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Aim: Lymph node (LN) metastases are associated with poor outcomes in patients with recurrent larynx squamous cell carcinoma (LSCC). Neck dissection (ND) is therefore commonly performed along with salvage total laryngectomy (STL). Here, we assess the rate of occult LN metastases and the diagnostic value of MRI and PET/CT for detecting them in recurrent LSCC.Methods: This retrospective study included patients with recurrent LSCC after primary (chemo)radiotherapy [(C)RT] who were re-staged by MRI and/or PET/CT and treated with STL and ND between 2004 and 2019. The histopathology of ND samples was used as the reference standard.Results: Forty-one patients were included. The prevalence of occult metastases in MRI-negative and PET/CT-negative neck nodes was between 3.2% and 6.1%. Negative predictive values of neck node re-staging were 93.9% for MRI, 96.8% for PET/CT, and 96.2% for MRI and PET/CT combined.Conclusion: Both MRI and PET/CT afforded good negative predictive values for nodal staging in patients with recurrent LSCC after (C)RT prior to STL. In selected patients, these radiological modalities, particularly PET/CT, could help to avoid unnecessary surgery to the neck and its associated morbidity. LESS      Full article

Malignant pleural mesothelioma (MPM) is an aggressive and recalcitrant surface neoplasm that defies current multimodality treatments. MicroRNAs (miRNAs) are small noncoding RNAs that epigenetically regulate multiple gene networks and cellular processes. In cancer, miRNA dysregulation is associated with tumorigenesis, with tumor suppressor miRNAs underexpressed or lost, while oncogenic miRNAs are overexpressed. Consequently, miRNAs have emerged as potential therapeutic candidates. Because loss of tumor suppressors predominates the pathophysiology of MPM, re-expressing tumor suppressor miRNAs could be an effective therapeutic strategy. This review highlights the most promising MPM-specific tumor suppressor miRNAs that could be developed into novel therapeutics, the supporting data, and what is known about their molecular mechanism(s). LESS      Full article

Clinical development of new treatment options for patients with pancreatic cancer has been slow and expensive and resulted in few effective therapies. With a dismal five-year survival rate of 11% in the U.S., pancreatic cancer remains the third leading cause of cancer-related deaths and is poised to move to second by 2030. Standard clinical trials typically compare one investigational treatment to one standard of care, encompass one phase of clinical investigation at a time, and treat one patient population. Accrual and data analysis are often very slow, and unfortunately, the vast majority of clinical trials targeting pancreatic cancer patients are unsuccessful. More efficient clinical trial designs can include combining phases I and II or phases II and III, and trials that involve a master protocol approach can also answer multiple clinical questions simultaneously. These modern clinical trial designs can allow a faster, more efficient and cost-effective approach to testing investigational therapies in patients with pancreatic cancer and, most importantly, fewer patients may be required to determine the efficacy of treatment. Herein we summarize some of the recent innovative clinical trials in pancreatic cancer to provide meaningful data toward developing new treatment options to benefit patients with a dismal disease like pancreatic cancer. LESS      Full article

Radiological imaging has a critical role in the diagnosis of sarcomas and in evaluating therapy response assessment. The current gold standard for response assessment in solid tumors is the Response Evaluation Criteria in Solid Tumors, which evaluates changes in tumor size as a surrogate endpoint for therapeutic efficacy. However, tumors may undergo necrosis, changes in vascularization or become cystic in response to therapy, with no significant volume changes; thus, size assessments alone may not be adequate. Such morphological changes may give rise to radiographic phenotypes that are not easily detected by human operators. Fortunately, recent advances in high-performance computing and machine learning algorithms have enabled deep analysis of radiological images to extract features that can provide richer information about intensity, shape, size or volume, and texture of tumor phenotypes. There is growing evidence to suggest that these image-derived or “radiomic features” are sensitive to biological processes such as necrosis and glucose metabolism. Thus, radiomics could prove to be a critical tool for assessing treatment response and may present an integral complement to existing response criteria, opening new avenues for patient assessment in sarcoma trials. LESS      Full article

Malignant pleural mesothelioma (MPM) is an aggressive and rare disease, mainly due to asbestos exposure, characterized by a poor prognosis. For almost two decades, platinum-based chemotherapy has been the only approved therapeutic regimen for first-line MPM, with an overall survival of 12 months. In the last years, the therapeutic scenario of different tumor types, including MPM, has dramatically changed due to immune checkpoint inhibition. The promising results of this approach have promoted new efforts into clinical research, and many trials investigating novel therapeutic combinations are currently ongoing. The aim of the present review is to provide a comprehensive overview of the most promising immunotherapeutic-based strategies currently under investigation for advanced MPM. LESS      Full article

This review provides an overview of articles about peritoneal mesothelioma (PM) to analyze the effect of treatment modalities on response rates, post-treatment side effects, morbidity and mortality, and survival. Median survival in months following systemic chemotherapy (SC) ranged from 8.7 to 26.8 months. However, no patient was reported to have survived for more than five years with SC alone. In contrast, comprehensive treatment that included cytoreductive surgery (CRS) + perioperative chemotherapy (POC) showed a significantly longer median survival time than SC alone. Additionally, CRS + POC demonstrated 10-year survival rates of 12%-35%. Accordingly, CRS + POC is an innovative treatment that provides long-term survival in selected patients with PM. Selection criteria are performance status (ECOG PS ≤ 1), the absence of extraperitoneal metastasis, PCI less than cutoff levels (from < 10 to < 28), MIB-1 index (< 10), and histologic type (epithelioid type). Postoperative morbidity and mortality rates after CRS + POC were significantly higher than with more conventional operations. Accordingly, CRS and POC should be done at the specialized peritoneal surface malignancy centers. LESS      Full article

Aim: Neuroblastoma is the most common extracranial solid tumor in children. Recent advances in immunotherapy Approaches, including in neuroblastoma, have shown the important role of the immune system in mounting an effective anti-tumor response. In this study, we aimed to provide a comprehensive investigation of immune cell infiltration in neuroblastoma utilizing a large number of gene expression datasets.Methods: We inferred immune cell infiltration using an established immune inference method and evaluated the association between immune cell abundance and patient prognosis as well as common chromosomal abnormalities found in neuroblastoma. In addition, we evaluated co-infiltration patterns among distinct immune cell types.Results: The infiltration of naïve B cells, NK cells, and CD8+ T cells was associated with improved patient prognosis. Naïve B cells were the most consistent indicator of prognosis and associated with an active immune tumor microenvironment. Patients with high B cell infiltration showed high co-infiltration of other immune cell types and the enrichment of immune-related pathways. The presence of high B cell infiltration was associated with both recurrence-free and overall survival, even after adjusting for clinical variables.Conclusion: In this study, we have provided a comprehensive evaluation of immune cell infiltration in neuroblastoma using gene expression data. We propose an important role for B cells in the neuroblastoma tumor microenvironment and suggest that B cells can be used as a prognostic biomarker to predict recurrence-free and overall survival independently of currently utilized prognostic variables. LESS      Full article

The RAS gene family, responsible for signal transduction within the mitogen activated protein kinase (MAPK) and phosphatidylinositol 3 kinase (PI3K) pathways, is frequently involved in carcinogenesis, and alterations in its member genes can be detected, with variable frequency, in a wide variety of solid and hematological cancers. These alterations may behave as prognostic-predictive biomarkers and driver mutations, making them an interesting therapeutic target. Since their discovery, many strategies have been pursued to act on their signaling pathways. Indeed, in clinical practice, KRAS, the most prominent member of the RAS gene family, represents an especially elusive target in most malignancies; pathway inhibition is carried out upstream, on the EGFR receptor, or downstream, most frequently on the BRAF/MEK/ERK cascade. Recently, clinically relevant direct RAS inhibition has been successfully achieved with the development of potent and selective covalent inhibitors of KRAS c.34G>T (p.G12C). These latest-generation drugs represent both a new and interesting tool in the therapeutic armamentarium and a symbolic end to the myth of KRAS undruggability. However, their clinical relevance and appropriate place in treatment strategies remain to be determined. LESS      Full article

Liquid biopsy, including both circulating tumor cells and circulating tumor DNA, is gaining momentum as a diagnostic modality adopted in the clinical management of breast cancer. Prospective studies testing several technologies demonstrated clinical validity and, in some cases, achieved the United States Food and Drug Administration approval. The initial testing and clinical application of liquid biopsy focused primarily on the diagnosis, while molecular characterization and monitoring of metastatic disease, with larger data from prospective studies, came in the last two decades. Although its role in metastatic setting is thus widely recognized, the current evidence does not provide support for the routine clinical use of liquid biopsy methods for the earlier stage of this disease. Considering the relevance of early detection, characterization, and management of breast cancer in the early-stage, this clinical setting is the most suitable to increase the chances for effective treatment selection and improved prognosis, and a better understanding of the main application of liquid biopsy tools in the earlier stage of breast cancer is therefore crucial. The aim of this review is to provide an overview of the clinical evidence and subsequent potential applications of liquid biopsy in early breast cancer, identifying the main existing caveats and the possible future scenarios. LESS      Full article

Aim: The present in silico study aimed to evaluate the ATP-binding cassette (ABC) transporter inhibition potential of Bulbine frutescens (B. frutescens) phytochemicals.Methods: Several previous studies and databases were used to retrieve the ligands and target protein structure. The molecular docking study was performed using the Auto Dock Tools, and the GROMACS package was applied to accomplish molecular dynamics simulation.Results: Utilizing the molecular docking and simulation approach, ~25 phytochemicals were screened against the ABC transporter protein. Docking score analysis revealed that B. frutescens phytochemical 4’-Demethylknipholone 2’-β-D-glucopyranoside exhibited strong binding on the ABC transporter protein with a minimum binding score -9.8 kcal/mol in comparison to the standard ABC transporter inhibitor diltiazem (-6.86 kcal/mol). Furthermore, molecular dynamics simulation for 4’-Demethylknipholone 2’-β-D-glucopyranoside showed an acceptable root mean square deviation, radius of gyration, root mean square fluctuation, and hydrogen bond, in addition to other lead compounds.Conclusion: The in-silico study demonstrated that B. frutescens phytochemical 4’-Demethylknipholone 2’-β-D-glucopyranoside possesses anti-drug resistance properties and requires further testing in preclinical settings. LESS      Full article