Cryoablation combined with dual immune checkpoint blockade enhances antitumor efficacy in hepatocellular carcinoma model mice.

BACKGROUND: Cryoablation (Cryo) is a minimally invasive treatment for tumors. Cryo can activate the body's immune response, although it is typically weak. The immune response induced by Cryo in hepatocellular carcinoma (HCC) is poorly understood. PD-1 and CTLA-4 monoclonal antibodies are immune checkpoint inhibitors used in immunotherapy for tumors. The combined use of these antibodies with Cryo may enhance the immune effect. METHODS: A Balb/c mouse model of HCC was established and treated with Cryo, immune checkpoint blockade (ICB), or Cryo + ICB (combination therapy). The growth trend of right untreated tumors and survival time of mice were determined. The expression of apoptosis-related proteins was detected by Western blot (WB) assay. The percentages of immune cells and immunosuppressive cells were analyzed by flow cytometry. The numbers of infiltrating T lymphocytes were checked by immunohistochemistry, and the levels of T-cell-associated cytokines were detected by Quantitative real-time Polymerase Chain Reaction (qRT-PCR) assays and Enzyme-Linked Immunosorbent Assays (ELISA) assays. RESULTS: Cryo + ICB inhibited the growth of right untreated tumors, promoted tumor cell apoptosis, and prolonged the survival time of mice. Local T-cell infiltration in right tumor tissues increased after the combination therapy, while the number of immunosuppressive cells was significantly reduced. In addition, the combination therapy may induce the production of multiple Th1-type cytokines but reduce the production of Th2-type cytokines. CONCLUSIONS: Cryo can activate CD8+ and CD4+ T-cell immune responses. Cryo + ICB can relieve the immunosuppressive tumor microenvironment and shift the Th1/Th2 balance toward Th1 dominance, further enhancing the Cryo-induced T-cell immune response and resulting in a stronger antitumor immune response.

PD-1 monoclonal antibodies enhance the cryoablation-induced antitumor immune response: a breast cancer murine model research.

BACKGROUND: It has been demonstrated that cryoablation (Cryo) causes specific T-cell immune responses in the body; however, it is not sufficient to prevent tumor recurrence and metastasis. In this report, we evaluated changes in the tumor immune microenvironment (TIME) in distant tumor tissues after Cryo and investigated the immunosuppressive mechanisms that limit the efficacy of Cryo. METHODS: Bilateral mammary tumor models were established in mice, and we first observed the dynamic changes in immune cells and cytokines at different time points after Cryo. Then, we confirmed that the upregulation of PD-1 and PD-L1 signaling in the contralateral tumor tissue was closely related to the immunosuppressive state in the TIME at the later stage after Cryo. Finally, we also evaluated the synergistic antitumor effects of Cryo combined with PD-1 monoclonal antibody (mAb) in the treatment of breast cancer (BC) mouse. RESULTS: We found that Cryo can stimulate the body's immune response, but it also induces immunosuppression. The elevated PD-1/PD-L1 expression in distant tumor tissues at the later stage after Cryo was closely related to the immunosuppressive state in the TIME but also created the conditions for Cryo combined with PD-1 mAb for BC mouse treatment. Cryo + PD-1 mAb could improve the immunosuppressive state of tumors and enhance the Cryo-induced immune response, thus exerting a synergistic antitumor effect. CONCLUSIONS: The PD-1/PD-L1 axis plays an important role in suppressing Cryo-induced antitumor immune responses. This study provides a theoretical basis for Cryo combined with PD-1 mAb therapy in clinical BC patients.

Healing Diabetic Ulcers with MoO3-X Nanodots Possessing Intrinsic ROS-Scavenging and Bacteria-Killing Capacities.

Diabetic ulcers (DUs) appearing as chronic wounds are difficult to heal due to the oxidative stress in the wound microenvironment and their high susceptibility to bacterial infection. A routine treatment combining surgical debridement with anti-infection therapy is widely used for treating DUs in the clinic, but hardly offers a satisfying wound healing outcome. It is known that a long-term antibiotic treatment may also lead to the drug resistance of pathogens. To address these challenges, new strategies combining both reactive oxygen species (ROS) scavenging and bacterial sterilization have been proposed for fighting against DUs. Following this idea, oxygen deficient molybdenum-based nanodots (MoO3-X ) for healing the DUs are reported. The ROS scavenging ability of MoO3-X nanodots is investigated and the antibacterial property of the nanodots is also demonstrated. The systematic cell and animal experimental results indicate that the MoO3-X nanodots can effectively reduce inflammation, promote epithelial cell regeneration, accelerate angiogenesis, and facilitate DUs recovery. Most importantly, they present excellent capacity to diminish infection of methicillin-resistant Staphylococcus aureus, manifesting the potent application prospect of MoO3-X nanodots for diabetic wound therapy.

BMP9 promotes osteogenic differentiation of SMSCs by activating the JNK/Smad2/3 signaling pathway.

Synovial mesenchymal stem cells (SMSCs) with high proliferation and multi differentiation ability, and low immunogenicity have attracted research attention for their potential application in tissue engineering. Once their ability of osteogenesis is strengthened, it will be of practical value to apply the SMSCs in the field of bone regeneration. The current study aimed to investigate the osteogenic characteristics of SMSCs induced by bone morphogenetic protein 9 (BMP9) both in vitro and in vivo and to elucidate the mechanism underlying these characteristics. Specifically, different BMPs were assessed to determine the protein that would be the most favorable for stimulating osteogenic differentiation of SMSCs following their separation. The BMP9-enhanced osteogenesis of SMSCs was fully investigated in vitro and in vivo, and the c-Jun N-terminal kinase (JNK)/Smad2/3 signaling pathway stimulated by BMP9 was further explored. Our data suggested that BMP9 could significantly promote gene and protein expression of runt-related transcription factor 2, alkaline phosphatase, osteopontin, and osteocalcin, and SP600125, a JNK-specific inhibitor, could effectively decrease this tendency. Similar results were also confirmed in rats with cranial defects. In conclusion, our study indicated that BMP9 promotes bone formation both in vitro and in vivo possibly by activating the JNK/Smad2/3 signaling pathway.

Covered metallic stent for the treatment of malignant esophageal fistula combined with stricture.

BACKGROUND: Esophageal fistula and stricture is rare but life-threatening complication for esophageal cancer. The management of esophageal fistula and stricture remains challenging. We aimed to determine the safety, feasibility and efficacy of covered metallic stent and three tubes placement for the management of esophageal fistula and stricture. METHODS: Between May 2012 and March 2018, all patients with esophageal fistula and stricture were treated using three tubes or covered metallic stent placement. Patients in group A received covered stents and three tubes placement. Patients in group B only received three tubes placement. Continue abscess drainage and nutritional support was performed after procedure. Three tubes or esophageal stents were removed once esophageal fistula heals. The related medical records were retrospectively assessed. RESULTS: Thirty-seven consecutive patients with esophageal fistula and stricture were enrolled, including 26 patients in group A and 11 patients in group B. Stent placement procedure was technically successful in 25 patients (96.2%). A total of 42 covered stents were inserted. Seventeen esophageal stents were successfully removed from 10 patients. The median retention duration was 3.3 months and 3.4 months for stent and abscess drainage tubes, respectively. One perioperative death due to massive hemorrhage was observed 21 days after stent placement. The abscess cavity was decreased or disappeared in 17 cases and 4 cases in group A and group B, respectively. During follow up, patients in group A still showed a significant better condition of normal diet than that in group B (p < 0.05). Fourteen patients died of cancer recurrence, 3 patients died of massive digestive bleeding and 2 patients died of severe pulmonary infection. The median survivals were 14.8 months and 13.2 months for group A and group B, respectively. CONCLUSIONS: Covered metallic stent placement is safe, feasible and efficacious for treatment of esophageal fistula and stricture, with a better condition of normal diet than patients only received three tubes placement.

Superselective embolization for high-flow priapism refractory to medical and surgical treatments.

BACKGROUND: This study aimed to report long-term outcome of superselective embolization in patients with high-flow priapism refractory to medical and surgical treatments. METHODS: From August 2011 until July 2016, 14 patients with high-flow priapism refractory to local treatments were treated and their charts were retrospective reviewed. Clinical evaluation, color Doppler ultrasonography, arteriography and selective embolization were performed. Follow up was performed in all patients. Fourteen men (18-63 years old) were enrolled, with priapism duration of 14 h to 28 days. Internal pudendal arteries or glutaea inferior arteriae were successfully embolized with gelatin sponge particles, polyvinyl alcohol particles or microcoils. RESULTS: Pseudoaneurysm in right femoral artery was found in one case after intervention. The follow-up 1 week later showed that 13 patients were in good condition, the priapism diminished 1-7 days (mean 3.2 ± 0.5 days) after intervention, and 1 patient received second intervention. Mean follow-up was (range 10.8-69.6) months. One patient had recurrent priapism months after embolization and had his penis surgically removed for severe necrosis. CONCLUSIONS: Superselective embolization is safe and effective in high-flow priapism refractory local treatments, with a good long-term prognosis.

Self-expanding segmental radioactive metal stents for palliation of malignant esophageal strictures.

BACKGROUND: Traditional metal stents are not always suitable for patients with circuitous malignant esophageal stricture. PURPOSE: We aimed to report the safety and effectiveness of stent insertion using self-expanding segmental radioactive metal stent in the palliation of malignant esophageal stricture. MATERIAL AND METHODS: We conducted a retrospective analysis of 22 consecutive patients who underwent insertion of segmental radioactive metal stents from November 2016 to March 2019. Technical success, dysphagia score, and complications were analyzed. Kaplan-Meier analysis was used to analyze the survival time. RESULTS: The stenting procedure was successful in all 22 patients with no procedure-related deaths. Twenty-four segmental radioactive metal stents were successfully implanted. A total of 6 (27.3%) complications were found, mainly 5 (22.7%) stent migrations. The median follow-up period was 3.3 months. Stent removal was required in 4 (12.5%) patients due to complete stent migration. The mean dysphagia score decreased significantly after stent insertion (P<0.0001). During follow up, 13 patients survived with no obvious clinical symptom and nine patients died. The mean survival was 9.9 months. CONCLUSION: The stenting procedure using self-expanding segmental radioactive metal stents is safe and effective in dysphagia palliation of malignant esophageal stricture.

Clinical outcomes of transarterial chemotherapy and embolization for vaginal cancer.

AIM: We report clinical outcomes of transarterial embolization in 19 cases of vaginal cancer. METHODS: From August 2011 to October 2019, 19 patients with histologically diagnosed vaginal cancer were identified in our department. Transarterial chemotherapy and embolization was performed for all patients. Patient characteristics, treatment plans and the clinical outcomes, were recorded. RESULTS: Among 19 identified cases, nine of them are squamous cell carcinoma, five of adenocarcinoma, one of adenosquamous carcinoma, two of vaginal malignant melanoma, one leiomyosarcoma and one of stromal sarcoma. Transarterial chemotherapy and embolization was successfully performed in all patients. No related complication was found after intervention treatment. Besides, eight patients received adjuvant chemotherapy, four received both adjuvant chemotherapy and radiotherapy and seven received no therapies. Four patients were cured and seven were stable during follow-up. CONCLUSION: Transarterial embolization appears safe and effective for vaginal cancer, with a currently acceptable prognosis.

Radioactive feeding tube in the palliation of esophageal malignant obstruction.

PURPOSE: A radioactive feeding tube was used to achieve both nutrition and brachytherapy for the treatment for malignant esophageal obstruction. We report the safety and effectiveness of this technique. METHODS: We conducted a retrospective analysis of 16 consecutive patients who employed this technique from January 2015 to March 2018. The radioactive feeding tube was made by binding the 125I seed chain on the feeding tube. Under fluoroscopic guidance, the tube was inserted into the obstructed esophagus, with the seed chain crossing over the segment of malignant esophageal obstruction. Technical success rate, dysphagia score, procedure time and complications were analyzed. Kaplan-Meier analysis was used to analyze the survival time. RESULTS: The radioactive feeding tube was easy to prepare. The technical success rate was 100%, without serious complications such as bleeding or infection. The median procedure time of tube insertion was 44.0 min. The Kamofsky score and Neuhaus dysphagia grading were significantly improved after tube insertion (p < 0.01). On esophageal radiography, the contrast agent passed through the narrow area smoothly. Complete remission (n = 1) and partial remission (n = 13) of local tumor were obtained in 14 patients, and the local tumor control rate was 87.5% (14/16). During follow-up, four patients survived with no obvious clinical symptom and 10 patients died of cancer. The median survival was 12.0 months. CONCLUSION: Preparation of the radioactive feeding tube is simple and easy. The insertion of this kind of tube achieves parenteral nutrition and brachytherapy simultaneously and is safe and effective in dysphagia palliation of malignant esophageal stricture. The radiological-radiotherapeutic procedure could be an alternative tool in the case of refusing other treatments by the patients.

Clinical outcomes of metallic Y-shaped covered stents for bronchopleural fistula around upper carina after lobectomy.

BACKGROUND: Few studies have reported the placement of metallic Y-shaped covered stents (Y stents) for bronchopleural fistula around the upper carina. METHODS: Eighteen patients were treated with Y stents insertion under the guidance of fluoroscopy. All covered stents were custom-designed and inserted to fit the upper carina anatomy. Clinical data and medical imaging data were analyzed retrospectively. RESULTS: The stents were implanted successfully for the first time in 17 patients, and one patient needed a second attempt due to stent migration during withdrawal of the guide wires. In total, 19 small Y single-plugged stents were inserted in the upper carina and 5 large Y stents additionally in the main carina. Nineteen complications were observed in 14 patients, including 4 major complications. Stents were successfully removed in 12 patients due to complications or cure efficacy, for a median duration in place of 89.5 days. One patient lost follow-up. Nine patients were cured, and three had clinical improvement. One patient died of ventricular fibrillation the second day after the procedure and 4 patients died of tumors 7.8 to 91.7 months after stent placement. The 1-, 3-, and 5-year survival rates were 87.5, 80.8 and 80.8%, respectively. CONCLUSIONS: Metallic Y stent placement is technically feasible, effective and safe for bronchopleural fistula disease around the upper carina.

Metallic stent insertion and removal for post-tracheotomy and post-intubation tracheal stenosis.

PURPOSE: To study the safety and effectiveness of fluoroscopic insertion and removal of self-expandable metallic airway stent for post-tracheotomy tracheal stenosis (PTTS) and post-intubation tracheal stenosis (PITS). METHODS: We conducted a retrospective analysis of 32 patients who underwent fluoroscopic stenting from September 2011 to March 2017. The patients ranged in age from 12 to 69 years. Thirty-eight airway stents were implanted, 35 covered stents and three bare stents. Nineteen airway stents were used for 16 cases of PITS or PTTS. All patients underwent chest CT scans with/without bronchoscopy prior to stent removal. The indication of stent removal and post-interventional complications were analyzed. RESULTS: All 38 airway stents were successfully inserted. Insufficient expansion and tissue hyperplasia were most common complications after stenting. Thirty five of 38 airway stents were successfully removed fluoroscopically, with a technical success rate of 92.1%. Routine removal was performed after 2.9 ± 0.3 months, and stent restenosis was found after a mean duration of 2.7 ± 0.3 months. There were six complications of stent removal with no death. Four stents showed strut fracture after removal, of which three stent pieces retained. Two patients showed dyspnea immediately after removal and required mechanical ventilation in PTTS. One patient with PTTS lost of follow-up during a mean period of 33.7 ± 3.9 months. The one-, three- and five-year patency rates were 87.1%, 76.2% and 70.8%, respectively. There was no significant difference between PITS and PTTS. CONCLUSIONS: Fluoroscopic insertion and removal of airway stent is safe and effective for PITS and PTTS. A three-month retention time is reasonable for airway stents.

Interventional radiology protocol for treatment of esophagogastric anastomotic leakage.

PURPOSE: We aimed to determine the safety, feasibility and efficacy of interventional radiology method for the management of esophagogastric anastomotic leakage. METHODS: We retrospectively assessed the medical records of 23 consecutive patients with esophagogastric anastomotic leakage treated using intervention protocol. Patients received three-tube method (abscess drainage tube, gastrointestinal decompression tube and jejunal feeding tube) with or without temporary covered esophageal stent placement. Abscess drainage, anti-inflammatory treatment and nutritional support were performed thereafter. The esophageal stents and three tubes were removed after leakage healing. RESULTS: All patient received three-tube method and eight patients received covered stent placement. All operations were technically successful. After a median of 2.4 months, the stents were successfully removed from five patients. No death, esophageal rupture or massive hemorrhage occurred during procedures. The abscess cavity had markedly decreased in seven patients or disappeared in 16 cases. During follow-up, four patients died of cancer recurrence, one died of heart dysfunction and one died of pulmonary infection. The 1-, 3-, 5-year survival rates were 86.4%, 52.3% and 52.3%, respectively. CONCLUSION: Interventional radiology protocol is safe, feasible and efficacious for treatment for esophagogastric anastomotic leakage.

Metallic small y stent placement at primary right carina for bronchial disease.

BACKGROUND: Metallic large Y stent placement has been used mainly for airway disease around the main carina. However, few studies have reported this treatment for bronchial disease around the primary right carina. METHODS: Twenty-eight patients were treated by small y stent. All stents were custom-designed and placed under fluoroscopic guidance. Clinical and imaging data were analyzed retrospectively. RESULTS: Thirty-one stents were successfully inserted in 28 patients. Twenty-five patients succeed at the first attempt (89.3%), and 3 patients needed a second attempt. Twelve complications occurred in 10 patients (35.7%). Stent restenosis and sputum retention were the most common complications. Five patients underwent successful stent removal due to complications or cure efficacy. During follow up, 17 patients died of tumors and one died of myocardial infarction. The 1-, 3-, and 5-year survival rates were 49.3, 19.6 and 19.6%, respectively. CONCLUSIONS: Metallic small y stent placement is technically feasible, effective and safe for bronchial disease around the primary right carina.

Clinical outcomes and quality of life in patients with Stanford type B aortic dissection after endovascular repair.

BACKGROUND: Aortic dissection is a severe and life-threatening disease that is usually linked with numerous possible complications. Stanford type B aortic dissection patients often choose endovascular repair due to its mini-invasiveness and quick recovery. This study concerns with medial-term outcome and quality of life (QoL) in patients with Stanford type B aortic dissection after endovascular repair. METHODS: From January 2014 until July 2016, 40 patients with Stanford type B aortic dissection received an endovascular repair. Of the total number of patients, 35 were males (87.5%) and 5 females (12.5%), mean aged 80.9±14.1 years. The Medical Outcomes Study-Short Form-36 (MOS SF-36) was used to assess the QoL preoperatively and after endovascular repair. The first follow-up (FU) of SF-36 questionnaire (FU1) was obtained within 3.9±0.3 months after repair, and the second (FU2), 25.6±6.5 months thereafter. RESULTS: None of patient died during the observational period, and one patient lost to FU. SF-36 observation showed the best-scoring domain was 'Role emotion', 'Vitality' and 'Mental health' were also scored well preoperatively. Except for 'Role emotion' and 'Mental health', all remained domains were significantly improved both FU1 and FU2. CONCLUSIONS: Endovascular repair in patients with Stanford type B aortic dissection enables excellent clinical outcomes and QoL.

Agitation thrombolysis and catheter-directed thrombolysis for normotensive patients with acute pulmonary thromboembolism.

OBJECTIVE: To assess the feasibility, efficacy, and safety of agitation thrombolysis and catheter-directed thrombolysis (AT-CDT) in the treatment of normotensive patients with acute pulmonary thromboembolism (PTE). METHODS: A total of 37 consecutive patients of normotensive PTE were treated by AT-CDT between October 2011 and January 2016. Clinical outcomes and mortality were evaluated after the treatment, and follow-up was carried out after hospital discharge. RESULTS: AT-CDT was technically successful in 93.7% (36/37) patients, with one case died from respiratory failure during procedure. The clinical success rate was 91.9% (34/37), one patient died from intracranial hemorrhage 9 days after agitation, and one case showed no improvement. A total of 83.8% (31/37) cases were clinical cured and 8.1% (3/37) cases were relieved during hospitalization. Three cases died of respiratory failure caused by PTE, and two cases died of diseases unrelated to PTE (lung carcinoma/hemoptysis) during a 20-1524 days of follow-up. CONCLUSION: AT-CDT may be a feasible, effective, and safe treatment for normotensive patients with acute PTE.

Predictors of activation among persons with spinal cord injury during hospitalization: A cross-sectional study.

AIM: To test the contributions of self-efficacy, resilience, social support, and negative moods (i.e., anxiety, depression) to patient activation among persons with spinal cord injury (SCI). METHODS: One hundred and twenty-two participants with SCI were recruited from the spinal surgery department at a large general hospital. During the period before discharge after surgery, standardized self-assessment questionnaires were used to collect data on patient activation, self-efficacy, resilience, social support, anxiety, depression, demographics (age, gender, education, marital status), and disease-related information (etiologies, level of injury, American Spinal Injury Association Impairment Scale score). Hierarchical regression analysis, mediation analysis, and moderation analysis were performed in SPSS, Amos, and Jamovi to determine the influencing factors of patient activation. RESULTS: Self-efficacy, resilience, social support, anxiety, and depression uniquely explained 38.2% (p < .001) of the variance in patient activation after controlling for demographic and disease-related covariates. The full model explained 53.7% (p < .001) of the variance in patient activation. In the mediation analysis, self-efficacy, resilience, and social support had partial mediating effects (p < .05). In the moderation analysis, marital status moderated the relationship between self-efficacy and patient activation (p < .05). CONCLUSIONS: Activation of persons with SCI is a positive psychosocial resource related to higher self-efficacy, resilience, and social support. Marital status may affect activation in persons with SCI. The causal relationship between these psychosocial variables needs to be proved by further intervention studies.

CD163 Monoclonal Antibody Modified Polymer Prodrug Nanoparticles for Targeting Tumor-Associated Macrophages (TAMs) to Enhance Anti-Tumor Effects.

Tumor-associated macrophages (TAMs)-based immunotherapy is a promising strategy. Since TAMs are mainly composed of M2-type macrophages, they have a promoting effect on tumor growth, invasion, and metastasis. M2-type macrophages contain a specific receptor CD163 on their surface, providing a prerequisite for active targeting to TAMs. In this study, we prepared CD163 monoclonal antibody modified doxorubicin-polymer prodrug nanoparticles (abbreviated as mAb-CD163-PDNPs) with pH responsiveness and targeted delivery. First, DOX was bonded with the aldehyde group of a copolymer by Schiff base reaction to form an amphiphilic polymer prodrug, which could self-assemble into nanoparticles in the aqueous solution. Then, mAb-CD163-PDNPs were generated through a "Click" reaction between the azide group on the surface of the prodrug nanoparticles and dibenzocyclocytyl-coupled CD163 monoclonal antibody (mAb-CD163-DBCO). The structure and assembly morphology of the prodrug and nanoparticles were characterized by 1H NMR, MALDI-TOF MS, FT-IR UV-vis spectroscopy, and dynamic light scattering (DLS). In vitro drug release behavior, cytotoxicity, and cell uptake were also investigated. The results show that the prodrug nanoparticles have regular morphology and stable structure, especially mAb-CD163-PDNPs, which can actively target TAMs at tumor sites, respond to the acidic environment in tumor cells, and release drugs. While depleting TAMs, mAb-CD163-PDNPs can actively enrich drugs at the tumor site and have a strong inhibitory effect on TAMs and tumor cells. The result of the in vivo test also shows a good therapeutic effect, with a tumor inhibition rate of 81%. This strategy of delivering anticancer drugs in TAMs provides a new way to develop targeted drugs for immunotherapy of malignant tumors.

Liquid metal microspheres with an eddy-thermal effect for magnetic hyperthermia-enhanced cancer embolization-immunotherapy.

Patients with hepatocellular carcinoma (HCC) display poor prognosis because HCC involves a high rate of metastasis and regrowth. Herein, we present an effective strategy to treat HCC using magnetic hyperthermia therapy (MHT)-enhanced cancer immunotherapy combined with transcatheter arterial embolization (TAE). Uniform liquid metal microspheres (LM MSs) obtained by microfluidic technology with powerful eddy-thermal effects could be used as both MHT and TAE agents for effective cancer therapy. The eddy-thermal effect of LM MSs demonstrated effective MHT, whereas LM MS-induced MHT boosted the immune system, promoted immune cell infiltration, and further stimulated powerful immune responses to suppress the growth of distant tumors, together with immune checkpoint blockade therapy. Furthermore, LM MS-lipiodol dispersion displayed excellent efficacy of the combined MHT-TAE in the orthotopic rabbit liver cancer model. Our work not only highlighted that LM MSs could act as effective MHT agents to achieve MHT-enhanced immunotherapy but also presented the significant promise of combining MHT with TAE for the efficient treatment of large orthotopic liver tumors.

Predicting glioblastoma molecular subtypes and prognosis with a multimodal model integrating convolutional neural network, radiomics, and semantics.

OBJECTIVE: The aim of this study was to build a convolutional neural network (CNN)-based prediction model of glioblastoma (GBM) molecular subtype diagnosis and prognosis with multimodal features. METHODS: In total, 222 GBM patients were included in the training set from Sun Yat-sen University Cancer Center (SYSUCC) and 107 GBM patients were included in the validation set from SYSUCC, Xuanwu Hospital Capital Medical University, and the First Hospital of Jilin University. The multimodal model was trained with MR images (pre- and postcontrast T1-weighted images and T2-weighted images), corresponding MRI impression, and clinical patient information. First, the original images were segmented using the Multimodal Brain Tumor Image Segmentation Benchmark toolkit. Convolutional features were extracted using 3D residual deep neural network (ResNet50) and convolutional 3D (C3D). Radiomic features were extracted using pyradiomics. Report texts were converted to word embedding using word2vec. These three types of features were then integrated to train neural networks. Accuracy, precision, recall, and F1-score were used to evaluate the model performance. RESULTS: The C3D-based model yielded the highest accuracy of 91.11% in the prediction of IDH1 mutation status. Importantly, the addition of semantics improved precision by 11.21% and recall in MGMT promoter methylation status prediction by 14.28%. The areas under the receiver operating characteristic curves of the C3D-based model in the IDH1, ATRX, MGMT, and 1-year prognosis groups were 0.976, 0.953, 0.955, and 0.976, respectively. In external validation, the C3D-based model showed significant improvement in accuracy in the IDH1, ATRX, MGMT, and 1-year prognosis groups, which were 88.30%, 76.67%, 85.71%, and 85.71%, respectively (compared with 3D ResNet50: 83.51%, 66.67%, 82.14%, and 70.79%, respectively). CONCLUSIONS: The authors propose a novel multimodal model integrating C3D, radiomics, and semantics, which had a great performance in predicting IDH1, ATRX, and MGMT molecular subtypes and the 1-year prognosis of GBM.