Invasive squamous cell carcinoma of the vulva: defining low and high risk groups for recurrence

1991 ◽  
Vol 1 (1) ◽  
pp. 25-31 ◽  
Author(s):  
Peter S. C. Bryson ◽  
A. J. Dembo ◽  
T. J. Colgan ◽  
G. M. Thomas ◽  
G. Deboer ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
High Risk ◽  
Risk Group ◽  
High Risk Group ◽  
Tumor Thickness ◽  
Low Risk ◽  
Stage Ii ◽  
Invasive Squamous Cell Carcinoma ◽  
Cure Rates ◽  
Free Rate

One hundred and ten patients with invasive squamous cell carcinoma of the vulva, treated primarily with surgery at Toronto General Hospital between 1970 and 1981, were studied to determine recurrence patterns and factors predictive of relapse and survival. The overall and cause-specific actuarial 5-year survival rates were 63 and 73%, respectively. Eleven factors were studied for their prognostic value. Only Stage and, within Stage II, tumor thickness and nodal status, were independently prognostic. Six relapses occured in 8 Stage II patients who had both positive nodes and tumor thickness > 5 mm (Unfavorable Stage II), compared to 0/17 with neither or just one factor present (favorable Stage II,P= 0.0002). These results were used to define a low-risk group (Stages I and favorable II) and a high-risk group (Stages III, IV and unfavorable II). In the low-risk group, 6/69 relapsed and the 10-year actuarial relapse-free rate was 88%. This was significantly different from the high-risk group, where 24/32 relapsed (P< 10-6) and the 10-year relapse-free rate was only 11% (P< 0.00005). The recognition of these two prognostic groups brings the therapeutic challenges in vulvar cancer into clearer focus. In the low-risk group there is a need to reduce surgical morbidity without compromising cure rates. In the high-risk group, locoregional control rates must be improved in order to improve cure rates. As 27 of the 30 relapses in the high-risk group were confined to the vulva or groin, adjunctive radiotherapy might improve cure rates if used in these patients.

A Four-gene Autophagy-related Prognostic Signature and Its Association With Immune Landscape in Lung Squamous Cell Carcinoma

2020 ◽  
Author(s):  
Lumeng Luo ◽  
Minghe Lv ◽  
Xuan Li ◽  
Tiankui Qiao ◽  
Kuaile Zhao ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
High Risk ◽  
Cell Carcinoma ◽  
Risk Score ◽  
Squamous Cell ◽  
Immune Suppression ◽  
Risk Group ◽  
Lung Squamous Cell Carcinoma ◽  
High Risk Group ◽  
Low Risk

Abstract Background: Recent advances in immune checkpoint inhibitors (ICIs) have dramatically changed the therapeutic strategy against lung squamous cell carcinoma (LUSC). In the era of immunotherapy, effective biomarkers to better predict outcomes and inform treatment decisions for patients diagnosed with LUSC are urgently needed. We hypothesized that immune contexture of LUSC is potentially dictated by tumor intrinsic events, such as autophagy. Thus, we attempted to construct an autophagy-related risk signature and examine its prediction value for immune phenotype in LUSC.Method: The expression profile of LUSC was obtained from the cancer genome atlas (TCGA) database and the profile of autophagy-related genes (ARGs) was extracted. The survival‑related ARGs (sARGs) was screened out through survival analyses. Random forest was performed to select the sARGs and construct a prognostic risk signature based on these sARGs. The signature was further validated by receiver operating characteristic (ROC) analysis and Cox regression. GEO dataset was used as an independent testing dataset. Patients were divided into high-risk and low-risk group based on the risk score. Then, gene set enrichment analysis (GSEA) was conducted between the two groups. The Single-Sample GSEA (ssGSEA) was introduced to quantify the relative infiltration of immune cells. The correlations between risk score and several main immune checkpoints were examined. And the ESTIMATE algorithm was used to calculate the estimate/immune/stromal scores of the LUSC. Results: Four ARGs (CFLAR, RGS19, PINK1 and CTSD) with the most significant prognostic values were enrolled to construct the risk signature. Patients in high-risk group had better prognosis than the low-risk group (P < 0.0001 in TCGA; P < 0.01 in GEO) and considered as an independent prognosis factor. We also found that high-risk group indicated an immune-suppression status and had higher levels of infiltrating regulatory T cells and macrophages, which are correlated with worse outcome. Besides, risk score showed a significantly positive correlation with the expression of PD-1 and CTLA4, as well as estimate score and immune score.Conclusion: This study established a novel autophagy-related four-gene prognostic risk signature, and the autophagy-related scores are associated with immune landscape of LUSC, with higher score indicating a stronger immune-suppression status.

scholarly journals Chemo-resistant gestational trophoblastic neoplasia: a review of cases at a tertiary cancer centre

2019 ◽  
Vol 8 (4) ◽  
pp. 1620
Author(s):  
Sharayu R. Mirji ◽  
Shilpa M. Patel ◽  
Ruchi S. Arora ◽  
Ava D. Desai ◽  
Meeta H. Mankad ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Group ◽  
Complete Response ◽  
High Risk Group ◽  
Low Risk ◽  
Gestational Trophoblastic Neoplasia ◽  
First Line ◽  
Β Hcg ◽  
Cure Rates ◽  
Line Chemotherapy

Background: Gestational trophoblastic neoplasia (GTN) was earlier a dreaded malignancy with high mortality rates. GTN is now considered to be one of the most curable solid tumours in women with cure rates greater than 90% even in the presence of metastases. Despite the high chemo sensitivity, treatment failure or drug resistance has been described in both groups.Methods: In this study, available records of GTN cases over 6 years were reviewed with emphasis on those who were resistant to the first line of chemotherapy. Of these, 37(34.58%) were resistant to the first line of chemotherapy. These cases were studied with respect to age, parity, antecedent pregnancy, interval from antecedent pregnancy, pretreatment β hCG, risk score and presence of metastases. The data was analyzed in order to find any risk factors associated with chemo-resistance.Results: Total number of cases of GTN was 107. Out of these 107 cases, 63 (58.88%) were low risk and 44 (41.12%) were high risk according to FIGO scoring system. Complete response was achieved with first line chemotherapy in 70 (65.42%) patients. The remaining 37 (34.57%) were resistant to first line chemotherapy. In the low risk group, 30 (47.62%) cases, and in the high-risk group, 7(15.91%) were resistant to first line of chemotherapy.Conclusions: Despite the high chemo sensitivity of GTN, resistance to first line chemotherapy may be encountered in up to 40% of cases.  It is important to identify the patients who are at risk to develop resistance, early identification of resistance and change of chemotherapy so as to minimize the exposure of these patients to ineffective chemotherapy.

Guanylyl cyclase C (GCC) expression in lymph nodes (LNs) as a determinant of recurrence in stage II colon cancer (CC) patients (pts).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3639-3639
Author(s):  
Daniel J. Sargent ◽  
Qian Shi ◽  
Sharlene Gill ◽  
Christophe Louvet ◽  
Richard Bernard Everson ◽  
...  
Keyword(s):  
High Risk ◽  
Cox Regression ◽  
Risk Group ◽  
Tumor Grade ◽  
High Risk Group ◽  
Low Risk ◽  
Stage Ii ◽  
Risk Class ◽  
Tissue Procurement ◽  
The Relationship

3639 Background: The first phase of the multi-center prospectively specified retrospective study Validating Indicators To Associate Recurrence (VITAR), assessing the relationship between GCC gene expression in formalin fixed (FFPE) LNs and time to recurrence (TTR) in stage II CC pts not treated with adjuvant chemotherapy (Sargent, Annals Surg Onc 2011), showed promising initial results. Here we report a validation set of 463 new stage II CC pts. Methods: GCC mRNA was quantified by RT-qPCR using FFPE LNs from untreated T3N0 CC pts diagnosed from 1999-2008 with at least 12 LNs examined , blinded to clinical outcomes. Patients were classified by GCC LN ratio (LNR) (high risk: LNR > 0.1; low risk: LNR ≤ 0.1), with LNR defined as ratio of GCC positive to GCC informative LNs. Cox regression models tested the relationship between GCC and the primary endpoint of TTR, adjusted for age, tumor grade, number of LN examined pathologically, and lymphovascular invasion. Mismatch repair (MMR) status was also assessed. All primary analyses and cut-points were pre-specified. Results: 46pts (10%) recurred (rec), median follow-up was 65 months, median LNs examined was 20, and 42% (195/463) were classified high risk. Overall, TTR was not significantly associated with binary GCC LNR risk class (HR=1.47, p=.208) or DFS (HR= 1.39, p=.097). One site’s (n=97) tissue grossing method precluded appropriate LN assessment with existing GCC qualification methods. Excluding this site resulted in a TTR HR=1.91, p=0.051 (multivariate). In a post-hocanalysis excluding this site and using a 3-level GCC risk group of high (LNR > 0.20), intermediate (0.10 < LNR < 0.20) and low (LNR < 0.10), high risk group pts had a 5-yr rec risk of 22% versus 8% in low risk (HR 2.72, p=0.006). MMR status was not significantly associated with TTR (multivariate p=0.30). Conclusions: GCC status is a promising prognostic factor in appropriately staged stage II CC pts not treated with adjuvant therapy independent of traditional histopathology risk factors, but GCC determination must be performed with methodology adapted to the tissue procurement and fixation technique. Outcome associations were strengthened when considering a 3-level GCC categorization.

Identification of a novel CpG methylation signature to predict prognosis in lung squamous cell carcinoma

2020 ◽  
pp. 1-11
Author(s):  
Nan Lee ◽  
Xuelian Xia ◽  
Hui Meng ◽  
Weiliang Zhu ◽  
Xiankai Wang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Regression Analysis ◽  
High Risk ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Risk Group ◽  
Lung Squamous Cell Carcinoma ◽  
High Risk Group ◽  
Low Risk ◽  
Risk Patients

BACKGROUND: DNA methylation plays a vital role in modulating genomic function and warrants evaluation as a biomarker for the diagnosis and treatment of lung squamous cell carcinoma (LUSC). OBJECTIVE: In this study, we aimed to identify effective potential biomarkers for predicting prognosis and drug sensitivity in LUSC. METHODS: A univariate Cox proportional hazards regression analysis, a random survival forests-variable hunting (RSFVH) algorithm, and a multivariate Cox regression analysis were adopted to analyze the methylation profile of patients with LUSC included in public databases: The Cancer Genome Atlas (TCGA), and the Gene Expression Omnibus (GEO). RESULTS: A methylated region consisting of 3 sites (cg06675147, cg07064331, cg20429172) was selected. Patients were divided into a high-risk group and a low-risk group in the training dataset. High-risk patients had shorter overall survival (OS) (hazard ratio [HR]: 2.72, 95% confidence interval [CI]: 1.82–4.07, P< 0.001) compared with low-risk patients. The accuracy of the prognostic signature was validated in the test and validation cohorts (TCGA, n= 94; GSE56044, n= 23). Gene set variation analysis (GSVA) showed that activity in the cell cycle/mitotic, ERBB, and ERK/MAPK pathways was higher in the high-risk compared with the low-risk group, which may lead to differences in OS.Interestingly, we observed that patients in the high-risk group were more sensitive to gemcitabine and docetaxel than the low-risk group, which is consistent with results of the GSVA. CONCLUSION: We report novel methylation sites that could be used as powerful tools for predicting risk factors for poorer survival in patients with LUSC.

scholarly journals A Nomogram for the Determination of the Necessity of Concurrent Chemotherapy in Patients With Stage II–IVa Nasopharyngeal Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Kaixuan Yang ◽  
Qian Zhang ◽  
Mengxi Zhang ◽  
Wenji Xie ◽  
Mei Li ◽  
...  
Keyword(s):  
High Risk ◽  
Nasopharyngeal Carcinoma ◽  
Cox Regression ◽  
Risk Group ◽  
Intensity Modulated Radiotherapy ◽  
Concurrent Chemotherapy ◽  
High Risk Group ◽  
Low Risk ◽  
Stage Ii ◽  
Risk Recurrence

BackgroundThe efficiency of concurrent chemotherapy (CC) remains controversial for stage II–IVa nasopharyngeal carcinoma (NPC) patients treated with induction chemotherapy (IC) followed by intensity-modulated radiotherapy (IMRT). Therefore, we aimed to propose a nomogram to identify patients who would benefit from CC.MethodsA total of 434 NPC patients (stage II–IVa) treated with IC followed by IMRT between January 2010 and December 2015 were included. There were 808 dosimetric parameters extracted by the in-house script for each patient. A dosimetric signature was developed with the least absolute shrinkage and selection operator algorithm. A nomogram was built by incorporating clinical factors and dosimetric signature using Cox regression to predict recurrence-free survival (RFS). The C-index was used to evaluate the performance of the nomogram. The patients were stratified into low- and high-risk recurrence according to the optimal cutoff of risk score.ResultsThe nomogram incorporating age, TNM stage, and dosimetric signature yielded a C-index of 0.719 (95% confidence interval, 0.658–0.78). In the low-risk group, CC was associated with a 9.4% increase of 5-year locoregional RFS and an 8.8% increase of 5-year overall survival (OS), whereas it was not significantly associated with an improvement of locoregional RFS (LRFS) and OS in the high-risk group. However, in the high-risk group, patients could benefit from adjuvant chemotherapy (AC) by improving 33.6% of the 5-year LRFS.ConclusionsThe nomogram performed an individualized risk quantification of RFS in patients with stage II–IVa NPC treated with IC followed by IMRT. Patients with low risk could benefit from CC, whereas patients with high risk may require additional AC.

Invasive Squamous Cell Carcinoma of the Skin: Defining a High-Risk Group

2006 ◽  
Vol 13 (7) ◽  
pp. 902-909 ◽  
Author(s):  
John T. Mullen ◽  
Lei Feng ◽  
Yan Xing ◽  
Paul F. Mansfield ◽  
Jeffrey E. Gershenwald ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
High Risk ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Risk Group ◽  
High Risk Group ◽  
Invasive Squamous Cell Carcinoma

scholarly journals Identification of Immune-Related Prognostic Biomarkers Associated with HPV-Positive Head and Neck Squamous Cell Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-23
Author(s):  
Yifei Chen ◽  
Jin Nie ◽  
Xiangsheng Li ◽  
Tao Fan ◽  
Xiaowen Deng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Squamous Cell Carcinoma ◽  
High Risk ◽  
Cell Carcinoma ◽  
Risk Group ◽  
High Risk Group ◽  
Low Risk ◽  
Survival Prognosis ◽  
Scoring Model ◽  
Risk Scoring

Background. As a type of malignant tumor, head and neck squamous cell carcinoma (HNSCC) seriously threatens human health. This study is aimed at constructing a new, reliable prognostic model. Method. The gene expression profile data of HNSCC patients were downloaded from the Gene Expression Omnibus and The Cancer Genome Atlas databases. The immune-related differentially expressed genes (IRDEGs) related to HNSCC were identified. We then used Cox regression analysis and least absolute shrinkage and selection operator (LASSO) analysis to explore IRDEGs related to the HNSCC prognosis and to construct and validate a risk scoring model and used ESTIMATE to evaluate tumor immune infiltration in HNSCC patients. Finally, we validated IGSF5 expression and function in HNSCC cells. Results. A total of 1,195 IRDEGs were found from the GSE65858 dataset. Thirty-one of the 1,195 IRDEGs were associated with the prognosis of HNSCC. Nine key IRDEGs were further selected using the LASSO method, and a risk scoring model was established for predicting the survival of HNSCC patients. According to the risk scoring model, the prognosis of patients in the high-risk group was worse than that of the low-risk group; the high-risk group had significantly higher immune scores than the low-risk group; and between the high- and low-risk samples, there were significant differences in the proportion of 10 types of cells, including naive cells, plasma cells, and resting CD4+ memory T cells. IGSF5 has low expression in HNSCC, and overexpression of IGSF5 significantly impaired HNSCC cell proliferation. Conclusion. This prognostic risk assessment model can help systematically evaluate the survival prognosis of HNSCC patients and provides a new research direction for the improvement of the survival prognosis of HNSCC patients in clinical practice.

scholarly journals A Ferroptosis-Related Long Non-Coding RNA Signature Predicts Prognosis and Immune Microenvironment for Lung Squamous Cell Carcinoma

2021 ◽  
Author(s):  
Zhiyang Liu ◽  
Zhongcheng Xie ◽  
Chenxi Zhi ◽  
Xiaoyan Lin ◽  
Wentao Ma ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
High Risk ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Prognostic Value ◽  
Risk Group ◽  
Lung Squamous Cell Carcinoma ◽  
High Risk Group ◽  
Low Risk ◽  
Immune Checkpoints

Abstract Background: Ferroptosis-related lncRNAs (FerLncRNAs) were developed to play a significant role in cancer treatment and prognosis. However, the relationship between FerLncRNAs and Lung squamous cell carcinoma (LUSC) remains unclear.Method: Based on ferroptosis-related differentially expressed lncRNAs in LUSC, we established a prognostic 8-lncRNA signature.Results: 8 Ferroptosis-related lncRNAs (LUCAT1, AL161431.1, AL122125.1, AC104248.1, AC016924.1, MIR3945HG, C10orf55 and AP006545.2) had prognostic value for LUSC by multivariate COX analysis (P<0.05), and possessed significant association with patient outcomes. Kaplan–Meier curves showed an obvious difference in OS that the high-risk group patients exhibited poorer survival than the low-risk group patients. The clinical receiver operating characteristic (ROC) curve and decision curve analysis (DCA) revealed that the ferroptosis-related lncRNAs prognostic signature can (FerRLSig) emerged more outstanding performance than clinical features in predicting the prognosis of LUSC. GSEA revealed that the majority of the novel Ferroptosis-related lncRNAs signature-regulated immune responses and the immune system processes were enriched in the high-risk group. 34 immune checkpoints (ICs) were detected significantly different expression between high-risk and low-risk groups.Conclusion: A novel FerRLSig based on 8 Ferroptosis-related lncRNAs provided important prognostic value for LUSC patients and developed new insights about ferroptosis-related immunotherapy targets in clinic.

scholarly journals A Novel Clinical Six-Flavoprotein-Gene Signature Predicts Prognosis in Esophageal Squamous Cell Carcinoma

2019 ◽  
Vol 2019 ◽  
pp. 1-13
Author(s):  
Liu Peng ◽  
Jin-Cheng Guo ◽  
Lin Long ◽  
Feng Pan ◽  
Jian-Mei Zhao ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
High Risk ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Clinical Significance ◽  
Squamous Cell ◽  
Risk Group ◽  
Gene Signature ◽  
High Risk Group ◽  
Low Risk

Flavoproteins and their interacting proteins play important roles in mitochondrial electron transport, fatty acid degradation, and redox regulation. However, their clinical significance and function in esophageal squamous cell carcinoma (ESCC) are little known. Here, using survival analysis and machine learning, we mined 179 patient expression profiles with ESCC in GSE53625 from the Gene Expression Omnibus (GEO) database and constructed a signature consisting of two flavoprotein genes (GPD2 and PYROXD2) and four flavoprotein interacting protein genes (CTTN, GGH, SRC, and SYNJ2BP). Kaplan–Meier analysis revealed the signature was significantly associated with the survival of ESCC patients (mean survival time: 26.77 months in the high-risk group vs. 54.97 months in the low-risk group, P<0.001, n = 179), and time-dependent ROC analysis demonstrated that the six-gene signature had good predictive ability for six-year survival for ESCC (AUC = 0.86, 95% CI: 0.81–0.90). We then validated its prediction performance in an independent set by RT-PCR (mean survival: 15.73 months in the high-risk group vs. 21.1 months in the low-risk group, P=0.032, n = 121). Furthermore, RNAi-mediated knockdown of genes in the flavoprotein signature led to decreased proliferation and migration of ESCC cells. Taken together, CTTN, GGH, GPD2, PYROXD2, SRC, and SYNJ2BP have an important clinical significance for prognosis of ESCC patients, suggesting they are efficient prognostic markers and potential targets for ESCC therapy.

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