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Background Bruton tyrosine kinase (BTK) inhibitors have demonstrated a high degree of efficacy in the treatment of B cell malignancies characterized by constitutive B cell receptor activation, including chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Methods The efficacy and safety of zanubrutinib, an investigational highly selective BTK inhibitor, was evaluated in this single-arm, phase 2 study of Chinese patients with relapsed/refractory CLL/SLL. The primary endpoint was overall response rate as assessed by an independent review committee. Results Of the 91 evaluable patients, 77 (84.6%) achieved a response, with three (3.3%), 54 (59.3%), and 20 (22%) patients achieving a complete response, partial response, and partial response with lymphocytosis, respectively, after a median follow-up of 15.1 months. The estimated 12-month event-free rate for duration of response was 92.9%. The most commonly reported grade ≥ 3 adverse events (AEs) were neutropenia (44%), thrombocytopenia (15.4%), lung infection/pneumonia (13.2%), upper respiratory tract infection (9.9%), and anemia (8.8%). The 12-month overall survival rate was 96%. Eight (9.0%) patients discontinued zanubrutinib due to AEs, and seven (8.0%) patients required at least one dose reduction. Conclusion Treatment of patients with relapsed/refractory CLL/SLL with zanubrutinib was generally well tolerated and resulted in a high overall response rate, thereby conferring a favorable benefit-risk profile. Trial registration Prospectively registered in China public registry (CTR20160890) on December 7, 2016: http://www.chinadrugtrials.org.cn/ . Retrospectively registered in ClinicalTrials.gov ( NCT03206918 ) on July 2, 2017.

Background The objective of this meta-analysis was to compare the clinical and oncologic outcomes of robotic low anterior resection (R-LAR) with conventional laparoscopic low anterior resection (L-LAR). Methods A search in the MEDLINE, Embase, and Ovid databases was performed for studies published before July 2014 that compared the clinical and oncologic outcomes of R-LAR and L-LAR. The methodological quality of the selected studies was assessed. Depending on statistical heterogeneity, a fixed or random effects model was used for the meta-analysis. The clinical and oncologic outcomes evaluated included operative time, estimated blood loss, length of hospital stay, rate of conversion to open surgery, post-operative complications, circumferential margin status, and number of lymph nodes collected. Results Eight studies, including 324 R-LAR cases and 268 conventional L-LAR cases, were analyzed. The meta-analysis showed that R-LAR was associated with a shorter hospital stay (mean difference (MD) = −1.03; 95 % confidence interval (CI) = −1.78, −0.28; P  = 0.007), lower conversion rate (odds ratio (OR) = 0.08; 95 % CI = 0.02, 0.31; P  = 0.0002), lower rate of circumferential margin involvement (OR = 0.5; 95 % CI = 0.25, 1.01; P  = 0.05), and lower overall complication rate (MD = 0.65; 95 % CI = 0.43, 0.99; P  = 0.04) compared with L-LAR. There was no difference in operative time (MD = 28.4; 95 % CI = −3.48, 60.27; P  = 0.08), the number of lymph nodes removed (MD = −0.63; 95 % CI = −0.78, 2.05; P  = 0.38), and days to return of bowel function (MD = −0.15; 95 % CI = −0.37, 0.06; P  = 0.17). Conclusions R-LAR was shown to be associated with a shorter hospital stay, lower conversion rate, lower rate of circumferential margin involvement, and lower overall complication rate compared with L-LAR. There were no differences in operative time, the number of lymph nodes removed, and days to return of bowel function.

Plasmablastic lymphoma (PBL) is a rare and highly aggressive form of non-Hodgkin lymphoma that is associated with a poor prognosis. Traditional chemotherapy has demonstrated limited efficacy for PBL. There is currently no standard treatment for patients with refractory or relapsing PBL. While CAR-T therapy has shown promising outcomes in leukemia, lymphoma and myeloma, evidence of its application in PBL remains scarce. We describe a 56-year-old patient diagnosed with PBL. The patient achieved short-term remission with bortezomib in combination with etoposide, dexamethasone, cyclophosphamide, and doxorubicin as first-line therapy. After disease progression, the patient received daratumumab combined with GemOx as second-line treatment but showed no response. Tumor biopsy after disease progression revealed strong positive CD22 and partial positive CD19 expression. The patient received CD19 and CD22 CAR-T therapies as the third-line treatment and achieved durable complete remission for more than one year with good tolerance. A patient with refractory PBL achieved durable complete remission after CD19 and CD22 CAR-T therapies, suggesting this treatment may be effective for patients with refractory or relapsing PBL.

Recent attempts have focused on identifying fewer magnitude of minimal residual disease (MRD) rather than exploring the biological and genetic features of the residual plasma cells (PCs). Here, a cohort of 193 patients with at least one cytogenetic abnormalities (CA) at diagnosis were analyzed, and interphase fluorescence in situ hybridization (iFISH) analyses were performed in patient-paired diagnostic and posttherapy samples. Persistent CA in residual PCs were observed for the majority of patients (63%), even detectable in 28/63 (44%) patients with MRD negativity (<10–4). The absence of CA in residual PCs was associated with prolonged survival regardless of MRD status. According to the change of the clonal size of specific CA, patients were clustered into five groups, reflecting different patterns of clone selection under therapy pressure. Therapy-induced clonal selection exerted a significant impact on survival (HR = 4.0; P < 0.001). According to the longitudinal cytogenetic studies at relapse, sequential cytogenetic dynamics were observed in most patients, and cytogenetic architecture of residual PCs could to some extent predict the evolutional pattern at relapse. Collectively, the repeat cytogenetic evaluation in residual PCs could not only serves as a good complementary tool for MRD detection, but also provides a better understanding of clinical response and clonal evolution.

Objectives This study aimed to integrate positron emission tomography/computed tomography (PET/CT) metrics and genetic mutations to optimize the risk stratification for diffuse large B‐cell lymphoma (DLBCL) patients. Methods The data of 94 primary DLBCL patients with baseline PET/CT examination completed in the Shandong Cancer Hospital and Institute (Jinan, China) were analyzed to establish a training cohort. An independent cohort of 45 DLBCL patients with baseline PET/CT examination from other hospitals was established for external validation. The baseline total metabolic tumor volume (TMTV) and the largest distance between two lesions (Dmax) standardized by patient body surface area (SDmax) were calculated. The pretreatment pathological tissues of all patients were sequenced by a lymphopanel including 43 genes. Results The optimal TMTV cutoff was 285.3 cm3 and the optimal SDmax cutoff was 0.135 m−1. TP53 status was found as an independent predictive factor significantly affecting complete remission (p = 0.001). TMTV, SDmax, and TP53 status were the main factors of the nomogram and could stratify the patients into four distinct subgroups based on their predicted progression‐free survival (PFS). The calibration curve demonstrated satisfactory agreement between the predicted and actual 1‐year PFS of the patients. The receiver operating characteristic curves showed this nomogram based on PET/CT metrics and TP53 mutations had a better predictive ability than the clinic risk scores. Similar results were identified upon external validation. Conclusions The nomogram based on imaging factors and TP53 mutations could lead to a more accurate selection of DLBCL patients with rapid progression, to increase tailor therapy. In the era of immunity and targeted therapy, the existing International Prognostic Index scoring system has failed to fully identify high‐risk population for diffuse large B‐cell lymphoma (DLBCL). By analyzing the positron emission tomography/computed tomography parameters and next‐generation sequencing of primary DLBCL patients in the training cohort and validation cohort, we found the nomogram based on imaging factors and TP53 status could lead to a more accurate selection of DLBCL patients with rapid progression, to increase tailor therapy.

YY-20394, an oral phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitor, was investigated in a first-in-human study of patients with relapsed or refractory B-cell malignancies. During dose escalation, 25 patients received 20–200 mg of YY-20394 daily. The primary outcome measures were tolerability and dose-limiting toxicity (DLT). The secondary outcomes were pharmacokinetic parameters, progression-free survival (PFS) and the objective response rate (ORR). Since no patients experienced DLT, the maximum tolerated dose (MTD) was not reached. The majority (≥ 5%) of drug-related adverse events were ≥ grade III, being neutropenia (44.0%), pneumonia (16.0%), hyperuricemia (12.0%), lymphocythemia (8.0%), leukopenia (8.0%) and pneumonitis (8.0%). The overall ORR was 64.0% (95% confidence interval (CI): 45.2, 82.8%) including 5 patients with complete remission (CR), 11 with partial remission (PR), 2 with stable disease (SD) and 7 with progressive disease (PD), while the disease control rate (DCR) was 72.0% (95% CI: 54.4, 89.6%). The ORR of 10 patients with follicular lymphoma was 90%. The median PFS time was 255 days. One PR patient with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) who received 40 mg q.d. had a durable response of around 36 months. The median PFS time of 10 patients with follicular lymphoma was 300 days. A recommended phase 2 dose of 80 mg q.d. was established. Considering that YY-20394 was well-tolerated with promising preliminary efficacy, further development is warranted. Trial registration clinicaltrials.gov, NCT03757000, retrospectively registered, November 28, 2018, https://clinicaltrials.gov/ct2/show/NCT03757000?term=NCT03757000&draw=2&rank=1 .

Accumulating evidence shows that immunogenic cell death (ICD) enhances immunotherapy effectiveness. In this study, we aimed to develop a prognostic model combining ICD, immunity, and long non-coding RNA biomarkers for predicting hepatocellular carcinoma (HCC) outcomes. Immune- and immunogenic cell death-related lncRNAs (IICDLs) were identified from The Cancer Genome Atlas and Ensembl databases. IICDLs were extracted based on the results of differential expression and univariate Cox analyses and used to generate molecular subtypes using ConsensusClusterPlus. We created a prognostic signature based on IICDLs and a nomogram based on risk scores. Clinical characteristics, immune landscapes, immune checkpoint blocking (ICB) responses, stemness, and chemotherapy responses were also analyzed for different molecular subtypes and risk groups. A total of 81 IICDLs were identified, 20 of which were significantly associated with overall survival (OS) in patients with HCC. Cluster analysis divided patients with HCC into two distinct molecular subtypes (C1 and C2), with patients in C1 having a shorter survival time than those in C2. Four IICDLs (TMEM220-AS1, LINC02362, LINC01554, and LINC02499) were selected to develop a prognostic model that was an independent prognostic factor of HCC outcomes. C1 and the high-risk group had worse OS (hazard ratio > 1.5, < 0.01), higher T stage ( < 0.05), higher clinical stage ( < 0.05), higher pathological grade ( < 0.05), low immune cell infiltration (CD4 T cells, B cells, macrophages, neutrophils, and myeloid dendritic cells), low immune checkpoint gene expression, poor response to ICB therapy, and high stemness. Different molecular subtypes and risk groups showed significantly different responses to several chemotherapy drugs, such as doxorubicin ( < 0.001), 5-fluorouracil ( < 0.001), gemcitabine ( < 0.001), and sorafenib ( < 0.01). Our study identified molecular subtypes and a prognostic signature based on IICDLs that could help predict the clinical prognosis and treatment response in patients with HCC.

Background and Aims Stool DNA testing is an emerging and attractive option for colorectal cancer (CRC) screening. We previously evaluated the feasibility of a stool DNA (sDNA) test of methylated SDC2 for CRC detection. The aim of this study was to assess its performance in a multicenter clinical trial setting. Methods Each participant was required to undergo a sDNA test and a reference colonoscopy. The sDNA test consists of quantitative assessment of methylation status of SDC2 promoter. Results of real-time quantitative methylation-specific PCR were dichotomized as positive and negative, and the main evaluation indexes were sensitivity, specificity, and kappa value. All sDNA tests were performed and analyzed independently of colonoscopy. Results Among the 1110 participants from three clinical sites analyzed, 359 and 38 were diagnosed, respectively, with CRC and advanced adenomas by colonoscopy. The sensitivity of the sDNA test was 301/359 (83.8%) for CRC, 16/38 (42.1%) for advanced adenomas, and 134/154 (87.0%) for early stage CRC (stage I–II). Detection rate did not vary significantly according to age, tumor location, differentiation, and TNM stage, except for gender. The follow-up testing of 40 postoperative patients with CRC returned negative results as their tumors had been surgically removed. The specificity of the sDNA test was 699/713 (98.0%), and unrelated cancers and diseases did not seem to interfere with the testing. The kappa value was 0.84, implying an excellent diagnostic consistency between the sDNA test and colonoscopy. Conclusion Noninvasive sDNA test using methylated SDC2 as the exclusive biomarker is a clinically viable and accurate CRC detection method. Chinese Clinical Trial Registry Chi-CTR-TRC-1900026409, retrospectively registered on October 8, 2019; http://www.chictr.org.cn/edit.aspx?pid=43888&htm=4 .

Central nervous system (CNS) involvement in peripheral T‐cell lymphoma (PTCL) is rare and is associated with poor prognosis. This report presents two pathologically confirmed PTCL cases. Although cerebrospinal fluid (CSF) flow cytometry did not detect tumor cells, CSF analysis revealed significantly elevated interleukin (IL)‐10 levels and an increased IL‐10/IL‐6 ratio, suggesting CNS involvement. Following effective chemotherapy, which crossed the blood‐brain barrier, IL‐10 levels and the IL‐10/IL‐6 ratio decreased significantly, with clinical improvement. These findings suggest that IL‐10 is a valuable supplementary diagnostic marker for CNS involvement in PTCL. Whole‐brain radiation therapy, as a consolidative treatment, may be effective for residual or refractory lesions and improve prognosis. We review these patients’ clinical and diagnostic features and discuss the role of radiotherapy in the treatment of CNS involvement in PTCL.