Αρχειοθήκη ιστολογίου

Αναζήτηση αυτού του ιστολογίου

Δευτέρα 18 Ιανουαρίου 2021

Preoperative predictors of dysphagia after transoral surgery

Cancer shared this article with you from Inoreader

10147.jpg

Abstract

Background

Transoral surgery (TOS) has been used to remove pharyngeal and laryngeal cancers with the objective of improving functional without worsening survival. However, there is a risk of postoperative dysphagia, which can severely impair quality of life. The aim of this study was to evaluate the preoperative predictive factors for postoperative dysphagia in patients undergoing TOS.

Methods

One hundred and twenty patients who underwent TOS were evaluated in this study. The degree of dysphagia was evaluated using the Functional Outcome Swallowing Scale (FOSS) both preoperatively and 3 months postoperatively. Those whose FOSS stage was maintained postoperatively were classified into the FOSS-M group, while those with increased FOSS stage postopratively were classified into the FOSS-I group. The following parameters were assessed before surgery: age, weight, height, body mass index (BMI), forced expiratory volume in 1 s, and history of head and neck radiotherapy. Videofluoroscopy (VF) was performed preoperatively to evaluate swallowing function using the Penetration-Aspiration Scale (PAS).

Results

The BMI of the FOSS-M group was significantly higher than that of the FOSS-I group. A history of radiotherapy was significantly more common in the FOSS-I group than in the FOSS-M group. Finally, preoperative PAS in the FOSS-M group was lower than that in the FOSS-I group.

Conclusion

This study suggested that patients with preoperative aspiration detected using VF might develop postoperative dysphagia severely. In addition, preoperative low BMI and a history of previous radiotherapy for head and neck cancer were associated with postoperative dysphagia. Objective examinations such as VF should be performed preoperatively.

View on the web

The role of m 6 A, m 5 C and Ψ RNA modifications in cancer: Novel therapeutic opportunities

Cancer shared this article with you from Inoreader

12943.jpg

Abstract

RNA modifications have recently emerged as critical posttranscriptional regulators of gene expression programmes. Significant advances have been made in understanding the functional role of RNA modifications in regulating coding and non-coding RNA processing and function, which in turn thoroughly shape distinct gene expression programmes. They affect diverse biological processes, and the correct deposition of many of these modifications is required for normal development. Alterations of their deposition are implicated in several diseases, including cancer. In this Review, we focus on the occurrence of N6-methyladenosine (m6A), 5-methylcytosine (m5C) and pseudouridine (Ψ) in coding and non-coding RNAs and describe their physiopathological role in cancer. We will highlight the latest insights into the mechanisms of how these posttranscriptional modifications influence tumour development, maintenance, and progression. Finally, we will summarize the latest advances on the development of small molecule inhibitors that target specific writers or erasers to rewind the epitranscriptome of a cancer cell and their therapeutic potential.

View on the web

Tumor-draining lymph nodes are survival niches that support T cell priming against lymphatic transported tumor antigen and effects of immune checkpoint blockade in TNBC

Cancer shared this article with you from Inoreader

262.jpg

Abstract

Triple negative breast cancer (TNBC) is a significant clinical problem to which immunotherapeutic strategies have been applied with limited success. Using the syngeneic E0771 TNBC mouse model, this work explores the potential for antitumor CD8+ T cell immunity to be primed extratumorally in lymphoid tissues and therapeutically leveraged. CD8+ T cell viability and responses within the tumor microenvironment (TME) were found to be severely impaired, effects coincident with local immunosuppression that is recapitulated in lymphoid tissues in late stage disease. Prior to onset of a locally suppressed immune microenvironment, however, CD8+ T cell priming within lymph nodes (LN) that depended on tumor lymphatic drainage remained intact. These results demonstrate tumor-draining LNs (TdLN) to be lymphoid tissue niches that support the survival and antigenic priming of CD8+ T lymphocytes against lymph-draining antigen. The thera peutic effects of and CD8+ T cells response to immune checkpoint blockade were furthermore improved when directed to LNs within the tumor-draining lymphatic basin. Therefore, TdLNs represent a unique potential tumor immunity reservoir in TNBC for which strategies may be developed to improve the effects of ICB immunotherapy.

View on the web

Cosmetic outcomes of a phase I dose escalation study of 5-fraction stereotactic partial breast irradiation for early stage breast cancer

Cancer shared this article with you from Inoreader

1-s2.0-S0360301620X00265-cov150h.gif

Publication date: Available online 18 January 2021

Source: International Journal of Radiation Oncology*Biology*Physics

Author(s): Asal Rahimi, Howard E. Morgan, Dong W. Kim, Yuanyuan Zhang, Marilyn Leitch, Rachel Wooldridge, Sally Goudreau, Barbara Haley, Roshni Rao, Aeisha Rivers, Ann E. Spangler, Ryan T. Jones, Stella Stevenson, Jason Staley, Kevin Albuquerque, Chul Ahn, Sarah Neufeld, Prasanna G. Alluri, Chuxiong Ding, Dan Garwood

View on the web

“SQiD, the Single Question in Delirium; can a single question help clinicians to detect delirium in hospitalised cancer patients?” running heading Single Question in Delirium” (Bcan-D-20-01665)

Cancer shared this article with you from Inoreader

12885.jpg

Abstract

Aim

A serious syndrome for cancer in-patients, delirium risk increases with age and medical acuity. Screening tools exist but detection is frequently delayed or missed. We test the 'Single Question in Delirium' (SQiD), in comparison to psychiatrist clinical interview.

Methods

Inpatients in two comprehensive cancer centres were prospectively screened. Clinical staff asked informants to respond to the SQiD: "Do you feel that [patient's name] has been more confused lately?". The primary endpoint was negative predictive value (NPV) of the SQiD versus psychiatrist diagnosis (Diagnostic and Statistics Manual criteria). Secondary endpoints included: NPV of the Confusion Assessment Method (CAM), sensitivity, specificity and Cohen's Kappa coefficient.

Results

Between May 2012 and July 2015, the SQiD plus CAM was applied to 122 patients; 73 had the SQiD and psychiatrist interview. Median age was 65 yrs. (interquartile range 54–74), 46% were female; median length of hospital stay was 12 days (5–18 days). Major cancer types were lung (19%), gastric or other upper GI (15%) and breast (14%). 70% of participants had stage 4 cancer. Diagnostic values were similar between the SQiD (NPV = 74, 95% CI 67–81; kappa = 0.32) and CAM (NPV = 72, 95% CI 67–77, kappa = 0.32), compared with psychiatrist interview. Overall the CAM identified only a small number of delirious cases but all were true positives. The specificity of the SQiD was 87% (74–95) The SQiD had higher sensitivity than CAM (44% [95% CI 41–80] vs 26% [10–48]).

Conclusion

The SQiD, administered by bedside clinical staff, was feasible and its psychometric properties are now better understood. The SQiD can contribute to delirium detection and clinical care for hospitalised cancer patients.

View on the web

CAR19/22 T cell therapy in adult refractory Burkitt’s lymphoma

Cancer shared this article with you from Inoreader

262.jpg

Abstract

The treatment of refractory Burkitt's lymphoma (BL) is still a challenge. Although CAR-T cell therapy has achieved good responses in diffuse large B cell lymphoma, there is no case series report about the efficacy of CAR-T cell therapy in adult Burkitt's lymphoma. In this study, we evaluate the efficacy and safety of CAR19/22 T cell therapy in six refractory Burkitt's lymphoma cases with poor genetic prognostic factors. After CAR-T cell therapy, five cases had grade 1 and one had grade 3 cytokine release syndrome. Three patients achieved an objective response (3/6 50%), including two partial remission and one complete remission. One CR patient received allogeneic hematopoietic stem cell transplantation (HSCT) and one PR patient received CAR22/19-T cells following auto-HSCT, and they were still in remission at 37 and 22 months of follow-up, respectively. Interestingly, patients with bulky disease (case 2, 4 and 5) had higher levels of serum IL-2R, which was secreted by regulatory T cells, lower CAR lentiviral amplification and poorer prognosis with shorter survival time than cases with non-bulky disease. It is suggested that high tumor burden, more immune suppressive cells and limited CAR-T cell expansion might affect the efficacy of CAR-T cell therapy. CAR-T cell therapy in adult BL patients whose best response cannot achieve CR may need to bridge to other treatments (such as HSCT) early.

View on the web

Integrated analysis of mRNA and miRNA profiles revealed the role of miR-193 and miR-210 as potential regulatory biomarkers in different molecular subtypes of breast cancer

Cancer shared this article with you from Inoreader

12885.jpg

Abstract

Background

Breast cancer is the most frequently diagnosed malignancy among women. However, the role of microRNA (miRNA) expression in breast cancer progression is not fully understood. In this study we examined predictive interactions between differentially expressed miRNAs and mRNAs in breast cancer cell lines representative of the common molecular subtypes. Integrative bioinformatics analysis identified miR-193 and miR-210 as potential regulatory biomarkers of mRNA in breast cancer. Several recent studies have investigated these miRNAs in a broad range of tumors, but the mechanism of their involvement in cancer progression has not previously been investigated.

Methods

The miRNA-mRNA interactions in breast cancer cell lines were identified by parallel expression analysis and miRNA target prediction programs. The expression profiles of mRNA and miRNAs from luminal (MCF-7, MCF-7/AZ and T47D), HER2 (BT20 and SK-BR3) and triple negative subtypes (Hs578T e MDA-MB-231) could be clearly separated by unsupervised analysis using HB4A cell line as a control. Breast cancer miRNA data from TCGA patients were grouped according to molecular subtypes and then used to validate these findings. Expression of miR-193 and miR-210 was investigated by miRNA transient silencing assays using the MCF7, BT20 and MDA-MB-231 cell lines. Functional studies included, xCELLigence system, ApoTox-Glo triplex assay, flow cytometry and transwell inserts were performed to determine cell proliferation, cytotoxicity, apoptosis, migration and invasion, respectively.

Results

The most evident effects were associated with cell proliferation after miR-210 silencing in triple negative subtype cell line MDA-MB-231. Using in silico prediction algorithms, TNFRSF10 was identified as one of the potential regulated downstream targets for both miRNAs. The TNFRSF10C and TNFRSF10D mRNA expression inversely correlated with the expression levels of miR-193 and miR210 in breast cell lines and breast cancer patients, respectively. Other potential regulated genes whose expression also inversely correlated with both miRNAs were CCND1, a known mediator on invasion and metastasis, and the tumor suppressor gene RUNX3.

Conclusions

In summary, our findings identify miR-193 and miR-210 as potential regulatory miRNA in different molecular subtypes of breast cancer and suggest that miR-210 may have a specific role in MDA-MB-231 proliferation. Our results highlight important new downstream regulated targets that may serve as promising therapeutic pathways for aggressive breast cancers

View on the web

New maintenance option for AML

Cancer shared this article with you from Inoreader

Message:

Approximately 50% of patients with acute myeloid leukaemia (AML) aged ≥55 years have complete remission after standard induction chemotherapy, but eventually the majority have disease relapse. Haematopoietic stem-cell transplantation (HSCT) is not always feasible for patients in this age group and, therefore, maintenance therapies might be warranted to prolong remission. Now, data from the phase III QUAZAR AML-001 trial demonstrate promising overall survival (OS) outcomes with oral azacitidine in this setting.

In QUAZAR AML-001, patients with AML in complete remission after induction with cytarabine-based chemotherapy and aged ≥55 years were randomly assigned to receive oral azacitidine (n = 238) or placebo (n = 234). The median age was 68 years; 91% of patients had de novo AML, 86% had intermediate-risk cytogenetic characteristics and 80% had received consolidation chemotherapy.

Median OS was significantly longer for patients receiving oral azacitidine than for those receiving placebo (24.7 months versus 14.8 months; P < 0.001). Median relapse-free survival was also significantly longer with oral azacitidine (10.2 months versus 4.8 months; P < 0.001). "The OS benefit with oral azacitidine was observed across different subgroups, including patients with persistent measurable residual disease after intensive chemotherapy," comments lead investigator Andrew Wei.

The incidence of grade 3–4 adverse events (72% versus 63%) and the number of treatment-related deaths (9 versus 4) were higher in the oral azacitidine group than in the placebo group. However, no meaningful differences in patient-reported quality of life were observed between treatment groups using questionnaires to evaluate changes from baseline scores.

"this oral agent represents an attractive option for patients for whom outpatient treatment is preferred"

On the basis of these findings, on 1 September 2020 the FDA approved oral azacitidine for the maintenance treatment of adults with AML in first remission after intensive chemotherapy. "Looking forward, this oral agent represents an attractive option for patients for whom outpatient treatment is preferred," explains Wei. "Future clinical trials will address the feasibility and efficacy of oral azacitidine in combination with other orally administered targeted agents, for example, venetoclax," he adds. In addition, a randomized trial is evaluating oral azacitidine as maintenance therapy for AML after consolidative HSCT. The results of this study are eagerly awaited.

References
Original article
Wei, A. H. et al. Oral azacitidine maintenance therapy for acute myeloid leukemia in first remission. N. Engl. J. Med. 383, 2526–2537 (2020)

CAS

Article

Google Scholar

Nature Reviews Clinical Oncology, Published online: 18 January 2021; doi:10.1038/s41571-021-00475-3

New maintenance option for AML
View on the web

Clinical significance of skeletal muscle density and sarcopenia in patients with pancreatic cancer undergoing first-line chemotherapy: a retrospective observational study

Cancer shared this article with you from Inoreader

12885.jpg

Abstract

Background

To investigate the clinical impact of sarcopenia and skeletal muscle density (SMD) among patients with metastatic pancreatic adenocarcinoma who underwent palliative first line gemcitabine-based chemotherapy.

Methods

A total of 330 patients treated with first line gemcitabine-based chemotherapy between January 2010 and March 2017 were included. CT scans before chemotherapy and after 8±2 weeks were evaluated. The L3 skeletal muscle index (SMI) was used to detect sarcopenia and calculated as the total area of the L3 skeletal muscle divided by the height-squared (cm2/m2). SMD was quantified as the mean muscle radiation attenuation of the muscle cross-sectional area across the L3 vertebral body level and was assessed between − 29 and + 150 Hounsfield units.

Results

A SMI to SMD comparison revealed a positive correlation (R2 = 0.058, P < 0.001). Compared with high SMD, the risks of low SMI were 1.516 (95% confidence interval [CI]: 1.164–1.973) among patients with low SMD. Kaplan–Meier analysis showed that the low SMD was related to poor overall survival (OS, median, 6.1 versus [vs.] 7.9 months, P = 0.010). Multivariate analysis using Cox regression showed that low SMI (hazard ratio [HR]: 1.35, 95% CI: 1.03–1.78, P = 0.032) and low SMD (HR: 1.45, 95% CI: 1.09–1.93, P = 0.011) were poor prognostic factors for OS, respectively. Co-presence of low SMI and low SMD had more powerful prognostic implication for OS (HR: 1.58, 95% CI: 1.12–2.23, P = 0.010). Grade 3 or higher toxicity of chemotherapy was more frequently observed in patients who have a low SMI (43% vs. 59%, P = 0.019) and low SMD (44% vs. 60%, P = 0.023). OS was not related to S MD status among patients who were chemotherapy responders (complete or partial responses). However, among non-responders (stable or progressive disease), low SMD groups had significantly poorer OS in comparison with high SMD groups (median, 5.6 vs 7.4 months, P = 0.006).

Conclusions

Sarcopenia and SMD status can be considered a prognostic factor in patients with metastatic pancreatic adenocarcinoma who received palliative first line gemcitabine-based chemotherapy. Severe chemotherapy toxicity occurred in the sarcopenia and low SMD groups. Our data suggest that a comprehensive assessment of skeletal muscle parameters may be more useful prognostic factors.

View on the web

Racial/ethnic differences in average CA125 and CA15.3 values and its correlates among postmenopausal women

Cancer shared this article with you from Inoreader

10552.jpg

Abstract

Purpose

Among healthy postmenopausal women, levels of CA125 and CA15.3 are influenced by demographic and reproductive factors, including race/ethnicity. In this study, we sought to examine the interaction between race/ethnicity and other correlates of these biomarkers and whether the racial differences observed are simply determined by other correlates with racial differences.

Methods

In archived sera from 946 postmenopausal women who participated in the 2001–2002 cycle of the National Health and Nutrition Examination Survey, we measured CA125 and CA15.3 and examined their associations with health survey and examination data available in this cohort. We used multivariable linear regression to examine the association between CA125 and CA15.3 and race/ethnicity. We then calculated geometric means of these markers by demographic and reproductive factors stratified by race/ethnicity and used likelihood ratio tests to evaluate heterogeneity.

Results

Non-white race was associated with lower CA125, with Non-Hispanic Black women being associated with − 29.0% (95% CI − 42.5%, − 12.2%) difference and Mexican American women being associated with − 6.4% (95% CI − 18.1%, 6.9%) difference on average compared to Non-Hispanic White women. Associations between CA125 and age and parity varied by race/ethnicity. Non-Hispanic Black women were associated with higher CA15.3 compared to Non-Hispanic White women, with 17.3% (95% CI − 0.5%, 38.3%) differences on average. Associations between CA15.3 and age, number of births, and age at natural menopause varied by race/ethnicity.

Conclusions

Among postmenopausal women, Non-Hispanic Black women were associated with lower CA125 and higher CA15.3 levels compared to Non-Hispanic White women. Our results support that race/ethnicity should be considered when assigning thresholds for these biomarkers being tested for diagnostic or screening purposes.

View on the web

Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy versus cytoreductive surgery alone for colorectal peritoneal metastases (PRODIGE 7): a multicentre, randomised, open-label, phase 3 trial

Cancer shared this article with you from Inoreader
Considering the absence of an overall survival benefit after adding HIPEC to cytoreductive surgery and more frequent postoperative late complications with this combination, our data suggest that cytoreductive surgery alone should be the cornerstone of therapeutic strategies with curative intent for colorectal peritoneal metastases.
View on the web