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J. Zhao
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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
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.02-037 - Thoracic Radiation-Induced Pleural Effusion and Risk Factors in Patients with Lung Cancer (ID 1397)
09:30 - 09:30 | Author(s): J. Zhao
- Abstract
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
- 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): J. Zhao
- 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: 2
- 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): J. Zhao
- 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.
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P3.04-104 - Radiation Pneumonitis: Assessment by Inflammation Imaging with Tc-99m HMPAO - Clinical Trial in Progress (ID 2790)
09:30 - 09:30 | Author(s): J. Zhao
- Abstract
Background:
Background: Over 60% of patients with non-small-cell lung carcinoma (NSCLC) require radiation treatment, with an overall cure rate < 10-15% and moderate toxicity in 10-30% of treated patients. While high-dose radiation improves survival, concern over radiation-induced toxicities including radiation pneumonitis (RP) have limited its use. Predicting probability of tumor control and lung toxicity offers a promising strategy for individualized radiation therapy (RT), such as giving higher dose radiation to resistant tumors when probability of toxicity is low, improving the therapeutic ratio. Technetium-99m (Tc-99m) hexamethylpropylene amine oxime (HMPAO) imaging is an established method for evaluation of brain perfusion, tissue inflammation, infection, and abscess localization. Tc-99m HMPAO, a lipophilic biogenic amine that easily crosses the cell membrane into the endothelial cytoplasm, is a sensitive indicator of endothelial cell damage and microvascular injury, penetrating into the alveolar macrophage reflecting impaired alveolar integrity proportional to inflammation and lung toxicity. Once intracellular, it is retained by conversion to hydrophilic nondiffusable form mediated by glutathione oxidation/reduction within the epithelial lining and bronchoalveolar cell, and has been used for non-invasive detection of lung injury proportional to severity. We used Tc-99m HMPAO scintigraphy to semiquantitatively document the presence and severity of lung toxicity in 4 patients undergoing RT for NSCLC.
Methods:
Methods: Four patients with NSCLC (3 Stage IIIB receiving concurrent RT and carboplatin/paclitaxel chemotherapy, 1 Stage IB RT alone) underwent lung computed tomography (CT), positron emission tomography (PET)/CT with 2-deoxy-2-[fluorine-18]fluoro-D-glucose (FDG), ventilation (V)/perfusion (Q) lung imaging with Tc-99m diethylene triamine pentaacetic acid/Tc-99m macroaggregated albumin, and inflammation imaging with Tc-99m HMPAO; at baseline prior to treatment, during RT after 36-50 Gray, and at 3 months following radiation completion.
Results:
Results: All patients had matching V/Q lung abnormalities in the areas of tumor and RT, and tumor-positive baseline FDG PET/CT imaging that showed response to therapy. Three patients without RP had HMPAO imaging that mimicked Q lung imaging on all 3 sequential imaging studies. No patient experienced RP during RT, while one patient experienced grade 1 RP at 3 months, showing progressive increase in HMPAO inflammatory uptake in adjacent lung from baseline to during-RT to 3 months post-RT imaging, not appreciated on FDG PET/CT imaging (Figure 1).
Conclusion:
Conclusion: Tc-99m HMPAO nuclear imaging may provide more sensitive evaluation of the presence and severity of RP. In this case, uptake on during-RT imaging predated, predicted, and confirmed development of grade 1 RP at 3 months. Figure 1
