• Efficacy and safety
• Gastric cancer
• Network meta-analysis
• Perioperative treatment

• Complications
• Gastric cancer
• Neoadjuvant therapy
• Outcomes
• Stomach neoplasms

Oesophageal (food pipe) and stomach cancers are amongst the hard-to-treat cancers that result in significant illness and deaths around the globe. Over the last few decades, there has been remarkable progress in the treatment of these cancers as a result of advances in diagnosis, surgical techniques, systemic therapy and radiotherapy. However, even if caught in the early stages, most patients with these cancers will unfortunately have their cancers come back, usually becoming widespread and difficult to treat. Therefore, optimising the early treatment strategy of these cancers is essential to improve the outcome and reduce the risk of recurrence. There are currently various geographically influenced standard of care management practices of early stomach and oesophageal cancers, ranging from using chemotherapy before and after surgery to the use of combined chemoradiotherapy before surgery and more recently the use of immunotherapy after surgery. However, it is not very clear if one strategy is significantly better than the others and there are some ongoing studies aiming to directly compare these treatment options. In addition, our understanding of the molecular and genetic features of these cancers can help improve our clinical practice and inform our choice of the best treatment strategy for the individual patient.

Oesophago–gastric adenocarcinoma remains a leading cause of cancer-related morbidity and mortality worldwide. Although there has been an enormous progress in the multimodality management of resectable oesophago–gastric adenocarcinoma, most patients still develop a recurrent disease that eventually becomes resistant to systemic therapy. Currently, there is no global consensus on the optimal multimodality approach and there are variations in accepted standards of care, ranging from preoperative chemoradiation to perioperative chemotherapy and, more recently, adjuvant immune checkpoint inhibitors. Ongoing clinical trials are aimed to directly compare multimodal treatment options as well as the additional benefit of targeted therapies and immunotherapies. Furthermore, our understanding of the molecular and genetic features of oesophago–gastric cancer has improved significantly over the last decade and these data may help inform the best approach for the individual patient, utilising biomarker selection and precision medicine.

• gastric cancer
• immunotherapy
• multimodality treatment
• oesophageal cancer
• precision oncology

• Apatinib
• DOS
• LAGC
• Neoadjuvant chemotherapy

Gastric cancer (GC) is a leading cause of cancer death in Chile. Although recommended in international guidelines since 2006, perioperative chemotherapy was not available to patients in the public health system in Chile until 2016. We conducted an observational study to assess the feasibility of this strategy in public hospitals in Chile (Observational Study of Perioperative Chemotherapy in Locally Advanced Gastric Cancer – PRECISO). Patients with locally advanced, operable GC were offered to receive preoperative chemotherapy with Epirubicin + Cisplatin + Capecitabine (ECX) for three cycles followed by curative surgery. Staging included abdominal CT scan and laparoscopy if peritoneal carcinomatosis was suspected. Postoperative ECX for three cycles was recommended. Between August 2010 and March 2013, 110 patients were screened and 61 enrolled. Median age was 62 years (23–76 years) and most patients had good performance status at baseline (Eastern Cooperative Oncology Group performance status score (ECOG) 0: 42, ECOG 1: 19). Tumour site was proximal in 32 (52%) and medial and distal in 29 (48%) patients. All but four patients (n = 57, 93%) completed three cycles of preoperative chemotherapy. Fifty-six patients were operated and 54 (89%) had a curative resection. Thirty-three patients (54%) had pT0-2, and 18 (30%) had pN0 tumours, with two patients achieving a complete response. As of 20 December 2020, 39 patients died, 32 due to GC, one within 30 days of surgery, two due to intestinal obstruction at 5 and 3 months after surgery and four due to other causes. Five-year survival rate was 38%. We conclude that perioperative chemotherapy is feasible in public hospitals in Chile and should be offered to patients with locally advanced GC.

• feasibility studies
• laparoscopy
• public health
• stomach neoplasms
• survival rate

• Gastric cancer
• Gastroesophageal adenocarcinoma
• Intensified chemotherapy
• Neoadjuvant chemotherapy
• Perioperative results

Neoadjuvant/perioperative chemotherapy is the recommended treatment for advanced stages of gastric cancer (> T2, N+) before tumour resection in many European guidelines. However, there is no consensus as to whether perioperative chemotherapy is as effective in distal as in proximal tumours, in addition to a relevant uncertainty concerning appropriate treatment modalities for elderly patients.

To investigate the role of perioperative chemotherapy in advanced gastric cancer in patients from a German tertiary clinic with respect to efficacy, localisation, and age.

We performed a retrospective analysis of 158 patients from our clinic with adenocarcinoma of the stomach or the gastroesophageal junction who underwent resection between 2008 and 2016. The data were evaluated particularly in relation to patient age, tumour site, and perioperative therapy.

Administration of perioperative chemotherapy did not lead to a significant survival advantage in our study population. The 5-year survival rates were 40% for patients who received perioperative chemotherapy and 29% for the group without perioperative chemotherapy (P = 0.125). Our patients were on average distinctly older than patients in most of the published randomised controlled trials. Patients elder than 75 years received perioperative chemotherapy far less frequently. Patients with a proximal tumour received perioperative chemotherapy much more often.

This analysis reconfirms our previous data concerning the effectiveness of perioperative chemotherapy for advanced gastric cancer. There is reasonable doubt that the quality of the existing randomized controlled trials is sufficient to generally justify perioperative chemotherapy in patients with advanced gastric cancer independent of tumour localization or age.

• Gastric cancer
• Perioperative
• Chemotherapy
• Tumour localisation
• Age distribution
• Validity

Gastric cancer, which has a high incidence and poor prognosis, remains a therapeutic challenge. Recently, neoadjuvant therapy has attracted increasing attention due to high recurrence rate and low survival rate after resection in most patients with advanced stage. Clinical trials show that neoadjuvant approaches confer a significant survival advantage for resectable locally advanced gastric cancer. The specific advantages of chemoradiotherapy compared with chemotherapy have not been clarified; optimal regimens and cycles, particularly in the preoperative setting, should be studied further; and trials aimed at determining the role of targeted and immunological therapies should be conducted.

• Chemotherapy
• Gastric cancer
• Neoadjuvant therapy
• Radiotherapy

• Treatment change
• advanced gastric cancer
• graded histologic response
• neoadjuvant chemotherapy

• D2 lymphadenectomy
• Locally advanced gastric cancer
• multimodality treatment
• perioperative chemotherapy

Although radical surgery remains the cornerstone of cure in resectable gastric cancer, survival remains poor. Current evidence-based (neo)adjuvant strategies have shown to improve outcome, including perioperative chemotherapy, postoperative chemoradiotherapy and postoperative chemotherapy. However, these regimens suffer from poor patient compliance, particularly in the postoperative phase of treatment. The CRITICS-II trial aims to optimize preoperative treatment by comparing three treatment regimens: (1) chemotherapy, (2) chemotherapy followed by chemoradiotherapy and (3) chemoradiotherapy.

In this multicentre phase II non-comparative study, patients with clinical stage IB-IIIC (TNM 8th edition) resectable gastric adenocarcinoma are randomised between: (1) 4 cycles of docetaxel+oxaliplatin+capecitabine (DOC), (2) 2 cycles of DOC followed by chemoradiotherapy (45Gy in combination with weekly paclitaxel and carboplatin) or (3) chemoradiotherapy. Primary endpoint is event-free survival, 1 year after randomisation (events are local and/or regional recurrence or progression, distant recurrence, or death from any cause). Secondary endpoints include: toxicity, surgical outcomes, percentage radical (R0) resections, pathological tumour response, disease recurrence, overall survival, and health related quality of life. Exploratory endpoints include translational studies on predictive and prognostic biomarkers.

The aim of this study is to select the most promising among three preoperative treatment arms in patients with resectable gastric adenocarcinoma. This treatment regimen will subsequently be compared with the standard therapy in a phase III trial.

clinicaltrials.gov NCT02931890; registered 13 October 2016. Date of first enrolment: 21 December 2017.

• Chemoradiotherapy
• Chemotherapy
• Gastric cancer
• Preoperative treatment
• Resectable
• Surgery

Evidence has shown that neoadjuvant chemotherapy (NACT) is correlated with patients’ overall postoperative complications. But investigations on relationship between NACT and postoperative infectious complications, which is closely linked to intestinal barrier damage, were scanty. Accordingly, 90 patients with advanced gastric cancer were included in this study. The differences in postoperative infectious complications were determined between NACT group in which patients received NACT before surgery and SURG group in which received surgical treatment immediately after diagnosis. The damage of mechanical structure of intestinal barrier was assessed by hematoxylin and eosin staining, transmission electron microscopy, and immunohistochemistry. Mucosal microbiota changes were determined by using a 16S rRNA gene sequencing approach. Results showed that the incidence of postoperative infectious complications were significantly higher in the NACT group. Tight junctions were disrupted, and claudin-1, ZO-1 and occludin were down-regulated in patients with infectious complications in overall compared with those without. And similarly, the patients in the NACT group also showed damaged intestinal barrier compared with those in SURG group. Besides, the total diversity of mucosal related bacteria was decreased and relative abundance of some probiotics, such as Bifidobacterium, Faecalibacterium and Ruminococcus, was reduced in the NACT group as well. In conclusion, our study identifies a higher incidence of postoperative infection in gastric cancer patients who underwent NACT treatment, and these changes might be caused by a significant damage in the intestinal barrier as well as reduced probiotics.

• gastric cancer
• intestinal barrier dysfunction
• intestinal microbiology
• neoadjuvant chemotherapy
• postoperative infectious complications

To investigate the neoadjuvant chemotherapy (NAC) effect on the survival of patients with proper stomach cancer submitted to D2 gastrectomy.

We proceeded to a review of the literature with PubMed, Embase, ASCO and ESMO meeting abstracts as well as computerized use of the Cochrane Library for randomized controlled trials (RCTs) comparing NAC followed by surgery (NAC + S) with surgery alone (SA) for gastric cancer (GC). The primary outcome was the overall survival rate. Secondary outcomes were the site of the primary tumor, extension of node dissection according to Japanese Gastric Cancer Association (JGCA) performed in both arms, disease-specific (DSS) and disease-free survival (DFS) rates, clinical and pathological response rates and resectability rates after perioperative treatment.

We identified a total of 16 randomized controlled trials comparing NAC + S (n = 1089) with SA (n = 973) published in the period from January 1993 - March 2017. Only 6 of these studies were well-designed, structured trials in which the type of lymph node (LN) dissection performed or at least suggested in the trial protocol was reported. Two out of three of the RCTs with D2 lymphadenectomy performed in almost all cases failed to show survival benefit in the NAC arm. In the third RCT, the survival rate was not even reported, and the primary end points were the clinical outcomes of surgery with and without NAC. In the remaining three RCTs, D2 lymph node dissection was performed in less than 50% of cases or only recommended in the “Study Treatment” protocol without any description in the results of the procedure really perfomed. In one of the two studies, the benefit of NAC was evident only for esophagogastric junction (EGJ) cancers. In the second study, there was no overall survival benefit of NAC. In the last trial, which documented a survival benefit for the NAC arm, the chemotherapy effect was mostly evident for EGJ cancer, and more than one-fourth of patients did not have a proper stomach cancer. Additionally, several patients did not receive resectional surgery. Furthermore, the survival rates of international reference centers that provide adequate surgery for homogeneous stomach cancer patients’ populations are even higher than the survival rates reported after NAC followed by incomplete surgery.

NAC for GC has been rapidly introduced in international western guidelines without an evidence-based medicine-related demonstration of its efficacy for a homogeneous population of patients with only stomach tumors submitted to adequate surgery following JGCA guidelines with extended (D2) LN dissection. Additional larger sample-size multicentre RCTs comparing the newer NAC regimens including molecular therapies followed by adequate extended surgery with surgery alone are needed.

• Gastric cancer
• Neoadjuvant chemotherapy
• Perioperative chemotherapy
• D2 lymphadenectomy
• Randomized control trial

• Antineoplastic Combined Chemotherapy Protocols/administration & dosage
• Antineoplastic Combined Chemotherapy Protocols/adverse effects
• Chemotherapy, Adjuvant
• Disease Progression
• Disease-Free Survival
• Evidence-Based Medicine
• Gastrectomy/adverse effects
• Gastrectomy/mortality
• Humans
• Lymph Node Excision
• Neoadjuvant Therapy/adverse effects
• Neoadjuvant Therapy/mortality
• Neoplasm Staging
• Randomized Controlled Trials as Topic
• Risk Factors
• Stomach Neoplasms/drug therapy
• Stomach Neoplasms/mortality
• Stomach Neoplasms/pathology
• Stomach Neoplasms/surgery
• Time Factors
• Treatment Outcome

• Chemoradiation
• Chemotherapy
• Esophageal adenocarcinoma
• Esophagogastric junction
• Gastric adenocarcinoma
• Neoadjuvant
• Perioperative
• Targeted agents
• Treatment approach

To investigate the feasibility of preoperative docetaxel, cisplatin and capecitabine (DCC) in patients with resectable gastric cancer.

Patients with resectable gastric cancer fulfilling the inclusion criteria, were treated with 4 cycles of docetaxel (60 mg/m²), cisplatin (60 mg/m²) and capecitabine (1.875 mg/m² orally on day 1-14, two daily doses) repeated every three weeks, followed by surgery. Primary end point was the feasibility and toxicity/safety profile of DCC, secondary endpoints were pathological complete resection rate and pathological complete response (pCR) rate.

All of the patients (51) were assessable for the feasibility and safety of the regimen. The entire preoperative regimen was completed by 68.6% of the patients. Grade III/IV febrile neutropenia occurred in 10% of all courses. Three patients died due to treatment related toxicity (5.9%), one of them (also) because of refusing further treatment for toxicity. Of the 45 patients who were evaluable for secondary endpoints, four developed metastatic disease and 76.5% received a curative resection. In 3 patients a pCR was seen (5.9%), two patients underwent a R1 resection (3.9%).

Four courses of DCC as a preoperative regimen for patients with primarily resectable gastric cancer is highly demanding. The high occurrence of febrile neutropenia is of concern. To decrease the occurrence of febrile neutropenia the prophylactic use of granulocyte colony-stimulating factor (G-CSF) should be explored. A curative resection rate of 76.5% is acceptable. The use of DCC without G-CSF support as preoperative regimen in resectable gastric cancer is debatable.

• Gastric cancer
• Preoperative chemotherapy
• Docetaxel
• Capecitabine

• gastric outlet obstruction
• neoadjuvant therapy
• nutritional support
• preoperative chemotherapy
• pyloric stenosis
• stomach neoplasm

• Gastric cancer
• TGOP
• neoadjuvant chemotherapy
• oxaliplatin

• Adenocarcinoma/drug therapy
• Adenocarcinoma/mortality
• Adenocarcinoma/surgery
• Chemotherapy, Adjuvant
• Disease-Free Survival
• Humans
• Neoadjuvant Therapy
• Randomized Controlled Trials as Topic
• Stomach Neoplasms/drug therapy
• Stomach Neoplasms/mortality
• Stomach Neoplasms/surgery
• Survival Rate
• Treatment Outcome

• Adenocarcinoma/drug therapy
• Adenocarcinoma/mortality
• Adenocarcinoma/surgery
• Chemotherapy, Adjuvant
• Disease-Free Survival
• Humans
• Neoadjuvant Therapy
• Randomized Controlled Trials as Topic
• Stomach Neoplasms/drug therapy
• Stomach Neoplasms/mortality
• Stomach Neoplasms/surgery
• Survival Rate
• Treatment Outcome

• gastric adenocarcinoma
• stomach cancer
• esophageal adenocarcinoma
• esophagogastric (gastroesophageal) junction cancer
• chemotherapy
• chemoradiotherapy
• multi-disciplinary care

• Adenocarcinoma/pathology
• Adenocarcinoma/surgery
• Adenocarcinoma/therapy
• Consensus
• Humans
• Neoadjuvant Therapy
• Stomach Neoplasms/pathology
• Stomach Neoplasms/surgery
• Stomach Neoplasms/therapy

• K23 CA178203 NCI NIH HHS

• chemotherapy
• gastric cancer
• radiotherapy
• standard of care
• surgery

• Chemotherapy
• Operable gastric cancer

• Gastrectomy
• Gastric cancer
• Morbidity
• Survival
• Treatment

• Adult
• Aged
• Aged, 80 and over
• Female
• Gastrectomy/mortality
• Gastrectomy/statistics & numerical data
• Humans
• Kaplan-Meier Estimate
• Logistic Models
• Male
• Middle Aged
• Nigeria/epidemiology
• Postoperative Complications/epidemiology
• Retrospective Studies
• Stomach Neoplasms/diagnosis
• Stomach Neoplasms/mortality
• Stomach Neoplasms/surgery
• Survival Analysis
• Young Adult