Τετάρτη 2 Δεκεμβρίου 2020

Allogeneic stem cell transplant in patients with acute myeloid leukemia and karnofsky performance status score less than or equal to 80%: A study from the acute leukemia working party of the European Society for Blood and Marrow Transplantation (EBMT)

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Allogeneic stem cell transplant in patients with acute myeloid leukemia and karnofsky performance status score less than or equal to 80%: A study from the acute leukemia working party of the European Society for Blood and Marrow Transplantation (EBMT)

Graft‐versus‐host disease‐free, relapse‐free survival in patients with KPS score < 80% receiving MAC or RIC regimen.


Abstract

Limited data are currently available on the outcome of patients with acute myeloid leukemia (AML) undergoing allogeneic stem cell transplantation (allo‐SCT) with a reduced performance status. We herein present the results of a registry study on 2,936 AML patients undergoing allo‐SCT in first remission (CR1) with a Karnofsky Performance Status (KPS) score less than or equal to 80%. Two‐year leukemia‐free survival (LFS), overall survival (OS) and graft‐versus‐host disease (GVHD)‐free, and relapse‐free survival (GRFS) rates were 54%, 59%, and 41%, respectively. In multivariable analysis, patients with a KPS score = 80% had lower non‐relapse mortality (NRM) and superior OS in comparison to patients with a KPS score <80% (p < 0.001). In the subgroup of patients with a KPS score =80%, a reduced‐intensity conditioning (RIC) regimen was associated with an increased risk of relapse (p = 0.002) and lower GRFS (< i>p < 0.001) compared to myeloablative conditioning (MAC). Differently, in patients with a KPS score <80%, a RIC regimen resulted in lower NRM (p < 0.001), whereas relapse incidence did not differ, thus leading to an improved GRFS (p = 0.008) as compared to MAC. A transplant from a matched sibling donor (MSD) was associated with a reduced incidence of grade III‐IV acute GVHD (p < 0.01) and NRM (p < 0.01) in comparison to other donor types. In conclusion, allo‐SCT appears feasible in AML patients with a jeopardized KPS score. Survival is significantly affected by the conditioning intensity, which should be adjusted according to the severity of KPS impairment.

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Patterns of distant metastases in patients with clear cell renal cell carcinoma

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Patterns of distant metastases in patients with clear cell renal cell carcinoma––A population‐based analysis

Lung was the most common metastatic site in ccRCC patients. Different survivals and prognostic factors were identified for different metastatic patterns. Hence, our study would have great value for clinical practice in the future.


Abstract

We developed this study to describe the patterns of distant metastasis (DM) and explore the predictive and prognostic factors of DM in clear cell renal cell carcinoma (ccRCC) patients. We collected the eligible patients from the Surveillance, Epidemiology, and End Result (SEER) database from 2010 to 2015. Then, comparisons of baseline characteristics between patients in different metastatic patterns were made. In addition, proportional mortality ratios (PMRs) and proportion trends of different patterns were calculated. Afterward, survival outcomes were explored by Kaplan–Meier (KM) analyses. Finally, predictive and prognostic factors of DM were investigated. A total of 33,449 ccRCC patients were eventually identified, including 2931 patients with DM and 30,518 patients without DM. 8.76% of patients suffered DM at their initial diagnosis, 35.01% of them had multiple metastases. Generally, lung (6.19%) was the most common metastatic site in patients with DM, and brain (1.20%) was the least frequent metastatic organ. The proportion trends of different metastatic patterns tended to be stable between 2010 and 2015. Moreover, higher tumor grade, T stage, and N stage were identified as risk factors of DM. Finally, age at diagnosis, grade, T stage, N stage, the administration of surgery, the number of metastatic sties, marital status, and household income were found to be significantly associated with prognosis. Lung was the most common metastatic site in ccRCC patients. Different survival outcomes and prognostic factors were identified for different metastatic patterns. Hence, our study would have great value for clinical practice in the future.

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Evaluating determinants of receipt of molecular imaging in biochemical recurrent prostate cancer

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Evaluating determinants of receipt of molecular imaging in biochemical recurrent prostate cancer

This study evaluated the determinants of and cost associated with utilization of molecular imaging for biochemically recurrent prostate cancer. Higher prostate‐specific antigen level was associated with lower likelihood for molecular imaging and higher cost in a 1‐year timeframe.


Abstract

Background

Molecular imaging with novel radiotracers is changing the treatment landscape in prostate cancer (PCa). Currently, standard of care includes either conventional and molecular imaging at time of biochemical recurrence (BCR). This study evaluated the determinants of and cost associated with utilization of molecular imaging for BCR PCa.

Methods

This is a retrospective observational cohort study among men with BCR PCa from June 2018 to May 2019. Multivariate logistic regression models were employed to analyze the primary outcome: receipt of molecular imaging (e.g. Fluciclovine PET and Prostate Specific Membrane Antigen PET) as part of diagnostic work‐up for BCR PCa. Multivariate linear regression models were used to analyze the secondary outcome: overall healthcare cost within a 1‐year time frame.

Results

The study sample included 234 patients; 79.1% White, 2.1% Black, 8.5% Asian/Pacific Islander, and 10.3% Other. The majority were 55 years or older (97.9%) and publicly insured (74.8%). Analysis indicated a one‐unit reduction in PSA is associated with 1.3 times higher likelihood of receiving molecular imaging (p < 0.01). Analysis found that privately insured patients were associated with approximately $500,000 more in hospital reimbursement (p < 0.01) as compared to the publicly insured. Additionally, a one‐unit increase in PSA is associated with $6254 increase in hospital reimbursement or an increase in total payments by 2.1% (p < 0.05).

Conclusions

Higher PSA was associated with lower likelihood for molecular imaging and higher cost in a one‐year time frame. Higher cost was also associated with private insurance, but there was no clear relationship between insurance type and imaging type.

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Risk of breast cancer in women after a salivary gland carcinoma or pleomorphic adenoma

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Risk of breast cancer in women after a salivary gland carcinoma or pleomorphic adenoma in the Netherlands

Salivary and mammary gland tumors share biological and epidemiological characteristics, suggesting common risk factors. Investigation of nationwide cohorts of patients with salivary gland cancer or pleomorphic adenoma with long‐term follow‐up data and complete cancer incidence information, highlights an increased risk of breast cancer in these patients.


Abstract

Salivary and mammary gland tumors show morphological similarities and share various characteristics, including frequent overexpression of hormone receptors and female preponderance. Although this may suggest a common etiology, it remains unclear whether patients with a salivary gland tumor carry an increased risk of breast cancer (BC). Our purpose was to determine the risk of BC in women diagnosed with salivary gland carcinoma (SGC) or pleomorphic adenoma (SGPA). BC incidence (invasive and in situ) was assessed in two nationwide cohorts: one comprising 1567 women diagnosed with SGC and one with 2083 women with SGPA. BC incidence was compared with general population rates using standardized incidence ratio (SIR). BC risk was assessed according to age at SGC/SGPA diagnosis, follow‐up time and (for SGC patients) histological subtype. The mean follow‐up was 7.0 years after SGC and 9.9 after SGPA diagnosis. During follow‐up, 52 patients with SGC and 74 patients with SGPA dev eloped BC. The median time to BC was 6 years after SGC and 7 after SGPA. The cumulative risk at 10 years of follow‐up was 3.1% after SGC and 3.5% after SGPA (95% Confidence Interval (95%CI) 2.1%–4.7% and 2.6%–4.6%, respectively). BC incidence was 1.59 times (95%CI 1.19–2.09) higher in the SGC‐cohort than expected based on incidence rates in the general population. SGPA‐patients showed a 1.48 times (95%CI 1.16–1.86) higher incidence. Women with SGC or SGPA have a slightly increased risk of BC. The magnitude of risk justifies raising awareness, but is no reason for BC screening.

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The stage‐specific roles of radiotherapy and chemotherapy in nodular lymphocyte predominant Hodgkin lymphoma patients: a propensity score‐matched analysis of the SEER database

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The stage‐specific roles of radiotherapy and chemotherapy in nodular lymphocyte predominant Hodgkin lymphoma patients: a propensity score‐matched analysis of the SEER database

Combined radiotherapy and chemotherapy (CRT) is associated with the best survival of patients with the early‐stage nodular lymphocyte predominant Hodgkin lymphoma (NLPHL). Timely intervention is beneficial to survival of patients with NLPHL, especially for elderly patients in early stages. For advanced‐stage NLPHL, chemotherapy alone and CRT are likely to be associated with the long‐term survival benefits.


Abstract

Background

The stage‐specific roles of radiotherapy (RT) alone, chemotherapy alone, and combined RT and chemotherapy (CRT) for patients with nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) have not been adequately evaluated.

Methods

We analyzed patients with all stages of NLPHL enrolled in the Surveillance, Epidemiology, and End Results (SEER) registry from January 2000 to December 2015. Propensity score (PS) analysis with 1:1 matching (PSM) was performed to ensure the well‐balanced characteristics of the comparison groups. Kaplan–Meier and Cox proportional‐hazards models were used to evaluate the overall survival (OS), cancer‐specific survival (CSS), hazard ratios (HRs), and corresponding 95% confidence intervals (95% CI). Restricted mean survival times (RMST) were also used for the survival analyses.

Results

For early‐stage patients, CRT was associated with the best survival, the mean OS was significantly improved by approximately 20 months (20 m), and the risk of death was reduced by more than 80%, both before and after PSM (p < 0.05). For advanced‐stage patients, none of RT alone, chemotherapy alone, or CRT had a significant effect on survival. Chemotherapy alone and CRT might be more beneficial for long‐term survival (RMST120 m: neither RT nor chemotherapy vs. chemotherapy alone vs. CRT = 104 m vs. 111 m vs. 108 m). Subgroup analysis of patients with early‐stage NLPHL showed that CRT was associated with better survival of elderly patients (improved OS = 43.8 m, HR = 0.14, p < 0.05). However, the survival benefits of treatments for young patients were not statistically significant. The efficacy of RT was significantly different between the age groups (p for interaction = 0.020).

Conclusions

These results from SEER data suggest that CRT may be considered for early‐stage NLPHL, especially for elderly patients. Further studies are needed to identify effective treatments in patients with advanced‐stage NLPHL.

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Trifluridine/tipiracil plus bevacizumab as a first‐line treatment for elderly patients with metastatic colorectal cancer (KSCC1602): A multicenter phase II trial

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Trifluridine/tipiracil plus bevacizumab as a first‐line treatment for elderly patients with metastatic colorectal cancer (KSCC1602): A multicenter phase II trial

We aimed to assess the efficacy and safety of FTD/TPI plus Bev in elderly patients with previously untreated metastatic colorectal cancer. The median PFS was 9.4 months as a primary endpoint, the median OS was 22.4 month, ORR was 40.5% and AEs were manageable. The combination of FTD/TPI plus Bev is an effective and well‐tolerated regimen for elderly patients with previously untreated metastatic colorectal cancer.


ABSTRACT

Background

A previous Phase I/II study demonstrated that TAS‐102 (trifluridine/tipiracil [FTD/TPI]) plus bevacizumab (Bev) has encouraging efficacy and controllable safety for patients with previously treated metastatic colorectal cancer. Therefore, we designed for assessing the efficacy and safety of FTD/TPI plus Bev in elderly patients with previously untreated metastatic colorectal cancer.

Methods

This is a multicenter, single‐arm Phase II study included patients ≥70 years old with previously untreated, unresectable metastatic colorectal cancer. Treatment consisted of FTD/TPI plus Bev given every 4 weeks. The primary endpoint was progression‐free survival (PFS), assuming a null hypothesis of a PFS of 5 months. The secondary endpoints were the overall survival (OS), overall response rate (ORR), and adverse events (AEs).

Results

Between 5 January 2017 and 13 March 2018, 39 patients were enrolled from 18 institutions. The median patient age was 76.0 years (range, 70–88); the ECOG‐PS was 0 in 24 patients and 1 in 15 patients. The median PFS was 9.4 months as a primary endpoint, and the median OS was 22.4 months. The ORR was 40.5% and the disease control rate was 86.5%. Grade 3–4 AEs included neutropenia (71.8%), leukopenia (51.3%), anorexia (15.4%), febrile neutropenia (10.3%), and fatigue (10.3%).

Conclusions

FTD/TPI plus Bev is an effective and well‐tolerated regimen for elderly patients with previously untreated metastatic colorectal cancer. Capecitabine/bevacizumab can be selected as a subsequent maintenance therapy without irinotecan and oxaliplatin because FTD/TPI has no cross‐resistance with 5‐fluorouracil.

Clinical trial registration: UMIN clinical trials registry (UMIN000025241).

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Low sodium diet for gastric cancer prevention

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Low sodium diet for gastric cancer prevention in the United States: Results of a Markov model

Using a Markov model of gastric cancer risk, we found that adherence to a low sodium‐DASH diet decreases the risk of gastric cancer in the U.S. population. This intervention was not cost‐effective due to the high cost of a low sodium‐DASH accordant diet, but significantly improved for certain high‐risk populations and when the cost of the diet became slightly more affordable.


Abstract

Background and Aims

High sodium consumption has been associated with an increased risk of gastric cancer. The mean daily sodium intake in the United States substantially exceeds the national recommended amount. The low sodium‐DASH diet has been shown to decrease the risk of cardiovascular disease in the United States, but its impact on gastric cancer has not been well studied. We therefore aimed to model the impact and cost‐effectiveness of the low sodium‐DASH diet for gastric cancer prevention in the U.S. population.

Methods

A Markov cohort state‐transition model was developed to simulate the impact of the low sodium‐DASH diet on gastric cancer outcomes for the average 40‐year‐old in the United States compared to no intervention. Primary outcomes of interest were gastric cancer incidence and incremental cost‐effectiveness ratios (ICER).

Results

Our model found that compared to the no intervention cohort, the risk of gastric cancer decreased by 24.8% for males and 21.2% for females on the low sodium‐DASH diet. 27 cases and 14 cases per 10,000 individuals were prevented for males and females, respectively, in the intervention group. The ICER for the low sodium‐DASH diet strategy was $287,726 for males and $423,878 for females compared to the no intervention strategy.

Conclusions

Using a Markov model of gastric cancer risk, we found that adherence to a low sodium‐DASH diet could decrease the risk of gastric cancer. This intervention was not cost‐effective due to the high cost of a low sodium‐DASH accordant diet, but significantly improved for high‐risk populations and when the cost of the diet became slightly more affordable.

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Tumor suppressing effects of tristetraprolin and its small double‐stranded RNAs in bladder cancer

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Tumor suppressing effects of tristetraprolin and its small double‐stranded RNAs in bladder cancer

TTP overexpression can inhibit the malignant biological behaviors of BCa, and can be a potential therapeutic target for BCa. dsTTP‐973 which can induce TTP expression in BCa is able to suppress BCa progression, and dsTTP‐973 may be a potential treatment for BCa in the future.


Abstract

Bladder cancer (BCa) is a common malignant tumor of urinary system with few treatments, so more useful therapeutic targets are still needed. Antitumor effects of tristetraprolin (TTP) have been explored in many type tumors, but its roles in bladder cancer are still unknown until now. In this study, public expression profiles and tissue microarray analysis showed that TTP mRNA and protein levels decreased in BCa relative to the normal bladder tissue. To explore biological functions of TTP in BCa, 488 TTP target genes, which could be both suppressed and bound by TTP, were identified by comprehensively analyzing publicly available high‐throughput data obtained from Gene Expression Omnibus (GEO). Gene enrichment analysis showed that these genes were enriched in pathways such as cell cycle, epithelial to mesenchymal transition (EMT), and Wnt signaling. Clustering analysis and gene set variation analysis indicated that patients with high expression of TTP target genes had poorer progn osis and stronger tumor proliferation ability relative to the BCa patients with low expression of TTP target genes. In vitro experiments validated that TTP could suppress proliferation, migration, and invasiveness of BCa cells. And TTP could suppress mRNA expression of cyclin‐dependent kinase 1 (CDK1) in BCa cells by target its 3′ UTR. Then, we identified a new small double‐stranded RNA (dsRNA) named dsTTP‐973 which could increase TTP expression in BCa cells, in vivo and in vitro experiments revealed that dsTTP‐973 could suppress aggressiveness of BCa. In conclusion, TTP played a role of tumor suppressor gene in BCa like other tumors, and its dsRNA named dsTTP‐973 could induce TTP expression in BCa and suppress aggressiveness of BCa. With the help of materials science, dsTTP‐973 may become a potential treatment for BCa in the future.

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Prediction of the World Health Organization Grade of rectal neuroendocrine tumors based on CT histogram analysis

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Prediction of the World Health Organization Grade of rectal neuroendocrine tumors based on CT histogram analysis

CECT histogram parameters, including arterial phase and venous phase, can be used as excellent indicators for predicting G1 and HG of rectal neuroendocrine tumors, and the size of the tumor is also an important independent predictor.


Abstract

Objectives

To investigate the diagnostic value of contrast‐enhanced computed tomography (CECT) histogram analysis in predicting the World Health Organization (WHO) grade of rectal neuroendocrine tumors (R‐NETs).

Materials and Methods

A total of 61 (35 G1, 12 G2, 10 G3, and 4 NECs) patients who underwent preoperative CECT and treated with surgery to be confirmed as R‐NETs were included in this study from January 2014 to May 2019. We depicted ROIs and measured the CECT texture parameters (mean, median, 10th, 25th, 75th, 90th percentiles, skewness, kurtosis, and entropy) from arterial phase (AP) and venous phase (VP) images by two radiologists. We calculated intraclass correlation coefficient (ICC) and compared the histogram parameters between low‐grade (G1) and higher grade (HG) (G2/G3/NECs) by applying appropriate statistical method. We obtained the optimal parameters to identify G1 from HG using receiver operating characteristic (ROC) curves.

Results

The capability of AP and VP histogram parameters for differentiating G1 from HG was similar in several histogram parameters (mean, median, 10th, 25th, 75th, and 90th percentiles) (all p < 0.001). Skewness, kurtosis, and entropy on AP images showed no significant differences between G1 and HG (p = 0.853, 0.512, 0.557, respectively). Entropy on VP images was significantly different (p = 0.017) between G1 and HG, however, skewness and kurtosis showed no significant differences (p = 0.654, 0.172, respectively). ROC analysis showed a good predictive performance between G1 and HG, and the 75th (AP) generated the highest area under the curve (AUC = 0.871), followed by the 25th (AP), mean (VP), and median (VP) (AUC = 0.864). Combined the size of tumor and the 75th (AP) generated the highest AUC.

Conclusions

CECT histogram parameters, including arterial and venous phases, can be used as excellent indicators for predicting G1 and HG of rectal neuroendocrine tumors, and the size of the tumor is also an important independent predictor.

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Impact of insurance and neighborhood socioeconomic status on clinical outcomes in therapeutic clinical trials for breast cancer

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Abstract

The objective of this study was to evaluate the impact of insurance and neighborhood SES (nSES) on chemotherapy completion and overall mortality among participants in breast cancer clinical trials. The data sources for this study were two adjuvant breast cancer trials (ECOG E1199 and E5103) collectively including 9790 women. Insurance status at trial registration was categorized into private, government (Medicaid, Medicare, and other government type insurance), and self‐pay. An Agency for Healthcare Research Quality (AHRQ) nSES index was calculated using residential zip codes linked to county level data on occupation, income, poverty, wealth, education, and crowding. Logistic regression and Cox Proportional Hazard models estimated odds ratios (OR) for chemotherapy treatment completion and hazard ratios (HR) for mortality, respectively, for insurance status and nSES. The models adjusted for: race, age, tumor size, nodal status, hormone receptor status, and primary surgery. The ma jority of patients had private insurance at trial registration: E1199: 85.6% (4154/4854) and E5103: 82.4% (3987/4836); median SES index was 53.8 (range: 41.8‐66.8) and 54.1 (range: 44.5‐66.1), respectively. Patients with government insurance were less likely to complete chemotherapy treatment (E1199 OR (95%CI): 0.73 (0.57‐0.94); E5103 0.76 (0.64‐0.91)) and had an increased risk of death (E1199 HR (95%CI): 1.44 (1.22‐1.70); E5103 1.29 (1.06‐1.58)) compared to the privately insured patients. There was no association between nSES and chemotherapy completion or overall mortality. Patients with government insurance at trial registration appeared to face barriers in chemotherapy completion and had a higher overall mortality compared to their privately insured counterparts.

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N6‐methyladenine‐related genes affect biological behavior and the prognosis of glioma

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N6‐methyladenine‐related genes affect biological behavior and the prognosis of glioma

The nine m6A‐related genes risk score was identified as a new potential prognostic biomarker in gliomas. The nomogram based on the nine m6A‐related genes signature and clinicopathological features had good efficacy in predicting the survival probability, which is pivotal to design individual therapy for patients with glioma


Abstract

Background

Although aberrant expression of N6‐methyladenine (m6A) methylation‐related genes contribute to tumorigenesis in many solid tumors, the prognostic value of the m6A‐related genes and their correlation with clinicopathological features in gliomas need advanced study.

Methods

The clinical and sequencing data of 288 patients with glioma were extracted from Chinese Glioma Genome Atlas database. By univariate and multivariable Cox regression analysis, the m6A‐related prognostic genes were identified, and their correlation with clinicopathological features was further analysis. A nomogram was constructed by R software and the performance of it was assessed by calibration and time‐dependent receiver operating characteristic curve.

Results

Nine m6A‐related genes were identified as independent prognostic factors, which were mostly enriched in RNA splicing, regulation of immune response and vesicle‐mediated transport. By expression value and regression coefficient of these genes, we constructed risk score of each patient, which was highly associated with clinicopathological features. Kaplan–Meier curve showed that the prognosis of patients with high‐risk scores was significantly worse than that with low‐risk scores (HR = 4.30, 95% CI = 3.16–5.85, p < 0.0001). A nomogram was constructed based on the nine m6A‐related genes signature and clinicopathological features with well‐fitted calibration curves (c‐index = 0.82), showing high specificity and sensitivity (area under the curve for 1‐, 3‐, and 5‐years survival probability = 0.874, 0.918, and 0.934).

Conclusions

A nine m6A‐related genes signature was identified in gliomas. The m6A‐related risk score is a novel prognostic factor for patients with glioma, and is associated with clinicopathological features. Moreover, the nomogram based on the nine m6A‐related genes signature and clinicopathological features had good efficacy in predicting the survival probability.

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