bluuebunny/crossref_metadata_2025_split huggingface dataset:
Myofibroblastic sarcoma: A study of demographic and socioeconomic factors.
Authors: Loken Delaney , Ng Sandy , Moroz Mark , Reddy Nisha , Silberstein Peter T. , Heise Craig , Hsia Beau 
Published: June 2024

e23545 Background: Myofibroblastic sarcoma is a type of non-rhabdomyosarcoma soft tissue sarcoma originating from spindle cells of mesenchymal origin with myofibroblastic differentiation. First described in 1998, there is little known about the prognostic factors of this rare and relatively new cancer. This typically non-metastasizing tumor is primarily found in the head, neck, or extremities. Treatment focuses on tumor excision, and the 5-year overall survival of low-grade myofibroblastic sarcoma cancer is 72%. This study analyzed data from the National Cancer Database (NCDB) to understand how demographic factors contribute to the treatment and prognosis of myofibroblastic sarcoma. Methods: A retrospective cohort analysis was conducted on demographic factors of patients with confirmed myofibroblastic sarcoma (ICD-8825-3) using the NCDB from 2004-2020. Regression analysis was used to study trends of patient age, sex, race, education, insurance status, distance from facility, and Charles/Deyo score within this population. Results: A total of 111 patients (N = 111) were identified in the database with a confirmed diagnosis of myofibroblastic sarcoma from 2004 to 2020 with an increasing frequency of diagnoses per year (R^2 = 0.6283). The average age of diagnosis was 47.3 (SD = 24.17, range = 0 - 90 years). Although Myofibroblastic sarcoma appeared throughout the body, the most prominent sites were the long bones of the lower limb and associative joints (6%) followed by the uterus (5%). The majority of patients were white (83%), non-Hispanic (86%), and female (63%). A higher percentage of patients lived in metropolitan areas with a population greater than 1 million (58%) compared to smaller metropolitan, urban, or rural counties (42%). Most of the patients were treated at an academic/research program (30%) followed by a comprehensive community cancer program (21%). More facility locations were based in the Pacific (15%) and the Middle Atlantic (11%) regions. The primary payer at diagnosis was private insurance/managed care (44%) followed by Medicare (32%) and Medicaid (19%). Few patients (5%) received palliative care. Conclusions: To the best of our knowledge, this is the first NCDB analysis on Myofibroblastic sarcoma. Based on our dataset, Myofibroblastic sarcoma tends to occur in the long bones of the lower limb and associative joints which differed slightly from what we found in previous reports, which described the head and neck as the two areas of highest prevalence. This is the first time the socioeconomic factors have been described in the literature: these patients are more likely to be non-Hispanic, female individuals, living in smaller towns. This study offers insight on how much further investigation is required to better understand the impact of demographic and socioeconomic factors on early diagnosis and treatments.
An analysis of treatment trends in sclerosing epithelioid fibrosarcoma.
Authors: Saldhi Prachi , Samuel Maya Mary , Silberstein Peter T. , Chaddha Jasleen Kaur 
Published: June 2024

e23547 Background: Sclerosing Epithelioid Fibrosarcoma (SEF) is a rare, malignant, soft tissue sarcoma found in the arms, legs, head, and neck. Histologically, SEF is characterized by a distinctive architecture composed of cords, nests, and/or sheets of uniform epithelioid cells. Previous studies have demonstrated that surgery with wide surgical margins is associated with superior outcomes in SEF patients. However, on account of the rare nature of SEF, insufficient research has been conducted on the association of treatment types with long-term survival. Using the National Cancer Database (NCDB), this study analyzed the receipt of different types of surgery and adjuvant treatments on the overall survival of patients with SEF. Methods: The National Cancer Database (NCDB) was used to identify patients diagnosed with SEF from 2004 to 2020 using histology code 8840 as assigned by the Commission on Cancer Accreditation program. Kaplan-Meier, ANOVA Chi-Square, and Logistic Regression tests were performed, and data were analyzed using SPSS version 29. Statistical significance was set at α = 0.05. Results: Out of the 1226 patients with SEF, 1088 patients ( 88.7%) received a tumor resection at the primary site. Receipt of surgery was associated with a greater median overall survival compared to not receiving surgery ( 123.6 months vs 45.7 months; p < 0.05). Of the surgical patients, 419 patients received a wedge/segmental resection ( 38.5%) and 609 patients received a lobectomy ( 56%). Wedge/segmental resections and lobectomy had improved outcomes compared to other surgery types ( p < 0.001). In addition to tumor resection, 140 patients ( 12.9%) received adjuvant chemotherapy, 21 patients ( 1.9%) received adjuvant radiation, and 11(1%) patients received adjuvant chemoradiation. Furthermore, the receipt of adjuvant therapies including adjuvant chemo, adjuvant radiation, and adjuvant chemoradiation, was associated with improved overall survival compared to receiving surgery alone ( p = 0.03; p = 0.005; p < 0.001, respectively). Patients who received adjuvant chemoradiation experienced 9.5 months longer median survival time than patients who received adjuvant chemotherapy ( p < 0.001). Conclusions: SEF patients who received tumor resection had a marked increase in overall survival. Receiving wedge/segmental and lobectomy surgery types were associated with improved patient outcomes compared to other surgery types. Furthermore, receiving any adjuvant therapy was associated with improved overall survival compared to receiving surgery alone. Receiving adjuvant chemoradiation was associated with superior outcomes in SEF patients compared to receiving other adjuvant therapies and surgery alone. To improve overall survival in SEF patients, further research is needed to assess what factors influence treatment trends.
Revealing the crucial roles of myxoma cells and CD206+ macrophages in cardiac myxoma progression based on single-cell sequencing.
Authors: Jiang Zedong , Kang Qianlong , Tong Huan , Li Guangqi , Ma Xuelei 
Published: June 2024

e23549 Background: Cardiac myxoma is a commonly encountered tumor within the heart that has the potential to be life-threatening. However, the cellular composition and molecular characteristics of this condition are still not well understood. Methods: We performed single-cell sequencing on cardiac myxoma tissues obtained from 5 patients, focusing on the identification and characterization of cellular subtypes, cell trajectory analysis, and intercellular communication analysis. We performed a comparative analysis of the changes in cell types and states between cardiac myxoma and normal heart tissues. Furthermore, we retrospectively collected pathological sections from 49 cardiac myxoma cases and employed the multi-color immunohistochemistry (mIHC) technology to analyze the relationship between cellular infiltration and the severity of disease. Results: In total, 75,641 cells in cardiac myxoma tissues formed 9 distinct cell populations. Myxoma cells exhibited a significant resemblance to fibroblasts, yet they were distinguished by an increased expression of phosphodiesterases and genes associated with cell proliferation, differentiation, adhesion, and migration. Myxoma cells displayed cellular heterogeneity and demonstrated two distinct evolutionary pathways. One involves the transition from stem cell-like cells to stromal cells and the other involves enhancement of blood coagulation function. Immune cells surrounding the myxoma displayed suppressive features, with the presence of CD8+ T cells expressing TOX and GZMK, as well as a decrease in the secretion of cytotoxic molecules, indicating an impaired effector function. Macrophages were found to express growth factors such as EREG and PDGFC which played a role in promoting myxoma growth. Conversely, myxoma cells were also observed to secrete ANGPTL4 and ANXA1 which in turn induced the transformation of CD206+ macrophages. Extensive mIHC experiments indicated that a higher proportion of CD206+macrophages and myxoma cells infiltrating the myxoma tissues, along with their enhanced spatial interaction, were found to significantly contribute to the increased occurrence of embolism in cardiac myxoma patients. Conclusions: In summary, this study presents a comprehensive single-cell atlas of cardiac myxoma, highlighting the heterogeneity of myxoma cells and their collaborative impact on immune cells. These findings shed light on the complex pathobiology of cardiac myxoma and present potential targets for intervention.
Association of mutational status with metastatic pattern, race, ethnicity, and overall survival (OS) in leiomyosarcoma (LMS).
Authors: Pearce Hayes , Yu-Cherng Chang , Rose Brandon Edward , Jonczak Emily E. , Grossman Julie , D'Amato Gina Z. , Huang Marilyn , Trent Jonathan C. , Alessandrino Francesco 
Published: June 2024

e23553 Background: LMS, one of the most common soft tissue sarcomas, can arise from the uterus, retroperitoneum, vessels, or extremities. It is unclear if the metastatic pattern and potentially the mutational status differs among the different types of LMS. We investigated the association between sites of metastases, mutations, race, ethnicity, and OS in different LMS types. Methods: This single-center retrospective study evaluated patients with biopsy-proven LMS that underwent genomic testing between January 2009 and May 2023. Association between genomic profile, sites of metastases, types of LMS (extremity, retroperitoneal, uterine, vascular), self-reported race and ethnicity was performed using Fisher’s exact test. Survival curves for self-reported race and ethnicity, mutations, sites of metastases, and types of LMS were estimated using the Kaplan-Meier method and compared with a log-rank test. Cox proportional hazard regression models were used to examine the association between OS with types of LMS, self-reported race and ethnicity, mutational status, and sites of metastases. Results: The study included 110 subjects (F/M:81/29; median age 57 years, 99/110 with metastatic disease). 27/110 (25%) subjects self-reported as Hispanic, and 27/110 (25%) as Black. The most common type of LMS was uterine (50/110, 45%), followed by retroperitoneal (27/110, 25%), extremities (23/110, 21%) and vascular (10/110, 9%). The most common mutation was TP53 (74/110, 67%), followed by RB1 (24/110, 22%). ER/PR expression was present in 25/110 subjects (23%). The lungs were the most common site of metastasis (79/99, 80%), followed by the liver (37/99, 37%), and pelvis (29/99, 29%). Peritoneal and pelvic metastases were more common in uterine LMS (p = 0.0001 and 0.002, respectively). Liver metastases were more common in retroperitoneal LMS (p = 0.03). TP53 mutation was more common in vascular LMS (p = 0.03), whereas intermediate/high tumor burden was more common in LMS arising from the extremities (p = 0.004). BRCA1/2 mutations were more common in subjects with liver (p = 0.02) and intramuscular metastases (p = 0.04). Pleural metastases (11/99, 11%) were associated with lower OS (Risk Ratio: 2.7; 95% CI: 1.13, 6.32; p = 0.02). ATRX mutation (17/110, 15%) was more common in Hispanic subjects (p = 0.005), in which it was associated with lower OS (p = 0.0007). Conclusions: The mutational status and metastatic pattern of LMS varies based on the LMS types, and potentially provides prognostic data. In our sample, OS was reduced in Hispanic subjects with ATRX mutation, and the presence of pleural metastases was also independently associated with shorter OS.
Assessing response and adherence to neoadjuvant treatment in soft tissue sarcomas of the extremities.
Authors: Alamilla-Garcia Gabriela , Williams Haydée , Garcia-Ortega Dorian Yarih 
Published: June 2024

e23559 Background: The standard treatment for large, intermediate, and high-grade extremity soft tissue sarcoma (ESTS) involves surgery and radiotherapy. The addition of chemotherapy has improved oncological outcomes, such as reduced recurrence and prolonged survival. However, the relationship between neoadjuvant treatment and tumor response in ESTS is not well understood. Pathological evaluation of viable tumor cells after treatment is an indicator of tumor response, yet the proportion of viable tumor cells remains high, particularly in high-risk sarcomas. Combining radiotherapy with chemotherapy may enhance the response of tumor cells. Objective: This study aims to evaluate the effects of neoadjuvant chemotherapy (NCT) and chemoradiotherapy (CRT) on patients with high-risk ESTS and to determine its impact on the pathological response. Methods: We enrolled adult patients with high-risk ESTS (SARCULATOR OS < 60%) at a single center in Latin America. The study was designed to analyze the pathological response in patients with high-risk sarcomas who underwent neoadjuvant CRT and resection and to correlate these responses with various variables. The treatment response was evaluated using the EORTC–STBSG criteria. Results: Thirty-four patients were recruited, with a median age of 44 years (IQR 23-74). Fifty-two percent had T3 tumors (mean size 18 cm), and 79.4% were diagnosed at stage III. The predominant histological subtypes were synovial sarcoma (35.3%) and dedifferentiated liposarcoma (29.4%). The most used NCT regimen was doxorubicin/ifosfamide (84.4%), with 62.5% receiving a dosage intensity of Q4W, affected by overcapacity, and 25% received Q3W. Concurrent CRT was administered to 64.7% of patients, with a median delay to onset of 36 days due to overcapacity (43.5%). Only 79.4% completed three preoperative cycles of treatment. As for the response, 41.2% had an EORTC-E response, and 17.6% had an EORTC-D response. Grade 3 neutropenia and anemia occurred in 17.2% and 8.8% of patients, respectively. Disease progression during NCT was observed in six patients. No significant difference was found in the pathological response between the Q4W and Q3W dosage intensities (p = 0.62). Conclusions: The impact of NCT on pathological responses was not significantly high, which may be due to the predominant histological type in our series. The main cause of treatment delay at our center was due to overcapacity; however, this did not influence the pathological response relative to dose intensity. Additional follow-up assessments are required to determine the influence on relapse-free and overall survival based on the response after preoperative CRT.
Update on GALLANT: A phase 2 study using metronomic gemcitabine, doxorubicin, and docetaxel plus nivolumab in previously treated sarcoma (NCT04535713).
Authors: Omelchenko Nadezhda , Chawla Sant P. , Agarwal Anmol Dia , Jeffrey Samantha , Sena Cota Luisa , Chua Victoria , Moradkhani Ania , Quon Doris V. , Wong Steven , Gordon Erlinda Maria 
Published: June 2024

e23569 Background: Metronomic dosing of gemcitabine, doxorubicin and docetaxel causes less severe side effects than standard chemotherapy for advanced sarcoma. Hypothesis: The addition of nivolumab to this regimen will have synergistic effects and improve treatment outcomes. Objectives: Primary objective: To assess progression-free survival (PFS); Secondary objectives: (1) To evaluate best overall response during treatment period confirmed in a 6-week follow-up, (2) PFS rate at 6 and 9 months, (3) Overall survival (OS) rate at 6, 12 months, and (4) Incidence of treatment-related adverse events (TRAEs). Methods: Inclusion criteria: Previously treated male and female subjects, &gt; 18 years of age, pathologically confirmed diagnosis of locally advanced, unresectable, or metastatic sarcoma, measurable disease by RECIST v1.1, and acceptable hematologic and organ functions. Exclusion Criteria: History of autoimmune disorder. Treatment schedule: Metronomic doses of gemcitabine (600 mg/m2 max:1000 mg), doxorubicin (18 mg/m2; max: 32 mg), docetaxel (25 mg/m2; max:42 mg) on Day 1 and Day 8, and nivolumab (240 mg) on Day 1 only. Repeat treatment cycles may be given every three weeks if the toxicity grade is &lt;1. Results: Efficacy (n = 70). This population completed at least one treatment cycle and had a follow-up CT or MRI scan at week 6. Best Overall Response = 14 PR, 47 SD, 9 PD. ORR = 20%; DCR (CR+PR+SD) was 87%. Median PFS was 8.2 (95% CI: 5.85-10.55) months; 6- month PFS rate of 59%. Median OS was 17.6 (95% CI: 13.53-21.67) months, with 6-month OS of 84%. Safety (n = 75): Grade 3/4 TRAEs include thrombocytopenia (n = 26), white blood cell count decreased (n = 17), neutropenia (n = 16), fatigue (n = 15), anemia (n = 13), nausea (n = 9), anorexia (n = 5), diarrhea (n = 2), emesis (n = 1), febrile neutropenia (n = 1), sepsis (n = 1), rectal bleeding (n = 1), transaminitis (n = 1), dizziness (n = 1), shortness of breath (n = 1). There were no unexpected adverse events reported. Conclusions: Taken together, the data suggests that nivolumab plus metronomic doses of gemcitabine, doxorubicin and docetaxel (1) may have synergistic activity, and (2) by indirect comparison, may be as effective as standard first line therapy for advanced sarcoma with manageable toxicity. Clinical trial information: NCT04535713 .
Epidemiology of undifferentiated sarcomas: A rare entity.
Authors: Ali Hassan , Prabhakaran Sivaguha Yadunath , Saleem Hafiz Muhammad Ajmal , Thirumaran Rajesh , Desai Krishna 
Published: June 2024

e23571 Background: Undifferentiated Sarcomas (USar), previously known as malignant fibrous histiocytomas, are a group of rare and diverse malignant tumors of mesenchymal origin with a prevalence of 0.08-1 per 100,000. These are aggressive tumors with often high-grade morphology. The diagnosis is made by exclusion of other sarcoma entities upon bone marrow biopsy (criteria listed below). Undifferentiated sarcomas are of four major types, i.e. Pleomorphic, Epithelioid, spindle and round cells. The exact etiology of these sarcomas remains obscure, although many signaling pathways with various genetic alterations may be implicated in their development. The goal of this epidemiologic study is to assist in better understanding of this lesser known aggressive malignancy. Methods: The data was collected from Surveillance, Epidemiology and End Result database Research Plus Data, 17 Registries, Nov 2022 Sub (2000-2020). We extracted undifferentiated sarcoma cases diagnosed between 0-90 years of age, using the ICD Code 8805/3. The analysis was stratified age, gender, race, & primary site labeled. The analysis was further completed by comparing survival using the Log-rank test (GraphPad Prism). Results: A total of 1680 cases of USar were identified, which were diagnosed between 2000 and 2020. Median age of diagnosis was 59.5 years. 50.54% were males and 49.46% were females. Of these cases, ~64.05% were Caucasians, ~15.18% Hispanics, ~10.48% Asians or Pacific Islanders, ~9.35% Black, and < 1% were Alaskan natives/American Indian and Non-Hispanics of unknown race. Further survival curves were compared based on gender, race and organ system. The average months of survival (MoS) based on gender showed no statistical significance (p value 0.6077). MoS calculated for Whites (28), Blacks (16), Asian & Pacific islanders (1), Alaskan natives & American-Indians (15), & Hispanics (21) (p value < 0.0001). MoS based on involved organ system were compared for: head/face/neck (18), GI tract (10), respiratory tract (4), heart/mediastinum/pleura (9), skin & soft tissue (51), bone (32), breast (30), GU (19), CNS (26), gynecological tract (12) and male reproductive system (29) (p < 0.0001). Conclusions: Undifferentiated Sarcoma accounts for less than 1% of all adult tumors. Only 1680 cases were found in the past twenty years, rendering it one of the rarest seen malignancies. Of the reported data, USar was most commonly observed in Caucasians. Comparing the survival curves also showed that there was no difference in survival based on gender. The highest MoS was seen in undifferentiated sarcomas of skin and soft tissues while respiratory tract tumors had the lowest average survival time. More research and analysis is warranted to understand this lesser known malignancy given its extremely low incidence.
Phase II Efficacy and Safety of 80 mg Osimertinib in Patients With Leptomeningeal Metastases Associated With Epidermal Growth Factor Receptor Mutation–Positive Non–Small Cell Lung Cancer (BLOSSOM)
Authors: Park Sehhoon , Baldry Richard , Jung Hyun Ae , Sun Jong-Mu , Lee Se-Hoon , Ahn Jin Seok , Kim Yu Jung , Lee Youngjoo , Kim Dong-Wan , Kim Sang-We , Lee Ki Hyeong , Lee Won Jae , Choi Jung Won , Chong Kyuha , Lee Jung-Il , Gwon So-Hyeon , Son Nak-Hoon , Ahn Myung-Ju 
Published: June 2024

PURPOSE Leptomeningeal metastases (LMs) exhibit a high incidence in patients with epidermal growth factor receptor (EGFR)–mutated non–small cell lung cancer (NSCLC) post-treatment with first- or second-generation EGFR tyrosine kinase inhibitors (TKIs). This investigation evaluates the efficacy, safety, and pharmacokinetics of 80 mg once daily osimertinib in patients with LMs resistant to prior first- or second-generation EGFR TKIs. MATERIALS AND METHODS In this phase II multicenter, open-label, single-arm study, 80 mg osimertinib was administered to patients with EGFR-mutated NSCLC who had developed LMs subsequent to treatment with prior EGFR TKIs. The primary end point was overall survival (OS), assessed alongside objective response rate by the blinded independent central review (BICR) and a pharmacokinetic analysis of plasma and cerebrospinal fluid (CSF) on the first day of cycles 3 and 6. RESULTS A total of 73 patients diagnosed with LM were treated with osimertinib, including 64 patients evaluable for the LM efficacy set—T790M negative (n = 62) and T790M positive (n = 2). The median OS in the full-analysis set was 15.6 months (95% CI, 11.5 to 20.2). The objective response rate for LM was 51.6%, including a 15.6% complete response, and the disease control rate was 81.3% by BICR in the LM efficacy evaluable set. The median LM progression-free survival by BICR was 11.2 months (95% CI, 7.7 to 15.3), the duration of response was 12.6 months (95% CI, 7.6 to 17.7), and OS was 15.0 months (95% CI, 11.3 to 18.7). Pharmacokinetic analysis showed that the CSF to free plasma osimertinib ratio was 22%. Most safety profiles were grade 1 and 2. CONCLUSION The study demonstrates significant intracranial efficacy and survival benefits of 80 mg once daily osimertinib in NSCLC patients with LMs. The data support considering daily 80 mg of osimertinib as a treatment option for EGFR-mutated NSCLC patients with LMs, irrespective of T790M mutation status.