bluuebunny/crossref_metadata_2025 huggingface dataset:
CancerX Data Sprint: Advancing national oncology data standards through a unique public-private partnership.
Authors: Patel Smit , Goldsack Jennifer C. , Mirsky Douglas E. , Konya Stephen , Wood William Allen
Published: June 2024

e23283

Background: In a concerted effort to enhance the quality, accessibility, and effectiveness of comprehensive real-world cancer datasets, CancerX, a public-private partnership announced by the White House recently conducted a demonstration project, the CancerX Data Sprint. CancerX Data Sprint attempted a novel approach to quickly inform collective efforts of the Center for Medicare and Medicaid Innovation (CMMI), the National Cancer Institute (NCI), the US Food and Drug Administration (FDA), and the Office of the National Coordinator for Health Information Technology (ONC) to advance cancer-related data standards. Specifically, at the intersection of CMMI’s Enhancing Oncology Model (EOM) and the development of ONC’s United States Core Data for Interoperability (USCDI+) – Oncology extension, CancerX leveraged its unique model and broad membership to report novel insights to advance data-driven innovations in oncology research, care, and policy. Methods: From Sept to Dec 2023, the Data Sprint convened 150+ member organizations from industry and government partners to 1) Identify the high-value research questions that could be asked about the standardized real-world data (RWD) generated through EOM 2) Supplement the existing data elements with new ones to extend and enhance the ability to conduct scientific, clinical, and research inquiries with comprehensive datasets. The CancerX community opined via surveys, written feedback, and live workshops to identify key data elements, discuss their clinical value and technical feasibility, and consider their use in real-world settings as part of the comprehensive datasets. Results: Building on the current EOM clinical data elements, we identified and reported 15 new clinical data elements for considerations with high clinical utility and ease of technical abstraction. This comprehensive RWD encompasses a diverse range of patient demographics, clinical details, treatment histories, and outcomes, creating a more accurate and inclusive portrayal of cancer treatment effectiveness and patient journeys. This depth of information is crucial for optimizing the personalization of treatment pathways, conducting impact assessments, and addressing healthcare disparities. Essentially, the new datasets serve as a valuable repository of insights, driving advancements in cancer research, treatment and elevating care quality. Conclusions: CancerX remains committed to supporting federal data initiatives like USCDI+ Cancer standards development and others by providing recommendations for essential data elements implementation to enhance clinical utility, technical feasibility, and exchange of standardized cancer data. By adopting a unique approach and assembling an interdisciplinary group, we can ensure that data standardization efforts prioritize high-utility data elements, ultimately maximizing benefits for our patients.
Disparities in incidence and mortality of hematologic cancers in Southeast Asia: A 2020 analysis.
Authors: Feliciano Erin Jay Garbes , Jain Urvish , Dee Edward Christopher Christopher , Jain Bhav , Patel Tej A. , Selokar Aryan , Eala Michelle Ann , Ting Frederic Ivan Leong , Gin Gin Gan , Bhoo Pathy Nirmala
Published: June 2024

e23291

Background: Hematologic cancers (HCs) in Southeast Asia (SEA), a diverse population of over 680 million, are still understudied. Data from the 2020 Global Cancer Observatory (GCO) was used to estimate the incidence and mortality of HCs in the region to provide direction for effective disease control and improve population outcomes. Methods: The International Agency for Research on Cancer’s publicly available GCO data aggregates global cancer incidence and mortality. We report cumulative incidence rate (CIR) and cumulative mortality rate (CMR) defined per 100,000 people, and weighted average age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) in 2020. Data for Hodgkin Lymphoma (HL), Non-Hodgkin's Lymphoma (NHL), Leukemia, and Multiple Myeloma (MM) in the world, in SEA, and in the 11 individual SEA countries are presented. Results: The table presents CIR, ASIR, CMR, and ASMR of hematologic cancers in SEA compared to overall global data. CIR, ASIR, CMR, and ASMR were higher for males than females in SEA. For NHL, CIR was highest in Singapore (18.8), Thailand (10.2), and Brunei (9.6) and lowest in Myanmar & Cambodia (3.6), and Timor-Leste (2.7). ASIR trends were parallel albeit differences were smaller. CMR was highest in Singapore (6.2) and Thailand (5.9) and lowest in Timor-Leste (1.5). ASMR was highest in Brunei (4.5) and lowest in Timor-Leste (2.0). For leukemia, CIR was highest in Singapore (11.1) and lowest in Myanmar (3.1) and Timor-Leste (2.6); ASIR was highest in Singapore (8.9) and lowest in Myanmar (3.2) and Timor-Leste (2.9). CMR was highest in Singapore (5.2) and lowest in Myanmar (2.6) and Timor-Leste (2.3). ASMR was highest in Lao PDR (4.7) and Vietnam (4.5), and lowest in Singapore (3.1) and Timor-Leste (2.9). For MM, CIR was highest in Singapore (4.1), ASIR was highest in Brunei (2.4) and both are lowest in Myanmar (0.4). CMR was highest in Singapore & Thailand (1.8) and lowest in Myanmar (0.35); ASMR rates were similar. For HL, CIR was highest in Brunei Darussalam (1.8) and Singapore (1.4) and lowest in Myanmar (0.2). ASIR trends were similar. CMR was highest in Vietnam (0.26) and lowest in Singapore (0.1) and Myanmar (0.08). ASMR trends were similar. Conclusions: Despite lower regional average incidence and mortality, significant intra-regional variations exist reflecting disparities in the management of HCs. In addition, while data suggests lower disease burden in SEA, mortality rates are still comparable and in some cases worse than the global average. More work is needed to investigate HC epidemiology in SEA to inform cancer control in the region and improve its blood cancer outcomes. [Table: see text]
Usage pattern of anticoagulants in oncology patients receiving active anticancer therapies in Europe and Asia.
Authors: Jindal Kriti , Ruiz Magdalena , García José Luis , Anger Caroline , Heitner Enschede Sari , Pérez Ezequiel Cayetano
Published: June 2024

e23297

Background: Risks and benefits associated with use of anticoagulants (ACs) in cancer patients should be carefully assessed due to an increased risk of both thrombotic recurrences and bleeding events. Vitamin K antagonists (AVK) have been the most used ACs for patients with atrial fibrillation and venous thromboembolism for many years. Low molecular weight heparins (LMWH) and direct oral anticoagulants (DOACs) are preferred over AVK for cancer associated thrombosis. To better define the current scenario for ACs in cancer patients we propose to use market research data to describe treatment patterns in Europe and Asia. Methods: This study was conducted using Oncology Dynamics, an online secondary market research survey collecting anonymized patient data, from a representative panel of physicians. Data for 11,568 drug-treated oncology patients (p) (9,178 Europe p; 2,390 Asia p) with active cancer and anticoagulant therapies, collected between Q3 2021 and Q3 2023, from 5 European (France, Spain, Germany, Italy, & UK) and 3 Asian countries (China, Japan, & S. Korea), were analyzed. Patients with Genitourinary (GU) tumors were 36%, Lung 19%, Gastrointestinal (GI) 18%, Hepatobiliary/pancreas 12%, Gynecologic (Gyn) 12%, and Melanoma and Brain < 5%. Results: 94% p were aged > 50 years and 49% > 70 years. 64% p were male and 36% female. 67% p showed advanced/metastatic stage vs 33% local/locally advanced stage. Globally, DOACs use was 55%, LMWH 35%, and AVK < 10%; DOACs were the preferred ACs in Europe (64% p) and LMWH in Asia (59% p). Prescription of AVKs in Asia population was higher (17% p) compared with Europe (7% p). Difference in use of ACs by tumor type in European countries in favor of DOACs vs LMWH was noticeable in GU (75% p vs 13% p), GI (61% vs 34%) and Melanoma (71% vs 22%). In Asia population, predominance of LMWH vs DOACs was observable in Gyn (86% p vs 5% p), GI (57% vs 24%) and Hepatobiliary/pancreas (56% vs 35%). AVK were administered in 53% of GU Asia p and DOACs in 31%. Overall, bleeding was more frequently associated with AVK (32% p), compared to DOACs (15% p) and LMWH (9% p). Conclusions: This research highlights the differences in ACs prescription in oncology patients between Asia and Europe, with a preference for LMWH in former and DOACs in the latter. DOACs are the most common ACs prescribed overall, while AVK, associated with higher incidence of bleeding, are used in a small population. A more comprehensive analysis of the included variables will be shared.
Evaluating reflexive NGS and testing rates in community oncology.
Authors: Cripps Amy Patricia , Prakash Akshay
Published: June 2024

e23302

Background: In oncology, NGS allows for the identification of DNA sequence variations within a cancer. The goal of testing is to identify/define therapeutic targets & improve patient outcomes, employing specific therapies directed at those targets. In breast cancer, reflex tumor testing (ER/PR/Her2neu) has been performed for > 20 yrs. In CRC, as published by ASCO, guideline-adherent biomarker testing rates for RAS, BRAF, & MSI/MMR-d were 41%, 43%, and 51%, respectively1. In lung cancer, recent data has shown overall testing rates minimally better at 58%2. Methods: The study was conducted on historical data of lung, colorectal, and breast cancer patients seen in Verdi community oncology clinics between 4/1/2022-7/31/2023. Clinical & social health data were collected & abstracted from patient medical history (Doctor’s notes, Pathology studies, NGS results). The database contains demographic & clinical data features for each patient. Results: 153 lung cancer patients were identified, median age 71(44 – 96). 82 F, 71 M. 85% of patients were smokers (130 smokers, 22 non-smokers, 1 unknown). Self-identified race: Asian 1, Black 22, white 106, 24 patients declined to identify. 61.9% (65) of later stage (≥IIB) patients had NGS testing. Of 258 colon/rectal cancer patients (anal cancer was excluded), median age 67(29-96), 122 M,146 F. Self-identified race: Asian 3, Black 26, 181 white, 34 patients declined to identify, 14 were unknown. Overall, 34.5% (89) of patients had NGS testing, and 76.2% (34) of Stage IV patients. There were 511 breast cancer patients, median age 63(25-85), 506 F, 5 M. Self-identified race: Asian/HPI 2, Black 137, white 299, 56 patients declined to identify, 17 were unknown. 100% had NGS, with minimum testing of ER/PR/Her2neu status. In the lung & colorectal patients, statistically significant differences in rates of testing were seen in males (p < 0.0001), older age (p < 0.0001), and non-whites (p = 0.002). Conclusions: Testing at Verdi clinics were higher than reported testing. We propose that to improve testing rates, NGS should be reflexively ordered in other tumor types, as is the standard of care in breast cancer. This would eliminate many issues, including waiting time patients must undergo when testing is not ordered until the patient is seen by the medical oncologist. Proactive testing allows potential targeted treatments to be delivered in real-time and thus improve patient outcomes. 1Genomic Profiling for KRAS, NRAS, BRAF, Microsatellite Instability, and Mismatch Repair Deficiency Among Patients With Metastatic Colon Cancer. JCO Precision Oncology (2019)3(3). 2Improving biomarker testing in advanced non-small cell lung cancer and metastatic colorectal cancer: experience from a large community oncology network in the USA. Future Oncology (2023)19(20),1397-1414.
Evaluation of recurrence rate in Canadian patients with stage II/III HR+/HER2- early breast cancer in the real-world setting.
Authors: Marques Maud , Gambaro Karen , Basik Mark , Saad Fred , Hassan Saima Noor , Boudreau Dominique , Vincent Francois , St-Hilaire Eve , Mackay Helen , Abdelsalam Mahmoud , Guillemette Stephanie , Leite Ricardo , Caron Marc-Andre , Patel Chandni , Batist Gerald
Published: June 2024

e23303

Background: Breast cancer is the most prevalent cancer and second leading cause of cancer-related mortality among Canadian women. Most of cases belong to the HR+/HER2- subtype, representing approximately two-thirds of all instances. Treatment for this subtype encompasses a multifaceted approach with a curative intent. This real-world evidence study aims to comprehensively analyze the clinical outcomes of Canadian patients diagnosed with early-stage HR+/HER2- breast cancer, focusing on recurrence rates after initiation of adjuvant endocrine therapy to identify opportunities for enhancing patient care. Methods: This is a retrospective, longitudinal cohort study involving 541 patients enrolled in the pan-Canadian cancer patient registry PMT (Personalize My Treatment), with newly diagnosed or recurrent stage II or III HR+/HER2- breast cancer between January 1st, 1996, and May 31st, 2022. We evaluated disease recurrence rates, time to recurrence, and overall survival (OS). Furthermore, the study explored duration of endocrine therapy (ET) in the adjuvant setting. Results: 409 patients received adjuvant ET representing 75.6% of the total cohort, emphasizing the role of ET as standard of care for adjuvant treatment in this patient population. The median duration of adjuvant ET was 4.5 years. In the overall adjuvant patient population, recurrence rates progressively increased over time from 13.2% after 2 years, 21.4% after 3 years, 30.3% after 5 years, and peaking at 58.4% after 10 years. Median time to recurrence for the overall patient population on ET was 7.76 years. OS rate for patients on ET was 94.6% at 5 years and 78.3% at 10 years. Conclusions: This study marks a pioneering real-world analysis utilizing pan-Canadian EHR data, demonstrating increasing recurrence rates over time in HR+/HER2- early breast cancer. It highlights the high unmet need in stage II and stage III breast cancer, with 1 patient out of 3 recurring after 5 years, and more than half recurring after 10 years despites adjuvant treatment with ET alone. This indicates the need for more efficacious and tolerable treatment options to reduce short- and long-term recurrence and to prolong survival, not only in the higher risk patient population, but in the overall HR+/HER2- breast cancer patients at increased risk of recurrence.
Evidence into practice: Changes in haploidentical versus double umbilical cord blood graft utilization for hematopoietic cell transplantation in the U.S. in relation to a pivotal randomized clinical trial.
Authors: Tran Danh T. , Jin Ruyun , Zhu Hong , Schmidt Gabrielle , Spellman Stephen R. , Ballen Karen K.
Published: June 2024

e23306

Background: Randomized clinical trials are the “gold standard”, but expensive and not always practice changing. Umbilical cord blood (UCB) and haploidentical (haplo) are donor sources for hematopoietic cell transplant (HCT) patients who do not have a fully matched donor. The Blood and Marrow Transplant Clinical Trials Network (CTN) 1101 trial (2012-2018) compared outcomes of double UCB and haplo bone marrow (BM) transplantation. The trial showed a lower two-year overall survival after UCB compared to haplo (46% vs 57%, p = 0.04). Here, we quantified the change in graft selection in clinical practice in the U.S. after publication of the trial’s primary results. Methods: 11,190 U.S. HCT recipients 18-70 years of age who received either UCB (single or double units) or haplo transplants (BM or peripheral blood stem cells), for leukemias, lymphomas, myelodysplastic syndrome, myeloproliferative neoplasms, who reported to the Center for International Blood and Marrow Transplant Research database, were analyzed. Graft utilization was analyzed in 3 time periods: 2010-2012 (pre-study), 2013-2018 (during study), and 2019-2022 (post-study), using Chi-square test and multivariable logistic regression. Results: Over the 3 time periods, there was a practice change with an increasing proportion of haplo transplants vs UCB (32%, 68% and 91% of transplants, p < 0.001; odds ratio (OR) of 4.67 and 21.38 for during-study and post-study periods, respectively, both with p < 0.001, compared to pre-study period). Males and older patients were more likely to receive haplo (OR = 1.32, p < 0.001, and OR = 1.74, p < 0.001, respectively). Compared to White recipients, Black recipients were more likely to receive haplo (OR = 1.74, p < 0.001), whereas Asian recipients were less likely to receive haplo (OR = 0.75, p = 0.002). Hispanic recipients had a similar likelihood of receiving haplo to White patients (OR = 1.03, p = 0.665). Conclusions: Practice change toward haploidentical graft utilization had begun before the CTN 1101 trial’s publication and continued to increase over time. Black patients were more likely than White patients to receive haplo, and Asian patients were more likely than White patients to receive UCB. Availability of both UCB and haplo as alternative graft sources allowed for HCT for a diverse population. [Table: see text]
Clinicopathologic features of patients with breast cancer in a single tertiary hospital in the Philippines.
Authors: Vistal Maria Carmela Yasay , Francia Marie Belle Dela Cruz , Gorospe Agnes Evangelista , Guevarra Margarita , Unson Sofia Dominique
Published: June 2024

e23313

Background: Breast cancer incidence in the Philippines is among the highest in Asia - the WHO reported it to be as high as 33,079 in 2022. Data provided by the Philippine Cancer Society and Department of Health Rizal Cancer Registry in 2009 included 1,615 breast cancer patients and noted a significant increase in breast cancer incidence from the year 1980 to 2002 in 7 cities in Metro Manila. This retrospective study aims to describe and analyze clinicopathologic and treatment data of Filipino breast cancer patients in a tertiary hospital. This study represents the largest pooled data in the Philippines on breast cancer demographics. Methods: Patients diagnosed with invasive breast cancer in St. Luke’s Medical Center (SLMC) from 2009 to 2020 were included. Patients diagnosed with other breast histopathologic results [i.e. ductal and lobular carcinoma in situ without invasive component] and double primaries were excluded. The study was approved by the Ethics Review Committee (Reference No.: SL-19157). Results: A total of 5,462 breast cancer patients were included. Majority of the patients were late perimenopausal (50-59 yo, 30.06%), menopausal (60-69 yo, 23.03%), and premenopausal (below 44 yo, 19.28%,) at the time of diagnosis. Patients were diagnosed with stage II (N = 1,816, 47.24%), followed by stage I (N = 943, 24%), and stage III (N = 662, 17%). Sixty four percent (N = 1,498) were node negative while 46% (N = 1,300) were node positive. Among patients with de novo metastasis, 14.6% metastasized to the bone while visceral sites include chest wall (17.4%), lung (16.6%), liver (11.5%) and brain (7.45%). Luminal her2- (48.9%) was the most common clinical subtype followed by non-luminal her2+ (15.6%) and triple negative (6.7%). Definitive surgery was the mainstay of treatment – 94% (N = 4116) underwent modified radical mastectomy (MRM) while 5% (N = 223) underwent breast conserving surgery (BCS). Eight hundred patients (19%) received neoadjuvant treatment (hormonal and/or systemic chemotherapy) while 2,246 patients (54%) received adjuvant treatment. Total number of breast cancer patients who underwent adjuvant radiation was 1,399 (25.6%). Conclusions: Compared to middle-high income countries, data suggests that MRM is the preferred surgical technique over BCS. Majority of patients in the study are luminal her2-. However, only 54% received adjuvant treatment. Another observation is the low rate of neoadjuvant treatment by the study population. Further research on the risk factors or reasons for not receiving treatment as well as the outcomes of these patient cohorts is needed to shed light on these cancer care gaps.
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]
Myofibroblastic sarcoma: A study of demographic and socioeconomic factors.
Authors: Loken Delaney , Ng Sandy , Moroz Mark , Reddy Nisha , Silberstein Peter T. , Heise Craig , Hsia Beau
Published: June 2024

e23545

Background: Myofibroblastic sarcoma is a type of non-rhabdomyosarcoma soft tissue sarcoma originating from spindle cells of mesenchymal origin with myofibroblastic differentiation. First described in 1998, there is little known about the prognostic factors of this rare and relatively new cancer. This typically non-metastasizing tumor is primarily found in the head, neck, or extremities. Treatment focuses on tumor excision, and the 5-year overall survival of low-grade myofibroblastic sarcoma cancer is 72%. This study analyzed data from the National Cancer Database (NCDB) to understand how demographic factors contribute to the treatment and prognosis of myofibroblastic sarcoma. Methods: A retrospective cohort analysis was conducted on demographic factors of patients with confirmed myofibroblastic sarcoma (ICD-8825-3) using the NCDB from 2004-2020. Regression analysis was used to study trends of patient age, sex, race, education, insurance status, distance from facility, and Charles/Deyo score within this population. Results: A total of 111 patients (N = 111) were identified in the database with a confirmed diagnosis of myofibroblastic sarcoma from 2004 to 2020 with an increasing frequency of diagnoses per year (R^2 = 0.6283). The average age of diagnosis was 47.3 (SD = 24.17, range = 0 - 90 years). Although Myofibroblastic sarcoma appeared throughout the body, the most prominent sites were the long bones of the lower limb and associative joints (6%) followed by the uterus (5%). The majority of patients were white (83%), non-Hispanic (86%), and female (63%). A higher percentage of patients lived in metropolitan areas with a population greater than 1 million (58%) compared to smaller metropolitan, urban, or rural counties (42%). Most of the patients were treated at an academic/research program (30%) followed by a comprehensive community cancer program (21%). More facility locations were based in the Pacific (15%) and the Middle Atlantic (11%) regions. The primary payer at diagnosis was private insurance/managed care (44%) followed by Medicare (32%) and Medicaid (19%). Few patients (5%) received palliative care. Conclusions: To the best of our knowledge, this is the first NCDB analysis on Myofibroblastic sarcoma. Based on our dataset, Myofibroblastic sarcoma tends to occur in the long bones of the lower limb and associative joints which differed slightly from what we found in previous reports, which described the head and neck as the two areas of highest prevalence. This is the first time the socioeconomic factors have been described in the literature: these patients are more likely to be non-Hispanic, female individuals, living in smaller towns. This study offers insight on how much further investigation is required to better understand the impact of demographic and socioeconomic factors on early diagnosis and treatments.
An analysis of treatment trends in sclerosing epithelioid fibrosarcoma.
Authors: Saldhi Prachi , Samuel Maya Mary , Silberstein Peter T. , Chaddha Jasleen Kaur
Published: June 2024

e23547

Background: Sclerosing Epithelioid Fibrosarcoma (SEF) is a rare, malignant, soft tissue sarcoma found in the arms, legs, head, and neck. Histologically, SEF is characterized by a distinctive architecture composed of cords, nests, and/or sheets of uniform epithelioid cells. Previous studies have demonstrated that surgery with wide surgical margins is associated with superior outcomes in SEF patients. However, on account of the rare nature of SEF, insufficient research has been conducted on the association of treatment types with long-term survival. Using the National Cancer Database (NCDB), this study analyzed the receipt of different types of surgery and adjuvant treatments on the overall survival of patients with SEF. Methods: The National Cancer Database (NCDB) was used to identify patients diagnosed with SEF from 2004 to 2020 using histology code 8840 as assigned by the Commission on Cancer Accreditation program. Kaplan-Meier, ANOVA Chi-Square, and Logistic Regression tests were performed, and data were analyzed using SPSS version 29. Statistical significance was set at α = 0.05. Results: Out of the 1226 patients with SEF, 1088 patients ( 88.7%) received a tumor resection at the primary site. Receipt of surgery was associated with a greater median overall survival compared to not receiving surgery ( 123.6 months vs 45.7 months; p < 0.05). Of the surgical patients, 419 patients received a wedge/segmental resection ( 38.5%) and 609 patients received a lobectomy ( 56%). Wedge/segmental resections and lobectomy had improved outcomes compared to other surgery types ( p < 0.001). In addition to tumor resection, 140 patients ( 12.9%) received adjuvant chemotherapy, 21 patients ( 1.9%) received adjuvant radiation, and 11(1%) patients received adjuvant chemoradiation. Furthermore, the receipt of adjuvant therapies including adjuvant chemo, adjuvant radiation, and adjuvant chemoradiation, was associated with improved overall survival compared to receiving surgery alone ( p = 0.03; p = 0.005; p < 0.001, respectively). Patients who received adjuvant chemoradiation experienced 9.5 months longer median survival time than patients who received adjuvant chemotherapy ( p < 0.001). Conclusions: SEF patients who received tumor resection had a marked increase in overall survival. Receiving wedge/segmental and lobectomy surgery types were associated with improved patient outcomes compared to other surgery types. Furthermore, receiving any adjuvant therapy was associated with improved overall survival compared to receiving surgery alone. Receiving adjuvant chemoradiation was associated with superior outcomes in SEF patients compared to receiving other adjuvant therapies and surgery alone. To improve overall survival in SEF patients, further research is needed to assess what factors influence treatment trends.