1. KShotaro Nakamura,1 Toshiro Sugiyama,2 Takayuki Matsumoto,1 Katsunori Iijima,3 Shouko Ono,4 Masahiro Tajika,5 Akira Tari,6 Yasuhiko Kitadai,7 Hiroshi Matsumoto,8 Tadanobu Nagaya,9 Toshiro Kamoshida,10 Norihiko Watanabe,11 Toshimi Chiba,12 Hideki Origasa,13 Masahiro Asaka,14 for the JAPAN GAST Study Group Gut 2012;61:507-513 Long-term clinical outcome of gastric MALT lymphoma after eradication of Helicobacter pylori : a multicentre cohort follow up study of 420 patients in Japan R2 Jin suk Kim / Prof. Young woon Chang

2. Introduction Gastric MALT lymphoma : 40-50% of primary gastric lymphomas : 20-40% of extranodal lymphomas : 4-9% of all malignant lymphomas : 1-6% of all gastric malignancies H.pylori Gastric MALT lymphoma Causative role Complete remission (CR) of lymphoma Lead to H.pylori X

3. Introduction H.pylori eradication : Regarded as the 1 st -line Tx. of gastric MALT lymphoma Large scale long-term F/U after eradication : Limited with regard to relapse or progression and survival To elucidate the long-term clinical outcome of Helicobacter pylori eradication therapy

4. Methods - Study design - Japanese multicentre cohort follow-up study - Patients with primary gastric MALT lymphoma diagnosed and treated by H.pylori eradication between March 1994 - March 2007 Inclusion criteria - Presence of gastric MALT lmyphoma ( according to the WHO classification and compatible with Wotherspoon’s histological score of 4 or 5 in the pretreatment gastric biopsy specimens) - H.pylori eradication using PPI + combination of two antibiotics as the 1 st line treatment - F/U period of at least 3yrs after successful eradication therapy Exclusion criteria - Primary MALT lymphoma arising in the extragastric organs - Presence of DLBCL prior to the H pylori eradication - Positive H. pylori infection after the final eradication therapy

5. Methods - Subjects - 420 patients, 21 institutes - H.pylori status : Histology, culture, rapid urease test, C urea breath test - H.pylori infection : Positive  one or more of the test showed positive result : Negative  all test showed negative result - Endoscopy type : Superficial, Ulcerative Polypoid or others

6. Methods - Subjects - Clinical stage : Basis of the Lugano staging system (modification of the Ann-Arbor classification) - EUS : Perfomed to evaluate the depth of invasion & dgree of perigastric lymphadenopathy

7. Methods - Assessment after H.pylori eradication therapy -Bx. Specimens (the GELA histological grading system) - Complete histological response (ChR) - Probable minimal residual disease (pMRD) - Responding residual disease (rRD) - No change (NC) - Follow up endoscopy with Bx. : Every 3-6months until confirmation of ChR/pMRD - Treatment failure : Relapse after ChR/pMRD or Progressive disease Responders Non-Responders

8. Methods - Second line treatments for non- responders - Patients with treatment failure or persistence of lymphoma (1) Watch and wait strategy : No treatment (2) Various antineoplastic treatments : Radiotherapy, chemotherapy with or without rituximab, chemoradiotherapy, rituximab alone, surgical resection or others

9. Methods - Prognostic factors and statistical analysis Supplemental table A Clinicopathologic characteristics of 420 patients with gastric MALT lymphoma

10. Results - Response to H.pylori eradication Table 1. Association between Clinicopathological factors & response to the H pylori eradication

11. Results - Response to H.pylori eradication Table 2. Predictive factors for resistance to Helicobacter pylori eradication therapy as determined by logistic regression analysis

12. Results - Response in responders Figure 1. Clinical course of the 420 study patients 77 % 23% 1 patient : Surgical resection 6 patients: CTx. or RTx. Re-eradication of H.pylori spontaneousl y achieved ChR again

13. Results - Treatments for non-responders Figure 1. Clinical course of the 420 study patients. 77 % 23% Lung meta. CTx, RTx, Surgical resection  PR Antibiotics CTx, RTx, Surgical resection

14. Results - Treatment failure, long term outcome and prognostic factors Figure 2. KaplaneMeier curves of 420 patients with gastric MALT lymphoma after H.pylori eradication FFT F 92%90% 80% OS 99%95% 91%

15. Results - Treatment failure, long term outcome and prognostic factors Figure 2. KaplaneMeier curves of 420 patients with gastric MALT lymphoma after H.pylori eradication EFS 92%86% 76%

16. Conclusion The excellent long-term outcome of gastric MALT lymphoma after H pylori eradication was confirmed by this large-scale follow-up study.