bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of prognostic reliability of TNM staging systems version 7/8 and SARCULATOR in primary localized liposarcomas of the extremity or trunk wall.
Authors: Kosela-Paterczyk Hanna , Teterycz Pawel , Mariuk-Jarema Anna , Wagrodzki Michal , Zdzienicki Marcin , Rutkowski Piotr 
Published: June 2022

e23529 Background: The oncological staging system should provide meaningful information regarding the patients’ prognosis. For soft tissue sarcomas, available staging systems include AJCC version 8, AJCC version 7, and nomogram-based approaches such as SARCULATOR (which additionally includes age and subtype). This work compares these systems using a group of extremity/trunk wall cases of liposarcoma (LPS). Methods: We have included all (N = 147) consecutive, newly diagnosed LPS patients treated in our institution between 2010 and 2021. We have excluded atypical lipomatous tumors. Patients’ and tumor characteristics were collected, and AJCC staging and SARCULATOR risk assessment were performed. Appropriate Cox proportional hazard models were fitted. The results were compared using the concordance index, Akaike information criterion (AIC), and partial likelihood ratio (PLR) test for non-nested Cox models. Results: In this group, 81 (55.1%) patients were male; the mean age in the group was 54 years (SD:16). Most tumors (83%) were localized on the lower extremity, with 8.8% on the upper extremity and 8.2% on the trunk. 66% of cases were myxoid LPS, 17.7% - dedifferentiated and 16.3% - pleomorphic. The median tumor size was 12 cm (IQR 9 – 18). Patients’ prognostic groups are summarized in Table. The median follow-up was 43 months (95%CI:38-51). The median overall survival (OS) was not reached. The 5-year survival rate was 68% (95%CI:62-75). The concordance for AJCC version 7, AJCC version 8, and SARCULATOR were respectively 0.625, 0.705, and 0.778. The AIC in the same order were: 311, 301, 274. The PLR test showed that AJCC version 8 fits better than AJCC version 7 (p for superiority = 0.036) while SARCULATOR fits better than AJCC version 8 (p for superiority = 0.028). Conclusions: New staging systems improve in better predicting patients outcome. In rare diseases such as sarcomas, it is crucial to have access to more personalized nomograms such as SARCULATOR.[Table: see text]
A novel pan-RAS inhibitor for malignant peripheral nerve sheath tumors.
Authors: Arshad Tariq 
Published: June 2022

e23531 Background: Malignant Peripheral Nerve Sheath Tumors (MPNST) are a rare but deadly form of sarcoma originating from the Schwann cell compartment. They are usually driven by loss of function of the NF1 tumor suppressor. This can happen spontaneously but is also the cause of disease in the inheritable syndrome of Neurofibromatosis. Neurofibromatosis is a member of the family of genetic diseases known as “Rasopathies” and is one of the most common inherited neurological disorders. NF1 serves as an important negative regulator or GAP for the RAS oncoprotein. Loss of function of NF1 thus results in the upregulation of non-mutant RAS activity and this appears to be a driving event in the disease. Therapeutic options remain poor. An obvious approach to effective treatment would be targeted therapy directed at non-mutant Ras proteins. There are currently no approved pan-RAS inhibitors. We have developed a small molecule pan-RAS inhibitor which binds directly to all forms of RAS. It acts to block the ability of RAS and to bind and signal through its effectors. It is active in vitro and in vivo against multiple models of MPNST. Methods: In silico screening of a virtual compound library was performed to identify an initial candidate inhibitor. Iterative rounds of Medicinal Chemistry informed by structural modeling and bioassay in 3D vs 2D growth assays were performed to identify an enhanced activity derivative. Target binding was confirmed by Microscale Thermophoresis and NMR. RAS/RAF complex status was measured by co-immunoprecipitation of the endogenous proteins. Ras signaling was assayed by Western analysis of Phospho-ERK and RAL-GTP pull down assays. In vitro activity was measured using 3D soft agar assays. In vivo activity was measured by ip or po administration against MPNST pdx systems. Results: The current lead, designated RAS-F binds all three main isoforms of RAS at low uM kd and modulates the RAS effector domain in NMR studies. It suppresses RAS signaling pathways in transient assays and suppresses MPNST tumor cell growth in soft agar with IC50s ̃ 250nM. It suppresses MPNST pdx growth. Conclusions: We have developed a pre-clinical pan-RAS inhibitor that is active in vitro and in vivo against MPNST cancer models. The agent also has potential uses against non-tumor manifestations of Neurofibromatosis such as Plexiform and Cutaneous neurofibromas. Funding: NIH 5U01HL127518-03, Kentucky Lung Cancer Research Program CDMRP NF180094 (GJC). Qualigen Therapeutics LLC (GJC, JOT).
Genomic co-genotype classification and clinical prognosis in Ewing sarcoma.
Authors: You Yang , Guo Xi , Zhuang Rongyuan , Li Wei , Zhang Chenlu , Wang Zhiming , Shen Feng , Zhou Qiwen , Song Zhengqing , Zhang Yong , Lu Weiqi , Jiang Zhengzeng , Zhou Xiaoyu , Sun Ying , Zhou Yuhong , Ji Yuan 
Published: June 2022

e23532 Background: Ewing sarcoma is a highly aggressive round cell mesenchymal tumor that commonly occurs in children and young adults. It is molecularly characterized by chromosomal translocations, most commonly t (11;22), resulting in the abnormal EWSR1-FLI1 fusion. In addition to EWSR1-FLI1, patients may have other genomic variants that can be used for risk stratification. In the present study, we retrospectively investigated the association between co-variant genes and prognosis in patients with Ewing sarcoma. Methods: From 2019 to 2021, 10 patients with Ewing sarcoma were enrolled in the study, and their standard first-line treatment consisted of five-drug regimen chemotherapy including vincristine, doxorubicin (Adriamycin) and cyclophosphamide, alternating with ifosfamide and etoposide (VAC/IE). We carried out whole-exome sequencing on collected tumor samples and matched leukocyte DNA from these patients. Mutations, indels, gene deletions, and amplifications were identified, and survival analysis was performed. Results: In general, median progression-free survival (PFS) of the 10 confirmed Ewing sarcoma (with EWSR1-FLI1 fusion) patients was 10.5 months. We found that 60%, 30%, and 30% of patients had genetic variants (including mutation and copy number variation) in the three signaling pathways of cell cycle, WNT, and NOTCH, respectively. Their PFS was shorter than patients without these variants (log-rank test, p = 0.0345, 0.0053, and 0.0053, respectively). Median PFS was 7 vs 17 months in cell cycle pathway (the former with variants and the latter without variants), 5 vs 14 months in WNT pathway, and 5 vs 14 months in NOTCH pathway. However, there was no difference in PFS between patients with and without variants in other pathways (including TP53, RTK-RAS, MYC, DDR, PI3K) (log-rank test, p＞0.05). Conclusions: We found that the variants in cell cycle, WNT and NOTCH signaling pathway were associated with poor prognosis of Ewing sarcoma. This study provides important molecular markers for risk stratification in patients with Ewing sarcoma, which may provide insights into later clinical trials.
Clinical characteristics, treatment and clinical outcomes of leiomyosarcoma: A retrospective study from single center.
Authors: Liu Yang , Wang Xiao-Wen , Ji Hong-Chen , Yang Jing-Yue , Chen Yan , Wang Zhen , Zhang Hong-Mei 
Published: June 2022

e23536 Background: Leiomyosarcomas are genetically heterogeneous tumors with highly variable survival. The clinical efficacy of different treatments has not been determined. This retrospective study analyzed the clinical pathological features, treatments and outcomes of leiomyosarcoma patients. Methods: A retrospective review was performed of leiomyosarcoma patients between 2000 to 2021. 214 patients were initially investigated, 102 patients were excluded owing to a lack of follow-up or loss of data., and 112 patients were finally analyzed. Treatment outcomes were measured using overall survival (OS), disease-free survival (DFS) and progression-free survival (PFS). Optimal responses of first-line chemotherapies were also investigated under RECIST criteria. Results: Mean age of patients was 52.63 years, and male to female ratio was 1/2.2. Tumors mainly located in head and neck (2.68%), trunk and extremities (35.71%), abdomen and thoracic organs (16.07%), retroperitoneum (17.86%) and pelvis (27.68%). Patients with ⅠA, ⅠB, II, IIIA, IIIB and IV stage was 15.18%, 23.21%, 9.82%, 12.50%, 7.14% and 9.82% respectively. 2 patients received only chemotherapy after diagnosis, and 109 patients underwent surgery, among them 33.04% (37 cases) of patients had further radiation or chemotherapy. The median OS (mOS) of all patients was 42.65 months (95% CI 33.77-50.43). Adjuvant therapy had no significant influence on median DFS (mDFS) (28.63 months vs 30.33 months, P= 0.888). Significantly, R0 resection prolonged mDFS (33.30 months vs 7.37 months, P = 0.019) and mOS (102.5 months vs 35.83 months, P= 0.001). 32 patients occurred recurrence and all had surgery. 28 patients occurred metastases and 6 of them received surgery alone, 11 patients had systemic treatment, 6 patients received both treatments, 5 of them were untreated. In patients with metastases, the median PFS of systemic treatment (15.33 months) was shorter than median DFS of local treatment (48.83 months), while systemic treatment achieved similar survival time as surgery (78.03 months vs 79.27 months, P= 0.651). The disease control rate (DCR) of anthracycline-based regimens, ifosfamide (IFO), gemcitabine-based regimens and targeted therapy was 52.94%, 33.33%, 33.33%, 50% respectively. Conclusions: Surgery with R0 margin improved survival significantly of leiomyosarcoma patients. For survival time of patients with metastases, systemic treatment was not inferior to surgery, and anthracycline-based regimens had a higher disease control rate.
Desmoplastic small round cell tumor: Analysis of surveillance, epidemiology, and end results (SEER) database 1975 to 2018.
Authors: Waqar Syed Hamza Bin , Ali Hassam , Sheikh Taha , Hamouda Danae M. 
Published: June 2022

e23540 Background: Desmoplastic small round cell tumor (DSRCT) is a rare and aggressive soft tissue sarcoma with a poor prognosis. The incidence and prognosis of patients with DSRCT have been inadequately understood. Survival analysis for DSRCT has been sparsely investigated in a population-based study. Methods: We conducted a retrospective cohort study using the SEER 9 Registry (1975-2018). Site recode International Classification of Diseases for Oncology (ICD-O-3) 8806/3 was used via SEER*Stat software to select DSRCT cases. SEER*Stat software estimated annual percent changes, and Poisson regression estimated risk ratios. Cox regression models were constructed to estimate the hazard ratio for survival at five years. The period-specific rates were portrayed as rate per 1,000,000. Results: The male and female age adjusted DSRCT incidence rates were 0.22 and 0.05, respectively (p < 0.05). Incidence rate of DSRCT has been rising in the last two decades from 1975–2000 to 2001-2018 (0.013 vs. 0.31,p < 0.05). Males have a higher age adjusted DSRCT incidence rate (0.22 vs. 0.05,p < 0.05), and non-metropolitan counties had a higher incidence rate than metro counties (1.14 vs. 0.14,p < 0.05). The observed survival at 12, 36, and 60 months was 81%, 39.9%, and 23.4%, respectively. There was no significant difference in survival between females and males. Ages greater than 70 years had poor survival compared to ages less than 60 years (p < 0.001). Compared to surgery with chemotherapy, surgery combined with radiotherapy and chemotherapy was associated with a 62% lower risk of mortality (p< 0.001). Conclusions: This study reveals that DSRCT incidence has been increasing since 2000, is more common in white males. Gender may not affect survival in DSRCT, and surgery combined with chemoradiotherapy is associated with improved survival outcomes compared to surgical management with chemotherapy alone. Further comparative data would be beneficial to confirm reported findings.[Table: see text]
Radiotherapy, volume reduction, and short-term surgical outcomes in the treatment of large myxoid liposarcomas.
Authors: Lee Linus , Tepper Sarah , Owen Grant , Wang Dian , Lopez-Hisijos Nicolas , Colman Matthew W. , Gitelis Steven , Blank Alan T. 
Published: June 2022

e23546 Background: While tumor volume reduction following radiation has been documented in myxoid liposarcomas, it is unclear whether large tumors experience similar volume reduction to smaller tumors. Methods: MRI studies performed before and after completion of pre-operative radiation therapy (RT) were examined. Tumor sizes were noted and categorized as large vs. small based on size > 10 cm. Tumor volumes were calculated, and operative duration and major wound complications were recorded. Results: The median largest tumor dimension was 12.4 cm before RT and 8.7 cm after RT. The median tumor volume was 298.9 cm3 before RT and 106.9 cm3 after RT. There was no significant difference in the mean percent tumor volume reduction between large tumors and small tumors (p = 0.11, 56.3% vs. 64.5%). Operative duration most strongly correlated to post-RT MRI volume (R2= 0.674, p < 0.001). Despite volume reduction, tumors that were large on presentation were more likely to experience major wound complications post-operatively. Conclusions: Radiation appears to be as effective at reducing myxoid liposarcoma tumor volume in large and small tumors. However, large tumors on presentation appear more likely to experience wound complications despite tumor volume reduction. Future studies should investigate disease-related outcomes as a factor of volume reduction in myxoid liposarcoma.[Table: see text]
A nomogram to predict the prognosis of advanced soft tissue sarcoma patients treated with anlotinib: A real-world population-based study.
Authors: Wang Bin , Liu Jie , Zhang Ren shu , Jiang Yu 
Published: June 2022

e23550 Background: The ALTER0203 randomized controlled trial proved the antitumor activity of anlotinib, a multitargeted tyrosine kinase inhibitor, in 8 subtypes of advanced refractory soft tissue sarcoma (STS). Our previous studies have shown that anlotinib showed antitumor activity in more than 30 STS pathological subtypes in the real world. This study further constructed a nomogram to predict the prognosis of advanced STS patients treated with anlotinib based on real-world data. Methods: We retrospectively analyzed the data of patients with unresectable locally advanced or metastatic STS who received at least one dose of anlotinib from June 2018 to March 2021. A nomogram was developed to predict the survival probability based on the multivariate analysis. The performance of the nomogram was evaluated by concordance index, bootstrap resampling calibration curve and time-dependent ROC curve. Results: A total of 209 patients were included in this study. The median age was 48 years (range 11-85 years), and the median follow-up time was 18.7 months. Based on five independent prognostic factors including ECOG performance status, FNCLCC grade G2-3, poor nutrition, increased neutrophil count, and treatment patterns according to the multivariate analysis, we constructed a nomogram to predict the prognosis of advanced STS patients treated with anlotinib. The concordance index was 0.780. For the prediction of 1-year and 2-year overall survival probability according to the nomogram, the area under the receiver operating characteristic curve was 0.833 and 0.829, respectively. Conclusions: The nomogram based on ECOG performance status, FNCLCC grade, nutritional status, neutrophil count, and treatment patterns can accurately predict the 1-year and 2-year OS probability for advanced STS patients treated with anlotinib.
In vitro evidence that combination treatment with anti-PD-1 and anti-CD47 immunotherapy may not be efficient in human soft tissue sarcoma.
Authors: Strizova Zuzana , Ozaniak Andrej , Smetanova Jitka , Capkova Linda , Bartolini Robin , Lischke Robert , Bartunkova Jirina 
Published: June 2022

e23560 Background: Soft tissue sarcomas (STSs) are rare mesenchymal tumors. With more than 70 histological subtypes of STSs, studies defining robust biomarkers of therapeutic value are lacking. Even with the improvements in local control rates, metastases and death occur in 50% of patients that are diagnosed with high-risk STSs. Across nearly all sarcoma types, macrophages dominate the immune landscape of STSs. While immune checkpoint inhibitors (ICIs) represent the major immunotherapeutic approach in malignancies with a high load of T cells, the anti-CD47 anti-cancer therapy mostly promotes macrophage-mediated phagocytosis. The efficacy of both therapies is critically dependent on the composition of the tumor microenvironment. Methods: In our study, we evaluated the potential additive effects of combining the anti-PD-1 immunotherapy and anti-CD47 immunotherapy ex vivo. The proportions of tumor cells and tumor-infiltrating lymphocytes were characterized ex vivo from resected tumors of 73 patients who underwent surgery for STS. The expression of CD47 on tumor cells was analyzed by immunohistochemistry. Cell suspensions were obtained from freshly resected tumors and the proportions of CD45+, CD45-, CD3+, CD4+, and CD8+ cells were measured by flow cytometry. The effect of the anti-PD-1 blockade, anti-CD47 blockade, and the combinatorial application of anti-PD-1 and anti-CD47 therapies on the immune cell activation in vitro was investigated by culturing of cell suspensions at a concentration 0.3x106/ul in the presence/absence of therapeutic monoclonal antibody (Nivolumab 2 ug/ml; anti-CD47 clone MIAP410 20ug/ml) and evaluated by a cytokine Luminex assay (Milliplex® MAP Human Cytokine Bead Panel (Sigma Aldrich) for TNFα, IFNγ, and IL-2 cytokines analysis). Results: The addition of anti-PD1 to CD3/CD28 stimulation drastically increased the production of all cytokines analyzed. This increase in pro-inflammatory cytokine secretion was even more pronounced after adding an anti-CD47 monoclonal antibody to the cell culture. However, a combinatorial application of anti-PD-1 and anti-CD47 agents in vitro was found to limit rather than potentiate the immune activation in the TME of human STS. On an individual level, the most profound response to anti-PD-1 was observed in high-grade leiomyosarcoma and the most profound response to anti-CD47 therapy was observed in an undifferentiated pleiomorphic sarcoma. Conclusions: Our data suggest that combinatorial strategies based on ICIs and anti-CD47 blockade may not provide the desired outcome in STSs. Both therapies, anti-PD-1, and anti-CD47 alone, could however bear a therapeutic potential in selected tumors after close evaluation of the CD47 and PD-1 expression status, as well as the extent of T cell/macrophage infiltration.
Symptoms and psychosocial distress associated with malignant wounds: Secondary analysis of a prospective cohort study.
Authors: Takamizawa Shigemasa , Ishiki Hiroto , Oyamada Shunsuke , Kiuchi Daisuke , Amano Koji , Satomi Eriko 
Published: June 2022

e24008 Background: Symptoms associated with malignant wounds (MWs) worsen a patient's quality of life. However, MWs’ impact on psychosocial health and end-of-life status is unknown. Methods: This is a secondary analysis of the results of a large prospective cohort study conducted in 23 palliative care units in Japan. Consecutive patients were enrolled and followed up until their death or for six months. Patient demographics, symptom burden, medication use, and MW status were documented on admission. Healthcare professionals rated the symptoms using the Integrated Palliative care Outcome Scale (IPOS), a 5-point Likert scale. Quality of death (QOD) was evaluated at death using the Good Death Scale (GDS). The primary outcome was the prevalence of severe psychological symptom burden, evaluated as an IPOS-feeling score of 2–4. Factors that affected psychological symptoms and their relationship with GDS were also investigated. Results: Among the 1896 enrolled patients, 156 (8.2%) had MWs. MWs predominantly affected females and younger patients, and the most common primary sites were the breast (28.2%) and head and neck (19.2%). Among the patients with MWs, 75 (50.3%), 59 (39.6%), and 42 (28.2%) had exudate, pain, and bleeding, respectively. Among the 32 patients with MWs requiring dressing change at least twice a day and 117 patients with MWs requiring dressing change less than once a day, 20 (62.5%) and 44 (37.6%) had an IPOS-feeling score of 2–4, respectively (p = .015). Patients with MWs required antidepressants and opioids more frequently and received higher doses of opioids. Between the patients with and without MW, there were significant differences in IPOS-feeling and pain scores but not in breathlessness, fatigue, anorexia, somnolence, or dry mouth scores. IPOS-feeling and pain scores were worse in patients with MWs. Patients without MWs did not have better GDS scores (p = .48). Conclusions: Patients with MWs frequently required antidepressants and opioids, suggesting an increased prevalence of depression and severe pain. Psychological distress was influenced by the frequency of dressing changes. The presence of MWs did not affect the QOD.[Table: see text]