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M. Stenmark



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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): M. Stenmark

      • 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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    P3.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 235)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 1
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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 - 17:00  |  Author(s): M. Stenmark

      • Abstract
      • Slides

      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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