bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chondrosarcoma: The OSU experience.
Authors: Husain Marium , Tinoco Gabriel , Chen James Lin , Mayerson Joel L , Scharschmidt Thomas , Alexander John , Konieczkowski David Joseph , Haglund Karl , Grignol Valerie Patrice , Beane Joal , Kim Hangil , Xu Menglin , Liebner David A. 
Published: June 2023

e23505 Background: Chondrosarcomas (CSC) constitute a diverse group of malignant bone tumors whose optimal management remains controversial, and patients with advanced disease have a dismal prognosis. Methods: Patients evaluated at The Ohio State University between January 1, 2010, to March 7, 2022, were included in the analysis. Data includes demographics, pathology, next-generation sequencing results, treatment combinations and responses, survival, time to progression, and recurrence. Results: 147 patients were eligible for this retrospective study. 29 patients were censored as they received no treatment or were lost to follow-up, leaving 118 evaluable patients. 83 patients had Conventional CSC, 16 had Dedifferentiated CSC, 4 Mesenchymal/Clear cell CSC, and 15 Myxoid/Extraskeletal myxoid CSC. 108 of 118 were white (91.5%), and 60 of 118 were male (50.8%). The median age at diagnosis was 57, ranging from 21-84 years old. 107 (92.2%) patients in the dataset had localized disease (Stage 1 or 2) and had curative treatment intent. The median tumor size was 6.3 cm for all patients. The most common site of the tumor was in the lower extremities (36.4%), followed by thoracoabdominal in 46 patients (38.9%), skull base/head and Neck in 17 patients (14.4%), and upper extremities in 12 of 118 (10.2%). The Median survival time differed significantly by subtype: Conventional CSC 104.6 months, dedifferentiated CSC 25.9 months, mesenchymal + clear cell CSC 57.2 months, myxoid or extraskeletal myxoid CSC 108.3 months, Overall survival in the entire cohort was 90.6 months. Overall comparison among subtypes Chi-square 57.41, ( p = 0.0). No association was seen between anatomic subsite and overall survival (upper extremities 202.80 months, lower extremities 85.30 months, and Pelvis & Retroperitoneal & lower back & Chest/Abdomen Wall/Upper Back 82.3 months, p = 0.216). The grade was associated with overall survival: grade 1 median 202.80 months, grade II 80.87 months, and grade III 21.067 months (p = 0.000). 18 patients received chemotherapy, 116 received surgery, and 12 received radiation. Among the 18 patients that received chemotherapy ( 4 patients had localized disease and 14 had the metastatic disease), the most used systemic therapy was Pazopanib 10/18 (55%), which had the longest time to progression of 22.42 months. The median time to progression of the 18 patients that received chemotherapy was 9.71 months. Conclusions: CSC remains a clinical challenge due to its rarity and limited treatment options. While surgical resection remains the mainstay of treatment for localized disease, systemic therapy and radiation can have important roles in selected subsets of patients. Further refinement of these care paradigms will require a multi-institutional/consortium effort to create a data repository and develop clinical trials to improve outcomes for these patients.
Racial differences in prognostic role of white blood cell ratios in gastrointestinal stromal tumors.
Authors: Chintapally Nikita , Kashiouris Markos , Liu Zhonghua , Bautista Enrico , Desai Aalisha , Haber Jamie Kayla , Boikos Sosipatros Alexandros 
Published: June 2023

e23507 Background: Gastrointestinal stromal tumors (GIST) are rare mesenchymal tumors with an estimated 3,300 to 6,000 new cases per year in the United States. Per SEER database, significant racial disparity exists with an incidence rate twice as high for African Americans as compared to Whites. Currently, parameters used in stratification of disease risk can only be determined by postoperative histopathological evaluation. Cancer-related inflammation is linked to different stages of tumor development so markers found in peripheral blood have been studied as surrogates. We present a study comparing the predictive prognostic ability of preoperative serum inflammatory markers in primary untreated GIST and highlight the differences between Black and White patients. Methods: This is a retrospective analysis of 149 patients who underwent operative resection of primary untreated GIST. Preoperative blood samples were used for the analysis. Patients were excluded if they showed clinical signs of infection during time of pre-operative blood sampling or had non-GIST synchronous malignancy. Clinicopathological data was obtained from patient chart review and logistic regression models were used to evaluate data. There is ongoing next-generation sequencing data analysis. Results: 149 patients were included: 80 (53.7%) Black, 43 (28.9%) White, 26 (17.5%) were other. The mean values for neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and monocyte to lymphocyte ratio (MLR) were 3.62 (SD 3.07), 191.55 (SD 119.15), and 0.47 (SD 0.49) respectively. On univariate analysis NLR and PLR were significant prognostic indicators of high and intermediate risk GISTs per the National Institute of Health (NIH) categories [NLR p = 0.008, PLR p = 0.007]. Upon subgroup analysis, NLR and PLR showed the highest statistical significance for predictors of high and intermediate risk GISTs among the Black patient population [NLR odds ratio (OR) 2.685; 95% confidence interval (CI) 0.976-7.381; p = 0.05 and PLR OR 1.792; 95% CI 1.054-3.049; p = 0.031]. The same was not shown to be true for the White patient population. 11 out 149 patients progressed since diagnosis of which 8 were Black and 3 White. 7 were in the high risk category, 3 in low risk and 1 in intermediate risk with an overall mean NLR and PLR 5.25 and 244 respectively. The average time to progression was noted to 28 months. Conclusions: The NLR and PLR are easily obtainable and cost-effective indexes which have the prognostic ability to serve as surrogates for high and intermediate risk GISTs. They appear to be more predictive in the Black patient population than in White. Further study is warranted for incorporation into risk stratification systems.
MSI analysis in patients with GIST with lynch syndrome.
Authors: Gasperoni Silvia , Messerini Luca , Castiglione Francesca , Papi Laura , Gensini Francesca , Cianchi Fabio , Taddei Antonio , Prosperi Paolo , Perna Federico , Coratti Francesco , Antonuzzo Lorenzo 
Published: June 2023

e23510 Background: Lynch Syndrome due to mutations in one of DNA mismatch repair (MMR) genes, is found in patients with colon cancer (3%).The mutations in these DNA repair genes induce genetic instability and development of ovarian, endometrial, urothelial, gastrointestinal and biliary tract carcinoma. Methods: In our center, 31 patients with Lynch syndrome are followed in Oncology Department in multidisciplinary team according to regional diagnostic therapeutic assistance paths and international guidelines. Immunohistochemical staining (IC) for mismatch repair proteins (MLH1, MSH2, MSH6, PMS2) and microsatellite instability testing (MSI) by PCR real time easyPGX were performed in colon cancer, genetic testing has been preceded by genetic counseling. When GIST diagnosis occurred in patients with colon cancers and Lynch syndrome, IC and MSI were performed in GIST too. Results: MSI-H has been detected in synchronous colo-rectal cancer in 2 patients with GIST. Pathogenetic germline mutations in MSH2 gene were observed in both patients. In 1 female patient with gist of duodenum (very low risk according to Miettinen classification) with previous endometrial cancer and sincronous PT3N0 rectal cancer, we observed MSI-stable in IC and PCR, KIT/PDGFRα wild type in Next GenSequencing analysis, BRAF wild type (PCR-real time), SDH-B + (IC), NTRK 1 (exon 9-10, exon 1-12 del, exon 12), NTRK 2 (exon 12-15.exon 16-17), exon 14, NTRK 3 (exon 14, exon 15) no gene fusion by PCR-real time (CE.IVD kit easy NTRK). In 1 male patient with ileal GIST (intermediate risk according to Miettinen classification ) with ileal adenocarcinoma pT3N0, we observed KIT exon 11 mutated, MSI-stable in IC, when we repeated the analysis using PCR real time EasyPGX, we observed high instability of microsatellites. Conclusions: For the first time we observed in Lynch Syndrome MSH2 mutated, simolutaneous GIST and colon cancer in the same site of ileum and PCR analisys detected a rare exemple of microsatellite instability in GIST.
Ripretinib therapy in treating advanced gastrointestinal stromal tumors: A single-center analysis in a real-world setting.
Authors: Guan Zhaoming , Zhang Xinhua , Xia Yanzhe , Huang Shaoqing , Wu Chunhui , Cai Shirong , He Yulong 
Published: June 2023

e23514 Background: Ripretinib has been proven effective in inhibiting various primary and secondary mutants of KIT/PDGFRA but with limited clinical data. This study is aimed to investigate the efficacy and safety of ripretinib and prognostic predictors based on the current treatment pattern in Chinese patients in a single center. Methods: This retrospective cohort study was based on the prospectively registered database of the First Affiliated Hospital, Sun Yat-sen University. Patients with confirmed recurrent and/or metastatic GIST who received ripretinib as ≥ 2nd line therapy between June 1, 2020, and January 1, 2023 were enrolled. Results: Forty patients receiving ripretinib were enrolled. The median age of the patients was 58.0 years, and the most common primary site of tumor was the small intestine (75.0%). KIT exon 11 (65.0%) was the most common primary mutation, followed by exon 9 (20.0%). Ripretinib was administered as 2nd- and 3rd-line therapy in 17.5% of patients, respectively; as 4th-line therapy in 45% of patients, and as 5th- or later-line therapy in 20% of patients. Thirty patients who received ripretinib as > = 3rd-line therapy were eligible for efficacy evaluation. There was no complete remission. Two patients (6.7%) were partial response, and 20 (66.7%) patients were disease stable for at least 8 weeks. The median follow-up time was 18.0 months. The median progression free survival (PFS) (95% confidence interval [CI]) was 5.9 (2.0, 9.7) months, and the median overall survival (OS) was 13.8 (11.5, 16.0) months. In the univariate analysis, patients with a primary mutation in KIT exon 11 (P = 0.002), better ECOG performance status (P = 0.041), and lower tumor burden, including the number (P = 0.016) and cumulative size (P＜0.001) of tumors, had longer PFS. Patients with a primary mutation in KIT exon 11 (P = 0.019), better ECOG performance status (P＜0.001), fewer tumors (P = 0.014), and a younger age (P = 0.039) had longer OS. In the multivariate analysis, the primary mutation (P = 0.004) and the number and cumulative size of tumors (P = 0.024, P = 0.015, respectively) were independent predictors of PFS. The primary mutation (P = 0.025), the number of tumors (P = 0.002), and ECOG performance status (P = 0.002) were independent factors of OS. Ripretinib was generally well tolerated, and no unexpected toxicities were observed. The most common AEs were anemia (45%), alopecia (28%), constipation (25%), and hypoalbuminemia (25%). Grade 3/4 AEs were reported in 25% of patients, and the most common ones were hand-foot syndrome (8%), anemia (5%), and increased aspartate aminotransferase (5%). Conclusions: Ripretinib was safe and effective in Chinese patients with imatinib-resistant GISTs in a real-world setting. Primary KIT exon 11 mutation, lower tumor burden and better performance status were associated with better survival benefit.
B7H3 expression in sarcoma.
Authors: Lynch Meghan Maureen , Obeidin Farres , Alexiev Borislav A. , Chen Eleanor Y. , Viveiros Pedro , Schroeder Brett , Hudkins Kelly , Fan Timothy M. , Redman Mary Weber , Baker Kelsey K. , Jour George , Pollack Seth 
Published: June 2023

e23517 Background: Targeted therapy development in sarcoma has been burdened by the heterogeneity of this rare group of tumors. B7H3 is an immune checkpoint molecule in the same family as PD-L1 (also known as B7H1). Its limited expression in non-cancerous tissues and over-expression in numerous tumor types makes it an attractive target for cancer immunotherapy. Available data suggests high expression of B7H3 in certain sarcoma subtypes, including rhabdomyosarcoma, osteosarcoma, liposarcoma, Ewing sarcoma, synovial sarcoma and chondrosarcoma. This study was conducted to further explore B7H3 expression patterns across sarcoma subtypes and the relationship, if any, with PD-1 and PD-L1 expression. Methods: This single-institution, retrospective analysis evaluated soft tissue sarcoma Formalin-Fixed Paraffin-Embedded tumor specimens in patients with a variety of different subtypes. Specimens were evaluated for expression of B7H3, vessel positivity for B7H3, B7H3 staining pattern, and expression of PD-L1 and PD-1. The association between B7H3 expression and baseline and tumor factors was tested using the Mantel Haenszel test or two-sample T-test. Overall survival was estimated using the Kaplan-Meier method where survival time was calculated from diagnosis to death (or last follow-up for those last known to be alive). Results: 156 sarcoma specimens encompassing 16 subtypes were included. B7H3 was broadly expressed across sarcoma subtypes, with some degree of expression found in 91% of samples and 61% demonstrating high levels of B7H3 expression. All tumor samples expressing B7H3 exhibited the biomarker in at least 80% of tumor cells per sample (with a mean of 92.34% of cells testing positive for B7H3). All samples positive for B7H3 showed both cytoplasmic and membranous expression, and B7H3 vessel positivity was found in 90% (137/152) of samples. There were no significant differences in expression or level of expression when stratified by sarcoma subtype, prior treatment(s), tumor size, tumor grade or patient age. No significant difference in overall survival was seen regardless of B7H3 expression or expression levels across sarcoma subtypes. There was no correlation between B7H3 expression and expression of PD-L1 or PD-1 in tumor cells. Conclusions: This is the most comprehensive analysis of B7H3 expression in sarcoma to date. This data shows high levels of B7H3 expression across sarcoma subtypes, suggesting its feasibility as a therapeutic target for future sarcoma treatments. Future clinical trials are needed to evaluate its numerous actions and if manipulation of B7H3 can be employed to improve outcomes in sarcoma. [Table: see text]
Identification of novel actionable SNVs using targeted comprehensive genome profiling in patients with sarcoma.
Authors: Bhonde Mandar , Bose Chirantan , Gupta Vineet Govinda , Tiwari Priya , D'Souza Alain , Kad Trupti , Prajapati Sangeeta , Jadhav Bhagwat , Hariramani Kanchan , Basavalingegowda Madhura , Mobeen Fauzul , Rani Aditi , Mehra Vatsal , Kumaran Manoj Kumar , Haldar Sumit , Saha Rajat , Mehta Prashant , Uttarwar Mohan , Khandare Jayant , Shafi Gowhar 
Published: June 2023

e23520 Background: The utility of comprehensive genome profiling is not well validated in early-stage sarcoma. The 5-year survival rate for metastatic sarcoma is less than 20%. The application of comprehensive Next Generation Sequencing (NGS) on tumor DNA has led to the identification of a multitude of actionable alterations in oncogenes & tumor suppressor genes alongside the detection of immunotherapy markers like microsatellite instability, tumor mutational burden, and homologous recombinant deficiency. Methods: We retrospectively analyzed ccfDNA and gDNA in 13 sarcoma patients by targeted Next Generation Sequencing (NGS) using OncoIndx proprietary gene panel that targets exonic regions of 600 cancer-related genes. Illumina-compatible libraries were prepared by the target hybridization method and sequenced on Nextseq 2000 platform in a pair-end fashion. Variant calling was performed using an indigenously developed bioinformatics pipeline. Results: Here we report for the first time the identification of several, novel mutations in rare sarcomas such as IDH2R140W (in epithelioid hemangioendothelioma), CTNNB1D32V (in undifferentiated small round cell sarcoma) and DDR2M754I (in osteosarcoma). Furthermore, we observed, JAK1 amplification and BRAF-GUSBP1 fusion in osteosarcoma and a sarcomatoid carcinoma case, respectively. JAK1 amplification and DDR2M754I were found in the same patient. The IDH2 mutation and JAK1 amplification could find potential applications for JAK1 and IDH2 inhibitors respectively. Similarly, cancers having DDR2 mutations are known to respond to multikinase inhibitors such as Imatinib and Dasatinib, thus making a strong case for the potential repurposing of these drugs in sarcomas. ~93% of patients demonstrated genome-wide instabilities as evidenced by LOH, LST, TAI, and high TMB. Homologous Recombinant deficiency was found in 66.7% of patients. Although this is a small patient population, the high HRD+ percentages point to the underappreciated importance of HRD testing in sarcoma and herald the use of PARPi therapy for sarcoma. Conclusions: We identified several actionable mutations in rare sarcoma cases. These findings highlight the power of comprehensive genome profiling like the OncoIndx panel and warrant further studies on the role of IDH2, JAK1, and BRAF fusion in sarcomas. Moreover, they also present a strong potential case for repurposing of TKI such as Imatinib and Dasatinib in sarcomas.
Publication trends in sarcoma research: A bibliometric analysis.
Authors: Fanfan Dino , Olorunlogbon Oreoluwa , Figueroa Yandhira Thalia , Trent Jonathan C. 
Published: June 2023

e23530 Background: Sarcomas are rare primary malignant tumors originating from connective tissue, worldwide research trends on this topic are unclear. We conducted a bibliometric analysis of the 100 most influential articles on sarcoma. Methods: We sourced the literature published in academic journals indexed by the Scopus Database. Using the key words “sarcoma,” “soft-tissue tumor,” “bone sarcoma,” “soft-tissue sarcoma,” “connective tissue malignancy.” A list of the 100 most-cited articles were extracted and sorted by number of citations, excluding articles related to Kaposi’s Sarcoma. The papers were checked independently by our authors for accuracy of topic. R was used to extract the publishing journal, year of publication, country of origin, affiliated institutions, authors, and total citations. Results: The total number of citations for 100 articles was 73,483. Citations for individual articles ranged from 453 to 3,064, with a median of 588 (IQR: 341).The United States contributed the most papers (n = 70), followed by France and the United Kingdom (n = 5). Most articles, 67, were published prior to the 21st century and only 3 were in the last 10 years. The most cited study was Malkin et al.’s Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms with 3,064 citations. Of the top 10, 8 were published between 1978 and 1998. Journal of Clinical Oncology made the greatest number of contribution to the research on sarcoma with a total of 18 articles (citations = 12,166), followed by Cancer with 15 (citations = 9,052), and Proceedings of the National Academy of Sciences of the United States with 10 (citations = 8,431). The median Scopus CiteScore for publishing journals was 19.7, the highest being The Lancet (115.3) and The Iowa Orthopaedic Journal with the lowest score (1.5). Conclusions: Within the United States, the institutions producing the most literature were the NCI and Memorial Sloan Kettering Cancer Center. The majority of the 100 most cited studies are cited an average of 735 times, indicating that these sources are providing a substantial foundation for emerging research in the field. This begs the question of the quality and relevance of evidence in the literature, given the amount of citations. The Lancet produced literature with the highest journalistic impact, having a CiteScore of 115.3 based on Scopus metrics. While the majority of the 100 most cited pieces of literature (67%) on sarcomas were published prior the 21st century, a small portion, eight, were produced in the last decade. This information could indicate either a lull in the frequency of research being conducted, or an effort on the part of institutions to create more substantial investigations that provide more valuable contributions to the field of research in sarcomas. We hope to continue seeing the field of sarcoma expand with new advances in its management.
Clinicopathological features and treatment profile of patients referred to a sarcoma medical oncology centre in India: Challenges and insights from the developing world.
Authors: Tansir Ghazal , Rastogi Sameer , Barwad Adarsh 
Published: June 2023

e23533 Background: Sarcomas are rare cancers that warrant expert pathologic diagnosis (dx) and multidisciplinary treatment (MDT). We analysed details of patients (pts) diagnosed with soft tissue sarcomas (STS) and bone sarcomas (BS) referred to our centre. Methods: This is a retrospective study of pts diagnosed with STS or BS referred to All India Institute of Medical Sciences, Delhi between January 2021 and December 2022. Histopathological discrepancies were noted as change of primary dx or differences in grading or sarcoma subtyping on pathology review. Surgical and/or medical deviations from standard practise were identified. SPSS 26.0 was used for statistical analysis. Results: 268 pts with median age of 35 years (range 8 months-85 years) and male predominance (n = 140, 52.2%) were included. 121 (45%) pts belonged to adolescent and young age (AYA) group. 163 (61%) pts came from urban/semi-urban background and from a median distance of 90 miles (range 6.2-1587). Median symptom duration prior to referral was 9 months (range 6 months-12 years). Based on biopsy or cytopathological evidence, referred pts included 186 (69.4%) with STS, 73 (27.2%) with BS, 7 with undifferentiated sarcoma (2.6%) and 2 with carcinoma (0.7%). The most common STS (n = 186) were leiomyosarcoma (14%), synovial sarcoma (12%) and liposarcoma (8.3%); BS (n = 73) included osteosarcoma (44%), Ewing sarcoma (44%), chondrosarcoma (9.5%). Molecular and/or germline mutation tests were performed only in 9 of 131 (6.8%) indicated cases before referral. Localized/locally advanced and metastatic stages were found in 94 (35.6%) and 116 (43.2%) resp; rest (21.2%) did not undergo staging work-up outside. Common primary sites were extremity (n = 127, 44.4%), abdomen (n = 71, 24.8%), thorax (n = 24, 8.3%). 125 (43.7%) and 91 (31.8%) pts had undergone surgery and chemotherapy resp outside. 1st line chemotherapy (n = 85) was anthracycline-based (n = 65, 76.4%), ifosfamide-based (n = 6, 7%), gemcitabine-docetaxel (n = 5, 5.8%). 2nd line (n = 29) was gemcitabine +/- docetaxel (n = 7, 24.1%), anthracycline (n = 6, 20.6%), ifosfamide-based (n = 6, 20.6%), pazopanib (n = 6, 20.6%). Pathologic discrepancies found in 87 (30.4%) pts included change of primary diagnosis in 44 (15%), sarcoma subtype variation in 35 (12.2%) and benign disorder misclassified as malignancy in 5 (1.7%) pts. Deviations in chemotherapy (n = 43, 47.2%) included inadequate dose/cycles in 18 (42%), no chemotherapy despite indication in 8 (18.6%), non-standard regimens in 10 (23%) pts. Distance/rural residence did not correlate with pathology/treatment deviations. Conclusions: In this era of precision medicine and targeted oncology, our findings reflect the need for well-equipped diagnostic and treatment facilities. The lack of expert centres catering to pts with sarcomas remains a challenge in developing countries.