Independent Prognostic Factor For Progression-free Survival Research Articles

Comparison of oncological outcomes between sentinel lymph node biopsy and complete lymphadenectomy for endometrial cancer.

Sentinel lymph node (SLN) mapping allows node-negative patients to be spared from the surgical comorbidities associated with total lymphadenectomy. This study aimed to evaluate the oncological outcomes of SLN biopsy versus complete lymph node dissection in patients with early-stage endometrial carcinoma. Retrospective analyses were performed in patients with pathologically confirmed endometrioid endometrial carcinoma, who underwent minimally invasive surgical staging with SLN biopsy or complete lymph node dissection at Yonsei Cancer Center between 2015 and 2019. A total of 301 patients were included in this study. Eighty-two patients underwent SLN biopsy, while 219 underwent complete lymph node dissection. There were no significant differences in patient characteristics between the two groups. In terms of operative characteristics, the SLN biopsy-only group had a significantly shorter surgical duration (p < 0.001) than the lymphadenectomy group. The mean follow-up period was 41.4 months. There were no differences in progression-free survival (PFS) and overall survival (OS) between the two groups (SLN biopsy vs. complete lymph node dissection; p = 0.798 and 0.301, respectively). Multivariate analysis revealed that SLN biopsy was not an independent prognostic factor for PFS or OS. Our results showed that SLN biopsy provided oncological outcomes similar to those of lymphadenectomy.

Prognostic and predictive significance of circulating biomarkers in patients with advanced upper gastrointestinal cancer undergoing systemic chemotherapy.

The prognosis of patients with advanced cancers of the upper gastrointestinal (UGI) tract is poor. Systemic chemotherapy forms the basis for their treatment, with limited efficacy. Biomarkers have been introduced into clinical practice for cancer management. This study aimed to investigate the predictive and prognostic values of circulating biomarkers in patients with advanced esophageal and gastric cancers receiving chemotherapy. Overall, 92 patients with advanced esophageal squamous cell carcinoma (ESCC; n = 38) and gastric adenocarcinoma (GAC; n = 54) were enrolled. We analyzed the association of circulating lymphocyte subsets, inflammatory markers, and blood cell counts with treatment efficacy and patient survival. Significant differences were identified in peripheral blood parameters between the groups with different clinicopathological features. Hemoglobin (Hb, p = 0.014), eosinophil counts (p = 0.028), CD4+CD28+T/CD4+T percentage (p = 0.049), CD8+CD38+T/CD8+T percentage (p = 0.044), memory CD4+T (p = 0.007), and CD4+CD28+T (p = 0.007) were determined as predictors for achieving non-PD (progression disease) in the ESCC cohort. High levels of eosinophils (p = 0.030) and memory CD4+T cells (p = 0.026) and high eosinophil-to-lymphocyte ratio (ELR, p = 0.013) were predictors of non-PD in patients with GAC. The combined detection models exhibited good ability to distinguish between partial response (PR)/non-PR and PD/non-PD in patients with ESCC and GAC, respectively. Using the multivariate Cox model, the Eastern Cooperative Oncology Group (ECOG) score status (hazard ratio [HR]: 4.818, 95% confidence intervals [CI]: 2.076-11.184, p < 0.001) and eosinophil count (HR: 0.276, 95% CI: 0.120-0.636, p = 0.003) were independent prognostic factors of progression-free survival (PFS) in patients with ESCC. Metastatic sites (HR: 2.092, 95% CI: 1.307-3.351, p = 0.002) and eosinophil-to-lymphocyte ratio (ELR; HR: 0.379, 95% CI: 0.161-0.893, p = 0.027) were independent prognostic factors for overall survival (OS) in patients with ESCC. Differentiation (HR: 0.041, 95% CI: 0.200-0.803, p = 0.010), memory CD4+T (HR: 0.304, 95% CI: 0.137-0.675, p = 0.003), NK cells (HR: 2.302, 95% CI: 1.044-3.953, p = 0.037), and C-reactive protein-to-lymphocyte ratio (CLR; HR: 2.070, 95% CI: 1.024-4.186, p = 0.043) were independent prognostic factors for PFS in patients with GAC. Total lymphocyte counts (HR: 0.260, 95% CI: 0.086-0.783, p = 0.017), CD8+T (HR: 0.405, 95% CI: 0.165-0.997, p = 0.049), NK cells (HR: 3.395, 95% CI: 1.592-7.238, p = 0.002), and monocyte-to-lymphocyte ratio (MLR; HR: 3.076, 95% CI: 1.488-6.360, p = 0.002) were identified as independent prognostic factors associated with OS of GAC. Lymphocyte subsets, blood cell counts, and inflammatory parameters may predict the chemotherapeutic response and prognosis in ESCC and GAC. A combination of these markers can be used to stratify patients into risk groups, which could improve treatment strategies.

Comparison of clinical outcomes in patients with advanced pulmonary sarcomatoid carcinoma treated with immunotherapy-based regimen or chemotherapy: A study based on the SEER database and multicentric real-world settings.

e20573 Background: Pulmonary sarcomatoid carcinoma (PSC) is a rare pulmonary cancer characterised by early metastasis and invasion, predominantly diagnosed with locally advanced or metastasis, hindering the possibility of surgical intervention. However, a standardised treatment strategy for advanced PSC is yet to be established. Herein, we aimed to evaluate the effects of immunotherapy-based strategies or chemotherapy on patients with advanced PSC. Methods: We conducted a retrospective study to compare the clinical outcomes of immunotherapy-based regimens and chemotherapy in patients with advanced PSC using the Surveillance, Epidemiology, and End Results (SEER) database and data from three cancer centres. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan–Meier method. Univariate and multivariate analyses were performed to identify prognostic factors. Results: In total, 202 patients with stage IV PSC were identified from the SEER database. The median OS was 5 months. The median follow-up time of PSC patients from three cancer centres was 27.5 months Considering all three cancer centres, first-line treatment with a first-line immunotherapy-based regimen and chemotherapy were administered to 12 and 16 patients, respectively. The median PFS was 2.1 (95% confidence interval [CI] [2.1, 4.1]) and 7.2 (95% CI [6.8, 7.6]) months for the chemotherapy- and immune-based groups, respectively (p &lt; 0.001). The median OS was 3.6 (95% CI [1.6, 5.6]) and 13.7 (95% CI [5.1, 22.3]) months for the chemotherapy and immune-based groups, respectively (p = 0.003). Multivariate analysis revealed that the immunotherapy-based regimen was an independent prognostic factor for PFS and OS (p &lt; 0.01, hazard ratio [HR] = 0.22, 95% CI [0.07,0.67] and p &lt; 0.01 HR = 0.27 95% CI [0.11,0.68], respectively). Conclusions: Conventional chemotherapy has limited benefits in patients with stage IV PSC. However, patients with advanced PSC who received first-line immunotherapy-based regimens exhibited a remarkable response. The immunotherapy-based regimen was an independent prognostic factor for PFS and OS.

The prognostic impact of NKA dynamics in first-line treatment of metastatic colorectal cancer.

e15514 Background: Metastatic colorectal cancer (mCRC) remains a therapeutic challenge and new markers hold high priority. Natural Killer (NK) cells are immune cells with potent antitumor properties. The association between neoplastic development and level of effector functions of this cell type is well known. Moreover, it is recognized that NK cells are subject to tumor-mediated immune suppression. The present study aimed at elucidating a potential relationship between NK cell activity (NKA) and response to folinic acid, 5-fluorouracil, oxaliplatin, and irinotecan (FOLFOXIRI) in mCRC. Methods: NKA was analyzed in patients enrolled in a randomized trial of mCRC receiving FOLFOXIRI and either tocotrienol or placebo as first-line treatment. Blood (1 mL) was sampled into NK Vue tubes at baseline and before treatment cycles 2-3, placed at 37°C for 24 hours, and after incubation, the level of interferon-γ (IFNγ) in the plasma was a surrogate measure for NKA. A cutoff of 250 pg/mL IFNγ distinguished normal and low NKA. The endpoints were response rate (RR), progression-free survival (PFS), and overall survival (OS). Results: A total of 70 patients were enrolled in the randomized clinical trial. The results showed that tocotrienol had no effect on either RR (p = 0.62), PFS (p = 0.52), or OS (p = 0.80). Patients were classified into two groups according to the dynamics of NKA measured at the available time points. Patients that dropped from a normal to a low level of NKA in samples taken between baseline and before cycle 3 and patients with continuous low NKA (IFNγ &lt; 250 pg/mL) were categorized as NKA-low. The NKA-high group included patients that increased from an abnormal to a normal level of NKA and patients that remained within the normal range (IFNγ &gt; 250pg/mL) in all available samples. The RR in the two groups were 38% (8/21) and 69% (24/35), respectively (p = 0.0496). The median PFS was 186 days (95% confidence interval (CI) 136-225 days, n = 23) for the NKA-low group and 252 days (95% CI 223-305 days, n = 37) for NKA-high (p = 0.0005). The hazard ratio (HR) was 2.65 (95% CI 1.28-5.50). After adjusting for age, performance status (PS), and tumor location, NKA remained an independent prognostic factor for PFS (HR = 3.32, 95% CI 1.67-6.61, p = 0.001). Median OS was 408 days (95% CI 219-679 days, n = 23) and 1051 days (95% CI 645-1225 days, n = 37), respectively (p = 0.0034). For OS, the NKA-low group also showed a poor prognosis, HR 2.23 (95% CI 1.17-4.25). NKA dynamics remained an independent prognostic marker for OS after adjusting for age, PS, and tumor location (HR = 2.74, 95% CI 1.50-5.03, p = 0.001). Conclusions: The results suggest that NKA dynamics within the first two cycles of treatment may hold relevant prognostic information in first-line treatment of mCRC. The possible causative relationship between NKA and treatment effect needs further elucidation, but calls for experimental trials combining chemotherapy with NK cell therapy in mCRC.

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

e16124 Background: Immune checkpoint inhibitors (ICIs) targeting programmed cell death-1 (PD-1) or programmed cell death ligand-1 (PD-L1) has 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. This study aims to assess the efficacy of ICIs in GBC and explore the clinicopathological and molecular markers of ICI benefit. Methods: This was a single center, retrospective study, including 80 GBC patients who had received ICI (anti-PD-1 monoclonal antibody) therapy at Eastern Hepatobiliary Surgery Hospital (Shanghai, China) between January 2016 and December 2020. Tumor samples from 31 of these patients who had previously underwent surgical resection before ICI therapy were obtained and conducted for whole exome sequencing and immunohistochemical analysis. The primary outcome was progression-free survival (PFS). The secondary outcomes were overall survival (OS), objective response rate (ORR) and disease control rate (DCR). The associations between efficacy with clinicopathological factors, genetic variations and PD-L1/CD8 expression were further explored. Results: Of 80 patients with GBC, 36 were male, the median age was 61 years (range, 30-79). The median PFS and OS was 4.5 months (95% CI, 2.99-5.95) and 8.7 months (95% CI, 7.07-10.26) respectively. Multivariate analysis indicated that alcohol intake history (HR, 2.66; 95% CI, 1.31-5.40; p=0.007), extrahepatic metastasis (HR, 2.03; 95% CI, 1.15-3.59; p=0.015), carcinoma embryonic antigen (CEA) level ≥100U/mL (HR, 3.58; 95% CI, 1.65-7.74; p=0.001) and immune-related adverse events (irAEs) (HR, 0.24; 95% CI, 0.10-0.57; p=0.001) were independent prognostic factors for PFS. Extrahepatic metastasis (HR, 2.42; 95% CI, 1.37-4.31; p=0.003), CEA level ≥100U/mL (HR, 2.82; 95% CI, 1.33-5.95; p=0.007) and irAEs (HR, 0.32; 95% CI, 0.14-0.72; p=0.006) were independent prognostic factors for OS. ORR and DCR were 13.75% and 37.5%, respectively. Patients with irAEs (85.7%, OR, 16.00; 95% CI, 3.26-78.61; p&lt;0.001), high CD8+ T-cells-infiltrated GBCs (87.5%, OR, 19.83; 95% CI, 2.00-196.38; p=0.011), immune inflamed phenotype (66.7%, OR, 5.60; 95% CI, 1.16-27.08; p=0.032) had higher DCR, while patients with high level of total bilirubin (TBIL&gt;34.2μmol/L) (8.3%, OR, 0.12; 95% CI, 0.01-0.97; p=0.048) had lower DCR. Patients with high CD8+ T-cells-infiltrated or immune inflamed GBCs also had a notably improved PFS and OS. Conclusions: ICIs were effective in patients with GBC. Alcohol intake history, extrahepatic metastasis, CEA level ≥100U/mL, irAEs, high positivity of CD8+ T-cells and immune inflamed phenotype may be useful for predicting the efficacy of ICIs in GBC.

An Individualized Prognostic Model in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma Based on Serum Metabolomic Profiling.

This study aims to evaluate the value of a serum metabolomics-based metabolic signature for locoregionally advanced nasopharyngeal carcinoma (LA-NPC) patients, thereby assisting clinical decisions. In this retrospective study, a total of 320 LA-NPC patients were randomly divided into a training set (ca. 70%; n = 224) and a validation set (ca. 30%; n = 96). Serum samples were analyzed using widely targeted metabolomics. Univariate and multivariate Cox regression analyses were used to identify candidate metabolites related to progression-free survival (PFS). Patients were categorized into high-risk and low-risk groups based on the median metabolic risk score (Met score), and the PFS difference between the two groups was compared using Kaplan-Meier curves. The predictive performance of the metabolic signature was evaluated using the concordance index (C-index) and the time-dependent receiver operating characteristic (ROC), and a comprehensive nomogram was constructed using the Met score and other clinical factors. Nine metabolites were screened to build the metabolic signature and generate the Met score, which effectively separated patients into low- and high-risk groups. The C-index in the training and validation sets was 0.71 and 0.73, respectively. The 5-year PFS was 53.7% (95% CI, 45.12-63.86) in the high-risk group and 83.0% (95%CI, 76.31-90.26) in the low-risk group. During the construction of the nomogram, Met score, clinical stage, pre-treatment EBV DNA level, and gender were identified as independent prognostic factors for PFS. The predictive performance of the comprehensive model was better than that of the traditional model. The metabolic signature developed through serum metabolomics is a reliable prognostic indicator of PFS in LA-NPC patients and has important clinical significance.

Minimal residual disease status improved the response evaluation in patients with Waldenström's macroglobulinemia.

Minimal residual disease (MRD) has been recognized as an important prognostic factor of survival in patients with hematological malignancies. However, the prognostic value of MRD in Waldenström macroglobulinemia (WM) remains unexplored. We analyzed 108 newly diagnosed WM patients receiving systematic therapy and assessed for MRD by multiparameter flow cytometry (MFC) using bone marrow samples. Of the total patients, 34 (31.5%) achieved undetectable MRD (uMRD). A hemoglobin level of >115 g/L (P=0.03), a serum albumin level of >35 g/L (P=0.01), a β2-MG level of ≤3 mg/L (P=0.03), and a low-risk International Prognostic Scoring System for WM (IPSSWM) stage (P<0.01) were associated with a higher rate of uMRD. Improvements in monoclonal immunoglobulin (P<0.01) and hemoglobin (P=0.03) levels were more evident in uMRD patients compared with that in MRD-positive patients. The 3-year progression-free survival (PFS) was better in uMRD patients compared with that in MRD-positive patients (96.2% vs. 52.8%; P=0.0012). Landmark analysis also showed that uMRD patients had better PFS compared with MRD-positive patients after 6 and 12 months. Patients who achieved partial response (PR) and uMRD had a 3-year PFS of 100%, which was significantly higher than that of patients with MRD-positive PR (62.6%, P=0.029). Multivariate analysis showed that MRD positivity was an independent factor of PFS (HR: 2.55, P=0.03). Moreover, the combination of the 6th International Workshop on WM assessment (IWWM-6 Criteria) and MRD assessment had a higher 3-year AUC compared with the IWWM-6 criteria alone (0.71 vs. 0.67). MRD status assessed by MFC is an independent prognostic factor for PFS in patients with WM, and its determination could improve the precision of response evaluation, especially in patients who achieved PR.

Hypothyroidism in induction chemotherapy of children with acute lymphoblastic leukaemia: A single-centre study.

Hypothyroidism as a long-term complication in cancer survivors has been an issue, but few studies have focused on changes in thyroid hormone levels during chemotherapy for leukaemia. This retrospective study was conducted to assess the characteristics of children with acute lymphoblastic leukaemia (ALL) and hypothyroidism during induction chemotherapy and to investigate the prognostic value of hypothyroidism in ALL. Patients with a detailed thyroid hormone profile at ALL diagnosis were enrolled. Hypothyroidism was defined as low serum levels of free tetraiodothyronine (FT4) and/or free triiodothyronine (FT3). The Kaplan-Meier method was used to create survival curves, and multivariate Cox regression analysis was used to screen prognostic factors associated with progression-free survival (PFS) and overall survival (OS). There were 276 children eligible for the study, and 184 patients (66.67%) were diagnosed with hypothyroidism, including 90 cases (48.91%) with functional central hypothyroidism and 82 cases (44.57%) with low T3 syndrome. Hypothyroidism was correlated with the dosages of L-Asparaginase (L-Asp) (P = .004) and glucocorticoids (P = .010), central nervous system (CNS) status (P = .012), number of severe infections (grade 3, 4 or 5) (P = .026) and serum albumin level (P = .032). Hypothyroidism was an independent prognostic factor for PFS in ALL children (P = .024, 95% CI: 1.1-4.1). We conclude that hypothyroidism is commonly present in ALL children during induction remission, which is related to chemotherapy drugs and severe infections. Hypothyroidism was a predictor of poor prognosis in childhood ALL.

Young patients show poor efficacy for immune checkpoint inhibitor combined therapy in metastatic gastrointestinal cancers.

The impact of age on the efficacy and safety of immunotherapy remains controversial. The previous studies simply classified patients into younger and older groups, which might not reflect the real impact of young age on immunotherapy efficacy. The current study aimed to explore the efficacy and safety of immune checkpoint inhibitor (ICI) combined therapy in young (aged 18-44 years), middle-aged (aged 45-65 years), and old (aged >65 years) patients with metastatic gastrointestinal cancers (GICs), and further determine the role of immunotherapy in young patients. Patients with metastatic GIC including esophageal cancer (EC), gastric cancer (GC), hepatocellular cancer (HCC), and biliary tract cancer (BTC) who received ICI combination therapy were enrolled, divided into young (aged 18-44 years), middle-aged (aged 45-65 years), and old (aged >65 years) groups. The clinical characteristics, objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAEs) were compared among three groups. A total of 254 patients were finally included, with 18, 139, and 97 cases in the young (aged 18-44 years), middle-aged (aged 45-65 years), and old (aged >65 years) groups, respectively. Compared to middle-aged and old patients, young patients had lower DCR (all p < 0.05) and also had inferior PFS (p < 0.001) and OS (p = 0.017). The multivariate analyses showed that young age was an independent prognostic factor for PFS [hazard ratio (HR) 3.474, 95% confidence interval (CI) 1.962-6.150, p < 0.001] and OS (HR 2.740, 95% CI 1.348-5.570, p = 0.005). Subsequent safety analyses referring to irAEs demonstrated no significant differences for distribution frequency among each age group (all p > 0.05), whereas patients with irAEs displayed better DCR (p = 0.035) and PFS (p = 0.037). Younger GIC patients (aged 18-44 years) showed poor efficacy for ICI combined therapy, and irAEs could be used as a clinical biomarker to predict ICI efficacy in metastatic GIC patients.

Perioperative Chemotherapy Could Not Improve the Prognosis of Gastric Cancer Patients With Mismatch Repair Deficiency: A Multicenter, Real-World Study.

To date, the role of deficient mismatch repair (dMMR) remains to be proven in gastric cancer, and it is difficult to judge its value in clinical application. Our study aimed to investigate how MMR status affected the prognosis in patients with gastrectomy, as well as the efficacy of neoadjuvant chemotherapy and adjuvant chemotherapy in patients with dMMR with gastric cancer. Patients with gastric cancer with certain pathologic diagnosis of dMMR or proficient MMR (pMMR) using immunohistochemistry from 4 high-volume hospitals in China were included. Propensity score matching was used to match patients with dMMR or pMMR in 1:2 ratios. Overall survival (OS) and progression-free survival (PFS) curves were plotted using the Kaplan-Meier method and compared statistically using the log-rank test. Univariate and multivariate Cox proportional hazards models based on hazard ratios (HRs) and 95% confidence intervals (CIs) were used to determine the risk factors for survival. In total, data from 6176 patients with gastric cancer were ultimately analyzed, and loss of expression of one or more MMR proteins was observed in 293 patients (293/6176, 4.74%). Compared to patients with pMMR, patients with dMMR are more likely to be older (≥66, 45.70% vs. 27.94%, P < .001), distal location (83.51% vs. 64.19%, P < .001), intestinal type (42.21% vs. 34.46%, P < .001), and in the earlier pTNM stage (pTNM I, 32.79% vs. 29.09%, P = .009). Patients with gastric cancer with dMMR showed better OS than those with pMMR before PSM (P = .002); however, this survival advantage was not observed for patients with dMMR after PSM (P = .467). As for perioperative chemotherapy, results of multivariable Cox regression analysis showed that perioperative chemotherapy was not an independent prognostic factor for PFS and OS in patients with dMMR with gastric cancer (HR = 0.558, 95% CI, 0.270-1.152, P = .186 and HR = 0.912, 95% CI, 0.464-1.793, P = .822, respectively). In conclusion, perioperative chemotherapy could not prolong the OS and PFS of patients with dMMR with gastric cancer.

Hepatic arterial infusion chemotherapy combined with anti-PD-1/PD-L1 immunotherapy and molecularly targeted agents for advanced hepatocellular carcinoma: a real world study.

Molecular targeted therapy combined with immunotherapy significantly improves the prognosis of patients with advanced liver cancer. Additionally, hepatic arterial infusion chemotherapy (HAIC) can improve the prognosis of patients with advanced liver cancer. This real-world study aimed to evaluate the clinical efficacy and safety of HAIC combined with molecular targeted therapy and immunotherapy in the treatment of primary unresectable hepatocellular carcinoma (uHCC). A total of 135 patients with uHCC were enrolled in this study. Progression-free survival (PFS) was the primary endpoint. The efficacy of the combination therapy was assessed based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST) guidelines. Overall survival (OS), adverse events (AEs) and surgical conversion rate were the secondary endpoints. Univariate and multivariate Cox regression analyses were performed to examine independent prognostic factors. For sensitivity analysis, inverse probability weighting (IPW) was used to balance the influence of the tested confounding factors between groups to verify the robustness of conversion surgery for survival benefits. The E-values were estimated to assess robustness to unmeasured confounders. The median number of therapies was three. Approximately 60% of the patients had portal vein tumour thrombosis (PVTT). The most common targeted drugs were lenvatinib and bevacizumab, whereas the most common immunotherapy drug was sintilimab. The overall objective response rate (ORR) was 54.1%, and the disease control rate (DCR) was 94.6%. A total of 97 (72%) patients experienced AEs of grades 3-4. Fatigue, pain and fever were the most common symptoms of grade 3-4 AEs. The median PFS was 28 months and 7 months in the successful and unsuccessful conversion groups, respectively. The median OS was 30 months and 15 months in the successful and unsuccessful conversion groups, respectively. Successful conversion surgery, sex, hapatic vein invasion, BCLC stage, baseline tumour size, AFP levels and maximum therapeutic response were independent prognostic factors for PFS. Successful conversion surgery, number of interventions, hapatic vein invasion and total bilirubin levels were independent prognostic factors for OS. After IPTW, no standardised differences exceeding 0.1 were found. IPW-adjusted Kaplan-Meier curves showed that successful conversion surgery was an independent prognostic factor for both PFS and OS. The E-values of successful conversion surgery were 7.57 and 6.53 for OS and PFS, respectively, which indicated a relatively robust impact of successful conversion surgery on the prognosis of patients. Patients with primary uHCC undergoing HAIC combined with immunotherapy and molecular targeted therapy have a higher tumour regression rate and the side effects are manageable. Patients undergoing surgery after combination therapy have survival benefits.

A combination of pre-infusion serum ferritin, CRP and IL-6 predicts outcome in relapsed/refractory multiple myeloma patients treated with CAR-T cells.

Chimeric antigen receptor - T (CAR-T) cell therapy has shown remarkable efficacy in patients with relapsed/refractory multiple myeloma (R/R MM). However, a subset of patients still experienced progression or relapse, and the predictors of prognosis are little known. We analyzed the inflammatory markers before CAR-T cell infusion, to clarify their correlation with survival and toxicity. This study involved 109 R/R MM patients who received CAR-T therapy between June 2017 and July 2021. Inflammatory markers, including ferritin, c-reactive protein (CRP), and interleukin-6 (IL-6) before CAR-T cell infusion were detected and then categorized by quartiles. Adverse events and clinical outcomes were compared between patients with upper quartile of inflammatory markers and patients with lower three quartiles of inflammatory markers. An inflammatory prognostic index (InPI) based on these three inflammatory markers was developed in this study. Patients were divided into 3 groups according to the InPI score, progression-free survival (PFS) and overall survival (OS) were compared among the groups. In addition, we explored the correlation between cytokine release syndrome (CRS) and pre-infusion inflammatory markers. We found that the pre-infusion high ferritin (hazard ratio [HR], 3.382; 95% confidence interval [CI], 1.667 to 6.863; P = .0007), high CRP (HR, 2.043; 95% CI, 1.019 to 4.097; P = .044), and high IL-6 (HR, 3.298; 95% CI, 1.598 to 6.808; P = .0013) were significantly associated with inferior OS. The formula of the InPI score was based on the HR value of these 3 variables. Three risk groups were formed: (good, 0 to 0.5 point; intermediate, 1 to 1.5 points; poor, 2 to 2.5 points). Median OS for patients with good, intermediate, and poor InPI was not reached, 24 months, and 4 months, respectively, and median PFS was 19.1 months, 12.3 months, and 2.9 months, respectively. In the cox proportional hazards model, poor InPI remained an independent prognostic factor for PFS and OS. Pre-infusion ferritin was negatively associated with CAR T-cell expansion normalized to baseline tumor burden. Spearman correlation analysis showed that pre-infusion ferritin and IL-6 levels positively correlated with the grade of CRS (P = .0369 and P = .0117, respectively). The incidence of severe CRS was higher in patients with high IL-6 compared with patients with low IL-6 (26% vs. 9%, P = .0405). Pre-infusion ferritin, CRP and IL-6 were positively correlated with each peak values within the first month after infusion. Our results suggest that patients with elevated inflammation markers before CAR-T cell infusion are more likely to have poor prognosis.

Clinical Characteristics, Course, and Long-Term Outcomes in Patients with Talaromyces marneffei Infection: A 10-Year Retrospective Cohort Study.

Talaromycesmarneffei (T.marneffei), a dimorphic fungus, causes local or disseminated infection in humans. We aimed to analyze the clinical characteristics, prognosticfactors, and survival outcomes of patients with T.marneffei infection and compare the differences betweenhuman immunodeficiency virus (HIV)-positive and HIV-negative subgroups. We retrospectively analyzed 241 patients with T.marneffei infection at the First Affiliated Hospital of Guangxi Medical University between January 2012 and January 2022. The overall population was stratified into HIV-positive (n = 98) and HIV-negative (n = 143) groups according to HIV status. Kaplan-Meier analysis and multivariate Cox regression models were used to determine the prognostic factors for overall survival (OS) and progression-free survival (PFS). With a median follow-up time of 58.9months, 120 patients (49.8%) experienced disease progression and 85 patients (70.8%) died. The 5-year rates of OS and PFS were 61.4% (95% CI 55.0-68.6%) and 47.8% (95% CI 41.5-55.1%), respectively. As an independent factor, patients who were HIV positive had better PFS (HR 0.50, 95% CI 0.31-0.82; p < 0.01) than patients who were HIV negative. Compared with patients who were HIV positive, patients who were HIV negative were older and had more probabilities of underlying diseases, chest involvement, bone destruction, and higher count of neutrophils (all p < 0.05). Hemoglobin (PFS: HR 0.62; 95% CI 0.39-1.00; p < 0.05; OS: HR 0.45; 95% CI 0.22-0.89; p = 0.02) and lymphocyte count (PFS: HR 0.06; 95% CI 0.01-0.26; p < 0.01; OS: HR 0.08; 95% CI 0.01-0.40; p < 0.01) were independent prognostic factors for PFS and OS in patients who were HIV negative. Patients with T.marneffei infection have a poor prognosis. Patients who are HIV positive and HIV negative have relatively independent clinical characteristics. Multiple organ involvement and disease progression are more common in patients who are HIV negative.

Efficacy and safety of lenvatinib plus PD-1 inhibitor with or without transarterial chemoembolization in unresectable hepatocellular carcinoma.

To compare the clinical benefit and tolerability of triple therapy of lenvatinib, programmed death 1 (PD-1) inhibitor, and transarterial chemoembolization (TACE) versus dual therapy of lenvatinib and PD-1 inhibitor in unresectable hepatocellular carcinoma (HCC) patients. Between October 2018 and September 2021, patients with unresectable HCC who received triple therapy of lenvatinib, PD-1 inhibitor, and TACE or dual therapy of lenvatinib and PD-1 inhibitor participated in this study. The efficacy was evaluated by survival and therapeutic response, and the tolerability was evaluated by the frequency and severity of key adverse events (AEs). In total, 118 eligible patients with unresectable HCC who received combination therapy were included in this study. Among them, 60 patients received triple therapy of lenvatinib, PD-1 inhibitor, and TACE (L-P-T group), and 58 eligible patients received dual therapy of lenvatinib and PD-1 inhibitor (L-P group). Patients who received triple therapy had better overall survival (OS) [median, 29.0 vs. 17.8months, p < 0.01] and progression-free survival (PFS) [median, 16.2 vs. 10.2months, p < 0.01] than those who received dual therapy. The objective response rate (76.7 vs. 44.9%, p < 0.01) and disease control rate (96.7 vs. 75.9%, p < 0.01) in the L-P-T group were higher than in the L-P group, respectively. Multivariate analyses revealed that the treatment option and BCLC stage were independent prognostic factors for OS, while treatment option and tumor number were independent prognostic factors for PFS. The incidence and severity of AEs in the L-P-T group were comparable to those in the L-P group (any grade, 95.0 vs. 94.8%, p = 1.00; grade ≥ 3, 30.0 vs. 27.6%, p = 0.93). Triple therapy of lenvatinib, PD-1 inhibitor, and TACE may achieve more favorable survival benefits than dual therapy of lenvatinib and PD-1 inhibitor in unresectable HCC patients with manageable safety profiles.

Real-World Experience of PD-1 Inhibitors for Relapsed and Refractory Hodgkin Lymphoma: A Multicenter Retrospective Analysis of Patients in China

Introduction: Despite the promising clinical trial data regarding programmed death 1 (PD-1) inhibitors in relapsed/refractory classical Hodgkin lymphoma (R/R cHL), there remains a paucity of studies describing the outcomes of patients in a real-world setting, especially for Asian cohort. Methods: We present a multicenter retrospective analysis of patients with R/R cHL who had failed ≥2 prior lines of therapies and received sintilimab or tislelizumab developed in China (sintilimab or tislelizumab monotherapy) at 3 medical centers from January 2019 to September 2021. Efficacy was evaluated with progression-free survival (PFS), overall survival, duration of response (DOR), best overall response (BOR) including objective response rate (ORR), complete response rate (CRR). Safety data were also recorded. Results: 74 patients were reviewed. The median age was 38 years (range, 14–85 years). The ORR, CRR, and disease control rate were 78.3%, 52.7%, and 91.9%, respectively. The median duration of follow-up was 22 (4–36) months. Four patients (5.4%) died of disease progression. The median PFS and DOR was 22.1 and 23.5 months. BOR as a new emergent endpoint was found to be the only independent prognostic factor for PFS in our study (HR = 6.234, p = 0.005), suggesting this endpoint carries stronger prognostic value over traditional endpoints in the immunotherapy era. 66 (89.2%) patients reported adverse event (AE) with any grade, with the majority of AEs being grade 1 or 2. Conclusion: We presented a unique real-life experience and conducted a relatively long follow-up of PD-1 antibodies developed in China for R/R HL patients which confirmed their promising effectiveness and manageable side effects given in real world in an Asian cohort. Even for those who would usually be excluded in most of clinical trials such as elderly or minor patients, anti-PD-1 monotherapy also showed a significant improvement of outcomes. Furthermore, the depth of response seemed to be a more powerful predictive tool in new era, which might serve as a basis for future immune risk-adapted strategies.

Clinicopathologic analysis of pineal parenchymal tumors of intermediate differentiation: a multi-institutional cohort study by the Kyushu Neuro-Oncology Study Group.

Pineal parenchymal tumors of intermediate differentiation (PPTIDs), which were recognized in the 2007 World Health Organization (WHO) classification, are rare, accounting for less than 1% of all central nervous system tumors. This rarity and novelty complicate the diagnosis and treatments of PPTID. We therefore aimed to evaluate the clinicopathological significance of this tumor. At 11 institutions participating in the Kyushu Neuro-Oncology Study Group, data for patients diagnosed with PPTID were collected. Central pathology review and KBTBD4 mutation analysis were applied to attain the diagnostically accurate cohort. PPTID was officially diagnosed in 28 patients: 11 (39%) with WHO grade 2 and 17 (61%) with WHO grade 3 tumors. Median age was 49years, and the male:female ratio was 1:2.1. Surgery was attempted in all 28 patients, and gross total resection (GTR) was achieved in 46% (13/28). Adjuvant radiotherapy and chemotherapy were administered to, respectively, 82% (23/28) and 46% (13/28). The 5-year progression-free survival (PFS) and overall survival rates were 64.9% and 70.4% respectively. Female sex (p = 0.018) and GTR (p < 0.01) were found to be independent prognostic factors for PFS and female sex (p = 0.019) was that for OS. Initial and second recurrences were most often leptomeningeal (67% and 100% respectively). 80% (20/25) of patients harbored a KBTBD4 mutation. Female sex and GTR were independent prognostic factors in our patients with PPTID. Leptomeningeal recurrence was observed to be particularly characteristic of this tumor. The rate of KBTBD4 mutation observed in our cohort was acceptable and this could prove the accuracy of our PPTID cohort.

Brain metastasis and survival outcomes after first-line therapy in metastatic melanoma: a multicenter DeCOG study on 1704 patients from the prospective skin cancer registry ADOREG

BackgroundDespite the availability of effective systemic therapies, a significant number of advanced melanoma patients develops brain metastases. This study investigated differences in incidence and time to diagnosis of brain metastasis...

Low body mass index is associated with poor treatment outcome following radiotherapy in esophageal squamous cell carcinoma.

We aimed to determine whether patients with esophageal cancer with a low baseline body mass index (BMI) have a poor prognosis following radiotherapy (RT). We retrospectively analyzed data from 50 patients with esophageal cancer to determine whether a low starting BMI (before RT) was associated with a poor outcome. All study participants were diagnosed with non-metastatic esophageal squamous cell carcinoma (SCC). The number of patients at each T stage were as follows: 7 (14%) patients at T1, 18 (36%) at T2, 19 (38%) at T3, and 6 (12%) at T4. Based on BMI, 7 (14%) patients were defined as underweight. A low BMI was common in patients with T3/T4 stage esophageal cancer (7/43, p = 0.01). Overall, the 3-year progression-free survival (PFS) and overall survival (OS) rates were 26.3% and 69.2%, respectively. In univariate analysis, clinical factors associated with poor PFS included being underweight (BMI <18.5 kg/m2; p = 0.011) and a positive N status (p = 0.017). Univariate analysis also revealed that being underweight was associated with a decrease in OS (p = 0.003). However, being underweight was not an independent prognostic factor for PFS and OS. Patients with esophageal SCC with a low starting BMI (BMI <18.5 kg/m2) are more prone to have a negative survival outcome following RT than patients who are considered to be normal weight or overweight. For this reason, it is important that clinicians pay more attention to BMI when treating patients with esophageal SCC.

CT-guided 125I brachytherapy for hepatocellular carcinoma in high-risk locations after transarterial chemoembolization combined with microwave ablation: a propensity score-matched study.

This study aimed to evaluate the safety and efficacy of 125I brachytherapy combined with transarterial chemoembolization (TACE) and microwave ablation (MWA) for unresectable hepatocellular carcinoma (HCC) in high-risk locations. After 1:2 propensity score matching (PSM), this retrospectively study analyzed 49 patients who underwent TACE +MWA+125I brachytherapy (group A) and 98 patients who only received TACE +MWA (group B). The evaluated outcomes were progression-free survival (PFS), overall survival (OS), and treatment complications. Cox proportional hazards regression analysis survival was used to compare the two groups. The patients in group A showed a longer PFS than group B (7.9 vs. 3.3 months, P = 0.007). No significant differences were observed in median OS between the two groups (P = 0.928). The objective response rate (ORR), disease control rate of tumors in high-risk locations, and the ORR of intrahepatic tumors were 67.3%, 93.9%, and 51.0%, respectively, in group A, and 38.8%, 79.6% and 29.6%, respectively, in group B (P < 0.001, P = 0.025 and P = 0.011, respectively). TACE-MWA-125I (HR = 0.479, P < 0.001) was a significant favorable prognostic factor that affected PFS. The present of portal vein tumor thrombosis was an independent prognostic factor for PFS (HR = 1.625, P = 0.040). The Barcelona clinic liver cancer (BCLC) stage (BCLC C vs. B) was an independent factor affecting OS (HR = 1.941, P = 0.038). The incidence of complications was similar between the two groups, except that the incidence of abdominal pain was reduced in the group A (P = 0.007). TACE-MWA-125I resulted in longer PFS and better tumor control than did TACE-MWA in patients with unresectable hepatocellular carcinoma in high-risk locations.

Adjuvant therapy for cholangiocarcinoma after surgery and prognosis factors for cholangiocarcinoma: A single-center retrospective cohort study.

Cholangiocarcinoma (CCA) is a highly heterogeneous malignant tumor, and more than 60% of patients have recurrence and metastasis after surgery. The efficacy of postoperative adjuvant therapy for CCA remains unclear. This study aimed to explore whether adjuvant therapy benefits patients with CCA and examine the independent prognostic factors for overall survival (OS) and progression-free survival (PFS). Patients with CCA undergoing surgery were retrospectively enrolled in this study from June 2016 to June 2022. The chi-square test or Fisher exact test was used to analyze the correlation between clinicopathologic characteristics. Survival curves were plotted using the Kaplan-Meier method, and the Cox regression model was used for univariate and multivariate analysis to search for independent prognostic factors. Of the 215 eligible patients, 119 patients received adjuvant therapy, and the other 96 patients did not. The median follow-up was 37.5 months. The median OS of CCA patients with and without adjuvant therapy was 45 and 18 months (P < 0.001), respectively. The median PFS of CCA patients with and without adjuvant therapy was 34 and 8 months (P < 0.001), respectively. The Cox univariate and multivariate regression analysis showed that preoperative aspartate transaminase and carbohydrate antigen 19-9, microvascular invasion, lymph node metastasis, differentiation degree, and adjuvant therapy were independent prognostic factors for OS (all P values < 0.05). Preoperative carbohydrate antigen 125, microvascular invasion, lymph node metastasis, differentiation degree, and adjuvant therapy were independent prognostic factors for PFS (all P values < 0.05). The stratified analysis by TMN stage detected significant differences in the early stages (median OS [mOS]: P=0.0128; median PFS [mPFS]: P=0.0209) and advanced stages (mOS and mPFS: both P values < 0.001). Adjuvant therapy was also identified as a significantly favorable prognostic factor for OS and PFS in the early stages and advanced stages. Postoperative adjuvant therapy can improve the prognosis of patients with CCA, even in the early stages and advanced stages. All data suggest that adjuvant therapy should be incorporated into the treatment of CCA in all cases, where appropriate.