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Purpose. To analyse the efficacy of high-dose methotrexate + adriamycin + cisplatin (HD-MTX + ADR + PDD, MAP) regimens applied to osteosarcoma and the pretreatment and resolution of chemotherapeutic reactions. Methods. The clinical data of 21 patients with osteosarcoma in our hospital from January 2015 to January 2018 were retrospectively analysed. All patients were treated with the MAP protocol, 21 days for 1 cycle, and treated with artificial joint replacement or amputation after 3∼4 cycles of treatment. The tumour tissue necrosis rate, limb preservation success rate after treatment, and chemotherapy response during chemotherapy were counted and analysed for all patients. A local recurrence rate, a distant metastasis rate, and an overall survival rate were recorded during the 3-year follow-up period. Results. After treatment, the percentage of tumour tissue necrosis ≥90% was 85.71% (18/21) and the percentage of successful limb preservation was 57.14% (12/21) in 21 patients with osteosarcoma. During chemotherapy, all 21 patients with osteosarcoma experienced various degrees of chemotherapy reactions, mainly bone marrow suppression of 100% (21/21), gastrointestinal reactions of 100% (21/21), liver function impairment of 66.67% (14/21), and cardiotoxicity of 52.38% (11/21), all of which improved and completed treatment after treatment. During the 3-year follow-up period, the 21 patients with osteosarcoma had a local recurrence rate of 9.52% (2/21), a distant metastasis rate of 28.57% (6/21), and an overall survival rate of 80.95% (17/21). Conclusion. With stringent protection and relief measures, patients with osteosarcoma treated with the MAP regimen have promising near-term outcomes, with high survival rates over 3 years and tolerable chemotherapy responses. The clinical trial is registered under L2015093.

Synthetic signalling receptors enable programmable cellular responses coupling with a customized input. However, engineering a designer force-sensing receptor to rewire mechanotransduction remains largely unexplored. Herein, we introduce nongenetically engineered artificial mechanoreceptors (AMRs) capable of reprogramming non-mechanoresponsive receptor tyrosine kinases (RTKs) to sense user-defined force cues, enabling a de novo designed mechanotransduction. AMR is a modular DNA-protein chimera comprising a mechanosensing-and-transmitting DNA nanodevice grafted on natural RTKs via aptameric anchors. AMR senses intercellular tensile force via an allosteric DNA mechano-switch with tuneable piconewton-sensitive force tolerance, actuating a force-triggered dynamic DNA assembly to manipulate RTK dimerization and activate intracellular signalling. By swapping the force-reception ligands, we demonstrate the AMR-mediated activation of c-Met, a representative RTK, in response to the cellular tensile forces mediated by cell-adhesion proteins (integrin, E-cadherin) or membrane protein endocytosis (CI-M6PR). Moreover, the versatility of AMR allows the reprogramming of FGFR1, another RTK, to customize mechanobiological function, e.g., adhesion-mediated neural stem cell maintenance.

To evaluate the comprehensive complication index(CCI) and Clavien-Dindo classification(CDC) for short-term postoperative complications in radical cystectomy and assess cumulative surgical morbidity to compare sufficient surgical skill.From September 30, 2010, to October 1, 2020, clinical data of patients with urothelial carcinoma who underwent radical cystectomy with urinary diversion were gathered, patients who had only a urinary diversion, bladder sparing surgery, additional abdominal surgeries at the same time were all excluded. The CDC and CCI were utilized to evaluate 30-d complications after radical cystectomy and the relevance of hospital stay was compared between CCI and CDC. The cumulative sum control models (CUSUM) were used to evaluate the overall surgical morbidity of radical cystectomy in our facility and for comparisons between surgeons.This study enrolled a total of 635 individuals, 548 (86.3%) of whom had 1124 problems. The incidence of severe complications (CDC≥ Grade III) was 10.2%. The average CCI was 20.2 ± 14.7. Gender, urinary diversion subtype, procedure method, and surgeon were significantly correlated with the increase of CCI (p 0.05). The CCI demonstrated a better relationship with hospital stay (RCCI can better reflect the incidence of complications for radical cystectomy than CDC, and CCI is more strongly correlated with postoperative hospital stay. The CUSUM-CCI model can reflect the quality of surgical skill for each surgeon instantaneously.

4589 Background: The current strategy for bladder preservation is focused on trimodality treatment, including complete transurethral resection of bladder tumor (cTURBT), with concurrent chemotherapy and radiotherapy. Chemotherapy is usually a cisplatin-based regimen. However, many pts cannot tolerate cisplatin-based chemotherapy and radiation therapy. It fails to meet clinical needs. Meanwhile, the efficacy and safety of checkpoint inhibitors (ICIs) have now been demonstrated. We conduct a study to evaluate ICIs in combination with second-line chemotherapy agents for patients with MIBC. Methods: TRUCE-01 is a phase II trial (NCT04730219) of tislelizumab combined with nab-paclitaxel before cTURBT or radical cystectomy. Pts with pure or mixed urothelial bladder cancer (T2-4a Nx M0) received tislelizumab 200mg on days 1 plus paclitaxel 200mg on days 2 every 3 weeks (Q3W) x 3 cycles followed by cTURBT or radical cystectomy. Imaging evaluation is usually done before and after the drug administration using the same tests to assess the efficacy. Pts who choose to preserve bladder usually continue their medication after cTURBT. This abstract focuses on patients with bladder preservation. Results: Between July 2020 and November 2021, 47 pts completed at least 2 cycles of treatment, 22 (47%) pts received cTURBT, 16 (34%) pts received radical cystectomy and 9 (19%) pts refuse surgery. As for radiological response, 22 achieved complete response (CR), 16 achieved partial response (PR). In the bladder-preserving subgroup, 13 CR pts and 9 PR pts selected cTURBT, pathology showed 17 pT0, 1 pTa, 3 pT1 and 1 pTis. The median medication cycle is 9 (6-11). There were 3 pts experienced grade 3-4 adverse events (CTCAE), a grade 3 rash, a grade 3 gastric perforation and a grade 4 acute renal failure. In addition, The most common grade 1-2 adverse events include alopecia (86%), fatigue (77%), rash (41%), appetite decreases (41%), hyperglycemia (36%), fever (18%), and creatinine increased (14%). Median follow-up 357 (438-291) days with 3 recurrences and 1 death. The 1-year recurrence-free survival rate was 82%. Conclusions: The early efficacy data further support the role of tislelizumab combined with paclitaxel in bladder preservation setting with an acceptable adverse events. Patients with imaging CR or PR after neoadjuvant therapy are preferred for bladder preservation. Enrollment is ongoing. Clinical trial information: NCT04730219.

4507 Background: Pts with multiple or tumors with large invasion areas which are un-completely-resectable through TURBT would be recommended radical cystectomy in the clinical treatment. The KEYNOTE-057 study has illuminated the efficiency of immune checkpoint inhibitors monotherapy in HR-NMIBC pts, with acceptable adverse events (AEs). However, the role of PD-1/PD-L1 inhibitor in combination with chemotherapy in NMIBC pts remains unclear. We report preliminary treatment efficiency, safety data, and exploratory work of TRUCE-02 trial. Methods: TRUCE-02 is a phase II study for NMIBC pts with uncompletely resectable tumour by TURBT. The primary endpoint was complete response(absence of non-muscle-invasive bladder cancer or progressive disease). Pts that meet the criteria would receive tislelizumab 200mg on days 1 plus paclitaxel 200mg on days 2 every 3 weeks (Q3W) x 3 or 4 cycles followed by a comprehensive assessment including pathology, urine cytology, and imageology. Meanwhile, biomarker analyses included programmed death-ligand 1 (PD-L1) expression using the combined positive score (CPS; Dako 22C3 pharmDx assay) and whole transcriptome RNA sequencing of the tumor. Results: Between July 2020 and January 2022, 54 pts were enrolled. 42 pts have completed whole 3 or 4 treatment cycles and reached the primary endpoint. 23 pts achieved CR condition (56%, 95%CI, 43.6% and 74.4%). ORR of 60% (N=25/42, 95%CI, 45.2% and 74.8%). As a secondary endpoint, 33 pts remain cystectomy-free condition (78.6%, 95%CI, 66.2% and 91%). Grade 3-4 AEs were lower than 2%. Urine cytology showed its diagnostic efficiency of 68.42% (95%CI, 61.3% and 75.6%), urine FISH showed a diagnostic efficiency of 45.71% (95%CI, 37.7% and 53.4%) before pathological assessment. As for PD-L1 expression, 47.3% (N = 9/19) of response pts (CR+PR) showed positive, 50% (N = 5/10) of un-response pts (PD+SD) showed positive. We also found out through sequencing results that AR, TCF7L2 might be underlying markers that predict adverse outcomes for pts in this crew. HRR mutation may predict a positive prognosis and mutations in NMIBC which might predict the prognosis of this treatment plan. Conclusions: Tislelizumab with nab-paclitaxel represents a novel treatment option with a satisfactory benefit in treating NMIBC. PD-L1 expression has no obvious correlation with the efficiency of this treatment plan. WGS result also showed that there are mutation markers that may predict whether pts would benefit from this treatment plan. Clinical trial information: NCT04730232. [Table: see text]

4590 Background: Urine cytology is a noninvasive and relatively inexpensive approach that plays an important role in both screening/initial diagnosis of urothelial carcinoma, and surveillance of tumor recurrence; However, interpretation of urine cytology is labor-intensive and time-consuming. Artificial intelligence (AI) has been widely used in the field of medically assisted diagnosis, but it is almost blank in the field of urothelial carcinoma diagnosis based on urine cytology. In this study, artificial intelligence (AI) algorithms have been developed to efficiently and automatically analyze urinary cytological specimens stained with Acridine orange fluorescence for screening and diagnosis of urothelial carcinoma with a good clinical application prospect. Methods: To develop the algorithms, images of urinary cytological specimens with Acridine orange Fluorescence staining were collected from patients who underwent examination, surgery, or both at the Second Hospital of Tianjin Medical University from August 2015 to August 2021. To standardize the urine cytological determination, the images were determined by 3 certified and experienced cytopathologists in this hospital. Images were collected to establish a dataset containing two major categories: Malignant (Defined as images containing malignant cells) and Benign (Defined as images containing malignant cells). From the acquired database, 2794 malignant and 2787 benign eligible images were selected for AI training/validation/testing. Inception V3, a specific type of neural network optimized for image classification called a deep convolutional neural network was trained based on the database. To prevent the model from over-fitting during training, data augmentation methods, such as rotation and flipping were adopted. The diagnosing performance of the binary classification model was analyzed using accuracy, F1 score, operating characteristic (ROC), and the area under the curve (AUC) generated from the sensitivity and specificity to evaluate. Results: A total of 21022 slides of urine cytological specimens with Acridine orange Fluorescence staining were collected. The AI algorithms achieved excellent performance, which showed the best prediction with an accuracy of 92.25%, a sensitivity of 98.50% along with a specificity of 86.00%, the F1score was 0.9271, and the area under the ROC curve was 0.96. Conclusions: Our novel artificial intelligence algorithms could accurately classify urine specimens as malignant or benign efficiently and automatically. The use of AI during cytopathology screening provides a new strategy and technical support for the diagnosis and screen of urothelial carcinoma. [Table: see text]