Successful ECMO therapy in a child with COVID-19-associated ARDS and Ewing's Sarcoma. (preprint)

Most children and adolescents with SARS-CoV-2 infection shows asymptomatically or with mild symptoms. 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, which was successfully supported by veno-venous 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.

Extended Neoadjuvant Chemotherapy in Delayed Primary Resection of Ewing Sarcoma During the COVID-19 Era: A Case Report.

CASE: A 13-year-old adolescent boy visited our hospital with a growing mass on his left leg. Investigations and examinations were performed to obtain a final diagnosis of Ewing sarcoma in the head of the left fibula with lung metastasis. Neoadjuvant chemotherapy was extended to 11 courses with radiation before wide tumor resection could be performed. The final 3 adjuvant chemotherapy courses were administered to complete the original protocol while surgical resection complications were also treated. The pathological report revealed free margin resection with nonviable tumor cells. CONCLUSION: An extended neoadjuvant chemotherapy regimen with additional radiation therapy for Ewing sarcoma provided extra local control and allowed limb salvage.

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.

The impact of lag time to cancer diagnosis and treatment on clinical outcomes prior to the COVID-19 pandemic: a scoping review of systematic reviews and meta-analyses (preprint)

Background: The COVID-19 pandemic has disrupted cancer care, raising concerns regarding the impact of wait time, or lag time, on clinical outcomes. We aimed to contextualize pandemic-related lag times by mapping pre-pandemic evidence from systematic reviews and/or meta-analyses on the association between lag time to cancer diagnosis and treatment with mortality- and morbidity-related outcomes. Methods: We systematically searched MEDLINE, EMBASE, Web of Science, and Cochrane Library of Systematic Reviews for reviews published prior to the pandemic (1 January 2010-31 December 2019). We extracted data on methodological characteristics, lag time interval start and endpoints, qualitative findings from systematic reviews, and pooled risk estimates of mortality- (i.e., overall survival) and morbidity- (i.e., local regional control) related outcomes from meta-analyses. We categorized lag times according to milestones across the cancer care continuum and summarized outcomes by cancer site and lag time interval. Results: We identified 9,032 records through database searches, of which 29 were eligible. We classified 33 unique types of lag time intervals across 10 cancer sites, of which breast, colorectal, head and neck, and ovarian cancers were investigated most. Two systematic reviews investigating lag time to diagnosis reported contradictory findings regarding survival outcomes among pediatric patients with Ewing's sarcomas or central nervous system tumours. Comparable risk estimates of mortality were found for lag time intervals from surgery to adjuvant chemotherapy for breast, colorectal, and ovarian cancers. Risk estimates of pathologic complete response indicated an optimal time window of 7-8 weeks for neoadjuvant chemotherapy completion prior to surgery for rectal cancers. In comparing methods across meta-analyses on the same cancer sites, lag times, and outcomes, we identified critical variations in lag time research design. Conclusions: Our review highlighted measured associations between lag time and cancer-related outcomes and identified the need for a standardized methodological approach in areas such as lag time definitions and accounting for the waiting-time paradox. Prioritization of lag time research is integral for revised cancer care guidelines under pandemic contingency and assessing the pandemic's long-term effect on patients with cancer.

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.

Metastatic pulmonary dissemination as differential diagnosis of COVID-19 disease.

A 13-year-old boy presented to hospital with 3-day self-limited fever, followed by dry cough, persistent asthenia and impaired general condition of 2 weeks' duration. Blood analyses showed a severe inflammatory status and chest X-ray images were consistent with bilateral COVID-19 pneumonia. He developed an acute respiratory failure that required paediatric intensive care admission and non-invasive ventilation. A targeted COVID-19 treatment was initiated with hydroxicloroquine, corticosteroids, enoxaparine and a single dose of tocilizumab. Repeated serological tests and real-time reverse transcription PCR for SARS-CoV-2 were negative. Other infectious pathogens were also ruled out. Thoracic high resolution CT showed an intense bilateral pulmonary dissemination with lytic vertebral bone lesions. After diagnostic investigations, Ewing's sarcoma with metastatic pulmonary dissemination was diagnosed. Nowadays, in the context of SARS-CoV-2 community pandemic, we cannot forget that COVID-19 clinical presentation is not specific and other entities can mimic its clinical features.

Two Cases of SARS-CoV-2 Infection in Pediatric Oncohematologic Patients in Spain.

Since December 2019, severe acute respiratory syndrome coronavirus 2 infection has spread worldwide. We all are concerned about immunocompromised children, especially hematologic and oncologic pediatric patients. We want to share our experience with 2 pediatric cancer patients with severe acute respiratory syndrome coronavirus 2 infection. Both presented mild disease and good outcome. No respiratory symptoms were identified, but both developed diarrhea, one probably secondary to lopinavir/ritonavir. Pediatric cancer patients may have milder disease than adults, but larger studies are needed to make conclusions.

Bone sarcoma surgery in times of COVID-19 pandemic lockdown-early experience from a tertiary centre in India.

BACKGROUND AND OBJECTIVES: Coronavirus disease 2019 (COVID-19) lockdown has presented a unique challenge for sarcoma care. The purpose of this study is to evaluate the early results and feasibility of surgeries for bone sarcomas during the COVID-19 lockdown. METHODS: Our prospectively collected orthopaedic oncological database was reviewed to include two groups of patients- those who underwent surgery in the immediate 4 weeks before lockdown (non-lockdown group) and those operated in the first 4 weeks of lockdown (lockdown group). All patients were followed-up clinically and telephonically to collect the outcome data. RESULTS: Out of the 91 patients who qualified for inclusion, fifty were classified into the non-lockdown group while 41 patients formed the lockdown group. Both the groups were comparable with respect to baseline demographic parameters. However, during the lockdown period 37 patients (90%) had undergone a major surgical intervention as against 24 patients (48%) in the non-lockdown group (P < .001). There was no significant difference in type of anaesthesia, median estimated blood loss and procedure duration. None of the patients/health care workers had evidence of severe acute respiratory syndrome-coronavirus 2 infection at 15 days follow-up. CONCLUSION: Our study results suggest that appendicular bone tumours can be safely operated with adequate precautions during the lockdown period.