scholarly journals What Can Be Done to Improve Research Biopsy Quality in Oncology Clinical Trials?

2018 ◽  
Vol 14 (11) ◽  
pp. e722-e728 ◽  
Author(s):  
Katherine V. Ferry-Galow ◽  
Vivekananda Datta ◽  
Hala R. Makhlouf ◽  
John Wright ◽  
Bradford J. Wood ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Anticancer Agents ◽  
Biopsy Specimen ◽  
Tissue Quality ◽  
Tumor Biopsy ◽  
Time Investment ◽  
Biopsy Specimens ◽  
Oncology Clinical Trials ◽  
Specimen Quality ◽  
Academic Recognition

Purpose: Research biopsy specimens collected in clinical trials often present requirements beyond those of tumor biopsy specimens collected for diagnostic purposes. Research biopsies underpin hypothesis-driven drug development, pharmacodynamic assessment of molecularly targeted anticancer agents, and, increasingly, genomic assessment for precision medicine; insufficient biopsy specimen quality or quantity therefore compromises the scientific value of a study and the resources devoted to it, as well as each patient’s contribution to and potential benefit from a clinical trial. Methods: To improve research biopsy specimen quality, we consulted with other translational oncology teams and reviewed current best practices. Results: Among the recommendations were improving communication between oncologists and interventional radiologists, providing feedback on specimen sufficiency, increasing academic recognition and financial support for the time investment required by radiologists to collect and preserve research biopsy specimens, and improving real-time assessment of tissue quality. Conclusion: Implementing these recommendations at the National Cancer Institute’s Developmental Therapeutics Clinic has demonstrably improved the quality of biopsy specimens collected; more widespread dissemination of these recommendations beyond large clinical cancer centers is possible and will be of value to the community in improving clinical research and, ultimately, patient care.

scholarly journals Urinary Cell mRNA Profiles Predictive of Human Kidney Allograft Status

2021 ◽  
pp. CJN.14010820
Author(s):  
Michelle L. Lubetzky ◽  
Thalia Salinas ◽  
Joseph E. Schwartz ◽  
Manikkam Suthanthiran
Keyword(s):  
Clinical Trials ◽  
T Cell ◽  
Acute Rejection ◽  
Biopsy Specimen ◽  
Acute Cellular Rejection ◽  
Kidney Allograft ◽  
Antibody Mediated Rejection ◽  
Biopsy Specimens ◽  
Allograft Biopsy ◽  
Cellular Rejection

Immune monitoring of kidney allograft recipients and personalized therapeutics may help reach the aspirational goal of “one transplant for life.” The invasive kidney biopsy procedure, the diagnostic tool of choice, has become safer and the biopsy classification more refined. Nevertheless, biopsy-associated complications, interobserver variability in biopsy specimen scoring, and costs continue to be significant concerns. The dynamics of the immune repertoire make frequent assessments of allograft status necessary, but repeat biopsies of the kidney are neither practical nor safe. To address the existing challenges, we developed urinary cell mRNA profiling and investigated the diagnostic, prognostic, and predictive accuracy of absolute levels of a hypothesis-based panel of mRNAs encoding immunoregulatory proteins. Enabled by our refinements of the PCR assay and by investigating mechanistic hypotheses, our single-center studies identified urinary cell mRNAs associated with T cell–mediated rejection, antibody-mediated rejection, interstitial fibrosis and tubular atrophy, and BK virus nephropathy. In the multicenter National Institutes of Health Clinical Trials in Organ Transplantation-04, we discovered and validated a urinary cell three-gene signature of T-cell CD3 ε chain mRNA, interferon gamma inducible protein 10 (IP-10) mRNA, and 18s ribosomal RNA that is diagnostic of subclinical acute cellular rejection and acute cellular rejection and prognostic of acute cellular rejection and graft function. The trajectory of the signature score remained flat and below the diagnostic threshold for acute cellular rejection in the patients with no rejection biopsy specimens, whereas a sharp rise was observed during the weeks before the biopsy specimen that showed acute cellular rejection. Our RNA sequencing and bioinformatics identified kidney allograft biopsy specimen gene signatures of acute rejection to be enriched in urinary cells matched to acute rejection biopsy specimens. The urinary cellular landscape was more diverse and more enriched for immune cell types compared with kidney allograft biopsy specimens. Urinary cell mRNA profile–guided clinical trials are needed to evaluate their value compared with current standard of care.

Review of Clinical Equipoise: Examples from Oncology Trials

2021 ◽  
Vol 17 ◽  
Author(s):  
Majd A. Hamaly ◽  
Karem H. Alzoubi ◽  
Omar F. Khabour ◽  
Ruba A. Jaber ◽  
Wael Al-delaimy
Keyword(s):  
Clinical Trials ◽  
Anticancer Agents ◽  
Human Subjects ◽  
Specific Reference ◽  
Clinical Equipoise ◽  
Equal Distribution ◽  
Randomized Controlled Clinical Trials ◽  
Randomized Controlled ◽  
Oncology Clinical Trials ◽  
The Status

Background: The current standards that govern clinical research have been shaped over the years through many historical, social, and political events. The third principle of the Belmont report, Justice, guides the scientific community toward equal distribution of benefits and risks in research involving human subjects. Clinical equipoise is the status of genuine uncertainty by the investigator about the superiority of one treatment arm over the other. The term clinical equipoise was proposed to provide an ethical ground to conduct randomized controlled clinical trials. Objective: The objective of this review is to provide the reader with an overview about the emergence of the term equipoise and its utilization in randomized controlled trials. Methods: In the current review article, the major oncology clinical trials and relevant patents were reviewed for the application/utilization of clinical equipoise. Results: The concept of clinical equipoise has been challenged and different alternatives were proposed. Yet, these alternatives received numerous critiques and failed to fully replace equipoise. In addition, several patents related to anticancer agents tested in the described studies were examined. No specific reference was made as part of the patent to the status of clinical equipoise. Alternatively, a description of the study arms was provided. Conclusion: There is a need for revisiting the concept of equipoise and its suggested alternatives, for its ethical essence while addressing related challenges.

The intravenous to oral switch of taxanes: strategies and current clinical developments

2020 ◽  
Author(s):  
Marit AC Vermunt ◽  
Andries M Bergman ◽  
Eric van der Putten ◽  
Jos H Beijnen
Keyword(s):  
Clinical Trials ◽  
Anticancer Agents ◽  
Hospital Care ◽  
Oral Treatment ◽  
Chemotherapy Treatment ◽  
Intravenous Treatment ◽  
Improve Cost Effectiveness ◽  
Oral Switch ◽  
Tumor Types ◽  
Improve Cost

The taxanes paclitaxel, docetaxel and cabazitaxel are important anticancer agents that are widely used as intravenous treatment for several solid tumor types. Switching from intravenous to oral treatment can be more convenient for patients, improve cost–effectiveness and reduce the demands of chemotherapy treatment on hospital care. However, oral treatment with taxanes is challenging because of pharmaceutical and pharmacological factors that lead to low oral bioavailability. This review summarizes the current clinical developments in oral taxane treatment. Intravenous parent drugs, strategies in the oral switch, individual agents in clinical trials, challenges and further perspectives on treatment with oral taxanes are subsequently discussed.

scholarly journals The number of osteoclasts in a biopsy specimen can predict the efficacy of neoadjuvant chemotherapy for primary osteosarcoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Y. Araki ◽  
N. Yamamoto ◽  
K. Hayashi ◽  
A. Takeuchi ◽  
S. Miwa ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Biopsy Specimen ◽  
Osteoclast Differentiation ◽  
Poor Response ◽  
Underlying Mechanism ◽  
Biopsy Specimens ◽  
Response To Chemotherapy ◽  
Simple Factor ◽  
Chemotherapy Agents ◽  
Chemotherapy Efficacy

AbstractOsteosarcoma is the most common primary malignant bone tumor, and its standard treatment is a combination of surgery and chemotherapy. A poor response to chemotherapy causes unfavorable oncological outcomes. We investigated the correlation between osteoclast differentiation in biopsy specimens and the efficacy of neoadjuvant chemotherapy in resected specimens. Forty-nine patients who underwent neoadjuvant chemotherapy and subsequent surgical treatment at our institution between 1999 and 2018 were enrolled. Using medical records, we investigated the age, sex, tumor size, location, subtype, staging, chemotherapy agents (doxorubicin, cisplatin, ifosfamide, and methotrexate), number of neoadjuvant chemotherapy courses, number of osteoclasts in biopsy specimens, and efficacy of neoadjuvant chemotherapy according to the Rosen and Huvos classification (Grade I-IV) in resected specimens. Univariate and multivariate analyses were performed to identify factors predictive of a good response in resected specimens after neoadjuvant chemotherapy. A good response (Grade III/IV) was detected in 25, while a poor response (Grade I/II) was detected in 24. According to the multivariate analysis, ≥ 46 years old (odds ratio [OR], 0.05; 95% confidence interval [CI], 0.01–0.45; p < 0.01) and ≥ 5 mature osteoclasts in a biopsy specimen (OR, 36.9; 95% CI, 6.03–225; p < 0.01) were significantly associated with the neoadjuvant chemotherapy efficacy. The accuracy for predicting a good response to chemotherapy based on ≥ 5 osteoclasts in a biopsy specimen in patients < 46 years old was 85%. The number of mature osteoclasts in biopsy specimens is a simple factor for predicting the efficacy of chemotherapy before treatment, although further studies will be required to determine the underlying mechanism.

scholarly journals COVID-19 vaccine guidance for patients with cancer participating in oncology clinical trials

2021 ◽  
Author(s):  
Aakash Desai ◽  
◽  
Justin F. Gainor ◽  
Aparna Hegde ◽  
Alison M. Schram ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Patients With Cancer ◽  
Oncology Clinical Trials

Z max test for delayed effect in immuno-oncology clinical trials

2019 ◽  
Vol 30 (2) ◽  
pp. 244-266 ◽  
Author(s):  
Miao Yang ◽  
Zhaowei Hua ◽  
Lan Xue ◽  
Mingxiu Hu
Keyword(s):  
Clinical Trials ◽  
Delayed Effect ◽  
Oncology Clinical Trials
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