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C. Brink



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

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Radiation Oncology + Radiotherapy
    • Presentations: 3
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      P2.08-014 - The influence of age on the outcome of concurrent chemo-radiotherapy in locally advanced NSCLC (ID 1677)

      09:30 - 09:30  |  Author(s): C. Brink

      • Abstract

      Background
      Concomitant chemo-radiotherapy (CRT) has been shown to be superior to single modality radiotherapy (RT) and to neoadjuvant chemotherapy (NeoCT) followed by RT. In this retrospective study we report the influence of age on survival in two groups of patients with locally advanced radiotherapy treated from 1995 to June 2012: 1) NoCRT-group: RT +/- NeoCT without CRT and 2) CRT-group: NeoCT followed by CRT.

      Methods
      Data for 446 patients that completed 3-D conformal RT or IMRT in planned doses of 60-66 Gy at 2 Gy/F without elective nodal irradiation was obtained. CRT was used for 114 patients with the regimens: weekly Docetaxel (N=43), Carboplatin-Vinorelbine (N=70) and Cisplatin-Vinorelbine (N=1). The NoCRT group consisted of 332 patients

      Results
      Figure 1 The median and 5 year survival was 17.2 months and 15% for NoCRT, and 21.4 months and 29% for CRT (p<0.02). The data was analyzed in the age groups ≤65 and >65 years. For NoCRT, no differences in survival was found (17.2 vs. 17.1 months), but in the CRT group significant longer survival was found in the younger age group, 29.2 vs. 20.0 months in the older group (p=0.03). CRT was the only significant factor among patients ≤65, while CRT was an insignificant factor among patients >65. The patients treated with CRT had significantly lower frequency of local relapse (33%) compared with patients treated without (46%, p = 0.016), while the rate of distant metastases was unaffected by the use of CRT. Patients ≤65 years had a low complication death rate (1-2%) independent of CRT, while the complication death rate among patients >65 years was 6-8%, also independent of CRT.

      Conclusion
      Patients ≤65 years had a very positive effect of CRT while CRT did not influence survival in older patients. The reason for this is unknown

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      P2.08-017 - Increasing expected local control for locally advanced NSCLC patients with inhomogeneous dose-escalation (ID 2105)

      09:30 - 09:30  |  Author(s): C. Brink

      • Abstract

      Background
      Radiotherapy treatments of locally advanced NSCLC patients are associated with poor local control and low overall survival rates. Local recurrence often occurs within the initial primary tumour. Therefore, higher doses to locally advanced NSCLC tumours with conventional fractionation are required in order to increase the local control. However, current tumour dose levels are limited by the toxicity levels of the surrounding normal tissue, e.g. healthy lung tissue and mediastinal region. This study presents the concept of clinically applicable inhomogeneous dose plans that distribute higher doses in the tumour without compromising the expected lung toxicity, not only for isolated lung tumours, but also for patients with involved lymph nodes.

      Methods
      Twenty consecutive NSCLC patients previously treated with conventional radiotherapy treatment with a prescribed dose of 66Gy/33F were included in this planning study. The patients were staged T1b-T4 N0-N3 with a median tumour size of 56.7 cm[3] (range 3.2-399.2 cm[3]). Highly modulated IMRT plans were used for treatment with standard dose coverage of 95%-107% of the prescribed dose. For each patient, a new dose-escalated treatment plan was created with the same mean lung dose as obtained in the standard plan using an inhomogeneous dose distribution with minimum dose coverage of ≥95% of the prescribed dose. The maximum tumour dose was only limited by conservative tolerance levels of the surrounding healthy tissue: maximum doses of 45 to spinal canal, 66 Gy to oesophagus, and 74 Gy to less than 1 cm[3] within the mediastinal region. Two different tumour control probability (TCP) models were used to evaluate the homogeneous and inhomogeneous treatment plans. Furthermore, in order to estimate the reliability of the calculated doses in comparison to actual delivered doses, the treatment plans were re-calculated in 4D by accounting for uncertainties arisen from respiration, delineation, setup, and baseline shift.

      Results
      Dose escalation was possible for all patients. TCP values increased approximately 15 and 10 percentage points based on calculations related to the GTV and CTV, respectively, from an initial level of 18%. This increase in expected local control was obtained without increasing the mean lung dose. However, small increases in maximum doses to the mediastinum were observed: 2.5 Gy for aorta, 4.4 Gy for the connective tissue, 1.6 Gy for the heart, and 2.6 Gy for trachea and bronchi. The increase in TCP predictions from 4D calculations differed only slightly from the corresponding 3D calculation.

      Conclusion
      Increased target doses and TCP values using dose-escalated inhomogeneous dose distributions could be achieved for all patients, regardless of lymph node involvement, tumour stage, location, and size. These new treatment plans have the potential to increase the local tumour control with 10-15 percentage points without increasing the mean lung dose, which is often regarded as a measure for the expected lung toxicity. The conservative dose constraints used for the organs at risk ensures clinical applicable treatment plans that can be implemented today. Based on these promising results, a national randomised phase III study is under development.

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      P2.08-018 - Interobserver Variability in Target Volume Delineations in Postoperative Radiotherapy for NSCLC. (ID 2298)

      09:30 - 09:30  |  Author(s): C. Brink

      • Abstract

      Background
      The aim of this study is to determine the interobserver variability between thoracic surgeons and radiation oncologists in defining and delineating target volume for postoperative radiotherapy for patients with non small cell lung cancer (NSCLC). These patients were offered postoperative RT due to microscopic non-radical operation.

      Methods
      Between 2002 and 2010, 48 NSCLC patients were offered postoperative radiotherapy at Department of Oncology, Odense University Hospital due to microscopic non-radical operation. Two thoracic surgeons (S1 and S2) and two clinical oncologists (O1 and O2) were retrospectively asked to delineate clinical target volume (CTV) on the 3D CT scanning used for radiotherapy planning in each patient. Instruction were given to include the non-radical site on basis of surgical-, pathological-, and radiological reports. The delineation was done independently by each physician. There are no local guidelines for delineation postoperative volume after non radical microscopic operation. The spatial volume discrepancy between the different physicians was the end-point.

      Results
      The mean volumes were very different between the physicians: S1 20.5 (SD 17.4) cm[3], S2 21.5 (28.1) cm[3], O1 14.4 (20.5) cm[3], and O2 32.9 (SD 35.6) cm[3]. A large spatial volume discrepancy between the different physicians was observed as well. Mean discrepancies were O1-O2 18.5 (SD 25.3) cm[3 ](p<0.0001), O1-S1 6.1 (SD 21.4) cm[3] (p=0.06), S1-S2 1.3 (SD 22.9) cm[3] (p=0.7). Mean Soerensen-Dice index O1-O2 0.27 (SD 0.19), O1-S1 0.27 (SD 0.16), S1-S2 0.29 (SD 0.18). There was a reasonable overlap in 25 patients (52%) between all 4 physicians. In another 9 cases (19%) 3 physicians had a reasonable overlap and one “outlier”. Figure 1 illustrates one case with reasonable overlap, and another case with one “outlier”.

      Conclusion
      Figure 1 Several conclusions can be drawn from this study. At first it is very challenging to define postoperative volume, when there is no gross tumor volume as is the case when RT it is due to microscopic non-radical operation. Secondly, it is important to have guidelines in order to define the approximate size of the CTV, this in context of the large difference in the size of the volume between the oncologists. Thirdly, surgeon and oncologist should delineate the postoperative target volume in collaboration to ensure the correct conclusion is drawn on the basis of operation and pathological reports, in order to hit the right target and reduce irradiated volume.

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    P3.08 - Poster Session 3 - Radiotherapy (ID 199)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Radiation Oncology + Radiotherapy
    • Presentations: 1
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      P3.08-023 - Acute Esophagitis and concomittant Chemoradiotherapy with Navelbine. Results from NARLAL, a Phase II randomized Trial. (ID 2686)

      09:30 - 09:30  |  Author(s): C. Brink

      • Abstract

      Background
      Radiotherapy (RT) for non-small cell lung cancer (NSCLC) is associated with important side effects with acute esophagitis (AE) as one of the main acute toxicities. RT dose and concomitant chemo-radiotherapy as well as volume of oesophagus treated are known risk factors for development of AE.

      Methods
      This is a multicentre national protocol on RT for locally advanced NSCLC. From 2009-2013 117 patients were randomized between 60 Gy/ 30 F (arm A) and 66 Gy/ 33 F (Arm B), 5 FW. Navelbine[®] 50 mg 3 days a week was given concomitant with RT. Before randomization patients were treated with 2 cycles of carboplatin and Navelbine[®] as induction chemotherapy. During RT, patients were registered for side effects once a week. After RT follow up schedule was every 3[th] month from RT start. Side effects were registered according to NCI CTCAE version 3.

      Results
      A total of 117 patients were randomized in this protocol. Baseline characteristics are summarized in table 1. Since last patient was randomized August 2013, all CRF are not available for the moment. There are complete esophagitis data on 103 patients. Grade 0-1 AE were seen in 66 patients (37 in arm A vs. 29 in Arm B), grade 2 in 27 patients (11 vs. 16), 10 patients experienced grade 3 (3 vs. 7), and none grade 4 AE. In a logistic regression analysis with N2/3, age ≥64 years, histology, gender and dose as covariates; treatment arm B was the only significant covariate (p=0.02) for developing grade 2 esophagitis. Dose volumetric data will be ready for WCLC.Figure 1

      Table 1 Number %
      Performance status 0 59 50
      1 57 49
      missing 1 1
      Gender Male 68 58
      Female 49 42
      Histology Squamos cell carcinoma 41 35
      Adenocarcinoma 54 46

      Conclusion
      From this study we conclude, that the risk of developing grade 2 esophagitis is related to dose 66 Gy but the severity is manageable. Acknowledgements Supported by CIRRO- The Lundbeck Foundation Center for Interventional Research in Radiation Oncology.