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P. Ye
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P2.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 234)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.04-090 - Changes in Circulating Epidermal Growth Factor Receptor (EGFR) during Radiotherapy in Non-Small Cell Lung Cancer (NSCLC) Patients (ID 2436)
09:30 - 09:30 | Author(s): P. Ye
- Abstract
Background:
Epidermal growth factor receptor (EGFR) is overexpressed in a variety of malignant tumors including lung cancer. A circulating isoform of EGFR has been detected in the blood of lung cancer patients. Previous reports suggest that low baseline plasma EGFR concentrations are associated with reduced survival in patients with stage IV non-small cell lung cancer (NSCLC) post-chemotherapy. The goal of the present study was to determine whether: 1) plasma EGFR concentrations change during- and/or after radiotherapy, 2) the changes are associated with overall survival (OS) in stage I-III NSCLC following radiation treatment.
Methods:
Patients enrolled in prospective studies in which platelet poor plasma samples had been collected were eligible. All patients received radiation-based treatment. Patient age, gender, ECOG score, clinical stage, pathology, smoking history, chemotherapy and radiotherapy were all included in this analysis. Blood samples were collected pre-radiotherapy (pre-), during radiotherapy (2 weeks) (2w), during radiotherapy (4 weeks) (4w) and post-radiotherapy (more than 4 weeks post-radiotherapy). Plasma EGFR concentrations were measured using a commercial enzyme-linked immunoassay kit (BosterBio Inc., Pleasanton, CA) that detects the extracellular domain of EGFR. The primary endpoint was OS.
Results:
183 patients with median age of 66, 143 male and 40 female, were included in this study. The median OS was 15.5 months (95% confidence interval [CI]: 20.8-27.3). The mean plasma concentration of EGFR was 35.6 ng/ml for pre- (n=116, 95% CI: 33.9-37.4); 22.4 ng/ml for 2w (n=114, 95% CI: 20.8-24.0); 34.5 ng/ml for 4w (n=114, 95% CI: 31.4-37.7); and 45.0 ng/ml for post (n=114, 95% CI: 40.1-49.9). The plasma level at 2w was significantly lower than pre-levels (p < 0.01). The plasma EGFR level at 4w was significantly higher than at 2w (p < 0.01), though it was not significantly different from that of pre-RT levels. There is a significant increase in EGFR levels in post-RT treated patients (p < 0.01). Post-treatment levels are above all other points observed in cancer patients, including at baseline and during-RT. However, no significant correlation between the levels of EGFR and OS, or between the ratio 2w/pre or post/pre and OS were observed. Kaplan-Meier survival analysis showed pre- EGFR concentrations [22.2 months (95% CI: 6.8-37.7) versus 23.5 months (95% CI: 14.1-32.9) (p = 0.527)] and fold changes of 2w/pre- [24.5 months (95% CI: 11.2-35.9) versus 23.7 months (95% CI: 12.2-42.3) (p=0.928)] respectively.
Conclusion:
In parallel with previous reports for the treatment of NSCLC patients with gefitinib, RT results in a decrease in EGFR plasma concentrations shortly after therapy (2 weeks), but an increase relative to baseline levels by 4 weeks, followed by a further increase (to above baseline levels) by 3 months post-treatment. In patients treated with gefitinib, this increase correlated with worse response to therapy. Here there does not appear to be a correlation between increased plasma EGFR levels and OS following RT. The biologic mechanism(s) underlying these observations, and their clinical implications warrant further study.
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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)
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P3.04-067 - Inflammatory Cytokines Are Associated with the Development of Fatigue in Patients with NSCLC Treated with Definitive Radiotherapy (ID 2821)
09:30 - 09:30 | Author(s): P. Ye
- Abstract
Background:
Fatigue is one of the most common symptoms in cancer patients at baseline and or treatment which affects cancer patients’ quality of life. This study is to evaluate the association of inflammatory cytokines with the development of fatigue in patients with NSCLC treated with definitive radiation therapy (RT).
Methods:
109 patients with stage I-IIINSCLC and ECOG 0-2 treated with definitive RT from prospective studies were included. The median age was 66 years (range 43-85), and 84 patients (77.1%) had stage IIIdisease. The median RT dose was 70 Gy (range 34-87.9) at 1.8~2.9 Gy/fx for 103 patients and 6 (5.5%) received stereotactic body RT (SBRT) to a total dose of 50-55Gy at 10-11 Gy/fx. Seventy-six (69.7%) received concurrent and 31 (28.4%) consolidated chemotherapy. Thirty inflammatory, pro-inflammatory, immunomodulation cytokines were measured in plasma samples before RT, using ELISA. Fatigue was evaluated and scored according to CTCAE 3.0 before, 2, 4, 6 weeks during- and 3, 6, 9, 12, 18, 24 months after RT. The fatigue scores from all time points are averaged for each person to create a composite score, which is the endpoint of this analysis. Spearman's rho test was used to check the association of cytokine levels and other clinical factors with fatigue. ​The p-value of the cytokines are adjusted using the Benjamini-Hochberg procedure.
Results:
109 patients had fatigue information available before, 2, 4 and 6 weeks during RT, and 106, 101, 98, 97, 92 and 88 had fatigue information available at 3, 6, 9, 12, 18, 24 months after RT, respectively. The incidence of grade 1-3 fatigue was 37.6% before RT, 52.3%, 60.6%, 65.1% at 2, 4, 6 weeks during RT, and 62.3%, 50.5%, 33.7%, 28.9%, 14.1%, 13.6% at 3, 6, 9, 12, 18, 24 months after RT, respectively. Grade 3 fatigue was rare, less than 1% and no grade 4-5 fatigue occurred. Among 30 cytokines, IL-10 (p=0.019) and IP-10 (p=0.054) were significantly associated with fatigue. Lower level of IL-10 and higher level of IP-10 were associated with less fatigue score. SBRT (p=0.002), and consolidated chemotherapy (p=0.049) were significantly associated with fatigue. Patients treated with SBRT had lower fatigue score, but those with consolidated chemotherapy had higher fatigue score. IL-10 was not related with the use of SBRT (p=0.26) or consolidated chemotherapy (p=0.11). IP-10 was not related with the use of consolidated chemotherapy (p=0.76), but it is significantly related with the use of SBRT (p=0.01) and SBRT individuals had higher IP-10 levels. By excluding the 6 SBRT patients, IP-10 was significantly associated with fatigue for non-SBRT patients (p=0.02). Age (p=0.09), gender (p=0.59), histology (p=0.56), ECOG (p=0.16), weight loss (p=0.85), COPD (p=0.16), smoking (p=0.99), stage (p=0.89), biological equivalent RT dose for non-SBRT patients (p=0.12), and concurrent chemotherapy (p=0.59), were not associated with fatigue.
Conclusion:
For patients with NSCLC treated with definitive RT, fatigue increases during RT and decreases over time after completion of RT, with peak severity at 6 weeks during RT. Plasma level of IL-10 and IP-10 before RT, SBRT and consolidated chemotherapy play important roles in the development of fatigue.
