Risk of interstitial lung disease with the use of programmed cell death 1 (PD-1) inhibitor compared with programmed cell death ligand 1 (PD-L1) inhibitor in patients with breast cancer: A systematic review and meta-analysis.

Background: Programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors have become integral elements within the current landscape of breast cancer treatment modalities; however, they are associated with interstitial lung disease (ILD), which is rare but potentially fatal. Notably, only a few studies have compared the difference in ILD incidence between PD-1 and PD-L1 inhibitors. Therefore, this study aimed to assess the discrepancies regarding ILD risk between the two immune checkpoint inhibitors. We also reported three cases of ILD after PD-1 inhibitor treatment. Methods: We comprehensively searched PubMed, EMBASE, and the Cochrane Library to identify clinical trials that investigated PD-1/PD-L1 inhibitor treatment for patients with breast cancer. Pooled overall estimates of incidence and risk ratio (RR) were calculated with a 95% confidence interval (CI), and a mirror group analysis was performed using eligible studies. Results: This meta-analysis included 29 studies with 4639 patients who received PD-1/PD-L1 inhibitor treatment. A higher ILD incidence was observed among 2508 patients treated with PD-1 inhibitors than among 2131 patients treated with PD-L1 inhibitors (0.05 vs. 0.02). The mirror group analysis further revealed a higher ILD event risk in patients treated with PD-1 inhibitors than in those treated with PD-L1 inhibitors (RR = 2.34, 95% CI, 1.13-4.82, P = 0.02). Conclusion: Our findings suggest a greater risk of ILD with PD-1 inhibitors than with PD-L1 inhibitors. These findings are instrumental for clinicians in treatment deliberations, and the adoption of more structured diagnostic approaches and management protocols is necessary to mitigate the risk of ILD.

Application of TiLOOP bra in implant-based breast reconstruction is associated with decreased complication risk compared with other meshes: A systematic review and meta-analysis.

BACKGROUND: TiLOOP bra has been used for over 15 years, however, evidence regarding its safety in implant-based breast reconstruction (IBBR) for patients with breast cancer after mastectomy is still limited. We performed this meta-analysis to evaluate its risks and benefits in IBBR comparing with other meshes. METHODS: Electronic databases were searched to identify relevant studies comparing postoperative complications between TiLOOP bra and other reconstruction techniques in IBBR with or without meshes. We also compared patient satisfaction in physical well-being between two groups. Risk ratios (RRs) and mean differences with 95% confidence interval (CI) were calculated. RESULTS: Seven studies representing 1203 cases were analyzed. Compared with other meshes, the use of TiLOOP bra significantly reduced the risk of infection (RR = 0.53, 95% CI, 0.32-0.86), seroma (RR = 0.21, 95% CI, 0.07-0.61), red breast syndrome (RR = 0.10, 95% CI, 0.02-0.45), and capsular contracture (RR = 0.20, 95% CI, 0.05-0.75). Patient satisfaction in physical well-being was comparable between two groups. CONCLUSIONS: TiLOOP bra in IBBR has a favored safety profile over other meshes, which significantly reduced postoperative complication risk and did not affect patient satisfaction. Although prospective well-designed controlled studies are still warranted, TiLOOP bra is safe and reliable at present.

Concomitant PIK3CA and TP53 Mutations in Breast Cancer: An Analysis of Clinicopathologic and Mutational Features, Neoadjuvant Therapeutic Response, and Prognosis.

PURPOSE: PIK3CA and TP53 are the most prevalently mutated genes in breast cancer (BC). Previous studies have indicated an association between concomitant PIK3CA/TP53 mutations and shorter disease-free survival. As its clinical utility remains largely unknown, we aimed to analyze the prognostic and predictive roles of this co-mutation. METHODS: We retrospectively analyzed patients who were diagnosed with BC at Guangdong Provincial People's Hospital (GDPH) who underwent next-generation sequencing. The correlation of concomitant PIK3CA/TP53 mutations with clinicopathological and mutational characteristics, and neoadjuvant systemic therapy (NST) responses was analyzed. The Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset was used to verify associations between concurrent mutations and survival outcomes. RESULTS: In the GDPH cohort, concomitant PIK3CA/TP53 mutations were associated with more aggressive phenotypes, including human epidermal growth factor receptor 2 positive status, hormone receptor negative status, high Ki-67 expression, high histological grade, advanced TNM stage, and additional genetic alterations. Co-mutations also portended a worse response to NST, especially taxane-containing regimens, when compared with the TP53 mutant alone (odds ratio, 3.767; 95% confidence interval, 1.205-13.087; p = 0.028). A significant association was observed between concomitant PIK3CA/TP53 mutations and poor survival outcomes in the METABRIC cohort. CONCLUSION: Concomitant PIK3CA/TP53 mutations not only suggested unfavorable features and poor prognosis in BC but also conferred less benefit to NST than TP53 mutations alone.

Classification of temporal lobe epilepsy based on neuropsychological tests and exploration of its underlying neurobiology.

Objective: To assist improving long-term postoperative seizure-free rate, we aimed to use machine learning algorithms based on neuropsychological data to differentiate temporal lobe epilepsy (TLE) from extratemporal lobe epilepsy (extraTLE), as well as explore the relationship between magnetic resonance imaging (MRI) and neuropsychological tests. Methods: Twenty-three patients with TLE and 23 patients with extraTLE underwent neuropsychological tests and MRI scans before surgery. The least absolute shrinkage and selection operator were firstly employed for feature selection, and a machine learning approach with neuropsychological tests was employed to classify TLE using leave-one-out cross-validation. A generalized linear model was used to analyze the relationship between brain alterations and neuropsychological tests. Results: We found that logistic regression with the selected neuropsychological tests generated classification accuracies of 87.0%, with an area under the receiver operating characteristic curve (AUC) of 0.89. Three neuropsychological tests were acquired as significant neuropsychological signatures for the diagnosis of TLE. We also found that the Right-Left Orientation Test difference was related to the superior temporal and the banks of the superior temporal sulcus (bankssts). The Conditional Association Learning Test (CALT) was associated with the cortical thickness difference in the lateral orbitofrontal area between the two groups, and the Component Verbal Fluency Test was associated with the cortical thickness difference in the lateral occipital cortex between the two groups. Conclusion: These results showed that machine learning-based classification with the selected neuropsychological data can successfully classify TLE with high accuracy compared to previous studies, which could provide kind of warning sign for surgery candidate of TLE patients. In addition, understanding the mechanism of cognitive behavior by neuroimaging information could assist doctors in the presurgical evaluation of TLE.

Improving Tumor Classification by Reusing Self-predicted Segmentation of Medical Images as Guiding Knowledge.

Differential diagnosis of tumors is important for computer-aided diagnosis. In computer-aided diagnosis systems, expert knowledge of lesion segmentation masks is limited as it is only used during preprocessing or as supervision to guide feature extraction. To improve the utilization of lesion segmentation masks, this study proposes a simple and effective multitask learning network that improves medical image classification using self-predicted segmentation as guiding knowledge; we call this network RS 2-net. In RS 2-net, the predicted segmentation probability map obtained from the initial segmentation inference is added to the original image to form a new input, which is then reinput to the network for the final classification inference. We validated the proposed RS 2-net using three datasets: the pNENs-Grade dataset, which tested the prediction of pancreatic neuroendocrine neoplasm grading, and the HCC-MVI dataset, which tested the prediction of microvascular invasion of hepatocellular carcinoma, and ISIC 2017 public skin lesion dataset. The experimental results indicate that the proposed strategy of reusing self-predicted segmentation is effective, and RS 2-net outperforms other popular networks and existing state-of-the-art studies. Interpretive analytics based on feature visualization demonstrates that the improved classification performance of our reuse strategy is due to the semantic information that can be acquired in advance in a shallow network.

Distinct clinicopathological characteristics, genomic alteration and prognosis in breast cancer with concurrent TP53 mutation and MYC amplification.

BACKGROUND: Both TP53 mutation and MYC amplification indicate poor outcomes in breast cancer (BC), but the clinical values of concurrent TP53 and MYC alterations have not been well-characterized. METHODS: A total of 494 BC patients diagnosed at Guangdong Provincial People's Hospital (GDPH) were retrospectively analyzed. Genomic alterations were determined using next-generation sequencing. Survival analysis was applied to assess the effects of genetic alterations on relapse-free survival. The prognosis was verified based on 1405 patients from METABRIC cohort. Additionally, we used logistic regression to identify the factors associated with pathological complete response (pCR) after neoadjuvant chemotherapy. RESULTS: In GDPH cohort, patients with TP53/MYC co-alteration exhibited higher grade and stage, more positive HER2 status and higher Ki67 levels, but less luminal A subtypes. They also had more mutations in genes involved in ERBB and TGF-ß signaling pathways, as well as exclusive FANCG/CDKN2B/QKI copy number amplifications and SUFU/HIST3H3/ERCC4/JUN/BCR mutations. Concurrent TP53 and MYC alterations independently increased hazards of relapse (HR, 5.425; 95% CI: 2.019-14.579; p < 0.001). They maintained independent significance for relapse-free (HR, 1.310; 95% CI: 1.012-1.697; p = 0.041) and overall survival (HR, 1.373; 95% CI: 1.093-1.725; p = 0.006) in METABRIC cohort. Among the 81 patients receiving chemotherapy, TP53 mutation (OR, 5.750; 95% CI: 1.553-25.776; p = 0.013) and earlier stage (OR, 0.275; 95% CI 0.088-0.788; p = 0.020) were associated with pCR, while the co-alteration did not serve as an independent predictor (p = 0.199). CONCLUSIONS: TP53/MYC co-alteration was associated with distinct clinicopathological and genomic features. They also conferred unfavorable prognosis in BC patients, and did not improve pCR after neoadjuvant chemotherapy.

Expression and prognosis analysis of mitochondrial ribosomal protein family in breast cancer.

Breast cancer (BC) is characterized by high morbidity. Mitochondrial ribosomal protein (MRP) family participates in mitochondrial energy metabolism, underlying BC progression. This study aims to analyze the expression and prognosis effect of the MRP genes in BC patients. GEPIA2, UALCAN, cBioPortal, and MethSurv were used to demonstrate the differential expression, genomic alteration profiles, and DNA methylation of the MRP gene family in BC. Functional enrichment analysis and protein-protein interaction network construction were performed to understand the biological function. Based on 1056 TCGA samples with the transcriptional level of MRPs, Kaplan-Meier curves, Cox, and LASSO regression were applied to explore their prognostic effects. 12 MRPs were upregulated in BC, which were associated with gene amplification and DNA methylation. MRP genetic alteration occurred in 42% of BC patients, and amplification was the most frequent variation. Functioning in its entirety, the MRP family was involved in mitochondrial translational termination, elongation, translation, and poly(A) RNA binding. High expression of MRPL1, MRPL13, MRPS6, MRPS18C, and MRPS35, as well as low levels of MRPL16, and MRPL40 significantly indicated poor prognosis in BC patients. Thus, a novel MRP-based prognostic nomogram was established and verified with favorable discrimination and calibration. We not only provided a thorough expression and prognosis analysis of the MRP family in BC patients but also constructed an MRP-based prognostic nomogram. It was suggested that MRPs acted as biomarkers in individualized risk prediction and may serve as potential therapeutic targets in BC patients.

Clinicopathologic and Genomic Features in Triple-Negative Breast Cancer Between Special and No-Special Morphologic Pattern.

Background: Triple-negative breast cancer (TNBC) is refractory and heterogeneous, comprising various entities with divergent phenotype, biology, and clinical presentation. As an aggressive subtype, Chinese TNBC patients with special morphologic patterns (STs) were restricted to its incidence of 10-15% in total TNBC population. Methods: We recruited 89 patients with TNBC at Guangdong Provincial People's Hospital (GDPH) from October 2014 to May 2021, comprising 72 cases of invasive ductal carcinoma of no-special type (NSTs) and 17 cases of STs. The clinical data of these patients was collected and statistically analyzed. Formalin-fixed, paraffin-embedded (FFPE) tumor tissues and matched blood samples were collected for targeted next-generation sequencing (NGS) with cancer-related, 520- or 33-gene assay. Immunohistochemical analysis of FFPE tissue sections was performed using anti-programmed cell death-ligand 1(PD-L1) and anti-androgen receptor antibodies. Results: Cases with NSTs presented with higher histologic grade and Ki-67 index rate than ST patients (NSTs to STs: grade I/II/III 1.4%, 16.7%,81.9% vs 0%, 29.4%, 58.8%; p<0.05; Ki-67 ≥30%: 83.3% vs. 58.8%, p<0.05), while androgen receptor (AR) and PD-L1 positive (combined positive score≥10) rates were lower than of STs cases (AR: 11.1% vs. 47.1%; PD-L1: 9.6% vs. 33.3%, p<0.05). The most commonly altered genes were TP53 (88.7%), PIK3CA (26.8%), MYC (18.3%) in NSTs, and TP53 (68.8%), PIK3CA (50%), JAK3 (18.8%), KMT2C (18.8%) in STs respectively. Compared with NSTs, PIK3CA and TP53 mutation frequency showed difference in STs (47.1% vs 19.4%, p=0.039; 64.7% vs 87.5%, p=0.035). Conclusions: In TNBC patients with STs, decrease in histologic grade and ki-67 index, as well as increase in PD-L1 and AR expression were observed when compared to those with NSTs, suggesting that TNBC patients with STs may better benefit from immune checkpoint inhibitors and/or AR inhibitors. Additionally, lower TP53 and higher PIK3CA mutation rates were also found in STs patients, providing genetic evidence for deciphering at least partly potential mechanism of action.

Submuscular Implant-Based Breast Reconstruction Using a Musculofascial Pocket Formed by the Pectoralis Major Muscle and the Serratus Anterior Muscle Fascia: A Novel Surgical Approach.

BACKGROUND: Subpectoral implant-based breast reconstruction following mastectomy commonly severs the inferior border of the pectoralis major muscle for better projection of the lower pole. This can affect a patient's postoperative motor function and result in animation deformity. Implant-based breast reconstruction using partial muscle coverage with an acellular dermal matrix (ADM) can be costly. There is an unmet clinical need for a novel surgical method for submuscular implant-based breast reconstruction. METHODS: We describe an innovative technique for submuscular implant-based breast reconstruction following mastectomy. The approach utilizes the serratus anterior muscle fascia connected to the lateral margin of the pectoralis major muscle to form a lateral tissue pocket for implant coverage. This method preserves the inferior border of the pectoralis major muscle and minimizes the size of ADM coverage. Patient satisfaction on the BREAST-Q Reconstruction Module and complications were assessed 12 months after surgery. RESULTS: The novel surgical design was safe and used minimal ADM (6 × 5cm2). Mean satisfaction with breasts was 61 ± 4.7 (range, 48-73), mean psychosocial well-being was 66 ± 10 (range, 50-93), and mean sexual well-being was 47 ± 7.8 (range, 27-70). Animation deformity was avoided by preserving the inferior border of the pectoralis major muscle. Rates of revision (7.6%) and postsurgical seroma (3.4%) were low, and capsular contracture was minimal. CONCLUSIONS: Submuscular implant-based breast reconstruction following mastectomy utilizing the serratus anterior muscle fascia connected to the lateral margin of the pectoralis major muscle to form a lateral tissue pocket for implant coverage is safe, feasible, and generates good aesthetic outcomes.

MiR-151b inhibits osteoblast differentiation via downregulating Msx2.

PURPOSE: MicroRNA-151b (miR-151b) showed altered expression in ovariectomized rat model of osteoporosis. This study established an ovariectomy-induced osteoporotic rat model to investigate the role of miR-151b in osteoblasts. METHODS: Eighteen female Sprague-Dawley (SD) rats were divided randomly into Sham and OVX group (n = 9). The transfections with different miRNAs and expression vectors were confirmed by RT-qPCR. The protein expression of Msx2 was detected by Western blots. The interaction between miR-151b and Msx2D was evaluated by RNA pull-down and dual luciferase reporter assay. RESULTS: The expression of miR-151b was significantly increased in femoral tissues of ovariectomy-induced osteoporotic rats. The expression of osteogenesis marker genes including RUNX2, ALP, OCN, OSX, and Msx2 were all significantly increased in osteogenic medium (OM) incubated primary osteoblasts and MC3T3-E1 cells. The interaction between miR-151b and Msx2 was confirmed by luciferase reporter assay and RNA pull-down. Moreover, overexpression of miR-151b significantly inhibited Msx2 in both MC3T3-E1 cells and primary osteoblasts, while miR-151b inhibitor had the opposite effect on the expression of Msx2. In addition, in primary osteoblasts and MC3T3-E1 cells, miR-151b overexpression, or Msx2 silence significantly decreased the expression of OSX, ALP, RUNX2, and OCN. CONCLUSION: MiR-151b could inhibit osteoblast proliferation, differentiation, and mineralization via downregulating Msx2 in both MC3T3-E1 cells and primary osteoblasts. MiR-151b might serve as a novel therapeutic target for osteoporosis. ABBREVIATIONS: miR-151b: microRNA-151b; miRNAs: microRNAs; Msx2: Msh homeobox 2; MAPK: mitogen-activated protein kinase; STAT: signal transducer and activator of transcription; SD: Sprague-Dawley; BMD: bone mineral density; qRT-PCR: quantitative reverse transcription PCR; MTT: methyl thiazolyl tetrazolium; OVX: ovariectomy; ALP: alkaline phosphatase.

Integrated analysis of cell cycle-related genes in HR+/HER2- breast cancer.

PURPOSE: This study aimed to explore the mutational characteristics and significance of cell cycle-related genes (CCGs) in hormone-receptor positive, human epidermal growth factor receptor 2 negative breast cancer (HR+/HER2- BC). METHODS: A total of 1668 HR+/HER2- BC patients from the Guangdong Provincial People's Hospital (GDPH) cohort (n = 321) and METABRIC cohort (n = 1347) were included. Tumor samples from HR+/HER2- BC patients were collected for a next-generation sequencing assay in GDPH cohort, including 15 key CCGs. The association between CCGs alterations and overall survival were identified via the Cox regression analysis. The functional roles of the CCGs were explored via the Metascape database. RESULTS: Based on multivariate Cox regression analysis, a set of five key CCGs (CDK4, CCND1, CDKN1A, CDKN1C, and CHEK2) were identified as independent prognostic variables in HR+/HER2- BC patients. Besides, the five-CCGs-based risk score was used to effectively classify patients into the low-risk and high-risk groups (P < 0.0001). The potential functional pathways of the CCGs included cell cycle, cyclin D associated events in G1, and regulation of G1/S transition of mitotic cell cycle. CONCLUSION: We performed the integrated analysis of the CCGs in HR+/HER2- BC patients. It has the potential to guide individualized precision oncology therapeutic schemes in HR+/HER2- BC patients.

Differential Second Primary Malignancy Occurrence After Breast Cancer According to HER2 Status: A Population-Based Study.

PURPOSE: Our study aims to analyze the association between HER2 status of breast cancer (BC) and second primary malignancy (SPM) occurrence. MATERIALS AND METHODS: Based on BC patients registered between 2010 and 2018 in the NCI SEER database, we utilized standardized incidence ratio (SIR) and Poisson regression to quantify SPM occurrence compared with the general population. Then, adjusted for competing death risk, cumulative incidence function and Gray's test were adopted to estimate the probability of SPM. Subsequent proportional subdistribution hazards regression was executed to identify the HER2 status impact on SPM risk. Finally, survival analysis was performed. RESULTS: A total of 409,796 first BC patients were included and 18,283 were identified with at least one SPM. The SIR of SPM after HER2+ BC was significantly lower than HER2- BC (1.03 vs 1.13; RR, 0.92; 95% CI, 0.88-0.96; p<0.001). The predominantly declining SPM risk was only observed for second BC (RR, 0.89; 95% CI, 0.82-0.96; p=0.003) and lung cancer (RR, 0.84; 95% CI, 0.74-0.95; p=0.007). Furthermore, competing risk analysis verified the protective effect of HER2 positivity status on SPM occurrence. The 5-year cumulative incidence of SPM following HER2+ and HER2- BC were 4.09% and 5.16%, respectively (p<0.001). In addition, among patients suffering from SPM, HER2 positivity status contributed to better overall survival. CONCLUSION: It is demonstrated that HER2+ BC patients had lower SPM incidence, which was remarkable for second BC and lung cancer.

CDKN1C as a prognostic biomarker correlated with immune infiltrates and therapeutic responses in breast cancer patients.

Breast cancer (BC) prognosis and therapeutic sensitivity could not be predicted efficiently. Previous evidence have shown the vital roles of CDKN1C in BC. Therefore, we aimed to construct a CDKN1C-based model to accurately predicting overall survival (OS) and treatment responses in BC patients. In this study, 995 BC patients from The Cancer Genome Atlas database were selected. Kaplan-Meier curve, Gene set enrichment and immune infiltrates analyses were executed. We developed a novel CDKN1C-based nomogram to predict the OS, verified by the time-dependent receiver operating characteristic curve, calibration curve and decision curve. Therapeutic response prediction was followed based on the low- and high-nomogram score groups. Our results indicated that low-CDKN1C expression was associated with shorter OS and lower proportion of naïve B cells, CD8 T cells, activated NK cells. The predictive accuracy of the nomogram for 5-year OS was superior to the tumour-node-metastasis stage (area under the curve: 0.746 vs. 0.634, p < 0.001). The nomogram exhibited excellent predictive performance, calibration ability and clinical utility. Moreover, low-risk patients were identified with stronger sensitivity to therapeutic agents. This tool can improve BC prognosis and therapeutic responses prediction, thus guiding individualized treatment decisions.

Mitofusin-2 is a novel anti-angiogenic factor in pancreatic cancer.

BACKGROUND: Aberrant expression of mitofusin-2 (MFN2) has been found to be associated with vascular endothelial growth factor A (VEGFA)-mediated angiogenesis in human umbilical vein endothelial cells (HUVECs). This study aimed to investigate the expression of MFN2 in pancreatic cancer (PC) and the role of MFN2 in vascular endothelial cell growth and angiogenesis. METHODS: Protein and mRNA expression of MFN2 and VEGFA were measured. The CCK-8 assay, tube formation assay, flow cytometry, and transmission electron microscopy were used to examine the effects of MFN2 overexpression on HUVEC growth, angiogenesis, and apoptosis. Western blot and immunocytochemical staining were conducted to measure alterations in cell cycle and apoptosis regulators and vascular endothelial growth factor receptor 2 (VEGFR2), angiopoietin-1 gene (ANGPT1), and tissue inhibitor of metalloproteinase 1 (TIMP1) expression in HUVECs. RESULTS: The results showed that MFN2 levels were significantly decreased in tumor tissues. Contrasting results were observed for VEGFA mRNA levels. MFN2 overexpression inhibited cell growth while promoting the formation of apoptotic bodies in HUVECs. Additionally, MFN2 overexpression enhanced the protein expression of p21 and p27 while attenuating the expression of proliferating cell nuclear antigen, VEGFA, VEGFR2, ANGPT1, and TIPM1 in HUVECs. CONCLUSIONS: In conclusion, MFN2 expression negatively correlates with VEGFA expression in PC and inhibits endothelial cell growth and angiogenesis.

Accurate and Feasible Deep Learning Based Semi-Automatic Segmentation in CT for Radiomics Analysis in Pancreatic Neuroendocrine Neoplasms.

Current clinical practice or radiomics studies of pancreatic neuroendocrine neoplasms (pNENs) require manual delineation of the lesions in computed tomography (CT) images, which is time-consuming and subjective. We used a semi-automatic deep learning (DL) method for segmentation of pNENs and verified its feasibility in radiomics analysis. This retrospective study included two datasets: Dataset 1, contrast-enhanced CT images (CECT) of 80 and 18 patients respectively collected from two centers; and Dataset 2, CECT of 56 and 16 patients respectively from two centers. A DL-based semi-automatic segmentation model was developed and validated with Dataset 1 and Dataset 2, and the segmentation results were used for radiomics analysis from which the performance was compared against that based on manual segmentation. The mean Dice similarity coefficient of the trained segmentation model was 81.8% and 74.8% for external validation with Dataset 1 and Dataset 2 respectively. Four classifiers frequently used in radiomics studies were trained and tested with leave-one-out cross-validation strategy. For pathological grading prediction with Dataset 1, the area under the receiver operating characteristic curve (AUC) with semi-automatic segmentation was up to 0.76 and 0.87 respectively for internal and external validation. For recurrence study with Dataset 2, the AUC with semi-automatic segmentation was up to 0.78. All these AUCs were not statistically significant from the corresponding results based on manual segmentation. Our study showed that DL-based semi-automatic segmentation is accurate and feasible for the radiomics analysis in pNENs.

Assessment of the expression and response of PD-1, LAG-3, and TIM-3 after neoadjuvant radiotherapy in rectal cancer.

Many studies have verified the safety of combined radiotherapy and immune checkpoint blockades (ICBs) without the specific radiation dose or sequencing of combination. We aimed to evaluate the expression and response of PD-1, TIM-3, LAG-3 after neoadjuvant radiotherapy (NRT) and explore the possibility and optimal schedule of combining immunotherapy with radiotherapy in treating rectal cancer. Immunohistochemistry was performed to detect the expression of PD-1, TIM-3, LAG-3, CD8, and CD3. These molecules' expression was detected on the specimens of 76 rectal cancer patients following NRT and 13 of these patients before NRT. The expression of ICBs was assessed by the percentage of positive cells. The levels of PD-1 and immune cells (ICs) LAG-3 in rectal cancer increased after NRT (0% vs. 3%, p=0.043 and 5% vs. 45%, p=0.039, respectively). However, TIM-3 in ICs and tumor cells (TCs) were both decreased (80% vs. 50%, p=0.011, 90% vs. 0%, p=0.000, respectively). The LAG-3 expression was higher in patients treated with short-course RT than long-course RT (22.5% vs. 8.0%, p=0.0440 in ICs; 0% vs. 70%, p<0.001 in TCs). On the contrary, CD8 was higher after long-course RT (15% vs. 8%, p=0.0146). Interestingly, the level of ICs TIM-3 was low in > eight weeks after long-course RT (p=0.045). The expressions of PD-1, ICs TIM-3, ICs LAG-3, CD3, and CD8 were associated with the disease-free survival (DFS) in univariate analysis (p=0.036, 0.008, 0.018, 0.025, and 0.004, respectively). Adjusted by the relevant variables, PD-1 (HR 0.274; 95% CI 0.089-0.840; p=0.024) and ICs TIM-3 (HR 0.425; 95% CI 0.203-0.890; p=0.023) were independent prognostic factors of DFS in rectal cancer patients following NRT. In conclusion, we have identified that PD-1 and ICs LAG-3 presented a trend towards increased expression after NRT, supporting the ICBs and NRT combination as a potential treatment option for local advanced rectal cancer patients. The radiotherapeutic mode and timing of the treatment might significantly affect the expression of ICBs, which indicated that the sequencing and time window of ICBs immunotherapy utility might deserve a high value.

Application of a treatment planning system-assisted large-aperture computed tomography simulator to percutaneous biopsy: initial experience of a radiation therapist.

OBJECTIVE: To evaluate the application of treatment planning system (TPS)-assisted large-aperture computed tomography (CT) simulator to percutaneous biopsy. METHODS: This retrospective study enrolled patients that underwent TPS-assisted large-aperture CT simulator-guided percutaneous biopsy from November 2018 to December 2019. Retrospective analyses of puncture accuracy were compared using paired t-test and a Wilcoxon rank sum test. The risk factors for puncture accuracy and complications were identified. RESULTS: A total of 38 patients were included in this study. There were no significant differences between the planned and actual puncture depth and angle. Pulmonary puncture was significantly associated with the accuracy of the puncture angle. The diagnostic rate of malignancy was 76% (29 of 38), of which 20 of 25 patients were in the group initially diagnosed with unconfirmed lesions and nine of 13 patients were in the group of treated patients that needed additional pathological analyses. For patients that underwent a pulmonary biopsy, 12 had minor pneumothorax and three suffered needle track bleeding. No other complications were observed. Regression analyses indicated a significant correlation between puncture angle and the incidence of pneumothorax. CONCLUSION: TPS-assisted large-aperture CT simulator may improve the percutaneous biopsy procedure by combining the advantages of radiotherapy specialties with computer targeting.

The value of color Doppler ultrasound in the diagnosis of thyroid nodules: a systematic review and meta-analysis.

BACKGROUND: This study aimed to analyze the value of color Doppler ultrasound in the diagnosis of thyroid nodules. METHODS: We searched the PubMed, Web of Science, Embase, and Cochrane Library databases for randomized controlled trials (RCTs) on using color Doppler ultrasound, thyroid nodules, thyroid tumors, and Doppler ultrasound to diagnose the thyroid nodules. The outcome indicators in the articles had to include the numbers of true positives (TP), false positives (FP), false negatives (FN), and true negatives (TN). Subsequently, the Jadad tool was adopted to evaluate the quality of the included articles, and Review Manager 5.3 software was used to conduct a meta-analysis of the experimental data. RESULTS: A total of eight suitable articles were selected. The results showed that the estimated sensitivity and specificity of color Doppler ultrasound for the diagnostic of thyroid nodules were 0.46-0.89 and 0.00-1.00, respectively. The pooled estimate of sensitivity for the different articles was 0.71 [95% confidence interval (CI): 0.46-0.89], and the pooled estimate of specificity was 0.77 (95% CI: 0.00-1.00). The area under the summary receiver operating characteristic (SROC) curve (AUC) was 0.917, which was larger than 0.9, signifying high diagnostic accuracy. This suggests that color doppler ultrasound can realize the clinical diagnosis of thyroid nodules. DISCUSSION: In summary, the results of this study could provide a clinical data for the promotion and application of color Doppler ultrasound in the clinical diagnosis of thyroid nodules, as well as further reliable data for follow-up clinical research on the diagnosis and treatment of thyroid nodules.

Role of postoperative radiotherapy in dermatofibrosarcoma protuberans: a propensity score-matched analysis.

OBJECTIVE: This study aimed to evaluate the role of postoperative radiotherapy (RT) in dermatofibrosarcoma protuberans (DFSP) and identify the prognostic factors influencing the disease-free survival (DFS). METHODS: A total of 184 patients with DFSP were analyzed from 2000 to 2016. The regression model was used to examine the prognostic factors for DFS. Baseline covariates were balanced using a propensity score model. The role of RT was assessed by comparing the DFS of the surgery + RT group with that of the surgery group. RESULTS: The median follow-up was 58 months (range, 6-203 months). The 5-year DFS rate was 89.8%. The univariate analysis showed that age ≥ 50 years, presence of fibrosarcoma, margins < 2 cm, and tumor size ≥5 cm were associated with worse DFS (P = 0.002, P <  0.001, P = 0.030, and P = 0.032, respectively). The multivariate Cox regression model revealed that age, margin width, lesion number, and histological subtype independently affected DFS. The Ki-67 expression was related to age and histological subtype. Patients with Ki-67 ≥ 17% showed a worse DFS than those with Ki-67 < 17% (35.8% vs 87.8%, P = 0.002). In the matched cohort, DFS was significantly higher in the S + RT group than in the S group (5-year DFS, 88.1% vs 56.2%, P = 0.044). CONCLUSIONS: Age, margin width, lesion number, and histological subtype were independent risk factors for DFS in patients with DFSP. The high expression of Ki-67 could predict a poor prognosis. Postoperative RT could improve DFS for patients with DFSP.