Computational fluid dynamics study of intra-arterial chemotherapy for oral cancer

Abstract Background Intra-arterial chemotherapy (IAC) for oral cancer can deliver a higher concentration of anticancer agent into a tumor-feeding artery than intravenous systemic chemotherapy. However, distribution of anticancer agent into several branches of the external carotid artery (ECA) in IAC has not demonstrated sufficient treatment efficacy. To improve the effectiveness of IAC, the flow distribution of anticancer agent into the branches of the ECA in several IAC methods was investigated using computational fluid dynamics (CFD). Methods Patient-specific three-dimensional vessel models were created from CT images of 2 patients with tongue cancer. Catheter models were combined with the vessel models. Thirty-two models were generated with varying vertical and horizontal positions of the catheter tip. With the use of a zero-dimensional resistance model of the peripheral vessel network, conventional IAC and superselective IAC were simulated in 30 and 2 models, respectively. The flow distribution of anticancer agent into the branches of the ECA was investigated in 32 models. Additionally, the blood streamline was traced from the inlet of the common carotid artery toward each outlet to examine the flow of anticancer agent in all models, and the wall shear stress of the vessel was calculated for some models. Results The CFD simulations could be conducted within a reasonable computational time. In several models, the anticancer agent flowed into the target artery only when the catheter tip was located below the bifurcation of the ECA and each target artery. Furthermore, the anticancer agent tended to flow into the target artery when the catheter tip was shifted toward the target artery. In all ECA branches that had flow of anticancer agent, the blood streamlines to the target arteries contacted the catheter tip. Anticancer agent flowed into only the target artery in patients’ models for superselective IAC. However, high wall shear stress was observed at the target artery in one patient’s model. Conclusions This CFD study showed that location of the catheter tip was important in controlling the anticancer agent in conventional IAC. The distribution rate of anticancer agent into the tumor-feeding artery tended to increase when the catheter tip was placed below and toward the target artery. Although superselective IAC can reliably supply anticancer agent to the target artery, high wall shear stress at the target artery can occur, depending on vessel geometry of the patient, which may cause serious complications during the treatment

Late Onset of Non-islet Cell Tumor Hypoglycemia Managed via Multidisciplinary Treatment in a Patient with a Solitary Fibrous Tumor

Solitary fibrous tumor (SFT) is a rare subtype of soft tissue sarcoma (STS). We herein describe a case of late onset of non-islet cell tumor hypoglycemia (NICTH) that was managed via multidisciplinary treatment in a patient with SFT. A 67-year-old man previously diagnosed with SFT 4 years prior to this presentation and treated with several rounds of surgery, presented with massive tumors. Eighteen months following his prescribed chemotherapy, the patient developed hypoglycemia. He was diagnosed with NICTH, after confirming the presence of high molecular weight insulin-like growth factor-2. This case suggests that paraneoplastic syndrome can occur even in cases of rare cancers, such as STS

Clinicopathologic Features and Immune Microenvironment of Non-Small-cell Lung Cancer With Primary Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors

We evaluated the clinical and immunopathological features of non-small cell lung cancer with primary resistance to epidermal growth factor receptor-tyrosine kinase inhibitors. The rate of smoking was significantly higher in primary resistance. The immune microenvironment characterized by low total tumor infiltrating lymphocytes and negative programmed death ligand 1 correlated significantly with primary resistance. Background: Approximately 20% to 30% of nonesmall-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR)-activating mutations are not responsive to EGFR tyrosine kinase inhibitors (TKIs). Although primary resistance to EGFR-TKIs has been attributed to various genetic alterations, little is known about the clinical and immunopathologic features of patients with primary resistance. The tumor immune microenvironment, including tumorinfiltrating lymphocytes (TILs) and programmed cell death ligand 1 (PD-L1), has been reported to play an important role in tumor progression in those with NSCLC. However, few studies have directly focused on the relationship between the tumor immunemicroenvironment and primary resistance to EGFR-TKIs. Materials and Methods: The characteristics of 124 NSCLC patients with EGFR mutations who had received EGFR-TKIs were analyzed. Primary resistance was defined as disease progression within 3 months after EGFR-TKI treatment. Tumor specimens obtained before EGFRTKI treatment were assessed for the density of TILs expressing CD4 or CD8 and for the expression rate of PD-L1 on tumor cells and tumor-infiltrating immune cells, immunohistochemically. Results: Primary resistance was observed in 13.7% of the patients (17 of 124). A significant difference in smoking history was observed between patients with primary resistance and those with noneprimary resistance. A lower density of total TILs and negative PD-L1 expression on immunohistochemical analysis correlated significantly with primary resistance, in contrast to that with noneprimary resistance. Moreover, the negative PD-L1 expression with low TIL density, indicating immune ignorant phenotype of tumor microenvironment, was observed in those with primary resistance with a significant difference. Conclusion: Smoking and immune ignorance in the tumor microenvironment might result in primary resistance to EGFR-TKIs

Early prediction of lenvatinib treatment efficacy by using 18F-FDG PET/CT in patients with unresectable or advanced thyroid carcinoma that is refractory to radioiodine treatment : a protocol for a non-randomized single-arm multicenter observational study

Introduction: Lenvatinib, an oral molecular targeted drug, is used to treat patients with unresectable or advanced thyroid carcinoma that is refractory to radioiodine treatment. Effective methods for evaluating molecular targeted drugs are a critical unmet need owing to their expensive costs and unique adverse events. The aim of this study is to determine whether 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT at 1 week after commencing lenvatinib can predict treatment outcomes. Design and methods: This study is planned as a non-randomised single-arm multicentre study; patients with pathologically confirmed differentiated thyroid carcinoma (DTC) with lesions that are refractory to radioiodine treatment are eligible. The main exclusion criteria are medullary or anaplastic carcinoma, prior treatment with chemotherapy, poor general condition and thromboembolism-requiring treatment. Patients to be included in the study will be treated with lenvatinib and undergo FDG-PET/CT examination twice: before and 1 week after the initiation of treatment. Contrast-enhanced CT, the gold standard for evaluation, will be performed at least 4 weeks after the initiation of treatment. The primary objective is to evaluate the ability of the lesion maximum standard uptake value for FDG PET/CT performed 1 week after the initiation of treatment to predict outcomes compared with the response evaluation obtained via contrast-enhanced CT performed at least 4 weeks after the initiation of treatment. Ethics and dissemination: This study is conducted in accordance with the Declaration of Helsinki and has received ethical approval from the institutional review board of the Hokkaido University Hospital (approval number: 015-402). The results of this study will be disseminated through a presentation at a conference and the publication of the data in a peer-reviewed journal. The study will be implemented and reported in line with the SPIRIT statement. Trial registration number: UMIN000022592

Impact of clinical targeted sequencing on endocrine responsiveness in estrogen receptor-positive, HER2-negative metastatic breast cancer

Clinical targeted sequencing allows for the selection of patients expected to have a better treatment response, and reveals mechanisms of resistance to molecular targeted therapies based on actionable gene mutations. We underwent comprehensive genomic testing with either our original in-house CLHURC system or with OncoPrime. Samples from 24 patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer underwent targeted sequencing between 2016 and 2018. Germline and somatic gene alterations and patients' prognosis were retrospectively analyzed according to the response to endocrine therapy. All of the patients had one or more germline and/or somatic gene alterations. Four patients with primary or secondary endocrine-resistant breast cancer harbored germline pathogenic variants of BRCA1, BRCA2, or PTEN. Among somatic gene alterations, TP53, PIK3CA, AKT1, ESR1, and MYC were the most frequently mutated genes. TP53 gene mutation was more frequently observed in patients with primary endocrine resistance compared to those with secondary endocrine resistance or endocrine-responsive breast cancer. Recurrent breast cancer patients carrying TP53-mutant tumors had significantly worse overall survival compared to those with TP53-wild type tumors. Our 160-gene cancer panel will be useful to identify clinically actionable gene alterations in breast cancer in clinical practice