Precision Medicine

Biliary tract carcinoma (BTC) includes cancers of the gallbladder, intrahepatic cholangiocarcinoma, and extrahepatic cholangiocarcinoma. It is a highly aggressive cancer with poor outcomes, ranking sixth in gastrointestinal cancer incidence and tenth in cancer-related deaths worldwide. Because early symptoms are often absent and the disease tends to recur and spread, only about 16.5% of patients can have curative surgery, and the overall 5-year survival rate is under 5%. Early and accurate detection is crucial to improve patient outcomes. This research aims to assess the use of cell-free DNA (cfDNA) methylation in blood as a liquid biopsy for diagnosing and managing BTC. The study involves several groups, including healthy individuals, patients with confirmed benign biliary lesions, other gastrointestinal cancers, and those with confirmed or suspected BTC. Researchers will analyze methylation patterns in circulating tumor DNA (ctDNA), a small fraction of cfDNA that carries tumor genetic and epigenetic information. This approach is studied for its potential to detect BTC early, assist in differential diagnosis, monitor prognosis, and guide therapy. Different cohorts serve as internal training, validation sets, and independent validation groups. Participants will provide blood samples and undergo clinical evaluations to measure the accuracy of the ctDNA methylation test in diagnosing BTC. The study will assess diagnostic performance by cancer subtype and stage, and ability to distinguish BTC from other conditions. Vital signs, organ function, and other health markers will be monitored to ensure participant safety. The study welcomes adults aged 18 to 80 years, with follow-up and assessments continuing until May 2026 to evaluate the test's clinical utility.

Pancreatic neuroendocrine neoplasms (pNENs) are tumors with increasing incidence and limited treatment options, especially after disease progression or drug resistance from current therapies like somatostatin analogues, chemotherapy, and targeted drugs. Existing treatments such as sunitinib and everolimus have shown limited clinical efficacy with low objective response rates. Researchers are investigating new combinations, including sorafenib and gefitinib, based on evidence linking the EGFR pathway to tumor progression and poor survival in pNEN patients. This study evaluates a single treatment group receiving oral sorafenib (250mg) and gefitinib (250mg) daily, each dose taken once a day. Treatment cycles last 4 weeks, aiming to explore the effectiveness and safety of this combination for patients with pNENs who have progressed after prior treatments. Sorafenib is a tyrosine kinase inhibitor targeting VEGFR, FGFR1, and CSF1R, which may help inhibit tumor angiogenesis and regulate immune responses, while gefitinib targets EGFR. Participants will be assessed regularly with imaging every 8 weeks to measure tumor response and progression-free survival, with survival assessments every 12 weeks up to two years. Safety and tolerability of the drug combination will also be evaluated over two years. The study involves a screening process, treatment period, and follow-up evaluations to monitor outcomes and side effects, supporting comprehensive observation of the treatment's impact on disease progression.

Researchers are studying a new treatment approach for patients with surgically removable head and neck squamous cell carcinoma (HNSCC), a common and serious type of cancer in the head and neck region. The study evaluates the safety and tolerability of combining immune-targeted therapy with a lysogenic herpes simplex virus (HSV) as a neoadjuvant treatment to reduce tumor size before surgery. This innovative combination aims to improve surgery outcomes and lower the chances of cancer returning or spreading. Participants receive a combination of treatments including Tislelizumab given on days 1 and 22, and continuous daily Afatinib from days 1 to 42. They also receive injections of the lysogenic HSV virus directly into lymph nodes, with dosing based on lymph node size, given twice two weeks apart. After these treatments, patients undergo standard surgical removal of the tumor. The HSV virus injection includes an initial dose-escalation phase followed by a dose-expansion phase to find the most effective dose. During the study, patients are closely monitored for side effects and treatment tolerance, including checking for dose-limiting toxicities during surgery. Researchers will assess how well the tumor responds to treatment by examining major and complete pathological responses and overall tumor shrinkage up to eight weeks after treatment. They will also monitor adverse events for up to 12 weeks and follow disease-free survival for one year. The study duration and procedures are planned to provide detailed information on the safety and effects of this combined therapy.

Researchers are investigating treatments for head and neck squamous cell carcinoma (HNSCC), a common and serious cancer affecting patients' appearance and functions. The study compares the effects of adding low-dose radiotherapy to a combination of targeted therapy and immunotherapy before surgery, aiming to improve surgery outcomes and organ preservation. This Phase 2 trial follows promising earlier research showing potential benefits of combining these therapies. Participants are randomly assigned to one of two groups: one group receives low-dose radiotherapy along with targeted therapy (afatinib) and immunotherapy (tislelizumab), while the other group receives only targeted therapy and immunotherapy. Treatments include tislelizumab given intravenously on days 1 and 22, afatinib taken continuously for 42 days, and low-dose radiotherapy at 4 Gy in two fractions for the experimental group. Surgery is performed after the neoadjuvant therapies. During the study, participants undergo evaluations including intraoperative assessments of major pathologic response, pathologic complete response, and objective response rate over approximately two months of neoadjuvant therapy. The research team monitors safety, treatment effects, and surgical outcomes. Participation lasts from treatment initiation through surgery and follow-up assessments, aiming to provide new options for managing operable HNSCC.

Researchers are evaluating a combination of immune-targeted therapy and lysogenic herpes simplex virus (HSV) virotherapy as a neoadjuvant treatment for patients with surgically resectable head and neck squamous cell carcinoma (HNSCC). This study aims to improve surgical success and reduce the risk of recurrence and metastasis by using these therapies before surgery. The trial is a prospective, single-arm study focused on the safety and tolerability of this innovative approach for patients with locally advanced HNSCC without distant metastasis. Participants will receive tislelizumab on days 1 and 22, afatinib daily from days 1 to 42, and injections of lysogenic HSV virus into lymph nodes in two doses spaced two weeks apart. The virus dose will be adjusted based on lymph node size, with a dose-escalation phase followed by a dose-expansion phase using the most effective dose. After these treatments, patients will undergo standard surgery to remove the tumor. During the study, researchers will monitor participants for dose-limiting toxicities during surgery and evaluate responses such as major pathologic response and complete pathologic response. Additional assessments include adverse events up to 12 weeks, objective response rate up to 8 weeks, and one-year disease-free survival. Participants will attend scheduled visits for treatment administration, surgery, and follow-up to assess safety and treatment effects throughout the trial period.

Researchers are investigating the relationship between gut microbiota dysfunction and Alzheimer's disease (AD), focusing on how gut-derived short-chain fatty acids (SCFAs) may influence brain function through the "gut microbiota-SCFAs-brain networks" pathway. This observational study will explore differences in SCFAs among people across the AD spectrum, including cognitively normal individuals, those with subjective cognitive decline (SCD), mild cognitive impairment (MCI), and AD dementia. The project aims to clarify the interactions between gut microbiome, metabolites, and brain changes using high-throughput metabolomics and multi-modal MRI techniques. Participants will be grouped into four categories: cognitively normal, SCD, MCI, and AD dementia. The study involves collecting multi-omics data, including gut microbiome analysis, metabolomics, and neuroimaging, to establish a diagnostic model for SCD due to preclinical AD using machine learning methods. The study spans five years, during which gut microbiome changes, SCFAs levels, and multi-omics biomarkers related to cognitive impairment conversion will be monitored. Participants will undergo cognitive tests and brain imaging scans, along with gut microbiome and metabolite sample collection. Researchers will assess the interaction mechanisms of the gut microbiota-SCFAs-brain networks over five years. The study includes both healthy volunteers and patients aged 60 to 80. Outcome measures focus on changes in gut microbiome, SCFAs, and biomarkers linked to cognitive decline, with long-term follow-up to better understand the disease progression and its early detection.

Esophageal squamous cell carcinoma (ESCC) is a common and deadly cancer in China, with many patients diagnosed at advanced stages. This study evaluates a combined treatment approach using induction immunochemotherapy followed by concurrent chemoradiotherapy, aiming to improve outcomes for patients with locally advanced, unresectable ESCC. Researchers also focus on using circulating tumor DNA (ctDNA) to monitor treatment response and predict tumor progression, as ctDNA changes can appear before imaging detects recurrence. Participants receive induction immunochemotherapy consisting of toripalimab combined with paclitaxel and cisplatin every three weeks for two cycles. This is followed by radical concurrent chemoradiotherapy with weekly paclitaxel and cisplatin for five cycles along with radiotherapy delivered five days per week. The study dynamically monitors ctDNA levels at several points: before treatment, before chemoradiotherapy, after 20 radiotherapy fractions, and every three months after treatment completion. During the study, participants undergo regular assessments including blood tests for ctDNA analysis and monitoring of tumor status. The main outcome measured is progression-free survival at one year. Safety and efficacy are tracked throughout the treatment and follow-up periods. The total participation duration and timing of assessments are carefully planned to evaluate the treatment strategy and its correlation with patient prognosis.

Childhood obesity is a growing global health concern linked to serious health problems such as type 2 diabetes, high blood pressure, certain cancers, and mental health challenges. Researchers are evaluating a digital support system called Evira to help improve treatment outcomes for children with obesity. This randomized controlled study aims to assess the effects of adding Evira to the usual lifestyle treatment for childhood obesity in children aged 4 to 17 years. The study compares two groups: one receiving Evira Care combined with standard lifestyle treatment, and the other receiving standard lifestyle care alone. Evira Care involves daily weight monitoring at home using a special scale connected to a mobile app and website, allowing parents and clinicians to track weight changes and communicate easily. The intervention group will receive guidance on how to use the system and make feasible lifestyle changes, with weight targets set for the first three months. The control group continues with standard care without restrictions on visits or clinical support. Participants will be involved for 12 months, undergoing clinical exams including puberty assessment, cardio-respiratory, thyroid, skin, and abdominal checks, along with measurements of weight, height, and blood pressure. Blood tests may be done as needed. All participants will complete questionnaires about quality of life, eating disorders, and treatment satisfaction. Researchers will monitor weight change as the primary outcome, along with treatment compliance and psychosocial health measures, while collecting information on any side effects.

Researchers are studying whether a combination of two drugs, fruquintinib and tislelizumab, can help control colorectal cancer in patients who have completed treatment but still show signs of minimal residual disease (MRD) through positive ctDNA tests. This phase 2 trial focuses on patients with microsatellite stable colorectal adenocarcinoma who have finished curative treatments including chemotherapy. The study aims to measure how well the treatment clears ctDNA at 3 and 6 months, as well as to assess disease-free survival, overall survival, and safety. Participants will receive treatment with fruquintinib taken orally and tislelizumab given intravenously. The study does not include randomization or placebo groups; all participants receive the combination therapy. The treatment period and dosing schedules are designed to evaluate the effects on MRD as detected by the Signatera assay. The trial includes careful monitoring of organ function and blood counts to ensure participant safety. Throughout the study, participants will undergo regular ctDNA testing to monitor minimal residual disease status, along with assessments for disease progression and survival. Safety and adverse events will be tracked for about one year from the start of treatment. Participants must be able to provide informed consent and will be closely observed for treatment tolerability and effectiveness. The study will continue until April 2028, allowing long-term follow-up on outcomes and safety.

Researchers are studying the effects of a low-protein diet on cancer patients receiving immunotherapy treatments. The study aims to see if reducing protein intake can change the tumor environment and boost the body's immune response, potentially enhancing the effects of immune checkpoint inhibitors. This is a randomized, open-label study conducted at a single center to explore the feasibility of this dietary approach. Participants will be randomly assigned to one of two groups: one receiving immunotherapy plus a control diet containing about 20% protein, and the other receiving immunotherapy combined with a low-protein diet containing 10% protein. The study intervention lasts for 4 months, during which the dietary impact on immune response and treatment effects will be evaluated. Throughout the 4-month study period, participants will be monitored for their ability to follow the dietary plan and for any changes in immune response to immunotherapy. Researchers will assess safety, tolerability, clinical efficacy using RECIST v1.1 criteria, and enrollment and drop-out rates. Laboratory tests and imaging scans will also be conducted to evaluate disease progression and treatment impact.