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M.J. Fidler
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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
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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): M.J. Fidler
- 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.
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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
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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): M.J. Fidler
- 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.
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P1.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 206)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.01-052 - Retreatment with Platinum-Based Regimen for Patients with Metastatic NSCLC Is a Reasonable Therapy (ID 2444)
09:30 - 09:30 | Author(s): M.J. Fidler
- Abstract
Background:
Standard first-line therapy in stage IV NSCLC patients remains a platinum-based regimen. Currently, there are limited FDA approved agents for second line therapy following progressive disease. The purpose of this study was to evaluate the response to retreatment with platinum-based regimens upon progression in a group of platinum-sensitive patients.
Methods:
Patients with stage IV NSCLC previously treated with a platinum-based first-line regimen were retrospectively reviewed. We examined the outcomes of 52 patients retreated with a platinum-based regimen upon progression between February 2002 and March 2015. Patients were evaluated for response rate, progression free survival, overall survival and platinum reactions.
Results:
Of the 52 patients reviewed, 31 were women (59.6%) and 21 were men (40.4%). Median age was 62.6 (range 42-89) and adenocarcinoma was the most prevalent histology (86.5%). The response rate for retreatment was 21.15%. A notable 57.69% of patients had stable disease. The median PFS for the first line platinum regimen was 9.2 months (CI 95%; 6.28-12.13) and for the retreatment was 4.8 months (CI 95%; 3.17-6.42). The median OS from diagnosis was 23.31 months (CI 95%; 11.76-34.85). A platinum reaction was noted in 9 of the patients (17.3%) though none were fatal.
Conclusion:
Patients with prolonged PFS with frontline chemotherapy appear to benefit from retreatment with a platinum-based regimen. This cohort demonstrated by a PFS of 4.8 months upon retreatment. Patients with prolonged progression free survivals with frontline chemotherapy may be reasonable candidates to consider for retreatment with a platinum-based regimen.
