Optimal treatment strategy after first-line induction therapy in advanced HER2-positive oeso-gastric adenocarcinoma-a retrospective, international, multicentric AGEO study.

BACKGROUND: The optimal treatment strategy after first-line induction therapy in advanced HER2-positive oeso-gastric adenocarcinoma (OGA) remains challenging. METHODS: Patients treated with trastuzumab (T) plus platinum salts and fluoropyrimidine (F) as first-line chemotherapy between 2010 and 2020 for HER2-positive advanced OGA at 17 academic care centers in France, Italy, and Austria were included. The primary objective was the comparison of F + T vs T alone as maintenance regimen in terms of progression-free survival (PFS) and overall survival (OS) after a platinum-based chemotherapy induction + T. As secondary objective, PFS and OS between patients treated with reintroduction of initial chemotherapy or standard second-line chemotherapy at progression were assessed. RESULTS: Among the 157 patients included, 86 (55%) received F + T and 71 (45%) T alone as a maintenance regimen after a median of 4 months of induction chemotherapy. Median PFS from start of maintenance therapy was 5.1 months in both groups (95% CI 4.2-7.7 for F + T and 95% CI 3.7-7.5 for T alone; p = 0.60) and median OS was 15.2 (95% CI 10.9-19.1) and 17.0 months (95% CI 15.5-21.6) for F + T and T alone, respectively (p = 0.40). Of 112/157 patients (71%) receiving systemic therapy after progression under maintenance, 26/112 (23%) were treated with a reintroduction of initial chemotherapy + T and 86/112 (77%) with a standard second-line regimen. Here, median OS was significantly longer with the reintroduction (13.8 (95% CI 12.1-19.9) vs 9.0 months (95% CI 7.1-11.9); p = 0.007) as confirmed by multivariate analysis (HR 0.49; 95% CI 0.28-0.85; p = 0.01). CONCLUSION: No additional benefit of adding F to T monotherapy as a maintenance treatment could be observed. Reintroduction of initial therapy at first progression may be a feasible approach to preserve later treatment lines.

Assessment of the reliability of MSI status and dMMR proteins deficiency screening on endoscopic biopsy material in esophagus and gastric adenocarcinoma.

BACKGROUND: Microsatellite instability (MSI) is a negative predictive factor for neoadjuvant chemotherapy in resectable oesogastric adenocarcinoma and a crucial determinant for immunotherapy. We aimed to evaluate reliability of dMMR/MSI status screening performed on preoperative endoscopic biopsies. METHODS: Paired pathological samples from biopsies and surgical specimen of oesogastric adenocarcinoma were retrospectively collected between 2009 and 2019. We compared dMMR status obtained by immunohistochemistry (IHC) and MSI status by PCR. dMMR/MSI status on surgical specimen was considered as reference. RESULTS: PCR and IHC were conclusive on biopsies respectively for 53 (96.4%) and 47 (85.5%) of the 55 patients enrolled. IHC was not contributive for 1 surgical specimen. A third reading of IHC was carried out for 3 biopsies. MSI status was observed in 7 (12.5%) surgical specimens. When analyses were contributive, sensitivity and specificity of biopsies for dMMR/MSI were respectively 85% and 98% for PCR vs. 86% and 98% for IHC. Concordance rate between biopsies and surgical specimen was 96.2% for PCR and 97.8% for IHC. CONCLUSIONS: Endoscopic biopsies are a suitable source of tissue for dMMR/MSI status determination in oesogastric adenocarcinoma which should be routinely performed at diagnosis to better adapt neoadjuvant treatment. MINIABSTRACT: By comparison of dMMR phenotype obtained by immunohistochemistry and MSI status by PCR between match-paired samples of oesogastric cancer's endoscopic biopsies and surgical specimen, we observed that biopsies are a suitable source of tissue for dMMR/MSI status determination.

Routine surveillance endoscopy before and after sleeve gastrectomy?

There is no consensus when it comes to the necessity of an oeso-gastroduodenal fibroscopy (OGDF) before and after bariatric surgery. Many reports expressed the preoccupations about a gastroesophagal reflux disease (an acute risk of Barrett's esophagus) and its consequences after a sleeve gastrectomy (SG) and the risk of leaving a premalignant lesion in an excluded stomach after a Roux-en-Y gastric bypass. The International Federation for the Surgery of Obesity and Metabolic Disorders recommends a surveillance endoscopy, routinely after a SG. After review of the literature, we set out the arguments in favor of performing a systematic preoperative and post-operative OGDF.

Surgical robotics for esophageal cancer.

We present an update on robotic techniques and their advantages and use in esophageal cancer surgery. Recent work has shown tremendous progress in robotic-assisted minimally invasive esophagectomy (RAMIE) and lymphadenectomy for esophageal cancer, as well as benefits of robotic surgery in high upper esophageal tumors and T4b disease. We discuss the different RAMIE techniques, especially for intrathoracic anastomosis. The ongoing ROBOT trial had demonstrated superiority of robotic esophageal cancer surgery over open esophagectomy. There are various putative technical advantages of RAMIE over minimally invasive esophagectomy, which need to be proven in future trials.

Evaluation of the metabolic response to open and minimally invasive resection of the oesophagus due to oesophageal cancer.

AIM: The aim of this study was to compare the metabolic response in the early postoperative period after radical resection of stage I and II oesophageal cancer applying a minimally invasive procedure and an open procedure involving classical laparotomy and thoracotomy. MATERIAL AND METHODS: Serum concentrations of interleukin 6 (IL-6), procalcitonin (PCT), C-reactive protein (CRP), tumour necrosis factor-α (TNF-α), and total serum protein (TP) and leukocyte count (WBC) in blood collected on the day of surgery prior to the procedure (day 0) and on days 1, 2 and 7 after the surgery were measured in two groups of patients undergoing oesophageal resection due to cancer: applying a minimally invasive procedure involving laparoscopy and videothoracoscopy (group A) and applying a classical procedure involving full opening of the chest and abdominal cavity (group B). The study involved a total of 24 patients divided into two groups of 12 patients each. RESULTS: Tumour necrosis factor-α concentration was lower in group A compared to group B on day 0, PCT concentration was lower in group A compared to group B on day 2 after surgery, and on the remaining days TNF-α and PCT concentrations were not statistically different between groups. CONCLUSIONS: Lower concentration of PCT on post-surgery day 2 in the group of patients undergoing minimally invasive oesophageal resection seems to be associated with a smaller perioperative injury. Lower TNF-α concentration in serum collected on day 0 in the group of patients undergoing minimally invasive resection is associated with a lower stage of oesophageal cancer in this group.

Establishment of an international database for genetic variants in esophageal cancer.

The establishment of a database has been suggested in order to collect, organize, and distribute genetic information about esophageal cancer. The World Organization for Specialized Studies on Diseases of the Esophagus and the Human Variome Project will be in charge of a central database of information about esophageal cancer-related variations from publications, databases, and laboratories; in addition to genetic details, clinical parameters will also be included. The aim will be to get all the central players in research, clinical, and commercial laboratories to contribute. The database will follow established recommendations and guidelines. The database will require a team of dedicated curators with different backgrounds. Numerous layers of systematics will be applied to facilitate computational analyses. The data items will be extensively integrated with other information sources. The database will be distributed as open access to ensure exchange of the data with other databases. Variations will be reported in relation to reference sequences on three levels--DNA, RNA, and protein-whenever applicable. In the first phase, the database will concentrate on genetic variations including both somatic and germline variations for susceptibility genes. Additional types of information can be integrated at a later stage.

Esophageal stem cells and genetics/epigenetics in esophageal cancer.

The following, from the 12th OESO World Conference: Cancers of the Esophagus, includes commentaries on the relationship between stem cells, cancer, and the esophagus; the behavior of esophageal stem cells; and the role of genetics and epigenetics in approaches to translational research.

Esophageal stenting in cancer therapy.

The following, from the 12th OESO World Conference: Cancers of the Esophagus, includes commentaries on nutritional support during chemoradiation, esophageal stents before surgery, and stenting the cervical esophagus.

Surgical treatments for esophageal cancers.

The following, from the 12th OESO World Conference: Cancers of the Esophagus, includes commentaries on the role of the nurse in preparation of esophageal resection (ER); the management of patients who develop high-grade dysplasia after having undergone Nissen fundoplication; the trajectory of care for the patient with esophageal cancer; the influence of the site of tumor in the choice of treatment; the best location for esophagogastrostomy; management of chylous leak after esophagectomy; the optimal approach to manage thoracic esophageal leak after esophagectomy; the choice for operational approach in surgery of cardioesophageal crossing; the advantages of robot esophagectomy; the place of open esophagectomy; the advantages of esophagectomy compared to definitive chemoradiotherapy; the pathologist report in the resected specimen; the best way to manage patients with unsuspected positive microscopic margin after ER; enhanced recovery after surgery for ER: expedited care protocols; and long-term quality of life in patients following esophagectomy.

On endocytoscopy and posttherapy pathologic staging in esophageal cancers, and on evidence-based methodology.

The following, from the 12th OESO World Conference: Cancers of the Esophagus, includes commentaries on the value of endocytoscopy to replace biopsy histology for squamous cell carcinoma and the clinical significance of posttherapy pathologic stage in patients with esophageal adenocarcinoma following preoperative chemoradiation; a short discussion of evidence-based methodology is also included.

Molecular epidemiology of and genetic susceptibility to esophageal cancer.

The following, from the 12th OESO World Conference: Cancers of the Esophagus, includes commentaries on clonal evolution in Barrett's carcinogenesis; biomarkers for early detection of esophageal cancer; the role of the methylguanine methyl transferase biomarker in the management of adenocarcinoma; and the discovery of high-risk genes in families.

Upper esophageal and pharyngeal cancers.

The following, from the 12th OESO World Conference: Cancers of the Esophagus, includes commentaries on laryngopharyngeal reflux as a risk factor for laryngeal cancer; the role of pepsin in laryngopharyngeal neoplasia; natural fruit and vegetable compounds for the prevention and treatment of pharyngeal and esophageal cancers; and evaluation of cranberry constituents as inhibitors of esophageal adenocarcinoma utilizing in vitro assay and in vivo models.

Comparative genomic analysis of esophageal cancers.

The following, from the 12th OESO World Conference: Cancers of the Esophagus, includes commentaries on comparative genomic analysis of esophageal cancers: genomic polymorphisms, the genetic and epigenetic drivers in esophageal cancers, and the collection of data in the UK Barrett's Oesophagus Registry.

Endoscopy for diagnosis and treatment in esophageal cancers: high-technology assessment.

The following, from the 12th OESO World Conference: Cancers of the Esophagus, includes commentaries on the endoscopic tools to recognize squamous cell dysplasia; confocal laser endomicroscopy for Barrett's esophagus; confocal microscopy in the cancer patient; optical coherence tomography in the assessment of subsquamous Barrett's metaplasia; endoscopic mucosal resection for high-grade dysplasia in Barrett's esophagus; HALO in the treatment of squamous dysplasia; and the use of fluorescence in situ hybridization to detect dysplasia and adenocarcinoma in patients with Barrett's esophagus.

Progression of esophageal dysplasia to cancer.

The following, from the 12th OESO World Conference: Cancers of the Esophagus, includes commentaries on the evolution of low-grade squamous and glandular dysplasia to invasive carcinoma; the mutational spectra of Barrett's esophagus and adenocarcinoma; the risk of p53-immunoreactive glandular dysplasia compared to non-immunoreactive mucosa for progression to cancer; the role of lectins in progression to adenocarcinoma; and the role of racemase immunoreactivity in the prediction of risk of adenocarcinoma.

Diet and esophageal disease.

The following, from the 12th OESO World Conference: Cancers of the Esophagus, includes commentaries on macronutrients, dietary patterns, and risk of adenocarcinoma in Barrett's esophagus; micronutrients, trace elements, and risk of Barrett's esophagus and esophageal adenocarcinoma; the role of mate consumption in the development of squamous cell carcinoma; the relationship between energy excess and development of esophageal adenocarcinoma; and the nutritional management of the esophageal cancer patient.

Translational research on Barrett's esophagus.

The following, from the 12th OESO World Conference: Cancers of the Esophagus, includes commentaries on translational research on Barrett's esophagus that address evidence for genetic instability in esophageal cancer; the role of microsatellite instability; the use of histologic and serum Doublecortin-like kinase 1 expression for progression of Barrett's esophagus to adenocarcinoma; the oxidative stress in Barrett's tumorigenesis; the genomic alterations in esophageal cancer; in vivo modeling in Barrett's esophagus; epigenetic and transcriptional regulation in Barrett's esophagus and esophageal adenocarcinoma; and normal and disordered regeneration in Barrett's esophagus.

Infection and esophageal cancer.

The following, from the 12th OESO World Conference: Cancers of the Esophagus, includes commentaries on infection and cancer, and includes commentaries on the influence of bacterial infections on mucin expression and cancer risk; the role of esophageal bacterial biota in the incidence of esophageal disease; the association between human papilloma virus (HPV) and esophageal squamous cell carcinoma; the role of HPV in esophageal adenocarcinoma; the role of Helicobacter pylori in cardiac carcinoma; and the role of Epstein-Barr virus infection in esophageal cancer.

Benign and precursor lesions in the esophagus.

The following, from the 12th OESO World Conference: Cancers of the Esophagus, includes commentaries on the role of salivary stimulation and esophageal secretion of protective factors in prevention of adenocarcinoma sequelae in gastroesophageal reflux disease; the pediatric conditions associated with esophageal cancer; the relationship of achalasia and pseudoachalasia with esophageal cancer; the potential for malignant transformation in eosinophilic esophagitis and overlap syndromes; the role of lymphocytic esophagitis as an overlapping phenotype; the role of Barrett's esophagus as a premalignant condition; the indications and type of treatment of premalignant conditions of the esophagus; and the decision for use of endoscopical procedures in premalignant conditions of the esophagus.

Immune signaling and regulation in esophageal cancer.

The following, from the 12th OESO World Conference: Cancers of the Esophagus, includes commentaries on signaling pathways that can be targeted with immunotherapy; the role of micro-RNAs in the immune response to esophageal cancer; and the association between obesity, the immune system, and esophageal adenocarcinoma.