bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spine high-grade osteosarcoma in the era of radiotherapy with high-energy charged particles: A single institution retrospective analysis.
Authors: Evangelisti Gisberto , Falzetti Luigi , Palmerini Emanuela , Cianchetti Marco , Schwab Joseph H. , Boriani Stefano , Ibrahim Toni , Gasbarrini Alessandro 
Published: June 2022

11532 Background: Limited are data on high-grade osteosarcoma occurring in the spine. Wide resection is recommended, but it is a difficult and high morbidity procedure in the spine. High-energy particle therapy has been recently used. The goal of this study was to examine treatment and outcome of patients with osteosarcoma in the mobile spine. Methods: Spine high grade osteosarcoma patients who underwent surgery at the Rizzoli Institute between 2009 and 2020 were identified. Treatment, outcome, and prognostic factors in patients treated in a single institution were examined. Results: Characteristics of the 20 patients (8 female; 12 male) included: median age, 39.7 years (range, 14-71 years), 5 (25%) with tumors in the cervical spine, 6 (30%) with tumors in the thoracic spine, and 9 with tumors in the lumbar spine (45%); 14 (70%) patients with localized disease and 6 (30%) with metastatic disease at the time of presentation. Nineteen patients (95%) underwent chemotherapy, the majority were treated with MAP (methotrexate, doxorubicin, cisplatin) regimen. In 12 patients undergoing preoperative chemotherapy (n = 11) or chemotherapy and radiotherapy (n = 1), the median tumor % necrosis was 20 (IQR 20 - 40), with none achieving a good histologic response (> 90%). All patients underwent surgery. Adequate surgical margins were achieved in 5 patients (25%). In patients with positive margins, radiotherapy was administered to 8 (40%) patients. Four patients with positive margins after resection received photon neoadjuvant or adjuvant therapy. Four patients received high-energy particles as adjuvant therapy after planned gross total excision. The median overall survival rate was 10.5 months (IQR 5.8 - 15.0) for patients with metastatic disease and 25.5 months (IQR 8.3 - 46.0) for patients with localized disease (P =.0501). Patients treated with planned intralesional gross total resection followed by adjuvant high-energy particle therapy had a significant higher disease-specific survival than patients with positive margins after resection with or without additional conventional radiotherapy (P =.023). Conclusions: Metastatic disease, is a poor prognostic factor for high grade osteosarcoma of the spine. Post-operative high-energy particle therapy improved overall survival in patients undergoing a planned gross total resection compared to intralesional resection in this series. Chemotherapy induced necrosis was low underscoring the need of more aggressive multidisciplinary approaches for these patients.
Regorafenib third-lined therapy in advanced GISTs: A single center analysis based on different genotypes.
Authors: Chen Sile , Xia Yanzhe , Yang Shaohua , Qian Yan , Zhai Ertao , Huang Shaoqing , Shi Yihang , He Yulong , Cai Shirong , Zhang Xinhua 
Published: June 2022

11537 Background: The relationship between primary and secondary mutational status and efficacy of regorafenib in third-line therapy on GISTs is yet clear. Methods: From Jun 2017 to Dec 2021, a total of 62 patients with advanced GIST refractory to imatinib and/or sunitinib were enrolled in this study from the First Affiliated Hospital, Sun Yat-sen University. Results: Primary mutational was most common in KIT exon 11(40/62, 64.5%), followed by exon 9 (19.4%), exon 17 (4.8%). Six cases (9.7%) belonged to SDH deficiency and one case (1.6%) was NF1-associated GISTs. Before receiving treatment of regorafenib, specimens obtaining for secondary mutations were as follows: 39 cases from surgery，12 from core-needle biopsy; ctDNA alone was performed in 9 cases and 2 patients refused to secondary mutational test. Excluding 6 patients with SDH deficiency, 14 patients (25.8%) had mutations in exon 11+13, 15 (27.7%) in exon 11+17, 7 (13.0%) in exon 9+17, 4 (7.4%) in exon 11+13+17. Exon 11 + 18, exon 11 + 13 + 18, exon 11 + 13 + 17 + 18, exon 9 + 16, exon 11 + 17 + 18 and NF-1 were found in 1 case, respectively (1.9%). Eight (14.7%) patients with primary KIT mutation were not detected any secondary mutation（2nd-not-detected）. There was no complete response, 4 of partial response (4/54, 7.4%), 27 of stable disease (50.0%). Progression disease was seen in 23 patients (42.6%) and 8 were not applicable (no assessable lesion) to imaging response assessment due to R0/1 surgery before using regorafenib. The median follow-up time was 19.0 months. The median progression-free survival (mPFS) was 5.4 months (0.2-29.1 months) and the median overall survival (mOS) was 20.3 months (0.2-37.0 months). For primary mutation analysis, it was found that SDH-deficient patients had longer mPFS (29.1 months) than those with mutations in exon 9 or exon 11 (5.4 and 4.8 months, respectively; P= 0.013). In terms of secondary mutations, patients with activation loop mutations (exon 17+18) showed both longer mPFS (7.3 months vs 1.9 months, P= 0.001) and longer mOS (20.3 months vs 7.7 months, P= 0.059) than those patients with non-activation loop mutations. Not any specific or new adverse reaction was found in all patients. By Cox-regression analysis, response to regorafenib and mutational status were independent predictors of PFS，response to regorafenib was also an independent predictor of OS. Conclusions: Regorafenib seems to have better treatment efficacy in GIST patients with SDH deficiency compared to those with primary KIT mutations, and better with secondary mutations in activation loop than those with non-activation loop mutations. It is necessary to carry out clinical research for later-line treatment choice based on different genotypes for imatinib-resistant GISTs.
Interruption of imatinib in advanced gastrointestinal stromal tumor after prolonged imatinib maintenance in the absence of gross tumor lesions.
Authors: Kang Yoon-Koo , Kim Hyung-Don , Kim Hyun Jin , Park Young Soo , Beck Moyeol , Ryu Min-Hee 
Published: June 2022

11539 Background: Although current guidelines recommend indefinite imatinib treatment in advanced gastrointestinal stromal tumor (GIST) patients, prolonged imatinib treatment is often challenging. Imatinib-refractory progression-free survival (PFS) and overall survival were reportedly not different between those who interrupted imatinib and those did not. Methods: Clinical outcomes of 77 consecutive patients with recurrent or metastatic GIST who interrupted imatinib treatment after maintaining around 5 years of imatinib treatment in the absence of gross tumor lesions were retrospectively analyzed. Association between clinical factors and progression-free survival (PFS) following imatinib interruption was analyzed. Results: Median time from the absence of gross tumor lesions to imatinib interruption was 61.5 months (range 41.4–122.7 months). Since imatinib interruption, median PFS was 19.6 months, and the PFS rate at 60 months was 26.3%. Among patients who had progressive disease following interruption, imatinib re-introduction led to 88.6% objective response rate and 100% disease control rate, with the median imatinib-refractory PFS since re-introduction of 112.4 months. Complete removal of initial gross tumor lesion(s) (hazard ratio [HR] 0.32, 95% confidence interval [CI] 0.12–0.81, P = 0.016) and complete removal of residual gross tumor lesion(s) (HR 0.45, 95% CI 0.21–0.94, P = 0.033) by local treatment (vs. no local treatment or residual lesions after local treatment) were independently associated with favorable PFS. Conclusions: Interruption of imatinib may be considered with close surveillance in selected patients who maintained years of imatinib treatment in the absence of gross tumor lesions, especially for those who had complete removal of gross tumor lesions by local treatment.
Excess of blood TNFa-R as a sign of recurrence of G1 soft tissue sarcomas in older men and G3 soft tissue sarcomas in older women.
Authors: Kaplieva Irina V. , Sagatelyan Susan A. , Frantsiyants Elena M. , Vashchenko Larisa N. , Goroshinskaya Irina A. , Ausheva Tatiana V. , Chernogorov Pavel V. , Pogorelova Yulia A. , Sheiko Elena A. , Nemashkalova Ludmila A. , Gusareva Marina A. , Serdyukova Elizaveta V. , Bykadorova Oksana V. , Atmachidi Dmitriy P. , Maslov Andrey A. , Kit Oleg I. 
Published: June 2022

11556 Background: Tumor necrosis factor alpha (TNFa) and its receptor (TNFa-R) play an important role in tumor genesis. However, their involvement in the recurrence of sarcomas is poorly studied. The purpose of this study was to analyze levels of TNFa and TNFa-R in the blood of patients with recurrent soft tissue sarcomas. Methods: The study included 64 male and female patients, mean age 63.4±5.2 years. Main groups included patients with recurrent G1 and G3 soft tissue sarcomas T2bN0M0; comparison groups included patients with primary G1 and G3 soft tissue sarcomas T2bN0M0. 95% of tumors were liposarcomas, with solitary rhabdamyosarcomas, myxofibrosarcomas, epithelioid and undifferentiated sarcomas. All recurrent patients had previously underwent surgical and radiation treatment for primary sarcomas and their relapses (up to 2 episodes), with the last surgery more than 1 year ago. Control groups (n = 10 each) included healthy donors of similar age. Levels of TNFa and TNFa-R were measured in the blood serum by ELISA before the treatment. Results: No significant differences were found between TNFa levels in patients with primary and recurrent soft tissue sarcomas and in donors. Levels of TNFa-R in men with primary G3 sarcomas were 1.5 times (p < 0.05) higher compared with donors, 1.7 times (p < 0.05) higher than in men with primary G1 sarcomas, and 1.3 times (p < 0.05) higher than in women with primary G3 sarcomas. TNFa-R increased by 1.7 times (p < 0.05) in all men with recurrent sarcomas regardless of the tumor grade, compared with the levels in healthy men; however, in G1 it was 1.9 times (p < 0.05) higher than in men with primary G1 sarcomas, while in G3 it did not differ significantly from the levels in men with primary G3 sarcomas. TNFa-R in women increased only in recurrent G3 sarcomas by 2.5 times compared to healthy women. No differences were observed in TNFa-R levels between men and women with recurrent G3 sarcomas. Conclusions: An excess of TNFa-R in the blood is characteristic for the recurrent soft tissue sarcomas G1 in older men and G3 in older women. At the same time, high grade tumors in men are accompanied by an increase in TNFa-R in the blood in both primary and recurrent sarcomas.
Synergistic activity of PARP inhibitors (PARPi) in combination with standard chemotherapy (CTx) in leiomyosarcoma.
Authors: Vornicova Olga , Babichev Yael , Al-awar Rima , Marcellus Richard , Abdul Razak Albiruni Ryan , Gladdy Rebecca Anne 
Published: June 2022

11560 Background: Leiomyosarcomas (LMS) are genetically heterogeneous tumors that arise from smooth muscle. Currently, the mainstay of systemic treatment for patients with advanced/metastatic disease is doxorubicin (Dox) based CTx. Several genomic analyses of LMS reveal defects in homologous recombination (HR) DNA repair pathway in about half of patients, consistent with a druggable “BRCAness” phenotype. Thus, we sought to determine which combinations of standard CTx and PARPi might be synergistic promising therapeutic strategies for LMS. Methods: Dox, Docetaxel (Doc), Temozolomide (Tmz) were evaluated in combination with PARPi (Olaparib [Ola], Niraparib [Nira] and Talazoparib [Tala]) at 12 different drug concentrations. Four LMS cell lines of different origins (gynecological - GY, abdominal - A, extremity - E) were tested in a high throughput manner. All drug concentrations were chosen according to EC50. Cells were incubated with each combination for 7 days. Viability was assessed by ATPlite Luminescence Assay System.Evaluation of drug combination effect was performed using a Bliss synergy score. This system quantifies the degree of synergy as multiplicative effect of single drugs as if they acted independently. With a synergy score of -5 to 5, the interaction between two drugs is considered as additive; <-5 antagonistic and > 5 synergistic, and therefore a promising combination. Results: Anticancer activity, ranging from additive to synergistic was seen with all combinations. Results were consistent among all cell lines, independent of site of cell line origin (Table) Most synergistic combination in the majority of LMS cell lines were Dox or Tmz when combined with Tala, reaching up to 15 % and 27% above Bliss respectively. In contrast, Doc showed only additive effect with all analyzed PARPi. Conclusions: The data suggest that the combination of Dox or Tmz with PARPi may represent promising treatment options for LMS patients. Recent clinical studies support this notion in uterine LMS. Importantly these results suggest that such approach may be extended to all sites of LMS. Pre-clinical studies are underway to identify the most promising combinations for future clinical trial design. [Table: see text]
Five-year results of a phase 2 trial using ipilimumab (I), nivolumab (N), and trabectedin (T) for previously untreated advanced soft tissue sarcoma (NCT03138161).
Authors: Gordon Erlinda Maria , Chawla Sant P. , Chua-Alcala Victoria S. , Kim Ted T. , Adnan Noufil , Sekhon Simranjit , Angel Nicole , Fernando Mitchel , Brigham Don Arlen , Quon Doris V. , Moradkhani Ania , Wong Steve 
Published: June 2022

11573 Background: Understanding the bifunctional role that the immune system plays in tumor eradication vs growth promotion is critical in the design and timing of tumoricidal and immunologic therapies for sarcomas. Hypothesis: Immune checkpoint inhibitors that promote sustained T cell activation would be most effective when given as first line therapy, together with a tumoricidal agent. Methods: Eligible patients for this Phase 2 study are males or females ≥ 18 years of age with locally advanced unresectable or metastatic soft tissue sarcoma, previously untreated, with measurable disease by RECIST v1.1. Treatment protocol: (I) mg/kg i.v. q 12 wks, (N) 3 mg/kg i.v. q 2 wks, (T) 1.2 mg/m2 CIV q 3 wks. Treatment Outcome Parameters: (1) Best objective response rate by RECIST v1.1, (2) Progression-free survival (PFS), (3) Overall survival (OS), and (4) Incidence of treatment-related adverse events. Results: Ninety-nine patients were enrolled. Efficacy analysis (n = 88): There were 8CR (1 surgical CR), 11PR, 58SD, 11PD. Overall response rate was 21.6%, Disease Control Rate, 87.5%. The median PFS was 7 (range:1-44) months, median OS, 14 (range: 1-46) months. Grade 3 TRAEs include fatigue (n = 8), adrenal insufficiency (n = 1), dehydration (n = 1), hyponatremia (n = 2), increased AST (n = 8), increased ALT (n = 24), increased ALP (n = 2), port site infection (n = 2), psoriasis exacerbation (n = 1), anemia (n = 9), thrombocytopenia (n = 2), and neutropenia (n = 5). Grade 4 TRAES include anemia (n = 1), neutropenia (n = 1), thrombocytopenia (n = 2), increased AST (n = 2), increased ALT (n = 2), and increased CPK (n = 2). Grade 5 TRAES include rhabdomyolysis (n = 1). There was no incidence of alopecia nor cardiac toxicity reported. Conclusions: Taken together, these data indicate that first-line combinatorial therapy with Ipilimumab, Nivolumab, and Trabectedin (1) may be more effective than standard first line therapy (doxorubicin/ifosfamide/mesna), and (2) is safer than standard first line therapy for advanced soft tissue sarcoma. Clinical trial information: NCT03138161.
Efficacy and safety of eribulin in the treatment of advanced adult soft tissue sarcoma (STS): First real-world data in Chinese population.
Authors: Guo Xi , Zhou Yuhong , Zhuang Rongyuan , You Yang , Zhang Chenlu , Wang Zhiming 
Published: June 2022

11577 Background: Eribulin has shown efficacy in STS, especially for the L-type sarcomas, including liposarcoma (LPS) and leiomyosarcoma (LMS). We investigated the efficacy and safety of eribulin in the treatment of advanced adult STS in Chinese population. Methods: The study retrospectively analyzed data from patients diagnosed as advanced STS and received eribulin monotherapy or combination regimens in the Department of Oncology, Zhongshan Hospital affiliated to Fudan University from January 2020 to February 2021. Primary endpoint was objective response rate (ORR) by RECIST v1.1. Secondary endpoints included disease control rate (DCR), progress-free survival (PFS) and treatment-related adverse events (TRAE) by CTCAE v5.0. Results: A total of 40 patients who received at least two doses of eribulin and underwent at least one post-baseline response assessment were included in analysis. The mean age was 48 years. 82.5% (33/40) had L-type sarcomas, and 17.5% (7/40) had non-L-type sarcomas. Overall, 25% (10/40) of patients received eribulin alone; and 75% (30/40) received combination regimens. Drugs used with eribulin included gemcitabine, tyrosine kinase inhibitors (TKIs), anti-PD-1 antibodies, or TKIs plus anti-PD-1 antibodies. For the 40 patients, the ORR was 27.5% (11/40) and the DCR was 60% (24/40). The ORR for myxoid liposarcoma was especially encouraging: 54.5% (6/11) and the DCR was 72.7% (8/11). 10 patients received the combined therapy of anti-PD-1 antibodies, TKIs, and eribulin and showed a likely better ORR of 30% (3/10) and DCR of 70% (7/10). After a median follow-up time of 12.57 months (IQR, 8.43-16.30), the median PFS was 4.13 months (95% CI, 2.17-8.40). 10 out of 33 (30.3%) patients with L-type sarcomas had achieved PR and the median PFS was 4.45 months, 1 out of 7 (14.3%) patients with non-L-type sarcomas had achieved PR and the median PFS is 2.67 months. Common TRAEs were bone marrow suppression (42.5%), hypertriglyceridemia (25%), fatigue (10%), hypertension (7.5%). No treatment-related death happened. Logistic regression analysis of the multiple factors influencing ORR revealed no difference between taxane-treated and taxane-naïve patient groups. Conclusions: This study presents the first real-world data on the use of eribulin in STS in Chinese population. Eribulin monotherapy or combination therapy were likely more effective in this population, as well-tolerated as with Study 309, especially in treating liposarcoma. Eribulin used in combination with TKI and anti-PD-1 antibody showed potential efficacy in STSs. Further clinical exploration of front-line eribulin monotherapy and combination strategies in this setting is warranted.
The emerging fifth epidemiologic subtype of Kaposi sarcoma in HIV-negative men who have sex with men at a tertiary care center in NYC from 2000 to 2021.
Authors: Morales Ayana E , Benson Gabrielle , Glavan Stephanie , Giuliano Rosemary , Dickson Mark Andrew 
Published: June 2022

11579 Background: Kaposi sarcoma (KS) is a vascular tumor caused by human herpesvirus 8, also known as Kaposi sarcoma herpesvirus. There are 4 widely accepted distinct epidemiologic subtypes of KS: classic, endemic, iatrogenic, and epidemic (HIV-associated) forms. An emerging 5th subtype is increasingly recognized: non-epidemic KS in men who have sex with men (MSM) who are HIV-negative and have no other known causes for immunodeficiency. Objectives: To characterize a cohort of non-epidemic KS seen at the Sarcoma Medical Oncology or Dermatology Clinics at Memorial Sloan Kettering Cancer Center in New York City from 2000 to 2021 to identify risk factors, presentation, treatment course, and prognosis of these patients. Methods: Following IRB approval, a retrospective observational study was performed. Eligible patients were identified through the Electronic Health Records (EHR). The patients were characterized based on age at presentation, sex, gender identity, comorbidities, coinfections, and treatments and outcomes amongst other factors. Study data were collected and managed using REDCap electronic data capture tools. Results: Seventy-two patients were identified. The median age at time of diagnosis was 58 (range: 32-83). At initial diagnosis, 46% (33/72) of patients underwent observation, 50% (36/72) received localized treatment (i.e. excision, cryotherapy or topical therapy), and 4% (3/72) received systemic treatment with chemotherapy. The median duration of follow-up was 22 months. In follow-up, 43% (31/72) of patients had progression of disease requiring recurrent treatment: 24% (17/72) received localized treatment while 18% (13/72) received chemotherapy. Patients who received chemotherapy, predominantly pegylated liposomal doxorubicin, received treatment for a median duration of 13 months (range: 2-72 months). By the end of the follow-up period, 7 patients had died, of which 2 deaths were attributed to KS. During follow up, 10% (7/72) of patients were diagnosed with a lymphoproliferative disorder. Conclusions: This study is the largest yet, to our knowledge, to characterize the non-epidemic KS subtype in HIV-negative MSM. It is important to recognize this KS subtype to identify these individuals, who despite not having HIV are at increased risk for KS. Accurate recognition of this subtype may also allay patient concerns regarding overall prognosis, given that the majority of these patients present with indolent disease and have favorable outcomes compared to the epidemic variant of KS. Additional research is needed to understand the potential increased risk of lymphoproliferative disorders.