Medicine Trials Research Articles

Cross-sectional study on evaluation of diagnostic interval in children with newly diagnosed paediatric cancers and factors affecting it

BackgroundDiagnostic interval/delay (DI) denotes the duration between first presentations to healthcare provider to the definitive diagnosis of cancer. Prolonged DI is a major contributor to deaths among children with malignancies in low-middle-income countries (LMICs). The data on DI and factors affecting it are limited from LMIC. MethodsThis cross-sectional study enrolled patients/children<12 years with proven/suspected malignancies. Children already on definitive chemotherapy, who died before a definitive diagnosis and with benign tumours were excluded. The parents or caregivers were interviewed individually using a customized questionnaire. Various intervals in referral chain like patient interval/delay (PI), DI and treatment interval/delay (TI) and factors affecting DI were evaluated. ResultsOut of 120 eligible children; 79 with median age 43 months (interquartile range [IQR]: 28–81) were analyzed. Haematological malignancies (n = 40) and non-haematological malignancies (n = 39) were equally distributed. Median total delay was 74 days (14–88 days). Median DI was 17 days (IQR: 8–54). The main contributor to delay was due to referral delay by primary and secondary physician (p < 0.05). The median PI was 2 day (IQR: 0–7.5) and median TI was 1 day (IQR: 0–4). Prolonged DI (DI > 30 days) was seen in 33 (41.8%) children. Trial of alternative medicine was the only significant factor associated with prolonged DI in univariate and multivariate analysis with odds ratio of 6.24. Other demographic, socioeconomic, health-seeking journey and disease-related factors were not found to be associated with prolonged DI. ConclusionsSignificant delay exists in paediatric cancer management in LMIC. Augmentation of physician and parental awareness is the key to decrease these delays.

ОПЫТ РЕАЛИЗАЦИИ ПИЛОТНОГО ПРОЕКТА «ГРОДНЕНСКАЯ УНИВЕРСИТЕТСКАЯ КЛИНИКА» В АСПЕКТЕ ЭФФЕКТИВНОСТИ НАУЧНОЙ ДЕЯТЕЛЬНОСТИ

The development and prompt implementation of advanced medical methods of diagnosis, treatment and prevention, based on the latest achievements of science and technology is a healthcare focus area for any state. The purpose of this publication is to summarize the experience of the pilot project “Grodno University Clinic” implementation regarding the efficiency of scientific activities. 12 indices of the University clinic innovative development were included in the model for final results activities of the clinic’s departments. Significant growth in innovation has been achieved, 25 employees of the clinic participate in the educational process of the medical university, 15 theses are being carried out by the clinic staff and teaching staff, and 6 patents have been jointly received. 11 initiative research projects are planned and carried out at the clinic. In addition, funded projects are being implemented, the implementation of which made it possible to attract 209,850 BYN in 2022. Scientific and practical conference “Innovative achievements in the work of Grodno University Clinic” is held annually as a part of the “Perspective plan for the development of the health care institution “Grodno University Clinic” implementation regarding the increase of the efficiency of scientific activities and personnel of the highest scientific qualifications. The clinic conducts clinical trials of medicines and medical products; income for 2022 amounted to 523.88K BYN. The experience of this project implementation makes it possible to draw the following conclusions. The presented interim results of pilot project “Grodno University Clinic” implementation regarding the efficiency of scientific activities allow us to assess positively this initiative transformation of the model for organizing the functioning of a multidisciplinary medical healthcare institution. The marked tendencies in the dynamics of the main indices reflect the efficiency of scientific research in the applied healthcare areas of high priority. The positive influence on innovation impacted by this favorable environment under a new integration project of science and practice for national healthcare is shown. Further research on the role and place of university clinics in the Republic of Belarus under their contribution and influence on the training of highly qualified scientific staff for healthcare, the development and implementation of import-substituting and export-oriented innovative methods of diagnosis, treatment and prevention in practical medicine are considered to be relevant.

2-Year Outcomes of an Atrial Shunt Device in HFpEF/HFmrEF: Results From REDUCE LAP-HF II

BackgroundThe REDUCE LAP-HF II (Reduce Elevated Left Atrial Pressure in Patients With Heart Failure II) trial found that, compared with a sham procedure, the Corvia Atrial Shunt did not improve outcomes in heart failure with preserved or mildly reduced ejection fraction. However, after 12-month follow-up, “responders” (peak-exercise pulmonary vascular resistance <1.74 WU and absence of a cardiac rhythm management device) were identified. ObjectivesThis study sought to determine: 1) the overall efficacy and safety of the atrial shunt vs sham control after 2 years of follow-up; and 2) whether the benefits of atrial shunting are sustained in responders during longer-term follow-up or are offset by adverse effects of the shunt. MethodsThe study analyzed 2-year outcomes in the overall REDUCE LAP-HF II trial, as well as in responder and nonresponder subgroups. The primary endpoint was a hierarchical composite of cardiovascular death or nonfatal ischemic/embolic stroke, total heart failure events, and change in health status. ResultsIn 621 randomized patients, there was no difference between the shunt (n = 309) and sham (n = 312) groups in the primary endpoint (win ratio: 1.01 [95% CI: 0.82-1.24]) or its individual components at 2 years. Shunt patency at 24 months was 98% in shunt-treated patients. Cardiovascular mortality and nonfatal ischemic stroke were not different between the groups; however, major adverse cardiac events were more common in those patients assigned to the shunt compared with sham (6.9% vs 2.7%; P = 0.018). More patients randomized to the shunt had an increase in right ventricular volume of ≥30% compared with the sham control (39% vs 28%, respectively; P < 0.001), but right ventricular dysfunction was uncommon and not different between the treatment groups. In responders (n = 313), the shunt was superior to sham (win ratio: 1.36 [95% CI: 1.02-1.83]; P = 0.037, with 51% fewer HF events [incidence rate ratio: 0.49 [95% CI: 0.25-0.95]; P = 0.034]). In nonresponders (n = 265), atrial shunting was inferior to sham (win ratio: 0.73 [95% CI: 0.54-0.98]). ConclusionsAt 2 years of follow-up in REDUCE LAP-HF II, there was no difference in efficacy between the atrial shunt and sham groups in the overall trial group. The potential clinical benefit identified in the responder group after 1 and 2 years of follow-up is currently being evaluated in the RESPONDER-HF (Re-Evaluation of the Corvia Atrial Shunt Device in a Precision Medicine Trial to Determine Efficacy in Mildly Reduced or Preserved Ejection Fraction Heart Failure) trial. (Reduce Elevated Left Atrial Pressure in Patients With Heart Failure II [REDUCE LAP-HF II]; NCT03088033)

Management of Chronic Heart Failure in Dialysis Patients: A Challenging but Rewarding Path.

Chronic heart failure (CHF) is a common complication and cause of death in dialysis patients. Although several clinical guidelines and expert consensus on heart failure (HF) in the general population have been issued in China and abroad, due to abnormal renal function or even no residual renal function (RRF) in dialysis patients, the high number of chronic complications, as well as the specificity, variability, and limitations of hemodialysis (HD) and peritoneal dialysis (PD) treatments, there are significant differences between dialysis patients and the general population in terms of the treatment and management of HF. The current studies are not relevant to all dialysis-combined HF populations, and there is an urgent need for high-quality studies on managing HF in dialysis patients to guide and standardize treatment. After reviewing the existing guidelines and literature, we focused on the staging and diagnosis of HF, management of risk factors, pharmacotherapy, and dialysis treatment in patients on dialysis. Based on evidence-based medicine and clinical trial data, this report reflects new perspectives and future trends in the diagnosis and treatment of HF in dialysis patients, which will further enhance the clinicians' understanding of HF in dialysis patients.

Social ecological model of alcohol use among youth living with HIV

ABSTRACT The goal of this study was to identify predictors of alcohol use among youth living with HIV (YWH) using a social ecological approach that examines the individual and the context in which they are embedded. The sample consisted of 183 YWH ages 17–24 from five sites within the Adolescent Medicine Trials Network (ATN). Structural equation modeling was used to test the social ecological model of alcohol use in this sample. The model tested predictors at the individual, interpersonal, and environmental level. Results showed that mental health distress (b = 0.21, p < 0.05), social norms of alcohol use (b = 0.29, p < 0.05) and alcohol outlets (b = 0.23, p < 0.05) were associated with alcohol use. Externalizing behaviors were indirectly associated with problematic alcohol use, while social norms of alcohol use mediated this relationship (z = 2.42, p = 0.015). Our findings identified factors across multiple systems related to alcohol use among YWH supporting the social ecological model. Findings suggest treatment for alcohol use behavior would benefit from also addressing the individual by focusing on mental health issues as well. Additionally, at the interpersonal level, considering one’s social norms of drinking in their social network, especially among youth who are more prone to externalizing behaviors, would lower alcohol use. Furthermore, public policy should examine ways to limit the accessibility of alcohol in higher risk environments.

Precision Medicine and Clinical Trials in Advanced and Metastatic Oral Cancer.

Oral cancer is a significant global health concern, with high morbidity and mortality rates, particularly in regions with prevalent tobacco usage such as Asia. Majority of oral cancers are detected at an advanced stage resulting in poor survival outcomes. Moreover, the treatment modalities of oral cancers have remained constant with surgery and concurrent chemoradiotherapy being mainstays of the treatment. This review provides a significant progress made in understanding the molecular landscape of oral cancers and the evolution of therapeutic strategies toward precision medicine. A comprehensive literature review was conducted to gather recent studies on the molecular landscape of oral cancers, genomic insights, and clinical trials. Firstly, genomic insights into oral cancers, including key driver mutations and copy number alterations, are discussed in the context of personalized medicine approaches. Subsequently, advancements in therapeutic strategies, particularly focusing on clinical trials investigating immunotherapy and targeted agents, are highlighted. Despite promising results, challenges persist in identifying reliable biomarkers for treatment response and resistance. Continued research efforts are warranted to validate biomarkers and optimize therapeutic interventions, with the goal of enhancing patient outcomes and reducing the global burden of oral cancer.

Experience of Health professionals in the implementation of Clinical trials of Traditional Herbal Medicines: A cross-sectional study in Mali

Objective: The objective of this study was to determine the experience of health professionals in clinical trials of traditional herbal medicines in Mali. Material and methods: This was a cross-sectional study conducted from June to December 2022 among healthcare professionals in three randomly selected localities: the district of Bamako and the regions of Koulikoro and Sikasso. Data were collected by direct interview using an anonymous questionnaire. The Chi-square (χ2) test was used to assess factors associated with participation in clinical trials of traditional medicines. Results: The involvement of healthcare professionals in clinical trials of traditional medicines was low (3.5%) and was associated with age (p=0.021). The obstacles to conducting these trials reported by healthcare professionals were lack of funding and failure to take account of the specificities of traditional medicines in clinical trial regulations. Some healthcare professionals suggest ethnomedical evaluation of recipes proposed by traditional practitioners and the use of reverse pharmacology as alternatives. Conclusion: Research into traditional medicines could be given greater impetus by the long-term funding of clinical trials and by less costly alternatives such as the ethnomedical evaluation of recipes proposed by traditional healers and reverse pharmacology.

Clinical Validation of Digitally Acquired Clinical Data and Machine Learning Models for Remote Measurement of Psoriasis and Psoriatic Arthritis: A Proof-of-Concept Study.

Psoriatic disease remains underdiagnosed and undertreated. We developed and validated a suite of novel, sensor-based smartphone assessments (Psorcast app) that can be self-administered to measure cutaneous and musculoskeletal signs and symptoms of psoriatic disease. Participants with psoriasis (PsO) or psoriatic arthritis (PsA) and healthy controls were recruited between June 5, 2019, and November 10, 2021, at 2 academic medical centers. Concordance and accuracy of digital measures and image-based machine learning models were compared to their analogous clinical measures from trained rheumatologists and dermatologists. Of 104 study participants, 51 (49%) were female and 53 (51%) were male, with a mean age of 42.3 years (SD 12.6). Seventy-nine (76%) participants had PsA, 16 (15.4%) had PsO, and 9 (8.7%) were healthy controls. Digital patient assessment of percent body surface area (BSA) affected with PsO demonstrated very strong concordance (Lin concordance correlation coefficient [CCC] 0.94 [95% CI 0.91-0.96]) with physician-assessed BSA. The in-clinic and remote target plaque physician global assessments showed fair-to-moderate concordance (CCCerythema 0.72 [0.59-0.85]; CCCinduration 0.72 [0.62-0.82]; CCCscaling 0.60 [0.48-0.72]). Machine learning models of hand photos taken by patients accurately identified clinically diagnosed nail PsO with an accuracy of 0.76. The Digital Jar Open assessment categorized physician-assessed upper extremity involvement, considering joint tenderness or enthesitis (AUROC 0.68 [0.47-0.85]). The Psorcast digital assessments achieved significant clinical validity, although they require further validation in larger cohorts before use in evidence-based medicine or clinical trial settings. The smartphone software and analysis pipelines from the Psorcast suite are open source and freely available.

Clinical research report on traditional Chinese patent medicines and traditional Chinese classic famous prescriptions (2022)

Objective: The paper is to comprehensively summarize and analyze the basic situation and methodological quality of clinical randomized controlled trials (RCTs) of traditional Chinese patent medicines and traditional Chinese classic famous prescriptions published in 2022, to provide evidence and reasonable suggestions for the advancement of clinical research and the formulation of policies and guidelines. Methods: The Evidence Database System of clinical evidence-based evaluation of traditional Chinese medicine was searched, and data from China National Knowledge Infrastructure (CNKI), PubMed, and other databases were supplemented. The search duration was from January 1, 2022, to December 31, 2022. RCTs of traditional Chinese patent medicines and traditional Chinese classic famous prescriptions were included as the source of clinical evidence, and published information, sample size, intervention, control measures, treatment course, methodological quality, and key link report were analyzed and evaluated. Results: A total of 1,464 RCTs of traditional Chinese patent medicines were included, which comprised 667 types of traditional Chinese patent medicines; “traditional Chinese patent medicines + Western medicine vs. Western medicine” was the most widely used intervention and control setting, involving 417 RCTs (28.48%). A total of 245 RCTs of traditional Chinese classic famous prescriptions were included, comprising 55 types of traditional Chinese classic famous prescriptions. “Decoction + conventional treatment vs. conventional treatment” was the most widely used intervention and control setting, with 87 RCTs (35.51%). Published RCTs on traditional Chinese patent medicines and traditional Chinese classic famous prescriptions were limited by the study design and implementation. Most “allocation concealment” and “blinding of patients and personnel” were rated as medium to high risk. There are insufficient reports on key research links such as experimental registration and ethical approval. Conclusions: The number of RCTs on traditional Chinese patent medicines has decreased in 2022, but there has been a slight improvement in the research quality and impact. There are relatively few studies on traditional Chinese classic famous prescriptions. Measures must be taken to improve clinical trial design, implementation, and reporting. Methodological experts should be invited to provide professional technical guidance on the trial design. In the research implementation process, attention should be paid to quality control, particularly the standardization of the randomized execution.

Effect of herbal medicine on postoperative nausea and vomiting after laparoscopic surgery: A systematic review and meta-analysis.

Traditionally, herbal medicines have been used to alleviate nausea and vomiting; however, a comprehensive clinical evaluation for postoperative nausea and vomiting (PONV), especially after laparoscopic surgery, remains limited. This review aimed to evaluate the efficacy and safety of herbal medicine as an alternative therapy to prevent and manage nausea and vomiting after laparoscopic surgery compared with untreated, placebo, and Western medicine groups. We searched 11 databases, including EMBASE, PubMed, and the Cochrane Library, to collect randomized controlled trials (RCTs) of herbal medicines on PONV after laparoscopic surgery on July 7, 2022. Two independent reviewers screened and selected eligible studies, extracted clinical data, and evaluated the quality of evidence using the Cochrane risk-of-bias tool. The primary outcome was the incidence of PONV, whereas the secondary outcomes included the frequency and intensity of PONV, symptom improvement time, antiemetic requirement frequency, and incidence of adverse events. Review Manager Version 5.3. was used for the meta-analysis. We identified 19 RCTs with 2726 participants comparing herbal medicine with no treatment, placebo, and Western medicine. The findings showed that compared with no treatment, herbal medicine demonstrated significant effects on vomiting incidence (risk ratio [RR] = 0.43, 95% confidence interval [CI] 0.32-0.57, P < .00001). Compared with placebo, herbal medicine revealed a significant effect on the severity of nausea 12 hours after laparoscopic surgery (standardized mean difference = -2.04, 95% CI -3.67 to -0.41, P = .01). Herbal medicines showed similar effects with Western medicine on the incidence of postoperative nausea (RR = 0.94, 95% CI 0.63-1.42, P = .77) and vomiting (RR = 0.68, 95% CI 0.25-1.84, P = .45). Furthermore, comparing the experimental group containing herbal medicine and control group excluding herbal medicine, adverse events were considerably lower in the group with herbal medicine (RR = 0.45, 95% CI 0.27-0.72, P = .001). Herbal medicine is an effective and safe treatment for nausea and vomiting secondary to laparoscopic surgery. However, the number of studies was small and their quality was not high; thus, more well-designed RCTs are warranted in the future.

Rapid label expansion based on public-private collaboration in IMPRESS-Norway.

e13529 Background: Access to new cancer drugs requires knowledge of biomarkers. As a consequence, there is an increasing access gap to new treatments between different cancer subgroups. Several precision medicine trials aim to address this gap through drug repurposing (1-3). IMPRESS-Norway is a national precision cancer medicine trial providing treatment to patients with advanced-stage disease after standard therapy. Patients with biomarkers are identified through the national infrastructure for precision diagnostics, InPreD, a part of the national healthcare services for stratification into biomarker-driven clinical trials. IMPRESS-Norway opened for inclusion on April 1st, 2021. Currently InPreD identifies biomarker in 31% of patients, and 50 % of patients included in treatment cohorts in IMPRESS-Norway are diagnosed with a rare cancer (4). The IMPRESS-Norway has, together with the public-private partnership CONNECT (Norwegian Cancer Precision Medicine Implementation Consortium), developed a roadmap for expanding access through ordinary reimbursement decisions. Methods: New drugs can efficiently be incorporated into the IMPRESS-Norway drug portfolio and tested across all relevant indications through a three-stage process. In stage 1 and 2, a total of 24 patients are recruited into a drug/diagnosis/biomarker-specific cohort, with drug provided by the company and a per-patient fee. If ≥ 5 patients exhibit clinical benefit (stable disease or better at week 16), the drug may undergo further testing in stage 3 (expansion cohorts). The company provides drugs during the first 16 weeks of treatment and with public reimbursement after week 16 for all patients experiencing clinical benefit. Results: Positive reimbursement decisions in Norway can be made based on knowledge of effect from single armed studies (5). Norwegian payers can therefore make reimbursement decisions based on results from the expansion cohort. Similar systems are set-up in the Netherlands (6). Several drugs are currently concluding stage 2 in IMPRESS-Norway. The first expansion cohort in IMPRESS-Norway (jointly with other DRUP-like trials in the EU Cancer Mission project PRIME-ROSE), exploring the effect of olaparib in patients with biallelic BRCA1/2 inactivation in non-approved diagnosis, is based on the DRUP-trial, exemplifying the European collaboration in these trials. Conclusions: Public-private collaboration facilitates rapid identification of eligible patients, irrespective of cancer subgroup, providing potential for new indications. IMPRESS-Norway presents a feasible strategy for rapid label expansion. 1. DLvan der Velden et al, Nature 2019; 574:127-31. 2. PM Mangat et al, JCO Prec Oncol 2018; 10. 3. Å Helland et al, J Trans Oncol 2022; 20. 4. Puco K et al., 2024 in press. 5. GL Fagereng et al, Front Pharmacol 2014; doi:10.3389. 6. SBW Doorn-Khosrovani et al. Ann Oncol 2019; 30: 663-5. Clinical trial information: NCT04817956 .

Single point of entry to the European precision cancer medicine trial network PRIME-ROSE.

e23024 Background: Over the last decades, there has been a surge in the development and approval of targeted drugs and immunotherapies for treating cancer patients, as seen by the 757 % increase in approvals by the FDA for new cancer treatments since 2000 (1). This has significantly impacted cancer care and contributed to improving overall survival in various cancer subgroups. However, access to these new treatments is constrained by the market access strategy of the patent-owning company and available knowledge of treatment effects. Only a few treatments have received pan-cancer approval from EMA or FDA, and most drugs receive market authorization per indication. As a result, there is a widening access gap between patients with different cancer types (2). Methods: Exploring the effect of biomarker-driven treatments in new cancer subtypes requires the ability to find patients with rare biomarkers. PRIME-ROSE is a European precision medicine network comprising 11 ongoing or soon-to-start national DRUP-like clinical trials testing registered drugs outside their current label ( www.prime-rose.eu ). Patients with relevant tumor biomarkers are identified and treated with matched drugs available in each trial’s drug portfolio. The ambition is to swiftly and systematically evaluate the effectiveness of approved precision cancer medicines in new indications through pragmatic trial designs and with RWE control cohorts, ensuring expansion into all relevant patient groups to maximize societal benefit. This is particularly relevant for rare cancers, which are enriched in precision medicine trials (3). Results: In PRIME-ROSE, the trials now share and aggregate data to build evidence faster and more effectively impact patient care by addressing key challenges in precision cancer medicine implementation (increasing the recruitment area to 71 million inhabitants). This will significantly reduce the time for filling treatment cohorts and contribute to closing the indication/drug-specific knowledge gap. In fact, several pharmaceutical companies have already shown their interest in and commitment to participating in PRIME-ROSE, as it offers the unique advantage of entering the trials in the network simultaneously (single point of entry) and with a floating allocation of treatment slots between trials, increasing efficiency in finding patients with specific biomarkers to fill treatment cohorts. Conclusions: A unified entry point to the PRIME-ROSE network is feasible and can facilitate building the knowledge base faster for label expansion and/or country-specific approvals/ reimbursement. National multi-stakeholder ecosystems that include pragmatic, RWE-controlled DRUP-like clinical trials may advance precision medicine implementation.

Analysis of current situation of outcome indicators in randomized controlled trials on traditional Chinese medicine in treatment of Alzheimer's disease

This study aims to analyze the current situation of outcome indicators in randomized controlled trial(RCT) of traditional Chinese medicine(TCM) treatment for Alzheimer's disease(AD), so as to provide a reference for establishing a core indicator set in this field. The researchers systematically searched CNKI, Wanfang, VIP, Sino Med, EMbase, PubMed, Medline, and Cochrane Library. Independent screening of literature and extraction of information was conducted according to the inclusion and exclusion criteria. In addition, the Ro B 2. 0 tool was used for bias risk assessment. A total of 78 RCTs were included, involving 6 379 patients,with 122 kinds of outcome indicators. According to functional attributes, the outcome indicators could be categorized into seven groups:TCM diseases(3 kinds, 13 times), symptoms and signs(26 kinds, 196 times), physical and chemical tests(68 kinds, 149 times),qua-lity of life(1 kind, 2 times), long-term prognosis(2 kinds, 2 times), economic evaluation(0 kind), safety events(21 kinds,194 times), and other indicators(1 kind, 1 time). The results show that the literature evaluation of RCTs of TCM treatment for AD is generally risky, and there are some problems in the selection of outcome indicators, such as lack of TCM characteristics, insignificant distinction between primary and secondary outcome indicators, lack of long-term prognosis and economic evaluation indicators, and non-standard safety event reports. It is suggested that future researchers should establish a core indicator set for AD that highlights the characteristics of TCM and then work to improve the quality of clinical trials.

The feasibility and acceptability of collecting psychosocial outcome measures embedded within a precision medicine trial for childhood cancer.

Patient-reported outcomes measures (PROMs) are increasingly being collected within cancer clinical trials, yet limited literature on the feasibility and acceptability of doing so. We collected parent-proxy and adolescent (≥12 years old) PROMs through a longitudinal, psychosocial sub-study ('PRISM-Impact') embedded in a precision medicine trial for children with poor prognosis cancer ('PRISM'). We report on feasibility (response, participation, and attrition rates; follow-up and responding to elevated distress) and acceptability (parents' perceived benefit/burden of participation; and impact on decision to participate in PRISM) of PRISM-Impact. Over the reporting period, 462 families were eligible for PRISM-Impact. Family and adolescent response rates were 53% and 45%, respectively. Parents whose child had relapsed were more likely to participate in PRISM-Impact than parents whose child had not (p < 0.001). Parent and adolescent attrition rates were 30% and 56% respectively. We conducted 478 calls for intake and to follow-up on missing questionnaires, and 122 calls to respond to elevated distress. Parents reported wanting to participate in PRISM-Impact for altruistic reasons and because they valued psychosocial research. Parents reported little-to-no burden and some benefit from participating in PRISM-Impact, with little change in ratings overtime. Most parents felt that participating in PRISM-Impact did not impact their desire to participate in PRISM (72%), with some feeling more eager to participate (19%). PRISM-Impact response rates were comparable to other psycho-oncology studies, despite the poor prognosis population. Integration of PROMs within a paediatric oncology trial is acceptable to parents, and may provide a more comprehensive assessment of the impact of trial participation.

Clinical utility and accessibility of functional precision medicine for relapsed/refractory pediatric and adult cancers.

1551 Background: Pediatric and adult patients with rare, relapsed, or refractory cancers often have few treatment options. Precision medicine approaches are often the first strategy used to identify salvage therapy options when standard treatments fail. Despite the significant clinical benefit to advanced cancer patients, multiple genomics precision medicine trials have revealed important constraints for patients that lack treatments matched to mutations or biomarkers and have highlighted challenges in drug accessibility associated with novel targeted therapies identified through genomics precision medicine. Current clinical findings from large-scale studies demonstrate ~10% of cancer patients receive clinical benefit from genomics-guided therapies - in part due to limited insight into the complex relationship between tumor molecular characteristics and patient response. Methods: We implemented a functional precision medicine (FPM) approach combining genomic tumor profiling with high-throughput drug sensitivity testing (DST) of FDA-approved agents on patient-derived tumor cells to identify treatment options when standard-of-care is exhausted. Clinical utility and benefit of this program was investigated via a clinical trial (NCT03860376) at Nicklaus Children’s Hospital in Miami, FL. Results: We were returned DST data on 21 of 24 patients DST (median = 102 agents per sample) and genomic profiling on 20 of 24 patients. DST turnaround time was significantly below the 14 days required for clinical use (median = 10 days, p = 0.0012). FPM recommendations were returned to 19 (76%) patients, of which 14 patients underwent therapeutic intervention. Six patients received FPM-guided treatments, and five (83%) patients experienced a &gt;1.3-fold improved progression-free survival over their previous therapy, significantly above the rate from physician’s choice (p = 0.0104). We subsequently opened pan-cancer FPM clinical studies for adults (n = 36 patients) and children (n = 65 patients). A key objective in these trials is optimizing our DST protocol for tissue samples of various sizes. Here, we report preliminary efforts to optimize our DST approach for tissue samples from resections, core biopsies, and fine-needle biopsies from primary and metastatic lesions. Conclusions: The findings from our feasibility study illustrate the potential for FPM to positively impact clinical care for pediatric/adolescent patients with relapsed/refractory cancers, and have supported initiation of currently enrolling clinical studies. An NIMHD-funded expansion cohort now enrolling at Nicklaus Children’s Hospital (NCT05857969, n = 65 patients), and a rare/relapsed/refractory adult patient cohort at Cleveland Clinic Florida (NCT06024603, n = 36 patients). These studies aim to further investigate the impact on clinical outcomes through the use of FPM to recommend treatment options. Clinical trial information: NCT06024603 , NCT05857969 , NCT04956198 , NCT03860376 .

On the right TRACK: Providing comprehensive genomic profiling (CGP) and molecular tumor board (MTB) for patients (pts) with rare cancers.

3127 Background: Patients (pts) with rare cancers are under-represented in precision medicine trials despite making up ~22% of cancer incidence. We created the TCF-001 TRACK (Target RAre Cancer Knowledge, NCT04504604) study to provide a home-based, patient-centered trial utilizing comprehensive genomic profiling (CGP) at enrollment and progression with review by a molecular tumor board (MTB). Methods: Pts with rare cancers (incidence&lt;6/100,000) were enrolled and consented remotely (WCG IRB 1287011). Liquid (blood via mobile phlebotomy) and tissue biopsy samples were sent for CGP at Foundation Medicine. A fully remote MTB was convened following availability of each test. MTB notes and therapy recommendations were returned to patients and local physicians. Results: TRACK activated on 1 Oct 2020. The MTB included medical/surgical oncologists, genomics experts, molecular pathologists, a basic scientist, a pharmacist, a genetic counselor, regulatory staff, a scribe, an oncology fellow (“mentern”), and a medication acquisition specialist. MTB members were from 8 states. 132 eligible pts with evaluable results were enrolled from 41 states. Tissue and liquid biopsy results were available in 89 pts; tissue only in 5; liquid only in 38. 128 pts had an MTB before the 30 June2023 cut-off date (mean age 54.1 y; female 61.7%). There were &gt;40 rare/ultra-rare cancers, including cholangiocarcinoma (62) and soft tissue tumors (24). No pts had identical molecular alterations. The median number of pathogenic alterations per tissue sample was 3 (range: 0-14) and blood was 2 (range: 0-40). 3 patients had no pathogenic alterations on tissue or liquid CGP. The most commonly altered genes found by tissue biopsy CGP on study (n=68) were TP53(33.8%), CDKN2A (25.0%), KRAS (23.5%), CDKN2B (17.6%), IDH1 (17.6%), and MTAP (14.7%); by liquid biopsy (n=126), they were TP53 (31.7%), KRAS (11.9%), and IDH1 (8.7%), as well as genes often associated with clonal hematopoiesis: DNMT3A (22.2%), ATM (12.7%), and CHEK2 (8.7%). The sensitivity of liquid biopsy for pathogenic alterations found in tissue was 89.3% for pts with ctDNA tumor fraction (TF) ≥1% and 28.1% for TF &lt;1%. 1 pt had microsatellite instability. Median tumor mutational burden (TMB) by tissue was 2.5 mutations/megabase and by blood was 1.3. 3 pts had TMB≥10. Liquid biopsy results were available more quickly than tissue (median processing time, 9.1 vs 13.3 days); time from submission to processing was shorter for blood than tissue (2.4 vs 4.9 weeks). TRACK staff encountered 0.94 queries/sample. MTB recommendations based on CGP were generated for 87.5% of the 128 pts presented. Conclusions: A fully remote, advocacy driven, national precision genomics trial is feasible for managing rare cancers. CGP with expert MTB review can identify potentially targetable alterations and inform therapeutic options. Clinical trial information: NCT04504604 .

The French multicentric molecular analysis platforms and personalized medicine trials MOST, MOST Plus and MEGAMOST.

In this manuscript we describe the academic French multicentric molecular analysis platforms including PROFILER, promoted by Centre Léon Berard, and the multicentric personalized medicine trials MOST, MOST Plus and MEGAMOST. MOST, MOST Plus and MEGAMOST comprise 14 cohorts with different targeted agents and immunotherapies. PROFILER has recruited 5,991 patients in 10 years, MOST and MOST Plus 875 patients since 2014 and MEGAMOST 172 patients since 2020, and are still ongoing. We provide a description of the local, national and international implications of these initiatives, and we review the results of the sorafenib and olaparib cohorts.

IMPRESS-Norway: improving public cancer care by implementing precision medicine in Norway; inclusion rates and preliminary results.

In Norway, comprehensive molecular tumour profiling is implemented as part of the public healthcare system. A substantial number of tumours harbour potentially targetable molecular alterations. Therapy outcomes may improve if targeted treatments are matched with actionable genomic alterations. In the IMPRESS-Norway trial (NCT04817956), patients are treated with drugs outside the labelled indication based on their tumours molecular profile. IMPRESS-Norway is a national, prospective, non-randomised, precision cancer medicine trial, offering treatment to patients with advanced-stage disease, progressing on standard treatment. Comprehensive next-generation sequencing, TruSight Oncology 500, is used for screening. Patients with tumours harbouring molecular alterations with matched targeted therapies available in IMPRESS-Norway, are offered treatment. Currently, 24 drugs are available in the study. Primary study endpoints are percentage of patients offered treatment in the trial, and disease control rate (DCR) defined as complete or partial response or stable disease in evaluable patients at 16 weeks (W16) of treatment. Secondary endpoint presented is DCR in all treated patients. Between April 2021 and October 2023, 1,167 patients were screened, and an actionable mutation with matching drug was identified for 358 patients. By the data cut off 186 patients have initiated treatment, 170 had a minimum follow-up time of 16 weeks, and 145 also had evaluable disease. In patients with evaluable disease, the DCR was 40% (58/145). Secondary endpoint analysis of DCR in all treated patients, showed DCR of 34% (58/170). Precision cancer medicine demonstrates encouraging clinical effect in a subset of patients included in the IMPRESS-Norway trial.

Investigation of acute, sub-chronic toxicity, effects of mangiferin and mangiferin solid dispersion (HPTR) on Triton WR1339-induced hyperlipidemia on Swiss albino mice

Mangiferin is a xanthonoid found in Mango leaves in abundance with many effects as a hypoglycemic, antioxidant, and anti-inflammatory agent, plant metabolite, and so on. However, nowadays, mango leaves are merely a waste product in Vietnam. To take advantage of this valuable medicinal resource, extraction conditions of mangiferin using classical and ultrasound methods were researched, and mangiferin was purified from Cat Chu mango leaves (Mangifera indica L., Anacardiaceae) collected in Dong Thap. Ultrasound-assisted extraction method was conducted with the following conditions and mangiferin was extracted at a percentage of 6.728% with a purity of 91.11%. Purified mangiferin was evaluated using molecular absorption spectroscopy UV-Vis, scanning electron microscopy (SEM), X-ray diffraction (XRD) spectroscopy, simultaneous thermal analysis (STA: TGA/DSC), and dissolution measurement method. To optimize the solubility and permeability of mangiferin, the solid dispersion system (HPTR) was made by the combination of HPMC 6M:mangiferin at the ratio of 1:5. To investigate the acute, sub-chronic toxicity and hypolipidemia effect of HPTR as compared to purified mangiferin, we followed guidelines for preclinical and clinical trials of Traditional Medicine and Herbal Medicines by the Vietnam Ministry of Health and OECD, and used tyloxapol (Triton WR1339, 400 mg/kg, i.p.) to induce hyperlipidemia. Our results indicated that purified mangiferin and HPTR extract showed no acute toxicity and sub-chronic toxicity and has potential as an antihyperlipidemic agent. The HPTR brought about a significant decrease in total cholesterol, triglycerides and LDL-c when compared to mangiferin, however there was no significance between them.

The Reporting Quality and Risk of Bias of Randomized Controlled Trials in Traditional Persian Medicine: A Systematic Review

The Reporting Quality and Risk of Bias of Randomized Controlled Trials in Traditional Persian Medicine: A Systematic Review