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S. Siva



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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): S. Siva

      • 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): S. Siva

      • 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: 3
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      P3.08-005 - IAEA RCA 6065: Improving access to stereotactic ablative body radiotherapy (SABR) for lung cancer patients in Asia. (ID 988)

      09:30 - 09:30  |  Author(s): S. Siva

      • Abstract

      Background
      The IAEA/RCA Project “Strengthening the Application of Stereotactic Body Radiotherapy” aims to increase the capacity to deliver SABR in Asia. Lung cancer is one of the most common cancers in Asia. Most patients present with locally advanced or metastatic disease, but increased access to diagnostic scanning will result in earlier detection of lung cancers suitable for SABR. The shorter treatment time is beneficial in reducing the burden of treatment and economic costs of radiotherapy treatment. The clinical efficacy and socio-economic benefits of SABR have led to rapid implementation in the US[1], Europe[2] and parts of Asia[3]. SABR lung demands specialised expertise, physical infrastructure, and a long-term commitment to rigorous quality assurance. There is significant heterogeneity in the resources and expertise between the RCA Member States. This project aims to identify and ameliorate obstacles to the safe and effective implementation of SABR within Asia. Figure 1

      Methods
      Each country developed a work-plan specific to their capacities and needs. Key strategies for implementation of the project are: Development of treatment protocols Regional training courses Advocacy with Government bodies responsible for policy-making and funding, and education of the wider medical community and public about the benefits of SABR Expert missions with on-site training Publications including educational materials and the results of implementation( utilisation rates, local control and clinical outcomes) Formation of regional training hubs Specific goals identified for Australia were the need to standardise protocols, advocacy for access to funding through Medicare for advanced radiotherapy technologies, and the safe implementation of SABR in regional centres. The Tripartite Collaboration being developed at a national level between RANZCR, AIR and ACPSEM and the NSW SABR Collaboration will address these concerns.

      Results
      Australia has already contributed physics expertise to facilitate the success of the first regional training course, held in Singapore in December 2012. Sydney will host the final regional training course in 2015 on SABR for lung and spine. We continue to contribute our technical and clinical expertise in developing training materials and resources for the project.

      Conclusion
      Collaboration between well-resourced and developing countries in Asia is helping to sustainably develop resources and expertise to improve access to SABR for lung cancer patients. This networking provides future opportunities for large scale clinical trials and research in diseases with a high prevalence in the region. 1. Pan H et al. Cancer 2011 117(19):4566 2. Palma D et al. J Clin Oncol. 2010;28(35):5153 3. Teshima T al. J Radiati. Res 53.5 (2012): 710

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      P3.08-021 - Patient Specific Quality Assurance for Lung Cancer Stereotactic Ablative Body Radiotherapy (ID 2559)

      09:30 - 09:30  |  Author(s): S. Siva

      • Abstract

      Background
      Hypofractionated image guided radiotherapy of extracranial targets has become increasingly popular as a treatment modality for inoperable patients with one or more small lesions, often referred to as Stereotactic Ablative Body Radiotherapy (SABR). Our institution is using SABR for lung, liver, spine and kidney tumours and is the lead in a multicentre clinical trial of radical SABR for early stage lung cancer. Current and future trends in patient safety and quality assurance (QA) programs are towards ensuring patient safety using the most efficient methods. There is limited published work on patient specific QA for lung SABR treatments on which to base risk management QA programs. Thus, we have performed a review of the first two years of lung SABR patient specific QA process with the aims of highlighting specific areas of uncertainty in lung SABR delivery with the aims of improving efficiency and effectiveness of our QA program. This presentation will detail the results of the review and the evolution of the QA program to a risk-management based approach.

      Methods
      SABR involves one or few fractions of high radiation dose typically delivered in many small fields or arcs. Tight margins are often applied to mobile targets through heterogeneous tissue density with non-coplanar beams. We have conducted thorough QA for individual patients similar to the more common IMRT QA with particular reference to motion management. Individual patient QA was performed in a Perspex phantom (Modus Medical) using a point dose verification and radiochromic film for verification of the dose distribution. The results for the first 33 plans were analysed with the aim of revising QA procedures for future lung SABR plans. The results from these plans were then used to highlight particular areas of delivery uncertainty which require attention during patient specific QA.

      Results
      While individual beams could vary by up to 7%, the total dose in the target was found to be within ±2% of the prescribed dose for all 33 plans. The QA process verified all aspects of the plan delivery including non-coplanar geometry, isocentre accuracy under couch rotation and internal target volume construction. The QA process highlighted the importance of accounting for couch transmission and demonstrated the need for accurate motion management strategies. The review of the first 33 plans lead to the creation of a risk-management based approach to QA of subsequent treatment plans. Particular emphasis is now placed on verification of small field dosimetry and motion management strategies for lesions with large motion.

      Conclusion
      QA is essential for complex radiotherapy deliveries such as SABR. We found individual patient QA helpful in setting up the technique and understanding weak points in the process chain. Ongoing review of the patient specific QA results has lead to improvements in efficiency in the process, facilitating a risk-management based approach to patient specific QA for SABR.

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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): S. Siva

      • 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.