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M. Matuszak



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    MO25 - NSCLC - Combined Modality Therapy II (ID 112)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Mesothelioma
    • Presentations: 1
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      MO25.10 - A Phase II trial of mid-treatment FDG-PET adaptive, individualized radiation therapy plus concurrent chemotherapy in patients with inoperable non-small cell lung cancer (NSCLC) (ID 3461)

      11:25 - 11:30  |  Author(s): M. Matuszak

      • Abstract
      • Presentation
      • Slides

      Background
      We hypothesized that individualized radiation treatment targeting to the FDG-avid tumor identified mid-treatment would improve local tumor control.

      Methods
      This is a phase II trial for patients with inoperable/unresectable NSCLC. Conformal radiotherapy (RT) was given in 30 daily fractions. RT dose was individualized to a fixed rate of grade >2 lung toxicity and adaptively escalated to the residual tumor on mid-tx FDG-PET upto a total dose of 86 Gy. Patients were given concurrent weekly followed by consolidation carboplatin/paclitaxel. The primary endpoint was local-regional tumor control (LRTC) and local-regional progression free survival (LRPFS) at 2 years.

      Results
      42 patients were enrolled: median age 63 years (range 45-83); 28 (67%) male; 39 (93%) smokers; 38 (92%) stage III; and 45% squamous cell. Median physical dose reached was 83 Gy (range 63-86 Gy), equivalent to 90 Gy in 2 Gy fractions (biological effective dose 107 Gy). Minimum and median follow-up were 9 and 27 months, respectively. The 2-year rates of in-field LRTC, overall LRTC, and LR-PFS were 84% (62-94%), 61% (39-77%), and 37% (22-52%), respectively. 15 patients progressed: 2 (13%) at primary tumor alone; 4 (27%) first at distant sites alone; 2 (13%) at nodal regions alone; 5 (33%) at both distant sites and nodal regions; 1 (7%) at both distant site and primary tumor; 1 (7%) at both nodal region and primary tumor. Median overall survival was 22 months (10-33 months) and 2-year overall survival rate was 49% (32-63%). These results compared favorably to stage-matched patients treated with standard-dose RT in our center 2-year overall survival 23% (8-41%) during the same time period.

      Conclusion
      Adapting RT by targeting high dose radiation to the FDG avid region detected mid-treatment provides outstanding 2-year local-regional tumor control. RTOG 1106 is currently testing this regimen in a randomized fashion.

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    P1.06 - Poster Session 1 - Prognostic and Predictive Biomarkers (ID 161)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P1.06-045 - Serum microRNA as a predictive marker for radiation pneumonitis in patients with inoperable/unresectablenon-small cell lung cancer (NSCLC) (ID 2795)

      09:30 - 09:30  |  Author(s): M. Matuszak

      • Abstract

      Background
      Radiation pneumonitis (RP) is a major dose-limiting toxicity after thoracic radiotherapy (RT), with no good models available to accurately predict the individual risk.MicroRNAs (miRNAs) are found to be stable in serum and other body fluids,with exciting potential as novel non-invasive biomarkers. This study is to investigate serum microRNAs associated with RP grade ≥ 2 in inoperable/unresectable NSCLC patients treated with definitive RT.

      Methods
      134 patients with inoperable/unresectable NSCLC treated with definitive RT (18-month minimum follow-up) were eligible. Serum samples were collected prospectively before treatment. 100 patients who had enough serum and reliable miRNA profile quality were included in this study. MiRNA profiling was performed using real-time PCR-based array, containing a panel of 84 miRNAs detectable in human bodily fluids. Spiked-in cel-miR-39 was used for normalization. The primary endpoint was symptomatic RP (grade 2 and higher). 2-sample mean comparisons were used between the RP and non-RP subgroups.Stepwise Logistic regression model building was used to build a miRNA signature. Receiver operator characteristic (ROC) analysis was used to assess the predictive ability of single-marker and signature of RP.

      Results
      Of 100 patients enrolled, 17 (17.0%) patients developed symptomatic RP. Patients received a median of 70 Gy (34-85.6Gy) of RT with a mean lung dose (MLD) of 16.9 Gy (2.1-25.5 Gy). Serum miRNA profiling identified pre-treatment expressions of 9miRNAs were significantly associated with risk of RP (p<0.05). Significant correlations were not found for any clinical or dosimetric parameters including age, gender, stage, MLD (p>0.05). Stepwise regression modeling identified only has-miR-191 as significant predictors of symptomatic RP (HR=4.94, 95%CI:1.46-16.66, p=0.01). Using ROC curves, we found has-miR-191 was independent predictors of symptomatic RP (p=0.01). A model of combining has-miR-191 and MLD had AUC of 0.72 (p=0.004) comparing to 0.64 of MLD alone (p=0.08).

      Conclusion
      In our preliminary analysis, baseline serum has-miR-191 may help predictingsymptomaticRP. However, analysis on larger and independent datasets will be required to verify our findings.

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    P1.08 - Poster Session 1 - Radiotherapy (ID 195)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Radiation Oncology + Radiotherapy
    • Presentations: 1
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      P1.08-026 - Functional dosimetric metrics based on the ventilation and perfusion SPECT-CT during the course of radiotherapy and association with radiation-induced lung toxicity in patients with non-small-cell lung cancer (ID 3325)

      09:30 - 09:30  |  Author(s): M. Matuszak

      • Abstract

      Background
      To investigate volume changes in single photon emission computed tomography (SPECT) ventilation (V) and perfusion (Q) - weighted functional lung (FL), and dose-volume histogram of functional lung (FDVH) from V or Q SPECT and factors associated with radiation-induced lung toxicity (RILT) during the course of radiotherapy (RT) in patients with non-small-cell lung cancer (NSCLC).

      Methods
      Seventy NSCLC patients treated with definitive RT were enrolled prospectively. V and Q SPECT-computed tomography (CT) were performed prior to and during RT at approximately 45 Gy. FL was created from the whole lung (WL) in V and Q SPECT using a threshold of 30% of the maximum uptake of normal lung. Patients had dose calculated on CT scan to provide a standard dose-volume histogram (DVH). V and Q SPECT scans provided FDVH and functional dosimetric parameters. From the FDVH; the percent of FL receiving from 5 to 60 Gy and the mean doses of functional lungs (FMLD) were computed. Differences of volume and volume change of WL and FL between pre-RT and during-RT were compared. Differences of functional and standard dosimetric parameters between the patients with and without RILT were compared. Clinical fibrosis and pneumonitis were graded according to Common Terminology Criteria for Adverse Events version 3.0, grade 2 and above were considered to be clinically significant.

      Results
      The accumulative incidence of ≥ grade 2 clinical fibrosis and pneumonitis were 23.4%. The volume of lung measured by using CT or V and Q SPECT did not change significantly during radiotherapy (All p>0.05). The difference of lung volume between standard CT or V and Q SPECT was not significant in patients with RILT and without RILT (All p>0.05). However, the volume of V and Q both functional lung changed -12.4% (95% CI, -29.6% to 4.9%) in patients with RILT and 13.3% (95% CI, 2.7% to 23.9%) in patients without RILT during RT (p=0.02). The difference of mean lung dose (MLD) measured by using CT or V and Q SPECT was not significant in patients with RILT and without RILT (All p>0.05). However, the MLD was significantly higher in patients with RILT in during-RT than pre-RT CT (17.1 Gy and 15.4 Gy, p=0.01); the FMLD was significantly higher in patients with RILT in during-RT than pre-RT V and Q SPECT (16.7 Gy and 13.0 Gy, p=0.03). The V20-V55 by using during-RT CT were higher in the patients with RILT than without RILT (V20:29.0% and 22.0%, p=0.06; V25: 26.4 % and 19.0 % p=0.04; V30: 23.7 % and 16.6 %, p=0.03; V35: 21.1 % and 14.6 %, p=0.03; V40: 18.9 % and 12.6 %, p=0.02; V45: 16.4 % and 10.9 %, p=0.03; V50: 14.3 % and 9.1 % p=0.03; V55: 11.6 % and 7.5 %, p=0.04). The V5-V60 by using during-RT V and Q SPECT was higher in patients with RILT than without RILT, but not statistically significant.

      Conclusion
      Functional DVH metrics of V and Q SPECT and during-RT CT based DVH may be more significant in their association with RILT than pre-CT. However, these results need to be validated.