bluuebunny/crossref_metadata_2025_split huggingface dataset:
Are people in the US getting cancer at a younger age?
Authors: Levent Ayse , Adabra Serafina 
Published: June 2024

e23321 Background: Advanced age is a well-known risk factor for the development of cancer. One-third of all cancer diagnoses occur in patients aged 75 or older1. In general, cancer incidence rates are very low in younger populations, with only 25 cases per 100,000 in those aged 20 years or younger and about 350 cases per 100,000 in those between the ages of 45 and 492. However, in recent years, studies have started to show an uncharacteristic rise in cancer diagnoses amongst young people in the United States. Methods: The Ipsos Oncology monitor is an online, multi-center medical chart review of oncology patients receiving drug therapy. Over 2,200 cancer treating physicians in the United States were screened for seniority and caseload and submitted data on 385,912 cancer patients (aggregate; all tumour types) between January 2018 to December 2023. Data captured included tumor type, patient age, whether the patient was newly diagnosed, follow-up or relapsed patient status and the treatment they received. Results: Reported patient age across all cancer types remained stable over time, recording an average age of 64.19 years in 2023. However, shifts in prevalence amongst younger age groups were recorded in select tumor indications. Within reported newly diagnosed breast cancer patients, the proportion of those aged 55 years or younger shifted significantly from 23% in December 2018, to 27% in December 2023. Over this same period, a similar trend was recorded in reported newly diagnosed colorectal cancer patients, with the proportion of those 55 years or younger rising from 17% to 22%. In contrast, sampled newly diagnosed melanoma and prostate patients reported decreased diagnoses in the 55 or younger age group. Conclusions: This demonstrates that the oncology patient cohort in this study remains mostly stable in age overall. However, the declining age of diagnosis in both reported breast and colorectal cancer may merit concern. These results outline the importance of robust screening efforts and suggest performance of routine screening at an earlier age may be beneficial. In addition, expansion of clinical trials and other oncology research to younger patient populations may be needed. Further investigation using comparator cohort is warranted. Age and cancer (2023) Cancer Research UK. Available at: https://www.cancerresearchuk.org/about-cancer/causes-of-cancer/age-and-cancer (Accessed: 31 January 2024). Risk factors: Age (no date) National Cancer Institute. Available at: https://www.cancer.gov/about-cancer/causes-prevention/risk/age (Accessed: 31 January 2024). Ugai, T. et al. (2022) ‘Is early-onset cancer an emerging global epidemic? current evidence and future implications’, Nature Reviews Clinical Oncology, 19(10), pp. 656–673. doi:10.1038/s41571-022-00672-8.
Eribulin and irinotecan for refractory or recurrent Ewing sarcoma: A retrospective study.
Authors: Xu Jie , Xie Lu , Sun Xin , Liu Kuisheng , Liang Xin , Tang Xiaodong 
Published: June 2024

e23502 Background: The effectiveness of eribulin and irinotecan in treatment of xenograft models of Ewing sarcoma is well-established but little clinical data has been reported. Encouraging results from preclinical models and a shortage of temozolomide in our hospital have prompted the administration of the eribulin as substitute for temozolomide and vincristine in combination of irinotecan at our institution from 2022 to 2023 in an off-label way. Methods: We retrospectively reviewed the medical records of patients treated for refractory or recurrent Ewing sarcoma with 1.4mg/m2 D1,8 eribulin and 20mg/m2/d D1-5,8-12 irinotecan at 21 day intervals (ERII) at Peking University People’s Hospital. Results: Finally, a total of 17 patients with median age 18.6 years were treated with a total of 77 courses of ERII between February 2022 and February 2023. The objective response rate was 35.3%, the disease control rate 58.9% and the median event-free survival (EFS) 2.07 months. 35.3% patients had 6 months EFS and overall survival was 66.9%. Grade 3 or 4 toxicities were observed in 37.6% courses and in 64.7% of the patients, with myelosuppression, especially neutropenia, being the most common and diarrhea / abdominal pain the second most common. In the dx5x2 VIT protocol the later portion was given two days after the end of early portion. However, in this substitute regimen of eribulin, the median time interval between the end of the early portion to the start of later portion was 5 days. The dose intensity of the regimen was reduced by 21% per cycle. The later portion was delayed mostly because of unrecovered myelosuppression. Conclusions: The efficacy and safety of eribulin and irinotecan as a second-line regimen was inferior to historical reports of temozolomide and irinotecan in the same institute. There was no need for further prospective trials on this combination unless mechanisms of synergy and biomarkers are identified. [Table: see text]
High-grade surface osteosarcoma: A National Cancer Database study of demographic characteristics.
Authors: Dudic Ahmed , Tade Yanick , Sachs Anton , Rafie Susan , Silberstein Peter T. , Heise Craig , Hsia Beau 
Published: June 2024

e23508 Background: High-grade surface osteosarcoma (HGSO) is an extremely rare malignant subtype of osteosarcoma. HGSO often affects long bones, particularly the femur, and is the rarest subtype of surface osteosarcomas. Though data is limited, current information suggests this cancer presents with a poor prognosis, generally affecting adults aged 20 to 40. Current treatment standards involve wide resection and chemotherapy. The National Cancer Database (NCDB) was examined to establish the demographic factors among HGSO patients and identify diagnostic and treatment trends. Methods: A retrospective cohort study from 2005-2020 was conducted using the NCDB. A total of 99 patients were found with a histologically confirmed diagnosis of high-grade surface osteosarcoma (ICD-9194-3). Factors such as gender, age, race, insurance status, rural/urban residence, treatments, mortality rates, and Charles/Deyo scores were analyzed using descriptive statistics, and trends in incidence were interpreted via regression analysis. Results: Yearly HGSO incidence rates increased from 2005 to 2020 (R2 = 0.19). The average age of diagnosis was 41 years (SD = 24.9, range = 10-90) with men diagnosed (54%) slightly more than women. The majority of patients were non-Hispanic white (73%), had private insurance (55%), and lived in a metropolitan area with over 250,000 in population (89%). The average patient was diagnosed at a hospital 40.4 miles away from their home (SD = 84.9, range 0.4-648.4 miles). Most patients (55%) were in stage II at diagnosis, and 86% of patients had a Charlson-Deyo comorbidity score of 0. The most common primary site of this malignancy was the long bones of the lower limb and associated joints (67%), while the upper extremities (8%) and pelvic bone (8%) served as less common primary sites. Surgery was the most common primary treatment (62%). Data from 69 patients revealed the 90-day mortality post-surgery was 3%. The mean survival rate was 70% at two years and 52% at five years. Conclusions: To the best of our knowledge, this study represents the first NCDB analysis of HGSO. Our analysis demonstrated that HGSO occurs most often, but not exclusively, within the lower extremity long bones, which may be an important diagnostic distinction. It was previously indicated that the average age at HGSO diagnosis is 20-40 years, but our analysis suggested it is closer to 40. Our analysis revealed a five-year survival rate of 52% which is worse than prior studies have indicated. Demographic data has revealed the majority of patients were non-Hispanic white, privately insured, and living within a metropolitan area. This trend may suggest access to healthcare resources is influencing this cancer’s diagnosis and treatment. Further research is warranted to explore whether the demographic patterns seen in HGSO are indicative of biological causes or socioeconomic factors that are significantly influencing diagnosis.
Molecular characteristics of dedifferentiated liposarcoma with broad rhabdomyosarcomatous differentiation.
Authors: Hu Wanming , Wang Zhouyu , Ge Minghui , Luo Ningning , Chen Dong-sheng , Zhang Xin-ke 
Published: June 2024

e23530 Background: Dedifferentiated liposarcoma (DDLPS) with broad rhabdomyosarcomatous differentiation has a worse prognosis compared with other types of DDLPS. Therefore, it is of importance to recognize its molecular characteristics in order to investigate individualized treatment strategies. Methods: We conduct next-generation sequencing (NGS) including DNA and RNA sequencing analysis in 5 DDLPS patients with broad rhabdomyosarcomatous differentiation and perform comparative analysis between well-differentiated and dedifferentiated components from the patients. Results: In the ten samples, several somatic copy-number variations (CNVs) including the gain of 12q are considered as frequent molecular alterations. IGFN1, FGFR4, BLM, RICTOR, RUNX1 and TOP1 mutation is the high-frequency single-nucleotide variations (SNVs). Novel BEST3/CD63/LGR5/CENPL-MDM2 and ERBB3-TAFA2 fusion genes are identified in this subtype of tumor. The comparative analysis between well-differentiated and dedifferentiated components recognized two categories of molecular variations: shared variations, such as FGFR4 and BLM mutation, ERBB3-TAFA2 fusion, and MYC amplification that are associated with tumorigenesis, and dedifferentiated-specific variations including GRIN2A, FOXP1 and TP53 mutation, CERS4-PTPRB and TRIO-TERT fusion, and ESR1 amplification, which are related with malignant progression. After surgery, the patient received adjuvant therapy. The mean follow-up of the patients was 30 months, and the mean recurrence-free survival (RFS) was 9.6 months. Conclusions: This NGS analysis disclosed the possible progression mechanisms and therapeutic targets in DDLPS with broad rhabdomyosarcomatous differentiation and provided insights contributing to the refinement of management in this tumor. [Table: see text]
The role of next-generation sequencing in achieving diagnostic precision for dermatofibrosarcoma protuberans and its fibrosarcomatous variant.
Authors: Smith Steven Christopher , Sweeney Kieran , Evans Mark Gordon , Angara Kartik , Reynolds Celia , Hubbard Gretchen , Park Soo J. , Elliott Andrew , Oberley Matthew James , D'Amato Gina Z. , Boikos Sosipatros A. , Bahrami Armita 
Published: June 2024

e23531 Background: Dermatofibrosarcoma protuberans (DFSP) is a locally aggressive skin and subcutaneous fibroblastic neoplasm, characterized by COL1A1:: PDGFB fusions and, less frequently, PDGFD fusions. Approximately 10-15% of DFSP cases progress to distant metastases, yet the genetic mechanisms behind this transformation to fibrosarcomatous DFSP (FS-DFSP) or metastatic development remain unclear. Reports of DFSP in deeper tissues suggest a broader occurrence than previously recognized. We hypothesize that conventional histopathology may not adequately identify certain DFSP variants, especially those in deep tissues, potentially missing critical opportunities for targeted therapy with FDA-approved tyrosine kinase inhibitors. Methods: We searched Caris’s database to identify solid tumors with PDGFB or PDGFD fusions, markers of DFSP or FS-DFSP. We reviewed histologic features and clinical information, along with exome sequencing and copy number amplifications. Significance was tested using Mann Whitney U and Fisher’s exact tests as appropriate. Results: We identified 59 cases with PDGFB or PDGFD fusions: 55 COL1A1:: PDGFB, 3 EMILIN2:: PDGFD, and 1 COL1A2:: PDGFB cases. Of these, 51 were primary specimens and 8 metastatic. The patients included 31 males and 28 females, with a median age of 49 years (range: 14-93). Primary tumors occurred mainly in the skin/subcutis or deep soft tissues (35 trunk, 9 head and neck, 7 lower extremity, 2 upper extremity), but 6 were found in visceral organs (4 uterus, 1 cervix, 1 lung). Histologically, 20 cases were conventional DFSP and 32 were FS-DFSP. Notably, 21 tumors (36%) had been initially misclassified; most of which had metastatic presentation, unusual histology, or atypical location. Tumor sequencing revealed a higher incidence of genetic changes in addition to the PDGFB/ PDGFD fusions: concurrent mutations were detected in 66% of FS-DFSP cases versus 25% of DFSP cases (p = 0.009). Moreover, tumor mutational burden was significantly higher in FS-DFSP than DFSP (p = 0.006). The most prevalent mutations were in the TERT promoter and NF1, found exclusively in FS-DFSP cases. Conclusions: Conventional histology commonly fails to recognize FS-DFSP, leading to missed opportunities for targeted therapy. This highlights the essential role of next-generation sequencing in achieving greater diagnostic accuracy for DFSP and its fibrosarcomatous variant. While no single gene mutation consistently differentiates DFSP from FS-DFSP, the occurrence of additional genetic alterations is notably more common in FS-DFSP cases.
Comparative analysis of targetable mutations and genomic-directed therapy by tumor genomic profile in soft tissue sarcoma: A single-center retrospective study.
Authors: Zamora DIana , Braat Jonathan , Ikram Waleed , Dinh Han , Azevedo Chelsea , Patel Shyamal , Wiseman Jason T. , Gonzalez Velez Miguel 
Published: June 2024

e23534 Background: The use of tumor genomic profile (TGP) has led to improved genomic-directed therapies in many solid cancers. Due to its heterogeneity, soft tissues sarcomas (STS) have not benefited much from these genomic advances. Emerging research indicates that about 30% STS have actionable alterations which can lead to potential treatment options (Gounder et al. Nature 2022). Our study aimed to compare the differences in genomic-directed therapy between Non-Hispanic White (NHW) and Hispanic (H) patients with STS at Dignity Health Cancer Institute. Methods: We performed a retrospective analysis of medical records using the electronic medical record. Our study specifically examined patients diagnosed with STS, with a sample size of 14 NHW and 19 H individuals.The eligibility criteria consisted of known diagnosis of STS with completed TGP. We conducted a descriptive analysis using GraphPad Prism Software, where mutations were evaluated as continuous variables. The statistical significance of differences between groups was assessed using an unpaired t-test, with a significance level of < 0.05. Results: We found 73 tumor alterations, with 11 potentially targetable (15.2%). Most patients had negative to low tumor mutational burden (0-2 mut/Mb) with only 2 patients with high TMB ( > 10 mut/Mb). The most common mutations were TP53 and CDK4 with 9 patients (12%) each. The NHW group had an average of 2.57 mutations (standard deviation = 2.87), whereas the H group had an average of 1.42 mutations (standard deviation = 1.35). The median values were 2 and 1, respectively, with no statistically significant difference (p = 0.21). The average for mutations of unknown significance was 1.54 in NHW individuals, while it was 1.00 in Hispanics. In the NHW group showed 11 males and 3 females, while the H group included 14 males and 5 females. There was no significant difference in gender representation between the two groups (p = 1). 3 patients (9%) received non-FDA approved treatments based on TGP (1 CDKN2A-abemaciclib, 1 CDK4-ribociclib and 1 IDH1-ivosidenib) and 2 patients (6.6%) were enrolled in clinical trials. Conclusions: Our investigation reveals that there is no statistically significant disparity in the frequency of mutations between NHW and H groups in our sample. Nevertheless, there was an evident inclination towards an increased frequency of mutations in NHW. Similarly, the occurrence of mutations with uncertain significance was slightly higher in NHWs, although the difference was not statistically significant. Only a minority of patients had targetable mutations or were enrolled in clinical trials. However, the routine use of genomic profiles may lead to more personalized treatments. Our research emphasizes the need to expand the use of comprehensive genomic profiles to increase directed treatments for patients with STS.
Spindle cell rhabdomyosarcoma: A study of demographics and socioeconomic factors using NCDB.
Authors: Gill Sukhmani Kaur , Khatib Rawaan , Tandon Nikhita , Sadighian Sadaf , Silberstein Peter T. , Heise Craig , Hsia Beau 
Published: June 2024

e23539 Background: Spindle cell rhabdomyosarcoma (SC-RMS) is a rare malignancy characterized by elongated spindle cells displaying eosinophilic and fibrillar cytoplasm, resembling smooth muscle fibers. SC-RMS is primarily diagnosed in children with particular involvement of the nasopharynx, parotid gland, nasal cavity, and paratesticular regions. Though surgical resection and chemotherapy are the current recommendations, definitive treatment guidelines remain unestablished. Because SC-RMS is a novel cancer type, evaluating the diagnostic trend of the disease has the potential to provide valuable insights into its epidemiology. An analysis of the National Cancer Database (NCDB) was conducted to identify the demographic factors associated with patients who have been diagnosed with SC-RMS. Methods: A retrospective cohort analysis of the 2004–2020 NCDB, using ICD-O-3 code 8912/3, included patients with a histologically-confirmed diagnosis of SC-RMS (N = 132). Demographic factors (age, sex, race, Hispanic status, educational attainment, insurance status, facility type, distance from facility, and Charles/Deyo score) were analyzed by descriptive statistics and incidence trends were interpreted in regression analysis. Results: A total of 132 patients with a confirmed diagnosis of SC-RMS were identified, with a declining incidence of diagnoses per year (R² = 0.4507). The average age of diagnosis was 33.9 years (SD = 27.2, Range = 1-90). SC-RMS was more commonly observed among males (63%), with a majority of patients being non-Hispanic (87%) and White (74.2%). The top primary site was the testis (20%). Most patients (83%) had a Charlson/Deyo comorbidity score of 0. The majority (69%) of patients received surgery as their primary treatment. Most patients were privately insured (49%) and resided in metropolitan areas with a population greater than 1 million (48%). More (29%) patients were in the highest quartile of income earners of $74,063 or greater. Patients were treated most often at an academic/research program (19%) or comprehensive community care program (12%). Patients lived an average of 68.2 miles (SD = 267.9, Range = 0.6 - 2403.1) from the treatment facility. Conclusions: To the best of our knowledge, this is the first NCDB analysis on SC-RMS. Our analysis revealed that the majority of SC-RMS patients were young males with primary involvement of the testis, supporting previous studies. Analysis of the socioeconomic factors of SC-RMS patients revealed that more patients were privately insured, resided in densely populated metropolitan areas, and were part of the top quartile of income earners. Further research is supported to better understand the impact of socioeconomic factors on diagnosis, treatment options, and overall mortality rates associated with SC-RMS.
Clinicopathological analysis and management of primary cardiac sarcomas: A retrospective study from two cancer centers in China.
Authors: Ji Qing , Tan Zhichao , Cao Jun , Fang Meiyu , Liu Jiayong 
Published: June 2024

e23544 Background: Primary cardiac sarcomas (PCS) are rare malignant tumors associated with a poor prognosis. The clinical and pathological features of PCS remain elusive. Methods: We retrospectively collected records of patients with PCS at Peking University Cancer Hospital and Zhejiang Cancer Hospital from 2016 to 2023. Clinicopathological data, treatments, and outcomes were included and analyzed. Results: Between January 2016 and October 2023, a total of 26 patients with primary cardiac sarcoma were included, with the majority of patients being female (57.7%). The median age of the patients was 38.5 years (range: 15-82). Tumors were most frequently located in the right (42.3%) and left (26.9%) atria. The predominant histological subtype was angiosarcoma (46.1%), followed by myxoid fibrosarcoma (15.4%) and intimal sarcoma (11.5%). At baseline, the LDH level was elevated in 42.3% of patients. Metastases were observed in 21 (80.8%) patients, predominantly in lung (61.9%), bone (42.9%) and liver (28.6%). Nineteen patients (73.1%) underwent surgery for the primary tumor, with 8 (42.1%) achieving a complete (R0) resection and 11 (57.9%) achieving a microscopically (R1) or macroscopically (R2) incomplete resection. Sixteen patients (61.5%) received anthracycline-based chemotherapy as their first-line palliative treatment. The median overall survival (OS) for all patients was 19.2 months (95% CI: 16.7-31.2). Patients with normal baseline LDH levels had a significantly longer median OS (25.4 months) compared to patients with elevated LDH levels (11.6 months, P= 0.001). The median OS was 25.4 months for patients who underwent R0 resection, compared to 18.7 months for those who underwent R1/R2 resection, and 6.03 months for those who did not undergo surgery. Patients who received anthracycline-based chemotherapy had a moderately better survival than those who received paclitaxel-based chemotherapy (mOS 19.2 vs.14.8 months, P= 0.13). Conclusions: In patients with PCS, angiosarcoma is the predominant histological subtype, and the most common sites of metastasis are the lung, bone, and liver. Elevated LDH is associated with a poorer prognosis. Complete surgical resection of the cardiac sarcoma after diagnosis may benefit long-term survival. [Table: see text]