e23545 Background: LMS is an aggressive soft-tissue sarcoma with an immunologically “cold” tumor microenvironment and historically poor responsiveness to ICB. With limited benefit from cytotoxic therapy beyond first-line and low ICB monotherapy activity, defining real-world ICB outcomes and identifying patients (pts) who may benefit remain an unmet clinical need. Methods: Adults with advanced/metastatic LMS treated with ICB at MD Anderson (2010–2025) were retrospectively identified via the pharmacy database. Response was assessed per trial RECIST v1.1 when available; otherwise, partial response/stable disease/progressive disease (PR/SD/PD) were extracted from documentation with radiology impressions. Disease control rate (DCR) was defined as PR+SD, and clinical benefit rate (CBR) as PR or SD ≥6 months (mo). Toxicity was graded per CTCAE v5. Subgroups were compared using chi-square/Fisher’s exact tests. Progression-free survival (PFS) was estimated by Kaplan–Meier, compared by log-rank, and evaluated with Cox regression. Results: Among 41 pts (median age 59; 76% female), 90% (n = 37) had metastatic disease at ICB start, 59% (n = 24) had ≥2 prior systemic therapy lines; 90% (n = 37) had doxorubicin; 76% (n = 31) had gemcitabine. Metastases involved lung in 83% (n = 34), liver in 66% (n = 27), and bone in 32% (n = 13). Primary sites were uterus in 29% (n = 12), retroperitoneum in 39% (n = 16), and other soft-tissue sites in 32% (n = 13). Overall, 85% (35/41) received ICB on a trial and 90% (37/41) received combination therapy: 57% (21) dual ICB, 24% (9) investigational targeted combinations, 11% (4) with concomitant radiotherapy, and 8% (3) with TKI. Best response was PR in 2 pts (5%), SD in 24 (59%), and PD in 15 (37%), yielding DCR 63% and CBR 22%. CBR differed by LMS type: 0/12 uterine LMS (uLMS) vs 9/29 (31%) for soft-tissue LMS (ST-LMS; p = 0.04) and by primary site (retroperitoneum 19% [3/16] vs other sites 46% [6/13]; Fisher’s exact p = 0.008). Median PFS was 3 mo overall and was longer with DCR vs PD (4.5 vs 1.5 mo; p < 0.001). PFS was longer with lung metastases (4.1 vs 1.3 mo; p < 0.001) and shorter with bone metastases (2.7 vs 4.1 mo; p = 0.02) and with prior gemcitabine exposure (2.8 vs 4.5 mo; p = 0.03), reflecting heavier pretreatment. In multivariable Cox regression, lung metastases (aHR 0.06; p < 0.001), bone metastases (aHR 4.8; p < 0.001), prior gemcitabine exposure (aHR 2.4; p = 0.04), and trial participation (aHR 0.2; p = 0.002; reflecting selection/regimen differences) remained independently associated with PFS. Toxicity occurred in 51%, with grade ≥3 events in 24%. Conclusions: In this real-world cohort of ICB-treated advanced LMS, trial participation and lung metastases predicted better PFS while bone metastases and prior gemcitabine exposure predicted worse PFS. ST-LMS had greater CBR than uLMS. Translational efforts are ongoing to identify LMS-specific biomarkers of ICB response.

11578 Background: Advanced LMS has limited effective therapies, with gem-based regimens being the most prescribed. Preclinical data suggest gemcitabine induces activation of the PI3K–mTOR pathway, supporting combination strategies with mTOR inhibition. Nab-S is a nanoparticle albumin-bound, IV formulation of sirolimus and has demonstrated greater intratumoral accumulation and antitumor activity in preclinical models compared to conventional mTOR inhibitors. Methods: This investigator-initiated, single-center phase I study evaluates gem (900mg/m2) plus nab-s (dose levels [DL]: DL1=75mg/m2 or DL2=100mg/m2) in patients (pts) using a Bayesian optimal interval (BOIN) design. Primary objective was to estimate the maximum tolerated dose (MTD) of the combination based on cycle 1 dose-limiting toxicities (DLT). Secondary objectives were to estimate objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Responses were assessed by RECIST1.1 and adverse events (AE) graded per CTCAEv5. Results: As of 01/22/26, all 12 pts initially planned for accrual have completed the DLT period. The original dosing schedule consisted of drug administration on Days 1 and 8 of a 21-day cycle. After the first 6 pts were enrolled, the protocol was amended to administer drugs on Days 1 and 15 of a 28-day cycle. This modification was implemented for all pts due to hematologic toxicities. While expected based on the known safety profile of nab-s and of gem, this frequently prevented Day 8 administration under the original schedule. All pts had advanced LMS, 10 pts were female and 7 had uterine LMS, the median age at time of consent was 55 yo. Three pts were included at DL1, and there was no DLT. DL2 included 9 pts: only one pt experienced a DLT of mucositis and diarrhea grade (Gr) 3 lasting for 3 days. The most frequent treatment-related Gr3-4 AE was thrombocytopenia. One pt had Gr3 pneumonitis attributed to gem and discontinued trial after 2 cycles. There was no other concern for safety. Ten pts were evaluable for response (1 pt died of disease and 1 pt chose to discontinue the trial before their first evaluation). ORR is 30% (n=3/10) at time of data cutoff and 90% pt had clinical benefit: 6 pts had stable disease with 5 pts experiencing shrinkage of disease (range: -8% to -21%) and 1 pt with 0% change. Only 1 pt had progressive disease as best response. With a median follow-up of 4 months (mo) for PFS, the median PFS (95% confidence interval [CI]) is 8.38 (1.68, not reached) mo, the 3-mo PFS (95% CI) is 78% (36%,94%), and the 6-mo PFS (95% CI) is 58% (16%,85%). With a median follow-up of 5.8 mo for OS, the 6-mo OS (95% CI) is 80% (39%,95%). Conclusions: The MTD was determined to be gem 900mg/m2 with nab-s 100mg/m2 on Days 1 and 15 of a 28-day cycle. Based on this preliminary safety and efficacy, an expansion with an additional 6 pts at this DL is ongoing. Clinical trial information: NCT06308419 .

e23531 Background: LMS is a rare, aggressive malignant tumor of smooth muscle origin, and its clinical heterogeneity complicates diagnosis, treatment, and research. Clinical trial enrollment among adult sarcoma patients (pts) remains low, with many eligible pts not routinely identified or referred. Understanding enrollment barriers and improving screening are critical to increase trial access. This study evaluated a standardized manual pre-identification and referral process for LMS pts at MDACC and assessed its impact on screening, enrollment, and participation barriers. Methods: This prospective study implemented a systematic pre-identification and referral workflow for LMS pts (Sept-Dec 2025). Medical charts were reviewed 2-3 days before each outpatient sarcoma oncology visit in EPIC to document tumor site, histopathology, prior therapy, stage, and inclusion/exclusion criteria for 6 active LMS trials in pre- and post-intervention periods. Eligible pts were identified and referred to physicians and the trial team by email. Primary outcomes: % improvement in monthly screening and enrollment. Secondary outcomes: the average monthly pts screened and enrolled during pre-intervention (03/2025-08/2025: 6 months) vs post-intervention (09/2025-12/2025: 4 months) periods, and recording of reasons for non-inclusion. Results: A total of 13 pts were screened and 12 enrolled during the pre-intervention period, versus 15 screened and 12 enrolled during the post-intervention period. Implementation of the pre-identification and referral workflow led to 73% and 50% improvement in monthly screening and enrollment, respectively. The average monthly screening of pts increased from 2.2 (±1.2) to 3.8 (±1.9), and the enrollment from 2.0 (±1.4) to 3.0 (±1.4). Example from one LMS trial (protocol 2023-0710): no pts screened/enrolled pre-intervention; post-intervention: 25 pre-identified, 2 screened and enrolled. Reasons for non-enrollment across all trials: summarized in Table 1, with clinical/protocol ineligibility most common. Post-intervention data collection is ongoing; a full 6-month comparison to be included in the final presentation. Conclusions: The implementation of pre-identification and referral workflow showed a trend toward increased screening and enrollment in LMS trials, with trial-level examples suggesting improved pt identification. The study also identified LMS-specific barriers, defining targets for future interventions. Incorporating AI-assisted screening may further increase pt identification, reduce manual workload, and improve trial enrollment. Reasons for non-enrollment among screened pts (%). Reason for non-enrollment (%) Clinical/protocol ineligibility 58 Difficulty in traveling to MDACC 17 Patient preference 14 Alternative treatment selection 7 Communication/administrative barriers 4

e18143 Background: Myoepithelial carcinoma (MEC) is a neoplasm derived from myoepithelial cells and characterized by an infiltrative growth pattern. These are very rare malignancies with limited published data describing outcomes. We sought to define the natural history of MEC and to identify best available treatments. Methods: In this retrospective series, we identified 70 patients with MEC seen at our institution from 1997-2025. Electronic medical records were reviewed to determine the patient and tumor characteristics, treatment regimens and response, and outcomes. The Kaplan Meier method was used to estimate survival, and log-rank tests were used to compare groups. Results: In our institutional cohort of 70 patients, MEC was most common in middle-aged individuals (median age = 52 years), with a predilection for head and neck sites (54/70, 77%). There was a slight predilection for male sex (40/70, 57%). The median overall survival (mOS) in our cohort was 87.2 months. Of 24 patients who developed metastatic disease, the predominant location was lung (n = 15, 62.5%) followed by bone (n = 11, 45%). For patients with localized disease (n = 66), the median recurrence-free survival (mRFS) was 55.4 months. The mRFS was not significantly different in patients who had resection alone (n = 39, mRFS = 60.0 months) compared with those treated with adjuvant radiation and/or chemotherapy (n = 27, mRFS = 51.1 months, p = 0.70). The primary systemic therapy utilized was platinum-based with few patients receiving doxorubicin or gemcitabine-based regimens. There were no significant clinical responses noted with systemic therapy. The median progression-free survival (mPFS) in patients with metastatic disease who received any systemic therapy was 3.1 months (n = 16). No significant difference in mOS was observed based on age, though there was a trend toward worse outcomes in younger patients (mOS for <30 years = 62.5 months, mOS for >30 years = 93.5 months, p = 0.88). The sample size of patients in the younger age group (n = 11) was small and only three patients in that subset were free of disease for >15 years. Conclusions: In our institutional experience with MEC, most patients were middle-aged with head and neck as the most common primary site. Outcomes were generally worse for younger patients. The lack of significant difference between the mOS between these age groups is attributed to a small sample size of patients in the younger age group with a wide confidence interval. Outcomes with currently available systemic therapy for metastatic disease were uniformly poor, emphasizing the need to develop novel treatment regimens moving forward. Future work is needed to discern the impact of specific genomic alterations (e.g. EWSR1-KLF15 fusion) on tumor biology and response to therapy.

e23536 Background: LMS-04 trial shows improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) with D+T followed by trabectedin (T) alone compared with doxorubicin alone in advanced LMS. Real-world outcomes with this regimen remain limited. This single-center retrospective study reports on the standard-of-care use of D+T in localized and advanced uterine LMS (ULMS) and soft-tissue LMS (STLMS). Methods: We included patients with confirmed histologic diagnosis of LMS treated with D+T at any point in routine clinical practice at MD Anderson Cancer Center (MDACC). The objective was to assess recurrence-free survival (RFS)/PFS, OS, ORR, and toxicity for both advanced and localized LMS patients treated with D+T in a real-world setting. Kaplan Meier method and log rank tests were used to assess survival outcomes and compare outcomes in subgroups. Data collection is ongoing with over 100 patients to date. Results: Fifty patients were included in this primary analysis (26 with ULMS, 24 with STLMS, cf. Table). In STLMS, primary tumor location was retroperitoneum in 20% (n=10), visceral in 10% (n=5), limb in 10% (n=5), abdominal wall in 4% (n=2), and scalp in 4% (n=2). In those with advanced LMS (n=40), median PFS was 10.5mo, PFS at 1 year was 37%. Overall, the ORR was 42% (21/50), and 40% (16/40) in patients with advanced disease. Median PFS for patients with advanced ULMS and STLMS was 9.6mo and 11mo months, respectively (p=0.73). Among 10 patients with localized disease, 5 underwent surgery before D+T (1 STLMS, 4 ULMS), and 6 received post-induction local therapy, including surgery alone (2 STLMS, 1 ULMS) or surgery and radiotherapy (3 STLMS). Nine patients with advanced disease received post-induction local therapy with surgery alone (1 ULMS, 4 STLMS), surgery plus radiotherapy (1 ULMS, 1 STLMS), surgery plus ablation (1 STLMS), or ablation alone (1 ULMS), with median PFS not reached (NR) versus 8.6 months in those without local therapy (p=0.011). Median OS for patients with advanced disease was 32.6mo. Grade ≥3 toxicity occurred in 92% (46/50), with 46% (23/50) requiring dose reductions; common toxicities were anemia, fatigue, and thrombocytopenia. Conclusions: In a real-world setting, outcomes with D+T are consistent with LMS-04 for ORR though slightly inferior in PFS for ULMS. We observe improved PFS in patients receiving local treatments after induction. ORR, toxicity, and dose-reduction rates were also comparable. Updated results with larger cohorts will be presented. Localized ULMS (N=5) Advanced ULMS (N=21) Localized STLMS (N=5) Advanced STLMS (N=19) Median age, yrs 45 48 49 54 Gender - - 60% F40% M 53% F47% M Size≥10 cm 4 (80%) 13 (62%) 3 (60%) 4 (21%) ORR 40% 42.9% 60.0% 36.8% RFS/PFS, mo (95% CI) 9.7 (5.1 – NR) 9.6 (4.5 – 14.7) NR 11 (8.6 – 16.6) RFS/PFS at 12 mo 40% 40.4% 100% 34.2% OS, mo NR 22.5 NR 32.6 Dose reduction, N (%) 2 (40%) 10 (48%) 2 (40%) 9 (48%) % of grade ≥3 toxicity 100% 90.5% 80.0% 89.5%

Treemap of most common drug mechanisms for patients treated in biomarker-matched studies.

Undifferentiated pleomorphic sarcoma (UPS) is the largest subgroup of soft-tissue sarcomas. It demonstrates post-therapeutic hemosiderin deposition, granulation tissue formation, fibrosis, and calcification. Our research aims to establish the multiparametric MRI (mp-MRI) value for predicting UPS treatment response. An IRB-approved retrospective study included 33 extremity UPS patients with pre-operative mp-MRI, including diffusion-weighted imaging (DWI), contrast-enhanced susceptibility-weighted imaging (CE-SWI), and perfusion-weighted imaging with dynamic contrast-enhancement (PWI/DCE), and surgical resection between February 2021 and May 2023. Lesions were visually classified on CE-SWI into one of 6 morphology patterns. On PWI/DCE, lesions were classified into one of 6 patterns, and time-intensity curves (TICs) were classified as types I-V. Patients were categorized into three groups based on the percentage of pathology-assessed treatment effect (PATE) in the surgical specimen: Responders (> = 90

PURPOSE Undifferentiated pleomorphic sarcomas (UPSs) demonstrate therapy-induced hemosiderin deposition, granulation tissue formation, fibrosis, and calcification. We aimed to determine the treatment-assessment value of morphologic tumoral hemorrhage patterns and first- and high-order radiomic features extracted from contrast-enhanced susceptibility-weighted imaging (CE-SWI). MATERIALS AND METHODS This retrospective institutional review board–authorized study included 33 patients with extremity UPS with magnetic resonance imaging and resection performed from February 2021 to May 2023. Volumetric tumor segmentation was obtained at baseline, postsystemic chemotherapy (PC), and postradiation therapy (PRT). The pathology-assessed treatment effect (PATE) in surgical specimens separated patients into responders (R; ≥90%, n = 16), partial responders (PR; 89%-31%, n = 10), and nonresponders (NR; ≤30%, n = 7). RECIST, WHO, and volume were assessed for all time points. CE-SWI T2* morphologic patterns and 107 radiomic features were analyzed. RESULTS A Complete-Ring (CR) pattern was observed in PRT in 71.4% of R ( P = 7.71 × 10 –6 ), an Incomplete-Ring pattern in 33.3% of PR ( P = .2751), and a Globular pattern in 50% of NR ( P = .1562). The first-order radiomic analysis from the CE-SWI intensity histogram outlined the values of the 10th and 90th percentiles and their skewness. R showed a 280% increase in 10th percentile voxels ( P = .061) and a 241% increase in skewness ( P = .0449) at PC. PR/NR showed a 690% increase in the 90th percentile voxels ( P = .03) at PC. Multiple high-order radiomic texture features observed at PRT discriminated better R versus PR/NR than the first-order features. CONCLUSION CE-SWI morphologic patterns strongly correlate with PATE. The CR morphology pattern was the most frequent in R and had the highest statistical association predicting response at PRT, easily recognized by a radiologist not requiring postprocessing software. It can potentially outperform size-based metrics, such as RECIST. The first- and high-order radiomic analysis found several features separating R versus PR/NR.

Background: Primary intrathoracic synovial sarcoma (SS) is a rare entity. The objective of this study was to evaluate survival outcomes for patients with intrathoracic SS presenting with localized disease at diagnosis. Methods: We conducted a retrospective review of 63 patients diagnosed with intrathoracic SS between 1997 and 2020. The Kaplan-Meier method and log-rank test were used to estimate the progression-free survival (PFS), overall survival (OS), local recurrence-free survival (LRFS), and metastasis-free survival (MFS). The hazard ratios were estimated by using Cox proportional hazards regression. Median follow-up time, age-at-diagnosis, and primary tumor size were 31 months (range: 4-218 months), 43 years (range: 18-77), and 7 cm (range: 1-23), respectively. Results: Sixty-two of sixty-three (98%) patients had their primary tumor resected, from whom eighteen (29%) and forty-three (69%) had received neo/adjuvant radiotherapy and chemotherapy, respectively. Median PFS, OS, and MFS were 1.2, 3.0, and 1.1 years, respectively. Based on multivariable analyses, patients with ≥5 cm tumor size had poorer OS (versus < 5 cm; HR: 2.66; 95% CI: 1.16, 6.11; LR-p = 0.014). Importantly, the receipt of neo/adjuvant chemotherapy was the only factor associated with both a more favorable PFS (HR: 0.33; 95% CI: 0.17, 0.65; LR-p = 0.0002) and a more favorable MFS (median 1.33 years versus no chemo 0.5 years; HR: 0.35; 95% CI: 0.17, 0.73; LR-p = 0.005). Conclusions: Outcomes associated with intrathoracic SS remain poor. Factors associated with poorer outcomes include larger tumors and omission of chemotherapy in the management of localized disease. We recommend providing perioperative chemotherapy to all patients with ≥5 cm tumor size to improve progression and metastasis-free survival.

Summary of response outcomes across subgroups

11576 Background: MPNSTs are aggressive sarcomas with poor prognosis due to their high propensity for metastasis, rapid growth and limited response to standard chemotherapy (CT). While commonly associated with neurofibromatosis type 1 (NF1), they can also occur sporadically (non-NF1). This study aims to evaluate baseline characteristics and outcomes in NF1 and non-NF1 associated MPNST in order to understand CT effectiveness and set a benchmark for future therapies. Methods: A retrospective chart review was conducted at MDACC, including 258 patients diagnosed with MPNST (173 NF1 and 85 non-NF1). Data collected included demographic information, primary tumor location and size, disease stage at diagnosis (localized vs. metastatic), efficacy of CT regimens utilized, and survival data. Descriptive statistics were used to summarize patient characteristics. Chi squared tests or Fisher’s exact tests, and t-test/ANOVA were used to compare patient’s characteristics and distributions of overall survival (OS), and progression-free survival (PFS) were estimated by the Kaplan-Meier method. Results: Median age at diagnosis was 33 yrs (IQR 22-44) and 50 yrs (IQR 38-61), and median tumor size at diagnosis 7.4cm and 6.3cm for the NF1 and non-NF1 cohorts, respectively. Tumors were most commonly located in the trunk, followed by the lower extremity, with head and neck involvement more frequent in non-NF1 cases. Metastatic disease was present at diagnosis in 28.3% of NF1 (49/173) and 22.4% (19/85) of non-NF1 cases. Adriamycin with Ifosfamide (AI) was the most utilized first-line CT regimen while gemcitabine plus docetaxel was the preferred second-line regimen. 154 patients, 87 patients, and 37 patients received frontline, second-line, and third-line CT, respectively. Median PFS for front-line CT was 8.0 months (4.7, NR) for patients with metastatic disease at presentation and 11.7 months (8.94, NR) for patients who received AI. Median OS was 2.34 yrs (1.88, 3.15) vs 1.81 yrs (0.89, 3.76) for NF1 and non-NF1 cohorts (p = 0.038), respectively. 5-yr OS was 42% (33, 51) for local disease and 9% (3, 19) for metastatic disease at presentation. Additional analysis of PFS by NF1 status, lines of therapy, and regimen will be presented at the conference. Conclusions: Patients with metastatic MPNST have dismal outcomes and CT efficacy and utilization drops after frontline treatment. These findings highlight the importance of early diagnosis and tailored novel therapeutics for MPNST patients.

Supplement Table 1: Histologic Make-up of common sarcomas Supplement Table 2: List of common alterations among URS population by frequency Supplement Table 3: Sarcomas experiencing without clinical benefit (e.g. SD for <6 months or PD as best response) Supplement Table 4: Immunotherapy Responses and Clinical Benefit

OBJECTIVES:Synovial sarcoma (SS) of the abdomen and pelvis is a rare and understudied condition. This study aimed to evaluate survival outcomes, assess calculated versus observed outcomes, and describe radiographic features among patients with localized abdominal/pelvic SS. METHODS:A retrospective chart review of 58 patients diagnosed with localized abdominal/pelvic SS between 1992 and 2022 was performed. Overall survival (OS), local recurrence-free survival (LRFS), and metastasis-free survival (MFS) were assessed. Sarculator-predicted 5-year OS and disease-free survival (DFS) were compared with observed outcomes. RESULTS:Twenty-four (41%) patients had tumors located in the extra-abdominal/pelvic region, and 34 (59%) had tumors located in the intra-abdominal/pelvic region. Most of the patients were female (62%). Survival outcomes revealed a median OS: 5.5 years, 5-year OS: 53%, median MFS: 1.5 years, and 5-year MFS: 32%. Patients with intra-abdominal/pelvic tumors had significantly worse MFS than those with extra-abdominal/pelvic tumors (median 1.3 vs. 2.7 y; P =0.023). Larger tumor size (≥5 cm MFS HR: 4.20, 95% CI: 1.48-11.95), poorly differentiated histology (MFS HR: 2.92, 95% CI: 1.13-7.53), and positive/unknown margins (OS HR: 2.96, 95% CI: 1.29-6.78; LRFS HR: 6.61, 95% CI: 1.65-26.50; MFS HR: 2.45, 95% CI: 1.23-4.89) were associated with worse outcomes. Sarculator-predicted and observed 5-year OS (49% vs. 52%) and DFS (30% vs. 26%) were consistent. Imaging features such as cystic changes and calcification were more frequent in larger and monophasic tumors. CONCLUSIONS:In localized abdomen/pelvic SS patients, tumor size, location, and surgical margins are critical prognostic factors. Sarculator may aid in risk stratification.

Background and purpose: Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma in the pediatric population and an aggressive cancer subtyped as embryonal, alveolar, pleomorphic, or not otherwise specified (NOS). It demonstrates post-therapeutic hemosiderin deposition, granulation tissue formation, fibrosis, and calcification. This pilot study aims to provide initial evidence for developing a multiparametric MRI-feature-derived (mp-MRI) predictive response model to outperform RECIST.Methods: A UT MD Anderson Cancer Center IRB-approved retrospective pilot study of 11 extremity and pelvic RMS patients with presurgical mp-MRI, including diffusion-weighted imaging (DWI), contrast-enhanced susceptibility-weighted imaging (CE-SWI), and perfusion-weighted imaging with dynamic-contrast-enhancement (PWI/DCE), with surgical resection between 02/2021-06/2024. Lesions were categorized into 6 CE-SWI and 6 PWI/DCE morphologic patterns. Time-intensity curves (TICs) were classified as types I-V. Patients were categorized by the percentage of pathology-assessed treatment effect (PATE) in the surgical specimen as responders (PATE> 90%, n = 3) and partial/non-responders (PATE < 90%, n = 8).Results: The ADC-mean for the 6 extremity RMS increased minimally from 1,425 ± 476 x 10-6 mm2/s at baseline (BL) to 1,494 ± 386 x 10-6 mm2/s at the presurgical time point (PS). The ADC-mean for the 5 pelvic RMS increased from 1,093 ± 342 x 10-6 mm2/s at BL to 1,677 ± 313 x 10-6 mm2/s at PS. All responders and partial/non-responders presented presurgical RECIST, WHO, and volume stability. At PS, 50% of responders displayed CE-SWI Complete Ring pattern (p = 0.5578), PWI/DCE Capsular pattern (p = 0.6065), and TIC Type-2 (p = 0.6065). No statistically significant differences were observed at PS in ADC or CE-SWI first- or high-order radiomics and PWI/DCE semi-quantitative parameters comparing responders vs. partial/non-responders at PS. PS ROC Analysis: The model based on the CE-SWI textural radiomic GLSZM Large-Area-High-Gray-Level-Emphasis yielded perfect classification performance (AUC = 1.0) separating responders vs. partial/non-responders, outperforming other radiomic, morphologic, and qualitative features such as ADC-Maximum-2D-Diameter-Slice (0.83), CE-SWI Complete Ring (AUC = 0.67), PWI/DCE Capsular (0.67), RECIST (0.67), and TIC type-2 (0.6).Conclusion: Our pilot study provides initial evidence supporting a model utilizing a single CE-SWI-derived high-order texture GLSZM radiomic feature that, in our small sample, obtained a perfect classification performance (AUC = 1.0), further building on the body of evidence supporting the use of mp-MRI with CE-SWI in soft-tissue sarcoma response assessment and suggesting its potential in predicting RMS response, outperforming RECIST (AUC = 0.67). These promising early results are hindered by a limited statistical power (10%) inherent to the small sample size and the retrospective nature of an exploratory pilot study, highlighting the necessity for further validation through a larger, more representative, and balanced prospective study.

Background: Rhabdomyosarcomas are the most common soft tissue sarcoma in children, and pediatric alveolar rhabdomyosarcoma (ARMS) prognosis has improved based on cooperative studies. However, in adults, ARMS is significantly rarer, has poorer outcomes, and currently lacks optimal treatment strategies. Objective: This study aimed to evaluate the clinical outcome of an adult ARMS population with different front-line systemic chemotherapies and determine if any chemotherapy regimen is associated with improved survival. Materials and methods: This is a retrospective study of histologically confirmed fusion-positive ARMS patients over 18 years of age, who were treated at MD Anderson Cancer Center (MDACC) from 2004 to 2021 and received systemic chemotherapy. Descriptive clinical statistics were performed, including staging, front-line chemotherapy, multimodal therapy usage, response rates, and survival analyses. Results: 49 ARMS patients who received upfront chemotherapy were identified. Locoregional treatments included radiotherapy (RT) alone (29%, n = 14), surgery alone (10%, n = 5), or both (45%, n = 22). Median overall survival (OS) for the entire cohort was 3.6 years, and the overall response rate to systemic therapy was 89%. No chemotherapy regimen showed OS benefit, specifically analyzing the pediatric-based vincristine, actinomycin-D, cyclophosphamide (VAC) or adult-based vincristine, doxorubicin, ifosfamide (VDI) regimens, even when controlled for other clinical risk factors. Conclusion: In this single-center contemporary series, adult ARMS patient outcomes remain poor. There was no statistically significant OS difference in patients who did or did not receive adult or pediatric based ARMS regimens, although a high overall response rate to chemotherapy was seen across the entire cohort. Based on these observations, further randomized prospective studies are necessary to delineate which frontline chemotherapy regimen is most beneficial in this rare adult cancer.

Background: this study aims to evaluate the survival outcomes of patients suffering from head and neck synovial sarcoma (HNSS), especially in relation to patients with a localized disease at diagnosis. Methods: this retrospective chart review includes 57 patients diagnosed with primary HNSS between 1981 and 2020 who presented with a localized disease at diagnosis. Overall survival (OS) from diagnosis, local recurrence-free survival (LRFS), and metastasis-free survival (MFS) from the end of the primary tumor treatment are estimated. The Kaplan–Meier method, the log-rank test, and the Cox proportional hazards regression are used. Results: the 5-year OS, LRFS, and MFS are estimated at 80.4% (95% CI: 66.6%, 88.9%), 67.7% (95% CI: 50.0%, 80.4%), and 50.6% (95% CI: 34.4%, 64.8), respectively. Compared to patients undergoing surgical resection alone, those receiving radiation therapy (RT) with surgery have better LRFS (HR: 0.03, 95% CI: 0.001, 0.57), and those undergoing neo/adjuvant chemotherapy with surgery and RT have better MFS (HR: 0.10, 95% CI: 0.01, 0.95). Moreover, among the patients with tumors ≥ 4 cm, those subject to neo/adjuvant chemotherapy have significantly better MFS (5-year MFS: 53.2%, 95% CI: 29.0%, 72.5%) than those treated with surgery and RT alone (5-year MFS: 20.0%, 95% CI: 0.8%, 58.2%) (LR-p = 0.003). Conclusions: overall, the prognosis of HNSS patients looks favorable. Perioperative RT significantly improves local control, and perioperative chemotherapy plays a vital role in delaying metastasis formation in patients with primary HNSS when diagnosed with a localized disease. Importantly, we recommend that systemic therapy should be considered for HNSS patients with tumors ≥ 4 cm.

Based on the demonstrated clinical activity of immune-checkpoint blockade (ICB) in advanced dedifferentiated liposarcoma (DDLPS) and undifferentiated pleomorphic sarcoma (UPS), we conducted a randomized, non-comparative phase 2 trial ( NCT03307616 ) of neoadjuvant nivolumab or nivolumab/ipilimumab in patients with resectable retroperitoneal DDLPS ( n = 17) and extremity/truncal UPS (+ concurrent nivolumab/radiation therapy; n = 10). The primary end point of pathologic response (percent hyalinization) was a median of 8.8% in DDLPS and 89% in UPS. Secondary end points were the changes in immune infiltrate, radiographic response, 12- and 24-month relapse-free survival and overall survival. Lower densities of regulatory T cells before treatment were associated with a major pathologic response (hyalinization > 30%). Tumor infiltration by B cells was increased following neoadjuvant treatment and was associated with overall survival in DDLPS. B cell infiltration was associated with higher densities of regulatory T cells before treatment, which was lost upon ICB treatment. Our data demonstrate that neoadjuvant ICB is associated with complex immune changes within the tumor microenvironment in DDLPS and UPS and that neoadjuvant ICB with concurrent radiotherapy has significant efficacy in UPS.

Objective: We evaluated survival outcomes by primary tumor site in synovial sarcoma (SS) patients with localized and metastatic disease at diagnosis. Methods: We conducted a retrospective review of 504 SS patients diagnosed from 1974 to 2020. Kaplan-Meier method, log-rank test, and Cox-proportional hazards regression were used. Results: Among 504 patients, 401 (79.6%) presented with localized disease, and 103 (20.4%) with metastases. For patients with localized disease, (1) 5-year OS by tumor site was as follows: 80% (95% CI, 67%-89%) for head/neck, 30% (95% CI, 18%-42%) for intrathoracic, 51% (95% CI, 35%-65%) for abdomen/pelvis, 71% (95% CI, 62%-79%) for proximal-extremity, and 83% (71%, 91%) for distal-extremity. (2) On multivariable analysis, tumor site (compared with proximal-extremity: intrathoracic tumors [HR: 1.95; 95% CI, 1.22-3.16]; hand/foot [HR: 0.52; 95% CI, 0.28-0.97]), tumor size (compared with <5 cm, 5-10 cm [HR: 1.80; 95% CI, 1.14-2.85]; ≥10 cm [HR: 4.37; 95% CI, 2.69-7.11]), and use of neo/adjuvant radiation (HR: 0.54; 95% CI, 0.37-0.79) remained significantly associated with OS. For patients with metastatic disease, (1) 5-year OS was 12% (95% CI, 6%-21%) and (2) the only factor that remained significantly associated with OS on multivariable analysis was surgical resection for the primary tumor (HR: 0.14; 95% CI, 0.08-0.26). Conclusions: The primary tumor location plays a significant role in predicting outcomes for patients with localized SS. Even though patients present with metastatic disease, surgical resection of the primary tumor improves their survival. These findings are critical for patient counseling and designing a personalized treatment plan that reflects the corresponding outcomes.