Predictive Value of a New Muscle Parameter in Patients with Resectable Gastric Cancer: A Pooled Analysis of Three Prospective Trials.

BACKGROUND: Sarcopenia is closely associated with gastric cancer (GC) prognosis. However, its exact definition remains controversial. METHODS: This study included computed tomography images and clinical data of patients from three prospective studies. The skeletal muscle index (SMI) and skeletal muscle radiation attenuation (SMRA) were analyzed, and a new muscle parameter, skeletal muscle gauge (SMG), was obtained by multiplying the two parameters. The values of the three indices for predicting the prognosis of patients with GC were compared. RESULTS: The study included 717 patients. The findings showed median values of 42 cm2/m2 (range, 36.8-48.2 cm2/m2) for SMI, 45 HU (range, 41-49 HU) for SMRA, and 1842 (range, 1454-2260) for SMG. Postoperatively, 111 patients (15.5%) experienced complications. The 3-year overall survival (OS), disease-free survival (DFS), and recurrence-free survival (RFS) were 74.3%, 68.2%, and 70%, respectively. Univariate logistic analysis showed that postoperative complications were associated with SMI (odds ratio [OR] 0.94; 95% confidence interval [CI] 0.92-0.96), SMRA (OR, 0.87; 95% CI 0.84-0.90), and SMG (OR 0.99; 95% CI 0.98-0.99). After a two-step multivariate analysis, only SMG (OR 0.98, 95% CI 0.97-0.99) was an independent protective factor of postoperative complications. Multivariate analysis showed that SMG also was an independent protective factor of OS, DFS, and RFS. The patients were divided into low-SMG (L-SMG) group and high-SMG (H-SMG) groups. Chemotherapy benefit analysis of the patients with stage II low SMG showed that the OS, DFS, and RFS of the chemotherapy group were significantly better than those of the non-chemotherapy group (p < 0.05). CONCLUSION: The prospective large sample data showed that the new muscle parameter, SMG, can effectively predict the short-term outcome and long-term prognosis of patients with resectable gastric cancer. As a new muscle parameter index, SMG is worthy of further study.

An international multi-institution real-world study of the optimal surveillance frequency for stage II/III gastric cancer: the more, the better?

BACKGROUND: Due to lacking evidence on surveillance for gastric cancer (GC), this study aimed to determine the optimal postsurgical surveillance strategy for pathological stage (pStage) II/III GC patients and compare its cost-effectiveness with traditional surveillance strategies. METHODS: Prospectively collected data from stage II/III GC patients ( n =1661) who underwent upfront surgery at a large-volume tertiary cancer center in China (FJMUUH cohort) between January 2010 and October 2015. For external validation, two independent cohorts were included, which were composed of 380 stage II/III GC patients at an tertiary cancer center in U.S.A (Mayo cohort) between July 1991 and July 2012 and 270 stage II/III GC patients at another tertiary cancer center in China (QUAH cohort) between May 2010 and October 2014. Random forest models were used to predict dynamic recurrence hazards and to construct individual surveillance strategies for stage II/III GC. Cost-effectiveness was assessed by the Markov model. RESULTS: The median follow-up period of the FJMUUH, the Mayo, and QUAH cohorts were 55, 158, and 70 months, respectively. In the FJMUUH cohort, the 5-year recurrence risk was higher in pStage III compared with pStage II GC patients ( P <0.001). Our novel individual surveillance strategy achieved optimal cost-effectiveness for pStage II GC patients (ICER =$490/QALY). The most intensive NCCN surveillance guideline was more cost-effective (ICER =$983/QALY) for pStage III GC patients. The external validations confirmed our results. CONCLUSION: For patients with pStage II GC, individualized risk-based surveillance outperformed the JGCTG and NCCN surveillance guidelines. However, the NCCN surveillance guideline may be more suitable for patients with pStage III GC. Even though our results are limited by the retrospective study design, the authors believe that our findings should be considered when recommending postoperative surveillance for stage II/III GC with upfront surgery in the absence of a randomized clinical trial.

Evaluation of dynamic recurrence risk for locally advanced gastric cancer in the clinical setting of adjuvant chemotherapy: a real-world study with IPTW-based conditional recurrence analysis.

BACKGROUND: The long-term dynamic recurrence hazard of locally advanced gastric cancer (LAGC) in the clinical setting of adjuvant chemotherapy (ACT) remains unclear. PURPOSE: This study aimed to investigate the dynamic recurrence risk of LAGC in patients who received ACT or not. METHODS: The study assessed data from patients with LAGC who underwent radical gastrectomy between January, 2010 and October, 2015. Inverse probability of treatment weighting (IPTW) was performed to reduce selection bias between the ACT and observational (OBS) groups. Conditional recurrence-free survival (cRFS) and restricted mean survival time (RMST) were used to assess the survival differences. RESULTS: In total, 1,661 LAGC patients were included (ACT group, n = 1,236 and OBS group, n = 425). The recurrence hazard gradually declined; in contrast, cRFS increased with RFS already accrued. Following IPTW adjustment, the cRFS rates were higher in the ACT group than those in the OBS group for patients at baseline or with accrued RFS of 1 and 2 years (p˂0.05). However, the cRFS rates of the ACT group were comparable with those of the OBS group for patients with accrued RFS of 3 or more years (p > 0.05). Likewise, the 5-year △RMST between the ACT and OBS groups demonstrated a similar trend. Moreover, the hematological metastasis rate of the ACT group was significantly lower than that of the OBS group for patients at baseline or with accrued RFS of 1 and 2 years, respectively (p˂0.05). CONCLUSIONS: Although ACT could provide substantial benefits for patients with LAGC, the differences in recurrence hazard between the ACT and OBS groups may attenuate over time, which could help guide surveillance and alleviate patients' anxiety. Further prospective large-scale studies are warranted.

Comparison of robotic versus laparoscopic versus open distal gastrectomy for locally advanced gastric cancer: a prospective trial-based economic evaluation.

IMPORTANCE: It is largely unclear whether robotic distal gastrectomy (RDG) is cost-effective for locally advanced gastric cancer (LAGC). OBJECTIVE: To evaluate the cost-effectiveness of RDG, laparoscopic distal gastrectomy (LDG), and open distal gastrectomy (ODG) for patients with LAGC. DESIGN, SETTING, AND PARTICIPANTS: Inverse probability of treatment weighting (IPTW) was used to balance baseline characteristics. A decision-analytic model was constructed to evaluate the cost-effectiveness of RDG, LDG, and ODG. EXPOSURES: RDG, LDG, and ODG. MAIN OUTCOMES AND MEASURES: Incremental cost-effectiveness ratio (ICER) and quality-adjusted life year (QALY). RESULTS: This pooled analysis of two randomized controlled trials included 449 patients: 117, 254, and 78 patients in the RDG, LDG, and ODG groups, respectively. After IPTW, RDG demonstrated its priority in terms of less blood loss, postoperative length, and complication rate (all P < 0.05). RDG also showed higher QOL with more cost, representing an ICER of $85,739.73 per QALY and $42,189.53 per QALY compared to LDG and ODG, respectively. In probabilistic sensitivity analysis, RDG achieved the best cost-effectiveness for patients with LAGC only when the willingness-to-pay threshold was > $85,739.73 per QALY, which significantly exceeded 3 times Chinese per capita GDP. Furthermore, one of the most important factors was the indirect costs of robotic surgery in terms of the cost-effectiveness of RDG compared to that of LDG or ODG. CONCLUSIONS AND RELEVANCE: Although improved short-term outcomes and QOL were seen in patients underwent RDG, the economic burden should be considered in the clinical decision-making regarding robotic surgery use for patients with LAGC. Our findings may vary in different health care settings and affordability. Trial registration CLASS-01 trial (ClinicalTrials.gov, CT01609309) and FUGES-011 trial (ClinicalTrials.gov, NCT03313700).

Factors affecting the quality of laparoscopic D2 lymph node dissection for gastric cancer: a cohort study from two randomized controlled trials.

BACKGROUND: Laparoscopic D2 lymph node dissection (LND) for gastric cancer has a wide range and high difficulty. In the past, the quality of surgery was often judged by the time of the operation or the amount of blood loss, but the analysis based on surgical video was rarely reported. The purpose of this study was to analyze the relationship between the quality of laparoscopic D2 LND for gastric cancer and postoperative complications. METHODS: The surgical video and clinicopathological data of 610 patients in two randomized controlled trials in our center from 2013 to 2016 were retrospectively analyzed. Klass-02-QC LND scale and general error score tool were used to quantitatively evaluate the intraoperative performance of D2 LND. Logistic regression was used to analyze the influencing factors of postoperative complications. RESULTS: The overall incidence of complications (CD classification≥2) was 20.6%; the incidence of surgical complications was 6.9%. According to whether the LND score reached 44, patients were divided into a qualified group (73%) and a not-qualified group (27%). Event score (ES) by quartile was divided into grade 1 (21.7%), grade 2 (26%), grade 3 (28%), and grade 4 (24.3%) from low to high. Univariate logistic regression analysis showed that ES greater than or equal to 3, tumor size greater than or equal to 35 mm, and cTNM >II were independent risk factors for not-qualified LND. Male,tumor size greater than or equal to 35 mm and cTNM >II were independent risk factors for grade 4 ES. Not-qualified LND (OR=1.62, 95% CI: 1.16-3.89, P =0.021), grade 4 ES (OR=3.21, 95% CI: 1.52-3.90, P =0.035), and cTNM >II (OR=1.74, 95% CI: 1.39-7.33, P =0.041) were independent risk factors for postoperative surgical complications. CONCLUSIONS: The qualification of LND and intraoperative events based on surgical video are the independent influencing factors of postoperative complications of laparoscopic gastric cancer surgery. Specialist training and teaching based on surgical video may help to improve the surgical skills of specialists and improve the postoperative outcome of patients.

The GLIM criteria as an effective tool for survival prediction in gastric cancer patients.

BACKGROUND: The Global Leadership Initiative on Malnutrition released a new version of the malnutrition criteria (GLIM criteria). To investigate the influence of the GLIM criteria on the long-term efficacy of radical gastric cancer surgery and establish a nomogram to predict the long-term prognosis of patients with gastric cancer. METHODS: A retrospective analysis of 1121 patients with gastric cancer in our department from 2010 to 2013 was performed. A nomogram was established to predict overall survival (OS) based on the GLIM criteria. Patients were divided into the low-risk group (LRG) and high-risk group (HRG) based on the established nomogram. RESULTS: Multivariate Cox regression analyses showed that GLIM criteria was an independent risk factor for the 5-year OS (HR = 1.768, Cl:1.341-2.329, p < 0.001). The C index, AUC and Time-ROC of the nomogram were significantly better than that of GLIM criteria and traditional criteria. The 5-year OS of patients receiving adjuvant chemotherapy in the high-risk group was significantly higher than that of patients without chemotherapy (45.77% vs. 24.73%,p < 0.001). CONCLUSIONS: The GLIM criteria independently influence the long-term outcome of patients after radical gastric cancer surgery. The established nomogram can predict the long-term survival of patients with gastric cancer, and postoperative adjuvant chemotherapy for HRG can significantly improve the 5-year OS of patients.

Body composition parameters for predicting the efficacy of neoadjuvant chemotherapy with immunotherapy for gastric cancer.

Background: Immune checkpoint inhibitors are increasingly used in neoadjuvant therapy for locally advanced gastric cancer. However, the effect of body composition on the efficacy of neoadjuvant therapy has not been reported. Methods: The computed tomography (CT) images and clinicopathological data of 101 patients with locally advanced gastric cancer who received neoadjuvant chemotherapy combined with immunotherapy (NCI) from 2019 to 2021 were collected. The CT image of L3 vertebral body section was selected, and the body composition before and after the neoadjuvant treatment was calculated using the SliceOmatic software, mainly including skeletal muscle index (SMI), subcutaneous adipose index (SAI), and visceral adipose index (VAI). The relationship between body composition and the efficacy and adverse events of NCI was analyzed. Results: Of the 101 patients, 81 with evaluable data were included in the analysis. Of the included patients, 77.8% were male; the median age of all the patients was 62 years, and the median neoadjuvant therapy cycle was three. After the neoadjuvant therapy, 62.9% of the tumors were in remission (residual tumor cells ≤ 50%), and 37.1% of the tumors had no remission (residual tumor cells>50%). Moreover, 61.7% of the patients had treatment-related adverse events (TRAEs), and 18.5% had immune-related adverse events (irAEs). After neoadjuvant therapy, the body mass index (from 23 to 22.6 cm2/m2, p=0.042), SAI (from 34.7 to 32.9 cm2/m2, p=0.01) and VAI (from 32.4 to 26.8 cm2/m2, p=0.005) were significantly lower than those before treatment, while the SMI had no significant change (44.7 vs 42.5 cm2/m2, p=0.278). The multivariate logistics regression analysis revealed that low SMI (odds ratio [OR]: 3.23,95% confidence interval [CI]: 1.06-9.81, p=0.047), SMI attenuation (△SMI) ≥ 1.8(OR: 1.45,95%CI: 1.20-3.48, p=0.048), and clinical node positivity (OR: 6.99,95%CI: 2.35-20.82, p=0.001) were independent risk factors for non-remission. Additionally, high SAI is an independent risk factor for irAEs (OR: 14, 95%CI: 1.73-112.7, p=0.013). Conclusion: Low SMI and △SMI≥1.8 are independent risk factors for poor tumor regression in patients with advanced gastric cancer receiving NCI. Patients with a high SAI are more likely to develop irAEs.

A national advanced training program for laparoscopic radical gastrectomy has a positive impact on surgical trainees: A before and after study (ATP-LRG-1).

BACKGROUND: Due to the high technical requirements of laparoscopic radical gastrectomy (LRG), establishing an effective training system to promote clinical technology and operation specifications is necessary. We aimed to evaluate the effect of a national advanced training program for LRG (ATP-LRG). MATERIALS AND METHODS: The contents of the training include the following: 1) detailed technique descriptions; 2) prevention and solving of intraoperative complications; 3) live surgery performance; 4) theory and practice of clinical research; 5) comments on trainees' videos; and 6) questions, answers, and discussions. This retrospective before and after study surveyed 875 trainees from January 2015 to October 2020. Endpoints were general surgical skills (GSS), laparoscopic gastrectomy acceptance (LGA), and clinical research possibilities (CRP). The analysis took place in December 2021. RESULTS: The response rate was 70.5% (617/875). ATP-LRG reportedly had a positive impact on the LRG practice of 99.5% (614/617) of trainees. Their GSS (before vs. after: 16.5 ± 3.7 vs. 20.3 ± 3.1, P < 0.001), LGA (4.2 ± 0.9 vs. 4.6 ± 0.7, P < 0.001), and CRP (2.6 ± 1.2 vs. 3.2 ± 1.1, P < 0.001) significantly improved. The improvement in GSS for those with professional titles of associate chief surgeons and below was significantly higher than that for chief surgeons (4.0 ± 3.0 vs 3.3 ± 2.4, P = 0.017), while those of LGA and CRP were not. The annual number of operations before training was negatively correlated with improvement in GSS (P < 0.001, Pearson's correlation coefficient: 0.14). Multivariate logistic regression showed that those with professional titles of associate chief surgeons and below (odds ratio [OR]: 1.719, 95% confidence interval [CI]: 1.038-2.846, P = 0.035), and with annual number of operations before training being <60, (OR: 5.257, 95% CI: 2.573-10.742, P < 0.001) were most prone to high-GSS improvement. CONCLUSION: The nationwide ATP-LRG facilitates the improvement of trainees' GSS, LGA, and CRP levels. Surgeons with lower professional titles and fewer performed operations are most likely to improve their GSS through training.

A novel hematological classifier predicting chemotherapy benefit and recurrence hazard for locally advanced gastric cancer A multicenter IPTW analysis.

BACKGROUND: Effective classifiers for the prediction of individual adjuvant chemotherapy (AC) benefits are scarce. PURPOSE: This study aimed to construct a useful classifier to predict the AC benefit and recurrence hazard based on preoperative hematological indices through a multicenter database. METHODS AND RESULTS: Multivariate analysis revealing GCRF (comprehensive deep learning classifier) as an independent prognostic factor associated with overall survival (OS) and disease-free survival (DFS). Locally advanced gastric cancer (LAGC) patients are categorized into the high-risk group (HRG) and low-risk group (LRG). In HRG, OS and DFS of the AC group are significantly higher than those of the non-AC group (all p˂0.05), whereas in LRG, OS and DFS of the AC group are comparable to those of the non-AC group (all p > 0.05). Furthermore, combined GCRF with 8th AJCC TNM staging system, only 650 (51.1%) patients can benefit most from AC among 1273 patients with pStage II-III. From the perspective of recurrence pattern, the recurrence rate of HRG is significantly higher than that of LRG in any recurrence type, including local recurrence, peritoneal recurrence, and distant recurrence (all p˂0.05). Furthermore, the mean time to peritoneal recurrence and lung metastasis in HRG is earlier than that in the LRG (p = 0.028 and 0.011, respectively). CONCLUSION: In summary, our novel classifier based on deep learning preoperative hematological indices can predict not only the AC benefit of LAGC patients, but also the recurrence hazard after surgery. This classifier is expected to be an effective supplement to the 8th AJCC TNM staging system for the prediction of AC benefits and is helpful for clinical decision in AC individual administration. Further large-scale western studies are warranted.

Is Adjuvant Chemotherapy Beneficial to All Patients With pT3N0M0 Stage Gastric Cancer?

BACKGROUND: The efficacy and benefits of adjuvant chemotherapy (AC) for patients with gastric cancer pT3N0M0 remain controversial. METHODS: We prospectively collected and retrospectively analyzed 235 patients with pT3N0M0 gastric cancer who underwent radical resection between February 2010 and January 2016. Patients were divided into two groups: the surgery-alone (SA) group (n = 82) and the AC group (n = 153). We analyzed the effects of AC on the overall survival (OS) and recurrence-free survival (RFS), and the relationship between the number of chemotherapy cycles (CC) and recurrence rate (RR). RESULTS: The 5-year OS and RFS of the participants were 80.9% and 87.7%, respectively, and those in the AC group were significantly higher than those in the SA group (86.9% vs. 69.5%, p = 0.003). The RFS of the AC and SA groups were 88.9% and 85.4%, respectively; the difference was not statistically significant (p = 0.35). The independent risk factors affecting the OS were perineural invasion-positive (PNI+) (HR = 2.64, 95%CI: 1.45-4.82, p = 0.003) and age ≥ 65 years (HR = 2.58, 95%CI: 1.39-4.8, p = 0.003). The independent risk factor affecting the RFS was also PNI+ (HR3.11; 95%CI: 1.48-6.54, p = 0.003). Stratified analysis revealed that postoperative AC can significantly improve the OS of PNI+ patients (AC group versus SA group: 84.1% vs. 45.5%, p = 0.001) and RFS (86.4% vs. 63.6%, p = 0.017). However, perineural invasion negative (PNI-) patients did not show the same results (p = 0.13 and p = 0.48, respectively). According to the number of CC, divided into CC < 3 groups and CC ≥ 3 groups, the cumulative RR in the CC ≥ 3 group of patients with PNI+ was significantly lower than that of the CC < 3 group (7.4% vs. 28.2%, p = 0.037). CONCLUSION: For pT3N0M0 gastric cancer patients with PNI+, at least three cycles of postoperative AC can significantly reduce the overall RR. This finding should be verified by using large external sample data.