

scholarly journals Toxicity profile of approved anti-PD-1 monoclonal antibodies in solid tumors: a systematic review and meta-analysis of randomized clinical trials

Oncotarget ◽  
2016 ◽  
Vol 8 (5) ◽  
pp. 8910-8920 ◽  
Author(s):  
Ricardo Costa ◽  
Benedito A. Carneiro ◽  
Mark Agulnik ◽  
Alfred W. Rademaker ◽  
Sachin G. Pai ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Monoclonal Antibodies ◽  
Solid Tumors ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Toxicity Profile

scholarly journals Aztreonam for Neisseria gonorrhoeae: a systematic review and meta-analysis

2020 ◽  
Vol 75 (7) ◽  
pp. 1685-1688 ◽  
Author(s):  
Lindley A Barbee ◽  
Matthew R Golden
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Neisseria Gonorrhoeae ◽  
Treatment Efficacy ◽  
Meta Analysis ◽  
Treatment Options ◽  
Case Series ◽  
Trial Data ◽  
Anatomical Site ◽  
Near Term

Abstract Background Ceftriaxone is the only consistently active antimicrobial agent recommended for the treatment of Neisseria gonorrhoeae. Although some new antimicrobials are in development, the necessity to expand treatment options in the near term may require using older drugs that have not been widely used to treat gonorrhoea. Methods We conducted a literature review of clinical trials and case series, published from 1983 to 2017, reporting treatment efficacy results following administration of 1 g aztreonam intramuscularly or IV for uncomplicated gonococcal infections. We summed trial data, stratified by anatomical site of infection, and calculated summary efficacy estimates and 95% CI for each site of infection. Results The 10 identified clinical trials enrolled 678, 38 and 16 individuals with urogenital, rectal and pharyngeal gonorrhoea, respectively. Aztreonam had an efficacy of 98.6% (95% CI: 97.5%–99.4%) for urogenital, 94.7% (95% CI: 82.3%–99.4%) for rectal and 81.3% (95% CI: 54.4%–96.0%) for pharyngeal gonococcal infections. Conclusions Although most clinical trials included in this meta-analysis were conducted >30 years ago, aztreonam appears to have excellent efficacy for urogenital gonorrhoea; its efficacy at extragenital sites remains uncertain.

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