Claudin 18.2 as a New Biomarker in Gastric Cancer-What Should We Know?

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.

Germline pathogenic variants in patients with early-onset neuroendocrine neoplasms.

Neuroendocrine neoplasms (NENs) are a rare group of cancers with heterogeneous behaviour and mostly of unknown aetiology. Excluding some infrequent hereditary cancer syndromes, the extent and clinical significance of mutations in other cancer predisposing genes (CPGs) are not known. We aimed to investigate the frequency of pathogenic and likely germline pathogenic variants (GPVs) in known CPGs in young adults with NEN and the clinical and molecular characteristics of these patients. We recruited 108 patients with lung or digestive NEN diagnosed between 18 and 50 years and performed targeted sequencing of 113 CPGs on germline DNA. For some patients, tumour features such as loss of heterozygosity (LOH), tumour mutation burden and microsatellite instability were evaluated. GPVs were detected in 17 patients (15.7%). Median age, sex, stage at diagnosis, family history of NENs or any personal history of neoplasm were similar between patients with or without GPVs. GPV carriers had more gastric (P = 0.084), functioning NEN (P = 0.041), positive family history of cancer (P = 0.015) and exclusively well-differentiated histology. Genes affected were mostly involved in DNA repair (CHEK2, ERCC2, ERCC3, XPC, MSH6, POLE and SLX4), with most GPVs found in MUTYH (four cases). LOH was performed in eight tumours and detected only in an SLX4-positive case. Overall, our findings indicate a role of inherited genetic alterations, particularly in DNA repair genes, in NEN carcinogenesis in young adults. These patients more often had a family history of cancer and functioning NENs.

Dihydropyrimidine dehydrogenase (DPD) polymorphisms knocking on the door.

Identifying polymorphisms in the dihydropyrimidine dehydrogenase (DPYD) genes is gaining importance as predictors of fluoropyrimidine-associated toxicity. The recommendation of dose adjustment for chemotherapy guided by the presence of polymorphisms of the DPYD gene can potentially improve treatment safety for a large number of patients, saving lives, avoiding complications and reducing health care costs. This article discusses how personalisation of fluoropyrimidine treatment based on the identification of DPYD variants can mitigate toxicities and be cost effective.

Clinico-pathological features and survival of patients with malignant exocrine pancreatic neoplasms: The AC Camargo Cancer Center experience.

BACKGROUND: Pancreatic cancer plays an important role in cancer-related mortality. Few studies have been performed in Brazil to characterize patients affected by this disease. We aimed to describe the clinico-pathological characteristics and the survival of patients with pancreatic cancer seen at AC Camargo Cancer Center (ACCCC). METHODS: We included patients ≥ 18-year old, with a histologically confirmed diagnosis of exocrine pancreatic cancer, that attended at least one visit at ACCCC from 2008 to 2016. RESULTS: The study included 739 patients. Median age at diagnosis was 64 years. Most patients were male. About 5% presented a family history of pancreatic cancer. A total of 40% had diabetes and 51.4% presented with ECOG performance status 1. Tumors most often arose in the pancreatic head and roughly half of the patients had metastatic disease at presentation. Median overall survival of patients with potentially resectable disease submitted to surgery at ACCCC was 35.4 months. Median overall survival times of patients with the unresectable and metastatic disease were 14.1 and 9.3 months, respectively. CONCLUSIONS: The features of our population match those of studies done in developed countries. We believe multicentric data from patients with pancreatic cancer in Brazil could enable more effective preventive and therapeutic approaches to the disease.

Retrospective analysis of efficacy and safety of Gemcitabine-based chemotherapy in patients with metastatic pancreatic adenocarcinoma experiencing disease progression on FOLFIRINOX.

BACKGROUND: Metastatic pancreatic adenocarcinoma (MPA) represents a highly lethal condition. Despite the improvements seen with FOLFIRINOX, there is no randomized data to guide treatment selection beyond this regimen. We aimed to evaluate the outcomes of patients with MPA progressing on FOLFIRINOX who were treated with Gemcitabine-based chemotherapy afterwards. METHODS: We included patients aged 18 years or older, treated for MPA with FOLFIRINOX in the first-line setting and who experienced disease progression, with Eastern Cooperative Oncology Group (ECOG) performance status 0-2, and treated with at least one cycle of Gemcitabine-based chemotherapy in second or further lines of treatment. We used descriptive statistics to characterize the study population and Cox proportional-hazards models to describe factors associated with survival. As an exploratory analysis, we compared the outcomes of patients treated with single-agent Gemcitabine with those of patients undergoing Gemcitabine-based polychemotherapy. RESULTS: The study population consisted of 42 patients. Median age was 59 years and 78.6% of patients presented ECOG 0-1. Thirty-three patients (78.6%) were treated with Gemcitabine-based chemotherapy in the second-line setting and 27 patients (64.3%) were treated with single-agent Gemcitabine. Objective response rate and disease control rate were 2.4% and 33.4%, respectively. Median progression-free survival (PFS) and median overall survival (OS) were 2.9 and 5.5 months, respectively. Six-month PFS and OS rates were 19.2% and 46.2%, respectively. We observed no significant difference in OS according to the type of Gemcitabine-based chemotherapy, despite numerically improved disease control rate and PFS for those treated with Gemcitabine-based polychemotherapy. In multivariate analysis, ECOG 2 (vs. ECOG 0-1) was the only factor significantly associated with inferior PFS and OS. CONCLUSIONS: a subgroup of patients with MPA derives benefit from treatment with Gemcitabine-based regimens after FOLFIRINOX. There is a suggestion that Gemcitabine-based combinations, in particular Gemcitabine plus Nab-Paclitaxel, provide superior outcomes compared to single-agent Gemcitabine. Additionally, treatment in this setting should be offered carefully to patients with ECOG 2, as they present shorter survival and increased risk of toxicity.

Retrospective comparison of the efficacy and the toxicity of standard and modified FOLFIRINOX regimens in patients with metastatic pancreatic adenocarcinoma.

BACKGROUND: FOLFIRINOX stands a major breakthrough in the management of metastatic pancreatic adenocarcinoma (MPA). Nonetheless, significant side-effects have been reported using standard FOLFIRINOX. We aimed to compare survival outcomes, response rates and toxicity of patients treated with standard or modified FOLFIRINOX in MPA. METHODS: We included patients aged ≥18 years old, with pathologically confirmed MPA, treated with FOLFIRINOX in the first-line setting. Patients submitted to at least one cycle of full-dose FOLFIRINOX were grouped in the standard FOLFIRINOX group. RESULTS: Patients treated with standard FOLFIRINOX were younger and had less comorbidity. We observed no differences in overall survival or in progression-free survival between the two treatment arms. The only variable independently associated with OS was log10[neutrophil-to-lymphocyte ratio (NLR)]. Modified FOLFIRINOX was associated with a lower dose reduction rate, but a slightly increased incidence of severe toxicity. CONCLUSIONS: Modified FOLFIRINOX presents the same activity against MPA as standard FOLFIRINOX. We found no significant differences in toxicity, possibly due to patient selection and a higher dose reduction rate in the standard FOLFIRINOX arm. NLR stood as an important prognostic marker and further research is needed to comprehend its biological meaning in pancreatic cancer.

Experiência do PSF com atividade em grupo de saúde do homem na UBS Vila Teresinha – São Paulo/SP / Experience the PSF group activity of health of men in UBS Vila Teresinha - São Paulo / SP

Experiência de equipe multiprofissional realizando atividade em grupo focada na saúde do homem em que acreditamos ser possível promover prevenção, educação e diagnóstico de agravos de relevância epidemiológica e ao mesmo tempo acolher e vincular essa parcela da população no serviço de saúde (AU)

Experiência do PSF com atividade em grupo de saúde do homem na UBS Vila Teresinha – São Paulo/SP

Experiência de equipe multiprofissional realizando atividade em grupo focada na saúde do homem em que acreditamos ser possível promover prevenção, educação e diagnóstico de agravos de relevância epidemiológica e ao mesmo tempo acolher e vincular essa parcela da população no serviço de saúde

Experiência do PSF com atividade em grupo de saúde do homem na UBS Vila Teresinha – São Paulo/SP / Experience the PSF group activity of health of men in UBS Vila Teresinha - São Paulo / SP

Experiência de equipe multiprofissional realizando atividade em grupo focada na saúde do homem em que acreditamos ser possível promover prevenção, educação e diagnóstico de agravos de relevância epidemiológica e ao mesmo tempo acolher e vincular essa parcela da população no serviço de saúde.