Virtual Library
Start Your Search
J.A. Borgia
Author of
-
+
MINI 04 - Clinical Care of Lung Cancer (ID 102)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:L. Gaspar, V. Westeel
- Coordinates: 9/07/2015, 16:45 - 18:15, Mile High Ballroom 2c-3c
-
+
MINI04.07 - Changes in Skeletal Muscle Index and Body Mass Are Prognostic Factors in First Line Stage IV Non-Small Cell Lung Cancer (NCSCL) Patients (ID 3091)
17:20 - 17:25 | Author(s): J.A. Borgia
- Abstract
- Presentation
Background:
Cancer cachexia is a complex metabolic syndrome affecting 60-80% of patients with non-small cell lung cancer (NSCLC). The characteristic involuntary weight loss observed in cachexia is associated with poor outcomes in advanced NSCLC; however, reduced muscle mass may be a more reliable prognostic indicator. In this study, we examine the impact of changes in weight and skeletal muscle index (SMI) in the first 12-weeks of therapy on clinical outcome parameters for front line stage IV NSCLC patients.
Methods:
Cancer cachexia is a complex metabolic syndrome affecting 60-80% of patients with non-small cell lung cancer (NSCLC). The characteristic involuntary weight loss observed in cachexia is associated with poor outcomes in advanced NSCLC; however, reduced muscle mass may be a more reliable prognostic indicator. In this study, we examine the impact of changes in weight and skeletal muscle index (SMI) in the first 12-weeks of therapy on clinical outcome parameters for front line stage IV NSCLC patients.
Results:
119 patients had serial weights available and were included for analysis: 49% were male, median age of males was 71, and females were 63 years; 82% had smoking history. Histology was predominantly adenocarcinoma and squamous (62% and 22%). Median PFS was 159 days, and medial OS was 314 days. Median weights for males at baseline, 6 weeks, and 12 weeks were 77.3, 76.9, and 77.3 kilograms respectively. Median weights for females at baseline, 6 weeks, and 12 weeks were 67.1, 66.7, 65.8 kilograms respectively. Baseline weights were less for women than men (p<0.0007) but the change in weight with time was not significantly different at measured time points. Weight loss of greater than 10.39 pounds in the first six weeks of treatment was strongly associated with inferior outcomes (PFS 2.35 vs. 6.44 months, p=2.02 x 10[-7]; OS 3.96 vs. 15.48 months, p=8.71 x 10[-9]). Persistent weight loss at 12 weeks was also associated with worse outcomes (PFS p=1.72x10[-7 ], OS p= 0.00286). Within this cohort, 41 patients had baseline SMI measured from their CT scans, 27 patients had additional CT-derived SMI available at 6- and 12- weeks. Patients with SMI decrease at 12 weeks of at least 2.6 units (n=9, 33%) had an inferior median PFS compared with those not meeting this threshold (2.79 months vs. 9.75 months p<0.05). In a multivariate analysis, this loss, when adjusted by gender, remained significantly associated with PFS (HR=2.37, p < 0.05).
Conclusion:
This study shows the prognostic value of weight loss for progression on first line chemotherapy as early as six weeks following therapy initiation. This analysis confirms the significant association between weight loss on serial measurements and inferior survival in stage IV NSCLC pts. Additionally, this is the first report of decreasing CT-derived SMI correlating with inferior progression free survival on front line platinum doublet therapy for NSCLC.
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
-
+
MINI 29 - Meta Analyses and Trial Conduct (ID 156)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:D. Morgensztern, M. Redman
- Coordinates: 9/09/2015, 18:30 - 20:00, Mile High Ballroom 2a-3b
-
+
MINI29.03 - Prognostic Value of Biomarkers Associated with Glucose Metabolism and Systemic Inflammation in Advanced On-Small Cell Lung Cancer (NSCLC) (ID 3061)
18:40 - 18:45 | Author(s): J.A. Borgia
- Abstract
- Presentation
Background:
Alterations in glucose metabolism and appetite stimulating hormones have been correlated with inflammation but there is little information on frequency and prognosis in newly diagnosed stage IV non-small cell lung cancer (NSCLC) This study objective was to identify associations of circulating biomarkers of glucose metabolism and inflammation with prognosis in pre-treatment sera from stage IV NSCLC patients selected for platinum doublet based chemotherapy.
Methods:
Pretreatment serum from 118 Pts with frontline stage IV NSCLC were evaluated with the Bio-Plex Pro Human Diabetes Assay panel (adiponectin, adipsin, c-peptide, ghrelin, gastrin inhibitory peptide (GIP), glucagon-like peptide-1 (GLP-1), glucagon, IL-6, insulin, leptin, Plasminogen activator inhibitor-1, resistin, TNFα, vistatin) and HSTCMAG-28SK | MILLIPLEX MAP Human High Sensitivity T Cell Panel - Immunology Multiplex Assay (Fractalkin, GM-CSF, IFNγ, IL-1 β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 (p70), IL-13, IL-17A, IL-21, IL-23, ITAC, macrophage inflammatory protein (MIP)-1α, MIP-1β, MIP-3α, TNFα) on a FlexMAP 3D system (Luminex Corp.). Pts were treated with standard platinum doublets based chemotherapy. Associations of biomarkers with progression free and overall survival (PFS,OS) outcomes were assessed using multivariate Cox PH analyses.
Results:
Most patients had metabolic levels below the prognostic threshold. However, high levels of insulin, GIP, glucagon, visfatin, ghrelin, GLP-1 were significantly associated (p<0.05) with shorter PFS. Low levels of adipisin (deficiency of which is associated with obesity) was associated with shorter PFS (p=.0185). High levels of pro-inflammatory markers: ITAC, GM-CSF, Fratalkine, INF-ϒ, IL-12p70, IL-13, IL17A, IL-4, IL-23, IL8.4, MIP-α, MIP-1 were also associated with poor PFS (p<0.05) (See Table I for more details on select biomarkers) High levels of these endocrine markers (except insulin and GIP) were associated with shorter OS as were ITAC, GMCSF, IL12p70, IL-13, IL4, IL23, IL5 (p<0.05). Table I. Biomarker correlation with progression free survivalMarker Cutoff-pg/mL N < N > Median PFS < Median PFS> Logrank p Insulin 1004.9 82 36 6.08 4.04 0.026161 Glucagon 361.2 110 8 5.46 1.71 0.010219 Visfatin 8298.3 109 9 5.65 1.45 8.77E-06 Ghrelin 2897.2 104 14 6.02 2.12 0.009423 GLP.1 268.8 109 9 5.65 1.97 0.000618 ITAC 104.7 99 19 5.82 2.96 0.012529 Fractalkine 271.7 97 21 6.08 3.16 0.0067 IL.12.p70. 17.0 109 9 5.65 3.16 0.010631 IL.13 14.9 105 13 5.82 2.76 0.001533 IL.17A 49.4 102 16 5.82 3.65 0.004862 IL.4 66.1 104 14 6.02 2.96 0.000917 IL.8.4 3.0 25 93 12.8 4.8 0.008985
Conclusion:
Imbalances in the glucose metabolism pathway and increased levels of pro-inflammatory circulating markers were uncommon but consistently associated with a poor prognosis in stage IV NSCLC patients early in their treatment cycle. Alterations in these systems have been associated with cancer cachexia and may be targets for intervention in improving prognosis for select patients with NSCLC.
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
-
+
MINI 32 - Topics in Localized Lung Cancer (ID 166)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Localized Disease - NSCLC
- Presentations: 1
- Moderators:D. Boffa, T. D'Amico
- Coordinates: 9/09/2015, 18:30 - 20:00, 201+203
-
+
MINI32.08 - Identification of a Meta-Gene Network Associated with Metformin Sensitivity and Recurrence in Stage I Non-Small Cell Lung Cancer (ID 1727)
19:10 - 19:15 | Author(s): J.A. Borgia
- Abstract
- Presentation
Background:
We recently reported an association between progression-free survival and metformin exposure in patients with early stage non-small cell lung cancer (NSCLC). Local recurrence in stage I disease is estimated to be as high as 50% in US populations. Therefore, a method to identify NSCLC patients who are most likely to benefit from metformin treatment has potential clinical relevance.
Methods:
Three previously published, publically available gene expression array data sets documenting the effects of metformin treatment on transcriptional activity in human cell lines were used for the initial stages of the present study. These data sets were evaluated individually for enrichment of differentially expressed genes with a gene set analysis related to biological processes also performed. Differentially expressed genes common to all three studies were then used to form a metformin meta-gene. This combined meta-gene was evaluated topologically using a protein-protein interaction database to determine if any gene products had previously observed direct interactions. The metformin meta-gene network was then examined in expression array data sets from stage I NSCLC patients (n=293) assembled from multiple published studies.
Results:
We identified several biological themes resulting from metformin treatment, including: immune cell differentiation, response to hypoxia, steroid receptor signaling, alternate splicing, and changes in cellular metabolism. Intersecting the differentially expressed genes from each data set, we identified 105 genes consistently up-regulated and 30 genes consistently down-regulated by metformin treatment, forming a tissue-independent meta-gene for metformin effects. Two networks of interacting genes were identified in this analysis; the first network consisting of 27 genes (22 up-regulated and 5 down-regulated) and the second consisting of three up-regulated genes.This meta-gene was then examined in two independent cohorts of stage I adenocarcinoma. In the first cohort (n=125), patients clustered into two groups when k-means analysis was performed with respect to the 30 genes in the metformin meta-gene network. These patients had a significantly (p=0.014) different incidence of recurrence between the two clusters. This result was independently validated in the second data set (n=168) where patients clustered into two groups and also demonstrated significant stratification of recurrence (HR=1.21; p=0.001).
Conclusion:
We have identified a meta-gene of interacting proteins associated with both metformin therapy and recurrence-free survival in early stage lung cancer patients. This suggests a potential method for identifying NSCLC patients most likely to benefit from metformin therapy, and furthermore, identifies mechanistic avenues by which metformin treatment may benefit early stage lung cancer patients.
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
-
+
P2.06 - Poster Session/ Screening and Early Detection (ID 219)
- Event: WCLC 2015
- Type: Poster
- Track: Screening and Early Detection
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
-
+
P2.06-012 - A Model Incorporating Clinical, Radiographic, and Biomarker Characteristics Predicts Malignancy in Indeterminate Pulmonary Nodules (ID 2890)
09:30 - 09:30 | Author(s): J.A. Borgia
- Abstract
Background:
The high false-positive rate associated with low-dose computed tomography (CT) lung cancer screening results in unnecessary testing, cost, and patient anxiety. We hypothesized that an algorithm incorporating clinical, radiographic, and serum biomarker data would be capable of differentiating benign from malignant pulmonary nodules.
Methods:
An institutional biorepository was used to identify 84 patients with ≤ 2 cm indeterminate pulmonary nodules identified on CT scan, including 50 patients with biopsy-proven, node-negative, non-small cell lung cancer (NSCLC) and 34 patients with benign, non-calcified, solitary pulmonary nodules. Clinical and radiographic data were collected from patient charts and imaging studies. Serum specimens were evaluated in a blinded manner for 55 biomarkers using multiplex immunoassays. Random forest analyses were used to generate a multivariate cross-validation prediction model incorporating clinical, radiographic, and serum biomarker data.
Results:
A total of 84 patients were identified with a median nodule size of 5 mm for benign nodules and 15 mm for NSCLC. Median smoking histories were 21 and 28 pack-years and patient age was 62 and 70 years, respectively. An algorithm incorporating serum biomarker profile (IGFBP-4, IGFBP-5, IL-10, IL-1ra, IL-6, SDF-1alpha, IGF-2), age, sex, BMI, COPD, smoking history, hemoptysis, previous cancer, nodule size, nodule location, spiculation, nodule type, and nodule count provided the optimal performance with a sensitivity 92%, specificity 65%, NPV 85%, and PPV 79%. This model performed with an overall accuracy of 81% with a cross-validated AUC=0.904.
Conclusion:
An algorithm incorporating clinical, radiographic, and serum biomarker characteristics may help differentiate benign from malignant pulmonary nodules. This model is currently being externally validated in a second-site patient cohort.
-
+
P3.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 235)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
-
+
P3.04-093 - Neutrophil/Lymphocyte Ratios Inversely Related to Weight Change, Overall Survival; ALI Inversely Related to OS in NSCLC Pts (ID 3078)
09:30 - 09:30 | Author(s): J.A. Borgia
- Abstract
Background:
A high neutrophil/lymphocyte ratio (NLR) at baseline and at follow-up is associated with shorter survival in cancer patients and may be a surrogate for ongoing inflammation which is implicated in promoting cancer cachexia and tumor progression. The objective of this study is to explore potential relationships between OS, serial weights, and serial NLRs and ALI (Advanced Lung cancer Inflammatory) index in advanced NSCLC patients receiving chemotherapy.
Methods:
139 stage III/IV NSCLC pts were treated with first-line platinum doublets from June, 2011 to August, 2012. NLR and body weight were recorded at baseline, 6, and 12 weeks from initiation of therapy and correlated with OS. The association between NLR and OS was assessed using Cox PH analysis, and the association between NLR and weight change was assessed using a simple regression analysis. ALI index was defined as BMI (Body Mass Index) x (Albumin)/NLR. ALI was calculated at baseline, 6, and 12 weeks from initiation of therapy and correlated with OS for some pts.
Results:
139 pts with median age 68, PS 0-1/2 = 83/17%, male/ female = 48%/52%. NLR at baseline median 3.6, range 0.1898 to 30.910; at 6wks median 3.11, range 0.2703 to 42.11; at 12wks median 3.52 range 0.2147 to 42.93. Increase in the NLR at baseline, 6, and 12 weeks were associated with a decrease in OS (baseline HR 1.06, p < 0.001; 6 wks HR 1.07, p = 0.001; 12wks HR 1.05, p < 0.001). The effect of NLR on hazard is multiplicative (i.e. a change of 5 in baseline NLR results in a HR of 1.065). Initial weight and NLR were negatively correlated (cor = -0.267, p = 0.001), and weight change and NLR were also negatively correlated at 12wks (cor = -0.371, p < 0.001; weight change -13.17kg to +16.61kg, median -0.5kg, mean -0.89kg). 96, 93 and 84 pts had ALI score available at baseline, 6wks, and 12 wks respectively. 38 pts with baseline ALI score <= 18 had significantly lower OS (median OS=9.63 mos) compared to 58 pts with ALI > 18 (median not reached, p = 0.001). 41 pts with 6 week ALI <= 18 had significantly lower OS (median OS=11.4 mos) compared to 52 pts with ALI > 18 (median not reached, p = 0.03). 30 pts with 12 week ALI <= 18 had significantly lower OS (median OS=9 mos) compared to 54 pts with ALI > 18 (median not reached, p < 0.001).
Conclusion:
High baseline and progressive increase in NLRs are associated with inferior OS and weight loss in advanced NSCLC patients. In addition to having prognostic significance, these observations suggest that studying molecular mediators of cachexia/inflammation and their relationships to tumor progression may identify new therapeutic targets in the large subset of NSCLC patients who have cancer cachexia. We also confirmed findings by Jafri at all 2013, that ALI score <=18 is associated with lower OS at any time before or during treatment.
