SWISS TUMOR BOARD Pancreatic Cancer March 26, 2009 Novotel Bern Prof. Dr. Mahmut Ozsahin Lausanne University Medical Center (CHUV), Lausanne

Case #1 J. Metzger Male patient, 55-yr-old G3, pT2pN1 (1+/16), R0 (close margin) Adjuvant ttt?, Cx alone?, Cx and RT?

Case #1 Short literature review on adjuvant CT/RT GITSG study including patients (Kalser, Arch Surg 1985; Cancer 1987) = RT/CT (40 Gy/5FU) better than observation (20 vs. 11 months median survival) EORTC study including 114 patients (Klinkenbijl, Ann Surg 1999) = No difference RT/CT (split course 40 Gy/5FU) vs. observation (17 vs.13 months median survival) ESPAC-1 study including 289 patients (pooled analysis 541 patients) (Neoptolemos, Lancet 2001, NEJM 2004) = 2x2 factorial design; CT vs. RT/CT vs. CT/RT+CT vs. observation. RT worsens the outcome whereas chemo. increases it (very complex study with a lot of criticism) CONKO study including 368 R0/R1 patients (Oettle, JAMA 2007, ProcASCO 2008) = gemcitabine vs. observation (23 vs 20 months median survival; 21 vs. 9% OS; gemcitabine better). Very clean data. RTOG 9704 including 388 pancreatic head patients (Regine, JAMA 2008) compared conventional RT/CT (5FU) vs. 3-wk gemcitabine + RT/CT (5FU) + 3 mo. gemcitabine. Gemcitabine arm better (20.5 vs. 17 months median survival). Meta-analyses assessing the impact of chemotherapy (Stocken, BJC 2005; Butturini, Arch Surg 2008): Chemotherapy is better, and more pronounced in negative-margin patients. NCCN guidelines and current evidence: waiting the ESPAC-3 results (observation vs. leucovorin/5FU vs. gemcitabine), the standard is CONKO or RTOG 9704 type treament

EORTC study

Case #1 Short literature review on adjuvant CT/RT GITSG study including patients (Kalser, Arch Surg 1985; Cancer 1987) = RT/CT (40 Gy/5FU) better than observation (20 vs. 11 months median survival) EORTC study including 114 patients (Klinkenbijl, Ann Surg 1999) = No difference RT/CT (split course 40 Gy/5FU) vs. observation (17 vs.13 months median survival) ESPAC-1 study including 289 patients (pooled analysis 541 patients) (Neoptolemos, Lancet 2001, NEJM 2004) = 2x2 factorial design; CT vs. RT/CT vs. CT/RT+CT vs. observation. RT worsens the outcome whereas chemo. increases it (very complex study with a lot of criticism) CONKO study including 368 R0/R1 patients (Oettle, JAMA 2007, ProcASCO 2008) = gemcitabine vs. observation (23 vs 20 months median survival; 21 vs. 9% OS; gemcitabine better). Very clean data. RTOG 9704 including 388 pancreatic head patients (Regine, JAMA 2008) compared conventional RT/CT (5FU) vs. 3-wk gemcitabine + RT/CT (5FU) + 3 mo. gemcitabine. Gemcitabine arm better (20.5 vs. 17 months median survival). Meta-analyses assessing the impact of chemotherapy (Stocken, BJC 2005; Butturini, Arch Surg 2008): Chemotherapy is better, and more pronounced in negative-margin patients. NCCN guidelines and current evidence: waiting the ESPAC-3 results (observation vs. leucovorin/5FU vs. gemcitabine), the standard is CONKO or RTOG 9704 type treament

ESPAC-1 study, Lancet 2001

ESPAC-1 trial New Engl J Med 2004

Case #1 Short literature review on adjuvant CT/RT GITSG study including patients (Kalser, Arch Surg 1985; Cancer 1987) = RT/CT (40 Gy/5FU) better than observation (20 vs. 11 months median survival) EORTC study including 114 patients (Klinkenbijl, Ann Surg 1999) = No difference RT/CT (split course 40 Gy/5FU) vs. observation (17 vs.13 months median survival) ESPAC-1 study including 289 patients (pooled analysis 541 patients) (Neoptolemos, Lancet 2001, NEJM 2004) = 2x2 factorial design; CT vs. RT/CT vs. CT/RT+CT vs. observation. RT worsens the outcome whereas chemo. increases it (very complex study with a lot of criticism) CONKO study including 368 R0/R1 patients (Oettle, JAMA 2007, ProcASCO 2008) = gemcitabine vs. observation (23 vs 20 months median survival; 21 vs. 9% OS; gemcitabine better). Very clean data. RTOG 9704 including 388 pancreatic head patients (Regine, JAMA 2008) compared conventional RT/CT (5FU) vs. 3-wk gemcitabine + RT/CT (5FU) + 3 mo. gemcitabine. Gemcitabine arm better (20.5 vs. 17 months median survival). Meta-analyses assessing the impact of chemotherapy (Stocken, BJC 2005; Butturini, Arch Surg 2008): Chemotherapy is better, and more pronounced in negative-margin patients. NCCN guidelines and current evidence: waiting the ESPAC-3 results (observation vs. leucovorin/5FU vs. gemcitabine), the standard is CONKO or RTOG 9704 type treament

CONKO study, JAMA 2007

Neuhaus, ASCO 2008

Case #1 Short literature review on adjuvant CT/RT GITSG study including patients (Kalser, Arch Surg 1985; Cancer 1987) = RT/CT (40 Gy/5FU) better than observation (20 vs. 11 months median survival) EORTC study including 114 patients (Klinkenbijl, Ann Surg 1999) = No difference RT/CT (split course 40 Gy/5FU) vs. observation (17 vs.13 months median survival) ESPAC-1 study including 289 patients (pooled analysis 541 patients) (Neoptolemos, Lancet 2001, NEJM 2004) = 2x2 factorial design; CT vs. RT/CT vs. CT/RT+CT vs. observation. RT worsens the outcome whereas chemo. increases it (very complex study with a lot of criticism) CONKO study including 368 R0/R1 patients (Oettle, JAMA 2007, ProcASCO 2008) = gemcitabine vs. observation (23 vs 20 months median survival; 21 vs. 9% OS; gemcitabine better). Very clean data. RTOG 9704 including 388 pancreatic head patients (Regine, JAMA 2008) compared conventional RT/CT (50.4 Gy/5FU) vs. 3-wk gemcitabine + RT/CT (5FU) + 3 mo. gemcitabine. Gemcitabine arm better (20.5 vs. 17 months median survival). Meta-analyses assessing the impact of chemotherapy (Stocken, BJC 2005; Butturini, Arch Surg 2008): Chemotherapy is better, and more pronounced in negative-margin patients. NCCN guidelines and current evidence: waiting the ESPAC-3 results (observation vs. leucovorin/5FU vs. gemcitabine), the standard is CONKO or RTOG 9704 type treament

RTOG 9704 study Regine, JAMA 2008

Case #1 J. Metzger Male patient, 55-yr-old G3, pT2pN1 (1+/16), R0 (close margin) Adjuvant ttt?, Cx alone?, Cx and RT? GITSG (RT/CT better than observation) EORTC (RT/CT vs. Observation) = no difference ESPAC-1 (CT vs. RT/CT vs. CT/RT+CT vs. observation) = RT group worse CONKO (gemcitabine vs. observation) = gemcitabine better RTOG 9704 (conventional RT/CT vs. gemcitabine + RT/CT + gemcitabine) = gemcitabine arm better (borderline significance) Conlusion: pT2pN1 R0; therefore adjuvant gemcitabine would be the right decision (CONKO) (young patient = RTOG 9704? not accepted in Europe) NCCN guidelines: RT/CT vs. gemcitabine, both OK