bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence and clinical correlations of Lynch syndrome (LS) in northeast Brazil.
Authors: Sant'Ana Rosane Oliveira , Silva-Fernandes Isabelle Joyce de Lima , Aquino Pedro Lucena , De Arruda Larissa Mont'Alverne , Bitencourt Flávio da Silveira , Luciano Maria Claudia dos Santos , Bezerra Maria Júlia Barbosa , Silva Paulo Goberlânio de Barros , Picanço-Albuquerque Clarissa Gondim , Barbosa Oliveira Francisca Fernanda
Published: June 2023

e22547

Background: LS is an autosomal dominant inherited condition with high risk for colorectal (CRC) and endometrial cancer, mostly. The LS is determined by a deficient Mismacht Repair (dMMR) system following germline mutations of MSH2, MLH1, MSH6, PMS2 and EPCAM genes. Identification of LS patients promotes adequate prevention and possible reduction of mortality for these population. The present study objetives to determine the frequencies of LS in a mixed race population from Northeast of Brazil, usually not represented in literature and characterize its genotype-fenotype feature. Methods: Our study prospectively screened 150 cancer patients (mostly CRC) with risk for LS according to NCCN guideline v2020 and performed germline mutational testing with a 33-multigene panel by NGS. Results: Median age was 48years and mainly female gender (63,3%). CRC was the most frequent tumor (n = 121, 80.7%), followed by breast cancer (11.3%), endometrium cancer (9.3%) and others (3,3% each). CCR patients presented MMR deficiency (dMMR) detected by IHC in a frequency of 29.3%. It was identified 32.7% of PV or PPV (according to ACMG criteria) with 20.7% for LS genes (mMMR). Two patients had 2 genes mutated. For CRC patients there was association of stage I-II tumors (p = 0,009) and right location (p < 0,001) with mutational status. There is no significant correlation of mutational status and other clinical caractheristics. MSH2 was the most frequently mutated (11) followed by MSH6 (10), heterozygous MUTYH (5), homozygous MUTHY (3), PMS2 (7), APC (4) and MLH1 (3) and others. MSH2 most frequent variants were c.388 389del (4) and c.2581C > T (2). Of the NCCN criteria for LS, personal history of CRC or endometrial cancer under 50 years of age was the most prevalent (67.3%) followed by tumoral dMMR (37.3%). dMMR tumor was the criteria with the best accuracy (sensibility 80.0 – 100.0% and specificity 76.6 – 93.5%) for LS detection. Patients with more than three criteria presented high sensibility and specificity values (80.6 and 90.3%, respectively). There were more than 60% of variants of uncertain significance variants (VUS). Conclusions: Our study detected a lower frequency of PV of LS genes (20,7%) than others even from Brazil, however it differs from these on criteria for LS (more inclusive), sequencing method (NGS multigene painel) and the population (derived from mixed caucasians, africans and native Indians). LS genotype correlates with CRC stages I-II and from right colon location. The most frequent mutated gene was MSH2 (c.388 389del and c.2581C > T). MLH1 was the less frequent mutated gene in our cohort.
Intervening factors for participation and non-participation in colorectal cancer screening in Spain.
Authors: Amador Maria Luz
Published: June 2023

e22552

Background: The Spanish Ministry of Health introduced a population-based colorectal screening program within its common services portfolio in 2014. The program targeted adults from 50 to 69 years. They receive a personal invitation letter asking them to perform the fecal occult blood test (FOBT). To achieve public health benefits on incidence, mortality and cost-effectiveness from this screening program a 65% participation in the program is needed1.Although participation rates have been improved since 2014, there is still room from improvement as only 56% of the Spanish regions reach the participacion threshold2. In this study we examined attitudinal and social factors impacting on participation in the target population. Methods: A CAWI survey was conducted among the target population of the screening program using a nation-wide citizen panel. A representative sample of the Spanish population, with size of 5131 valid responses, was obtained. The fieldwork was conducted in June 22nd. The data was analyzed using a descriptive analysis for the entire sample as well as the logistic regression technique using the maximum likelihood estimation. This technique allows us to determine the variables that have the greatest predictive capacity with respect to the participation (or non-participation) on the (FOBT). Results: We found that 97.6% of people have heard of colon cancer, 86.8% are aware of the test, 72.5% have received the program information letter and 62.5% have performed the test (FOBT). Furthermore, logistic regression demonstrates that the reception of a program information letter (OR=7,381, p<0.01), and the prior knowledge of the screening test (FOBT) (OR=6,768, p<0,01) significantly predicted the participation. Other variables with a high contribution were age between 62-69 (OR= 1,470, p<0.01), the frequency of routine medical check-ups (OR= 1,717, p<0.01), a positive perception of routine medical checkups (OR= 1,659, p<0.01), and personal risk of colon cancer perception (OR= 1,404, p<0.01). Conclusions: The effective participation in the program is influenced by factors that are unrelated to the implementation process (including the reception of the invitation letter). Most influential factors on actual participation on the program are the prior knowledge of the program and the importance attributed to routine heath checkups. Specific interventions on these variables should be done concurrently with expanding coverage in order to achieve the goals of higher effective participation. References: 1. Segnan N, Patnick J, von Karsa L. European guidelines for quality assurance in colorectal cancer screening and diagnosis. Office for Official Publications of the European Communities, 2010. 2. Molina-Barceló A, Moreno Salas J, Peiró-Pérez R, Arroyo G, Ibáñez Cabanell. REC. Desigualdades de acceso a los programas de cribado del cáncer en España y cómo reducirlas. Rev Esp Salud Pública. 2021; 95.
Real-world impact of oncology education on clinical practices at five community cancer care centers.
Authors: Johnson Elizabeth , Stefan Margaret , Theriault Nicolette , Waknine Yael , Weiss Jared
Published: June 2023

e23003

Background: Broad based molecular testing is an underutilized but essential factor in determining patient candidacy for frontline immunotherapy (IO) for advanced NSCLC. Findings from previous educational initiatives and real-world studies such as Nadler et al. and Velcheti, et al. indicate that understanding the importance of molecular testing to optimize therapy in NSCLC, remains an educational gap among oncology clinicians. Based on this real-world data, an educational initiative was developed to impart demonstrable change in clinician’s molecular testing practices and IO treatment selection. Methods: Grand round modules held at 5 community cancer centers facilitated learners’ ability to incorporate molecular testing and treatment strategies into clinical practice, which may improve patient outcomes. Physician leaders were leveraged at each center in order to increase learner engagement, encourage peer-to-peer learning and foster a learning community and potentially encourage institutional changes. Educational impact was assessed via a matched Pre/Post Test methodology which incorporated fact based and procedural information as well as asking learners to rate their confidence and intent to perform. To evaluate educational impact, pre and post educational intervention, 100 tumor board patient cases collected by OncoLens from the five centers were analyzed to assess any change in molecular testing practices, and therapeutic selection. Results: 174 learners participated in the grand round modules, results from matched Pre- and Post-Test showed significant improvements in overall proficiency, +51% in module 1 and +89% in module 2, alongside self-reported increased intent to utilize broad-based molecular testing +93% and IO +236% in advanced NSCLC. Post-intervention tumor board cases demonstrated that effective education can lead to real-world practice changes; there was an increase (+207%) in molecular testing of NSCLC, 75% increased use of liquid biopsy, the shift towards more comprehensive testing was accompanied by more judicious determination of IO candidacy, and a 52% increase in IO implementation. Additionally, feedback from the physician leaders reported that institutional changes were implemented following the educational initiative; 3 centers now actively consider liquid biopsy if tissue quantity is not sufficient (QNS), one institution has implemented reflex testing to improve time to treatment. Conclusions: Findings suggest that onsite CME/CE targeting understanding and proficiency in molecular testing for advanced NSCLC, can translate into real-world change to clinical practice that optimizes therapeutic decision-making in patient care; community cancer center case data supports the efficacy of the education on real-world clinical practices. Nadler E, et al.doi: 10.1016/j.ctarc.2022.100522. Velcheti V, et al.doi: 10.1371/journal.pone.0206370.
Global impact of a video education platform on oncology education amongst healthcare professionals.
Authors: Leyfman Yan , Joshi Muskan , Pawar Shubhadarshini , Menon Gayathri P. , Balasubramanian Maduri , Azeez Ahmed , Wilkerson William B. , Kannan Shreevikaa , Jackewicz Sean , Zahid Emad B , Van de Kieft Alexandra , Chorya Harshal , Nadar Soumiya , Vallabhaneni Harashita , Pai Pallavi , Coloma Helena S , Wilson Steven , Park Chandler H.
Published: June 2023

e23005

Background: Lower socioeconomic (SE) regions are often plagued extensively by healthcare outcome disparities. In searching for the root of this injustice, lack of access to the latest medical information has frequently been cited as a major contributor to these inequities. To address this, MedNews Week (MNW), a free, virtual education platform was developed to provide global health education through weekly oncology programming. The leading show, Keynote Conference, features live virtual presentations from oncology’s premier global leaders discussing the latest developments in the field. The aim of this study was to assess the global reach and impact of this platform for healthcare professionals (HCP). Methods: From September 2022 to January 2023, 37 MNW lectures on solid tumors and heme malignancies were showcased on VuMedi—a video platform providing free education content to HCP. Data collected from VuMedi included location, total page/video views, impressions, tumor subtype views and impressions, and occupation demographics. This information was analyzed to evaluate and assess the global reach of MNW on the VuMedi platform. Results: During this 5-month period, MNW experienced steady linear growth generating 5,643,257 page/video views with global viewership from 22 countries, including US, England, Canada, Brazil, and India (Table). Significant viewership was also observed from lower SE countries including Nigeria, Sudan, Georgia, and Bangladesh. Viewers were largely surgeons compared to Allied HCP (11:2). Higher viewership was observed for solid tumor presentations [706 (0.012%) page views and 9717 (7%) impressions] compared to heme malignancies [689 (0.001%) page views and 1688 (1.22%) impressions]. Within solid tumors, GI oncology keynotes were most viewed— generating 3755 (0.06%) page views and 28067 (20%) impressions, and the highest number of registrations recorded for this category. Conclusions: MNW continued growth in viewership and global reach amongst HCPs and demonstrates its emergence as a viable outlet to contribute to global oncology education, especially in lower SE areas. While previous studies have identified internet access and cost as barriers to high-quality medical information, MNW has experienced steady growth and reachability especially within these limited areas. The platform’s ability to showcase global leaders to HCP offers a practical approach to combat educational inequity and positively impact oncology education globally. [Table: see text]
Authorship diversity in global evidence synthesis in genitourinary oncology: A 1998-2022 analysis of cochrane reviews.
Authors: Khosla Atulya Aman , Ozair Ahmad , Subash Nishanth , Kumar Abhishek , Pereslete Alyssa , Mirza Sahaam , Bellur Shreyas S , Garje Rohan , Ahluwalia Manmeet Singh
Published: June 2023

e23006

Background: Women and individuals from low- and lower-middle-income countries (LMICs) are under-represented in oncology literature, particularly in high-impact publications. LMIC clinicians face multipronged barriers to impactful research. Unlike practice guidelines of oncology societies like ASCO, authors worldwide can potentially contribute to genitourinary (GU) oncology-related Cochrane Reviews, a potentially representative sample of global evidence synthesis efforts in the field. However, the state of authorship diversity here is unknown, which this study sought to determine. Methods: We retrospectively searched the Cochrane Database, using the filter “Topic: Urology”, and extracted authorship data for all reviews related to genitourinary cancers, published until 25 July 2022. We divided authors’ national affiliation into either low- and lower-middle-income countries (LMICs) or non-LMICs based on World Bank 2022 classification. For reviews having collaboratives listed as group authors, we treated the collaborative belonging to one country as a single author, instead of analyzing all collaborators separately to prevent data skew from several included individuals. Given the higher accuracy of manual web-searches for ascertaining gender over algorithmic estimation, we utilized the former to achieve ≥90% ascertainment. We endeavored to capture at least one webpage that demonstrated their gender or pronouns, like institutional profile, and used historical gender conventions. Results: A total of 54 GU oncology-related reviews, co-authored by a total of 324 authors, were included. 53 reviews were published by the Cochrane Urology Group, while one review was published by the Cochrane Incontinence Group. Countries with the highest representation of co-authors were the US (24.1%), UK (25.3%), Germany (23.5%), South Korea (6.8%), Australia (6.2%), Netherlands (3.7%), China (2.8%), Canada (2.5%), Brazil (1.5%). No authors were from LMICs. Gender could be ascertained for 94.14% (N = 305/324) of co-authors. Women made up 27.5% (N = 84/305) of co-authors, 16.0% (N = 8/50) of first authors, and 16.89% (N = 9/53) of corresponding authors. Conclusions: Women authors are better-represented in Cochrane Reviews related to genitourinary cancers compared to urology-specific journals, while LMICs were noted to have no representation. Global capacity-building efforts are warranted for enhancing the involvement of LMIC urologists with evidence synthesis. Equitable authorship representation may help expand both the focus and the utilization of high-impact evidence synthesis literature.
Website and social media presence for National Cancer Institute Community Oncology Research Program (NCORP) sites.
Authors: Steinmetz Carsten Z , Roberts Katie , Kennedy Alaina , Foust Melyssa , Mertz-Rivera Kamara L. , Curtis Amarinthia E.
Published: June 2023

e23009

Background: The National Cancer Institute Community Oncology Research program (NCORP) is a network which brings cancer clinical trials and care to patients within their own communities. Currently, NCORP consists of 46 sites throughout the United States which receive grant funding through the NCI. We aim to describe the scope of social media use and NCORP dedicated websites. We also aim to describe the correlation between media usage and funding. Methods: We searched NCORP websites and online search engines to identify the social media presence of different NCORP sites. Facebook, Instagram, LinkedIn, and Twitter were the social media sites chosen. Additionally, we searched for NCORP dedicated websites that were separate and distinct from the host institution. We were able to gather public data outlining the total funding received by each site in a three-year span (2019-2021) using the NIH RePORTER. Data was summarized using descriptive statistics. Results: A total of 15 out of 46 sites were determined to have a social media presence, 11 out of 46 sites had NCORP dedicated websites, and 7 out of 46 had both a social media presence and a dedicated website. The social media sites used for the NCORPs were as follows Facebook 8, Twitter 5, LinkedIn 3, and Instagram 1. The content information within the 11 dedicated websites were as follows clinical trials 9, newsletters 2, and provider information 8. All 11 websites had the NCI watermark badge (100% of NCORP websites). The average three-year funding for NCORP sites utilizing social media was $5,371,610. The average three-year funding for NCORP sites without social media was $4,230,552. The average three-year funding for NCORP sites utilizing dedicated websites was $4,681,708. The average three-year funding for NCORP sites without dedicated websites was 4,584,321. There was no statistical significance between funding and websites or social media accounts. Conclusions: NCORPs have an opportunity to disseminate high quality reliable information about cancer clinical trials that meet the need of patients and clinical care providers. However, NCORP sites are rarely a distinct voice on social media or with dedicated websites. Sites may not have resources for this type of communication or may promote the work of NCORP through the communication channels of the host institution(s). Sites with websites or social media accounts had higher average funding. However, this was not significant. Whether social media and NCORP dedicated websites contribute meaningfully to the work of NCI clinical trials remains to be seen and is beyond the scope of this investigation.
Effect of dual properties of regorafenib in osteosarcoma on tumor progression and bone parameters in mouse preclinical models.
Authors: Munoz Garcia Javier , Vargas-Franco Jorge William , Bompas Emmanuelle , Cochonneau Denis , Ollivier Emilie , Kerzerho Jerome , Brahmi Mehdi , Blay Jean-Yves , Heymann Maire-Francoise , Lezot Frederic , Heymann Dominique
Published: June 2023

e23501

Background: Osteosarcoma (OS) constitutes the most frequent malignant primary bone tumor in children and young adults. Actual treatments in OS are based in a multimodal therapy that combines pre- and post-surgery polychemotherapies including cisplatin, doxorubicin, ifosfamide and/or methotrexate. Regardless the use of this polychemotherapeutic approach, the five years overall survival for patients has not improved during the last four decades and there is a clinical need to identify new active drugs in OS. An interesting strategy implies the use of compounds that showed therapeutic benefits in other solid tumors. Regorafenib, a small molecule with multi-target tyrosine kinase inhibitory activity against FGFR-1 and -2, KIT, PDGFR, RAF, RET, TIE2 and VEGFR-1, -2 and -3, showed an anti-angiogenic/oncogenic properties in various solid tumors that includes metastatic colorectal cancer, hepatocarcinoma and breast cancer. In addition, regorafenib also inhibits in vitro the proliferation of several pediatric solid tumor cell lines such as rhabdomyosarcoma, Ewing sarcoma and OS. Methods: The present work aims to decipher the in vitro and in vivo effects of regorafenib in OS preclinical models. Results: The treatment of MNNG-HOS, KHOS and 143B osteosarcoma cell lines with Regorafenib resulted in the inhibition of cell proliferation in a dose dependent manner. The gene expression profiles of MNNG-HOS and 143B cells treated or not with regorafenib and analyzed by NanoString technology revealed a specific regulation of molecular pathways by regorafenib in both cell lines. The in vivo effect of regorafenib was then analyzed in immunocompetent (mouse MOS-J cells inoculated in C57Bl/6 mice) and immunodeficient (human MNNG-HOS and 143B OS cells injected in Nude mice) murine osteosarcoma models. In all the cases, a significant reduction of primary tumor growth was observed as well as a significant decrease of lung metastases compared to untreated mice. Interestingly, the cortical and trabecular bone mineral density were significantly increased in regorafenib treated mice compared to untreated groups as demonstrated by X ray microtomodensitometry in all models. Conclusions: Our results support the use of regorafenib as an alternative treatment in metastatic OS and demonstrated for the first time the its bone protective effect.
The impact of demographic factors on patients with intraosseous well-differentiated osteosarcoma.
Authors: Cook Madison , Wu Xinxin , Keirns Darby , Silberstein Peter T. , Hsia Beau
Published: June 2023

e23502

Background: Well-differentiated intraosseous osteosarcoma (WDIO) is a rare cancer that primarily affects the medullary cavity of the femur and tibia. While WDIO accounts for only 2% of osteosarcomas, 10% of patients do not survive past 5 years. Due to its rare nature, there is difficulty diagnosing WDIO, and as such, patients present in later stages of the disease with more secondary complications. There is no standard of treatment for WDIO. The socioeconomic factors of WDIO have yet to be addressed in literature using data from the NCDB. The purpose of this study is to analyze the demographic and socioeconomic factors of patients diagnosed with WDIO, using the National Cancer Database (NCDB) to better understand its epidemiology. Methods: The National Cancer Database (NCDB) was used to create a retrospective cohort analysis of histologically-confirmed WDIO patients (N = 30) from 2004 – 2020. Regression analysis was performed to interpret incidence trends and descriptive statistics on specific demographic factors (sex, race, age, insurance status, income, type of treatment, facility type, and Charleson-Deyco score) on patients with WDIO. Results: There were a total of 30 patients in the NCDB database identified with a diagnosis of WDIO. From 2004 – 2020, there has been an increasing incidence rate (R2 = 0.3). The mean age of WDIO diagnosis is 37.9 (SD = 18.6 range = 8 – 80 years). The long bones of the upper and lower limbs accounted for 63.4% of the primary sites of the cancer. More women (63.3%) than men were diagnosed. The majority (83.3%) of the patients had Charlson-Deyo comorbidity scores of 0. The upper income quartile contained the highest percentage of patients (42.3%) compared to each of the other lower quartiles. There were more privately insured patients (63.3%) than patients on Medicaid/Medicare. Over half of the patients (51.9%) came from metropolitan areas with a population greater than 1 million. More than half of the patients were treated at research/academic facilities (51.3%). The main form of treatment in patients with WDIO was radical excision with limb salvage (60%). Local and partial resection occurred in 30% of the cases. Conclusions: This study addresses a significant gap in knowledge on the diagnosis of WDIO and its relation to socio-demographic factors. The majority of the patients present with WDIO in the long bones of the upper and lower body, which is concurrent with previous reports of WDIO. From our analysis, patients with WDIO tend to be in the upper income quartile, live in densely-populated urban areas, and receive radical excision surgery in academic programs. This preliminary research on the impacts of demographic and socioeconomic factors on WDIO could bring more awareness to its diagnosis. Further research on the impacts of these demographics on treatment options and overall prognosis would significantly enhance our knowledge regarding the social inequality surrounding WDIO.
Clear cell chondrosarcoma: A national analysis exploring the demographic features.
Authors: Tade Yanick , Hsia Beau , Keirns Darby , Silberstein Peter T. , Wu Xinxin
Published: June 2023

e23503

Background: Clear cell chondrosarcoma (CCCS) is an uncommon cancer and variant of chondrosarcoma affecting the proximal portion of long bones, commonly the femur or humerus. This low-grade and slowly progressing malignant tumor is often mistaken for benign tumors (i.e. chondroblastoma), but its histological features of benign giant cells and cells with clear cytoplasm alongside pathologic, roentgenographic, and clinical characteristics aid in its distinction. Accurate identification will guide the establishment of standard treatment algorithms and further improve treatment outcomes. CCCS has an overall 10-year survival rate of 89% with a median time to death from disease of 15.3 years. The National Cancer Database (NCDB) was analyzed to determine how patient demographic characteristics affect the diagnosis of CCCS. Methods: A retrospective cohort study from 2004 to 2020 was conducted using the NCDB. 188 patients were found with a histologically confirmed diagnosis of CCCS (ICD-9242-3). Gender, race, Hispanic origin, insurance coverage, type of treatment facility, and distance from patient residence to treatment facility were analyzed via descriptive statistics and trends in incidence were interpreted using regression analysis. Results: The frequency of patients diagnosed with CCCS has remained consistent since 2004 (R2 = 0.1) with over 11 diagnoses per year. Of the 188 patients found, the average age of diagnosis was 47.8 years (SD = 16.7, range = 14 – 90 years). Approximately two-thirds of patients were male (68.1%) and the remainder were female (31.9%). Most of the patients were White (84.6%). Patient Hispanic status could not be accurately determined due to limited data. More patients were in the top income quartile (31.9%) than those in the second (26.1%), third (19.7%), or fourth (12.2%) quartiles. The other 10.1% were of unknown income status. Most patients were privately insured (61.7%), followed by coverage under Medicare/Medicaid (27.1%). More patients lived in metropolitan counties with a population of 250,000 or more (85%) compared to less-populated urban or rural areas (15%). A large percentage of patients were treated at an academic/research program (61.6%) compared to non-academic programs (38.4%). Patients traveled an average of 65.8 miles (SD = 101.4, range = 0.8 – 793.0) to get to the treatment facility. Conclusions: CCCS remains a rare diagnosis. This study explores a significant gap in existing knowledge on patient characteristics that might present with CCCS. Most patients were White, insured by private insurance, in the top quartile of income earners, and lived in metropolitan areas. This novel study of socioeconomic factors in CCCS patients suggests that patients with higher socioeconomic status in highly-populated areas might have better access to this uncommon diagnosis. As such, additional research to comprehend the role that socioeconomic status might have on CCCS would be beneficial.
Chondrosarcoma: The OSU experience.
Authors: Husain Marium , Tinoco Gabriel , Chen James Lin , Mayerson Joel L , Scharschmidt Thomas , Alexander John , Konieczkowski David Joseph , Haglund Karl , Grignol Valerie Patrice , Beane Joal , Kim Hangil , Xu Menglin , Liebner David A.
Published: June 2023

e23505

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

e23507

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

e23510

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

e23514

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

e23517

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

e23520

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

e23530

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