A phase II study of preoperative chemotherapy with irinotecan(CPT) and cisplatin(CIS) for gastric cancer(NCI 5917): FDG-PET/CT predicts patient outcome

Abstract

4502 Introduction: Preoperative chemotherapy is a standard option for the treatment of locally advanced gastric cancer(GC). FDG-PET scans have been examined to identify early treatment response in esophagus and GEJ adenocarcinoma. We evaluated the utility of an early change in FDG-PET/CT at several time points in predicting response to preoperative chemotherapy in gastric cancer. Methods: 42 pts with locally advanced GC(preoperative stage T2N+M0 or T3–4NanyM0) were treated with CPT 65 mg/m2 and CIS 30mg/m2 on day(d)1 and d8, every 21 days for 4 cycles. FDG-PET/CT scans were performed at baseline, and in FDG avid patients, again on d15 and d35. The primary objective was to demonstrate that a decrease in FDG-SUV discriminates treatment response. Response was defined pathologically based on microscopic inspection for residual cancer cells and fibrosis(Mandard, Cancer 1994). Disease free survival(DFS) and overall survival(OS) were secondary endpoints. Results: Pt characteristics are as follows: median age 59(35–77), KPS 90%(70–100%), 27 male, gastric:GEJ 31:11. Median follow up is 23.3 months, with median DFS 23.8 months(95%CI 14-infinity) and median OS 39.1 months(95%CI 31–39months). Surgical resection occurred at a median of 101 days from study initiation. Pathologic response correlates significantly with DFS(p=0.005) and with OS(p=0.01). Amongst 31 FDG avid pts, a drop in SUV from baseline to d35 significantly predicts pathologic response(p=0.007) and DFS(p=0.01), whereas the change at d15 does not. 45% decrease in SUV at d35 best distinguishes good from poor pathologic response. With this cutoff, median DFS has not been reached(eg.>23.3 months) for patients with good PET response, and is 14.4 months(95%CI 8.3-infinity) for poor PET responders, p=0.03. Conclusions: Following preoperative chemotherapy, pathologic response at the time of resection significantly correlates with DFS and OS. We confirm that FDG-PET/CT response predicts both pathologic response and DFS following preoperative chemotherapy for locally advanced GC, although at d35. An early PET response assessment provides an opportunity to change therapy in non responding patients, and is currently under investigation(supported by ASCO CDA). No significant financial relationships to disclose.

Recurrence and survival after pathologic complete response to preoperative therapy followed by surgery for gastric or gastrooesophageal adenocarcinoma

“…The low frequency of pCR and varied overall histologic response rates to preoperative therapy highlight the importance of ongoing research to identify response to therapy early. We and others have examined FDG-PET/CT for this purpose ( Lordick et al , 2007 ; Shah, 2007 ; Ott et al , 2008 ; Wieder and Weber, 2009 ). A presently accruing study at our institution is studying the ability of FDG-PET to discriminate responders vs non-responders to preoperative chemotherapy for locally advanced gastric cancer and to salvage non-responding patients with alternate chemotherapy ( Shah, 2011 ).…”

Approaches and genetic determinants in predicting response to neoadjuvant chemotherapy in locally advanced gastric cancer

“…On the contrary, patients with less than 50% residual tumor cells were classified by Shah et al . [ 36 ], Liu et al . [ 37 ] and Mansour et al .…”

“…Similar results with different cutoff value was reported by another study. Shah et al demonstrated that responders (less than 50% having residual tumors) were those with 45% decrease after 35 days post-NAC[ 36 ]. It has been proposed that defined cutoff values, standardized test methodology, and homogenized histopathological regression criteria should be established and validated before 18 FDG-PET are clinically utilized[ 70 ].…”

Clinical trials in gastric cancer and the future

“…Although histopathologic response evaluation is currently accepted as the gold standard, no universally accepted scoring system exist for gastric cancer patients and the evaluation is still very much investigator and experience‐dependent. Two scoring systems commonly applied are those by Becker et al and Shah et al 84. Although they both correlate with prognosis, they are differ in many respects as to what is defined as histopathologic responder.…”