bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pathologic complete response in patients with localized soft tissue sarcoma treated with neoadjuvant therapy and its correlation with clinical outcomes: A systematic review.
Authors: Kyriazoglou Anastasios , Boulouta Anna , Kotsantis Ioannis , Economopoulou Panagiota , Kirkasiadou Maria , Anastasiou Maria , Pantazopoulos Anastasios , Moutafi Myrto , Gavrielatou Niki , Zazas Evangelos , Nasiadi Chrysanthi , Kavourakis George John , Psyrri Amanda 
Published: June 2024

e23529 Background: Soft tissue sarcomas (STS), comprising approximately 1% of adult solid malignancies, are primarily treated with surgery, with the choice of perioperative treatment being a challenging and highly individualized decision. Clinical trials assessing neoadjuvant modalities in STS predominantly use clinical outcomes or radiologic response as endpoints, with pathologic complete response (pCR) typically not being employed as a designated study endpoint. There is a growing inclination towards neoadjuvant treatment for STS. While pCR serves as a crucial marker guiding treatment decisions in other neoplasms like breast cancer and urothelial cancer, it is not yet used in a similar setting for STS. Our systematic review aimed to assess the rates of pCR in clinical trials of different neoadjuvant modalities for STS and its correlation with patient clinical outcomes. Methods: A systematic literature search was conducted, with eligibility criteria being prospective or retrospective, phase I, II or III trials testing neoadjuvant treatments for STS. Neoadjuvant treatments were chemotherapy, radiotherapy, TKIs or combinations of the above. 23 studies were included, from which data regarding rates of pCR with each treatment, as well as the correlation of pCR with clinical outcomes, were retrieved. Results: Of the 23 trials included, seven did not assess pCR. In the remaining 16 trials, pCR was defined by either ≥90% or ≥95% pathologic necrosis in the tumor specimen. The percentage of patients who achieved pCR ranged from 8 to 58%. Most of these trials did not assess an association between pCR and clinical outcomes. However, among those investigating this correlation, a positive association was identified between pCR and both 5-year disease-specific survival (DSS) and 5-year overall survival (OS). Table 1 summarizes the eight trials that sought to correlate rates of pCR with clinical outcomes. Conclusions: Our findings indicate pCR variability across different neoadjuvant treatments for STS and a possible positive correlation with patient outcomes. Consequently, we propose considering pCR as a surrogate endpoint in future prospective trials for STS that might guide further treatment decisions. [Table: see text]
Correlation of ctDNA with hematologic ratios (NLR, MLR, PLR, ELR) in predicting disease progression in soft tissue sarcomas among non-Hispanic Whites and Hispanics: Single-center experience.
Authors: Braat Jonathan , Zamora DIana , Ikram Waleed , Behara Murali Ranjani , Azevedo Chelsea , Dinh Han , Patel Shyamal , Wiseman Jason T. , Gonzalez Velez Miguel 
Published: June 2024

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.
Clinical profile and response to adjuvant treatments in patients with follicular dendritic cell sarcoma in the United States: Insights from SEER analysis.
Authors: Vojjala Nikhil , Yadav Sumeet Kumar , Aldecoa Kim Abbegail Tan , Liu Bolun , Hussein Guleid , Azar Ibrahim , Yadlapalli Sri , Krishnamoorthy Geetha , Goodman Judie R. 
Published: June 2024

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.
Real world effectiveness of immunotherapy combined with anti-angiogenic therapy in patients with anthracycline-resistant soft tissue sarcomas.
Authors: He Mengye , Xu Suzhen , Wang Xiaoting , Zhang Xiaochen , Shen Peng 
Published: June 2024

e23543 Background: Soft tissue sarcomas are a heterogeneous group of malignant tumors of mesenchymal origin with more than 50 histologic subtypes. They have distinct molecular, genetic and clinical features and account for 1% of adult malignancies, the most common being liposarcoma, undifferentiated pleomorphic sarcoma and leiomyosarcoma. Immune checkpoint inhibitors (ICIs) have limited efficacy in sarcomas compared to other solid tumors; however, they have shown some activity in certain subtypes. The use of immunotherapy in sarcoma faces many challenges due to tumor heterogeneity, scarcity of therapeutic antibodies and chimeric antigen receptors to target antigens in sarcoma subtypes. However, combining ICIs with other therapies seems to improve the therapeutic efficacy to some extent. Antiangiogenic targeted therapy has been recommended by major guidelines as the treatment of choice for second-line soft tissue sarcomas. However, there are limited results from large clinical studies on whether immunotherapy combined with antiangiogenic therapy improves the efficacy. Methods: In this real-world single-center retrospective cohort study conducted at the First Affiliated Hospital of Zhejiang University School of Medicine, the efficacy of immunotherapy combined with antivascular therapy was assessed by progression-free survival (PFS) and overall survival (OS). Safety was assessed using the Common Terminology Criteria for Adverse Events version 5.0. Results: In this study, we enrolled a total of 21 eligible patients, of which 6 were liposarcoma, 4 were leiomyosarcoma, 4 were rhabdomyosarcoma, and 7 were other types. The immunotherapy used in all patients was anti-PD-1 antibody, with bevacizumab as the antivascular therapy drug in four of them and antiangiogenic tyrosine kinase inhibitors in the others. 12(57%) patients had received one-line therapy, 9 (43%) had received ≥ second-line therapy. Median progression-free survival (mPFS) was 5.5 months and median overall survival (mOS) 16.1 months in the total population. mPFS was significantly longer in 2nd-line V.S. ≥3rd-line patients (9.6 months V.S. 3.1 months, P = 0.0007), with a tendency to be prolonged mOS in 2nd-line treatment (16.1 months V.S. 9.3 months), but with no statistically significant difference. The most common grade ≥3 adverse events were hypertension, hand-foot syndrome, and abnormal thyroid function. Conclusions: This study confirms that immunotherapy combined with antiangiogenic therapy is effective and tolerable in anthracycline-resistant soft tissue sarcomas in the real world.It is possible that use in the second line may lead to better efficacy than use in multiple lines, and more clinical studies are expected.
A phase 2 study of regorafenib in metastatic/unresectable, refractory synovial sarcomas.
Authors: Fernandes Sanal Canute , Rastogi Sameer , Shamim Shamim Ahmed , Barwad Adarsh , Panday Rambha , Dhamija Ekta 
Published: June 2024

e23551 Background: Current therapeutic options for advanced synovial sarcomas remain limited. Adoptive T-cell therapies against NY-ESO-1 and MAGE-4 benefit a subset of patients, but is of limited value in Asian patients due to the absence of the HLA-A*02 genotype. Methods: The trial had a single arm, Simon two-stage design that included patients with advanced synovial sarcomas who had progressed on 2 lines of therapy, one of which could be an anti-VEGF therapy. Regorafenib was administered orally in a continuous regimen with 80mg and 120 mg doses on alternate days. The primary end point was 3-month progression-free rate (PFR). A 3-month PFR of greater than 40% was taken to be a marker of drug efficacy. Secondary end points included median PFS, OS and safety analysis. Quality of life assessment was carried out at baseline and at 3 months using the EORTC C-30 questionnaire. Radiological responses were assessed using RECIST 1.1 criteria after independent review by 2 radiologists. Results: A total of 22 patients were included in the study during the period from January 2022 to December 2023 with baseline characteristics as shown in Table 1. 18 patients were eligible for assessment of the primary outcome. The 3-month PFR with regorafenib was 57% with an ORR of 5%. At a median follow up of 9 months, the median PFS was 5.0 (2.9-7.0) months, and the median OS was 10.0 (7.8-11.2) months. In an exploratory analysis, the subset of patients previously exposed to pazopanib showed a 3-month PFR of 46% and a median PFS of 3 months. The grade ¾ toxicities seen included HFSR (52%), diarrhea (5%) and oral mucositis (5%). The quality-of-life analysis showed symptom burden to be highest in the fatigue, pain and financial difficulties domain at baseline. No worsening of symptom burden scores was seen over the study period. The global health status score showed a numerical improvement at 3 months. Conclusions: The study had a significant number of patients with poor PS. Regorafenib in the above-mentioned dosing regimen demonstrated meaningful clinical activity in a heavily pre-treated population of patients with synovial sarcoma, including those previously exposed to pazopanib, with a preserved quality of life. The treatment was associated with manageable toxicities and no new safety signals, albeit with higher HFSR rates. [Table: see text]
Clinical features, molecular findings, and clinical outcomes of follicular dendritic cell sarcoma.
Authors: Yi Dongni , Rech Karen , Lester Scott , Breen William , Zanwar Saurabh , Ruan Gordon , Robinson Steven Ian , Okuno Scott H. , Siontis Brittany L. , Garrity James , Kimball Brittany , Ravindran Aishwarya , Shah Mithun Vinod , Bennani Nabila Nora , Goyal Gaurav , Go Ronald S. , Abeykoon Jithma P. 
Published: June 2024

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]
Efficacy and safety of anthracycline combined with alkylating agent for treatment of advanced leiomyosarcoma.
Authors: Tan Huijing , Zuo Lijie , Sun Yuting , Chi Yihebali 
Published: June 2024

e23558 Background: Leiomyosarcoma(LMS) accounts for 12-14% of all soft tissue sarcomas(STSs) and this STS subtype has high metastatic potential. We evaluated the efficacy and safety of epirubicin combined with temozolomide(EPI-TMZ) for treatment of advanced LMS. Methods: Oral TMZ(200 or 300 mg) was administered each day on days 1-5, and intravenous EPI(60 mg/m2) was administered on days 1-4, with even distribution over these 96h within a 21‐day cycle. After 8 cycles of intensive chemotherapy, monodrug maintenance therapy consisted of TMZ alone(dosing as in the primary therapy, most choices, stop taking medication after 1 year control), and two-drug maintenance therapy consisted of TMZ with thalidomide(only 3 patients). All patients-initiated EPI-TMZ treatment between January 2018 and January 2024. Results: We examined 31 patients who received EPI-TMZ. There were 25 females and 6 males, with average age 50.5 years old. All were unresectable patients derived from abdominal retroperitoneum, uterus, inferior vena cava, mesentery, small intestine, stomach, thighs, elbows, wrists, pancreas, nasal cavity, meantime with distant metastasis. Average Ki67 is above 40%. This was a first-line treatment in 16 patients, a second- or third-line in 13, and a fourth-line in 2. At the time of data cutoff (January 31, 2024), the median PFS was 12.6 months, 1 patient had cCR, 9 PR and 20 SD. The ORR was 32.3%(10/31) and DCR was 96.8%(30/31). The only patient who progressed after two cycles of medication had PMS2 deficiency, and studies have reported that it may have a primary resistance mechanism. Even the shortest disease control period is also 5 months, indicating this regime has significant clinical benefit. Some patients have undergone tumor reduction surgery to improve quality of life after achieving significant tumor relief. The current longest PFS is 42 months up to now and under continuous tumor control. Previous retrospective studies indicated the best mPFS was 9.2 months and the best ORR was 30.9%. 2023 ESMO declared prospective doxorubicin with trabectedin obtained mPFS of 12.19 months. The most common treatment-related adverse effects were leukopenia, neutropenia, thrombocytopenia, anemia, nausea, vomiting, fatigue, and oral mucositis. Two patients had severe febrile neutropenia, but there were no treatment-related deaths, survival data follow-up. Conclusions: EPI-TMZ is potentially effective for treatment of advanced LMS, and the adverse effects appear tolerable. EPI-TMZ may provide better outcomes than reported in previous studies of other treatments for advanced LMS, worth further prospective research.
Characterizing the transformation and diagnosis of atypical lipomatous tumors to dedifferentiated liposarcoma: Single-institutional outcomes.
Authors: Yu Austin , Honore Lesly , Timmermann Anne Patricia , Demetrious Matthew , Gitelis Steven , Miller Ira , Blank Alan T. 
Published: June 2024

e23560 Background: Atypical lipomatous tumor (ALT) is a locally aggressive, benign adipocytic tissue mass with risk of transformation into dedifferentiated liposarcoma (DDLS), a mixed-grade, non-lipogenic tumor with increased risk for metastasis and mortality. Studies have evaluated the dedifferentiation rate of DDLS but seldom report the methodology of obtaining their diagnosis, which is crucial due to their heterogeneous architecture and relatively low core needle biopsy (CNB) accuracy. We included a longitudinal cohort of ALT/DDLS patients characterizing how and when patients received their diagnoses. Methods: 168 patients diagnosed with ALT-only (n = 129), DDLS-only (n = 22), or both (n = 17) were included. Among DDLS patients, the presence of a prior ALT diagnosis along with time between their ALT and DDLS diagnosis was measured. Histology, location, results, and methods of each diagnosis were recorded including, CNB, surgical resection, or both. Disease-specific survival (DSS) and recurrence free-survival (RFS) were calculated with univariate/multivariate analysis for risk factors. Results: Among patients who received a diagnosis with CNB consistent with ALT, 7 were subsequently diagnosed with DDLS after surgical resection, representing 4.8% of ALT patients. Mean time between diagnoses was 2.3 months (STD 2.0). 5 (3.4%) patients were diagnosed with a DDLS recurrence after initial ALT diagnosis confirmed with CNB and surgical resection. Median time between diagnoses was 37.0 months (IQR 16.0, 63.0). 5 (3.4%) had tumors with a heterogeneous composition on initial surgical resection, described as an ALT with dedifferentiated components. 22 DDLS patients had no prior ALT diagnosis. 9 were diagnosed from both CNB and surgical resection, and 13 were diagnosed from surgical resection directly after clinical suspicion and imaging concerning for sarcoma. DSS in the DDLS was significantly lower than ALT-only DSS (p < 0.0001). There was no significant difference in RFS. Conclusions: DDLS may arise after an extended period of time after ALT resection or simultaneously with an ALT diagnosis. Due to its varied diagnostic timeline and appearance, caution is advised when evaluating and treating ALT. [Table: see text]