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M. Macmanus



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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): M. Macmanus

      • 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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    MS01 - Radiation as a Systemic Therapy (ID 18)

    • Event: WCLC 2013
    • Type: Mini Symposia
    • Track: Radiation Oncology + Radiotherapy
    • Presentations: 1
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      MS01.2 - Circulating Tumour Cells as a Mechanism of Radio Resistance (ID 458)

      14:25 - 14:45  |  Author(s): M. Macmanus

      • Abstract
      • Slides

      Abstract not provided

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    P1.13 - Poster Session 1 - SCLC (ID 200)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P1.13-002 - Prognostic Value of 18F-fluorodeoxyglucose Uptake in Small Cell Lung Cancer Patients Treated with Concomitant Chemo-radiotherapy or Chemotherapy alone (ID 1277)

      09:30 - 09:30  |  Author(s): M. Macmanus

      • Abstract

      Background
      There is some evidence that the standard uptake value (SUV) measured using 18F- fluorodeoxyglucose positron emission tomography ([18]FDG-PET) in patients with non-small cell lung cancer (NSCLC) may be prognostic for survival. Small cell lung cancer (SCLC) clinically differs from NSCLC by its rapid proliferation and is staged as either limited disease (LD) defined as disease confined to one hemithorax and the regional lymph nodes or extensive disease (ED) which is disease that has spread beyond this. There is much less information available on the potential prognostic value of the SUV obtained during [18]FDG-PET scanning in SCLC. This study thus aims to explore whether SUV can be effective in the prognostic stratification of SCLC patients with LD and ED.

      Methods
      Retrospective study of patients diagnosed with SCLC who underwent a pre-treatment 18FDG-PET scan between 1999 – 2008 at the Peter MacCallum Cancer Centre and 2004 -2011 at the Austin Hospital. Patients with LD were treated with radical concomitant chemo-radiotherapy and those with ED treated with chemotherapy alone. Maximum and mean SUVs were retrieved, and survival of patients measured. The correlation between SUV and other patients’ clinicopathological factors, including age, sex, performance status, weight loss and tumour stage (TNM) were also explored.

      Results
      Thirty-six eligible patients were identified, with a median follow-up of 14 months (range, 3-103 months). There were 23 males and 13 females. The median age was 69 years (55-84 years). Twenty patients had LD and 16 had ED. Thirteen patients had stage IV disease and 10 patients each had stage IIIA and IIIB disease (3 patients were unable to be staged according to TNM classification system). Higher TNM stage was associated with higher SUVmax (r~s~=0.37, p=0.036) but not with SUVmean (r~s~=0.30, p=0.086). There was no evidence of a significant association between clinicopathological factors with SUVmax in patients with LD and ED, except for age in patients with ED. Increasing age was associated with higher SUVmax (r~s~=0.72, p=0.002) and higher SUVmean in patients with ED (r~s~=0.81, p<0.001). SUVmax and SUVmean were not significantly associated with OS in patients with LD or ED or in the whole sample.

      Conclusion
      In patients with SCLC there was an association between higher SUVmax and higher TNM stage, as observed in patients with NSCLC. However, in this small patient cohort, we were unable to find evidence of an independent prognostic effect of SUVmax on overall survival.