Paradigm Shift in Gastric Cancer Prevention: Harnessing the Potential of Aristolochia olivieri Extract

Gastric cancer, particularly adenocarcinoma, is a significant global health concern. Environmental risk factors, such as Helicobacter pylori infection and diet, play a role in its development. This study aimed to characterize the chemical composition and evaluate the in vitro antibacterial and antitumor activities of an Aristolochia olivieri Colleg. ex Boiss. Leaves’ methanolic extract (AOME). Additionally, morphological changes in gastric cancer cell lines were analyzed. AOME was analyzed using HPLC-MS/MS, and its antibacterial activity against H. pylori was assessed using the broth microdilution method. MIC and MBC values were determined, and positive and negative controls were included in the evaluation. Anticancer effects were assessed through in vitro experiments using AGS, KATO-III, and SNU-1 cancer cell lines. The morphological changes were examined through SEM and TEM analyses. AOME contained several compounds, including caffeic acid, rutin, and hyperoside. The extract displayed significant antimicrobial effects against H. pylori, with consistent MIC and MBC values of 3.70 ± 0.09 mg/mL. AOME reduced cell viability in all gastric cancer cells in a dose- and time-dependent manner. Morphological analyses revealed significant ultrastructural changes in all tumor cell lines, suggesting the occurrence of cellular apoptosis. This study demonstrated that AOME possesses antimicrobial activity against H. pylori and potent antineoplastic properties in gastric cancer cell lines. AOME holds promise as a natural resource for innovative nutraceutical approaches in gastric cancer management. Further research and in vivo studies are warranted to validate its potential clinical applications

FIRST LINE AVELUMAB IN PD-L1+VE METASTATIC OR LOCALLY ADVANCED UROTHELIAL CANCER (AUC) PATIENTS UNFIT FOR CISPLATIN (CIS): THE ARIES TRIAL

Background: Avelumab (ave) was approved as maintenance therapy after platinum-based first line (1L) therapy for patients (pts) with aUC based on ph. 3 Javelin Bladder 100 study (NCT02603432), showing significant overall survival (OS) improvement. Here we tested the activity of ave as 1L of therapy in pts with aUC and PD-L1+ve expression. Methods: ARIES is a single-arm, multi-site, open-label phase II trial. Enrolled pts had aUC, were cis-unfit (at least one of: ECOG-PS=2, CrCl <60 mL/min, grade ⩾2 peripheral neuropathy/hearing loss, progression within 6-mos before the end of neo/adj chemo), had not previously received chemo for aUC and PD-L1⩾5% (SP263) centrally assessed. Pts received ave 10 mg/Kg IV Q2W until progression, unacceptable toxicity and withdrawal, whichever occurred first. The primary endpoint was the 1-year OS. Key secondary endpoints were median-OS, -PFS, ORR, DOR and safety. The outcome based on PDL1 expression >10 has also been investigated. Results: A total of 198 eligible cis-unfit pts have been tested for PD-L1 and 71 (35.6%) have been found positive. Among enrolled patients (N=71), median age was 75 y, 35 (49.3%) had visceral disease, and 22 (31.0%) had ECOG-PS=2; 50 (70.4%) had CrCl <60 mL/min and 9 (12.7%) progressed within 6-mos from the end of neo/adj chemo. At the cut-off data (Feb 2, 2022), median follow up was 10.0 mos and 14 patients are still on treatment. The median OS was 10.0 mos (95% CI, 5.5-14.5), and 43.0% of patients were alive at 1-year. The ORR for all patients was 24.0%; complete response, 8.5% (n=6); partial response, 15.5% (n=11). Clinical benefit was 43.6% (n=31). Median PFS was 2.0 mos (95% CI, 1.7-2.3). Among the 17 pts who had tumour response 13 had DOR > 1y and 5 > 2y. A total of 67 patients have been evaluated for CPS and among these 56 (83.6%) have been classified as high expression. The median OS was 11.0 mos (95%CI, 0.1 – 22.9) for those with high CPS and 7.0 mos (95%CI 2.8 – 11.2) for low CPS (p=0.13). The median PFS was 2.0 mos for both high and low CPS (p=0.34). Five (7.0%) grade 3 ave-related adverse events, and no treatment-related death were reported. Conclusions: Ave is active and safe in pts with cis-unfit, PD-L1+ve aUC and poor baseline characteristics

Epidemiological, clinical and pathological characteristics of gastric neoplasms in the province of Cremona: the experience of the first population-based specialized gastric cancer registry in Italy

Abstract Background The gastric cancer incidence rate differs widely across geographical areas. In Italy, in the province of Cremona the incidence is high, compared to the national situation. For this reason a specialized population-based registry was set up. Methods The collection encompasses all gastric cancers diagnosed in the three districts of the province since January 1, 2010. The main data sources were the pathological and Hospital Discharge Records and patient clinical charts. Only diagnoses of primary gastric cancer were considered. For each case the following variables were registered: personal data, medical history and symptoms at diagnosis; imaging assessments performed, details on surgery and other treatments received; genetic background and biomolecular characteristics; social and environmental factors. Results As of November 2017, 1087 cases were collected; of which 876, diagnosed up to December 2015, were analyzed. Male/female ratio was 1.4. The European Age-standardized Incidence Rate was 41.4 for males and 28.3 for females as compared to a national average of 33.3 and 17.0 respectively. Median age at diagnosis was 73 for male and 78 for female. Helicobacter Pylori infection was present in fewer than 20% of cases. HER-2 gene was amplified in about 25% of cases. Primary tumour location was the gastro-esophageal junction or cardia in 17.5% in males and 8.3% in females. The majority of cases (58.3%) were diagnosed at an advanced stage and overall only 41.2% underwent surgery. Median overall survival was 14.8 months for men and 18.5 for women. Age standardized 5-year relative survival was 31.4% for men and 40.5% for females. Neoadjuvant treatment was performed in fewer than 10% of patients who underwent surgery, and the rate of postoperative therapy adherence was low. Discussion This study shows a high gastric cancer incidence in the province of Cremona, with a geographical spread across different districts. Moreover, a high percentage of gastric cancers were detected at an advanced stage of disease and a low rate of 5-year relative survival was registered. Based on these findings, effective preventive interventional health strategies and screening procedures need to be implemented to reduce the impact of this pathology in this geographical area

First-line dose-dense chemotherapy with docetaxel, cisplatin, folinic acid and 5-fluorouracil (DCF) plus panitumumab in patients with locally advanced or metastatic cancer of the stomach or gastroesophageal junction: final results and biomarker analysis from an Italian oncology group for clinical research (GOIRC) phase II study.

Survival for patients with advanced gastroesophageal cancer (AGC) using standard treatment regimens is poor. EGFR overexpression is common in AGC and associated with poor prognosis. We hypothesized that increasing the dose intensity of chemotherapy and adding panitumumab could improve efficacy.HER2 negative, PS 0-1 patients, received up to 4 cycles of panitumumab 6 mg/kg d 1, docetaxel 60 mg/m2 d 1, cisplatin 50 mg/m2 d 1, l-folinic acid 100 mg/m2 d 1-2, followed by 5-FU 400 mg/m2 bolus d 1-2, and then 600 mg/m2 as a 22 h c.i. on d 1-2, q15 d, plus pegfilgrastim 6 mg on d 3. Patients with disease control after 4 cycles received panitumumab until progression.From 05/2010 to 01/2014, 52 patients (75% male; median age 64.5 y; metastatic 90%, locally advanced 10%; 96% adenocarcinoma; 25% GEJ) were recruited. Three CR, 29 PR, 10 SD and 8 PD were observed, for an ORR by ITT (primary endpoint) of 62% (95% CI, 48%-75%) and a DCR of 81%. Median TTP was 4.9 months (95% CI, 4.2-7.0) and mOS 10 months (95% CI, 8.2- 13.5). Most frequent G3-4 toxicities: leucopenia (29%), asthenia (27%), skin rash (25%), neutropenia (19%), anorexia (17%), febrile neutropenia (13%), and diarrhea (15%). EGFR expression tested both with dd-PCR and FISH was not associated with any significant clinical benefit from treatment.Dose-dense DCF plus panitumumab is an active regimen. However, the toxicity profile of this limits further development. Further research on predictive biomarkers for treatment efficacy in AGC is required.Clinical trial information: 2009-016962-10