bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genitourinary embryonal rhabdomyosarcoma clinicopathologic determinants of clinical outcomes: Analysis of a pooled database.
Authors: Graham Christopher , Yelamanchili Ankita , Amankwah Millicent , Haddad Philip A. 
Published: June 2023

e23536 Background: Embryonal rhabdomyosarcoma (ERS) refers to malignant soft tissue tumors with phenotypical, histological features of primitive skeletal muscle. ERS commonly involves the head and neck region and genitourinary system. Genitourinary embryonal rhabdomyosarcoma (GUERS) is considered an entity similar to other ERS based on Intergroup Rhabdomyosarcoma Study Group (IRSG) with non-prostate GUERS considered low risk. This study seeks to define other high-risk subtypes in this population. Methods: To study the demographic and molecular characteristics, therapeutic interventions, survival, and prognostic factors, we compiled a pooled database of 137 cases of GUERS. Kaplan-Meier survival curves, Cox proportional-hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathologic factors on overall survival (OS) and disease-free survival (DFS). Results: 137 patients with confirmed GUERS were identified: median age was 16 and F:M ratio of 1.6. Female reproductive organs (49%), renal and urinary tract (24%), male reproductive organs (23%), and abdomino-pelvis (4%) were involved. Lymph node involvement and metastasis occurred in 11% and 13%, respectively. Staging consisted of stage I (65%), stage II (15%), stage III (8%), and stage IV (12%). Rhabdomyosarcoma clinical groups were mostly IA (41%), IIIA (31%) and IV (13%). Risk groups consisted of low (71%), intermediate (17%), and high (13%). Median OS and DFS were 96 and 42 months, respectively. The primary site of involvement impacted OS, with urinary tract organ involvement having the best median OS, compared to female reproductive organs, male reproductive organs, and abdomino-pelvis involvement (p = 0.01). While primary pelvic disease (p = 0.03), prostate (p = 0.008), and lymph node involvement (p = 0.001) were associated with worse OS, cervix/vaginal involvement tended to have better OS (p = 0.06). Constitutional symptoms (p = 0.0007), obstruction (p = 0.047) and metastases (p = 0.02) were associated with worse OS. Clinical staging system (p = 0.0008), risk groupings (p = 0.06) correlated with OS, but not clinical groupings (p = 0.26). GUERS with vimentin+, CD99- and SMA+ had worse survival (only the latter was statistically significant). Compared to no treatment, RT, CT+/-RT, S+CT+RT were superior with mOS of 2, 6, NR, 96 months, respectively (p < 0.0001). Achieving CR had superior OS (p < 0.0001). OS was not impacted by age, sex, or extent of surgery. Conclusions: Genitourinary embryonal rhabdomyosarcoma is a distinct clinical entity with outcomes worse than other forms of ERS defined by the Clinical Groups of IRSG. Prostate, primary pelvic and obstructive symptoms have worse OS compared to bladder and cervical involvement and we propose their inclusion in the current Clinical Group. This study presents updated clinicopathologic data from a pooled cohort of patients with GUERS.
Head and neck embryonal rhabdomyosarcoma clinical outcomes determinates: A pooled database analysis.
Authors: lakra rachaita , Haddad Philip A. , Zaheer Usman , Graham Christopher 
Published: June 2023

e23537 Background: Embryonal rhabdomyosarcoma (ERS) is a soft tissue sarcoma of skeletal muscle with mesenchymal precursor cells that involve the genitourinary system or head and neck. Currently, head and neck embryonal rhabdomyosarcoma (HNERS) is considered a similar entity to other ERS subtypes by the Intergroup Rhabdomyosarcoma Study Group (IRSG), with only parameningeal disease being considered as high risk. We seek to identify other higher risk phenotypes in this population. Methods: To study the demographic, molecular and IHC characteristics, therapeutic interventions, survival, and prognostic factors, we compiled a pooled database of 101 cases of HNERS. Kaplan-Meier survival curves, Cox proportional-hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathologic factors on overall survival (OS). Results: 101 patients with confirmed HNERS were identified: median age of 6.5 years, male predominance with M:F ratio of 1.7. While R0 was achieved in 44%, surgical R1 and R2 were feasible in 13% and 44% of the cases. HNERS involved the following anatomic sites: Parameningeal (49%), Skull (40%), Maxilla (39%), Nasopharynx (34%), Ears (25%), Oropharynx (17%), Nervous system (16%), Larynx (14%), Mandible (12%), Internal Jugular (7%), Orbit and Carotids (6% each), Tongue (3%), and thyroid (2%). Lymph nodes, and bone marrow were involved in 11% and 2%, respectively. Metastases occurred in 4%. The stage distribution consisted of stage I (41%), stage II (34%), stage III (19%), and stage IV (6%). Clinical groups comprised: IA(23%), IB(4%), IIA(8%), IIB(3%), IIIA(45%), IIIB(12%), and IVA(4%). Risk groups consisted of low (53%), intermediate (41%), and high (6%). The cohort’s median DFS was 240 months whereas the median OS was not reached. OS was negatively affected by parameningeal (p = 0.01), nasopharyngeal (p = 0.02), ear (p = 0.02), nerve (p = 0.0001), bone (p = 0.002), and LN (p = 0.0004) involvement. The presence of metastases was associated with worse OS (p = 0.0001). The IRSG staging system (p < 0.0001), the risk groupings (p = 0.0001), and the clinical groupings (p = 0.06) correlated with OS, though the latter did not reach statistical significance. Compared to no treatment, localized therapies such as surgery and radiation therapy, and combination chemotherapy had statistically significant improvement in OS (p = 0.027). Achieving CR was associated with superior OS (p < 0.0001). OS wasn't impacted by age, sex, extent of surgery, IHC, BM involvement or other head and neck anatomic site involvement. Conclusions: Embryonal Rhabdomyosarcoma of the Head and Neck is a distinct clinical subtype of ERS not fully defined by IRSG clinical groups when compared to other types of embryonal rhabdomyosarcoma. Parameningeal, nasopharyngeal, ear involvement had poor OS and should be considered as a clinical grouping. This study presents updated data from a pooled cohort of patients with HNERS.
Phase I study of anlotinib in pediatric patients with high-risk, recurrent, or refractory sarcomas.
Authors: Lu Suying , Wang Juan , Sun Feifei , Huang Junting , Zhu Jia , Cai Ruiqing , Zhen Zijun , Zhang Yizhuo 
Published: June 2023

e23538 Background: Anlotinib is an orally available, highly potent, novel multitargeted tyrosine kinase inhibitor, which blocks VEGF signaling by selectively targeting VEGFR-2, -3 as well as FGFR-1, -2, -3, -4 with high affinity. We evaluated the toxicity, and pharmacokinetic profile of anlotinib in children with high-risk, recurrent, or refractory sarcomas. Methods: This was an open-label, single-center, single-arm phase I study, which enrolled pediatric patients with sarcoma. Pediatric patients aged 5-18 years diagnosed with high-risk, recurrent, or refractory sarcomas were enrolled and further categorized into cohort A (＜35 kg) or cohort B (≥ 35kg). Anlotinib was administered orally, once daily, 2-week on off, until disease progression, death, unacceptable toxicity, or withdrawal of consent for any reasons. A fixed anlotinib level of 8 mg was given to cohort A and three dose levels (8mg, 10mg, 12mg) were evaluated using a “3 + 3” design in cohort B. Results: Between December 29, 2020, and September 7, 2022, 34 patients were enrolled to evaluate the safety and 19 (55.9%) were evaluable for efficacy. The median age was 12 (range 5-18) years old. The main subtype eligible was rhabdomyosarcoma (23.5%). Two of fifteen patients in cohort A at a dose level of 8 mg experienced dose-limiting toxicity, including grade 3 hematuria and grade 3 hand-foot syndrome. The grade 3 treatment-related adverse events (AEs) included neutropenia (3 [8.8%]), hand-foot syndrome (2 [5.9%]), headache (1 [2.9%]), hematuria (1 [2.9%]), hypertension (1 [2.9%]), and hyperbilirubinemia (1 [2.9%]). The most common AEs were grade 1 or 2 hypothyroidism (58.8%) and abdominal pain (55.9%). Twelve of 19 (63.2%) patients had a best response of stable disease with seven patients receiving ≥ 6 cycles. Age has no significant effect on the level of body exposure per unit body surface area dose, and patients younger than 12 years old had a faster elimination. Conclusions: Anlotinib in pediatric patients with sarcoma was well tolerated. The RP2D of anlotinib for future studies is 8 mg for patients＜ 35 kg and 12 mg for patients with ≥ 35kg. Clinical trial information: NCT04659733 . [Table: see text]
Study of microwave ablation in patients with unresectable soft tissue sarcoma.
Authors: Weitao Yao , Du Xinhui 
Published: June 2023

e23545 Background: Currently, the main treatment for soft tissue sarcoma is a combination of radiotherapy, chemotherapy and complete surgical resection. However, there is no ideal method for soft tissue sarcoma after multiple recurrences, large tumours, insensitivity to radiotherapy or failure of down grade therapy. Microwave ablation is one of the main techniques for tumour thermal therapy, but its use in soft tissue sarcoma is not yet widespread. The aim of this study was to investigate the safety and efficacy of microwave ablation in refractory soft tissue sarcoma. Methods: Fourteen eligible patients with refractory soft tissue sarcoma were treated with local anaesthesia, multi-point intra-tumour needle placement under ultrasound guidance and local radiofrequency ablation (20-40 J, 2-5 minutes). For tumours larger than 5 cm in diameter, repeat ablation can be performed after 3-4 weeks. Of the 14 patients, 8 were male and 6 were female, with a mean age of 58.91 years. There were 4 cases of myxofibrosarcoma, 3 cases of dedifferentiated liposarcoma, 2 cases of malignant nerve sheath tumour, 2 cases of clear cell sarcoma and 3 cases of other sarcomas. Tumours were located in the trunk in 7 cases, in the upper limbs in 3 cases and in the lower limbs in 4 cases. Of these, 5 patients had two operations and 9 patients had three or more operations. Four cases had received first-line therapy, five cases had received second-line therapy, and five cases had received third-line therapy or more. Postoperative pain relief and wound complications were recorded. MRI was performed regularly to assess tumour shrinkage. Results: Post-operatively, all patients experienced a significant reduction in local swelling and pain. Post-operative imaging showed partial response (PR) in 11 cases and stable disease (SD) in 3 cases. The overall response rate (ORR) was 78.57%. Progression-free survival (PFS) ranged from 2-18 months with a median of 5.82 months. Complications included tumour ulceration in 2 cases, skin burns with necrosis in 2 cases and postoperative fever in 5 cases. Conclusions: For soft tissue sarcomas that cannot be removed by surgery, where tumour growth is slow and insensitive to radio/chemotherapy, local microwave ablation can achieve tumour shrinkage and reduce patient symptoms such as local swelling and pain. It is an effective treatment option for some specific sarcoma patients.
A phase II study of fruquintinib in the first- (1L) or second-line (2L) treatment of unresectable metastatic soft tissue sarcoma.
Authors: Luo Zhiguo , Zhang Xiaowei , Zhao Ting , Zheng Bi-Qiang , Yan Wangjun , Chen Yong , Xu Yu , Wang Chun-Meng , Zhang Junhua , Wang Jian , Yu Lin , Liu Xin 
Published: June 2023

e23547 Background: Standard treatment for patients with unresectable metastatic soft-tissue sarcoma is chemotherapy based on anthracyclines, while the tolerance of chemotherapy is limited. We assessed if fruquintinib, a highly selective tyrosine kinase inhibitor of VEGFR-1, -2, and -3 is effective and safe in the 1L or 2L treatment for these patients. Methods: This is a single-arm, prospective, single-center clinical study. The inclusion criteria were patients with pathologically confirmed unresectable metastatic STS (including desmoplastic small round cell tumors, epithelioid hemangioendothelioma, hemangiopericytoma/malignant solitary fibroma, and chemotherapy-failed hemangiosarcoma), at least one measurable lesion (according to RECIST 1.1), with the normal function of main organs. Other inclusion criteria included ECOG PS 0-2 and anti-angiogenesis treatment naïve. Patients were administrated 5mg fruquintinib once daily for 3 weeks every 4 weeks until disease progression or unacceptable toxicity. The primary study endpoint was Progression free survival (PFS). Objective response rate (ORR), disease control rate (DCR), duration of response (DoR) and adverse event was also calculated. Results: Data cutoff date was January 31 2023. 14 patients (9 males and 5 females) were enrolled. The median age is 50.1 (range 21-69). Pathological types included: Hemangiopericytoma/malignant solitary fibroma (n=6); Epithelioid Hemangioendothelioma (n=6) and Hemangiosarcoma (n=2). 2 patients were died, the median PFS was 8.1 m. 14 patients were eligible for the evaluation of tumor response. 3 patients (2 cases of Hemangiosarcoma and 1 case of Epithelioid Hemangioendothelioma) achieved partial response (PR) and the ORR was 21.4 %(3/14). 10 patients had stable disease (SD) and the DCR was 92.9% (13/14). Most adverse events were hypertension, fatigue, and hemorrhage. The most Grade 3/4 adverse effect is hypertension and abnormal liver function. Conclusions: The fruquintinib showed a promising efficacy and favorable tolerance in the 1L or 2L treatment of unresectable metastatic soft-tissue sarcoma. Clinical trial information: NCT05142631 .
Comparative analysis between the 8th and 7th AJCC as a prognostic tool for patients diagnosed with nonmetastatic head and neck soft-tissue sarcoma.
Authors: Brito Angelo Borsarelli Carvalho , Zanetta Giulia Kodja , Costa Felipe D'Almeida , Formiga Maria Nirvana da Cruz , Mello Celso Lopes , Filho Joao Goncalves , Ikeda Mauro Kazuo , Camillo Cláudia Malheiros , Pinto Clovis Antonio Lopes , de Jesus Victor Hugo Fonseca , Campos Fernando Augusto Batista , Kowalski Luiz Paulo , Nicolau Ulisses Ribaldo 
Published: June 2023

e23550 Background: Head and neck soft-tissue sarcoma (HN-STS) is a rare entity for which a new prognostic risk stratification has been proposed in the 8th AJCC. The tumor size 2cm and 4cm have been adopted as cutoffs for T1 to T3 classification and the invasion of surrounding structures denotes T4. In opposite, in the 7th edition the primary tumor size of 5 cm determines T1 and T2 classification. This study aimed to compare the 8th and 7th AJCC as a prognostic tool for HN-STS. Additionally, we sought to investigate prognostic factors in this group of patients. Methods: This is a single Tertiary Hospital study approved by the institutional ethical review committee from the AC Camargo Cancer Center. We retrospectively evaluated patients with non-metastatic HN-STS whose histology subtypes are included in the 40th chapter of the 8th AJCC version. We compared the AJCC 7th and 8th T staging with Cohen’s kappa coefficient using inter-rater agreement analysis. The Kaplan-Meier (KM) estimator was used to calculate median survival times; differences in time-to-event outcomes were assessed using the log-rank test. Cox proportional hazard model was used to assess the effect of features in overall survival (OS). Results: Ninety-five HN-STS treated with curative intent from 2005 from 2021 patients diagnosed were evaluated. Surgical resection (94.7%), radiotherapy (48.4%) and chemotherapy (23.1%) were the employed therapeutic approaches. Leiomyosarcoma and liposarcoma (10 of each subtype) were the most common histology subtypes; High grade disease was present in 66.3%. Kappa coefficient of inter-rater agreement was 0.46 with statistical significance (p = 0.03), which indicates poor agreement between AJCC 7th and 8th T staging system. Regarding OS stratified by T size in the AJCC 7th (T1 and T2) and 8th (T1, T2, T3 and T4) was not statistically different between groups (P = 0.83 and P = 0.21, respectively). Patients with T4 (47.6% vs 78.7%, P = 0.04) and high grade (64.0% vs 96.2%, P = 0.003) had worst 5-years OS. In Cox multivariate analysis, patients with 8th edition T4 and high grade had 3.15- and 4.16-fold increased risk of death, respectively. Conclusions: In our series of patients with HN-STS, neither 7th nor 8th AJCC T size category groups discriminated prognosis. Tumor with local invasion (8th AJCC T4) and high grade were all associated with increased risk of mortality.
Presentation of congenital soft-tissue sarcomas: A single institution experience.
Authors: Parra Del Riego Angela , Olsen Braden , Gonzalez Keishla , Pabon Camila , Chamyan Gabriel , Fader Maggie Eidson 
Published: June 2023

e23551 Background: Pediatric sarcomas make up 10% of pediatric tumors and involve a varied range of histological patterns with different prognosis which creates therapeutic challenges. Neonatal presentation is rare among sarcomas and poses further challenges in therapy. Methods: We present 5 cases of congenital sarcomas reporting pathology, genetics, treatment, and outcomes. We retrospectively identified 5 patients with sarcomas diagnosed in the neonatal period from a single institution in Miami from 2017 – 2022 in order to identify similarities between neonatal sarcomas. Our sarcomas included an embryonal rhabdomyosarcoma (RMS), infantile fibrosarcoma (IFS), rhabdoid tumor, and two undifferentiated sarcomas. Results: The presentation occurred between birth and four days old. Location at presentation was varied. Four of our patients were Nonrhabdomyosarcoma Soft Tissue Sarcomas (NRSTS). Only one patient was diagnosed prenatally, while three were diagnosed at birth, and one at 4 days of life. Three patients presented spindle cell pathology. One of our undifferentiated sarcomas was classified as IFS-like, Archer FusionPlex was negative for mutation. Our other undifferentiated sarcoma showed a COL1A1 gene rearrangement on chromosome 17q.21 with immunostains positive for BCOR, SMARCB1, SMARCA4. Congenital fibrosarcoma showed ETV6 fusion with NTRK and immunostains positive for FLI-1, SMA, CD34, INI-1. The RMS showed focal loss of PTCH1 and FANCC and had immunostains positive for desmin and myogenin. The metastatic rhabdoid tumor showed SMARCB1 whole gene deletion as well as a 570kB deletion in chromosome 22q11.23. Three patients were treated on ARST 0331 with vincristine, doxorubicin, and cyclophosphamide (VAC), with the undifferentiated sarcoma requiring advancement to ARST 0332. The patient with metastatic rhabdoid tumor was treated with AREN 0321. Four patients required surgery. We had 1-year-survival in three patients, all treated on ARST 0331 or ARST 0332. The patient with metastatic rhabdoid tumor died at 4 months of age while on AREN 0321, and our patient with IFS-like sarcoma decompensate and died at ten days old, prior to starting therapy. Conclusions: We show multiple genetic mutations with SMARCB1 alteration in both an undifferentiated sarcoma and a malignant rhabdoid tumor but otherwise found no significant pattern among individual sarcomas. Our cases show good outcomes for patients qualifying for ARST 0331. We highlight the need for improved methods of detection of pediatric tumors in utero.
Concordance between orthotopic-patient derived xenograft models and patient treatment responses.
Authors: Nakashima Jonathan , Sperry Jantzen , Lofftus Serena , Federman Noah , Singh Arun S. , Eilber Frederick C. 
Published: June 2023

e23553 Background: Patient-derived xenografts (PDX) have shown promise in identifying personalized therapies for cancer patients. We have previously shown that orthotopic-PDX models from untreated, high-grade sarcomas demonstrate a 62% establishment rate with a median time of 54 days. Methods: We performed a retrospective study by collecting oncologic patient treatment history and response data to carry out in vivo pharmacology studies on corresponding O-PDX models using therapies that the patients received. Results: Among 16 patients and 26 therapies, we identified an overall concordance of 84.6%. Specifically, we show a positive predictive value of 82.4% among responders and a negative predictive value of 88.9% among non-responders. Conclusions: This study demonstrates that O-PDX models replicate clinical response in patients and are valuable screening platforms for guiding therapeutic decision-making for rare cancers such as sarcoma.
Analysis of demographic characteristics of malignant peripheral nerve sheath tumor in adults: A National Cancer Database study.
Authors: Voth Caitlyn , Wu Xinxin , Keirns Darby , Silberstein Peter T. , Hsia Beau 
Published: June 2023

e23555 Background: Malignant peripheral nerve sheath tumor (MPNST) is a rare cancer involving the peripheral nerve sheath. Even though the 5-year post-surgical resection survival rate is only 30 to 40%, the epidemiology is not well understood, and looking at trends in demographics could provide insight into factors potentially contributing to poor prognosis. A previous National Cancer Database (NCDB) study investigated demographics in pediatric patients with MPNST. This study analyzed NCDB data to investigate the demographics of adults with MPNST. Methods: Adult patients with a histologic diagnosis of MPNST were retrospectively examined in a cohort analysis using demographic information from the NCDB from 2004 – 2020 (N = 414). Regression analysis was used to describe incidence trends. Demographics (age, sex, race, Hispanic origin, income, insurance status, area of residence, facility type, distance from facility, and Charlson-Deyo score) were explored through descriptive statistics. Palliative care enrollment and mortality rate was examined. Results: 414 patients with age > 18 were identified in the NCDB database with a confirmed diagnosis of MPNST between the years 2004 – 2020. There was a slight increase in incidence of patients diagnosed per year (R2 = 0.254). The average age of diagnosis was 47.0 years (SD = 17.2, range = 19 – 88 years) with more males (51.4%) affected than females (48.6%). The most common primary sites were the retroperitoneum (32.4%), spinal cord (24.4%), and cranial nerves (15.0%). A majority of individuals (82.6%) had Charlson-Deyo comorbidity scores of 0. Individuals most commonly affected were White (79.7%) or Black (14.3%), and non-Hispanic (87.4%). Patients most commonly were in the top quartile of household income (31.6%), had private insurance (53.6%), lived in metropolitan counties (83.8%), and received treatment at an academic/research program (62.2%). Patients lived on average 61.6 miles (SD = 145.7, range = 0.5 – 1454.9) from the facility. The 90-day mortality rate post-surgery was 10.5%. The overwhelming majority of patients did not receive palliative care (94.4%). Conclusions: This is the first NCDB analysis on the demographics of MPNST in adults, providing information that bridges the gap in knowledge. This analysis showed that the retroperitoneum was the most common tumor site, and that the average age of diagnosis was 47 years, consistent with previous reports. Patients were most likely to be White, non-Hispanic, upper quartile income earners, privately insured, treated at an academic facility, and live in metropolitan counties. With the majority of patients receiving no palliative care, it’s possible that palliative care is underutilized and may benefit MPNST patients given the poor prognosis. Additional research on the relationship between socioeconomic status and palliative care access may provide information on this discrepancy.