Parastomal Hernia Following Ileal Conduit: Incidence, Risk Factors, and Health-Related Quality of Life.

PURPOSE: The purpose of this study was to measure the incidence of parastomal hernia (PH) after radical cystectomy and ileal conduit. Secondary aims were the identification of risk factors for PH and to compare the health-related quality of life (QOL) between patients with and without PH. DESIGN: Retrospective review of medical records combined with cross-sectional administration of the QOL instrument and telephone follow-up. SUBJECTS AND SETTING: The study sample comprised 219 patients who underwent radical cystectomy and ileal conduit for urothelial cancer between February 2014 and December 2018. The study setting was Peking University First Hospital (Beijing, China). METHODS: Demographic and pertinent clinical data, including development of PH, were gathered via the retrospective review of medical records. Participants were also asked to complete the traditional Chinese language version of the City of Hope Quality of Life-Ostomy Questionnaire (C-COH). Multiple linear regression analysis was used to identify the effect of PH on C-COH scores. Logistic regression analysis was used to identify risk factors for PH development. RESULTS: At a median follow-up of 34 months (IQR = 21-48), 43 of 219 (19.63%) patients had developed a PH. A body mass index (BMI) indicating overweight (OR = 3.548; 95% CI, 1.562-8.061; P = .002), a prior history of hernia (OR = 5.147; 95% CI, 1.195-22.159; P = .028), and chronic high abdominal pressure postdischarge (CHAP-pd) (OR = 3.197; 95% CI, 1.445-7.075; P = .004) were predictors of PH after operation. There was no significant difference between C-COH scores of patients with or without PH. No significant differences were found when participants with PH were compared to those without PH on 4 factors of the C-COH: physical scores (ß= .347, P = .110), psychological scores (ß= .316, P = .070), spiritual scores (ß=-.125, P = .714), and social scores (ß= .054, P = .833). CONCLUSION: Parastomal hernia is prevalent in patients undergoing radical cystectomy and ileal conduit urinary diversion. Overweight, hernia history, and CHAP-pd were predictors of PH development. No significant differences in QOL were found when patients with PH were compared to those without PH.

Indirect comparisons of efficacy of zanubrutinib versus orelabrutinib in patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma or relapsed or refractory mantle cell lymphoma.

We conducted two indirect comparisons to estimate the efficacy of zanubrutinib versus orelabrutinib in Chinese patients with relapsed or refractory (R/R) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) or R/R mantle cell lymphoma (MCL). An unanchored matching-adjusted indirect comparison (MAIC) was performed in R/R CLL/SLL patients. Individual patient data from zanubrutinib trial (BGB-3111-205) were adjusted to match the aggregated data from the orelabrutinib trial (ICP-CL-00103). A naïve comparison was performed in R/R MCL for the different response assessment methodology and efficacy analysis set between the zanubrutinib (BGB-3111-206) and orelabrutinib (ICP-CL-00102) trials. Efficacy outcomes included ORR and PFS. In R/R CLL/SLL patients, after matching, IRC-assessed ORR was comparable (86.6% vs. 92.5%; risk difference, -5.9% [95% CI: -15.8%-3.8%]); IRC-assessed PFS was similar with a favorable trend in zanubrutinib over orelabrutinib (HR, 0.74 [95% CI: 0.37-1.47]) and the 18-month PFS rate was numerically higher in zanubrutinib (82.9% vs. 78.7%). In R/R MCL patients, naïve comparison showed investigator-assessed ORR was similar (83.7% vs. 87.9%; risk difference, -4.2% [95% CI: -14.8%-6.0%]), and CR rate was significantly higher in zanubrutinib over orelabrutinib (77.9% vs. 42.9%; risk difference, 35.0% [95% CI: 14.5%, 53.7%]). Investigator-assessed PFS was similar with a favorable trend (HR, 0.77 [95% CI: 0.45-1.32]) in zanubrutinib over orelabrutinib and the 12-month PFS rate was numerically higher in zanubrutinib (77.5% vs. 70.8%). MAIC result showed zanubrutinib demonstrated favorable PFS over orelabrutinib for R/R CLL/SLL patients. The naïve comparison showed zanubrutinib had favorable PFS and higher CR rate than orelabrutinib for R/R MCL patients.

Venetoclax-based combination therapy in R/R DLBCL patients with failure of CAR-T therapy.

There are few effective therapeutic options available for R/R DLBCL patients who have undergone CAR-T therapy. We retrospectively assessed 10 R/R DLBCL patients with complete clinical records who received venetoclax-based combination therapy following CAR-T therapy failed in our center between July 2020 and December 2021. After receiving CAR-T therapy, they all relapsed within a few months. As salvage regimens, they were all given venetoclax-based combination therapy. The objective response rate (ORR) was 80 percent, and the complete response rate was 30 percent. At the time of the analysis, 7 patients were still living. Our research has demonstrated that venetoclax-based combination treatment for R/R DLBCL patients who failed CAR-T therapy has a high effectiveness and manageable toxicity.

Orelabrutinib for the treatment of relapsed or refractory marginal zone lymphoma: A phase 2, multicenter, open-label study.

Marginal zone lymphoma (MZL) is an indolent type of non-Hodgkin lymphoma that develops through pathological B cell receptor signaling. Orelabrutinib, a new-generation oral small molecule Bruton's tyrosine kinase inhibitor, was evaluated in relapsed/refractory (r/r) MZL patients. Previously treated r/r MZL patients received orelabrutinib 150 mg once daily in a phase 2, multicenter, single-arm study conducted in China. The primary endpoint was overall response rate (ORR) assessed by an Independent Review Committee (IRC) based on the Lugano 2014 classification. Other efficacy, safety, and pharmacokinetic profiles were evaluated as secondary outcome measures. A total of 111 patients were enrolled, of which 90 patients had MZL confirmed by central pathology review, who were mainly with extra-nodal MZL of mucosa-associated lymphoid tissue (MALT, 46.7%) and nodal MZL (35.6%). The majority had late-stage disease, with stage IV accounting for 75.6%. After a median follow-up duration of 24.3 months, the IRC-assessed ORR was 58.9% (95% confidence interval [CI], 48.0-69.2), with rates of complete response and partial response being 11.1% and 47.8%, respectively. The IRC-assessed median duration of response was 34.3 months, and the IRC-assessed median progression-free survival (PFS) was not reached with a 12-month PFS rate of 82.8% (95% CI, 72.6-89.5). The rate of overall survival at 12 months was 91.0% (95% CI, 82.8-95.4). Common all-grade treatment-related adverse events (TRAEs) included anemia (27.9%), neutrophil count decrease (23.4%), white blood cell count decrease (18.0%), platelet count decrease (17.1%), blood present in urine (16.2%), rash (14.4%), and upper respiratory tract infection (10.8%). Thirty-four patients (30.6%) experienced grade 3 or higher TRAEs. Serious TRAEs occurred in 18 patients (16.2%), of which pneumonia (5.4%) was the most common. Seven patients (6.3%) discontinued orelabrutinib due to TRAEs. Orelabrutinib demonstrated high response rates with durable disease remission and was well tolerated in Chinese patients with r/r MZL.

Immune-induced pneumonia in patients with advanced solid tumors treated with immunotherapy: a real-world assessment.

Aim: To investigate the computed tomography (CT) and clinical characteristics of immunotherapy-induced pneumonitis (IIP) in patients with advanced solid tumors. Patients & methods: CT and clinical data of 254 patients with advanced solid tumors treated with immune checkpoint inhibitors in our hospital were collected retrospectively. Results: The incidences of IIP in patients with non-small-cell lung cancer, lymphoma and gastrointestinal tumors were 19% (19/100), 9.8% (6/61) and 6.2% (4/65), respectively. The median onset time for all 31 IIP patients was 44 days (interquartile range: 24-65). Most IIP patients (21/31) had grade 1-2 disease. Multifocal ground-glass opacities (seen in 21/31 patients) were the main CT findings of IIP. Conclusion: Patients should be alerted to the risk of IIP, an adverse reaction that has a relatively low incidence but which is sometimes life-threatening.

The study aimed to investigate the clinical and computed tomography (CT) features of immunotherapy-induced pneumonitis (IIP) in patients with advanced solid tumors. To describe these characteristics, clinical and CT information of 254 patients with advanced solid tumors who were treated with drugs called immune checkpoint inhibitors were collected. The incidences of IIP in patients with non-small-cell lung cancer, lymphoma and gastrointestinal tumors were 19% (19/100), 9.8% (6/61) and 6.2% (4/65), respectively. The median time taken to develop IIP for all 31 IIP patients was 44 days. Most IIP patients had mild or moderate (grade 1­2) disease. The main CT findings of IIP were abnormalities called multifocal ground-glass opacities (21/31). Most IIP patients can recover well after glucocorticoid discontinuation. This real-world study was done to raise physicians' awareness of the possible development of IIP, an adverse reaction with a relatively low incidence but which is sometimes life-threatening, to highlight the variety of CT manifestations, and to provide advice on regulating the timing and method of glucocorticoid therapy.

Correlation Analysis of Serum 3-NT, NPASDP-4, and S100ß Protein Levels with Cognitive Function in Patients Diagnosed with Cerebral Infarction.

Objective: To observe the levels of serum 3-nitrotyrosine (3-NT), neuronal PAS domain protein 4 (NPASDP-4), and S100ß protein in patients diagnosed with cerebral infarction and analyze their correlation with cognitive dysfunction in these patients. Methods: The study included a cohort of 158 patients suffering from cerebral infarction who were admitted to the Liwan District Hospital of Traditional Chinese Medicine between January 2021 and December 2022. After stabilizing vital signs, all patients underwent the Montreal Cognitive Assessment (MoCA) to assess their cognitive function. Based on the assessment results, they were divided into two groups: the cognitive dysfunction group (121 cases) and the normal cognitive function group (37 cases). The baseline characteristics and serum levels of 3-NT, neuronal PAS domain protein 4 (NPASDP-4), and S100ß protein were compared in the patient cohorts. Furthermore, the correlation between these three indicators and cognitive function in patients suffering from cerebral infarction was analyzed. A logistic regression model was constructed to analyze how serum levels of 3-NT, NPASDP-4, and S100ß protein levels affected cognitive function in patients suffering from cerebral infarction. ROC curve analysis was conducted to assess the predictive value of serum 3-NT, NPASDP-4, and S100ß protein levels for cognitive function in patients suffering from cerebral infarction. Results: Among the 158 patients with cerebral infarction, 121 (76.58%) had cognitive dysfunction, while 37 (23.42%) had normal cognitive function. The levels of 3-NT, NPASDP-4, and S100ß protein were found to be significantly higher in the cognitive dysfunction group compared to the normal cognitive function group (t = 5.788, 7.774, 6.460; P = .000, .000, .000). The point-biserial correlation analysis results showed a positive correlation between serum levels of 3-NT, NPASDP-4, and S100ß protein and the occurrence of cognitive dysfunction in patients suffering from cerebral infarction (r=0.420, 0.529, 0.424; P = .000, .000, .000). The logistic regression model demonstrated that serum levels of 3-NT(95%CI: 1.299-2.603), NPASDP-4(95%CI: 1.487-3.386), and S100ß protein(95%CI: 1.153-8.746) were risk factors for cognitive dysfunction in patients suffering from cerebral infarction (OR=1.839, 2.244, 1.429; P = .001, .000, .240). ROC curve analysis demonstrated that serum 3-NT, NPASDP-4, and S100ß protein levels exhibited a certain predictive value for cognitive function in patients with cerebral infarction (AUC = 0.789, 0.881, 0.820). Conclusion: Serum levels of 3-NT, NPASDP-4, and S100ß protein are closely related to the cognitive function of patients with cerebral infarction, and abnormal changes in these levels may exacerbate cognitive dysfunction in these patients.

Camrelizumab for relapsed or refractory classical Hodgkin lymphoma: Extended follow-up of the multicenter, single-arm, Phase 2 study.

Camrelizumab (a humanized high-affinity IgG4 mAb against programmed death-l) showed potent antitumor activity, well tolerance and controllable safety in patients with relapsed or refractory classical Hodgkin lymphoma (r/r cHL), based on the primary analysis of a Phase 2 study. Here, we present the extended follow-up outcomes. Seventy-five patients who had failed to achieve a remission or experienced progression after autologous stem cell transplantation or had received at least two lines of systemic chemotherapies were enrolled to receive camrelizumab 200 mg every 2 weeks. With a median follow-up of 36.2 months (range, 7.2-38.1), objective response rate per independent central review was 76.0% (95% confidence interval [CI], 64.7-85.1). Among the 57 responders, 31 (54.4%) had ongoing responses. Median duration of response was 31.7 months (95% CI, 16.7-not reached). Median progression-free survival was 22.5 months (95% CI, 14.7-not reached). Thirty-six-month overall survival rate was 82.7% (95% CI, 72.0-89.5). Reactive capillary endothelial proliferation (RCEP) occurred in 97.3% of patients (73/75), but all RCEP were Grade 1 or 2 in severity and 67.1% of these patients (49/73) achieved complete resolution. Occurrence of new RCEP lesions was rare (8/42 [19.0%] at 12 months; 2/32 [6.3%] at 24 months). No treatment-related deaths occurred, and no new toxicities were reported. With extended follow-up, camrelizumab monotherapy continues to provide a robust and durable response, long survival and manageable safety in r/r cHL patients.

Epstein-Barr virus and cytomegalovirus reactivation after allogeneic hematopoietic cell transplantation in patients with non-Hodgkin lymphoma: the prevalence and impacts on outcomes : EBV and CMV reactivation post allo-HCT in NHL.

Epstein-Barr virus (EBV) and cytomegalovirus (CMV) reactivations are common complications after allogeneic hematopoietic cell transplantation (allo-HCT), but data focusing on non-Hodgkin lymphoma (NHL) are limited. We retrospectively analyzed the prevalence of EBV and CMV reactivation post-allo-HCT and the impacts on transplant outcomes in 160 NHL patients. The 1-year incidences of EBV and CMV reactivation were 22.58% and 25.55%, respectively. Independent impactors for EBV reactivation were more than 6 lines of chemotherapy (P = 0.030), use of rituximab (P = 0.004), and neutrophil recovery within 30 days post-HCT (P = 0.022). For T-cell lymphoblastic lymphoma patients, the International Prognostic Index (IPI) (P = 0.015) and chronic GVHD (P = 0.001) increased the risk of CMV reactivation. CMV reactivation was independently related to a lower risk of relapse (P = 0.027) but higher transplant-related mortality (TRM) (P = 0.038). Although viral reactivation had no significant impact on overall survival (OS) in the whole cohort, it led to an inferior 2-year OS (67.6% versus 92.5%, P = 0.005) and TRM (20.1% versus 4.7%, P = 0.020) in recipients surviving for more than 180 days. We concluded that EBV and CMV reactivation post-allotransplant still deserved concern particularly in NHL patients with high-risk factors, since it is generally related to a deteriorated prognosis. Large-scale studies are warranted to validate our findings.

Laparoscopic versus open radical cystectomy in 607 patients with bladder cancer: Comparative survival analysis.

OBJECTIVES: To compare perioperative and oncologic survival outcomes between laparoscopic radical cystectomy and open radical cystectomy. METHODS: A total of 607 patients underwent open radical cystectomy (n = 412) or laparoscopic radical cystectomy (n = 195) at a single academic institution from January 2006 to April 2017. Their medical records were retrospectively analyzed. One-to-one propensity score matching was carried out to reduce selection bias. Estimated blood loss and complications were compared. Overall survival, cancer-specific survival and progression-free survival estimates for all patients and patients with locally advanced bladder cancer were analyzed using the Kaplan-Meier method. RESULTS: Either before or after matching, the laparoscopic radical cystectomy group had less estimated blood loss (P < 0.001 and P < 0.001) and fewer complications (P < 0.001 and P = 0.008). There was no difference in the overall survival (P = 0.216 and P = 0.961) and progression-free survival (P = 0.826 and P = 0.462) for all the patients having either laparoscopic radical cystectomy or open radical cystectomy. However, the 5-year progression-free survival of open radical cystectomy was higher than that of laparoscopic radical cystectomy (P = 0.019 and P = 0.021) for patients with locally advanced bladder cancer. CONCLUSIONS: Laparoscopic radical cystectomy is superior to open radical cystectomy in terms of perioperative outcomes, and similar to open radical cystectomy in terms of oncologic outcomes for patients with early stage bladder cancer. However, for patients with locally advanced bladder cancer, laparoscopic radical cystectomy seems to be associated with shorter progression-free survival than open radical cystectomy.

MYC-regulated lncRNA NEAT1 promotes B cell proliferation and lymphomagenesis via the miR-34b-5p-GLI1 pathway in diffuse large B-cell lymphoma.

BACKGROUND: LncRNA NEAT1 has been identified as a tumour driver in many human cancers. However, the underlying mechanism of lncRNA NEAT1 in diffuse large B-cell lymphoma (DLBCL) progression is unclear. METHODS: The expression levels of NEAT1, GLI1 and miR-34b-5p were detected by RT-qPCR and Western blotting in DLBCL tissues and cell lines. MTT and colony formation assays were performed to examine cell proliferation, while annexin-V staining and TUNEL assays were performed to measure cell apoptosis. The effect of NEAT1, GLI1 and miR-34b-5p on cell cycle-associated proteins was evaluated by Western blotting. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were employed to investigate the interaction between NEAT1 and miR-34b-5p or GLI1 and miR-34b-5p. Moreover, chromatin immunoprecipitation (ChIP) was performed to demonstrate the interaction between MYC and NEAT1. RESULTS: NEAT1 and GLI1 were upregulated while miR-34b-5p was downregulated in DLBCL tissues and cell lines compared to normal controls. Knockdown of NEAT1 or overexpression of miR-34b-5p inhibited cell proliferation but promoted cell apoptosis. Overexpression of NEAT1 reversed GLI1-knockdown induced attenuation of cell proliferation. In other words, NEAT1 acted as a competing endogenous RNA (ceRNA), regulating the miR-34b-5p-GLI1 axis, further affecting the proliferation of DLBCL. Moreover, MYC modulated NEAT1 transcription by directly binding to the NEAT1 promoter. CONCLUSION: We revealed that MYC-regulated NEAT1 promoted DLBCL proliferation via the miR-34b-5p-GLI1 pathway, which could provide a novel therapeutic target for DLBCL.

Modified BuCy is an alternative conditioning regimen for lymphoma patients undergoing autologous stem cell transplantation.

The aim of this study is to determine whether the modified BuCy (semustine, cytarabine, busulfan, and cyclophosphamide, mBuCy) conditioning regimen can be safely used as an alternative to the SEAM (semustine, etoposide, cytarabine, and melphalan) regimen by comparing the efficacy and toxicity of the mBuCy and SEAM regimens. We matched 34 pairs of patients with regard to disease status at the time of autologous stem cell transplantation (auto-SCT). We found no significant difference in the time of platelet engraftment between the two groups. Furthermore, neutrophil engraftment was somewhat faster in the mBuCy group than in the SEAM group (median: 9 days vs 10 days, p = 0.015). With regard to toxicity, the incidence of nausea/vomiting, hepatic impairment, renal impairment, pulmonary infection, and treatment-related mortality (TRM) was similar between the two groups. In addition, compared to patients conditioned with SEAM, patients conditioned with mBuCy were less likely to develop mucositis and diarrhea (p = 0.027; p = 0.050). The 2-year progression-free survival (PFS) rates in the mBuCy and SEAM groups were 79% and 70% (p = 0.378), respectively, and the 2-year overall survival (OS) rates were 81% and 78.0%, respectively (p = 0.789). These analyses showed that the mBuCy conditioning regimen was well tolerated and can be used as an alternative to the SEAM regimen for lymphoma.

Is hysterectomy beneficial in radical cystectomy for female patient with urothelial carcinoma of bladder? A retrospective analysis of consecutive 112 cases from a single institution.

BACKGROUND: There is no criterion for determining whether female patients operated with cystectomy would benefit from hysterectomy. This study compares the oncological outcomes between female patients receiving uterus preserving cystectomy (UPC) and uterus excision cystectomy (UEC). METHODS: Retrospective review of 121 female patients with urothelial carcinoma of bladder undergoing UPC (n = 63) or UEC (n = 49) at a single institute between January 2006 and April 2017. Individual postoperative follow-up plans were performed for patients through outpatient visits. Overall survival (OS) and progression-free survival (PFS) estimates were analyzed using Kaplan-Meier method and multivariable Cox regression. RESULTS: The median follow-up time was 36 months (interquartile range 16-69). Among patients, 5 (4.1%) had uterus invasion. OS probability (p = 0.939) and PFS probability (p = 0.565) were similar in two groups. In multivariable Cox regression analysis, hysterectomy was not found to be a predictor of OS (hazard ratio 0.908, 95%CI 0.428-1.924, p = 0.801) and PFS (hazard ratio 1.109, 95%CI 0.439-2.805, p = 0.826) after adjusting for age, preoperative clinical stage, pathological stage, pathological nodal stage, neoadjuvant/adjuvant chemotherapy, location of the tumor, and surgical margin. No significant difference of overall survival probability was observed in the patients with organ-confined bladder cancer (p = 0.675) and in patients with no organ-confined bladder cancer (p = 0.695). CONCLUSIONS: The results showed that the rate of uterus invasion was low in patients analyzed in this cohort. It was also found that hysterectomy was not an independent predictor of OS and PFS after radical cystectomy in patients with bladder cancer.

Outcome of Allogeneic and Autologous Hematopoietic Cell Transplantation for High-Risk Peripheral T Cell Lymphomas: A Retrospective Analysis From a Chinese Center.

Peripheral T cell lymphomas (PTCLs) often carry poor outcomes with conventional chemotherapy, and hematopoietic cell transplantation (HCT) can benefit patients with PTCL. We conducted a retrospective review of 67 patients with PTCL who underwent autologous HCT (autoHCT, n = 43; median age, 40 years) or allogeneic HCT (alloHCT, n = 24; median age, 36.5 years) from 2004 to 2016. With a median follow-up of 27 months, 5-year progression-free survival (PFS) and overall survival (OS) of autoHCT patients were 49% and 57%, respectively. Among alloHCT recipients, the 5-year PFS and OS were 54% and 55%, respectively. When considering incidence of disease relapse or progression (CIR) and nonrelapse mortality (NRM), the 5-year CIR and 1-year NRM of alloHCT recipients were 38% and 18%, respectively, and 58% and 7% for autoHCT patients, respectively. There were no differences between autoHCT and alloHCT in 5-year PFS (P = .499), OS (P = .566), CIR (P = .555), and NRM (P = .202). When specifically examining recipients in primary refractory disease, 3-year PFS rates of autoHCT and alloHCT were 20% and 49% (P = .054); 3-year OS rates were 20% and 53% (P = .042), respectively. Based on these results, we favor proceeding to alloHCT in patients with PTCL in primary refractory disease.

Outcomes of allogeneic hematopoietic stem cell transplantation in R/R DLBCL patients with failure of CAR-T therapy.

From October 2017 to June 2022, we retrospectively report outcomes of R/R DLBCL patients with failure of CAR-T therapy, then receiving allo-HSCT. Among 10 patients, 5 were males and 5 females, with a median age of 43.5 (27-52) years. All patients were diagnosed refractory/relapsed diffuse large B cell lymphoma. The median time from CAR-T treatment to transplantation was 84.5 (31-370) days. The median follow-up was 21 (3-69) months. 5/10 patients attained CR and 1/10 patient attained PR during the follow up. The objective response rate (ORR) was 60%. The 1-year overall survival (OS) and progression-free survival (PFS) were 70% and 40%, respectively. At the time of the analysis, 6 patients were still living. During the follow up, four patients have died and the causes were disease relapses and progressions (2 patients), acute renal failure (1 patient), severe pulmonary infection (1 patient). Non-relapse was 20.0%.

Development of a radiomic-clinical nomogram for prediction of survival in patients with diffuse large B-cell lymphoma treated with chimeric antigen receptor T cells.

BACKGROUND: In our current work, an 18F-FDG PET/CT radiomics-based model was developed to assess the progression-free survival (PFS) and overall survival (OS) of patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who received chimeric antigen receptor (CAR)-T cell therapy. METHODS: A total of 61 DLBCL cases receiving 18F-FDG PET/CT before CAR-T cell infusion were included in the current analysis, and these patients were randomly assigned to a training cohort (n = 42) and a validation cohort (n = 19). Radiomic features from PET and CT images were obtained using LIFEx software, and radiomics signatures (R-signatures) were then constructed by choosing the optimal parameters according to their PFS and OS. Subsequently, the radiomics model and clinical model were constructed and validated. RESULTS: The radiomics model that integrated R-signatures and clinical risk factors showed superior prognostic performance compared with the clinical models in terms of both PFS (C-index: 0.710 vs. 0.716; AUC: 0.776 vs. 0.712) and OS (C-index: 0.780 vs. 0.762; AUC: 0.828 vs. 0.728). For validation, the C-index of the two approaches was 0.640 vs. 0.619 and 0.676 vs. 0.699 for predicting PFS and OS, respectively. Moreover, the AUC was 0.886 vs. 0.635 and 0.778 vs. 0.705, respectively. The calibration curves indicated good agreement, and the decision curve analysis suggested that the net benefit of radiomics models was higher than that of clinical models. CONCLUSIONS: PET/CT-derived R-signature could be a potential prognostic biomarker for R/R DLBCL patients undergoing CAR-T cell therapy. Moreover, the risk stratification could be further enhanced when the PET/CT-derived R-signature was combined with clinical factors.

Chimeric antigen receptor T cells targeting FcRH5 provide robust tumour-specific responses in murine xenograft models of multiple myeloma.

BCMA-targeting chimeric antigen receptor (CAR) T cell therapy demonstrates impressive clinical response in multiple myeloma (MM). However, some patients with BCMA-deficient tumours cannot benefit from this therapy, and others can experience BCMA antigen loss leading to relapse, thus necessitating the identification of additional CAR-T targets. Here, we show that FcRH5 is expressed on multiple myeloma cells and can be targeted with CAR-T cells. FcRH5 CAR-T cells elicited antigen-specific activation, cytokine secretion and cytotoxicity against MM cells. Moreover, FcRH5 CAR-T cells exhibited robust tumoricidal efficacy in murine xenograft models, including one deficient in BCMA expression. We also show that different forms of soluble FcRH5 can interfere with the efficacy of FcRH5 CAR-T cells. Lastly, FcRH5/BCMA-bispecific CAR-T cells efficiently recognized MM cells expressing FcRH5 and/or BCMA and displayed improved efficacy, compared with mono-specific CAR-T cells in vivo. These findings suggest that targeting FcRH5 with CAR-T cells may represent a promising therapeutic avenue for MM.

[Influence of rosiglitazone and all-trans-retinoic acid on angiogenesis and growth of myeloma xenograft in nude mice].

OBJECTIVE: To observe the effect of rosiglitazone (RGZ) and all-trans-retinoic acid (ATRA) on the growth of myeloma xenograft in nude mice and to explore the influence of RGZ and ATRA on VEGF expression and angiogenesis in the tumor. METHODS: VEGF gene expression in myeloma cell line U266 cells was analyzed by semi-quantitative RT-PCR after incubation with RGZ, ATRA, or RGZ + ATRA for 24 h. Myeloma xenograft was established by subcutaneous injection of 10(7) U266 cells in the scapula area of 4-week old nude mice. 7 days later, the nude mice were administered with RGZ, ATRA or RGZ + ATRA, respectively, by intraperitoneal injection once every day for 21 days. The control mice were given equal volume of normal saline instead of the drug. On the 21(st) day of treatment, the mice were sacrificed and the tumors were taken off, and the tumor volume and weight were measured. The tumors were examined by histopathology with HE staining, and microvessel density (MVD), CD34 and VEGF expression in the tumors were analyzed by immunohistochemical staining. RESULTS: VEGF mRNA was highly expressed in U266 cells and was decreased in a dose-dependent manner after incubation with RGZ. The VEGF mRNA level was further more decreased after RGZ + ATRA treatment. Xenografts of U266 cells were developed in all nude mice. The volume and weight of xenografts in the RGZ group were (785 ± 262) mm(3) and (1748 ± 365) mg, respectively, significantly lower than those of the control group (both P < 0.01). More significant inhibition was in the RGZ + ATRA group, (154 ± 89) mm(3) and (626 ± 102) mg, respectively, both were P < 0.05 vs. the RGZ group. RGZ inhibited the angiogenesis in U266 xenografts and immunohistochemical staining showed that the tumor MVD and VEGF expression were significantly decreased by RGZ treatment, and further more inhibited in the RGZ + ATRA group. VEGF protein was expressed in all xenografts in the nude mice. Its immunohistochemical staining intensity was 2.20 ± 0.40 in the control group, significantly higher than that of 1.48 ± 0.37 in the RGZ group (P < 0.01), and that of RGZ + ATRA group was 0.58 ± 0.26, further significantly lower than that of the RGZ group (P < 0.01). CD34 was expressed in all xenografts, most highly in the control group and lowest in the RGZ + ATRA group. The microvessel density (MVD) was highest in the control group (56.4 ± 15.2), significantly lower in the RGZ group (44.6 ± 11.2) (P < 0.05), and lowest in the RGZ + ATRA group (21.5 ± 8.6, P < 0.01). CONCLUSIONS: The growth of myeloma cells can also be inhibited by RGZ and ATRA in nude mice in vivo. In addition to differentiation and apoptosis induction, RGZ can inhibit the formation of myeloma xenograft probably also through the downregulation of VEGF expression and subsequent angiogenesis.

Comparative Study of Perioperative and Oncological Outcomes Between Elderly Patients and Younger Patients Who Received Radical Cystectomy and Pelvic Lymph Node Dissection: A Single-Center Retrospective Study.

PURPOSE: To compare the perioperative and survival outcomes of patients over 75 years and younger patients who received radical cystectomy. PATIENTS AND METHODS: A total of 119 patients aged ≥75 years and 488 patients aged <75 years were enrolled. All patients underwent radical cystectomy with pelvic lymph node dissection. Clinical characteristics and perioperative outcomes were compared between the two groups. Overall survival and progression-free survival were analyzed by using the Kaplan-Meier method. Cox regression analysis and logistic regression analysis were used to identify the risk factors affecting the outcomes observed. RESULTS: There was no significant difference in perioperative complications between the elderly patient group and the younger patient group (p = 0.349). The 5-year overall survival of elderly patients was lower than that of young patients (p < 0.001). Age ≥75 years was a risk factor for overall survival (HR = 1.69 [95% CI: 1.22-2.35]; p = 0.002) and progression-free survival (HR = 1.69 [95% CI: 1.14-2.50]; p = 0.008) for patients who received radical cystectomy but was not a poor risk factor for major complications (HR = 1.25 [95% CI: 0.47-3.31]; p = 0.658) after radical cystectomy. In addition, preoperative renal insufficiency was associated with a higher risk of major complications. CONCLUSION: In our cohort, compared with younger patients, elderly patients aged ≥75 years had worse survival outcomes, but age ≥75 years was not a risk factor for major complications after radical cystectomy with pelvic lymph node dissection. Radical surgery should be encouraged for elderly patients who can tolerate aggressive treatments.

The comprehensive complication index is more sensitive than the Clavien-Dindo classification for grading complications in elderly patients after radical cystectomy and pelvic lymph node dissection: Implementing the European Association of Urology guideline.

Objectives: Lack of assessment of 90-d perioperative morbidity in elderly patients after radical cystectomy and pelvic lymph node dissection (PLND) using a standard reporting methodology, and the Clavien-Dindo classification (CDC) does not accurately reflect the burden of complications. We aim to report the 90-d complications of elderly patients after radical cystectomy, and to compare the validity of the Comprehensive Complication Index (CCI) and CDC. Methods: Retrospective review of 280 patients aged ≥75 years who received radical cystectomy between 2006 and 2021. The 90-d complications of elderly patients after radical cystectomy were reported by implementing the EAU criteria. The CDC and CCI were both used for grading complications. The Spearman rank correlation coefficient was used to estimate the correlation between postoperative stay and CDC/CCI. Logistic regression was used to identify the risk factors for major complications. The sample size for a fictive superiority trial was calculated for different endpoints. Results: A total of 225 (80.36%) patients suffered from 528 complications. The cumulative CCI had a more accurate prediction of postoperative stay than the CDC (r = 0.378, p < 0.001 vs. r = 0.349, p < 0.001). The need for sample size could decrease when CCI was used for the primary endpoint. More risk factors for major complications were identified when CCI ≥33.7 was defined as the endpoint of major complications. Conclusion: CCI is better than CDC for grading the severity of complications in elderly patients after radical cystectomy and PLND.