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T. Kron



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    E06 - Issues in Current Multidisciplinary Practice (ID 6)

    • Event: WCLC 2013
    • Type: Educational Session
    • Track: Combined Modality
    • Presentations: 1
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      E06.2 - Staging and Early Response Assessment in Combined Modality Therapy for NSCLC (ID 399)

      14:25 - 14:45  |  Author(s): T. Kron

      • Abstract
      • Presentation
      • Slides

      Abstract
      For years radiation oncologists have dreamed of being able to dynamically adapt treatment to the response of normal and tumor tissues observed during a protracted course of radiotherapy. An obvious goal is to adjust the PTV as the GTV shrinks during treatment, which may improve dose volume metrics in the organs at risk, especially lung. Reinflation of atelectatic lung in response to tumour size reduction may require adjustment of PTV size and position to avoid geographic miss. Cone beam CT (CBCT) has revolutionised the ability to regularly image soft tissue, although it is less useful for targets within the mediastinum or those defined primarily by FDG PET. The main limiting step is the time required to develop an adaptive treatment plan without interrupting treatment. Experience suggests that tumor reduction needs to be substantial to have a meaningful impact on the dose volume metrics. The use of serial FDG PET during treatment to detect residual activity and to use this as a surrogate for persistent disease for adaptive radiotherapy is under investigation. This is however based on an unproven assumption that such FDG activity is due to tumor and not inflammation. Tumor motion adds further uncertainty, affecting both SUV and intrafraction location of the residual FDG uptake. CBCT may also detect tumor progression. This seems to be uncommon.(1) When it occurs, apart from discontinuing futile treatment to avoid unnecessary toxicity, can anything else be done? Our group has investigated the use of PET tracers to detect functional changes in tumour during treatment, including FDG and the thymidine based tracer FLT which we hypothesise images tumour proliferation. Preliminary results indicate that FLT detects functional changes in the tumour earlier than FDG, but the clinical implications of this are unknown.(2) One patient with clinical progression had increased uptake of FLT detected at 20 Gy, suggesting accelerated repopulation. The rate of treatment was accelerated with twice daily fractionation, resulting in a reduction in FLT uptake, providing anecdotal proof of principle. Accelerated repopulation has also been indirectly observed with induction chemotherapy.(3) Imaging with FLT may present an opportunity to detect altered proliferation pre-radiotherapy which may benefit from accelerated fractionation.(4) A further change that may occur during fractionated treatment is reoxygenation. We have observed changes in uptake of the hypoxia PET tracer FAZA during a course of radiotherapy,(5) indicating that hypoxia is present in some tumors pre-treatment, although surprisingly little use is made of this knowledge in clinical practice. Changes observed in normal tissue response may also present opportunities for adaptive treatment. The patient can be used as a biological dosemeter, and the occasional patient will require truncation of treatment because of esophagitis. Is this increased sensitivity a surrogate for inherently increased radiosensitivity within the tumor, indicating that a higher tumor dose is unnecessary for such patients? Our group has observed changes in normal lung during treatment using ventilation/perfusion imaging, opening up prospects of avoiding functioning (as opposed to anatomical) lung with beam redirection.(6) Conclusions: A number of tools are now available to detect tumor and normal tissue response to radiotherapy during treatment. These changes may be anatomic or functional, including changes in tumor kinetics or the micro-environment. The challenge now is to turn these observations into clinically useful patient benefits. References 1. Lim G, Bezjak A, Higgins J, Moseley D, Hope AJ, Sun A, et al. Tumor regression and positional changes in non-small cell lung cancer during radical radiotherapy. J Thorac Oncol. 2011;6:531-6. 2. Ball D, Everitt S, Hicks R, Callahan J, Plumridge N, Collins M, et al. Differential Uptake of F18-fluoro-deoxy-glucose (FDG) and F18-fluoro-deoxy-l-thymidine (FLT) Detected by Serial PET/CT Imaging During Radical Chemoradiation for Non-Small Cell Lung Cancer (NSCLC). . J Thorac Oncol 2012;7:S238. 3. El Sharouni SY, Kal HB, Battermann JJ. Accelerated regrowth of non-small-cell lung tumours after induction chemotherapy. Br J Cancer. 2003;89:2184-9. 4. Baumann M, Herrmann T, Koch R, Matthiessen W, Appold S, Wahlers B, et al. Final results of the randomized phase III CHARTWEL-trial (ARO 97-1) comparing hyperfractionated-accelerated versus conventionally fractionated radiotherapy in non-small cell lung cancer (NSCLC). Radiother Oncol. 2011;100:76-85. 5. Trinkaus ME, Blum R, Rischin D, Callahan J, Bressel M, Segard T, et al. Imaging of hypoxia with (18) F-FAZA PET in patients with locally advanced non-small cell lung cancer treated with definitive chemoradiotherapy. J Med Imaging Radiat Oncol. 2013;57:475-81. 6. Siva S, Callahan J, Hofman MS, Eu P, Martin O, Pope K, Ball D, MacManus M, Kron T, Hicks RJ. Technical considerations and preliminary experience of a pilot study of Gallium-68 VQ 4D-PET/CT in lung radiotherapy. J Thorac Oncol 2012;7: S1182.

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    P2.08 - Poster Session 2 - Radiotherapy (ID 198)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Radiation Oncology + Radiotherapy
    • Presentations: 1
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      P2.08-025 - A study of respiratory-induced tumour motion based on anatomical lung location using 4DCT in lung cancer patients (ID 2976)

      09:30 - 09:30  |  Author(s): T. Kron

      • Abstract

      Background
      Respiratory induced tumour motion is one of several challenges encountered when delivering radical radiotherapy to lung cancer patients. In recent years, four-dimensional computed tomography (4DCT) has improved our ability to accurately define lung tumour motion during breathing. Using 4DCT images, our study aims to compare the magnitude of lung tumour motion due to respiration, amongst different anatomical lobes and pulmonary zones. This may help guide personalised radiotherapy margins for patients with lung cancer.

      Methods
      This is a retrospective study of 100 consecutive patients from the Peter MacCallum Cancer Centre treated with curative intent radiotherapy for lung cancer. All 4DCT scans accessible from patients scanned between December 2009 and May 2013 were included. Images were analysed using the MIM v5.6 software. Tumour volumes were delineated by a single observer and propagated to include all 10 phases of the respiratory cycle. Movements were tracked in the superior-inferior (SI), anterior-posterior (AP) and medio-lateral (ML) directions by changes in the gross tumour volume centroid coordinates. Tumour motion characteristics were correlated with anatomical lobe, pulmonary zone, tumour volume, histopathology, spirometry and T-stage. Tumours with chest wall or mediastinal invasion were excluded. Statistical analyses were performed using Prism v6.0.

      Results
      Preliminary data from 82 patients showed the greatest mean movement in the SI direction among lower lobe tumours compared to those located in the upper lobes [Left lower, 8.0mm, n = 13, vs. Left upper, 1.3mm, n = 24] [Right lower, 6.4mm, n = 19, vs Right upper, 1.9mm, n = 28], p < 0.01. In all lobes, mean movements were similar in the AP [1.6mm, Right lower; 2.1mm, Right middle; 1.8mm, Right upper; 2.3mm, Left lower; 1.6mm, Left upper] and lateral directions [0.9mm, Right lower; 2.4mm, Right middle; 1.2mm, Right upper; 1.5mm, Left lower; 1.2mm, Left upper]. 35 patients were staged as T1, 30 as T2 and 14 as T3. Mean lung tumour motion decreased with increasing T stage in the SI direction [3.9mm, T1; 3.7mm, T2; 3.5mm, T3], however this was not statistically significant. Assessment of the association between tumour motion and spirometry findings is ongoing. Figure 1

      Conclusion
      The degree of lung tumour motion varies widely according to its position within the lung. The largest differences in tumour motion was between the upper and lower lobes in the SI direction. Analysis of all 100 patient datasets is ongoing.

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    P3.08 - Poster Session 3 - Radiotherapy (ID 199)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Radiation Oncology + Radiotherapy
    • Presentations: 1
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      P3.08-024 - Preliminary experience in bronchoscopic placement and in-treatment imaging of two different fiducial markers for guidance of lung cancer radiation. (ID 2758)

      09:30 - 09:30  |  Author(s): T. Kron

      • Abstract

      Background
      During conventional radiation therapy, treatment image guidance is largely indirect relying on slow acquisition 3D volumetric imaging or the use of bony surrogates. Fiducial marker placement within/adjacent to lung tumours facilitates image guided radiation therapy by …….. Marker placement has been attempted percutaneously but is associated with pneumothorax in up to 45%, with frequent use of chest drain tubes. Furthermore, in-treatment imaging protocols are not standardized, and the impact of marker characteristics on accuracy of in-treatment imaging has not previously been reported. We describe our preliminary experience in bronchoscopic implantation and in-treatment tracking/imaging of two different types of lung fiducial marker.

      Methods
      Study design: Prospective observational case series of NSCLC patients undergoing radical radiation treatment . Bronchoscopic implantation: performed under conscious sedation using radial probe endobronchial ultrasound and fluoroscopic guidance to achieve tumour localization and placement within/adjacent to peripheral tumours. Post-implantation/ in-treatment imaging: Time-resolved 4D CT (Philips Brilliance+bellows system) for treatment planning and after completion of treatment to investigate marker movement. Throughout treatment delivery MV electronic portal images (EPI) were acquired plus kV planar and Cone Beam CT (CBCT) (Varian Medical System) images.

      Results
      Four patients with T1N0 NSCLC underwent bronchoscopic implantation of fiducial markers (two using Visicoil[TM] linear fiducial 10x0.75mm, two using SuperDimension® superLock™ 2-band 13x0.9mm markers. Confirmation of tumour localization was achieved with EBUS in all four patients. Two markers were placed in adjacent airways in one patient, and the remainder had a single marker placed within/adjacent to their peripheral tumour. No complications related to bronchoscopy or marker implantation were observed. No marker migration was observed over the treatment time for both marker types. Visibility of the markers in EPI was only possibly in selected beam directions though they were easily discernible in kV planar images (Figure 1a). While diagnostic CT scanning was able to demonstrate the markers in great clarity (Figure 1b), they caused significant image artefacts in CBCT. Figure 1 Figure 1: Image-guided radiotherapy images demonstrating: a) 4DCT image showing visicoil fiducial on maximum intensity projection images, tumour+motion contoured in red, & b) kV orthogonal image showing superLock™ 2-band marker.

      Conclusion
      Our preliminary experience indicates bronchoscopic implantation of fiducial markers is safe, and is achievable with a high degree of accuracy on initial imaging, and stability on subsequent in-treatment imaging. There is a fine balance of marker size minimising CBCT artefacts while allowing visualisation in EPI imaging which would be an ideal tool to verify gated radiotherapy delivery.