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David Catharina Petrus Cobben



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    OA01 - Improving Outcomes in Locoregional NSCLC I (ID 892)

    • Event: WCLC 2018
    • Type: Oral Abstract Session
    • Track: Treatment of Locoregional Disease - NSCLC
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 10:30 - 12:00, Room 107
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      OA01.03 - Interaction Between Dose and Calcifications Is a Predictor for Overall Survival in Lung Cancer Patients Receiving Radiotherapy (ID 13920)

      10:50 - 11:00  |  Author(s): David Catharina Petrus Cobben

      • Abstract
      • Presentation
      • Slides

      Background

      Recently, incidental dose to the heart was found to be predictive for overall survival in lung cancer patients receiving radiotherapy [McWilliam et al EJC 2017, Johnson et al Radiother Oncol 2018]. These patients often present with multiple comorbidities that should be incorporated in survival analysis. However, such data is often missing. We investigated whether calcifications, identified on the radiotherapy planning CT, can be used as a surrogate for cardiac health. In particular, we investigated the interaction between calcifications, dose and survival.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Data from 814 unselected non-small cell lung cancer patients was used, all treated with 55Gy in 20 fractions. Methodology was developed to automatically segment calcifications within the heart, the aortic arch and their surroundings. The 3D planning CT scans, and the associated lung and spinal cord delineations were processed using well-established image processing algorithms, e.g., convex hull, thresholding, morphological operations, connected pixel analysis and flood filling to detect calcifications. Moreover, shape analysis was included to enhance regions that presented tubular or plate-like appearance. The detection algorithm was validated in a small subset of 10 patients, and this group was used to determine the success and error rate of the automatic segmentation. Finally, a Cox-proportional hazards multivariate analysis was performed for overall survival of all patients accounting for tumour size, total calcification volume, mean dose across all identified calcifications, and interaction between calcification volume and dose.

      4c3880bb027f159e801041b1021e88e8 Result

      The success rate of the algorithm for identifying calcifications was 81.8%, its error rate was 8.8%. The multivariate survival analysis identified tumour size (continuous, p<<0.0001) and the interaction of calcification volume and their mean dose (continuous, p=0.029) as significant. Calcification volume (p=0.57) or mean calcification radiation dose alone (p=0.269) were not found to be significant.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Multivariate analysis shows a significant interaction between volume of the identified calcifications and their mean radiotherapy dose predicting survival. Further improvements to identify calcifications in the descending thoracic aorta and validation of our methodology are required. Further work linking our results with the established Agatston or Coronary Artery Calcium score is in progress.

      * EVO-FB share first authorship

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    P2.01 - Advanced NSCLC (Not CME Accredited Session) (ID 950)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 2
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.01-15 - A Radiologist-Led Training Workshop for MR Based Normal Tissue and Tumour Delineation for Lung Cancer Radiotherapy. (ID 13857)

      16:45 - 18:00  |  Author(s): David Catharina Petrus Cobben

      • Abstract
      • Slides

      Background

      A potential benefit of MR-image guided radiotherapy (MRIgRT) in lung cancer is the reduction of treatment related uncertainties through improved soft tissue contrast. However, this benefit may be obscured by inter-observer variation in gross tumour volume (GTV) and organ at risk (OAR) contouring. A radiologist led workshop was organised to provide training in such contouring on MR.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Planning CT, PET-CT and MRI were acquired in four lung cancer patients. MR sequences included 3D radial gradient echo, T2 DIXON Turbo Spin Echo (TSE), and T2 TSE with and without fat-sat. Data sets were local rigidly registered and imported into the so-called “Big Brother” contouring software.

      The radiologist led teaching on OAR and GTV contouring used an MR lung atlas (produced by this group). Seven radiation oncologists contoured the brachial plexus (BP), heart, proximal bronchial tree, oesophagus and GTV. This was followed by a multi-disciplinary group discussion (oncologists, radiologists and physicists) on the contouring challenges and subsequently contours were reviewed and the atlas adjusted.

      4c3880bb027f159e801041b1021e88e8 Result

      The BP and heart were the most difficult OARs to contour and showed the largest inter-observer variation. Following contour review and discussion between radiologist and oncologists updates to atlas and protocols were made. The GTV was found to be most challenging at the soft tissue interfaces and requires further work (Figure 1).

      contours.jpg

      8eea62084ca7e541d918e823422bd82e Conclusion

      This early work demonstrates the need for radiologist-led training in OAR and GTV contouring in lung cancer patients using MR images. This will be especially important for the integration of MR into treatment planning and an MRIgRT adaptive workflow. We have arranged future workshops in order to provide further training and to assess inter-observer variation in OAR and GTV contouring using MR on more cases.

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      P2.01-27 - MR, CT and Cone-Beam CT for Lymph Node Visualisation in Locally-Advanced Lung Cancer (ID 11800)

      16:45 - 18:00  |  Author(s): David Catharina Petrus Cobben

      • Abstract
      • Slides

      Background

      The largest benefit of MR-guided radiotherapy in lung cancer may be on-board visualisation of malignant lymph nodes (LNs). In this study, we assessed whether MR images were suitable for LN visualisation for treatment adaptation. We hypothesised that MR would outperform CT and Cone-Beam-CT (CBCT).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      CT, CBCT and MR images were acquired in four lung cancer patients with malignant LNs, confirmed using PET-CT and/or endobronchial ultrasound-guided biopsies. A total of 15 LNs from mediastinal and hilar nodal stations were assessed. Imaging datasets included: (1) CT planning scan with IV contrast; (2) MR1 (within 1 week of CT); (3) Mid-treatment CBCT (without contrast); and (4) MR2 (day of CBCT). MR sequences included: Turbo Spin Echo (TSE), TSE with fat-sat and 3D radial gradient echo. The images were randomised and independently scored by four thoracic radiation oncologists according to whether the malignant LN in each nodal station was visualised well enough to permit contouring. Scores were: not visible (1), unclear (2), clear (3) and very clear (4). Scores 3 and 4 were designated as ‘suitable for contouring’.

      4c3880bb027f159e801041b1021e88e8 Result

      As shown in figure 1, there was no significant difference in the number of LNs deemed suitable for contouring on CT (87%) compared to MR1 (82%). A significant difference was found between CBCT (10%) and MR2 (80%).

      picture11.png

      8eea62084ca7e541d918e823422bd82e Conclusion

      MR did not out-perform CT with contrast for malignant LN visualisation, possibly due to greater observer familiarity with CT. MR was significantly better than CBCT, likely due to superior soft tissue contrast. These findings support the use of MR-guided radiotherapy in locally-advanced lung cancer for adaptive planning or treatment verification. The greater variation in MR scores between oncologists (especially between sequences) could be due to lack of experience with thoracic MR. Future research will optimise MR for this task and assess LN localisation on a larger dataset.

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    P2.17 - Treatment of Locoregional Disease - NSCLC (Not CME Accredited Session) (ID 966)

    • 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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      P2.17-08 - Heart Motion in Lung Radiotherapy: How Representative Are Delineations Based on 3DCT, Average and Maximum Projection Scans? (ID 13946)

      16:45 - 18:00  |  Presenting Author(s): David Catharina Petrus Cobben

      • Abstract
      • Slides

      Background

      Evidence is emerging that the heart is more radiosensitive than previously assumed [1-2]. However, only delineations on the average projection or 3D CT scans are used for treatment planning. Therefore the motion of this organ due to respiration and contraction is not accounted for. In this pilot study, we assessed how representative the delineations based on the 3D CT scan, average (AVG) and maximum intensity projections (MIP) are.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Both 3D and 4D CT scans for 7 lung cancer patients treated by SABR were used in this study. Median delineations, derived from 3 independent observers following a previously agreed protocol, were calculated on the 3D CT, AVG, MIP and 25% exhale scans.

      Delineations on each 4D phase scan (n=8) were created by propagating the median 25% exhale contours using RayStation v5.99. The volume representing the maximum extent of motion was estimated as the union of all 4D phase delineations (U4D). Surface distances from the U4D to 3D, AVG, MIP volumes were calculated. Distances in the most extreme surface points (1cm most superior/inferior, 10% most right/left/anterior/posterior) are reported.

      4c3880bb027f159e801041b1021e88e8 Result

      Figure 1 shows the distances for the most extreme surface points, for all patients and for each delineation. Patterns vary widely among patients. From the three delineations, MIP is the ‘closest’ to the maximum extent of motion, followed by AVG and 3D.

      fig.png

      8eea62084ca7e541d918e823422bd82e Conclusion

      None of the delineations represented the heart’s maximum extent of motion for all patients, the MIP being the ‘most representative’ volume. All delineations would require an expansion to include all motion. Research including dosimetry measurements and inter-observer variability is required to determine the relevance of expanding the original delineations, and the corresponding margin magnitudes.

      [1] Johnson et al. Radiotherapy & Oncology. 2018. Volume 127:S170-1
      [2] Wang et al. J Clin Oncol. 2017. 35(13):1387-94.

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    P3.01 - Advanced NSCLC (Not CME Accredited Session) (ID 967)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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      P3.01-26 - A Framework for Systematic Clinical Evaluation of Technical Innovations in Lung Cancer Patients Treated on the MR-Linac (MRL) (ID 12562)

      12:00 - 13:30  |  Author(s): David Catharina Petrus Cobben

      • Abstract
      • Slides

      Background

      A recent innovation in radiotherapy is the MRL developed by Elekta and Philips. The MRL combines a 1.5 T MRI with a 7 MV linac. It allows the acquisition of high resolution MR images for on treatment verification, adaption and response monitoring.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Seven cancer institutions from Europe and North America, are working within the Elekta MR-Linac Consortium to evaluate the MRL within a framework called ‘R-IDEAL’ (Radiotherapy Idea Development Exploration Assessment Long-term Evaluation) 1.

      4c3880bb027f159e801041b1021e88e8 Result

      The table below summarizes the ongoing and planned work within the Elekta MR-Linac Consortium.

      table for wlcc 3-5-2018.jpg

      Progress to date:
      Stage 0:
      We defined in 80 patients the optimal MRI sequences suitable for GTV and organ at risk (OAR) contouring: T2 Turbo Spin Echo (TSE), T2 TSE with fat sat, T1 radial gradient echo, and DIXON TSE. Two radiology-led workshops were organized and inter-observer agreement was assessed for OARs. These led to a consensus-based OAR atlas. A study is being prepared to compare the image quality of the current standard CBCT and MR images at baseline and mid-treatment for treatment verification and set-up correction.
      Stage 1: we will investigate the clinical feasibility of the MRL for standard of care radiotherapy and the scope for adaptive radiotherapy (margin reductions) and detecting changes in oxygenation during treatment on the MRL in patients with locally advanced (LA) NSCLC .
      Stage 2a/b : Based on the results from stage 1 we will design a study aiming to reduce margins around the tumour and dose escalate in patients with LA NSCLC.

      8eea62084ca7e541d918e823422bd82e Conclusion

      The aim of this programme of work is to generate robust evidence to support the introduction of the MRL and to improve outcomes of patients with LA NSCLC.

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