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C. Oberije



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    MO25 - NSCLC - Combined Modality Therapy II (ID 112)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Mesothelioma
    • Presentations: 1
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      MO25.07 - Early onset body weight loss during concurrent chemo-radiotherapy for non-small cell lung cancer is not due to dysphagia or reduced calorie intake (ID 3409)

      10:30 - 12:00  |  Author(s): C. Oberije

      • Abstract
      • Presentation
      • Slides

      Background
      Increased treatment-associated esophagitis could be responsible for concurrent chemo-radiotherapy (CT-RT)-induced weight loss in patients with non-small cell lung cancer (NSCLC). However, based on clinical observations, we hypothesized that weight loss already starts early after initiation of concurrent CT-RT and might therefore be not solely dependent on decreased intake due to esophagitis symptoms.

      Methods
      In a retrospective cohort, the onset and frequency of weight changes and their association with esophagitis grade ≥2 were assessed in patients with NSCLC treated with concurrent (n=102) or sequential (n=92) CT-RT. The findings in the retrospective cohort were validated in a prospective study in which weight loss and esophagitis grade ≥2 was assessed over a longer time period and additional data on nutritional intake, muscle strength and quality of life was obtained of patients treated with concurrent CT-RT (n=9).

      Results
      In the retrospective cohort, both the number of patients with weight loss and the magnitude of weight loss was significantly higher in concurrent than sequential treated patients in week 2, 3 and 4 of (CT-)RT (p<0.05). Longitudinal data analysis showed no significant associations between weight loss and grade esophagitis ≥2 in patients treated with concurrent CT-RT (p=0.10). In the prospective cohort, a similar pattern of ‘early’ weight loss was observed in the first weeks of concurrent CT-RT (p<0.05). This early weight loss was not accompanied by significant decreases in nutritional intake but muscle strength did already decline in this early stage (p<0.05). In the following weeks of concurrent CT-RT, the weight further decreased and reached its minimum at the end of treatment (p<0.05), while the number of patients with grade esophagitis ≥2 increased during this time period. During the later part of concurrent CT-RT, dietary intake was significantly lower and patients became more reliant on supplemental nutrition (p<0.05). Although the weight increased again in the weeks after concurrent CT-RT, it had still not reached the baseline level after 4 weeks post treatment (p<0.05).

      Conclusion
      Weight loss is a common complication of concurrent CT-RT for locally advanced NSCLC, starts early after initiation of CT-RT and is not dependent of esophagitis. It is presumably caused by active catabolism as this ‘early’ weight loss is accompanied by decreased muscle strength, despite stable dietary intake. In the later weeks of treatment, concurrent CT-RT is characterized by a further decline in body weight, decreased dietary intake and higher reliance on nutritional support. In this phase the occurrence of radiation-induced esophagitis grade ≥2 increases. In the weeks following concurrent CT-RT, partial recovery of body weight takes place but this is still not complete after 4 weeks post CT-RT. The sustained weight loss during and following concurrent CT-RT might have major negative consequences as weight loss in patients with underlying malignant disease might has been associated with higher mortality, lower treatment responses and decreases in quality of life. Though the origin of weight loss during concurrent CT-RT seems to be different in the subsequent phases, more aggressive supportive nutritional support throughout the treatment course seems conceivable to prevent negative energy balances and optimize concurrent CT-RT management.

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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): C. Oberije

      • 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): C. Oberije

      • 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.