Gastric cancer is not a top-10 malignancy in the United States but represents one of the most common causes of cancer death worldwide. Biological differences between tumors from Eastern and Western countries add to the complexity of identifying standard-of-care therapy based on international trials. Systemic chemotherapy, radiotherapy, surgery, immunotherapy, and targeted therapy all have proven efficacy in gastric adenocarcinoma; therefore, multidisciplinary treatment is paramount to treatment selection. Triplet chemotherapy for resectable gastric cancer is now accepted and could represent a plateau of standard cytotoxic chemotherapy for localized disease. Classification of gastric cancer based on molecular subtypes is providing an opportunity for personalized therapy. Biomarkers, in particular microsatellite instability (MSI), programmed cell death ligand 1 (PD-L1), human epidermal growth factor receptor 2 (HER2), tumor mutation burden, and Epstein-Barr virus, are increasingly driving systemic therapy approaches and allowing for the identification of populations most likely to benefit from immunotherapy and targeted therapy. Significant research opportunities remain for the less differentiated histologic subtypes of gastric adenocarcinoma and those without markers of immunotherapy activity.

https://acsjournals.onlinelibrary.wiley.com/doi/pdf/10.3322/caac.21657

Current treatment and recent progress in gastric cancer.

Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Combined with Surgery: A 12-Year Meta-Analysis of this Promising Treatment Strategy for Advanced Gastric Cancer at Different Stages

Background Detailed information on metastatic patterns in of patients with esophageal and gastric cancer is limited. Early recognition of metastases is important to avoid futile locoregional treatments. Furthermore, knowledge on metastatic patterns is necessary for further development of personalized treatment modalities. Aim To gain insight into the metastatic pattern of gastroesophageal cancer. Methods A nationwide retrospective autopsy study of 3876 patients with adenocarcinoma (AC) or squamous cell carcinoma (SCC) of the esophagus or stomach between 1990 and 2017 was performed. Only patient with metastases were included for analysis. The metastatic pattern was analyzed according to the primary tumor location and histological subtype. Results Metastatic disease was found in 268 esophageal and 331 gastric cancer patients. In esophageal cancer, the most common metastatic locations were liver (56%), distant lymph nodes (53%) and lung (50%). Esophageal AC showed more frequently metastases to the peritoneum and bone compared with esophageal SCC. In gastric cancer, the most common metastatic locations were distant lymph nodes (56%), liver (53%) and peritoneum (51%). Intestinal-type AC of the stomach showed metastases to the liver more frequently, whereas metastases to the bone, female reproductive organs and colorectum were observed more frequently in diffuse-type gastric AC. Conclusion This study showed differences in metastatic patterns of patients with esophageal and gastric cancer according to the primary tumor location and histological subtype.

Metastatic pattern in esophageal and gastric cancer: Influenced by site and histology.

Current national guidelines do not include hyperthermic intraperitoneal chemoperfusion (HIPEC) as treatment for gastric cancer, and there are no completed clinical trials of cytoreduction, gastrectomy, and HIPEC from the US Patients with gastric adenocarcinoma and positive peritoneal cytology or carcinomatosis who had completed systemic chemotherapy and laparoscopic HIPEC underwent cytoreduction, gastrectomy, and HIPEC with 30 mg mitomycin C and 200 mg cisplatin The primary endpoint was overall survival (OS), with a secondary endpoint of postoperative complications (NCT02891447) We enrolled 20 patients from September 2016 to March 2019 Six patients had positive cytology only and 14 had carcinomatosis All patients were treated with systemic chemotherapy with a median of eight cycles (range 5–11 cycles) and at least one laparoscopic HIPEC The median peritoneal carcinomatosis index at cytoreduction/gastrectomy/HIPEC was 2 (range 0–13) After surgery, the 90-day morbidity and mortality rates were 70% and 0%, respectively Median length of hospital stay was 13 days (range 7–23 days); median follow-up was 335 months; median OS from the date of diagnosis of metastatic disease was 242 months; and median OS from the date of cytoreduction, gastrectomy, and HIPEC was 161 months 1-, 2-, and 3-year OS rates from the diagnosis of metastatic disease were 90%, 50%, and 28%, respectively Survival rates for patients with gastric adenocarcinoma and peritoneal disease treated with cytoreduction, gastrectomy, and HIPEC are encouraging; our early results are similar to those of recent prospective registry studies Multi-institutional and cooperative group trials should be supported to confirm survival and safety outcomes

A Phase II Trial of Cytoreduction, Gastrectomy, and Hyperthermic Intraperitoneal Perfusion with Chemotherapy for Patients with Gastric Cancer and Carcinomatosis or Positive Cytology

The peritoneum is a predilection site for gastric cancer metastases. Current standard treatment for gastric cancer patients with synchronous peritoneal metastases is palliative systemic therapy. However, its efficacy is largely unknown. The aim of this study was to investigate the incidence, treatment and survival patterns of gastric cancer patients with synchronous peritoneal metastases in the Netherlands. All newly diagnosed gastric adenocarcinoma patients with synchronous peritoneal metastases between 1999 and 2017 were selected from the Netherlands Cancer Registry (NCR). Incidence, treatment and survival patterns were analyzed. In total, 3,773 patients were identified from the NCR. The incidence of synchronous peritoneal metastases in gastric cancer patients increased from 18% in 2008 to 27% in 2017. The use of systemic therapy increased from 15% in 1999–2002 to 43% in 2013–2017 (p < 0.001). The median survival of the entire cohort did not significantly increase over time. Median survival of patients treated with systemic therapy increased from 7.4 months in 1999–2002 to 9.4 months in 2013–2017 (p = 0.005). In contrast, median survival of patients not treated with systemic therapy decreased from 3.3 months in 1999–2002 to 2.1 months in 2013–2017 (p < 0.001). Some clinical and pathological data such as the extent of the peritoneal metastases were not available. Synchronous peritoneal metastases are increasingly diagnosed in gastric cancer patients. In recent years, more patients were treated with systemic treatment and survival of these patients increased. However, as survival of the entire group did not improve over time, the effect of systemic therapy remains unknown.

Synchronous peritoneal metastases of gastric cancer origin: incidence, treatment and survival of a nationwide Dutch cohort.

At present, palliative systemic chemotherapy is the standard treatment in the Netherlands for gastric cancer patients with peritoneal dissemination. In contrast to lymphatic and haematogenous dissemination, peritoneal dissemination may be regarded as locoregional spread of disease. Administering cytotoxic drugs directly into the peritoneal cavity has an advantage over systemic chemotherapy since high concentrations can be delivered directly into the peritoneal cavity with limited systemic toxicity. The combination of a radical gastrectomy with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has shown promising results in patients with gastric cancer in Asia. However, the results obtained in Asian patients cannot be extrapolated to Western patients. The aim of this study is to compare the overall survival between patients with gastric cancer with limited peritoneal dissemination and/or tumour positive peritoneal cytology treated with palliative systemic chemotherapy, and those treated with gastrectomy, CRS and HIPEC after neoadjuvant systemic chemotherapy. In this multicentre randomised controlled two-armed phase III trial, 106 patients will be randomised (1:1) between palliative systemic chemotherapy only (standard treatment) and gastrectomy, CRS and HIPEC (experimental treatment) after 3–4 cycles of systemic chemotherapy.Patients with gastric cancer are eligible for inclusion if (1) the primary cT3-cT4 gastric tumour including regional lymph nodes is considered to be resectable, (2) limited peritoneal dissemination (Peritoneal Cancer Index < 7) and/or tumour positive peritoneal cytology are confirmed by laparoscopy or laparotomy, and (3) systemic chemotherapy was given (prior to inclusion) without disease progression. The PERISCOPE II study will determine whether gastric cancer patients with limited peritoneal dissemination and/or tumour positive peritoneal cytology treated with systemic chemotherapy, gastrectomy, CRS and HIPEC have a survival benefit over patients treated with palliative systemic chemotherapy only. clinicaltrials.gov NCT03348150
 ; registration date November 2017; first enrolment November 2017; expected end date December 2022; trial status: Ongoing.

/pdf/cytoreductive-surgery-and-hyperthermic-intraperitoneal-2fkft30s9a.pdf

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy versus palliative systemic chemotherapy in stomach cancer patients with peritoneal dissemination, the study protocol of a multicentre randomised controlled trial (PERISCOPE II)

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Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy versus palliative systemic chemotherapy in stomach cancer patients with peritoneal dissemination, the study protocol of a multicentre randomised controlled trial (PERISCOPE II)