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Zusammenfassung: HINTERGRUND: Zum Zeitpunkt der Diagnosestellung des Magenkarzinoms haben ca. zwei Drittel der Patienten bereits Metastasen. Wichtig ist es, die Oligometastasierung von der diffus metastasierten Situation abzugrenzen. Die S3-Leitlinie hat die Definition der Oligometastasierung erstmals in die Leitlinie aufgenommen.Fragestellung: Kann das Überleben von Patienten mit Oligometastasierung mittels Resektion des Tumors und der Metastase kombiniert mit perioperativer Chemotherapie verbessert werden?Material und methoden: In dieser Übersichtsarbeit wird die Datenlage der aktuellen Literatur dargestellt.Ergebnisse: Die holländische Magenkarzinomstudie stellte ein verbessertes medianes Überleben für Patienten mit singulären Metastasen fest, wenn diese reseziert wurden. Aufgrund der Resultate der deutschen AIO-FLOT3-Studie, in der sich das mediane Überleben von Patienten mit Oligometastasen mit multimodaler Therapie verdoppelte, wurde die AIO-FLOT5(RENAISSANCE)-Studie initiiert. Diese randomisiert limitiert metastatische Patienten nach neoadjuvanter Chemotherapie entweder zu Resektion gefolgt von Chemotherapie oder zu definitiver Chemotherapie. Weitere randomisierende Studien untersuchen den Nutzen von Antikörpern und Immun-Checkpoint-Inhibitoren beim lokoregionalen und metastasierten Magenkarzinom mit vielversprechenden Resultaten.Diskussion: Die Resultate der aktuellen Studien werden zeigen, ob Patienten mit Oligometastasierung von einer multimodalen Therapie mit Resektion profitieren. Die eindeutige Definition der Oligometastasierung, eine Beurteilung des Ansprechens nach neoadjuvanter Chemotherapie und eine realistische Einschätzung der R0-Resektion werden bei der entsprechenden Patientenselektion hilfreich sein. Background: At the time of diagnosis of gastric cancer approximately one third of patients already have metastases. It is important to differentiate between oligometastasis and the diffuse metastatic situation. For the first time the definition of oligometastasis has been integrated into the German S3 guidelines.Objective: Can multimodal treatment with tumor resection and metastasectomy combined with perioperative chemotherapy, increase the chances of survival in oligometastatic patients?Material and methods: In this review article the data situation of the current literature is discussed.Results: The Dutch D1/D2 trial reported an increased median survival for a subgroup of patients with single metastasis who underwent resection. Multimodal treatment with resection doubled the median survival of oligometastatic patients in the German AIO-FLOT 3 study and as a consequence, the AIO-FLOT 5 (RENAISSANCE) trial was designed. Patients with oligometastatic gastric and esophagogastric junction cancer are randomized after chemotherapy to either undergo resection followed by adjuvant chemotherapy or to undergo definitive chemotherapy. Further randomized trials investigate the benefit of antibodies and immune checkpoint inhibitors in locoregional and advanced metastatic gastric cancer with promising results.Conclusion: The results of the ongoing randomized trials will show if oligometastatic patients benefit from a multimodal treatment with resection. The clear definition of the oligometastatic state, assessment of the response to neoadjuvant chemotherapy and realistic estimation of the R0 resectability will be useful for patient selection.

© The International Gastric Cancer Association and The Japanese Gastric Cancer Association 2018, Background: Perioperative complications can affect outcomes after gastrectomy for cancer, with high mortality and morbidity rates ranging between 10 and 40%. The absence of a standardized system for recording complications generates wide variation in evaluating their impacts on outcomes and hinders proposals of quality-improvement projects. The aim of this study was to provide a list of defined gastrectomy complications approved through international consensus. Methods: The Gastrectomy Complications Consensus Group consists of 34 European gastric cancer experts who are members of the International Gastric Cancer Association. A group meeting established the work plan for study implementation through Delphi surveys. A consensus was reached regarding a set of standardized methods to define gastrectomy complications. Results: A standardized list of 27 defined complications (grouped into 3 intraoperative, 14 postoperative general, and 10 postoperative surgical complications) was created to provide a simple but accurate template for recording individual gastrectomy complications. A consensus was reached for both the list of complications that should be considered major adverse events after gastrectomy for cancer and their specific definitions. The study group also agreed that an assessment of each surgical case should be completed at patient discharge and 90 days postoperatively using a Complication Recording Sheet. Conclusion: The list of defined complications (soon to be validated in an international multicenter study) and the ongoing development of an electronic datasheet app to record them provide the basic infrastructure to reach the ultimate goals of standardized international data collection, establishment of benchmark results, and fostering of quality-improvement projects.

The impact of the weekday of surgery in major elective cases of the upper-GI has been discussed controversially. The objective of this study was to assess whether weekday of surgery influences outcome in patients undergoing D2-gastrectomy. Patients who underwent D2-gastrectomy for gastric adenocarcinoma between 1996 and 2016 were included. Weekday of surgery was recognized, and subgroups were analyzed regarding clinical and histopathological differences. Survival analysis was performed based on weekday of surgery, and early weekdays (Monday–Tuesday) were compared with late weekdays (Wednesday–Friday). In total, 460 patients, 71% male and 29% female, were included into analysis. The median age was 65 years. Distribution to each weekday was equal and ranged from 86 cases (Wednesday) to 96 cases (Tuesday). The pT, pN and M category and the rate of patients who underwent neoadjuvant treatment did not show significant differences (p = 0.641; p = 0.337; p = 0.752; p = 0.342, respectively). The subgroups did not differ regarding the number of dissected lymph nodes and rate of R-1/2 resections (p = 0.590; p = 0.241, respectively). Survival analysis showed a median survival of 43 months (95% CI 31–55 months), and there was no single weekday or a combination of weekdays (Mon/Tue vs Wed/Thu/Fri) with a significant favorable or worse outcome (p = 0.863; p = 0.30, respectively). The outcome did not differ regarding mortality within the first 90 days after surgery (p = 0.948). The present study does not show any evidence for a significant impact of weekday of surgery on short- and long-term outcome of patients undergoing gastrectomy for gastric adenocarcinoma.

IMPORTANCE: Surgical resection has a potential benefit for patients with metastatic adenocarcinoma of the stomach and gastroesophageal junction. OBJECTIVE: To evaluate outcome in patients with limited metastatic disease who receive chemotherapy first and proceed to surgical resection. DESIGN, SETTING, AND PARTICIPANTS: The AIO-FLOT3 (Arbeitsgemeinschaft Internistische Onkologie-fluorouracil, leucovorin, oxaliplatin, and docetaxel) trial is a prospective, phase 2 trial of 252 patients with resectable or metastatic gastric or gastroesophageal junction adenocarcinoma. Patients were enrolled from 52 cancer care centers in Germany between February 1, 2009, and January 31, 2010, and stratified to 1 of 3 groups: resectable (arm A), limited metastatic (arm B), or extensive metastatic (arm C). Data cutoff was January 2012, and the analysis was performed in March 2013. INTERVENTIONS: Patients in arm A received 4 preoperative cycles of fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) followed by surgery and 4 postoperative cycles. Patients in arm B received at least 4 cycles of neoadjuvant FLOT and proceeded to surgical resection if restaging (using computed tomography and magnetic resonance imaging) showed a chance of margin-free (R0) resection of the primary tumor and at least a macroscopic complete resection of the metastatic lesions. Patients in arm C were offered FLOT chemotherapy and surgery only if required for palliation. Patients received a median (range) of 8 (1-15) cycles of FLOT. MAIN OUTCOMES AND MEASURES: The primary end point was overall survival. RESULTS: In total, 238 of 252 patients (94.4%) were eligible to participate. The median (range) age of participants was 66 (36-79) years in arm A (n = 51), 63 (28-79) years in arm B (n = 60), and 65 (23-83) years in arm C (n = 127). Patients in arm B (n = 60) had only retroperitoneal lymph node involvement (27 patients [45%]), liver involvement (11 [18.3%]), lung involvement (10 [16.7%]), localized peritoneal involvement (4 [6.7%]), or other (8 [13.3%]) incurable sites. Median overall survival was 22.9 months (95% CI, 16.5 to upper level not achieved) for arm B, compared with 10.7 months (95% CI, 9.1-12.8) for arm C (hazard ratio, 0.37; 95% CI, 0.25-0.55) (P

In den aktuell gültigen deutschen S3-Leitlinien wird bei metastasierten Magenkarzinomen und metastasierten Adenokarzinomen des ösophagogastralen Übergangs eine chirurgische Therapie in der Regel nicht empfohlen. In der täglichen Praxis findet jedoch schon heute in Einzelfällen eine Erweiterung der Indikation statt, sodass auch solche Patienten in kurativer Zielsetzung im Rahmen eines multimodalen Therapiekonzepts ausgedehnt und radikal operiert werden. Diese Arbeit stellt die wissenschaftliche Rationale eines solchen Vorgehens anhand der vorliegenden Literatur und unter Einbeziehung moderner, multimodaler Konzepte dar und verweist auf Kriterien, die für eine Erweiterung der Indikation gegeben sein sollten. Bislang existieren lediglich retrospektive Untersuchungen und wenige aktuelle Metaanalysen, die eine chirurgische Behandlung bei metastasierten Adenokarzinomen rechtfertigen. Es liegen zudem erste Ergebnisse der als Abstract publizierten FLOT-3-Studie vor, die eine Patientensubgruppe identifizieren konnte, die von einer Resektion im metastasierten Stadium profitiert. Ob die chirurgische Therapie zukünftig ein fester Bestandteil in der Behandlung des begrenzt metastasierten Adenokarzinoms des Magens und des Ösophagus wird, müssen große prospektiv randomisierte Studien wie die RENAISSANCE/FLOT-5-Studie zeigen. In the current German S3 guidelines surgical treatment is not recommended for metastatic gastric cancer or metastatic adenocarcinoma of the esophagogastric junction; however, in routine practice the indications can be extended so that there may be occasions in which radical surgical intervention for specific individuals may be appropriate as part of a multimodal therapy with curative intent. This article presents the scientific rationale of such an approach based on the available literature considering modern, multimodal therapy concepts including criteria to be met for radical surgery. Currently only retrospective trials and limited current meta-analysis data are available for justifying surgical treatment for metastatic adenocarcinoma. The recently published initial results of the FLOT-3 study identified a patient subgroup that benefits from a resection even though metastasis has occurred. Whether surgical therapy will become an integral part of the treatment of limited metastatic adenocarcinoma of the stomach and esophagus in the future, has to be demonstrated by large prospective randomized studies, such as the RENAISSANCE/FLOT-5 study.

Background: Docetaxel-based chemotherapy is effective in metastatic gastric and gastro-oesophageal junction adenocarcinoma, but has not yet been evaluated in the context of resectable patients. Here we report findings from the phase 2 part of the phase 2/3 FLOT4 trial, which compared histopathological regression in patients treated with a docetaxel-based triplet chemotherapy versus an anthracycline-based triplet chemotherapy before surgical resection.Methods: In this randomised, open-label, phase 2/3 study, eligible participants were recruited from 28 German oncology centres. Patients with resectable gastric or gastro-oesophageal junction cancer who had clinical stage cT2 or higher, nodal positive (cN+) disease, or both were randomly assigned (1:1) to either three preoperative and three postoperative 3-week cycles of intravenous epirubicin 50 mg/m2on day 1, intravenous cisplatin 60 mg/m2on day 1, and either fluorouracil 200 mg/m2as continuous intravenous infusion or capecitabine 1250 mg/m2orally (two doses of 625 mg/m2per day) on days 1 to 21 (ECF/ECX group) or four preoperative and four postoperative 2-week cycles of docetaxel 50 mg/m2, intravenous oxaliplatin 85 mg/m2, intravenous leucovorin 200 mg/m2, and fluorouracil 2600 mg/m2as a 24 h infusion, all on day 1 (FLOT group). Randomisation was done centrally with an interactive web-response system based on a sequence generated with blocks (block size 2) stratified by Eastern Cooperative Oncology Group performance status, location of primary tumour, age, and nodal status. No masking was done. Central assessment of pathological regression was done according to the Becker criteria. The primary endpoint was pathological complete regression (tumour regression grade TRG1a) and was analysed in the modified intention-to-treat population, defined as all patients who were randomly assigned to treatment excluding patients who had surgery but did not provide resection specimens for central evaluation. The study (including the phase 3 part) has completed enrolment, but follow-up is ongoing and this is an interim analysis. The trial is registered with ClinicalTrials.gov, number NCT01216644. Findings: Between Aug 18, 2010, and Aug 10, 2012, 300 patients (152 patients in the ECF/ECX group; 148 patients in the FLOT group) were enrolled into the phase 2 part of the study, 265 of whom (137 in the ECF/ECX group; 128 in the FLOT group) were assessable on a modified intention-to-treat basis. 119 (93%) of 128 patients in the FLOT group and 126 (92%) of 137 patients in the ECF/ECX group were given all planned preoperative cycles of treatment. FLOT was associated with significantly higher proportions of patients achieving pathological complete regression than was ECF/ECX (20 [16%; 95% CI 10-23] of 128 patients vs eight [6%; 3-11] of 137 patients; p=0·02). 44 (40%) of 111 patients in the ECF/ECX group and 30 (25%) of 119 patients in the FLOT group had at least one serious adverse event involving a perioperative medical or surgical complication. The most common non-surgical grade 3-4 adverse events were neutropenia (52 [38%] of 137 patients in the ECF/ECX group vs 67 [52%] of 128 patients in the FLOT group), leucopenia (28 [20%] vs 36 [28%]), nausea (23 [17%] vs 12 [9%]), infection (16 [12%] vs 15 [12%]), fatigue (19 [14%] vs 11 [9%]), and vomiting (13 [10%] vs four [3%]). Interpretation: Perioperative FLOT was active and feasible to administer, and might represent an option for patients with locally advanced, resectable gastric or gastro-eosophageal junction adenocarcinoma.

Background: Esophagectomy with gastric tube reconstruction and extended transhiatal gastrectomy with Roux-en-Y reconstruction are alternative procedures in current therapeutic concepts for adenocarcinoma of the esophagogastric junction (AEG). The impact of these operations on long-term health-related quality of life (HRQL) is incompletely understood.Methods: Patients with cancer-free survival of at least 24 months after esophagectomy (ESO) or extended gastrectomy (GAST) for AEG were identified from a prospectively maintained database. EORTC questionnaires were sent out to assess health-related general (QLQ-C30) and cancer-specific (OG-25) quality of life. Numeric scores were calculated for each conceptual area and compared with those of healthy reference populations.Results: 123 patients (ESO n = 71; GAST n = 52) completed the self-rated questionnaires. HRQL was consistently lower in surgical patients (GAST and ESO) compared with healthy reference populations. Also, there was a general trend for a better HRQL in GAST compared with ESO patients. This trend was statistically significant for physical function (p = 0.04), dyspnea (p = 0.02), and reflux (p = 0.03). Subgroup analysis revealed no significant differences between patients with or without prior neoadjuvant therapy.Conclusions: After mid- and long-term follow-up, HRQL after extended gastrectomy with Roux-en-Y reconstruction is superior to that after esophagectomy and gastric tube reconstruction. Improved HRQL after gastrectomy is mainly due to less pulmonary and reflux-related symptoms. Our findings may influence the choice of the surgical strategy for patients with AEG.

Presently, there is no scientific evidence supporting a definite role for follow-up after gastrectomy for cancer, and clinical practices are quite different around the globe. The aim of this consensus conference was to present an ideal prototype of follow-up after gastrectomy for cancer, based on shared experiences and taking into account the need to rationalize the diagnostic course without losing the possibility of detecting local recurrence at a potentially curable stage. On June 19–22, 2013 in Verona (Italy), during the 10th International Gastric Cancer Congress (IGCC) of the International Gastric Cancer Association, a consensus meeting was held, concluding a 6-month, Web-based, consensus conference entitled “Rationale of oncological follow-up after gastrectomy for cancer.” Forty-eight experts, with a geographical distribution reflecting different health cultures worldwide, participated in the consensus conference, and 39 attended the consensus meeting. Six statements were finally approved, displayed in a plenary session and signed by the vast majority of the 10th IGCC participants. These statements are attached as an annex to the Charter Scaligero on Gastric Cancer. After gastrectomy for cancer, oncological follow-up should be offered to patients; it should be tailored to the stage of the disease, mainly based on cross-sectional imaging, and should be discontinued after 5 years.