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Poster Session ASCO GI, San Franciso, CA, 15 January 2009

Poster Session ASCO GI, San Franciso, CA, 15 January 2009. Sequential FDG-PET and Induction Chemotherapy in Locally Advanced Adenocarcinoma of the Esophagogastric Junction (AEG): Implementation of a Response-guided Treatment Algorithm at the National Center for Tumor Diseases (NCT).

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Poster Session ASCO GI, San Franciso, CA, 15 January 2009

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  1. Poster Session ASCO GI, San Franciso, CA, 15 January 2009 Sequential FDG-PET and Induction Chemotherapy in Locally Advanced Adenocarcinoma of the Esophagogastric Junction (AEG): Implementation of a Response-guided Treatment Algorithm at theNational Center for Tumor Diseases (NCT) F.Lordick1, K. Ott2, I. Buchmann3, C. Kahlert2, C. von Gall3, H. Bläker4,P. Schirmacher4, Weitz J2, Haberkorn U3, Jäger D1 1National Center for Tumor Diseases (NCT)2 Department of Surgery3Department of Nuclear Medicine4 Department of Pathology, University of Heidelberg, Germany

  2. Background • MUNICON-1 showed a superior R0 resection rate and superior survival in patients with early response to preoperative chemotherapy. • Continuation of neoadjuvant chemotherapy in metabolic non- responders may even deteriorate the outcome compared to early resection of resectable AEG. • But these results have not yet been reproduced at other centers. • Therefore, we implented sequential FDG-PET assessments and an early response-guided treatment algorithm at the National Center for Tumor Diseases (Heidelberg).

  3. Treatment Plan Non-Responder Resection CTx AEGtype I-II PET d14 CTx: 3 months PET d0 Responder Resection Response definition: Decrease of the SUVmean PETd14 / PETbaseline> 35% Weber et al. J Clin Oncol 2001;19:3058-65 Ott et al. J Clin Oncol 2006;24:4692-8

  4. SUV Definition Region of interest (ROI) 1 cm around maximal SUV(corresponding to 10 pixel) Standard uptake value (SUV) Qtumor [MBq/l] x W [kg] SUVBW = Qinjected [MBq/l]

  5. Study Population • Histologically proven adenocarcinoma of the esophagus or cardia(AEG type I or II according to Siewert‘s classification) • Staged uT3/4 Nx M0 (EUS, CT and PET) • Adequate 18-FDG-uptake (tumor) in baseline-PET(> 1.35 x liver-SUV + 2 x SA of the liver-SUV) • Medically fit for chemotherapy and esophagectomy • > 18 years • Written informed consent

  6. Chemotherapy Epirubicin 50 mg/m2 Oxaliplatin 130 mg/m2 Capecitabine 1250 mg/m2/d p.o. 3 weeks EOX: Epirubicin d1, Oxaliplatin d1, Capecitabine d1-14, 3 cycles

  7. Surgery AEG Siewert type I Abdomino-thoracic esophagectomy (Ivor-Lewis operation) AEG Siewert type IITotal gastrectomy with transhiatal distal esophagectomy

  8. Patients‘ Characteristics Evaluable patients (enrolled 8/2007-8/2008) n = 24 Age (years) median 62 (39-81)Gender female 1 (4 %) male 23 (96 %) Tumor localization AEG type 1 14 (58 %) AEG type 2 10 (42 %)Stage uT3 24 (100 %) cN0 1 (4 %) cN+ 23 (96 %) cM0 22 (92 %) cM1b (lymph nodes) 2 (8 %)

  9. Resection n = 24 Resection 22 (92%)Not resected 2 (8%)(reasons: M1b disease and consent withdrawal) Type of resection Subtotal abdomino-thoracic esophagectomy 15 (68%)Extended transhiatal gastrectomy 7 (32%) Residual tumor R0 16 (72%)R1 6 (28%) Postoperative course Relevant complications 7 (32%)Mortality (hospital) 0 (0%)

  10. Metabolic Response Evaluable patients 23 Response assessed by PET Responder 14 (60%) Non-Responder 9 (40%) One patient was not evaluable due to insufficient baseline tumor 18-FDG uptake

  11. Postoperative Course

  12. Histological Remissions Remissions scored according toBecker et al. Cancer 2003; 98: 1521-30

  13. ypT-Category 29% 7%

  14. ypN-category

  15. Resectability

  16. Conclusions • These results confirm the feasibility of an early metabolic response (PET)-guided treatment algorithm for locally advanced AEG. • R0 resectability in pts with early metabolic non-response remains dismal. • Therefore, we started to investigate alternative CTx combined with radiation as salvage treatment in early metabolic non-responders

  17. Future Perspective IMAGE study designR-CTx vs S in PET non-responders Resect immediately Rando-mize Non-Responder Resect Radio-CTx PETd 14 CTx Responder Resect CTx CTx CTx

  18. References • Weber WA, Ott K, Becker K, et al. Prediction of response topreoperative chemotherapy in adenocarcinomas of the esophagogastric junction by metabolic imaging.J Clin Oncol 2001; 19:3058–3065. • Ott K, Weber WA, Lordick F, et al. Metabolic imaging predicts response, survival, and recurrence in adenocarcinomas of the esophagogastric junction. J Clin Oncol 2006; 24:4692–4698. • Wieder HA, Beer AJ, Lordick F, et al. Comparison of changes in tumor metabolic activity and tumor size during chemotherapy of adenocarcinomas of the esophagogastric junction. J Nucl Med 2005; 46:2029–2034. • Lordick F, Ott K, Krause BJ, et al. Use of PET to assess early metabolic response and guide treatment of locally advanced adenocarcinoma of the oesophagus and oesophagogastric junction: a feasibility study. Lancet Oncology 2007; 8: 797-805 • Siewert JR, Lordick F, Ott K, et al. Induction chemotherapy in Barrett Cancer. Influence on Surgical Risk and Outcome. Ann Surg 2007; 246: 624-631 • Lordick F, Ruers T, Aust DE, et al; European Organisation of Research and Treatment of Cancer Gastrointestinal Group. European Organisation of Research and Treatment of Cancer (EORTC) Gastrointestinal Group: Workshop on the role of metabolic imaging in the neoadjuvant treatment of gastrointestinal cancer. Eur J Cancer. 2008; 44: 1807-19

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