ABSTRACT
BACKGROUND: FLASH therapy is a treatment technique in which radiation is delivered at ultra-high dose rates (≥ 40 Gy/s). The first-in-human FAST-01 clinical trial demonstrated the clinical feasibility of proton FLASH in the treatment of extremity bone metastases. The objectives of this investigation are to assess the toxicities of treatment and pain relief in study participants with painful thoracic bone metastases treated with FLASH radiotherapy, as well as workflow metrics in a clinical setting. METHODS: This single-arm clinical trial is being conducted under an FDA investigational device exemption (IDE) approved for 10 patients with 1-3 painful bone metastases in the thorax, excluding bone metastases in the spine. Treatment will be 8 Gy in a single fraction administered at ≥ 40 Gy/s on a FLASH-enabled proton therapy system delivering a single transmission proton beam. Primary study endpoints are efficacy (pain relief) and safety. Patient questionnaires evaluating pain flare at the treatment site will be completed for 10 consecutive days post-RT. Pain response and adverse events (AEs) will be evaluated on the day of treatment and on day 7, day 15, months 1, 2, 3, 6, 9, and 12, and every 6 months thereafter. The outcomes for clinical workflow feasibility are the occurrence of any device issues as well as time on the treatment table. DISCUSSION: This prospective clinical trial will provide clinical data for evaluating the efficacy and safety of proton FLASH for palliation of bony metastases in the thorax. Positive findings will support the further exploration of FLASH radiation for other clinical indications including patient populations treated with curative intent. REGISTRATION: ClinicalTrials.gov NCT05524064.
Subject(s)
Bone Neoplasms , Protons , Humans , Bone Neoplasms/radiotherapy , Pain , Prospective Studies , ThoraxABSTRACT
BACKGROUND: It is known that exposure to either arsenic or hyperglycemia can induce male reproductive damages. However, their combined effects on male reproductive organs are still unclear. Therefore, the present study investigated morphological and functional parameters of the testis, epididymis, and spermatozoa in diabetic rats exposed to arsenate. MATERIALS AND METHODS: Diabetes was induced in male rats by intraperitoneal streptozotocin injection. While a set of healthy and diabetic animals received saline solution (negative control and diabetes control, respectively), the other set received 10 mg/L sodium arsenate (arsenic control and diabetes + arsenic groups, respectively) for 40 days in drinking water. Testosterone concentration, daily sperm production, sperm counts in the testis and epididymis, and sperm parameters were evaluated in the groups. Moreover, testis and epididymis were subjected to antioxidant enzymes analysis, micromineral determination, and histopathological evaluation. RESULTS: Arsenate exposure reduced serum testosterone concentration in healthy animals and worsened this reduction in diabetic rats. In addition, the number of spermatozoa in testis and epididymis tissues, as well as the daily sperm production, was decreased in these groups. Sperm parameters such as motility, morphology, and integrity of acrosomal and plasma membranes were impaired in health animals exposed to arsenate. The combination of diabetes and arsenate, in turn, increased only the percentage of spermatozoa with abnormal morphology. Moreover, the proportion of arsenic increased in the testis and epididymis of both groups receiving arsenate. Its bioaccumulation in these organs caused an imbalance in antioxidant enzymes activities and mineral content in healthy animals, enhancing these changes in diabetic rats. Testicular pathologies occurred mainly in animals co-exposed to diabetes and arsenate. CONCLUSION: Our results indicate that arsenate exposure enhances several damages to male reproductive functions in diabetic rats, mainly by impairing testosterone levels and inducing nitrosative stress in testis and epididymis.
