bluuebunny/crossref_metadata_2025_split huggingface dataset:
Developing a deep learning algorithm to support decision making for the classification of microsatellite instability (MSI) in cancer, using artificial intelligence(AI).
Authors: Pombo Maria Teresa , Chirkes Julieta , Erbetti Andrea , Sanguinetti Olivia , Perez Adrian , Paschetta Federico , O'Connor Juan Manuel , Gorodisch Ana 
Published: June 2024

11152 Background: Digital pathology (DP) is an image-based environment, which allows the acquisition, and interpretation of pathological information from a digitized slide. The objective of this work was to build an AI model for predicting MSI in endometrial, colorectal, and gastric carcinomas, to simplify laboratory processes, in a developing country. Nowadays, it is crucial to recognize patients who will respond to treatments such as immunotherapy. Methods: The computational tool utilized was CLAM (clustering-constrained-attention multiple instance learning). This architecture developed by Lu et al. is a deep learning method that utilizes weak supervision and attention based learning, to identify the most relevant regions for tumor classification, in whole slide images (WSI). CLAM was designed to excel in tumor subtyping tasks which are discernible to human visual perception. We are challenging this architecture by employing it in the detection of a molecular phenomenon. For training and internal evaluation, images from TCGA and CPTAC were obtained for endometrial cancer (EC). For colorectal (CCR) and gastric cancer (GC), only images from TCGA. Archived histological samples with MSI/MMR status from a donor lab , were used for external validation. Results: Tests conducted on an internal cohort of 58 samples for CCR and GC revealed a sensitivity of 76.9%, a specificity of 78.1%, and an AUC-ROC of 76.3%. In the case of EC, where 38 cases were evaluated, the sensitivity was 100%, specificity was 68%, and AUC-ROC reached 92%. Notably, regarding the externalcohort consisting of 109 samples, both models demonstrated a high sensitivity of up to 90% in recognizing positive cases. Due to the models’ specificity (approximately 45%), it was not possible to accurately predict MSS samples in all three types of tumors. Conclusions: Promising results were obtained for the first approach in detecting molecular biology events, such as MSI, using AI. CLAM is a useful platform for digital pathology, but new validations are needed to enhance our work and strengthen the model. It is hypothesized that CLAM may not be the best tool for AI in identifying molecular biology events, so other directions are being explored. For external cohorts, preanalytical changes play an important role in obtaining accurate results with scanners and digitalization. It is crucial to teach healthcare professionals about AI in order to ensure its availability, in every diagnostic laboratory.
Real-world treatment patterns and outcomes of zanubrutinib in chronic lymphocytic leukemia and small lymphocytic leukemia (CLL/SLL).
Authors: Krackeler Margaret , Chee Bryant , Orchanian Arthur K , Law Lisa Y. , Lopez Alfredo R. , Buchanan Susan , Maglinte Gregory A. , Liu Raymond , Zhu Zheng , Sakoda Lori C. , Tavakoli Jahan 
Published: June 2024

11158 Background: Zanubrutinib (zanu) is a next-generation selective Bruton’s tyrosine kinase inhibitor (BTKi) with superior efficacy over first generation ibrutinib (ibru) in CLL/SLL patients (pts). Herein we present real-world treatment patterns based on a formulary change from ibrutinib to zanubrutinib in pts with CLL/SLL in an integrated community oncology practice. Methods: We retrospectively analyzed CLL/SLL pts 18 years and older who received at least 3 months of zanubrutinib from October 1, 2018 to September 15, 2023 at Kaiser Permanente Northern California. Treatment patterns, treatment-emergent adverse events (TEAEs: AEs reported during BTKi use), treatment-limiting adverse events (TLAEs: AEs leading to BTKi discontinuation), and mortality were reported. Results: A total of 281 pts received zanu (median age: 71 years; 64% male); 190 pts switched from ibru (ibru-zanu), and 91 pts received zanu only. Most pts were White (75%) followed by Black (10%). Compared with ibru-zanu pts, zanu-only pts were older (median age 74 vs 69 years) and had more comorbidities but were comparable in sex, race, and insurance type. The primary reasons for switching to zanu were formulary change (73%) and progression (15%). Median follow-up time after initiation of first BTKi was longer in the ibru-zanu group (Table). Similar TEAE rates were seen with use of both BTKi therapies, with lower TLAE rates with zanu (Table). Most common TLAE were atrial fibrillation and fatigue for ibru, and cytopenias and rash/bruising for zanu. Cardiac TLAE and non-TLAE rates overall were higher with ibru than zanu, and the rates decreased while on zanu after switching from ibru (Table). Dose modification occurred in 34 pts on ibru and 50 pts on zanu (18 ibru-zanu pts, 32 zanu-only pts), with reductions primarily for grade 1-2 AEs. Of the 281 pts who received zanu, 79% remain on treatment at the end of data collection; 13 pts died (8 from infection, including 5 from COVID), with no reports of treatment-related deaths. Conclusions: In the real-world setting post-formulary change, zanu is effective and safe in pts with or without prior ibru use. Zanu use had lower cardiotoxicity and TLAE rates than ibru though data was limited by a difference in follow-up time. Similar results were seen in zanu-only pts despite being older and having more comorbidities, with discontinuation most often due to grade <3 AEs. [Table: see text]
The benefit of chart curation of electronic health record (EHR) data: Comparing data completeness between curated and structured data.
Authors: Blanc Simon , Rui Anna , Vasudevan Anupama , Gart Mike , Sura Teena , Morgan Erin , Varughese Prateesh , Mena-Allauca Mercedes , Scott Jeffrey A. 
Published: June 2024

11165 Background: The main objective of an EHR is to effectively standardize clinical workflow. However, EHR data is also utilized extensively as secondary data for clinical research and quality improvement. Healthcare data exists in different forms such as paper, digital images, and notes, only some of which are recorded as structured data in the EHR. It is therefore essential to curate detailed information from unstructured data so that the patient’s journey can be understood in depth for research and quality studies. Methods: Patients diagnosed with metastatic breast cancer (mBC) between 01-Jan-2020 and 31-Dec-2022 were identified from the Integra Connect PrecisionQ de-identified database of 3 million cancer patients across 500 sites of care across ~80% community oncology and ~20% academic practices. Manual curation was conducted for a sample of these patients and the fill rates of crucial elements were captured as part of this study. Results: A total of 13,763 mBC patients were identified during this study period. The availability of data for the different variables was assessed from structured data in 13,120 patients. Additional information was obtained by manual curation for 643 patients. Information on staging and grade were available for 62.8% in the structured data, while curation increased the availability of these details to 99.5% among those 643 patients. The fill rates for patients’ tumor size and nodal status, as defined by the T and N values, were found to be 99% in the curated data compared to 60% in the structured data. Similarly, the fill rates were more than 98% for estrogen, progesterone, and HER2 receptor by curation, while they were only approximately 65% in the structured data. HER2 low, HER2-ve, and HER2+ve status was identified in 8%, 45.2%, and 10.1% by structured data and in 57.1%, 84.1%, and 14.0%, respectively, by curated data. Furthermore, the fill rates via curation were 97.1% for HER2 immunohistochemistry tests compared to 49.0% for structured data, while the fill rates for in-situ hybridization (ISH) or fluorescent in-situ hybridization (FISH) tests were 61.3% for curated data compared to 28.4% for structured data. This discrepancy is caused by the fact that IHC and FISH/ISH tests are primarily found only in PDF format. Conclusions: This study highlights the need for curation in order to maximize the utilization of EHR data for secondary research purposes and quality studies. Natural language processing and augmented curation methods can further enhance the quality of EHR data for secondary research.
Fragility index analysis of systemic therapy clinical trials in soft tissue sarcoma (STS).
Authors: Braik Dina , Wilson Brooke , Abdul Razak Albiruni Ryan , Salawu Abdulazeez 
Published: June 2024

11581 Background: The fragility index (FI) measures the robustness of randomized clinical trials (RCT) that have positive results based on statistical p-values. It estimates the minimum number of events that are needed to reverse the trial results from positive to negative. Here, we perform FI analysis on RCTs evaluating systemic treatments for STS. Methods: A systematic search of the Medline and Embase databases for RCTs in adults with advanced STS (Jan 1998 to Dec 2023) was conducted. Gastrointestinal stromal tumor trials were excluded. The FI framework was adapted to allow the use of time-to-event (TTE) outcomes – progression-free survival (PFS) or overall survival (OS) as previously described (Desnoyers et al 2021). Survival tables were reconstructed from published data on positive TTE outcomes, using the Parmar Toolkit. Positive secondary endpoints were used only if the primary endpoint was negative. The number of additional events that would result in a non-significant effect for the hazard ratio (HR) of the positive endpoint of each trial (FI) was calculated and expressed as a proportion of the size of the experimental arm (fragility quotient; FQ). The number of censored patients – those who withdrew consent or were lost to follow-up (Cn) was noted. Results: Among 47 RCTs, 16 (8 phase II; 8 phase III) trials had positive outcomes. The primary endpoint was positive and used for FI analysis in 11/16 trials (68.8%). PFS was the most common positive outcome, evaluated in 13 trials (81.3%). The median FI was 6 (range 2 – 52), with FI < 10 observed in 11 trials (68.8%). Median FQ was 7% (range 1 – 59%) and 10 trials (62.5%) had FQ < 10%. Among 14 trials that reported data, Cn was ≥ FI in 7 trials (50%). Only 2 of 4 trials (50%) that led to regulatory approval had FI > 10 or FQ > 10%. Of the other 2, one drug approval was subsequently withdrawn (Table). Conclusions: Most positive clinical trials in STS were fragile and their outcomes may be confounded by the level of censoring. Real-world evaluation of approved systemic therapies and value scales such as ESMO Magnitude of Clinical Benefit scale or ASCO value framework are needed to confirm clinical benefit of systemic treatments in STS.[Table: see text]
Systemic therapy in NF-1 associated malignant peripheral nerve sheath tumors (MPNST).
Authors: Munnangi Pujita , King Bridgette L , Chiang Y. Sabrina , Conley Anthony Paul , Araujo Dejka M. , Livingston J. Andrew , Ludwig Joseph Aloysius , Nakazawa Michael , Nassif Haddad Elise F , Ravi Vinod , Ratan Ravin , Zarzour Maria Alejandra , Patel Shreyaskumar , Torres Keila E , Somaiah Neeta 
Published: June 2024

11583 Background: MPNST are rare sarcomas that have a poor prognosis and are challenging to treat. Around 50% of MPNSTs are associated with NF1, 40% are sporadic, and 10% are radiation-associated. Doxorubicin (D) based chemotherapy (CT) regimens are commonly used in the front-line, and combinations have better response rates than single agents. Response to second-line regimens is not well documented. The objective of this study is to document efficacy of systemic regimens in MPNST as a benchmark for future novel therapeutics in this space. Methods: 72 patients (pts) with NF1-associated MPNSTs in an MD Anderson database were reviewed retrospectively from EMR. Variables collected included demographics, primary MPNST location, localized vs metastatic, and treatments received (+/- radiation, +/-surgery, +/- lines of CT). Responses (progressive disease (PD), stable disease (SD), partial response (PR)) as interpreted by treating physician and radiology reports and time on treatment for 1st and 2nd line chemotherapy regimens were assessed. Cox proportional-hazard regression was used to investigate associations of variables with overall survival (OS: from time of diagnosis to death or last follow-up). Results: Demographic and CT details are provided (Table). The median age at diagnosis was 34.5 yrs (range: 9-71). The most common MPNST location was the trunk (56.94%). D based regimens were the most frequent 1st-line CT (65.7%), and gemcitabine- docetaxel was the most frequent 2nd-line CT (33.3%). In pts with metastases, 74.4% got 1st line, 44.7% 2nd line, 25.5% 3rd line, and 12.7% got 4th line therapy. Median follow-up was 2.46 yrs (IQR 1.24-9.52). The median time on treatment for 1st and 2nd line CT was 110 (IQR 48-153) and 57 (IQR 41-133) days, respectively. In the multivariate COX model for the entire cohort, male sex (HR: 0.35, 95%CI: 0.18-0.68), lower extremity primary (HR: 0.09, 95%CI: 0.02-0.40), and absence of metastases at last follow up (HR: 0.05, 95%CI: 0.02-0.17) were associated with decreased risk of death. Additional analysis on efficacy and survival of the systemic therapy regimens will be presented at the meeting. Conclusions: In this study < 50% pts with advanced NF1 related MPNST made it to 2nd line CT and outcomes were inferior to the predominantly D based 1st line regimens. This highlights an area of high unmet need. [Table: see text]
Off-label use of fam-trastuzumab deruxtecan-nxki with early activity in a cohort of patients with desmoplastic small round cell tumor.
Authors: Slotkin Emily K , Burke Chelsey , Hameed Meera , Antonescu Cristina R. , Agaram Narasimhan P , Bhanot Umesh , Behr Gerald , Price Anita , Pandit-Taskar Neeta , Domenico Dylan , Glade Bender Julia Lynne , Dela Cruz Filemon S , Reed Damon R. 
Published: June 2024

11584 Background: Desmoplastic small round cell tumor (DSRCT) is a rare and aggressive sarcoma occurring predominantly in pediatric, adolescent and young adult biologic males, and is molecularly characterized by the pathognomonic EWSR1-WT1 fusion. Despite aggressive multi-modality therapy outcomes for those with DSRCT remain poor, and more effective therapies are urgently required. Prior pre-clinical data and transcriptomic analyses of DSRCT patients has suggested the relevance of the ERBB2 pathway in this disease, prompting the off-label use of fam-trastuzumab deruxtecan-nxki (T-DXd) in the treatment of patients of DSRCT patient with relapsed and refractory disease. Methods: Patients with relapsed/refractory DSRCT received T-DXd 5.4 mg/kg intravenously in 21-day cycles. Whole body PET and CT of the chest, abdomen and pelvis were used for monitoring. Response was correlated with HER2 immunohistochemistry (IHC) status and transcriptomic analysis by RNA sequencing (RNAseq) when available. Results: Seven patients received the agent, and at the time of submission 3 patients had at least one follow up imaging test after receiving between 6 and 9 cycles of T-DXd. Treatment was overall well tolerated with the only grade 3 toxicity of transaminitis (in patients with known liver metastases), which self-resolved. All other toxicities including constipation, nausea, and fatigue were grade 2 or less. All 3 patients have experienced clinical benefit including one patient with a RECIST 1.1 partial response and two patients with stable disease. Additionally, favorable responses were noted by PET imaging. Four additional patients with relapsed/refractory DSRCT have initiated off-label treatment with T-DXd and are pending imaging responses. 7/7 and 4/7 patients have available IHC and ERBB2 RNA expression data available respectively. All ERBB2 RNA expression data is elevated when compared with the median across all evaluated pediatric tumors in our institutional series. Conclusions: The use of anti-HER2 therapy in a limited and unselected group of heavily pre-treated DSRCT patients is demonstrating an early signal of activity with minimal toxicity and suggests that formal assessment as monotherapy or in other relevant combinations in clinical trials is warranted. Further correlation with IHC and RNAseq expression data may help optimize correlatives and/or generate biomarkers for future clinical trials.
Patient-reported symptom interference with activity- and mood-related functioning prior to start of an early-phase oncology combination trial including immune checkpoint blockade.
Authors: George Goldy C , Piha-Paul Sarina A. , Dumbrava Ecaterina Elena , Subbiah Vivek , Fu Siqing , Tsimberidou Apostolia Maria , Pant Shubham , Appleton Grace , Noor Laila , Yap Timothy A. , Rodon Ahnert Jordi , Meric-Bernstam Funda , Cleeland Charles S , Mendoza Tito R. , Hong David S. 
Published: June 2024

12084 Background: We examined symptom interference with activity- and mood-related functioning at baseline in early-stage trials of combination treatments that included at least one immune checkpoint inhibitor, and its association with quality of life (QOL)-, clinical-, and trial-related factors. Methods: Patients scheduled to begin an early-phase trial of a combination treatment with immune checkpoint blockade, and who had not received trial-related treatment were recruited into a prospective longitudinal study design (NCI R01CA242565), and completed the following validated patient-reported outcome (PRO) measures prior to trial start: MD Anderson Symptom Inventory- Immunotherapy (score range: 0-10, higher scores = worse symptom interference); NCI’s PRO Common Terminology Criteria for Adverse Events (0-4, higher = worse severity); EuroQoL-5 dimensions assessing health status (0-100, higher = better health) and problems with self-care, and the Sloan Global QOL scale (0-10, higher = better QOL). Statistical tests included Spearman’s correlation rho (r) and multivariable linear regression. Results: 977 baseline PRO measures were completed by 247 patients (median age = 59 y; 46% female). Worst symptom-related interference was with activity (3.0 on a 0-10 scale), work (2.9), and enjoyment of life (2.4). Composite score means were 2.8 for symptom interference with walking, activity, and work (WAW; activity-related functioning), and 2.1 for interference with relationships, enjoyment of life, and mood (REM; mood-related functioning). Symptoms most associated with worse WAW were fatigue (P<0.001) and appetite loss (P=0.001). Worse WAW was linked to worse REM (r=0.78, P<0.001). Diminished sexual interest/mood (DSI) was associated with worse WAW (r=0.35, P<0.001) and REM (r=0.33, P<0.001). Worse WAW was linked to shorter trial duration (P=0.003) and worse response (progression of disease/immune-related progression) on the clinical trial (P=0.05). Conclusions: This first, comprehensive and prospective examination of symptom interference with functioning at trial baseline found that worse symptom interference was linked to worse QOL, poorer clinical outcomes, and shorter trial duration. These findings suggest that baseline patient-reported symptom interference with functioning can serve as a potential biomarker of poor prognosis in investigational trials, and that trial patients may benefit from initiation of supportive care prior to trial start. [Table: see text]
Prescribers of opioids for head and neck cancer (HNC) survivors.
Authors: Salz Talya , Mishra Meza Akriti , Bradshaw Patrick T , Jinna Sankeerth , Moryl Natalie , Kriplani Anuja , Tringale Kathryn Ries , Flory James , Korenstein Deborah , Lipitz-Snyderman Allison 
Published: June 2024

12085 Background: Older HNC survivors often experience post-treatment pain, and they have concerningly high rates of unsafe opioid prescribing per CDC guidelines (e.g., high doses, concurrent benzodiazepines). Because interventions to improve opioid safety should target providers who prescribe opioids to HNC survivors, we aimed to identify post-treatment opioid prescriber specialty. Methods: Using the national linked Surveillance, Epidemiology, and End Results (SEER) registry and Medicare claims data, we identified adults age >65 diagnosed 2014-2017 with stage I-III HNC and who had ≥6 months treatment-free follow-up prior to censoring at further treatment, new cancer, hospice, death, or end 2019. Each opioid fill was assigned to a prescriber specialty: oncology (medical, radiation), surgery, primary care (internal medicine, family practice, geriatrics), pain, or other. Prescriber patterns (number of fills, duration of fill, annual opioid receipt) were summarized across follow-up and stratified by year. Multinomial logistic regression models captured trends in prescribing, accounting for clinical and sociodemographic characteristics. Results: Among 5547 HNC survivors, 2951 (53%) had ≥1 opioid fill (median 2.1 years follow-up). Primary care providers (PCPs) prescribed 49% of all fills (46%-53% each year). PCPs prescribed opioids to 49% of survivors with ≥1 opioid fill, a greater share than other specialties. PCPs prescribed longer supplies of opioids (median 30 days/fill and median 45 days/year) than oncologists or surgeons. The likelihood of an opioid being prescribed by an oncologist or surgeon was ≥5 times lower than by a PCP. Over follow-up, rates of opioid prescribing by oncologists decreased relative to rates of prescribing by PCPs (Table). Conclusions: Primary care involvement in opioid prescribing remains high over post-treatment HNC survivorship. Interventions to address unsafe opioid prescribing for HNC survivors should target the primary care setting, as is typical for opioid-reduction efforts in the non-cancer population. [Table: see text]