Integrating a deep neural network and Transformer architecture for the automatic segmentation and survival prediction in cervical cancer.

Background: Automated tumor segmentation and survival prediction are critical to clinical diagnosis and treatment. This study aimed to develop deep-learning models for automatic tumor segmentation and survival prediction in magnetic resonance imaging (MRI) of cervical cancer (CC) by combining deep neural networks and Transformer architecture. Methods: This study included 406 patients with CC, each with comprehensive clinical information and MRI scans. We randomly divided patients into training, validation, and independent test cohorts in a 6:2:2 ratio. During the model training, we employed two architecture types: one being a hybrid model combining convolutional neural network (CNN) and ransformer (CoTr) and one of pure CNNs. For survival prediction, the hybrid model combined tumor image features extracted by segmentation models with clinical information. The performance of the segmentation models was evaluated using the Dice similarity coefficient (DSC) and 95% Hausdorff distance (HD95). The performance of the survival models was assessed using the concordance index. Results: The CoTr model performed well in both contrast-enhanced T1-weighted (ceT1W) and T2-weighted (T2W) imaging segmentation tasks, with average DSCs of 0.827 and 0.820, respectively, which outperformed other the CNN models such as U-Net (DSC: 0.807 and 0.808), attention U-Net (DSC: 0.814 and 0.811), and V-Net (DSC: 0.805 and 0.807). For survival prediction, the proposed deep-learning model significantly outperformed traditional methods, yielding a concordance index of 0.732. Moreover, it effectively divided patients into low-risk and high-risk groups for disease progression (P<0.001). Conclusions: Combining Transformer architecture with a CNN can improve MRI tumor segmentation, and this deep-learning model excelled in the survival prediction of patients with CC as compared to traditional methods.

A Comprehensive Analysis of Prognostic Indicators in Serous Ovarian Cancer Based on Leukocyte Migration and Immune Microenvironment.

BACKGROUND: High-grade serous ovarian cancer (HGSOC) treatment is facing clinical challenges. The tumor immune microenvironment (TME) has recently been shown to perform a critical function in the prediction of clinical outcomes as well as the effectiveness of treatment. Leukocyte migration is enhanced in malignant tumors and promotes immunity. However, its role in how to underlie the migration of immune cells into the TME remains to be further explained in HGSOC. METHODS: We built a prognostic multigene signature with leukocyte migration-related differentially expressed genes (LMDGs), which is associated with TME by single-sample gene set enrichment analysis (ssGSEA), in the The Cancer Genome Atlas (TCGA) cohort. Furthermore, we systematically correlated risk signature with immunological characteris-tics in TME, mutational profiles of HGSOC, and potential value in predicting efficacy of platinum-based chemotherapy and immunotherapy. Screening of the most important prognostic factor among risk signatures by Friends analysis, and immunofluorescence was employed to examine both the expression of CD2 as well as its relationship with CD8 and PD-1. RESULTS: LMDGs-related prognostic model showed good prediction performance. Patients who had high-risk scores exhibited significantly reduced progression-free survival (PFS) and overall survival (OS) than those with low-risk scores, according to the results of the survival analysis (p < 0.001). In the TCGA cohort, the risk signature was found to have independent prognostic sig-nificance for HGSOC (HR =1.829, 95% CI = 1.460-2.290, p < 0.001) and validated in the Gene Expression Omnibus (GEO) cohort. Samples with high-risk scores had lower levels of CD8+ T cells infiltration. The low-risk signature shapes an inflamed TME in HGSOC. Furthermore, immune therapy might be effective for the low-risk subtype of HGSOC patients (p < 0.001). Friends analysis revealed that CD2 was the most important prognostic gene among risk signatures. Real-time quantitative PCR analysis showed the expression of CD2 was greater in tumor cells as opposed to normal ovarian cells. CD8, PD-1, and CD2 were shown to be co-localized in HGSOC tissues, according to immunofluorescence analyses. CD2 was significantly correlated with CD8 (r = 0.47). CONCLUSIONS: Our study identified and validated a promising LMDGs signature associated with inflamed TME, which might offer some prospective clinical implications for the treatment of SOC. CD2 might be a novel biomarker to predict immune efficacy.

Genomic landscape, immune characteristics and prognostic mutation signature of cervical cancer in China.

PURPOSE: This study aimed to analyse the genomic alteration profiles and immune characteristics of a cohort of Chinese cervical cancer patients to understand why certain patients benefited from molecular targeted therapies and immunotherapy as well as their prognostic significance. METHODS: PD-L1 expression and clinicopathological information were obtained from 98 cervical cancer patients. Differences in PD-L1 expression and gene mutations between squamous cell carcinoma (SCC) and adenocarcinoma (AC) were analysed by the chi-square test or Fisher's exact test. Differences in gene mutations between our cohort and The Cancer Genome Atlas (TCGA) cohort were tested by Fisher's exact test. Logistic regression was used to analyse factors influencing TMB-high. RESULTS: Positive PD-L1 expression was significantly higher in cervical SCC than in cervical AC (87% vs. 39%, p < 0.001). Frequently mutated genes in cervical cancer included the PIK3CA, KMT2D, and KMT2C genes, among others. PIK3CA gene mutation rates were significantly higher in SCC than in AC (p = 0.004). The TERT gene mutation rate was significantly higher in our cohort than in the TCGA cohort (12% vs. 1%, p < 0.001). The independent predictors of high TMB were KMT2C and LRP1B gene mutations (p < 0.05). We also found that PTEN mutations were associated with worse survival (median PFS, 12.16 vs. 21.75 months, p = 0.0024). CONCLUSION: Cervical SCC and AC have different molecular profiles and immune characteristics, suggesting that targeted treatments for SCC and AC patients may improve clinical outcomes. KMT2C and LRP1B gene mutations are independent predictors of TMB-high status in cervical cancer. We also proposed the prognostic value of PTEN mutations.

Efficacy and Safety of Sintilimab Plus Anlotinib for PD-L1-Positive Recurrent or Metastatic Cervical Cancer: A Multicenter, Single-Arm, Prospective Phase II Trial.

PURPOSE: No combined immunotherapy and antiangiogenic therapy have been investigated in exclusively programmed death-ligand 1 (PD-L1)-positive advanced cervical cancer (CA). We investigated the efficacy and safety of sintilimab plus anlotinib as second-line or later therapy for PD-L1-positive recurrent or metastatic (R/M) CA. PATIENTS AND METHODS: Patients with PD-L1-positive (Combined Positive Score ≥ 1) R/M CA who progressed after at least one prior systemic chemotherapeutic regimen or could not tolerate chemotherapy were eligible for the phase II trial. The patients received 200 mg sintilimab once on day 1 and 10 mg anlotinib once daily on days 1-14 every 3 weeks. The primary end point was investigator-confirmed objective response rate (ORR) per RECIST v1.1. Secondary end points included progression-free survival (PFS), overall survival, and disease control rate. Biomarkers were explored. RESULTS: Forty-two patients were enrolled. The ORR was 54.8% (95% CI, 38.7 to 70.2). In 39 efficacy-evaluable patients, the ORR was 59.0% (95% CI, 42.1 to 74.4); the disease control rate was 94.9% (95% CI, 82.7 to 99.4). The median PFS was 9.4 months (95% CI, 8.0 to 14.6). The median overall survival was not reached. Furthermore, 85.8% of the patients experienced treatment-related adverse events. The most frequent treatment-related adverse events were hypothyroidism (33.3%), elevated aspartate aminotransferase levels (21.4%), and hypertension (19.0%). Patients with altered PIK3CA, PI3K-AKT signaling, or KMT2D had a higher ORR, whereas those with altered STK11 and/or JAK2 had a significantly shorter PFS. CONCLUSION: Sintilimab plus anlotinib as second-line or later therapy is efficacious and safe for patients with advanced CA who have failed prior chemotherapy.

A Metastatic Cervical Adenocarcinoma Patient Carrying HER2 G292R Achieved Complete Response Upon Pyrotinib Treatment.

Cervical cancer patients who develop distant metastasis are rarely curable with very limited treatment options. Chemotherapy is often administered but with limited efficacy. Immunotherapy and anti-angiogenesis therapy are recommended for selected cases of recurrent or metastatic cervical cancers. The clinical efficacy of inhibitors targeting HER2, a commonly mutated gene in cervical cancer, has not been elucidated. Herein, we report a metastatic cervical adenocarcinoma patient carrying HER2 G292R who benefited from pyrotinib after progression on radio-chemotherapy, achieving complete response (CR) with a progression-free survival of 25 months and counting. Our study sheds light on the treatment options for previously treated metastatic cervical adenocarcinoma patients harboring activating HER2 mutations.

Evaluation of clinical efficacy of silver-needle warm acupuncture in treating adults with acute low back pain due to lumbosacral disc herniation: study protocol for a randomized controlled trial.

BACKGROUND: As a common cause of low back pain, lumbosacral disc herniation (LDH) is usually dealt with using non-surgical interventions. In the face of concerns about prescription opioid abuse, alternative and complementary treatments may be promising, among which silver-needle warm acupuncture is considered as an upgrading option for its potential anti-inflammatory and strong analgesic effect for patients with chronic pain. In this proposed study, we aim to assess its clinical efficacy in comparison with conventional stainless steel filiform-needle warm acupuncture. METHODS/DESIGN: This is a randomized, two-armed, patient- and assessor-blinded trial. One hundred and sixty eligible patients recruited from December 2018 to June 2020 in three centers will be assigned for warm acupuncture treatment with either stainless steel filiform or silver needles. Nine sessions of 20-min treatment will be conducted during 3 consecutive weeks. Assessments with instruments including the Oswestry Disability Index, the visual analog scale, and the Japanese Orthopedic Association Back Pain Evaluation Questionnaire will be performed at four time points to explore the difference of clinical efficacy between two groups. DISCUSSION: If the results show that participants treated with silver-needle warm acupuncture gain a greater improvement in terms of pain intensity, physical function, and quality of life, this study is expected to offer reliable evidence to widely push this treatment for LDH in clinical practice. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1800019051 . Registered on 24 October 2018.