Disagreement between patient‐ and physician‐reported outcomes on symptomatic adverse events as poor prognosis in patients treated with first‐line cetuximab plus chemotherapy for unresectable metastatic colorectal cancer: Results of Phase II QUACK trial

xloma.fota13 shared this article with you from Inoreader Disagreement between patient‐ and physician‐reported outcomes on symptomatic adverse events as poor prognosis in patients treated with first‐line cetuximab plus chemotherapy for unresectable metastatic colorectal cancer: Results of Phase II QUACK trial Via Cancer Medicine The routine use of PROs could be complementary to physician‐reported outcomes to ensure the accurate assessment of symptomatic AEs and facilitate patient‐centered healthcare in clinical practice. Abstract The status and prognostic value of the disagreement between physician and patient assessments of symptomatic adverse events (AEs) remain unclear for patients with metastatic colorectal cancer treated with first‐line cetuximab plus chemotherapy. Paired data on patient‐reported outcomes using the EORTC QLQ‐C30 and physician‐reported outcomes using the NCI‐CTCAE for eight symptomatic AEs (fatigue, pain, insomnia, dyspnea, constipation, appetite loss, nausea/vomiting, and diarrhea) were collected from a prospective trial assessing the relationships between treatment efficacy, AEs, and quality of life. The overall agreement rates between patient and physician reporting at 4 weeks ranged from 40.2% to 76.5% for 129 patients. The level of agreement based on Cohen's κ statistics was slight to poor for dyspnea, pain, fatigue, and insomnia, while it was moderate to fair for the remaining AEs. No clinicopathological characteristics of disagreement were found. The underreporti ng by physicians ranged from 12.5% (nausea/vomiting) to 56.7% (fatigue). The 2‐year overall survival (OS) rate was more favorable for patients with high agreement than for those with low agreement (71.2% vs. 46.5%, p = .016), and the agreement status was an independent factor of OS (HR, 2.31; 95% CI, 1.13–4.71; p = .022). For patients who were reported as asymptomatic by the physician, the presence of patient‐reported symptoms resulted in a trend toward poor prognostic outcomes for appetite loss, dyspnea, diarrhea, and constipation. These findings provide the clinical importance of the monitoring of patient‐reported symptoms that can be complementary to physician‐reported data to ensure more accurate clinical outcomes. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Clinical outcomes of immune checkpoint blockades and the underlying immune escape mechanisms in squamous and adenocarcinoma NSCLC

xloma.fota13 shared this article with you from Inoreader Clinical outcomes of immune checkpoint blockades and the underlying immune escape mechanisms in squamous and adenocarcinoma NSCLC Via Cancer Medicine We reviewed the clinical outcomes of immune checkpoint blockades and the underlying immune escape mechanisms in squamous and adenocarcinoma NSCLC, and prospected the strategies to improve the clinical efficacy of ICBs in NSCLC. Abstract Immune checkpoint blockades (ICBs) have changed the standard of care of squamous and adenocarcinoma non‐small cell lung cancer (NSCLC). Whereas detailed researches regarding ICBs in the two major histological subtypes are rare. In order to uncover the clinical efficacy differences between squamous and adenocarcinoma NSCLC and better understand the underlying immune‐regulatory mechanisms, we compared the survival benefits of ICBs between the two subtypes by revealing phase 3 randomized trials and attempted to uncover the immune‐regulatory discrepancy. Generally, compared with nonsquamous NSCLC, squamous NSCLC benefited more from ICBs in Keynote 024, CheckMate 026, CheckMate 227 and CheckMate 017 and similar in OAK, but less in Keynote 010 and PACIFIC. We revealed that the tumor mutation burden (TMB) level, the programmed cell death ligand 1 (PD‐L1) expression, tumor infiltrating lymphocytes (TILs) in the tumor microenvironment (TME), chemokines, and oncogenic driver alterat ions within the two subtypes may contributed to the clinical outcomes of ICBs. We prospected that the combinations of ICBs with chemotherapy, radiation therapy, and antiangiogenic therapy could be promising strategies to re‐immunize the less immunogenic tumors and further enhance the efficacy of ICBs. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Smoking status before and after colorectal cancer diagnosis and mortality

xloma.fota13 shared this article with you from Inoreader Smoking status before and after colorectal cancer diagnosis and mortality in Korean men: A population‐based cohort study Via Cancer Medicine This study found that both smoking before and after cancer diagnosis is associated with increased mortality rate among colorectal cancer patient. Quitting smoking after diagnosis was significantly related to diminished mortality among colorectal cancer patients receiving only operation, who is considered as early stage colorectal cancer patients, though smoking cessation after diagnosis among colorectal cancer patients who received radiotherapy or chemotherapy was not associated with significantly decreased mortality. Abstract Background Smoking is a well‐known risk factor for colorectal cancer incidence; however, the effect of smoking before and after cancer diagnosis on mortality has not been addressed well. Thus, we aimed to evaluate the association of prediagnosis and postdiagnosis smoking status and mortality among colorectal cancer patients. Methods A retrospective cohort consisted of 37,079 male colorectal cancer patients. Smoking status was defined from information within 2 years of colorectal cancer diagnosis for prediagnosis and at least 1 year later for postdiagnosis. The prediagnostic and postdiagnostic smoking status were categorized into four groups (nonsmoker/nonsmoker, nonsmoker/smoker, smoker/nonsmoker, and smoker/smoker). Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using the Cox proportional hazard model. Results During a median of 6.3 years of follow‐up, a total of 3980 deaths and 2137 deaths from colorectal cancer occurred. The number of prediagnosis smokers were 11,100 and 62.4% of them quitted smoking after the diagnosis. Significantly elevated mortality rate in prediagnosis smokers was observed regardless of postdiagnosis smoking status (smoker/nonsmoker [HR, 1.30; 95% CI, 1.20–1.41] and smoker/smoker [HR, 1.21; 95% CI, 1.09–1.34]). Among patients treated with surgical operation only, those who quit smoking after diagnosis showed lower mortality rates compared to continual smokers (HR, 0.80; 95% CI, 0.67–0.96). Conclusions Smoking before cancer diagnosis rather than postdiagnosis has stronger impact on prognosis colorectal cancer patients, and quitting smoking may improve survival, especially among early stage colorectal cancer patients. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Investigation of drugs affecting hypertension in bevacizumab‐treated patients and examination of the impact on the therapeutic effect

xloma.fota13 shared this article with you from Inoreader Investigation of drugs affecting hypertension in bevacizumab‐treated patients and examination of the impact on the therapeutic effect Via Cancer Medicine The use of PPIs prevents hypertension in bevacizumab‐treated patients. However, it may reduce the anti‐tumor effect of bevacizumab by inducing the expression of VEGF. Abstract Background In patients treated with bevacizumab, hypertension may be a biomarker of therapeutic efficacy. However, it is not clear whether drugs that control blood pressure influence bevacizumab's efficacy. In this study, we investigated drugs that may affect hypertension in bevacizumab‐treated patients and examined the impact on the therapeutic effect. Patients and methods We analyzed 3,724,555 reports from the third quarter of 2010 to the second quarter of 2015. All data were obtained from the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) analysis. In this retrospective cohort study, we investigated a total of 58 patients diagnosed with colorectal cancer and treated for the first time with bevacizumab containing XELOX or mFOLFOX6 at The University of Tokushima Hospital between January 2010 and December 2015. The effect of the treatment was evaluated according to Response Evaluation Criteria in Solid Tumors version 1.0. Thereafter, the effect was confirmed using Gene Expression Omnibus (GEO) and cultured cells. Results There are few reports in FAERS of hypertension in patients treated with omeprazole on bevacizumab. Based on the chart review, patients who used proton pump inhibitors (PPI) had a lower response to treatment than those who did not (response rate: 25% vs 50%). Furthermore, experiments on GEO and cell lines suggested that induction of vascular endothelial growth factor (VEGF) gene expression by PPIs is the cause of the reduced therapeutic effect. Conclusion PPIs prevent hypertension in bevacizumab‐treated patients but may reduce bevacizumab's anti‐tumoral effects by inducing VEGF expression. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Periplocin inhibits the growth of pancreatic cancer by inducing apoptosis via AMPK‐mTOR signaling

xloma.fota13 shared this article with you from Inoreader Periplocin inhibits the growth of pancreatic cancer by inducing apoptosis via AMPK‐mTOR signaling Via Cancer Medicine In this work, we evaluated the effect of Periplocin on pancreatic cancer growth and tried to clarify its molecular mechanism. ABSTRACT Background Periplocin is a monomeric compound that exhibits anti‐tumor activities. It is extracted from Cortex Periplocae. Objective This study aimed at determining the effect of periplocin treatment on the apoptosis and proliferation of human pancreatic cancer cells, and to elucidate on its mechanisms of action. Methods PANC1 and cfpac1 cells were treated with periplocin. Cell proliferation was detected by RTCA, Ki67 immunofluorescence, and a clonogenic assay. The transwell assay was used to examine cell migration and invasion functions. The expression of apoptosis‐associated proteins was detected by flow cytometry and western blotting. Total RNA was extracted from the treated and untreated group of PANC1 cells for RNA‐seq detection and analysis. Differentially expressed genes were screened for GO biological process and KEGG pathway analysis. Finally, CFPAC1 cells were subcutaneously inoculated into BALB / c nude mice to assess tumor growth. Results Periplocin inhibited the proliferation of PANC1 and CFPAC1 cells and induced their apoptosis by activating the AMPK/mTOR pathway and inhibiting p70 S6K. It also attenuated the cell migration, invasion, and inhibited the growth of cfpac1 xenografts in nude mice. Conclusions Periplocin inhibits human pancreatic cancer cell proliferation and induces their apoptosis by activating the AMPK / mTOR pathway. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Construction of a disease‐specific lncRNA‐miRNA‐mRNA regulatory network reveals potential regulatory axes and prognostic biomarkers for hepatocellular carcinoma

xloma.fota13 shared this article with you from Inoreader Construction of a disease‐specific lncRNA‐miRNA‐mRNA regulatory network reveals potential regulatory axes and prognostic biomarkers for hepatocellular carcinoma Via Cancer Medicine This article constructed an HCC‐specific ceRNA network by integrating a differential lncRNA‐miRNA‐mRNA regulatory network and an online tool‐based ceRNA network. As a result, four lncRNA–miRNA–mRNA regulatory axes were extracted, and a prognostic signature (CRNDE, MYLK‐AS1 and CHEK1) was identified for overall survival (OS) of HCC. A nomogram comprising the prognostic signature and pathological stage was established and showed some net clinical benefits. Abstract Hepatocellular carcinoma (HCC) is a heterogeneous malignancy with a high incidence and poor prognosis. Exploration of the underlying mechanisms and effective prognostic indicators is conducive to clinical management and optimization of treatment. The RNA‐seq and clinical phenotype data of HCC were retrieved from The Cancer Genome Atlas (TCGA), and differential expression analysis was performed. Then, a differential lncRNA‐miRNA‐mRNA regulatory network was constructed, and the key genes were further identified and validated. By integrating this network with the online tool‐based ceRNA network, an HCC‐specific ceRNA network was obtained, and lncRNA‐miRNA‐mRNA regulatory axes were extracted. RNAs associated with prognosis were further obtained, and multivariate Cox regression models were established to identify the prognostic signature and nomogram. As a result, 198 DElncRNAs, 120 DEmiRNAs, and 2827 DEmRNAs were identified, and 30 key genes identified from the different ial network were enriched in four cancer‐related pathways. Four HCC‐specific lncRNA‐miRNA‐mRNA regulatory axes were extracted, and SNHG11, CRNDE, MYLK‐AS1, E2F3, and CHEK1 were found to be related with HCC prognosis. Multivariate Cox regression analysis identified a prognostic signature, comprised of CRNDE, MYLK‐AS1, and CHEK1, for overall survival (OS) of HCC. A nomogram comprising the prognostic signature and pathological stage was established and showed some net clinical benefits. The AUC of the prognostic signature and nomogram for 1‐year, 3‐year, and 5‐year survival was 0.777 (0.657‐0.865), 0.722 (0.640‐0.848), and 0.630 (0.528‐0.823), and 0.751 (0.664‐0.870), 0.773 (0.707‐0.849), and 0.734 (0.638‐0.845), respectively. These results provided clues for the study of potential biomarkers and therapeutic targets for HCC. In addition, the obtained 30 key genes and 4 regulatory axes might also help elucidate the underlying mechanism of HCC. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Minimally invasive surgery vs laparotomy for early stage cervical cancer: A propensity score‐matched cohort study

xloma.fota13 shared this article with you from Inoreader Minimally invasive surgery vs laparotomy for early stage cervical cancer: A propensity score‐matched cohort study Via Cancer Medicine Recent studies have shown that patients with early‐stage cervical cancer who underwent minimally invasive surgery (MIS) had a worse prognosis than that of laparotomy; However, whether minimally invasive radical hysterectomy is available for relatively low‐risk early patients under the 2018 FIGO guidelines have yet to be studied. A propensity score‐matched cohort study examining patients with stage IB (2018 FIGO) cervical cancer of relatively low‐risk who underwent radical hysterectomy found that the five‐year overall survival and disease‐free survival of MIS respectively reduced by 5.8% and 6.6% compared with laparotomy. The surgical approaches do have a significant difference for survival of patients with early cervical cancer who underwent radical hysterectomy. Even in stage IB1 patients with low‐risk, the oncologic outcomes of laparotomy is better compared with MIS. Abstract Objective To compare the long‐term oncologic outcomes of minimally invasive surgery (MIS) vs laparotomy for patients with stage IB (2018 FIGO) cervical cancer. Methods A matched retrospective study of cervical cancer patients who underwent MIS or laparotomy at Sun Yat‐sen University Cancer Center from January 2012 to December 2015 was carried out. Patients were restaged according to the 2018 FIGO staging system for cervical cancer, 700 cases with stage IB cervical cancer were enrolled. Propensity score matching (PSM) was performed by software SPSS version 22.0, and a total of 426 patients were enrolled and analyzed. Oncologic outcomes were compared between patients undergoing MIS vs laparotomy. Results After PSM, there were no statistical differences in other baseline characteristics between MIS and laparotomy, except for age (p = 0.008). In all stage IB patients, MIS group had significantly lower disease‐free survival (DFS) rate and overall survival (OS) rate compared with laparotomy group (5‐year DFS rate, 87.5% vs 94.1%, hazard ratio for disease recurrence, 2.403; 95% CI, 1.216‐4.744; 5‐year OS rate, 92.3% vs 98.1%, hazard ratio for death, 3.719; 95% CI, 1.370‐10.093). In stage IB1 patients population, MIS was still associated with worse DFS and OS compared to laparotomy (5‐year DFS rate: 89.5% vs 100%, p = 0.012; 5‐year OS rate: 93.4% vs 100%, p = 0.043). Even in stage IB1 patients without lymph vascular space invasion, worse oncologic outcome could be observed in MIS group (DFS: p = 0.021; OS: p = 0.076). Conclusion Our study suggested that laparotomy resulted in better OS and DFS compared with MIS among patients with stage IB cervical cancer. Even in stage IB1 patients without lymph vascular space invasion (2018 FIGO), laparotomy might be still an oncologically safer approach. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.