Prognostic Risk Factors For Overall Survival Research Articles

The Baseline Serum Lipid Levels and Outcomes of NSCLC Patients Receiving Immunotherapy Combined or Non-Combined with Radiotherapy: A Single Center Retrospective Study

In recent years, many studies have shown that lipids and lipid-like substances are key regulatory factors in tumor development and play an important role in immune regulation. However, it remains unclear whether serum lipids influence the outcome of immunotherapy. Therefore, determining the serum lipid levels of the immune treatment-beneficiary population may be valuable. The aim of this study is to evaluate the prognostic value of baseline serum lipid levels in non-small cell lung cancer (NSCLC) patients receiving immunotherapy. We retrospectively included 294 patients with stage III-IV NSCLC who received immunotherapy continuously from December 2018 to November 2021 at our hospital, collecting their pre-treatment lipid levels, such as total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C). Of these, 160 receiving immunotherapy without combined radiotherapy (ICIs-nRT) and 134 combined with radiotherapy (iRT). The endpoint was the correlation between pre-treatment serum lipid levels and overall survival (OS), as well as progression-free survival (PFS). The X-tile tool was used to determine the optimal cut-off value of the indicators. The Kaplan-Meier survival curves were used to calculate OS and PFS and log rank tests were used for comparison. And the Cox proportional hazard model were used for univariate and multivariate analysis. In all 294 patients, low TG, low TC, and low HDL-C predicted poor OS (P<0.001) and poor PFS (P<0.05). Low LDL-C was associated with poor OS (P = 0.0001). Among 160 patients receiving ICIs-nRT and 134 iRT patients, low levels of TG (P = 0.0134, 0.0024), TC (P = 0.0003, 0.0023), HDL-C (P = 0.0004, 0.0043), and LDL-C (P = 0.0003, 0.0419) were associated with worse OS compared to high levels of them. In the ICIs-nRT patients, low HDL-C predicted poor PFS (P = 0.0011). In 134 iRT patients, low levels of TG (P = 0.0017), TC (P = 0.0028), and LDL-C (P = 0.0330) were poor prognostic factors for PFS. In the univariate and multivariate analysis with OS in all patients, TG and HDL-C were independent risk factors, while TG was an independent risk factor in the analysis with PFS. In ICIs-nRT patients, HDL-C was an independent prognostic factor for patients' OS and PFS. In iRT patients, both TG and HDL-C were prognostic risk factors for OS. These data confirm that higher serum lipid levels are associated with better outcomes in patients with NSCLC undergoing immunotherapy. Serum lipids may identify tumors that are more likely to respond to immunotherapy. Radiation therapy may affect lipid metabolism within the body to enhance the efficacy of immunotherapy.

The percentages of signet-ring cells (SRCs) affects the prognosis after radical gastrectomy for advanced gastric cancer.

Only recently has the percentage of signet-ring cells (SRCs) been shown to affect the prognosis following gastric cancer surgery. It is uncertain whether the SRC percentage has a role in tumour biology or prognosis of gastric signet-ring cell carcinoma (GSRCC). For this research, we assessed the effect of the SRC percentage on the clinicopathological and prognostic characteristics of gastric cancer (GC) tumours and created and verified a prognostic nomogram to assess the overall survival (OS) of GSRCC patients. In our study, 1100 GC patients with signet-ring cell carcinoma (SRCC) at Zhejiang Cancer Hospital from December 2013 to December 2018 who underwent curative gastric cancer resection were retrospectively analysed. The patients were separated into two groups: those with SRCC (SRC percentage >50%; n = 157) and those with partial signet-ring cell carcinoma (PSRCC) (SRC percentage ≤50%; n = 943). We compared the clinicopathological characteristics of both groups. To estimate OS and determine correlations with the SRC percentage, the Kaplan-Meier method and log-rank test were used. To develop the prognostic nomogram, independent prognostic indicators for OS were identified using Cox regression analyses. Predictions were assessed using the calibration curve and C-index. Our research showed that there was no discernible difference in OS between the two groups. The preoperative CA242 level, pT stage, pN stage, age, nerve invasion, neoadjuvant chemotherapy, postoperative chemotherapy, and maximum tumour diameter were independent prognostic risk factors for OS for GC (all p < 0.05). However, for advanced GC, the SRC percentage (HR = 1.571, 95% CI 1.072-2.302, p = 0.020) was an independent prognostic factor of OS. Other independent prognostic risk factors were age, pT stage, pN stage, nerve invasion, tumour location, neoadjuvant chemotherapy, postoperative chemotherapy, preoperative CA50 level, and preoperative CEA level (all p < 0.05). On these bases, nomograms were constructed for GC and advanced GC, with C-indexes of 0.806 (95%CI 0.782-0.830) and 0.728 (95%CI 0.697-0.759), respectively. In cases of advanced gastric cancer, the SRC percentage served as a standalone prognostic indicator for OS. An effective tool for assessing the prognosis of GSRCC was offered by the nomogram.

Timing of surgery in patients with synchronous colorectal cancer liver metastases undergoing neoadjuvant chemotherapy: a propensity score analysis

BackgroundThe optimal timing of surgery after neoadjuvant chemotherapy (NAC) in patients with synchronous colorectal cancer liver metastases (SLM) remains controversial. We plan to analyze whether the choice of different surgical timings will have different effects on the perioperative and oncologic outcomes of patients.MethodWe retrospectively collected all patients who met the inclusion and exclusion criteria from 2010 to 2020 in West China Hospital. Patients were grouped according to time interval (TI) after NAC to surgery. The perioperative and oncologic outcomes of the two groups were compared after propensity score matching. Univariate and multivariate analyzes were used to screen factors associated with prognosis.ResultAmong 255 enrolled patients, 188 were matched with comparable baseline (94 each group). Patients in the 6≦TI≦8 group had longer operation time, less intraoperative blood loss, and less postoperative complications than those in the 4≦TI < 6 group. However, the overall survival (OS) (p = 0.012) and disease-free survival (DFS) (p = 0.013) of the patients in the 4≦TI < 6 group were better than those in the 6≦TI≦8 group. Subgroup analysis found that the above conclusions still apply in age ≥ 60, non-anemic patients, and patients who underwent R0 resection. OS was inversely correlated with TI in patients without preoperative jaundice. DFS was negatively correlated with TI in patients with preoperative jaundice. Multivariate analysis showed that the prolongation of TI after NAC to surgery was an independent prognostic risk factor for OS and DFS.ConclusionsPatients with SLM may be a better choice for surgery within 4–6 weeks after receiving NAC. Although patients with SLM undergoing surgery 4–6 weeks after NAC has a higher rate of postoperative complications, radical surgery is still recommended for a better survival benefit.

Efficacy and safety of transarterial chemoembolization plus sorafenib in patients with recurrent hepatocellular carcinoma after liver transplantation.

To explore the benefit and safety of transarterial chemoembolization (TACE) in combination with sorafenib in patients with recurrent hepatocellular carcinoma (HCC) after orthotopic liver transplantation (OLT). In this multi-center retrospective study, 106 patients with recurrent HCC after OLT were included. Fifty-two patients were treated with TACE plus sorafenib (TS group) and 54 were treated with TACE alone (TC group). Primary and secondary endpoints including overall survival (OS) and progression-free survival (PFS), and safety were assessed. The median OS (17 vs 10 months, P=0.035) and PFS (12 vs 6 months, P=0.004) in the TS group were longer than those in the TC group. On multivariate analysis, BCLC stage (HR [hazard ratio]=0.73 [95% CI, 0.27-0.99], P=0.036) and sorafenib medication (HR=2.26 [95% CI, 1.35-3.69], P=0.01) were identified as independent prognostic risk factors for OS. No severe adverse events related to sorafenib were noted in the TS group. Four patients discontinued sorafenib due to intolerance. TACE in combination with sorafenib is a feasible regimen to improve the survival with mild toxicity in patients with recurrent HCC after OLT.

Clinical prognostic risk analysis and progression factor exploration of primary breast lymphoma

ABSTRACT Purpose : A primary breast lymphomais a rare form of extranodal lymphoma type. We aimed to analyze prognosticriskfactors and explore relapse factors in primary breast diffuse large B cell lymphoma (PB-DLBCL). Methods : From November 2003 to September 2020, sixty-three patients from two medical centers newly diagnosed with PB-DLBCL patients were analyzed retrospectively. Results : The median age was 52, and >50% of patients were post-menopausal. The international prognostics index (IPI) (0–1) was mainlyin the low-risk group (84%), and there were four patients with stage IV (6%) who had bilateral breast involvement. With a median follow-up time of 4.92 years (3.17–8.00), five-year overall survival (OS) and progression-free survival (PFS) were 78.9% and 67.1%, respectively. Univariate and multivariate analyses showed that elevated erythrocyte sedimentation rate (ESR) and B symptoms were independent adverse prognostic risk factors for OS, whereas bilateral breast involvement was unfavorable for PFS. Disease recurrence and relapse occurred in 40% (25/63) patients, mainly in the breast, followed by the central nervous system (CNS) and skin/soft tissue. Conclusion : This is the first study to explore the prognostic risk factors and relapse factorsof PB-DLBCL in a relatively large Chinese PBL cohort. Local breast and CNS recurrence after standard R-CHOP treatment were the main issues we are facing now.

Single Centre, Retrospective Analysis of Treatment Outcomes and Prognostic Factors in Blastic Phase Chronic Myeloid Leukemia (CML-BP) Following Systemic Therapy

Introduction: Despite the introduction of BCR-ABL1 tyrosine kinase inhibitors (TKI), the prognosis of blastic phase chronic myeloid leukemia (CML-BP) remains dismal. Due to its low incidence, prospective evaluation of outcomes of CML-BP following systemic treatment is challenging. Thus, we aimed to evaluate the outcomes of CML-BP following systemic therapy, and to analyze prognostic factors affecting treatment outcomes. Methods: We retrospectively identified 55 patients with CML-BP per the European LeukaemiaNet 2013 criteria who treated at the Princess Margaret Cancer Centre in Toronto, Canada between 2000 and 2022. Patient and disease characteristics at the time of CML-BP diagnosis are presented in Table 1. Multiparametric flow cytometry data are described below, with percentages reflecting the proportion of positive antigen expression in evaluable patients. Treatment outcomes measured included: complete response (CR), leukaemia-free survival (LFS) and overall survival (OS). Prognostic factors evaluated include: age, transformation from chronic/accelerated phase (CP/AP), clonal evolution (CE), additional cytogenetic abnormalities (ACA), ABL1 KD mutation, extramedullary disease, blast immunophenotype, systemic treatment modality (intensive chemotherapy (IC) +/- TKI vs TKI monotherapy) and allogeneic haematopoietic stem cell transplantation (HCT). Results: Among the 55 patients, the median age at time of CML-BP diagnosis was 45 years (17 - 68) and included 35 (64%) cases of CML in myeloid BP (MBP) and 20 (36%) cases of lymphoid BP (LBP). 40 (72%) patients had transformed from a previous CP/AP with a median time of 2.4 years (0.1 - 19.3) from initial diagnosis to transformation. Extramedullary disease was present in 18/53 (34%) patients. The blast immunophenotype of MBP patients (n=31) was: CD34+ (84%), CD117+ (52%), HLA-DR+ (68%), CD13+ (87%), CD33+ (97%), MPO+ (40%), CD38+ (100%) and CD123+ (50%). Nine MBP patients (36%) had aberrant CD7 expression. Among 17 evaluable LBP patients, the immunophenotypic profile was: CD34+ (94%), HLA-DR+ (76%), CD19+ (94%), CD20+ (41%), CD10+ (94%), TdT (88%), CD38+ (100%) and CD7+ (18%). Nine patients (53%) had aberrant CD13 expression and five (29%) displayed aberrant CD33 expression. At CML-BP diagnosis, 21/42 (50%) had an ACA, of which 11 (26%) patients had high risk ACA, defined as −7/7q, 11q23 or 3q26.2 aberrations, or complex karyotype. Among transformed patients, CE was present in 16/43 (37%) patients. In 18 patients evaluated with Sanger sequencing at time of BP transformation, 9 patients (50%) had an ABL1-KD mutation. 54/55 received systemic therapy: 31 (57%) intensive chemotherapy (IC) + TKI, 7 (13%) IC alone, and 16 (30%) TKI monotherapy. Two patients died before response assessment, one after IC and one after TKI monotherapy. Among 46 patients with available post-treatment bone marrow assessments, CR/CRi rates were similar in those treated with IC+ TKI (29/31; 94%), IC only (5/6; 83%) or TKI only (7/9; 78%). Overall, 40/54 (74%) patients proceeded to allogeneic HCT after achieving CR/CRi or second CP. After a median follow-up of 39 months, the 3-year LFS and OS rates of all patients were 34.9% (20.7-49.6%) and 44.9% (95% CI, 30.4-58.4%), respectively. Patients with CML-LBP had a significantly higher OS compared to those with CML-MBP (p=0.0463), however, no significant difference in LFS was seen (p= 0.0913). Median duration of LFS and OS was 1.56 and 2.51 years, respectively. The following variables were found to be independently prognostic for OS: Transformation from CP/AP (p=0.0489, HR 4.328 [1.007, 18.60]), CD117 expression at time of CML-BP (p=0.0291, HR 2.809 [1.111, 7.102]), and IC + TKI (vs TKI monotherapy) (p=0.0068, HR 0.268 [0.104, 0.689]). CE at BP, transformation from CP/AP and IC +TKI (vs TKI monotherapy) were prognostic for LFS by univariate analysis, however, none was identified as independent risk factors. Conclusion The prognosis of CML-BP remains poor despite systemic therapy. Transformation from CP/AP, CD117 positivity at diagnosis of CML-BP and TKI monotherapy were identified as independent, adverse prognostic risk factors for OS. However, treatment with IC + TKI appeared to improve survival outcomes compared with TKI therapy alone. Therefore, combination therapy with IC + TKI should be considered the optimal strategy in treatment patients with CML-BP. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Gallbladder neuroendocrine carcinoma diagnosis, treatment and prognosis based on the SEER database: A literature review.

BACKGROUNDGallbladder neuroendocrine carcinoma (GB-NEC) has a low incidence rate; therefore, its clinical characteristics, diagnosis, treatment and prognosis are not well explored. AIMTo review recent research and analyze corresponding data in the Surveillance Epidemiology and End Results (SEER) database. METHODSData of GB-NEC (n = 287) and gallbladder adenocarcinoma (GB-ADC) (n = 19 484) patients from 1975 to 2016 were extracted from the SEER database. Survival analysis was performed using Kaplan–Meier and Cox proportional hazards regression. P < 0.05 was considered statistically significant. We also reviewed 108 studies retrieved from PubMed and Reference Citation Analysis (https://www.referencecitationanalysis.com/). The keywords used for the search were: "(Carcinoma, Neuroendocrine) AND (Gallbladder Neoplasms)". RESULTSThe GB-NEC incidence rate was 1.6% (of all gallbladder carcinomas), male to female ratio was 1:2 and the median survival time was 7 mo. The 1-, 2-, 3- and 5-year overall survival (OS) was 36.6%, 17.8%, 13.2% and 7.3% respectively. Serum chromogranin A levels may be a specific tumor marker for the diagnosis of GB-NEC. Elevated carcinoembryonic antigen, carbohydrate antigen (CA)-19-9 and CA-125 levels were associated with poor prognosis. Age [hazard ratio (HR) = 1.027, 95% confidence interval (CI): 1.006–1.047, P = 0.01] and liver metastasis (HR = 3.055, 95% CI: 1.839–5.075, P < 0.001) are independent prognostic risk factors for OS. Patients with advanced GB-NEC treated with surgical resection combined with radiotherapy and/or chemotherapy may have a better prognosis than those treated with surgical resection alone. There was no significant difference in OS between GB-NEC and GB-ADC.CONCLUSIONThe clinical manifestations and prognosis of GB-NEC are similar to GB-ADC, but the treatment is completely different. Early diagnosis and treatment are the top priorities.

Analysis of Treatment Outcomes and Prognosis After Concurrent Chemoradiotherapy for Locally Advanced Cervical Cancer.

The aims of this study were to investigate the short-term and long-term efficacies and chronic radiotoxicity of concurrent chemoradiotherapy (CCRT) combined with image-guided adaptive brachytherapy (IGABT) in patients with locally advanced cervical cancer (LACC) and identify prognostic factors in this patient population. The clinical data of 204 patients with cervical cancer who completed CCRT and subsequent brachytherapy in our hospital between February 2015 and March 2017 were retrospectively analyzed. Short-term and long-term outcomes, chronic radiotoxicity, and prognostic factors were assessed. The median follow-up was 61.1 months. The short-term objective response (OR) rate was 85%. Lymph node metastasis before treatment was an independent predictor of OR (HR = 6.290, 95% CI: 2.211-17.897, p = 0.001). Fifty-two patients developed recurrence, with a median recurrence-free survival of 9.9 months (range, 2.4-52.2 months) and a post-recurrence survival of 12.1 months (range, 2.9-58.1 months). At 3 years, the cumulative incidence of overall recurrence was 26% (95% CI: 17-36). Multivariate analysis showed that Stage IIIB (HR = 2.332, 95% CI: 1.195-4.551, p = 0.013; reference, Stage IIB) and lymph node metastasis (HR = 4.462, 95% CI: 2.365-8.419, p < 0.001) were significant independent predictors of recurrence. Fifty-three patients developed chronic radiation proctitis (CRP). The incidence of severe CRP was approximately 5%, and the average rectal accumulation in patients with severe CRP was 73.4 Gy which is 3.9 Gy higher than that in patients without CRP (p = 0.013). At 4 years, the overall survival (OS) and disease-free survival rates were 65% and 62%, respectively, and lymph node metastasis before treatment was an independent prognostic risk factor for OS. The short-term and long-term efficacies of CCRT combined with IGABT for the treatment of LACC patients were relatively satisfactory. However, the short-term and long-term efficacies of patients with lymph node metastasis before treatment were poor. For patients with lymph node metastasis before treatment, more active individualized treatment strategies should be adopted. When designing a radiotherapy plan, it is necessary to strictly limit the rectal accumulation to prevent serious CRP.

IL-12RB1: a novel immune prognostic biomarker for oral squamous cell carcinoma and linked to PD-1/PD-L1 expression in the tumor immune microenvironment.

BackgroundThis study aimed to screen and identify potential immune biomarker to predict the prognosis of oral squamous cell carcinoma (OSCC).MethodsData of OSCC patient from The Cancer Genome Atlas (TCGA) database were downloaded, and the ESTIMATE algorithm was used to calculate stromal and immune scores. Differentially expressed genes (DEGs) between the high and low immune score groups were screened, and Kaplan-Meier survival analysis was performed to identify the DEGs linked to the overall survival (OS) time of OSCC patients. Then, those DEGs were validated in anther cohort. A correlation analysis was used to further screen the prognostic genes which were tightly linked to the expression of programmed cell death 1 (PD-1)/programmed death-ligand 1 (PD-L1). The expression profiles of the candidate genes interleukin 12 receptor subunit beta 1 (IL-12RB1), cytotoxic T-lymphocyte associated protein 4 (CTLA4), and G protein-coupled receptor 25 (GPR25) were identified in the single-cell RNA sequence OSCC dataset from GSE103322. Finally, immunohistochemistry (IHC) and immunofluorescence (IF) were applied to confirm the expression pattern of IL-12RB1 in OSCC tissue microarray. Kaplan-Meier analysis was used to assess the prognostic significance of IL-12RB1 staining score in the malignant and non-malignant cells among the patients.ResultsThe high immune score group showed better OS compared with that of the low immune scores group. Among 339 DEGs, 90 were identified as being tightly linked to OS time. In the validation set, 23 genes were confirmed to be closely associated with survival prognosis, and the expression levels of IL-12RB1, CTLA4, and GPR25 were commonly associated with the expression of PD-1/PD-L1. The RNA-sequencing showed that IL-12RB1 was expressed in epithelial and immune cells, whereas CTLA4 and GPR25 were relatively poorly expressed in the OSCC tissue. IHC showed that IL-12RB1 was positively expressed in both malignant and non-malignant cells. IF showed that IL-12RB1 was co-expressed with CD3, CD68, PD-1, and PD-L1 on the cytomembrane. Additionally, high score of IL-12RB1 expression in the non-malignant cells was a prognostic risk factor for OS of OSCC.ConclusionsIL-12RB1 was tightly associated with survival of OSCC and with the expression levels of PD-1/PD-L1 in the tumor immune microenvironment.

Comprehensive treatment experience of anal squamous cell carcinoma from a tertiary cancer center in South China.

BackgroundAnal squamous cell carcinoma (ASCC) is a rare malignant tumor with increasing incidence. The goal of our study was to analyze the treatment outcome and prognostic factors of ASCC in South China in the past half‐century.MethodsThis study retrospectively included 59 patients with ASCC admitted from 1975 to 2018 in Sun Yat‐sen University cancer center. The clinical records and follow‐up information of all patients were collected. Survival analysis and univariate and multivariate regression analyses were performed using the “survival” and “survminer” packages of R software.ResultsIn 59 patients, 5 patients had distant metastasis at diagnosis. Among 54 M0 stage patients, 33 patients received chemoradiotherapy (CRT), 19 patients received local surgery, and 2 patients refused curative treatment and received the best supportive treatment (BST). The most common grade 3–4 acute toxicities during treatment were myelosuppression and radiation dermatitis. The median follow‐up time was 32 months. For the whole group, the 3‐year and 5‐year overall survival (OS) rates and disease‐free survival (DFS) were 71.1% and 63.6%, and 73.4% and 69.0%, respectively. Multivariate regression analysis showed that the T3–4 stage was an independent prognostic risk factor for OS, progression‐free survival (PFS), and DFS. And M1 was an independent prognostic risk factor for PFS and DFS. Patients in stage M0 mainly treated with CRT had better local control than those mainly treated with surgery (p = 0.027). For M0 patients, induction chemotherapy combined with CRT tends to prolong OS compared with CRT alone (p = 0.26). The 3‐year colostomy‐free survival for the whole group was 81.1%.ConclusionsCRT is recommended as the first choice for the treatment of M0 stage ASCC. Induction chemotherapy may bring better survival benefits for some patients. Patients with ASCC in China seem to have a better local control rate, which suggested different treatment strategies may be needed in China.

Association between baseline Controlling Nutritional Status score and clinical outcomes of patients with multiple myeloma.

The Controlling Nutritional Status (CONUT) score, a novel immuno-nutritional index, was reported as a predictor of overall survival (OS) in some tumors. We aimed to investigate the association between baseline CONUT Score and clinical outcomes in patients with multiple myeloma (MM). We performed a retrospective analysis of 245 patients with MM. The CONUT score was determined prior to therapy. Among the entire cohort, the complete remission rate was markedly higher in the low-CONUT (⩽ 3) group compared to the mid-CONUT (4-9) group or high-CONUT (> 9) group (44.1% vs 25.8%, P= 0.039; 44.1% vs 12.5%, P= 0.002). Patients with CONUT score > 9 had significant poor prognosis, and CONUT score ⩽ 3 group showed better survival outcome than other groups in OS (P< 0.001). Besides, we stratified the patients by combining International Staging System (ISS) stage and CONUT score in a model, and found that CONUT score could improve the prognostic impact of ISS stages on OS. In multivariate analysis, older age (⩾ 70 years) and a high CONUT score (⩾ 4) were independent prognostic risk factors for OS. The CONUT score was a predictor of OS in MM patients especially in cases with both low ISS staging and CONUT score. The baseline CONUT score may be an early and practical indicator of the efficacy of anti-myeloma treatment.

Nomogram Based on Lactate Dehydrogenase-to-Albumin Ratio (LAR) and Platelet-to-Lymphocyte Ratio (PLR) for Predicting Survival in Nasopharyngeal Carcinoma.

PurposeThe prognosis of inflammation-related indicators like lactate dehydrogenase/albumin ratio (LAR) and the platelet/lymphocyte ratio (PLR) in nasopharyngeal carcinoma (NPC) is not yet clear. Our objective is to establish and verify the nomogram using LAR and PLR ratio for the first time to explore the prognostic value in NPC.Patients and MethodsThis was a retrospective collection of 1661 patients with non-metastatic NPC admitted to our hospital from 2010 to 2017. The final variables of overall survival (OS) and progression-free survival (PFS) were selected by Cox regression analysis to establish nomograms, and the methods to verify the prediction precision and discriminative ability of the nomograms were concordance index (C index), the receiver operating characteristic (ROC) curve and calibration curve. The risk stratification was carried out through the nomograms and compared with the current staging system by the Kaplan–Meier methods.ResultsMultivariate Cox analysis resulted that age, plasma Epstein–Barr Virus (EBV) DNA, T stage, N stage, white blood cells (WBC), PLR and LAR were independent prognostic risk factors for OS and PFS, and sex is an independent prognostic risk factor for OS. The C-indexes of OS nomogram were 0.722 (95% CI: 0.706–0.738) and 0.747 (95% CI: 0.717–0.777) in the training cohort and validation cohort, which were statistically higher than the current 8th AJCC staging system (0.646 and 0.688). The C-indexes of PFS nomogram were 0.696 (95% CI: 0.680–0.713) and 0.690 (95% CI: 0.660–0.720), which were also statistically higher than the current 8th AJCC staging system (0.632 and 0.666). Otherwise, ROC curves and the calibration curve for probability also confirmed satisfied consistency with actual observations.ConclusionLAR is a novel useful independent factor in NPC. The proposed nomogram LAR and PLR resulted in more accurate prognostic prediction than current staging system for NPC patients.

The prognostic significance of different proportion of signet-ring cells of colorectal carcinoma.

While the prognosis of patients with partial signet-ring cell carcinoma (PSRCC) has been rarely reported, colorectal signet-ring cell carcinoma (SRCC) has been associated with poor prognosis. The aim of this study was to analyze the prognosis of patients with different signet-ring cell (SRC) composition and establish a prediction model. A total of 91 patients with SRC component were included in the study. These patients were divided into two groups: SRCC group (SRC composition >50%; n = 41) and PSRCC group (SRC composition ≤50%; n = 50). COX regression model was used to identify independent prognostic factors for overall survival (OS). A predictive nomogram was established and compared with the 7th American Joint Committee on Cancer (AJCC) staging system. After a median follow-up of 16 months, no significant difference in OS was observed in either group. Pre-operative carcinoembryonic antigen level, pN stage, M stage, pre-operative ileus, and adjuvant chemotherapy were independent prognostic risk factors for OS (p < 0.05). A nomogram for predicting the OS of colorectal SRCC was established with a C-index of 0.800, and it showed better performance than that of the 7th AJCC staging system (p < 0.001). In summary, the ratio of SRC component was not an independent prognostic factor of the OS. Those patients with <50% of SRC component should be given the same clinical attention. A predictive nomogram for survival based on five independent prognostic factors was developed and showed better performance than the 7th AJCC staging system. This resulted to be helpful for individualized prognosis prediction and risk assessment.

Prognostic factors for overall survival in patients with primary duodenal adenocarcinoma.

The complete resection of primary duodenal adenocarcinoma (PDA) offers a chance for a cure, but the clinical and pathological characteristics of survivors have not been well studied. Patients with stage I-III PDA who underwent surgical resection between 2013 and 2018 were identified retrospectively and followed until December 2019. All patients are from the Cancer Hospital Chinese Academy of Medical Sciences. The clinical and pathological information of the patients, such as age, gender, tumor location, operative procedure, pathologic features, TNM stage, common presenting symptoms, lymph node dissection status, serum tumor markers, etc., was collected in detail. The KaplanMeier method and a Cox proportional hazards model were used for the survival analysis. In total, 85 patients with PDA were eligible for this study. Among these patients, 48 were male (56.5%), 37 were female (43.5%), the median age was 59 (range, 22-79) years, 44 (51.8%) patients were aged <60 years, and 41 (48.2%) patients were aged ≥60 years. The 1-, 3-, and 5-year survival rates were 93.7%, 79.4%, and 64.9%, respectively. The median overall survival (OS) was 27 months (range, 2-82 months), and the median follow-up was 27 months (range, 3-82 months). The patients with stage III disease had the worst prognosis (P=0.001). The univariate analysis showed that lymph node positivity (P=0.000), the N stage (P=0.000), the TNM stage (P=0.001) and carbohydrate antigen 19-9 (CA19-9) positivity (P=0.038) were related to OS. However, the total number of lymph nodes (LN) retrieved (P=0.723), tumor differentiation (P=0.136), carcinoembryonic antigen (CEA) (P=0.812), gender (P=0.477), operation type (P=0.860), tumor size (P=0.869), tumor site (P=0.120), age (P=0.733), intraoperative blood loss (P=0.660), and intraoperative blood transfusion (P=0.748) were not correlated with OS. The multivariate analysis suggested that the lymph node status was an independent prognostic risk factor for OS. In our study the median OS was 27 months (range, 2-82 months), and the 5-year survival rates was 64.9%. The lymph node status was the only prognostic factor for OS in PDA.

Prognostic role of docetaxel-induced reduction of free testosterone serum levels in metastatic prostate cancer patients.

144 Background: We have recently demonstrated that a salvage therapy with carboplatin plus weekly docetaxel is effective in docetaxel-refractory prostate cancer (PC) and interferes with testosterone biosynthesis (Reuter et al.; Oncol Res &amp; Treat. 2018, 41 (suppl.1): p.10). In this study, the impact of docetaxel monotherapy on free and total testosterone serum levels (fT, TT) and the prognostic role of fT and TT were analyzed in mPC patients. Methods: 62 consecutive mPC patients were treated with at least two cycles of docetaxel (75 mg/m2 q3w; 50 mg/m2 q2w, or 35 mg/m2 q1w) until disease progression, occurrence of intolerable adverse effects or completion of the planned cycle number. Efficacy measures were done following PCWG2 recommendations. FT and TT were measured before and during chemotherapy. Results: At the current analysis (August 31, 2020), the median follow-up time was 21.2 months. Response of prostate-specific antigen (PSAR; ≥50% PSA reduction) was observed in 42/62 (67.7%) and 12/36 (33.3%) patients with measurable disease exhibited a partial remission (PR). Median progression-free survival (PFS) for all patients was 8.1 months (CI 95% 3.6, 12.5) and median overall survival (OS) was 25.7 months (CI 95% 19.4, 32.1). The most common reversible grade 3/4 toxicity was leukopenia/neutropenia (29/33.9%). Median fT and TT serum levels were reduced below the detection limit during docetaxel treatment (fT: from 0.34 pg/mL to &lt; 0.01 pg/mL and TT: from 0.12 to &lt; 0.05 ng/mL, respectively). Multivariate Cox regression analyses identified PSAR &gt; 50%, fT reduction of 100% and number of organs involved as independent prognostic risk factors for PFS. Furthermore, fT reduction of 100% and FT nadir values &lt; 0.01 pg/mL were independent prognostic risk factors for OS (p &lt; 0.05). Conclusions: These data demonstrate that fT is an important prognostic factor for PFS and OS in mPC patients.

Prognostic Value of CD123 in Acute Myeloid Leukemia Patients with Intermediate Risk in Normal Karyotype

To investigate the expression of CD123 in patients with acute myeloid leukemia (AML) and its relationship between clinical features, concomitant fusion gene or gene mutation, efficacy and prognosis. 365 patients with newly diagnosed AML (except M3) treated in the First Affiliated Hospital of Zhengzhou University were enrolled and retrospective analysis, and multi-parameter flow cytometry was performed to detect the expression of CD123 in myeloid leukemia cell population. CD123≥20% was defined as positive. Clinical features, concomitant fusion gene or gene mutation, efficacy and prognosis of CD123+ and CD123- patients were compared and analyzed. The positive rate of CD123 in 365 newly diagnosed AML patients was 38.9%. Compared with the CD123- group, the white blood cell count (WBC), lactate dehydrogenase (LDH) level and bone marrow blast cell ratio were higher in the CD123+ group, and the ratio of NPM1 and DMNT3a gene mutations and the CBFβ-MYH11 fusion gene was significantly increased, while the ratio of CEBPA gene mutation and AML-ETO fusion gene was significantly reduced. The rate of first inducing complete remission and total remission in CD123+ group was significantly lower than that in CD123- group. There was no significant difference in recurrence rate between the two groups (P>0.05). Survival analysis showed that in 77 AML patients with normal karyotype and intermediate risk, the 2-year overall survival (OS) rate and event-free survival (EFS) rate of the CD123+ group were significantly lower than those of the CD123- group. Multivariate analysis showed that CD123 was an independent prognostic risk factor for OS and EFS in AML patients with normal karyotype and intermediate risk. CD123 positive indicates that AML patients have higher tumor burden and are more difficult to reach remission. It is an independent risk factor for OS and EFS in patients with normal karyotype and intermediate risk, which is important to evaluate the prognosis of patients with AML without specific prognostic marker.

Identification of Early Recurrence Factors in Childhood and Adolescent B-Cell Acute Lymphoblastic Leukemia Based on Integrated Bioinformatics Analysis.

Over the past 50 years, great progress has been made in the diagnosis and treatment of acute lymphoblastic leukemia (ALL), especially in pediatric patients. However, early recurrence is still an important threat to the survival of patients. In this study, we used integrated bioinformatics analysis to look for biomarkers of early recurrence of B-cell ALL (B-ALL) in childhood and adolescent patients. Firstly, we obtained gene expression profiles from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database and the Gene Expression Omnibus (GEO) database. Then, we identified differentially expressed genes (DEGs) based on whether the disease relapsed early. LASSO and Cox regression analysis were applied to identify a subset of four genes: HOXA7, S100A11, S100A10, and IFI44L. A genetic risk score model was constructed based on these four optimal prognostic genes. Time-dependent receiver operating characteristic (ROC) curves were used to evaluate the predictive value of this prognostic model (3-, 5-, and 10-year AUC values >0.7). The risk model was significantly associated with overall survival (OS) and event-free survival in B-ALL (all p < 0.0001). In addition, a high risk score was an independent poor prognostic risk factor for OS (p < 0.001; HR = 3.396; 95% CI: 2.387–4.832). Finally, the genetic risk model was successfully tested in B-ALL using an external validation set. The results suggested that this model could be a novel predictive tool for early recurrence and prognosis of B-ALL.

DNA-methylated gene markers for colorectal cancer in TCGA database.

Colorectal cancer (CRC) is characterized by the accumulation of genetic and epigenetic alterations in neoplastic processes. DNA methylation, as an important epigenetic process, contributes to the development of CRC. In the present study, the epigenetic landscape of genes in CRC was characterized by analyzing the dataset from The Cancer Genome Atlas database and 177 DNA-methylated genes were screened based on the criterion of the Pearson correlation (R) between expression and methylation levels being >0.4. Pathway enrichment analysis revealed prominent pathways, including transcription and metabolism, further implying their significant role in tumorigenesis. Among the methylated genes, only zinc finger protein (ZNF)726 with aberrant expression was determined to affect overall survival (OS) as well as disease-free survival of patients with CRC. In addition, ZNF726 was identified as an independent prognostic risk factor for OS in patients with CRC. The methylation-based regulation of ZNF726 expression in CRC cells was further assessed using the Cancer Cell Line Encyclopedia database. Finally, the CpG island methylation of the ZNF726 promoter was evaluated to further elucidate its role in the development of CRC. In conclusion, the epigenetic landscape of genes in terms of promoter methylation in CRC was characterized, revealing that aberrant expression of ZNF726 may be an independent prognostic risk factor for OS in patients with CRC.

Plasma YKL-40 as a biomarker in patients with nonmetastatic bone and soft tissue sarcomas: a prospective exploratory clinical study

Purpose: YKL-40 is a glycoprotein with a role in inflammation, tissue remodeling, tumor angiogenesis, and protection against apoptosis. We hypothesized that high preoperative plasma YKL-40 in patients with nonmetastatic bone and soft tissue sarcoma (STS) is associated with short overall survival (OS), and that plasma YKL-40 is an independent predictor for OS. Materials and methods: Plasma was collected preoperatively from 65 patients with nonmetastatic bone (n=14) or STS (n=51) in the lower extremities (n=43), the upper extremities (n=16) or the trunk wall/spine (n=6). All patients underwent surgical cancer treatment. Twenty patients developed metastases during the follow-up period (minimum 5 y). The plasma concentration of YKL-40 was determined by enzyme-linked immunosorbent assay. Results: Twenty-seven patients died [mean: 3.2 (range: 0.2–7.3) y postoperatively] and 38 patients were still alive after a follow-up of mean 6.9 (5.8–8.2) years postoperatively. Plasma YKL-40 was higher in patients who died during follow-up (P=0.008), in males (P=0.007) and in patients 61 years of age and above (P=0.001). The 5-year OS was 68% and OS was lower in patients with high (≥95% percentile age-corrected) plasma YKL-40 (P=0.021), age 61 years and above (P=0.013), high histologic malignancy grade (P=0.047) and male sex (P=0.051). Multivariable analysis showed that only plasma YKL-40 (age-corrected (hazard ratio=2.80, 95% confidence interval: 1.13–6.91, P=0.026) and malignancy grade (hazard ratio=9.9×107, 95% confidence interval: 0–∞, P=0.007) remained independent prognostic factors for OS. Conclusions: High preoperative plasma YKL-40 was related to short OS in patients with nonmetastatic bone and STS and plasma YKL-40 (age-corrected) was an independent prognostic risk factor for OS.

Clinicopathological characteristics, diagnosis, and prognosis of pregnancy-associated breast cancer.

BackgroundThe aim of this study was to evaluate the characteristics, diagnosis, prognosis, and effective treatment modalities of pregnancy‐associated breast cancer (PABC).MethodsFrom 1 January 2005 to 31 December 2015, 142 patients with PABC were identified in the Cancer Institute and Hospital of Tianjin Medical University database. The clinicopathological features, treatment methods, and outcomes were retrospectively evaluated.ResultsThe median age at diagnosis was 30 years. All patients presented with a palpable mass in the breast. The sensitivity of ultrasound and mammography in PABC diagnosis was 86% and 83.3%, respectively, which increased to 91.3% when a combination of mammography and ultrasound was used. The median tumor size was 5.5 cm, and 63.1% of patients had associated axillary lymph node metastases. The proportions of ER negative, PR negative and HER2 positive were 45.7%, 45.7% and 30%, respectively. The five‐year overall survival (OS) and disease‐free survival (DFS) rates were 76.8% and 63.5%, respectively. According to univariate analysis, T stage, N stage, and HER2 status were significant prognostic factors for OS and DFS. The time interval between the onset of the first symptom and the first meeting with a health professional was also significant for OS. Multivariate analysis showed that T stage and HER2 status were independent prognostic risk factors for OS and DFS.ConclusionPABC is an aggressive form of breast cancer associated with advanced stage at diagnosis. Despite the existing difficulties in diagnosis, imaging examinations are indispensable. Early diagnosis and multidisciplinary therapy, including anti‐HER2 targeted therapy, may be important to improve prognosis.