Impact of concomitant systemic treatments on toxicity and intracerebral response after stereotactic radiotherapy for brain metastases

Cancer shared this article with you from Inoreader Impact of concomitant systemic treatments on toxicity and intracerebral response after stereotactic radiotherapy for brain metastases Via Latest Results for BMC Cancer Abstract Background The aim of this study was to determine the safety and efficacy of fractionated stereotactic radiotherapy (SRT) in combination with systemic therapies (ST) for brain metastases (BM). Methods Ninety-nine patients (171 BM) received SRT and concurrent ST (group 1) and 95 patients (131 BM) received SRT alone without concurrent ST (group 2). SRT was planned on a linear accelerator, using volumetric modulated arc therapy. All ST were allowed including chemotherapy (CT), immunotherapy (IT), targeted therapy (TT) and hormonotherapy (HT). Treatment was considered to be concurrent if the timing between the drug administration and SRT did not exceed 1 month. Local control (LC), freedom for distant brain metastases (FFDBM), overall survival (OS) and radionecrosis (RN) were evaluated. Results After a median follow-up of 11.9 months (range 0.7–29.7), there was no significant difference between the two groups. However, patients who received concurrent IT (n = 30) had better 1-year LC, OS, FFDBM but a higher RN rate compared to patients who did not: 96% versus 78% (p = 0.02), 89% versus 77% (p = 0.02), 76% versus 53% (p = 0.004) and 80% versus 90% (p = 0.03), respectively. In multivariate analysis, concurrent IT (p = 0.022) and tumor volume < 2.07 cc (p = 0.039) were significantly correlated with improvement of LC. The addition of IT to SRT compared to SRT alone was associated with an increased risk of RN (p = 0.03). Conclusion SRT delivered concurrently with IT seems to be associated with improved LC, FFDBM and OS as well as with a higher rate of RN. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

A novel nomogram to predict the overall survival in esthesinoeroblastoma

Cancer shared this article with you from Inoreader A novel nomogram to predict the overall survival in esthesinoeroblastoma Via Latest Results for BMC Cancer Abstract Background Increasing evidence indicates that the pathology and the modified Kadish system have some influence on the prognosis of esthesioneuroblastoma (ENB). However, an accurate system to combine pathology with a modified Kadish system has not been established. Methods This study aimed to set up and evaluate a model to predict overall survival (OS) accurately in ENB, including clinical characteristics, treatment and pathological variables. We screened the information of patients with ENB between January 1, 1976, and December 30, 2016 from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) program as a training cohort. The validation cohort consisted of patients with ENB at Sun Yat-sen University Cancer Center and The First Affiliated Hospital of Sun Yat-sen University in the same period, and 87 patients were included. The Pearson's chi-squared test was used to assess significance of clinicopathological and demographic characteristics. We used the Cox proportional hazards model to examine univariate and multivariate analyses. The model coefficients were used to calculate the Hazard ratios (HR) with 95% confidence intervals (CI). Prognostic factors with a p-value < 0.05 in multiva riate analysis were included in the nomogram. The concordance index (c-index) and calibration curve were used to evaluate the predictive power of the nomogram. Results The c-index of training cohort and validation cohort are 0.737 (95% CI, 0.709 to 0.765) and 0.791 (95% CI, 0.767 to 0.815) respectively. The calibration curves revealed a good agreement between the nomogram prediction and actual observation regarding the probability of 3-year and 5-year survival. We used a nomogram to calculate the 3-year and 5-year growth probability and stratified patients into three risk groups. Conclusions The nomogram provided the risk group information and identified mortality risk and can serve as a reference for designing a reasonable follow-up plan. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Clinical characteristics and prognostic implications of BRCA-associated tumors in males: a pan-tumor survey

Cancer shared this article with you from Inoreader Clinical characteristics and prognostic implications of BRCA-associated tumors in males: a pan-tumor survey Via Latest Results for BMC Cancer Abstract Background The BRCA mutation (BRCAm) in males has been reported to confer a higher risk for the development of various tumors. However, little is known about its clinicopathologic features and prognostic implications. Design We conducted a retrospective pan-tumor survey on 346 cases of BRCA-associated tumors in males. Comparative analyses were conducted among male and female patients with BRCAm (n = 349), as well as in male patients without BRCAm (n = 4577). Results Similar incidences of BRCAm (6.0 vs. 6.6%) and age at diagnosis of tumor (median, 65 vs. 60 years) were observed in male and female patients. Carcinomas of the lung, bladder, stomach, and cutaneous melanoma were the frequent tumors demonstrating BRCAm in males, of which the majority were stage II or III diseases with a higher frequency of BRCA2 mutations. Compared to that in the non-BRCAm group, cutaneous melanoma (16.3 vs. 5.0%), lung cancer (19.4 vs. 11.8%), bladder cancer (15.6 vs. 5.6%), and stomach cancer (11.9 vs. 5.5%) accounted for a higher proportion in the BRCAm group. Advanced disease and more mutation counts (median, 322 vs. 63 mutations) were also found in the BRCAm group. A total of 127 BRCA1 and 311 BRCA2 mutations were identified, of which 21.8 and 28.6% were deleterious, respectively. Frequent deleterious variants were identified in carcinomas of the breast (100.0%), colorectum (62.2%), prostate (43.3%), and stomach (42.9%). BRCA1 fusions w ith NF1, FAM134C, BECN1, or LSM12 and recurrent BRCA2 mutations at P606L/S, E832K/G, and T3033Lfs*29 were detected. Frameshift mutations in BRCA2 at N1784 (N1784Kfs*3, N1784Tfs*3) were frequently observed in both male and female patients. Compared with those in females, BRCA mutations in males were associated with decreased overall survival (OS) and progression-free survival (PFS). Male patients with deleterious BRCAm displayed increased OS compared with non-BRCAm carriers. The subgroup analysis demonstrated that BRCAm was associated with increased OS in gastric and bladder cancers, decreased PFS in prostate, esophageal, and head and neck cancers, and decreased OS in glioma/glioblastoma in males. Conclusion These findings provide an overview of the distinct characteristics and clinical outcomes of male patients with BRCA-associated tumors, suggesting the importance of further genetic BRCA testing in males. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Limb salvage versus amputation in patients with osteosarcoma of the extremities: an update in the modern era using the National Cancer Database

Cancer shared this article with you from Inoreader Limb salvage versus amputation in patients with osteosarcoma of the extremities: an update in the modern era using the National Cancer Database Via Latest Results for BMC Cancer Abstract Background Historically, amputation was the primary surgical treatment for osteosarcoma of the extremities; however, with advancements in surgical techniques and chemotherapies limb salvage has replaced amputation as the dominant treatment paradigm. This study assessed the type of surgical resection chosen for osteosarcoma patients in the twenty-first century. Methods Utilizing the largest registry of primary osteosarcoma, the National Cancer Database (NCDB), we retrospectively analyzed patients with high grade osteosarcoma of the extremities from 2004 through 2015. Differences between patients undergoing amputation and patients undergoing limb salvage are described. Unadjusted five-year overall survival between patients who received limb salvage and amputation was assessed utilizing Kaplan Meier curves. A multivariate Cox proportional hazard model and propensity matched analysis was used to determine the variables independently correlated with survival. Results From a total of 2442 patients, 1855 underwent limb salvage and 587 underwent amputation. Patients undergoing amputation were more likely to be older, male, uninsured, and live in zip codes associated with lower income. Patients undergoing amputation were also more likely to have larger tumors, more comorbid conditions, and metastatic disease at presentation. After controlling for confounders, limb salvage was associated with a significant survival benefit over amputation (HR: 0.70; p < 0.001). Although this may well reflect underlying biases impacting choice of treatment, this survival benefit remained significant after propensity matched analysis of all significantly different independent variables (HR: 0.71; p < 0.01). Conclusion Among patients in the NCDB, amputation for osteosarcoma is associated with advanced age, advanced stage, larger tumors, greater comorbidities, and lower income. Limb salvage is associated with a significant survival benefit, even when controlling for significant confounding variables and differences between cohorts. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

YB-1 transferred by gastric cancer exosomes promotes angiogenesis via enhancing the expression of angiogenic factors in vascular endothelial cells

Cancer shared this article with you from Inoreader YB-1 transferred by gastric cancer exosomes promotes angiogenesis via enhancing the expression of angiogenic factors in vascular endothelial cells Via Latest Results for BMC Cancer Abstract Background Angiogenesis is important for the progression of gastric cancer (GC). Y-box binding protein 1 (YB-1) predicts advanced disease and indicates neovasculature formation in GC tissues, while the related mechanisms remain elusive. Exosomes mediate intercellular communications via transferring various molecules including proteins, lipids, mRNAs, and microRNAs, while the cargos of GC exosomes and the related mechanisms in GC angiogenesis were rarely reported except for several microRNAs. Methods In this study, human umbilical vein endothelial cells (HUVECs) were, respectively, treated by the exosomes isolated from the YB-1 transfected and the control SGC-7901 cells (SGC-7901-OE-Exo and SGC-7901-NC-Exo), and their apoptosis, proliferation, migration, invasion, and angiogenesis were, sequentially, compared. The levels of angiogenic factors including VEGF, Ang-1, MMP-9 and IL-8 in the exosome-treated HUVECs and the GC-derived exosomes were, separately, detected using PCR and Western blotting as well as RNA sequencing assays. Results We observed the consistent level of YB-1 in the exosomes and their originated GC cells, and the internalization of exosomes into HUVECs. Comparing with SGC-7901-NC-Exo, SGC-7901-OE-Exo significantly inhibited the apoptosis but promoted the proliferation, migration, invasion, and angiogenesis of HUVECs, within which the increased mRNA and protein levels of VEGF, Ang-1, MMP-9 and IL-8 were demonstrated. Meanwhile, mRNA levels of VEGF, Ang-1, MMP-9 and IL-8 showed no significant difference between SGC-7901-NC-Exo and SGC-7901-OE-Exo, although statistically higher mRNA of YB-1 was detected in the SGC-7901-OE-Exo. Conclusions Our findings illustrate YB-1 as the key component of exosome to promote GC angiogenesis by upregulating specific angiogenic factors in the exosome-treated endothelial cells but not in the exosomes themselves. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

USP6NL mediated by LINC00689/miR-142-3p promotes the development of triple-negative breast cancer

Cancer shared this article with you from Inoreader USP6NL mediated by LINC00689/miR-142-3p promotes the development of triple-negative breast cancer Via Latest Results for BMC Cancer Abstract Background Triple-negative breast cancer (TNBC), in part because of the high metastasis rate, is one of the most prevalent causes of malignancy-related mortality globally. Ubiquitin specific peptidase 6 N-terminal like (USP6NL) has been unmasked to be implicated in some human cancers. However, the precise biological function of USP6NL in TNBC has not been defined. Methods RNA expression was examined by real-time quantitative PCR (RT-qPCR), while USP6NL protein level was tested through western blot. Besides, cell proliferation was assessed by using colony formation assay, whereas cell apoptosis estimated by flow cytometry analysis, JC-1 assay and TUNEL assay. Transwell assays were adopted to detect the migration and invasion of indicated TNBC cells. Immunofluorescence (IF) assay evaluated epithelial-mesenchymal transitions (EMT) progress in TNBC. Further, RNA immunoprecipitation (RIP), RNA pull down and luciferase reporter assays were implemented for measuring the mutual interplay among USP6NL, miR-142-3p and long intergenic non-protein coding RNA 689 (LINC00689). Results Elevated USP6NL level was uncovered in TNBC cells. RNA interference-mediated knockdown of USP6NL inhibited TNBC cell growth, motility and EMT. Further, USP6NL was proved as the target of a tumor-inhibitor miR-142-3p, and LINC00689 augmented USP6NL expression by absorbing miR-142-3p. Importantly, miR-142-3p deficiency or USP6NL overexpression fully abolished the inhibitory effect of LINC00689 silence on TNBC cellular behaviors. Conclusion All data revealed the important role of USP6NL/LINC00689/miR-142-3p signaling in TNBC. The findings might provide a new and promising therapeutic biomarker for treating patients with TNBC. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Analyses of the local control of pulmonary Oligometastases after stereotactic body radiotherapy and the impact of local control on survival

Cancer shared this article with you from Inoreader Analyses of the local control of pulmonary Oligometastases after stereotactic body radiotherapy and the impact of local control on survival Via Latest Results for BMC Cancer Abstract Background Successful local therapy for oligometastases may lead to longer survival. The purpose of this multicentre retrospective study was to investigate factors affecting the local control (LC) of pulmonary oligometastases treated by stereotactic body radiotherapy (SBRT) and to investigate the impact of LC on survival. Methods The inclusion criteria included 1 to 5 metastases, the primary lesion and other extrathoracic metastases were controlled before SBRT, and the biological effective dose (BED10) of the SBRT was 75 Gy or more. The Cox proportional hazards model was used for analyses. Results Data of 1378 patients with 1547 tumours from 68 institutions were analysed. The median follow-up period was 24.2 months. The one-year, 3-year and 5-year LC rates were 92.1, 81.3 and 78.6%, respectively, and the 1-year, 3-year and 5-year overall survival rates were 90.1, 60.3 and 45.5%, respectively. Multivariate analysis for LC showed that increased maximum tumour diameter (p = 0.011), type A dose calculation algorithm (p = 0.005), shorter overall treatment time of SBRT (p = 0.035) and colorectal primary origin (p < 0.001 excluding oesophagus origin) were significantly associated with a lower LC rate. In the survival analysis, local failure (p < 0.001), worse performance status (1 vs. 0, p = 0.013; 2–3 vs. 0, p < 0.001), oesophageal primary origin (vs. colorectal origin, p = 0.038), squamous cell carcinoma (vs. adenocarcinoma, p = 0.006) an d increased maximum tumour diameter (p < 0.001) showed significant relationships with shorter survival. Conclusions Several factors of oligometastases and SBRT affected LC. LC of pulmonary oligometastases by SBRT showed a significant survival benefit compared to patients with local failure. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Analysis of the role of the human papillomavirus 16/18 E7 protein assay in screening for cervical intraepithelial neoplasia: a case control study

Cancer shared this article with you from Inoreader Analysis of the role of the human papillomavirus 16/18 E7 protein assay in screening for cervical intraepithelial neoplasia: a case control study Via Latest Results for BMC Cancer Abstract Background Cervical cancer is the second-most common gynecological cancer, early screening plays a key role in the diagnosis and treatment of cervical intraepithelial neoplasia (CIN). Sustained E7 protein expression is the pathological basis for CIN and cervical cancer. Methods We collected the cervical cell samples of women who visited the gynecological clinic of Peking Union Medical College Hospital between September 2018 and September 2019 and submitted them to the high-risk human papillomavirus (Hr-HPV) test. We performed a magnetic particle–based chemiluminescence enzyme immunoassay to analyze the HPV16/18 E7 protein level in CIN of different severities and compared the results with those of cervical pathology (gold standard) and the HPV test. Results The positive rate of HPV16/18 E7 protein increased with the severity of CIN: 26.6% in normal tissue, 58.3% in CIN1, and 70.6% in CIN2 or higher (CIN2+). For CIN2+, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the E7 protein were 70.6, 67.9, 52.2, and 82.3%, respectively. These values of the HPV test were 86.8, 44.5, 43.7, and 87.1%, respectively. With the combination of the E7 protein assay and HPV test, the specificity for diagnosing CIN2+ was 78.1%, which was significantly higher than that of the HPV test alone. Conclusions HPV16/18 E7 protein level is correlated with the severity of CIN and has a high concordance rate with the pathological result. For cervical cancer screening, the combination of HPV16/18 E7 protein assay and HPV test improves the CIN diagnostic specificity, detection rate, and detection accuracy. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

CKD-5, a novel pan-histone deacetylase inhibitor, synergistically enhances the efficacy of sorafenib for hepatocellular carcinoma

Cancer shared this article with you from Inoreader CKD-5, a novel pan-histone deacetylase inhibitor, synergistically enhances the efficacy of sorafenib for hepatocellular carcinoma Via Latest Results for BMC Cancer Abstract Background Histone deacetylase inhibitors (HDACIs) have distinctive epigenetic targets involved in hepatocarcinogenesis and chemoresistance. A recent phase I/II study reported the possibility of HDACI as a chemosensitizer in sorafenib-resistant patients. In this study, we evaluated whether CKD-5, a novel pan-HDACI, can potentiate the efficacy of sorafenib. Methods The anticancer effect of CKD-5 with and without sorafenib was evaluated in vitro using an MTS assay with human HCC cells (SNU-3058 and SNU-761) under both normoxic and hypoxic conditions. Microarray analysis was performed to investigate the mechanism of cell death, which was also evaluated by small interfering RNA (siRNA) transfection and subsequent immunoblot assays. In vivo experiments were conducted using two different murine HCC models. C3H mice implanted with MH134 cells and C57BL/6 mice implanted with RIL-175 cells were treated with weekly CKD-5 with and without sorafenib for 2 weeks. Results CKD-5 treatment significantly suppressed human HCC cell growth in both normoxic and hypoxic conditions. Microarray analysis and real-time PCR showed that CKD-5 treatment significantly increased peripherin expression in HCC cells and that downregulation of peripherin by siRNA decreased CKD-5-induced apoptosis. The combination of CKD-5 and sorafenib decreased cell viability more effectively than sorafenib or CKD-5 monotherapy in human and murine HCC cells. The effectiveness of the combination therapy was consistently demonstrated in the animal models. Histological and biochemical analyses demonstrated good tolerance of CKD-5 plus sorafenib in vivo. Conclusion CKD-5 may enhance sorafenib efficacy through epigenetic regulation. The combination of CKD-5 and sorafenib might be a novel therapeutic option for the treatment of HCC. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Detection of MCM5 as a novel non-invasive aid for the diagnosis of endometrial and ovarian tumours

Cancer shared this article with you from Inoreader Detection of MCM5 as a novel non-invasive aid for the diagnosis of endometrial and ovarian tumours Via Latest Results for BMC Cancer Abstract Background MCM5 is a protein involved in DNA replication, facilitating cell proliferation. In normal epithelium MCM5 expression is restricted to the cells in the basal proliferative compartments, however in the presence of a tumour MCM5 positive cells are present at the surface epithelium and are shed into bodily fluids. The aim of this study was to determine the sensitivity of MCM5 as a biomarker for the detection of endometrial and ovarian cancer. Methods Patients with known ovarian or endometrial cancers, or known benign gynaecological conditions, were enrolled. Informed consent was obtained prior to the collection of full void urine, and either a vaginal tampon (worn for 6–8 h), or a vaginal swab. Vaginal secretions were extracted from the tampon or swab, centrifuged and lysed. Urine samples were centrifuged and lysed. MCM5 levels were determined by MCM5-ELISA (Arquer Diagnostics Ltd). Results 125 patients completed the study protocol, 41 patients had endometrial cancer, 26 ovarian cancer, and 58 benign controls. All patients provided a urine sample and either a tampon or vaginal swab sample. Urine MCM5 levels were higher in cancer patients than controls (p < 0.0001), there was no significant difference in levels between tampon samples or vaginal swab samples in cancer patients when compared to controls. Performance of MCM5 to discriminate cancer from benign disease was high with an area under the ROC curve of 0.83 for endometrial cancer and 0.68 for ovarian cancer. Using a cut off of 12 pg/mL, overall sensitivity for endometrial cancer was 87.8, and 61.5% for ovarian cancer with a specificity of 75.9%. Conclusions MCM5 is a novel sensitive and specific biomarker for the detection of ovarian and endometrial tumours in urine samples, which is likely to have clinical utility as a diagnostic aid. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Effect of sarcopenia on short- and long-term outcomes in patients with gastric neuroendocrine neoplasms after radical gastrectomy: results from a large, two-institution series

Cancer shared this article with you from Inoreader Effect of sarcopenia on short- and long-term outcomes in patients with gastric neuroendocrine neoplasms after radical gastrectomy: results from a large, two-institution series Via Latest Results for BMC Cancer Abstract Background The relationship between sarcopenia and the prognoses of patients with gastric neuroendocrine neoplasms (g-NENs) is unclear. This study was designed to explore the effects of sarcopenia on short-term and long-term outcomes of patients with g-NENs after radical gastrectomy. Methods This study retrospectively collected data from 138 patients with g-NENs after radical gastrectomy. The skeletal muscle index (SMI) diagnostic threshold for sarcopenia was determined using X-tile software. Cox regression analyses were performed to determine the independent risk factors for 3-year overall survival (OS) and 3-year recurrence-free survival (RFS). Results In this study, 59 patients (42.8%) were diagnosed with sarcopenia. Among patients in the sarcopenia group and nonsarcopenia group, the incidences of total postoperative complications were 33.9 and 30.4%, incidences of serious postoperative complications were 0 and 3.7%, incidences of postoperative surgical complications were 13.6 and 15.2%, and incidences of postoperative systemic complications were 20.3 and 15.2%, respectively (all p > 0.05). The 3-year OS and RFS rates were significantly worse in the sarcopenia group than in the nonsarcopenia group (OS: 42.37% vs 65.82%, p = 0.004; RFS: 52.54% vs 68.35%, p = 0.036). The multivariate analysis revealed a relation between sarcopenia and the long-term prognoses of patients with g-NENs. A stratified analysis based on the pathological type revealed that the Kaplan-Meier curve was only significantly different in patients with gastric mixed adenoneuroendocrine carcinoma (gM ANEC) (OS: 40.00% vs 71.79%, p = 0.007; RFS: 51.43% vs 74.36%, p = 0.026); furthermore, the multivariate analysis identified sarcopenia as an independent risk factor for patients with gMANEC (p < 0.05). Conclusions Sarcopenia is not related to the short-term prognoses of patients with g-NENs. Sarcopenia is an independent risk factor for patients with gMANEC after radical surgery. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.