Circulating TNF-RII, IP-10 and HGF are associated with severity of COVID-19 in oncologic patients.

The COVID-19 patients showed hyperinflammatory response depending on the severity of the disease but little have been reported about this response in oncologic patients that also were infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Sixty-five circulating cytokines/chemokines were quantified in 15 oncologic patients, just after SARS-CoV-2 infection and fourteen days later, and their levels were compared in patients who required hospitalisation by COVID-19 versus non-hospitalised patients. A higher median age of 72 years (range 61-83) in oncologic patients after SARS-CoV-2 infection was associated with hospitalisation requirement by COVID-19 versus a median age of 49 years (20-75) observed in the non-hospitalised oncologic patients (p = 0.008). Moreover, oncologic patients at metastatic stage or with lung cancer were significantly associated with hospitalisation by COVID-19 (p = 0.044). None of these hospitalised patients required ICU treatment. Higher basal levels of tumour necrosis factor receptor II (TNF-RII), interferon-γ (IFNγ)-induced protein 10 (IP-10) and hepatocyte growth factor (HGF) in plasma were significantly observed in oncologic patients who required hospitalisation by COVID-19. Higher TNF-RII, IP-10 and HGF levels after the SARS-CoV-2 infection in oncologic patients could be used as biomarkers of COVID-19 severity associated with hospitalisation requirements.

Delays in diagnosis and surgery of sarcoma patients during the COVID-19 outbreak in Spain.

Background and objectives: Social distancing and quarantine implanted during the COVID-19 outbreak could have delayed the accession of oncologic patients to hospitals and treatments. This study analysed the management of sarcoma patients during this period in five Spanish hospitals. Design and methods: Clinical data from adult sarcoma patients, soft tissue and bone sarcomas, managed during the COVID-19 outbreak, from 15 March to 14 September 2020 (Covid cohort), were retrospectively collected and time for diagnosis, surgery and active treatments were compared with sarcoma patients managed during the same pre-pandemic period in 2018 (Control cohort). Results: A total of 126 and 182 new sarcoma patients were enrolled in the Covid and Control cohorts, respectively, who were mainly diagnosed as soft tissue sarcomas (81.0% and 80.8%) and at localized stage (80.2% and 79.1%). A diagnostic delay was observed in the Covid cohort with a median time for the diagnosis of 102.5 days (range 6-355) versus 83 days (range 5-328) in the Control cohort (p = 0.034). Moreover, a delay in surgery was observed in cases with localized disease from the Covid cohort with a median time of 96.0 days (range 11-265) versus 54.5 days (range 2-331) in the Control cohort (p = 0.034). However, a lower delay for neoadjuvant radiotherapy was observed in the Covid cohort with a median time from the diagnosis to the neoadjuvant radiotherapy of 47 days (range 27-105) versus 91 days (range 27-294) in the Control cohort (p = 0.039). No significant differences for adjuvant radiotherapy, neoadjuvant/adjuvant chemotherapy and neoadjuvant/adjuvant palliative chemotherapy were observed between both cohorts. Neither progression-free survival (PFS) nor overall survival (OS) was significantly different. Conclusion: Delays in diagnosis and surgery were retrospectively observed in sarcoma patients during the COVID-19 outbreak in Spain, while the time for neoadjuvant radiotherapy was reduced. However, no impact on the PFS and OS was observed.

Platinum-Based Regimens Are Active in Advanced Pediatric-Type Rhabdomyosarcoma in Adults and Depending on HMGB1 Expression.

Rhabdomyosarcoma (RMS) in adults is a rare and aggressive disease, which lacks standard therapies for relapsed or advanced disease. This retrospective study aimed to describe the activity of BOMP-EPI (bleomycin, vincristine, methotrexate and cisplatin alternating with etoposide, cisplatin and ifosfamide), an alternative platinum-based regimen, in adult patients with relapsed/metastatic RMS. In the study, 10 patients with RMS with a median age at diagnosis of 20.8 years and a female/male distribution of 6/4 received a mean of 2.5 cycles of BOMP-EPI. The best RECIST response was a complete response in 1/10 (10%) patients, a partial response in 5/10 (50%), stable disease in 3/10 (30%) and progression in 1/10 (10%). With a median follow-up in the alive patients from the start of therapy of 30.5 months (15.7-258), all patients progressed with a median progression-free survival of 8.47 months (95% CI 8.1-8.8), and 7/10 patients died with a median overall survival of 24.7 months (95% CI 13.7-35.6). BOMP-EPI was an active chemotherapy regimen in adults with pediatric-type metastatic RMS, with outcomes in terms of survival that seem superior to what was expected for this poor-prognosis population. Low HMGB1 expression level was identified as a predictive factor of better response to this treatment.

Efficacy of Eribulin Plus Gemcitabine Combination in L-Sarcomas.

Although the overall survival of advanced soft-tissue sarcoma (STS) patients has increased in recent years, the median progression-free survival is lower than 5 months, meaning that there is an unmet need in this population. Among second-line treatments for advanced STS, eribulin is an anti-microtubule agent that has been approved for liposarcoma. Here, we tested the combination of eribulin with gemcitabine in preclinical models of L-sarcoma. The effect in cell viability was measured by MTS and clonogenic assay. Cell cycle profiling was studied by flow cytometry, while apoptosis was measured by flow cytometry and Western blotting. The activity of eribulin plus gemcitabine was evaluated in in vivo patient-derived xenograft (PDX) models. In L-sarcoma cell lines, eribulin plus gemcitabine showed to be synergistic, increasing the number of hypodiploid events (increased subG1 population) and the accumulation of DNA damage. In in vivo PDX models of L-sarcomas, eribulin combined with gemcitabine was a viable scheme, delaying tumour growth after one cycle of treatment, being more effective in leiomyosarcoma. The combination of eribulin and gemcitabine was synergistic in L-sarcoma cultures and it showed to be active in in vivo studies. This combination deserves further exploration in the clinical context.