popescu razvan gastric cancer locally advanced

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  • 1. Treatment of operable gastric cancer Razvan Popescu MD, MRCP(UK) ESO Balkan Masterclass in Clinical Oncology 11.5.2011- 15.5.2011 Dubrovnik, CroaKa
  • 2. Gastric Cancer Incidence in Males GLOBOCAN 2008, Interna3onal Agency for Research on Cancer 0 3.2 6.9 11.6 21.9 63 Age-standardised incidence rates per 100,000
  • 3. Cancer Incidence in Central and Eastern Europe GLOBOCAN 2008, Interna3onal Agency for Research on Cancer
  • 4. Work-up of Gastric Cancer Physical examinaKon, blood count and dierenKal, liver and renal funcKon tests Endoscopy / EUS CT scan of the thorax, abdomen and pelvis Laparoscopy (+ peritoneal washings) +ve washings not independent prognosKc factor, conversion to ve washings up to 1/3 with preop chemotherapy (S. Lorenzen ASCO GI 2010) PET scans can be negaKve, especially in paKents with mucinous tumours (up to 30%) If posiKve can be used for early response assessment
  • 5. Gastric Cancer Survival 100% 91.6 82.0 79.2 Stage 0 66.9 Stage I 47.6 50 36.4 Stage II 21.9 14.7 Stage III 0 5 10 years CADO,1985 Years after surgery
  • 6. EGJ Cancers and Gastric cancers are dierent enKKes !! Distal esophagus GE junction Proximal stomach Distal stomach
  • 7. OGJ Cancers and Gastric cancers are dierent !!
  • 8. Treatment of M0 Gastric Cancer Surgical resecKon is the only modality that is potenKally curaKve, and is recommended for all non- metastaKc cancers The extent of opKmal regional lymphadenectomy is sKll debated. A minimum of 15 lymph-nodes should be recovered (even if a formal D2 lymphadenectomy is not performed)
  • 9. Dutch D1D2 surgical trial 996 eligible paKents randomized beteween 1989 and 1993 to D1 or D2 lymphadenectomy 771 paKents underwent assigned treatment, data reanalysed aaer 15 years Outcome D1 D2 P 15-y survival 21% 29% 0.34 Gastric cancer death 48% 37% 0.01 Local recurrence 22% 12% - OperaKve mortality 4% 10% 0.004 ComplicaKons 25% 43% 0.001
  • 10. Strategies that increase cure rate in potenKally operable gastric cancer Adjuvant chemotherapy Adjuvant Chemo-Radiotherapy Peri-operaKve Chemotherapy Pre-operaKve Chemotherapy, postoperaKve chemoradiotherapy
  • 11. Benefit of adjuvant chemotherapy forresectable gastric cancer: a meta-analysis 17 RCT 3838 pts 5 year survival:Overall effort 55.3% vs. 49.6%HR: 0.82 (95% CI 0.76-0.91)P3 McDonald JS et al. N Engl J Med 2001 Sep 6;345(10):725-30
  • 17. Postoperative Chemoradiotherapy For Localised Gastric Cancer : INT-0116 Clear benet in disease free and overall survival with median follow-up of 6 years. Risk reducKon of death by 24%. Surgery: D2 resecKon less than 10%, 54 % of paKents fewer than 15 nodes (less than D1) Planning of RadiaKon to be modied aaer central review in 35% of cases due to protocol deviaKons McDonald JS et al. N Engl J Med 2001 Sep 6;345(10):725-30
  • 18. Postoperative Chemoradiotherapy For Localised Gastric Cancer : INT-0116 Complex RT schedule with signicant toxicity SubopKmal chemotherapy schedule, role of the 2 anking Mayo 5-FU/FA cycles unclear Not an approach that has taken root in Europe In the context of subopKmal surgery or if preoperaKve MDT is lacking an acceptable approach if good RT available McDonald JS et al. N Engl J Med 2001 Sep 6;345(10):725-30
  • 19. Impact of Extent of Surgery and PostoperaKve CRT on Recurrence Pamern Leyden retrospecKve analysis of 2 Dutch trials : 91 paKents receiving postop CRT vs. Cohort from Dutch Gastric Cancer Trial (694) split by D1 vs. D2 resecKon PaKents with D2 resecKon had as good an outcome as paKents receiving postop. CRT Clear benet for D1 resected paKents, R1 resecKons and high Maruyama Index of unresected disease (computed from data base of cases giving likelihood of involvement of unresected LN staKons) JL Dikken, JCO May 10, 2010
  • 20. Strategies that increase cure rate in potenKally operable gastric cancer Adjuvant chemotherapy Adjuvant Chemo-Radiotherapy Peri-operaKve Chemotherapy Pre-operaKve Chemotherapy, postoperaKve chemoradiotherapy
  • 21. MAGIC TrialEligible patients: Adenocarcinoma of the stomach Study entry and randomizationor lower third of the oesophagus(from 1999), suitable for curativeresection Non-metastatic disease S arm CSC arm Stage II or greater N=253 N=250Primary Surgery Pre-operative chemotherapy:Overall survival ECFx3SecondaryProgression-free survival 3-6 weeksSurgical resectabilityQuality of Life SurgeryChemotherapy (ECF): 6-12 weeksEpirubicin 50mg/m2, IV day 1Cisplatin 60mg/m2, IV day 15-FU 200mg/m2/day, continuous Post-operative chemotherapy:infusion, days 1-21 ECFx3(cycles repeated every 3 weeks)Recruitment: July 1994-April 2002 Cunningham et al NEJM 2006
  • 22. MAGIC Trial CSC S N=250 N=253 Commenced pre-operative chemotherapy N=237 (95%) Completed pre-operative chemotherapy N=215 (86%) Proceeded to surgery Proceeded to surgery N=219 (88%) N=240(95%)Cunningham et al NEJM 2006
  • 23. MAGIC Trial Postoperative Morbidity/ Mortality CSC S Postoperative deaths 6% 6% (14/219) (15/240) Postoperative complications 46% 46% Median duration of 13 days 13 days post-operative hospital stayCunningham et al NEJM 2006
  • 24. MAGIC Trial Pathology Findings Median maximum diameter of the resected tumor was smaller in the perioperaKve- chemotherapy group than in the surgery group (3 cm vs. 5 cm, P