Medicine Clinical Trials Research Articles

Factors associated with non-publication of clinical trials in cardiovascular medicine: a cross-sectional analysis

Abstract Background/introduction Cardiovascular medicine is the fourth most-funded area of clinical research as it received an estimate for 7% of the total research funding. Nearly 8% of all clinical trials are cardiovascular-related (1,2). Non-publication of the registered clinical trials wastes money and time, encourages dissemination bias, and creates a body of possibly inaccurate literature, all of which obstruct scientific advancement. (3) Purpose To study the factors associated with the non-publication of cardiovascular clinical trials between January 2000 and June 2022. Methods We performed a cross-sectional analysis using ClinicalTrials.gov to determine all completed, discontinued, published, and unpublished cardiovascular medicine clinical trials between January 2000 and June 2022. For each trial, data on the trial phase, funding source, intervention type, enrolment size, trial completion, and publication status were extracted and subjected to logistic regression to determine clinical trial publication predictor factors. Results Among 3946 trials in cardiovascular medicine registered in ClinicalTrials.gov, there were 3215 completed trials included in the analysis. Of these, 34.2% (n=1100) were unpublished. On multivariate logistic regression, triple-blinded and quadruple-blinded trials were less likely to be unpublished compared to open-label trials (odds ratio [OR] 0.622; 95% confidence interval [CI] 0.45-0.85; p=0.003) and (OR 0.54; CI 0.42-0.69; p<0.001), respectively. Enrolment of 100 participants or more was associated with a decreased likelihood of non-publication (OR 0.46; CI 0.39-0.55; p<0.001). In addition, randomised trials were less likely to be unpublished than non-randomised trials (OR 0.67; CI 0.50-0.88; p=0.004). There was no significant effect of the intervention type, phase of the trial, trial participants' age and gender, or the trial funding resource on the publication status of cardiovascular medicine clinical trials. Conclusions It is observed that a considerable number of clinical trials in cardiovascular medicine remain unpublished. This issue raises some concerns regarding the risks and discomfort participants may encounter during the trial, while no results are added to the literature. Blinding of the trials, enrolment size, and allocation methods are the main predictors of trial publication.Forest plot of logistic regression

Effectiveness of different types of toothbrushes on periodontal health in orthodontic patients with gingivitis: A randomized controlled study

BackgroundThe aim of the study is to evaluate the effectiveness of different toothbrushes in reducing gingival inflammation and dental biofilm removal in gingivitis patients with fixed orthodontic appliances.MethodsFollowing baseline clinical assessments, including the Turesky modification of the Quigley-Hein plaque index (TQHI), gingival index (GI), bleeding on probing (BOP), and probing pocket depth (PPD), all patients received nonsurgical periodontal therapy. Patients were then randomly assigned to one of three groups: conventional toothbrush (C-TB), orthodontic toothbrush (O-TB), or single-tufted toothbrush (ST-TB). Each group received tailored oral hygiene instructions based on their assigned toothbrush type. Clinical assessments were repeated and recorded in the first week, sixth week, and third month.ResultsThirty-six patients with a mean age of 23.14 ± 3.86 (18–32 years) participated in the study. All groups with twelve patients each demonstrated significant improvements in clinical parameters compared to baseline. In the sixth week, the O-TB and ST-TB groups showed significantly greater improvements in TQHI and BOP scores compared to the C-TB group (p < 0.05). By the third month, the ST-TB group maintained significantly lower TQHI and BOP scores, while the O-TB group’s scores became similar to those of the C-TB group. ST-TB and C-TB groups had significantly lower GI scores than the O-TB group in all time points. Although the effectiveness of ST-TB was significantly higher than that of other toothbrushes, all toothbrushes demonstrated lower efficacy in the posterior region.ConclusionsThe ST-TB was shown to be more effective in reducing gingival inflammation over three months, while it demonstrated similar efficacy to the O-TB in dental biofilm removal. Further research is necessary to substantiate these findings and to demonstrate the efficacy of this approach in promoting periodontal tissue health in patients with fixed orthodontic appliances.Trial registrationThis study was registered with the National Library of Medicine Clinical Trials Registry Platform on 19/07/2024 as NCT06510179.

Salvia miltiorrhiza in osteoporosis: a review of its phytochemistry, traditional clinical uses and preclinical studies (2014-2024).

Osteoporosis becomes a global public health concern due to its rising prevalence and substantial impact on life quality. Salvia miltiorrhiza Bunge (Salviae Miltiorrhizae Radix et Rhizoma, SM) has been firstly recorded in Shen Nong's Herbal Classic, and is frequently prescribed in conjunction with other herbs for the management of osteoporosis. This systematic review aims to comprehensively analyze the recent advances of SM on osteoporosis in traditional Chinese clinical uses and preclinical investigations. Literature encompassing pertinent studies were systematically retrieved across multiple databases, including the PubMed, Web of Science, Chinese National Knowledge Infrastructure, Chinese VIP Database, and Chinese Biomedical Literature Database. Original investigations spanning from February 2014 to March 2024, including traditional Chinese medicine (TCM) clinical trials and preclinical studies, were employed to analyze the effects and actions of SM on osteoporosis. Thirty-eight TCM clinical trials were identified to employ SM in combination with other herbs for the management of primary and secondary osteoporosis. The overall efficacy was between 77% and 96.67%. Forty preclinical studies were identified to investigate the effects and actions of SM and/or its ingredients on osteoporosis. The anti-osteoporosis actions of this herb may be attributed to inhibit osteoclastogenesis/bone resorption and promote osteoblastogenesis/osteogenesis. The ethanol extracts and its ingredients (tanshinones) inhibit osteoclastogenesis/bone resorption by inhibiting the MAPK/NF-κB/NFATc1 signaling pathway and cathepsin K-induced collagen degradation. Both ethanol extracts (tanshinones) and water extracts (Sal B and tanshinol) contribute to osteoblastogenesis by promoting osteogenesis and angiogenesis via activation of the Wnt/β-catenin/VEGF and ERK/TAZ pathways, and eliminating ROS production targeting Nrf2/ARE/HO-1 pathway. In conclusions, SM may offer a novel strategy for osteoporosis management. Well-designed clinical trials are still needed to evaluate the actions of this herb and its ingredients on bone remodeling.

A high-flow nasal cannula versus noninvasive ventilation in acute exacerbations of chronic obstructive pulmonary disease

PurposeWe investigated the efficacy and safety of a high-flow nasal cannula (HFNC) at different flow rates compared to noninvasive ventilation (NIV) in patients with acute chronic obstructive pulmonary disease (COPD) exacerbations. MethodsThis prospective, randomized, single-blind study assigned patients to one of three study groups. The NIV group (n = 47) received bilevel positive airway pressure. The HFNC-30 (n = 44) and HFNC-50 (n = 46) groups received HFNC therapy at flow rates of 30 and 50 L/min, respectively. Demographic and clinical characteristics and arterial blood gas parameters before and 30, 60, and 120 min after treatment were compared among the treatment groups. ResultsThis study included 137 consecutive patients with acute exacerbations of COPD, comprising 90 males and 47 females, with a mean age of 68.1 ± 10.5 years. A total of 21 patients (15.33 %) were intubated, and the overall mortality rate was 10.2 %. The mean PaCO2 levels on admission were 64.69 ± 10.81, 61.51 ± 9.03, and 62.29 ± 9.87 in the NIV, HFNC-30, and HFNC-50 groups, respectively, with no significant differences observed (p = 0.372). A significant reduction in mean PaCO2 was observed in all treatment groups at 30, 60, and 120 min (p < 0.05 for all). However, the ΔPaCO2 at 60 min was significantly higher in the HFNC-30 group compared to the NIV group (p = 0.042). Additionally, neither intubation rates nor 28-day mortality differed among the treatment groups (p = 0.368 and p = 0.775, respectively). ConclusionHFNC was not inferior to NIV in improving arterial blood gas parameters, particularly PaCO2 in patients with COPD exacerbations, especially those with hypercarbia. Moreover, HFNC at a flow rate of 30 L/min was superior to NIV for reducing PaCO2 levels at 60 min. Trial RegistryNational Library of Medicine Clinical Trial Registry; No.: NCT06495086; URL: https://clinicaltrials.gov/study/NCT06495086

Influence of Peanut Consumption on the Gut Microbiome: A Randomized Clinical Trial.

Background: Peanut consumption could impact cardiometabolic health through gut microbiota, a hypothesis that remains to be investigated. A randomized clinical trial in Vietnam evaluated whether peanut consumption alters gut microbiome communities. Methods: One hundred individuals were included and randomly assigned to the peanut intervention and control groups. A total of 51 participants were provided with and asked to consume 50 g of peanuts daily, while 49 controls maintained their usual dietary intake for 16 weeks. Stool samples were collected before and on the last day of the trial. After excluding 22 non-compliant participants and those who received antibiotic treatment, 35 participants from the intervention and 43 from the control were included in the analysis. Gut microbiota composition was measured by shotgun metagenomic sequencing. Associations of changes in gut microbial diversity with peanut intervention were evaluated via linear regression analysis. Linear mixed-effects models were used to analyze associations of composition, sub-community structure, and microbial metabolic pathways with peanut intervention. We also performed beta regression analysis to examine the impact of peanut intervention on the overall and individual stability of microbial taxa and metabolic pathways. All associations with false discovery rate (FDR)-corrected p-values of <0.1 were considered statistically significant. Results: No significant changes were found in α- and β-diversities and overall gut microbial stability after peanut intervention. However, the peanut intervention led to lower enrichment of five phyla, five classes, two orders, twenty-four metabolic pathways, and six species-level sub-communities, with a dominant representation of Bifidobacterium pseudocatenulatum, Escherichia coli D, Holdemanella biformis, Ruminococcus D bicirculans, Roseburia inulinivorans, and MGYG-HGUT-00200 (p < 0.05 and FDR < 0.1). The peanut intervention led to the short-term stability of several species, such as Faecalibacterium prausnitzii F and H, and a metabolic pathway involved in nitrate reduction V (p < 0.05; FDR < 0.1), known for their potential roles in human health, especially cardiovascular health. Conclusions: In summary, a 16-week peanut intervention led to significant changes in gut microbial composition, species-level sub-communities, and the short-term stability of several bacteria, but not overall gut microbial diversity and stability. Further research with a larger sample size and a longer intervention period is needed to confirm these findings and investigate the direct impact of gut-microbiome-mediated health effects of peanut consumption. Trial registration: The International Traditional Medicine Clinical Trial Registry (ITMCTR). Registration number: ITMCTR2024000050. Retrospectively Registered 24 April 2024.

Correction: Reproducing the normal and the pathological in personalized cancer medicine clinical trials

Correction: Reproducing the normal and the pathological in personalized cancer medicine clinical trials

The order of green and red LEDs irradiation affects the neural differentiation of human umbilical cord matrix-derived mesenchymal cells

Different wavelengths emitted from light-emitting diodes (LEDs) are known as an influential factor in proliferation and differentiation of various cell types. Since human umbilical cord matrix-derived mesenchymal cells (hUCMs) are ideal tools for human regenerative medicine clinical trials and stem cell researches, in the present study we investigated the neurogenesis effects of single and intermittent green and red LED irradiation on hUCM cells. Exposure of hUCMs to single and intermittent green (530 nm, 1.59 J/cm2) and red (630 nm, 0.318 J/cm2) lights significantly increased the expression of specific genes including nestin, β-tubulin III and Olig2. Additionally, immunocytochemical analysis confirmed the expression of specific neural-related proteins including nestin, β-tubulin III, Olig2 and GFAP. Also, alternating exposure of hUCM cells to green and red lights increased the expression of some neural markers more than either light alone. Further research are required to develop the application of LED irradiation as a useful tool for therapeutic purposes including neural repair and regeneration.

International Traditional Medicine Clinical Trial Registry: A meaningful initiative and its future development.

International Traditional Medicine Clinical Trial Registry: A meaningful initiative and its future development.

Barriers to access of precision guided therapies for children with high-risk cancer.

Accessing compassionate access schemes to obtain novel therapeutic agents for children with hard-to-treat cancers can be fraught with challenges such as regulatory barriers and limited resources. This study aimed to explore clinician perspectives on the barriers, impacts and ethical considerations of accessing novel therapeutic agents within the context of a paediatric oncology precision medicine trial. We gathered data from 37 semi-structured interviews with paediatric oncologists participating in the PRecISion Medicine for Children with Cancer (PRISM) study, a precision medicine clinical trial in Australia. The interviews, conducted over 2years, focused on paediatric oncologist's experiences with the PRISM trial. Interviews were re-analysed to identify themes related to access pathways and any challenges in obtaining novel agents through thematic analysis. The resulting thematic framework was discussed and refined by a multidisciplinary team. Three main themes were identified: (i) barriers to access, including poor drug availability, lack of evidence and the time burden of the application process; (ii) impacts of inaccessibility, encompassing medical consequences and financial burden on families; and (iii) ethical considerations, centred around balancing realistic expectations and providing compassionate care to patients and families. Paediatric oncologists expressed frustration with the complex regulatory landscape and the lack of systematic reporting on applications and outcomes of obtaining novel agents. Lengthy wait times for decision notifications were also highlighted, raising concerns about missed therapeutic opportunities for patients. This study provides insight to the challenges faced when seeking access to novel therapies for paediatric oncology patients. There is a clear need for improved communication, streamlining processes and increased resources to facilitate access to novel agents. Further resource development is necessary to address these complexities in accessing novel therapy agents to ultimately ensure equitable and timely access.

An introduction to International Traditional Medicine Clinical Trial Registry (ITMCTR): A cross-regional registry focusing on theme of traditional medicine

An introduction to International Traditional Medicine Clinical Trial Registry (ITMCTR): A cross-regional registry focusing on theme of traditional medicine

Publication bias in clinical trials in cataract therapies: implications for evidence-based decision-making.

Evidence-based decision-making is generally based on published evidence. Therefore, if the published evidence is biased, so will the decision-making. One possible bias is the "positive-results" publication bias. This study attempts to characterize this phenomenon in cataract therapy trials. Studies were categorized as "positive" if their results were congruent with the hypothesis and "negative" if not. Secondary outcomes included the influence of funding source and differences in publication metrics between "positive" and "negative" publications. The U.S. National Library of Medicine Clinical Trials database was reviewed for cataract trials, yielding 248 trials. Trials with less than 2 treatment arms, less than 5 participants, or insufficient reporting were excluded. Data were collected on intervention, treatment arms, funding type, publication rates, citation rate, and the impact factor/H-index of journals. Of the 132 trials included, there were 69 positive and 63 negative results. Publication rate for positive results (71%) was significantly greater than negative results (17%) ( P < .01), with no significant difference in the other publication metrics. In conclusion, "negative" result trials are published less frequently, but are equally valued, if published. There are implications for evidence-based medicine with these findings.

Community-Engaged Approaches for Improving Inclusion of Diverse Communities in a Nutrition Precision Medicine Clinical Trial

Community-Engaged Approaches for Improving Inclusion of Diverse Communities in a Nutrition Precision Medicine Clinical Trial

Reproducing the normal and the pathological in personalized cancer medicine clinical trials

AbstractThe medical practice termed Personalized Medicine ideally uses all the patient’s possible characteristics in predicting disease predisposition and response to therapy, but primarily employs the individual’s unique molecular make-up in the tailoring of treatment. This change in medical practice also entails an epistemic shift towards ‘molecularization’: individuals and disease are now understood and governed through life’s basic building blocks. In this paper we argue that underlying personalized medicine is a continued understanding of the pathological state as a quantitative deviation from a normal state. In this we build on the critique of French philosopher Georges Canguilhem who positioned the quantitative interpretation of the pathological in nineteenth century medical thinking. Personalized cancer medicine takes each patient’s cancer as singular, implying that there is no ‘normal’ baseline for comparing individual pathology. We analyze cases of personalized cancer clinical trials from recent years to show that each displays a quantitative understanding of the pathological reminiscent of past thinking in two main modes: a molecularized interpretation of cancer pathology and a quantitative measuring of targeted therapy efficacy. We situate the analysis in broader discussions of historical medical shifts and in current studies of personalized medicine, to outline implications of this form of continuity.

Screening for social determinants of health among patients with advanced and metastatic cancer undergoing comprehensive genomic profiling in underserved communities.

e13545 Background: Many patients with advanced and metastatic cancer, who are potentially eligible for biomarker-directed targeted agents, do not receive them, with biomarker undertesting reported as a major factor. Little is known about non-medical factors that negatively impact treatment and outcomes, particularly in underserved communities. This study implemented screening for social determinants of health (SDOH) to identify barriers to precision medicine beyond biomarker testing for these patients. Methods: Four community oncology practice sites (GA, SC, FL), selected for their focus on underserved populations, consented patients to a prospective clinico-genomic database registry (May 2021-Dec 2023). Registry participants completed an SDOH questionnaire at the time of comprehensive genomic profile (CGP) test order. Questionnaire items were grouped by SDOH domain (economic stability, education, health care access, neighborhood/built environment, and social/community), with each potential response coded as either a positive or negative indicator for patient health. Negative indicators were summed at the item, domain, and survey levels for each patient, and aggregate frequencies tabulated. Results: Among 447 CGP-tested registry participants (24 solid tumor types, stage III/IV), 331 (74%) completed SDOH screening. Although non-White registry participants were highly represented among patients who completed SDOH screening (31.7%), unscreened patients had an even higher frequency of non-Whites (49.1%), particularly Black (14.2% v 24.8%) and American Indian/Alaska Native (10.3% v 18.1%) patients. Nearly all patients (99%) reported having health insurance, most frequently Medicare (69.2%). A small number of patients (5.4%) reported transportation issues that kept them from medical appointments. By domain, negative indicators for economic stability (46.2%), and social and community context (42.3%) were the most frequently reported, while healthcare access (14.5%), and neighborhood and built environment (9.4%) were the least common. Lack of socialization (27.5%), depression (21.5%), and very low income &lt;$1200/month (20.8%), were the most frequently reported individual indicators. Overall, 74.5% of CGP-tested patients harboring genomic variants for oncology practice guideline-indicated therapies and/or marker-driven clinical trials reported having at least one negative indicator. Conclusions: SDOH-screening in community practice is feasible and identifies specific interventional areas among disadvantaged, vulnerable, advanced cancer patients. Increased screening among underserved, particularly for non-White patients, is needed to address their support needs beyond health insurance and biomarker testing, and improve their access to and participation in precision medicine clinical trials.

#1668 The 60:40 conundrum: are women with CKD discriminated against after referral to a nephrology clinic?

Abstract Background and Aims The representation of women in kidney medicine clinical trials has diffused the belief that women are discriminated although epidemiological data suggest that chronic kidney disease (CKD) is more prevalent among females than males. We aimed to test whether sex distribution varies at nephrology referral, inclusion in a clinical study or at the starting of dialysis. Method This was a retrospective, monocentric study conducted in a large non-university hospital in central France. We exploited data from patients included in the PRO-RE-RE-PRO study on the effect of diet on the progression of CKD. We evaluated patients’ characteristics and gender at the time of the first consultation in the Unit for the Care of Advanced CKD (UIRAV), at the inclusion in the PRO-RE-RE-PRO study and at the beginning of the kidney replacement therapy. Results 866 patients were included in this study as they were referred to the UIRAV, 59% males and 41% females. Female patients were older but less comorbid and were referred at the same eGFR than males. The same proportion of males/females was observed in patients included in the PRO-RE-RE-PRO study. No sex differences were observed at dialysis start. Survival was significantly higher in females. Overall, distribution across sex remained stable over time. Conclusion The main result of this study is the stability of the approximately 35-40% female to 60-65% male ratio from start of follow-up in all subsets of cases: patients referred to the unit dedicated to advanced CKD, patients recruited in the observational study, patients not included, or who refused to participate, patients on follow-up at the completion of the database. Furthermore, the same distribution is observed in dialysis patients, from dialysis start to the most recent update. Our data suggest that if a gender-selection bias exists in nephrology, it should be sought before the first nephrology referral. However, further studies are needed to ensure health equity.

Abstract A010: Cancer associated fibroblast dependency in a novel immunocompetent mouse model of bladder cancer

Abstract Introduction: The relationship between genotype and phenotype in targeted therapy has proven to be crucial for the successful use of most kinase inhibitors. In bladder cancer, the PI3K/AKT/mTOR pathway is widely activated by mutation but untargeted. Our study focuses on developing an immunocompetent, CRISPR-edited bladder cancer mouse model that mirrors common PI3K/AKT/mTOR pathway mutations. We established effective genotype-kinase inhibitor pairings using CRISPR-edited organoids and cancer associated fibroblasts (CAFs) to create a pro-tumorigenic environment in vivo. Methods and Results: Urothelial cells were isolated from the bladder of Rosa26 Lox-Stop-Lox-Cas9/GFP transgenic mice and grown as organoids in matrigel. These organoids were co-edited for Trp53 and Rb1 KO, and further editing of the Pten gene resulted in a nine-fold increase in sensitivity to the kinase inhibitor ipatasertib. Despite successful initial engraftment into mouse bladder, these edited cells regressed before tumor formation, and subcutaneous injection did not yield subcutaneous tumors. An alternate model featuring a 9p21 deletion with Trp53 KO also displayed similar regression post-engraftment into bladder or subcutaneous injections. However, co-injection with a previously established CAF line subcutaneously yielded palpable subcutaneous tumors that enlarged for 12 weeks. We then established a BBN bladder-tumor-derived CAF line, leading to the formation of tumors with squamous differentiation upon intramural co-injection with edited organoids. These models displayed immune-excluded architecture and a predominance of M2 over M1 macrophages. We also aimed to enhance the model's adaptability by introducing common PI3K/AKT/mTOR mutations, specifically TSC1/TSC2 KO, and Pik3ca hotspots, into our 9p21/Trp53 KO model. While TSC1/TSC2 KO lines exhibited elevated P-S6K signaling, they displayed resistance to Torin 1, Voxtalisib, and Everolimus—kinase inhibitors targeting mTORC1/2. In parallel, we employed CRISPR-mediated homologous recombination to successfully introduce a Pik3ca H1047R hotspot into the 9p21/Trp53 KO genotype, as evidenced by increased Phosphorylation of AKT compared to wild-type 9p21/Trp53 KO cell lines. This genotype resulted in approximately 80-fold selective increased sensitivity to pictilisib, a PI3K inhibitor compared to Pik3ca WT control. Conclusions: In this model, CAFs were required for successful engraftment of tumors into the bladder wall or subcutaneously. BUTU is a customizable model of bladder cancer and is suitable for direct targeting by kinase inhibitors while providing a platform for understanding the genotype-phenotype relationship in bladder cancer. We hope to use it as a tool to develop preclinical evidence on which to base precision medicine clinical trials. Citation Format: Philip H. Abbosh, Henkel Valentine. Cancer associated fibroblast dependency in a novel immunocompetent mouse model of bladder cancer [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2024 May 17-20; Charlotte, NC. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(10_Suppl):Abstract nr A010.

Publication Bias in Upper Gastrointestinal Oncology Clinical Trials.

Evidence-based medicine requires evaluation of the medical literature to guide clinical reasoning and treatment recommendations. The presence of publication bias towards exclusion of non-statistically significant clinical trials may be leading to an incomplete evaluation of the literature and cause potentially incomplete guidance for patients. We aimed to compare publication rates and impact of publications of positive and negative outcome clinical trials. We queried the US National Library of Medicine Clinical Trials database identifying clinical trials with reported results on the topics of pancreatic, liver, and gastric cancer. A "positive" trial was defined as having a statistically significant difference between the treatment arms, while a "negative" did not. Data collected included termination cause, intervention, funding type, publication rates, and journal characteristics. In total, 535 clinical trials were examined, across all pathologies clinical trials with significant findings for the primary outcome were published at a higher rate (99%) compared to those with non-significant findings (77%) (p < 0.01). Significantly, more studies with significant findings reached at least 80% of their estimated enrollment goal versus non-significant studies, 72% and 53% respectively (p < 0.01). Three of four metrics for impact of publication showed no difference between significant and non-significant studies once they reached publication. These findings suggest that clinical trials of three of the most common upper gastrointestinal malignancies have a publication bias towards studies with significant primary outcome findings. This study has implications to the way evidence-based medicine is practiced as the medical literature appears to be failing to capture important data for consideration of clinical decision making.

Abstract 235: Application of high-grade serous ovarian cancer organoids in functional precision medicine

Abstract High-grade serous ovarian cancer (HGSC) is the most frequent and lethal ovarian cancer type. Despite responding favorably to first-line therapy, most HGSC patients eventually relapse. HGSC is characterized by high interpatient genomic heterogeneity and few recurrent mutations that could be used as therapeutic biomarkers. Thus, except the introduction of PARP inhibitors for BRCA1/2-mutated patients, there has been little progress with personalizing HGSC treatment. Functional precision medicine - tailoring personalized therapies based on functional assays on patient-derived cells - has been applied in cancer clinical trials to address this issue. Organoids - three-dimensional cell cultures, recapitulating aspects of original tumors’ structure and function - have often been used as models in these efforts. However, inefficient and time-consuming organoid derivation protocols have been hindering the application of HGSC organoids in functional precision medicine clinical trials, due to the short time during which the therapy must be selected. To address this, we here aimed to establish whether we could predict second-line therapy drug sensitivities in relapsed HGSC using organoids from tumor material from first-line therapy. We have previously derived a collection of 23 organoid models from 16 patients, sampled sequentially at different times of their treatment (1). Here, for several organoid primary-relapse pairs, we performed drug screens using a library of 370 compounds (approved, in clinical development or tool compounds). We found that 90% of the hit compounds in the primary organoids also were hits in the matched relapse-derived organoid models. In several patients, we observed a pronounced cytotoxicity of several cyclin-dependent kinase (CDK) inhibitors, all of which potently inhibit CDK9, including two selective inhibitors (AZD4573 and VIP152) in clinical development. Screening of CDK9 inhibitors in an extended panel of organoid models revealed that most organoids are sensitive to CDK9 inhibition in nanomolar range. CDK9 inhibitors also prevented organoid outgrowth in long-term culture (&amp;gt;1.5 month) in drug-free medium. Taken together, we demonstrate that HGSC organoids from material sampled during first-line treatment predict most drug sensitivities of relapse-derived organoids. This suggests a feasibility of functional precision approach for selection of second-line therapy using only primary tumor material, circumventing the problem of limited time available for the therapy choice after tumor sampling. This work also highlights that CDK9 inhibitors, currently in clinical development for hematological malignancies, are worthwhile to be explored in HGSC. 1. Senkowski et al. A platform for efficient establishment and drug-response profiling of high-grade serous ovarian cancer organoids. Developmental Cell (2023) Citation Format: Wojciech Senkowski, Laura Gall-Mas, Matias M. Falco, Yilin Li, Kari Lavikka, Aura Crispino, Jaana Oikkonen, Daria Bulanova, Yan-Jun Chen, Elena M. Doncel, Karolin Voßgröne, Erdogan P. Erkan, Jun Dai, Anastasia Lundgren, Jutta Huvila, Kaisa Huhtinen, Johanna Hynninen, Sampsa Hautaniemi, Anna Vähärautio, Krister Wennerberg. Application of high-grade serous ovarian cancer organoids in functional precision medicine [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 235.

Effectiveness of Chinese Herbal Medicine as a Complementary Treatment for Neutropenia Prevention and Immunity Modulation During Chemotherapy in Patients With Breast Cancer: Protocol for a Real-World Pragmatic Clinical Trial.

In recent years, advancements in cancer treatment have enabled cancer cell inhibition, leading to improved patient outcomes. However, the side effects of chemotherapy, especially leukopenia, impact patients' ability to tolerate their treatments and affect their quality of life. Traditional Chinese medicine is thought to provide complementary cancer treatment to improve the quality of life and prolong survival time among patients with cancer. This study aims to evaluate the effectiveness of Chinese herbal medicine (CHM) as a complementary treatment for neutropenia prevention and immunity modulation during chemotherapy in patients with breast cancer. We will conduct a real-world pragmatic clinical trial to evaluate the effectiveness of CHM as a supplementary therapy to prevent neutropenia in patients with breast cancer undergoing chemotherapy. Patients will be classified into CHM or non-CHM groups based on whether they received CHM during chemotherapy. Using generalized estimating equations or repeated measures ANOVA, we will assess differences in white blood cell counts, absolute neutrophil counts, immune cells, and programmed cell death protein 1 (PD-1) expression levels between the 2 groups. This study was approved by the research ethics committee of Hualien Tzu Chi Hospital (IRB 110-168-A). The enrollment process began in September 2021 and will stop in December 2024. A total of 140 patients will be recruited. Data cleaning and analysis are expected to finish in the middle of 2025. Traditional Chinese medicine is the most commonly used complementary medicine, and it has been reported to significantly alleviate chemotherapy-related side effects. This study's findings may contribute to developing effective interventions targeting chemotherapy-related neutropenia among patients with breast cancer in clinical practice. International Traditional Medicine Clinical Trial Registry ITMCTR2023000054; https://tinyurl.com/yc353hes. DERR1-10.2196/55662.

PERSONALIZED MEDICINE AS TREND IN PHARMACEUTICAL INDUSTRY

Personalized medicine is indeed a significant trend in the pharmaceutical industry, revolutionizing the way treatments are developed and administered. It is an innovative perspective that ultimately magnifies the quality of healthcare and creates multiple opportunities in transforming the prospects of medicine development, clinical trials, and patient care. Genomics and data analytics are essential in advancing personalized medicine. The challenges in implementing personalized medicine are numerous, yet the opportunities to remodel healthcare are immense. The perspectives of personalized medicine in the pharmaceutical industry are encouraging, with great potential to inspire innovation and establish transformation od drug development.