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M. Hofman



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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): M. Hofman

      • 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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    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): M. Hofman

      • 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.