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Anastasios Gkountakos
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P1.16 - Treatment in the Real World - Support, Survivorship, Systems Research (ID 186)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Treatment in the Real World - Support, Survivorship, Systems Research
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.16-43 - Prevalence of Clinical and Sub-Clinical Malnutrition in Advanced Non-Small-Cell Lung Cancer Patients and Association with Outcome (ID 1757)
09:45 - 18:00 | Author(s): Anastasios Gkountakos
- Abstract
Background
While weight loss and lean body mass wasting are common hallmarks of non-small-cell lung cancer (NSCLC), their early detection and management are usually overlooked in clinical routine. The present study aimed to explore the prevalence of malnutrition and its correlation with outcome in advance (A)-NSCLC pts.
Method
A-NSCLC pts treated at AOUI of Verona (2016-2018) received nutritional counseling by a qualified dietitian. Prevalence of malnutrition was assessed by nutritional screening score (NRS). Bilateral psoas major muscles were measured at L3 vertebrae level with routine staging-computed tomography (CT). Changes in psoas muscles observed in subsequent scans were evaluated using Wilcoxon signed-rank test. Clinical, pathological and nutritional data were correlated to progression-free/overall survival (PFS/OS) and response rate (ORR) using a Cox and logistic regression model. Kaplan-Meier curves were compared with Log-Rank.
Result
Data from 38 pts (20 males [52.6%], 18 females [47.4%]) were gathered (median age 59 years [range 42-82], with a median follow-up of 21 months (range 1-197). At baseline, 18.4% were underweight, 18.4% normal weight, 34.2% overweight and 31.6% obese. The majority (65.8%) were at risk of malnutrition (NRS≥3). At multivariate analysis, stage (HR 4.99, 95% CI 1.05-27.74, p = 0.04), performance status (HR 4.99, 95% CI 1.55-16.03, p = 0.007) and NRS (HR 7.61, 95% CI 1.52-38.11, p = 0.01), were significant independent predictors for PFS. Pts with baseline NRS≤3 had significantly longer 1-year PFS (58.6% vs 16.7%, p = 0.04) and 2-year OS (90.6% vs 68.3%, p = 0.03) and a better ORR than those with NRS > 3 (66.7% vs 21.4%). Conversely, BMI did not affect PFS/OS. A significant loss in psoas muscle mass was detected in pts treated with both immunotherapy and other therapies (p = 0.01 and p=0.002, respectively). Of interest, in immunotherapy-treated pts (n = 16) loss in psoas muscle mass correlated with worse ORR, PFS and OS, although differences did not reach a statistical significance due to the limited sample.
Conclusion
Our analysis suggests that malnutrition has a detrimental impact on ORR, PFS and OS in A-NSCLC. Particularly, in pts treated with immunotherapy, muscle mass wasting seems to impact on efficacy outcome, suggesting a potential interaction between immunological and nutritional parameters. Therefore, the introduction in the clinical routine of a comprehensive nutritional profiling and monitoring, beyond body weight and BMI, is highly recommended in A-NSCLC. A comparison between NSCLC pts who underwent a personalized nutritional intervention during therapy and who did not is ongoing, together with a series of biomolecular analysis.
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P2.04 - Immuno-oncology (ID 167)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.04-51 - A 6-Gene Immune Genomic Signature (IGS) Predicts Resistance to Nivolumab [NIV] in Advanced Pretreated NSCLC: Results of PRINCiPe Trial (ID 1885)
10:15 - 18:15 | Author(s): Anastasios Gkountakos
- Abstract
Background
Genomic abnormalities detected in immune-escape/editing-related genes may promote immunotherapy resistance. In the light of this hypothesis, we designed the PRINCiPe (Predictors of Resistance to Immunotherapy with NIV) study in APNSCLC.
Method
FFPE-tumor blocks of APNSCLC pts undergone NIV were retrospectively sequenced for Somatic Mutations/Copy Number Variations (SM/CNV) (Ampliseq 17-genes customized panel: APLNR, B2M, IFNAR1, IFNAR2, IFNGR1, IFNGR2, IRF9, JAK1, JAK2, JAK3, PIAS4, PTPN2, SOCS1, STAT1, STAT2, STAT3, TYK2). End-points of the PRINCiPe study were overall-, progression-free-survival (OS/PFS) and objective response rate (ORR).
Result
Forty-four APNSCLC pts were gathered (median age 69.5 yrs, median number of previous lines 3 [2-5], 2nd line NIV [75.0%], male/female 77.3/22.7%, squamous/non-squamous 31.8/68.2%, EGFR mutant 5 [11.4%], median follow-up 6.8 months [range 1-23], deaths 24 [54.5%]). JAK3/JAK2 (7/3 pts, 15.9/6.8%) CNV and IFNAR2 SM (4 pts, 9.1%) were the most frequent (>1 pts) abnormalities. Pts (n=15) with JAK3, PIAS4, PTPN2, STAT3, IFNAR2 SM and/or JAK2/3 CNV (IGS+) had a significantly lower PFS than those without (IGS-) (median PFS 2.8 vs. 6.6 months; p=0.006), while a trend towards significance was observed in terms of OS (median OS 5.1 vs. 13.0 months for IGS+ and IGS-, respectively; p=0.06 log-rank, p=0.05 Tarone-Ware). At multivariate analysis, IGS+ was independently associated with a shorter PFS (HR 2.64, 95% CI 1.3-5.4, p=0.008). IGS+ pts were significantly more probable to be affected by liver metastases than those without (p=0.01).
Conclusion
The identified IGS appears to select APNSCLC pts with a significant lower chance to benefit from NIV, supporting intrinsic resistance. A prospective larger and external validation is ongoing, as well as the comprehensive transcriptome analysis.
