Predictors for Adherence to Treatment Strategies in Elderly HNSCC Patients

Finding a cure may be less important than ensuring the quality of life in elderly patients with head and neck squamous cell carcinoma (HNSCC). The aim of this study was to determine predictors for adherence. Clinical and pathological data from patients ≥70 years with HNSCC (initial diagnoses 2004-2018) were investigated retrospectively. Evaluated clinical predictors included biological age (Charlson Comorbidity Index; CCI), patient health (Karnofsky Performance Status; KPS) and therapy data. A total of 1125 patients were included. The median age was 75 years, 33.1% reached CCI ≥6, and 53.7% reached KPS ≤ 70%. In total, 968 patients were adherent, whereas 157 were nonadherent. Nonadherent patients were significantly more often smokers (p = 0.003), frequent drinkers (p = 0.001), had a worse health status (p ≤ 0.001) and a lower biological age (p = 0.003), an advanced T classification and lymph node involvement or UICC stage (each p ≤ 0.001). Approximately 88.0% of the included patients received a curative treatment recommendation. A total of 6.9% discontinued the therapy, and 7.0% refused the therapy. With the increasing complexity of a recommended therapy, adherence decreased. The 5-year overall survival was significantly higher in adherent patients (45.1% versus 19.2%). In contrast to the chronological patient age, biological age is a significant predictor for adherence. The evaluated predictors for nonadherence need to be verified prospectively.

Establishment and Validation of Prognostic Nomograms for Patients With Parotid Gland Adenocarcinoma Not Otherwise Specified: A SEER Analysis From 2004 to 2016

Background: Parotid gland adenocarcinoma not otherwise specified (PANOS) is a rare malignant tumor with limited data on its characteristics and prognosis. This research is aimed at characterizing PANOS and developing prognostic prediction models for patients with PANOS.Methods: Cases from 2004–2016 were selected from the Surveillance, Epidemiology, and End Results (SEER) Program database. Univariate and multivariate Cox regression were applied to ascertain the factors associated with survival. Competing risk analysis and Gray's tests were employed to analyze cancer-specific death. Propensity score matching (1:1) was conducted to reduce the influence of confounding variables.Results: A total of 446 patients with a median age of 66 years were selected, of which 307 were diagnosed with stage III/IV PANOS. The 5-year overall survival (OS) rate of all patients was 51.8%, and the median survival time was 66 months. Surgical treatment clearly improved survival time (p < 0.001). In the subgroup analysis, radiotherapy showed survival benefits in patients with stage III/IV disease (p < 0.001). Multivariate Cox regression analyses showed that age, T classification, N classification, M classification and surgery were independent prognostic indicators for OS; T classification, N classification, M classification and surgery were independent risk factors for cancer-specific survival (CSS). In addition, age was independently associated with other cause-specific death. Based on the results of multivariate analysis, two nomograms were developed and verified by the concordance index (C-index) (0.747 and 0.780 for OS and CSS) and the area under the time-dependent receiver operating characteristic (ROC) curve (0.756, 0.764, and 0.819 regarding for nomograms predicting 3-, 5-, and 10- year OS, respectively and 0.794, 0.789, and 0.806 for CSS, respectively).Conclusions: Our study clearly presents the clinicopathological features and survival analysis of patients with PANOS. In addition, our constructed nomogram prediction models may assist physicians in evaluating the individualized prognosis and deciding on treatment for patients.

Comparison of Long-Term Survival Outcomes of T4a and T4b Colorectal Cancer

BackgroundAlthough T4b is known to have worse oncologic outcomes, it is unclear whether it truly shows a worse prognosis. This study aims to compare the survival differences between T4a and T4b.MethodsPatients who were pathologically diagnosed with T3 and T4 colorectal adenocarcinoma from 2010 to 2014 were included (T3, n = 1822; T4a, n = 424; T4b, n = 67). Overall survival (OS) and cancer-specific survival (CSS) were compared between T4a and T4b using the Kaplan-Meier method and log-rank test.ResultsIn stage II, T4a had better OS and CSS than T4b (5-year OS, 89.5% vs. 72.6%; 5-year CSS, 94.4% vs. 81.7%, all p < 0.05), however, in stage III, there were no significant differences in survivals between groups (all p > 0.05). In multivariable analysis, T classification was not an independent risk factor for OS (p > 0.05). However, for CSS, when respectively compared to T3, T4b (HR 3.53, p < 0.001) showed a relatively higher hazard ratio than T4a (HR 2.27, p < 0.001).ConclusionsT4a showed more favorable OS and CSS than T4b, especially in stage II. Our findings support the current AJCC guidelines, in which T4b is presented as a more advanced stage than T4a.

Adaptor protein XB130 regulates the aggressiveness of cholangiocarcinoma

Cholangiocarcinoma (CCA) is a group of heterogenous malignancies arising from bile duct epithelium with distinct pathological features. Adaptor proteins have implicated in cell proliferation, migration, and invasion of different cancer cells. The objective of this study was to assess whether the adaptor protein XB130 (AFAP1L2) is a critical biological determinant of CCA outcome. XB130 expression levels were investigated in four CCA cell lines compared to an immortalized cholangiocyte cell line by Western blotting. Small interfering (si) RNA-mediated XB130 gene silencing was conducted to evaluate the effects of reduced XB130 expression on cell proliferation, migration, and invasion by MTT, transwell migration and cell invasion assay. The immunohistochemical quantification of XB130 levels were performed in surgically resected formalin-fixed, paraffin-embedded specimens obtained from 151 CCA patients. The relationship between XB130 expression and the clinicopathological parameters of CCA patients were analyzed. Our results showed that XB130 was highly expressed in KKU-213A cell line. Knockdown of XB130 using siRNA significantly decreased the proliferation, migration, and invasion properties of KKU-213A cells through the inhibition of PI3K/Akt pathway, suggesting that XB130 plays an important role in CCA progression. Moreover, elevated XB130 expression levels were positive relationship with lymphovascular space invasion (LVSI), intrahepatic type of CCA, high TNM staging (stage III, IV), high T classification (T3, T4), and lymph node metastasis. We provide the first evidence that the overexpression of XB130 is associated with tumorigenic properties of CCA cells, leading to CCA progression with aggressive clinical outcomes.

Integrating Depth of Invasion in T Classification Improves the Prognostic Performance of the American Joint Committee on Cancer Staging System for Laryngeal Squamous Cell Carcinoma: a Retrospective Multicenter Study

Background: It has been recognized that depth of invasion (DOI) is closely associated with patient survival for all types of cancer. The purpose of this study was to determine the optimal threshold and prognostic value in laryngeal squamous carcinoma (LSCC). Most importantly, we evaluated the prognostic performance of five candidate modified T-classification models in patients with LSCC. Methods: LSCC patients from Harbin Medical University Cancer Hospital and Chinese Academy of Medical Sciences Cancer Hospital were divided into training group (n=412) and validation group (n=147). The primary outcomes were overall survival (OS) and relapse-free survival (RFS), and the effect of DOI on prognosis was analyzed using a multivariable regression model. We identified the optimal model based on its simplicity, goodness of fit and Harrell's consistency index. Further independent testing was performed on the external validation queue. The nomograms was constructed to predict an individual's OS rate at one, three, and five years.Results: In multivariate analysis, we found significant associations between DOI and OS (Depth of Medium-risk invasion HR, 2.631; P <0.001. Depth of high-risk invasion: HR, 5.287; P <0.001) and RFS(Depth of high-risk invasion: HR, 1.937; P =0.016). Model 5 outperformed the American Joint Committee on Cancer (AJCC) staging system based on a low Akaike information criterion score, improvement in the concordance index, and Kaplan-Meier curves.Conclusions: Inclusion of DOI in the current AJCC staging system can improve the differentiation of T classification in LSCC patients.

MiR-1224 Acts as a Prognostic Biomarker and Inhibits the Progression of Gastric Cancer by Targeting SATB1

ObjectiveMiR-1224 has been reported to exhibit abnormal expression in several tumors. However, the expressing pattern and roles of miR-1224 in gastric cancer (GC) remain unclear. Our current research aimed to explore the potential involvement of miR-1224 in the GC progression.Materials and MethodsThe expression of miR-1224 was examined in tissue samples of 128 GC patients and cell lines by RT-PCR. Besides, the associations of miR-1224 expressions with clinicopathologic features and prognosis of GC patients were analyzed. Then, the possible influences of miR-1224 on cell proliferation and cell migration were determined. Afterward, the molecular target of miR-1224 was identified using bioinformatics assays and confirmed experimentally. Finally, RT-PCR and Western blot assays were performed to investigate the effect of the abnormal miR-1224 expression on the EMT and Wnt/β-catenin pathway.ResultsmiR-1224 was lowly expressed in the GC specimens and cell lines due to T classification and TNM stage. Survival assays demonstrated that GC patients with low expressions of miR-1224 possessed poor overall survivals. Moreover, in vitro and in vivo assays revealed that the overexpression of miR-1224 inhibited cell proliferation, migration, and invasion in GC cells. SATB homeobox 1 (SATB1) was verified as a direct target of miR-1224 in GC. Furthermore, β-catenin and c-myc were significantly inhibited in miR-1224-overexpression cells.ConclusionsOur findings highlight the potential of miR-1224 as a therapeutic target and novel biomarker for GC patients

The Role of Regional Disease and Patterns of Treatment Failure in Primary Sinonasal Malignancies

Background The question how to treat the clinically negative neck in sinonasal malignancies is controversial. Objectives To investigate patterns of treatment failure and to assess outcome measures in patients with primary sinonasal malignancies. Methods Retrospective cohort study of patients treated for primary malignant sinonasal malignancies. Results Lymph node (LN) metastases at initial presentation were present in 8 of 152 patients (5.3%). Ipsi- and contralateral LN levels 1 and 2 were identified as nodal basins at risk. We found a 5-year overall survival (OS) of 75.2% and disease free survival of 61.1%. Among patients with cN0 neck, nodal recurrence free survival was not different between patients with and without elective neck treatment ( P = .23). On logistic regression analysis, we found initial T classification as an independent factor for achievement of complete remission (CR) and OS. Conclusions LN metastases at initial presentation are rare and initial T classification was identified as the most important prognostic factor for OS and CR, emphasizing the need for a thorough initial staging of the primary tumor.

Elevating PKM2 Expression Indicates a Biomarker of Poor Prognosis in Patients With Liver Cancer

M2 isoform of pyruvate kinase (PKM2) plays an important role in reprogramming of cell metabolism which is a hall-marker of tumorigenesis. PKM2 expression altering is closely related to cancer metabolism and tumor growth. In the present study, we analyzed the role of PKM2 expression in liver cancer in order to clarify its potential application value in the diagnosis and prognosis of liver cancer patients. In cancerous liver tissues, the PKM2 expression was significantly higher than normal tissues. High PKM2 expressing was related to patient’s age, gender, histological type, grade, stage, T classification and poor survival. Patients with Higher PKM2 expression had a shorter OS (P = 0.0013) and RFS (P = 0.027). ROC and Multivariate Cox analysis showed that high PKM2expression was a risk factor for patients’ poor prognosis. GSEA identified mitotic spindle, PI3K/Akt/mTOR signaling, notch signaling, apoptosis, G2M checkpoint and Wnt/β- Cantenin signaling were enriched with high PKM2 expression phenotype. These findings suggested PKM2 expression has potential as a predictive biomarker for the diagnosis and prognosis of patients with liver cancer.