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J. Belderbos



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    MA13 - Modern Technologies and Biological Factors in Radiotherapy (ID 395)

    • Event: WCLC 2016
    • Type: Mini Oral Session
    • Track: Radiotherapy
    • Presentations: 1
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      MA13.03 - Analysis of Intra-Thoracic Anatomical Changes Observed in Clinical Workflow of Cone-Beam CT Guided Radiotherapy for Lung Cancer (ID 4478)

      16:00 - 17:30  |  Author(s): J. Belderbos

      • Abstract
      • Presentation
      • Slides

      Background:
      Objectives: In lung cancer patients treated with image-guided radiotherapy we use daily Cone-Beam CT (CBCT) guidance for setup verification and to check on intra-thoracic anatomical changes (ITACs). ITACs like tumor baseline shifts, the occurrence or dissolving of an atelectasis, tumor progression or regression, pleural fluid- and infiltrative changes have been reported in 72% of lung cancer patients (Kwint M R&O 2014) during the course of irradiation. A traffic light protocol has been in use by the radiation technologists since 2010 to classify anatomical changes seen on the CBCT with anticipated different influences on the dose distribution using 4 action levels. The purpose of this study was to quantify how often the ITACs occurred in daily clinical practice and for which action level.

      Methods:
      All lung cancer patients irradiated in 2015 (excluding stereotactic treatments) with a dose >44 Gy were included. All patients had a daily CBCT guided online correction protocol and the traffic light action level of each CBCT was recorded. The following action levels have been defined: code red for immediate consultation with the physician before beam-on, code orange for a decision on the notification of the physician before the next fraction, code yellow to inform the physician; no action is required- and green for no change so no intervention necessary. We also analyzed the percentage of patients that received a new planning-CTscan and/or a new treatment plan.

      Results:
      In 2015 a total of 299 lung cancer patients were conventionally irradiated with radical intent and 5971 CBCT scans were made. Of these CBCTs 51% were scored as code green, 24% as code yellow, 24% as code orange and code red in less than 1% of the CBCTs. Forty patients (13%) had a new treatment plan, of which 34 patients (11%) had a new planning CT-scan and 6 patients (2%) had a new treatment plan on the original planning CT-scan.

      Conclusion:
      Image-guided irradiation for 299 conventionally fractionated lung cancer patients (>44 Gy) in 2015 revealed lTACs in 25% of the CBCT’s made and a physician’s decision on the notification was necessary. A total of 13% of the patients treated received an unscheduled adaptive treatment plan during the course of treatment. The traffic light protocol in daily clinical workflow worked well as a tool to prioritize a physician’s decision based on the ITACs seen on the CBCT images.

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    OA09 - Locally Advanced NSCLC: Innovative Treatment Strategies (ID 384)

    • Event: WCLC 2016
    • Type: Oral Session
    • Track: Locally Advanced NSCLC
    • Presentations: 1
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      OA09.06 - Metformin Use during Concurrent Chemoradiotherapy for Locally Advanced Non-Small Cell Lung Cancer (NSCLC) (Abstract under Embargo until December 6, 7:00 CET) (ID 3753)

      11:00 - 12:30  |  Author(s): J. Belderbos

      • Abstract
      • Presentation
      • Slides

      Background:
      An increasing body of (pre)clinical evidence has suggested that metformin has an anticancer effect. The aim of this study was to investigate whether the use of metformin during concurrent chemoradiotherapy (cCRT) for locally advanced non-small cell lung cancer (NSCLC) improved treatment outcome.

      Methods:
      A total of 682 patients were included in this retrospective cohort study (59 metformin users, 623 control patients). All received cCRT in one of three participating radiation oncology departments in the Netherlands between January 2008 and January 2013. Primary endpoint was locoregional recurrence free survival (LRFS), secondary endpoints were overall survival (OS), progression-free survival (PFS) and distant metastasis free survival (DMFS)

      Results:
      No significant differences in LRFS or OS were found. Metformin use was associated with an improved DMFS (74% versus 53% at 2 years; p = 0.01) and PFS (58% versus 37% at 2 years and a median PFS of 41 months versus 15 months; p = 0.01). In a multivariate cox-regression analysis, the use of metformin was a statistically significant independent variable for DMFS and PFS (p = 0.02 and 0.03).

      Conclusion:
      Metformin use during cCRT is associated with an improved DMFS and PFS for locally advanced NSCLC patients, suggesting that metformin may be a valuable treatment addition in these patients. Evidently, our results merit to be verified in a prospective trial.

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    P2.02 - Poster Session with Presenters Present (ID 462)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Locally Advanced NSCLC
    • Presentations: 1
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      P2.02-021 - Extracranial Progression (ePD) after Chemoradiotherapy (CRT) for Stage III NSCLC: Does the Chemotherapy Regimen Matter? (ID 4887)

      14:30 - 15:45  |  Author(s): J. Belderbos

      • Abstract

      Background:
      In stage III NSCLC concurrent chemoradiation (cCRT) compares favourably to sequential CRT (sCRT). No superior chemotherapy regimen has been identified regarding (extracranial)PD. Previously we reported that the specific chemotherapy did not influence symptomatic brain metastases incidence. Here we analyse whether the specific chemotherapy influences occurrence of extracranialPD as first PD site (ePD~first~) after CRT.

      Methods:
      This retrospective multicenter study included all consecutive stage III NSCLC patients that completed CRT between 01-2006 and 06-2014. Primary endpoint was ePD~first ~(with/without cranial PD). Differences between regimens were assessed using logistic regression modelling including known relapse risk factors (age, gender, stage, histology) and the specific chemotherapy: cCRT versus sCRT. Within cCRT: daily low dose cisplatin (LDC) versus cyclic dose polychemotherapy (CDC); LDC versus (non-)taxane CDC; LDC versus subgroups of ≥50 CDC patients).

      Results:
      838 patients (737 cCRT, 101 sCRT) from 5 institutions were eligible. Median follow-up [95% CI] was 45.1 [42.3-47.8] months. 530 (63.2%) had PD, of which 463 (87.4%) had ePD~first. ~Median time to ePD~first~ was 16.6 [14.5-18.7] months. Patients with ePD~first~ had more often squamous histology (p=0.04). ePD~first~% or median time to ePD~first~ was not different for sCRT versus cCRT (table 1). 461 (62.6%) patients had PD after cCRT, of whom 401 (87.0%) had ePD~first~. ePD~first~% or median time to ePD~first~ did not differ between LDC and CDC. The chemotherapy regimen (cCRT versus sCRT) did not influence ePD~first~ on multivariate analysis: OR 0.81 [0.52-1.24] (p=0.33). LDC versus CDC cCRT did not differ: OR 0.96 [0.72-1.29] (p=0.80). Comparable results were found for LDC versus CDC non-taxane (N=277) and CDC taxane regimens (N=69) and for cCRT regimens with ≥50 patients (LDC versus cisplatin/etoposide (N=188), cisplatin/vinorelbin (N=65), weekly cisplatin/docetaxel (N=60)).

      Table1
      concurrent N=737 sequential N=101 p-value
      PD N(%) 461 (62.6) 68 (68.3) 0.18
      ePDfirst N(%) -patients with concomitant brain metastases 401 (87.0) -38 (9.5) 62 (89.9) -8 (12.9) 0.19
      median time to ePD [95%CI] months 17.5 [15.0-20.0] 14.3 [11.9-16.7] 0.16
      LDC N=391 cyclic dose N=346 p-value
      PD N(%) 245 (62.7) 216 (62.4) 0.33
      ePDfirst N(%) -patients with concomitant brain metastases 211 (86.1) -17 (8.1) 190 (88.0) -21 (11.1) 0.80
      median time to ePD [95%CI] months 17.4 [14.3-20.5] 18.3 [14.2-22.5] 0.59


      Conclusion:
      Sixty-three percent of stage III NSCLC patients developed PD, of whom 87% had ePD~first~. Incidence of ePD~first~ is independent of the specific chemotherapy regimen.

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    P2.05 - Poster Session with Presenters Present (ID 463)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Radiotherapy
    • Presentations: 1
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      P2.05-040 - Interobserver Variability in the Definition of the Primary Lung Cancer and Lymph Nodes on Different 4DCT Reconstructions (ID 5156)

      14:30 - 15:45  |  Author(s): J. Belderbos

      • Abstract
      • Slides

      Background:
      Delineation variability is a major uncertainty in radiotherapy for lung cancer. As respiratory motion is an important part of this uncertainty, respiratory correlated computed tomography (4DCT) imaging is widely used. Several image reconstruction techniques are available to generate 3D data for delineation, such as the Maximum Intensity Projection (MIP) and the mid-ventilation (MidV) technique. The latter selects data at the time weighted mean tumour position. Both techniques are prone to motion artefacts. The new Mid-position (MidP) technique averages CT data after motion compensation to the mean position reducing such artefacts. The aim of this study is to evaluate interobserver variation for tumour delineation for these three image reconstruction techniques.

      Methods:
      4DCTS of 10 patients were reconstructed using MIP, MidV and MidP methods. Seven specialised radiation oncologists delineated the primary tumour (GTVp) and lymph nodes (GTVln) on each reconstruction with a minimum of 4 weeks interval between delineations, using a provided protocol. The interobserver variation in the delineation of the GTVs was evaluated by calculating delineated volumes, conformity index (CI), and local SD between delineated contours (SDlocal) for GTVp and GTVln.

      Results:
      The differences in delineation variability are small (Table 1), with the only significant differences in overall volume (Friedman test): the MidP volume is slightly smaller than the MidV volume indicating a larger confidence in delineation. Counter-intuitively the observer variation was higher on the Midp images for the GTVln which seems to be related to increased reliance on the PET-CT images when delineation on the lower quality MIP images.

      Table 1: Interobserver variability in the delineation of the GTVp and GTVln
      Image Mean Volume (cc) Mean CI Mean SDlocal (cm)
      ALL GTVp GTVln
      MIP 81.91 0.568 0.363 0.330 0.477
      MidV 66.17 0.576 0.327 0.314 0.425
      MidP 62.23 0.602 0.337 0.261 0.543
      MIP>MidV (p=0.000) MIP>MidP (p=0.000) MidP p=0.354 p=0.655 p=0.648 p=0.834p


      Conclusion:
      Although not statistically significant, the MidP images had the highest CI, lowest volume and the lowest SD for the GTVp but not for the GTVln. Overall the MidP had the smallest interobserver variation. Adherence to delineation protocols for lymph nodes must be improved to benefit from the better image quality of MidP.

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