Thymic Carcinoid Responds to Neoadjuvant Therapy with Sunitinib and Octreotide: A Case Report

Carcinoids are malignant neuroendocrine tumors consisting of a spectrum of neoplasms from low-grade typical carcinoid to high-grade small cell carcinoma. We report a case of atypical thymic carcinoid that responded to neoadjuvant therapy with octreotide and sunitinib, an oral multikinase inhibitor. After 3 weeks of treatment, tumor size significantly decreased to allow for a safe surgical resection with clear margins. We believe that further study of sunitinib and octreotide with the neoadjuvant intent of preparing tumors for resection is warranted as a strategy to improve curative management of neuroendocrine tumors

Exploring Complex Networks with Graph Investigator Research Application

This paper describes Graph Investigator, the application intended for analysis of complex networks. A rich set of application functions is briefly described including graph feature generation, comparison, visualization and edition. The program enables to analyze global and local structural properties of networks with the use of various descriptors derived from graph theory. Furthermore, it allows to quantify inter-graph similarity by embedding graph patterns into low-dimensional space or distance measurement based on feature vectors. The set of available graph descriptors includes over eighty statistical and algebraic measures. We present two examples of real-world networks analysis performed with Graph Investigator: comparison of brain vasculature with structurally similar artificial networks and analysis of vertices importance in a macaque cortical connectivity network. The third example describes tracking parameters of artificial vascular network evolving in the process of angiogenesis, modelled with the use of cellular automata

Convolutional Neural Networks for Segmentation of Malignant Pleural Mesothelioma: Analysis of Probability Map Thresholds (CALGB 30901, Alliance)

Malignant pleural mesothelioma (MPM) is the most common form of mesothelioma. To assess response to treatment, tumor measurements are acquired and evaluated based on a patient's longitudinal computed tomography (CT) scans. Tumor volume, however, is the more accurate metric for assessing tumor burden and response. Automated segmentation methods using deep learning can be employed to acquire volume, which otherwise is a tedious task performed manually. The deep learning-based tumor volume and contours can then be compared with a standard reference to assess the robustness of the automated segmentations. The purpose of this study was to evaluate the impact of probability map threshold on MPM tumor delineations generated using a convolutional neural network (CNN). Eighty-eight CT scans from 21 MPM patients were segmented by a VGG16/U-Net CNN. A radiologist modified the contours generated at a 0.5 probability threshold. Percent difference of tumor volume and overlap using the Dice Similarity Coefficient (DSC) were compared between the standard reference provided by the radiologist and CNN outputs for thresholds ranging from 0.001 to 0.9. CNN annotations consistently yielded smaller tumor volumes than radiologist contours. Reducing the probability threshold from 0.5 to 0.1 decreased the absolute percent volume difference, on average, from 43.96% to 24.18%. Median and mean DSC ranged from 0.58 to 0.60, with a peak at a threshold of 0.5; no distinct threshold was found for percent volume difference. No single output threshold in the CNN probability maps was optimal for both tumor volume and DSC. This work underscores the need to assess tumor volume and spatial overlap when evaluating CNN performance. While automated segmentations may yield comparable tumor volumes to that of the reference standard, the spatial region delineated by the CNN at a specific threshold is equally important.Comment: 10 pages, 7 figures, 2 table

Large-cell neuroendocrine carcinoma of the cervix

Large cell neuroendocrine carcinoma (LCNEC) of the uterine cervix is a rare and aggressive malignancy with poor prognosis even in its early stage, despite multimodality treatment strategy. Here, we report a case of a woman with clinical polypoid stage IB LCNEC of the cervix, which was detected in her 6-week postpartum checkup. A literature review was also conducted to evaluate current therapeutic approaches and potential new strategies

Alliance Foundation Trial 09: A randomized, multicenter, phase 2 trial evaluating two sequences of pembrolizumab and standard platinum-based chemotherapy in patients with metastatic NSCLC

INTRODUCTION: The sequence of chemotherapy and pembrolizumab may affect antitumor immune response and efficacy of immunotherapy. METHODS: This multicenter, randomized, phase 2 trial was designed to evaluate the efficacy of two sequences of chemotherapy and pembrolizumab in patients with stage 4 NSCLC. Both arms were considered investigational, and the study used a pick a winner design. The primary end point was objective response rate by independent radiologic review after eight cycles (24 wk). Patients were randomized 1:1 to arm A (chemotherapy for four cycles followed by pembrolizumab for four cycles) or arm B (pembrolizumab for four cycles followed by chemotherapy for four cycles). Patients in both arms without disease progression after the initial eight cycles continued pembrolizumab until disease progression, unacceptable toxicity, or a maximum of 2 years. RESULTS: From March 2016 to July 2018, a total of 90 eligible patients were randomized (43 patients to arm A and 47 patients to arm B). The objective response rate at 24 weeks in arms A and B was 39.5 % (95 % confidence interval [CI]: 24.9%-54.1 %) and 40.4 % (95 % CI: 26.4%-54.5 %), respectively ( CONCLUSIONS: Additional evaluation of either sequence in a phase 3 trial is not warranted

Metanephric adenoma of the kidney: an unusual diagnostic challenge

Although metanephric adenoma (MA) is a rare, benign neoplasm of epithelial cells, it is often difficult to distinguish this entity from other malignant neoplasms preoperatively. We report a case of a large renal mass for which preoperative diagnosis was indeterminate, with the differential diagnosis including Wilm’s tumor, MA, and papillary renal cell carcinoma (PRCC). Accurate postoperative differentiation of MA from PRCC is critical because adjuvant therapy is considered after surgical resection of PRCC tumors

Phase 1/2 Dose Escalating Study of Twice-Monthly Pemetrexed and Gemcitabine in Patients with Advanced Cancer and Non-small Cell Lung Cancer

IntroductionPemetrexed is synergistic with gemcitabine in preclinical models of non-small cell lung cancer (NSCLC). The optimal dose and utility of gemcitabine and pemetrexed was evaluated in a dose-escalating study.MethodsThe phase 1 study included patients with advanced tumors, whereas the phase 2 study included patients with locally advanced or metastatic NSCLC. Gemcitabine was infused over 30 minutes, followed by pemetrexed administered over 10 minutes on day 1 of a 14-day cycle. Treatment continued for 12 cycles or until disease progression. All patients received folic acid, Vitamin B12, and steroid prophylaxis.ResultsMaximum tolerated dose was gemcitabine 1500 mg/m2, followed by pemetrexed 500 mg/m2. Fifty-three patients (29 male, 24 female) were enrolled in the phase 2 study. Response rate was 20.8% (95% CI: 0.108–0.341), and the clinical benefit rate (CR + PR + SD) was 64.2%. Median time to disease progression was 4.6 months (95% CI: 2.79–6.18), median survival was 10.1 month (95% CI: 5.95–14.09, censorship = 20.75%), and 1-year survival was 41.0%. Common grade 3 or 4 adverse events (% of patients) were neutropenia (28.3%), fatigue (22.6%), and febrile neutropenia (9.4%).ConclusionsTwice-monthly gemcitabine and pemetrexed was well tolerated, with overall survival and clinical benefit indicating disease activity in NSCLC patients

A phase I oncolytic virus trial with vesicular stomatitis virus expressing human interferon beta and tyrosinase related protein 1 administered intratumorally and intravenously in uveal melanoma: safety, efficacy, and T cell responses

IntroductionMetastatic uveal melanoma (MUM) has a poor prognosis and treatment options are limited. These patients do not typically experience durable responses to immune checkpoint inhibitors (ICIs). Oncolytic viruses (OV) represent a novel approach to immunotherapy for patients with MUM.MethodsWe developed an OV with a Vesicular Stomatitis Virus (VSV) vector modified to express interferon-beta (IFN-β) and Tyrosinase Related Protein 1 (TYRP1) (VSV-IFNβ-TYRP1), and conducted a Phase 1 clinical trial with a 3 + 3 design in patients with MUM. VSV-IFNβ-TYRP1 was injected into a liver metastasis, then administered on the same day as a single intravenous (IV) infusion. The primary objective was safety. Efficacy was a secondary objective.Results12 patients with previously treated MUM were enrolled. Median follow up was 19.1 months. 4 dose levels (DLs) were evaluated. One patient at DL4 experienced dose limiting toxicities (DLTs), including decreased platelet count (grade 3), increased aspartate aminotransferase (AST), and cytokine release syndrome (CRS). 4 patients had stable disease (SD) and 8 patients had progressive disease (PD). Interferon gamma (IFNγ) ELIspot data showed that more patients developed a T cell response to virus encoded TYRP1 at higher DLs, and a subset of patients also had a response to other melanoma antigens, including gp100, suggesting epitope spreading. 3 of the patients who responded to additional melanoma antigens were next treated with ICIs, and 2 of these patients experienced durable responses.DiscussionOur study found that VSV-IFNβ -TYRP1 can be safely administered via intratumoral (IT) and IV routes in a previously treated population of patients with MUM. Although there were no clear objective radiographic responses to VSV-IFNβ-TYRP1, dose-dependent immunogenicity to TYRP1 and other melanoma antigens was seen