EXTH-56. ZIKA VIRUS TREATMENT SIGNIFICANTLY PROLONGS SURVIVAL IN A GLIOBLASTOMA PATIENT DERIVED XENOGRAFT MODEL

The poor median survival for patients with glioblastoma (GBM) of 15 months has not budged for the past 15 years, when the current standard treatment was first approved. There is no standard of care chemotherapy for recurrent GBM. We previously showed that Zika virus (ZIKV) tropism for GBM cells is mediated through the receptor tyrosine kinase, AXL. This infection is cytotoxic. In this study we show that ZIKV is an effective oncolytic virus in a patient derived xenograft model. Fox N1 Nude homozygous female mice 6-8-weeks-old were grouped into 4 experimental arms: two patient derived cell lines, each with a ZIKV treated and a control group. There were 12 mice in each arm. Animals received subcutaneous flank injections of GBM 8049 or its AXL CRISPR knockout 8049 AXLKO (2x106 cells). When tumors reached 200 mm3, mice received intra-tumoral injection of 2.5x106 ZIKV particles or saline. ZIKV induced complete tumor remission in 22 of 24 animals (8049: 11/12; 8049 AXLKO: 11/12). There was no tumor remission in the saline treated animals. Median survival of 8049 and 8049 AXLKO ZIKV treated mice was 124 days and 125 days, respectively. This is compared to median survival of control animals 8049: 42 days; 8049 AXLKO: 46 days (P= 0.001). Among ZIKV treated mice, there were two recurrences: one in the 8049 tumor (24 days after significant tumor remission) and one 8049 AXLKO tumor (7 days after significant tumor remission). We conclude that ZIKV should be considered a candidate oncolytic virus for GBM.

Resolution of pituitary microadenoma after coronavirus disease 2019: a case report

Background This report describes the case of a patient whose pituitary microadenoma resolved after he contracted coronavirus disease 2019. To our knowledge, this is one of the first reported cases of pituitary tumor resolution due to viral illness. We present this case to further investigate the relationship between inflammatory response and tumor remission. Case presentation A 32-year-old man in Yemen presented to the hospital with fever, low blood oxygen saturation, and shortness of breath. The patient was diagnosed with coronavirus disease 2019. Past medical history included pituitary microadenoma that was diagnosed using magnetic resonance imaging and secondary adrenal insufficiency, which was treated with steroids. Due to the severity of coronavirus disease 2019, he was treated with steroids and supportive care. Three months after his initial presentation to the hospital, brain magnetic resonance imaging was performed and compared with past scans. Magnetic resonance imaging revealed changes in the microadenoma, including the disappearance of the hypointense lesion and hyperintense enhancement observed on the previous scan. Conclusions Pituitary adenomas rarely undergo spontaneous resolution. Therefore, we hypothesized that tumor resolution was secondary to an immune response to coronavirus disease 2019.

Two cases reports comparing histopathological features of canine transmissible venereal tumor after treatment with decimal potencies of Viscum Album and Vincristin

The aim of the study was to evaluate the histopathological features of two canine transmissible venereal tumor (TVT) cases: one treated with Viscum album (Q) protocol in serial decimal potencies and the other with Vincristin conventional protocol (treated control). Tumor infiltrating leukocytes pattern and apoptosis were analyzed quantitatively, using a computer image analysis system, twice: before the beginning of treatment and after six weeks. Both female dogs were sujected to weekly clinical evaluation for three months, focusing on tumor remission and eventual adverse effects manifestations (local or systemic). In both the cases, animals had a round cells tumor growth, with weak intercellular stroma connection, typical of a TVT mass. The lysozyme positivity in immunohistochemistry analysis, associated with typical morphology confirmed the diagnosis. Ten fields were randomly photographed by a digital photomicrography system NIKON Eclipse 2 – Coolpix. Each captured image was analyzed quantitatively by the Metamorph® software, considering the number of leukocyte infiltrated and mitosis per field. Caspase 3 positivity index was also evaluated. In Vincristin treated dog, the number of leukocytes infiltrating tumor was bigger than that found in Viscum album treated dog, even before the beginning of the treatment, indicating an initial conditions compatible to a more favorable prognosis, however, the number of leukocytes increased in the Viscum album treated dog during the observation period (Kruskal Wallis, p < 0.05). The animal treated with Vincristine has no statistical significant variation in the number of infiltrating mononuclear cells during the treatment, but presented 10 times more mitotic figures (Kruskal Wallis, p < 0.001) in the second biopsy, compared to the other stages of treatment. There was a statistical significant increase in the rate of positivity for Caspase 3 between biopsies taken before and after treatment with Viscum album (ANOVA, p=0.01), but not after Vincristin treatment. Even though, the tumor remission could be achieved only in Vincristin treated dog, with an abrupt reduction of mitosis number and tumor mass in the last 20 days of treatment. In contrast, a secondary infection of the tumor led to clinical worsening of TVT in Viscum album treated dog, which could explain the increase in the local leukocytes number. The increase in Caspase 3 positivity after treatment shows the Viscum album anti-neoplastic mechanism of action, but in this case it was not enough to reach a complete tumor remission.

Remission of Thymoma on Steroid Therapy in a Patient With Atypical Thymoma-Associated Multiorgan Autoimmunity: A Case Report and Literature Review

In up to 34% of cases, thymoma, itself a rare neoplasm, is accompanied by autoimmune disorders, two of which are thymoma-associated multiorgan autoimmunity (TAMA) and paraneoplastic autoimmune multiorgan syndrome (PAMS). Unfortunately, differential diagnosis between these two entities can be challenging since no strict PAMS definition exists and PAMS can overlap with a subgroup of TAMA patients with skin lesions as leading presentation. We present a case of a 68-year-old woman with a diagnosis of thymoma accompanied by myasthenia gravis, hypothyroidism and GvHD-like mucocutaneous lesions that initially could account to both TAMA and PAMS diagnosis. However, following the exclusion of humoral autoimmunity against components of epithelial cells junction, TAMA was finally established. Interestingly, the introduction of corticosteroid therapy for TAMA symptom management resulted in unexpected partial remission of thymoma with no impact on mucocutaneous lesions. Our case study is an example of two extremely rare phenomena accompanying thymomas: unprecedented TAMA presentation with GvHD-like mucositis, which as we postulate should be placed in the spectrum of TAMA, and tumor remission on steroids.

Immune-Therapy-Related Toxicity Events and Dramatic Remission After a Single Dose of Pembrolizumab Treatment in Metastatic Thymoma: A Case Report

Immune checkpoint inhibitor therapy has become a promising option for the treatment of late-stage thymic epithelial tumors. In this manuscript, we presented a patient with metastatic thymoma administrated of anti-programmed cell death protein 1 (PD-1) antibody pembrolizumab. Although the patient underwent a rapid and dramatic response to one dose of pembrolizumab, she suffered a storm of immune-therapy related toxicity events (irAEs), including liver and kidney dysfunction, hypothyroidism and myocarditis. We didn’t observe &gt;grade 3 irAEs, and proceed with pembrolizumab therapy after the function recovered. Although no guidelines recommend dose reduction of immunotherapy re-treating following initial irAEs, we optimize dose of pembrolizumab to minimize the irAEs induced by PD-1 antibody while maintaining clinical effectiveness. Excitingly, we observe remarkable tumor remission and mild toxicities of half dose of pembrolizumab in this case. In conclusion, the clinical utilization of immunotherapy is an encouraging therapeutic alternative for advanced thymomas. At the same time, patients have to be monitored very carefully, because of the risk to develop irAEs.

Primary nasal cavity Ewing’s sarcoma in pediatric practice: A clinical case

Ewing’s sarcoma is an aggressive tumor rarely found in the head and neck region and extremely rare in the nasal cavity or paranasal sinuses (2-3% of all Ewing’s sarcomas). Purpose: The article presents a clinical diagnostic case of nasal cavity Ewing’s sarcoma finally verified only by IHC test. Results: The presented clinical case describes Ewing’s sarcoma of the nasal cavity in a 14-year-old girl and presents the clinical picture, the results of MRI and CT examination of the sinuses, histopathological and IHC tests. Adequate diagnostical tools made it possible to establish a diagnosis. Timely determined treatment tactics, taking into account the tumor localization and possible postoperative complications, led to tumor remission. At present, the patient is under dynamic observation. Conclusion: The presented clinical case confirms that a primary nasal cavity Ewing’s sarcoma diagnostic largely depends on histopathological examination since visual diagnostic techniques do not provide reliable information on the tumor type.

Primary nasal cavity Ewing’s sarcoma in pediatric practice: A clinical case

Relevance: Ewing’s sarcoma is an aggressive tumor rarely found in the head and neck region and extremely rare in the nasal cavity or paranasal sinuses (2-3% of all Ewing’s sarcomas). Purpose: To presents a clinical diagnostic case of nasal cavity Ewing’s sarcoma finally verified only by IHC test. Results: The presented clinical case describes Ewing’s sarcoma of the nasal cavity in a 14-year-old girl and presents the clinical picture, the results of MRI and CT examination of the sinuses, histopathological and IHC tests. Adequate diagnostical tools made it possible to establish a diagnosis. Timely determined treatment tactics, taking into account the tumor localization and possible postoperative complications, led to tumor remission. At present, the patient is under dynamic observation. Conclusion: The presented clinical case confirms that a primary nasal cavity Ewing’s sarcoma diagnostic largely depends on histopathological examination since visual diagnostic techniques do not provide reliable information on the tumor type.

A Serpin27A-dependent Toll Signaling Underlies Host Genetics of Cancer Resistance in Drosophila

Cancer resistance varies amongst individuals, although its host genetic underpinnings remain largely elusive. Remissions of sarcomas were first reported following repeated injections of patients with mixtures of killed bacteria, Coleys toxins, a phenomenon, which was subsequently causally traced to induction of innate immunity. Here we reveal remission of Drosophila epithelial neoplasms by genetically triggered host innate immunity via Toll signaling. These neoplasms display capacities to receive and, in rare instances, induce Toll signaling. A tumor-induced and progressive Toll signaling, however, did not culminate in tumor suppression. By contrast, Drosophila hosts heterozygous for spn27A1 mutation, which constitutively produce activated Toll ligand, SpzAct, displayed comprehensive tumor remission via Toll-induced, NF-kB-mediated, tumor cell death. Our results reveal a novel node of host genetic cancer resistance via serpin-dependent Toll signaling.