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Walter John Curran, Jr.



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    MA05 - Improving Outcomes in Locoregional NSCLC II (ID 901)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Treatment of Locoregional Disease - NSCLC
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 13:30 - 15:00, Room 105
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      MA05.05 - Photon-Based Cardiac Sparing Via Volumetric Modulated Arc Therapy in Thoracic Radiation Therapy for Locally Advanced Non-Small Cell Lung Cancer (ID 13419)

      14:00 - 14:05  |  Author(s): Walter John Curran, Jr.

      • Abstract
      • Presentation
      • Slides

      Background

      Increasing radiation dose to the heart is associated with worse survival in stage III non-small cell lung cancer. Techniques to reduce the dose to the heart, including proton beam therapy (PBT), are being evaluated in ongoing clinical trials. However, advanced technologies such as PBT are not readily accessible for most patients. We therefore sought to evaluate the efficacy of volumetric modulated arc therapy (VMAT), a readily available technology in the United States, to spare cardiac substructures and determine how a cardiac optimization treatment planning algorithm influences dose distribution to other thoracic organs at risk (OARs).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We selected stage III non-small cell lung cancer patients who were treated at our institution with VMAT to 60 Gy in 2 Gy fractions. Cardiac substructures were retrospectively contoured, and included: valves, atrioventricular node (AVN), coronary arteries (CA), chambers, and great vessels. New radiation treatment plans were created to spare these structures while preserving planning target volume (PTV) coverage and maintaining standard dose constraints to OARs. Dosimetry variables—maximum dose (Dmax), mean dose (Dmean), and common clinically relevant dose-volume relationships—for the new cardiac-sparing radiation treatment plans were compared via paired t-test to the original radiation treatment plans.

      4c3880bb027f159e801041b1021e88e8 Result

      Twenty-six patients, treated from July 2013 to September 2017, were included. Statistically significant improvements were demonstrated for all cardiac structures for the new cardiac-sparing plans compared to the original plans, while maintaining appropriate lung, esophagus, and spinal cord constraints, and PTV coverage goals, as demonstrated in Table 1 (significant P-values in bold).

      Table 1

      Dosimetry variable

      Cardiac-sparing plan (mean)

      Original plan (mean)

      P-value*

      Cardiac parameters

      Heart Dmax

      64.9 Gy

      63.6 Gy

      0.928

      Heart Dmean

      12.3

      16.1

      < 0.001

      Heart V5Gy

      55.4

      64.1

      0.003

      Heart V30Gy

      12.5

      18.7

      < 0.001

      Heart V40Gy

      7.9

      11.5

      < 0.001

      Heart V45Gy

      6.5

      11.5

      < 0.001

      Heart V60Gy

      2.7

      3.4

      0.001

      Aortic valve Dmax

      22.9

      31.7

      < 0.001

      Aortic valve Dmean

      11.4

      31.7

      < 0.001

      Mitral valve Dmax

      24.6

      29.4

      0.002

      Mitral valve Dmean

      11.2

      16.7

      < 0.001

      Pulmonic valve Dmax

      26.8

      35.4

      < 0.001

      Pulmonic valve Dmean

      14.1

      25.1

      < 0.001

      Tricuspid valve Dmax

      9.7

      16.6

      < 0.001

      Tricuspid valve Dmean

      5.6

      10.3

      < 0.001

      AVN Dmax

      13.4

      20.4

      < 0.001

      AVN Dmean

      8.1

      14.0

      < 0.001

      Left main CA Dmax

      26.4

      38.8

      < 0.001

      Left main CA Dmean

      16.4

      30.2

      < 0.001

      Left anterior descending CA Dmax

      27.4

      34.8

      < 0.001

      Left anterior descending CA Dmean

      14.4

      22.6

      < 0.001

      Left circumflex CA Dmean

      32.6

      36.8

      0.001

      Left circumflex CA Dmean

      19.3

      26.9

      < 0.001

      Right CA Dmax

      18.1

      26.1

      < 0.001

      Right CA Dmean

      9.4

      15.7

      < 0.001

      Left atrium Dmax

      51.8

      54.8

      0.091

      Left atrium Dmean

      17.5

      21.0

      < 0.001

      Left ventricle Dmax

      35.7

      40.1

      < 0.001

      Left ventricle Dmean

      8.3

      11.3

      < 0.001

      Right atrium Dmax

      31.4

      36.1

      0.004

      Right atrium Dmean

      11.1

      13.9

      < 0.001

      Right ventricle Dmax

      23.7

      33.2

      < 0.001

      Right ventricle Dmean

      6.9

      12.2

      < 0.001

      Aorta Dmax

      50.8

      55.3

      0.001

      Aorta Dmean

      20.4

      27.9

      < 0.001

      Pulmonary artery Dmax

      65.2

      65.1

      0.895

      Pulmonary artery Dmean

      32.3

      37.9

      < 0.001

      Superior vena cava Dmax

      47.4

      51.7

      0.002

      Superior vena cava Dmean

      29.4

      33.1

      0.006

      Other OAR parameters

      Lungs V5Gy

      56.5

      58.2

      0.121

      Lungs V20

      22.4

      23.3

      0.083

      Lungs Dmean

      13.6

      14.8

      0.012

      Spinal cord Dmax

      28.0

      31.1

      0.013

      Esophagus Dmean

      21.2

      22.1

      0.023

      PTV coverage parameters

      PTV Dmax

      65.5

      67.2

      0.189

      PTV minimum dose

      51.2

      52.7

      0.019

      PTV V100%

      95.2%

      95.4%

      0.195

      8eea62084ca7e541d918e823422bd82e Conclusion

      Dose to the heart and cardiac substructures can be substantially lowered using a cardiac-sparing optimization algorithm with VMAT, without increasing radiation dose other thoracic OARs or compromising PTV coverage. Though time-consuming, delineation of the full complement of cardiac substructures provides an effective means of improving the quality of radiation treatment plans with readily available technologies.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P2.03 - Biology (Not CME Accredited Session) (ID 952)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.03-07 - Radiomic Signatures Linked to Genetic Alterations as Detected by Next-Generation Sequencing: A Radiogenomics Analysis of Early-Stage NSCLC (ID 11858)

      16:45 - 18:00  |  Author(s): Walter John Curran, Jr.

      • Abstract
      • Slides

      Background

      Radiomics uses large-scale quantitative analysis of extracted image-based features to identify tumor phenotypes. Such frameworks based on computed tomography (CT) have identified informative features in lung cancer related to treatment response and prognosis. Molecular profiles have been increasingly recognized in non-small cell lung carcinoma (NSCLC) as predictors of clinical outcomes. The aim of this study is to isolate radiomic signatures which are associated with genomic alterations discoverable by extended panel testing.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Patients with early-stage NSCLC who received definitive local treatment and underwent next-generation sequencing were included for this analysis. 35 genomic alterations representing 32 genes were evaluated using SNaPshot (Life Technologies), TruSight (Illumina Inc), Guardant360 (Guardant Health) or a FISH panel of ALK, MET, ROS1 and RET. Regions of interest including each primary tumor volume were delineated on diagnostic CTs datasets; they were defined as either tumor only (TO), or tumor with a 1cm anatomically-modified anisotropic margin (TM). Measures describing delineation and tumor appearance within each volume were extracted using in-house software, recording HU characteristics, inhomogeneity, and first and second-degree texture statistics. 91 structural, textural, and intensity features were extracted. Univariate logistic regression was performed to test the performance between each extracted feature and the presence of genomic alterations.

      4c3880bb027f159e801041b1021e88e8 Result

      40 patients with diagnostic CTs available for feature extraction were included for analysis. The rate of mutation prevalence in the most commonly altered genes were: TP53 (52.1%), cMET (34.5%), KRAS (27%), PTEN (13.8%), EGFR (13.2%), and MET (12.1%). 5 features were associated with TP53 mutations using TO-extracted features, and 4 using the TM-based approach. cMET was linked to Hounsfield minimum (odds ratio [OR] 1.01, p=0.027), and Sobel minimum (p=0.049) using the TO approach. Long run emphasis standard deviation (STD) [OR 0.36, p=0.04], and long run low grey level emphasis STD (OR 0.37, p=0.04) correlated with cMET mutations using the TM approach. Laplacian sharpening mean was associated with the presence of EGFR mutations using both extraction approaches; finding OR 1.10 (p=0.04, TO method) and OR 1.12 (p=0.02, TM method). No other features were linked to EGFR alterations. Gradient magnitude variance was associated with PTEN using tumor-with-margin volumes (OR 0.83, p=0.028). No features were significantly linked to KRAS mutations using either extraction approach.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Multiple radiomic features were associated with TP53, cMET, EGFR, and PTEN mutations. Integration of such signatures may help inform prognosis for a heterogenous cohort of patients with early-stage non-small cell lung carcinoma.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    PC09 - Approaches to Management of Advanced NSCLC (ID 848)

    • Event: WCLC 2018
    • Type: Pro-Con Session
    • Track: Advanced NSCLC
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 10:30 - 12:00, Room 107
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      PC09.02 - Debate 1: Early vs Delayed Treatment of Asymptomatic Brain Metastases in Wild-Type NSCLC - Delayed (ID 11640)

      10:45 - 11:00  |  Presenting Author(s): Walter John Curran, Jr.

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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