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S. Everitt



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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. Everitt

      • 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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    P1.08 - Poster Session 1 - Radiotherapy (ID 195)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Radiation Oncology + Radiotherapy
    • Presentations: 1
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      P1.08-012 - Significant association between radiation induced oesophagitis, neutropenia and V20 in patients with non-small cell lung cancer (ID 1518)

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

      • Abstract

      Background
      Radiation induced oesophagitis (RIO) is frequently associated with high dose thoracic radiation therapy (RT). Although RIO is uncommonly life threatening, it is a distressing toxicity associated with pain, decreased oral intake and can significantly impact on patient’s quality of life. The aim of this retrospective analysis was to assess the rates of acute and late RIO and investigate the association of RIO with radiation dosimetrics and neutropenia.

      Methods
      Criteria for inclusion of patient data included a pathological confirmation of non-small cell lung cancer (NSCLC), treatment with concurrent chemotherapy and radical or high dose palliative RT at our centre between 03/04 and 08/07. Exclusion criteria included previous thoracic RT, RT alone, treatment breaks of > five days, inconsistent radiation dose per fraction and hyper-fractionated RT. Acute and late RIO and neutropenia were scored using the Common Toxicity Criteria for Adverse Events (CTCAE v3.0) criteria. Using Focal (Computerized Medical Systems CMS, St Louis, MO, USA), the outer muscular border of the oesophagus was delineated from the cricoid (superior border) to the gastro-oesophageal junction (inferior border) on CT derived images, using pre-defined soft-tissue window/level settings. Dosimetric data was derived from Xio (CMS) plans (three-dimensional conformal RT (3DCRT) with 6MV photons), including the oesophageal length and volume, maximum and mean doses, percentage of oesophagus receiving 20 to 60 Gy (in 5 Gy increments) and percentage length of oesophagus (whole and partial circumference) receiving 20 to 60 Gy (10 Gy increments). Assessment of potential prognostic factors with respect to acute oesophagitis was done using Wilcoxon rank sum test and Spearman’s correlation. Acute oesophagitis and acute neutropenia reaction were dichotomised as grade 0+1 vs. grade 2+3+4. The association of acute oesophagitis with acute neutropenia was examined using Barnard’s test.

      Results
      The data of 54 patients were eligible for inclusion in this trial. 48 (89%) patients had acute RIO of at least grade 1 (95% CI [78% to 95%]) and five patients (9%) had late RIO of at least grade 1 (95% CI [4% to 20%]). There was a statistically significant correlation between the grade of acute RIO, oesophagus V20 (r=0.303, p=0.026) and length oesophagus receiving 20Gy (whole circumference) (r=0.319, p=0.019). The mean (SD) maximum dose to the oesophagus was 50.2 Gy (18) (r=0.143, p=0.302) and the mean (SD) mean oesophageal dose was 20.8 Gy (10.8) (r=0.269, p=0.049). The maximum grade of acute oesophagitis was significantly associated with acute neutropenia (p=0.035).

      Conclusion
      Acute neutropenia, mean oesophageal dose and the volume and length of oesophagus receiving low radiation doses were significantly associated with acute RIO in our patient cohort. No association was demonstrated between RIO and maximum radiation dose.

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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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      P3.08-015 - Dosimetric factors associated with weight loss during radiotherapy treatment for non-small cell lung cancer (ID 2033)

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

      • Abstract

      Background
      Thoracic radiotherapy is associated with significant acute toxicities including oesophagitis, anorexia and fatigue which can impact on the ability to achieve adequate nutritional intake, subsequently leading to weight loss and malnutrition. Malnutrition during cancer treatment is associated with poorer patient and treatment outcomes. Understanding factors associated with weight loss assists with the early identification and intervention of patients at nutritional risk. This study aimed to identify radiotherapy dosimetric factors associated with clinically significant weight loss (greater than or equal to 5%) in patients receiving treatment for non-small cell lung cancer (NSCLC).

      Methods
      A retrospective analysis of an existing cohort of 54 NSCLC patients treated with concurrent chemoradiotherapy for whom oesophageal dose distributions had previously been calculated. Weight change was calculated at any time point from the start up to 90 days from radiotherapy commencement to determine those with clinically significant weight loss. Chi-squared tests, Pearson correlation, Mann-Whitney U-test and logistic regression were used to examine associations.

      Results
      Four patients for whom weight was not available at the start or end of treatment were excluded leaving 50 patients for analysis. The prevalence of clinically significant weight loss was 22% (median weight loss 9.1%, range 5.9 – 22.1). Dosimetric factors associated with clinically significant weight loss were maximum dose to the oesophagus (z= -1.99, p=.046), absolute oesophageal length receiving 40Gy (r=.32, p=.03), 50Gy (r=.36, p=.01) and 60Gy (r=.45, p=.001) to the partial circumference, relative oesophageal length receiving 50Gy (r=.32, p=.02) and 60Gy(r=.44, p=.001) to the partial circumference. The odds of a patient receiving 40Gy (median length 10.6cm), 50Gy (median length 10.2cm) or 60Gy (median length 7.2cm) to the partial oesophagus experiencing clinically significant weight loss were 1.18 (95%CI 1.01,1.37, p=.04), 1.20 (95%CI 1.03,1.41, p=.02) and 1.32 (95%CI 1.09,1.60, p=.005) greater, respectively, than those with less oesophagus in the treatment field. Nine (82%) of the eleven patients who had clinically significant weight loss received a dose of 60Gy to at least 5cm of the partial circumference of the oesophagus.

      Conclusion
      The strongest dosimetric association with clinically significant weight loss was absolute oesophageal length receiving 60Gy to the partial circumference. A previous study identified an association between concurrent chemotherapy and late stage disease (stage III or IV) and clinically significant weight loss. Findings from both studies have been used to develop a model, currently undergoing validation, to assist clinicians in predicting NSCLC radiotherapy patients at high nutritional risk.