Professor Ramon Andrade De Mello

The endodermal sinus tumor (EST), also known as yolk sac tumor, accounts for 20% of germ cell tumor cases, typically occurring in gonadal locations. However, 1%-5% can present with an extragonadal localization. Primary hepatic EST is an extremely rare entity and poses a diagnostic challenge for the appropriate management of this pathology. We present the case of a 34-year-old woman who presented with a single hepatic mass associated with elevated alpha-fetoprotein (AFP) levels. Initially, hepatocellular carcinoma (HCC) was suspected, leading to a right hepatectomy, which resulted in pathology findings consistent with an EST. Following surgery, the patient underwent four courses of BEP chemotherapy, showing a partial response with residual lesions. The patient received two more courses of EP chemotherapy, with a PET CT showing a complete response. At over 5 years of follow-up, the patient remains clinically stable, with negative tumor markers, no evidence of disease, and leading a normal life. Primary hepatic EST is an infrequent but important differential diagnosis of HCC, particularly in young women without cirrhosis who present with markedly elevated AFP levels. Early biopsy confirmation and multidisciplinary management are essential, as this chemosensitive tumor may achieve long-term survival with timely systemic treatment.

From a complete literature review, we were able to present in this paper what is most current in the treatment with immunotherapy for advanced non-small cell lung cancer (NSCLC). Especially the use of immunotherapy, particularly inhibitors of PD-1 (programmed cell death protein 1), PDL-1 (programmed cell death protein ligand 1), and CTLA-4 (cytotoxic T-lymphocyte antigen 4). Since 2015, these drugs have transformed the treatment of advanced NSCLC lacking driver mutations, evolving from second-line therapy to first-line, with excellent results. The arrival of new checkpoint inhibitors such as cemiplimab and the use of checkpoint inhibitors earlier in the therapy of advanced and metastatic cancers has been making the future prospects for treating NSCLC lacking driver mutations more favorable and optimistic. In addition, for those patients who have low PDL-1 positivity tumors, the combination of cytotoxic chemotherapy, VEGF inhibitor, and immunotherapy have shown an important improvement in global survival and progression free survival regardless the PDL-1 status. We also explored the effectiveness of adding radiotherapy to immunotherapy and the most current results about this combination. One concern that cannot be overlooked is the safety profile of immune checkpoint inhibitors (ICI) and the most common toxicities are described throughout this paper as well as tumor resistance to ICI.

Introduction/objective: Significant advancements have been achieved with the use of targeted molecular therapies for the treatment of Soft Tissue Sarcomas (STS). However, data remain scarce about the potential benefits and toxicity of this therapeutic option. In this narrative review, we aim to better clarify the potential wound healing complications in STS patients undergoing neoadjuvant (NA) radiotherapy (RT) combined with targeted therapies.

Methods: We used the PubMed database to retrieve journal articles, and the inclusion criteria were all studies that illustrated the potential RT toxicity, combined with targeted therapies, in the NA setting of STS patients.

Results: Our search resulted in seven studies that fulfilled the inclusion criteria. Delayed wound complication rates were observed similarly to RT alone, while one study reported intolerable toxicity without referring specifically to wound complications.

Conclusion: The combination of RT with targeted therapies in STS seems to be effective and well tolerated. Due to the lack of studies with a high level of evidence, further research is required to enhance the existing knowledge for its potential value in this field.

Keywords: Soft tissue sarcomas; neoadjuvant treatment; radiotherapy; targeted therapy; vascular endothelial growth factor.; wound complications.

Background: Despite the recent advancements in the treatment of cancer, the 5-year survival of patients with non-small cell lung cancer (NSCLC) remains unsatisfactory. Lung adenocarcinoma (LUAD) is NSCLC's most common subtype, and metastasis is the major cause of death in patients with cancer. Therefore, identifying novel targets associated with metastasis in NSCLC is crucial to improving treatment. This study aimed to characterize the expression of GNGT1 in LUAD and to clarify the mechanism underlying the association between the higher expression level of GNGT1 and worse prognosis in patients.

Methods: The transcriptome datasets and clinical information of patients with LUAD were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. Bioinformatics analyses were performed in 515 patients who were stratified into two groups (high- and low-GNGT1 expression group) according to the GNGT1 level. Overall survival, DNA promotor methylation, immune cell infiltration, gene set enrichment analysis (GSEA), and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to elucidate the functions of GNGT1 and to identify the related hub genes in LUAD. Their expression and functions in LUAD were verified using tissues from patients and transgenic mice overexpressing GNGT1 under the control of a lung-specific promoter (Scgb1a1-Cre).

Results: GNGT1 was overexpressed in patients with LUAD and was associated with poor prognosis. GNGT1 expression was significantly correlated with gene alteration and hypomethylated promoter status. High GNGT1 expression in patients with LUAD was associated with advanced lymph node metastasis and the degree of immune cell infiltration. Functional enrichment analyses indicated that differentially expressed genes (DEGs) in the high-GNGT1 group participated in DNA replication, DNA replication preinitiation, and M phase, while cell adhesion molecules, apoptosis, and natural killer cell-mediated cytotoxicity were all downregulated. Messenger RNA and protein levels were correspondingly regulated in human LUAD tissues and the Scgb1a1-Cre; LSL-GNGT1 mouse model (GNGT1fl/+ mice).

Conclusions: GNGT1 was associated with tumor cell proliferation via the enhancement of tumor cell stemness and interaction with driver genes. Elevated GNGT1 expression promoted epithelial-mesenchymal transformation, remodeled the tumor microenvironment, and led to tumor metastasis, ultimately worsening the survival-related prognosis of patients with LUAD.