Efficacy and safety of pyrotinib combined with albumin-bound paclitaxel as first-line treatment for HER2-positive metastatic breast cancer in patients previously treated with adjuvant and/or neoadjuvant trastuzumab therapy: The stage 1 results of a single-arm, phase 2 prospective clinical trial.

OBJECTIVE: It has been observed that the prognosis of patients with HER2-positive metastatic breast cancer has improved significantly with HER2-targeted agents. However, there is still a lack of evidence regarding first-line anti-HER2 treatment options for patients who have received adjuvant and/or neoadjuvant trastuzumab for HER2-positive metastatic breast cancer. Besides, there are no reliable markers that can predict the efficacy of anti-HER2 treatment in these patients. METHODS: Patients who have received adjuvant and/or neoadjuvant trastuzumab for HER2-positive metastatic breast cancer were enrolled. Pyrotinib plus albumin-bound paclitaxel were used as first-line treatment. The primary endpoint was the objective response rate (ORR). The safety profile was also assessed. In order to explore predictive biomarkers using Olink technology, blood samples were collected dynamically. RESULTS: From December 2019 to August 2023, the first stage of the study involved 27 eligible patients. It has not yet reached the median PFS despite the median follow-up being 17.8 months. Efficacy evaluation showed that the ORR was 92.6%, and the DCR was 100%. Adverse events of grade 3 or higher included diarrhoea (29.6%), leukopenia (11.1%), neutropenia (25.9%), oral mucositis (3.7%), and hand-foot syndrome (3.7%). Toll-like receptor 3 (TLR3) and Proto-oncogene tyrosine-protein kinase receptor (RET) were proteins with significant relevance to PFS in these patients. CONCLUSIONS: This study demonstrates that pyrotinib plus albumin-bound paclitaxel as a first-line treatment regimen shows good efficacy and manageable safety for patients who have received adjuvant and/or neoadjuvant trastuzumab for HER2-positive metastatic breast cancer. Besides, a significant association was identified between the expression levels of TLR3 and RET and the PFS in patients.

Effect of longitudinal changes of cachexia on the efficacy and toxicity of immune checkpoint inhibitors in esophageal squamous cell cancer (ESCC) patients.

PURPOSE: Immune checkpoint inhibitors (ICIs) have enhanced survival in advanced esophageal squamous cell cancer (ESCC) patients, but their efficacy varies. Cachexia, characterized by muscle loss and significant weight loss, might influence ICI response. This study examines the relationship between cachexia's longitudinal changes and ICI outcomes in ESCC patients. METHODS: ESCC patients undergoing at least two ICI cycles from 2017 to 2021 were studied. Cachexia's baseline and evolving patterns during ICI treatment were observed. Kaplan-Meier and Cox regression analyses were used to assess cachexia's effect on ICI efficacy. Chi-square tests were used to determine cachexia's link to immune-related adverse effects (irAEs). RESULTS: Two hundred seventy-eight ICI-treated patients had a median progression-free survival (PFS) of 5.78 months and overall survival (OS) of 8.3 months. Pretreatment cachexia led to worse outcomes: PFS 7.87 versus 5.3 months, time to progression (TTP) 10.9 versus 6.1 months, and OS 14.3 versus 9.2 months. Irreversible cachexia showed the poorest results. Cachexia's changes weren't associated with irAEs. CONCLUSION: Baseline and evolving cachexia significantly impact ICI efficacy in ESCC patients. Continuous cachexia monitoring during ICI therapy is crucial for optimal ESCC management.

RAB22A as a predictor of exosome secretion in the progression and relapse of multiple myeloma.

BACKGROUND: Multiple myeloma (MM) is an incurable malignant plasma cell disease. We explored the role of RAB22A in exosome secretion, epithelial-mesenchymal transition (EMT) and immune regulation. METHODS: We obtained MM samples from Gene Expression Omnibus (GEO) data sets. We downloaded the "IOBR" package, and used the "PCA" and "ssGSEA" algorithms to calculate the EMT scores and exosome scores. The "CIBERSORT" package was used to analyze the infiltration of immune cells. We extracted the exosomes of mesenchymal stem cell (MSC) to verify the biological function of RAB22A. RESULTS: The expression level of RAB22A in smoldering multiple myeloma (SMM) and MM patients was significantly higher than that in normal people and monoclonal gammopathy of undetermined significance (MGUS) patients, and the expression level of RAB22A in relapse MM patients was significantly higher than that in newly diagnosed patients. The EMT scores and exosome scores of high RAB22A group were significantly higher than those of low RAB22A group, and the exosome scores of MSC in recurrent patients were significantly higher than those of newly diagnosed patients. In addition, the infiltration levels of monocyte, NK cells resting, eosinophils, T cells regulatory and T cells CD4 memory activated were positively correlated with RAB22A. After down-regulating the expression of RAB22A in MM-MSC, the secretion of exosomes decreased. Compared with the exosomes of MSC in si-RAB22A group, the exosomes in control group significantly promoted the proliferation of MM. CONCLUSIONS: RAB22A is a potential therapeutic target to improve the prognosis of MM, which is closely related to exosome secretion, EMT and immune cell infiltration.

Clinical efficacy of acupuncture in treating postoperative gastrointestinal dysfunction of colorectal cancer, a systematic review and Meta analysis. / é’ˆåˆºæ²»ç–—ç»“ç›´è‚ ç™Œæœ¯åŽèƒƒè‚ åŠŸèƒ½éšœç¢ç–—æ•ˆçš„ 系统评价和Meta分析.

OBJECTIVES: To evaluate the efficacy of acupuncture in the treatment of postoperative gastrointestinal dysfunction(POGD) of colorectal cancer. METHODS: Randomized controlled trials of acupuncture in the treatment of POGD were retrieved from 7 databases including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, VIP Chinese Journal Service Platform, WanFang Data Knowledge Service Platform, and China Biology Medicine disc. The search period ranged from the inception of the databases to November 10th, 2022. The quality of the included literature was assessed using the Cochrane bias risk assessment tool and the modified Jadad scale. Meta analysis was conducted using RevMan 5.4. Regression analysis and bias risk analysis were performed using Stata 16.0. Trial sequential analysis was conducted using TSA 0.9 software. RESULTS: A total of 27 randomized controlled trials involving 2 629 patients were included. Intervention measures included manual acupuncture, electroacupuncture, transcutaneous acupoint electrical stimulation, warm acupuncture, and thumb-tack needle. The results showed that acupuncture treatment significantly reduced time to tolerance of liquid diet after surgery (MD=-13.70, 95% CI=ï¼»-17.94, -9.46ï¼½, P<0.000 01), time to first defecation (MD=-18.20, 95% CI=ï¼»-22.62, -13.78ï¼½, P<0.000 01), time to first flatus (MD=-16.31, 95% CI=ï¼»-20.32, -12.31ï¼½, P<0.000 01), time to bowel sounds recovery (MD=-11.91, 95% CI=ï¼»-14.01, -9.81ï¼½, P<0.000 01), and length of hospital stay (MD=-1.49, 95% CI=ï¼»-2.27, -0.70ï¼½, P=0.000 2). Regression analysis indicated that cancer type, study quality and number of acupuncture were the main sources of heterogeneity. Bias analysis suggested potential publication bias risks. Trial sequential analysis indicated that the required number of cases had been met and the conclusion was reliable. CONCLUSIONS: Acupuncture is an effective intervention for promoting gastrointestinal recovery in patients undergoing colorectal cancer surgery. Further large-sample and well-designed clinical trials are still needed to compare different acupuncture techniques.

From pixels to patient care: deep learning-enabled pathomics signature offers precise outcome predictions for immunotherapy in esophageal squamous cell cancer.

BACKGROUND: Immunotherapy has significantly improved survival of esophageal squamous cell cancer (ESCC) patients, however the clinical benefit was limited to only a small portion of patients. This study aimed to perform a deep learning signature based on H&E-stained pathological specimens to accurately predict the clinical benefit of PD-1 inhibitors in ESCC patients. METHODS: ESCC patients receiving PD-1 inhibitors from Shandong Cancer Hospital were included. WSI images of H&E-stained histological specimens of included patients were collected, and randomly divided into training (70%) and validation (30%) sets. The labels of images were defined by the progression-free survival (PFS) with the interval of 4 months. The pretrained ViT model was used for patch-level model training, and all patches were projected into probabilities after linear classifier. Then the most predictive patches were passed to RNN for final patient-level prediction to construct ESCC-pathomics signature (ESCC-PS). Accuracy rate and survival analysis were performed to evaluate the performance of ViT-RNN survival model in validation cohort. RESULTS: 163 ESCC patients receiving PD-1 inhibitors were included for model training. There were 486,188 patches of 1024*1024 pixels from 324 WSI images of H&E-stained histological specimens after image pre-processing. There were 120 patients with 227 images in training cohort and 43 patients with 97 images in validation cohort, with balanced baseline characteristics between two groups. The ESCC-PS achieved an accuracy of 84.5% in the validation cohort, and could distinguish patients into three risk groups with the median PFS of 2.6, 4.5 and 12.9 months (P < 0.001). The multivariate cox analysis revealed ESCC-PS could act as an independent predictor of survival from PD-1 inhibitors (P < 0.001). A combined signature incorporating ESCC-PS and expression of PD-L1 shows significantly improved accuracy in outcome prediction of PD-1 inhibitors compared to ESCC-PS and PD-L1 anlone, with the area under curve value of 0.904, 0.924, 0.610 for 6-month PFS and C-index of 0.814, 0.806, 0.601, respectively. CONCLUSIONS: The outcome supervised pathomics signature based on deep learning has the potential to enable superior prognostic stratification of ESCC patients receiving PD-1 inhibitors, which convert the images pixels to an effective and labour-saving tool to optimize clinical management of ESCC patients.

Developing geriatric nursing micro-credentials for undergraduate nursing students based on training objectives: A modified Delphi study.

BACKGROUND: China's population has begun to age rapidly in the past several years and this trend is predicted to continue. In the face of this growing older population, the existing number of aged care personnel, especially medical care professionals, can hardly meet the demand for aged care services. AIM: To develop geriatric nursing micro-credentials (MCs) for undergraduate nursing students based on standardized training objectives and to specify the learning goals and course modules that correspond to each specific MC. DESIGN: Modified Delphi study. METHODS: An initial set of geriatric nursing MCs were developed based on the training objectives. Expert group discussion (n=13) reviewed the clarity and intelligibility of the statements' wording and supplemented the framework. A three-round Delphi survey (n=15) was then employed to obtain a consensus on the learning goals and course modules via an online questionnaire. Descriptive statistics were used to analyze the data. RESULTS: The final geriatric nursing MCs consisted of six courses, namely fundamentals of geriatric nursing (8 modules), geriatric sociology (6 modules), geriatric clinical nursing (3 modules), geriatric psychological nursing (8 modules), geriatric rehabilitation nursing (8 modules) and geriatric hospice care (10 modules). CONCLUSION: Nursing faculty can use the geriatric nursing MCs developed in this study to train current undergraduate nursing students to become backups for current, fully credentialed geriatric caregivers.

The domestic elder abuse in China: Scale development and psychometric properties.

An effective screening tool is essential to elder abuse research. Although several instruments have been developed in China to measure elder abuse, they present several limitations. The instrument development involved three components: (1) generating questionnaire items; (2) questionnaire testing and data collection in older adults; and (3) psychometric evaluation of the Domestic Elder Abuse Scale (DEAS). We collected questionnaire responses from 3725 community-dwelling Chinese older adults. The 26-item DEAS showed good reliability and validity across five dimensions: physical abuse, psychological abuse, financial exploitation, neglect, and abandonment. These five factors accounted for 78.432 % of the total variance, and model fitting results were acceptable. The Cronbach's alpha coefficient of the scale was 0.975, and the test-retest intraclass correlation coefficient (ICC) was 0.934 after 2 weeks. This study developed a five-dimension instrument to measure elder abuse, with good psychometric properties, which can play an essential role in community-based studies in China.

Construction of durable antibacterial cellulose textiles through grafting dynamic disulfide-containing amino-compound and nanosilver deposition.

Cotton textile is very comfortable to wear, and also provides an ideal environment for bacterial propagation, easily causing harm to human health. In order to address this issue, various antibacterial techniques are employed for cotton finishing. However, some processes are complex and involve the use of environmentally unfriendly chemicals. In this work, a durable and efficient antibacterial cotton fabric was prepared via grafting of an amino-compound containing dynamic disulfide bonds, and then in-situ deposition of silver nanoparticles (AgNPs). Briefly, the reactive α-lipoic acid-modified polyethyleneimine (mPEI) was introduced to the cotton fibers via thiol-ene click reaction. Subsequently, the amino groups and dynamically-generated sulfhydryl groups in the mPEI molecules were used to initiate the ultrafast reduction of silver ions without the participation of additional reductant, constructing a stable antibacterial layer on fiber surface. The results reveal that the amino and thiol groups of mPEI could form coordination bonds with the deposited silver nanoparticles, and the antibacterial ability of AgNP@cotton-g-mPEI fabric remains at a high level even after 20 washing cycles. After 30 min of contact with Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), the antibacterial rates against both bacteria reached 99.99 %. Meanwhile, the network matrix constructed by the recombination of the dynamic disulfide bonds in mPEI endows the cotton fabric with detectable wrinkle resistance and encouraging anti-ultraviolet effect. The present work provides a novel alternative for preparation of durable and efficient antibacterial textiles.

Highly elastic photothermal nanofibrillated cellulose aerogels for solar-assisted efficient cleanup of viscous oil spill.

Frequent oil spills and illegal industrial pollutant discharge cause ecological and resource damages, so it is necessary to establish efficient adsorption and recovery strategies for oils in wastewater. Herein, inspired by solar-driven viscosity-breaking, we propose a facile approach to fabricate multifunctional nanofibrillated cellulose-based aerogel with high elasticity, excellent photothermal conversion, efficient selective oil adsorption and antibacterial properties. Firstly, copper sulfide (CuS) nanoparticles were in situ deposited on the template of oxidative nanofibrillated cellulose (ONC), aiming at achieving efficient photothermal effect and antibacterial properties. Ethylene glycol diglycidyl ether (EGDE) was employed to establish multiple crosslinking network between CuS@ONC and polyethyleneimine (PEI). A thin hydrophobic PMTS layer deposited on the surface of aerogel via a facile gas-solid reaction ensured stable oil selectivity. The resulting composite aerogel can rapidly adsorb oil under solar self-heating, significantly reducing the adsorption time from 25 to 5 min. Furthermore, it exhibits excellent adsorption capacities for various oils, retaining over 92 % of its initial capacity even after 20 adsorption-desorption cycles, and the antibacterial properties extend its lifespan. This work offers a promising method for constructing multifunctional aerogels for efficient oil-water separation, especially beneficial for high-viscosity and high-melting-point oil cleanup.

Oblique lateral interbody fusion (OLIF) compared with unilateral biportal endoscopic lumbar interbody fusion (ULIF) for degenerative lumbar spondylolisthesis: a 2-year follow-up study.

BACKGROUND: Oblique lumbar interbody fusion (OLIF) has been proven to be an effective method of indirect decompression for the treatment of Degenerative Lumbar Spondylolisthesis (DLS). However, its superiority over Unilateral biportal endoscopic Lumbar Interbody Fusion (ULIF) has not been reported yet. The current study aimed to compare the clinical and radiological outcomes of OLIF and ULIF in patients with DLS. METHODS: A total of 107 patients were included in this study, divided into two groups according to the surgical methods with 45 patients treated by OLIF combined with anterolateral single screwrod fixation, and 62 patients treated by ULIF. To compare the perioperative parameters (blood loss, operation time, and postop hospitalization) and clinical (the Visual Analog Scale (VAS) scores of the low back pain and leg pain and the Oswestry Disability Index (ODI)) and radiological (disk height (DH), lumbar lordosis (LL), segmental lordosis (SL), the cross-sectional area (CSA) of the spinal canal) results of the two surgical approaches to evaluate their efficacy. RESULTS: Compared with the ULIF group, the blood loss and operation time in the OLIF-AF group were significantly reduced, and the Postop hospitalization was comparable. The VAS scores in both groups were significantly improved compared to preop; however, the VAS score of low back pain in the OLIF-AF group was superior to that in ULIF group throughout the follow-up period (P < 0.05). The improvements in DH, LL, and Segmental angle were significantly lower in the ULIF group, and the expansion rate of CSA in the OLIF-AF group was superior to that in the ULIF group, but the difference was not statistically significant. The fusion rate in OLIF-AF group was significantly higher than that in ULIF group within 6 mo postop, and there was no significant difference at the last follow-up. The incidence of complications was comparable between the two groups, and there was no statistical difference. CONCLUSIONS: Both OLIF-AF and ULIF achieved good short-term results in the treatment of DLS, and both surgical approaches are desirable. However, OLIF-AF has advantages over ULIF in terms of postoperative restoration of lumbar sagittal parameters and earlier intervertebral fusion. Long-term follow-up and larger clinical studies are needed to confirm this result.

Expandable versus static cages in unilateral biportal endoscopy lumbar interbody fusion (ULIF) for treating degenerative lumbar spondylolisthesis (DLS): comparison of clinical and radiological results.

BACKGROUND: In recent years, early rehabilitation after spinal fusion and the recovery of physiological curvature have attracted much attention. Therefore, expandable cages have entered the field of vision of scientists. The goal of the current study was to compare the clinical and radiological results of unilateral portal endoscopic lumbar interbody fusion (ULIF) in the treatment of degenerative lumbar spondylolisthesis (DLS) with expandable versus static cages. METHODS: We retrospectively analysed patients who received ULIF treatment for DLS from May 2019 to February 2021. Patients were categorized by cage type (static vs. expandable), and the main study was the preop and postop clinical and radiological index changes of the patients. RESULTS: Eighty-four patients were included (38 in the static cages group; 46 in the expandable cages group). There was no difference in the preop results between the two groups. The VAS scores for low back and leg pain and ODI scores in the expandable cages group 7 d postop were significantly superior to those in the static cages group (P < 0.05), and the segmental angle and PDH in the expandable cages group postop were significantly higher than those in the static cages group (P < 0.05). The fusions at 6 m postop in the expandable cages group were superior to those in the Static Cages group (P < 0.05). CONCLUSIONS: The results of this study showed that compared with the stable cage group, the expandable cage group had unique advantages in restoring the physiological curvature of the lumbar spine, increasing the fusion rate, and relieving pain in the early postoperative period. ULIF can be used to treat single-segment, mild lumbar spondylolisthesis patients using expandable cages instead of static cages.

Pneumonitis with combined immune checkpoint inhibitors and chemoradiotherapy in locally advanced non-small-cell lung cancer: a systematic review and meta-analysis.

Aims: This study systematically evaluated cases of pneumonitis following combined immune checkpoint inhibitors (ICI) and chemoradiotherapy (CRT) for locally advanced non-small-cell lung cancer (LA-NSCLC). Methods: Studies from Embase, PubMed and the Cochrane Library on patients with LA-NSCLC who received CRT and ICIs were reviewed. The primary outcomes were rates of all-grade, grade 3-5 and grade 5 pneumonitis. Results: Overall, 35 studies involving 5000 patients were enrolled. The pooled rates of all-grade, grade 3-5 and grade 5 pneumonitis were 33.0% (95% CI: 23.5-42.6), 6.1% (95% CI: 4.7-7.4) and 0.8% (95% CI: 0.3-1.2), respectively, with 7.6% of patients discontinuing ICIs because of pneumonitis. Conclusion: The incidence rates of pneumonitis following combined CRT and ICIs for LA-NSCLC were acceptable. However, the pulmonary toxicity of concurrent CRT and nivolumab plus ipilimumab should be noted.

Combined immune checkpoint inhibitors (ICI) and chemoradiotherapy (CRT) may cause severe pneumonitis due to overlapped pulmonary toxicity. However, the safety data on pneumonitis are limited to a small number of prospective clinical trials and retrospective studies with limited evidence. Thus we conducted a systematic review of pneumonitis in relation to the combination treatment. A total of 35 studies, involving 5000 patients, were included for the final analysis. The pooled rates of all-grade, grade 3­5 and grade 5 pneumonitis were 33.0, 6.1 and 0.8%, respectively, and 7.6% of patients stopped taking ICIs because of pneumonitis. The pneumonitis rates following combined CRT and ICIs for LA-NSCLC were acceptable, but the pulmonary toxicity of concurrent CRT and nivolumab plus ipilimumab should be noted.

Highly compressible and hydrophobic nanofibrillated cellulose aerogels for cyclic oil/water separation.

Nanofibrillated cellulose (NFC)-based aerogels are ideal oil-sorbent materials, but the poor structural stability and hydrophilicity restrain their practical applications in the fields of oil/water separation. In the present work, we report a facile strategy for constructing a hydrophobic nanofibrillated cellulose aerogel for cyclic oil/water separation. Briefly, an aerogel matrix of C-g-PEI with multiple cross-linked network structures was constructed via the combined use of oxidized-NFC (ONC), polyethyleneimine (PEI), and ethylene glycol diglycidyl ether (EGDE), followed by rapid in situ deposition of poly(methyl trichlorosilane) (PMTS) through a low-temperature gas-solid reaction. The resulting ONC-based aerogel (C-g-PEI-PMTS) exhibits the advantages of ultralight (53.80 mg/cm3), high porosity (95.73 %), hydrophobicity (contact angle of 130.0°) and remarkable elasticity (95.86 %). Meanwhile, the composite aerogel of C-g-PEI-PMTS is extremely suitable for oil sorption-desorption by a simple mechanical squeezing method. After 10 cycles of sorption-desorption, the sorption capacity of the aerogel towards various oils reached almost the same level as in the first cycle. The filtration separation efficiency for the trichloromethane-water mixtures remained at 99 % after 50 cycles, demonstrating encouraging reusability. In summary, an efficient strategy to prepare NFC-based aerogel with highly compressible and hydrophobic properties is developed, which expands the applications of NFC in the fields of oil/water separation.

Prophylactic cranial irradiation-related lymphopenia affects survival in patients with limited-stage small cell lung cancer.

Background: The study aimed to identify the relations of the absolute lymphocyte count (ALC) nadir during prophylactic cranial irradiation (PCI) and patient outcomes in limited-stage small cell lung cancer (LS-SCLC). Methods: We analyzed 268 L S-SCLC patients who underwent PCI from 2012 to 2019. ALC values were collected prior, during, and 3 months post PCI. Kaplan-Meier and Cox regression analyses were performed to assess the relation of ALC to patient prognosis. Two nomograms were developed on the basis of clinical variables for survival prediction. Results: Compared with the ALC before PCI (1.13 × 109 cells/L), the ALC nadir during PCI was significantly reduced by 0.68 × 109 cells/L (P < 0.001) and raised to 1.02 × 109 cells/L 3 months post PCI. Patients with a low ALC nadir during PCI (<0.68 × 109 cells/L) had inferior progression free survival (PFS) (median PFS: 17.2 m vs. 43.7 m, P = 0.019) and overall survival (OS) (median OS: 29.0 m vs 39.1 m, P = 0.012). Multivariate Cox analysis revealed that age, smoking history, clinical stage, and ALC nadir were independent OS (P = 0.006, P = 0.005, P < 0.001 and P = 0.027, respectively), as well as independent PFS predictors (P = 0.032, P = 0.012, P = 0.012 and P = 0.018, respectively). After internal cross-validation, the corrected concordance indices of the predictive nomograms for PFS and OS were 0.637 and 0.663, respectively. Conclusion: LS-SCLC patients with a low ALC nadir during PCI likely have worse survival outcomes. Dynamic evaluation of the ALC during PCI is recommended for LS-SCLC patients.

Outcome-Supervised Deep Learning on Pathologic Whole Slide Images for Survival Prediction of Immunotherapy in Patients with Non-Small Cell Lung Cancer.

Although programmed death-(ligand) 1 (PD-(L)1) inhibitors are marked by durable efficacy in patients with non-small cell lung cancer (NSCLC), approximately 60% of the patients still suffer from recurrence and metastasis after PD-(L)1 inhibitor treatment. To accurately predict the response to PD-(L)1 inhibitors, we presented a deep learning model using a Vision Transformer (ViT) network based on hematoxylin and eosin (H&E)-stained specimens of patients with NSCLC. Two independent cohorts of patients with NSCLC receiving PD-(L)1 inhibitors from Shandong Cancer Hospital and Institute and Shandong Provincial Hospital were enrolled for model training and external validation, respectively. Whole slide images (WSIs) of H&E-stained histologic specimens were obtained from these patients and patched into 1024 × 1024 pixels. The patch-level model was trained based on ViT to identify the predictive patches, and patch-level probability distribution was performed. Then, we trained a patient-level survival model based on the ViT-Recursive Neural Network framework and externally validated it in the Shandong Provincial Hospital cohort. A total of 291 WSIs of H&E-stained histologic specimens from 198 patients with NSCLC in Shandong Cancer Hospital and 62 WSIs from 30 patients with NSCLC in Shandong Provincial Hospital were included in the model training and validation. The model achieved an accuracy of 88.6% in the internal validation cohort and 81% in the external validation cohort. The survival model also remained a statistically independent predictor of survival from PD-(L)1 inhibitors. In conclusion, the outcome-supervised ViT-Recursive Neural Network survival model based on pathologic WSIs could be used to predict immunotherapy efficacy in patients with NSCLC.

Impact of nab-paclitaxel plus PD-1/PD-L1 inhibitor on chemorefractory relapsed small-cell lung cancer.

Background: The present study evaluated the efficacy and safety of nab-paclitaxel (nab-PTX) with a concurrent PD-1/PD-L1 inhibitor in patients with refractory relapsed small-cell lung cancer (SCLC). Patients & methods: We retrospectively analyzed 240 patients with refractory relapsed SCLC: 40 patients were treated with nab-PTX plus PD-1/PD-L1 inhibitor, and 200 received traditional chemotherapy. Results: Median progression-free survival in the nab-PTX plus PD-1/PD-L1 inhibitor and traditional chemotherapy groups was 3.6 and 2.5 months (p = 0.0021), respectively. The median overall survival was 8.0 and 5.2 months (p = 0.0002), respectively. No new safety issues were identified. Conclusion: Nab-PTX plus PD-1/PD-L1 inhibitor significantly improved survival in patients with refractory relapsed SCLC compared with traditional chemotherapy.

Most patients with refractory relapsed small-cell lung cancer (SCLC) have few treatment options and dismal survival rates. This study analyzed the clinical outcomes and safety profiles of patients treated with nab-paclitaxel (nab-PTX) plus PD-1/PD-L1 inhibitor compared with patients treated with conventional chemotherapy. Notably, treatment with nab-paclitaxel and PD-1/PD-L1 inhibitor was associated with more favorable clinical outcomes, including better overall response and disease control rates, as well as longer overall survival and progression-free survival. In terms of side effect profiles, the two groups were balanced and had a similar incidence of grade ≥3 adverse events, including depleted blood cells and hair loss. To the best of our knowledge, we are the first to report the use of nab-PTX plus PD-1/PD-L1 inhibitor in the treatment of refractory relapsed SCLC. In addition, nab-PTX plus PD-1/PD-L1 inhibitor showed more effective antitumor activity in patients with secondary tumors in the liver, further confirming that nab-PTX plus PD-1/PD-L1 inhibitor is effective for patients with refractory relapsed SCLC.

Comparison of the Incidence Rate of Radiation Pneumonitis Observed in Patients with Advanced Lung Adenocarcinoma Treated with Simultaneous Thoracic Radiotherapy and 1G/2G/3G EGFR-TKIs.

Purpose: The present study aimed to evaluate the incidence rate of radiation pneumonitis (RP) in patients with advanced lung adenocarcinoma treated with first-generation (1G), second-generation (2G), or third-generation (3G) epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) combined with thoracic radiotherapy (TRT). Patients and Methods: Patients with advanced lung adenocarcinoma simultaneously treated with 1G/2G/3G EGFR-TKIs and TRT between 2015-2021 at Shandong Cancer Hospital and Institute were screened. The incidence rate of clinical and imaging RP was compared between the three groups. Results: A total of 200 patients treated with EGFR-TKIs were enrolled in this study, including 100 patients who were treated with 1G EGFR-TKIs, 50 patients who were treated with 2G EGFR-TKIs, and 50 patients who were treated with 3G EGFR-TKIs (patients matched in a 2:1:1 ratio for tumor characteristics). The overall incidence of clinical RP in the 1G, 2G, and 3G EGFR-TKI groups were 29%, 48%, and 28% (p=0.043), respectively, and that of imaging RP were 33%, 58%, and 36% (p=0.010), respectively. The incidence of RP with a clinical grade ≥3 in the three groups were 14%, 28%, and 12% (p=0.055), respectively, and that with an imaging grade ≥3 in the three groups were 11%, 32%, and 10% (p=0.002), respectively. The incidence of clinical RP was higher in the CFRT group than in the SBRT group, with an overall clinical grade of 38% vs 10% (p<0.001) and imaging grade of 46% vs 10% (p<0.001), respectively. In the multivariate analysis, only GTV volume was an independent predictive factor for all risks of clinical and imaging RP. V20 and grouping of 1G/2G/3G EGFR-TKIs were other independent predictive factors for the risk factors of RP for imaging grades. Conclusion: Compared with 2G EGFR-TKIs combined with TRT, 1G or 3G EGFR-TKIs combined with TRT achieved a lower incidence of RP.

Comparison of the Effect of Chemoradiotherapy and Chemotherapy on the Survival of Patients with Primary Diffuse Large B-Cell Lymphoma of the Spine: A SEER-Based Study.

OBJECTIVE: The role of radiotherapy in primary spinal diffuse large B-cell lymphoma (PB-DLBCL) remains controversial. This study explored the effects of chemoradiotherapy and chemotherapy alone on the survival of patients with PB-DLBCL and established an instructive nomogram. METHODS: Survival analysis using the Kaplan-Meier method and log-rank test was performed for patients diagnosed with PB-DLBCL from 1983 to 2016, identified in the Surveillance Epidemiology and End Results database. The Cox regression model was used to analyze the effects of each variable on the overall survival (OS) and construct a nomogram for predicting OS in patients. RESULTS: Overall, 873 patients with PB-DLBCL were included. The patients were divided into the 1983-2001 (227 [26%]) and 2002-2016 (646 [74%]) groups. The 5-and 10-year OS rates of patients with PB-DLBCL in the 2002-2016 group were 62.8% and 49.9%, respectively. The results of the multivariate Cox regression analysis in the 2002-2016 group showed that age, stage, marriage, and treatment strategy were independent prognostic factors. Kaplan-Meier analysis showed that the OS of patients who underwent chemoradiotherapy from 2002 to 2016 was significantly better than that of patients treated with chemotherapy alone. Further subgroup analysis of patients with different stages of DLBCL and at different ages showed that chemoradiotherapy had a better prognosis than chemotherapy alone in stages I-II and age >60 years, whereas the advantages of chemoradiotherapy were not reflected in stages III-IV and age <60 years. CONCLUSIONS: Chemoradiotherapy improves the OS of patients with PB-DLBCL who are aged >60 years or have stage I-II disease. The nomograms established in this study can help clinicians determine prognosis and select treatment strategies.

Integrated multi-dimensional deep neural network model improves prognosis prediction of advanced NSCLC patients receiving bevacizumab.

Background: The addition of bevacizumab was found to be associated with prolonged survival whether in combination with chemotherapy, tyrosine kinase inhibitors or immune checkpoint inhibitors in the treatment landscape of advanced non-small cell lung cancer (NSCLC) patients. However, the biomarkers for efficacy of bevacizumab were still largely unknown. This study aimed to develop a deep learning model to provide individual assessment of survival in advanced NSCLC patients receiving bevacizumab. Methods: All data were retrospectively collected from a cohort of 272 radiological and pathological proven advanced non-squamous NSCLC patients. A novel multi-dimensional deep neural network (DNN) models were trained based on clinicopathological, inflammatory and radiomics features using DeepSurv and N-MTLR algorithm. And concordance index (C-index) and bier score was used to demonstrate the discriminatory and predictive capacity of the model. Results: The integration of clinicopathologic, inflammatory and radiomics features representation was performed using DeepSurv and N-MTLR with the C-index of 0.712 and 0.701 in testing cohort. And Cox proportional hazard (CPH) and random survival forest (RSF) models were also developed after data pre-processing and feature selection with the C-index of 0.665 and 0.679 respectively. DeepSurv prognostic model, indicated with best performance, was used for individual prognosis prediction. And patients divided in high-risk group were significantly associated with inferior PFS (median PFS: 5.4 vs 13.1 months, P<0.0001) and OS (median OS: 16.4 vs 21.3 months, P<0.0001). Conclusions: The integration of clinicopathologic, inflammatory and radiomics features representation based on DeepSurv model exhibited superior predictive accuracy as non-invasive method to assist in patients counseling and guidance of optimal treatment strategies.

Integrating Preoperative Computed Tomography and Clinical Factors for Lymph Node Metastasis Prediction in Esophageal Squamous Cell Carcinoma by Feature-Wise Attentional Graph Neural Network.

PURPOSE: This study aimed to propose a regional lymph node (LN) metastasis prediction model for patients with esophageal squamous cell carcinoma (ESCC) that can learn and adaptively integrate preoperative computed tomography (CT) image features and nonimaging clinical parameters. METHODS AND MATERIALS: Contrast-enhanced CT scans taken 2 weeks before surgery and 20 clinical factors, including general, pathologic, hematological, and diagnostic information, were collected from 357 patients with ESCC between October 2013 and November 2018. There were 999 regional LNs (857 negative, 142 positive) with pathologically confirmed status after surgery. All LNs were randomly divided into a training set (n = 738) and a validation set (n = 261) for testing. The feature-wise attentional graph neural network (FAGNN) was composed of (1) deep image feature extraction by the encoder of 3-dimensional UNet and high-level nonimaging factor representation by the clinical parameter encoder; (2) a feature-wise attention module for feature embedding with learnable adaptive weights; and (3) a graph attention layer to integrate the embedded features for final LN level metastasis prediction. RESULTS: Among the 4 models we constructed, FAGNN using both CT and clinical parameters as input is the model with the best performance, and the area under the curve (AUC) reaches 0.872, which is better than manual CT diagnosis method, multivariable model using CT only (AUC = 0.797), multivariable model with combined CT and clinical parameters (AUC = 0.846), and our FAGNN using CT only (AUC = 0.853). CONCLUSIONS: Our adaptive integration model improved the metastatic LN prediction performance based on CT and clinical parameters. Our model has the potential to foster effective fusion of multisourced parameters and to support early prognosis and personalized surgery or radiation therapy planning in patients with ESCC.