Gastric cancer (GC) remains a formidable global health challenge, ranking among the top-five causes of cancer-related deaths worldwide. The majority of patients face advanced stages at diagnosis, with a mere 6% five-year survival rate. First-line treatment for metastatic GC typically involves a fluoropyrimidine and platinum agent combination; yet, predictive molecular markers have proven elusive. This review navigates the evolving landscape of GC biomarkers, with a specific focus on Claudin 18.2 (CLDN18.2) as an emerging and promising target. Recent phase III trials have unveiled the efficacy of Zolbetuximab, a CLDN18.2-targeting antibody, in combination with oxaliplatin-based chemotherapy for CLDN18.2-positive metastatic GC. As this novel therapeutic avenue unfolds, understanding the nuanced decision making regarding the selection of anti-CLDN18.2 therapies over other targeted agents in metastatic GC becomes crucial. This manuscript reviews the evolving role of CLDN18.2 as a biomarker in GC and explores the current status of CLDN18.2-targeting agents in clinical development. The aim is to provide concise insights into the potential of CLDN18.2 as a therapeutic target and guide future clinical decisions in the management of metastatic GC.

Pancreatic cancer is one of the deadliest malignancies in humans and it is expected to play a bigger part in cancer burden in the years to come. Pancreatic ductal adenocarcinoma (PDAC) represents 85% of all primary pancreatic malignancies. Recently, much attention has been given to PDAC, with significant advances in the understanding of the mechanisms underpinning disease initiation and progression, along with noticeable improvements in overall survival in both localized and metastatic settings. However, given their rarity, rare histological subtypes of pancreatic cancer have been underappreciated and are frequently treated as PDAC, even though they might present non-overlapping molecular alterations and clinical behavior. While some of these rare histological subtypes are true variants of PDAC that should be treated likewise, others represent separate clinicopathological entities, warranting a different therapeutic approach. In this review, we highlight clinical, pathological, and molecular aspects of rare histological types of pancreatic cancer, along with the currently available data to guide treatment decisions.

The standard treatment for patients (pts) with localized squamous cell carcinoma of the anal canal (SCCAC) is chemoradiation (ChRT). Yet nearly 30% of patients are not cured and undergo salvage anorectal amputation. SCCAC is mostly a virus-associated tumor and thus potentially immunogenic. In fact, immune checkpoint inhibitors are promising in trials of metastatic SCCAC. Recently, studies have shown that the composition of the intestinal microbiota influences response to immunotherapy in some solid tumors, and the replacement of the intestinal "carcinogenic" by a protective microbiota has led to investigations with prebiotics and probiotics (PreProbiotics). Yet, there are no studies on the use of these agents in SCCAC. Thus we are conducting a randomized phase II study to test the efficacy of PreProbiotics during definitive ChRT aiming to improve the cure rate of pts with localized SCCAC. Randomized open label parallel phase II trial, where eligible pts will be randomized 1:1 to receive PreProbiotics starting one week prior to ChRT and throughout treatment until response evaluation at 6 to 8 weeks post ChRT or conventional ChRT. Eligible pts are ≥ 18 years, with histologically confirmed SCCAC, localized disease (≥ T2N0M0), indication to start definitive ChRT; HIV seropositive pts are eligible. Pts with active infection requiring antibiotics will be excluded. Primary endpoint: complete clinical and radiological response (CR) at 6 to 8 weeks post ChRT. Secondary endpoints: CR at 6 months, progression free survival, colostomy-free survival, metabolic response measured by 18-FDG PET-CT (baseline and at 6-8 weeks), toxicity, incidence of HPV in tumor tissues. All pts will have the following biological samples collected for correlative studies at baseline, 6-8 weeks and 6 months post ChRT: blood samples for circulating tumor DNA, inflammatory cytokines, anal/rectal swabs and feces to evaluate microbiota. Sample size assumptions: the H0 is CR at week 6 - 8 of 70% and H1, 90%; with a type I error of 10%, power of 80% and attrition rate of 10%, the final sample size is 75 patients. NCT03870607. Rachel Riechelmann. AC Camargo Cancer Center. All authors have declared no conflicts of interest.

Introduction: Pancreatic neuroendocrine neoplasms (pNEN) have poor prognosis. Available treatment options are limited. We aimed to evaluate the clinical characteristics and outcomes in patients with pNEN undergoing systemic chemotherapy. Methods: Retrospective study of patients with metastatic pNEN diagnosed between January 2000 and April 2018 in A.C. Camargo Cancer Center. We evaluated epidemiological characteristics and outcomes of patients who received systemic chemotherapy between the first and third-lines. Results: 35 patients with median age of 54.4 years; 51.4% had diabetes mellitus and 62.9% had smoking history. Most primary tumors were located in pancreatic body or tail and 34.3% were described as well or moderately differentiated, 40% were of high grade. Overall, chemotherapy from first to third-line was prescribed 50 times, 62% consisted of platin doublet, the chosen schema 50% of times when Ki-6755%. The median PFS and RR were 7.8 months and 40.7%; 13 months and 33.3% and 3 months and 0% in the first, second and third-line, respectively. The estimated OS was 53.4 months. We found that female (HR 2.8, p=0.034), DM (HR 4.5, p=0.004), smoking (HR 3.5, p=0.017), high grade tumors (HR 3.8, p=0.025) and tumors localized in head/ neck of the pancreas (HR 7.1, p<0.001) were negative prognostic factors for OS in univariate analysis. Conclusion: Our real world data shows that doublet platin is a preferred and active schema for treating pNEN, especially in first and second line. It brings the greatest benefit for undifferentiated tumors. Nevertheless, the prognosis remains poor and some factors may contribute to worse outcomes, such as female gender, silent tumors that do not manifest DM, poorly differentiated tumours, smoking and location in the head and neck of the pancreas.