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Our objective was to examine the impact of elective neck dissection (END) on the prognosis of patients with cT2N0 maxillary sinus squamous cell carcinoma (MS-SCC) and to determine factors that predict the occurrence of occult metastasis in this patient population. A retrospective analysis was conducted using data from the SEER database. Patients with cT2N0 MS-SCC were included in the study and divided into two groups: those who received END and those who did not. The impact of END on disease-specific survival (DSS) and overall survival (OS) was assessed using propensity score matching. Multivariate logistic regression analysis was performed to determine predictors for occult metastasis. A total of 180 patients were included in the study, with 40 cases receiving END. Following propensity score matching, patients treated with END and those without showed similar DSS and OS rates. Occult metastasis was observed in 9 patients, corresponding to a rate of 22.5%. High-grade tumors were independently associated with a higher risk of occult metastasis compared to low-grade tumors (hazard ratio 1.52, 95% confidence interval 1.17-2.00). cT2 MS-SCC carries an occult metastasis rate of 22.5%, with histologic grade being the primary determinant of occult metastasis. END does not confer a significant survival benefit in this patient population.
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Carcinoma de Células Escamosas , Esvaziamento Cervical , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/mortalidade , Estadiamento de Neoplasias , Procedimentos Cirúrgicos Eletivos , Prognóstico , Neoplasias do Seio Maxilar/patologia , Neoplasias do Seio Maxilar/cirurgia , Neoplasias do Seio Maxilar/mortalidade , Adulto , Programa de SEER , Pontuação de PropensãoRESUMO
BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous malignancy characterized by varied responses to treatment and prognoses. Understanding the metabolic characteristics driving DLBCL progression is crucial for developing personalized therapies. METHODS: This study utilized multiple omics technologies including single-cell transcriptomics (n = 5), bulk transcriptomics (n = 966), spatial transcriptomics (n = 10), immunohistochemistry (n = 34), multiple immunofluorescence (n = 20) and to elucidate the metabolic features of highly malignant DLBCL cells and tumor-associated macrophages (TAMs), along with their associated tumor microenvironment. Metabolic pathway analysis facilitated by scMetabolism, and integrated analysis via hdWGCNA, identified glycolysis genes correlating with malignancy, and the prognostic value of glycolysis genes (STMN1, ENO1, PKM, and CDK1) and TAMs were verified. RESULTS: High-glycolysis malignant DLBCL tissues exhibited an immunosuppressive microenvironment characterized by abundant IFN_TAMs (CD68+CXCL10+PD-L1+) and diminished CD8+ T cell infiltration. Glycolysis genes were positively correlated with malignancy degree. IFN_TAMs exhibited high glycolysis activity and closely communicating with high-malignancy DLBCL cells identified within datasets. The glycolysis score, evaluated by seven genes, emerged as an independent prognostic factor (HR = 1.796, 95% CI: 1.077-2.995, p = 0.025 and HR = 2.631, 95% CI: 1.207-5.735, p = 0.015) along with IFN_TAMs were positively correlated with poor survival (p < 0.05) in DLBCL. Immunohistochemical validation of glycolysis markers (STMN1, ENO1, PKM, and CDK1) and multiple immunofluorescence validation of IFN_TAMs underscored their prognostic value (p < 0.05) in DLBCL. CONCLUSIONS: This study underscores the significance of glycolysis in tumor progression and modulation of the immune microenvironment. The identified glycolysis genes and IFN_TAMs represent potential prognostic markers and therapeutic targets in DLBCL.
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BACKGROUND: The study aimed to assess the impact of parotid lymph nodes (LNs) on the prognosis of patients with cutaneous squamous cell carcinomas of the head and neck (HNcSCC), and to develop an alternative LN assessment method to enhance locoregional control (LRC) and overall survival (OS) stratification. METHODS: We retrospectively enrolled patients with surgically treated HNcSCC. Primary outcome variables were LRC and OS. The influence of parotid LNs and different LN assessment methods on prognosis was analyzed using Cox models, and comparisons were made using the C-index, Akaike Information Criterion, and Bayesian Information Criterion. RESULTS: A total of 126 patients were included. Both intraparotid and periparotid LN statuses significantly linked with prognosis. The presence of extranodal extension (ENE) in cervical LNs, rather than parotid LNs, was predictive of decreased LRC and OS. In the Cox analysis, only N3 of the AJCC N classification, when compared to N0, showed reduced LRC and OS. In comparison to N0P1, only N0P3/N1P1 and N2P2/N2P3 of the O'Brien staging system tended to predict poorer LRC, with no subgroup emerging as an independent predictor for OS. The proposed LN assessment method, based on the number of metastatic LNs and ENE status in cervical LNs, demonstrated superior performance in terms of C-index, Akaike Information Criterion, and Bayesian Information Criterion compared to other systems. CONCLUSION: Parotid LNs were significant determinants of prognosis in metastatic HNcSCC. The novel LN assessment method proposed (1-2 vs. 3-4 vs. 5 + or ENE) displayed similar survival stratification to the AJCC N and O'Brien staging systems.
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Neoplasias de Cabeça e Pescoço , Linfonodos , Metástase Linfática , Estadiamento de Neoplasias , Neoplasias Cutâneas , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , Masculino , Feminino , Metástase Linfática/patologia , Idoso , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/mortalidade , Linfonodos/patologia , Linfonodos/cirurgia , Prognóstico , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/cirurgia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/cirurgia , Adulto , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/cirurgiaRESUMO
OBJECTIVE: To evaluate the oncologic safety and quality of life associated with the use of sentinel lymph node biopsy (SLNB) as compared to elective neck dissection (END) in patients with cT1/2N0 maxillary squamous cell carcinoma. METHODS: This study constituted a retrospective analysis of consecutively treated patients who underwent SLNB or END, with data collected prospectively. We analyzed the impact of the different neck procedures on regional control and disease-specific survival via the Cox model. Patients in both groups completed the University of Washington Quality of Life questionnaire. RESULTS: We included a total of 130 patients, with 47 receiving SLNB. In all cases, the sentinel lymph node could be identified, and of these, 5 had a positive result, yielding a sensitivity of 83.3 %, a specificity of 100 %, a false negative rate of 16.7 %, and a negative predictive value of 97.6 %. The sensitivity, specificity, false negative rate, and negative predictive value of END in detecting occult metastasis were 64.3 %, 100 %, 35.7 %, and 93.2 %, respectively. In comparison to END after propensity score matching, SLNB exhibited no significant difference in its effects on regional control (p = 0.519, HR: 1.05, 95 % CI: 0.52-1.93) and disease-specific survival (p = 0.634, HR: 1.22, 95 % CI: 0.53-1.99). Patients in SLNB group showed significantly higher mean scores of shoulder and taste domains at 3 months, 6 months, and 12 months postoperatively compared to those in END group. CONCLUSION: SLNB could act as a viable alternative to END in cT1/2N0 maxillary squamous cell carcinoma with comparable prognosis and better quality of life.
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Carcinoma de Células Escamosas , Esvaziamento Cervical , Qualidade de Vida , Biópsia de Linfonodo Sentinela , Humanos , Masculino , Feminino , Esvaziamento Cervical/métodos , Pessoa de Meia-Idade , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas/patologia , Biópsia de Linfonodo Sentinela/métodos , Idoso , Estudos Retrospectivos , Neoplasias Maxilares/patologia , Neoplasias Maxilares/cirurgia , Adulto , Idoso de 80 Anos ou maisRESUMO
Sentinel lymph node biopsy (SLNB) has gained considerable attention in the management of head and neck cutaneous squamous cell carcinoma (HNcSCC). The aim of this study was to compare the oncologic outcomes between observation and SLNB in cN0 high-risk HNcSCC patients. We retrospectively enrolled patients from the SEER database and evaluated the impact of observation versus SLNB on disease-specific survival (DSS) and overall survival (OS) using a Propensity Score Matching (PSM) analysis. A total of 9804 patients were included, with 1169 cases treated by SLNB. Successful retrieval of the sentinel lymph node was achieved in 1130 procedures. After PSM and subsequent multivariate analysis, SLNB was found to be an independent predictor for improved DSS, with a hazard ratio of 0.70 (95% confidence interval: 0.56-0.86). In patients presenting with two or three high-risk factors, SLNB was associated with better DSS (p = 0.021 and p = 0.044), but similar OS (p = 0.506 and p = 0.801) when compared to observation. However, in patients exhibiting four high-risk factors, SLNB demonstrated significantly improved DSS (p = 0.040) and OS (p = 0.028) compared to observation. Our findings suggest that SLNB is a highly feasible technique in HNcSCC and provides significant survival benefits. It is strongly recommended in patients with two or more high-risk factors, as it can help guide treatment decisions and improve patient outcomes.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Cutâneas , Humanos , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/cirurgia , Biópsia de Linfonodo Sentinela , Carcinoma de Células Escamosas de Cabeça e Pescoço , Pontuação de Propensão , Estudos Retrospectivos , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/cirurgia , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/cirurgiaRESUMO
Chemoimmunotherapy has evolved as a standard treatment for advanced non-small cell lung cancer (aNSCLC). However, inevitable drug resistance has limited its efficacy, highlighting the urgent need for biomarkers of chemoimmunotherapy. A three-phase strategy to discover, verify, and validate longitudinal predictive autoantibodies (AAbs) for aNSCLC before and after chemoimmunotherapy was employed. A total of 528 plasma samples from 267 aNSCLC patients before and after anti-PD1 immunotherapy were collected, plus 30 independent formalin-fixed paraffin-embedded samples. Candidate AAbs were firstly selected using a HuProt high-density microarray containing 21,000 proteins in the discovery phase, followed by validation using an aNSCLC-focused microarray. Longitudinal predictive AAbs were chosen for ELISA based on responders versus non-responders comparison and progression-free survival (PFS) survival analysis. Prognostic markers were also validated using immunohistochemistry and publicly available immunotherapy datasets. We identified and validated a panel of two AAbs (MAX and DHX29) as pre-treatment biomarkers and another panel of two AAbs (MAX and TAPBP) as on-treatment predictive markers in aNSCLC patients undergoing chemoimmunotherapy. All three AAbs exhibited a positive correlation with early responses and PFS (p < 0.05). The kinetics of MAX AAb showed an increasing trend in responders (p < 0.05) and a tendency to initially increase and then decrease in non-responders (p < 0.05). Importantly, MAX protein and mRNA levels effectively discriminated PFS (p < 0.05) in aNSCLC patients treated with immunotherapy. Our results present a longitudinal analysis of changes in prognostic AAbs in aNSCLC patients undergoing chemoimmunotherapy.
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Autoanticorpos , Carcinoma Pulmonar de Células não Pequenas , Imunoterapia , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Feminino , Masculino , Autoanticorpos/sangue , Pessoa de Meia-Idade , Idoso , Prognóstico , Biomarcadores Tumorais , AdultoRESUMO
BACKGROUND: Anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs) has demonstrated remarkable therapeutic effects in ALK-positive non-small cell lung cancer (NSCLC) patients. Identifying prognostic biomarkers can enhance the clinical efficacy of relapsed or refractory patients. METHODS: We profiled 737 plasma proteins from 159 pre-treatment and on-treatment plasma samples of 63 ALK-positive NSCLC patients using data-independent acquisition-mass spectrometry (DIA-MS). The consensus clustering algorithm was used to identify subtypes with distinct biological features. A plasma-based prognostic model was constructed using the LASSO-Cox method. We performed the Mfuzz analysis to classify the patterns of longitudinal changes in plasma proteins during treatment. 52 baseline plasma samples from another independent ALK-TKI treatment cohort were collected to validate the potential prognostic markers using ELISA. RESULTS: We identified three subtypes of ALK-positive NSCLC with distinct biological features and clinical efficacy. Patients in subgroup 1 exhibited activated humoral immunity and inflammatory responses, increased expression of positive acute-phase response proteins, and the worst prognosis. Then we constructed and verified a prognostic model that predicts the efficacy of ALK-TKI therapy using the expression levels of five plasma proteins (SERPINA4, ATRN, APOA4, TF, and MYOC) at baseline. Next, we explored the longitudinal changes in plasma protein expression during treatment and identified four distinct change patterns (Clusters 1-4). The longitudinal changes of acute-phase proteins during treatment can reflect the treatment status and tumor progression of patients. Finally, we validated the prognostic efficacy of baseline plasma CRP, SAA1, AHSG, SERPINA4, and TF in another independent NSCLC cohort undergoing ALK-TKI treatment. CONCLUSIONS: This study contributes to the search for prognostic and drug-resistance biomarkers in plasma samples for ALK-TKI therapy and provides new insights into the mechanism of drug resistance and the selection of follow-up treatment.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Quinase do Linfoma Anaplásico/genética , Proteômica , Proteínas Sanguíneas , Biomarcadores , Proteínas de Fusão OncogênicaRESUMO
OBJECTIVE: Our objective is to assess the oncologic outcomes of observation, elective neck dissection (END), and elective neck irradiation (ENI) in the neck management of head and neck cutaneous squamous cell carcinoma (HNcSCC) with parotid metastasis (P+) and to evaluate the quality of life (QoL) of patients who received END or ENI. METHODS: Patients with P+ HNcSCC were retrospectively enrolled. The impact of observation, END, and ENI on regional control (RC) and overall survival (OS) was analyzed using Cox proportional hazards model with presentation via hazard ratio (HR) with a 95% confidence interval (CI). QoL was evaluated using the University of Washington Quality of Life questionnaire. RESULTS: A total of 134 patients were included in our analysis. In the Cox model for RC, both END and ENI had decreased HRs of 0.27 (95% CI: 0.15-0.69) and 0.34 (95% CI: 0.18-0.86), respectively, in comparison with observation. In the Cox model for OS, both END (p = 0.001, HR: 0.22, 95% CI: 0.10-0.72) and ENI (p = 0.006, HR: 0.30, 95% CI: 0.17-0.83) were superior to observation. In patients with three or more positive parotid lymph nodes, END resulted in significantly better RC (p < 0.001) and OS (p = 0.001) compared with ENI. The two groups were found to be comparable in all 12 domains of the University of Washington Quality of Life questionnaire. CONCLUSION: In the neck management of P+ HNcSCC, observation is not recommended. END is the preferred option, but ENI is an alternative method without compromise to survival or QoL, except in cases with three or more metastatic parotid lymph nodes.
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Carcinoma de Células Escamosas , Esvaziamento Cervical , Neoplasias Parotídeas , Qualidade de Vida , Neoplasias Cutâneas , Humanos , Masculino , Feminino , Neoplasias Parotídeas/secundário , Neoplasias Parotídeas/patologia , Neoplasias Parotídeas/terapia , Neoplasias Parotídeas/mortalidade , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/mortalidade , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/secundário , Carcinoma de Células Escamosas/patologia , Adulto , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/terapia , Idoso de 80 Anos ou mais , Modelos de Riscos Proporcionais , Resultado do TratamentoRESUMO
BACKGROUND: R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) is a standard first-line treatment for diffuse large B-cell lymphoma (DLBCL). However, 20%-40% of patients survive less than 5 years. Novel prognostic biomarkers remain in demand. METHODS: Baseline plasma autoantibodies (AAbs) were assessed in 336 DLBCLs. In the discovery phase (n = 20), a high-density antigen microarray (â¼21,000 proteins) was used to expound AAb profiles. In the verification phase (n = 181), with a DLBCL-focused microarray, comparative results based on event-free survival at 24 months (EFS24) and lasso Cox regression models of progression-free survival (PFS) and overall survival (OS) were integrated to identify potential biomarkers. They were further validated by enzyme-linked immunosorbent assay in validation phase 1 (n = 135) and a dynamic cohort (n = 12). In validation phase 2, a two-AAb-based risk score was established. They were further validated in an immunohistochemistry cohort (n = 55) and four independent Gene Expression Omnibus datasets (n = 1598). RESULTS: Four AAbs (CREB1, N4BP1, UBAP2, and DEAF1) were identified that showed associations with EFS24 status (p < .05) and superior PFS and OS (p < .05). A novel risk score model based on CREB1 and N4BP1 AAbs was developed to predict PFS with areas under the curve of 0.72, 0.71, 0.76, and 0.82 at 1, 3, 5, and 7 years, respectively, in DLBCL treated with R-CHOP independent of the International Prognostic Index (IPI) and provided significant additional recurrence risk discrimination (p < .05) for the IPI. CREB1 and N4BP1 proteins and messenger RNAs were also associated with better PFS and OS (p < .05). CONCLUSIONS: This study identified a novel prognostic panel of CREB1, N4BP1, DEAF1, and UBAP2 AAbs that is independent of the IPI in DLBCL.
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Linfoma Difuso de Grandes Células B , Humanos , Prognóstico , Rituximab/uso terapêutico , Vincristina/uso terapêutico , Prednisona/uso terapêutico , Anticorpos Monoclonais Murinos/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/genética , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Biomarcadores , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Proteínas de Ligação a DNA , Fatores de TranscriçãoRESUMO
This study aimed to assess the impact of the number and ratio of metastatic lymph nodes (LNs) on prognosis in submandibular gland cancer. To this end, patients were selected from the Surveillance, Epidemiology, and End Results database retrospectively. The effect of the number and ratio of metastatic LNs and the American Joint Committee on Cancer (AJCC) N stage on disease-specific survival (DSS) and overall survival (OS) was analyzed. In addition, prognostic models based on LN evaluation methods were developed to predict the OS and DSS. A total of 914 patients were included. Binary recursive partitioning analysis determined the optimal cut-off number of metastatic LNs (0 vs. 1-2. vs. 3+). The presence of 3+ metastatic LNs carried the greatest impact on prognosis, followed by 1-2 positive LNs occurrences. The ratio of metastatic LNs was an independent factor for DSS and OS. The model had a higher likelihood ratio and C-index than those in the Cox model based on the AJCC N stage. Quantitative LN burden and ratio of metastatic LNs provides better survival stratification than the AJCC N stage.
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Neoplasias das Glândulas Salivares , Glândula Submandibular , Humanos , Estudos Retrospectivos , Estadiamento de Neoplasias , Metástase Linfática/patologia , Prognóstico , Linfonodos/patologia , Neoplasias das Glândulas Salivares/patologia , Excisão de Linfonodo/métodosRESUMO
BACKGROUND: Research on immunogenicity after 3rd SARS-CoV-2 vaccine in elder hepatocellular carcinoma (HCC) was limited. This study aimed to investigate the efficacy and influencing factors of inactivated SARS-CoV-2 vaccine in elder HCC. RESEARCH DESIGN AND METHODS: We assessed total antibodies, anti-RBD IgG, and neutralizing antibodies (NAb) toward SARS-CoV-2 wild type (WT) as well as BA.4/5 in 304 uninfected HCC, 147 matched healthy control (HC), and 53 SARS-CoV-2 infected HCC, all aged over 60 years. The levels of antibodies were compared in the period 7-90, 91-180, and >180 days after 2nd or 3rd vaccination, respectively. RESULTS: HCC had lower seropositivity than HC after 2nd dose (total antibodies, 64% vs. 92%, P < 0.0001; anti-RBD IgG, 50% vs. 77%, P < 0.0001). But 3rd dose can efficaciously close the gap (total antibodies, 96% vs. 100%, P = 0.1212; anti-RBD IgG: 87% vs. 87%, P > 0.9999). Booster effect of 3rd dose can persist >180 days in HCC (2nd vs. 3rd: total antibodies, 0.60 vs. 3.20, P < 0.0001; anti-RBD IgG, 13.86 vs. 68.85, P < 0.0001; WT NAb, 11.70 vs. 22.47, P < 0.0001). Vaccinated HCC had more evident humoral responses than unvaccinated ones after infection (total antibodies: 3.85 vs. 3.20, P < 0.0001; anti-RBD IgG: 910.92 vs. 68.85, P < 0.0001; WT NAb: 96.09 vs. 22.47, P < 0.0001; BA.4/5 NAb: 86.53 vs. 5.59, P < 0.0001). CONCLUSIONS: Our findings highlight the booster effect and protective role of 3rd dose. Our results could provide a theoretical foundation for informing decisions regarding SARS-CoV-2 vaccination in elder HCC.
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COVID-19 , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Pessoa de Meia-Idade , Idoso , COVID-19/prevenção & controle , Vacinas contra COVID-19 , SARS-CoV-2 , Anticorpos Neutralizantes , Vacinação , Imunoglobulina G , Anticorpos AntiviraisRESUMO
With the SARS-CoV-2 mutations evolving and prompt of SARS-CoV-2 vaccines, no information is available on SARS-CoV-2 vaccination status in Chinese patients with lung cancer. An electronic questionnaire including sociodemographic characteristics, vaccine status, side effect post-vaccination, and attitude towards a fourth dose of vaccine was conducted within 1018 Chinese patients with lung cancer from October 18th, 2022, to November 25th, 2022. Among 1018 patients, a total of 75 (13.7%) patients reported acceptable systemic adverse events in those had received the SARS-CoV-2 vaccine (549, 54%), the most common of which was fever (39, 7%). Factors including females (OR, 1.512; 95% CI, 1.076-2.124), residents in the municipality (OR, 2.048; 95% CI, 1.238-3.389), undergoing therapy (OR, 2.897; 95% CI, 1.348-6.226), disagree to vaccines is safe for patients with lung cancer (OR, 3.816; 95% CI, 2.198-6.626) contributed to hesitancy. Among 373 patients had received three doses, half respondents (206, 55.2%) were hesitant to receive a fourth dose due to the safety concern and efficacy towards the variants. In conclusion, low vaccine uptake rates in patients with lung cancer could be improved by increasing confidence in vaccine safety, particularly for those with negative beliefs. Appropriate guidance and individualized vaccination plans that meet the healthcare needs of patients with lung cancer were needed during the constantly evolving pandemic.
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COVID-19 , Neoplasias Pulmonares , Feminino , Humanos , Vacinas contra COVID-19/efeitos adversos , Estudos Transversais , População do Leste Asiático , COVID-19/prevenção & controle , SARS-CoV-2RESUMO
COVID-19 inactivated vaccine-induced humoral responses in patients with lung cancer (LCs) to SARS-CoV-2 wild-type (WT) strain and variants BA.4/5 after the primary 2-dose and booster vaccination remained unknown. We conducted a cross-sectional study in 260 LCs, 140 healthy controls (HC) and additional 40 LCs with serial samples by detecting total antibodies, IgG anti-RBD and neutralizing antibodies (NAb) toward WT and BA.4/5. SARS-CoV-2-specific antibody responses were augmented by the booster dose of inactivated vaccines in LCs, whereas they were lower than that in HCs. Enhanced humoral responses waned over time after triple injection, notably in NAb against WT and BA.4/5. The NAb against BA.4/5 was much lower than WT. Age ≥ 65 was risk factor for immunization of NAb to WT. Undergoing treatment resulted in a lower antibody response than those without and radiotherapy was a also risk factor for seroconversion of NAb to WT. Lower lymphocyte counts contributed to a lower titer of IgG anti-RBD and NAb against BA.4/5 in LCs than HCs. Specifically, total B cells, CD4+T cells and CD8+T counts were correlated with the humoral response. These results should be taken into consideration for the elderly patients under treatment.
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COVID-19 , Neoplasias Pulmonares , Idoso , Humanos , Vacinas contra COVID-19/uso terapêutico , Formação de Anticorpos , COVID-19/prevenção & controle , Estudos Transversais , Imunização Secundária , SARS-CoV-2 , Anticorpos Neutralizantes , Anticorpos Antivirais , Imunoglobulina GRESUMO
INTRODUCTION: Survival significance of parotid lymph node (LN) factors in parotid cancer remains unclear, our goal was to assess the impact of number, size, and extranodal extension (ENE) of metastatic parotid LNs on prognosis in parotid cancer. MATERIALS AND METHODS: Patients with surgically treated parotid cancer were retrospectively enrolled. Primary outcome variable was recurrence-free survival (RFS) and overall survival (OS). The hazard ratios (HRs) of main predictive variables including the number, size, and ENE of positive parotid LNs on RFS and OS were analyzed using Cox model. The secondary outcome variable was ENE of metastatic parotid LN, its association with clinicopathologic variables were evaluated using Chi-square test. RESULTS: In total, 453 patients (186 male and 267 female) were included. The 10-year RFS and OS rates were 73% (95%CI: 69%-77%) and 61% (95%CI: 55%-67%), respectively. In Cox model, compared none parotid LN metastasis, one metastatic parotid LN did not offer additional compromise of RFS (p = 0.224) or OS (p = 0.135), but two or more positive LNs decreased the control of RFS (HR: 2.017; 95%CI: 1.378-4.632) and OS (HR: 2.173; 95%CI: 1.367-4.275). When accounting for the number of metastatic LNs, LN size or ENE was no longer related to RFS or OS. ENE of parotid LN tended to develop if there was presence of T3/4 stage, lymphovascular invasion, high histologic grade, N2/3 stage, and three or more positive parotid LNs. CONCLUSION: Quantitative parotid LN burden but not ENE or LN size is an important determinant of survival in patients with parotid cancer.
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Neoplasias Parotídeas , Humanos , Masculino , Feminino , Neoplasias Parotídeas/cirurgia , Neoplasias Parotídeas/patologia , Estudos Retrospectivos , Estadiamento de Neoplasias , Linfonodos/cirurgia , Linfonodos/patologia , Prognóstico , Excisão de LinfonodoRESUMO
An emerging view regarding cancer-associated fibroblast (CAF) is that it plays a critical role in tumorigenesis and immunosuppression in the tumor microenvironment (TME), but the clinical significance and biological functions of CAFs in non-small cell lung cancer (NSCLC) are still poorly explored. Here, we aimed to identify the CAF-related signature for NSCLC through integrative analyses of bulk and single-cell genomics, transcriptomics, and proteomics profiling. Using CAF marker genes identified in weighted gene co-expression network analysis (WGCNA), we constructed and validated a CAF-based risk model that stratifies patients into two prognostic groups from four independent NSCLC cohorts. The high-score group exhibits a higher abundance of CAFs, decreased immune cell infiltration, increased epithelial-mesenchymal transition (EMT), activated transforming growth factor beta (TGFß) signaling, and a limited survival rate compared with the low-score group. Considering the immunosuppressive feature in the high-score group, we speculated an inferior clinical response for immunotherapy in these patients, and this association was successfully verified in two NSCLC cohorts treated with immune checkpoint blockades (ICBs). Furthermore, single-cell RNA sequence datasets were used to clarify the molecular mechanisms underlying the aggressive and immunosuppressive phenotype in the high-score group. We found that one of the genes in the risk model, filamin binding LIM protein 1 (FBLIM1), is mainly expressed in fibroblasts and upregulated in CAFs compared to fibroblasts from normal tissue. FBLIM1-positive CAF subtype was correlated with increased TGFß expression, higher mesenchymal marker level, and immunosuppressive tumor microenvironment. Finally, we demonstrated that FBLIM1 might serve as a poor prognostic marker for immunotherapy in clinical samples. In conclusion, we identified a novel CAF-based classifier with prognostic value in NSCLC patients and those treated with ICBs. Single-cell transcriptome profiling uncovered FBLIM1-positive CAFs as an aggressive subtype with a high abundance of TGFß, EMT, and an immunosuppressive phenotype in NSCLC.
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Fibroblastos Associados a Câncer , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Fibroblastos Associados a Câncer/patologia , Neoplasias Pulmonares/patologia , Prognóstico , Análise da Expressão Gênica de Célula Única , Fator de Crescimento Transformador beta/metabolismo , Imunoterapia , Microambiente Tumoral/genética , Proteínas do Citoesqueleto/genética , Proteínas do Citoesqueleto/metabolismo , Moléculas de Adesão Celular/genéticaRESUMO
Serum autoantibody markers have the advantages of easy specimen acquisition, simple detection technology and dynamic real-time monitoring. With the wide application of immune checkpoint inhibitors in the treatment of malignant tumors, autoantibody markers in predicting tumor immune checkpoint inhibitors efficacy and forecasting irAEs (immune related adverse events) show good prediction of potential. This review mainly focused on the progress of autoantibody markers in the prediction of therapeutic effect and the monitoring of irAE in tumor immunotherapy.â©.
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Neoplasias Pulmonares , Neoplasias , Humanos , Inibidores de Checkpoint Imunológico , Imunoterapia/efeitos adversos , Neoplasias Pulmonares/etiologia , Neoplasias/tratamento farmacológico , PrognósticoRESUMO
Objective: The aim of this study is to identify the risk factors associated with orocutaneous fistula (OCF) formation after free flap reconstruction for oral squamous cell carcinoma (SCC). Methods: Patients undergoing free flap reconstruction for oral SCC were retrospectively enrolled. The relationship between clinicopathologic variables and OCF formation was analyzed by univariate and multivariate analyses. Results: A total of 87 OCFs occurred in 856 patients. Univariate analysis revealed cachexia, tumor at the tongue/floor of the mouth (TFOM), T4 stage, preoperative hemoglobin level, pull-through procedure, preoperative albumin level, and surgical site infection were associated with the formation of OCF. Multivariate analysis confirmed the independence of cachexia, TFOM, T4 stage, and surgical site infection in predicting OCF development. Conventional wound care could achieve successful fistula closure in 82.4% of the patients with a median time of 28 days. Conclusions: OCF formation was common after free flap reconstruction. The presence of cachexia, TFOM tumor site, T4 stage, and surgical site infection significantly increased the risk of OCF formation. Although it required a long period, conventional wound care can obtain satisfactory outcomes in OCF management.
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OBJECTIVE: To determine predictors of malignancy in surgically treated Bethesda category III nodules. METHODS: Patients with surgically treated thyroid nodules classified as Bethesda category III were retrospectively enrolled. The association between clinical/sonographic features and postoperative pathology was evaluated using univariate and multivariate analyses. RESULTS: A total of 188 nodules from 184 patients were included. The overall malignancy rate was 54.3%. In univariate analysis, male sex, aspect ratio >1, microcalcification, unclear boundary, BRAFV600E mutation, and nuclear atypia were significantly associated with malignant disease in Bethesda category III nodules. Multivariate analysis confirmed that male sex, aspect ratio >1, microcalcification, and BRAFV600E mutation were independent predictors of malignant disease. CONCLUSIONS: Malignant disease was common in Bethesda category III nodules, and surgical treatment was strongly indicated in the presence of male sex, aspect ratio>1, microcalcification, and BRAFV600E mutation.
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Calcinose , Neoplasias da Glândula Tireoide , Nódulo da Glândula Tireoide , Biópsia por Agulha Fina , Calcinose/diagnóstico por imagem , Calcinose/genética , Humanos , Masculino , Proteínas Proto-Oncogênicas B-raf/genética , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/cirurgia , Nódulo da Glândula Tireoide/genética , Nódulo da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/cirurgiaRESUMO
AIM: There are still patients of stage I lung adenocarcinoma (ADC) suffering from local or distant recurrence. Herein we conducted a meta-analysis to investigate the prognostic value of tumor spread through air space (STAS), a new form of invasion pattern, in patients with pathologically confirmed stage I lung ADC. METHODS: Related literature was searched using PubMed, Embase, Cochrane Library, and Web of Science databases from the inception dates to September 4, 2021. Recurrence-free survival (RFS) and overall survival (OS) were set as primary outcome endpoints. In addition, subgroup analyses on operation mode, edition of the American Joint Committee on Cancer TNM staging, sample size, and research regions were also investigated. RESULTS: A total of 17 studies involving 9785 patients were included. The presence of STAS was detected in 31.2% of patients and was associated with poor RFS (adjusted hazard ratio [HR] = 1.93, p < 0.001) and OS (HR = 2.02, p < 0.001). In subgroup analysis on operation mode, the prognostic value of STAS was prominently shown in patients who underwent limited resection (RFS: HR = 3.58, p < 0.001; OS: HR = 3.37, p < 0.001), while for patients who underwent lobectomy, adverse impact of STAS on RFS was observed (HR = 1.60, p = 0.019), but no significant difference was observed on OS (HR = 1.56, p = 0.061). The results fluctuated in different regions while other factors did not alter the independent predictive value of STAS. CONCLUSION: Tumor STAS should be considered as an adverse prognostic indicator for patients with stage I lung ADC, especially for those under limited resection. More intensive medical care for those patients needs to be investigated in further studies.
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Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/cirurgia , Humanos , Neoplasias Pulmonares/patologia , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Estudos RetrospectivosRESUMO
BACKGROUND: Both fine-needle aspiration biopsy (FNAB) and frozen section (FS) examination are reliable methods for assessing cervical lymph node (level II-V) metastasis (LNM) in papillary thyroid carcinoma (PTC). Our goal was to compare the diagnostic accuracy of FNAB and FS in clinically positive neck (cN+) PTC patients. METHODS: Altogether, 264 lymph node samples from 220 patients were prospectively enrolled. Samples were assessed by FNAB cytology (FNAB-C), thyroglobulin (Tg) FNAB needle wash testing (FNAB-Tg), and FS simultaneously. Diagnostic performance of the different methods were analyzed by the Chi-square test. RESULTS: The sensitivity and specificity of FNAB-C alone in predicting LNM was 87.4% and 85.7%, respectively. Combined with FNAB-Tg, the sensitivity and specificity of FNAB-C increased to 98.9% and 81.6%, respectively. The sensitivity and specificity of FS in predicting LNM was 92.4% and 81.1%, respectively. FNAB-C and FNAB-Tg had better sensitivity than FS when applied to solid lymph nodes, and comparable sensitivity when applied to cystic and cystic-solid lymph nodes. CONCLUSION: The utilization of FNAB-Tg significantly improved the diagnostic ability of FNAB-C. FS can be replaced by preoperative FNAB combined with FNAB-Tg without compromising diagnostic accuracy.