Y. Kim1, M. H. Squires2, G. A. Poultsides3, R. C. Fields4, S. M. Weber5, K. I. Votanopoulos6, D. Kooby2, D. J. Worhunsky3, L. X. Jin4, W. G. Hawkins4, A. W. Acher5, C. S. Cho5, N. Saunders7, E. A. Levine6, C. R. Schmidt7, S. K. Maithel2, T. M. Pawlik1,7 1Johns Hopkins University School Of Medicine,Baltimore, MD, USA 2Emory University School Of Medicine,Atlanta, GA, USA 3Stanford University,Palo Alto, CA, USA 4Washington University,St. Louis, MO, USA 5University Of Wisconsin,Madison, WI, USA 6Wake Forest University School Of Medicine,Winston-Salem, NC, USA 7Ohio State University,Columbus, OH, USA
Introduction: The impact of adjuvant chemotherapy (CTx) and chemo-radiation therapy (cXRT) in the treatment of resectable gastric cancer remains varied. We sought to define the clinical impact of lymph node ratio (LNR) on the relative benefit of adjuvant CTx or cXRT among patients having undergone curative-intent resection for gastric cancer.
Methods: Using the multi-institutional U.S. Gastric Cancer Collaborative database, 769 patients with gastric adenocarcinoma who underwent curative-intent resection between 2000 and 2012 were identified. Patients with metastasis or an R2 margin were excluded. The impact of LNR on disease-free survival (DFS) among patients who received CTx or cXRT was evaluated.
Results: Median patient age was 65 years and the majority of patients were male (55.8%). The majority of patients underwent either subtotal (40.9%) or total gastrectomy (41.4%), with the remainder undergoing distal gastrectomy or wedge resection (17.7%). On pathology, median tumor size was 4 cm; more patients had a T3 (33.5%) or T4 (28.7%) lesion and lymph node metastasis (60.6%). Margin status was R0 in 92.2% of patients. A total of 361 (46.9%) patients underwent surgery alone, 257 (33.4%) patients received 5-FU based cXRT, whereas the remaining 151 (19.6%) received CTx. Recurrence occurred in 236 (30.7%) patients. At a median follow-up of 17.2 months, median disease-free survival (DFS) was 29.0 months and 5-year DFS was 34.7%. According to LNR categories, 5-year DFS for patients with LNR of 0, 0.1-0.10, >0.10-0.25, >0.25 were 52.2%, 40.0%, 43.0% and 13.9%, respectively. Factors associated with worse DFS included age (hazard ratio [HR] 1.01), tumor size (HR 1.08), tumor grade (moderate/poor: HR 1.27), GE junction (HR 1.87), T-stage (3-4: HR 2.66), and LNR (>0.25: HR 2.18) (all P<0.05). In contrast, receipt of adjuvant cXRT was associated with an improved DFS in the multivariable model (vs. surgery alone: HR 0.57; vs. CTx: HR 0.45, both P<0.001). The benefit of cXRT for resected gastric cancer was noted only among patients with LNR >0.25 (vs. surgery alone: HR 0.39; vs. CTx: HR 0.44, both P<0.001). In contrast, there was no noted DFS benefit of CTx or cXRT among patients with LNR ≤0.25 (all P>0.05) (Figure).
Conclusion: Adjuvant CTx or cXRT were utilized in over one-half of patients undergoing curative-intent resection for gastric cancer. LNR may be a useful tool to select patients for adjuvant cXRT, as the benefit of cXRT therapy was isolated to patients with higher degrees of lymphatic spread (i.e., LNR >0.25).
