Evaluation of the Implementation of FDG-PET/CT and Staging Laparoscopy for Gastric Cancer in The Netherlands

Background: The role of 18F-fluorodeoxyglucose positron emission tomography with computed tomography (FDG-PET/CT) and staging laparoscopy (SL) has increased in the preoperative staging of gastric cancer. Dutch national guidelines have recommended the use of FDG-PET/CT and SL for patients with locally advanced tumors since July 2016. Objective: The aim of this study was to evaluate the implementation of FDG-PET/CT and SL in The Netherlands. Methods: Between 2011 and 2018, all patients who underwent surgery for gastric cancer were included from the Dutch Upper GI Cancer Audit. The use of FDG-PET/CT and SL was evaluated before and after revision of the Dutch guidelines. Outcomes included the number of non-curative procedures (e.g. palliative and futile procedures) and the association of FDG-PET/CT and SL, with waiting times from diagnosis to the start of treatment. Results: A total of 3310 patients were analyzed. After July 2016, the use of FDG-PET/CT (23% vs. 61%; p < 0.001) and SL (21% vs. 58%; p < 0.001) increased. FDG-PET/CT was associated with additional waiting time to neoadjuvant therapy (4 days), as well as primary surgical treatment (20 days), and SL was associated with 8 additional days of waiting time to neoadjuvant therapy. Performing SL or both modalities consecutively in patients in whom it was indicated was not associated with the number of non-curative procedures. Conclusion

Factors influencing health-related quality of life after gastrectomy for cancer

_Aim:_ Insight in health-related quality of life (HRQoL) may improve clinical decision making and inform patients about the long-term effects of gastrectomy. This study aimed to evaluate and identify factors associated with HRQoL after gastrectomy. _Methods:_ This cross-sectional study used prospective databases from seven Dutch centers (2001–2015) including patients who underwent gastrectomy for cancer. Between July 2015 and November 2016, European Organization for Research and Treatment of Cancer HRQoL questionnaires QLQ-C30 and QLQ-STO22 were sent to all surviving patients without recurrence. The QLQ-C30 scores were compared to a Dutch reference population using a one-sample t test. Spearman’s rank test was used to correlate time after surgery to HRQoL, and multivariable linear regression was performed to identify factors associated with HRQoL. _Results:_ A total of 222 of 274 patients completed the questionnaires. Median follow-up was 29 months and 86.9% of patients had a follow-up >1 year. The majority of patients had undergone neoadjuvant treatme

Body Composition Is a Predictor for Postoperative Complications After Gastrectomy for Gastric Cancer:a Prospective Side Study of the LOGICA Trial

PURPOSE: There is a lack of prospective studies evaluating the effects of body composition on postoperative complications after gastrectomy in a Western population with predominantly advanced gastric cancer. METHODS: This is a prospective side study of the LOGICA trial, a multicenter randomized trial on laparoscopic versus open gastrectomy for gastric cancer. Trial patients who received preoperative chemotherapy followed by gastrectomy with an available preoperative restaging abdominal computed tomography (CT) scan were included. The CT scan was used to calculate the mass (M) and radiation attenuation (RA) of skeletal muscle (SM), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT). These variables were expressed as Z-scores, depicting how many standard deviations each patient’s CT value differs from the sex-specific study sample mean. Primary outcome was the association of each Z-score with the occurrence of a major postoperative complication (Clavien-Dindo grade ≥ 3b). RESULTS: From 2015 to 2018, a total of 112 patients were included. A major postoperative complication occurred in 9 patients (8%). A high SM-M Z-score was associated with a lower risk of major postoperative complications (RR 0.47, 95% CI 0.28–0.78, p = 0.004). Furthermore, high VAT-RA Z-scores and SAT-RA Z-scores were associated with a higher risk of major postoperative complications (RR 2.82, 95% CI 1.52–5.23, p = 0.001 and RR 1.95, 95% CI 1.14–3.34, p = 0.015, respectively). VAT-M, SAT-M, and SM-RA Z-scores showed no significant associations. CONCLUSION: Preoperative low skeletal muscle mass and high visceral and subcutaneous adipose tissue radiation attenuation (indicating fat depleted of triglycerides) were associated with a higher risk of developing a major postoperative complication in patients treated with preoperative chemotherapy followed by gastrectomy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11605-022-05321-0

Pain and Opioid Consumption After Laparoscopic Versus Open Gastrectomy for Gastric Cancer:A Secondary Analysis of a Multicenter Randomized Clinical Trial (LOGICA-Trial)

Background:Laparoscopic gastrectomy could reduce pain and opioid consumption, compared to open gastrectomy. However, it is difficult to judge the clinical relevance of this reduction, since these outcomes are reported in few randomized trials and in limited detail. Methods: This secondary analysis of a multicenter randomized trial compared laparoscopic versus open gastrectomy for resectable gastric adenocarcinoma (cT1-4aN0-3bM0). Postoperative pain was analyzed by opioid consumption in oral morphine equivalents (OME, mg/day) at postoperative day (POD) 1–5, WHO analgesic steps, and Numeric Rating Scales (NRS, 0–10) at POD 1–10 and discharge. Regression and mixed model analyses were performed, with and without correction for epidural analgesia. Results: Between 2015 and 2018, 115 patients in the laparoscopic group and 110 in the open group underwent surgery. Some 16 patients (14%) in the laparoscopic group and 73 patients (66%) in the open group received epidural analgesia. At POD 1–3, mean opioid consumption was 131, 118, and 53 mg OME lower in the laparoscopic group, compared to the open group, respectively (all p &lt; 0.001). After correcting for epidural analgesia, these differences remained significant at POD 1–2 (47 mg OME, p = 0.002 and 69 mg OME, p &lt; 0.001, respectively). At discharge, 27% of patients in the laparoscopic group and 43% patients in the open group used oral opioids (p = 0.006). Mean highest daily pain scores were between 2 and 4 at all PODs, &lt; 2 at discharge, and did not relevantly differ between treatment arms. Conclusion: In this multicenter randomized trial, postoperative pain was comparable between laparoscopic and open gastrectomy. After laparoscopic gastrectomy, this was generally achieved without epidural analgesia and with fewer opioids. Trial Registration: NCT02248519.</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

¹⁸F-Fludeoxyglucose-Positron Emission Tomography/Computed Tomography and Laparoscopy for Staging of Locally Advanced Gastric Cancer:A Multicenter Prospective Dutch Cohort Study (PLASTIC)

Importance: The optimal staging for gastric cancer remains a matter of debate. Objective: To evaluate the value of 18F-fludeoxyglucose-positron emission tomography with computed tomography (FDG-PET/CT) and staging laparoscopy (SL) in addition to initial staging by means of gastroscopy and CT in patients with locally advanced gastric cancer. Design, Setting, and Participants: This multicenter prospective, observational cohort study included 394 patients with locally advanced, clinically curable gastric adenocarcinoma (≥cT3 and/or N+, M0 category based on CT) between August 1, 2017, and February 1, 2020. Exposures: All patients underwent an FDG-PET/CT and/or SL in addition to initial staging. Main Outcomes and Measures: The primary outcome was the number of patients in whom the intent of treatment changed based on the results of these 2 investigations. Secondary outcomes included diagnostic performance, number of incidental findings on FDG-PET/CT, morbidity and mortality after SL, and diagnostic delay. Results: Of the 394 patients included, 256 (65%) were men and mean (SD) age was 67.6 (10.7) years. A total of 382 patients underwent FDG-PET/CT and 357 underwent SL. Treatment intent changed from curative to palliative in 65 patients (16%) based on the additional FDG-PET/CT and SL findings. FDG-PET/CT detected distant metastases in 12 patients (3%), and SL detected peritoneal or locally nonresectable disease in 73 patients (19%), with an overlap of 7 patients (2%). FDG-PET/CT had a sensitivity of 33% (95% CI, 17%-53%) and specificity of 97% (95% CI, 94%-99%) in detecting distant metastases. Secondary findings on FDG/PET were found in 83 of 382 patients (22%), which led to additional examinations in 65 of 394 patients (16%). Staging laparoscopy resulted in a complication requiring reintervention in 3 patients (0.8%) without postoperative mortality. The mean (SD) diagnostic delay was 19 (14) days. Conclusions and Relevance: This study's findings suggest an apparently limited additional value of FDG-PET/CT; however, SL added considerably to the staging process of locally advanced gastric cancer by detection of peritoneal and nonresectable disease. Therefore, it may be useful to include SL in guidelines for staging advanced gastric cancer, but not FDG-PET/CT

Laparoscopic versus open gastrectomy for gastric cancer, a multicenter prospectively randomized controlled trial (LOGICA-trial)

Background: For gastric cancer patients, surgical resection with en-bloc lymphadenectomy is the cornerstone of curative treatment. Open gastrectomy has long been the preferred surgical approach worldwide. However, this procedure is associated with considerable morbidity. Several meta-analyses have shown an advantage in short-term outcomes of laparoscopic gastrectomy compared to open procedures, with similar oncologic outcomes. However, it remains unclear whether the results of these Asian studies can be extrapolated to the Western population. In this trial from the Netherlands, patients with resectable gastric cancer will be randomized to laparoscopic or open gastrectomy. Methods: The study is a non-blinded, multicenter, prospectively randomized controlled superiority trial. Patients (≥18 years) with histologically proven, surgically resectable (cT1-4a, N0-3b, M0) gastric adenocarcinoma and European Clinical Oncology Group performance status 0, 1 or 2 are eligible to participate in the study after obtaining informed consent. Patients (n = 210) will be included in one of the ten participating Dutch centers and are randomized to either laparoscopic or open gastrectomy. The primary outcome is postoperative hospital stay (days). Secondary outcome parameters include postoperative morbidity and mortality, oncologic outcomes, readmissions, quality of life and cost-effectiveness. Discussion: In this randomized controlled trial laparoscopic and open gastrectomy are compared in patients with resectable gastric cancer. It is expected that laparoscopic gastrectomy will result in a faster recovery of the patient and a shorter hospital stay. Secondly, it is expected that laparoscopic gastrectomy will be associated with a lower postoperative morbidity, less readmissions, higher cost-effectiveness, better postoperative quality of life, but with similar mortality and oncologic outcomes, compared to open gastrectomy. The study started on 1 December 2014. Inclusion and follow-up will take 3 and 5 years respectively. Short-term results will be analyzed and published after discharge of the last randomized patient

Evaluation of PET and laparoscopy in STagIng advanced gastric cancer: A multicenter prospective study (PLASTIC-study)

Background: Initial staging of gastric cancer consists of computed tomography (CT) and gastroscopy. In locally advanced (cT3-4) gastric cancer, fluorodeoxyglucose positron emission tomography with CT (FDG-PET/CT or PET) and staging laparoscopy (SL) may have a role in staging, but evidence is scarce. The aim of this study is to evaluate the impact and cost-effectiveness of PET and SL in addition to initial staging in patients with locally advanced gastric cancer. Methods: This prospective observational cohort study will include all patients with a surgically resectable, advanced gastric adenocarcinoma (cT3-4b, N0-3, M0), that are scheduled for treatment with curative intent after initial staging with gastroscopy and CT. The modalities to be investigated in this study is the addition of PET and SL. The primary outcome of this study is the proportion of patients in whom the PET or SL lead to a change in treatment strategy. Secondary outcome parameters are: diagnostic performance, morbidity and mortality, quality of life, and cost-effectiveness of these additional diagnostic modalities. The study recently started in August 2017 with a duration of 36 months. At least 239 patients need to be included in this study to demonstrate that the diagnostic modalities are break-even. Based on the annual number of gastrectomies in the participating centers, it is estimated that approximately 543 patients are included in this study. Discussion: In this study, it is hypothesized that performing PET and SL for locally advanced gastric adenocarcinomas results in a change of treatment strategy in 27% of patients and an annual cost-reduction in the Netherlands of €916.438 in this patient group by reducing futile treatment. The results of this study may be applicable to all countries with comparable treatment algorithms and health care systems

Postoperative complications and weight loss following jejunostomy tube feeding after total gastrectomy for advanced adenocarcinomas

Objective: Patients undergoing total gastrectomy for cancer are at risk of malnourishment. The aim of this selfcontrolled study was to examine the effect of jejunostomy tube feeding (JTF) and other factors on postoperative weight and the incidence of jejunostomy-related complications in patients undergoing total gastrectomy for cancer. Methods: All consecutive patients who underwent total gastrectomy for gastric cancer with jejunostomy placement were included from a prospective single-center database (2003–2014). Jejunostomy-related complications and postoperative weight changes were evaluated up to 12 months after surgery. Multivariable linear regression analysis was performed to identify factors associated with weight loss 12 months after gastrectomy. Results: Of 113 patients operated in the study period, 65 received JTF after total gastrectomy for a median duration of 18 d [interquartile range (IQR), 10–55 d]. Jejunostomy-related complications occurred in 11 (17%) patients, including skin leakage (n=3) and peritoneal leakage (n=2), luxation (n=3), occlusion (n=2), infection (n=1) and torsion (n=1). In 2 (3%) patients, a reoperation was needed due to jejunostomy-related complications. The mean preoperative weight of patients was 71.8 kg (100%), and remained stable during JTF (73.9 kg, 103%, P=0.331). After JTF was stopped, the mean weight of patients decreased to 64.9 kg (90%) at 12 months after surgery (P<0.001). A high preoperative body mass index (BMI) (≥25 kg/m2) was associated with high postoperative weight loss compared to patients with a low BMI (<25 kg/m2) (16.3% vs. 8.6%, P=0.016). Conclusions: JTF can prevent weight loss in the early postoperative phase. However, this is at the prize of possible complications. As weight loss in the long term is not prevented, routine JTF should be re-evaluated and balanced against the selected use in preoperatively malnourished patients. Special attention should be paid to patients with a high preoperative BMI, who are at risk of more postoperative weight loss