Istituto Ortopedico Rizzoli

Malignant peripheral nerve sheath tumors (MPNSTs) are rare and have among the worst prognoses among all soft tissue sarcomas, with 5-year overall survival rates ranging from 16 to 52%. We report a case of a 50-year-old man with localized dorsal MPNST who developed local recurrence after 1 year and lung metastasis 3 years after diagnosis. He underwent primary tumor resection, two resections for local recurrence, one lung metastasectomy, seven lines of chemotherapy (epirubicin–ifosfamide, cisplatin–etoposide, trabectedin, pazopanib, carboplatin–etoposide, gemcitabine, and ifosfamide), and four courses of stereotactic body radiotherapy for lung metastases. The patient has shown long remission intervals and survival exceeding 7 years, with a good quality of life since the diagnosis of lung metastasis. We conducted a narrative review based on our treatment approach, considering the recent literature and drugs currently available for the treatment of MPNST.

Dynamic anterior stabilization (DAS) is a novel soft-tissue procedure for treating anterior shoulder instability in selected cases. The purpose of the present meta-analysis is to provide the up-to-date evidence on DAS's outcomes, safety and characterize study designs to improve future studies and accelerate technical advancements.

A PRISMA guided meta-analysis was performed. Inclusion criteria were human studies, comparative or non-comparative in which DAS was performed as an indication for anterior shoulder instability. Four databases were searched PubMed (via MEDLINE), EMBASE, Web of Science, and Science Direct. ROBINS-I was employed for risk of bias analysis. A random-effects meta-analysis was performed using mean difference (MD) as effect size estimator. Heterogeneity was reported using the I² statistic. Dichotomous variables were counted and reported as % out of total sample size for each study.

Five studies met the inclusion criteria. A total of 137 patients were available for analysis with a mean age of 27.8 ± 9 years and 108 patients were males. Mean follow-up duration was 37 ± 11 months. Postoperative ASES score showed an improvement of MD = -15.09 (95% CI: -22.35 to -7.38), p < 0.01, compared to the preoperative period. The ROWE score showed a similar improvement, MD = -58.38 (95% CI: -69.88 to -46.89), p < 0.01. Postoperative range of motion (ROM) was not significantly influenced. Active anterior elevation had a MD = -6.07° (95% CI: -15.04 to 2.91), p = 0.19, active external rotation had a MD = 3.7° (95% CI: -7.71 to 15.11), p = 0.53, and active internal rotation, MD = 0.16° (95% CI: -1.4 to 1.73), p = 0.84. Return to play ranged from 80 to 100% while return to competitive sports, reported by a single study, was 33%. The overall complication rate was 8.6%. The overall risk of bias was "serious" or "critical" for all included studies.

DAS has been shown to improve postoperative PROMs, does not restrict ROM compared to the preoperative period and has an overall complication rate of 8.6%.

A risk-adapted treatment strategy, the ISG/OS-2 trial, evaluated the use of mifamurtide in P-glycoprotein (Pgp)-positive localized osteosarcoma patients. The primary objective was the identification of prognostic classifiers based on tumor immune microenvironment (TME) gene profiling in all patients and in those undergoing mifamurtide.

RNA from pre-treatment FFPE non-decalcified tissues of 62 patients was analyzed with the PanCancer Immune profiling panel (NanoString Technologies, Seattle, WA, US). Thirty three out of sixty-two (53%) Pgp-positive patients underwent chemotherapy (CT)+mifamurtide, 29/62 (47%) Pgp-negative patients received CT alone. Univariate Cox regression, ROC curve and CIBERSORTx algorithm gene deconvolution analyses were performed.

A 21-gene signature able to stratify all patients into high-(Hi-R) and low-risk (Lo-R) was identified: 5-year OS for Hi-R 47%; 92% for Lo-R (p = 3e-06). TME of Lo-R vs Hi-R, was significantly enriched in CD8 T-cells, T-regs, and NK activated cells, and diminished in CD4 T- cells. The 21-gene signature was validated in two independent sets: Target-OS TCGA (n=62) and GSE33382 (n=57). For patients treated with CT+mifamurtide 31-mifamurtide related genes able to distinguish Hi-R and Lo-R in terms of OS (p = 1e-09) and EFS (p = 3e-06) were also identified. After multivariate analysis the 21-gene and the 31-gene mifamurtide-related signatures were independently associated with OS (p= 0.00044 and p = 0.000079, respectively).

A validated osteosarcoma TME prognostic gene signature has been identified, regardless of mifamurtide treatment. Importantly, a mifamurtide-related signature was also developed. Tumor-immune interactions possibly implicated in disease progression and treatment response were shown.