Long-term survivals of immune checkpoint inhibitors as neoadjuvant and adjuvant therapy in dMMR/MSI-H colorectal and gastric cancers.

BACKGROUND: The long-term survival benefit of immune checkpoint inhibitors (ICIs) in neoadjuvant and adjuvant settings is unclear for colorectal cancers (CRC) and gastric cancers (GC) with deficiency of mismatch repair (dMMR) or microsatellite instability-high (MSI-H). METHODS: This retrospective study enrolled patients with dMMR/MSI-H CRC and GC who received at least one dose of neoadjuvant ICIs (neoadjuvant cohort, NAC) or adjuvant ICIs (adjuvant cohort, AC) at 17 centers in China. Patients with stage IV disease were also eligible if all tumor lesions were radically resectable. RESULTS: In NAC (n = 124), objective response rates were 75.7% and 55.4%, respectively, in CRC and GC, and pathological complete response rates were 73.4% and 47.7%, respectively. The 3-year disease-free survival (DFS) and overall survival (OS) rates were 96% (95%CI 90-100%) and 100% for CRC (median follow-up [mFU] 29.4 months), respectively, and were 84% (72-96%) and 93% (85-100%) for GC (mFU 33.0 months), respectively. In AC (n = 48), the 3-year DFS and OS rates were 94% (84-100%) and 100% for CRC (mFU 35.5 months), respectively, and were 92% (82-100%) and 96% (88-100%) for GC (mFU 40.4 months), respectively. Among the seven patients with distant relapse, four received dual blockade of PD1 and CTLA4 combined with or without chemo- and targeted drugs, with three partial response and one progressive disease. CONCLUSION: With a relatively long follow-up, this study demonstrated that neoadjuvant and adjuvant ICIs might be both associated with promising DFS and OS in dMMR/MSI-H CRC and GC, which should be confirmed in further randomized clinical trials.

Impact of immediate breast reconstruction on perioperative therapy: insights from a Japanese Nationwide Registry.

BACKGROUND: Immediate breast reconstruction (IBR) is a common oncoplastic procedure used in breast cancer surgery. This study aims to investigate compliance with prosthetic breast reconstruction guidelines and its impact on perioperative treatment. METHODS: We reviewed data from the National Clinical Database-Breast Cancer Registry between January 2019 and December 2020. We compared perioperative treatment implementation between the IBR and non-IBR groups by subtype matching for age, menopausal status, T stage, N stage, and histology. RESULTS: A total of 8,860 patients with breast cancer who underwent IBR (6,075 breast prostheses, 2,492 autologous tissues, and 293 others) were identified. The compliance rate with the guidelines for prosthetic breast reconstruction was 97.7%. After matching, chemotherapy for luminal A-like diseases was significantly less frequent in the IBR group than in the non-IBR group (16.3% vs 20.5%, p < 0.001), and radiotherapy was less frequent in luminal A-like and HER2-positive patients (7.2% vs 9.0%, p = 0.010 and 7.1% vs 11.4%, p = 0.005, respectively). Among the 1-3 node-positive cases, fewer patients with prosthetic IBR received radiotherapy than those without IBR (15.7% vs 26.4%, p < 0.001). CONCLUSION: Prosthetic breast reconstruction was performed with strict adherence to the Japanese guidelines. The implementation rates of chemotherapy and radiotherapy were lower in the specific IBR group than those in the non-IBR group. Therefore, large-scale, long-term follow-up data are required.

[Progress and Discussion of Perioperative Targeted Therapy in Patients 
with EGFR-mutated Resectable Non-small Cell Lung Cancer].

Lung cancer is still the leading cause of cancer death worldwide. Non-small cell lung cancer (NSCLC) is the main pathological type of lung cancer, accounting for about 80%. Approximately 30% of all patients with NSCLC have resectable early and middle stage disease at the time of diagnosis. Recently, the epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have made a major breakthrough in the adjuvant targeted therapy of EGFR-mutated resectable NSCLC, and are recommended by the guidelines for clinical use. In this review, we summarize the clinical research progress of perioperative adjuvant targeted therapy for EGFR-mutated resectable NSCLC, and discuss the key issues in the clinical researches.
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Development of perioperative immune checkpoint inhibitor therapy for locally advanced esophageal squamous cell carcinoma.

The standard preoperative treatment for resectable locally advanced esophageal squamous cell carcinoma (ESCC) is chemoradiotherapy in western countries (based on the CROSS trial) and triplet chemotherapy in Japan (based on the JCOG1109 trial). Postoperative nivolumab has recently been shown to improve disease-free survival in resectable locally advanced esophageal cancer after preoperative chemoradiotherapy in patients who had residual pathological disease, based on the CheckMate 577 trial. Furthermore, preoperative immune checkpoint inhibitor-containing treatments have also been developed. The JCOG1804E trial is presently evaluating the safety and efficacy of preoperative nivolumab-containing chemotherapy for resectable locally advanced ESCC. This review discusses the treatment of resectable locally advanced ESCC and future perspectives on perioperative immune checkpoint inhibitor-containing treatments.

[Box: see text].

Surgical and Perioperative Treatments for Esophagogastric Junction Cancer.

Esophagogastric junction cancer (EGJC) is a rare malignant disease that occurs in the gastroesophageal transition zone. In recent years, its incidence has been rapidly increasing not only in Western countries but also in East Asia, and it has been attracting the attention of both clinicians and researchers. EGJC has a worse prognosis than gastric cancer (GC) and is characterized by complex lymphatic drainage pathways in the mediastinal and abdominal regions. EGJC was previously treated in the same way as GC or esophageal cancer, but, in recent years, it has been treated as an independent malignant disease, and treatment focusing only on EGJC has been developed. A recent multicenter prospective study revealed the frequency of lymph node metastasis by station and established the optimal extent of lymph node dissection. In perioperative treatment, the combination of multi-drug chemotherapy, radiation therapy, molecular targeted therapy, and immunotherapy is expected to improve the prognosis. In this review, we summarize previous clinical trials and their important evidence on surgical and perioperative treatments for EGJC.

Case report: Nutritionally supported perioperative chemo-immunotherapy for advanced gastric cancer with incomplete pyloric obstruction.

This case describes the benefits of perioperative chemo-immunotherapy for advanced gastric cancer and incomplete pyloric obstruction, supplemented with nutritional support. Early parenteral nutrition to stabilize nutritional status and mitigate nutrition impact symptoms, and in addition, throughout the chemo-immunotherapy perioperative period also maintained oral nutrition support and a tailored dietary plan. Above nutritional support maintained the patient's physical condition during immunotherapy. Eventually, this combination therapy plan leads to a partial response. On the other hand, a combination of therapies that focus more on immune checkpoint inhibitor may be able to mitigate the side effects of chemotherapy. Such findings may yield novel prospects for patients with advanced gastric cancer and incomplete pyloric obstruction, enabling them to achieve better outcomes.

Efficacy and safety of perioperative melatonin for postoperative delirium in patients undergoing surgery: a systematic review and meta-analysis.

OBJECTIVE: To assess the efficacy and safety of perioperative melatonin and melatonin agonists in preventing postoperative delirium (POD). METHODS: We conducted a systematic search for randomized controlled trials (RCTs) published through December 2022. The primary outcome was efficacy based on the incidence of POD (POD-I). Secondary outcomes included efficacy and safety according to the length of hospital or intensive care unit stay, in-hospital mortality, and adverse events. Subgroup analyses of POD-I were based on the type and dose of drug (low- and high-dose melatonin, ramelteon), the postoperative period (early or late), and the type of surgery. RESULTS: In the analysis (16 RCTs, 1981 patients), POD-I was lower in the treatment group than in the control group (risk ratio [RR] = 0.57). POD-I was lower in the high-dose melatonin group than in the control group (RR = 0.41), whereas no benefit was observed in the low-dose melatonin and ramelteon groups. POD-I was lower in the melatonin group in the early postoperative period (RR = 0.35) and in patients undergoing cardiopulmonary surgery (RR = 0.54). CONCLUSION: Perioperative melatonin or melatonin agonist treatment suppressed POD without severe adverse events, particularly at higher doses, during the early postoperative period, and after cardiopulmonary surgery.

Application of immune checkpoint inhibitors for resectable gastric/gastroesophageal cancer.

Gastric/gastroesophageal junction (G/GEJ) cancer represents a significant global health challenge. Radical surgery remains the cornerstone of treatment for resectable G/GEJ cancer. Supported by robust evidence from multiple clinical studies, therapeutic approaches, including adjuvant chemotherapy or chemoradiation, and perioperative chemotherapy, are generally recommended to reduce the risk of recurrence and enhance long-term survival outcomes post-surgery. In recent years, immune checkpoint inhibitors (ICIs) have altered the landscape of systemic treatment for advanced or metastatic G/GEJ cancer, becoming the standard first-line therapy for specific patients. Consequently, exploring the efficacy of ICIs in the adjuvant or neoadjuvant setting for resectable G/GEJ cancer is worthwhile. This review summarizes the current advances in the application of ICIs for resectable G/GEJ cancer.

Efficacy and safety of perioperative therapy for locally resectable gastric cancer: A network meta-analysis of randomized clinical trials.

BACKGROUND: Gastric cancer (GC) is the fifth most commonly diagnosed malignancy worldwide, with over 1 million new cases per year, and the third leading cause of cancer-related death. AIM: To determine the optimal perioperative treatment regimen for patients with locally resectable GC. METHODS: A comprehensive literature search was conducted, focusing on phase II/III randomized controlled trials (RCTs) assessing perioperative chemotherapy and chemoradiotherapy in treating locally resectable GC. The R0 resection rate, overall survival (OS), disease-free survival (DFS), and incidence of grade 3 or higher nonsurgical severe adverse events (SAEs) associated with various perioperative regimens were analyzed. A Bayesian network meta-analysis was performed to compare treatment regimens and rank their efficacy. RESULTS: Thirty RCTs involving 8346 patients were included in this study. Neoadjuvant XELOX plus neoadjuvant radiotherapy and neoadjuvant CF were found to significantly improve the R0 resection rate compared with surgery alone, and the former had the highest probability of being the most effective option in this context. Neoadjuvant plus adjuvant FLOT was associated with the highest probability of being the best regimen for improving OS. Owing to limited data, no definitive ranking could be determined for DFS. Considering nonsurgical SAEs, FLO has emerged as the safest treatment regimen. CONCLUSION: This study provides valuable insights for clinicians when selecting perioperative treatment regimens for patients with locally resectable GC. Further studies are required to validate these findings.

Perioperative immune checkpoint blockades improve prognosis of resectable non-small cell lung cancer.

OBJECTIVES: Immune checkpoint blockades (ICB) have been proven to improve prognosis of non-small cell lung cancer in the neoadjuvant setting, while whether its perioperative use could bring extra benefit remained unidentified. We aimed to demonstrate the prognostic benefit of perioperative ICB over preoperative-only use and investigate who could benefit from this 'sandwich ICB therapy'. METHODS: Patients undergoing neoadjuvant therapy followed by surgery from 2018 to 2022 were retrospectively reviewed, and were divided into 4 groups based on the perioperative regimens: pre-ICB + post-computed tomography (CT), pre-ICB-only, pre-CT + post-ICB and pre-CT-only. Treatment-related adverse events, surgical outcomes, therapeutic response, recurrence-free survival and overall survival were compared. RESULTS: Of 214 enrolled patients with preoperative therapy, 108 underwent immunochemotherapy and 106 underwent platinum-based chemotherapy. Compared with preoperative chemotherapy, preoperative immunochemotherapy was demonstrated with significantly higher major pathologic response (57/108 vs 12/106) and pathologic complete response (35/108 vs 4/106) rates with comparable adverse events. Regarding survival, perioperative ICB significantly improved the recurrence-free survival [versus pre-CT-only hazard ratio (HR) 0.15; 95% CI 0.09-0.27; versus pre-ICB-only HR 0.36; 95% CI 0.15-0.88] and overall survival (versus pre-CT-only HR 0.24; 95% CI 0.08-0.68). In patients without major pathologic response, perioperative ICB was observed to decrease the risk of recurrence (HR 0.31; 95% CI 0.11-0.83) compared with preoperative ICB, and was an independent prognostic factor (P < 0.05) for recurrence-free survival. CONCLUSIONS: Perioperative ICB showed promising efficacy in improving pathological response and survival outcomes of resectable non-small cell lung cancer. For patients without major pathologic response after resection followed by preoperative ICB, sequential ICB treatment could be considered.

[Treatment of proximal femoral fractures : Principles, tips and tricks]. / Therapie proximaler Femurfrakturen : Grundlagen, Tipps und Tricks.

Proximal femoral fractures occur at an annual incidence of approximately 200/100,000 inhabitants and mortality rates range up to 30% especially in geriatric patients where complications are not necessarily associated to surgery. In nearly all cases surgical treatment is required. Procedures to preserve the femoral head have to be performed as early as possible (as specified by the Federal Joint Committee, GBA, within 24 h). For joint-preserving approaches in medial femoral neck fractures a time to surgery within 6 h is considered to be advantageous. Perioperative patient care is of high importance regarding the prevention of pneumonia, renal failure, delirium and further complications. Postoperatively full weight bearing enables for early mobilization and prevention of surgery-related complications. Nonunions, avascular necrosis of the femoral head, cut-out and prosthetic dislocation must be avoided by the selection of the appropriate procedure. Minimally displaced femoral neck fractures are primarily treated by osteosynthesis and conservative management is only considered in isolated cases. For displaced femoral neck fractures, factors such as a young biological age with high activity levels, the absence of arthritis and good bone quality with a successful reduction favor for a femoral head-preserving osteosynthesis. Otherwise, (hybrid) total hip replacement (THR) is the preferred method for unstable and displaced fractures, whereby hemiarthroplasty should only be considered for very old and patients with pre-existing diseases. Fractures in the trochanteric region are treated with a proximal femoral nail and subtrochanteric fractures are managed using a long proximal femoral nail. To avoid secondary complications, the choice of optimal treatment should be based on a good understanding of the injury pattern, biomechanical and technical aspects of each procedure.

Perioperative NALIRIFOX in patients with resectable pancreatic ductal adenocarcinoma: The open-label, multicenter, phase II nITRO trial.

BACKGROUND: Upfront surgery followed by postoperative treatment is a commonly adopted treatment for resectable pancreatic ductal adenocarcinoma (rPDAC). However, the risk of positive surgical margins, the poor recovery that often impairs postoperative treatments, and the risk of recurrence might limit the outcome of this strategy. This study evaluated the safety and the activity of liposomal irinotecan 50 mg/m2 + 5-fluorouracil 2400 mg/m2 + leucovorin 400 mg/m2 + oxaliplatin 60 mg/m2 (NALIRIFOX) in the perioperative treatment of patients with rPDAC. METHODS: Eligible patients had a rPDAC with < 180° interface with major veins' wall. Patients received 3 cycles before and 3 cycles after resection with NALIRIFOX, days 1 and 15 of a 28-day cycle. The primary endpoint was the proportion of patients undergoing an R0 resection. RESULTS: 107 patients began preoperative treatment. Nine patients discontinued the treatment because of related or unrelated adverse events. Disease-control rate was 92.9%. 87 patients underwent surgical exploration, 11 had intraoperative evidence of metastatic disease, and 1 died for surgical complications. R0 resection rate was 65.3%. 49 patients completed the three postoperative cycles. The most common grade ≥ 3 adverse events were diarrhea and neutropenia. Median overall survival (OS) of ITT patients was 32.3 months (95% CI 27.8-44.3). Median disease-free and OS from surgery of resected patients were 19.3 (95% CI 12.6-34.1) and 40.3 months (95% CI 29-NA), respectively. CONCLUSION: Perioperative NALIRIFOX was manageable and active, and deserves further investigation in randomized trials comparing it with standard upfront surgery followed by adjuvant therapy.

Multimodal Therapy Versus Primary Surgery for Gastric and Gastroesophageal Junction Diffuse Type Carcinoma, with a Focus on Signet Ring Cell Carcinoma: A Nationwide Study.

BACKGROUND: Diffuse type adenocarcinoma and, more specifically, signet ring cell carcinoma (SRCC) of the stomach and gastroesophageal junction (GEJ) have a poor prognosis and the value of neoadjuvant chemo(radio)therapy (nCRT) is unclear. METHODS: All patients who underwent surgery for diffuse type gastric and GEJ carcinoma between 2004 and 2015 were retrospectively included from the Netherlands Cancer Registry. The primary outcome was overall survival after surgery. Kaplan-Meier curves were plotted. Furthermore, multivariable Poisson and Cox regressions were performed, correcting for confounders. To comply with the Cox regression proportional hazard assumption, gastric cancer survival was split into two groups, i.e. <90 days and >90 days, postoperatively by adding an interaction variable. RESULTS: Analyses included 2046 patients with diffuse type cancer: 1728 gastric cancers (50% SRCC) and 318 GEJ cancers (39% SRCC). In the gastric cancer group, 49% received neoadjuvant chemotherapy (nCT) and 51% received primary surgery (PS). All-cause mortality within 90 days postoperatively was lower after nCT (hazard ratio [HR] 0.29, 95% confidence interval [CI] 0.20-0.44; p < 0.001). Also after 90 days, mortality was lower in the nCT group (HR for the interaction variable 2.84, 95% CI 1.87-4.30, p < 0.001; total HR 0.29*2.84 = 0.84). In the GEJ group, 38% received nCT, 22% received nCRT, and 39% received PS. All-cause mortality was lower after nCT (HR 0.63, 95% CI 0.43-0.93; p = 0.020) compared with PS. The nCRT group was removed from the Cox regression analysis since the Kaplan-Meier curves of nCRT and PS intersected. The results for gastric and GEJ carcinomas were similar between the SRCC and non-SRCC subgroups. CONCLUSION: For gastric and GEJ diffuse type cancer, including SRCC, nCT was associated with increased survival.

Updated Adjuvant Chemotherapy for Gastric Cancer.

Surgical resection is currently the best curative approach for gastric cancer (GC); however, the prognosis of patients with advanced GC remains poor even with curative resection. For this reason, perioperative chemotherapy has been combined with surgery to reduce the risk of postoperative recurrence. Standard perioperative chemotherapy for resectable advanced GC varies from region to region. Postoperative S-1 therapy was standardized via the ACTS-GC study in East Asia, perioperative ECF (Epirubicin + Cisplatin + Fluorouracil) was standardized via the MAGIC study in Europe, and postoperative chemoradiotherapy was standardized via the US intergroup study in North America. Since then, more intensive regimens have been developed. In recent years, perioperative therapy using novel agents, such as molecular-targeted drugs and immune checkpoint inhibitors (ICIs), has also been tested and evaluated in the three major regions (East Asia, Europe, and North America) with promising results. Perioperative chemotherapy has become an integral part of many treatment strategies and requires continued research and evaluation.

Essential updates 2021/2022: Perioperative and surgical treatments for gastric and esophagogastric junction cancer.

In recent years, important clinical trials for gastric cancer (GC) and esophagogastric junction cancer (EGJC) have been reported, changing the strategies of surgical and perioperative treatment. Although laparoscopic gastrectomy has already been shown to be effective for early-stage cancer, recent evidence from both Asia (JLSSG0901, CLASS-01 and KLASS-02) and Europe (LOGICA and STOMACH trials) has demonstrated that it is useful for advanced GC. Robotic surgery has been rapidly gaining popularity in recent years, and randomized controlled trials are ongoing to evaluate its efficacy. A prospective nationwide multicenter study mapped sites with frequent metastasis and revealed lymphatic flow specific to EGJC, thus establishing the optimal lymph node dissection area and surgical approach based on esophageal involvement. Perioperative chemotherapy, the mainstay of treatment in Europe, also has been established in Asia by the PRODIGY and RESOLVE studies. New clinical trials have been conducted to evaluate the efficacy of combining immunotherapy or molecular-targeted therapy with perioperative chemotherapy or chemoradiotherapy. In this review, we present important recent clinical trials regarding the treatment of GC and EGJC published in 2021 or 2022.

A small-scale, exploratory real-world study of nab-paclitaxel combined with oxaliplatin and tegafur in the perioperative treatment of advanced gastric cancer: a study protocol for a real-world clinical trial.

Background: Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) is an optimized and improved derivative of paclitaxel with superior efficacy and fewer adverse reactions, and it is widely used in the treatment of advanced gastric cancer. However, there is a paucity of data regarding the safety and efficacy of nab-paclitaxel combined with oxaliplatin (LBP) and tegafur in the treatment of patients with advanced gastric cancer. Methods: This analysis is a prospective, single-center, open-label, historically controlled real-world study designed to include 10 patients with advanced gastric cancer treated with nab-paclitaxel combined with LBP and tegafur gimeracil oteracil potassium. The primary and main efficacy outcomes are safety indicators, including the incidence of adverse drug reactions and adverse events (AEs), as well as the outliers of laboratory indicators and vital signs. The secondary efficacy outcomes are overall survival (OS), objective response rate (ORR), disease control rate (DCR), and proportion of dose suspensions, dose reductions and discontinuations. Discussion: Based on the findings of previous studies, we wished to assess the safety and efficacy of nab-paclitaxel combined with LBP and tegafur in the treatment of advanced gastric cancer. The trial requires constant contact and monitoring. The purpose is to determine a superior protocol in terms of patient survival, and pathological and objective response. Trial Registration: This trial has been registered with the Clinical Trial Registry: NCT05052931 (registration date: 2021/9/12).

Current trends in perioperative treatment of resectable gastric cancer.

In the last few decades, the treatment strategy for locally advanced resectable gastric cancer (GC) has shifted to a multimodal approach, which potentially decreases recurrence risk and improves survival rates. Perioperative therapy leads to downstaging, increased curative resection rates, and prolonged disease-free and overall survival, by preventing micrometastases in patients with resectable GC. Application of neoadjuvant therapy provides information about tumor biology and in vivo sensitivity. A consensus regarding the therapeutic approach for non-metastatic GC does not exist, and many clinical trials aim to clarify this aspect. Advances in precision medicine and the role of immunotherapy have been the focus of research in GC treatment. Herein, the current status and possible future developments of perioperative therapy for locally advanced resectable GC are reviewed, based on the most recent randomized clinical trials.

Secondary prevention and treatment innovation of early stage non-small cell lung cancer: Impact on diagnostic-therapeutic pathway from a multidisciplinary perspective.

Lung cancer (LC) is the leading cause of cancer-related death worldwide, mostly because the lack of a screening program so far. Although smoking cessation has a central role in LC primary prevention, several trials on LC screening through low-dose computed tomography (LDCT) in a high risk population showed a significant reduction of LC related mortality. Most trials showed heterogeneity in terms of selection criteria, comparator arm, detection nodule method, timing and intervals of screening and duration of the follow-up. LC screening programs currently active in Europe as well as around the world will lead to a higher number of early-stage Non Small Cell Lung Cancer (NSCLC) at the diagnosis. Innovative drugs have been recently transposed from the metastatic to the perioperative setting, leading to improvements in terms of resection rates and pathological responses after induction chemoimmunotherapy, and disease free survival with targeted agents and immune checkpoint inhibitors. The present review summarizes available evidence about LC screening, highlighting potential pitfalls and benefits and underlining the impact on the diagnostic therapeutic pathway of NSCLC from a multidisciplinary perspective. Future perspectives in terms of circulating biomarkers under evaluation for patients' risk stratification as well as a focus on recent clinical trials results and ongoing studies in the perioperative setting will be also presented.

Perioperative FLOT plus ramucirumab for resectable esophagogastric adenocarcinoma: A randomized phase II/III trial of the German AIO and Italian GOIM.

This multicenter, randomized phase II/III study evaluated the addition of the vascular endothelial growth factor receptor-2 inhibitor ramucirumab to FLOT as perioperative treatment for resectable esophagogastric adenocarcinoma. Patients received either FLOT alone (Arm A) or combined with ramucirumab followed by ramucirumab monotherapy (Arm B). The primary endpoint for the phase II portion was the pathological complete or subtotal response (pCR/pSR) rate. Baseline characteristics were comparable between both arms with a high rate of tumors signet-ring cell component (A:47% B:43%). No between-arm difference in pCR/pSR rate was seen (A:29% B:26%), therefore the transition to phase III was not pursued. Nevertheless, the combination was associated with a significantly increased R0-resection rate compared with FLOT alone (A:82% B:96%; P = .009). In addition, the median disease-free survival was numerically improved in Arm B (A:21 months B:32 months, HR 0.75, P = 0.218), while the median overall survival was similar in both treatment arms (A:45 months B:46 months, HR 0.94, P = 0.803). Patients with Siewert type I tumors receiving transthoracic esophagectomy with intrathoracic anastomosis showed an increased risk of serious postoperative complications after ramucirumab treatment, therefore recruitment of those patients was stopped after the first-third of the study. Overall, surgical morbidity and mortality was comparable, whereas more non-surgical grade ≥ 3 adverse events were observed with the combination, especially anorexia (A:1% B:11%), hypertension (A:4% B:13%) and infections (A:19% B:33%). The combination of ramucirumab and FLOT as perioperative treatment shows efficacy signals, particularly in terms of R0 resection rates, for a study population with a high proportion of prognostically poor histological subtypes, and further evaluation in this subgroup seems warranted.