scholarly journals Pediatric versus Adult Medulloblastoma: Towards a Definition That Goes beyond Age

Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6313
Author(s):  
Joseph R. Wooley ◽  
Marta Penas-Prado
Keyword(s):  
Clinical Trials ◽  
Literature Review ◽  
Childhood Leukemia ◽  
Standard Of Care ◽  
Adjuvant Radiation ◽  
Molecular Alterations ◽  
Adult Medulloblastoma ◽  
Molecular Features ◽  
Trial History ◽  
Standard Of Care Treatment

Medulloblastoma is a rare malignant brain tumor that predominantly affects children but also occurs in adults. The incidence declines significantly after age 15, and distinct tumor molecular features are seen across the age spectrum. Standard of care treatment consists of maximal safe surgical resection followed by adjuvant radiation and/or chemotherapy. Adjuvant treatment decisions are based on individual patient risk factors and have been informed by decades of prospective clinical trials. These trials have historically relied on arbitrary age cutoffs for inclusion (age 16, 18, or 21, for example), while trials that include adult patients or stratify patients by molecular features of disease have been rare. The aim of this literature review is to review the history of clinical trials in medulloblastoma, with an emphasis on selection criteria, and argue in favor of rational and inclusive trials based on molecular features of disease as opposed to chronological age. We performed a scoping literature review for medulloblastoma and clinical trials and include a summary of those results. We also discuss some of the significant advances made in understanding the molecular biology of medulloblastoma within the past decade, most notably the identification of four distinct subgroups based on gene expression profiling. We will also cite the recent experiences of childhood leukemia and the emergence of tissue-agnostic therapies as examples of successes of rationally designed, inclusive trials translating to improved clinical outcomes for patients across the age spectrum. Despite the prior trial history and recent molecular advances outcomes remain poor for ~30% of medulloblastoma patients. We believe that defining patients by the specific molecular alterations their tumors harbor is the best way to ensure they can access potentially efficacious therapies on clinical trials.

scholarly journals Myoclonic jerks complicating treatment of acute promyelocytic leukemia: case report and literature review

2019 ◽  
Vol 3 (12) ◽  
pp. 1854-1857 ◽  
Author(s):  
John Y. Rhee ◽  
Douglas Tremblay ◽  
Amy M. Chan ◽  
Martin S. Tallman ◽  
John Mascarenhas
Keyword(s):  
Case Report ◽  
Literature Review ◽  
Acute Promyelocytic Leukemia ◽  
Standard Of Care ◽  
Promyelocytic Leukemia ◽  
Low Risk ◽  
Neurologic Complications ◽  
Care Treatment ◽  
Key Points ◽  
Standard Of Care Treatment

Key Points Myoclonic jerks and inattentiveness may be rare neurologic complications of ATO toxicity. Clinicians must be aware of this rare toxicity given that the ATO and ATRA combination is now standard-of-care treatment of low-risk APL.

Use of placebo in cancer medicine: The experience of a National Clinical Trials organization

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 6104-6104
Author(s):  
J. L. Pater ◽  
W. Parulekar
Keyword(s):  
Clinical Trials ◽  
Supportive Care ◽  
Study Design ◽  
Standard Of Care ◽  
Phase Iii ◽  
Design Data ◽  
Standard Of Care Treatment ◽  
Prevention Trials ◽  
The Impact ◽  
Phase Iii Studies

6104 Background: The use of placebos in cancer clinical trials requires careful evaluation. Factors that must be considered include the impact of placebo on endpoint measurement, the efficacy of placebo relative to standard of care treatment, patient altruism/acceptance of a non-active intervention and the resulting increase in complexity of study conduct with respect to randomization, drug supply, data management, analysis and the unblinding process. Methods: We reviewed the experience of the National Cancer Institute of Canada Clinical Trials Group with the use of placebo in the randomized phase III setting from 1982–2005. Results: Since 1982, 34 studies were identified that utilized a placebo as part of study design. Data is presented below according to the type of study and date of study activation. The numbers in brackets represent those studies in which placebo was used alone in the control arm. Supportive care studies were the most common type of study employing a placebo as part of study design and constituted almost 50% of our Group’s experience. Therapeutic studies involving placebo were conducted in multiple sites including breast (4), lung (6), myeloma (1), melanoma (1), ovary (1) and pancreas (1). Conclusion: Phase III studies involving a placebo constitute an important part of our clinical trial activity and cross the spectrum of supportive care, therapeutic and prevention trials. The use of placebo in cancer studies may increase due to the relative ease of blinding in studies that evaluate targeted, oral therapies with minimal toxicities as well as the need for unbiased assessment of increasingly used endpoints such as time to progression. [Table: see text] No significant financial relationships to disclose.

Clinical Trials in PBC Going Forward

2019 ◽  
Vol 39 (03) ◽  
pp. e1-e6
Author(s):  
Christophe Corpechot
Keyword(s):  
Clinical Trials ◽  
Ursodeoxycholic Acid ◽  
Standard Of Care ◽  
Farnesoid X Receptor ◽  
Primary Biliary Cholangitis ◽  
Peroxisome Proliferator ◽  
Personal View ◽  
Standard Of Care Treatment ◽  
Peroxisome Proliferator Activated Receptors ◽  
New Treatments

AbstractNew treatments for primary biliary cholangitis (PBC) are progressively emerging, including first and second generations of farnesoid X receptor and peroxisome proliferator-activated receptors agonists. Even though ursodeoxycholic acid monotherapy remains the standard of care treatment for PBC, these additional therapeutic options, already or soon to be available, lead us to revise our priorities and strategies with respect to future clinical trials. The present article is a personal view of where we currently stand in this field and where and how we should be going to achieve new progress.

scholarly journals Updates on clinical trials evaluating the regenerative potential of allogenic mesenchymal stem cells in COVID-19

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Dhavan Sharma ◽  
Feng Zhao
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Mesenchymal Stem Cells ◽  
Therapeutic Potential ◽  
Adaptive Immune Response ◽  
Standard Of Care ◽  
Multiple Organ ◽  
Current Standard ◽  
Number Of Patients ◽  
Standard Of Care Treatment

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected nearly 118 million people and caused ~2.6 million deaths worldwide by early 2021, during the coronavirus disease 2019 (COVID-19) pandemic. Although the majority of infected patients show mild-to-moderate symptoms, a small fraction of patients develops severe symptoms. Uncontrolled cytokine production and the lack of substantive adaptive immune response result in hypoxia, acute respiratory distress syndrome (ARDS), or multiple organ failure in severe COVID-19 patients. Since the current standard of care treatment is insufficient to alleviate severe COVID-19 symptoms, many clinics have been prompted to perform clinical trials involving the infusion of mesenchymal stem cells (MSCs) due to their immunomodulatory and therapeutic properties. Several phases I/II clinical trials involving the infusion of allogenic MSCs have been performed last year. The focus of this review is to critically evaluate the safety and efficacy outcomes of the most recent, placebo-controlled phase I/II clinical studies that enrolled a larger number of patients, in order to provide a statistically relevant and comprehensive understanding of MSC’s therapeutic potential in severe COVID-19 patients. Clinical outcomes obtained from these studies clearly indicate that: (i) allogenic MSC infusion in COVID-19 patients with ARDS is safe and effective enough to decreases a set of inflammatory cytokines that may drive COVID-19 associated cytokine storm, and (ii) MSC infusion efficiently improves COVID-19 patient survival and reduces recovery time. These findings strongly support further investigation into MSC-infusion in larger clinical trials for COVID-19 patients with ARDS, who currently have a nearly 50% of mortality rate.

scholarly journals Daily Lifestyle Modifications to Improve Quality of Life and Survival in Glioblastoma: A Review

2021 ◽  
Vol 11 (5) ◽  
pp. 533
Author(s):  
Sarah Travers ◽  
N. Scott Litofsky
Keyword(s):  
Quality Of Life ◽  
Clinical Trials ◽  
Animal Studies ◽  
Standard Of Care ◽  
Active Role ◽  
Lifestyle Changes ◽  
Comprehensive Treatment ◽  
Lifestyle Modifications ◽  
Standard Of Care Treatment

Survival in glioblastoma remains poor despite advancements in standard-of-care treatment. Some patients wish to take a more active role in their cancer treatment by adopting daily lifestyle changes to improve their quality of life or overall survival. We review the available literature through PubMed and Google Scholar to identify laboratory animal studies, human studies, and ongoing clinical trials. We discuss which health habits patients adopt and which have the most promise in glioblastoma. While results of clinical trials available on these topics are limited, dietary restrictions, exercise, use of supplements and cannabis, and smoking cessation all show some benefit in the comprehensive treatment of glioblastoma. Marital status also has an impact on survival. Further clinical trials combining standard treatments with lifestyle modifications are necessary to quantify their survival advantages.

scholarly journals Effects of culinary herbs and spices on obesity: A systematic literature review of clinical trials

2021 ◽  
Vol 81 ◽  
pp. 104449
Author(s):  
Chandana Deekshith ◽  
Markandeya Jois ◽  
Jessica Radcliffe ◽  
Jency Thomas
Keyword(s):  
Clinical Trials ◽  
Literature Review ◽  
Systematic Literature Review ◽  
Culinary Herbs ◽  
Herbs And Spices

scholarly journals TMOD-12. ESTABLISHING A CLINICALLY RELEVANT MODEL OF MESENCHYMAL GLIOBLASTOMA (GBM) TO STUDY RESPONSE TO STANDARD OF CARE TREATMENT AND IMMUNE CHECKPOINT INHIBITION (ICI).

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii230-ii230
Author(s):  
James Clerkin ◽  
Kate Connor ◽  
Kieron Sweeney ◽  
Kieron White ◽  
Liam Shiels ◽  
...  
Keyword(s):  
Surgical Resection ◽  
Standard Of Care ◽  
Resistance Mechanisms ◽  
Orthotopic Model ◽  
Aged Mice ◽  
Gl261 Cell ◽  
Standard Of Care Treatment ◽  
Clinical Models ◽  
Immune Contexture

Abstract GBM is a devastating disease with peak incidence in the seventh decade. Pre-clinical models are essential for studying resistance mechanisms and screening novel therapies. However, historically these models have failed to predict response in humans. Current models seldom incorporate surgical resection, and commonly use young animals whose immune contexture differs from older patients. Here, we have established an orthotopic model employing the syngeneic mesenchymal-NFpp10a-cell line which incorporates surgical resection in aged mice. We further characterise response to ICI and temozolomide monotherapy. NFpp10a and GL261-cell lines were exposed in vitro to irradiation (0Gy/2Gy/5Gy) and response assessed using colony formation assays. NFpp10a formed significantly more colonies at 5Gy compared to GL261 at both day 10 (NFpp10a 5.167 vs GL261 1.4; p=0.0017) and day 14 (NFpp10a 3.5 vs GL261 0; p< 0.0001). Hence, NFpp10a displays increased radioresistance. Next, NFpp10a-luciferin expressing cells were orthotopically implanted into young (6-8weeks;n=16) and aged (18months;n=16) C57BL/6-mice. Weekly bioluminescence imaging (BLI) was performed to monitor growth. Mice undergoing resection showed a median 18.47-fold drop in BLI signal. We demonstrated resection survival advantage in aged mice (Resection:33.5 days vs Non-Resection:18 days, p= 0.0166) and showed young age to be a positive prognostic factor (Young:62 days vs Aged:22 days, p=0.0002). Subsequently, we orthotopically implanted NFpp10a-Luc2 cells into C57BL/6 mice and treated with temozolomide (n=24) or PBS control (n=23), and anti-PD1 (n=24) or IgG (n=23). We observed that temozolomide and anti-PD1 monotherapy had no impact on NFpp10-Luc2 growth (temozolomide-overall:p=0.9001, anti-PD1-overall:p=0.7933) or survival (temozolomide-overall:p=0.3035, anti-PD1-overall:p=0.6328). Overall, we have established an NFpp10-Luc2 mesenchymal-GBM model in aged mice which incorporates surgical resection and accurately displays significant resistance to temozolomide and anti-PD1 monotherapy. We are currently employing this model to study the efficacy of neoadjuvant anti-PD1 therapy. Mechanistic analyses with multiplex-immunohistochemistry, scRNA and whole exome sequencing are planned to interrogate treatment effects on the tumor microenvironment.

scholarly journals Co-Clinical Trials: An Innovative Drug Development Platform for Cholangiocarcinoma

2021 ◽  
Vol 14 (1) ◽  
pp. 51
Author(s):  
Brinda Balasubramanian ◽  
Simran Venkatraman ◽  
Kyaw Zwar Myint ◽  
Tavan Janvilisri ◽  
Kanokpan Wongprasert ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Targeted Therapy ◽  
Drug Development ◽  
Surgical Resection ◽  
Treatment Options ◽  
Standard Of Care ◽  
Time Data ◽  
Current Standard ◽  
Innovative Drug ◽  
Curative Intent

Cholangiocarcinoma (CCA), a group of malignancies that originate from the biliary tract, is associated with a high mortality rate and a concerning increase in worldwide incidence. In Thailand, where the incidence of CCA is the highest, the socioeconomic burden is severe. Yet, treatment options are limited, with surgical resection being the only form of treatment with curative intent. The current standard-of-care remains adjuvant and palliative chemotherapy which is ineffective in most patients. The overall survival rate is dismal, even after surgical resection and the tumor heterogeneity further complicates treatment. Together, this makes CCA a significant burden in Southeast Asia. For effective management of CCA, treatment must be tailored to each patient, individually, for which an assortment of targeted therapies must be available. Despite the increasing numbers of clinical studies in CCA, targeted therapy drugs rarely get approved for clinical use. In this review, we discuss the shortcomings of the conventional clinical trial process and propose the implementation of a novel concept, co-clinical trials to expedite drug development for CCA patients. In co-clinical trials, the preclinical studies and clinical trials are conducted simultaneously, thus enabling real-time data integration to accurately stratify and customize treatment for patients, individually. Hence, co-clinical trials are expected to improve the outcomes of clinical trials and consequently, encourage the approval of targeted therapy drugs. The increased availability of targeted therapy drugs for treatment is expected to facilitate the application of precision medicine in CCA.

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