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Abstract Background This study aimed to assess the performance of currently available risk calculators in a cohort of patients with malignant peripheral nerve sheath tumors (MPNST) and to create an MPNST-specific prognostic model including type-specific predictors for overall survival (OS). Methods This is a retrospective multicenter cohort study of patients with MPNST from 11 secondary or tertiary centers in The Netherlands, Italy and the United States of America. All patients diagnosed with primary MPNST who underwent macroscopically complete surgical resection from 2000 to 2019 were included in this study. A multivariable Cox proportional hazard model for OS was estimated with prespecified predictors (age, grade, size, NF-1 status, triton status, depth, tumor location, and surgical margin). Model performance was assessed for the Sarculator and PERSARC calculators by examining discrimination (C-index) and calibration (calibration plots and observed-expected statistic; O/E-statistic). Internal–external cross-validation by different regions was performed to evaluate the generalizability of the model. Results A total of 507 patients with primary MPNSTs were included from 11 centers in 7 regions. During follow-up (median 8.7 years), 211 patients died. The C-index was 0.60 (95% CI 0.53–0.67) for both Sarculator and PERSARC. The MPNST-specific model had a pooled C-index of 0.69 (95%CI 0.65–0.73) at validation, with adequate discrimination and calibration across regions. Conclusions The MPNST-specific MONACO model can be used to predict 3-, 5-, and 10-year OS in patients with primary MPNST who underwent macroscopically complete surgical resection. Further validation may refine the model to inform patients and physicians on prognosis and support them in shared decision-making.

BACKGROUND: Narrative operative reports may omit or obscure data from an operation. OBJECTIVE: To develop a synoptic operative report for rectal prolapse that includes core descriptors as developed by an international consensus of expert pelvic floor surgeons. DESIGN: Descriptors for patients undergoing rectal prolapse surgery were generated through review. Members of the Pelvic Floor Disorders Consortium were recruited to participate in a 3-round Delphi process using a 9-point Likert scale. Descriptors that achieved 70% agreement were kept from the first round, and descriptors scoring 40% to 70% agreement were recirculated in subsequent rounds. A final list of operative descriptors was determined at a consensus meeting, with a final consensus meeting more than 70% agreement. SETTINGS: This survey was administered to members of the Pelvic Floor Disorders Consortium. PATIENTS: No patient data are included in this study. MAIN OUTCOME MEASURES: Descriptors meeting greater than 70% agreement were selected. RESULTS: One hundred seventy-six surgeons representing colorectal surgeons, urogynecologists, and urologists distributed throughout North America (56%), Latin America (4%), Western Europe (29%), Asia (4%), and Africa (1%) participated in the first round of Delphi voting. After 2 additional rounds and a final consensus meeting, 16 of 30 descriptors met 70% consensus. Descriptors that met consensus were surgery type, posterior dissection, ventral dissection, mesh used, type of mesh used, mesh location, sutures used, suture type, pouch of Douglas and peritoneum reclosed, length of rectum imbricated, length of bowel resected, levatoroplasty, simultaneous vaginal procedure, simultaneous gynecologic procedure, simultaneous enterocele repair, and simultaneous urinary incontinence procedure. LIMITATIONS: The survey represents the views of members of the Delphi panel and may not represent the viewpoints of all surgeons. CONCLUSIONS: This Delphi survey establishes international consensus descriptors for intraoperative variables that have been used to produce a synoptic operative report. This will help establish defined operative reporting to improve clinical communication, quality measures, and clinical research. See Video Abstract. DESARROLLO DE UN PROTOCOLO OPERATORIO SINÓPTICO DERIVADO DE CONSENSO PARA EL PROLAPSO RECTAL: UN INFORME DEL CONSORCIO DE TRASTORNOS DEL PISO PÉLVICO ANTECEDENTES: Los protocolos operativos narrativos frecuentemente pueden omitir u oscurecer datos de un procedimiento. OBJETIVO: Nuestro objetivo es desarrollar un protocolo operatorio sinóptico para el prolapso rectal que incluya descriptores básicos desarrollados por un consenso internacional de cirujanos expertos en piso pélvico. DISEÑO: Los descriptores para pacientes sometidos a cirugía de prolapso rectal se generaron mediante revisión. Se reclutó a miembros del Consorcio de Trastornos del Piso Pélvico para participar en un proceso Delphi de 3 rondas utilizando una escala Likert de 9 puntos. Los descriptores que lograron un 70% de acuerdo se mantuvieron en la primera ronda, los descriptores que obtuvieron un 40-70% de acuerdo se recircularon en rondas posteriores. Se determinó una lista final de descriptores operativos en una reunión de consenso, con una reunión de consenso final de más del 70% de acuerdo. ESCENARIO: Esta fue una encuesta administrada a miembros del Consorcio de Trastornos del Piso Pélvico. PRINCIPALES MEDIDAS DE RESULTADO: Se seleccionaron los descriptores que cumplieron más del 70% de acuerdo. RESULTADOS: Ciento setenta y seis cirujanos en representación de cirujanos colorrectales, uroginecólogos y urólogos distribuidos en América del Norte (56%), América Latina (4%), Europa Occidental (29%), Asia (4%) y África (1%) participaron en la primera ronda de votación Delphi. Después de dos rondas adicionales y una reunión de consenso final, 16 de 30 descriptores alcanzaron un 70% de consenso. Los descriptores que alcanzaron consenso fueron: tipo de cirugía, disección posterior, disección ventral, malla utilizada, tipo de malla utilizada, ubicación de la malla, suturas utilizadas, tipo de sutura, cierre del fondo de saco de Douglas y peritoneo, longitud del recto superpuesto, longitud del intestino resecado, plastía de los elevadores , procedimiento vaginal simultáneo, procedimiento ginecológico simultáneo, reparación simultánea de enterocele y procedimiento simultáneo de incontinencia urinaria. LIMITACIONES: La encuesta representa las opiniones de los miembros del panel Delphi y puede no representar los puntos de vista de todos los cirujanos. CONCLUSIONES/DISCUSIÓN: Esta encuesta Delphi establece descriptores de consenso internacional para las variables intraoperatorias que se han utilizado para producir un protocolo operatorio sinóptico. Esto ayudará a establecer protocolos operativos definidos para mejorar la comunicación clínica, las medidas de calidad y la investigación clínica. (Traducción—Dr. Felipe Bellolio)

12048 Background: Playing music has been an important part of human culture for millennia. Today more than half of American households have at least one person who plays music, and in the UK 43% of adults play an instrument. Despite the overlap between musicians and people diagnosed with cancer, the effect of cancer treatment on musicianship has not been well-studied. We previously reported that 26% of a musician breast cancer survivor cohort reported difficulty with musicianship after treatment, and here we conduct further analysis to identify treatment and disease factors associated with this difficulty, termed acute musical toxicity (AMT). Methods: The Musical Toxicity Questionnaire was distributed to participants who had previously enrolled in the Mayo Clinic Breast Cancer Registry. PROMIS (Patient-Reported Outcomes Measurement Information System) scores were available through the Registry and treatment details were collected retrospectively. Due to the inter-dependency and high correlation between treatment and disease-related variables, a classification tree analysis (CTA) was performed to identify the combination of variables that most accurately classified patients by AMT. Sixteen variables were analyzed by the algorithm. Logistic regression was utilized for examining associations between AMT and continuous variables. Results: Of the 4075 surveys distributed, 1871 were returned and 535 respondents identified as musicians. Median time from diagnosis was 5.2 years, respondents were mostly stage I or II (71%), and 32% were node positive (N+). Over a quarter (26% or 144 respondents) reported AMT. In the final CTA model, being N+ was strongly associated with AMT (42% of those N+ had AMT, 20% of those not N+ had AMT). For respondents who were N+, those who received endocrine therapy were more likely to have AMT than those who did not (46% vs 21% respectively). Subsequent leaves identified not undergoing axillary lymph node dissection (ALND) and receiving chemotherapy as associated with AMT. For respondents who did not receive chemotherapy, breast reconstruction was associated with AMT (60% vs 19%). Variables such as mastectomy, radiation volume, specific chemotherapies, and stage of disease were not selected by the algorithm. The odds of having AMT decreased by 9.7% and 17% with each additional point in the composite mental health (p=0.003) and physical health (p<0.001) PROMIS scores, respectively. The odds of having AMT increased by 3.5% with each lymph node removed (p=0.001). Conclusions: The final model suggests that the group with the largest proportion of AMT was N+, received endocrine therapy, did not have ALND, and received chemotherapy. Both physical and mental health PROMIS scores were associated with AMT, although the directionality of this relationship requires more study. Care teams should counsel patients on potential musical toxicity and engage in shared decision making with musical patients.

TPS11588 Background: Imatinib is the worldwide standard for first-line therapy of advanced KIT-mutant GIST. However, secondary resistance mutations in the KIT ATP-binding domain (exons 13, 14), activation loop (exons 17, 18), or both develop and result in loss of imatinib-sensitivity. Bezuclastinib has a highly selective inhibition profile, leading to minimal off-target toxicities and allowing for combination with sunitinib. While no single tyrosine kinase inhibitor (TKI) inhibits all KIT mutations, the combination of bezuclastinib + sunitinib targets commonly occurring primary (exons 9, 11) and secondary (exons 13, 14, 17, and 18) KIT mutations and may provide more durable responses. The early signs of clinical activity, tolerability, and safety observed with the combination thus far in Peak Part 1 (Somaiah et al. [presentation] CTOS 2023. Paper 62) are consistent with the completed Phase 1/2 study (PLX121-01). Methods: Peak (NCT05208047) is a global, randomized, open-label, multi-part Phase 3 study evaluating the efficacy and safety of bezuclastinib + sunitinib versus sunitinib as second-line treatment in adult pts who were intolerant to imatinib or whose tumors had imatinib-resistance. Current Peak study sites are located in North America (3 countries), South America (3 countries), Europe (12 countries), and Asia-Pacific (4 countries). The lead-in portion to test a new formulation of bezuclastinib, (Part 1) completed enrollment in April 2023. Based upon PK and safety, a dose of bezuclastinib 600 mg QD + sunitinib 37.5 mg QD was determined for Part 2 of the Peak study. Part 2 will enroll ~388 pts to be randomized (1:1) to bezuclastinib 600 mg QD + sunitinib 37.5 mg QD or sunitinib 37.5 mg QD alone. Key inclusion: >1 measurable lesion per modified Response Evaluation Criteria in Solid Tumors (mRECIST) v1.1, Eastern Cooperative Oncology Group Performance Status 0-2, adequate organ function, and prior imatinib therapy (no other prior therapy). Key exclusion: known PDGFR mutations or succinate dehydrogenase deficiency, clinically significant cardiac disease, and use of strong CYP3A4 inhibitors or inducers. The primary endpoint is progression-free survival (PFS) confirmed by blinded independent central review per mRECIST v1.1. Additional efficacy (including overall survival and objective response rate) and safety endpoints will be evaluated and circulating tumor DNA (ctDNA) will be collected and assessed. Clinical trial information: NCT05208047 .

e23554 Background: Follicular dendritic cell sarcoma (FDCS) is a low-grade neoplasm arising from follicular dendritic cells. Its diagnosis is challenging due to its extreme rarity, and the optimal management remains unknown. Methods: We conducted a retrospective study of FDCS patients (pts) seen at Mayo Clinic, MN since 2018. Time to event analyses were done from the time of diagnosis. Results: Ten pts with FDCS were identified (Table). The median age was 60 years (range, 38-76) and 5 were males. Abdominal pain was the most common presenting symptom (30%) followed by constitutional symptoms, shortness of breath, and vision change. In 3 pts, the diagnosis was incidental. The 2 most common primary locations were abdomen/pelvis (50%) and mediastinum (30%). Six pts (60%) presented with advanced disease and 3 (30%) had Castleman’s disease. Most (60%) had advanced disease. Six pts had Epstein-Barr virus in situ hybridization and all tested negative. Seven pts had next generation sequencing and 5 (83%) had genetic alterations detected with CDKN2A/B alterations being most frequent (3 pts, all with advanced disease). The median follow up was 4.3 years (range, 0.2-13.3). In the 4 patients with localized disease, 3 underwent complete surgical excision resulting in complete remissions (CRs). The one who received radiation had a partial remission (PR). The median time to progression after 1st line treatment was 4 months (all with advanced disease). All 3 pts who died had advanced disease and 2 had CDKN2A/B alterations. Conclusions: In FDCS, localized diseases managed by surgical excision with or without radiation can achieve long term remissions. Advanced diseases generally do not respond to multimodality therapy including immunotherapy but can have disease stabilization with variable survival. CDKN2A/B mutations were common and potentially associated with a worse outcome. Better understanding of the impact of the FDCS mutational landscape on prognosis may provide novel approaches to therapy. [Table: see text]

e23537 Background: Follicular Dendritic Cell Sarcoma (FDCS) is a rare, indolent, low-grade sarcoma known for local recurrences managed primarily by surgery. The role for adjuvant therapy has not been established for either radiation or chemotherapy. We aimed to comprehensively analyze clinical and epidemiological profiles and responses to treatment in these patients. Methods: This is a retrospective study using the National Cancer Institute (NCI) Surveillance, Epidemiology, and End Result (SEER) database. Cases of FDCS between 2001 to 2022 were identified utilizing the International Classification of Diseases for Oncology edition 3 (ICD-O-3) code 9758/3. Only adults > 18 years of age and diagnosed by positive histology or cytology were included. Descriptive statistics were used to describe demographic and tumor characteristics. Logistic regression was used to identify the factors influencing survival. Kaplan-Meier method was used to plot survival based on different treatment regimens and stages. Results: A total of 168 patients with FDCS were identified, with more than 50% of the patients ≥ 50 years of age. The mean age at diagnosis was 52.6 years, 56% were female, and 74.4% were white. Most of the patients had localized disease (63.7%), 17.9% had distant disease, and the remaining had unknown stages. About 90% of the patients underwent surgery, with 41% receiving local tumor excision. In Univariate analysis, older age, and distant disease were found to have poor outcomes. Surgery, irrespective of stage, was found to improve overall Survival (Table 1). While chemotherapy and distant disease had poor outcomes in univariate analysis, they were not statistically significant in multivariate analysis. The majority of the patients who received chemotherapy alone without surgical intervention had distant disease, explaining the poor outcome seen in univariate analysis. Among 107 patients with localized disease, 41 patients (41.1%) underwent only surgery and 43 patients (40.1%) received adjuvant therapy (either chemotherapy or radiation vs both) along with surgery. 5-year overall survival was significantly lower in patients who received adjuvant therapy. (88.4% vs 68.4%, p = 0.001). Conclusions: In conclusion, FDCS has a fair overall 5-year survival with surgery alone. Patients with localized disease, who received adjuvant therapies had poor survival outcomes as compared to the surgery-only group owing to disease burden. Large prospective studies are required to properly evaluate the benefit of adding chemotherapy or radiotherapy in resectable disease.

e23536 Background: Circulating tumor DNA (ctDNA) has gained prominence as a potential indirect marker for minimal residual disease (MRD) in various cancers, including soft tissue sarcomas (STS). Previous studies have suggested that indirect hematologic ratios – such as Neutrophil-Lymphocyte Ratio (NLR), Monocyte-Lymphocyte Ratio (MLR), Platelet-Lymphocyte Ratio (PLR), and Eosinophil-Lymphocyte Ratio (ELR) may correlate with worse outcomes. We sought to evaluate the correlation of NLR, MLR, PLR and ELR in a real world cohort of Non-Hispanic Whites (NHW) and Hispanics (H) with advanced STS. Methods: We performed a retrospective chart review at Dignity Health Cancer institute using our Electronic Medical Records (EMR) and Signatera™ assay to obtain our data points. Inclusion criteria were STS patients of all ages and stages of disease with complete records. We reviewed 33 patient charts, 14 NHW and 19 H patients. Of the NHW population, 11 were male (M) and 3 females (F). For the H population, 14 were M, and 5 were F. We utilized Spearman's rank correlation coefficient to assess monotonic relationships between ct-DNA levels and the hematologic ratios. ct-DNA was quantified through standardized assays per Protocol, with the resultant values treated as continuous variables in our statistical analyses. Power considerations, based on expected effect sizes and type I error rate adjustments were performed. Results: The Spearman’s correlation coefficients and p-values indicated varied associations across ethnic groups. For NHW, the correlations were generally weak and non-significant (NLR: r = 0.18, p = 0.54; MLR: r = -0.04, p = 0.89; PLR: r = 0.35, p = 0.21; ELR: r = 0.001, p = 1.00). Conversely, in the Hispanic cohort, stronger and statistically significant correlations were observed, particularly with NLR (r = 0.78, p < 0.0001) and MLR (r = 0.70, p < 0.001). Overall, the correlations across the entire study population did not reach statistical significance. Conclusions: This study revealed notable racial variations, particularly in the H population, in the relationship between ctDNA levels and hematologic ratios. The noteworthy associations found with NLR (r = 0.78, p < 0.0001) and MLR (r = 0.70, p < 0.001) highlight the possible usefulness of these ctDNA and these indirect biomarkers in assessing disease status in STS. These findings suggest the possibility of using hematologic ratios, particularly in the Hispanic population, as markers of disease progression similar as ctDNA. Hematologic ratios are more easily accessible to the general population compared to ctDNA in many underserved countries and communities. Future studies with larger cohorts are need to further analyze its validity.

e23535 Background: Our study aims to examine the relationship between the presence of circulating tumor DNA (ctDNA) and lactate dehydrogenase (LDH) in patients diagnosed with soft tissue sarcoma (STS). There is emerging yet limited data on the applicability of ctDNA in STS. LDH is a cheaper readily available test that has been associated with unfavorable overall survival in different malignancies. This research aims to understand the correlation between ctDNA and LDH as a tool to assess its utility as indirect markers of response to treatment in STS. Methods: This was a single-center retrospective chart review on patients diagnosed with STS. Eligibility criteria included a confirmed diagnosis and available measurements of both ctDNA and LDH levels. Correlation was compared between Non-hispanic whites (NHW) and Hispanics (H). Data was sourced from our electronic medical record and Signatera™ assay to obtain the primary endpoints. Specimens were standardized in accordance to Natera’s™ specifications. Study endpoints included the correlation coefficients between ctDNA and LDH levels. A two-stage study design was applied for a robust analysis. Spearman's rank correlation coefficient (denoted as r) was employed for statistical analysis, assessing the strength and direction of the monotonic relationship between ctDNA and LDH levels. Marker values were treated as continuous variables in these analyses. All analyses were executed in GraphPad Prism software. Results: The cohort comprised 33 patients with STS (14 NHW, 19 H). The median LDH in H was 189 (interquartile range (IQR) = 184) vs 184 (IQR = 105) in NHW. Comparatively, the median ctDNA in H was 0 (IQR = 39.3) and also 0 (IQR = 11.1) in NHW. The overall correlation between ctDNA and LDH levels was moderate positive (r = 0.5, p = 0.002), indicating a consistent, though not necessarily linear, relationship. Subgroup analysis showed r = 0.19 (p = 0.52) in NHW and r = 0.43 (p = 0.1) in H groups, suggesting ethnic variability in the ctDNA-LDH correlation. These findings were statistically significant within the predefined confidence limits and probability values. Conclusions: Our study demonstrated a significant correlation between ctDNA levels and LDH in STS patients, implying that higher ctDNA may be associated with higher LDH levels. This association can lead clinicians in monitoring LDH more frequently as an indirect marker of response to treatment in STS. This correlation suggests an increased tumor burden with a higher inflammatory response, with variations across different racial groups. The wider availability of LDH testing compared to ctDNA in many centers highlights LDH's potential as an indirect marker for STS. Further research with larger prospective cohorts is essential to confirm LDH's role paired with ctDNA in guiding treatment decisions in STS, enhancing its utility in clinical practice.

e23534 Background: The use of tumor genomic profile (TGP) has led to improved genomic-directed therapies in many solid cancers. Due to its heterogeneity, soft tissues sarcomas (STS) have not benefited much from these genomic advances. Emerging research indicates that about 30% STS have actionable alterations which can lead to potential treatment options (Gounder et al. Nature 2022). Our study aimed to compare the differences in genomic-directed therapy between Non-Hispanic White (NHW) and Hispanic (H) patients with STS at Dignity Health Cancer Institute. Methods: We performed a retrospective analysis of medical records using the electronic medical record. Our study specifically examined patients diagnosed with STS, with a sample size of 14 NHW and 19 H individuals.The eligibility criteria consisted of known diagnosis of STS with completed TGP. We conducted a descriptive analysis using GraphPad Prism Software, where mutations were evaluated as continuous variables. The statistical significance of differences between groups was assessed using an unpaired t-test, with a significance level of < 0.05. Results: We found 73 tumor alterations, with 11 potentially targetable (15.2%). Most patients had negative to low tumor mutational burden (0-2 mut/Mb) with only 2 patients with high TMB ( > 10 mut/Mb). The most common mutations were TP53 and CDK4 with 9 patients (12%) each. The NHW group had an average of 2.57 mutations (standard deviation = 2.87), whereas the H group had an average of 1.42 mutations (standard deviation = 1.35). The median values were 2 and 1, respectively, with no statistically significant difference (p = 0.21). The average for mutations of unknown significance was 1.54 in NHW individuals, while it was 1.00 in Hispanics. In the NHW group showed 11 males and 3 females, while the H group included 14 males and 5 females. There was no significant difference in gender representation between the two groups (p = 1). 3 patients (9%) received non-FDA approved treatments based on TGP (1 CDKN2A-abemaciclib, 1 CDK4-ribociclib and 1 IDH1-ivosidenib) and 2 patients (6.6%) were enrolled in clinical trials. Conclusions: Our investigation reveals that there is no statistically significant disparity in the frequency of mutations between NHW and H groups in our sample. Nevertheless, there was an evident inclination towards an increased frequency of mutations in NHW. Similarly, the occurrence of mutations with uncertain significance was slightly higher in NHWs, although the difference was not statistically significant. Only a minority of patients had targetable mutations or were enrolled in clinical trials. However, the routine use of genomic profiles may lead to more personalized treatments. Our research emphasizes the need to expand the use of comprehensive genomic profiles to increase directed treatments for patients with STS.

e23533 Background: Circulating tumor DNA (ctDNA) has shown promise as a biomarker for cancer detection and tracking in multiple malignancies like melanoma, colon and lung. Due to the heterogeneity of sarcoma, there has been limited research on ctDNA as a tool for measuring minimal residual disease (MRD). Differences in baseline in ctDNA for STS in racial minorities have been poorly studied. To identify potential racial differences in the efficacy of this tool, this study compares the quantitative values of baseline ctDNA between non-Hispanic white (NHW) and Hispanic (H) patients with soft tissue sarcoma (STS). Methods: The medical records of 33 STS patients who had ctDNA analysis from Natera™ were examined retrospectively at Dignity Health Cancer Institute.There were 19 H patients and 14 NHW patients in the group. All Black (B), Asian (A), and Other (O) racial groups were excluded due to lower numbers. GraphPad Prism software was used to examine the baseline ctDNA levels. Using continuous measures for statistical analysis, we conducted descriptive statistics and determined the mean, standard deviation, and median ctDNA levels for each group. The ctDNA levels were compared between groups using a two-tailed t-test with a significance level of p < 0.05. Results: The average ctDNA levels were 416.675 (standard deviation = 1349.394) in NHW and 300.305 (standard deviation = 1000.543) in H. The median levels were 0 for both groups. The statistical analysis showed that there was no significant differences in the baseline ctDNA levels between the two groups (p = 0.73). Furthermore, the gender distribution among NHW and Hs in the cohort was comparable, with a p-value of 1.00. Conclusions: This study establishes that there is no substantial differences in baseline levels of ctDNA between H and NHW patients with STS. These findings indicate that ctDNA levels in these populations can be equally utilized for diagnostic and monitoring reasons in clinical settings. Nevertheless, to gain a comprehensive understanding of the racial disparities in ctDNA utility and its implications in customized treatment for STS, it is necessary to conduct more extensive research with larger sample sizes and incorporate additional variables.