MicroRNA-182-5p and microRNA-205-5p as potential biomarkers for prognostic stratification of p16-positive oropharyngeal squamous cell carcinoma

2021 ◽  
pp. 1-17
Author(s):  
Bernhard G. Weiss ◽  
Mahalia Zoe Anczykowski ◽  
Friedrich Ihler ◽  
Mattis Bertlich ◽  
Jennifer L. Spiegel ◽  
...  
Keyword(s):  
Squamous Cell ◽  
Progression Free Survival ◽  
Clinicopathological Characteristics ◽  
Local Control Rate ◽  
Quantitative Real Time Pcr ◽  
Free Survival ◽  
Prognostic Groups ◽  
Fresh Frozen ◽  
Prognostic Stratification ◽  
Prognostic Implications

BACKGROUND: MicroRNAs constitute promising biomarkers. OBJECTIVE: The aim was to investigate diagnostic and prognostic implications of miR-182-5p and miR-205-5p in p16-positive and p16-negative oropharyngeal squamous cell carcinomas (OPSCCs). METHODS: Expression of miR-182-5p, miR-205-5p were determined via quantitative real-time-PCR in fresh frozen tissues of 26 p16-positive, 19 p16-negative OPSCCs and 18 HPV-negative oropharyngeal controls. Associations between miRNA-expression, clinicopathological characteristics and prognosis were analyzed. RESULTS: Higher miR-182-5p expression was associated with significant inferior disease-specific survival for p16-positive OPSCCs (HR = 1.98E+09, 95% CI 0–Inf; P= 0.028) and a similar trend was observed for p16-negative OPSCCs (HR = 1.56E+09, 95% CI 0–Inf; P= 0.051). Higher miR-205-5p expression was associated with an inferior progression-free survival (HR = 4.62, 95% CI 0.98–21.83; P= 0.034) and local control rate (HR = 2.18E+09, 95% CI 0–Inf; P= 0.048) for p16-positive OPSCCs. CONCLUSIONS: Results indicate that miR-182-5p and miR-205-5p can further stratify patients with p16-positive OPSCC into prognostic groups.

Immunophenotyping of ampullary carcinomata allows for stratification of treatment specific subgroups

2015 ◽  
Vol 69 (5) ◽  
pp. 431-439 ◽  
Author(s):  
Joyce M Leo ◽  
Steve E Kalloger ◽  
Renata D Peixoto ◽  
Nadia S Gale ◽  
Douglas L Webber ◽  
...  
Keyword(s):  
Prognostic Significance ◽  
Progression Free Survival ◽  
Clinicopathological Characteristics ◽  
Ductal Adenocarcinoma ◽  
Histological Subtype ◽  
Regional Lymph Nodes ◽  
Free Survival ◽  
Treatment Regimens ◽  
Molecular Differentiation ◽  
Prognostic Groups

BackgroundAmpullary carcinomata (AC) can be separated into intestinal (IT) or pancreatobiliary (PB) subtypes. Although morphological, immunohistochemical and molecular differentiation of IT and PB have been well documented; the prognostic significance of histological subtype and whether patients with either subtype benefit from differential chemotherapeutic regimens remains unclear.MethodsAs part of a larger cohort study, patients who underwent resection for AC or pancreatic ductal adenocarcinoma (PDAC) were retrospectively identified. Clinicopathological covariates and outcome were obtained and MUC1, MUC2, CDX2 and CK20 were assessed with immunohistochemistry.ResultsOf 99 ACs, the resultant immunophenotypes indicated 48% and 22% were IT and PB, respectively. Thirty (30%) cases were quadruple negative (QN). Within the PDAC cohort (N=257), the most prevalent immunophenotype was QN (53%). Subsequently, all QN ACs were classified as PB immunohistochemically yielding 47.5% and 52.5% classified as IT and PB, respectively. Involved regional lymph nodes and elevated T-stage were significantly associated with PB compared with IT AC (p=0.0032 and 0.0396, respectively). Progression-free survival revealed inferior survival for PB versus IT AC (p=0.0156).ConclusionsAC can be classified into prognostic groups with unique clinicopathological characteristics using immunohistochemistry. Immunophenotypical similarity of PB and PDAC suggests that treatment regimens similar to those used in PDAC should be explored.

scholarly journals Chemoradiotherapy as Definitive Treatment for Elderly Patients with Head and Neck Cancer

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Jens Müller von der Grün ◽  
Daniel Martin ◽  
Timo Stöver ◽  
Shahram Ghanaati ◽  
Claus Rödel ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Head And Neck ◽  
Progression Free Survival ◽  
Clinicopathological Characteristics ◽  
Local Control Rate ◽  
Definitive Treatment ◽  
Free Survival ◽  
Chemotherapy Dose ◽  
Rising Incidence

Background. With the aging population and a rising incidence of squamous cell carcinoma of the head and neck (SCCHN), there is an emerging need for developing strategies to treat elderly patients. Patients and Methods. We retrospectively analyzed 158 patients treated with definitive, concurrent chemoradiotherapy (CRT) for SCCHN. Clinicopathological characteristics, acute toxicities, and oncological outcomes were compared between patients younger and older than (or of age equal to) 65, 70, and 75 years. Results. RT dose, chemotherapy regimen, and total chemotherapy dose were balanced between the groups. After a median follow-up of 29 months, overall survival (OS), progression-free survival (PFS), local control rate, and distant metastasis-free survival stratified by age of ≥65, ≥70, or ≥75 years revealed no differences. The rate of acute toxicities was also not higher for older patients. Worse ECOG performance score (ECOG 2-3) was associated with impaired OS (p=0.004) and PFS (p=0.048). Conclusion. Definitive treatment with CRT for SCCHN is feasible and effective; even in advanced age treatment decisions should be made according to general condition and comorbidity, rather than calendar age alone.

Hyperfractionated Radiation Therapy With or Without Concurrent Low-Dose Daily Cisplatin in Locally Advanced Squamous Cell Carcinoma of the Head and Neck: A Prospective Randomized Trial

2000 ◽  
Vol 18 (7) ◽  
pp. 1458-1464 ◽  
Author(s):  
Branislav Jeremic ◽  
Yuta Shibamoto ◽  
Biljana Milicic ◽  
Nebojsa Nikolic ◽  
Aleksandar Dagovic ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Radiation Therapy ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Low Dose ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
High Grade ◽  
Free Survival

PURPOSE: To investigate whether the addition of cisplatin (CDDP) to hyperfractionation (Hfx) radiation therapy (RT) offers an advantage over the same Hfx RT given alone in locally advanced (stages III and IV) squamous cell carcinoma of the head and neck. PATIENTS AND METHODS: One hundred thirty patients were randomized to receive either Hfx RT alone to a tumor dose of 77 Gy in 70 fractions in 35 treatment days over 7 weeks (group I, n = 65) or the same Hfx RT and concurrent low-dose (6 mg/m2) daily CDDP (group II, n = 65). RESULTS: Hfx RT/chemotherapy offered significantly higher survival rates than Hfx RT alone (68% v 49% at 2 years and 46% v 25% at 5 years; P = .0075). It also offered higher progression-free survival (46% v 25% at 5 years; P = .0068), higher locoregional progression-free survival (LRPFS) (50% v 36% at 5 years; P = .041), and higher distant metastasis-free survival (DMFS) (86% v 57% at 5 years; P = .0013). However, there was no difference between the two treatment groups in the incidence of either acute or late high-grade RT-induced toxicity. Hematologic high-grade toxicity was more frequent in group II patients. CONCLUSION: As compared with Hfx RT alone, Hfx RT and concurrent low-dose daily CDDP offered a survival advantage, as well as improved LRPFS and DMFS.

scholarly journals P04.16 TP53 mutations in codon 273 is predictive of overall survival in astrocytoma patients

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii32-iii32
Author(s):  
H Noor ◽  
R Rapkins ◽  
K McDonald
Keyword(s):  
Overall Survival ◽  
Tp53 Mutation ◽  
Progression Free Survival ◽  
Low Grade Glioma ◽  
Low Grade ◽  
Wild Type ◽  
Mutation Status ◽  
Free Survival ◽  
Tp53 Mutations ◽  
Fresh Frozen

Abstract BACKGROUND Tumour Protein 53 (TP53) is a tumour suppressor gene that is mutated in at least 50% of human malignancies. The prevalence of TP53 mutation is much higher in astrocytomas with reports of up to 75% TP53 mutant cases. Rare cases of TP53 mutation also exist in oligodendroglial tumours (10–13%). P53 pathway is therefore an important factor in low-grade glioma tumorigenesis. Although the prognostic impact of TP53 mutations has been studied previously, no concrete concordance were reached between the studies. In this study, we investigated the prognostic effects of TP53 mutation in astrocytoma and oligodendroglioma. MATERIAL AND METHODS A cohort of 65 matched primary and recurrent fresh frozen tumours were sequenced to identify hotspot exons of TP53 mutation. Exons 1 to 10 were sequenced and pathogenic mutations were mostly predominant between Exons 4 and 8. The cohort was further expanded with 78 low grade glioma fresh frozen tissues and hotspot exons were sequenced. Selecting only the primary tumour from 65 matched tumours, a total of 50 Astrocytoma cases and 51 oligodendroglioma cases were analysed for prognostic effects of TP53. Only pathogenic TP53 mutations confirmed through COSMIC and NCBI databases were included in the over survival and progression-free survival analysis. RESULTS 62% (31/50) of astrocytomas and 16% (8/51) of oligodendrogliomas harboured pathogenic TP53 mutations. Pathogenic hotspot mutations in codon 273 (c.817 C>T and c.818 G>A) was prevalent in astrocytoma with 58% (18/31) of tumours with these mutations. TP53 mutation status was maintained between primary and recurrent tumours in 93% of cases. In astrocytoma, overall survival of TP53 mutant patients was longer compared to TP53 wild-type patients (p<0.01) but was not significant after adjusting for age, gender, grade and IDH1 mutation status. In contrast, astrocytoma patients with specific TP53 mutation in codon 273 showed significantly better survival compared to other TP53 mutant and TP53 wild-type patients combined (p<0.01) in our multivariate analysis. Time to first recurrence (progression-free survival) of TP53 mutant patients was significantly longer than TP53 wild-type patients (p<0.01) after adjustments were made, while TP53 mutation in codon 273 was not prognostic for progression-free survival. In oligodendroglioma patients, TP53 mutations did not significantly affect overall survival and progression-free survival. CONCLUSION In agreement with others, TP53 mutation is more prevalent in Astrocytoma and mutations in codon 273 are significantly associated with longer survival.

scholarly journals MRN (MRE11-RAD50-NBS1) Complex in Human Cancer and Prognostic Implications in Colorectal Cancer

2019 ◽  
Vol 20 (4) ◽  
pp. 816 ◽  
Author(s):  
Yiling Situ ◽  
Liping Chung ◽  
Cheok Lee ◽  
Vincent Ho
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Human Cancer ◽  
Progression Free Survival ◽  
Current Evidence ◽  
Treatment Target ◽  
Free Survival ◽  
Mrn Complex ◽  
Prognostic Implications ◽  
Relationship Of

The MRE11-RAD50-NBS1 (MRN) complex has been studied in multiple cancers. The identification of MRN complex mutations in mismatch repair (MMR)-defective cancers has sparked interest in its role in colorectal cancer (CRC). To date, there is evidence indicating a relationship of MRN expression with reduced progression-free survival, although the significance of the MRN complex in the clinical setting remains controversial. In this review, we present an overview of the function of the MRN complex, its role in cancer progression, and current evidence in colorectal cancer. The evidence indicates that the MRN complex has potential utilisation as a biomarker and as a putative treatment target to improve outcomes of colorectal cancer.

scholarly journals Induction Chemotherapy Followed by Cetuximab Radiotherapy Is Not Superior to Concurrent Chemoradiotherapy for Head and Neck Carcinomas: Results of the GORTEC 2007-02 Phase III Randomized Trial

2018 ◽  
Vol 36 (31) ◽  
pp. 3077-3083 ◽  
Author(s):  
Lionnel Geoffrois ◽  
Laurent Martin ◽  
Dominique De Raucourt ◽  
Xu Shan Sun ◽  
Yungan Tao ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Induction Chemotherapy ◽  
Squamous Cell ◽  
Concurrent Chemoradiotherapy ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Phase Iii ◽  
Free Survival

Purpose Both concurrent chemoradiotherapy (CT-RT) and cetuximab radiotherapy (cetux-RT) have been established as the standard of care for the treatment of locally advanced squamous cell carcinoma of the head and neck. It was not known whether the addition of induction chemotherapy before cetux-RT could improve outcomes compared with standard of care CT-RT. Patients and Methods The current trial was restricted to patients with nonmetastatic N2b, N2c, or N3 squamous cell carcinoma of the head and neck and fit for taxotere, cisplatin, fluorouracil (TPF). Patients were randomly assigned to receive three cycles of TPF followed by cetux-RT versus concurrent carboplatin fluorouracil and RT as recommended in National Comprehensive Cancer Network guidelines. The trial was powered to detect a hazard ratio (HR) of 0.66 in favor of TPF plus cetux-RT for progression-free survival at 2 years. The inclusion of 180 patients per arm was needed to achieve 80% power at a two-sided significance level of .05. Results Between 2009 and 2013, 370 patients were included. All patients and tumors characteristics were well balanced between arms. There were more cases of grade 3 and 4 neutropenia in the induction arm, and the induction TPF was associated with 6.6% treatment-related deaths. With a median follow-up of 2.8 years, 2-year progression-free survival was not different between both arms (CT-RT, 0.38 v TPF + cetux-RT, 0.36; HR, 0.93 [95% CI, 0.73 to 1.20]; P = .58). HR was 0.98 (95% CI, 0.74 to 1.3; P = .90) for locoregional control and 1.12 (95% CI, 0.86 to 1.46; P = .39) for overall survival. These effects were observed regardless of p16 status. The rate of distant metastases was lower in the TPF arm (HR, 0.54 [95% CI, 0.30 to 0.99]; P = .05). Conclusion Induction TPF followed by cetux-RT did not improve outcomes compared with CT-RT in a population of patients with advanced cervical lymphadenopathy.

scholarly journals Prognostic Analysis of Preoperative Inflammatory Biomarkers in Patients With Laryngeal Squamous Cell Carcinoma

2019 ◽  
Vol 99 (6) ◽  
pp. 371-378 ◽  
Author(s):  
Youfang Xun ◽  
Maohua Wang ◽  
Haiyong Sun ◽  
Shujun Shi ◽  
Bing Guan ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Progression Free Survival ◽  
Inflammatory Biomarkers ◽  
Distribution Width ◽  
Free Survival ◽  
Lymphocyte Ratio

Objective: The purpose of this study was to demonstrate the prognostic role of inflammatory biomarkers in patients with laryngeal squamous cell carcinoma. Methods: For this study, we enrolled 151 patients who had undergone surgery for laryngeal squamous cell carcinoma. We assessed the preoperative neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), monocyte to lymphocyte ratio (MLR), mean platelet volume, red cell distribution width, and alkaline phosphatase. The chi-square test, Kaplan-Meier survival analysis, and Cox proportional hazards model were conducted on overall survival, progression-free survival, locoregional recurrence-free survival, and distant metastasis-free survival of patients with laryngeal squamous cell carcinoma. Results: Both Kaplan-Meier analysis and univariate analysis showed significant prognostic differences with age, laryngectomy methods, Tumor Node Metastasis (TNM) staging, tumor location, NLR, PLR, MLR, and mean platelet volume. Multivariate analysis indicated that NLR (overall survival: hazard ratio [HR] = 3.02, 95% confidence interval [CI]: 1.28-7.10, P = .011), PLR (overall survival: HR = 0.33, 95% CI: 0.14-0.78, P = .011; progression-free survival: HR = 0.016,95% CI: 0.10-0.79, P = .016), and MLR (overall survival: HR = 0.29, 95% CI: 0.11-0.76, P = .012) were independent prognostic factors for 5-year survival. However, red cell distribution width and alkaline phosphatase had no significant difference in overall survival and progression-free survival. Conclusions: Preoperative high NLR, PLR, and MLR were associated with poor prognosis. They were found to be effective and reliable inflammatory biomarkers for patients with laryngeal squamous cell carcinoma.

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