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The genome of esophageal adenocarcinoma (EAC) is highly unstable and might evolve over time. Here, we track karyotype evolution in EACs in response to treatment and upon recurrence through multi-region and longitudinal analysis. To this end, we introduce L-PAC (low-purity inference of absolute copy-number alterations [CNAs]), a bio-informatics technique that allows inference of absolute CNAs of low-purity samples by leveraging the information of high-purity samples from the same cancer. Quantitative analysis of matched absolute CNAs reveals that the amount of karyotype evolution induced by chemoradiotherapy (CRT) is predictive for early recurrence and depends on the initial level of karyotype intra-tumor heterogeneity. We observe that CNAs acquired in response to CRT are partially reversed back to the initial state upon recurrence. Hence, CRT alters the fitness landscape to which tumors can adjust by adapting their karyotype. Together, our results indicate that karyotype plasticity contributes to the therapy resistance of EACs., Competing Interests: Declaration of interests B.C. has several patents pending and/or issued not related to this work. P.S. has done unrelated consultancy for MSD and Bayer and received payment from MEDtalks for educational presentation., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: This study evaluated the nationwide trends in care and accompanied postoperative outcomes for patients with distal esophageal and gastro-esophageal junction cancer., Summary of Background Data: The introduction of transthoracic esophagectomy, minimally invasive surgery, and neo-adjuvant chemo(radio)therapy changed care for patients with esophageal cancer., Methods: Patients after elective transthoracic and transhiatal esophagectomy for distal esophageal or gastroesophageal junction carcinoma in the Netherlands between 2007-2016 were included. The primary aim was to evaluate trends in both care and postoperative outcomes for the included patients. Additionally, postoperative outcomes after transthoracic and tran-shiatal esophagectomy were compared, stratified by time periods., Results: Among 4712 patients included, 74% had distal esophageal tumors and 87% had adenocarcinomas. Between 2007 and 2016, the proportion of transthoracic esophagectomy increased from 41% to 81%, and neo-adjuvant treatment and minimally invasive esophagectomy increased from 31% to 96%, and from 7% to 80%, respectively. Over this 10-year period, postoperative outcomes improved: postoperative morbidity decreased from 66.6% to 61.8% ( P = 0.001), R0 resection rate increased from 90.0% to 96.5% (P <0.001), median lymph node harvest increased from 15 to 19 ( P <0.001), and median survival increased from 35 to 41 months ( P = 0.027)., Conclusion: In this nationwide cohort, a transition towards more neo-adju-vant treatment, transthoracic esophagectomy and minimally invasive surgery was observed over a 10-year period, accompanied by decreased postoperative morbidity, improved surgical radicality and lymph node harvest, and improved survival., Competing Interests: Luyer received research grants from Galvani and Medtronic. Nieuwenhuijzen reports consulting fees and research grants from Medtronic. Rosman has received research grants from Johnson&Johnson and Medtronic. van Berge Henegouwen reports research grants from Olympus and Stryker, in addition to consulting fees from Medtronic, Alesi Surgical, Johnson&Johnson and Mylan. van Oijen has received unrestricted research grants from Bayer, Lilly, Merck Serono, Nordic, Servier, and Roche. The remaining authors have no conflict of interest to report. No funding was received for this study., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: This study investigated the patterns, predictors, and survival of recurrent disease following esophageal cancer surgery., Background: Survival of recurrent esophageal cancer is usually poor, with limited prospects of remission., Methods: This nationwide cohort study included patients with distal esophageal and gastroesophageal junction adenocarcinoma and squamous cell carcinoma after curatively intended esophagectomy in 2007 to 2016 (follow-up until January 2020). Patients with distant metastases detected during surgery were excluded. Univariable and multivariable logistic regression were used to identify predictors of recurrent disease. Multivariable Cox regression was used to determine the association of recurrence site and treatment intent with postrecurrence survival., Results: Among 4626 patients, 45.1% developed recurrent disease a median of 11 months postoperative, of whom most had solely distant metastases (59.8%). Disease recurrences were most frequently hepatic (26.2%) or pulmonary (25.1%). Factors significantly associated with disease recurrence included young age (≤65 y), male sex, adenocarcinoma, open surgery, transthoracic esophagectomy, nonradical resection, higher T-stage, and tumor positive lymph nodes. Overall, median postrecurrence survival was 4 months [95% confidence interval (95% CI): 3.6-4.4]. After curatively intended recurrence treatment, median survival was 20 months (95% CI: 16.4-23.7). Survival was more favorable after locoregional compared with distant recurrence (hazard ratio: 0.74, 95% CI: 0.65-0.84)., Conclusions: This study provides important prognostic information assisting in the surveillance and counseling of patients after curatively intended esophageal cancer surgery. Nearly half the patients developed recurrent disease, with limited prospects of survival. The risk of recurrence was higher in patients with a higher tumor stage, nonradical resection and positive lymph node harvest., Competing Interests: M.D.P.L. received research grants from Galvani and Medtronic. G.A.P.N. reports consulting fees and research grants from Medtronic. C.R. has received research grants from Johnson&Johnson and Medtronic. M.I.v.B.H. reports research grants from Olympus and Stryker, in addition to consulting fees from Medtronic, Alesi Surgical, Johnson&Johnson, and Mylan. M.G.H.v.O. has received unrestricted research grants from Bayer, Lilly, Merck Serono, Nordic, Servier, and Roche. The remaining authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Esophageal adenocarcinoma (EAC) is a highly aggressive cancer and its response to chemo- and radiotherapy is unpredictable. EACs are highly heterogeneous at the molecular level. The aim of this study was to perform gene expression analysis of EACs to identify distinct molecular subgroups and to investigate expression signatures in relation to treatment response. In this prospective observational study, RNA sequencing was performed on pre-treatment endoscopic EAC biopsies from a discovery cohort included between 2012 and 2017 in one Dutch Academic Center. Four additional cohorts were analyzed for validation purposes. Unsupervised clustering was performed on 107 patients to identify biological EAC subgroups. Specific cell signaling profiles were identified and evaluated with respect to predicting response to neo-adjuvant chemo(radio)therapy. We identified and validated three distinct biological EAC subgroups, characterized by (1) p38 MAPK/Toll-like receptor signaling; (2) activated immune system; and (3) impaired cell adhesion. Subgroup 1 was associated with poor response to chemo-radiotherapy. Moreover, an immune signature with activated T-cell signaling, and increased number of activated CD4 T memory cells, neutrophils and dendritic cells, and decreased M1 and M2 macrophages and plasma cells, was associated with complete histopathological response. This study provides a novel molecular classification for EACs. EAC subgroup 1 proved to be more therapy-resistant, while immune signaling was increased in patients with complete response to chemo-radiotherapy. Our findings give insight into the biology of EACs and in cellular signaling mechanisms underlying response to neo-adjuvant treatment. Future implementation of this classification will improve patient stratification and enhance the development of targeted therapies.

Aims: Determining prognosis following poor response to neoadjuvant chemoradiotherapy (nCRT) in oesophageal adenocarcinoma (OAC) remains challenging. An immunosuppressive tumour microenvironment (TME) as well as immune infiltrate density and composition are considered to play a critical role in the immune interaction between host and tumour and can predict therapy response and survival in many cancers, including gastrointestinal malignancies. The aim of this study was to establish the TME characteristics associated with survival following a poor response to nCRT., Methods and Results: The prognostic significance of OAC-associated CD3 + , CD4 + , CD8 + , forkhead box protein 3 (FoxP3 + ) and programmed cell death ligand 1 (PD-L1) expression was studied by immunohistochemistry and quantified by automated image analysis in 123 patients who underwent nCRT and curative resection. Results from good and poor responders were contrasted and immune infiltration was related to disease course in both groups. Subsequently a cohort of 57 patients with a moderate response to nCRT was analysed in a similar fashion. Tumour cell percentage positively correlated to immune infiltration markers. In good and moderate responders, none of the immune infiltrate parameters was associated with survival; in poor responders CD8 + was an independent negative predictor of OS in univariate analysis (P = 0.03) and high CD8 + infiltration was associated with worse OS (15 versus 32 months, P = 0.042)., Conclusion: A high CD8 + density is an independent biomarker of poor OS in poor responders to nCRT, but not in good and moderate responders. Our results suggest that patients with a poor response to nCRT but concomitant high CD8 + counts in the resection specimen require adjuvant therapy., (© 2021 John Wiley & Sons Ltd.)

Background: The PERISCOPE I study was designed to assess the safety and feasibility of (sub)total gastrectomy, cytoreductive surgery (CRS), and hyperthermic intraperitoneal chemotherapy (HIPEC) with oxaliplatin and docetaxel for gastric cancer patients who have limited peritoneal dissemination. The current analysis investigated changes in perioperative management together with their impact on postoperative outcomes., Methods: Patients with resectable gastric cancer and limited peritoneal dissemination were administered (sub)total gastrectomy, CRS, and HIPEC with oxaliplatin (460 mg/m 2 ) and docetaxel (escalating scheme: 0, 50, 75 mg/m 2 ). Of the 25 patients who completed the study protocol, 14 were treated in the dose-escalation cohort and 11 were treated in the expansion cohort (to optimize perioperative management)., Results: A significant proportion of the patients in the dose-escalation cohort (n = 7, 50%) had ileus-related complications. In this cohort, enteral nutrition was started immediately after surgery at 20 ml/h, which was increased on day 1 to meet nutritional needs. In the expansion cohort, enteral nutrition was administered at 10 ml/h until day 3, then restricted to 20 ml/h until day 6, supplemented with total parenteral nutrition to meet nutritional needs. Ileus-related complications occurred for two patients (18%) of the expansion cohort. The intensive care unit (ICU) readmission rate decreased from 50 (n = 7) to 9% (n = 1; p = 0.04)., Conclusion: The implementation of a strict nutritional protocol during the PERISCOPE I study was associated with a decrease in postoperative complications. Based on these results, a perioperative care path was described for the gastric cancer HIPEC patients in the PERISCOPE II study.

Introduction: 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., Methods: 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., Results: 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., Conclusion: 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.

Introduction: The PERISCOPE I (Treatment of PERItoneal dissemination in Stomach Cancer patients with cytOreductive surgery and hyPErthermic intraperitoneal chemotherapy) study was conducted to investigate the safety and feasibility of hyperthermic intraperitoneal chemotherapy (HIPEC) in gastric cancer patients with limited peritoneal dissemination. In this study, tumor characteristics and clinical outcome of the patients treated in the PERISCOPE I trial were investigated., Methods: Patients who had undergone the full study protocol were selected; that is, preoperative systemic chemotherapy, followed by a surgical procedure consisting of a (sub)total gastrectomy, cytoreductive surgery, and HIPEC with oxaliplatin (460 mg/m 2 ) and docetaxel (in escalating doses)., Results: Twenty-five PERISCOPE I patients underwent the full study protocol. Most patients had an ypT3-4 tumor (96%) and the diffuse-type histology was predominant (64%). Seven patients (28%) had a microscopically irradical (R1) resection. In all patients, a complete cytoreduction was achieved. Median follow-up was 37 (95% confidence interval [CI]: 34-39) months. Disease recurrence was detected in 17 patients (68%). Median disease-free and overall survival were 12 and 15 months, respectively., Conclusion: In this series of gastric cancer patients with limited peritoneal dissemination who underwent HIPEC surgery, unfavorable tumor characteristics were common. Survival might be encouraging but disease recurrence was frequent. The efficacy of an HIPEC procedure in improving prognosis is currently being investigated in the PERISCOPE II trial., (© 2021 Wiley Periodicals LLC.)

In the PERISCOPE I study, gastric cancer patients with limited peritoneal dissemination were treated with systemic chemotherapy followed by (sub)total gastrectomy, cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) with 460 mg/m 2 hyperthermic oxaliplatin followed by normothermic docetaxel in escalating doses (0, 50, 75 mg/m 2 ). In total, 25 patients completed the study protocol. Plasma samples were collected before the start of the HIPEC procedure, after oxaliplatin washing, after docetaxel washing and the following morning. Median peak plasma concentrations were 5.5∗10 -3  mg/ml for oxaliplatin, 89∗10 -6  mg/ml for docetaxel (dose 50 mg/m 2 ) and 113∗10 -6  mg/ml for docetacel (dose 75 mg/m2). The following morning median plasma concentrations were 32% and 4% of the measured peak concentrations for oxaliplatin and docetaxel, respectively. For both cytostatic agents, no correlation was found between intraperitoneal fluid concentration and peak plasma concentration. High doses oxaliplatin and docetaxel can be given intraperitoneally without causing potentially toxic systemic concentrations., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: The presence of lymph node metastasis (LNmets) is a poor prognostic factor in oesophageal cancer (OeC) patients treated with neoadjuvant chemoradiotherapy (nCRT) followed by surgery. Tumour regression grade (TRG) in LNmets has been suggested as a predictor for survival. The aim of this study was to investigate whether TRG in LNmets is related to their location within the radiotherapy (RT) field., Methods: Histopathological TRG was retrospectively classified in 2565 lymph nodes (LNs) from 117 OeC patients treated with nCRT and surgery as: (A) no tumour, no signs of regression; (B) tumour without regression; (C) viable tumour and regression; and (D) complete response. Multivariate survival analysis was used to investigate the relationship between LN location within the RT field, pathological TRG of the LN and TRG of the primary tumour., Results: In 63 (54%) patients, viable tumour cells or signs of regression were seen in 264 (10.2%) LNs which were classified as TRG-B (n = 56), C (n = 104) or D (n = 104) LNs. 73% of B, C and D LNs were located within the RT field. There was a trend towards a relationship between LN response and anatomical LN location with respect to the RT field (p = 0.052). Multivariate analysis showed that only the presence of LNmets within the RT field with TRG-B is related to poor overall survival., Conclusion: Patients have the best survival if all LNmets show tumour regression, even if LNmets are located outside the RT field. Response in LNmets to nCRT is heterogeneous which warrants further studies to better understand underlying mechanisms.

Introduction: The Lauren classification of gastric adenocarcinoma describes three histological subtypes, the intestinal, the diffuse and the mixed type carcinoma. The metastatic pattern of gastric adenocarcinoma by histological subtype has not been studied., Methods: Gastric adenocarcinoma patients with metastatic disease at the time of diagnosis between 1999 and 2017 were identified through the Netherlands Cancer Registry. The Lauren classification was determined based on pathology reports archived in the Dutch Pathology Registry and was linked to individual cases in the Netherlands Cancer Registry., Results: Among 8 231 newly diagnosed, metastatic and evaluable gastric adenocarcinoma patients, 57 % had an intestinal type carcinoma, 38 % patients had a diffuse type carcinoma and 5 % had a mixed type carcinoma. Intestinal type carcinomas more often metastasized to the liver (57 % versus 21 %, p < 0.0001) and lungs (13 % versus 7 %, p < 0.0001), whereas diffuse type carcinomas more often metastasized to the peritoneum (58 % versus 29 %, p < 0.0001) and bones (9 % versus 6 %, p < 0.0001). Patients with a diffuse type carcinoma had a worse survival perspective regardless of the number or the location of the metastases., Conclusion: In this national cohort study, metastatic gastric adenocarcinoma of the intestinal type had a predilection for the liver and that of the diffuse type for the peritoneum., (Copyright © 2020. Published by Elsevier Ltd.)

Background: The role of cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in gastric cancer is unknown. This non-randomized dose-finding phase I-II study was designed to assess the safety and feasibility of HIPEC, following systemic chemotherapy, in patients with gastric cancer and limited peritoneal dissemination. The maximum tolerated dose of normothermic intraperitoneal docetaxel in combination with a fixed dose of intraperitoneal oxaliplatin was also explored., Methods: Patients with resectable cT3-cT4a gastric adenocarcinoma with limited peritoneal metastases and/or tumour-positive peritoneal cytology were included. An open HIPEC technique was used with 460 mg/m 2 hyperthermic oxaliplatin for 30 min followed by normothermic docetaxel for 90 min in escalating doses (0, 50, 75 mg/m 2 )., Results: Between 2014 and 2017, 37 patients were included. Of 25 patients who completed the full study protocol, four were treated at dose level 1 (0 mg/m 2 docetaxel), six at dose level 2 (50 mg/m 2 ) and four at dose level 3 (75 mg/m 2 ). At dose level 3, two dose-limiting toxicities occurred, both associated with postoperative ileus. Thereafter, another 11 patients were treated at dose level 2, with no more dose-limiting toxicities. Based on this, the maximum tolerated dose was 50 mg/m 2 intraperitoneal docetaxel. Serious adverse events were scored in 17 of 25 patients. The reoperation rate was 16 per cent (4 of 25) and the treatment-related mortality rate was 8 per cent (2 patients, both in dose level 3)., Conclusion: Gastrectomy combined with cytoreductive surgery and HIPEC was feasible using 460 mg/m 2 oxaliplatin and 50 mg/m 2 normothermic docetaxel., (© 2020 BJS Society Ltd Published by John Wiley & Sons Ltd.)

BACKGROUND : The International Gastric Cancer Linkage Consortium (IGCLC) consensus guideline advises prophylactic gastrectomy in early adulthood to prevent gastric cancer development in CDH1 germline mutation carriers; psychosocial reasons may postpone gastrectomy. We analyzed the yield of signet-ring cell carcinoma (SRCC) during surveillance gastroscopy in CDH1 mutation carriers. METHODS : A retrospective analysis on surveillance gastroscopies in CDH1 mutation carriers was performed. The yield of SRCC in both targeted and random biopsies was studied. Endoscopic (biopsy) results were compared with the histopathologic outcomes in gastrectomy specimens. RESULTS : 42 CDH1 mutation carriers (18 men; mean age 43, range 20-82 years) underwent 96 surveillance gastroscopies. SRCC lesions were identified on surveillance gastroscopy in 21 patients (50 %), by either targeted biopsies only (n = 11), random biopsies only (n = 3), or both random and targeted biopsies (n = 7). SRCC was detected in 41 /377 targeted biopsies (11 %), whereas random biopsies revealed SRCC in 14/1563 biopsies (0.9 %). At least one SRCC lesion was found in 26 of 30 gastrectomy specimens. In 18 of these 26 specimens (69 %), SRCC had been identified by endoscopic biopsies. Missed lesions were all small superficial SRCC foci, mainly in the body of the stomach. CONCLUSION : In our cohort of CDH1 mutation carriers, SRCC lesions were identified by an extensive endoscopic surveillance protocol in 69 % of SRCC-positive patients who underwent a gastric resection. The low number of SRCC detected through random sampling demands a critical reappraisal of random biopsy sampling in the IGCLC guideline., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Aim: To investigate the nationwide time trends in incidence and survival of oesophageal and gastric adenocarcinomas according to the Laurén classification (intestinal, diffuse and mixed type)., Methods: All patients diagnosed in the Netherlands with oesophageal or gastric adenocarcinoma between 1989 and 2015 were included. A syntax was developed to determine the histological subtype based on pathology reports as archived in the Dutch pathology registry. These reports were linked to individual data from the Netherlands Cancer Registry. Relative survival was used to assess survival., Results: The histological subtype could be determined in 18.691 (84.1%) oesophageal and in 32.312 (83.5%) gastric adenocarcinomas. Among these, 79% were intestinal and 21% diffuse type in oesophageal cancers, compared to 55% intestinal and 44% diffuse type in gastric cancers. Relative median survival of intestinal type tumours was longer than that of diffuse type tumours, that is, 12.1 versus 9.4 months for oesophageal carcinomas, and 10.1 versus 7.6 months for gastric carcinomas, respectively. Between 1989 and 2015, the relative median survival of non-metastatic intestinal and diffuse type oesophageal adenocarcinoma improved from 12.0 to 30.0 months, and from 12.0 to 19.2 months, respectively. The same was true for intestinal type gastric carcinoma (from 22.8 to 27.6 months) but for diffuse type gastric carcinoma, the increase was less (from 16.8 to 18.0 months)., Conclusion: In this nationwide study, histological subtypes of oesophageal and gastric adenocarcinomas differed in incidence and survival times. These findings may call for a differentiated treatment approach., Competing Interests: Conflict of interest statement None declared., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: 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., Methods: 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., Discussion: 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., Trial Registration: clinicaltrials.gov NCT03348150 ; registration date November 2017; first enrolment November 2017; expected end date December 2022; trial status: Ongoing.

Gastric adenocarcinoma and esophageal adenocarcinoma are aggressive cancers with a poor prognosis. Therefore, new therapeutic strategies are needed, especially for patients refractory to conventional treatment. Cancer immunotherapy (CIT), is a promising new treatment option and is effective in a proportion of patients with gastroesophageal malignancies. Biomarkers for selecting patients likely to benefit from CIT in gastroesophageal malignancies remain unproven. Programmed cell death ligand-1 (PD-L1), which is a validated biomarker in non-small cell lung cancer (NSCLC), is often also used to select patients for CIT in the context of gastroesophageal cancer, although this marker has not been validated for this purpose. We question the use of PD-L1 as a biomarker in gastroesophageal cancers, as there are fundamental differences in PD-L1 expression between NSCLC and gastroesophageal cancers. This review discusses the value of PD-L1 in selecting patients for CIT in esophageal and gastric cancer. Potential alternatives, especially microsatellite instability and Epstein-Barr virus positivity, are discussed., (Copyright © 2018. Published by Elsevier B.V.)