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W. De Neve



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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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      P2.06-030 - Radiation-induced lung damage quantification with CT scans: Correlation with single nucleotide polymorphisms (ID 2420)

      09:30 - 09:30  |  Author(s): W. De Neve

      • Abstract

      Background
      Radiation-induced lung damage (RILD) is a dose-limiting toxicity of lung radiotherapy. Individual sensitivity can be measured by changes in Hounsfield Units over time (delta HU) on CT scans (De Ruysscher et al. Acta Oncol 2013). This endpoint is specific for lung damage and does not correlate with dyspnoea, which is multi-factorial. In this study, we investigated the association between density changes over time and SNPs aiming at finding individual sensitivity for RILD.

      Methods
      Delta HU/Gy and delta HU/Gy x MLD (Mean Lung Dose), the latter to take into account a volume factor for RILD, were correlated with 314 SNPs related to fibrosis and inflammation. The outcome variables were square root transformed because both were not normally distributed. Univariate ANOVA analyses were performed for comparisons of means. P-values of less than 0.01 were considered to be significant.

      Results
      Eighty-nine lung cancer patients were studied, 63 men and 26 females. Twenty patients were treated with radiotherapy alone, 31 with sequential chemo-RT and 38 with concurrent chemo-RT. Twenty percent of the patients developed grade 2 or more clinical dyspnoea after treatment. Three SNPs were significantly correlated with delta HU/Gy: rs2252070 (p=0.006, MMP13), rs2230588 (p=0.009, JAK1) and rs12901071 (p=0.009, SMAD3) [Table 1A]. For delta HU/Gy x MLD, significant associations were found for rs3819122 (p=0.008, SMAD4), rs2230529 (p=0.009, ITGB2) and rs2230588 (p=0.009, JAK1) [Table 1B]. Figure 1

      Conclusion
      Quantification of CT density changes due to radiotherapy, measured as HU changes over time as a specific and quantitative endpoint for RILD correlates with specific SNPs in genes involved in signal transduction of cytokines (SMAD3/4, JAK1), in the extracellular matrix (MMP13) and in cell adhesion (ITGB2). External validation will follow.

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    P2.08 - Poster Session 2 - Radiotherapy (ID 198)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Radiation Oncology + Radiotherapy
    • Presentations: 1
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      P2.08-013 - Proton radiotherapy for locally-advanced non-small cell lung cancer, a cost-effective alternative to photon radiotherapy in Belgium? (ID 1657)

      09:30 - 09:30  |  Author(s): W. De Neve

      • Abstract

      Background
      As part of a feasibility study for a Hadron Therapy Centre in Belgium, an economic evaluation was performed to assess the potential cost-effectiveness of proton radiotherapy (PT) delivered concurrently with chemotherapy for locally-advanced non-small cell lung cancer (LA-NSCLC), compared to concurrent chemoradiotherapy employing photon therapy, either 3D-conformal (3D-CRT) or intensity-modulated (IMRT) radiotherapy.

      Methods
      A Markov decision-analytic model was developed using Microsoft Excel 2007 software. The model was defined for a time horizon of 10 years, allowing patients to transition between 5 health states (treatment, controlled disease, loco-regional progression, distant progression and death) using transition cycles of 3 months. Transition probabilities were derived from photon and proton literature on LA-NSCLC and from nationally available data. Results were to be expressed in cost per (quality adjusted) life years (LY and QALY). The occurrence of grade 3 toxicity or higher in terms of radiation pneumonitis, radiation esophagitis/dysphagia and pulmonary radiation fibrosis was accounted for in the calculation of QALYs. Treatment costs of the standard 3D-CRT and IMRT treatments were obtained from an Activity-Based Costing (ABC) exercise in Belgian radiotherapy centers (KCE report 198). Similarly, the cost of PT was calculated using ABC in different technical (proton-only vs. combined proton and carbon-ion center) and financing (private vs. public) scenarios. Toxicity and follow-up costs were based on literature evidence but adapted to the Belgian context.

      Results
      The base case analysis used the scenario of a publicly financed combined center. The survival curves generated by the model demonstrated it accurately predicts survival of published literature and of the Belgian Cancer Registry. Compared to 3D-CRT res. IMRT, PT generates 0.837 res. 0.664 extra LYs and 0.549 res. 0.452 extra QALYs. When combined with the higher cost (18,875€ res. 14,257€), this translates into an incremental cost-effectiveness ratio (ICER) of 22,543€/LY for PT compared to 3D-CRT and of 21,489€/LY compared to IMRT. Expressed in cost per QALY, the ICERs amount to 34,396€/QALY and 31,541€/QALY respectively. Assessing the effect of different technical scenarios and/or financing methods, the ICER ranges between 21,489€ to 53,685€/LY and 31,541€ to 78,873€/QALY, with the highest figures found for a combined center with private financing. One-way sensitivity analyses reveal that the results are most sensitive to the effect of proton therapy on disease control, loco-regionally as well as at distance, and to the quality of life pre-progression.

      Conclusion
      Based on a public financing scenario for a combined center, PT delivered concurrently with chemotherapy is found borderline cost-effective in the Belgian health care context, compared to the best available photon radiotherapy alternatives. These results are however highly sensitive to the cost of PT (hence the financing scenario) and the expected clinical advantage of PT, both in terms of improved survival and decreased long-term toxicity impacting on quality of life. Apart from clinical appropriateness and budgetary possibilities, such results support decision-making on the feasibility and desirability of introducing hadron therapy in Belgium.