Purpose: Alveolar soft part sarcoma (ASPS) is an ultrarare soft-tissue sarcoma with a high rate of metastasis and no established treatment. This study aimed to explore the efficacy and safety of anlotinib (a tyrosine kinase inhibitor) and TQB2450 (a PD-L1 inhibitor) in patients with ASPS. Patients and Methods: This single-arm, phase II study evaluated the efficacy of TQB2450, an anti–PD-L1 agent, combined with anlotinib, a tyrosine kinase inhibitor, in adults with advanced ASPS. TQB2450 was given intravenously (1,200 mg) on day 1, and anlotinib (12 mg/day) was taken orally from day 1 to 14 every 3 weeks. The primary endpoint was overall response rate, with secondary endpoints including duration of response, progression-free survival, and overall survival. Lymphocyte infiltration and tertiary lymphoid structure (TLS) were also analyzed as potential prognostic biomarkers. Results: The study enrolled 29 patients, of whom 28 were evaluable (one withdrew because of acute pancreatitis). An objective response was achieved in 82.1% of patients, including 4 complete and 19 partial responses. The median time to response was 2.8 months, and the duration of response was not reached, with an estimated median progression-free survival of 35.2 months. Grade 3 to 4 treatment-related adverse events occurred in 44.8% of patients, with no study-related deaths. Responders had a higher proportion of TLS area, TLS density, and CD20-positive immune cells. Conclusions: The combination of anlotinib and TQB2450 is effective and tolerable in patients with ASPS. TLS may serve as a prognostic biomarker, meriting further investigation.

Background: Intratumoral oncolytic herpes simplex virus 2-GM CSF (OH2) injection has shown safety and antitumor efficacy in patients with solid tumors. Here, we examined the safety and efficacy of OH2 as a single agent or in combination with HX008, an NMPA-approved PD-1 inhibitor, in locally advanced or metastatic sarcoma patients. Methods: This multicenter, phase 1/2 trial enrolled patients with injectable sarcoma lesions, who had failed at least 1 or more lines of standard treatment. Patients were treated with OH2 at three dose levels (10⁶, 10⁷ and 10⁸ CCID₅₀/mL) as single agent or in combination with a fixed dose of HX008. The primary endpoints were safety and tolerability in phase 1 and objective response rate determined by RECIST (V.1.1) criteria and immune-RECIST in phase 2. Results: Between October 20, 2020 and December 30, 2023, 26 patients were enrolled. Seven patients were treated with single-agent OH2 and 19 with HX008 and OH2 combination. No dose-limiting toxicities were observed during the dose escalation. We documented four partial or complete responses in injected lesions, and one partial response in non-injected lesions, which were all from the combination group. Hence, the overall response rate was 0% and 16.7% in the single agent and combination groups, respectively. The duration of response was 3.9–6.5 months. The most frequent treatment-related adverse events (TRAEs) were fever (n=9). Grade 3 or 4 TRAEs were reported in four patients (15.4%). A clear increase in CD8+cell density in the tumor microenvironment was observed in the patients’ post-treatment specimens compared with baseline. Conclusions: Intratumoral injection of oncolytic virus OH2 is well tolerable in patients with sarcoma. Further investigation of OH2 with HX008 in select sarcoma subtypes is warranted.

Background: Alveolar soft part sarcoma (ASPS) is a rare sarcoma that has been shown to be highly effective to antiangiogenic agents and immune checkpoint inhibitors, but most reported studies about ASPS were concentrated on adult population. In this study, we aimed to describe the clinical features and therapeutic outcomes of ASPS in children.Methods: We retrospectively reviewed the records of patients with ASPS in our institution since Jan 2015. All patients included in this study were pathologically confirmed ASPS and aged under 12 years at the time of initial diagnosis. Demographic characteristics, tumor sizes, primary tumor sites, metastasis, treatments used, therapeutic responses and survivals were evaluated.Results: We identified a total of 56 patients to be initially diagnosed as ASPS since Jan 2015. A predisposition of high occurrence in head and neck (32.1%) was observed (versus 41.1% in limbs and 21.4% in trunk). 26 (46.4%) patients developed metastasis at the time of diagnosis or during follow-up. Tumors in tongue, pharynx and larynx had the least likelihood to metastasize (7.7%, P<0.05). Observation was recommended for 15 stage IV patients with only pulmonary metastasis. 7 (46.7%) patients remained stable until last follow up. The 1-year PFS rate was 83.3% and median progression-free survival time (PFS) was 29.4 months. 15 patients with progressive disease received mono or combined therapy. 11 patients received PD-1 monotherapy. 2 patients achieved partial response and 5 stable disease. The overall response rate was 18.2%. The median PFS of this group was 22.0 months, and the 1-year PFS rate was 70.0%. 4 patients received a combination therapy of PD-1 inhibitors plus tyrosine kinase inhibitors. All of them remained stable. No disease-related death occurred during follow-up.Conclusions: ASPS exhibits a higher occurrence in head and neck in children. ASPS originating from glossopharyngeal region tends to have a lower metastasis rate. ASPS displays a more indolent growth pattern in children, which makes observation a preferable choice for children with sole pulmonary metastasis. Pediatric ASPS appears to be less effective to targeted therapy and immunotherapy than adults. The treatment of progressive ASPS in children remains challenging.

Purpose: Alveolar soft part sarcoma (ASPS) is an ultrarare soft tissue sarcoma. Current standard therapy with PD-1/PD-L1 inhibitors achieves limited response rates (<40%). Lymphocyte-activation gene 3 (LAG-3) is coexpressed with PD-1 on exhausted T cells, and dual blockade has shown synergy in some solid tumors but remains unexplored in sarcoma. This trial evaluated the efficacy of IBI110 (anti–LAG-3) plus sintilimab (anti–PD-1) in advanced ASPS. Patients and Methods: This open-label, phase II study enrolled 28 patients from July 2022 to September 2023 (median follow-up, 33.6 months). Both drugs were given intravenously at 200 mg every 3 weeks. The primary endpoint was overall response rate (ORR) by RECIST v1.1. Results: Among 28 patients, 8 (28.6%) were resistant to prior immune checkpoint inhibitors (ICI), and 20 (71.4%) were ICI-naïve. The overall ORR was 51.8% (14/27 evaluable), including 4 complete responses and 10 partial responses. During a median follow-up of 33.6 months, the median progression-free survival (PFS) and overall survival (OS) were not reached in the whole population. In ICI-naïve patients, the ORR was 60%, with median PFS/OS not reached. In ICI-resistant patients, the ORR was 25%, with median PFS of 14.9 months and median OS of 25.4 months. The median time to response was 3.3 months; the median duration of response (DoR) was not reached. Grade 3 to 4 treatment-related adverse events occurred in nine patients (32.1%), with no treatment-related deaths. Exploratory analysis showed that responders had significantly higher baseline LAG-3+ cell density in tumor specimens. Conclusions: Dual LAG-3/PD-1 blockade demonstrated promising and durable antitumor activity with manageable safety in both ICI-naïve and ICI-resistant advanced ASPS, warranting further investigation.

We sought to evaluate the efficacy and predictive value of 99mTc-rituximab as a tracer for sentinel lymph node biopsy (SLNB) in acral melanoma (AM) patient