bluuebunny/crossref_metadata_2025 huggingface dataset:
Malignancy in patients with sickle cell disease: A single center experience.
Authors: Sharma Shivani , Walker Nakoma , Martinez Shidestini Chanta , Ramadas Poornima , Shi Runhua , Master Samip R. , Mansour Richard P.
Published: June 2023

e22551

Background: The development of malignancy in patients with sickle cell disease has been documented in multiple case reports and case series. The incidence of malignancy in patients with sickle cell disease is unknown. Large national databases like the National Cancer Database, North American Association of Central Cancer Registries, and SEER do not collect data on the presence of sickle cell disease. This has made it difficult to calculate the incidence of malignancy in this patient population. In our study, we aim to calculate the prevalence of malignancy in sickle cell patients following our institution. Methods: After IRB approval, a retrospective analysis was conducted of adult sickle cell disease patients being followed at our Hematology outpatient clinic. We included patients aged > / = 18 years with sickle cell disease (HBSS, HBSC, HBS-beta thalassemia) as per hemoglobin electrophoresis, who were followed at the clinic from 1/1/2017 to 10/1/2022. We excluded prisoners. We did an extensive chart review to identify patients with a diagnosis of malignancy by pathology. Variables of age, sex, race, type of sickle cell disease, type of malignancy, age at the diagnosis of malignancy, and treatment were collected. Continuous descriptive data were summarized as means. Categorical data were summarized with a sample percentage. The prevalence of malignancy was calculated. SAS for windows 9.4 was used for analysis. Results: 438 patients with sickle cell disease were identified from 2017 to 2022. All the patients were African American. Their ages ranged from 16 to 84 with a mean of 35 years. Of these patients 53 % were females and 47 % were male. 62% had HBSS disease, 25 % had HBSC and 13% had HBS beta thalassemia genotype. 4 patients were diagnosed with malignancy. All 4 patients were female. The prevalence of malignancy was calculated as 0.91%. Conclusions: We found four patients with malignancy in the patient population with sickle cell disease at our hematology clinic. This data is based on limited sample size. The incidence of malignancy in sickle cell patients should be calculated in a larger population base. Further studies can be done to determine if a single type of sickle cell genotype increases the risk of malignancy. All the centers where sickle cell patients are followed should monitor the patients prospectively for the development of malignancy.[Table: see text]
Burnout in oncology nurses.
Authors: Sharma Priyanshi Rajesh , Sharma Rajesh
Published: June 2023

e23000

Background: Burnout is a psychological condition that develops as a result of a sustained response to workplace interpersonal stressors. An overpowering sense of tiredness, feelings of cynicism and detachment from the job, and a sense of ineffectiveness & lack of accomplishment are the three primary dimensions of this response. Introduction: Specialties that is most impacted by burnout is oncology nursing. They work in environments with high patient: nurse ratios & demanding working conditions, which increases their load of emotional responsibility and increases the risk of burnout. The current research was done to determine the predictors of burnout in an Indian healthcare population due to the scarcity of Indian studies in this domain. Objective: The aim to this research is to investigate the level of burnout & fatigue in oncology nurses and how can we help them to recover from burnout. Outcomes are measured by Maslach Burnout Inventory test (MBI). Methods: In this study, total 300 nursing staff were included who are working in Oncology departments. The questionnaire comprised a total of 23 questions.The online surveys (Google form) were sent over 4-month period during April 2022 to June 2022 and nurses were met in person to interview and get the feedback submitted. The data were entered in the excel sheet and descriptive statistics were used to analyse the data using SPSS 20.0. The Mann-Whitney U test is used to compare differences between two independent groups. Logistic regression with stepwise selection was employed in multivariate analyses to find a group of demographic variables (age, gender) that were independently important in explaining the likelihood of burnout & fatigue in nurses. Results: In this study, 33.7% (101) male and 66.3% (199) of female nurses were included with highest number from the young age group 20-25 (51%, 153). The univariate analysis revealed that fatigue during daily routine shown significant association with gender and age classification, however positively dealing with anger, all the time energetic feelings, consideration themselves as happy person also shown statistical significance. It was found that the think of themselves during a busy time at work showed a significant association with gender classification in multivariate analysis. Similarly, dealing with anger was the most critical positive association with burnout variables in multivariate analysis. The overall multivariate test results on the basis of gender classification showed a significant difference for the burnout variables (p<0.01), while for age classification it was non-significant (p=0.87). Conclusions: The current study is a first step in understanding some of these mental health problems that Indian oncology nurses encounter and indicated prevalence of burnout consistent with age and gender criteria through standardizing measurement tools. It is helpful in raising awareness of the value of self-care and illnesses like burnout & fatigue among nursing professionals.
Incorporation of fellow-driven, interactive case-based discussions to improve fellowship education in a new fellowship program.
Authors: Sridhar Arthi , Ilyas Sama Imran , Rowe Julie H , Maithel Neha
Published: June 2023

e23001

Background: Evidence-based education is crucial for meeting the evolving needs of learners in the oncology workforce. In this new virtual era, engagement of trainees in educational presentations has become increasingly difficult and reaping the benefits of a conventional didactic learning environment is challenging. Case-based learning is a relatively newer modality that is being used more commonly in teaching programs. In this study, we aimed to incorporate a novel, interactive case-based learning paradigm to improve fundamental knowledge and engagement among oncology trainees. Methods: We conducted six case conferences over 6 months. The case conferences were designed to encourage open discussion of real-life oncology cases. A faculty expert and specific topics were assigned to the presenters: colon, breast, gastric, hepatocellular (HCC), prostate, and non-small cell lung (NSCLC) cancer. Guidelines on the preparation of the case presentation were provided with 5 main pillars: specific staging/workup, first-line management with a landmark trial, second-line management, case-specific challenges, and mechanism of action and monitoring parameters for discussed drugs. Fellows completed a pre- and post-conference survey that assessed their perceived comfort level with the topic, quality of the presentation (post-conference) utilizing the 1–5 Likert scale (5 being extremely satisfied/comfortable), and test questions. Results: Nearly all of the 6 fellows responded to all surveys. The table shows the mean scores given by fellows on the surveys using the Likert scale and the percentage of test questions answered correctly. Overall, the fellows felt that the case conferences were a worthwhile experience. When comparing pre- and post-conference questions, the percentage of test questions correct overall improved for 5 of 6 conferences. Conclusions: The results of our study could have implications for the curriculum planning of hematology/oncology fellowships. [Table: see text]
The power of writing: Impact of writing for health professionals working with oncology patients.
Authors: Chagas Sabrina , Coradazzi Ana , Caponero Ricardo
Published: June 2023

e23002

Background: Healthcare professionals are subject to stressful events, especially in areas such as oncology or palliative care. Writing is a valuable tool for dealing with stress, increasing empathy and job satisfaction. Narratives have therapeutic potential and can provide useful information for diagnosis and individualized strategies. Expressive Writing and Narrative Medicine have been studied in this field, resulting in physical and psychological benefits to health professionals, and can be a medical-educational tool. The practice of writing can promote healthier relationships between patients, professionals, and oneself. However, little is known about the perception that health professionals have about writing as a habit. These data can help to develop strategies for stimulating practice in universities, contributing to better professionals mental health. Methods: An online questionnaire was disseminated through social networks of the authors and professional associations inviting health professionals who deal with cancer patients and have the habit of writing to answer the questions, voluntarily and anonymously. The questionnaire was composed by 13 multiple choice questions and 1 free choice question, divided into 3 categories: 3 related to personal and professional data, 5 to the habit of writing and 5 to the impact that the habit of writing has on their lives. The data were analyzed descriptively, based on the results provided by the platform itself. Results: 177 responses to the form were obtained. Most participants were over 40 years old (53.9%). Eighty-seven participants were physicians (49.4%), 41 psychologists (23.3%), and 27.3% worked in other health fields. The majority (32.1%) declared they write sporadically when they feel the need. Only 17.8% wrote daily. Thirty-two percent write mainly short texts (blogs or social networks); 16.9% write mainly narratives. Most participants have been writing for more than ten years (63.2%). Using writing as a tool for self-knowledge was the main reason to start writing for 19.8%, and improving the ability to understand what is happening to other people for 18.7%. The themes of the texts were personal experiences (21.1%), personal feelings (19.4%), technical issues (14.8%), the process of getting sick (6.2%), or other topics (28.5%). Most reported that writing provides them with serenity (24.4%), comfort (23.8%), pride (19.3%), relief (13.6%), or other. Participants reported that the impact of writing on their lives is essential (32%), very positive (30.9%), or positive (33.7%), and the majority (48.8%) reported that the impact is both immediate and long-term. Conclusions: The personal perception about the impact of writing is extremely positive among healthcare professionals, suggesting that the practice should be stimulated during professional training and considered as a useful tool for the promotion of mental health.
Trends in application and match outcomes for hematology and oncology fellowship: An analysis of charting outcomes from 2008 to 2022.
Authors: Ojo Ademola Samuel , Ali Ahmed
Published: June 2023

e23004

Background: The rapidly evolving advances in the field of oncology make it attractive to many internal medicine residents and graduates who must secure a position through the hematology and oncology fellowship match to get a chance to complete training in oncology. We aim to evaluate the trends in the application, competitiveness, and match rates of the hematology and oncology fellowship match based on the category of applicants. Methods: This is a retrospective cohort study of applicants who applied for the hematology and oncology fellowship from 2008 to 2022 based on the match data released by the National Residency Match Program (NRMP). The number of applicants, type of applicants, number of positions, and match outcomes was evaluated. Applicant types were classified into US-allopathic graduates and non-US-allopathic graduates. Chi-square tests were used to compare the match outcomes and the applicant types. Results: A total of 11,357 applicants participated in the hematology and oncology fellowship match during the study period. The number of applicants increased from 724 in 2008 to 894 in 2022 (a 23% increase), while the number of positions increased from 424 to 663 (a 36% increase). The average match rate was 68.5% during the study period, rising from 57.5% in 2008 to 73.5% in 2022. US allopathic graduates have a higher match rate when compared to non-US allopathic graduates (83.8% vs 56.2%; p < 0.00001). Although this disparity is maintained over time, it progressively narrowed (77.2% vs 42.5% in 2008 compared to 85.4% vs 63.3% in 2022). Fifty-three percent of applicants matched in their top 3 programs (36.5% in 1st, 11.2% in 2nd, and 7.3% in 3rd). The percentage of applicants matched in their top 3 programs increased from 53.4% in 2009 to 57.4% in 2022 (range: 50-62%). Conclusions: The hematology and oncology fellowship match is highly competitive with outcomes more favorable to US-allopathic graduates than non-US allopathic graduates. Most successful applicants matched in one of their top three programs. [Table: see text]
From abstract to publication: Factors predictive of publication success in the field of breast and gynecological malignancy.
Authors: Kapoor Ankita , Roy Arya Mariam , Aggarwal Sanjana , Gill Simrat , Attwood Kristopher , George Anthony , Ahlawat Yagya , Gandhi Asha , Patel Riya Jayesh , Kapoor Harshit , Jizzini Mazen , Sarma Maithreyi , Gandhi Shipra
Published: June 2023

e23007

Background: Cancer research has rapidly evolved over the last few decades which has led to an improvement in patient care and outcomes. Dissemination of this research presented at meetings is essential to inform clinical practice. However, there continues to be a delay in the publication of data even after successful presentation of research as abstracts. In our study, we aim to determine abstract characteristics associated with successful peer-reviewed publication after presentation at the American Society of Clinical Oncology (ASCO) annual meeting for Breast and Gynecological malignancies. Methods: All oral abstracts (OA) & poster abstracts (PA) presented in the Breast & Gynecologic cancers categories from 2017/2018 ASCO annual meetings were included in the retrospective study. Manuscript publication was confirmed by searching PubMed using a data cut-off of December 2022. Publication characteristics like number of authors, time to publication (in months (mo)), study size, nature of results, impact factor, gender, H-index, citation of first author (FA) & last author (LA), NIH funding of LA were collected. Univariate logistic regression modeling was used to measure the association between publication status and select predictors. Results: 40/50 (80%) OA & 246/527 (46.6%) PA were published in PubMed indexed journals. Mean time to publication for OA was 17.41 mo & for PA was 19.52 mo. Mean IF for published OA was 28 & PA was 9.98. Of presented abstracts, 30/50 (60%) OA & 313/527 (59.39%) PA had positive results. Of the ones published, 23/40 (57.5%) of OA (p=0.72) & 190/246 (77.2%) of PA (p<0.001) had positive findings. 250/527 (49.14%) PA & 17/50 (33.3%) of OA were presented by females. Of the published OA, 15/40 (37.5%) had female FA & 10/40 (25%) female LA. For published PA, FA females were 118/246 (47.9%) while LA females were 86/246 (34.9%). For published PA, median H-index for FA was 33 & LA was 68. 16/40 (40%) LA of published OA & 62/246 (25%) of published PA had NIH funding. Conclusions: Our study reveals that poster abstracts with positive findings are more likely to be published, implying publication bias in research. In addition, there is also higher likelihood of publication if last author is NIH funded. Our study highlights the need to address these factors to maximize the chances of publication of impactful research. [Table: see text]
The impact of large oncology meetings (#ASCO, #AACR, #ASH) and health equity hashtags (#DEI+) on social media engagement.
Authors: Dizon Don S. , Florez Narjust , Subbiah Vivek , Weeks Lachelle Dawn , Dezzani Luca , Juneja Renu , Smith John , Edobor Wanda
Published: June 2023

e23008

Background: Social media has revolutionized scientific communication to extend engagement beyond peer-reviewed publications and traditional media channels. Hashtags (#) promote awareness of key topics and enable tracking of social media engagement (Katz et al. JAMA Oncol. 2016;2(3):392-4). We evaluated the utilization of Diversity, Equity, and Inclusion (#DEI) hashtags around large oncology meetings to describe the trends of DEI-focused social media conversations. Methods: Using Symplur Signals healthcare analytics on Twitter data, 5 dashboards with # datasets (#ASCO 18-22, #AACR 18-22, #ASH 18-22, #ASHDEI) were analyzed over 2018–2022. Data were then refined by content word filters (most used DEI hashtags: #cancerdisparities, #healthdisparities, #healthequity). Utilizing proprietary natural language processing combined with artificial intelligence, the Netbase Quid platform used a Boolean algorithm to collect ASCO DEI social media data (Twitter and others) to identify discussion themes between January 2021 – January 2023. Results: Use of the ASCO hashtag resulted in high and relatively stable social media activity from 2018-2022 (Table). In contrast, a major decline in both the DEI and DEI+ASCO hashtags occurred in 2022 after the peak in 2021 (Table). The peak use of DEI hashtags coincided with sentinel events in the US, including the deaths of George Floyd and Breonna Taylor and subsequent public protests. However, DEI conversations made up only 2% of ASCO’s social media conversations and accounted for far less for American Society of Hematology (ASH) and American Association for Cancer Research (AACR) (Table). Although smaller in number, AACR hashtags (#AACR, +DEI hashtags) were stable in 2021-22 compared with ASCO and ASH, coinciding with a dedicated conference focus on DEI topics during the AACR meeting. Conclusions: In general, oncology-associated Twitter activity appeared to be less frequent, possibly due to inconsistent use of DEI hashtags. To generate consistent and searchable DEI social media activity—and to communicate the outcomes of DEI initiatives—the oncology community should develop a lexicon of DEI hashtags. [Table: see text]
Distinguishing enchondroma from low-grade chondrosarcoma using a multi-stage deep learning model for patient radiographs and histopathology.
Authors: Nye Logan , Ghaednia Hamid , Schwab Joseph H.
Published: June 2023

e23500

Background: Enchondroma and low-grade (grade 1) chondrosarcoma are cartilaginous tumors of the peripheral bone. Enchondroma is benign, requiring only routine clinical monitoring. Chondrosarcoma is malignant, demanding prompt and aggressive treatment to prevent metastasis. Despite drastically different treatment protocols, these tumors are histologically and radiographically similar, making them difficult to tell apart. Even specialized treatment, years of experience, and access to both imaging modalities, pathologists and radiologists have reported low reliability in distinguishing between these two tumors. Better diagnostic and grading strategies are needed for these lesions. In this study, we propose a two-stage computer vision framework for distinguishing enchondroma from low-grade chondrosarcoma using deep learning. Methods: Our team compiled a ground truth dataset of radiographic and histological images from the annotated records of Dr. Henry Jaffe, a pioneering authority in musculoskeletal pathology. From his records, 55 cases of low-grade chondrosarcoma and 19 cases of enchondroma containing both radiology and histology imaging were identified and included. Radiographs and histology samples corresponding to the same individual were paired together to create 290 paired images of enchondroma and 318 paired images of low-grade chondrosarcoma (pair = 1 histology + 1 radiograph). These image pairings were randomly split into training (~80%) or validation (~20%) groups, excepting minimal reallocations to prevent leakage between training and validation data. All images were preprocessed and augmented for improved model training. Image pairings (one histology image, one radiograph) corresponding to the same patient case were passed through separate VGG16 models pre-trained on ImageNet weights. These models produced two feature vectors as outputs, which were concatenated and subsequently passed through a second-stage binary classification network to predict tumor identity. Results: After 17 epochs, the model recorded training loss and accuracy of 0.6723 and 0.7583, and validation loss and accuracy of 0.7362 and 0.7373, respectively – an improvement upon diagnostic accuracies reported in previous studies. Conclusions: We have created a two-stage deep learning model that predicts whether patient radiographs and histology show enchondroma or low-grade chondrosarcoma. The trained model’s validation accuracy of 73.7% improves upon past reported methods. This suggests that computer vision methods that utilize multiple imaging modalities might augment physicians' capability to discriminate between these two tumor types.
Comprehensive genomic and transcriptomic profiling analysis of the recurrent gastrointestinal stromal tumor (GIST).
Authors: Sun Lu , Wang Xiaohui , Wu Xin , Zhu Fengwei , Hong Liu , Chen Wen , Piao Yingshi , Luo Hong , Zhang Yiqun , Liu Ling , Zang Yuehua , Li Wenjing , Pei Zhihua , Wang Dongliang , Zhou Qiming , Shi Huaiyin
Published: June 2023

e23506

Background: The gastrointestinal stromal tumor (GIST) is a potentially malignant mesenchymal tumor (sarcoma), whose management has been transformed by approvals of TKIs. However, recurrence or metastasis is a formidable challenge in managing high-risk GIST. Comprehensive investigation of the transcriptome and genome in GIST is helpful to determine the therapy strategy for patients. This study aims to explore the molecular features of high-risk recurrence GIST. Methods: The tumor tissue samples of 42 patients with primary GIST were collected, in which all patients were divided into low-risk (n = 12), intermediate-risk (n = 11), and high-risk (n = 19) groups according to the NIH 2017th, in which 8 developed recurrence within three years and 11 without recurrence over three years in the high-risk group. Tumor-normal whole-exome and tumor mRNA sequencing was performed on baseline tissue DNA isolated from all patients. Results: Consistent with prior knowledge, KIT was the predominant mutation. The top mutated genes in GISTs were KIT (82%), PHLDA1 (39%), MUC6 (22%), ARID1B(20%), SURF2(20%), MGA(16%), MUC17(16%), MPRIP(16%) and PDGFRA(16%), which MUC6 was a significantly different mutation gene (DMG) associated with disease progression in terms of either high-risk(p = 0.04), recurrence(p = 0.02) or progression(p = 0.05). Interestingly, PDGFRA mutation co-occurs with CTNND2(p < 0.01) and its correlated genes. Additionally, we further explored the somatic copy number variations (CNVs). amp_RAD51B(49%), amp_MLH3(41%), amp_CHEK2(37%), and amp_RB1(12%) seemed to be more frequent in the recurrence group, while these observations were not significant (p > 0.05). Notably, del_NCOR1 or amp_NCOR1 was uniquely observed in the recurrence group. Compared with non-recurrence GIST, gene expression profiles revealed that mast cell activate (MCA)，M1-macrophages infiltration were higher in recurrence group, and mRNA was significantly upregulated in Systemic lupus erythematosus、Neutrophil extracellular trap formation、Viral carcinogenesis、Endocytosis. These pathways were indentified as being associated with recurrence and progression in other cancer studies. For example, the endocytosis pathway expression is positively associated with oncogenic pathway signaling in CRC, and neutrophil extracellular trap on cancer cells promotes liver metastasis in the tumor microenvironment. In the other, NCOR1 is a crucial regulator of T cell and B cell development. Conclusions: Here, we demonstrated the DNA/RNA profiles of GISTs. We observed higher CNVs in high-risk GIST. Especially, the high-risk recurred tumor presented different CNVs frequency and microenvironment. These results may contribute to understanding the mechanism of recurrence and improving recurrence detection.
Clinical characteristics of gastrointestinal stromal tumors with lymph node metastasis: A retrospective single-centre case-controlled study.
Authors: Zhang Xinhua , Guo Xiaodan , Huang Shaoqing , Xia Yanzhe , Zhou Xuefu
Published: June 2023

e23509

Background: Lymph node metastasis of gastrointestinal stromal tumors (GISTs) rarely occurs, and lymphadenectomy is not routinely performed in GIST resection. To date, the relevant characteristics and prognosis of GIST patients with lymph node metastasis are not well known. Methods: From January 2010 to December 2021, GIST patients who underwent lymph node resection were enrolled in this study from a GIST referral centre. All patients were divided into either the LN- group (GISTs without lymph node metastasis) or the LN+ group (GISTs with lymph node metastasis). The clinicopathological features and follow-up data were analysed, and propensity score matching (PSM) was conducted to reduce bias caused by confounders. Results: Out of 1024 surgical patients, 198 patients (age, 52.23±13.54 years; 56.6% males) underwent GIST resection with lymph node dissection for lymphadenopathy, and 17 patients had lymph node metastases (17/1024, 1.66%; 17/198, 8.59%). The LN+ group had a higher mitotic count (P = 0.012) and a higher proportion of distant metastasis (P < 0.001) than the LN- group. After PSM, 28 patients were included (18 in the LN- group and 10 in the LN+ group). The LN- group had both longer postoperative progression-free survival (PFS, not reached vs. 15.0 months, P = 0.002) and overall survival (OS) than the LN+ group, but the difference in OS was not statistically significant (not reached vs. 35.0 months, P = 0.069). Conclusions: The rate of lymph node metastasis in GISTs is low. Lymph node metastasis may be a less common form of distant metastasis. Moreover, GIST with lymph node metastasis has an unfavourable prognosis. Further studies are warranted to identify GISTs with lymph node involvement and the potential involved mechanism. [Table: see text]
Sex differences in localized gastrointestinal stromal tumor.
Authors: Boye Kjetil , Hompland Ivar , Berner Jeanne-Marie , Meza-Zepeda Leonardo A. , Hølmebakk Toto
Published: June 2023

e23511

Background: Sex plays an important role in the incidence and prognosis of several cancer types. Male patients with gastrointestinal stromal tumors (GISTs) have inferior outcomes compared to women, but the reasons behind the sex differences are not well understood. This study aimed to investigate whether sex was a prognostic factor in localized GIST and to explore the relationship between sex and established clinical, molecular and histopathological characteristics. Methods: The study cohort is population-based and consisted of patients who underwent surgical resection of primary, non-metastatic GIST at Oslo University Hospital, Norway between January 2000 and September 2017. Recurrence-free survival (RFS) was the primary endpoint. Mutation analysis was performed by Sanger sequencing or by the AmpliSeq for Illumina Cancer Hotspot Panel version 2. Results: The study cohort comprised 409 patients, 202 women and 207 men. There were 275 gastric tumors (67.2%) and 134 non-gastric tumors (32.8%). Disease recurrence was recorded in 87 patients (21%) after a median follow-up of 64 months. Men with gastric tumors had inferior RFS compared to women (HR 2.18; 95% CI 1.07-4.45; P= 0.029), while there was no difference for non-gastric tumors (HR 0.77; 95% CI 0.44-1.33; P= 0.341). There was a substantial sex variation in the type of primary KIT mutation related to tumor location. Men with gastric tumors had a deletion or insertion-deletion that involved codons 557 and 558 (del557/558) more than twice as frequently as women (34% versus 16%; P= 0.008). Men also had slightly larger tumors (mean 6.6 cm versus 5.5 cm; P= 0.035) and more often tumors located in the upper third of the stomach, but there was no difference in mitotic count (23% versus 22% with > 5 mitoses per 5 mm2). There was no difference in adjuvant imatinib treatment between men and women. No sex differences in primary mutation, tumor size or mitotic count were observed for non-gastric tumors. When KIT del557/558 mutation was included in the Cox regression analysis for gastric tumors, sex was not significantly associated with RFS (HR 1.49; 95% CI 0.70-3.18; P= 0.303), while del557/558 mutation was a strong prognostic factor (HR 6.40; 95% CI 3.17-12.94; P< 0.001). Del557/558 mutation was not associated with RFS in non-gastric tumors (HR 0.67; 95% CI 0.33-1.35; P= 0.262). Conclusions: Women with localized, gastric GISTs had a lower risk of recurrence compared to men. There was no sex difference in outcome or baseline characteristics for non-gastric tumors. Men with gastric tumors more often had KIT del557/558 primary mutations, which may explain their inferior outcome. The observed sex difference in primary mutations in GISTs is unexplained and should be further explored.
Predicting the immunotherapy response based on molecular subtypes of pan-immune signatures in gastrointestinal stromal tumor.
Authors: Liu Ling , Wang Xiaohui , Dai Chan , Pei Zhihua , Zhou Qiming , Wang Dongliang
Published: June 2023

e23512

Background: Gastrointestinal stromal tumor (GIST) is the most common sarcoma, often originate in the stomach or the small intestine. Although the application of imatinib has brought a breakthrough in the clinical treatment of GIST, not all GIST patients are effective, and most GIST patients who receive imatinib sensitivity will develop drug resistance and eventually malignant progression. The tumor microenvironment (TME) is a key mediator of cancer progression and treatment outcome, and plays an important role in predicting cancer prognosis and treatment response. This study aims to investigate the role of TME in the treatment of GIST and the response to immunotherapy. Methods: Raw microarray data of 199 GIST patients were downloaded from GEO, including 159 KIT-mutant, 21 PDGFRA-mutant and 19 WT. All affymetrix datasets were re-normalized using the gcRMA package with default parameters. We integrated 275 TME and malignant signaling pathways related signatures from different database and previous researches, including CIBERSORT, MCP-counter, TIMER, and others. Fisher exact test's was used to identify signatures that differential between KIT-mutant, PDGFRA-mutant, and WT (p < 0.05), and 85 signatures were finally obtained. To classify the molecular profiles, the expression patterns were assessed in all 199 GIST patients using unsupervised clustering based on their ssGSEA scores, and can be clustered into three distinct microenvironments. Results: Using GSEA with all TME signatures genes ranked by the log2(fold change) between the threee clustes, we found that gene sets were considered immune favorable in cluster A, including gene sets related to activated CD8+ T cells (p = 0.0003)and activated CD4 T cell signaling pathway (p = 0.009). Cluster B enriched to the epithelial mesenchymal transformation pathway (p = 0.04) and TGFb signaling pathway (p = 0.003), cluster C enriched into DNA-repair pathway (p = 0.02). In an independent skin cutaneous melanoma cohorts (n = 86) treated with anti-PD-1 therapy, patients were classified into three molecular clusters, which significantly corrleated with response to ipilimumab (p = 0.007). The percentage of responders to anti-PD-1 therapy in cluster A was 75% in contrast to only 10% in cluster B. The three molecular clusters discern a potential responder versus non-responder (AUC = 0.87; p = 0.0015), with essentially a 80% chance of correctly predicting the response, which supporting the utilization of the classification method. Conclusions: In this study, the immuno-infiltrating landscape was characterized based on pan-immune signatures using transcriptomic profile in GIST. The molecular subtypes derived from pan-immune signatures have the potential to predict the efficacy of immunotherapy.
National overview of gastrointestinal stromal tumors: Experience from middle income setting.
Authors: Mkhitaryan Benik , Zohrabyan Davit , Safaryan Liana , Bardakhchyan Samvel , Arzumanyan Armen , Harutyunyan Martin , Mkhitaryan Armen , Sargsyan Amalya , Rushanyan Marine , Mkrtchyan Gohar , Mailyan Mariam , Karapetyan Nune
Published: June 2023

e23515

Background: Gastrointestinal stromal tumors (GISTs) are mesenchymal malignancies representing 1-2% of all gastrointestinal cancers. There is a general shortage of reported data on GISTs from the Republic of Armenia (RA). This paper aims to conduct a national assessment of the epidemiological, diagnostic, and treatment approaches of the GISTs in RA. Methods: The study utilizes a cross-sectional design. Five-year retrospective data on patients with the moderate and high-risk group has been analyzed (from August 31, 2016, up to February 01, 2023). Data has been obtained through medical records. It was feasible to apply census sampling since each GIST patient receives Imatinib in the Hematology Center after prof. Yeolyan free of charge and all the medical records are centered in this facility. Descriptive analysis has been done to demonstrate patients’ demographic characteristics, the spread of the disease, pathological and genetic features of the tumor, and performed treatment. Results: In total 69 moderate and high-risk patients have been targeted. That counts for about 1% of all GI tumors diagnosed in Armenia in 2021. The mortality rate was 10%. The male-to-female ratio was 1.56:1. Age range was 30-81 years (median 58). Advanced disease was observed in 31.9% of cases. The primary site of the tumor (gastric vs non-gastric) was not significantly associated with the disease stage (p-value: 0.192). Expression of CD34, CD117, and DOG1 was positive in 97.3%, 100%, and 96.7% of cases respectively. However, it is worth mentioning that data on immunohistochemical (IHC) features are lacking due to the incompleteness of medical records and the absence of a joint e-health system in Armenia. Furthermore, significant under-testing of the tumor genetic profile was observed. Only 3 patients were tested for KiT mutation (positive in all cases) and no one for PDGFRA mutation. Under-testing is caused by the high cost of genetic profiling which is covered out-of-pocket in RA. All patients received first-line tyrosine kinase inhibitors (TKI). Adjuvant or palliative radiation therapy (RT) was not applied. The majority of patients (95%) underwent tumor resection for curative or palliative purposes. Conclusions: Demographic and epidemiological profile of GISTs in RA is similar to the reported international data. In contrast, the rate of advanced diseases is higher in RA, possibly due to diagnosis delays. [Table: see text]
Treatment response prediction with circulating tumor cell-derived organoids for soft tissue sarcoma.
Authors: Liu Yang-Wei , Burnouf Thierry , Chang Chia-Yau , Chen Shu-Huey , Chen Yin-Ju , Chen Yi-Hsuan , Ho Wan-Ling , Liao Yu-Mei , Lin Pei-Chin , Liu Yen-Lin , Miser James S. , Wang Jinn-Li , Wang Peng Yuan , Wang Shih-Chung , Wong Tai-Tong , Wu Shih-Pei , Wu Yuan-Hung , Chiou Jeng-Fong , Lu Long-Sheng
Published: June 2023

e23521

Background: Pharmacologic treatment for soft tissue sarcoma (STS) remains challenging. There is a lack to predict treatment responses to chemotherapy or targeted therapy to oncologic drivers. We hypothesize that circulating tumor cells may enrich cancer initiating cells and represent a window to probe personalized drug treatment response. In this study, we test if drug sensitivity profile of short-term culture of tumor organoids derived from circulating tumor cells (CTCs) correlates to clinical treatment response. Methods: From April 2019 to December 2020, 50 patients with biopsy-confirmed STS, who had either recurrent or metastatic tumors, were enrolled in a prospective observational study in Taipei Medical University Hospital. The median age of the patients was 47, and the top 3 diagnoses were leiomyosarcoma, aggressive fibromatosis and rhabdomyosarcoma. 74% of patients had metastatic diseases at the time of blood collection. Fifty-five blood samples were collected and processed for CTC organoid culture and drug sensitivity analysis (EVASelect, CancerFree Biotech, Taipei, Taiwan), which involves culturing nucleated blood cells on a binary colloid crystal-coated surface. Clinical response was evaluated using RECIST criteria 3 months after blood collection. The relationship between CTC viability and clinical response was analyzed using a contingency table and Chi-square analysis. Results: The success rate of CTC expansion was 87.2% (48/55), as defined by ATP abundance higher than 3000 U2OS cells after 18 days of culture. Clinical information from 32 of the 50 cases was eligible for analysis, and the results showed that CTC viability at a 70% cutoff correlated with clinical disease control at 3 months after blood collection. The odds ratio, sensitivity, specificity, and diagnostic accuracy were 12 (p = 0.036), 92.3%, 50%, and 79%, respectively. A demonstration of the interaction between this research and the Molecular Tumor Board (MTB) in the Taipei Medical University Healthcare System is presented through a case study of metastatic angiosarcoma and its correlation. Conclusions: The study highlights the potential of using CTC drug sensitivity as a biomarker for precision medicine in STS, despite limitations such as small sample size, short follow-up, and disease and treatment heterogeneity. Advancements in gene-based precision medicine have been made in the past decade, but only a small number of STS patients have seen benefits from it. This emphasizes the need for further research to thoroughly evaluate the potential of CTC drug sensitivity as a predictive biomarker in clinical practice. Key words: soft tissue sarcoma; circulating tumor cells; liquid biopsy; predictive biomarker; precision medicine.
Methylation classifier array and classification of solitary fibrous tumors.
Authors: Chelsky Zachary L , Obeidin Farres , Alexiev Borislav A. , Santana-Santos Lucas , Duckett Drew , Parker Stephanie , Baczkowski Joseph , Pollack Seth , Vormittag-Nocito Erica , Jennings Lawrence J
Published: June 2023

e23522

Background: Solitary fibrous tumors (SFTs) are fibroblastic tumors which carry a characteristic NAB2::STAT6 gene rearrangement. SFTs represent a heterogenous group that may arise in multiple locations and have variable risk of progression. Despite a consistent oncogenic driver, there is little biological data explaining this variability. Recently, the German Cancer Research Network (DKFZ) have modified their brain tumor methylation classifier for use in sarcomas. We subjected solitary fibrous tumors diagnosed at our institution to a validated, in-house sarcoma methylation array classifier modeled after that of the DKFZ in order to assess for differences in methylation patterns that may account for biological or clinical variances. Methods: Twenty-eight primary site SFTs from 2011-2021 were subjected to the sarcoma methylation classifier. Histologic diagnosis was confirmed by STAT6 immunohistochemistry or by the presence of the NAB2::STAT6 fusion. The methylation classifier was run on the Illumina iScan platform and the resulting IDAT files were analyzed via a custom bioinformatics pipeline. The sarcoma classifier was trained using the same samples and normalization strategies used by the DKFZ group and validated using the same publicly available samples. Results: Methylation data for each tumor was collected, given a classification score, and visualized by t-distributed stochastic neighbor embedding (t-SNE). We noted three distinct groups of SFTs on the t-SNE plot. Group 1 was comprised of all eight intracranial SFTs and were correctly classified as SFT (classifier score ≥0.9). Group 2 contained nine pleural-based tumors and one SFT each from the mediastinum and bladder wall. Classification was successful in only seven of eleven tumors. Group 3 SFTs predominantly arose in the soft tissues or bone (two pelvis, four extremity, and one mediastinum) and all failed accurate classification. Finally, two orbital SFTs stratified separately from all groups on t-SNE plot but did achieve an appropriate classification. There were no significant differences in grade or risk stratification among the three groups. Conclusions: Our preliminary data show differential clustering based on tumor location, suggesting biological differences between intracranial, pleural/visceral, and connective tissue locations. These results highlight the heterogeneity of these tumors and the inadequacy of the current methylation classification scheme for SFT. Future directions will include analysis of additional cases, gene expression patterns, and outcome data.
Pegylated liposomal doxorubicin combined with ifosfamide for advanced soft tissue sarcomas: A phase I dose-escalation study.
Authors: Ye Ting , Fan Li , Cao Rubo , Peng Ling , Chen Jing
Published: June 2023

e23525

Background: Doxorubicin combined with ifosfamide (IFO) is one of the preferred treatment options for non-specific soft tissue sarcomas (STS), but is limited by cumulative cardiotoxicity and severe myelosuppression. Pegylated liposomal doxorubicin (PLD) provides an effective alternative to conventional anthracyclines with reduced toxicity. However, there is no standard dose recommendation for PLD combined with IFO for STS. The present study aimed to investigate the maximum tolerated dose (MTD) of PLD combined with IFO in advanced STS patients. Methods: This was a phase I, open-label, single-center, dose-escalation study. Patients with locally advanced or metastatic STS were enrolled, except for gastrointestinal stromal tumors, Ewing's sarcomas, embryonal rhabdomyosarcomas, and alveolar rhabdomyosarcomas. We used a standard 3 + 3 dose-escalation design with progressively increasing PLD and IFO (3 g/m2 per day for 3 days, q3w) for one cycle, with a dose escalation ranged from 30 to 70 mg/m2 (5mg/m2 increment per step). The primary endpoint was determination of the MTD, and the secondary endpoint was the incidence/severity of adverse events (AEs). Results: From January 2020 to September 2022, 23 patients were enrolled in this study, including 3 patients at doses 30-45 mg/m2, 6 patients at dose 50 mg/m2, and 5 patients at 55 mg/m2. The median age was 49 years (ranges from 30 to 68 years), the male/female ratio was 12/11, and 22 (95.65%) patients had stage IV disease (AJCC staging system). Initially, no DLT was observed at doses of 30-50 mg/m2, with 3 patients in each dose phase. Two patients developed DLTs at the 55 mg/m2 dose, resulting in the 50 mg/m2 dose extending to a total of 6 patients who completed treatment without DLT. The DLTs at dose 55 mg/m2 of the first patient were grade 4 neutropenia lasting ≥ 5 days and grade 3 thrombocytopenia with hemorrhage tendency; the second patient had grade 4 neutropenia lasting ≥ 5 days, grade 4 thrombocytopenia relapsed after platelet transfusion, and grade 3 increased alanine aminotransferase. Therefore, the MTD of PLD was 50 mg/m2. The most common (≥ 10%) grade 3-4 AEs in all patients were lymphopenia (56.52%), neutropenia (82.61%), leukopenia (86.96%), and thrombocytopenia (13.04%). Conclusions: For patients with locally advanced or metastatic STS, single cycle PLD combined with IFO had a tolerable AE profile, with an MTD of 50 mg/m2 for PLD. Further researches are needed to confirm the multi-cycle recommendation. Clinical trial information: ChiCTR1900028270 .
Diverse genomic characterization of Chinese patients with osteosarcoma and soft tissue sarcoma.
Authors: Sun Mengxiong , Quan Fei , Yi Huan , Lu Zhongyu , Yu Yangyang , Chen Siqi , Ding Ran , Deng Wanglong , Bu Fanfeng
Published: June 2023

e23528

Background: Osteosarcoma(OST) differs from soft tissue sarcoma(STS) in terms of pathology and chemotherapy, but there is partial overlap in targeted therapy. Few articles have described the differences in genetic profiles of OST and STS in Chinese patients based on extensive sample data, at this point, identifying the difference genomic characterization between them may provide new drug targets for clinical diagnosis and treatment. Methods: A 551-gene targeted panel of DNA-based Next Generation Sequencing (NGS) assay was performed on tumor tissue(n = 613) and plasma(n = 136) obtained from STS(n = 586) and OST(n = 163) patients, the majority were male(n = 430, 57.4%), median age was 49(range 1-87), 101 patients also measured additional 67 gene fusions based on RNA-seq in tumor samples. All variants (SNV, INDEL, CNV and fusion) were entered into the result analysis. PD-L1expression was tested by IHC(SP263). Results: The top 5 mutant genes were TP53(28%), CDK4(20%), MDM2(18%), CDKN2A(15%), CDKN2B(15%) in STS, and TP53(26%), MYC(19%), CDK4(18%), MUC16(13%), CDKN2B(13%) in OST respectively. MDM2(18% vs 10%, p = 0.030) and PTEN(11% vs 4%, p = 0.007) were significantly higher in STS, while GNAS(7% vs 3%, p = 0.045) and IDH1(5% vs 1%, p = 0.002) were more common in OST. The most frequently affected pathways were Cell cycle(42%), Genome integrity(34%), RTK signaling(27%) in STS and Cell cycle(36%), Genome integrity(33%), transcription factor(28%) in OST. Additional significantly co-altered genes were RB1/PTEN, LRP1B/FAT3, FAT2/SPTA1 in STS, and MUC16/LRP1B, LRP1B/POLE, MED12/STAG2 in OST. More rare fusions were identified in STS. Wefound 15 PTPRB fusions, 14 of which were from STS. MDM2 fusions only detected in STS, 8 of which were from liposarcoma. Almost all patients were defined as MSS(625/629), with only 4 MSI-L and no MSI-H. 2.9%(17/589) STS and 3.1%(5/163) OST scored as TMB-H(≥10.00 Muts/Mb). TP53(p＜0.001), MUC16(p＜0.001), LRP1B(p＜0.001), FAT3(p＜0.001)were more likely to appear in the TMB-H group of STS, while MUC16(p＜0.001) was more likely to appear in TMB-H group of OST. 32.3%(83/257) STS and 29.6%(8/27) OST were PD-L1-positive(PD-L1≥1%). In STS, PDCD1LG2(p＜0.001), CD274(p＜0.001) and JAK2 (p = 0.001)were more common in the PD-L1-positive group, while MDM4 (p = 0.018) and PARP1(p = 0.003)were more common in the PD-L1-negtive group. There were no statistically significant differences due to limited PD-L1 data in OST. Conclusions: The analysis revealed that there are some differences in genetic profiles between Chinese OST and STS, which may provid more precise basis for personalized targeted therapy and immunotherapy.