NGS testing patterns in advanced non-small cell lung cancer (aNSCLC) and metastatic breast cancer (mBC): OneOncology (OO) sites compared to Flatiron Health Nationwide (NAT).

2021 ◽  
Vol 39 (28_suppl) ◽  
pp. 288-288
Author(s):  
Ari M. Vanderwalde ◽  
Esprit Ma ◽  
Elaine Yu ◽  
Tania Szado ◽  
Richard Price ◽  
...  
Keyword(s):  
Advanced Disease ◽  
Metastatic Breast ◽  
Precision Oncology ◽  
Cancer Type ◽  
Tumor Type ◽  
Future Studies ◽  
Testing Rate ◽  
Testing Patterns ◽  
Test Result ◽  
Over Time

288 Background: Personalized treatment (tx) decisions can be improved through diagnostic tests with NGS by detecting different actionable mutations. OO, a research-focused network of community practices, has a network-wide precision oncology initiative and has advocated for NGS testing in advanced cancers since 2019. This study evaluated NGS testing patterns in aNSCLC and mBC populations descriptively in OO community sites and Flatiron Health NAT. Methods: This study used the Flatiron Health EHR derived de-identified database from [1] four OO sites, and [2] NAT. Patients (pts) diagnosed (Dx) with aNSCLC (stage ≥ IIIb) or mBC from 1/1/2015 to 5/31/2020, aged ≥ 18 years, had ≥ 1 visit ≤ 90 days (d) of advanced or metastatic Dx, and had ≥ 1 biomarker test were included. NAT NGS was confirmed via abstraction from patient records. Descriptive analyses were conducted to assess NGS testing patterns and pts characteristics by tumor type. Results: Of biomarker tested pts at OO vs. NAT (community:academic: 90%:10% aNSCLC; 93%:7% mBC), 2,029 of 3,152 (64%) OO vs. 13,681 of 29,572 (46%) NAT in aNSCLC and 514 of 1,282 (40%) OO vs. 2,458 of 12,175 (20%) NAT in mBC received NGS ± other tests. Testing rate of all 5 aNSCLC biomarkers (ALK, BRAF, EGFR, ROS-1, and KRAS) was higher with NGS vs. other tests for OO (87% vs. 6%) and NAT (87% vs. 11%). In mBC, a higher testing rate of BRCA with NGS vs. other tests (OO: 68% vs. 26%, NAT: 71% vs. 28%) and similar testing rate on HER2 (OO: 98% vs. 98%, NAT: 100% vs. 99%). Median time from Dx to NGS test result at OO vs. NAT was 33 d vs. 32 d in aNSCLC and 70 d vs. 188 d in mBC. NGS testing rates increased over time, with higher rates at OO vs. NAT [Table]. Pts with NGS vs. other tests were slightly younger in aNSCLC (OO: 68 y vs. 70 y, p = 0.001; NAT: 69 y vs. 70 yr, p < 0.001) and mBC (OO: 61 y vs. 67 y, p < 0.001; NAT: 61 y vs. 66 y, p < 0.001), and slightly more commercially insured in aNSCLC (OO: 48% vs. 45%, p = 0.3; NAT: 37% vs. 33%, p < 0.001) and mBC (OO: 54% vs. 48% OO, p = 0.053; NAT: 42 % vs. 36 %, p < 0.001). Conclusions: The adoption of NGS differed by cancer type and NGS testing rates have increased over time in aNSCLC and mBC. While some pts may have received testing outside of the Flatiron network, OO had a higher NGS uptake than NAT, and had a shorter time to testing in mBC that was possibly related to a network wide strategy recommending testing at Dx of advanced disease. Future studies on tx pattern after NGS testing are warranted to improve the actionability of NGS to foster personalized tx. [Table: see text]

scholarly journals From Genetic Alterations to Tumor Microenvironment: The Ariadne’s String in Pancreatic Cancer

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 309 ◽  
Author(s):  
Chiara Bazzichetto ◽  
Fabiana Conciatori ◽  
Claudio Luchini ◽  
Francesca Simionato ◽  
Raffaela Santoro ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Microenvironment ◽  
Current Knowledge ◽  
Myeloid Cells ◽  
Genetic Alterations ◽  
Molecular Characteristics ◽  
Precision Oncology ◽  
Cancer Type ◽  
Tumor Type ◽  
Driver Genes

The threatening notoriety of pancreatic cancer mainly arises from its negligible early diagnosis, highly aggressive progression, failure of conventional therapeutic options and consequent very poor prognosis. The most important driver genes of pancreatic cancer are the oncogene KRAS and the tumor suppressors TP53, CDKN2A, and SMAD4. Although the presence of few drivers, several signaling pathways are involved in the oncogenesis of this cancer type, some of them with promising targets for precision oncology. Pancreatic cancer is recognized as one of immunosuppressive phenotype cancer: it is characterized by a fibrotic-desmoplastic stroma, in which there is an intensive cross-talk between several cellular (e.g., fibroblasts, myeloid cells, lymphocytes, endothelial, and myeloid cells) and acellular (collagen, fibronectin, and soluble factors) components. In this review; we aim to describe the current knowledge of the genetic/biological landscape of pancreatic cancer and the composition of its tumor microenvironment; in order to better direct in the intrinsic labyrinth of this complex tumor type. Indeed; disentangling the genetic and molecular characteristics of cancer cells and the environment in which they evolve may represent the crucial step towards more effective therapeutic strategies

scholarly journals The Incidence of Cancer Associated Thrombosis is Increasing Over Time

2021 ◽  
Author(s):  
Anjlee Mahajan ◽  
Ann Brunson ◽  
Oyebimpe Adesina ◽  
Theresa HM Keegan ◽  
Ted Wun
Keyword(s):  
Risk Factors ◽  
Cumulative Incidence ◽  
Temporal Trends ◽  
Individual Risk ◽  
Cancer Type ◽  
Tumor Type ◽  
Risk Of Death ◽  
Breast And Prostate Cancer ◽  
Cancer Associated Thrombosis ◽  
Over Time

Cancer associated thrombosis (CAT) is an important cause of morbidity and mortality for patients with malignancy and varies by primary cancer type, stage and therapy. We aimed to characterize the incidence, risk factors, temporal trends and the effect on mortality of CAT. The California Cancer Registry was linked to the statewide hospitalization database to identify individuals with the 13 most common malignancies diagnosed 2005 -2017 and determine the 6 and 12-month cumulative incidence of CAT by venous thromboembolism (VTE) location, tumor type and stage after adjusting for competing risk of death. Cox proportional hazard regression models were used to determine risk factors associated with CAT and the effect of CAT on all-cause mortality. 942,019 patients with cancer were identified; 62,003 (6.6%) had an incident diagnosis of CAT. Patients with pancreatic, brain, ovarian, and lung cancer had the highest and patients with breast and prostate cancer had the lowest 12-month cumulative incidence of CAT. For most malignancies, men, those with metastatic disease and more co-morbidities, and African-Americans (vs. non-Hispanic Whites) were at highest risk for CAT. Patients diagnosed with cancer 2014-2017 had higher risk of CAT compared to those diagnosed 2005-2007. CAT was associated with increased overall mortality for all malignancies (HR ranges 1.89 - 4.79). The incidence of CAT increased over time and was driven by an increase in PE±DVT. CAT incidence varies based on tumor type and stage, and on individual risk factors including gender, race/ethnicity, and co-morbidities. For all tumor types CAT is associated with an increased mortality.

Costs and outcomes associated with febrile neutropenia-related hospitalizations across patients with varying cancer types: A retrospective analysis

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e20560-e20560
Author(s):  
M. B. Schilling ◽  
C. Parks ◽  
R. G. Deeter
Keyword(s):  
Febrile Neutropenia ◽  
Healthcare Cost ◽  
Opportunistic Infections ◽  
Metastatic Breast ◽  
Clinical Impact ◽  
Cancer Type ◽  
Tumor Type ◽  
Healthcare Database ◽  
Hospitalization Costs ◽  
Cancer Types

e20560 Background: Neutropenia, the major dose-limiting toxicity of chemotherapy, is a frequent, often serious, and sometimes fatal complication of myelosuppressive chemotherapy. Its economic and clinical impact is often under-appreciated, and thus this study evaluates the contribution of febrile neutropenia (FN) by tumor type as related to healthcare cost and mortality. Methods: FN patients in this study were identified as having cancer (ICD-9-CM: 140.xx - 208.xx), neutropenia (288.0x) and either opportunistic infections (110 total codes) or fever of unknown origin (780.6) who were hospitalized between 1/05 and 6/08 in a retrospective cohort study from the Aspen US healthcare database (∼11 million pts, >342 inpatient facilities, and >300 million charge-detail records). Unadjusted mean healthcare cost of hospitalization, length of hospital stay (LOS), and mortality rates were calculated, stratifying by cancer type (breast, metastatic breast, and lung cancers, non-Hodgkin lymphoma (NHL), or other hematologic tumors). Results: Among 598 hospitalized patients (mean age 63 years; 53% female) with cancer experiencing FN, the mean cost of hospitalization, LOS and mortality varied significantly by tumor type ( Table ). Conclusions: FN hospitalizations are costly and may be associated with significant mortality. Considerable variations exist across cancer types for hospitalization costs, LOS and mortality. The tumor type is important in assessing the economic and clinical impact of FN hospitalizations. [Table: see text] [Table: see text]

Comprehensive analysis of advanced-stage solid tumors from TCGA reveal widespread variation of genomics evidence levels across cancer types.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13547-e13547
Author(s):  
Dilhan Weeraratne ◽  
Elisa Napolitano Ferreira ◽  
Miguel Mitne Neto ◽  
Hu Huang ◽  
David Brotman ◽  
...  
Keyword(s):  
Clinical Evidence ◽  
The Cancer Genome Atlas ◽  
Braf V600e ◽  
Precision Oncology ◽  
Cancer Type ◽  
Tumor Type ◽  
Advanced Stage ◽  
Level Of Evidence ◽  
Cancer Types ◽  
Level 1

e13547 Background: Improved scalability and affordability of next generation sequencing (NGS) has pivoted cancer care toward genomics-driven treatment decisions. Particularly in advanced-stage or refractory cancer, clinical insights gleaned from NGS have become an integral option as these patients have typically exhausted all lines of available therapy. As precision oncology evolves, NGS is expected to have a differential impact based on the cancer type. In this study, a comprehensive NGS panel was used to determine the strength of clinical evidence in various advanced stage tumor samples from The Cancer Genome Atlas (TCGA). Methods: A hybrid capture panel, Oncofoco, was developed to evaluate SNVs, INDELs, CNVs and TMB in 366 genes. The panel’s utility was validated by interrogating a broader cohort of 2847 TCGA samples (advanced tumors with T3 or T4; or N > = 1; or M > = 1). Watsonä for Genomics, an artificial intelligence offering, was used for variant interpretation and annotation of the 366 genes. A clinical evidence classification system that evaluated the strength of biomarker/drug response associations was used for annotation with level 1/R1 strongest and level 4 weakest from clinical literature, FDA drug labels and guidelines (PMID:28890946). Results: The highest level of evidence for the top nine frequently occurring advanced stage cancers in TCGA is shown in Table. Conclusions: Thyroid cancer and cutaneous melanoma have emerged as the cancer types with the most level 1 evidence (FDA approved drugs) owing to BRAF V600E mutations. Kidney and prostate cancers show no cases with level 1 evidence and also had the largest fraction of unactionable tumors. Over half of colorectal cancer cases had level R1 resistance evidence attributed to KRAS and NRAS mutations. The clinical utility of NGS in late-stage refractory cancer varies widely by tumor type. The presence of level 3 and level 4 evidence in all cancer types bodes well for the development of new targeted drugs. [Table: see text]

Biomarker testing patterns and actionability in advanced non-small cell lung cancer (aNSCLC) at OneOncology (OneOnc).

2021 ◽  
Vol 39 (28_suppl) ◽  
pp. 287-287
Author(s):  
Ari M. Vanderwalde ◽  
Esprit Ma ◽  
Elaine Yu ◽  
Tania Szado ◽  
Richard Price ◽  
...  
Keyword(s):  
Performance Status ◽  
Ecog Performance Status ◽  
Personalized Care ◽  
Specimen Collection ◽  
Targeted Treatments ◽  
Biomarker Testing ◽  
Next Generation Sequencing Ngs ◽  
To Receive ◽  
Testing Patterns ◽  
Test Result

287 Background: Recent approvals of targeted treatments (tx) have improved personalized care in aNSCLC. Biomarker testing is crucial for patients (pts) to receive optimal tx expeditiously. This study examined aNSCLC biomarker testing and tx patterns at OneOnc. Methods: Pts diagnosed with aNSCLC (stage ≥ IIIb) from 1/1/2015 to 5/31/2020, aged ≥ 18 years, and with ≥ 1 visit ≤ 90 days of advanced (Adv) diagnosis (Dx) were retrospectively evaluated using the nationwide Flatiron Health electronic health record derived de-identified database from selected OneOnc sites. Descriptive analyses were conducted to evaluate testing patterns for ALK, BRAF, EGFR, KRAS, PD-L1, and ROS-1 biomarkers and actionable mutation tx pattern. Results: Overall 3,860 aNSCLC pts were included, median age was 69 years, 47% females, 66% non-squamous, 29% squamous, 4% histology NOS, and 23% with ECOG performance status 0-1. Of the 3,152 (82%) pts tested for any biomarker, 64% received next-generation sequencing (NGS) vs. 36% received other biomarker tests only. Testing rates varied by biomarker: EGFR (74%), ALK (72%), ROS-1 (66%), PD-L1 (57%), BRAF (56%), KRAS (54%). Pts who received all 6 biomarker tests increased from 12% (2015), 23% (2016), 40% (2017), 41% (2018), 48% (2019) to 56% (2020). Among the tested pts, the median time from Adv Dx to the first test result was 20 days (d) and from specimen collection after Adv Dx to the first test result was 12 d. Pts tested and treated before test result available declined from 28% (2015) to 16% (2020). Of 1,207 pts with actionable mutations, 390 (32%) received tx before the test result: 35% chemotherapy (chemo) only, 28% chemo + cancer immunotherapy (CIT), and 15% CIT only. After the test result, 26% to 81% of pts received no or other tx not specific to actionable mutations [Table]. Conclusions: Findings from this study demonstrated an increase in aNSCLC biomarker testing at OneOnc over time, while 44% pts in 2020 did not receive testing on all 6 biomarkers. Some pts had tx prior to the test result, but this trend appeared to decline. Further studies are warranted to better understand the reasons for pts receiving tx that were not specific to their actionable mutations.[Table: see text]

scholarly journals CATCH: A Prospective Precision Oncology Trial in Metastatic Breast Cancer

2021 ◽  
pp. 676-686
Author(s):  
Mario Hlevnjak ◽  
Markus Schulze ◽  
Shaymaa Elgaafary ◽  
Carlo Fremd ◽  
Laura Michel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Clinical Management ◽  
Metastatic Breast ◽  
Previous Treatment ◽  
Progression Free Survival ◽  
Tumor Board ◽  
Precision Oncology ◽  
Whole Genome ◽  
Free Survival

PURPOSE CATCH (Comprehensive Assessment of clinical feaTures and biomarkers to identify patients with advanced or metastatic breast Cancer for marker driven trials in Humans) is a prospective precision oncology program that uses genomics and transcriptomics to guide therapeutic decisions in the clinical management of metastatic breast cancer. Herein, we report our single-center experience and results on the basis of the first 200 enrolled patients of an ongoing trial. METHODS From June 2017 to March 2019, 200 patients who had either primary metastatic or progressive disease, with any number of previous treatment lines and at least one metastatic site accessible to biopsy, were enrolled. DNA and RNA from tumor tissue and corresponding blood-derived nontumor DNA were profiled using whole-genome and transcriptome sequencing. Identified actionable alterations were brought into clinical context in a multidisciplinary molecular tumor board (MTB) with the aim of prioritizing personalized treatment recommendations. RESULTS Among the first 200 enrolled patients, 128 (64%) were discussed in the MTB, of which 64 (50%) were subsequently treated according to MTB recommendation. Of 53 evaluable patients, 21 (40%) achieved either stable disease (n = 13, 25%) or partial response (n = 8, 15%). Furthermore, 16 (30%) of those patients showed improvement in progression-free survival of at least 30% while on MTB-recommended treatment compared with the progression-free survival of the previous treatment line. CONCLUSION The initial phase of this study demonstrates that precision oncology on the basis of whole-genome and RNA sequencing is feasible when applied in the clinical management of patients with metastatic breast cancer and provides clinical benefit to a substantial proportion of patients.

scholarly journals Real-World Data Related to Non-Metastatic Breast Cancer in Young Women: Experience of a Single Institution

2018 ◽  
Vol 64 (1) ◽  
pp. 45-53
Author(s):  
Juliana Cunha e Silva Ominelli De Souza ◽  
Andrew Sá Nunes ◽  
Jesse Lopes Da Silva ◽  
Aline Coelho Gonçalves ◽  
Suzanne Crocamo Ventilari Da Costa
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Lymph Node ◽  
Young Women ◽  
Advanced Disease ◽  
Young Patients ◽  
Metastatic Breast ◽  
Lymph Node Involvement ◽  
Axillary Lymph ◽  
Node Involvement

Introduction: Breast cancer is the leading cause of cancer-related deaths in women aged 20-59 years. Younger women usually have more aggressive tumors and more advanced disease with larger size and axillary lymph node involvement. There have been few studies assessing the characteristics of breast cancer in very young women. Objective: Evaluate the epidemiological and clinical profile of non-metastatic very young patients with breast cancer. Method: We performed a retrospective analysis to evaluate the epidemiological and clinical profile of non-metastatic breast cancer in patients ≤ 30 years of age treated between 1993 and 2011 at the Brazilian National Cancer Institute José Alencar Gomes da Silva. We evaluated relapse-free survival (RFS) and overall survival (OS). Results: Of the 196 patients evaluated, 181 (90%) had ductal carcinoma, 79 (40%) had high-grade tumors, and 102 (52%) had hormone receptor-positive tumors. 117 patients(60%) had stage III disease at diagnosis. The median age was 29 years (range, 17-30 years). Of 185 patients who underwent surgery, 156 (84.3%) underwent total mastectomy and 171 (92%) underwent axillary lymph node dissection. 119 patients received neoadjuvant chemotherapy, and 14 patients (9.3%) underwent neoadjuvant radiotherapy. After a median follow-up of 81.5 months, 109 patients (55%) had relapsed and 81 (41%) had died. The median RFS and OS were 49.5 months and 134 months, respectively. Lymph node involvement and neoadjuvant chemotherapy were associated with shorter RFS and OS. Conclusion: Breast cancer is uncommon in young patients, especially in those ≤ 30 years of age. We found a predominance of locally advanced disease and worse prognostic pathological characteristics. Despite the aggressive treatment, our patients had worse outcomes than those reported by other authors.

scholarly journals Changes in Overall Survival Over Time for Patients With de Novo Metastatic Breast Cancer

2021 ◽  
Author(s):  
Toshiaki Iwase ◽  
Tushaar Vishal Shrimanker ◽  
Ruben Rodriguez-Bautista ◽  
Onur Sahin ◽  
Anjali James ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
De Novo ◽  
Metastatic Breast ◽  
Locoregional Therapy ◽  
Cancer Center ◽  
Her2 Positive ◽  
Time Periods ◽  
Over Time

The purpose of this study was to determine the change in overall survival (OS) for patients with de novo metastatic breast cancer (dnMBC) over time. We conducted a retrospective cohort study with 1981 patients with dnMBC diagnosed between January 1995 and December 2017 at The University of Texas MD Anderson Cancer Center. OS was measured from the date of diagnosis of dnMBC. OS was compared between patients diagnosed during different time periods: 5-year periods and periods defined according to when key agents were approved for clinical use. The median OS was 3.4 years. The 5- and 10-year OS rates improved over time across both types of time periods. A subgroup analysis showed that OS improved significantly over time for the estrogen-receptor-positive/HER2-positive (ER+/HER2+) subtype, and exhibited a tendency toward improvement over time for the ER-negative (ER-)/HER2+ subtype. Median OS was significantly longer in patients with non-inflammatory breast cancer (P = .02) and in patients with ER+ disease, progesterone-receptor-positive disease, HER2+ disease, lower nuclear grade, locoregional therapy, and metastasis to a single organ (all P &amp;lt;.0001). These findings showed that OS at 5 and 10 years after diagnosis in patients with dnMBC improved over time. The significant improvements in OS over time for the ER+/HER2+ subtype and the tendency toward improvement for ER-/HER2+ subtype suggest the contribution of HER2-targeted therapy to survival.

scholarly journals Sex Work and Occupational Homicide: Analysis of a U.K. Murder Database

2018 ◽  
Vol 22 (3) ◽  
pp. 321-338 ◽  
Author(s):  
Stewart Cunningham ◽  
Teela Sanders ◽  
Lucy Platt ◽  
Pippa Grenfell ◽  
P.G. Macioti
Keyword(s):  
Sex Work ◽  
Sex Workers ◽  
Prostitution Policy ◽  
Sex Worker ◽  
Future Studies ◽  
Work Related ◽  
The United Kingdom ◽  
And Gender ◽  
Changes Over Time ◽  
Over Time

This article presents an analysis of occupational homicides of sex workers in the United Kingdom, 1990-2016. Characteristics of 110 people murdered between 1990 and 2016 are explored including the location of their murder, ethnicity, migration status, and gender. Key changes over time are noted including an increase in the number of sex workers murdered indoors as well as an increase in murdered migrant sex workers. By developing the concept of “occupational homicide,” we argue that sex worker homicide should be viewed as an occupational issue and that the distinction between work-related homicide and nonwork-related homicide should be accounted for in future studies and is essential to inform prostitution policy.

Irrational happiness beliefs and subjective well-being of undergraduate students: A longitudinal study

2021 ◽  
Vol 5 (1) ◽  
pp. 65-72
Author(s):  
Murat Yıldırım
Keyword(s):  
Negative Affect ◽  
Positive Affect ◽  
Undergraduate Students ◽  
Well Being ◽  
Subjective Well Being ◽  
Future Studies ◽  
Affective Components ◽  
The Impact ◽  
First Time ◽  
Over Time

Identifying factors that influence well-being are fruitful for improving the knowledge held about the correlates and predictors of well-being in both practice and theory. This research for the first time aimed to investigate whether irrational happiness beliefs, a newly presented construct, contribute to the affective components of subjective well-being over time. The sample included 103 undergraduate students (88 females and 15 males) whose ages varied from 18 to 29 years (M = 19.39 ±1.62). Participants completed measures of irrational happiness beliefs, positive affect, and negative affect both at Time 1 and Time 2 over three months apart. The findings showed that irrational happiness beliefs were significantly negatively related to positive affect only at Time 1. However, the research failed to provide evidence regarding the value of irrational happiness beliefs in predicting positive and negative affect over time. The results suggest that the impact of irrational happiness beliefs upon well-being may occur momentarily not over time. Implications and limitations of the findings are discussed and directions for future studies are provided.

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