Lung Cancer

SS 04 - Lung 2 - Stage III/IV

30 - Locally Advanced Non-Small Cell Lung Cancer: Excellent Results of Isotoxic Dose Escalation after FDG-PET-Guided Target Volume Reduction - Results of a Prospective Randomized Multicenter Trial

Sunday, October 21
4:45 PM - 4:55 PM
Location: Room 301

Locally Advanced Non-Small Cell Lung Cancer: Excellent Results of Isotoxic Dose Escalation after FDG-PET-Guided Target Volume Reduction – Results of a Prospective Randomized Multicenter Trial
U. Nestle1, T. Schimek-Jasch2, S. Kremp3, A. Schaefer-Schuler4, A. Kuesters5, M. Tosch6, T. Hehr7, S. Eschmann8, Y. P. Bultel9, P. Hass10, F. Jochen11, A. Thieme12, M. Stockinger13, M. Beck14, M. Miederer15, G. Holl16, H. C. Rischke17, S. Adebahr2, J. Koenig18, and A. Grosu19; 1Kliniken Maria Hilf, Department of Radiation Oncology, Moenchengladbach, Germany, 2Department of Radiation Oncology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany, 3Department of Radiation Oncology, Saarland University Hospital, Homburg/Saar, Germany, 4Department of Nuclear Medicine, Saarland University Hospital, Homburg/Saar, Germany, 5Department of Radiation Oncology, Kliniken Maria Hilf, Moenchengladbach, Germany, 6Department of Nuclear Medicine, Helios Klinikum Wuppertal, Wuppertal, Germany, 7Marienhospital Stuttgart, Stuttgart, Germany, 8MARIENHOSPITAL STUTTGART, DEPARTMENT FOR NUCLEAR MEDICINE, Stuttgart, Germany, 9MUTTERHAUS DER BOROMAEERINNEN, DEPARTMENT FOR RADIATION ONCOLOGY, Trier, Germany, 10UNIVERSITY HOSPITAL MAGDEBURG, DEPARTMENT FOR RADIATION ONCOLOGY, Magdeburg, Germany, 11UNIVERSITY HOSPITAL SAARLAND, DEPARTMENT FOR RADIATION ONCOLOGY, Homburg/Saar, Germany, 12CHARITE UNIVERSITY HOSPITAL, DEPARTMENT FOR RADIATION ONCOLOGY, Berlin, Germany, 13UNIVERSITY HOSPITAL MAINZ, DEPARTMENT FOR RADIATION ONCOLOGY, Mainz, Germany, 14GEMEINSCHAFTSPRAXIS FUER STRAHLENTHERAPIE, Neumuenster, Germany, 15UNIVERSITY HOSPITAL MAINZ, DEPARTMENT FOR Nuclear Medicine, Mainz, Germany, 16HELIOS KLINIKEN SCHWERIN, DEPARTMENT FOR NUCLEAR MEDICINE, Schwerin, Germany, 17UNIVERSITY HOSPITAL FREIBURG, DEPARTMENT FOR RADIATION ONCOLOGY, Freiburg, Germany, 18UNIVERSITY OF MAINZ, INSTITUTE OF MEDICAL BIOMETRY EPIDEMIOLOGY AND INFORMATICS, Mainz, Germany, 19Department of Radiation Oncology, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

Purpose/Objective(s): The impact of 18-FDG-PET/CT based target volume delineation on outcome in radio-chemotherapy for locally advanced (LA) non-small cell lung cancer (NSCLC) was evaluated in an international prospective randomized multicenter trial (PET-Plan).

Materials/Methods: A phase II non-inferiority study was performed with LA NSCLC scheduled for combined radio-chemotherapy in 23 trial sites. In 205 of 311 screened patients, target volumes were randomized between a conventional (adjuvant mediastinum to 50 Gy plus dose escalation volume of tumor, atelectasis, FDG- and CT-positive nodal stations; arm A) and an experimental (escalation volume FDG-positive tumor and nodal stations only; arm B) approach. In every case, respecting normal tissue constraints (pre-defined in analogy to RTOG 0617), isotoxic dose escalation was performed to achieve the individually highest achievable doses between 60 and 74 Gy/2 Gy. Stringent pro- and retrospective imaging- and RT-QA was done during recruitment and follow-up. Simultaneous chemotherapy was given, mainly using platinum and vinorelbine. Primary endpoint was loco-regional progression, main secondary endpoints were in- and outfield- progression-free-, overall survival and toxicity. After a minimum/mean follow up of 6/22 months, we here report the first results.

Results: In the well balanced patient group of 205 patients, 172 were treated as per protocol, being mainly in UICC-stage IIIa (36%) and IIIb (56%) with GTVs of in mean 105 ml. Dose escalation reached in mean 65.3 Gy (A) and 67.3 Gy (B; p=0.007). Loco-regional progression (LRP) was more frequent in arm A (conventional target volume) with a cumulative incidence of 0.29 / 0.39 vs. 0.14 / 0.20 (arm B) after 12 / 24 months (p=0.078). In stratified Cox-models, independent prognostic factors for LRP were study center (p=0.046) and tumor volume (GTV) (p=0.022) while study arm did not reach statistical significance. IMRT (50%) technique did not lead to significantly different results as compared to 3-D-CRT (50%). The 2-year overall survival was 57% (A) vs. 54% (B; n.s.). Neither for local control nor for survival, a positive or negative influence of radiation therapy dose was observed. There was no significant differente for in-field- (A: 23% vs. B: 11%; n.s.) and out-field- (A: 11% vs. B: 8%; n.s.) regional recurrences between the study arms. Acute and late toxicity (CTC/ RTOG-EORTC) was mild with no clinically significant difference between the treatment arms. However, SUEs appeared more frequent in arm B.

Conclusion: FDG-PET based radiation therapy planning is recommended for isotoxically dose escalated radio-chemotherapy in locally advanced NSCLC. It enabled higher dose escalation and a clear trend to improved local control as compared to conventional planning. The favourable survival results well compare to other recent trials. In contrast to RTOG 0617, no adverse effect of higher treatment doses were observed.

Author Disclosure: U. Nestle: None. T. Schimek-Jasch: None. S. Kremp: None. A. Schaefer-Schuler: None. A. Kuesters: None. T. Hehr: None. M. Stockinger: None. H. Rischke: None.

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30 - Locally Advanced Non-Small Cell Lung Cancer: Excellent Results of Isotoxic Dose Escalation after FDG-PET-Guided Target Volume Reduction - Results of a Prospective Randomized Multicenter Trial



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