MR-guided adaptive versus ITV-based stereotactic body radiotherapy for hepatic metastases (MAESTRO): a randomized controlled phase II trial.

BACKGROUND: Stereotactic body radiotherapy (SBRT) is an established local treatment method for patients with hepatic oligometastasis or oligoprogression. Liver metastases often occur in close proximity to radiosensitive organs at risk (OARs). This limits the possibility to apply sufficiently high doses needed for optimal local control. Online MR-guided radiotherapy (oMRgRT) is expected to hold potential to improve hepatic SBRT by offering superior soft-tissue contrast for enhanced target identification as well as the benefit of gating and daily real-time adaptive treatment. The MAESTRO trial therefore aims to assess the potential advantages of adaptive, gated MR-guided SBRT compared to conventional SBRT at a standard linac using an ITV (internal target volume) approach. METHODS: This trial is conducted as a prospective, randomized, three-armed phase II study in 82 patients with hepatic metastases (solid malignant tumor, 1-3 hepatic metastases confirmed by magnetic resonance imaging (MRI), maximum diameter of each metastasis ≤ 5 cm (in case of 3 metastases: sum of diameters ≤ 12 cm), age ≥ 18 years, Karnofsky Performance Score ≥ 60%). If a biologically effective dose (BED) ≥ 100 Gy (α/ß = 10 Gy) is feasible based on ITV-based planning, patients will be randomized to either MRgRT or ITV-based SBRT. If a lesion cannot be treated with a BED ≥ 100 Gy, the patient will be treated with MRgRT at the highest possible dose. Primary endpoint is the non-inferiority of MRgRT at the MRIdian Linac® system compared to ITV-based SBRT regarding hepatobiliary and gastrointestinal toxicity CTCAE III or higher. Secondary outcomes investigated are local, locoregional (intrahepatic) and distant tumor control, progression-free survival, overall survival, possible increase of BED using MRgRT if the BED is limited with ITV-based SBRT, treatment-related toxicity, quality of life, dosimetric parameters of radiotherapy plans as well as morphological and functional changes in MRI. Potential prognostic biomarkers will also be evaluated. DISCUSSION: MRgRT is known to be both highly cost- and labor-intensive. The MAESTRO trial aims to provide randomized, higher-level evidence for the dosimetric and possible consecutive clinical benefit of MR-guided, on-table adaptive and gated SBRT for dose escalation in critically located hepatic metastases adjacent to radiosensitive OARs. TRIAL REGISTRATION: The study has been prospectively registered on August 30th, 2021: Clinicaltrials.gov, "Magnetic Resonance-guided Adaptive Stereotactic Body Radiotherapy for Hepatic Metastases (MAESTRO)", NCT05027711.

[Occurrence of radiation-induced injury in vagina after radical radiotherapy of cervical cancer and its affecting factors].

Objective: To investigate the occurrence and degree of radiation-induced injury in vagina after radical radiotherapy of cervical cancer. Methods: A total of 282 cases of patients with cervical cancer were collected from November 2016 to September 2017. All of the above patients underwent radical radiotherapy from 2008 to 2017 in the First Affiliated Hospital of Xi'an Jiaotong University. The patients' International Federation of Gynecology and Obstetrics (FIGO) staging (2009) , brachytherapy dose, whether receive synchronous chemotherapy or not, age and body mass index (BMI) for the occurrence and severity of vaginal radiation injury at different time periods were analyzed by cross-sectional survey method. The single factor would be analyzed by the method of Chi-square test and the multiple factors would be analyzed by logistic regression method to checkout. Results: Of the 282 patients, the incidence of radiation-injury in vaginal was 84.4% (238/282) , with the incidence rate of degree Ⅰ,Ⅱ and Ⅲ radiation injury were respectively 50.7% (143/282), 29.8% (84/282) and 3.9% (11/282; χ(2)=153.375, P<0.05) , and there was no degree Ⅳ. Until the end of the follow-up time, the incidence of radiation-induced injury in vaginal after completing the treatment within 1 year, 1-2 years,>2-<5 years and ≥5 years were respectively 80.0% (24/30) , 87.2% (102/117) , 88.2% (60/68) and 77.6% (52/67; χ(2)=4.231, P=0.238) . There were 30 cases be followed within 1 year after treatment, the incidence rate of degreeⅠ,Ⅱ and Ⅲ of radiation injury in vagina was 60.0% (18/30) , 20.0% (6/30) and 0, respectively (χ(2)=28.636, P<0.05). There were 117 cases be followed between 1-2 years after treatment, the incidence rate of degreeⅠ,Ⅱ and Ⅲ vaginal radiation-induced injury were 54.7% (64/117) , 29.9% (35/117) and 2.6% (3/117) , respectively (χ(2)=77.198, P<0.05) . There were 68 cases be followed between >2-<5 years after treatment, the incidence rate of degree Ⅰ,Ⅱ and Ⅲ vaginal radiation-induced injury were 51.5% (35/68) ,33.8% (23/68) and 2.9% (2/68) , respectively (χ(2)=39.525, P<0.05) . There were 67 cases be followed ≥5 years after treatment, the incidence rate of degree Ⅰ,Ⅱ and Ⅲ vaginal radiation injury were 38.8% (26/67) , 29.9% (20/67) and 9.0% (6/67) , respectively (χ(2)=16.395, P<0.05) . The single-factor analysis result indicated that the brachytherapy dose had an obvious effect on vaginal radiation-induced injury (χ(2)=5.344, P=0.021) ; however, other factors, such as age, BMI, FIGO stages and synchronous chemotherapy, had no obvious effect on vaginal radiation-induced injury (all P>0.05) . The multifactor analysis indicated that the brachytherapy dose was an independent factor affecting the occurrence of vaginal radiation-induced injury (P=0.043) . Conclusion: After the radical radiotherapy of cervical cancer, the vaginal radiation-induced injury is associated with the dose of brachytherapy.

Effect of photoperiod on serum hormone concentrations during the annual reproductive cycle in geese.

The poor egg-laying rate of geese hinders the development of the goose industry; therefore, the reproductive performance of geese is an important area of investigation. To evaluate the relationship between photoperiod, reproductive hormones, and reproductive activity during the egg-laying cycle in geese under natural conditions, we collected blood samples from Sichuan white geese and Xupu geese to quantify changes in prolactin (PRL), estradiol (E2), vasoactive intestinal polypeptide (VIP), follicle stimulating hormone (FSH), gonadotropin-inhibitory hormone (GnIH), and luteinizing hormone (LH). We also calculated the rate of egg laying for the two populations during the egg-laying cycle. We show that the egg-laying rate and the serum concentration of some hormones (PRL, E2, VIP, FSH, GnIH, and LH) differed significantly between the two populations during the pre-laying, laying, and ceased-laying periods. Serum LH concentrations may be associated with maturation of the ovary and oviducts, whereas FSH, PRL, and GnIH play important roles in egg laying. These results provide a useful resource for future studies examining the laying rate in geese.

The activation of G protein-coupled receptor 30 (GPR30) inhibits proliferation of estrogen receptor-negative breast cancer cells in vitro and in vivo.

There is an urgent clinical need for safe and effective treatment agents and therapy targets for estrogen receptor negative (ER-) breast cancer. G protein-coupled receptor 30 (GPR30), which mediates non-genomic signaling of estrogen to regulate cell growth, is highly expressed in ER--breast cancer cells. We here showed that activation of GPR30 by the receptor-specific agonist G-1 inhibited the growth of ER--breast cancer cells in vitro. Treatment of ER--breast cancer cells with G-1 resulted in G2/M-phase arrest, downregulation of G2-checkpoint regulator cyclin B, and induction of mitochondrial-related apoptosis. The G-1 treatment increased expression of p53 and its phosphorylation levels at Serine 15, promoted its nuclear translocation, and inhibited its ubiquitylation, which mediated the growth arrest effects on cell proliferation. Further, the G-1 induced sustained activation and nuclear translocation of ERK1/2, which was mediated by GPR30/epidermal growth factor receptor (EGFR) signals, also mediated its inhibition effects of G-1. With extensive use of siRNA-knockdown experiments and inhibitors, we found that upregulation of p21 by the cross-talk of GPR30/EGFR and p53 was also involved in G-1-induced cell growth arrest. In vivo experiments showed that G-1 treatment significantly suppressed the growth of SkBr3 xenograft tumors and increased the survival rate, associated with proliferation suppression and upregulation of p53, p21 while downregulation of cyclin B. The discovery of multiple signal pathways mediated the suppression effects of G-1 makes it a promising candidate drug and lays the foundation for future development of GPR30-based therapies for ER- breast cancer treatment.