Leire Zubiri

712PA THREE-STEP STRATEGY OF INDUCTION CHEMOTHERAPY, CHEMO-RADIOTHERAPY AND SURGERY IN LOCALLY ADVANCED PANCREATIC CANCER (LAPC) PATIENTS. ROLE OF A NONLINEAR MIXED EFFECTS MODELING TO PREDICT OUTCOME

ABSTRACT Aim: The optimal strategy for patients with LAPC remain a therapeutic challenge. A growing evidence suggests that both, pts with borderline resectable and unresectable tumors may benefit from a multimodal approach aimed at improving resectability and survival times. In the present work our experience after a long-term follow-up period is reported. Methods: From December 2005 to July 2011, 67 histologically confirmed LAPC, endoscopic ultrasound (EUS) staged T3-4 and/or N+ were retrospectively analysed. They received induction gemcitabine/oxaliplatin- based chemotherapy followed, in case of radiological response or stable disease, by chemo-radiotherapy (50.4 Gy concurrently with daily capecitabine and weekly oxaliplatin). Salvage surgery was performed when technically feasible. We have applied a nonlinear mixed effects (NLME) modeling to evaluate the impact of dynamic changes in tumor size, Ca- 19.9, neutrophil-lymphocyte ratio and platelet-lymphocyte ratio on the clinical outcome of these patients. Results: The median age was 63 years (range 35-85). Male to female 36/31. Thirty eight pts (57%) completed the whole program (group A), whereas 27 (40%) received chemo and radioterapy but were not elegible for surgery (Group B). Two pts (3%) progressed after induction chemotherapy (Group C). EUS staged T4 or N+ was found in 20 (30%) and 24 (36%) respectively. Toxicity profile was mild, with no grade 4 toxicity being documented. On an intent to treat basis, R0 resection rate was 57%; ypT0ypN0 were observed in 11 (29%) of patients. Among resected patients, local and distant failure rates were 5% and 55%, respectively. The liver was the most frequent site of relapse 21(43%) pts. After a median follow up of 23 months (range 4 to 102), median PFS was 21, 10 and 1 month in groups A, B and C respectively (p = Conclusions: Our date suggest that this three-step strategy is feasible and active in LAPC patients. The NMLE population modeling will be presented at the meeting Disclosure: All authors have declared no conflicts of interest.

645PINDUCTION CHEMOTHERAPY, CHEMO-RADIOTHERAPY AND SURGERY IN LOCALLY ADVANCED GASTRIC CANCER (GC) PATIENTS: LONG TERM RESULTS FROM A SINGLE INSTITUTION

ABSTRACT Aim: Multimodal therapy is the standard of care in locally advanced esophagogastric adenocarcinomas. However, most trials include both, GEJ and GC. We aimed to specifically rule out in gastric cancer patients the R0 rate, pathological response degree, patterns of recurrence and long-term outcomes when treated with induction chemotherapy (ICT), followed by chemoradiotherapy (CRT) and salvage surgery. Methods: Patients (pts) with CT scan and endoscocopic ultrasound (EUS) T2-4 and/or N+ M0 GC were retrospectively analyzed. The neoadjuvant strategy consisted of 3-4 cycles of chemotherapy followed by CRT (weekly chemotherapy concurrently with daily external beam radiotherapy up to 45 Gy). Surgery was scheduled 4 to 6 weeks after the end of CRT. Pathological response was graded according to the Becker criteria. We have applied a nonlinear mixed effects (NLME) modeling to evaluate the impact of dynamic changes in tumor size, neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) on the clinical outcome of these patients. Results: From November 2004 to July 2013, 60 pts [M/F: 42/18, median age 60 (range 36-76), T2/T3/T4a/T4b: 2/24/26/8; N0/N + , 6/54; Diffuse/Intestinal: 35/25] were retrospectively analyzed. Thirty-four and 54 patients were stages by EUS as T4 or N +, respectively. Median preoperative NLR and PLR were both 2.43 and 148. Forty-nine pts underwent radical surgery (total/partial gastrectomy: 33/16) with an R0 resection rate of 92%. Pathological response according to Becker criteria was grade Ia (12%), grade Ib (39%), grade II (22%) and grade III (2%). pN0 was achieved in 26 pts (53,1%). Median harvested nodes were 13. Median DFS for pN0 and pN+ pts was NR and 23 months, respectively (p = 0.01), whereas median OS for pN0 and pN+ was NR and 30 months, respectively (p = 0.009). Among resected pts, distant failures were reported 22 pts, most of them in the peritoneal cavity (55%). After a median follow-up of 30 months (range 4-95 months) the 5-year overall and disease-free survival, were 31% and 39%, respectively. Conclusions: Our data suggest that a three-step strategy is feasible and active in locally advanced gastric cancer patients. The NMLE population modeling to evaluate the impact of dynamic markers on the clinical outcome will be presented at the meeting. Disclosure: All authors have declared no conflicts of interest.

644PINDUCTION CHEMOTHERAPY FOLLOWED BY CHEMORADIOTHERAPY IN LOCALLY ADVANCED ESOPHAGOGASTRIC ADENOCARCINOMA. HAS THE LOCATION OF THE PRIMARY TUMOR ANY INFLUENCE ON PATIENTS' OUTCOME? A RETROSPECTIVE ANALYSIS

ABSTRACT Aim: Multimodal therapy is the standard of care in locally advanced esophagogastric adenocarcinoma. However, most trials include both, gastric (GC) and gastroesophageal junction (GEJ) cancers. We aimed to rule out whether patients (pts) with either locally advanced GEJ (group A) or GC (group B) have different outcomes when treated with a neoadjuvant approach based on induction chemotherapy (ICT), chemoradiotherapy (CRT) and surgery. Methods: EUS-T2-4 and/or N+ M0 GEJ or GC adenocarcinoma patients were scheduled to receive preoperative therapy (3-4 cycles of chemotherapy followed by concurrent CRT). Surgery was scheduled 4 to 6 weeks after the end of CRT. Pathological response was graded according to the Becker criteria. Patterns of recurrence, progression-free survival (PFS) and overall survival (OS) were also evaluated. Results: From november 2004 to July 2013, 87 pts (27 in group A, 60 in group B) met the specified criteria. Pts characteristics were; Group A; M/F; 23/4; EUS-T3 52%, T4 40,7%, N+ 95%, median age 56 (31-81); Diffuse/Intestinal 55%/44%. Group B; M/F; 42/18; EUS-T3 40%, T4 56%, N+ 95%; median age 60.5 (36-76); Diffuse/Intestinal 57%/42%. Seventy-four pts underwent surgery (group A/ B; 92.6%/82%). Pathological response (Group A/B); Grade Ia-Ib according to Becker criteria (72%/51%), pN0 (60.3%/53%). R0 resection (Group A/B); (96%/94%). Among resected pts we analysed the impact of tumor location (GC vs GEJ) on known prognostic factors such as Lauren classification and degree of pathological response regarding PFS and OS. In group A, median OS and PFS did not difer according to Lauren neither classification nor pN status. In contrast, median PFS varied according to Becker response (Ia-b: Not Reached; II-III: 13m; p = 0.02). In group B, we found differences in PFS and OS according to; a)- Lauren Classification; Intestinal GC vs Diffuse GC pts [median PFS; NR vs 13.6m; p = 0.028, median OS: NR vs 15.3m; p = 0.026]. b)pN status (-/+) [median PFS; NR vs 18m; p Conclusions: When treated with ICT followed by CRT, GEJ and GC pts have different outcomes in terms of pathological response degree, patterns of recurrence and survival times. Disclosure: All authors have declared no conflicts of interest.