Independent Prognostic Factor For Progression-free Survival Research Articles

Efficacy and predictors of immune checkpoint inhibitors in patients with gallbladder cancer.

Immune checkpoint inhibitors (ICIs) have shown promising efficacy in multiple cancers including biliary tract cancers (BTCs). However, the data focusing on the efficacy of ICIs in patients with gallbladder cancer (GBC) is still limited. In this study, we aim to assess the efficacy of ICIs in GBC and explore the clinicopathologic and molecular markers associated with ICI benefit. We retrospective analyzed 69 GBC patients who had received ICI therapy between January 2016 and December 2020. Tumor samples were obtained for genomic sequencing and immunohistochemical analysis. The median progression-free survival (PFS) and overall survival (OS) was 4.4 months and 8.5 months, respectively. Multivariate analysis indicated that alcohol intake history, carcinoma embryonic antigen (CEA) level ≥100 U/mL, and cutaneous immune-related adverse events (irAEs) were independent prognostic factors for PFS. CEA level ≥100 U/mL and cutaneous irAEs were independent prognostic factors for OS. The objective response rate and disease control rate (DCR) were 15.9% and 37.7%, respectively. Patients with cutaneous irAEs, high CD8+ T cell infiltrated or immune inflamed GBCs had higher DCR. Patients with high CD8+ T cell infiltrated or immune inflamed GBCs also had a notably improved prognosis. These results suggest that ICIs were effective in patients with GBC. High CEA level, cutaneous irAEs, high CD8+ T cell infiltration, and immune inflamed phenotype could be useful for predicting the efficacy of ICIs in GBC.

Efficacy and safety of first-line PD-L1/PD-1 inhibitors in limited-stage small cell lung cancer: a multicenter propensity score matched retrospective study.

The prognosis of small cell lung cancer (SCLC) patients is poor, and the standard first-line treatment for limited-stage small cell lung cancer (LS-SCLC) is still chemotherapy and thoracic radiotherapy. The primary objectives of our study were to confirm the superior efficacy of first-line immune checkpoint inhibitors (ICIs) plus etoposide and platinum (EP) for LS-SCLC and find crucial biomarkers. We analyzed LS-SCLC patients from three medical centers, employing propensity score matching for group comparability. Survival outcomes were estimated by Kaplan-Meier and Cox regression analyses. Additionally, we conducted univariate and multivariate analyses to investigate potential predictive factors. Among 150 patients in our study, we successfully matched 41 pairs. The median overall survival (OS) was 29.5 months in the EP + ICIs group and 20.0 months in the EP group {hazard ratio (HR) =0.64 [95% confidence interval (CI): 0.41-1.02], P=0.059}. The median progression-free survival (PFS) was significantly extended in the EP + ICIs group (14.6 months), compared to the EP group (8.6 months) [HR =0.42 (95% CI: 0.28-0.63), P<0.001]. After matching, patients receiving chemo-immunotherapy had a median OS of 36.1 months, significantly surpassing those receiving chemotherapy alone (19.0 months) [HR =0.51 (95% CI: 0.28-0.93), P=0.02]. And the patients in the EP + ICIs group also had longer PFS after matching [HR =0.42 (95% CI: 0.25-0.71), P=0.001]. No significant difference in the objective response rate (ORR) and treatment-related adverse events (trAEs) between the two groups was found (ORR: EP: 81.0%, EP + ICIs: 90.0%, P=0.14; trAEs: EP: grade 1-2, 49.3%; grade 3-4, 42.5%; EP + ICIs: grade 1-2, 40.0%; grade 3-4, 49.1%, P=0.62). The multivariate analysis presented that the history of immunotherapy [EP + PD-1 inhibitors: HR =0.33 (95% CI: 0.17-0.62), P=0.001; EP + PD-L1 inhibitors: HR =0.18 (95% CI: 0.06-0.60), P=0.005] and baseline lung immune prognostic index (LIPI) [intermediate: HR =2.22 (95% CI: 1.20-4.13), P=0.01; poor: HR =2.03 (95% CI: 0.71-5.77), P=0.18] were independent prognostic factors for PFS among all LS-SCLC cases. However, no independent prognostic factor was identified for OS. Our real-world data showed promising clinical efficacy and tolerable safety of first-line programmed cell death protein 1 (PD-1) inhibitors or programmed cell death ligand 1 (PD-L1) inhibitors in cases with LS-SCLC. Additionally, LIPI may serve as a valuable prognostic factor.

Efficacy and safety of thoracic radiotherapy in extensive-stage small-cell lung cancer patients receiving first-line immunotherapy plus chemotherapy: a propensity score matched multicentre retrospective analysis

BackgroundPlatinum-etoposide chemotherapy combined with immune checkpoint inhibitors (ICIs) has been recommended as the first-line standard treatment for extensive-stage small-cell lung cancer (ES-SCLC). However, the effect of thoracic radiotherapy (TRT) on these patients is still unknown. This study aimed to evaluate the efficacy and safety of TRT for ES-SCLC patients who responded to first-line ICIs and chemotherapy (CHT).MethodsPatients who received 4 to 6 cycles of ICIs and CHT as first-line therapy at three hospitals between 2018 and 2022 were included in the analysis. All patients were divided into two groups based on whether they received TRT as first-line treatment, and propensity score matching (PSM) was performed to ensure that the characteristics of two groups were well-balanced. The primary endpoints were overall survival (OS) and progression-free survival (PFS), and the secondary endpoint was toxic effects.ResultsA total of 276 patients were included, and the median follow-up time was 22.3 (range, 4.0-53.73) months. After PSM, 197 patients were further analysed, and 99 of whom received TRT. The baseline characteristics were well-balanced between patients in the TRT and non-TRT groups. There were significant differences in PFS between the TRT and non-TRT groups, with the median PFS of 10.76 and 7.63 months, respectively (P = 0.014). Significantly improved OS was observed in the TRT group (21.67 vs. 16.6 months, P = 0.009). In addition, the use of TRT was an independent prognostic factor for PFS and OS of ES-SCLC patients receiving ICIs plus CHT. In terms of safety, no significant increase of any grades adverse event (AE) (P = 0.874) and G3-4 AE (P = 0.909) was observed for patients receiving TRT. Radiation esophagitis, gastrointestinal and hematologic toxicities were the most common AEs in TRT group, which were tolerable. And high-dose radiotherapy was associated with higher incidence of pneumonitis.ConclusionAddition of TRT showed significant survival benefits and well tolerability in ES-SCLC patients receiving platinum-etoposide CHT and ICIs, which could be a feasible first-line treatment strategy for ES-SCLC patients.

Prognosis of non-small cell lung cancer with postoperative regional lymph node recurrence.

Regional lymph node recurrence after radical surgery for non-small cell lung cancer (NSCLC) is an oligo-recurrent disease; however, no treatment strategy has been established. In the present study we aimed to determine the clinical outcomes of postoperative regional lymph node recurrence and identify prognostic predictors in the era of molecular-targeted therapy. We retrospectively analyzed data on clinical characteristics and outcomes of patients with regional lymph node recurrence after surgery who underwent treatment for NSCLC between 2002 and 2022. A total of 53 patients were included in this study. The median time between surgery and detection of recurrence was 1.21 years. Radiotherapy (RT) alone and chemoradiotherapy (CRT) were performed in 38 and six patients, respectively. Driver gene alterations were detected in eight patients (EGFR: 6, ROS1:1, and BRAF: 1) and programmed death-ligand 1 (PD-L1) expression was examined in 22 patients after 2016. Median progression-free survival (PFS) and overall survival (OS) after lymph node recurrences were 1.32 and 4.34 years, respectively. Multiple lymph node recurrence was an independent prognostic factor for PFS, whereas driver gene alteration was the only prognostic factor for OS. There was no significant difference in the OS between patients stratified according to the initial treatment modality for lymph node recurrence. Our results suggest that the number of tumor recurrences may correlate with PFS, while detection of driver gene alterations could guide decision-making for the appropriate molecular-targeted therapy to achieve longer OS.

The therapeutic effect and prognostic value of oligoclonal bands after autologous stem cell transplant in patients with multiple myeloma

Objective: To investigate the therapeutic effect and prognostic value of oligoclonal bands (OB) in multiple myeloma (MM) patients after autologous stem cell transplant (ASCT). Methods: The data of 156 patients with MM who underwent ASCT after inductive treatment in the Department of Hematology, Jiangsu Provincial People's Hospital from December 2013 to February 2022 were retrospectively analyzed, including 91 males and 65 females. The median age was 56 (26, 71) years. Patients were divided into two groups according to OB formation after ASCT treatment, including OB group (n=60) and non-OB group (n=96). The last follow-up date was August 31, 2023, and the follow-up period was 42 (18, 117) months. The clinical baseline characteristics and efficacy of the two groups were compared. Progression-free survival (PFS) and overall survival (OS) were compared between the two groups by Kaplan-Meier method. Cox risk regression modal was used to analyze the risk factors associated with prognosis. Results: There were no significant differences in age, type, stage, risk stratification, extramedullary disease (EMD), proportion of circulating plasma cells and induction therapy regimen between OB and non-OB groups (all P>0.05). The proportion of patients in OB group who achieved complete response (CR) or above after ASCT treatment was 93.3% (56/60), which was higher than that in non-OB group (80.2%, 77/96) (P=0.024). The negative rate of minimal residual disease (MRD) in OB group was 66.7% (40/60), which was higher than that in non-OB group (34.4%, 33/96) (P=0.001). The median PFS and OS in the OB group were not reached, and the median PFS and OS in the non-OB group were 28 (2, 80) months and 86 (2, 100) months, respectively. The PFS (P<0.001) and OS (P=0.017) of patients with OB were considerably longer. In the Cox multivariate analysis, OB was an independent prognostic factor for PFS in MM patients (HR=0.314, 95%CI: 0.153-0.644, P=0.002). Subgroup analysis showed that among high-risk patients with mSMART, the OS of patients in OB group was not reached, which was significantly better than that of non-OB group [71 (2, 90) months, P=0.046]. However, no significant difference was observed in the OS of patients with OB and those with non-OB in standard risk group (not reached vs not reached, P=0.103). In those with EMD at diagnosis, patients with OB had significantly better OS than those with non-OB [not reached vs 47 (6, 74) months, P=0.037]. However, no significant difference was observed in the OS of patients with OB and those with non-OB in those without EMD at diagnosis [not reached vs 86 (2, 100) months, P=0.130]. Conclusions: OB formation after ASCT treatment in MM patients is related to the efficacy and prognosis. OB formation can increase the negative MRD rate, prolong the OS and improve the prognosis, especially for newly diagnosed patients with extramedullary disease or patients with high-risk genetic characteristics.

Accumulation of circulating myeloid-derived suppressor cell subsets: predicting poor clinical efficacy and prognosis through T cell suppression in non-Hodgkin's lymphoma.

Myeloid-derived suppressor cells (MDSCs) are implicated in the regulation of immune responses closely associated with poor clinical outcomes in cancer. However, the MDSC subtypes in non-Hodgkin's lymphoma (NHL) have not been systematically investigated. So, we investigated the percentage of MDSC subsets in 78 newly diagnosed NHL patients by flow cytometry. The results showed that all MDSC subsets increased in NHL patients compared with healthy donors. Notably, MDSCs, monocytic MDSCs, and CD14 + CD66b + MDSCs significantly increased in NHL patients compared with those with lymphadenitis donors. polymorphonuclear MDSCs (PMN-MDSCs), early-stage MDSCs (e-MDSCs), and the International Prognostic Index were independent risk factors for poor clinical efficacy and were involved in constructing the nomogram for predicting clinical efficacy. Progression-free survival (PFS) was significantly shorter in patients with high level of MDSC subsets, and PMN-MDSCs emerged as an independent prognostic factor for PFS. PMN-MDSCs, e-MDSCs, and the International Prognostic Index were involved in constructing the nomogram for predicting PFS. Patients with a higher percentage of MDSCs, PMN-MDSCs, e-MDSCs, and CD14 + CD66b + MDSCs experienced a shorter overall survival compared with those with lower percentages. In addition, research on mechanisms found that T cell function was suppressed and mediated by the expansion of MDSCs via involving arginase-1 and interleukin-10 in vitro and in vivo. In conclusion, our study demonstrates that the increased circulating MDSC subsets predict poor clinical efficacy and prognosis in NHL, potentially involving T cell suppression through MDSC subset expansion. These findings indicate the potential of MDSC subsets as comprehensive diagnostic, prognostic biomarkers, and therapeutic targets for NHL.

Relationship Between Adverse Events and Progression-free Survival in Patients Receiving Cabozantinib for Previously Treated Metastatic Renal Cell Carcinoma.

Although the adverse events (AEs) of drugs, such as sunitinib and axitinib, have been shown to predict treatment responses, evidence to support cabozantinib-induced AEs as predictors of responses to treatment for metastatic renal cell carcinoma (mRCC) is limited. Therefore, we herein investigated the relationship between AE profiles and progression-free survival (PFS) in patients receiving cabozantinib for previously treated mRCC. The present study retrospectively analyzed 40 patients receiving cabozantinib for previously treated mRCC between July 2020 and August 2022. PFS was estimated using the Kaplan-Meier method and the impact of several parameters, including cabozantinib-induced AEs, on PFS was investigated by a Cox proportional regression analysis. The median observation period was 15 (2-29) months, during which time 31 patients (77.5%) progressed, with median PFS of 11 months. Thirty-nine patients (97.5%) developed at least one AE. Liver toxicity occurred in 16 patients (40.0%) and hand-foot syndrome, hypertension, and diarrhea in 14 each (17.5%). Only hypertension correlated with longer PFS. A multivariate analysis identified hypertension as an independent prognostic factor for PFS (p=0.049). These results suggest the potential of treatment-induced hypertension as a significant predictor of prolonged PFS in patients receiving cabozantinib for mRCC.

Optimal Time-to-Surgery Recommendations Based on Primary Tumor Volume Regression for Patients with Resectable Esophageal Cancer after Neoadjuvant Chemoradiotherapy: A Retrospective Study.

Neoadjuvant chemoradiotherapy (NCRT) has shown promise in improving the prognosis of individuals with locally advanced esophageal squamous cell carcinoma (LA-ESCC). However, the factors influencing tumor response and long-term survival in these patients remain unknown. The optimal timing for surgery after the completion of radiotherapy in LA-ESCC remains controversial. Therefore, this study was designed to identify biomarkers and to determine the optimal post-NCRT time-to-surgery (TTS) for patients with LA-ESCC. This retrospective study included patients with resectable LA-ESCC who underwent NCRT between May 2017 and June 2021. The tumor shrinkage rate was calculated as the difference between the pre- and post-primary gross tumor volume (GTVp) divided by the pre-GTVp. Univariate and multivariate Cox regression analyses and Kaplan-Meier curves were used to calculate overall survival (OS) and progression-free survival (PFS). We collected data from 248 patients with resectable LA-ESCC who underwent computed tomography (CT) scans before the initiation of treatment. The median follow-up time was 37.7 months. The optimal cutoff of tumor shrinkage was 45%. In the univariate and multivariate analyses, we found a significant association between the tumor shrinkage rate and PFS (p = 0.001). Among the subgroup of patients who responded to treatment, extending the TTS was associated with improved OS (p = 0.037) and PFS (p = 0.028). For patients with resectable LA-ESCC, the tumor shrinkage rate is an independent prognostic factor for PFS. Thus, for responders, prolonging TTS is recommended to obtain a better OS.

C-reactive protein to albumin ratio predict responses to programmed cell death-1 inhibitors in hepatocellular carcinoma patients.

Over the years, programmed cell death-1 (PD-1) inhibitors have been routinely used for hepatocellular carcinoma (HCC) treatment and yielded improved survival outcomes. Nonetheless, significant heterogeneity surrounds the outcomes of most studies. Therefore, it is critical to search for biomarkers that predict the efficacy of PD-1 inhibitors in patients with HCC. To investigate the role of the C-reactive protein to albumin ratio (CAR) in evaluating the efficacy of PD-1 inhibitors for HCC. The clinical data of 160 patients with HCC treated with PD-1 inhibitors from January 2018 to November 2022 at the First Affiliated Hospital of Guangxi Medical University were retrospectively analyzed. The optimal cut-off value for CAR based on progression-free survival (PFS) was determined to be 1.20 using x-tile software. Cox proportional risk model was used to determine the factors affecting prognosis. Eastern Cooperative Oncology Group performance status [hazard ratio (HR) = 1.754, 95% confidence interval (95%CI) = 1.045-2.944, P = 0.033], CAR (HR = 2.118, 95%CI = 1.057-4.243, P = 0.034) and tumor number (HR = 2.932, 95%CI = 1.246-6.897, P = 0.014) were independent prognostic factors for overall survival. CAR (HR = 2.730, 95%CI = 1.502-4.961, P = 0.001), tumor number (HR = 1.584, 95%CI = 1.003-2.500, P = 0.048) and neutrophil to lymphocyte ratio (HR = 1.120, 95%CI = 1.022-1.228, P = 0.015) were independent prognostic factors for PFS. Two nomograms were constructed based on independent prognostic factors. The C-index index and calibration plots confirmed that the nomogram is a reliable risk prediction tool. The ROC curve and decision curve analysis confirmed that the nomogram has a good predictive effect as well as a net clinical benefit. Overall, we reveal that the CAR is a potential predictor of short- and long-term prognosis in patients with HCC treated with PD-1 inhibitors. If further verified, CAR-based nomogram may increase the number of markers that predict individualized prognosis.

Prognostic factors and treatment choice for stage IV, low-volume metastasis hormone-sensitive prostate cancer: cross-sectional study of real-world data.

Many metastatic prostate cancer prognostics have been suggested, but few are validated. Nodal metastasis burden and baseline biochemical characteristics are overlooked in the currently accepted stratifications for metastatic hormone-sensitive prostate cancer (mHSPC). Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) is likely to increase the incidence of pelvic nodal and mHSPC undetected by conventional scans. However, there is no consensus on managing regional nodal metastasis (N1M0) and no separate guidelines for non-regional nodal (M1a) and low-volume bone (M1b) spread but collectively as a part of low-volume CHAARTED disease. To assess the different prognostic factors for stage IV disease classified as CHAARTED low-volume on a real-world series of patients and to examine treatment preference for each of the disease subcategories. This retrospective cross-sectional study included patients diagnosed with HSPC at stage IV, with low-volume disease according to the CHAARTED criteria. Data were collected from the database of Portsmouth and St. Mary NHS Hospitals between February 2017 and August 2023. Patient characteristics were analysed, and prognostic factors were evaluated using Cox regression analysis. 5-year progression-free survival (PFS) was the primary outcome measure. Data on 126 patients were analysed. Seven patients (6%) had N1M0, 28 (22%) M1a, and 91 (72%) M1b. 5-year PFS was 80.9% for M1a and 54.9% for M1b metastases, p = 0.3. High prostate-specific antigen (PSA) value (⩾25) was identified as an independent prognostic factor for PFS with HR = 2.80 (95% CI: 1.19-6.56), p = 0.0179. Variable treatment preference for each subclass reflects the uncertainty regarding the best regimen and the importance of consolidation prostate radiotherapy (cRT) in clinical practice. Early results of our data analysis underscore the significance of baseline PSA as an independent prognostic factor alongside anatomical tumour extent of spread in stage IV low-volume metastasis prostate cancer. There is no agreement on treatment for each subcategory, necessitating further real-world studies and clinical trials. Further follow-up would assess the prognostic benefit of cRT.

Efficacy and safety of transarterial chemoembolization plus lenvatinib combined with PD-1 inhibitors versus transarterial chemoembolization plus lenvatinib for unresectable hepatocellular carcinoma: a meta-analysis.

Locoregional treatment combined with systemic therapy is expected to play a synergistic anticancer role. We conducted this systemic meta-analysis to examine the efficacy and safety of transarterial chemoembolization (TACE) plus lenvatinib with or without programmed cell death protein-1 (PD-1) inhibitors (TLP group) compared with TACE + lenvatinib (TL group) for unresectable hepatocellular carcinoma (uHCC). From the inception date to April 2024, the data from PubMed, EMBASE, the Cochrane Library, Ovid, Web of Science, and Clinical Trials. gov were used for meta-analysis. All clinical outcomes of interest included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). The hazard ratio (HR) and risk ratio (RR) with 95% confidence intervals (CI) were used to measure the pooled effect. This study included 10 retrospective cohort studies, including 1128 patients. The OS (HR=0.51; 95% CI: 0.43-0.60, P < 0.05), PFS (HR=0.52; 95% CI: 0.45-0.61, P < 0.05), ORR (RR = 1.58; 95% CI: 1.37-1.83; P < 0.05) and DCR (RR = 1.31; 95% CI: 1.20-1.43; P < 0.05) were significantly higher in TLP group than in the TL group. The incidence of AEs was acceptable. Prognostic factor analysis identified that ECOG PS (1/0), Child-Pugh class (B/A), BCLC stage (C/B) and main portal vein invasion (yes/no) were independent prognostic factors for OS. BCLC stage (C/B) and main portal vein invasion (yes/no) were independent prognostic factors for PFS. The TLP group had better efficacy for uHCC than that of the TL group, with acceptable safety. PROSPERO, identifier (CRD42023420093).

Efficacy, safety, and prognostic factors of capecitabine plus temozolomide regimen in patients with atypical thymic carcinoids.

Atypical thymic carcinoids (ATCs) are rare mediastinal malignancies that lack established treatment guidelines. Capecitabine and temozolomide (CapTem) has demonstrated significant efficacy in pancreatic neuroendocrine neoplasms (NENs), while its applicability and effectiveness in ATCs remain underexplored. This study seeks to investigate the efficacy, safety, and prognostic factors associated with CapTem in ATC patients. Thirty-eight ATC patients treated with CapTem at our center were analyzed. We assessed the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse effects. We also examined patients' clinicopathological characteristics and their correlations with CapTem efficacy. The cohort achieved a 15.8% ORR and 89.5% DCR, with a median PFS of 13.0 months. Multivariate analysis identified the platelet-to-lymphocyte ratio (PLR) as a significant independent prognostic factor for PFS, with a PLR ⩾ 235 associated with shorter PFS (7 months vs. undefined, p = 0.0004). Age was an independent prognostic factor for OS, with patients over 50 years experiencing shorter OS (36 months vs. undefined, p = 0.015). Safety analysis showed rare severe toxicities and no treatment-related fatalities. CapTem is an effective and well-tolerated treatment for ATC patients. Pretreatment PLR and age appear to be potential prognostic markers for CapTem therapy; however, these results warrant validation in larger patient cohorts.

Effect of Serum Interleukin-6 Concentration on the Prognosis After Radiotherapy for Patients With Hepatocellular Carcinoma.

Objective: The aim of this study was to explore the association between interleukin-6 (IL-6) concentration before radiotherapy (RT) and the prognosis after RT for patients with hepatocellular carcinoma (HCC). Methods: The clinical data for 101 patients with HCC who received RT from October 2016 to June 2021 were retrospectively analyzed. In these patients, the tumors were confined to the liver, and IL-6 concentration was measured before RT. The survival rate was calculated using the Kaplan-Meier method, and the Cox proportional hazards regression model was used to explore the independent factors affecting the patients' prognosis. X-tile software was used to obtain the optimal cut-off value of pre-RT IL-6 concentration (7.8 pg/mL) for overall survival (OS). Results: The 1-, 2-, and 3-year OS rates were 84.4%, 55.8%, and 34.7%, respectively, for patients with a pre-RT IL-6 concentration > 7.8 pg/mL versus 96.0%, 80.1%, and 80.1%, respectively, for those with a pre-RT IL-6 concentration ≤ 7.8 pg/mL. The OS rates of the two groups were significantly different (p < 0.001). The median progression-free survival (PFS) time was 7.5 months versus 15.1 months for patients with pre-RT IL-6 concentrations > 7.8 pg/mL and ≤ 7.8 pg/mL, respectively (p=0.001). Pre-RT IL-6 concentration was an independent prognostic factor of OS (hazard ratio [HR] = 3.421, 95% confidence interval [CI]: 1.477-7.927, p=0.004). Pre-RT IL-6 concentration (HR = 2.235, 95% CI: 1.176-4.246, p=0.014) and age (HR = 0.615, 95% CI: 0.383-0.987, p=0.044) were independent prognostic factors for PFS. Conclusions: The prognosis of HCC patients receiving RT was worse for those with a pre-RT serum IL-6 concentration > 7.8 pg/mL than those with a pre-RT serum IL-6 concentration ≤ 7.8 pg/mL. Pre-RT IL-6 concentrations may affect the prognosis of HCC patients.

Real-world efficacy of chidamide plus R-CHOP in newly diagnosed double-expressor diffuse large B-cell lymphoma

Background: Approximately 20%–30% of diffuse large B-cell lymphoma (DLBCL) cases are classified as double-expressor lymphoma (DEL), characterized by the co-expression of the MYC and BCL2 proteins. However, the most effective therapeutic strategy for DEL remains unidentified. Objectives: To evaluate the efficacy of a novel histone deacetylase inhibitor, chidamide, in combination with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (CR-CHOP) in the treatment of DEL. Design: This was a retrospective study. Methods: This study included 62 DEL patients from December 2016 to December 2020. All patients were administered a first-line treatment with CR-CHOP. The short-term efficacy, survival status, and adverse reactions in this population were observed, and the prognostic factors were analyzed. Results: The median age was 53.9 years (range, 19–77). All patients received a median of six cycles (range, 1–8) of treatment, with 79.0% achieving complete response (CR) and an overall response rate of 88.7%. With a median follow-up of 45.5 months (range, 1–82), the median progression-free survival (PFS) and median overall survival (OS) had not yet been reached. However, the 3-year PFS rate was 71% (95% CI: 61–83), the 3-year OS rate was 87% (95% CI: 79–96), the 5-year PFS rate was 67% (95% CI: 55–80), and the 5-year OS rate was 85% (95% CI: 77–95). Age and autologous stem cell transplantation after CR or partial response were independent prognostic factors for PFS, while various clinical factors were not associated with OS outcomes. The most common grades 3–4 hematologic and nonhematologic toxicity were leukopenia (46.7%) and infection (21%), respectively. Conclusion: This long-term follow-up study indicates that CR-CHOP in untreated DLBCL with the DEL phenotype demonstrates high short-term efficacy and safety as well as promising survival outcomes.

Construction of a prognostic nomogram combining PET/CT metabolic parameters and blood inflammatory markers for non-small cell lung cancer treated with first-line chemotherapy

To investigate the prognostic value of 18F-FDG-PET/CT metabolic parameters and blood inflammatory markers for advanced non-small cell lung cancer (NSCLC, stage Ⅳ/ⅢB) treated with first-line chemotherapy combined with immunotherapy and construct a nomogram prediction model for NSCLC. We retrospectively analyzed the metabolic parameters (SUVmax, MTV and TLG) and blood markers of inflammation (NLR, DNLR, PLR and SII) in 105 patients with advanced NSCLC receiving chemotherapy combined with baseline 18F-FDG-PET/CT prior to immunotherapy from March, 2019 to June, 2021. ROC curve was used to calculate the best cut-off points for grouping, and univariate and multivariate COX regression analyses were performed to screen the independent predictors of prognosis for a combined diagnostic analysis. The effective biomarkers were included in the prediction model, and the nomogram model was constructed using the cph function in the rms function package of R language software. The patients were followed up for a median of 17.5 months, and their median progression-free survival (PFS) was 16 months with a median overall survival (OS) of 13.6 months. A high PLR (≥151.050) and a high TLG (≥101.940) were significant independent prognostic factors for PFS, and a high SII (≥941.385) and a high TLG (≥101.940) were independent prognostic factors for OS. The nomogram combining PET and blood markers of inflammation showed a good performance for prognostic prediction (with C-index of 0.682 for PFS and of 0.727 for OS) and good fitting of the calibration curve. The clinical decision curve showed good clinical utility of the nomogram. The baseline PET/CT metabolic parameters and blood inflammatory markers are associated with PFS and OS of patients with advanced NSCLC receiving first-line chemotherapy, and the constructed nomogram based on these parameters has a good performance for prognostic prediction in these patients.

Efficacy and safety of radiotherapy combined with anti-angiogenic therapy and immune checkpoint inhibitors in MSS/pMMR metastatic colorectal cancer.

Several studies have demonstrated the effectiveness of anti-angiogenic drugs in combination with immune checkpoint inhibitors (ICIs) in patients with microsatellite stable (MSS) or mismatch repair proficient (pMMR) metastatic colorectal cancer (mCRC). However, whether combination radiotherapy (RT) can further improve the prognosis of mCRC patients after second-line treatment remains to be explored. Retrospective analysis of data from mCRC patients who received anti-angiogenic targeted therapy (TT) and immunotherapy (IT) with or without RT after the failure of standard therapy. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety were evaluated. A total of 82 patients who received TT + IT were analyzed. For RT group (n = 42) versus NRT group (n = 40), ORR was 21.4% (9/42) versus 5.0% (2/40); DCR was 83.8% (35/42) versus 65.0% (26/40). Compared with NRT group, RT improved PFS (median: 5.0 vs. 3.6 months; p = 0.04) and OS (median: 15.2 vs. 7.2 months; p = 0.01). In addition, in the population receiving RT, the PFS of RT sequential/simultaneous TT + IT was superior to TT + IT sequential RT (median: 7.1 vs. 6.2 vs. 3.5 months, p = 0.004). Multivariate analysis suggested RT was an independent prognostic factor for PFS and OS. No treatment-related deaths were reported. Compared with TT + IT, RT combined with TT + IT improved survival outcomes in MSS/pMMR mCRC patients, with manageable toxicity. RT sequential/simultaneous TT + IT treatment is expected to be the optimal strategy for MSS/PMMR mCRC.

Albumin‑bilirubin grade is an independent prognostic factor for small lung cell cancer

Albumin‑bilirubin grade is an independent prognostic factor for small lung cell cancer

Nomogram incorporating Epstein-Barr virus DNA and a novel immune-nutritional marker for survival prediction in nasopharyngeal carcinoma

BackgroundSince Immune response, nutritional status and Epstein–Barr Virus (EBV) DNA status have been confirmed to be relevant to the prognosis of patients with nasopharyngeal carcinoma (NPC), we believe that the combination of these factors is of great value for improving the predictive ability. LA (lymphocytes × albumin), a novel indicator, had not been studied yet in NPC. We combined it with EBV DNA and used nomograms to increase the accuracy of prognosis.MethodsA total of 688 NPC patients were retrospectively reviewed and further divided into training and validation cohort randomly. Kaplan–Meier analyses were used to to distinguish the different survival outcomes. Multivariate Cox analyses were used to identify the independent prognostic factors for progression-free survival (PFS) and overall survival (OS). Calibration curves, concordance indexes (C-indexes) and decision curve analyses (DCA) were used to evaluate the nomograms’ predictive value.ResultsPatients with low LA and positive EBV DNA correlated with poorer 5-year PFS and OS (all P < 0.005). In multivariate Cox analyses, LA and EBV DNA were both confirmed to be independent prognostic factors for PFS and OS (all P < 0.05). Prognostic nomograms incorporating LA and EBV DNA achieved ideal C-indexes of 0.69 (95% CI: 0.65–0.73) and 0.77 (95% CI: 0.71–0.82) in the prediction of PFS and OS. Otherwise, the calibration curves and DCA curves also revealed that our nomograms had pleasant predictive power.ConclusionsLA is a novel and powerful biomarker for predicting clinical outcomes in NPC. Our nomograms based on LA and EBV DNA can predict individual prognosis more accurately and effectively.

Efficacy and toxicity of anlotinib plus camrelizumab versus anlotinib plus S-1 as second-line therapy for advanced esophageal squamous cell carcinoma: A real-world retrospective study

BackgroundNo data exist on the efficacy and safety of anlotinib plus camrelizumab doublet as second-line therapy for advanced esophageal squamous cell carcinoma (ESCC). Although anlotinib and the programmed death-1 (PD-1) inhibitor camrelizumab are used as treatments for ESCC, the combined use of anlotinib and camrelizumab as a second-line therapy has not been reported. Therefore, this study explored the efficacy and toxicity of anlotinib plus camrelizumab as second-line therapy for advanced ESCC. MethodsFifty-eight patients with advanced ESCC undergoing second-line therapy, either with anlotinib plus camrelizumab or anlotinib plus S-1, were enrolled and retrospectively analyzed at Jiangsu Province Hospital of Chinese Medicine from January 2020 to December 2021. The primary endpoint was progression-free survival (PFS), with secondary endpoints including the objective response rate (ORR), disease control rate (DCR), and assessment of toxicity. ResultsIn patients with advanced ESCC, the anlotinib plus camrelizumab group (N = 32) exhibited longer PFS (8.00 vs. 4.53 months, P < 0.001), higher ORR (28.1 vs. 19.2%, P = 0.431), and higher DCR (87.5 vs. 65.4%, P = 0.045) than those in the anlotinib plus S-1 group (N = 26). Treatment-related adverse events (TRAEs) were predominantly grade 1/2 in both groups, with a higher incidence of grade 1/2 skin toxicity in patients treated with anlotinib plus camrelizumab (P = 0.033). Two patients (6.3%) developed grade 1/2 immune-related pneumonia. The incidence of grade 3/4 TRAEs did not differ significantly between the two groups. Multivariable Cox regression analysis identified that the drug regimen (P < 0.001), Eastern Cooperative Oncology Group performance status (P = 0.008), and differentiation grade (P = 0.008) were independent prognostic factors for PFS. ConclusionsAnlotinib plus camrelizumab exhibited promising antitumor efficacy and manageable toxicity when used as a second-line treatment for advanced ESCC.

Oligomannose-Type Glycans in the Antigen Binding Site Identify Origin and Prognosis of Diffuse Large B Cell Lymphoma

The acquisition of N-glycosylation sites (AGS) in the complementarity-determining region (CDR) of the tumor immunoglobulin (Ig) is an early clonal requirement of classic follicular lymphoma (FL). In FL, the AGS are occupied by oligomannose-type glycans, which mediate lymphoma Ig interaction with the microenvironmental lectin dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN). This interaction induces a persistent low-level signal, favouring adhesion and ultimately survival and growth of the lymphoma cells in their protected environment . Oligomannose-type glycans can also occupy the CDR-located AGS of a subset of germinal-centre B cell-like (GCB) diffuse large B-cell lymphomas (DLBCL) but the consequences of AGS in DLBCL are less known. We determined the frequency, distribution, and composition of the glycan structures occupying the AGS in DLBCL using a discovery-validation approach with two large independent international public cohorts (BCC, dataset ID: EGAD00001003783; NCI accession phs001444.v1.p1), following our RNAseq Ig assembly pipeline (Ig-Seq-R) and high-resolution mass-spectrometry. Glycan types were compared to our FL cohort (12 samples) and correlated with DLBCL cell of origin (COO), genetic, clinical characteristics and outcome. The full IGHV-IGHD-IGHJ-IGHC transcript sequences were obtained from 251 DLBCL of the BCC, and 339 of the NCI cohort. Sample distribution by COO, clinical or molecular features, LymphGen subtype, progression-free survival (PFS) and overall survival (OS) were not different from the extended public cohorts. AGS were observed in 48-55% GCB-DLBCL, with 84-85% of them located in the CDR. Overall, frequency of CDR-located AGS contrasted dramatically between GCB-DLBCL (41-46%) and activated B-cell like (ABC)-DLBCL (7-10%). Also, within GCB-DLBCL, CDR-located AGS associated mostly with the EZB subtype (68-73%). However, only 66-61% EZB were AGS+ve, all of which were CDR+ve, while the remaining 34-39% had no AGS (AGS-ve EZB). The glycan structures of the synthetic F(ab)s from 35 AGS+ve DLBCL and 12 FL were analyzed by site-specific mass spectrometry. The DLBCL comprised 12 AGS+ve EZB and 23 AGS+ve non-EZB (14 CDR+ve, 9 located in the framework region). Glycan analysis revealed that all AGS+ve EZB and FL were invariably occupied by oligomannose-type glycans (Ig-Mann+ve DLBCL). In contrast, the other AGS+ve DLBCL were not occupied by oligomannose type glycans. They were either occupied by complex glycans (the remaining non-EZB GCB-DLBCL) or not occupied (preferentially the ABC-DLBCL), irrespective of AGS location. These data indicated that CDR+ve EZB Ig were universally and exclusively Ig-Mann+ve DLBCL, share the COO of FL, and have likely been influenced by an environmental driver distinct from the other GCB-DLBCL and ABC-DLBCL. We compared the clinical behavior of Ig-Mann+ve DLBCL versus other DLBCL subtypes including AGS-ve EZB and the other non-EZB GCB-DLBCL and ABC-DLBCL. In both the BCC and NCI cohorts, Ig-Mann+ve DLBCL status identified the subset with the worst PFS and OS of all GCB-DLBCL, not different from ABC-DLBCL (Figure 1A). This contrasted with the other GCB-DLBCL (AGS-ve/EZB and AGS+ve/non-EZB), which all shared an extremely good PFS and OS (Figure 1A). Univariate and multivariate analyses revealed that Ig-Mann+ve status was an independent prognostic factor for PFS and OS (Figure 1B). Gene expression profile analysis revealed that Ig-Mann+ve status associated with an enrichment of MYC, PI3K-Akt-mTORC1, pro-survival, and cell cycle pathways, while proinflammatory and apoptotic pathways were decreased in the Ig-Mann+ve DLBCL compared to AGS-ve/EZB and AGS+ve/non-EZB, independently of MYC translocations and double-hit signature. These data indicate identical COO of a EZB subset with FL cells, and point to a highly selective chronic environmental pressure on Ig-Mann+ve DLBCL negatively affecting patients survival. The combination of Ig gene analysis with the lymphGen classification can predict Ig glycan structure and provide a new fundamental approach to identifying the most aggressive GCB-DLBCL subtype, and the precise environmental tumour interaction (DC-SIGN:Ig-Mann) to intercept therapeutically early in the natural history of Ig-Mann+ve DLBCL.