Neoadjuvant and adjuvant pembrolizumab plus chemotherapy in locally advanced gastric or gastro-oesophageal cancer (KEYNOTE-585): an interim analysis of the multicentre, double-blind, randomised phase 3 study.

BACKGROUND: The benefit of combination neoadjuvant and adjuvant chemotherapy and immune checkpoint inhibition in patients with locally advanced, resectable gastric or gastro-oesophageal adenocarcinoma is unknown. We assess the antitumor activity of neoadjuvant and adjuvant pembrolizumab plus chemotherapy in patients with locally advanced resectable gastric or gastro-oesophageal adenocarcinoma. METHODS: The KEYNOTE-585 study is a multicentre, randomised, placebo-controlled, double-blind, phase 3 study done at 143 medical centres in 24 countries. Eligible patients were aged 18 years or older with untreated, locally advanced, resectable gastric or gastro-oesophageal adenocarcinoma, and an Eastern Cooperative Oncology Group performance status 0-1. Patients were randomly assigned (1:1) by an interactive voice response system and integrated web response system to neoadjuvant pembrolizumab 200 mg intravenously or placebo (saline) plus cisplatin-based doublet chemotherapy (main cohort) every 3 weeks for 3 cycles, followed by surgery, adjuvant pembrolizumab or placebo plus chemotherapy for 3 cycles, then adjuvant pembrolizumab or placebo for 11 cycles. A small cohort was also randomly assigned (1:1) to pembrolizumab or placebo plus fluorouracil, docetaxel, and oxaliplatin (FLOT)-based chemotherapy (FLOT cohort) every 2 weeks for four cycles, followed by surgery, adjuvant pembrolizumab, or placebo plus FLOT for four cycles, then adjuvant pembrolizumab or placebo for 11 cycles. Patients were stratified by geographic region, tumour stage, and chemotherapy backbone. Primary endpoints were pathological complete response (reviewed centrally), event-free survival (reviewed by the investigator), and overall survival in the intention-to-treat population, and safety assessed in all patients who received at least one dose of study treatment. The study is registered at ClinicalTrials.gov, NCT03221426, and is closed to accrual. FINDINGS: Between Oct 9, 2017, and Jan 25, 2021, of 1254 patients screened, 804 were randomly assigned to the main cohort, of whom 402 were assigned to the pembrolizumab plus cisplatin-based chemotherapy group and 402 to the placebo plus cisplatin-based chemotherapy group, and 203 to the FLOT cohort, of whom 100 were assigned to the pembrolizumab plus FLOT group and 103 to placebo plus FLOT group. In the main cohort of 804 participants, 575 (72%) were male and 229 (28%) were female. In the main cohort, after median follow-up of 47·7 months (IQR 38·0-54·8), pembrolizumab was superior to placebo for pathological complete response (52 [12·9%; 95% CI 9·8-16·6] of 402 vs eight [2·0%; 0·9-3·9] of 402; difference 10·9%, 95% CI 7·5 to 14·8; p<0·00001). Median event-free survival was longer with pembrolizumab versus placebo (44·4 months, 95% CI 33·0 to not reached vs 25·3 months, 20·6 to 33·9; hazard ratio [HR] 0·81, 95% CI 0·67 to 0·99; p=0·0198) but did not meet the threshold for statistical significance (p=0·0178). Median overall survival was 60·7 months (95% CI 51·5 to not reached) in the pembrolizumab group versus 58·0 months (41·5 to not reached) in the placebo group (HR 0·90, 95% CI 0·73 to 1·12; p=0·174). Grade 3 or worse adverse events of any cause occurred in 312 (78%) of 399 patients in the pembrolizumab group and 297 (74%) of 400 patients in the placebo group; the most common were nausea (240 [60%] vs 247 [62%]), anaemia (168 [42%] vs 158 [40%]), and decreased appetite (163 [41%] vs 172 [43%]). Treatment-related serious adverse events were reported in 102 (26%) and 97 (24%) patients. Treatment-related adverse events that led to death occurred in four (1%) patients in the pembrolizumab group (interstitial ischaemia, pneumonia, decreased appetite, and acute kidney injury [n=1 each]) and two (<1%) patients in the placebo group (neutropenic sepsis and neutropenic colitis [n=1 each]). INTERPRETATION: Although neoadjuvant and adjuvant pembrolizumab versus placebo improved the pathological complete response, it did not translate to significant improvement in event-free survival in patients with untreated, locally advanced resectable gastric or gastro-oesophageal cancer. FUNDING: Merck Sharp & Dohme.

Adjuvant and post-recurrent treatment patterns in patients with resectable gastric cancer in japan: a retrospective database cohort study.

BACKGROUND: This study examined temporal shifts in adjuvant therapy patterns in Japanese patients with resectable gastric cancer (GC) and treatment patterns of first-line and subsequent therapy among those with recurrent disease. METHODS: This retrospective analysis of hospital-based administrative claims data (April 1, 2008 to March 31, 2022) included adults (aged ≥ 20 years) with GC who started adjuvant therapy on or after October 1, 2008 (adjuvant cohort) and patients in the adjuvant cohort with disease recurrence (recurrent cohort), further defined by the time to recurrence (≤ 180 or > 180 days after adjuvant therapy). RESULTS: In the adjuvant cohort (n = 17,062), the most common regimen during October 2008-May 2016 was tegafur/gimeracil/oteracil potassium (S-1; 95.7%). As new standard adjuvant regimen options were established, adjuvant S-1 use decreased to 65.0% and fluoropyrimidine plus oxaliplatin or docetaxel plus S-1 use increased to 15.0% and 20.0%, respectively, in September 2019-March 2022. In the recurrent cohort with no history of trastuzumab/trastuzumab deruxtecan treatment (n = 1257), the most common first-line regimens were paclitaxel plus ramucirumab (34.0%), capecitabine plus oxaliplatin (CapeOX; 17.0%), and nab-paclitaxel plus ramucirumab (10.1%) in patients with early recurrence, and S-1 plus oxaliplatin (26.3%), S-1 plus cisplatin (15.3%), CapeOX (14.0%), S-1 (13.2%), and paclitaxel plus ramucirumab (10.8%) in those with late recurrence. CONCLUSIONS: This study demonstrated temporal shifts in adjuvant treatment patterns that followed the establishment of novel regimens, and confirmed that post-recurrent treatment patterns were consistent with the Japanese Gastric Cancer Association guideline recommendations.

Short-term outcomes of preoperative chemotherapy with docetaxel, oxaliplatin, and S-1 for gastric cancer with extensive lymph node metastasis (JCOG1704).

BACKGROUND: The prognosis for marginally resectable gastric cancer with extensive lymph node metastasis (ELM) remains unfavorable, even after R0 resection. To assess the safety and efficacy of preoperative docetaxel, oxaliplatin, and S-1 (DOS), we conducted a multicenter phase II trial. METHODS: Eligibility criteria included histologically proven HER2-negative gastric adenocarcinoma with bulky nodal (bulky N) involvement around major branched arteries or para-aortic node (PAN) metastases. Patients received three cycles of docetaxel (40 mg/m2, day 1), oxaliplatin (100 mg/m2, day 1), and S-1 (80-120 mg/body, days 1-14), followed by gastrectomy with D2 plus PAN dissection. Subsequently, patients underwent postoperative chemotherapy with S-1 for 1 year. The primary endpoint was major (grade ≥ 2a) pathological response rate (pRR) according to the Japanese Classification of Gastric Carcinoma criteria. RESULTS: Between October 2018 and March 2022, 47 patients (bulky N, 20; PAN, 17; both, 10) were enrolled in the trial. One patient was ineligible. Another declined any protocol treatments before initiation. Among the 45 eligible patients who initiated DOS chemotherapy, 44 (98%) completed 3 cycles and 42 (93%) underwent R0 resection. Major pRR and pathological complete response rates among the 46 eligible patients, including the patient who declined treatment, were 57% (26/46) and 24% (11/46), respectively. Common grade 3 or 4 toxicities were neutropenia (24%), anorexia (16%), febrile neutropenia (9%), and diarrhea (9%). No treatment-related deaths occurred. CONCLUSIONS: Preoperative chemotherapy with DOS yielded favorable pathological responses with an acceptable toxicity profile. This multimodal approach is highly promising for treating gastric cancer with ELM.

Early endpoints of a randomized phase II trial of preoperative chemotherapy with S-1/CDDP with or without trastuzumab followed by surgery for HER2-positive resectable gastric or esophagogastric junction adenocarcinoma with extensive lymph node metastasis: Japan Clinical Oncology Group study JCOG1301C (Trigger Study).

BACKGROUND: This randomized phase II study explored the superiority of trastuzumab plus S-1 plus cisplatin (SP) over SP alone as neoadjuvant chemotherapy (NAC) for HER2-positive resectable gastric cancer with extensive lymph node metastasis. METHODS: Eligible patients with HER2-positive gastric or esophagogastric junction cancer and extensive lymph node metastasis were randomized to receive three or four courses of preoperative chemotherapy with SP (arm A) or SP plus trastuzumab (arm B). Following gastrectomy, adjuvant chemotherapy with S-1 was administered for 1 year in both arms. The primary endpoint was overall survival, and the sample size was 130 patients in total. The trial is registered with the Japan Registry of Clinical Trials, jRCTs031180006. RESULTS: This report elucidates the early endpoints, including pathological findings and safety. The study was terminated early due to slow patient accruals. In total, 46 patients were allocated to arm A (n = 22) and arm B (n = 24). NAC was completed in 20 patients (91%) in arm A and 23 patients (96%) in arm B, with similar incidences of grade 3-4 hematological and non-hematological adverse events. Objective response rates were 50% in arm A and 84% in arm B (p = 0·065). %R0 resection rates were 91% and 92%, and pathological response rates (≥ grade 1b in Japanese classification) were 23% and 50% (p = 0·072) in resected patients, respectively. CONCLUSIONS: Trastuzumab can be safely added to platinum-containing doublet chemotherapy as NAC, and it has the potential to contribute to higher antitumor activity against locally advanced, HER2-positive gastric or esophagogastric junction cancer with extensive nodal metastasis.

Clinical impact of skeletal muscle mass change during the neoadjuvant chemotherapy period in patients with gastric cancer: An ancillary study of JCOG1002.

BACKGROUND: Recent studies have revealed that sarcopenia is associated with postoperative complications and poor prognosis. Although neoadjuvant chemotherapy is a promising treatment for gastric cancer, its toxicity may lead to the loss of skeletal muscle mass. This study investigates the changes in skeletal muscle mass during neoadjuvant chemotherapy and its clinical impact on patients with locally advanced gastric cancer. METHODS: Fifty patients who completed two courses of neoadjuvant chemotherapy followed by surgery were included. Skeletal muscle mass was measured using computed tomography images before and after chemotherapy. The proportion of skeletal muscle mass change (%SMC) during neoadjuvant chemotherapy and its cutoff value was explored using the receiver operating characteristic for the overall survival of patients undergoing R0 resection. Risk factors of skeletal muscle mass loss were also evaluated. RESULTS: Overall, 64% of patients had skeletal muscle mass loss during neoadjuvant chemotherapy (median %SMC -3.4%; range: -18.9% to 10.3%). Multivariable analysis identified older age (≥70 years) as an independent predictor of skeletal muscle mass loss (mean [95% confidence interval]: -4.70% [-8.83 to -0.58], p = 0.026). Among 43 patients undergoing R0 resection, %SMC <-6.9% was an independent poor prognostic factor for overall survival (hazard ratio, 11.53; 95% confidence interval, 2.78-47.80) and relapse-free survival (hazard ratio 4.54, 95% confidence interval 1.50-13.81). CONCLUSIONS: Skeletal muscle mass loss occurs frequently during neoadjuvant chemotherapy for locally advanced gastric cancer and could adversely affect survival outcomes.

[Gentle Method to Elevate Left Liver Lobe in Robot Assisted Gastrectomy].

Robot-assisted gastrectomy with the Davinci XiTM has been performed in our department since August 2019. This technique requires elevation of the left liver lobe. In order to prevent perioperative liver injury and expansion of postoperative subcutaneous emphysema, we use a silicone disc(HAKKO MEDICAL Co., Ltd.)and thread to elevate the liver. After docking the Davinci system, we move the needle as follows:(ⅰ). left side peritoneum near the left triangular ligament, (ⅱ). silicone rubber(, ⅲ). center of crus(, ⅳ). silicone rubber(, ⅴ). hepatic cirrus, and(ⅵ). right side peritoneum. Both ends of the thread are guided out of the abdominal cavity from both hepatic circumflex by end-close, forming a V-shape with the center of crus at the bottom, which provides a stable and effective view of the liver. Fifty-three cases were performed after introduction of this elevation technique. Median AST and ALT on postoperative day 1 were 37(14-1,556)IU/L and 30(10- 1,676)IU/L, respectively, although small subcutaneous emphysema confined to the anterior chest and upper abdominal wall was observed in 2 patients(3.8%). No cases of extensive subcutaneous emphysema involving the neck or extremities were observed. This elevation technique protects the liver and may reduce the incidence of postoperative subcutaneous emphysema.

Impact of D2 Total Gastrectomy Including Splenectomy for Scirrhous Gastric Cancer in the Era of Effective Adjuvant Chemotherapy.

BACKGROUND: Total gastrectomy with D2 dissection including splenectomy (TGS) is usually selected for locally resectable scirrhous gastric cancer (SGC), which was established in the era of surgery alone. However, it remains unclear whether TGS for SGC is justified in the era of effective adjuvant chemotherapy. METHODS: This study included 112 SGC patients, consisting of 60 cases treated between January 2000 and December 2006 (Former group), and 52 cases treated between January 2007 and December 2016 (Latter group). We collected clinicopathological data and then examined the survival and the therapeutic value indexes. RESULTS: The background characteristics were well-balanced, except for sex and physical status. The Latter group might be characterized by frequent female (P = 0.037) and poorer physical status (P = 0.048). Adjuvant chemotherapy was administered to 86.5% of the Latter group and was 11.7% of the Former group (P < 0.001). The 5-year-overall survival rate of the Latter group was 58.7% (95% confidence interval: 43.5-71.1), seems better than that of the Former group (44.5%; 95% confidence interval 31.7-56.6) (hazard ratio = 0.758, P = 0.291). Improvement of the index from the Former group was observed in the Latter group at almost all stations. The ratio of the index between two groups was 1.42 at the D1 station and 1.67 at the D2 station. Index of splenic hilar node ranked similarly high in both groups. CONCLUSION: The therapeutic value index was improved in almost all nodal stations by S-1 adjuvant chemotherapy, especially in D2 nodes. TGS would be more important for locally resectable SGC in the era of effective adjuvant chemotherapy.

Prognostic Impact of Post-operative Infectious Complications in Gastric Cancer Patients Receiving Neoadjuvant Chemotherapy: Post Hoc Analysis of a Randomized Controlled Trial, JCOG0501.

PURPOSE: Post-operative infectious complication (IC) is a well-known negative prognostic factor, while showing neoadjuvant chemotherapy (NAC) may cancel out the negative influence of IC. This analysis compared the clinical impacts of IC according to the presence or absence of NAC in gastric cancer patients enrolled in the phase III clinical trial (JCOG0501) which compared upfront surgery (arm A) and NAC followed by surgery (arm B) in type 4 and large type 3 gastric cancer. METHODS: The subjects were 224 patients who underwent R0 resection out of 316 patients enrolled in JCOG0501. The prognoses of the patients with or without ICs in each arm were investigated by univariable and multivariable Cox regression analyses. RESULTS: There were 21 (20.0%) IC occurrences in arm A and 15 (12.6%) in arm B. In arm A, the overall survival (OS) of patients with ICs was slightly worse than those without IC (3-year OS, 57.1% in patients with ICs, 79.8% in those without ICs; adjusted hazard ratio (95% confidence interval), 1.292 (0.655-2.546)). In arm B, patients with ICs showed a trend of better survival than those without ICs (3-year OS, 80.0% in patients with IC, 74.0% in those without IC; adjusted hazard ratio, 0.573 (0.226-1.456)). CONCLUSION: This study could not indicate the negative prognostic influence of ICs in gastric cancer patients receiving NAC, which might be canceled by NAC. To build exact evidence, further investigation with prospective and large numbers of data might be expected.

Key nodal stations for predicting splenic hilar nodal metastasis in upper advanced gastric cancer without invasion of the greater curvature.

Background: Standard surgery for upper advanced gastric cancer without invasion of the greater curvature (UGC-GC) is spleen-preserving D2 total gastrectomy without dissection of the splenic-hilar nodes (#10). However, some patients with nodal metastasis to #10 survive more than 5 years due to nodal dissection of #10. If nodal metastasis to #10 is predictable based on the positivity of other nodes dissected by the current standard surgery without #10 nodal dissection, physicians may be able to consider #10 dissection. Methods: This study retrospectively reviewed data from the National Cancer Center Hospital in Japan between 2000 and 2012. We selected cases that met the following criteria: (1) D2 or more total gastrectomy with splenectomy, (2) UGC-GC, and (3) histological type is gastric adenocarcinoma. We performed univariate and multivariate analyses concerning lymph node stations associated with #10 metastasis. Results: A total of 366 patients were examined. A multivariate analysis revealed that #10 metastasis was associated with positivity of the nodes along the short gastric arteries (#4sa) and distal nodes along the splenic artery (#11d) (#4sa: p = 0.003, #11d: p = 0.016). When either key node was positive, the metastatic rate of #10 was 24.4%, and the therapeutic value index was 13.3. Conclusions: #4sa and #11d were key lymph nodes predicting #10 nodal metastasis in UGC-GC. When these key nodes are positive on computed tomography before surgery or according to a rapid pathological examination during surgery, dissection of #10 should be considered even if upper advanced tumors are not invading the greater curvature.

Characteristics of Metachronous Remnant Gastric Cancer After Proximal Gastrectomy: A Retrospective Analysis.

PURPOSE: Despite annual endoscopy, patients with metachronous remnant gastric cancer (MRGC) following proximal gastrectomy (PG) are at times ineligible for endoscopic resection (ER). This study aimed to clarify the clinical risk factors for ER inapplicability. MATERIALS AND METHODS: We reviewed the records of 203 patients who underwent PG for cT1 gastric cancer between 2006 and 2015. The remnant stomach was categorized as a pseudofornix, corpus, or antrum. RESULTS: Thirty-two MRGCs were identified in the 29 patients. Twenty MRGCs were classified as ER (ER group, 62.5%), whereas 12 were not (non-ER group, 37.5%). MRGCs were located in the pseudo-fornix in 1, corpus in 5, and antrum in 14 in the ER group, and in the pseudo-fornix in 6, corpus in 4, and antrum in 2 in the non-ER group (P=0.019). Multivariate analysis revealed that the pseudo-fornix was an independent risk factor for non-ER (P=0.014). In the non-ER group, MRGCs at the pseudo-fornix (n=6) had more frequent undifferentiated-type histology (4/6 vs. 0/6), deeper (≥pT1b2; 6/6 vs. 2/6) and nodal metastasis (3/6 vs. 0/6) than non-pseudo-fornix lesions (n=6). We examined the visibility of the region developing MRGC on an annual follow-up endoscopy one year before MRGC detection. In seven lesions at the pseudofornix, visibility was only secured in two (28.6%) because of food residues. Of the 25 lesions in the non-pseudo-fornix, visibility was secured in 21 lesions (84%; P=0.010). CONCLUSIONS: Endoscopic visibility increases the chances of ER applicability. Special preparation is required to ensure the complete clearance of food residues in the pseudo-fornix.

Risk factors for abdominal surgical infectious complications after distal gastrectomy for gastric cancer: A post-hoc analysis of a randomized controlled trial (JCOG0912).

BACKGROUND: Abdominal surgical infectious complications (ASIC) after gastrectomy for gastric cancer impair patients' survival and quality of life. JCOG0912 was conducted to compare laparoscopy-assisted distal gastrectomy with open distal gastrectomy for clinical stage IA or IB gastric cancer. The present study aimed to identify risk factors for ASIC using prospectively collected data. METHODS: We performed a post-hoc analysis of the risk factors for ASIC using the dataset from JCOG0912. All complications were evaluated according to the Clavien-Dindo classification (CD). ASIC was defined as CD grade I or higher anastomotic leakage, pancreatic fistula, abdominal abscess, and wound infection. Analyses were performed using the logistic regression model for univariable and multivariable analyses. RESULTS: A total of 910 patients were included (median age, 63 years; male sex, 61 %). Among them, ASIC occurred in 5.8 % of patients. In the univariable analysis, male sex (odds ratio [OR] 2.855, P = 0.003), diabetes (OR 2.565, P = 0.029), and Roux-en-Y (R-Y) reconstruction (vs. Billroth Ⅰ, OR 2.707, P = 0.002) were significant risk factors for ASIC. In the multivariable analysis, male sex (OR 2.364, P = 0.028) and R-Y reconstruction (vs. Billroth Ⅰ, OR 2.310, P = 0.015) were independent risk factors for ASIC. CONCLUSIONS: Male sex and R-Y reconstruction were risk factors for ASIC after distal gastrectomy. Therefore, when performing surgery on male patients or when R-Y reconstruction is selected after gastrectomy for gastric cancer, surgeons should pay special attention to prevent ASIC.

Preoperative Visceral-to-Subcutaneous Fat Ratio by Sex as a Predictor of Postoperative Survival in Patients With Gastric Cancer.

BACKGROUND/AIM: The sex-specific effect of the visceral-to-subcutaneous fat ratio (VSR) before gastrectomy on postoperative survival in patients with gastric cancer (GC) remains unclear. This study measured the preoperative VSR in patients with GC and analyzed its relationship with 5-year overall survival (OS) and relapse-free survival (RFS) by sex. PATIENTS AND METHODS: This prospective study included 540 patients with GC undergoing gastrectomy. Preoperative visceral and subcutaneous fat volumes were measured using computed tomography, and the VSR was calculated. A cutoff value for the VSR was established using 5-year survival data, and its association with survival was analyzed using the Kaplan-Meier method, log-rank tests, and multivariate regression analysis. RESULTS: Among the 459 patients analyzed (300 males and 159 females), OS and RFS were significantly lower in the low-VSR group than in the high-VSR group in males (OS: 76.2% vs. 88.1%, p=0.01; RFS: 74.6% vs. 86.0%, p=0.02). In females, no difference in OS was observed between the groups, whereas the high-VSR group had significantly lower RFS than that of the low-VSR group (RFS: 74.7% vs. 88.9%, p=0.01). Multivariate analysis showed that a low VSR was an independent poor predictor of OS in males and a high VSR was an independent poor predictor of RFS in females. CONCLUSION: In patients with GC, the sex-dependent preoperative VSR was a potentially useful predictor of postoperative survival.

Association between the antiadhesion membrane and small bowel obstruction after open gastrectomy: A supplemental analysis of the randomized controlled JCOG1001 trial.

Aim: Postoperative small bowel obstruction (SBO) is one of the major complications that is mainly caused by postoperative adhesion. Recently, the antiadhesion membrane has become popular for postoperative SBO prevention. However, its efficacy is yet to be confirmed in the gastric cancer surgery field. Here, we conducted the supplemental analysis of the randomized controlled trial JCOG1001 to investigate the efficacy of the antiadhesion membrane on SBO prevention in patients with open gastrectomy for gastric cancer. Methods: Of the 1204 patients enrolled in JCOG1001, 1200 patients were included. The development of SBO of Grade ≥ IIIa according to the Clavien-Dindo classification was recorded. Univariable and multivariable analyses were performed using the Fine and Gray model to determine the risk factors for SBO. Results: Fifty-one patients developed SBO (median follow-up duration: 5.6 years). Total gastrectomy, combined resection, and blood loss significantly increased the risk for SBO development in the univariable analysis. Large amount of blood loss was independently associated with SBO development in the multivariable analysis (hazard ratio [HR], 3.089; 95% confidence interval [CI], 1.562-6.109, p = 0.0012). Antiadhesion membrane did not reduce the risk for SBO (HR, 1.299; 95% CI 0.683-2.470; p = 0.4246). In the patients belonging to subgroup analyses who received distal and total gastrectomy, the antiadhesion membrane was not associated with the incidence of SBO. Conclusions: Antiadhesion membrane did not decrease SBO occurrence rate after open gastrectomy. Therefore, the use of antiadhesion membrane would not be effective for preventing SBO in gastric cancer surgery.

Prognostic value of computed tomography­derived skeletal muscle index and radiodensity in patients with gastric cancer after curative gastrectomy.

The association of computed tomography (CT)-derived skeletal muscle index (SMI) and skeletal muscle radiodensity (SMD) with postoperative prognosis in patients with gastric cancer (GC) remains unknown. Therefore, the present study aimed to assess the association between SMI and SMD with 5-year overall survival (OS) and recurrence-free survival (RFS) in patients with GC. SMI and SMD were measured preoperatively in patients who underwent gastrectomy. Patients were categorized into Groups 1 (high SMI and SMD), 2 (high SMI or SMD) and 3 (low SMI and SMD). OS and RFS rates were assessed using Kaplan-Meier analysis and the log-rank test. Among 459 patients, OS and RFS rates were significantly lower in the low-SMD group than in the high-SMD group (OS, 83.4% vs. 88.8%, respectively; P=0.04 and RFS, 80.5% vs. 87.2%, respectively; P=0.02). OS and RFS rates were also significantly lower in Group 3 than in Groups 2 and 1 (P=0.006). Multivariate analysis revealed that a low SMI and SMD (Group 3) was a significant independent prognostic factor for OS [hazard ratio (HR), 2.32; 95% confidence interval (CI), 1.17-4.59; P=0.016] and RFS (HR, 2.28; 95% CI, 1.19-4.37; P=0.013). In summary, low SMI and SMD values may be useful postoperative prognostic indicators for patients with GC.