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J. Jin



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    P1.02 - Poster Session/ Treatment of Localized Disease – NSCLC (ID 209)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Treatment of Localized Disease - NSCLC
    • Presentations: 1
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      P1.02-037 - Thoracic Radiation-Induced Pleural Effusion and Risk Factors in Patients with Lung Cancer (ID 1397)

      09:30 - 17:00  |  Author(s): J. Jin

      • Abstract
      • Slides

      Background:
      Pleural effusion is regarded as a frequent late toxicity after thoracic radiotherapy (TRT). However, recent literature is lacking on this toxicity. This study aimed to examine the patient and dosimetric risk factors associated with radiation induced pleural effusion (RIPE) in lung cancer patients treated with TRT.

      Methods:
      Lung cancer patients treated with TRT having follow-up imaging, CT or PET/CT, were eligible. Pleural effusion of increased volume after TRT without evidence of tumor progression was considered to be RIPE. Parameters of lung dose-volume histogram including percent volumes irradiated with 5 to 55 Gy (V5-V55) and mean lung dose (MLD) were analyzed. Optimal dosimetric thresholds for RIPE were calculated by receiver operating characteristic (ROC) analysis. Associating clinical and treatment-related risk factors for RIPE were detected by univariate and multivariate analyses with SPSS 18.0. Data were considered statistically significant at value of p < 0.05.

      Results:
      Of 806 consecutive patients who received TRT at two institutions, 205 had post-treatment imaging available and were included in this study. The median (range) age was 63 (34-85) years; Male, Caucasian race, current smokers, stage III and squamous cell cancer accounted for 73.2%, 81.0%, 50.7%, 66.8% and 27.8%, respectively. The median follow-up duration was 14.6 (range, 0.7-80.8) months. Of 51 patients (24.9%) who developed RIPE, 40 had symptomatic RIPE including chest pain (47.1%), cough (23.5%) and short of breath or dyspnea (35.3%). The median (range) RIPE interval from end of TRT was 3.7 (0.6-18.0) months. The RIPE rates of the two institutions were 20.2% and 32.1% with a borderline significance (p = 0.053). Caucasian race (HR = 2.930, 95% CI: 1.197-7.172, p = 0.019) and histology of squamous cell lung cancer (HR = 0.645, 95% CI: 0.425-0.980, p = 0.04) were significantly associated with the low risk of RIPE, while age (p = 0.378), gender (p = 0.071), stage (p = 0.148), radiation dose (p = 0.782) and concurrent chemotherapy (p = 0.173) were not. The whole lung V5, V10, V15, V20, V25, V30, V35, V40, V45, V50 and MLD were significantly higher in patients with RIPE than in those without RIPE (p = 0.007, 0.022, 0.044, 0.048, 0.034, 0.016, 0.010, 0.026, 0.040 and 0.014), and only V5 was the significant predictive factor for both RIPE and symptomatic RIPE (p = 0.007 and 0.021) with the largest areas under ROC curve (AUC = 0.779). Using a cutpoint of 41.5% for V5, the sensitivity and specificity were 100% and 61.5%, respectively.

      Conclusion:
      Radiation induced pleural effusion is notable. Caucasian race and squamous cell tumor histology may be associated with lower risk of RIPE. The whole lung V5 seems to be a significant risk factor for symptomatic RIPE.

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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
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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 - 17:00  |  Author(s): J. Jin

      • 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.