scholarly journals Integration of Tumor Heterogeneity for Recurrence Prediction in Patients with Esophageal Squamous Cell Cancer

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 6084
Author(s):  
Zihang Mai ◽  
Qianwen Liu ◽  
Xinye Wang ◽  
Jiaxin Xie ◽  
Jianye Yuan ◽  
...  

Esophageal squamous cell carcinoma (ESCC) is one of the deadliest malignancies in China. The prognostic value of mutations, especially those in minor tumor clones, has not been systematically investigated. We conducted targeted deep sequencing to analyze the mutation status and the cancer cell fraction (CCF) of mutations in 201 ESCC patients. Our analysis showed that the prognostic effect of mutations was relevant to the CCF, and it should be considered in prognosis prediction. EP300 was a promising biomarker for overall survival, impairing prognosis in a CCF dose-dependent manner. We constructed a CCF-based predictor using a smooth clipped absolute deviation Cox model in the training set of 143 patients. The 3-year disease-free survival rates were 6.3% (95% CI: 1.6–23.9%), 29.8% (20.9–42.6%) and 70.5% (56.6–87.7%) in high-, intermediate- and low-risk patients, respectively, in the training set. The prognostic accuracy was verified in a validation set of 58 patients and the TCGA-ESCC cohort. The eight-gene model predicted prognosis independent of clinicopathological factors and the combination of our model and pathological staging markedly improved the prognostic accuracy of pathological staging alone. Our study describes a novel recurrence predictor for ESCC patients and provides a new perspective for the clinical translation of genomic findings.

2002 ◽  
Vol 20 (4) ◽  
pp. 966-972 ◽  
Author(s):  
R. Pearcey ◽  
M. Brundage ◽  
P. Drouin ◽  
J. Jeffrey ◽  
D. Johnston ◽  
...  

PURPOSE: To test the hypothesis that cisplatin (CDDP) administered concurrently with standard radiotherapy (RT) would improve pelvic control and survival in patients with advanced squamous cell cancer of the cervix. PATIENTS AND METHODS: A total of 259 patients with International Federation of Gynecology and Obstetrics stage IB to IVA squamous cell cervical cancer with central disease ≥ 5 cm or histologically confirmed pelvic lymph node involvement were randomized to receive RT (external-beam RT plus brachytherapy) plus weekly CDDP chemotherapy (40 mg/m2) (arm 1) or the same RT without chemotherapy (arm 2). RESULTS: A total of 253 patients were available for analysis. Median follow-up was 82 months. No significant difference was found in progression-free survival (P = .33). No significant difference in 3- and 5-year survival rates was found (69% v 66% and 62% v 58%, respectively; P = .42). The hazard ratio for survival (arm 2 to arm 1) was 1.10 (95% confidence interval, 0.75 to 1.62). CONCLUSION: This study did not show a benefit to either pelvic control or survival by adding concurrent weekly CDDP chemotherapy in a dose of 40 mg/m2 to radical RT as given in this trial. Careful attention to RT details is important for achieving optimum outcome for patients with this disease.


2020 ◽  
Vol 21 (20) ◽  
pp. 7646
Author(s):  
Chang-Min Lee ◽  
Young-IL Jeong ◽  
Min-Suk Kook ◽  
Byung-Hoon Kim

Cold atmospheric plasma (CAP) has been extensively investigated in the local treatment of cancer due to its potential of reactive oxygen species (ROS) generation in biological systems. In this study, we examined the synergistic effect of combination of CAP and cisplatin-mediated chemotherapy of oral squamous cell carcinoma (OSCC) in vitro. SCC-15 OSCC cells and human gingival fibroblasts (HGF-1) cells were treated with cisplatin, and then, the cells were irradiated with CAP. Following this, viability and apoptosis behavior of the cells were investigated. The viability of SCC-15 cells was inhibited by cisplatin with a dose-dependent manner and CAP treatment time. HGF-1 cells also showed decreased viability by treatment with cisplatin and CAP. Combination of 1 μM cisplatin plus 3 min of CAP treatment or 3 μM cisplatin plus 1 min of CAP treatment showed a synergistic anticancer effect with appropriate cytotoxicity against normal cells. ROS generation and dead cell staining were also increased by the increase in CAP treatment time. Furthermore, tumor-suppressor proteins and apoptosis-related enzymes also increased according to the treatment time of CAP. We showed the synergistic effect of cisplatin and CAP treatment against SCC-15 cells with low cytotoxicity against normal cells.


2019 ◽  
Vol 8 (5) ◽  
pp. 611 ◽  
Author(s):  
Priyanka Shah O’Brien ◽  
Yue Xi ◽  
Justin R. Miller ◽  
Amy L. Brownell ◽  
Qinghua Zeng ◽  
...  

A paucity of advances in the development of novel therapeutic agents for squamous cell carcinomas of the head and neck, oral cavity (OSCC) and oropharynx, has stagnated disease free survival rates over the past two decades. Although immunotherapies targeted against checkpoint inhibitors such as PD-1 or CTLA-4 are just now entering the clinic for late stage disease with regularity the median improvement in overall survival is only about three months. There is an urgent unmet clinical need to identify new therapies that can be used alone or in combination with current approaches to increase survival by more than a few months. Activation of the apoptotic arm of the unfolded response (UPR) with small molecules and natural products has recently been demonstrated to be a productive approach in pre-clinical models of OSCC and several other cancers. The aim of current study was to perform a high throughput screen (HTS) with a diverse chemical library to identify compounds that could induce CHOP, a component of the apoptotic arm of the UPR. Disulfiram (DSF, also known as Antabuse) the well-known aversion therapy used to treat chronic alcoholism emerged as a hit that could generate reactive oxygen species, activate the UPR and apoptosis and reduce proliferation in OSCC cell cultures and xenografts. A panel of murine embryonic fibroblasts null for key UPR intermediates (e.g., Chop and Atf4) was resistant to DSF suggesting that an intact UPR is a key element of the mechanism regulating the antiproliferative effects of DSF.


2007 ◽  
Vol 17 (1) ◽  
pp. 154-158 ◽  
Author(s):  
S. E. Hyde ◽  
S. Valmadre ◽  
N. F. Hacker ◽  
M. S. Schilthuis ◽  
P. T. Grant ◽  
...  

Patients with clinical palpable involved groin lymph nodes and squamous cell cancer of the vulva are frequently treated by a full inguinal-femoral lymph node dissection followed by adjuvant radiotherapy to the groins and pelvis. Theoretically, less radical surgery for the groin such as nodal debulking, where only the macroscopically involved nodes are resected, allowing radiotherapy to treat any remaining microscopic disease may potentially decrease morbidity without compromising survival The objective of this retrospective study was to compare the groin recurrence rate and survival (disease specific and overall survival) of patients with clinically involved groin nodes and squamous cell carcinoma of the vulva treated either by a full inguino-femoral lymphadenectomy or by a nodal debulking followed by radiotherapy. Forty patients from three separate databases who met these criteria were identified. Patients were treated either by a full inguino-femoral lymphadenectomy or by a debulking of the clinically involved inguinal lymph nodes. All patients received adjuvant radiotherapy to the groins. In these two groups, there was no difference in groin recurrence rate expressed as groin recurrence-free survival (P= 0.247). In a univariate analysis, both overall and disease-free survival were better in the group of patients treated by nodal debulking. However, in a multivariate analysis, other variables such as extracapsular growth were independent predictors for survival while the method of surgical dissection for the groin had no independent significant impact on survival.


2020 ◽  
Author(s):  
Hesan Luo ◽  
Shao-Fu Huang ◽  
Hong-Yao Xu ◽  
Xu-Yuan Li ◽  
Sheng-Xi Wu ◽  
...  

Abstract Purpose: To develop and validate a nomogram model to predict complete response (CR) after concurrent chemoradiotherapy (CCRT) in esophageal squamous cell carcinoma (ESCC) patients using pretreatment CT radiomic features. Methods: Data of patients diagnosed as ESCC and treated with CCRT in Shantou Central Hospital during the period from January 2013 to December 2015 were retrospectively collected. Eligible patients were included in this study and randomize divided into a training set and a validation set after successive screening. The least absolute shrinkage and selection operator (LASSO) with logistic regression to select radiomics features calculating Rad-score in the training set. The logistic regression analysis was performed to identify the predictive clinical factors for developing a nomogram model. The area under the receiver operating characteristic curves (AUC) was used to assess the performance of the predictive nomogram model and decision curve was used to analyze the impact of the nomogram model on clinical treatment decisions. Results: A total of 226 patients were included and randomly divided into two groups, 160 patients in training set and 66 patients in validation set. After LASSO analysis, seven radiomics features were screened out to develop a radiomics signature Rad-score. The AUC of Rad-score was 0.812 (95%CI: 0.742-0.869, p<0.001) in the training set and 0.744 (95%CI: 0.632-0.851, p=0.003) in the validation set. Multivariate analysis showed that Rad-score and clinical staging were independent predictors of CR status, with P values of 0.035 and 0.023, respectively. A nomogram model incorporating Rad-socre and clinical staging was developed and validated, with an AUC of 0.844 (95%CI: 0.779-0.897) in the training set and 0.807 (95%CI: 0.691-0.894) in the validation set.Delong test showed that the nomogram model was significantly superior to the clinical staging, with P<0.001 in the training set and P=0.026 in the validation set. The decision curve showed that the nomogram model was superior to the clinical staging when the risk threshold was greater than 25%. Conclusion: We developed and validated a nomogram model for predicting CR status of ESCC patients after CCRT. The nomogram model was combined radiomics signature Rad-score and clinical staging. This model provided us with an economical and simple method for evaluating the response of chemoradiotherapy for patients with ESCC.


Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 138
Author(s):  
Leonard Simon Brandenburg ◽  
Marc Christian Metzger ◽  
Philipp Poxleitner ◽  
Pit Jacob Voss ◽  
Kirstin Vach ◽  
...  

There is no consensus on the effect of red blood cell (RBC) transfusions on patients with oral squamous cell carcinoma (OSCC). The aim of this study was to investigate the association between RBC administration and the occurrence of distant metastases (M+) after surgical treatment of OSCC. All medical records of patients who underwent primary surgery for OSCC in our department (2003–2019) were analyzed retrospectively (n = 609). Chi and Cox regression models were used to analyze the influence of transfusion on the development of M+, and survival rates. Kaplan–Meier curves were used for graphical presentation. A multitude of patient-specific factors showed a statistical impact in univariate analysis (transfusion, age, gender, diabetes, pT, pN, L, V, Pn, G, UICC, adjuvant therapy, free microvascular transplant, preoperative hemoglobin level). Transfusion status and pN stage were the only variables that showed a significant correlation to M+ in the multivariate Cox model. The hazard ratios for the occurrence of M+ were 2.42 for RBC transfusions and 2.99 for pN+. Administration of RBC transfusions was identified as a significant prognostic parameter for the occurrence of distant metastases after surgical treatment of OSCC. Hence, the administration of RBC transfusions should be considered carefully in the perioperative management.


2021 ◽  
Vol 8 ◽  
Author(s):  
Hui Zhao ◽  
Shengnan Zhang ◽  
Jinji Ma ◽  
Xiaodong Sun

Objective: We aimed to analyze the significance of oral hygiene in patients with squamous cell carcinoma of the lower gingiva.Methods: Oral hygiene was assessed using a questionnaire by calculating the oral health (OH) score and the dental care (DC) score. The association of oral hygiene with clinical pathologic variables, disease free survival (DFS), and overall survival (OS) was analyzed.Results: Four out of 53 non-smokers and 19 out of 90 current or former smokers had an OH score of 6 (statistically significant difference, p = 0.036). Fifteen out of 63 patients with a T3/T4 tumor and 8 out of 80 patients with a T1/T2 tumor had an OH score of 6 (statistically significant difference, p = 0.026). Similar statistically significant findings were noted with respect to the DC scores, smoking status, and tumor stage. Among patients with an OH score of 0–5, the 5-year DFS and OS rates were 55 and 50%, respectively, and among patients with an OH score &gt;5, they were 46 and 43%, respectively (both differences statistically significant, p &lt; 0.05). Among patients with a DC score of 0–2, the 5-year DFS and OS rates were 69 and 51%, respectively and among patients with a DC score &gt;2, they were 50 and 47%, respectively (both differences statistically significant, p &lt; 0.05). Cox model confirmed OH and DC scores as independent factors affecting the DFS and OS.Conclusion: Poor oral hygiene was associated with decreased DFS and OS.


2020 ◽  
Author(s):  
Hesan Luo ◽  
Shao-Fu Huang ◽  
Hong-Yao Xu ◽  
Xu-Yuan Li ◽  
Sheng-Xi Wu ◽  
...  

Abstract Purpose To develop and validate a nomogram model to predict complete response (CR) after concurrent chemoradiotherapy (CCRT) in esophageal squamous cell carcinoma (ESCC) patients using pretreatment CT radiomic features. Methods Data of patients diagnosed as ESCC and treated with CCRT in Shantou Central Hospital during the period from January 2013 to December 2015 were retrospectively collected. Eligible patients were included in this study and randomize divided into a training set and a validation set after successive screening. The least absolute shrinkage and selection operator (LASSO) with logistic regression to select radiomics features calculating Rad-score in the training set. The logistic regression analysis was performed to identify the predictive clinical factors for developing a nomogram model. The area under the receiver operating characteristic curves (AUC) was used to assess the performance of the predictive nomogram model and decision curve was used to analyze the impact of the nomogram model on clinical treatment decisions. Results A total of 226 patients were included and randomly divided into two groups, 160 patients in training set and 66 patients in validation set. After LASSO analysis, seven radiomics features were screened out to develop a radiomics signature Rad-score. The AUCs of Rad-score was 0.812 (95%CI: 0.742–0.869) in the training set and 0.744 (95%CI: 0.632–0.851) in the validation set. Multivariate analysis showed that Rad-score and clinical staging were independent predictors of CR status, with P values of 0.035 and 0.023, respectively. A nomogram model incorporating Rad-socre and clinical staging was developed and validated, with an AUC of 0.844 (95%CI: 0.779–0.897) in the training set and 0.807 (95༅CI: 0.691–0.894) in the validation set༎Delong test showed that the nomogram model was significantly superior to the clinical staging, with P < 0.001 in the training set and P = 0.026 in the validation set. The decision curve showed that the nomogram model was superior to the clinical staging when the risk threshold was greater than 25%. Conclusion We developed and validated a nomogram model for predicting CR status of ESCC patients after CCRT. The nomogram model was combined radiomics signature Rad-score and clinical staging. This model provided us with an economical and simple method for evaluating the response of chemoradiotherapy for patients with ESCC.


2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Suzana Stojanovic-Rundic ◽  
Mladen Marinkovic ◽  
Milena Cavic ◽  
Vesna Plesinac Karapandzic ◽  
Dusica Gavrilovic ◽  
...  

Abstract Background Historically, the treatment of choice for anal cancer had been abdominoperineal resection (APR). Radical radiotherapy with concurrent 5-fluorouracil plus mitomycin C chemotherapy was later established as standard therapy, although with a failure rate of 20–30%. The aim of this study was to evaluate the outcomes after radical chemoradiotherapy (CRT), prognostic and predictive factors and patterns of failure. Patients and methods This study included 47 patients treated with radical CRT for patohistologicaly confirmed anal squamous cell carcinoma. Analysed haematological parameters included: neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and haemoglobin level. The final logistic regression model included treatment break period. Tumour response was assessed at 24 weeks from CRT completion. Follow-up was performed every 3 months during the first two years, and every 6 months thereafter. Results A complete clinical response (CR) was detected in 30 patients (63.8%). Patients who did not achieve a 6-months CR and those who had a CR after 6 months but then relapsed were referred to surgical treatment. With combined CRT and surgical salvage treatment the CR rate was 80.9%. Patients with CR after 6 months had significantly longer disease-free survival (DFS), progression-free survival (PFS), and overall survival (OS). A significant effect on the 6-month response was confirmed for PLR (p = 0.03). Conclusions Important prognostic factors associated with CR were baseline haemoglobin level and period of treatment interruptions. Potential haematological prognostic factors could be PLR and NLR, which can be routinely determined by low-cost and minimally invasive methods.


2021 ◽  
Vol 11 ◽  
Author(s):  
Peng Li ◽  
Qigen Fang ◽  
Yanjie Yang ◽  
Defeng Chen ◽  
Wei Du ◽  
...  

Objectives: To analyze the significance of the number of positive lymph nodes in oral squamous cell carcinoma (SCC) stratified by p16.Methods: A total of 674 patients were retrospectively enrolled and divided into 4 groups based on their number of positive lymph nodes (0 vs. 1–2 vs. 3–4 vs. ≥5). The Kaplan-Meier method was used to calculate the disease-free survival (DFS) and disease-specific survival (DSS) rates. Cox model was used to evaluate the independent risk factor.Results: p16 showed positivity in 85 patients with a rate of 12.6%. In patients with p16 negativity, the 5-year DFS rates were 52%, 39%, and 21% in patients with 0, 1–2, and 3–4 positive lymph nodes, respectively, in patients with ≥5 positive lymph nodes, all patients developed recurrence within 2 years after operation, the difference was significant; the 5-year DSS rates were 60, 38, and 18% in patients with 0, 1–2, and 3–4 positive lymph nodes, respectively, in patients with ≥5 positive lymph nodes, all patients died within 4-years after operation. The difference was significant. In p16 positivity patients, the 3-year DFS rates were 41% and 17% in patients with 0–2 and ≥3 positive lymph nodes, respectively, the difference was significant; the 3-year DSS rates were 84 and 46% in patients with 0–2 and ≥3 positive lymph nodes, the difference was significant.Conclusions: The number of positive lymph nodes is significantly associated with the survival in oral SCC, its survival effect is not affected by p16 status.


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