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P. Lambin



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

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Radiation Oncology + Radiotherapy
    • Presentations: 2
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      P1.08-014 - PET-based radiotherapy planning is highly cost-effective compared to CT-based planning: a model-based evaluation. (ID 1608)

      09:30 - 16:30  |  Author(s): P. Lambin

      • Abstract

      Methods
      The cost-effectiveness analysis was performed using a previously developed decision model that simulates the disease progression of individual lung cancer patients until they are deceased or have reached a pre-specified time-horizon of 3 years. Simulated patients move from the start of radiotherapy treatment to the absorbing state of death, potentially visiting the intermediate health states ‘local recurrence’ and ‘metastasis’. Transition rates in the model were estimated by multi-state statistical modelling and include the impact of patient and tumour features on disease progression. Data for model quantification was available for 200 NSCLC patients with inoperable stage I-IIIB, provided by the Maastro Clinic. Resource use estimates, costs and utilities were obtained from the data of the Maastro Clinic, the literature and Dutch guidelines. Primary outcomes were the difference in life years, quality adjusted life years and costs and the incremental cost-effectiveness and cost-utility ratio (ICER and ICUR) of PET-CT versus CT based radiotherapy planning. Model outcomes were obtained from averaging the outcome for 50 000 simulated patients. A probabilistic sensitivity analysis was done as well as a number of scenario analyses.

      Results
      The incremental costs of PET-CT based planning were €581 (95% CI: €-4474 – €6064) for 0,42 incremental life years (95% CI: 0,20 – 0,62) and 0,33 quality adjusted life years gained (95% CI: 0,16 – 0,54) (figure 1). The base-case scenario resulted in an ICER of €1370 per life year gained and an ICUR of €1761 per quality adjusted life year gained. The probabilistic analysis gave a 35% probability that PET-CT based planning improves health outcomes at reduced costs and a 65% probability that PET-CT based planning is more effective at slightly higher costs.Figure 1 Figure 1. Results of probabilistic sensitivity analyses showing incremental costs and incremental life years for PET-CT-based radiotherapy treatment planning compared to CT-based radiotherapy treatment planning.

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      P1.08-022 - Number of pathologic nodes in regions closest to the oesophagus is the strongest predictor for esophagitis in small cell lung cancer patients treated with concurrent chemo-radiation: an analysis of 170 patients. (ID 2711)

      09:30 - 16:30  |  Author(s): P. Lambin

      • Abstract

      Background
      Radiation esophagitis grade III caused by chemo-radiation for small-cell lung cancer is a burden for patients and thus of concern to radiation oncologists. Neutropenia and radiation dose to the esophagus are known treatment factors influencing the rate of esophagitis during treatment, but currently the only factors that can be discussed with the patient at diagnosis are the choice of concurrent versus sequential chemo-radiation and the radiation dose fractionation schedule. In order to build predictive models to more accurately tailor treatment and advise patients on treatment options, more prognostic factors known at the moment of diagnosis are needed.

      Methods
      Analysis of all patients in our prospective database with stage I-III SCLC referred for concurrent chemo-radiotherapy between 5-2004 and 1-2012. All patients were PET-staged and received 45 Gy in 1.5 Gy fractions twice daily to the tumour and PET-or pathologically proven positive lymph nodes. Chemotherapy consisted of carboplatin-etoposide given concurrently with radiotherapy. All pathological lymph node regions were noted for each patient. Based on the Mountain Dressler atlas, the lymph node regions closest to the oesophagus were designated ``high risk`` regions for esophagitis, namely: 1R, 1L, 3P, 4L, 7, 8 and 9. Toxicity was scored according to CTC AE 3.0. Univariate analysis was done using the Chi-square test, reporting for p-value the Fischer exact Test for small numbers of events. Multivariate analysis was done using logistic regression. .

      Results
      170 patients were included in the present analysis. Thirty-seven (20%) patients developed grade III esophagitis. In univariate analysis the number of nodal regions (0, 1-4, ≥5) (p=0.02) and the number of high risk nodal regions (0, 1-2, ≥3) (p=0.001) had a significant effect on the risk of grade III esophagitis whereas the location of the primary tumour or having a T4 tumour did not. In multivariate analysis including age, gender and T4 tumour, the number of pathological nodal stations lost significance. In the multivariate analysis using age, gender, T4 tumour and the ``high risk`` count (0, 1-2, ≥3 areas) having nodes in ≥3 high risk areas was the only significant factor (p=0.002), with a hazard ratio (HR) of 7.4 for developing oesophagitis grade III (95% CI for HR: 2.2-25.2). The absolute rates of esophagitis grade III were: 5/51 (10%), 19/91 (21%), 12/28 (43%) for patients with respectively 0, 1-2 and ≥3 pathological high risk nodal areas.

      Conclusion
      In this series of stage I-III small cell lung cancer treated with radical chemo-radiation, the strongest predictor for esophagitis grade III known at diagnosis is the presence of nodal disease in ``high-risk regions`` 1R, 1L, 3P, 4L, 7, 8 and 9. Analysis of the correlation of this finding with the dose to the esophagus (Dmax/ Dmean) is ongoing and will also be presented at the conference.

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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 - 16:30  |  Author(s): P. Lambin

      • 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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    P2.09 - Poster Session 2 - Combined Modality (ID 213)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Combined Modality
    • Presentations: 1
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      P2.09-007 - Comparison of toxicity and outcomes of concurrent radiotherapy with carboplatin/paclitaxel and cisplatin/etoposide in stage III non-small cell lung cancer (ID 1497)

      09:30 - 16:30  |  Author(s): P. Lambin

      • Abstract

      Background
      Concurrent chemoradiotherapy (CCRT) has become the standard of care for patients with unresectable stage III non-small cell lung cancer (NSCLC). The comparative merits of two widely used regimens: carboplatin/paclitaxel (PC) and cisplatin/etoposide (PE), each given with concurrent radiotherapy, remain largely undefined.

      Methods
      Records for consecutive patients with stage III NSCLC treated with PC or PE and ≥60Gy chest radiotherapy between 2000-2011 were reviewed for outcomes and toxicity. Survival was estimated using the Kaplan-Meier method and Cox modeling with the Wald test. Comparison across groups was done using the student t and chi-squared tests.

      Results
      75 (PC: 44, PE: 31) patients were analyzed. PC patients were older (median 71 vs 63 years; p=0.0006). Other characteristics were comparable between groups. With PE, there was significantly increased grade ≥3 neutropenia (39% vs 14%, p=0.024) and thrombocytopenia (10% vs 0%, p=0.039). Radiation pneumonitis was more common with PC (66% vs 38%, p=0.033). Five treatment related deaths occurred (PC: 3 vs PE: 2, p=1.000). With a median follow up of 51.6 months, there were no significant differences in relapse free survival (median PC 12.0 vs PE 11.5 months, p=0.700) or overall survival (median PC 20.7 vs PE 13.7 months; p=0.989). In multivariate analyses, no factors predicted for improved survival for either regimen. Table 1: Non-hematological and hematological adverse events, by grade (CTCAE 4.0)

      Adverse events PC (n = 44) PE (n = 31)
      n (%) n P~χ2~
      Esophagitis 1 2 3 4 3 (7) 19 (43) 10 (23) 5 (11) 5 (16) 7 (23) 10 (32) 1 (3) 0.151
      Pneumonitis 1 2 3 4 5 21 (48) 6 (14) 0 (0) 1 (2) 1 (2) 4 (13) 6 (19) 1 (3) 1 (3) 0 (0) 0.033
      Neuropathy 1 2 1 (2) 1 (2) 0 (0) 0 (0) 0.485
      Nephropathy 1 2 3 3 (7) 0 (0) 0 (0) 4 (13) 0 (0) 1 (3) 0.314
      Nausea/vomiting 1 2 3 7 (16) 8 (18) 0 (0) 7 (23) 2 (6) 1 (3) 0.291
      Chest infection 1 2 3 4 5 1 (2) 1 (2) 11 (25) 1 (2) 1 (2) 0 (0) 3 (10) 5 (16) 2 (6) 1 (3) 0.534
      Neutropenia 1 2 3 4 4 (9) 5 (11) 6 (14) 0 (0) 2 (6) 0 (0) 8 (26) 4 (13) 0.024
      Febrile neutropenia 3 4 5 (11) 0 (0) 5 (16) 1 (3) 0.394
      Anemia 1 2 3 4 12 (27) 5 (11) 1 (2) 0 (0) 10 (32) 9 (29) 0 (0) 1 (3) 0.117
      Thrombocytopenia 1 2 3 1 (2) 3 (7) 0 (0) 4(13) 1 (3) 3 (10) 0.039
      Treatment-related deaths 3 (7) 2 (6) 1.000

      Conclusion
      PC was more likely to be used in elderly patients. Despite this, PC resulted in significantly less hematological toxicity but achieved similar survival outcomes as PE. PC is an acceptable CCRT regimen, especially in older patients with multiple comorbidities.