Development and validation of a prognostic nomogram for patients with laryngeal cancer with synchronous or metachronous lung cancer.

BACKGROUND: The objective of this study was to examine the independent prognostic factors of laryngeal cancer with synchronous or metachronous lung cancer (LCSMLC), and to generate and verify a clinical prediction model. METHODS: In this study, laryngeal cancer alone and LCSMLC were defined using the Surveillance, Epidemiology, and End Results (SEER) database. Risk factors of patients with LCSMLC were analyzed through univariate and multivariate logistic regression analysis. Independent prognostic factors were selected by Cox regression analyses, on the basis of which a nomogram was constructed using R code. Kaplan-Meier survival analyses were applied to test the application of a risk stratification system. Finally, we conducted a comparison of the American Joint Committee on Cancer (AJCC) staging system of laryngeal cancer with the new model of nomogram and risk stratification. For further validation of the nomogram, data from patients at two Chinese independent institutions were also analyzed. RESULTS: According to the eligibility criteria, 32 429 patients with laryngeal cancer alone and 641 patients with LCSMLC from the SEER database (the training cohort) and additional 61 patients from two Chinese independent institutions (the external validation cohort) were included for final analyses. Compared with patients with laryngeal cancer who did not have synchronous or metachronous lung cancer, age, sex, race, primary site of laryngeal cancer, grade, and stage were risk factors for LCSMLC, while marriage, surgery, radiation therapy, and chemotherapy are not their risk factors. Age, two cancers' interval, pathological type, stage, surgery, radiation, primary lung site, and primary throat site were independent prognostic predictors of LCSMLC. The risk stratification system of high-, medium-, and low-risk groups significantly distinguished the prognosis in different patients with LCSMLC, regardless of the training cohort or the validation cohort. Compared with the 6th AJCC TNM stage of laryngeal cancer, the new model of nomogram and risk stratification showed an improved net benefit. CONCLUSIONS: Age, sex, race, primary site of laryngeal cancer, grade, and stage were risk factors for LCSMLC. An individualized clinical prognostic predictive model by nomogram was generated and validated, which showed superior prediction ability for LCSMLC.

Model for Predicting Central Nervous System Relapse in Diffuse Large B-Cell Lymphoma and Discussion of Prophylaxis Measures.

OBJECTIVE: Relapse of the central nervous system (CNS) is a rare but fatal complication in diffuse large B-cell lymphoma (DLBCL). The purpose of this study is to learn how to identify high-risk patients and take effective preventive measures. METHODS: We retrospectively analyzed 1,290 adult patients with DLBCL at Peking University Cancer Hospital and Shanxi Bethune Hospital between 2010 and 2020. RESULTS: There were 55 patients with CNS relapse who had a median follow-up of 5 years. The risk of CNS relapse was 1.58% in the low-risk group, 5.66% in the moderate-risk group, and 11.67% in the high-risk group based on CNS International Prognostic Index (CNS-IPI). We found that CNS-IPI and testicular involvement were risk factors for CNS relapse, with OR 1.913 (95% CI: 1.036∼3.531; P = 0.038) versus. OR 3.526 (95% CI: 1.335∼9.313; P = 0.011), respectively. Intrathecal MTX and/or cytarabine prophylaxis was used in 166 patients (13.94%), intravenous (IV) high-dose methotrexate (HD-MTX) prophylaxis in 8 patients (0.67%), and intrathecal plus intravenous prophylaxis in 15 patients (1.26%). There was no significant difference in CNS relapse risk between IT, HD-MTX, and no prophylaxis recipients (12.7% vs. 0% vs. 23.6%, respectively, P = 0.170). The risk of CNS relapse was similar whether or not patients accepted prophylaxis (5-year risk 4.1% vs. 2.2%, P = 0.140). CONCLUSIONS: Central nervous system (CNS) relapse is associated with high risk CNS-IPI and testicular involvement. Therefore, it is necessary to pursue novel prophylactic strategies for CNS relapse.

CAPG facilitates diffuse large B-cell lymphoma cell progression through PI3K/AKT signaling pathway.

OBJECTIVE: Diffuse large B-cell lymphoma (DLBCL) is a genetically heterogeneous tumor. Currently, macrophage-capping protein (CAPG) has been discovered to play a crucial part as a regulator in various cancers. However, it still remains unclear regarding its regulatory mechanism in DLBCL. Therefore, this study focused on revealing the mechanism underlying CAPG in DLBCL. METHODS: The bioinformatics analysis was conducted to predict the expression of CAPG in DLBCL and its downstream target genes. qRT-PCR was utilized to detect mRNA expression levels of CAPG and CEBPA. Western blot was performed to examine the expression levels of related proteins. Then we employed flow cytometry for the analysis of cell cycle and apoptosis. We also used MTT assay to measure cell survival and IHC assay to detect CAPG expression in DLBLC tissues. Then, ChIP was used to determine the binding of CEBPA and CAPG. For in vivo experiments, xenograft models were employed to investigate the effect of CAPG on DLBCL. RESULTS: High-level of CAPG expression was found in DLBCL cells and tissues. CAPG could strengthen the proliferative and invasive abilities of DLBCL cells, inhibit cell apoptosis, and activate PI3K/AKT signaling pathway. CAPG overexpression accelerated malignant progression of DLBCL cells. In addition, CAPG expression was regulated by CEBPA. CONCLUSION: CAPG enhances the proliferation and invasion of DLBCL cells by promoting PI3K/AKT signaling pathway, which is expected to be a promising target for DLBCL.

Circulating Tumor DNA Characteristics Based on Next Generation Sequencing and Its Correlation With Clinical Parameters in Patients With Lymphoma.

Background: Lymphoma is a heterogeneous group of tumors in terms of morphological subtypes, molecular alterations, and management. However, data on circulating tumor DNA (ctDNA) mutated genes are limited. The purpose of this study was to investigate the features of the ctDNA mutated genes, the prognosis, and the association between the ctDNA mutated genes and the clinical parameters in lymphoma. Methods: Differences in the ctDNA between the mutated genes and the prognosis of 59 patients with Hodgkin's lymphoma (HL) (10.2%), germinal center B-cell-like lymphoma (GCB) (28.8%), nongerminal center B-cell-like lymphoma (non-GCB) (50.8%), and marginal zone lymphoma (MZL) (10.2%) were analyzed by next generation sequencing (NGS) targeting 121 lymphoma-relevant genes. Results: Genetic alterations were identified in the ctDNA samples with a median of 6 variants per sample. The genetic variation of the ctDNA in the plasma was found to be significantly correlated with the clinical indices in lymphoma. The genetic heterogeneity of different lymphoma subtypes was clearly observed in the ctDNAs from HL, GCB, non-GCB, and MZL, confirming that distinct molecular mechanisms are involved in the pathogenesis of different lymphomas. Conclusion: Our findings suggest that NGS-based ctDNA mutation analysis reveals genetic heterogeneity across lymphoma subtypes, with potential implications for discovering therapeutic targets, exploring genomic evolution, and developing risk-adaptive therapies.

[Risk Factors Analysis of Thromboembolism in Patients with Lymphoma Chemotherapy].

OBJECTIVE: To evaluate the risk factors affecting thromboembolism in lymphoma patients with chemotherapy. METHODS: Three hundred and four consecutive lymphoma patients treated by chemotherapy between January 2012 and July 2019 were enrolled and retrospectively analyzed, consisting of 111 patients with thromboembolism and 193 without thromboembolism. Univariate analysis was used to compare the clinical characteristics and related laboratory examination between the patients, while multivariate Logistic regression analysis were used to identify the risk factors affecting thromboembolism in lymphoma patients with chemotherapy. RESULTS: Univariate analysis showed that the female, BMI <18.5 or >24, ≥60 years old, with abnormal platelets before chemotherapy, prolonged single hospitalization days and patients at Ann Arbor stage III and IV could increase the incidence of thromboembolism in lymphoma patients treated by chemotherapy. Multivariate Logistic regression analysis showed that abnormal platelet count before chemotherapy, patients at Ann Arbor stage III and IV, and female were all the independent risk factors affecting thromboembolism in lymphoma patients thromboembolism after chemotherapy (P<0.05). CONCLUSION: For lymphoma chemotherapy patients, female, abnormal platelet count before chemotherapy and Ann Arbor stages III and IV show a significantly higher risk for thromboembolism. Thus, preventive anticoagulation therapy is recommended.

Systemic immune inflammation index, ratio of lymphocytes to monocytes, lactate dehydrogenase and prognosis of diffuse large B-cell lymphoma patients.

BACKGROUND: In malignant tumors, inflammation plays a vital role in the development, invasion, and metastasis of cancer cells. Diffuse large B-cell lymphoma (DLBCL), the most common malignant proliferative disease of the lymphatic system, is commonly associated with inflammation. The international prognostic index (IPI), which includes age, lactate dehydrogenase (LDH), number of extranodal lesions, Ann Arbor score, and Eastern Cooperative Oncology Group (ECOG) score, can evaluate the prognosis of DLBCL. However, its use in accurately identifying high-risk patients and guiding treatment is poor. Therefore, it is important to find novel immune markers in predicting the prognosis of DLBCL patients. AIM: To determine the association between the systemic immune inflammation index (SII), ratio of lymphocytes to monocytes (LMR), ratio of LMR to LDH (LMR/LDH), and prognosis of patients with DLBCL. METHODS: A total of 68 patients diagnosed with DLBCL, treated in our hospital between January 2016 and January 2020, were included. χ 2 test, Pearson's R correlation, Kaplan Meier curves, and Cox proportional risk regression analysis were used. The differences in the SII, LMR, and LMR/LDH among patients with different clinicopathological features were analyzed. The differences in progression-free survival time among patients with different SII, LMR, and LMR/LDH expressions and influencing factors affecting the prognosis of DLBCL patients, were also analyzed. RESULTS: The LMR and LMR/LDH in patients with Ann Arbor stage III-IV, ECOG score ≥ 2, and SII, IPI score 2-5 were significantly higher than those of patients with Ann Arbor stage I-II and ECOG score < 2 (P < 0.05). Patients with high SII, LMR, and LMR/LDH had progression-free survival times of 34 mo (95%CI: 32.52-38.50), 35 mo (95%CI: 33.42-36.58) and 35 mo (95%CI: 33.49-36.51), respectively, which were significantly lower than those with low SII, LMR, and LMR/LDH (P < 0.05); the SII, LMR, and LMR/LDH were positively correlated (P < 0.05). Cox proportional risk regression analysis showed that the SII, LMR, and LMR/LDH were influencing factors for the prognosis of DLBCL patients (hazard ratio = 1.143, 1.665, and 1.704, respectively; P < 0.05). CONCLUSION: The SII, LMR, and LMR/LDH are related to the clinicopathological features of DLCBL, and they also influence the prognosis of patients with the disease.

Risk Factors of Thromboembolism in Lymphoma Patients Undergoing Chemotherapy and its Clinical Significance.

This study investigated the risk factors of thromboembolism (TE) in lymphoma patients undergoing chemotherapy and its clinical significance. A total of 304 lymphoma patients who received chemotherapy from January 2012 to July 2019 were retrospectively analyzed, including 111 patients with and 193 patients without TE. The clinical characteristics and related laboratory test results were compared between the 2 groups using univariate analysis, while the risk factors for TE in lymphoma patients undergoing chemotherapy were analyzed using multivariate logistic regression analysis. Univariate analysis revealed an increase in the risk of TE among lymphoma patients with chemotherapy in the following categories: female patients, patients with body mass index <18.5 or > 24, patients aged ≥60 years, those with platelet abnormality before chemotherapy, single hospital-stay patients, and Ann Arbor stage III/IV patients. Multivariate logistic regression analysis revealed that for platelet count abnormality before chemotherapy, Ann Arbor stage III/IV and female patients represented independent risk factors for TE among lymphoma patients after chemotherapy (P < .05). For lymphoma patients treated with chemotherapy, the risk of TE occurring in women, patients with platelet abnormalities before chemotherapy, and patients at Ann Arbor stage III/IV was significantly higher compared with other patients. For these patients, we recommend prophylactic anticoagulant therapy.

Construction of a DLBCL Prognostic Signature Based on Tumor Microenvironment.

BACKGROUNDS: Diffuse large B-cell lymphoma (DLBCL) is a common curable non-Hodgkin's lymphoma. Patients with this disease can be cured after the R-CHOP immunochemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). Nonetheless, most cured patients will relapse again and have dismal prognosis. In this study, we aim to identify a potential biomarker by analyzing gene expression data, and to predict patient's survival rate by constructing a risk model. METHODS: Firstly, mRNA chip data (GSE87371) and clinical data of DLBCL patients were obtained from Gene Expression Omnibus (GEO). Samples were scored with estimate package. The obtained stromal score (P < 0.05) and ESTIMATE score (P < 0.05) were significantly correlated with the prognosis. Differentially expressed genes (DEGs) screened through the above two scoring methods were intersected and 279 DEGs were obtained. Next, five feature genes (CD163, CLEC4A, COL15A1, GABRB2, IFIT3) were identified by univariate Cox, LASSO and multivariate Cox regression analyses to establish a risk evaluation model. Thereafter, the 5-gene risk model was validated on a validation set. ROC and survival analyses were performed to assess the performance of the model. RESULTS: Further analysis showed that the risk model was capable of independently determining the prognosis of patients, and a nomogram was sequentially established. CONCLUSIONS: Authors screened DEGs related to ESTIMATE and stromal scores from GEO database, and established a 5-gene prognostic signature through Cox regression analysis and LASSO analysis. The risk model and nomogram will help individuals accurately predict the prognosis of DLBCL patients.

[Clinical Value of Serum Amyloid A and Misfolded Transthyretin for Relapsed/Refractory Diffuse Large B-Cell Lymphoma Patients].

OBJECTIVE: To evaluate the clinical value of serum amyloid A (SAA1/2) and misfolded transthyretin (TTR) for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) patients. METHODS: 30 R/R DLBCL patients were enrolled as observation group, 20 remission/stabilization DLBCL and 10 chronic lymphadenitis patients were enrolled as control group. SELDI technique, Tris-Tricine sodium dodecyl sulfate-polyacrylamide gel electro-phoresis, the shotgun-LTQ-MS method, and bioinformatics technique were used to detected and analyzed SAA and TTR in R/R DLBCL patients. SPSS 21.0 software was used to analyze the relationship between the high expression of SAA, misfolded TTR in serum and the clinicopathological features, survival time of R/R DLBCL. patients Chi-square test was used to analyze clinical count data, Kaplan-Meier curve was used for survival analysis, and Log-Rank test was used to compare single-factor survival differences. RESULTS: The high expression of SAA and TTR (SAA+TTR+) was significantly associated with extranodal lesion, high level of LDH, and NCCN-IPI scores, and also correlated with non-GCB type. TTR+ was correlated with C-MYC in pathological tissue, while SAA+ was also associated with B-symptoms. The survival time of patients in SAA+, TTR+, and SAA+TTR+ group were shorter than that in control group. CONCLUSION: Both SAA and misfolded TTR are poor prognosis factors of R/R DLBCL patients.

[Effect of P53 Expression on Prognosis of Patients with Double Expressor Lymphoma].

OBJECTIVE: To investigate the effect of P53 expression on prognosis of patients with double expressor lymphoma(DEL) and the interaction between the expression of MYC, BCL2 and P53 in diffuse large B-cell lymphoma(DLBCL). METHODS: Eighty-eight patients with newly diagnosed DLBCL from 1st September 2012 to 31th May 2018 in Shanxi Dayi Hospital affiliated to Shanxi Medical University were selected. The expressions of MYC、BCL2、P53、CD10、BCL6、MUM and Ki-67 were tested by immunohistochemistry method. The overall survival of patients was analyzed by the Kaplan-Meier method and compared by the log-rank test. The prognostic effect of MYC, BCL2 and P53 expression was analyzed by univariate and multivariate analysis. RESULTS: Compared with patients without P53 expression, the patients with P53 expression had higher LDH level, higher NCCN-IPI scores, lower response to chemotherapy，poorer overall survival(OS) and a higher rate of death(P<0.05). In patients who had diffuse large B-cell lymphoma associated with MYC, BCL2 expression or MYC+/BCL2+ double expression， compared with the patients whom without P53 expression, P53 expression associated with a significant worse OS (P<0.05). The patients with concurrent MYC and P53 expression had a worse OS, compared with patients with either P53 or MYC expression(P<0.05). In patients with MYC+/P53+ co-expression, BCL2 expression did not correlate with poorer survival significantly(P>0.05). Among lymphoma patients with MYC+/P53+, MYC+/BCL2+ and BCL2+/P53+ co-expression, the patients with MYC+/P53+ co-expression had the worse OS (3 year OS rate：31.6%), followed by the subgroup of patients with MYC-/BCL2+/P53+(3 year OS rate：46.2%), patients with MYC+/BCL2+/P53- expression(3 year OS rate： 636%) showed a longer OS compared with the other two subgroups（P<0.05）. Multivariate analysis demonstrated that P53 expression and NCCN-IPI were independent prognostic factors in this patient cohort. CONCLUSION: P53 and MYC expressions have a synergistically negative prognostic effect in DLBCL patients. P53 expression augments the negative prognostic effect of MYC+/BCL2+ double expression. Patients with MYC+/P53+ co-expression have a worse prognosis in comparison with the patients with MYC+/BCL2+ double expression.

Sleep Quality of Patients with Differentiated Thyroid Cancer.

OBJECTIVE: We aimed to measure prevalence of sleep disturbance in patients with differentiated thyroid cancer (DTC) by calculating Pittsburgh Sleep Quality Index (PSQI), and compare these data with patients with benign thyroid nodules or normal participants. METHODS: Three groups of patients participated in this cross-sectional study. In the first group, 162 patients with DTC received total thyroidectomy, and then 131I therapy. The second group consisted of 84 patients with benign thyroid nodules, who received partial thyroidectomy. The third group was 78 normal healthy control cases. PSQI was used to assess the sleep quality. Inter-group differences were analyzed by Kruskal-Wallis test or independent samples T test. χ2 test was also used to check prevalence differences of poor sleep quality among the groups. Differences of PSQI score and poor sleep quality prevalence before and after 131I therapy in the same group of DTC participants were analyzed by paired T test and Mcnemar's test. RESULTS: Higher PSQI score (7.59 ± 4.21) and higher rate of poor sleep quality (54.32%) were shown in DTC patients than in any other group. After 131I therapy, PSQI score and prevalence of poor sleep quality in DTC patients increased significantly to 8.78 ± 4.72 and 70.99%. Then DTC patients were divided into two subgroups based on their metastatic status. DTC patients with metastasis (87/162 cases, 53.70%) had significantly higher PSQI score (10.87 ± 5.18) and higher prevalence of poor sleep quality (79.31%). CONCLUSION: DTC patients suffer from sleep disturbance, 131I therapy and awareness of metastatic status could worsen sleep problem. Psychological fear of cancer, nuclear medicine therapy and metastasis could be one major underlying reason. Longitude and interventional studies are necessary for further investigations.

[Clinical characteristics and prognostic factors of 62 cases with Hodgkin lymphoma].

OBJECTIVE: To investigate the clinical characteristics, pathologic types and prognostic factors of Hodgkin lymphoma (HL). METHODS: Retrospective analyses of clinical data of 62 HL patients, including 45 from Peking University third hospital and 17 from Shanxi Dayi hospital. RESULTS: Sixty-two HL patients accounted for 5.66% of the total newly diagnosed patients with lymphoma (45/795) in the period with a ratio of male:female as 2.1:1. All the pathological types were classical Hodgkin lymphoma (cHL), including 33 cases (53.2%) of nodular sclerosis type (NS) and 19 cases (30.6%) of mixed cell type (MC). Of the 56 cases followed up, the total responsive rate was 92.9% , and 2- , 3- and 5- year overall survival (OS) rates were 97.7%, 92.2% and 80.5% respectively with the median OS as 45 (8-184) months. Analyses of the prognostic factors indicated that the involvement of spleen(P=0.042)and German Hodgkin Study Group(GHSG) risk score (P=0.002) were poor factors with statistic significance. CONCLUSION: HL is one of the curable malignant tumors, 5-year OS rate was 80.5% in this group. After recurrence, part of patients developed slowly and could be salvaged with second-line therapy with high remission rate. GHSG scoring system and involvement of spleen could predict the prognosis in HL setting.

The clinical study of extranodal natural killer cell lymphoma, nasal type.

To analyze the clinical characteristics, treatment of extranodal NK/T-cell lymphoma, nasal type, the term "nasal type" describes in the nasal cavity and also in the extranasal sites. There were 82 patients with nasal NK/T lymphoma (group 1) and 11 patients with extranasal NK/T lymphoma (group 2). In group 1, 4 patients gave up treatment. Five patients received radiotherapy (RT) alone. Fifty-seven patients were treated with combination of chemotherapy and RT. Sixteen patients received chemotherapy alone. Most patients (82.9%) had stage I/II disease and a high frequency (about one-third) of B symptoms. The CR rate was 53.8%. The OS rate was 62.8% (49/78 cases). Three patients died in relation to L-asparaginase. Three patients with late relapses occurred at 10 and 17 years from CR, respectively. In group 2, except that one patient received chemoradiotherapy, 10 patients received chemotherapy. Seven patients died. The OS rate was 36.4%. Our study suggested that nasal and extranasal variants of extranodal NK/T lymphoma, nasal type represented different clinical behavior and prognosis. For comparison, extranasal NK/T lymphoma is more aggressive and higher mortality than nasal NK/T lymphoma.