T Cells Directed against the Metastatic Driver Chondromodulin-1 in Ewing Sarcoma: Comparative Engineering with CRISPR/Cas9 vs. Retroviral Gene Transfer for Adoptive Transfer.

Ewing sarcoma (EwS) is a highly malignant sarcoma of bone and soft tissue with early metastatic spread and an age peak in early puberty. The prognosis in advanced stages is still dismal, and the long-term effects of established therapies are severe. Efficacious targeted therapies are urgently needed. Our previous work has provided preliminary safety and efficacy data utilizing T cell receptor (TCR) transgenic T cells, generated by retroviral gene transfer, targeting HLA-restricted peptides on the tumor cell derived from metastatic drivers. Here, we compared T cells engineered with either CRISPR/Cas9 or retroviral gene transfer. Firstly, we confirmed the feasibility of the orthotopic replacement of the endogenous TCR by CRISPR/Cas9 with a TCR targeting our canonical metastatic driver chondromodulin-1 (CHM1). CRISPR/Cas9-engineered T cell products specifically recognized and killed HLA-A*02:01+ EwS cell lines. The efficiency of retroviral transduction was higher compared to CRISPR/Cas9 gene editing. Both engineered T cell products specifically recognized tumor cells and elicited cytotoxicity, with CRISPR/Cas9 engineered T cells providing prolonged cytotoxic activity. In conclusion, T cells engineered with CRISPR/Cas9 could be feasible for immunotherapy of EwS and may have the advantage of more prolonged cytotoxic activity, as compared to T cells engineered with retroviral gene transfer.

Ewing's Sarcoma in a 58-Year-Old Man: Oncological Diagnosis in the Time of COVID-19

Ewing's sarcoma is a rare and extremely aggressive neoplasm with a tendency to recur even after radical surgery and a tendency to early metastasis. This cancer is characteristic of the pediatric population because the peak incidence of this type of cancer occurs in patients between 10 and 20 years of age, but about 30% of cases occur in older patients. We present a case of Ewing's sarcoma in a 58-year-old man with a foot tumor manifestation with a history of back and left leg pain. Due to a lung tumor in the chest X-ray, the patient was referred to the Pulmonology Department, however, the diagnosis was postponed for many months, which in the case of an aggressive tumor, such as Ewing's sarcoma, significantly worsened the initially unfavorable prognosis. The COVID-19 pandemic is having a strong impact on the healthcare systems of countries around the world. Reorganizing medical care and focusing on the pandemic has an impact on the diagnosis and treatment of other diseases. In the current situation, we observe an increase in the number of patients presenting at an advanced stage of the disease, which excludes the possibility of radical treatment. Fear of infection causes both patients to avoid diagnosing disease by focusing on acute symptomatic treatment. The discussed case shows the possible impact of the epidemiological situation of the COVID19 pandemic on the diagnosis and treatment of oncology.

Successful extracorporeal membrane oxygenation therapy in a child with coronavirus 2019 disease-associated ARDS and chemotherapy for Ewing's sarcoma.

Most children and adolescents with SARS-CoV-2 infection show no or mild symptoms, but those with medical histories can be susceptible to more severe forms of disease. There are few reported cases of extracorporeal membrane oxygenation (ECMO) in pediatric patients with coronavirus disease 2019 (COVID-19). We present a previously healthy 13-year-old male diagnosed with metastatic Ewing's sarcoma at the same time as catastrophic acute respiratory distress syndrome due to COVID-19, who was successfully supported by venovenous-ECMO while he received the corresponding chemotherapy protocol.ECMO can be used as salvage therapy in oncology pediatric patients with respiratory failure secondary to COVID-19. In addition, successful chemotherapy can be administered while patients are supported on ECMO.

Sudden unexpected death in a 17-year-old boy due to unacknowledged adamantinoma-like Ewing sarcoma.

A 17-year-old male with no previous medical history was admitted 2 days before his death to a local hospital after mild dyspnea. Electrocardiography, chest radiography, and blood analysis revealed no abnormalities. Blood oxygen saturation was 99%, and SARS-CoV-2 nasopharyngeal swabs tested negative; thus, he was discharged without prescriptions. After 2 days, the subject died suddenly during a pool party. Forensic autopsy was performed analyzing all anatomical districts. Cardiac causes were fully excluded after deep macroscopic and microscopic evaluation; lung and brain analyses showed no macroscopic pathology. Finally, a large subglottic solid mass was detected. The whitish neoplasm showed an aggressive invasion pattern to the thyroid and adjacent deep soft tissues and occluded the trachea. High-power microscopy showed sheets of small, uniform cells with scant cytoplasm; round nuclei; and small, punctate nucleoli, with immunohistochemical expression of CK8-18, AE1/AE3, and CD99. Using FISH analysis, the break-apart molecular probes (EWSR1 (22q12) Break - XL, Leica Biosystem, Nussloch, Germany) showed distinct broken red and green fluorochromes, diagnostic of Ewing sarcoma. The neoplasm was characterized as adamantinoma-like Ewing sarcoma, and the mechanism of death was identified as airway obstruction. The rarity of the case resides in the circumstances of death, which pointed to the possibility of sudden unexpected death due to heart disease, but an oncological cause and the underlying mechanism were finally diagnosed. The best method to perform autopsies is still complete, extensive, and systematic macroscopic sampling of organs and districts followed by histopathological analysis, in addition to immunohistochemical and molecular investigations in those cases in which they are necessary. In fact, when neoplasms are detected, the application of advanced techniques such as immunohistochemistry and molecular diagnostics is fundamental to accurately certify death.

Changes in the Management of Malignant Bone Tumors in the COVID-19 Pandemic in Developing Countries.

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has drastically affected healthcare delivery to cancer patients, including those with malignant bone tumors, worldwide. Such cancer patients are more susceptible to COVID-19 infection and risk contracting the severe disease, but their holistic tumor management has also suffered a significant impact. Because of the acute shortage of healthcare resources due to their diversion in COVID management, substantial changes are needed in various aspects of management for high-grade tumor patients, particularly in developing countries and population-dense regions, so that their evidence-based appropriate treatment is ensured. Owing to a lack of consensus regarding the ideal course of action for the management of malignant bone tumors in the current situation, many such patients often get neglected, leading to loss of life/limb. This review elaborates on various guidelines proposed by different healthcare organizations and institutes regarding the modified care pathways for malignant bone neoplasms in the current coronavirus pandemic. The early published results of these modified care pathways and the changes in the oncology practice brought about by the pandemic are also discussed.

International society for stem cell research (ISSCR) – 19thannual meeting

The Annual Meeting of the International Society for Stem Cell Research (ISSCR) brought together experts from across the world in the field of stem cell therapy research and regenerative medicine. The sessions were organized around 5 main themes: clinical applications, cellular identity, modeling development & disease, new technologies, and tissue stem cell & regeneration. This report covers some of the highlights of the virtual meeting.

Feasibility and safety of outpatient administration of ifosfamide and etoposide for pediatric patients with Ewing sarcoma in a resource-limited setting amid the COVID-19 pandemic.

BACKGROUND: To assess feasibility and safety of outpatient administration of ifosfamide and etoposide (IE) for pediatric Ewing sarcoma (EWS) patients in a resource-limited setting amid the COVID-19 pandemic. MATERIALS AND METHODS: Retrospective study of patients with EWS who received outpatient IE from January 2020 until January 2021 at our institution. Ifosfamide 1800 mg/m2 was given for 5 days with MESNA (2-mercaptoethane sulfonate sodium) infusion and additional boluses before and after 9 hours of hydration. Patients >10 years of age with the ability to drink orally at home, no pre-existing renal dysfunction or history of hematuria were included. They were monitored for hemorrhagic cystitis with a urine dipstick before, midway, and at end of infusion. A urine analysis was done 24 hours after the last dose of ifosfamide. RESULTS: Forty-seven (100%) cycles were given as outpatient during the study period. Thirty-five (74%) cycles were given on time, two (4%) cycles were delayed due to mucositis, two (4%) due to delayed count recovery, and eight (18%) due to unavailability of outpatient appointments. The median interval between these cycles was 15 days (range 14-44 days). No episode of hemorrhagic cystitis was reported. Urine analysis was not done at 24 hours for 27 (58%) cycles, so microscopic hematuria may have been missed. This outpatient protocol saved 32% (USD 299) per cycle in cost and 282 days of hospitalization. CONCLUSION: Outpatient administration of IE for pediatric patients with EWS is feasible, safe, and cost-effective during the COVID-19 pandemic.

A large femoral primary cutaneous Ewing's sarcoma in a 35-year-old woman: Case report.

INTRODUCTION: Extraskeletal Ewing's sarcoma is a rare malignant tumor of mesenchymal origin, which is histologically similar to primary osseous Ewing's sarcoma. It has been well described in deep soft tissues. However, location in cutaneous or subcutaneous tissue has rarely been reported. Being seen principally in children, it can be seen, rarely, in old men. CASE PRESENTATION: We present a case of large primary cutaneous Ewing sarcoma within the left thigh of a 35-year-old woman, without osseous involvement. Physical examination. Histologically, it was a small round cell tumor that marked strongly for CD99. The diagnosis of cutaneous Ewing sarcoma was performed. DISCUSSION: The things that distinguish our case are that it is the first case in Syria, in addition to the size of the large tumor with diameters of 15 × 20 cm, and it is in a 35-year-old woman. CONCLUSION: Ewing sarcoma is a rare malignant small round cell tumor of the skin and subcutaneous tissue. It should be differentiated from other cutaneous neoplasms composed of small round cells.