1. Association of Family History with Cancer Recurrence and Survival in Patients with Gastric Cancer Journal of Clinical Oncology 2012 30:701-708 R2 Hwang Jin Kyung

2. INTRODUCTION Gastric cancer is globally, –4 th most commonly diagnosed cancer. –2 nd most common cause or cancer motility. Family history of gastric cancer –Significantly associated with cancer development. –10.1~22.3% : have family history of the disease. –1~3% : cancer occur as part of an inherited cancer predisposition syndrome (hereditary non polyposis colorectal cancer, Li-Fraumeni syndrome, familial adenomatous polyposis, Peutz-Jeghers syndrome…)

3. INTRODUCTION Aim of this study –Effect of gastric cancer family history on the survival of patients with gastric cancer remains unclear! –Evaluate the effect of family history on the clinicopathologic characteristics and survival of patients with gastric cancer in a Korean population.

4. PATIENTS and METHODS Study population –National cancer center, a tertiary cancer center hospital, in Goyang, Korea. –Retrospective study : Aug. 2001 ~ Dec. 2005 –Korean ancestry. –Inclusion 20 years of age or older Histologically confirmed gastric adenocarcinoma Newly diagnosed cancer without previous treatment Gastrectomy with LN dissection in an curative intent Interviewed about family history and health behavior

5. PATIENTS and METHODS : Study population

6. PATIENTS and METHODS Personal characteristics and clinical data (1) –Demographic, health-related behavior Included age, sex, years of education, smoking/alcohol drinking status. –Clinicopathologic characteristics Included tumor location, size, differentiation, Lauren classification, gross type, depth of invasion, LN metastasis, stage at diagnosis, operation method, extent of LN dissection, adjuvant chemotherapy, H. pyroli infection status, multiplicity of tumor.

7. PATIENTS and METHODS Personal characteristics and clinical data (2) –Stage at diagnosis International Union Against Cancer/American Joint Committee on Cancer classification system (6 th edition). –In case of multiple synchronous gastric cancer, The lesion with deepest infiltration of the gastric wall  main lesion. The others  accessory lesion. The clinicopathologic charactoristics of the main lesion were used for analysis.

8. PATIENTS and METHODS Family history assessment –Self-reporting through an interview. –Classified according to first-degree or second-degree and cancer type. First-degree : parent, sibling, or offspring. Second-degree : aunt, uncle, niece, nephew, or grandparent. Cancer type : gastric cancer and all other cancer. If subjects had both first- and second-degree relatives  first-degree.

9. PATIENTS and METHODS Follow-up schedule –Advanced gastric cancer (T2 or more in TNM staging) First 3 years : every 3 months with physical exam, blood test every 6 months with abdomen CT. 2 years After that : biannually follow up. –Early gastric cancer (T1) Follow up at 3 months and then every 6 months for 5 years. Annual abdomen CT. –Annual endoscopy for 5 years in all patients. –Stage II~IV with LN metastasis : mainly received adjuvant CTx. Combination of fluoropyrimidine, platinum, irinotecan, and taxane.

10. PATIENTS and METHODS Statistical methods – Χ 2 test, Kaplan-Meier method, log-rank test, Cox proportional hazards model, SAS software (ver. 9.1) were used. –Two separate analysis were performed depending on the primary tumor stage (stage I~II vs. stage III~IV). –Terms of presenting outcome Disease-free survival (DFS) : time from surgery to tumor recurrence, occurrence of a new primary gastric cancer, or death of any cause. Recurrence-free survival (RFS) : time from surgery to tumor recurrence, death with evidence of recurrence, or occurrence of a new primary gastric cancer. Overall survival (OS) : time from surgery to death resulting from any cause.

11. RESULTS

12. RESULTS : Family history of study participants

13. RESULTS : Demographic and clinicopathologic characteristics

14. RESULTS : Effect of family history on the survival 84.4% vs 77.4% 87.0% vs 79.7% 90.8% vs 81.8%

15. RESULTS : Effect of family history on the survival of stage III~IV Family history was not associated with survival in stage I and II. Family history was associated with a significant reduction of cancer recurrence or mortality in stage III and IV.

16. RESULTS : Effect of family history on the survival of stage III~IV Significant associations between family history of gastric cancer in first-degree relatives and survival in patients with stage III and IV gastric cancer.

17. DISCUSSION Why a family history of gastric cancer affects patient survival? 1.Variability in adherence to surveillance monitoring. More likely to undergo regular gastric cancer screening. 2.Positive health-related behavior. Increased physical activity, quitting smoking, more sun-safe behavior, and positive dietary changes. 3.Genetic difference. Microsatellite instability (MSI) is associated with infrequent LN metastasis and lymph vessel invasion, intestinal type histology, and better overall prognosis.

18. DISCUSSION A major limitation of out study is… 1.Relied on self-reports of family history, without pathologic confirm. Reports of family history will always be clearer for those we know better and will be more uncertain as we extend to second-degree relatives. 2.Not include screening endoscopy history in our analyses. Might be different according to the family history and affect major outcomes. 3.Approximately 35% of patients were excluded because of uncertain H. pylori status H. pylori negative status is independent poor prognostic factor. 4.Did not perform genetic evaluation for MSI or CDH1 mutation.

19. A first-degree family history of gastric cancer is associated with improved survival after curative-intent surgery in patients with stage III or IV gastric cancer!