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D. Ball



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    MO17 - Radiotherapy I: Stereotactic Ablative Body Radiotherapy (ID 106)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Radiation Oncology + Radiotherapy
    • Presentations: 1
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      MO17.01 - Response assessment of Stereotactic Ablative Body Radiotherapy (SABR) for pulmonary metastases: utility of 4D-FDG-PET and CT perfusion (ID 2225)

      16:15 - 16:20  |  Author(s): D. Ball

      • Abstract
      • Presentation
      • Slides

      Background
      Response assessment using conventional RECIST criteria after SABR of lung targets can be confounded by fibrotic response. The purpose of this study was to evaluate the utility of 4D-FDG-PET/CT and CT perfusion scans in the response assessment of single fraction SABR for inoperable pulmonary oligometastases.

      Methods
      This is a prospective ethics approved clinical study of patients undergoing single fraction SABR with 26Gy for pulmonary metastases. Eligible patients had 1-2 metastases with no extrathoracic disease on staging FDG-PET. Serial 3D / 4D-FDG-PET and CT perfusion studies were performed at baseline, 14 days and 70 days after therapy. Two radiologists independently reported CT perfusion scans.

      Results
      At a median follow-up of 16 months (range 3-27), 10 patients with 13 metastases received SABR. A further 7 patients (41%) were screened from the study due to interval progression of disease between the time of the original FDG-PET and trial 4D-FDG-PET / perfusion CT. The mean time between the original FDG-PET and trial scans was 62 days. No patient progressed locally, 7/10 patients progressed distantly of which 2/7 received subsequent SABR. At the end of study period, 5/10 patients are alive without disease. The median progression free survival was 14 months. The change in SUVmax from baseline was higher on 3D than 4D-PET by a mean of 20.6% (range 0.2%-47.2%) at 14 days and 14.8% (range 0-37.8%) at 70 days. Overall, the SUVmax increased at 14 days (mean 104.9%, p<0.01) and decreased at 70 days (mean=55.5%, p<0.01), despite persistent morphological lesions on the concurrent late timepoint CT. There was strong level of inter-observer agreement of CT perfusion interpretation with a median intraclass correlation coefficient of 89% (range 57%-98%). Perfusion parameters of Time to Peak Blood Flow and Blood Volume showed a median increase of 18.8% and 23.0% at 2 weeks post-therapy and decreased below baseline by a median 7.0% and 14.0% at 70 days (non-significant).

      Conclusion
      High rates of interval progression between staging scans indicates a need to expedite management of oligometastases in a timely fashion. Increased tumour perfusion and FDG-PET intensity at 2 weeks post-RT is likely due to an inflammatory response to large single dose SABR. Late PET response was associated with tumour control despite CT apparent morphological lesions. Conventional 3D PET may overestimate change in PET intensity post SABR as compared to 4D PET. These findings, in particular CT perfusion findings, require a larger patient cohort for validation.

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    MO23 - Radiotherapy II: Lung Toxicity, Target Definition and Quality Assurance (ID 107)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Radiation Oncology + Radiotherapy
    • Presentations: 1
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      MO23.01 - Four-dimensional Gallium-68 perfusion PET/CT scans can improve radiotherapy planning through functional avoidance of lung (ID 2490)

      10:30 - 10:35  |  Author(s): D. Ball

      • Abstract
      • Presentation
      • Slides

      Background
      [68]Ga-macroaggregated-albumin ([68]Ga-MAA) perfusion PET/CT is a novel molecular imaging technique for the assessment of functional lung volumes. This prospective study aims to investigate the utility of four-dimensional (4D) [68]Ga-perfusion PET/CT for functional adaptation of radiation therapy (RT) planning in patients with non-small cell lung cancer (NSCLC).

      Methods
      An interim analysis was performed of a prospective clinical study of patients with NSCLC who underwent 4D-perfusion PET/CT scanning prior to curative intent RT. All patients were planned to 60Gy in 30fx with or without concurrent chemotherapy based on conventional anatomical lung volumes. Subsequently, a single nuclear medicine physician in conjunction with a single radiation oncologist contoured the functional ‘perfused’ lung using a visually adapted threshold. Functional lung was defined as lung parenchyma with Ga-MAA uptake. A second volume labeled as ‘high-perfused’ lung was created based on a visually adapted 30% max SUV threshold (figure 1). A single RT planner optimised the 3D conformal radiotherapy plan to spare the functionally ‘perfused’ and ‘high-perfused’ lung volumes respectively. Dose volumetrics were compared using mean lung dose (MLD), V5, V10, V20, V30, V40, V50 and V60 parameters. Figure 1 figure 1 - RT Plans optimised to each of the conventional, 'perfused' and 'high perfused' lung volumes.

      Results
      14 consecutive patients had RT plans adapted to functional lung volumes based on perfusion PET/CT. This patient cohort consisted of ex-smokers with pre-existing airways disease, with a mean FEV1 of 1.87L (0.83L-2.82L) and DLCO of 54% (27%-87%). The average MLD of the original treatment plans was 11.44Gy using conventional anatomical lung measurements. When considering the functional ‘perfused’ lung and ‘high perfused’ lung, the original plan produced an average MLD of 11.12Gy and 12.41Gy respectively. Plans optimized for ‘perfused’ lung only showed significant improvement of the V60 dose parameter (median 1.00Gy, p=0.04). However, plans optimized for ‘high perfused’ lung improved MLD, V30, V40, V50 and V60 (all p-values <0.05). The MLD was improved by a median of 0.86Gy, p<0.01. The largest improvement was found in the V30 parameter, with a median difference of 1.76Gy.

      Conclusion
      This is the first study of [68]Ga perfusion PET/CT for planning the treatment of lung cancer patients. RT plans adapted to ‘high perfused’ but not ‘perfused’ functional lung volumes allows for significant technical improvement of conventional RT for NSCLC patients. The clinical impact of this improvement in planning technique should be validated in the context of a prospective study measuring patient toxicity outcomes.

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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): D. Ball

      • 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.

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    P2.06 - Poster Session 2 - Prognostic and Predictive Biomarkers (ID 165)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P2.06-036 - DNA Damage Response during Curative Radiotherapy of Non-Small Cell Lung Cancer: In-Vivo Biodosimetry with Peripheral Blood Lymphocytes and Systemic Effects Measured in Hair Follicles (ID 2652)

      09:30 - 09:30  |  Author(s): D. Ball

      • Abstract

      Background
      The interactions between radiation dose, toxicity and systemic responses are poorly understood during radiotherapy of patients with NSCLC). The purpose of this study was to monitor DNA damage using the gamma-H2AX assay in tissues inside and outside irradiated volumes of patients with NSCLC.

      Methods
      This prospective ethics approved study assessed 12 patients receiving radiotherapy was planned to 60 Gy in 30 fractions over 6 weeks. Six patients receive concurrent platinum doublet chemotherapy (chemoRT), and six patients had radiotherapy alone. The number, distribution and kinetics of gamma-H2AX foci were compared with the irradiated volume. Lymphocytes and eyebrow hairs were processed for gamma-H2AX staining and microscopy at each of 5 time-points; baseline, 1 and 24 hours post-first fraction, 4 weeks into radiotherapy, and 3 months after treatment completion.

      Results
      The mean irradiated target volume was 384 cm[3] (range 87-1137 cm[3]). We observed the presence of a small subpopulation of lymphocytes with multiple (>5) gamma-H2AX foci at 1-hour post-first fraction. There was no difference in this subpopulation between patients receiving chemoradiotherapy or radiotherapy alone at baseline (p=0.26) nor at 1-hour (p=0.24) There was a strong correlation between the size of this subpopulation and irradiated volume (r=0.84, p<0.01), indicating direct radiation exposure. This suggests potential utility of the gamma-H2AX assay as a human in-vivo biodosimeter. This subpopulation was not detected at 24 hours due to DNA damage repair. A trend for reduction of this subpopulation and the average number of foci in lymphocytes analysed at 4 weeks of radiotherapy suggests an impaired radiation response after multiple radiotherapy fractions. By contrast, the mean number of observed hair follicle gamma-H2AX foci was not different from baseline to 1-hour post first-fraction (p=0.42), elevated at 24 hrs (p=0.10) and 4 weeks (p=<0.01) but was not different from baseline at 3 months (p=0.31). The scattered dose at the eyebrow was recorded at <0.01 Gy per fraction and was insufficient to directly induce the observed gamma-H2AX signal Figure 1 Figure 1 - a brisk DNA damage response in out-of-field eyebrow hair 24-hours post radiation (gamma-H2AX foci in green)

      Conclusion
      The Gamma-H2AX assay on peripheral blood at 1-hour may be a useful as a human in-vivo biodosimeter. To our knowledge, this study is the first report of abscopal DNA damage response in hair follicles associated with radiotherapy in cancer patients. Further validation of our findings on a larger patient cohort is warranted.