Dose Escalation

This research focuses on patients with newly diagnosed oropharyngeal and hypopharyngeal cancers, which are types of head and neck tumors. It evaluates adaptive radiotherapy (ART) compared to standard image-guided radiotherapy (IGRT) without online adaptation. The study aims to determine if ART, which adjusts radiation doses based on the patient's daily anatomy, can improve outcomes such as swallowing function and reduce side effects like dysphagia, which affects quality of life. Participants are randomly assigned to one of two groups: one receiving adaptive radiotherapy with daily dose adjustments by specialists, and the other receiving standard radiotherapy without such adaptation. This approach builds on previous findings suggesting that dysphagia-optimized intensity-modulated radiotherapy (IMRT) can improve swallowing compared to standard IMRT. The study is prospective and randomized, focusing on the potential benefits of ART in improving treatment precision and patient experience. During the study, patients will be monitored for several years, with assessments including the EORTC Common Toxicity Criteria adverse event scores and dysphagia scores from 2 months up to 5 years after treatment. Secondary outcomes include overall survival and progression-free survival over the same period. These evaluations help researchers understand the long-term effects and safety of adaptive radiotherapy. The total duration of participation may extend up to five years for follow-up assessments.

Researchers are evaluating adaptive radiotherapy (ART) in patients with locally advanced gynecological cancers such as cervical, endometrial, and vaginal carcinomas. This study compares ART, a newer method that adjusts radiation doses based on daily anatomical changes, with standard image-guided radiotherapy (IGRT) where the radiation plan remains fixed. The goal is to understand how many patients benefit from ART and whether it can reduce radiation exposure to healthy tissues and safety margins. Participants receive either ART or standard IGRT during their radiotherapy treatment. ART involves online adaptation of the radiation dose distribution before each session using cone-beam CT scans and expert review by a radiation oncologist and medical physicist. Treatments are delivered over an initial 10 radiation fractions using the Ethos therapy device. If ART does not provide dosimetric advantages, the original treatment plan is used as in IGRT. The study includes an experimental adaptive radiotherapy arm and a standard IGRT comparator arm. During the study, participants will be monitored for side effects using established toxicity scales for rectal, bladder, skin toxicities, and lymph-edema from 2 weeks up to 5 years. Overall survival and progression-free survival will be assessed over 5 years. Researchers will compare dose distributions and analyze safety margins. The study is randomized and double-blinded, with involvement lasting through treatment and long-term follow-up for outcomes and safety.

This research aims to explore the effective dose levels (ED50 and ED95) and clinical effects of combining intranasal dexmedetomidine and esketamine for preoperative sedation in children aged 1 to 6 years undergoing general anesthesia. The study focuses on improving sedation compliance to reduce adverse behavioral effects after surgery and provides a theoretical basis for using these drugs together for sedation in pediatric patients. Children are divided into two age groups: toddlers (1-3 years) and preschool children (3-6 years). Both groups receive an initial intranasal dose of dexmedetomidine (1 µg/kg) combined with esketamine (0.5 mg/kg). The dexmedetomidine dose is adjusted in increments of 0.25 µg/kg based on sedation success using a biased coin design. Sedation depth is assessed every 5 minutes with the Ramsay Sedation Scale, and sedation onset time is recorded. Intravenous cannulation and emotional state assessments occur 30 minutes after drug administration. Participants undergo continuous monitoring of vital signs including blood pressure, heart rate, respiratory rate, and oxygen saturation before and after drug administration. Sedation onset, surgical time, awakening time, and emergence delirium are recorded. The study also evaluates intravenous cannulation success and adverse effects up to 24 hours. The total observation includes perioperative and postoperative periods to assess sedation effectiveness and safety.

Researchers are studying the best dose of Dexmedetomidine to stop shivering in women undergoing scheduled elective cesarean deliveries. This trial focuses on patients who experience moderate to severe shivering during surgery and aims to find the dose that stops shivering in 90% of these patients within 5 minutes. The study uses a phase 4 design to evaluate this dosing in a real clinical setting. Participants who experience Grade 3 or 4 shivering during their cesarean delivery under spinal anesthesia will receive Dexmedetomidine intravenously. The dose for each patient will be determined using a sequential up-and-down method with a biased coin design, starting with an initial dose of 10 mcg. An anesthesia physician not involved in patient care prepares the drug to maintain objectivity. Spinal anesthesia is given with standard doses of bupivacaine, fentanyl, and morphine. During the study, shivering is graded using a five-point scale from no shivering to full body muscle activity. Researchers will monitor the effect of the drug on shivering within 5 minutes of administration while tracking maternal heart rate and dose amounts during surgery. The trial includes pre-operative screening, drug administration during the operation, and ongoing observation of responses. Participation ends after the intraoperative course, and safety is monitored throughout.

Researchers are examining whether peripheral nerve blocks work differently in people who regularly use opioids compared to those who do not. Peripheral nerve blocks are used to relieve postoperative pain, but prior studies suggest opioid tolerance may reduce their effectiveness. The study aims to compare the onset time and duration of a radial nerve block between opioid-tolerant and opioid-naive individuals to better understand if opioid use affects nerve block duration. Participants will receive an ultrasound-guided radial nerve block using 10 mL of Lidocaine 2%. Twenty opioid-tolerant individuals, who use at least 60 mg of morphine equivalent daily, will be matched by age and sex with opioid-naive individuals who have not used opioids in the last 30 days. The study will measure how long the sensory and motor blocks last and how quickly they begin after the nerve block. During the study, researchers will test and record the onset and duration of sensory and motor blockades up to one hour after the nerve block. Ultrasound images will be stored for documentation. The main focus is the difference in sensory block duration between the two groups. Secondary measures include onset times and motor block duration. The study will provide insights into whether opioid tolerance affects nerve block duration and if special postoperative care is needed for opioid users.

Locally advanced non-small cell lung cancer (LA-NSCLC) is a common and deadly form of lung cancer often treated with a combination of systemic therapy, radiotherapy, and immunotherapy. Researchers are studying adaptive radiotherapy (ART), which adjusts treatment plans during radiotherapy to account for tumor and anatomical changes, potentially improving survival. This trial focuses on improving the efficiency of ART by using modern AI tools and advanced imaging to reduce labor and patient burden. The study involves a prospective phase where 30 patients undergo mid-treatment plan adaptations using repeated four-dimensional CT scans and AI-assisted contouring and planning tools, such as Syngo.via® and RapidPlan®. A retrospective phase will then evaluate the feasibility of using cone-beam CT (CBCT) imaging, routinely used for position verification, as a replacement for repeated planning CTs. This approach aims to reduce additional radiation exposure and appointments by generating synthetic CTs from CBCT images for treatment adaptation. Participants will have repeated imaging and treatment plan adjustments during their radiotherapy course, which lasts up to seven weeks. Researchers will measure the time required for each step of the ART workflow, compare treatment plan quality using dose-volume histograms, and assess contour accuracy with similarity metrics. The study also includes quality checks by medical physicists and physicians. The retrospective phase will analyze the performance of the CBCT-based workflow up to six months after treatment completion.

Researchers are evaluating the safety and effectiveness of removing the planning target volume (PTV) margins during online adaptive stereotactic body radiotherapy (SBRT) for patients with early-stage non-small cell lung cancer (NSCLC) or pulmonary oligometastases. The study focuses on how this approach compares to standard SBRT in treating these lung conditions, aiming to improve treatment precision and patient outcomes in a controlled clinical setting. Participants are randomly assigned to one of two groups. The study group receives online adaptive SBRT without the usual PTV expansion margin, with a total radiation dose of 45-50 Gy delivered in 3 to 4 daily sessions. Both FBCT and 4DCT scans are used before each treatment session. The control group receives conventional SBRT with PTV expansion at the same dose and schedule, using CBCT scans prior to each session. This randomized design helps compare the new method against the standard approach. During the study, patients will be closely monitored through regular follow-up visits to evaluate safety and treatment effectiveness. Researchers will assess respiratory toxicity rates one year after treatment as the primary outcome. Secondary outcomes include tumor response two months post-radiotherapy and local tumor control over two years. Various tests and imaging techniques will be used to track progress and any side effects. The study duration includes treatment and extended observation to ensure comprehensive safety and efficacy data collection.

Researchers are evaluating adaptive radiotherapy techniques that target hypoxic areas in head and neck cancers, which are known to be resistant to radiation. The study focuses on patients with specific types of squamous cell carcinoma in the oropharynx, larynx, hypopharynx, or oral cavity, aiming to improve treatment precision by using FMISO PET/CT imaging to identify these hypoxic tumor regions for dose escalation. The study compares two radiotherapy approaches: a dose-escalation protocol delivering 75.9 to 79.2 Gy focused on hypoxic tumor volumes, and a standard fractionation regimen delivering 70 Gy to primary tumors and involved lymph nodes. Concurrent chemotherapy with cisplatin is given weekly or every three weeks, with total doses considered. Radiotherapy planning follows established guidelines, and treatment is delivered in 33 fractions. Patients are monitored regularly, at least every two weeks. Participants will undergo imaging assessments like CT or MRI for tumor evaluation and receive ongoing monitoring during treatment. Researchers will measure outcomes including complete response rate, locoregional progression-free survival, radiation-induced side effects, overall survival, distant metastasis-free survival, quality of life changes, and development of new hypoxic tumor areas. The study duration includes follow-ups up to four years to assess both short- and long-term effects of the treatments.

Researchers are evaluating moderated hypofractionated online adaptive radiotherapy combined with high-dose-rate brachytherapy in patients with cervical cancer. This multicenter, phase 3, randomized controlled study aims to compare this experimental treatment's safety and efficacy against the standard radiotherapy regimen. The study focuses on women aged 18 to 75 years with specific stages of cervical cancer and examines how this approach may reduce treatment duration and resource usage. Participants are randomly assigned to receive either the experimental treatment, which includes 43.35 Gy of external beam radiotherapy delivered in 17 fractions with online adaptive radiotherapy plus high-dose-rate brachytherapy and concurrent weekly chemotherapy or immunotherapy, or the standard treatment of 45 Gy external beam radiotherapy in 25 fractions with brachytherapy and concurrent chemotherapy or immunotherapy. Both groups receive weekly cisplatin or PD-1 inhibitors, and the study evaluates treatment over a defined period. Throughout the study, participants will be closely monitored for various outcomes including progression-free survival at 3 years, acute and late toxicities, overall survival, quality of life, tumor response, and treatment costs. Assessments include clinical evaluations and quality of life questionnaires over 3 years. The trial will also track locoregional progression, metastasis-free survival, and cervical cancer-specific survival. Safety and adherence will be carefully observed to understand the impact of the treatment regimens.

Researchers are evaluating the tolerability and effects of MR-linac based stereotactic ablative radiotherapy (MRL-SBRT) in patients with localized prostate cancer, including those with oligo-metastatic disease. The study aims to assess acute and late toxicities, treatment efficacy, quality of life, feasibility of dose planning with simultaneous-boosts for MRI-detected tumor areas, and the relationship between blood and tissue biomarkers with imaging changes before and after treatment. Participants receive ultra-hypofractionated radiotherapy using a 1.5-Tesla MR-linac device targeting the prostate without adjacent oligo-metastatic diseases. The treatment is delivered in a specialized manner guided by magnetic resonance imaging to focus on the tumor area. The study includes different risk groups of prostate cancer and allows treatment of all metastatic foci with radical SBRT dose where applicable. During the study, participants are monitored for treatment-related acute and late toxicities using standard criteria up to five years. Quality of life is evaluated regularly from treatment start through several years post-therapy. Researchers also measure biochemical relapse-free survival at two years. Assessments include imaging, biomarker analysis, and patient-reported outcomes. The total participation time includes frequent follow-ups to carefully observe treatment effects and safety.