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T. Kron



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    OA 01 - The New Aspect of Radiation Therapy (ID 652)

    • Event: WCLC 2017
    • Type: Oral
    • Track: Radiotherapy
    • Presentations: 1
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      OA 01.01 - A Randomized Trial of SABR vs Conventional Radiotherapy for Inoperable Stage I Non-Small Cell Lung Cancer: TROG 09.02 (CHISEL) (ID 8628)

      11:00 - 11:10  |  Author(s): T. Kron

      • Abstract
      • Presentation
      • Slides

      Background:
      Although stereotactic ablative body radiotherapy (SABR) is now well established as a treatment for stage I non-small cell lung cancer (NSCLC), there is limited evidence that it is as or more effective than conventional fully fractionated radiotherapy (CRT). We conducted a randomized trial to determine if SABR results in longer time to local failure than CRT.

      Method:
      This was a multicentre trial of the Trans-Tasman Radiation Oncology Group (TROG) and Australasian Lung Cancer Trials Group, registration number NCT01014130. Patients were eligible if they had biopsy proven stage I (T1- T2a N0M0) NSCLC based on PET and were medically inoperable or refused surgery. Patients had to be performance status ECOG 0 or 1, and the tumor had to be at least 2 cm or more from the bifurcation of the lobar bronchus. Patients were randomized 2:1 to SABR (54 Gy in 3 fractions, or 48 Gy in 4 fractions, depending on proximity to the chest wall, to the isodose covering the PTV) or to CRT (66 Gy in 33 fractions or 50 Gy in 20 fractions). The primary objective was to compare time to local failure between arms. Assuming that the rate of local failure at 2 years would be 10% in patients randomized to SABR versus 30% in patients randomized to CRT, 100 patients were required. All living patients were followed for a minimum of 2 years. Analysis was based on the intention to treat principle. Funding: In Australia: Grant #1060822 was awarded through Cancer Australia. In New Zealand, The Cancer Society of New Zealand and the Genesis Oncology Trust.

      Result:
      Between 12/09 and 6/15, 101 patients were enrolled. There were 56 males and 45 females with a median age of 74 years (range 55-89), ECOG performance status – 28 were 0, 71 were 1 and 1 was 2. TNM stage was T1N0M0 in 71 and T2aN0M0 in 30. Sixty six patients were randomized to SABR and 35 patients to CRT. Patients randomized to SABR had superior freedom from local failure (HR = 0.29, 95% CI 0.130, 0.662, P=0.002) and longer overall survival (HR = 0.51, 95% CI 0.51, 0.911, P=0.020). Worst toxicities by arm were: CRT grade 3, 2 patients; SABR grade 4, 1 patient and grade 3, 9 patients.

      Conclusion:
      In patients with inoperable stage I NSCLC, compared with CRT, SABR resulted in superior freedom from local failure and was associated with an improvement in overall survival.

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    P1.14 - Radiotherapy (ID 700)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Radiotherapy
    • Presentations: 1
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      P1.14-017 - Impact of Systematic EBUS-TBNA Mediastinal Staging on Radical Radiotherapy Planning in NSCLC (ID 8497)

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

      • Abstract
      • Slides

      Background:
      Radical radiotherapy often relies solely on radiological imaging to determine treatment volumes. Systematic mediastinal staging with endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) may identify PET-occult sites of mediastinal disease, or demonstrate benign causes for PET-positive LN. This study evaluated 1) Involved nodal coverage 2) Doses to organs-at-risk when planned based on PET-CT and EBUS-TBNA and 3) Incident dose to mediastinal nodes between 3D-CRT and Intensity-Modulated-Radiotherapy (IMRT).

      Method:
      Radical radiotherapy plans (60Gy/30 fractions) were created for patients with stage change following EBUS-TBNA from a prospective clinical trial. We compared lung Normal-Tissue-Complication-Probability (NTCP, pneumonitis), oesophageal and heart dose for planning to targets based on PET-CT versus PET-CT+EBUS-TBNA. The incidental dose to PET-negative/EBUS-TBNA-positive nodes from 3DCRT and IMRT was evaluated using volume receiving 35Gy as a surrogate for control of sub-clinical disease (Kepka, IJROBP, 73(5) 2009).

      Result:
      Of 30 patients enrolled, four were upstaged by EBUS-TBNA; these patients had a significant geographic miss of nodal GTV when planned to PET-positive nodes only (Figure 1). When planned based on PET-CT alone, the incidental dose to PET-negative/EBUS-TBNA-positive nodes was higher with IMRT for two patients (v35Gy increased by 17% & 6%; Figure 1a&b) and lower with IMRT (v35Gy reduced by 16% and 6%; Figure 1c&d) for two, dependent on nodal position relative to the primary. Six patients had negative pathology for PET avid nodal stations; Inclusion of EBUS-negative, PET-positive nodes resulted in an average increased lung NTCP of 5% (range 1%-13%), mean oesophagus dose of 13Gy (range 4-23Gy) and mean heart dose of 4Gy (range -0.1-11Gy) over plans based on EBUS-positive nodes alone. Figure 1



      Conclusion:
      Systematic EBUS-TBNA has the potential to improve loco-regional control and limit the probability of lung and heart toxicity. The incidental dose to adjacent tissue is inherently related to involved node/tumour position and not solely dictated by the radiation delivery technique.

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    P2.05 - Early Stage NSCLC (ID 706)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Early Stage NSCLC
    • Presentations: 1
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      P2.05-006 - Credentialing of Radiotherapy Centres in Australasia for a Phase III Clinical Trial on SABR (TROG 09.02 CHISEL) (ID 9985)

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

      • Abstract
      • Slides

      Background:
      A randomised phase III clinical trial comparing Stereotactic Ablative Body Radiotherapy (SABR) with conventional radiotherapy for early stage lung cancer in peripheral location has been conducted in Australia and New Zealand under the auspices of the Trans Tasman Radiation Oncology Group (TROG). As SABR technology at the commencement of the trial was new to most centres in our region and the techniques used are complex and technologically challenging a credentialing program was developed for centres wishing to join the trial.

      Method:
      The credentialing program used a prospective risk management approach with high risk elements considered to be (i) the ability to create a plan that meets all dosimetric constraints, (ii) the dose calculation in the presence of inhomogeneities and (iii) the management of motion. Participating centres were asked to develop treatment plans for two test cases made available in DICOM format, and inhomogeneity corrections and dose delivery was assessed during a site visit using a phantom with moving inserts (modified Modus Quasar).

      Result:
      Site visits were conducted in 17 Australian and 3 New Zealand radiotherapy facilities. All centres were able to produce acceptable plans for both test cases, in particular after the protocol was amended to allow delivery of 48Gy in 4 fractions for lesions close to the chest wall in addition to the original trial arm of 54Gy in 3 fractions. The tests conducted during site visit with lung and air inhomogenieties confirmed known shortcomings of the AAA algorithm for dose calculation behind the inhomogeneity. The dose was assessed using an ionisation chamber and radiochromic film in a stationary and moving cylinder (sinusoidal motion, 1cm amplitude, 4s period) in the phantom for a typical treatment delivery including at least one non-coplanar beam. The measurements confirmed in an end-to-end test that all participating centres were able to deliver SABR with the required accuracy. Overall, the site visit took 3 hours of time on the treatment unit and was well received by participating staff. For several facilities it proved to be a useful step in the process of developing a SABR program.

      Conclusion:
      The credentialing process including a site visit documented that participating centres were able to deliver dose to a phantom as required in the trial protocol. It also gave an opportunity to provide education about the trial and discuss technical issues such as 4D CT, small field dosimetry and patient immobilisation with staff in participating centres.

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    P2.14 - Radiotherapy (ID 715)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Radiotherapy
    • Presentations: 1
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      P2.14-001 - Mid-Treatment Perfusion PET/CT Is More Effective Than Ventilation PET/CT in Functionally-Adapted Radiotherapy for NSCLC (ID 8508)

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

      • Abstract
      • Slides

      Background:
      To assess the utility of four-dimensional (4D) ventilation/perfusion (V/Q) PET/CT lung imaging to facilitate mid-radiotherapy treatment adaption with volumetric modulated arc radiotherapy (VMAT).

      Method:
      In a prospective clinical trial, patients with non-small cell lung cancer (NSCLC) underwent [68]Ga-4D-V/Q PET/CT scanning before and during a six-week (60Gy) course of definitive chemoradiation. Functional lung volumes were delineated on both datasets as ‘highly perfused’ (HPLung) and ‘highly ventilated’ (HVLung), using a 70[th] centile SUV threshold. Three VMAT plans were created on the mid-treatment datatsets: optimised to anatomical lung, HPLung, and HVLung volumes, respectively. Functional dose volumetrics were assessed using the parameters of mean lung dose (MLD), and lung volume receiving 5, 20 or 30Gy, (V5, V20, and V30). Plan quality was assessed for consistency with respect to conformity indices, and doses to critical structures.

      Result:
      The study cohort consisted of 10 patients resulting in a total of 30 VMAT plans. PTV volumes reduced by a mean of 5.5% between scans. HVLung volume increased between scans by a median value of 39.2%. Subsequent volumetric and spatial changes were reflected in varying DICE similarity coefficients, or DSC (ranging from 0.336-0.923). HPLung decreased by a median value of 4.5% with spatial discrepancy represented by DSC of 0.568-0.805. Increase in ventilated function was most prevalent adjacent to the target, limiting the benefit of adaptive planning (Fig 1). Plan quality was consistent with the median PTV D95 ranging from 60.6-61.3Gy, and mean conformity index ranging from 1.23-1.25. Functional MLD of HPLung decreased by a mean of 7.3%, p=0.02. Plans optimised to HPLung resulted in a reduction of perfused lung V5 by a mean of 13.2%, p<0.01, with HVlung plans yielding a decrease in ventilated lung V5 of 9.6%, p=0.02. Fig 1 Figure 1



      Conclusion:
      To achieve reduced irradiation of functional lung, radiotherapy adaptation is more effectively facilitated by perfusion rather than ventilation imaging.

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