scholarly journals Preoperative clinical and tumor genomic features associated with pathologic lymph node metastasis in clinical stage I and II lung adenocarcinoma

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Raul Caso ◽  
James G. Connolly ◽  
Jian Zhou ◽  
Kay See Tan ◽  
James J. Choi ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Clinical Stage ◽  
Multivariable Analysis ◽  
Multivariable Logistic Regression Model ◽  
Genomic Features ◽  
Genome Doubling ◽  
Whole Genome Doubling ◽  
Metastatic Lung ◽  
Treatment Naïve ◽  
Patients At Risk

AbstractWhile next-generation sequencing (NGS) is used to guide therapy in patients with metastatic lung adenocarcinoma (LUAD), use of NGS to determine pathologic LN metastasis prior to surgery has not been assessed. To bridge this knowledge gap, we performed NGS using MSK-IMPACT in 426 treatment-naive patients with clinical N2-negative LUAD. A multivariable logistic regression model that considered preoperative clinical and genomic variables was constructed. Most patients had cN0 disease (85%) with pN0, pN1, and pN2 rates of 80%, 11%, and 9%, respectively. Genes altered at higher rates in pN-positive than in pN-negative tumors were STK11 (p = 0.024), SMARCA4 (p = 0.006), and SMAD4 (p = 0.011). Fraction of genome altered (p = 0.037), copy number amplifications (p = 0.001), and whole-genome doubling (p = 0.028) were higher in pN-positive tumors. Multivariable analysis revealed solid tumor morphology, tumor SUVmax, clinical stage, SMARCA4 and SMAD4 alterations were independently associated with pathologic LN metastasis. Incorporation of clinical and tumor genomic features can identify patients at risk of pathologic LN metastasis; this may guide therapy decisions before surgical resection.

scholarly journals Predicting Persistent Opioid Use, Abuse, and Toxicity Among Cancer Survivors

2019 ◽  
Vol 112 (7) ◽  
pp. 720-727 ◽  
Author(s):  
Lucas K Vitzthum ◽  
Paul Riviere ◽  
Paige Sheridan ◽  
Vinit Nalawade ◽  
Rishi Deka ◽  
...  
Keyword(s):  
Risk Factors ◽  
At Risk ◽  
Cancer Survivors ◽  
Critical Role ◽  
Multivariable Analysis ◽  
Area Under The Curve ◽  
Opioid Abuse ◽  
Opioid Use ◽  
Multivariable Logistic Regression Model ◽  
Patients At Risk

Abstract Background Although opioids play a critical role in the management of cancer pain, the ongoing opioid epidemic has raised concerns regarding their persistent use and abuse. We lack data-driven tools in oncology to understand the risk of adverse opioid-related outcomes. This project seeks to identify clinical risk factors and create a risk score to help identify patients at risk of persistent opioid use and abuse. Methods Within a cohort of 106 732 military veteran cancer survivors diagnosed between 2000 and 2015, we determined rates of persistent posttreatment opioid use, diagnoses of opioid abuse or dependence, and admissions for opioid toxicity. A multivariable logistic regression model was used to identify patient, cancer, and treatment risk factors associated with adverse opioid-related outcomes. Predictive risk models were developed and validated using a least absolute shrinkage and selection operator regression technique. Results The rate of persistent opioid use in cancer survivors was 8.3% (95% CI = 8.1% to 8.4%); the rate of opioid abuse or dependence was 2.9% (95% CI = 2.8% to 3.0%); and the rate of opioid-related admissions was 2.1% (95% CI = 2.0% to 2.2%). On multivariable analysis, several patient, demographic, and cancer and treatment factors were associated with risk of persistent opioid use. Predictive models showed a high level of discrimination when identifying individuals at risk of adverse opioid-related outcomes including persistent opioid use (area under the curve [AUC] = 0.85), future diagnoses of opioid abuse or dependence (AUC = 0.87), and admission for opioid abuse or toxicity (AUC = 0.78). Conclusion This study demonstrates the potential to predict adverse opioid-related outcomes among cancer survivors. With further validation, personalized risk-stratification approaches could guide management when prescribing opioids in cancer patients.

Utilization and predictors of neoadjuvant chemotherapy for muscle-invasive bladder cancer in the Veterans Health Administration.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4594-4594
Author(s):  
Gurdarshan Singh Sandhu ◽  
Suhong Luo ◽  
Angelique Zeringue ◽  
Kenneth Robert Carson ◽  
Kenneth Gerard Nepple ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Clinical Stage ◽  
Temporal Trends ◽  
Multivariable Analysis ◽  
Veterans Health Administration ◽  
Veterans Health ◽  
Health Administration ◽  
Multivariable Logistic Regression Model ◽  
Recent Diagnosis

4594 Background: The survival benefit with neoadjuvant chemotherapy for bladder cancer was established in 2003. However, adoption of this paradigm in clinical practice has been slow. We explored the use of neoadjuvant chemotherapy and identified predictors of its use in a contemporary cohort in the Veterans Health Administration (VA). Methods: Using the national VA Clinical Cancer Registry, all patients diagnosed with clinical stage T2-4, N0 or Nx, M0 bladder cancer from 1997 to 2007 were stratified into surgically (radical cystectomy [RC], n=1,211) and nonsurgically managed groups (n=2,125). Receipt of neoadjuvant chemotherapy was defined as chemotherapy treatment up to 6 months before RC as well as initial treatment only with chemotherapy (without subsequent surgery or radiation) in the nonsurgical group. Temporal trends in neoadjuvant chemotherapy use were evaluated with a chi square test. Predictors of neoadjuvant chemotherapy were examined using a multivariable logistic regression model incorporating demographic, socioeconomic, comorbid, pathologic and hospital factors. Results: 6.3% and 8.3% of patients received neoadjuvant chemotherapy in the surgical and non-surgical group, respectively. Analysis of temporal trends in chemotherapy use demonstrated an increase in neoadjuvant chemotherapy use over time (p<0.0001); from 3% (2003 and before) to 14% annually (2007). On multivariable analysis of both groups, older age and more recent diagnosis were predictive of neoadjuvant chemotherapy use (Table). Other covariates did not predict receipt of neoadjuvant chemotherapy. Conclusions: While overall use of neoadjuvant chemotherapy in the VA population with bladder cancer remains low, use thereof is slowly increasing, with a more recent diagnosis most strongly predicting its use. [Table: see text]

scholarly journals Evolution of late-stage metastatic melanoma is dominated by aneuploidy and whole genome doubling

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ismael A. Vergara ◽  
Christopher P. Mintoff ◽  
Shahneen Sandhu ◽  
Lachlan McIntosh ◽  
Richard J. Young ◽  
...  
Keyword(s):  
Large Scale ◽  
Point Mutations ◽  
Whole Genome ◽  
Sequencing Data ◽  
Genetic Changes ◽  
Genome Doubling ◽  
Whole Exome ◽  
Whole Genome Doubling ◽  
Treatment Naïve ◽  
Key Driver

AbstractAlthough melanoma is initiated by acquisition of point mutations and limited focal copy number alterations in melanocytes-of-origin, the nature of genetic changes that characterise lethal metastatic disease is poorly understood. Here, we analyze the evolution of human melanoma progressing from early to late disease in 13 patients by sampling their tumours at multiple sites and times. Whole exome and genome sequencing data from 88 tumour samples reveals only limited gain of point mutations generally, with net mutational loss in some metastases. In contrast, melanoma evolution is dominated by whole genome doubling and large-scale aneuploidy, in which widespread loss of heterozygosity sculpts the burden of point mutations, neoantigens and structural variants even in treatment-naïve and primary cutaneous melanomas in some patients. These results imply that dysregulation of genomic integrity is a key driver of selective clonal advantage during melanoma progression.

Improved Clinical Outcome in Recent Years for Men With Metastatic Nonseminomatous Germ Cell Tumors

2007 ◽  
Vol 25 (35) ◽  
pp. 5603-5608 ◽  
Author(s):  
Brett S. Carver ◽  
Angel M. Serio ◽  
Dean Bajorin ◽  
Robert J. Motzer ◽  
Jason Stasi ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Germ Cell ◽  
Clinical Stage ◽  
Multivariable Analysis ◽  
Germ Cell Tumors ◽  
Retroperitoneal Lymph Node Dissection ◽  
Stage Migration ◽  
Multivariable Logistic Regression Model ◽  
Nodal Size ◽  
Nonseminomatous Germ Cell Tumors

Purpose The integration of chemotherapy and surgery for metastatic nonseminomatous germ cell tumors (NSGCT) results in survival rates of greater than 80% overall. We evaluated men undergoing postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) for NSGCT to determine associations between year of treatment and clinical outcome. Patients and Methods We evaluated 504 men who underwent PC-RPLND from 1989 to 2002 for NSGCT at our center. Data were obtained from our prospective surgical database and a multivariable logistic regression model was constructed to evaluate variables associated with 15-month relapse in 392 patients with complete data. Results From 1989 to 1997, clinical stage IIa, IIb, IIc, and III NSGCT was seen in 4%, 20%, 23%, and 47% of patients, respectively, compared with 18%, 26%, 11%, and 38%, respectively, from 1998 to 2002 (P < .001). The median prechemotherapy nodal size for 1989 to 1997 and 1998 to 2002 was 5.0 and 3.5 cm, respectively (P < .001). On multivariable analysis, prechemotherapy retroperitoneal nodal size (odds ratio [OR], 1.12; 95% CI, 1.03 to 1.21; P = .005) and presence of visceral metastasis (OR, 2.10; 95% CI, 1.02 to 4.33; P = .04) were significantly associated with 15-month relapse. Men who received a complete RPLND were significantly less likely to experience relapse (OR, 0.22; 95% CI, 0.09 to 0.50; P < .0005). Conclusion In more recent years, men are presenting with less advanced metastatic NSGCT. This stage migration together with effective therapy has resulted in an improved relapse-free survival.

scholarly journals Whole-Genome Doubling Affects Pre-miRNA Expression in Plants

Plants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1004
Author(s):  
Salvatore Esposito ◽  
Riccardo Aversano ◽  
Pasquale Tripodi ◽  
Domenico Carputo
Keyword(s):  
Dna Repair ◽  
Mirna Expression ◽  
Building Blocks ◽  
Nucleotide Metabolism ◽  
Integrative Approach ◽  
Whole Genome ◽  
Solanum Commersonii ◽  
Genome Doubling ◽  
Whole Genome Doubling ◽  
Micro Rnas

Whole-genome doubling (polyploidy) is common in angiosperms. Several studies have indicated that it is often associated with molecular, physiological, and phenotypic changes. Mounting evidence has pointed out that micro-RNAs (miRNAs) may have an important role in whole-genome doubling. However, an integrative approach that compares miRNA expression in polyploids is still lacking. Here, a re-analysis of already published RNAseq datasets was performed to identify microRNAs’ precursors (pre-miRNAs) in diploids (2x) and tetraploids (4x) of five species (Arabidopsis thaliana L., Morus alba L., Brassica rapa L., Isatis indigotica Fort., and Solanum commersonii Dun). We found 3568 pre-miRNAs, three of which (pre-miR414, pre-miR5538, and pre-miR5141) were abundant in all 2x, and were absent/low in their 4x counterparts. They are predicted to target more than one mRNA transcript, many belonging to transcription factors (TFs), DNA repair mechanisms, and related to stress. Sixteen pre-miRNAs were found in common in all 2x and 4x. Among them, pre-miRNA482, pre-miRNA2916, and pre-miRNA167 changed their expression after polyploidization, being induced or repressed in 4x plants. Based on our results, a common ploidy-dependent response was triggered in all species under investigation, which involves DNA repair, ATP-synthesis, terpenoid biosynthesis, and several stress-responsive transcripts. In addition, an ad hoc pre-miRNA expression analysis carried out solely on 2x vs. 4x samples of S. commersonii indicated that ploidy-dependent pre-miRNAs seem to actively regulate the nucleotide metabolism, probably to cope with the increased requirement for DNA building blocks caused by the augmented DNA content. Overall, the results outline the critical role of microRNA-mediated responses following autopolyploidization in plants.

Long-term success of flexible endoscopic septal division with the stag beetle knife for Zenker’s diverticulum: a tertiary center study

2020 ◽  
Vol 33 (11) ◽  
Author(s):  
Sauid Ishaq ◽  
Keith Siau ◽  
Minhong Lee ◽  
Haleema Sultan ◽  
Shalmani H Mohaghegh ◽  
...  
Keyword(s):  
Cox Regression ◽  
Multivariable Analysis ◽  
Zenker’S Diverticulum ◽  
Long Term Outcome ◽  
Zenker's Diverticulum ◽  
Tertiary Center ◽  
Symptom Remission ◽  
Treatment Naïve ◽  
Symptom Recurrence

Summary Objectives Flexible endoscopic septum division is an established treatment for Zenker’s diverticulum (ZD); however, long-term outcome data are lacking. We aimed to evaluate the long-term efficacy of flexible endoscopic septal division (FESD) using the stag beetle knife for ZD and identify predictors of symptom recurrence. Methods Patients undergoing the procedure between 2013 and 2018 were prospectively enrolled. Procedures were performed by a single operator. Symptom severity pre- and postprocedure was recorded using the dysphagia, regurgitation, and complications scale. Symptom recurrence was defined as a total score &gt; 1 after the index procedure. Time-to-event analyses were performed using Kaplan–Meier plots, with multivariable analyses performed using Cox regression models. Results Altogether, 65 patients (mean age 74.0 years, 60% male) were included. Previous stapling had been performed in 44.6% of patients. Over the mean posttreatment follow-up period of 19 months, 5.6% of the treatment naïve group and 34.5% of the recurrent group underwent repeated FESD (P = 0.003), with rates of symptom remission and improvement of 75.4% and 92.7%, respectively. Recurrence at 48 months was higher in patients with recurrent ZD (84.7%) than in treatment-naïve patients (10.7%). On multivariable analysis, recurrent disease (hazard ratio [HR] 20.8, P = 0.005) and younger age (HR 0.96/year, P = 0.047) were associated with symptom recurrence. Conclusions In patients with treatment-naïve ZD, flexible endoscopic septal division is safe and provides durable symptom remission. However, in patients with poststapling recurrence, the risk of recurrence is high and time-dependent.

scholarly journals High prevalence of TP53 loss and whole-genome doubling in early-onset colorectal cancer

2021 ◽  
Author(s):  
Jeong Eun Kim ◽  
Jaeyong Choi ◽  
Chang-Ohk Sung ◽  
Yong Sang Hong ◽  
Sun Young Kim ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Early Onset ◽  
Large Scale ◽  
Late Onset ◽  
Age Groups ◽  
The Cancer Genome Atlas ◽  
Whole Genome ◽  
Genome Doubling ◽  
Whole Genome Doubling ◽  
Early Onset Colorectal Cancer

AbstractThe global incidence of early-onset colorectal cancer (EO-CRC) is rapidly rising. However, the reason for this rise in incidence as well as the genomic characteristics of EO-CRC remain largely unknown. We performed whole-exome sequencing in 47 cases of EO-CRC and targeted deep sequencing in 833 cases of CRC. Mutational profiles of EO-CRC were compared with previously published large-scale studies. EO-CRC and The Cancer Genome Atlas (TCGA) data were further investigated according to copy number profiles and mutation timing. We classified colorectal cancer into three subgroups: the hypermutated group consisted of mutations in POLE and mismatch repair genes; the whole-genome doubling group had early functional loss of TP53 that led to whole-genome doubling and focal oncogene amplification; the genome-stable group had mutations in APC and KRAS, similar to conventional colon cancer. Among non-hypermutated samples, whole-genome doubling was more prevalent in early-onset than in late-onset disease (54% vs 38%, Fisher’s exact P = 0.04). More than half of non-hypermutated EO-CRC cases involved early TP53 mutation and whole-genome doubling, which led to notable differences in mutation frequencies between age groups. Alternative carcinogenesis involving genomic instability via loss of TP53 may be related to the rise in EO-CRC.

High PD-L1 expression correlates with primary resistance to EGFR-TKIs in treatment naïve advanced EGFR-mutant lung adenocarcinoma patients

Lung Cancer ◽  
2019 ◽  
Vol 127 ◽  
pp. 37-43 ◽  
Author(s):  
Kuo-Hsuan Hsu ◽  
Yen-Hsiang Huang ◽  
Jeng-Sen Tseng ◽  
Kun-Chieh Chen ◽  
Wen-Hui Ku ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Primary Resistance ◽  
Treatment Naïve ◽  
Egfr Mutant ◽  
Egfr Tkis

scholarly journals Treatment Choices Based on OncotypeDx in the Breast Oncology Care Setting

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Teri L. Malo ◽  
Isaac Lipkus ◽  
Tobi Wilson ◽  
Hyo S. Han ◽  
Geza Acs ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Cancer Patients ◽  
Multivariable Analysis ◽  
Recurrence Score ◽  
Treatment Decision ◽  
Breast Cancer Patients ◽  
Multivariable Logistic Regression Model ◽  
Treatment Decision Making ◽  
Inform Treatment Decision

Introduction. This study aimed to evaluate whether OncotypeDx test results predict receipt of adjuvant chemotherapy in breast cancer patients who received an OncotypeDx recurrence score (RS).Materials and Methods. Pathology records were used to identify breast cancer patients who had OncotypeDx testing between December 2004 and January 2009 (n=118). Patient sociodemographic information, tumor characteristics, RS, and treatment-specific data were collected via chart review. RS was classified as follows: low (RS≤17), intermediate (RS = 18–30), or high (RS≥31). Bivariate analyses were conducted to investigate the relationship between adjuvant chemotherapy receipt and each sociodemographic and clinical characteristic; significant sociodemographic and clinical variables were included in a multivariable logistic regression model.Results. In multivariable analysis controlling for tumor size, histologic grade, and nuclear grade, only RS remained significantly associated with chemotherapy uptake. Relative to low RS, an intermediate (adjusted odds ratio [AOR], 21.24; 95% confidence interval [CI], 3.62–237.52) or high (AOR, 15.07; 95% CI, 1.28–288.21) RS was associated with a greater odds of chemotherapy uptake.Discussion. Results indicate that RS was significantly associated with adjuvant chemotherapy uptake, suggesting that OncotypeDx results were used to inform treatment decision making, although it is unclear if and how the information was conveyed to patients.

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