Distal Versus Total D2-Gastrectomy for Gastric Cancer:a Secondary Analysis of Surgical and Oncological Outcomes Including Quality of Life in the Multicenter Randomized LOGICA-Trial

Background: Distal gastrectomy (DG) for gastric cancer can cause less morbidity than total gastrectomy (TG), but may compromise radicality. No prospective studies administered neoadjuvant chemotherapy, and few assessed quality of life (QoL). Methods: The multicenter LOGICA-trial randomized laparoscopic versus open D2-gastrectomy for resectable gastric adenocarcinoma (cT1–4aN0–3bM0) in 10 Dutch hospitals. This secondary LOGICA-analysis compared surgical and oncological outcomes after DG versus TG. DG was performed for non-proximal tumors if R0-resection was deemed achievable, TG for other tumors. Postoperative complications, mortality, hospitalization, radicality, nodal yield, 1-year survival, and EORTC-QoL-questionnaires were analyzed using Χ 2-/Fisher’s exact tests and regression analyses. Results: Between 2015 and 2018, 211 patients underwent DG (n = 122) or TG (n = 89), and 75% of patients underwent neoadjuvant chemotherapy. DG-patients were older, had more comorbidities, less diffuse type tumors, and lower cT-stage than TG-patients (p &lt; 0.05). DG-patients experienced fewer overall complications (34% versus 57%; p &lt; 0.001), also after correcting for baseline differences, lower anastomotic leakage (3% versus 19%), pneumonia (4% versus 22%), atrial fibrillation (3% versus 14%), and Clavien-Dindo grading compared to TG-patients (p &lt; 0.05), and demonstrated shorter median hospital stay (6 versus 8 days; p &lt; 0.001). QoL was better after DG (statistically significant and clinically relevant) in most 1-year postoperative time points. DG-patients showed 98% R0-resections, and similar 30-/90-day mortality, nodal yield (28 versus 30 nodes; p = 0.490), and 1-year survival after correcting for baseline differences (p = 0.084) compared to TG-patients. Conclusions: If oncologically feasible, DG should be preferred over TG due to less complications, faster postoperative recovery, and better QoL while achieving equivalent oncological effectiveness. Mini-abstract: Distal D2-gastrectomy for gastric cancer resulted in less complications, shorter hospitalization, quicker recovery and better quality of life compared to total D2-gastrectomy, whereas radicality, nodal yield and survival were similar.</p

Distal Versus Total D2-Gastrectomy for Gastric Cancer:a Secondary Analysis of Surgical and Oncological Outcomes Including Quality of Life in the Multicenter Randomized LOGICA-Trial

Background: Distal gastrectomy (DG) for gastric cancer can cause less morbidity than total gastrectomy (TG), but may compromise radicality. No prospective studies administered neoadjuvant chemotherapy, and few assessed quality of life (QoL). Methods: The multicenter LOGICA-trial randomized laparoscopic versus open D2-gastrectomy for resectable gastric adenocarcinoma (cT1–4aN0–3bM0) in 10 Dutch hospitals. This secondary LOGICA-analysis compared surgical and oncological outcomes after DG versus TG. DG was performed for non-proximal tumors if R0-resection was deemed achievable, TG for other tumors. Postoperative complications, mortality, hospitalization, radicality, nodal yield, 1-year survival, and EORTC-QoL-questionnaires were analyzed using Χ 2-/Fisher’s exact tests and regression analyses. Results: Between 2015 and 2018, 211 patients underwent DG (n = 122) or TG (n = 89), and 75% of patients underwent neoadjuvant chemotherapy. DG-patients were older, had more comorbidities, less diffuse type tumors, and lower cT-stage than TG-patients (p &lt; 0.05). DG-patients experienced fewer overall complications (34% versus 57%; p &lt; 0.001), also after correcting for baseline differences, lower anastomotic leakage (3% versus 19%), pneumonia (4% versus 22%), atrial fibrillation (3% versus 14%), and Clavien-Dindo grading compared to TG-patients (p &lt; 0.05), and demonstrated shorter median hospital stay (6 versus 8 days; p &lt; 0.001). QoL was better after DG (statistically significant and clinically relevant) in most 1-year postoperative time points. DG-patients showed 98% R0-resections, and similar 30-/90-day mortality, nodal yield (28 versus 30 nodes; p = 0.490), and 1-year survival after correcting for baseline differences (p = 0.084) compared to TG-patients. Conclusions: If oncologically feasible, DG should be preferred over TG due to less complications, faster postoperative recovery, and better QoL while achieving equivalent oncological effectiveness. Mini-abstract: Distal D2-gastrectomy for gastric cancer resulted in less complications, shorter hospitalization, quicker recovery and better quality of life compared to total D2-gastrectomy, whereas radicality, nodal yield and survival were similar.</p

Prognostic Value of [¹⁸F]FDG PET Radiomics to Detect Peritoneal and Distant Metastases in Locally Advanced Gastric Cancer—A Side Study of the Prospective Multicentre PLASTIC Study

Aim: To improve identification of peritoneal and distant metastases in locally advanced gastric cancer using [18F]FDG-PET radiomics. Methods: [18F]FDG-PET scans of 206 patients acquired in 16 different Dutch hospitals in the prospective multicentre PLASTIC-study were analysed. Tumours were delineated and 105 radiomic features were extracted. Three classification models were developed to identify peritoneal and distant metastases (incidence: 21%): a model with clinical variables, a model with radiomic features, and a clinicoradiomic model, combining clinical variables and radiomic features. A least absolute shrinkage and selection operator (LASSO) regression classifier was trained and evaluated in a 100-times repeated random split, stratified for the presence of peritoneal and distant metastases. To exclude features with high mutual correlations, redundancy filtering of the Pearson correlation matrix was performed (r = 0.9). Model performances were expressed by the area under the receiver operating characteristic curve (AUC). In addition, subgroup analyses based on Lauren classification were performed. Results: None of the models could identify metastases with low AUCs of 0.59, 0.51, and 0.56, for the clinical, radiomic, and clinicoradiomic model, respectively. Subgroup analysis of intestinal and mixed-type tumours resulted in low AUCs of 0.67 and 0.60 for the clinical and radiomic models, and a moderate AUC of 0.71 in the clinicoradiomic model. Subgroup analysis of diffuse-type tumours did not improve the classification performance. Conclusion: Overall, [18F]FDG-PET-based radiomics did not contribute to the preoperative identification of peritoneal and distant metastases in patients with locally advanced gastric carcinoma. In intestinal and mixed-type tumours, the classification performance of the clinical model slightly improved with the addition of radiomic features, but this slight improvement does not outweigh the laborious radiomic analysis.</p

Surgical quality and prospective quality control of the D2-gastrectomy for gastric cancer in the multicenter randomized LOGICA-trial

Background: Quality of gastric cancer surgery is crucial for favorable prognosis. Generally, prospective trials lack quality control measures. This study assessed surgical quality and a novel D2-lymphadenectomy photo-scoring in the LOGICA-trial. Methods: The multicenter LOGICA-trial randomized laparoscopic versus open total/distal D2-gastrectomy for resectable gastric cancer (cT1-4aN0-3M0) in 10 Dutch hospitals. During the trial, two reviewers prospectively analyzed intraoperative photographs of dissected nodal stations for quality control, and provided centers weekly feedback on their D2-lymphadenectomy, as continuous quality-enhancing incentive. After the trial, these photographs were reanalyzed to develop a photo-scoring for future trials, rating the D2-lymphadenectomy dissection quality (optimal-good-suboptimal-unevaluable). Interobserver variability was calculated (weighted kappa). Regression analyses related the photo-scoring to nodal yield, recurrence and 5-years survival. Results: Between 2015 and 2018, 212 patients underwent total/distal D2-gastrectomy (n = 122/n = 90), and 158 (75%) received neoadjuvant chemotherapy. R0-resection rate was 95%. Rate of ≥15 retrieved lymph nodes was 95%. Moderate agreement was obtained in stations 8 + 9 (κ = 0.522), 11p/11d (κ = 0.446) and 12a (κ = 0.441). Consensus was reached for discordant cases (30%). Stations 8 + 9, 11p/11d and 12a were rated ‘optimal’ in 76%, 63% and 68%. Laparoscopic photographs could be rated better than open (2% versus 12% ‘unevaluable’; 73% versus 50% ‘optimal’; p = 0.042). The photo-scoring did not show associations with nodal yield (p = 0.214), recurrence (p = 0.406) and survival (p = 0.988). Conclusions: High radicality and nodal yield demonstrated good quality of D2-gastrectomy. The prospective quality control probably contributed to this. The photo-scoring did not show good performance, but can be refined. Laparoscopic D2-gastrectomy was better suited for standardized surgical photo-evaluation than open surgery.</p

Impact of ^18FFDG-PET/CT and Laparoscopy in Staging of Locally Advanced Gastric Cancer:A Cost Analysis in the Prospective Multicenter PLASTIC-Study

Background: Unnecessary D2-gastrectomy and associated costs can be prevented after detecting non-curable gastric cancer, but impact of staging on treatment costs is unclear. This study determined the cost impact of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18FFDG-PET/CT) and staging laparoscopy (SL) in gastric cancer staging. Materials and Methods:In this cost analysis, four staging strategies were modeled in a decision tree: (1) 18FFDG-PET/CT first, then SL, (2) SL only, (3) 18FFDG-PET/CT only, and (4) neither SL nor 18FFDG-PET/CT. Costs were assessed on the basis of the prospective PLASTIC-study, which evaluated adding 18FFDG-PET/CT and SL to staging advanced gastric cancer (cT3–4 and/or cN+) in 18 Dutch hospitals. The Dutch Healthcare Authority provided 18FFDG-PET/CT unit costs. SL unit costs were calculated bottom-up. Gastrectomy-associated costs were collected with hospital claim data until 30 days postoperatively. Uncertainty was assessed in a probabilistic sensitivity analysis (1000 iterations). Results: 18FFDG-PET/CT costs were €1104 including biopsy/cytology. Bottom-up calculations totaled €1537 per SL. D2-gastrectomy costs were €19,308. Total costs per patient were €18,137 for strategy 1, €17,079 for strategy 2, and €19,805 for strategy 3. If all patients undergo gastrectomy, total costs were €18,959 per patient (strategy 4). Performing SL only reduced costs by €1880 per patient. Adding 18FFDG-PET/CT to SL increased costs by €1058 per patient; IQR €870–1253 in the sensitivity analysis. Conclusions:For advanced gastric cancer, performing SL resulted in substantial cost savings by reducing unnecessary gastrectomies. In contrast, routine 18FFDG-PET/CT increased costs without substantially reducing unnecessary gastrectomies, and is not recommended due to limited impact with major costs. Trial registration: NCT03208621. This trial was registered prospectively on 30-06-2017.</p

Impact of ^18FFDG-PET/CT and Laparoscopy in Staging of Locally Advanced Gastric Cancer:A Cost Analysis in the Prospective Multicenter PLASTIC-Study

Background: Unnecessary D2-gastrectomy and associated costs can be prevented after detecting non-curable gastric cancer, but impact of staging on treatment costs is unclear. This study determined the cost impact of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18FFDG-PET/CT) and staging laparoscopy (SL) in gastric cancer staging. Materials and Methods:In this cost analysis, four staging strategies were modeled in a decision tree: (1) 18FFDG-PET/CT first, then SL, (2) SL only, (3) 18FFDG-PET/CT only, and (4) neither SL nor 18FFDG-PET/CT. Costs were assessed on the basis of the prospective PLASTIC-study, which evaluated adding 18FFDG-PET/CT and SL to staging advanced gastric cancer (cT3–4 and/or cN+) in 18 Dutch hospitals. The Dutch Healthcare Authority provided 18FFDG-PET/CT unit costs. SL unit costs were calculated bottom-up. Gastrectomy-associated costs were collected with hospital claim data until 30 days postoperatively. Uncertainty was assessed in a probabilistic sensitivity analysis (1000 iterations). Results: 18FFDG-PET/CT costs were €1104 including biopsy/cytology. Bottom-up calculations totaled €1537 per SL. D2-gastrectomy costs were €19,308. Total costs per patient were €18,137 for strategy 1, €17,079 for strategy 2, and €19,805 for strategy 3. If all patients undergo gastrectomy, total costs were €18,959 per patient (strategy 4). Performing SL only reduced costs by €1880 per patient. Adding 18FFDG-PET/CT to SL increased costs by €1058 per patient; IQR €870–1253 in the sensitivity analysis. Conclusions:For advanced gastric cancer, performing SL resulted in substantial cost savings by reducing unnecessary gastrectomies. In contrast, routine 18FFDG-PET/CT increased costs without substantially reducing unnecessary gastrectomies, and is not recommended due to limited impact with major costs. Trial registration: NCT03208621. This trial was registered prospectively on 30-06-2017.</p

Pattern of lymph node metastases in gastric cancer: a side-study of the multicenter LOGICA-trial

Background: The relation between gastric cancer characteristics and lymph node (LN) metastatic patterns is not fully clear, especially following neoadjuvant chemotherapy (NAC). This study analyzed nodal metastatic patterns. Methods: Individual LN stations were analyzed for all patients from the LOGICA-trial, a Dutch multicenter randomized trial comparing laparoscopic versus open D2-gastrectomy for gastric cancer. The pattern of metastases per LN station was related to tumor location, cT-stage, Lauren classification and NAC. Results: Between 2015–2018, 212 patients underwent D2-gastrectomy, of whom 158 (75%) received NAC. LN metastases were present in 120 patients (57%). Proximal tumors metastasized predominantly to proximal LN stations (no. 1, 2, 7 and 9; p 1, p > 0.05). However, distal tumors also metastasized to proximal LN stations, and vice versa. Despite NAC, each LN station (no. 1–9, 11 and 12a) showed metastases, regardless of tumor location, cT-stage, histological subtype and NAC treatment, including station 12a for cT1N0-tumors. LN metastases were present more frequently in diffuse versus intestinal tumors (66% versus 52%; p = 0,048), but not for cT3–4- versus cT1–2-stage (59% versus 51%; p = 0.259). However, the pattern of LN metastases was similar for these subgroups. Conclusions: The extent of lymphadenectomy cannot be reduced after NAC for gastric cancer. Although the pattern of LN metastases is related to tumor location, all LN stations contained metastases regardless of tumor location, cT-stage (including cT1N0-tumors), histological subtype, or NAC treatment. Therefore, D2-lymphadenectomy should be routinely performed during gastrectomy in Western patients

The Comprehensive Complication Index versus Clavien-Dindo grading after laparoscopic and open D2-gastrectomy in the multicenter randomized LOGICA-trial

Background:Complications can be classified using the most-severe Clavien-Dindo-Classification (CDC) per patient or the total complication burden per patient expressed in the Comprehensive Complication Index (CCI). This study determined the additional value of CCI to CDC in examining the impact of complications after gastric cancer surgery. Methods: The CCI and CDC were determined in the multicenter randomized LOGICA-trial comparing laparoscopic versus open D2-gastrectomy for cancer (cT1-4aN0-3M0). Differences in median CCI between laparoscopic and open gastrectomy were compared for overall postoperative complications and cardiovascular, gastrointestinal, infectious, pulmonary, and other complications. CCI and CDC were correlated to hospitalization, ICU-stay and reoperations using Spearman's rho-test and compared with standard Fisher's z-transformation. Results: Between 2015 and 2018, 211 patients underwent laparoscopic (n = 106) or open (n = 105) D2-gastrectomy, and 157 (74%) received neoadjuvant chemotherapy. Median CCI was comparable between laparoscopic versus open gastrectomy regarding overall complications (CCI 0 [IQR 0–23.5] versus 0 [IQR 0–22.6]; p = 0.755) and subgroups of complications (p &gt; 0.05). Both CCI and CDC showed moderate positive correlations for hospitalization (rs = 0.646 versus rs = 0.628; p = 0.001, difference clinically irrelevant), and reoperations (rs = 0.590 versus rs = 0.599; p = 0.070), and weak correlations for ICU-stay (rs = 0.446 versus rs = 0.440; p = 0.189).Conclusions: The CCI is a composite scoring system based on the CDC and reflects a subjective interpretation of complication burden from the perspectives of both physicians and patients, following abdominal surgery other than gastrectomy. Implementing CCI showed no clinically relevant benefit and caused additional workload compared to CDC for assessing complication burden. Therefore, using the CCI alongside the CDC after gastric cancer surgery is not recommended.</p