Background The value of neoadjuvant chemotherapy in soft tissue sarcoma (STS) is not completely understood. This study investigated the benefit of neoadjuvant chemotherapy according to prognostic stratification based on the Sarculator nomogram for STS. Methods This study analyzed data from ISG‐STS 1001, a randomized study that tested 3 cycles of neoadjuvant anthracycline plus ifosfamide (AI) or histology‐tailored (HT) chemotherapy in adult patients with STS. The 10‐year predicted overall survival (pr‐OS) was estimated with the Sarculator and was stratified into higher (10‐year pr‐OS < 60%) and lower risk subgroups (10‐year pr‐OS ≥ 60%). Results The median pr‐OS was 0.63 (interquartile range [IQR], 0.51‐0.72) for the entire study population, 0.62 (IQR, 0.51‐0.70) for the AI arm, and 0.64 (IQR, 0.51‐0.73) for the HT arm. Three‐ and 5‐year overall survival (OS) were 0.86 (95% confidence interval [CI], 0.82‐0.93) and 0.81 (95% CI, 0.71‐0.86) in lower risk patients and 0.69 (95% CI, 0.70‐0.85) and 0.59 (95% CI, 0.51‐0.72) in the higher risk patients (log‐rank test, P = .004). In higher risk patients, the 3‐ and 5‐year Sarculator‐predicted and study‐observed OS rates were 0.68 and 0.58, respectively, and 0.85 and 0.66, respectively, in the AI arm (P = .04); the corresponding figures in the HT arm were 0.69 and 0.60, respectively, and 0.69 and 0.55, respectively (P > .99). In lower risk patients, the 3‐ and 5‐year Sarculator‐predicted and study‐observed OS rates were 0.85 and 0.80, respectively, and 0.89 and 0.82, respectively, in the AI arm (P = .507); the corresponding figures in the HT arm were 0.87 and 0.81, respectively, and 0.86 and 0.74, respectively (P = .105). Conclusions High‐risk patients treated with AI performed better than predicted, and this adds to the evidence for the efficacy of neoadjuvant AI in STS. Lay Summary People affected by soft tissue sarcomas of the extremities and trunk wall are at some risk of developing metastasis after surgery. Preoperative or postoperative chemotherapy has been tested in clinical trials to reduce the chances of distant metastasis. However, study findings have not been conclusive. This study stratified the risk of metastasis for people affected by sarcomas who were included in a clinical trial testing neoadjuvant chemotherapy. Exploiting the prognostic nomogram Sarculator, it found a benefit for chemotherapy when the predicted risk, based on patient and tumor characteristics, was high.

BackgroundLiposarcomas represent the most common histological type of soft-tissue sarcomas (STS). Its main subgroups, WD/DD, is known to be poorly sensitive to chemotherapy, with few active agents, i.e., anthracyclines +/- ifosfamide and trabectedin. High-dose ifosfamide (HDIFX >12 g/m2) is active in STS pts pretreated with standard-dose IFX, though with greater toxicity. A prolonged continuous-infusion (ci) through a portable external pump may be an alternative way to administer HDIFX.MethodsFrom March 2002 to August 2013, 28 pts (median age =60, range =37–73 yrs) with advanced disease (6 WD and 22 WD/DD) were given ciHDIFX, at the dose of 14 g/m2 as a 14-day continuous infusion every 4 weeks. Twenty-four pts (86%) were previously treated with chemotherapy (19 with anthracyclines and ifosfamide; 4 with anthracycline monotherapy; 1 with trabectedin).ResultsSeven PR (all in DDLPS), 2 minor response (MR) and 11 SD were observed. Of interest, 6 of 9 patients with PR or MR had had SD with the previous therapy with anthracycline plus ifosfamide. The median progression-free survival was 7 months. Most common side effects were mild myelosuppression (anemia G2-3 in 3 pts; G2-3 neutropenia in 3 pts and G4 in 1; G3 thrombocytopenia in 1 pt); nausea (G3 in 3 pts) and fatigue (G3 in 6 pts). One pts had transient G3 confusion.ConclusionsThese data suggest that ciHDIFX is active in WD/DDLPS, even in patients already treated with a combination of anthracyclines plus ifosfamide. In this series, ciHDIFX regimen was better tolerated than HDIFX in published studies.

BackgroundPigmented villonodular synovitis (PVNS) is a rare locally aggressive tumor. PVNS is characterized in most cases by a specific t(1;2) translocation, which fuses the colony stimulating factor-1 (CSF1) gene to the collagen type VIa3 (COL6A3) promoter thus leading through a paracrine effect to the attraction of non-neoplastic inflammatory cells expressing CSF1-receptor. Imatinib is a tirosin-kinase inhibitors (TKI) active against CSF1-receptor whose activity in naïve PVNS was already described. We report on two PVNS patients who responded to imatinib after failure to nilotinib, another CSF1-receptor inhibitor.MethodsSince August 2012, 2 patients with progressive, locally advanced PVNS resistant to nilotinib (Patient 1: man, 34 years; Patient 2: woman, 24 years) have been treated with second-line imatinib 400 mg/day. Both patients are evaluable for response.ResultsBoth patients are still on treatment (7 and 4 months). Patient 1 had a dimensional response by MRI after 2 months from starting imatinib, together with symptomatic improvement. In Patient 2 a metabolic response was detected by [18F]fluorodeoxyglucose–positron emission tomography (PET) at 6 weeks coupled with tumor shrinkage by MRI, and symptomatic improvement.ConclusionsImatinib showed antitumor activity in 2 patients with nilotinib-resistant PVNS. This observation strengthen the idea that targeted agent with similar profile can give a different clinical result, as already described for gastrointestinal stromal tumor (GIST) patients treated with the same agents. Molecular studies are needed to clarify the biologic mechanism(s) underlying the response.

No abstract