bluuebunny/crossref_metadata_2025_split huggingface dataset:
An NCDB analysis of patient treatment trends in soft tissue angiosarcoma.
Authors: Chaddha Jasleen Kaur , Samuel Maya Mary , Saldhi Prachi , Silberstein Peter T. , Braaten Marco 
Published: June 2024

e23563 Background: Angiosarcoma is a rare subtype of soft tissue sarcoma associated with a generally poor prognosis and high mortality rate. Median survival of patients with angiosarcoma typically ranges from 15 to 24 months, with a 5-year survival of 12-33%. Angiosarcomas have a high propensity for local recurrence, metastasis, and multiple organ involvement as they originate from vascular endothelial cells. Though surgical excision currently plays a central role in the treatment of angiosarcoma, no significant study has analyzed NCDB for treatment trends in these patients. This study aims to characterize the effect of different treatment modalities on overall survival of angiosarcoma patients. Methods: The National Cancer Database (NCDB) was used to identify patients diagnosed with angiosarcoma from 2004 to 2020 using histology code 9120 as assigned by the Commission on Cancer Accreditation program. Kaplan-Meier, ANOVA, Chi-Square, Cox Proportional Hazards and Logistic Regression tests were performed, and data were analyzed using SPSS version 29. Statistical significance was set at α = 0.05. Results: 3560 patients with angiosarcoma of the soft tissue were queried. The most common primary site for a tumor was the head, neck, or face (920 patients, 31.3%). Of the initial sample, 1889 ( 53.1%) patients received surgery alone, 450 ( 12.6%) patients received adjuvant chemotherapy, 55 ( 1.54%) received adjuvant radiation, and 30 ( 0.84%) patients received adjuvant chemoradiation. Surgery alone conferred the greatest median survival; no surgery conferred the least ( 31.4 months vs. 7.2 months; p < 0.001). In the crude and adjusted logistic regression models, combined chemoradiation (OR = .210; 95% CI:.100-.400) and surgery alone were associated with the lowest odds of death (OR = .271; 95% CI: .224-.329) relative to no surgical procedure of the primary site. This finding persisted once the model was adjusted for age, stage, and tumor size. Surgery alone conferred the lowest hazard ratio (HR = .352; 95% CI: .323-.384) relative to no surgery. Conclusions: In angiosarcoma patients, surgical excision at the primary site alone was associated with the greatest median survival and the lowest hazard ratio. Additionally, angiosarcoma patients who did not receive surgery had the least median survival. Surgery with adjuvant chemoradiation and surgery alone had the lowest odds of death. These findings affirm that surgical excision at the site of the primary tumor plays a key role in increasing the survival of angiosarcoma patients. Further research is necessary in characterizing treatment trends in angiosarcoma patients to supplement current standardized treatment protocols and improve the mortality of this lethal cancer.
The efficacy of immune checkpoint inhibitors as a part of multimodality treatment in soft tissue and bone sarcoma in an academic community setting.
Authors: Zarifa Abdulrazzak , Britto Michele , Brockstein Bruce 
Published: June 2024

e23564 Background: Prior studies have shown response to immune checkpoint inhibitors (ICI) in a variety of sarcoma subtypes, however, much is still unknown about ICI use in specific sarcoma subtypes due to disease rarity. Patients (pts) are often treated with these agents as part of clinical trials, and real world data in the community setting is lacking. The aim of this study is to report real world efficacy and safety of ICI in sarcoma either alone or with radiation (RT) and/or surgery. Methods: A retrospective cohort review was conducted to identify pts with soft tissue and bone sarcoma who were administered ICI at Kellogg Cancer Center at NorthShore University HealthSystem/Endeavor Health. Pts who received ICI as part of a clinical trial were excluded. Results: A total of 29 pts receiving ICI were identified. Pts had a median of 1 prior systemic therapy. ICI included pembrolizumab (n = 23), nivolumab (n = 5), and ipilimumab/nivolumab (n = 1). Treatment was discontinued in 28 pts due to disease progression (n = 18), toxicities (n = 3), death (n = 2), and maximal response (n = 5). One patient is still undergoing treatment. Median progression-free survival (PFS) was 4.9 months. Median overall survival (OS) was 14 months. Overall response rate (ORR) is 31%. Median duration of response was not reached (44+ months). Complete response (CR) (n = 5) reported in 3 pts with undifferentiated pleomorphic sarcoma (UPS), 1 pt with SMARCA4 deficient undifferentiated sarcoma, and 1 pt with dedifferentiated chondrosarcoma. Partial response (PR) (n = 4) reported in 1 pt with UPS, 1 pt with dedifferentiated liposarcoma, 1 pt with high grade spindle sarcoma of bone, and 1 pt with malignant peripheral nerve sheath tumor. Of those pts with a CR, 2 patients received only pembrolizumab, 1 pt was administered concomitant RT, and 2 pts had administered concomitant surgery. Of the pts who had PR, 3 were also treated with concomitant RT. Grade 3 immune related adverse effects were reported in 5 of the 29 patients. Of these patients, 2 had documented CR and 3 documented PR. Conclusions: This study expands on the real world efficacy of ICI in a variety of sarcoma subtypes. CR and PR rates in this setting were high, and responses were durable, although selection bias for treatment may have played a role. This data supports the treatment of metastatic sarcoma with ICI, especially with concomitant RT and surgery, in a variety of subtypes.
Use of immunotherapy with check point inhibitors in soft tissue sarcoma: Analysis from single institution.
Authors: Pachika Pranali Santhoshini , Kalantri Shreyas , Kumar Rohit 
Published: June 2024

e23566 Background: Traditional treatments for soft tissue sarcomas include surgery, chemotherapy, and radiation. Effectiveness of Check point inhibitors for sarcoma has been unsatisfactory thus far. Major clinical trials PEMBROSARC and SARC028 revealed median PFS of 2 and 4.5 months, respectively. The FDA has approved three immunotherapy (IO) therapies for sarcoma. Atezolizumab was approved for alveolar soft part sarcoma. Dostarlimab is approved for sarcoma with DNA mismatch repair deficiency (dMMR), Sarcoma patients with high microsatellite instability (MSI-H), dMMR, or tumor mutational burden can receive pembrolizumab. A single-institution analysis of soft tissue sarcoma patients with IO is presented in this paper. Methods: All soft tissue sarcoma patients who have received IO from January 2021 to now have been included. At our institute, a total of seven patients received IO for soft tissue sarcoma. Observations were made regarding their fundamental characteristics and the progression free survival (PFS). The data was not statistically examined due to the small sample size and the heterogeneity of the data. Results: 2 of 7 trial patients were lost to follow-up. Recurrent autoimmune hepatitis terminated IO for another patient. Most of the patients are elderly with the median age of 78. Given their comorbidities and age, IO was chosen as the first line for 5 patients. Median PFS was 5.8 months. High PDL1 ( > / = 5%) patients had a median PFS of 5.6 months, while low PDL1 patients had 4.5 months. However, one patient with low PDL1 had PFS of 7 months. 5/7 patients didn’t have IO related side effects. Two patients developed Autoimmune (AI) hepatitis. Conclusions: The limited sample size prevented definitive conclusions from being drawn. Despite the unsatisfactory outcomes, it is worth mentioning that IO provided a certain degree of PFS in older patients with comorbidities who are not suitable candidates for chemotherapy. Based on limited data, patients with high PDL1 status appear to benefit more. IO alone has not shown promising results. In clinical trials, IO is being tested with chemotherapy and Tyrosine kinase inhibitors. The findings from these trials will provide valuable insights into the potential benefits of combination therapy. [Table: see text]
Preoperative and postoperative platelet-lymphocyte ratio as a prognostic marker for patients with soft tissue sarcoma treated with curative resection.
Authors: Lee Inhee , Na Jihyun , Lee Soo Jung 
Published: June 2024

e23568 Background: In cancer development and progression, systemic inflammation has been implicated. Inflammatory markers have been identified as prognostic indicators in numerous malignancies. In this study, we explored the prognostic relevance of initial and postoperative systemic inflammatory markers (neutrophil -lymphocyte ratio, platelet -lymphocyte ratio) on relapse-free survival (RFS) and overall survival (OS) in patients with soft -tissue sarcoma (STS) who underwent curative resection. Methods: We included a total of 89 patients with STS who underwent extensive and radical resection at the Kyungpook National University Chilgok Hospital (Daegu, Korea,) between 2004 and 2018. Kaplan-Meier curves and RFS and OS were calculated using multivariate Cox proportional models. Results: The median age of the patients was 55 years (range 27 - 86) and the ratio of male-to-female ratio was approximately 1:1. A total of 67 (75.3%) patients demonstrated a high initial neutrophil-lymphocyte ratio(NLR) (≥4.1) and 65 (75.3%) showed a high initial platelet-lymphocyte ratio(PLR) (≥231). After curative resection, the number of patients with high NLR and PLR was 16(18.0%) and 17 (29.3%). In both the NLR and PLR groups, including the postoperative NLR and postoperative PLR subgroups, no significant differences were observed in terms of age, sex, histologic type, tumor site, tumor size, tumor depth, or American Joint Committee on Cancer staging when stratified into high and low subgroups. In the univariate and multivariate analyses, an elevated initial PLR ratio was significantly associated with a decreased RFS (hazard ratio[HR]: 2.120; 95% confidence interval[CI]: 1.021 - 4.883, p = 0.017) and OS (HR: 5.073; 95% CI: 1.731 - 14.87, p = 0.003). Patients with a high PLR (PLR > 231) had a median RFS of 24 months, whereas those with a low PLR (PLR ≤231) had a median RFS of 96 months. The median OS was 50 and 298 months for the high PLR and low PLR groups, respectively. Furthermore, a high postoperative PLR ratio was significantly associated with a decreased RFS (HR: 3.921; 95% CI: 1.738 - 8.845, p = 0.001) and OS (HR: 5.702; 95% CI: 1.099 -29.576, p = 0.038). Conclusions: The present results suggest that the preoperative and postoperative PLR ratio can be used as a cost- effective prognostic marker for oncologic outcomes in patients with STS who underwent surgery.
Detection and surveillance of circulating tumor cells in sarcoma for predicting therapy response and prognosis.
Authors: Zhang Qing , Wang Zhe , Yang Yongkun , Deng Zhiping , Yu Feng , You Xia , He Peng 
Published: June 2024

e23573 Background: Generally sarcomas are categorized as soft tissue and bone sarcomas and represent heterogenous group of malignancies with more than 70 distinct histologic subtypes. Due to their rarity and heterogeneity, sarcomas present particular challenges for accurate diagnosis, prognosis, and treatment. The presence and persistence of circulating tumor cells (CTCs) in the peripheral blood are believed to be associated with poor prognosis and distant metastases. A blood-based CTCs test is thus greatly needed for monitoring disease progression and predicting clinical outcomes. Methods: In this study, we developed a CTCs test for the detection and surveillance of sarcoma patients’ CTCs, and subsequently explored its clinical value. 123 patients with sarcomas were enrolled as the cohort for serial CTCs tests. Dynamic CTCs counting, in combination with therapy evaluation and post-treatment follow-up, was used to explore predicting pre- and post-chemotherapy evaluation and prognosis. Results: Quantification of CTCs demonstrated a significant increase in sarcoma patients compared to healthy individuals. Furthermore, patients in stage III-IV had a higher CTC count than those in stage I-II (p<0.01), suggesting a correlation between CTCs and disease development. Remarkably, there was variation in the quantity of CTCs among different types of sarcomas. The highest number of CTCs was observed in undifferentiated small round cell sarcoma, followed by soft tissue tumor, while bone tumors had the lowest number. In addition, the number of CTCs in patients with positive PD-L1 expression was considerably greater than in those with negative expression (p<0.01). The count of CTCs shown a substantial decrease following neoadjuvant chemotherapy treatment. There was a decline in the number of CTCs both before and after postoperative adjuvant chemotherapy treatment, however, there was no significant statistical discrepancy. The number of CTCs at the baseline was shown to be considerably larger in the group of patients with progressive disease or stable disease (PD+SD) compared to the group with partial response or complete response (PR+CR) (p<0.05). This difference was particularly pronounced for interstitial-type CTCs (p<0.01). Conclusions: The rate of presence of CTCs in the peripheral blood of sarcoma patients is high, and patients with an increased percentage of CTCs after treatment have a poor treatment effect. The dynamic monitoring of changes in CTCs counts after treatment has clinical significance for the timely detection of recurrence or metastasis. CTCs also showed a clinical value in prediction of therapy efficiency or prognosis, and may be clinically valuable for the whole course management of patients.
A multicohort platform trial to improve drug access for pediatric cancer patients in Japan: The PARTNER trial (NCCH2220).
Authors: Miyazaki Bunpei , Shirakawa Nami , Sugiyama Minako , Arakawa Ayumu , Ando Yayoi , Anjo Kenta , Kai Yoko , Hoshina Yukari , Mizusawa Junki , Shibata Taro , Fukuda Haruhiko , Okita Natsuko Tsuda , Nakamura Kenichi , Ogawa Chitose 
Published: June 2024

TPS10079 Background: In Japan, there are no pediatric regulations that encourage drug development for pediatric cancer, such as Pediatric Investigation Plans (PIPs) which are mandated in Europe, or the RACE Act in the U.S. Therefore, there are fewer early-phase clinical trials and approved drugs for pediatric cancer than in Western countries. In addition, because there is no rapid compassionate use program, there are delays when using an unapproved drug. According to a report from the Japanese cancer genome profiling (CGP) testing data center, C-CAT, 51.3% of pediatric patients with solid tumors had targetable genetic abnormalities. However, only 5.8% of them had access to the recommended molecular targeted therapy (Tanimura K. et al., presented at the Japanese Society of Pediatric Hematology and Oncology annual meeting 2022). Thus, Japanese pediatric patients with relapsed or refractory solid tumors have limited access to novel drugs, even if they have druggable mutations. Therefore, we designed a platform study (NCCH2220, PARTNER trial) to rapidly deliver molecularly targeted drugs based on CGP testing. Methods: This study has two objectives: first, to administer some drugs to pediatric patients that are not approved for pediatric cancer in Japan. These drugs have been shown to be safe in pediatric patients in foreign countries and are expected to be effective. Second, to evaluate the safety and efficacy of the drug in Japanese pediatric patients and, if necessary, its pharmacokinetics. These data will be used for potential future regulatory filings. This is an open-label, multicenter, multicohort study. Eligible patients are aged 0–29 years with diseases having no standard therapy, which are refractory, or when there is intolerance to standard therapy. The study drug must be recommended for the patient by CGP testing or approved for pediatric use for their disease in the U.S. or Europe, or approved in Japan for use in adults only. The drugs are used as monotherapy in the study. The study schedules follow a master protocol. Up to 30 patients can be enrolled in each cohort. The primary endpoint is the incidence of dose-limiting toxicity in each cohort. The secondary endpoints are the incidence of adverse events, the overall response rate, and, if necessary, the pharmacokinetics in each cohort. As of January 2024, the study had five treatment cohorts with the following agents: imatinib, pazopanib, ruxolitinib, trametinib, and atezolizumab. Additional cohorts will be added. We started planning the study in November 2022, and enrollment began on January 18, 2024. This platform trial has enabled us to deliver drugs to patients more quickly and efficiently than by conducting individual early-phase trials for each drug. Clinical trial information: jRCTs031230544 .
Blood-based colorectal cancer (CRC) screening implementation into clinical practice in the outpatient clinical setting in the Appalachian highlands.
Authors: Talari Mridula Preetham , Haynes William , Elmore Karen , Jastan Rasmiyah , Mays Charles E , Chirculescu Camelia , Adada Haytham 
Published: June 2024

TPS10622 Background: Maximizing colorectal cancer (CRC) screening participation relies on tests that are acceptable, accessible, and patient-centered. While colonoscopy or stool-based tests have traditionally been the standard of care (SOC), they often present challenges related to timely completion and patient adherence. Blood-based tests (BBTs) detecting circulating tumor DNA (ctDNA) offer a quicker, less invasive alternative to previous methods of screening. While the BBTs exhibit comparable sensitivity and specificity to the existing noninvasive SOC, their user-friendly nature holds the potential to enhance adherence. This study aims to explore the implementation of a BBT and its impact on patient acceptability and adherence to CRC screening. The study focuses on the Appalachian population, known for higher CRC incidence1 and mortality rates2 compared to the general US population. Methods: The trial is being conducted at two primary care clinics. It consists of two phases over a 6-month period, aiming to enroll over 300 patients. Participants aged 45-84 years, identified as average risk for CRC according to USPSTF guidelines, and who have opted to be screened for CRC and are willing to participate in the study will be eligible. Exclusion criteria consist of higher-than-average risk for CRC according to the USPSTF standards. During Phase 1 (control period), patients meeting inclusion criteria will be offered SOC (colonoscopy and/or stool-based test) for 3 months followed by Phase 2 (intervention period) where a BBT in addition to SOC will be offered for another 3 months. Informed consent will be obtained prior to any study procedures. The BBT used for the study has a sensitivity of 83% and specificity of 90%. Patients who agree to BBT will undergo a single blood draw of 40 mL. Phase 1 has concluded with enrollment of 75 patients, while Phase 2 is currently ongoing and actively recruiting participants. Upon completion of study, an EMR review will be conducted on participants to evaluate screening rates before and after implementing the BBT and to assess adherence. The primary endpoint of the study involves calculating the total number of consented patients who opted for and completed either BBT or SOC during the interventional period compared to the total number of patients who opted for SOC during the control period. Final data analysis is expected by July 2024. References: 1. Wilson RJ, Ryerson AB, Singh SD, King JB. Cancer Epidemiol Biomarkers Prev. 2016;25(2):250-258. doi:10.1158/1055-9965.EPI-15-0946; 2. Siegel RL, Miller KD, Jemal A. CA Cancer J Clin. 2017;67(1):7-30. doi:10.3322/caac.21387. Clinical trial information: NCT06119425 .
CNS Protective Effect of Selpercatinib in First-Line RET Fusion-Positive Advanced Non–Small Cell Lung Cancer
Authors: Pérol Maurice , Solomon Benjamin J. , Goto Koichi , Park Keunchil , Nadal Ernest , Bria Emilio , Martin Claudio , Bar Jair , Williams Justin N. , Puri Tarun , Li Jian , Uh Minji K. , Lin Boris K. , Zhou Caicun 
Published: June 2024

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. Although the CNS activity of selpercatinib in patients with RET fusion-positive non–small cell lung cancer (NSCLC) has been previously described, the ability of potent RET inhibition to prevent new CNS metastases from developing has been challenging to measure without randomized data. Serial CNS scans were studied from LIBRETTO-431, a randomized phase III trial of selpercatinib versus platinum/pemetrexed ± pembrolizumab whose primary results have been previously disclosed. Intracranial outcomes were assessed by neuroradiologic blinded independent central review in patients with baseline and ≥1 postbaseline CNS scans. Of the 192 patients within the intention-to-treat pembrolizumab population with baseline CNS scans, 150 patients were without baseline CNS metastases. The cumulative incidence of CNS progression in these patients was reduced with selpercatinib versus chemotherapy + pembrolizumab (cause-specific hazard ratio [HR], 0.17 [95% CI, 0.04 to 0.69]). The HR for intracranial progression-free survival (PFS) was 0.46 (95% CI, 0.18 to 1.18). Among the 42 patients with baseline CNS metastases, similar trends were observed in the cumulative incidence of CNS progression (cause-specific HR, 0.61 [95% CI, 0.19 to 1.92]) and intracranial PFS (HR, 0.74 [95% CI, 0.28 to 1.97]). These data demonstrate that selpercatinib effectively treats existing CNS disease and prevents or delays the formation of new CNS metastases. These results reinforce the importance of identifying RET fusions in first-line patients with NSCLC and treating with selpercatinib.
Prolonged Adrenal Insufficiency After Osilodrostat Exposure With Eventual Recovery of Adrenal Function
Authors: Tejani Sanaa , Abramowitz Jessica , Tritos Nicholas A , Hamidi Oksana , Mirfakhraee Sasan 
Published: June 2024

Abstract
Osilodrostat is an 11β-hydroxylase inhibitor used in the treatment of adult patients with Cushing disease. Prolonged adrenal insufficiency (AI) after osilodrostat use is a rare but significant adverse effect. We present the case of a 41-year-old woman treated with osilodrostat for persistent hypercortisolism following pituitary surgery and Gamma Knife radiosurgery. After 11 months of osilodrostat therapy, she reported AI symptoms, and biochemical testing revealed low serum cortisol following cosyntropin stimulation as well as high plasma adrenocorticotropic hormone (ACTH). The patient was started on physiologic replacement dose of hydrocortisone, which was discontinued 23 months after last osilodrostat exposure when laboratory testing revealed recovery of endogenous cortisol production. The mechanism responsible for the prolonged AI noted with osilodrostat use is unclear and unexpected, given the short half-life of the drug. Although prolonged AI after osilodrostat use is not well understood, providers should be aware of this potential adverse effect and have a low threshold to test for AI in patients reporting AI-related symptoms.