En bloc resection consists in the surgical removal of a vertebral tumor in a single piece with a sufficient margin, to improve survival and reduce recurrence rate. This procedure is technically demanding and correlates with a high complication rate. The purpose of this study is to investigate the risk factors for complications in en bloc resection and evaluate if benefits overcome the risks in term of overall survival. We retrospectively analyzed prospectively collected data of patients treated with en bloc resection between 1980 and 2021. Complications were classified according to SAVES-V2. Overall Survival was estimated using Kaplan-Meier method. A total of 149 patients out of 298 (50%) suffered from at least one complication. Moreover, 220 adverse events were collected (67 intraoperative, 82 early post-operative, 71 late post-operative), 54% of these were classified as grade 3 (in a severity scale from 1 to 6). Ten years overall survival was 67% (95% CI 59–74). The occurrence of relapses was associated to an increased risk of mortality with OR 3.4 (95% CI 2.1–5.5), while complications did not affect the overall survival. Despite a high complication rate, en bloc resection allows for a better control of disease and should be performed in selected patients by specialized surgeons.

The Italian Sarcoma Group performed this retrospective analysis of patients with advanced soft tissue sarcoma, pretreated with ≥1 anthracycline-based treatment, and treated with trabectedin every three weeks. Primary endpoint was to describe real-life use of trabectedin across Italy. Secondary endpoints included objective response rate (ORR) and safety. Overall, 512 patients from 20 Italian centers were evaluated. Leiomyosarcoma (37.7%)/liposarcoma (30.3%) were the most prevalent histological types (abbreviated as L-sarcoma). Patients received a median of four trabectedin cycles (range: 1–40), mostly as a second-line treatment (~60% of patients). The ORR was 13.7% superior (p < 0.0001) in patients with L-sarcoma compared with patients with non-L-sarcoma (16.6% vs. 9.0%). Median progression-free survival (PFS) was 5.1 months, whereas median overall survival (OS) was 21.6 months. Significantly better PFS and OS were observed in patients with L-sarcoma, those with objective responses and/or disease stabilization, treated in an early line and treated with reduced dose. Bone marrow toxicity (61.4%) and transaminase increases (21.9%) were the most common grade 3/4 adverse events. The results of this real-life study suggest that trabectedin is an active treatment, which is mostly given as a second-line treatment to patients with a good performance status and high-grade, metastatic L-sarcoma (clinical trial information: NCT02793050).

PURPOSE: Outcome of patients with localized osteosarcoma is challenging. The role of mifamurtide is still a matter of debate. Two prospective trials were carried out in Italy (ISG/OS-2) and Spain (GEIS-33) with mifamurtide in ABCB1/P-glycoprotein (Pgp)–positive patients. PATIENTS AND METHODS: Patients age ≤40 years with localized extremity high-grade osteosarcoma were eligible. Analysis of Pgp expression from diagnostic biopsy was centralized. Patients received two cycles of preoperative methotrexate, doxorubicin, and cisplatinum (MAP) before surgery. Postoperatively, in case of Pgp overexpression (Pgp-positive), mifamurtide was added, combined with doxorubicin (one cycle) and four consecutive cycles of high-dose ifosfamide (HDIFO) for patients with poor histologic response, or with MAP in case of good response. Patients who were Pgp-negative received MAP postoperatively. We present the merged analysis of ISG/OS-2 and GEIS-33 trial, an observational study with same inclusion criteria and treatment of ISG/OS-2. The primary endpoint was 5-year event-free survival (EFS) according to the use of mifamurtide. Secondary endpoint was overall survival (OS). RESULTS: From March 2013 to April 2018, 398 patients were analyzed. The median age was 14 years (range, 4-40), male/female: 238/160 (1.48/1.0); 211 of 398 (53%) tumors were Pgp-positive, and 204 of 398 (51.3%) patients received mifamurtide. With a median follow-up of 70 months (IQR, 49-90 months), the 5-year EFS and OS were 65.2% (95% CI, 60.1 to 69.8) and 74.8% (95% CI, 69.8 to 79.0), respectively, with superior EFS for patients undergoing mifamurtide and chemotherapy as compared with EFS of patients undergoing chemotherapy alone (5-year EFS 71.4% v 58.3%; P = .0139) not confirmed at multivariable analysis ( P = .0593). CONCLUSION: In this merged analysis with a risk-adapted strategy for nonmetastatic osteosarcoma, the group with unfavorable prognoses, identified by Pgp expression, performed well when mifamurtide, combined with HDIFO in case of poor response, was administered after surgery.

Purpose: A risk-adapted treatment strategy, the ISG/OS-2 trial, evaluated the use of mifamurtide in patients with P-glycoprotein (Pgp)–positive localized osteosarcoma. The primary objective was the identification of prognostic classifiers based on tumor microenvironment (TME) gene profiling in all patients and in those undergoing mifamurtide treatment. Experimental Design: RNA from pretreatment formalin-fixed, paraffin-embedded nondecalcified tissues of 62 patients was analyzed with the PanCancer Immune Profiling Panel (NanoString Technologies). Thirty-three (53%) of 62 Pgp-positive patients underwent chemotherapy + mifamurtide; 29 (47%) of 62 Pgp-negative patients received chemotherapy alone. Univariate Cox regression, ROC curve, and CIBERSORTx algorithm gene deconvolution analyses were performed. Results: A 21-gene signature able to stratify all patients into high risk (Hi-R) and low risk (Lo-R) was identified: 5-year overall survival (OS) of 47% for Hi-R and 92% for Lo-R (P = 3e−06). TME of Lo-R compared with Hi-R was significantly enriched in CD8 T cells, regulatory T cells, and NK-activated cells and diminished in CD4 T cells. The 21-gene signature was validated in two independent sets: TARGET-OS The Cancer Genome Atlas (n = 62) and GSE33382 (n = 57). For patients treated with chemotherapy + mifamurtide, 31 mifamurtide-related genes able to distinguish Hi-R and Lo-R in terms of OS (P = 1e−09) and event-free survival (P = 3e−06) were also identified. After multivariate analysis, the 21- and 31-gene mifamurtide-related signatures were independently associated with OS (P = 0.00044 and P = 0.000079, respectively). Conclusions: 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.