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1.
Cancer Immunol Immunother ; 73(9): 166, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38954042

ABSTRACT

BACKGROUND: Vulvar squamous cell carcinoma (VSCC) arises after an HPV infection or the mutation of p53 or other driver genes and is treated by mutilating surgery and/or (chemo) radiation, with limited success and high morbidity. In-depth information on the immunological make up of VSCC is pivotal to assess whether immunotherapy may form an alternative treatment. METHODS: A total of 104 patient samples, comprising healthy vulva (n = 27) and VSCC (n = 77), were analyzed. Multispectral immunofluorescence (15 markers) was used to study both the myeloid and lymphoid immune cell composition, and this was linked to differences in transcriptomics (NanoString nCounter, 1258 genes) and in survival (Kaplan-Meier analyses). RESULTS: Healthy vulva and VSCC are both well infiltrated but with different subpopulations of lymphoid and myeloid cells. In contrast to the lymphoid cell infiltrate, the density and composition of the myeloid cell infiltrate strongly differed per VSCC molecular subtype. A relative strong infiltration with epithelial monocytes (HLADR-CD11c-CD14+CD68-CD163-CD33-) was prognostic for improved survival, independent of T cell infiltration, disease stage or molecular subtype. A strong infiltration with T cells and/or monocytes was associated with drastic superior survival: 5-year survival > 90% when either one is high, versus 40% when both are low (p < 0.001). CONCLUSION: A hot myeloid and/or lymphoid infiltrate predicts excellent survival in VSCC. Based on the response of similarly high-infiltrated other tumor types, we have started to explore the potential of neoadjuvant checkpoint blockade in VSCC.


Subject(s)
Biomarkers, Tumor , Carcinoma, Squamous Cell , Monocytes , Vulvar Neoplasms , Humans , Female , Vulvar Neoplasms/immunology , Vulvar Neoplasms/pathology , Vulvar Neoplasms/mortality , Vulvar Neoplasms/therapy , Prognosis , Carcinoma, Squamous Cell/immunology , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/therapy , Monocytes/immunology , Middle Aged , Aged , Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/metabolism , Adult , Aged, 80 and over
2.
Clin Exp Med ; 24(1): 145, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38960987

ABSTRACT

Pyroptosis-related long-noncoding RNAs (PRlncRNAs) play an important role in cancer progression. However, their role in lung squamous cell carcinoma (LUSC) is unclear. A risk model was constructed using the least absolute shrinkage and selection operator (LASSO) Cox regression analysis based on RNA sequencing data from The Cancer Genome Atlas database. The LUSC cohort was divided into high- and low-risk groups based on the median risk score. For the prognostic value of the model, the Kaplan-Meier analysis, log-rank test, and Cox regression analysis were performed. A nomogram was constructed to predict the prognosis of patients, using a risk score and clinical parameters such as age, sex, clinical stage, and tumor node metastasis classification (TNM) stage. Afterwards, six common algorithms were employed to assess the invasion of immune cells. The Gene Set Enrichment Analysis (GSEA) was conducted to identify differences between patients at high and low risk. Furthermore, the pRRophetic package was employed to forecast the half-maximal inhibitory doses of prevalent chemotherapeutic drugs, while the tumor immune dysfunction and exclusion score was computed to anticipate the response to immunotherapy. The expression levels of the seven PRlncRNAs were examined in both LUSC and normal lung epithelial cell lines using RT-qPCR. Proliferation, migration, and invasion assays were also carried out to investigate the role of MIR193BHG in LUSC cells. Patients in the low-risk group showed prolonged survival in the total cohort or subgroup analysis. The Cox regression analysis showed that the risk model could act as an independent prognostic factor for patients with LUSC. The results of GSEA analysis revealed that the high-risk group showed enrichment of cytokine pathways, Janus tyrosine kinase/signal transducer and activator of the transcription signalling pathway, and Toll-like receptor pathway. Conversely, the low-risk group showed enrichment of several gene repair pathways. Furthermore, the risk score was positively correlated with immune cell infiltration. Moreover, patients in the high-risk category showed reduced responsiveness to conventional chemotherapeutic medications and immunotherapy. The majority of the long noncoding RNAs in the risk model were confirmed to be overexpressed in LUSC cell lines compared to normal lung epithelial cell lines by in vitro tests. Further studies have shown that downregulating the expression of MIR193BHG may inhibit the growth, movement, and infiltration capabilities of LUSC cells, whereas increasing the expression of MIR193BHG could enhance these malignant tendencies. This study found that PRlncRNAs were linked to the prognosis of LUSC patients. The risk model, evaluated across various clinical parameters and treatment modalities, shows potential as a future reference for clinical applications.


Subject(s)
Carcinoma, Squamous Cell , Lung Neoplasms , Pyroptosis , RNA, Long Noncoding , Humans , RNA, Long Noncoding/genetics , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Lung Neoplasms/therapy , Lung Neoplasms/mortality , Male , Female , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/therapy , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/mortality , Prognosis , Pyroptosis/genetics , Immunotherapy , Middle Aged , Nomograms , Gene Expression Regulation, Neoplastic , Biomarkers, Tumor/genetics , Aged , Cell Line, Tumor
3.
BMC Cancer ; 24(1): 766, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38926643

ABSTRACT

BACKGROUND: In oral squamous cell carcinoma (OSCC), the tumor-node-metastasis (TNM) staging system is a significant factor that influences prognosis and treatment decisions for OSCC patients. Unfortunately, TNM staging does not consistently predict patient prognosis and patients with identical clinicopathological characteristics may have vastly different survival outcomes. Host immunity plays an important role in tumor progression but is not included in the TNM staging system. Tumor-infiltrating lymphocytes (TILs) are part of the host immune response that recognizes tumor cells; and the presence of TILs has emerged as potential candidates for prognostic markers for many types of cancers. The present study aims to determine the association of T cell-specific markers (CD3, CD4, CD8, and FOXP3) with clinicopathological characteristics and survival outcomes in OSCC patients. The prognostic value of CD3, CD4, and CD8 will also be evaluated based on tumor stage. METHODS: Tissue microarrays were constructed containing 231 OSCC cases and analyzed by immunohistochemical staining for the expression of CD3, CD4, CD8, and FOXP3. The expression scores for each marker were correlated with clinicopathological parameters and survival outcomes. The prognostic impact of CD3, CD4 and CD8 were further analyzed based on tumor stage (early or advanced). RESULTS: CD3, CD4, and CD8 were found to be significantly associated with both overall survival and progression-free survival using univariate analysis. However, none of these markers were found to independently predict the survival outcomes of OSCC using multivariate analysis. Only conventional factors such as nodal status, tumor differentiation and perineural invasion (PNI) were independent predictors of survival outcomes, with nodal status being the strongest independent predictor. Additionally, low CD4 (but not CD3 or CD8) expression was found to identify early-stage OSCC patients with exceptionally poor prognosis which was similar to that of advanced staged OSCC patients. CONCLUSIONS: TIL markers such as CD3, CD4, CD8, and FOXP3 can predict the survival outcomes of OSCC patients, but do not serve as independent prognostic markers as found with conventional factors (i.e. nodal status, tumor differentiation and PNI). CD4 expression may assist with risk stratification in early-stage OSCC patients which may influence treatment planning and decision making for early-stage OSCC patients.


Subject(s)
Carcinoma, Squamous Cell , Lymphocytes, Tumor-Infiltrating , Mouth Neoplasms , Neoplasm Staging , Humans , Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/metabolism , Mouth Neoplasms/pathology , Mouth Neoplasms/immunology , Mouth Neoplasms/mortality , Male , Female , Prognosis , Middle Aged , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/immunology , Carcinoma, Squamous Cell/mortality , Aged , Forkhead Transcription Factors/metabolism , Adult , Biomarkers, Tumor/metabolism , Aged, 80 and over , CD3 Complex/metabolism
4.
Front Immunol ; 15: 1413204, 2024.
Article in English | MEDLINE | ID: mdl-38911862

ABSTRACT

Backgroud: The study aimed to analyze the efficacy and safety of PD-1 inhibitors plus chemotherapy with or without endostatin for stage IV lung squamous cell carcinoma (LUSC). Methods: A total of 219 patients with stage IV LUSC were included. 120 received PD-1 inhibitors plus chemotherapy with or without endostatin (IC ± A), of which 39 received endostatin (IC+A) and 81 did not receive endostatin (IC-A). 99 received chemotherapy with or without endostatin (C ± A). Endpoints included overall survival (OS), progression-free survival (PFS), adverse events (AEs), and immune-related adverse events (irAEs). Results: The median PFS in the IC ± A group versus the C ± A group was 8 and 4 months (P < 0.001), and the median OS was 17 and 9 months (P < 0.001). There was no significant difference in any grade AEs between the IC ± A and C ± A groups (P > 0.05). The median PFS in the IC+A group versus the IC-A group was 11 and 7 months (P = 0.024), and the median OS was 34 and 15 months (P = 0.01). There was no significant difference between the IC+A group and the IC-A group for all grade AEs and irAEs (P > 0.05). The subgroup analysis showed that patients with LIPI = 0 had significant OS and PFS benefits in IC+A group, while for patients with LIPI = 1-2, there was no significant difference in OS and PFS benefits between the IC+A group and IC-A group. Conclusions: PD-1 inhibitors plus chemotherapy with endostatin might be first-line treatment for patients with stage IV LUSC.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Endostatins , Immune Checkpoint Inhibitors , Lung Neoplasms , Neoplasm Staging , Humans , Endostatins/therapeutic use , Endostatins/adverse effects , Male , Female , Lung Neoplasms/drug therapy , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Middle Aged , Retrospective Studies , Aged , Immune Checkpoint Inhibitors/adverse effects , Immune Checkpoint Inhibitors/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Adult , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Treatment Outcome
5.
Article in English | MEDLINE | ID: mdl-38881337

ABSTRACT

BACKGROUND: The prevalence of malignant central airway obstruction at diagnosis and its 5-year incidence are largely unknown, as are basic epidemiological data pertaining to this serious condition. To address these data limitations, we retrospectively collected data from the cohort of patients diagnosed with lung cancer at our institution in 2015 and followed cohort patients 5 years forward, until 2020. METHODS: We reviewed index PET/CT or CT scans at the time of lung cancer diagnosis to identify the presence, subtype, and severity of malignant central airway obstruction as well as progression/development over the next 5 years. RESULTS: The prevalence of malignant central airway obstruction affecting the airway lumen by 25% or greater was 17%, and its 5-year incidence of development was 8.2%. Notable associations from the multivariate analysis included a younger age and a stepwise increase in obstruction with increasing stage of disease. Squamous cell carcinoma and small-cell lung cancer were the 2 histologic subtypes with the strongest association with obstruction. The presence of malignant central airway obstruction either at time of diagnosis or on follow-up imaging was associated with significantly shortened survival (multivariate Cox proportional HR for MCAO=1.702, P<0.001). CONCLUSION: This study provides the first systematic characterization of fundamental epidemiological data on malignant central airway obstructions at a tertiary cancer center in the United States. This data is important to inform research directions and funding efforts of this serious complication. It also serves as a baseline value against which to compare for future studies.


Subject(s)
Airway Obstruction , Lung Neoplasms , Humans , Lung Neoplasms/complications , Lung Neoplasms/epidemiology , Lung Neoplasms/mortality , Airway Obstruction/epidemiology , Airway Obstruction/diagnostic imaging , Airway Obstruction/mortality , Male , Female , Aged , Retrospective Studies , Middle Aged , Prevalence , Positron Emission Tomography Computed Tomography , Carcinoma, Squamous Cell/epidemiology , Carcinoma, Squamous Cell/complications , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/diagnostic imaging , Small Cell Lung Carcinoma/complications , Small Cell Lung Carcinoma/epidemiology , Small Cell Lung Carcinoma/diagnostic imaging , Small Cell Lung Carcinoma/mortality , Incidence , Tomography, X-Ray Computed , Aged, 80 and over
6.
BMC Cancer ; 24(1): 730, 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38877437

ABSTRACT

BACKGROUND: Oral cavity squamous cell carcinoma (OCSCC) is the most common pathological type in oral tumors. This study intends to construct a novel prognostic nomogram model based on China populations for these resectable OCSCC patients, and then validate these nomograms. METHODS: A total of 607 postoperative patients with OCSCC diagnosed between June 2012 and June 2018 were obtained from two tertiary medical institutions in Xinxiang and Zhengzhou. Then, 70% of all the cases were randomly assigned to the training group and the rest to the validation group. The endpoint time was defined as overall survival (OS) and disease-free survival (DFS). The nomograms for predicting the 3-, and 5-year OS and DFS in postoperative OCSCC patients were established based on the independent prognostic factors, which were identified by the univariate analysis and multivariate analysis. A series of indexes were utilized to assess the performance and net benefit of these two newly constructed nomograms. Finally, the discrimination capability of OS and DFS was compared between the new risk stratification and the American Joint Committee on Cancer (AJCC) stage by Kaplan-Meier curves. RESULTS: 607 postoperative patients with OCSCC were selected and randomly assigned to the training cohort (n = 425) and validation cohort (n = 182). The nomograms for predicting OS and DFS in postoperative OCSCC patients had been established based on the independent prognostic factors. Moreover, dynamic nomograms were also established for more convenient clinical application. The C-index for predicting OS and DFS were 0.691, 0.674 in the training group, and 0.722, 0.680 in the validation group, respectively. Besides, the calibration curve displayed good consistency between the predicted survival probability and actual observations. Finally, the excellent performance of these two nomograms was verified by the NRI, IDI, and DCA curves in comparison to the AJCC stage system. CONCLUSION: The newly established and validated nomograms for predicting OS and DFS in postoperative patients with OCSCC perform well, which can be helpful for clinicians and contribute to clinical decision-making.


Subject(s)
Mouth Neoplasms , Nomograms , Humans , Male , Female , Middle Aged , China/epidemiology , Mouth Neoplasms/surgery , Mouth Neoplasms/mortality , Mouth Neoplasms/pathology , Prognosis , Aged , Postoperative Period , Adult , Disease-Free Survival , Kaplan-Meier Estimate , Squamous Cell Carcinoma of Head and Neck/surgery , Squamous Cell Carcinoma of Head and Neck/mortality , Squamous Cell Carcinoma of Head and Neck/pathology , Carcinoma, Squamous Cell/surgery , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Neoplasm Staging
7.
Cancer Med ; 13(12): e7213, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38888352

ABSTRACT

BACKGROUND: Elective tracheotomy is commonly performed in resected oral squamous cell carcinoma (OCSCC) to maintain airway patency. However, the indications for this procedure vary among surgeons. This nationwide study evaluated the impact of tracheotomy on both the duration of in-hospital stay and long-term survival outcomes in patients with OCSCC. METHODS: A total of 18,416 patients with OCSCC were included in the analysis, comprising 7981 patients who underwent elective tracheotomy and 10,435 who did not. The primary outcomes assessed were 5-year disease-specific survival (DSS) and overall survival (OS). To minimize potential confounding factors, a propensity score (PS)-matched analysis was performed on 4301 patients from each group. The duration of hospital stay was not included as a variable in the PS-matched analysis. RESULTS: Prior to PS matching, patients with tracheotomy had significantly lower 5-year DSS and OS rates compared to those without (71% vs. 82%, p < 0.0001; 62% vs. 75%, p < 0.0001, respectively). Multivariable analysis identified tracheotomy as an independent adverse prognostic factor for 5-year DSS (hazard ratio = 1.10 [1.03-1.18], p = 0.0063) and OS (hazard ratio = 1.10 [1.04-1.17], p = 0.0015). In the PS-matched cohort, the 5-year DSS was 75% for patients with tracheotomy and 76% for those without (p = 0.1488). Five-year OS rates were 66% and 67%, respectively (p = 0.0808). Prior to PS matching, patients with tracheotomy had a significantly longer mean hospital stay compared to those without (23.37 ± 10.56 days vs. 14.19 ± 8.34 days; p < 0.0001). Following PS matching, the difference in hospital stay duration between the two groups remained significant (22.34 ± 10.25 days vs. 17.59 ± 9.54 days; p < 0.0001). CONCLUSIONS: While elective tracheotomy in resected OCSCC patients may not significantly affect survival, it could be associated with prolonged hospital stays.


Subject(s)
Elective Surgical Procedures , Length of Stay , Mouth Neoplasms , Tracheotomy , Humans , Tracheotomy/methods , Male , Female , Middle Aged , Mouth Neoplasms/surgery , Mouth Neoplasms/mortality , Mouth Neoplasms/pathology , Prognosis , Aged , Elective Surgical Procedures/methods , Length of Stay/statistics & numerical data , Carcinoma, Squamous Cell/surgery , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Cohort Studies , Adult
8.
Cancer Immunol Immunother ; 73(8): 160, 2024 Jun 08.
Article in English | MEDLINE | ID: mdl-38850335

ABSTRACT

Treatment duration with checkpoint inhibitors must be optimized to prevent unjustified toxicity, but evidence for the management of cutaneous squamous cell carcinoma is lacking. A retrospective study was performed to evaluate the survival of patients with cutaneous squamous cell carcinoma (CSCC) who discontinued cemiplimab due to different causes and without progression. Among 95 patients with CSCC who received cemiplimab, 22 (23%) patients discontinued immunotherapy due to causes other than progression, such as comorbidities, toxicity, complete response or lack of compliance (group that discontinued before censoring [DBC]), then 73 patients had standard treatment scheduled (STS). The overall survival was 25.2 months (95% CI: 8.9-29.4) in STS group and 28.3 months (95% CI: 12.7-28.3) in the DBC group; deaths for all causes were 11/22 (50%) in the DBC group and 34/73 (46.6%) in the STS group (p = 0.32). 10/22 (45.4%) subjects died due to CSCC in the DBC after discontinuation and 34/73 (46.6%) in the STS group, and the difference between groups was not significant (p = 0.230). Duration of treatment was significantly lower in subjects with stable disease versus those with complete or partial response (16.9, 30.6 and 34.9 months, respectively; p = 0.004). Among the 22 STS patients, 12 received cemiplimab for less than 12 months (10 [83%] died) and 10 for at least 12 months (1 [10%] died). Our observation, finding no outcome difference between DBC and STS groups, suggests that ICI treatment after one year might expose patients to further treatment related events without efficacy advantages.


Subject(s)
Antibodies, Monoclonal, Humanized , Carcinoma, Squamous Cell , Skin Neoplasms , Humans , Male , Female , Skin Neoplasms/drug therapy , Skin Neoplasms/mortality , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/adverse effects , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/mortality , Aged , Retrospective Studies , Middle Aged , Aged, 80 and over , Treatment Outcome , Antineoplastic Agents, Immunological/therapeutic use , Antineoplastic Agents, Immunological/administration & dosage , Antineoplastic Agents, Immunological/adverse effects , Adult , Immune Checkpoint Inhibitors/therapeutic use , Immune Checkpoint Inhibitors/administration & dosage , Immune Checkpoint Inhibitors/adverse effects
9.
Article in Chinese | MEDLINE | ID: mdl-38858112

ABSTRACT

Objective:To analyze the difference in 5-year survival between maxillary sinus adenoidal cystic carcinoma(maxillary sinus adenoid cystic carcinoma, MSACC) and squamous cell carcinoma(maxillary sinus squamous cell carcinoma, MSSCC) using the National Cancer Institute's Surveillance, Epidemiology, and End. Results:database(SEER) and to explore the factors associated with the prognosis of the two tumors. Methods:The data of 161 patients with MSACC and 929 patients with MSSCC were collected from SEER database, and the 5-year overall survival rate(OS) and tumor specific survival rate(CSS) were compared between the two groups before and after propensity score matching. The forest map of multivariate Cox proportional hazard regression model was established to analyze the prognostic factors affecting the survival rate of patients with MSACC and MSSCC. Results:There were statistical differences in 5-year OS and CSS between MSACC and MSSCC before and after propensity score matching(P<0.001). Multivariate regression analysis showed that age, side of the disease, lymph node metastasis, operation and radiotherapy were the influencing factors of OS in MSACC, while age and operation were the influencing factors of CSS. Age, race, T grade, lymph node metastasis, systemic metastasis, surgery, radiotherapy and chemotherapy are the influencing factors of OS of MSSCC. Age, T grade, lymph node metastasis, systemic metastasis, surgery, radiotherapy and chemotherapy are the influencing factors of CSS. Conclusion:The 5-year survival rate of MSACC is higher than that of MSSCC. Surgery plays a positive role in the prognosis of the two kinds of tumors. The analysis results can provide some reference for their survival expectations and treatment choices.


Subject(s)
Carcinoma, Adenoid Cystic , Carcinoma, Squamous Cell , SEER Program , Humans , Female , Male , Carcinoma, Adenoid Cystic/mortality , Carcinoma, Adenoid Cystic/pathology , Prognosis , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Middle Aged , Survival Rate , Propensity Score , Maxillary Sinus Neoplasms/pathology , Maxillary Sinus Neoplasms/mortality , Maxillary Sinus/pathology , Proportional Hazards Models , Lymphatic Metastasis , Aged , Adult
10.
Oral Oncol ; 154: 106808, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38823172

ABSTRACT

BACKGROUND: An estimated 20% of patients with oral and oropharyngeal squamous cell carcinoma (OOSCC) have micrometastases (Mi) or isolated tumor cells (ITC) in the cervical lymph nodes that evade detection by standard histological evaluation of lymph node sections. Lymph node Mi and ITC could be one reason for regional recurrence after neck dissection. The aim of this study was to review the existing data regarding the impact of Mi on the survival of patients with OOSCC. METHODS: PubMed and the Cochrane Library were searched for articles reporting the impact of Mi and ITC on patient survival. Two authors independently assessed the methodological quality of retrieved studies using the Downs and Black index. Data were also extracted on study type, number of included patients, mode of histological analysis, statistical analysis, and prognostic impact. RESULTS: Sixteen articles with a total of 2064 patients were included in the review. Among the 16 included studies, eight revealed a statistically significant impact of Mi on at least one endpoint in the Kaplan-Meier and/or multivariate analysis. Three studies regarded Mi as Ma, while five studies found no impact of Mi on survival. Only one study demonstrated an impact of ITC on patient's prognosis in the univariate but not in the multivariate analysis. CONCLUSION: The majority of cases included in the review were patients with oral cancer. The findings provide low-certainty evidence that Mi negatively impacts survival. Data on ITC were scarcer, so no conclusions can be drawn about their effect on survival. The lower threshold to discriminate between Mi and ITC should be defined for OOSCC since the existing thresholds are based on data from different tumors. The histological, immunohistological, and anatomical characteristics of Mi and ITC in OOSCC as well as the effect of radiotherapy on Mi should be further investigated separately for oral and oropharyngeal carcinomas.


Subject(s)
Lymphatic Metastasis , Mouth Neoplasms , Neoplasm Micrometastasis , Oropharyngeal Neoplasms , Humans , Oropharyngeal Neoplasms/pathology , Oropharyngeal Neoplasms/mortality , Mouth Neoplasms/pathology , Mouth Neoplasms/mortality , Prognosis , Neoplasm Micrometastasis/pathology , Lymph Nodes/pathology , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/mortality
11.
Sci Rep ; 14(1): 14250, 2024 06 20.
Article in English | MEDLINE | ID: mdl-38902361

ABSTRACT

Carcinogenesis and tumor proliferation are characterized by a complex interaction of cancer cells with the tumor microenvironment. In particular, a tumor-promoting effect can be assumed for the stroma and its fibroblasts. An influence of the immune system on non small cell lung cancer (NSCLC) is now also suspected. In our study, we examined 309 sections of squamous cell carcinoma (SCC), a subtype of NSCLC. We determined the cell densities and areas of the different tissues in SCC using the software QuPath. Spearman rank correlation showed a significant positive correlation between the different tumor cell densities and stromal cell densities, and between tumor cell densities and immune cell densities. Overall survival curves by the Kaplan-Meier method revealed a prominent negative curve in cases of low immune cell density. Based on our results, we can assume a positive influence of the tumor microenvironment, especially the stromal cells, on tumor proliferation in SCC. We have also revealed that low density of immune cells is prognostically unfavorable.


Subject(s)
Carcinoma, Squamous Cell , Lung Neoplasms , Tumor Microenvironment , Humans , Lung Neoplasms/mortality , Lung Neoplasms/immunology , Lung Neoplasms/pathology , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/immunology , Carcinoma, Squamous Cell/pathology , Tumor Microenvironment/immunology , Male , Female , Aged , Prognosis , Middle Aged , Stromal Cells/pathology , Stromal Cells/immunology , Kaplan-Meier Estimate , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/immunology , Carcinoma, Non-Small-Cell Lung/pathology , Cell Count
13.
Eur J Surg Oncol ; 50(7): 108447, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38843661

ABSTRACT

INTRODUCTION: Vulval cancer is a rare gynaecological malignancy. In this study, we present a tertiary centre case analysis to examine the recurrence patterns and survival outcomes of vulval squamous cell carcinoma (SCC). METHODS: This is a retrospective cohort study of women who received treatment at Oxford University Hospitals between February 2010 and July 2022 for primary vulval SCC. RESULTS: We included 98 cases. The median age at diagnosis was 68 years. Human Papillomavirus (HPV) infection and lichen sclerosis were observed in 21 and 50 cases, respectively. Surgical excision was the primary treatment. Recurrence within 2 years was more common with advanced stage (p = 0.047, RR = 2.26) and extracapsular lymph node spread (p = 0.013, RR = 2.88). Local recurrence was not associated with a specific cut-off value for tumour-free margin. Poor survival outcomes were observed with higher grade (p = 0.01), advanced FIGO stage (p < 0.001), HPV-independent cancer (p = 0.048), lymph node involvement (p < 0.001, HR = 7.14), extracapsular spread (p < 0.001, HR = 7.93), lymphovascular space invasion (p = 0.002, HR = 3.17), tumour diameter wider than 23 mm (p = 0.029, HR = 2.53) and depth of invasion more than 6 mm (p = 0.006, HR = 3.62). Perineural invasion is associated with shorter disease-free survival. Five-year cancer-specific survival rates for stages I, III, and IV were 90.2%, 40.8%, and 14.3%, respectively.


Subject(s)
Carcinoma, Squamous Cell , Lymphatic Metastasis , Neoplasm Recurrence, Local , Neoplasm Staging , Tertiary Care Centers , Vulvar Neoplasms , Humans , Female , Vulvar Neoplasms/pathology , Vulvar Neoplasms/surgery , Vulvar Neoplasms/mortality , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/surgery , Retrospective Studies , Aged , Middle Aged , Prognosis , Survival Rate , Papillomavirus Infections/complications , Aged, 80 and over , Adult , Neoplasm Grading , Margins of Excision , Neoplasm Invasiveness
14.
Cancer Radiother ; 28(3): 242-250, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38876937

ABSTRACT

PURPOSE: The lack of reliable biomarkers for the prognosis and radiotherapy efficacy in esophageal cancer (EC) necessitates further research. The aim of our study was to investigate the predictive utility of plasma cell-free DNA (cfDNA) kinetics in patients with EC. MATERIALS AND METHODS: We retrospectively analyzed the clinical data and cfDNA levels (pre-radiotherapy [pre-RT] and post-radiotherapy [post-RT]) and the cfDNA kinetics (cfDNA ratio: post-RT cfDNA/pre-RT cfDNA) of 88 patients. We employed Kaplan-Meier curves to examine the relationship between cfDNA and overall survival (OS) as well as progression-free survival (PFS). Univariate and multivariate Cox regression analyses were executed to ascertain the independent risk factors in EC. RESULTS: The pre-RT cfDNA levels were positively correlated with clinical stage (P=0.001). The pre-RT cfDNA levels (cutoff value=16.915ng/mL), but not the post-RT cfDNA levels, were linked to a diminished OS (P<0.001) and PFS (P=0.0137). CfDNA kinetics (cutoff value=0.883) were positively associated with OS (P=0.0326) and PFS (P=0.0020). Notably, we identified independent risk factors for OS in EC treated with RT, including cfDNA ratio (high/low) (HR=0.447 [0.221-0.914] P=0.025), ECOG (0/1/2) (HR=0.501 [0.285-0.880] p=0.016), and histological type (esophagal squamous cell carcinoma [ESCC]/non-ESCC) (HR=3.973 [1.074-14.692] P=0.039). CONCLUSION: Plasma cfDNA kinetics is associated with prognosis and radiotherapy effect in EC undergoing RT, suggesting potential clinical application of a cheap and simple blood-based test.


Subject(s)
Biomarkers, Tumor , Cell-Free Nucleic Acids , Esophageal Neoplasms , Humans , Esophageal Neoplasms/radiotherapy , Esophageal Neoplasms/blood , Esophageal Neoplasms/mortality , Esophageal Neoplasms/pathology , Male , Female , Middle Aged , Retrospective Studies , Prognosis , Aged , Biomarkers, Tumor/blood , Cell-Free Nucleic Acids/blood , Kaplan-Meier Estimate , Progression-Free Survival , Esophageal Squamous Cell Carcinoma/radiotherapy , Esophageal Squamous Cell Carcinoma/blood , Adult , Carcinoma, Squamous Cell/radiotherapy , Carcinoma, Squamous Cell/blood , Carcinoma, Squamous Cell/mortality , Aged, 80 and over , Kinetics
15.
Nutr Cancer ; 76(7): 628-637, 2024.
Article in English | MEDLINE | ID: mdl-38757270

ABSTRACT

This study compared the effects of megestrol acetate (MA) prophylactic (p-MA) versus reactive (r-MA) use for critical body-weight loss (>5% from baseline) during concurrent chemoradiotherapy (CCRT) in patients with advanced pharyngolaryngeal squamous cell carcinoma (PLSCC).Patients receiving CCRT alone in two phase-II trials were included for analyses. Both the p-MA and r-MA cohorts received the same treatment protocol at the same institution, and the critical body-weight loss, survival, and adverse event profiles were compared.The mean (SD) weight loss was 5.1% (4.7%) in the p-MA cohort (n = 54) vs. 8.1% (4.6%) in the r-MA cohort (n = 50) (p = .001). The percentage of subjects with body-weight loss >5% was 42.6% in the p-MA cohort vs. 68.0% in the r-MA cohort (p = .011). Tube feeding was needed in 22.2% of p-MA vs. 62.0% of r-MA patients (p < .001). Less neutropenia (26.0% vs. 70.0% [p < .001]) and a shorter duration of grade 3-4 mucositis (2.4 ± 1.4 vs. 3.6 ± 2.0 wk [p = .009]) were observed with p-MA treatment. Disease-specific survival, locoregional control, or distant metastasis-free survival did not differ. Less competing mortality from secondary primary cancer resulted in a better overall survival trend in the p-MA cohort.p-MA may reduce body-weight loss and improve adverse event profiles during CCRT for patients with PLSCC.


Subject(s)
Carcinoma, Squamous Cell , Chemoradiotherapy , Laryngeal Neoplasms , Megestrol Acetate , Pharyngeal Neoplasms , Weight Loss , Humans , Chemoradiotherapy/methods , Chemoradiotherapy/adverse effects , Male , Female , Middle Aged , Laryngeal Neoplasms/therapy , Laryngeal Neoplasms/mortality , Laryngeal Neoplasms/pathology , Aged , Megestrol Acetate/therapeutic use , Carcinoma, Squamous Cell/therapy , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Pharyngeal Neoplasms/therapy , Pharyngeal Neoplasms/mortality , Adult , Squamous Cell Carcinoma of Head and Neck/therapy
16.
Surg Endosc ; 38(7): 3625-3635, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38767690

ABSTRACT

BACKGROUND: The total number of resected lymph nodes (LNs) is an important determinant of longer survival after esophagectomy for esophageal squamous cell carcinoma (ESCC). However, the resected LN counts from areas that affect long-term outcomes remain unclear. METHODS: This study included 406 patients who underwent minimally invasive esophagectomies (MIEs) at Kobe University Hospital. Resected LN counts were evaluated in the following areas: upper mediastinal (UM), middle mediastinal (MM), lower mediastinal (LM), and abdominal (Abd). Cut-off values for LN counts from each area were determined using receiver operating characteristics analysis of the survival status. Cox proportional hazards regression analyses were performed to identify prognostic factors. RESULTS: The cut-off values for large or small numbers of resected LN counts in the UM, MM, LM, and Abd areas were 4, 8, 5, and 18, respectively, in patients with upper and middle thoracic (Ut/Mt) ESCC and 7, 6, 5, and 24, respectively, in patients with lower thoracic (Lt) ESCC. Multivariate analysis in patients with Ut/Mt ESCC revealed that tumor invasion depth, LN metastasis, and the resected LN count from the UM area were independent risk factors for overall survival [hazard ratio (HR), 7.04; 95% confidence interval (CI) 4.47-11.1; HR, 4.01; 95% CI 1.96-8.21; HR, 2.18; 95% CI 1.24-3.82, respectively]. In patients with Lt ESCC, tumor invasion depth, LN metastasis, and pulmonary complications were independent risk factors for overall survival (HR, 4.23; 95% CI 2.14-8.35; HR, 3.83; 95% CI 1.75-8.38; HR, 2.80; 95% CI 1.38-5.65, respectively). Resected LN counts from no areas were prognostic factors. CONCLUSION: The number of resected LNs from the UM area influenced the survival outcomes of patients with Ut/Mt ESCC after MIE.


Subject(s)
Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Esophagectomy , Lymph Node Excision , Mediastinum , Humans , Esophagectomy/methods , Male , Female , Esophageal Neoplasms/surgery , Esophageal Neoplasms/pathology , Esophageal Neoplasms/mortality , Middle Aged , Lymph Node Excision/methods , Aged , Esophageal Squamous Cell Carcinoma/surgery , Esophageal Squamous Cell Carcinoma/pathology , Retrospective Studies , Lymph Nodes/pathology , Lymph Nodes/surgery , Lymphatic Metastasis , Prognosis , Treatment Outcome , Minimally Invasive Surgical Procedures/methods , Adult , Carcinoma, Squamous Cell/surgery , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/mortality
17.
J Gastrointest Surg ; 28(7): 1122-1125, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38723998

ABSTRACT

BACKGROUND: Squamous cell carcinoma of the colon (CSCC) is a rare subtype of colon cancer. This study aimed to evaluate treatment strategies and overall survival (OS). METHODS: Using the Surveillance, Epidemiology, and End Results program database from 2008 to 2019, patients aged 18 years with CSCC were identified. Treatment strategies and OS were summarized using the Kaplan-Meier analysis and the log-rank test. Adjusted Cox proportional hazards regression model ratios were calculated to evaluate the effect of confounding variables. RESULTS: After exclusions, 153 patients met the inclusion criteria. The most common treatment modalities included surgery alone (52.1%), surgery and adjuvant chemotherapy (12.9%), and no treatment (26.4%). Kaplan-Meier analysis revealed that patients who underwent surgery and adjuvant chemotherapy had significant improvements in OS (log-rank P = .002). Cox regression analysis revealed tumor grade (hazard ratio [HR], 2.12; 95% CI, 1.17-3.86) and receipt of chemotherapy (HR, 2.66; 95% CI, 1.23-5.76) as the only factors associated with improvements in OS. CONCLUSION: Patients who underwent surgery in combination with chemotherapy had better OS than those who underwent surgery alone. Tumor grade and receipt of chemotherapy were independently associated with OS.


Subject(s)
Carcinoma, Squamous Cell , Colonic Neoplasms , SEER Program , Humans , Male , Female , Carcinoma, Squamous Cell/therapy , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/surgery , Aged , Middle Aged , Colonic Neoplasms/mortality , Colonic Neoplasms/therapy , Colonic Neoplasms/pathology , Colonic Neoplasms/surgery , Chemotherapy, Adjuvant/statistics & numerical data , Survival Rate , Kaplan-Meier Estimate , Proportional Hazards Models , Retrospective Studies , Adult , Colectomy/methods , Neoplasm Grading
18.
BMC Cancer ; 24(1): 655, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38811880

ABSTRACT

PURPOSE: This study aims to compare treatment outcomes between neoadjuvant chemotherapy (NACT) followed by surgery and concurrent chemoradiotherapy (CCRT) in patients with stage IIB cervical squamous cell carcinoma (CSCC). MATERIALS AND METHODS: We conducted a retrospective cohort study involving patients with stage IIB CSCC treated at Guangxi Medical University Cancer Hospital between June 2012 and June 2019. We compared overall survival (OS), locoregional-free survival (LRFS), and distant metastasis-free survival (DMFS) between the NACT + surgery and CCRT groups. RESULTS: A total of 257 patients were enrolled: 165 underwent NACT + surgery and 92 received CCRT. Before propensity score matching, the NACT + surgery group exhibited lower 5-year OS (68.2% vs. 85.6%; hazard ratio [HR] = 2.50, 95% confidence interval [CI]: 1.26-4.96; P = 0.009), LRFS (85.2% vs. 96.9%; HR = 5.88, 95% CI: 1.33-25.94; P = 0.019), and DMFS (81.9% vs. 97.4%; HR = 6.65, 95% CI: 1.51-29.23; P = 0.012) compared to the CCRT group. After propensity score matching, OS, LRFS, and DMFS remained worse in the NACT + surgery group compared to the CCRT group. CONCLUSION: NACT followed by surgery is associated with decreased OS, LRFS, and DMFS compared to CCRT among patients with stage IIB CSCC.


Subject(s)
Carcinoma, Squamous Cell , Chemoradiotherapy , Neoadjuvant Therapy , Neoplasm Staging , Uterine Cervical Neoplasms , Humans , Female , Uterine Cervical Neoplasms/therapy , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/mortality , Retrospective Studies , Neoadjuvant Therapy/methods , Middle Aged , Chemoradiotherapy/methods , Carcinoma, Squamous Cell/therapy , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/mortality , Adult , Aged , Propensity Score , Treatment Outcome
19.
BMC Cancer ; 24(1): 656, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38811899

ABSTRACT

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.


Subject(s)
Head and Neck Neoplasms , Lymph Nodes , Lymphatic Metastasis , Neoplasm Staging , Skin Neoplasms , Squamous Cell Carcinoma of Head and Neck , Humans , Male , Female , Lymphatic Metastasis/pathology , Aged , Middle Aged , Retrospective Studies , Skin Neoplasms/pathology , Skin Neoplasms/mortality , Lymph Nodes/pathology , Lymph Nodes/surgery , Prognosis , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/mortality , Head and Neck Neoplasms/surgery , Squamous Cell Carcinoma of Head and Neck/pathology , Squamous Cell Carcinoma of Head and Neck/mortality , Squamous Cell Carcinoma of Head and Neck/surgery , Adult , Aged, 80 and over , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/surgery
20.
Oral Oncol ; 154: 106857, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38776623

ABSTRACT

OBJECTIVE: To analyze the impact of clinico-pathological prognostic factors on survival in patients with GBC OSCC. To evaluate the association between various clino-pathological and treatment factors influencing the 3-year and 5-year Overall survival (OS), and Disease specific survival (DSS) in patients with lower GBC OSCC. PATIENTS & METHODS: An Institutional Ethical Committee (IEC) approved retrospective chart audit was performed. Biopsy proven squamous cell cancer of gingivobuccal complex (GBC OSCC) patients from 2010 to 2019 who were treated primarily with surgery with or without adjuvant therapy having complete clinicopathological and follow up data were included. Survival outcomes including 2-year, 3-year & 5-year OS, and DSS were calculated and analyzed. A multivariate analysis was performed to identify significant predictor for the survival outcomes. A p-value < 0.05 was considered significant. RESULTS: 183 patients with primary OSCC were identified out of which 83 patients comprised of OSCC of lower GBC. Age (p < 0.001), tumor grade (p = 0.009), pN status (p = 0.002), PNI (p < 0.001), lymph node metastasis (p = 0.002), treatment given (p = 0.02) and adjuvant therapy (p = 0.02) were found as a significant prognostic factor in univariate analysis. CONCLUSION: The OS & DSS of the patients with lower GBC SCC is 78.3%. The 2-year, 3-year, and 5-year OS of the study population was reported to be 95.2%, 87.9%, and 78.8% respectively. PNI & lymph node metastasis were significant prognostic factor for OS with an adjusted hazard ratio 4.91 and 7.75 respectively.


Subject(s)
Carcinoma, Squamous Cell , Humans , Male , Female , Retrospective Studies , Middle Aged , Prognosis , Aged , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/therapy , Adult , Aged, 80 and over , Mouth Neoplasms/mortality , Mouth Neoplasms/pathology , Mouth Neoplasms/therapy
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