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H. Peulen



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    O10 - Stereotactic Ablative Body Radiotherapy (ID 104)

    • Event: WCLC 2013
    • Type: Oral Abstract Session
    • Track: Radiation Oncology + Radiotherapy
    • Presentations: 1
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      O10.07 - Dose-response analysis of radiation induced rib fractures after SBRT for NSCLC (ID 2690)

      17:20 - 17:30  |  Author(s): H. Peulen

      • Abstract
      • Presentation
      • Slides

      Background
      Symptomatic rib fractures occur in approximately 5% of patients treated with SBRT for early stage NSCLC. Only in small patient cohorts has the dose-effect relation of radiation induced rib fractures been determined. Recent developments in automatic rib segmentation allow determining the dose-effect relation in a large patient cohort, which is the aim of this study.

      Methods
      From 2006-2012 453 patients with early stage NSCLC were treated with SBRT (3x18 Gy). Follow-up (FU) consisted of a physical examination and a CT scan 4 months after treatment and every 6 months up to two years and yearly thereafter. For the first 101 patients with FU>6 months, all ribs were automatically segmented using 15 atlases of manually delineated ribcages. A non-rigid registration followed by a multi-level label fusion produced for each patient a set of ribs. The physical dose distributions were NTD (Normalized Total Dose) corrected with α/β=3 Gy. Cox proportional hazard regression analysis, which takes into account the time to event with patient as random intercept, was used to find the optimal dose parameter. Evaluated were the dose received by x% of the rib D~x~ (x ranged 1-30%) and equivalent uniform dose (EUD) (volume effect 1/n ranged 0.1-60). The Lyman-Kutcher-Burman (LKB) model based on this optimal dose parameter was used to model the dose-effect relationship. Using maximum-likelihood estimation, parameters were median toxic dose (TD~50~), steepness parameter m and 1/n were optimized.

      Results
      In 354 patients with FU>6 months (median 22 months), 38 patients(11%) were diagnosed with a total of 49 rib fractures, symptomatic (grade 2) for 9 patients(2.5%). Included in the dosimetric analysis were 2410 ribs (14 ribs outside field-of-view). 26 ribs in 15 patients(15%) were fractured, symptomatic for 4 patients(4%). In the univariate analysis, all dose parameters significantly correlate with rib fracture (p-values<0.001). Hazard ratios (95%CI) for the parameters with highest log likelihood: D~1~=1.022 (1.017-1.027) and EUD~0.033~=1.021 (1.016-1.026). Multivariate analysis identified EUD as the predictor with the highest log-likelihood and was used in the LKB model. The optimal LKB parameters to predict rib fracture in this dataset were (95% CI): TD~50~=395.5 Gy (244.3-555.1), m=0.348 (0.311-0.384) and 1/n=32.3 (4.82-inf). The risk of rib fracture was <5% in case the NTD-corrected EUD<170 Gy.Figure 1

      Conclusion
      In this subgroup of NSCLC patients treated with 3x18Gy, the risk of rib fracture was significantly correlated to the dose, and was <5% in case the biological dose is kept under 170 Gy.

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    P2.12 - Poster Session 2 - NSCLC Early Stage (ID 205)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P2.12-005 - Results of radical treatment of non-small cell lung cancer patients with a single synchronous metastasis (ID 1103)

      09:30 - 09:30  |  Author(s): H. Peulen

      • Abstract

      Background
      Stage IV non-small cell lung cancer (NSCLC) patients are considered incurable and mainly treated for palliation. The purpose of this study is to investigate the overall survival (OS) and disease free survival (DFS) of NSCLC patients, diagnosed with synchronous oligometastatic disease treated with curative intent of the intrathoracic disease as well as the metastasis.

      Methods
      Patients treated between 2008 and 2013 were included in this retrospective analysis. Main inclusion criteria were: synchronous presentation of NSCLC and oligometastatic disease at diagnosis with only 1 extra-thoracic metastasis, and multidisciplinary consent on a radical treatment of both the intrathoracic disease and the solitary metastasis. Treatment of the intrathoracic disease consisted of radical radiotherapy (> 55 Gy biological effective dose) or surgical resection. Treatment of the metastasis consisted of radical/stereotactic radiotherapy or surgical resection or radiofrequency ablation (RFA).

      Results
      Twenty-two patients, 13 men and 9 women, were included. The mean age was 61 years (range 41-79) and all were in good condition (WHO 0-1). The sites of the solitary metastases were brain (13), bone (6), liver (1), soft tissue (1) and adrenal gland (1). The intrathoracic tumor stage (ignoring M-status) was IA in 2 patients, IB in 1 patient, IIA in 4 patients, IIB in 1 patient, IIIA in 8 patients and IIIB in 6 patients. Nineteen patients were treated with radiotherapy and 3 patients had a surgical intervention for the primary tumor. Eighteen patients (82%) received chemotherapy, 3 concurrently and 15 sequentially. The metastases were treated with ablative/stereotactic radiotherapy (19), surgical intervention (2) and RFA (1). The median follow-up was 47 months (95% CI 24-69). Seventeen patients developed recurrent disease of whom 12 died. Only 2 recurrence occurred within the irradiated area. Both infield recurrences were brain metastasis after a stereotactic irradiation of 15 Gy and 18 Gy. The other recurrences where mostly pulmonary (7) and brain metastases (6). The median DFS was 14 months (range 1-47, 95% CI 9 – 19) and the median OS was 32 months (95% CI 12– 52). The 1- and 2-year OS was 78.7% (95% CI 52.7-91.5) and 59.5% (95% CI 32.8-78.5), respectively. The 1- and 2-year DFS was 54.5% (95% CI 30.5-73.2) and 24.9% (95% CI 8.1-46.3), respectively.

      Conclusion
      Radical treatment of a highly selected group of NSCLC patients in good condition presenting with a single synchronous extra-thoracic metastasis resulted not only in adequate local control, but also in favorable long-term DFS and OS.