Search

Background: Nonadherence to imatinib is common in patients with gastrointestinal stromal tumor (GIST), which is associated with poor prognosis and financial burden. The primary aim of this study was to investigate the adherence rate in patients with GIST and subsequently develop a model based on machine learning (ML) and deep learning (DL) techniques to identify the associated factors and predict the risk of imatinib nonadherence., Methods: All eligible patients completed four sections of questionnaires. After the data set was preprocessed, statistically significance variables were identified and further processed to modeling. Six ML and four DL algorithms were applied for modeling, including eXtreme gradient boosting, light gradient boosting machine (LGBM), categorical boosting, random forest, support vector machine, artificial neural network, multilayer perceptron, NaiveBayes, TabNet, and Wide&Deep. The optimal ML model was used to identify potential factors for predicting adherence., Results: A total of 397 GIST patients were recruited. Nonadherence was observed in 185 patients (53.4%). LGBM exhibited superior performance, achieving a mean f1_score of 0.65 and standard deviation of 0.12. The predominant indicators for nonadherent prediction of imatinib were cognitive functioning, whether to perform therapeutic drug monitoring (if_TDM), global health status score, social support, and gender., Conclusions: This study represents the first real-world investigation using ML techniques to predict risk factors associated with imatinib nonadherence in patients with GIST. By highlighting the potential factors and identifying high-risk patients, the multidisciplinary medical team can devise targeted strategies to effectively address the daily challenges of treatment adherence., (© 2024 American Cancer Society.)

Background: The emergence of novel and efficient antibody maintenance approaches has provided more options for post-induction treatment of advanced follicular lymphoma (FL), and further comparisons are required to determine the most clinically beneficial regimen. The authors conducted a systematic review and meta-analysis to evaluate the maintenance or consolidation strategy., Methods: The authors performed two independent searches in PubMed, Web of Science, the Cochrane library databases, Scopus, and Embase for randomized controlled trials (RCTs) evaluating maintenance or consolidation therapy in untreated FL patients. Extracted data included the clinical characteristics, treatment regimen, progression-free survival (PFS), overall survival (OS), and adverse effects. They then pooled the data and used a Bayesian random-effects model to combine direct comparisons with indirect evidence., Results: The authors screened 1515 records and identified 13 eligible RCTs that assessed nine different regimens in 5681 advanced FL patients. Reconstructed individual survival data presented that obinutuzumab had the highest effect sizes and certainty of the evidence for PFS (hazard ratio, 0.43; 95% confidence interval, 0.22-0.79) and tolerability compared with observation. However, no benefit was observed in patients according to the OS, regardless of which regimen was taken. Considering other regimens, although an extended course of rituximab maintenance and consolidation therapies presented PFS benefits compared with standard rituximab maintenance, they were also associated with higher toxicity., Conclusions: Although obinutuzumab and rituximab maintenance treatment improved PFS significantly, its clinical benefit requires further validation in larger populations. Furthermore, because few trials informed each treatment comparison, research is needed to refine the understanding of this complex and rapidly evolving treatment landscape., (© 2023 American Cancer Society.)

Background: Although colorectal cancer (CRC) mortality rates are declining, racial-ethnic disparities in CRC mortality nationally are widening. Herein, the authors attempted to identify county-level variations in this pattern, and to characterize counties with improving disparity trends., Methods: The authors examined 20-year trends in US county-level black-white disparities in CRC age-adjusted mortality rates during the study period between 1989 and 2010. Using a mixed linear model, counties were grouped into mutually exclusive patterns of black-white racial disparity trends in age-adjusted CRC mortality across 20 three-year rolling average data points. County-level characteristics from census data and from the Area Health Resources File were normalized and entered into a principal component analysis. Multinomial logistic regression models were used to test the relation between these factors (clusters of related contextual variables) and the disparity trend pattern group for each county., Results: Counties were grouped into 4 disparity trend pattern groups: 1) persistent disparity (parallel black and white trend lines); 2) diverging (widening disparity); 3) sustained equality; and 4) converging (moving from disparate outcomes toward equality). The initial principal component analysis clustered the 82 independent variables into a smaller number of components, 6 of which explained 47% of the county-level variation in disparity trend patterns., Conclusions: County-level variation in social determinants, health care workforce, and health systems all were found to contribute to variations in cancer mortality disparity trend patterns from 1990 through 2010. Counties sustaining equality over time or moving from disparities to equality in cancer mortality suggest that disparities are not inevitable, and provide hope that more communities can achieve optimal and equitable cancer outcomes for all. Cancer 2016;122:1735-48. © 2016 American Cancer Society., (© 2016 American Cancer Society.)

Background: The human double minute 2 (hdm2) oncogene is a negative regulator of the p53 gene. Expression and alternative splicing of the hdm2 gene may contribute to colorectal cancer development or progression. This study aimed to determine the presence and identification of aberrant mRNA transcripts of hdm2 in colorectal cancer tissues and cell lines, and determine the nature of their association with clinicopathological characteristics and survival of patients., Methods: A total of 69 colorectal cancer and corresponding normal tissue specimens and 10 colon cancer cell lines were recruited for polymerase chain reaction and DNA sequencing analyses of hdm2 mRNA. Genomic DNA from these tissues and cells was also extracted for p53 gene mutation analysis. The association of hdm2 fragmented transcripts and p53 gene mutation with clinicopathological data was then statistically analyzed., Results: In 62 cases (89.9%; 62 of 69) of colorectal cancer tissues the full-length hdm2 was amplified, whereas 7 cases had no hdm2 transcripts. Thirty-two of 62 cases (51.6%) and 6 of 10 cell lines (60%) showed at least 1 hdm2 spliced variant. A total of 4 hdm2 splicing variants were found in colorectal cancer tissues and cells, that is, lack of nucleotides between 157 and 292 bp in hdm2/1338, 81 to 901 bp in hdm2/707, 157 to 292, 407 to 505, and 668 to 901 bp in hdm2/1007, and 610 to 883 in hdm2/1200. Of these, hdm2/1338 is a novel hdm2 variant in colorectal cancer. Mutation in p53 was detected in 21 cases (33.8%; 21 of 62). Although there was no association found between expression of hdm2 splicing variants and p53 gene mutations, expression of hdm2 splicing variants was associated with advanced tumor stage (P = .022) and distant metastasis (P = .004) in wild-type p53 cases, and with poor survival of patients (P = .039)., Conclusions: The data from the current study provide the first evidence that hdm2 mRNA is frequently mutated by alternative splicing in colorectal cancer, and may play a role in colorectal tumorigenesis or cancer progression., (Copyright © 2011 American Cancer Society.)

Background: In patients with multiple myeloma, renal impairment (RI) at the time of diagnosis is associated with poor survival. To the authors' knowledge, the current retrospective analysis presented is the first to assess the impact of various degrees of renal dysfunction on safety and efficacy outcomes in a large cohort of patients with relapsed and/or refractory multiple myeloma who received treatment with lenalidomide plus dexamethasone., Methods: Three hundred fifty-three patients from 2 large phase 3 trials were randomized to receive lenalidomide (25 mg) plus dexamethasone (40 mg). For the purpose of this analysis, RI was defined according to the calculated creatinine clearance (CLCr) level as follows: mild or no RI (CLCr>or=60 mL/minute), moderate RI (CLCr from >or=30 mL/minute to <60 mL/minute), and severe RI (CLCr<30 mL/minute)., Results: The RI subgroups did not differ significantly in terms of the overall response rate (range, 50%-64%) or response quality (very good partial response or better, 27%-37%). In all RI subgroups, the time to progression and progression-free survival did not differ significantly compared with the mild or no RI group. Patients with RI experienced an increased incidence of thrombocytopenia, required more frequent lenalidomide dose reduction or interruption, and had shorter overall survival than patients with mild or no RI (P=.006). Lenalidomide plus dexamethasone led to improvement in renal function in the majority of patients., Conclusions: The results from this study indicated that, with careful monitoring of the CLCr level and adverse events as well as appropriate dose adjustments, lenalidomide plus dexamethasone is an effective and well tolerated treatment option for patients with multiple myeloma who have RI., (Copyright (c) 2010 American Cancer Society.)

Background: Hepatoma specific gamma-glutamyl transferase (HS-GGT) bands were expressed in the development of hepatocellular carcinoma (HCC) and were associated with a high incidence of HCC diagnosis. The objectives of this study were to determine the levels of HS-GGT quantitatively in the sera of patients with different liver diseases. The methylational status of GGT gene CCGG sites was analyzed in hepatoma tissues., Methods: The HS-GGT concentrations were quantitatively analyzed in the sera of 156 HCC patients and others with liver diseases or extrahepatic tumors. In 20 hepatoma tissues, the GGT enzyme proteins were purified, the activities of GGTs of different molecular form were examined, total RNAs were extracted and amplified by using a nested polymerase chain reaction (PCR) assay, and the methylational status of CCGG site (M3) in the 5'-noncoding region of GGT genes was investigated with the restriction enzyme Hpa II., Results: Total GGT activities in patients with liver diseases and extrahepatic tumors were abnormally increased. The levels of serum HS-GGT were significantly elevated (P < 0.001) in the HCC group; the incidence of HS-GGT over 5.5 IU/L was 86% in HCC patients and less than 3% in patients with other diseases. From liver cancer to distal noncancerous tissues, an increasing tendency (P < 0.05) of total RNA concentrations was found; the frequencies of amplified fragment and hypomethylated M3 site of GGT genes were 100% and 75% in HCC, 85% and 55% in paracancerous tissues, and 75% and 50% in noncancerous tissues, respectively. An inverse correlation was found between methylational degrees of GGT genes and expression levels of GGT., Conclusions: The abnormal alteration of serum HS-GGT level is a sensitive tumor marker for HCC diagnosis or differentiation, and the overexpression of GGT in HCC may be related to the hypomethylational status of CCGG sites of GGT genes., (Copyright 2000 American Cancer Society.)

Background: This study was conducted to determine whether the paranasal extension of a primary non-Hodgkin's lymphoma (NHL) of the nasal cavity has any deleterious effect on patient outcome., Methods: One hundred and seventy-five patients with previously untreated nasal NHL were reviewed. There were 2 with low grade, 107 with intermediate grade, 17 with high grade, and 49 with unclassifiable lymphomas. In 48 cases the immunophenotype was available and 46 were T-cell lymphoma. According to the Ann Arbor system, there were 133 patients with Stage IE, 28 with Stage IIE, 4 with Stage IIIE, and 10 with Stage IVE lymphomas. Stage IE was subdivided into limited Stage IE (i.e., confined to the nasal cavity [67 patients]) or extensive Stage IE (i.e., presenting with extension beyond the nasal cavity [66 patients]). For patients with limited Stage IE disease the treatment of choice was radiotherapy with or without chemotherapy. In patients with extensive Stage IE disease, treatment was comprised of a combination of chemotherapy and radiotherapy or radiotherapy alone. For patients with a more advanced stage of disease (IIE-IVE), chemotherapy was an integral part of the treatment and was completed by irradiation, especially for patients with Stage IIE disease., Results: The actuarial overall survival (OS) and disease free survival (DFS) rates at 5 years for the whole group were 65% and 57%, respectively. The 5-year OS and DFS rates were influenced by stage, with a gradual decrease from 75% and 68% for Stage IE disease to 35% and 28% for Stage IIE disease, and 31% and 19% for Stage IIIE/IVE disease. Patients with limited Stage IE disease survived significantly longer (90% 5-year OS) compared with those with extensive Stage IE disease (57% 5-year OS; P < 0.001). For 67 patients with limited Stage IE disease, the 5-year OS was 89% with radiotherapy alone and 92% with radiotherapy and chemotherapy, whereas for 66 patients with extensive Stage IE disease, the 5-year OS was 54% with radiotherapy and 58% with combined modality therapy or chemotherapy (P > 0.05)., Conclusions: The prognosis of patients with primary NHL of the nasal cavity is stage dependent. In this large cohort of Stage IE patients, it was demonstrated that the paranasal local extension was a significant prognostic factor associated with poorer treatment outcome. The authors believe that Ann Arbor Stage IE should be subclassified further into limited and extensive Stage IE. The addition of chemotherapy did not appear to modify significantly the survival of patients with either limited or extensive Stage IE disease. The extranodal progression observed in patients with extensive Stage IE and Stage IIE-IVE disease clearly illustrates the need for improvement of systemic treatment.

Lymphokine-activated killer (LAK) cells play a major role in the induction of the vascular leak syndrome (VLS). To understand the mechanism of this syndrome, the authors examined light and electron microscopic alterations in the lung, liver, spleen, kidney, and heart of mice in which VLS was produced by the administration of interleukin-2 (IL-2) (seven injections of 600,000 IU each for a period of 4 days). The results of these studies disclosed that considerable damage had been done to the endothelial cells that consisted of cytoplasmic edema, vacuoles, and myelin figures; in addition, there were frequent sites of transendothelial passage of lymphoid cells, probably IL-2-activated cells, that penetrated through their cytoplasm by means of "temporary migration pores" and accumulated in the perivascular spaces. The results of this study indicate that a direct in vivo interaction between IL-2-activated cells (probably LAK cells) and endothelium results in cytotoxicity to endothelial cells.