Project description:The incidence and impact of hepatocelluar carcinoma (HCC) continues to increase worldwide. While radical therapies such as resection, radiofrequency ablation or transplantation are potentially curative for patients with early-stage HCC, the majority of patients in routine practice present with more advanced tumors, where treatment goals are palliation and extending survival. With multiple new and promising treatment options emerging for these patients, the challenge for the medical oncologist is how best to integrate these therapies into routine clinical practice. Here we review the most recent data on the efficacy and safety of yttrium-90 radioembolization in HCC, the considerations involved in patient selection, and the optimal assessment and management of patients receiving treatment. We also examine the potential impact of several ongoing clinical trials.
Project description:Pancreatic cancer has traditionally been associated with a dismal prognosis, even in early stages of the disease. In recent years, the introduction of newer generation chemotherapy regimens in the adjuvant setting has improved the survival of patients treated with upfront resection. However, there are multiple theoretical advantages to deliver early systemic therapy in patients with localized pancreatic cancer. So far, the evidence supports the use of neoadjuvant therapy for patients with borderline resectable pancreatic cancer. The benefit of this treatment sequence for patients with resectable disease remains elusive. In this review, we summarize the data on adjuvant therapy for pancreatic cancer and describe which evidence backs the use of neoadjuvant therapy. Additionally, we address important issues faced in clinical practice when treating patients with localized pancreatic cancer.
Project description:Management of early-stage non-small cell lung cancer (NSCLC) consists in multimodal treatment, including surgery, radiotherapy and chemotherapy. The mainstay of treatment is radical surgery. Definitive radiotherapy using stereotactic techniques can provide adequate local disease control, and is the treatment of choice in medically inoperable patients. Most early-stage patients are at significant risk of disease relapse after local treatment. Adjuvant platinum-based chemotherapy has demonstrated to provide an absolute survival benefit of 5% compared to observation. However, unlike advanced/metastatic disease, little progress has been made in the treatment of early-stage NSCLC over the past decade. In recent years, plenty of research has focused on the optimization of adjuvant and neoadjuvant treatment. Several trials with novel drugs, such as targeted agents and immune-checkpoint inhibitors are currently underway, with preliminary positive results. Customization of treatment on patients' characteristics before, and major pathological response after therapy, will further improve survival outcomes in this subset of patients.
Project description:Perioperative treatment with conventional cytotoxic chemotherapy for resectable non-small cell lung cancer (NSCLC) has proven clinical benefits in terms of achieving a higher overall survival (OS) rate. With its success in the palliative treatment of NSCLC, immune checkpoint blockade (ICB) has now become an essential component of treatment, even as neoadjuvant or adjuvant therapy in patients with operable NSCLC. Both pre- and post-surgery ICB applications have proven clinical efficacy in preventing disease recurrence. In addition, neoadjuvant ICB combined with cytotoxic chemotherapy has shown a significantly higher rate of pathologic regression of viable tumors compared with cytotoxic chemotherapy alone. To confirm this, an early signal of OS benefit has been shown in a selected population, with programmed death ligand 1 expression ≥50%. Furthermore, applying ICB both pre- and post-surgery enhances its clinical benefits, as is currently under evaluation in ongoing phase III trials. Simultaneously, as the number of available perioperative treatment options increases, the variables to be considered for making treatment decisions become more complex. Thus, the role of a multidisciplinary team-based treatment approach has not been fully emphasized. This review presents up-to-date pivotal data that lead to practical changes in managing resectable NSCLC. From the medical oncologist's perspective, it is time to dance with surgeons to decide on the sequence of systemic treatment, particularly the ICB-based approach, accompanying surgery for operable NSCLC.
Project description:Thymic carcinoma is a rare neoplasm with a dismal prognosis, and there are no established therapeutic regimens for metastatic or recurrent disease. Immune checkpoint inhibitors (ICIs), such as PD-1/PD-L1 antibodies, are widely approved in several human cancers, contributing to prolonging survival in thoracic tumors. Thymic carcinoma exhibits histologic properties of squamous cell carcinoma (SQC), and resembles the SQC of the lung. ICIs are not approved in thymic carcinoma. Thus, several clinical trials have been undertaken to demonstrate if they are therapeutically effective for patients with thymic carcinoma. In our review, three prospective phase II studies and several case series were discussed in thymic carcinoma. We found that the objective response rate, disease control rate, and progression-free survival in PD-1 blockade monotherapy were approximately 20%, 73%, and four months, respectively. Two exploratory investigations indicated that PD-L1 within tumor cells exhibits a possibility of the therapeutic prediction of PD-1 blockade in thymic carcinoma. Several case reports, alongside their treatment content, have also been reviewed. The therapeutic efficacy of PD-1 blockade monotherapy is still limited in patients with thymic carcinoma. Future perspectives focus on the therapeutic implication of tyrokinase inhibitors plus ICIs or new experimental agents plus ICIs alongside several ongoing experimental studies.
Project description:Lung adenocarcinoma (LADC) and squamous cell carcinoma (LSCC) are the most common non-small cell lung cancer histological phenotypes. Accurate diagnosis distinguishing between these two lung cancer types has clinical significance. For this study, we analyzed four Gene Expression Omnibus (GEO) datasets (GSE28571, GSE37745, GSE43580, and GSE50081). We then imported the datasets into the Gene-Cloud of Biotechnology Information online platform to identify genes differentially expressed in LADC and LSCC. We identified DSG3 (desmoglein 3), KRT5 (keratin 5), KRT6A (keratin 6A), KRT6B (keratin 6B), NKX2-1 (NK2 homeobox 1), SFTA2 (surfactant associated 2), SFTA3 (surfactant associated 3), and TMC5 (transmembrane channel-like 5) as potential biomarkers for distinguishing between LADC and LSCC. Receiver operating characteristic curve analysis suggested that KRT5 had the highest diagnostic value for discriminating between these two cancer types. Using the PrognoScan online survival analysis tool and the Kaplan-Meier Plotter, we found that high KRT6A or KRT6B levels, or low NKX2-1, SFTA3, or TMC5 levels correlated with unfavorable prognoses in LADC patients. Further studies will be needed to verify our findings in additional patient samples, and to elucidate the mechanisms of action of these potential biomarkers in non-small cell lung cancer.
Project description:ObjectiveTo investigate whether computed tomography (CT) and fluorine-18-labeled fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) may be applied to distinguish thymic epithelial tumors (TETs) from benign cysts in the anterior mediastinum.Materials and methodsWe included 262 consecutive patients with pathologically proven TETs and benign cysts 5 cm or smaller who underwent preoperative CT scans. In addition to conventional morphological and ancillary CT findings, the relationship between the lesion and the adjacent mediastinal pleura was evaluated qualitatively and quantitatively. Mean lesion attenuation was measured on CT images. The maximum standardized uptake value (SUVmax) was obtained with FDG-PET scans in 40 patients. CT predictors for TETs were identified with multivariate logistic regression analysis. For validation, we assessed the diagnostic accuracy and inter-observer agreement between four radiologists in a size-matched set of 24 cysts and 24 TETs using a receiver operating characteristic curve before and after being informed of the study findings.ResultsThe multivariate analysis showed that post-contrast attenuation of 60 Hounsfield unit or higher (odds ratio [OR], 12.734; 95% confidence interval [CI], 2.506-64.705; p = 0.002) and the presence of protrusion from the mediastinal pleura (OR, 9.855; 95% CI, 1.749-55.535; p = 0.009) were the strongest CT predictors for TETs. SUVmax was significantly higher in TETs than in cysts (5.3 ± 2.4 vs. 1.1 ± 0.3; p < 0.001). After being informed of the study findings, the readers' area under the curve improved from 0.872-0.955 to 0.949-0.999 (p = 0.066-0.149). Inter-observer kappa values for protrusion were 0.630-0.941.ConclusionPost-contrast CT attenuation, protrusion from the mediastinal pleura, and SUVmax were useful imaging features for distinguishing TETs from cysts in the anterior mediastinum.
Project description:BackgroundLung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) are the leading major histological phenotypes of all non-small cell lung cancer (NSCLC). In this study, the candidate genes and the potential tumorigenesis distinguishing between LUAD and LUSC were analyzed.MethodsThe present study investigated two microarray datasets (GSE28571 and GSE10245) downloaded from the Gene Expression Omnibus (GEO) database. A protein-protein interaction (PPI) network was applied to screen out the candidate genes. In addition, differently expressed genes (DEGs) between lung adenocarcinoma and lung squamous cell carcinoma of the two datasets were functionally analyzed by Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. R 4.0.2 was used to perform Kaplan-Meier analysis of DSG3 (desmoglein 3) and KRT14 (keratin 14) by analyzing the expression and clinical data from The Cancer Genome Atlas (TCGA) database.ResultsThe results revealed that 47 DEGs of the two datasets were ascertained in our study. It was found that the DEGs were mainly involved in pathways related to p63 transcription factor network and validated transcriptional factor targeting TAp63, etc. Based on the analysis, we finally identified DSG3 and KRT14 as potential biomarkers for distinguishing between LUAD and LUSC. These results suggested that DSG3 and KRT14 could have the potential to play an important role in NSCLC patients, as diagnostic markers. At the same time, DSG3 or KRT14 indicated a worse prognosis in LUSC patients, which were associated with pathways relevant to the TRAIL signaling pathway and TNF receptor signaling pathway according to bioinformatic analysis.ConclusionThe DSG3 and KRT14 have the potential to be used as diagnostic markers, which presented here may facilitate improvements in distinguishing between LUAD and LUSC in advanced NSCLC patients.
Project description:Thymic carcinoma is a rare cancer that arises from thymic epithelial cells. Its nature and pathology differ from that of benign thymoma, presenting a poorer prognosis. If surgically resectable, surgery alone or surgery followed by chemoradiotherapy or radiotherapy is recommended by the National Comprehensive Cancer Network Guidelines. Metastatic and refractory thymic carcinomas require systemic pharmacotherapy. Combined carboplatin and paclitaxel, and cisplatin and anthracycline-based regimens have been shown a fair response rate and survival to provide a de facto standard of care when compared with other drugs employed as first-line chemotherapy. Cytotoxic agents have been pivotal for treating thymic carcinoma, as little is known regarding its tumorigenesis. In addition, genetic alterations, including driver mutations, which play an important role in treatments, have not yet been discovered. However, molecular pathways and biomarker studies assessing thymic epithelial tumors have been reported recently, resulting in the development of new agents, such as molecular targeted agents and immune checkpoint inhibitors. As treatment options are currently limited and the prognosis remains poor in metastases and recurrent thymic carcinoma, genetic alterations need to be assessed. In the present review, we focused on the current role of targeted therapies and immune checkpoint inhibitors in treating thymic carcinoma.
Project description:Since the first definition by Hellman and Weichselbaum in 1995, the concept of OligoMetastatic Disease (OMD) is a growing oncology field. It was hypothesized that OMD is a clinical temporal window between localized primary tumor and widespread metastases deserving of potentially curative treatment. In real-world clinical practice, OMD is a "spectrum of disease" that includes a highly heterogeneous population of patients with different prognosis. Metastasis directed therapy with local ablative treatment have proved to be a valid alternative to surgical approach. Stereotactic body radiation therapy demonstrated high local control rate and increased survival outcomes in this setting with a low rate of toxicity. However, there is a lack of consensus regarding many clinical, therapeutic, and prognostic aspects of this disease entity. In this review, we try to summarize the major critical features that could drive radiation oncologists toward a better selection of patients, treatments, and study endpoints. With the help of a set of practical questions, we aim to integrate the literature discussion.