Preoperative short-course radiotherapy followed by chemotherapy and PD-1 inhibitor administration for locally advanced rectal cancer: A study protocol of a randomized phase II/III trial (STELLAR II study).

AIM: For patients with locally advanced rectal cancer, previous STELLAR studies have shown that a new adjuvant treatment paradigm of short-course radiotherapy followed by neoadjuvant chemotherapy can achieve pathological complete response rates superior to those of standard care; however, the 3-year DFS is inferior to neoadjuvant concurrent radiotherapy. Recent studies have shown that immune checkpoint inhibitors may improve the prognosis of rectal cancer and have good synergy with radiotherapy. Therefore, neoadjuvant chemotherapy combined with immune checkpoint inhibitors after a short course of radiotherapy has the potential to further improve complete response rates and prognosis. METHOD: The STELLAR II study is a multicentre, open label, two-arm randomized, phase II/III trial of short-course radiotherapy followed by neoadjuvant chemotherapy concurrent with immunotherapy for locally advanced rectal cancer. A total of 588 patients with locally advanced rectal cancer (LARC) will be randomly assigned to the experimental and control groups. The experimental group will receive short-course radiotherapy and neoadjuvant chemotherapy in combination with sindilizumab, while the control group will receive short-course radiotherapy and neoadjuvant chemotherapy. Both groups will subsequently receive either total rectal mesenteric resection or a watch & wait (W&W) strategy. The phase II primary endpoint is the complete remission rate, and the secondary endpoints include grade 3-4 adverse events, perioperative complications, R0 resection rate, overall survival, local recurrence rate, distant metastasis rate and quality of life score. A seamless phase II/III randomized controlled design will be used to investigate the effectiveness and safety of the TNT strategy with the addition of immunotherapy. The trial opened, and the first patient was recruited on 31 August 2022. Trial registration number and date of registration: ClinicalTrials.gov NCT05484024, 29 July 2022. DISCUSSION: The STELLAR II trial will prospectively evaluate the efficacy of TNT treatment strategies that incorporate immune checkpoint inhibitors. The trial will yield important information to guide routine management of patients with local advanced rectal cancer.

A survey on brachytherapy training of gynecological cancer focusing on the competence of residents in China.

BACKGROUND: The brachytherapy is an indispensable treatment for gynecological tumors, but the quality and efficiency of brachytherapy training for residents is still unclear. METHODS: An anonymous questionnaire was designed to collect information on gynecological brachytherapy (GBT) training for radiation oncology residents from 28 training bases in China. The questionnaire content was designed based on the principle of competency based medical education (CBME). The Likert scale was employed to evaluate self-reported competence and comprehension regarding GBT. A total of 132 senior residents were included in the final analysis. RESULTS: 53.79% (71/132) of senior residents had experience in performing image-guided GBT, whereas 76.52% (101/132) had observed the procedure during their standardized residency training. The proportion of senior residents who reported having the self-reported competence to independently complete the GBT was 78.03% for intracavity GBT, 75.00% for vaginal stump GBT, and 50.03% for interstitial GBT, respectively. The number of successful completion of Interstitial, intracavity and vaginal GBT was correlated with the self- confidence of trainees after standardized training. In particular, the independent completion of interstitial GBT for more than 20 cases was an independent factor for the self-reported competence of senior residents. During the training period, 50.76% and 56.82% of the residents had not participated in the specialized examinations and professional GBT courses. CONCLUSIONS: The study revealed that the self-confidence of residents to independently complete brachytherapy was relatively high, and the specialized curriculum setting and training process assessment for brachytherapy training still need to be strengthened in the future.

Downregulation of miR-181c-5p in Alzheimer's disease weakens the response of microglia to Aß phagocytosis.

Alzheimer's disease (AD) is an age-associated neurodegenerative disease. Recently, studies have demonstrated the potential involvement of microRNA-181c-5p (miR-181c-5p) in AD. However, the mechanism through which miR-181c-5p is responsible for the onset and progression of this disease remains unclear, and our study aimed to explore this problem. Differential expression analysis of the AD dataset was performed to identify dysregulated genes. Based on hypergeometric analysis, AD differential the upstream regulation genes miR-181c-5p was found. We constructed a model where SH-SY5Y and BV2 cells were exposed to Aß1-42 to simulate AD. Levels of tumor necrosis factor-alpha, interleukin-6, and IL-1ß were determined using enzyme-linked immunosorbent assay or reverse transcription quantitative polymerase chain reaction. Phosphorylation levels of p-P38 and P38 were detected by Western blot. The level of apoptosis in BV2 cells under Aß1-42 stress was exacerbated by miR-181c-5p mimic. Downregulated miR-181c-5p impaired the phagocytosis and degradation of Aß by BV2 cells. The release of proinflammatory cytokines in BV2 cells with Aß1-42 stress was alleviated by miR-181c-5p upregulation. Additionally, miR-181c-5p downregulation alleviated the phosphorylation of P38 in Aß1-42-induced SH-SY5Y cells. In conclusion, miR-181c-5p improves the phagocytosis of Aß by microglial cells in AD patients, thereby reducing neuroinflammation.

Efficacy and safety of bevacizumab in neoadjuvant and concurrent chemoradiotherapy for refractory cervical cancer patients.

A platinum-based concurrent chemoradiotherapy (CCRT) is the standard treatment for refractory cervical cancer (CC). However, the recurrence of disease and the occurrence of metastasis remain prevalent. We observed the long-term efficacy and safety of bevacizumab combined with neoadjuvant chemotherapy (NACT) and CCRT in refractory CC. A total of 62 patients with refractory CC were enrolled in this study from January 2016 to December 2019. The NACT regimen included bevacizumab (7.5 mg/kg), docetaxel (75 mg/m2), and cisplatin (75 mg/m2), administered tri-weekly for 2 cycles. The CCRT regimen included bevacizumab (7.5 mg/kg) and cisplatin (75 mg/m2), administered tri-weekly for 2 cycles. A dose of 45-50 Gy was prescribed for external beam radiotherapy (EBRT), while 30-35 Gy in 4-5 fractions was prescribed for brachytherapy (BT). Among the patients, 21 patients (33.9%) were at stages IIB-IIIB, 8 patients (12.9%) were at stage IIIC1, 19 patients (30.6%) were at stage IIIC2, and 14 patients (22.6%) were at stage IVB. Pelvic, para-aortic, supraclavicular, and inguinal lymph node metastases were discovered in 41 patients (66.1%). The median follow-up was 49.8 months (12.3-82.7 months). The median tumor volumes pre-treatment, after NACT, and before BT were 84.64 ± 53.15 cm3, 1.64 ± 13.15 cm3, and 0 ± 1.5 cm3, respectively. Complete clinical response (cCR) rates after NACT and EBRT were 35.5% and 66.1%, respectively. Four years after the diagnosis, the overall survival (OS) rate was 78.6%, the local region-free survival (LRFS) rate was 91.3%, the disease-free survival (DFS) rate was 70.6%, and the distant metastasis-free survival (DMFS) rate was 81.4%. A total of 29 patients (46.8%) experienced grade 3/4 hematological toxicity, 3 patients (4.8%) experienced grade 3 gastrointestinal toxicities, and none experienced grade 5 adverse events. Bevacizumab combined with NACT and CCRT significantly improved cCR and OS in refractory CC with acceptable toxicity.

Prognostic values of tumor size and location in early stage endometrial cancer patients who received radiotherapy.

OBJECTIVE: To investigate the correlation between tumor size, tumor location, and prognosis in patients with early-stage endometrial cancer (EC) receiving adjuvant radiotherapy. METHODS: Data of patients who had been treated for stage I-II EC from March 1999 to September 2017 in 13 tertiary hospitals in China was screened. Cox regression analysis was performed to investigate associations between tumor size, tumor location, and other clinical or pathological factors with cancer-specific survival (CSS) and distant metastasis failure-free survival (DMFS). The relationship between tumor size as a continuous variable and prognosis was demonstrated by restricted cubic splines. Prognostic models were constructed as nomograms and evaluated by Harrell's C-index, calibration curves and receiver operating characteristic (ROC) curves. RESULTS: The study cohort comprised 805 patients with a median follow-up of 61 months and a median tumor size of 3.0 cm (range 0.2-15.0 cm). Lower uterine segment involvement (LUSI) was found in 243 patients (30.2%). Tumor size and LUSI were identified to be independent prognostic factors for CSS. Further, tumor size was an independent predictor of DMFS. A broadly positive relationship between poor survival and tumor size as a continuous variable was visualized in terms of hazard ratios. Nomograms constructed and evaluated for CSS and DMFS had satisfactory calibration curves and C-indexes of 0.847 and 0.716, respectively. The area under the ROC curves for 3- and 5-year ROC ranged from 0.718 to 0.890. CONCLUSION: Tumor size and LUSI are independent prognostic factors in early-stage EC patients who have received radiotherapy. Integrating these variables into prognostic models would improve predictive ability.

Clinical characteristics and radiation therapy modality of younger patients with early-stage endometrial cancer, a multicenter study in China's real world.

BACKGROUND: Endometrial cancer is a prevalent gynecologic malignancy found in postmenopausal women. However, in the last two decades, the incidence of early-stage has doubled in women under 40 years old. This study aimed to investigate the clinical and pathological characteristics and adjuvant therapeutic modalities of both young and not -young patients with early-stage endometrial cancer in China's real world. METHODS: This retrospective study analyzed patients with early-stage endometrial cancer at 13 medical institutions in China from 1999 to 2015. The patients were divided into two groups: young (≤ 45 years old) and non-young (> 45 years old). Statistical comparisons were conducted between the two groups for clinical characteristics, pathological features, and survival. The study also identified factors that affect local recurrence-free survival (LRFS) using Cox proportional risk regression analysis. Propensity score matching (1:1) was used to compare the effects of local control between vaginal brachytherapy (VBT) alone and pelvic external beam radiotherapy (EBRT) ± VBT. RESULTS: The study involved 1,280 patients, 150 of whom were 45 years old or younger. The young group exhibited a significantly higher proportion of stage II, low-risk, lower uterine segment infiltration (LUSI), and cervical invasion compared to the non-young group. Additionally, the young patients had significantly larger maximum tumor diameters. The young group also had a significantly higher five-year overall survival (OS) and a five-year LRFS. Age is an independent risk factor for LRFS. There was no significant difference in LRFS between young patients with intermediate- to high-risk early-stage endometrial cancer who received EBRT ± VBT and those who received VBT alone. CONCLUSIONS: In the present study, young patients had better characteristics than the non-young group, while they exhibited higher levels of aggressiveness in certain aspects. The LRFS and OS outcomes were better in young patients. Age is an independent risk factor for LRFS. Additionally, VBT alone may be a suitable option for patients under 45 years of age with intermediate- to high-risk early-stage endometrial cancer, as it reduces the risk of toxic reactions and future second cancers while maintaining similar local control as EBRT.

Automated Prediction of Neoadjuvant Chemoradiotherapy Response in Locally Advanced Cervical Cancer Using Hybrid Model-Based MRI Radiomics.

BACKGROUND: This study aimed to develop a model that automatically predicts the neoadjuvant chemoradiotherapy (nCRT) response for patients with locally advanced cervical cancer (LACC) based on T2-weighted MR images and clinical parameters. METHODS: A total of 138 patients were enrolled, and T2-weighted MR images and clinical information of the patients before treatment were collected. Clinical information included age, stage, pathological type, squamous cell carcinoma (SCC) level, and lymph node status. A hybrid model extracted the domain-specific features from the computational radiomics system, the abstract features from the deep learning network, and the clinical parameters. Then, it employed an ensemble learning classifier weighted by logistic regression (LR) classifier, support vector machine (SVM) classifier, K-Nearest Neighbor (KNN) classifier, and Bayesian classifier to predict the pathologic complete response (pCR). The area under the receiver operating characteristics curve (AUC), accuracy (ACC), true positive rate (TPR), true negative rate (TNR), and precision were used as evaluation metrics. RESULTS: Among the 138 LACC patients, 74 were in the pCR group, and 64 were in the non-pCR group. There was no significant difference between the two cohorts in terms of tumor diameter (p = 0.787), lymph node (p = 0.068), and stage before radiotherapy (p = 0.846), respectively. The 109-dimension domain features and 1472-dimension abstract features from MRI images were used to form a hybrid model. The average AUC, ACC, TPR, TNR, and precision of the proposed hybrid model were about 0.80, 0.71, 0.75, 0.66, and 0.71, while the AUC values of using clinical parameters, domain-specific features, and abstract features alone were 0.61, 0.67 and 0.76, respectively. The AUC value of the model without an ensemble learning classifier was 0.76. CONCLUSIONS: The proposed hybrid model can predict the radiotherapy response of patients with LACC, which might help radiation oncologists create personalized treatment plans for patients.