Impact of lymph node ratio in selecting patients with resected gastric cancer for adjuvant therapy

Abstract

Background: 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, 719 patients with gastric adenocarcinoma who underwent curative-intent resection between 2000 and 2013 were identified. Patients with metastasis or an R2 margin were excluded. The impact of LNR on overall survival (OS) among patients who received CTx or cXRT was evaluated. Results: Median patient age was 65 years, and the majority of patients were male (56.2%). The majority of patients underwent either subtotal (40.6%) or total gastrectomy (41.0%), with the remainder undergoing distal gastrectomy or wedge resection (18.4%). On pathology, median tumor size was 4 cm; most patients had a T3 (33.0%) or T4 (27.9%) lesion with lymph node metastasis (59.7%). Margin status was R0 in 92.5% of patients. A total of 325 (45.2%) patients underwent resection alone, 253 (35.2%) patients received 5-FU or capecitabine-based cXRT, whereas the remaining 141 (19.6%) received CTx. Median OS was 40.9 months, and 5-year OS was 40.3%. According to LNR categories, 5-year OS for patients with a LNR of 0, 0.1–0.10, >0.10–0.25, >0.25 were 54.1%, 53.1 %, 49.1 % and 19.8 %, respectively. Factors associated with worse OS included involvement of the gastroesophageal junction (hazard ratio [HR] 1.8), T-stage (3–4: HR 2.1), lymphovascular invasion (HR 1.4), and LNR (>0.25: HR 2.3) (all P<0.05). In contrast, receipt of adjuvant cXRT was associated with an improved OS in the multivariable model (vs. resection alone: HR 0.40; 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. resection alone: HR 0.34; vs. CTx: HR 0.45, both P<0.001). In contrast, there was no noted OS benefit of CTx or cXRT among patients with LNR ≤0.25 (all P>0.05). Conclusion: Adjuvant CTx or cXRT was 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, because the benefit of cXRT therapy was isolated to patients with greater degrees of lymphatic spread (i.e., LNR >0.25).

Positive node‐ratio in curative‐intent treatment for gastric cancer is a strong independent prognostic factor for 5‐year overall survival

“…Other previous studies also took into consideration the positive N‐ratio . Studies from Nitti et al, Marchet et al, and Wu et al also addressed lymphadenectomy with >15 nodes.…”

“…Four studies reported the investigation of N‐ratio as a prognostic factor for OS, however, they did not report any adjuvant treatment for gastric cancers . Three studies, all of them from this decade, reported the use of adjuvant therapy, and the N‐ratio was considered as a prognostic factor only in the study by Kim et al, after adjustment by propensity score matching . All those studies used the preestablished N‐ratio categories instead of determining the specific cutoffs for their respective populations .…”

“…11 Hartgrink et al 8 Other previous studies also took into consideration the positive N-ratio. [13][14][15][16][17][18][19] Studies from Nitti et al, 15 Marchet et al, 14 and Wu et al 16 also addressed lymphadenectomy with >15 nodes. Four studies reported the investigation of N-ratio as a prognostic factor for OS, however, they did not report any adjuvant treatment for gastric cancers.…”

“…[13][14][15]18 Three studies, all of them from this decade, reported the use of adjuvant therapy, and the N-ratio was considered as a prognostic factor only in the study by Kim et al, after adjustment by propensity score matching. 16,17,19 All those studies used the preestablished N-ratio categories instead of determining the specific cutoffs for their respective populations. [13][14][15][16][17][18][19] In our study, we used the best threshold for 5-year OS according to N-ratio in patients who underwent a minimal lymphadenectomy with at least 15 lymph nodes according to the area under the ROC.…”

“…16,17,19 All those studies used the preestablished N-ratio categories instead of determining the specific cutoffs for their respective populations. [13][14][15][16][17][18][19] In our study, we used the best threshold for 5-year OS according to N-ratio in patients who underwent a minimal lymphadenectomy with at least 15 lymph nodes according to the area under the ROC. We determined the best fit cut off of 11% as a positive node ratio, instead of others previously reported categories as 10%, 25%, or 50%.…”