Malignant peripheral nerve sheath tumor (MPNST) is a rare type of soft tissue sarcomas. The localized disease is usually treated with surgery along with perioperative chemo- or radiotherapy. However, up to 70% of patients can develop distant metastases. The study aimed to evaluate the modes and outcomes of systemic treatment of patients with diagnosed MPNST treated in a reference center. In total, 115 patients (56 female and 59 male) diagnosed with MPNST and treated due to unresectable or metastatic disease during 2000–2019 were included in the retrospective analysis. Schemes of systemic therapy and the outcomes—progression-free survival (PFS) and overall survival (OS)—were evaluated. The median PFS in the first line was 3.9 months (95% CI 2.5–5.4). Doxorubicin-based regimens were the most commonly used in the first line (50.4% of patients). There were no significant differences in PFS between chemotherapy regimens most commonly used in the first line (p = 0.111). The median OS was 15.0 months (95% CI 11.0–19.0) and the one-year OS rate was 63%. MPNST are resistant to the majority of systemic therapies, resulting in poor survival in advanced settings. Chemotherapy with doxorubicin and ifosfamide is associated with the best response and longest PFS. Future studies and the development of novel treatment options are necessary for the improvement of treatment outcomes.

We assessed the status of the BRAF V600E mutation in cell-free circulating tumor DNA (cfDNA) isolated from the plasma of patients with metastatic melanoma treated with the BRAF inhibitor vemurafenib, collected at different time points during therapy to evaluate the sensitivity and specificity of quantitative polymerase chain reaction and droplet digital polymerase chain reaction (ddPCR) and the correlation between the level of plasma cfDNA p.V600E and the long-term clinical outcome. cfDNA in patients with BRAF-mutated melanoma (n = 62) was analyzed at baseline and at 4−8 weeks from the start of vemurafenib therapy. BRAF mutations were assessed using tumor tissue-derived DNA and circulating cfDNA from plasma samples. Quantification of BRAF V600E was performed in cfDNA using ddPCR. cfDNA V600E was detected in the plasma of 48/62 (77%) patients at baseline and in 18/62 (29%) patients after 4–8 weeks of treatment. Patients positive for BRAF mutations in cfDNA at baseline had shorter progression-free survival (PFS) and overall survival (OS) compared with patients with undetectable cfDNA BRAF mutations. Undetectable cfDNA p.V600E at baseline and after 4–8 weeks of therapy was associated with the best prognosis. When treated as a continuous variable, the log-transformed concentration of baseline cfDNA p.V600E was significantly associated with both PFS and OS. This effect was retained in the multivariate OS Cox model adjusted for Eastern Cooperative Oncology Group performance status, the presence of brain metastases, patient age, and previous systemic treatment. Monitoring of plasma BRAF p.V600E cfDNA concentrations in patients with metastatic melanoma on targeted therapy may have prognostic value. Undetectable cfDNA p.V600E before and during treatment was associated with a favorable prognosis.

Ewing sarcoma (ES) is a rare and aggressive disease that requires multidisciplinary treatment with the use of chemotherapy, radiotherapy, and surgery. Our retrospective study aimed to analyze the prognostic factors and treatment results in different age groups of patients. Between 1998 and 2018, 569 patients with ES were treated in two referral centers. The patients were divided into four age groups (≤10 years; 11–18 years; 19–25, and >25). The treatment results and prognostic factors were assessed for each group. For statistical analyses, we used the Chi2 test, the Kaplan–Meier estimator with a log-rank test, and the multivariate Cox model. Five-year overall survival (OS) rate was 56%. In the age subgroups: ≤10 years, 11–18 years, 19–25 years, and >25 years, the 5-year OS rates were 75%, 58%, 41%, and 52%, respectively. Favorable prognostic factors: female gender (p = 0.024), non-axial localization (p = 0.005), VIDE regimen (p < 0.001), and surgery as a local treatment (p < 0.001) dominated in the group ≤10 years. In multivariate analysis, male (HR = 1.53), axial localization (HR = 1.46), M1 status at presentation (HR = 2.64), and age > 10 years (HR = 2.29) were associated with shorter OS. The treatment results in ES are significantly better in children aged ≤10 years; the challenge is to provide therapy for adolescents and young adults. The diagnostics and treatment of ES patients must be provided in referral centers.

Neoadjuvant therapy for locally advanced disease or potentially resectable metastatic melanoma is expected to improve operability and clinical outcomes over upfront surgery and adjuvant treatment as it is for sarcoma, breast, rectal, esophageal, or gastric cancers. Patients with locoregional recurrence after initial surgery and those with advanced regional lymphatic metastases are at a high risk of relapse and melanoma-related death. There is an unmet clinical need to improve the outcomes for such patients. Patients with resectable bulky stage III or resectable stage IV histologically confirmed melanoma were enrolled and received standard-dose BRAFi/MEKi for at least 12 weeks before feasible resection of the pre-therapy target and then received at least for the next 40 weeks further BRAFi/MEKi. Of these patients, 37 were treated with dabrafenib and trametinib, three were treated with vemurafenib and cobimetinib, five with vemurafenib, and one with dabrafenib alone. All patients underwent surgery with 78% microscopically margin-negative resection (R0) resection. Ten patients achieved a complete pathological response. In patients with a major pathological response with no, or less than 10%, viable cells in the tumor, median disease free survival and progression free survival were significantly longer than in patients with a minor pathological response. No patient discontinued neoadjuvant BRAFi/MEKi due to toxicity. BRAFi/MEKi pre-treatment did not result in any new specific complications of surgery. Fourteen patients experienced disease recurrence or progression during post-operative treatment. We confirmed that BRAFi/MEKi combination is an effective and safe regimen in the perioperative treatment of melanoma. Pathological response to neoadjuvant treatment may be considered as a surrogate biomarker of disease recurrence.

Assessment of BRAF mutation status is mandatory in advanced, treatment-naïve melanoma patients. Liquid biopsy can be an alternative in cases with inadequate or unavailable tumor tissue. The aim of our study was to evaluate the clinical utility of plasma circulating tumor DNA analysis for BRAF mutation testing and to assess outcomes of therapy with BRAF/MEK inhibitors initiated based on the liquid biopsy results. This was a retrospective single-center analysis of 46 patients (21 female, 25 male) with advanced melanoma who underwent circulating tumor DNA (ctDNA) BRAF mutation testing. A BRAF mutation was found in 45.7% (21/46) of liquid biopsies and 44.8% (13/29) of tissue samples. In patients with both ctDNA and tissue samples (n = 29), the concordance between the results of both tests was 82.8%. A BRAF mutation was detected in 7/17 (41.2%) patients with only ctDNA analysis. In 18 patients, therapy with BRAF/MEK inhibitors was initiated on the basis of the result of liquid biopsy. The objective response rate was 77.8 %, and the median PFS was 6.0 months. Our study confirms the clinical utility of BRAF mutation detection in plasma ctDNA. This study provides initial real-world data showing that treatment with BRAF/MEK inhibitors could be commenced based on liquid biopsy results.