tbuckley/cabot-search huggingface dataset:
Screening oncology articles in a qualitative literature review using large language models: A comparison of GPT4 versus fine-tuned open source models using expert-annotated data.
Authors: Kristian Thorlund, Lucy Lloyd-Price, Reza Jafar, Milad Nourizade, Claire Burbridge, Stacie Hudgens
Journal: Journal of Clinical Oncology (2024)

e23196 Background: Clinical Outcome Assessment (COA) conceptual gap analyses for oncology are complex and time consuming. Artificial Intelligence may efficiently reduce time to completion of such analyses. We aimed to assess two AI models’ performance for literature screening to identify relevant qualitative oncology research. We also compared accuracy and run-time for both AI models. Methods: We manually curated a dataset of title/abstract screening (n = 1,700 study references) across 17 landscape reviews. Among these, 11 landscape reviews (n = 951 study references) spanning over were in oncology, including 8 solid cancers (breast, lung, urothelial, colorectal, esophageal, head and neck, pancreatic, and stomach) and 3 non-solid cancers (lymphoma, acute myeloid leukemia, and multiple myeloma). Each citation was annotated for eligibility (Y/N) by population, study design (qualitative), and reporting of concepts (how patients feel or function). We then compared the accuracy of two AI models at predicting the screening decisions of expert researchers. The two AI models were Generative Pre-trained Transformers 4 (GPT4, OpenAI) prompts and a fine-tuned SciFive biomedical large language model (LLM). We used 70% of the data for training and 30% for test. Accuracy estimates were obtained only for the models’ ability to label eligibility within the 11 oncology datasets. Results: Both LLMs performed well for assessing relevance by oncology population, with F1-scores for the GPT4 and SciFive models being 0.92 and 0.83 respectively (precision was 0.92 and 0.93 respectively). For concept reporting the fine-tuned SciFive model outperformed GPT4 with an F1-score and precision 0.88 and 0.92 versus 0.81 and 0.79. The same was true but less pronounced for eligibility by study design, with an F1-score and precision 0.81 and 0.90 versus 0.86 and 0.76. For overall eligibility, the customized SciFive model outperformed the GPT4 model with an F1-score and precision of 0.84 and 0.92 versus 0.85 and 0.82. Lastly, it took the GPT4 prompts between 10-30 minutes to screen 100 abstracts. By contrast, the customized SciFive model took 1-2 minutes on a computer with a Quadro RTX 8000 GPU. Conclusions: In conclusion, both AI models are promising. The fine-tuned SciFive model appears slightly more accurate and performs substantially faster than the GPT4 model.
A phase I/II trial of neoadjuvant pegylated arginine deiminase (ADI-PEG 20) with ifosfamide and radiotherapy in soft tissue sarcomas (STS) of the trunk or extremity.
Authors: Mia C. Weiss, Sasha Haarberg, Chongliang Luo, Angela C. Hirbe, Anthony J. Apicelli, D. Ian English, Brian Andrew Van Tine
Journal: Journal of Clinical Oncology (2024)

TPS11591 Background: Outcomes for the treatment of metastatic STS remain poor. Better therapies are needed for local and distant control. Arginine is essential to neoplastic growth, yet up to 88% of STS do not express argininosuccinate synthetase (ASS1), an enzyme necessary to produce arginine. ADI-PEG 20 is a microbial enzyme that degrades arginine causing auxotrophy in cancer cells that are ASS1 negative. Pre-clinical data demonstrates that arginine deprivation shunts glutamine towards oxidation via the TCA cycle, thus depleting glutathione stores and increasing oxidative stress to the cell. We hypothesize that the combination of ADI-PEG 20, ifosfamide, and radiation therapy can potentiate cellular death. The encouraging safety and clinical data from the ADI-PEG 20 + radiation + temozolomide trial (NCT04587830) further support this combination. We are conducting a phase I/II trial examining the safety and tolerability to determine the recommended phase II dose (R2PD) and evaluate the efficacy of ADI-PEG 20 in combination with ifosfamide and radiation in patients with high-grade STS. Methods: Eligible patients include untreated intermediate or high-grade extremity or truncal STS planned for definitive resection with performance status 0-1 and adequate organ function. Metastatic disease is exclusionary as well as receiving prior treatment for the study cancer. The total number of patients to be enrolled is approximately 35. Up to 15 patients will be enrolled in the phase I portion with a 3 + 3 dose escalation design with ADI-PEG 20 in combination with escalating doses of ifosfamide and radiation. The primary objectives include determining safety and tolerability as well as the recommended phase II dose (RP2D). Patients will be treated neoadjuvantly with ADI-PEG 20 dosed once weekly starting on Cycle 1 Day -7 with ifosfamide for up to three cycles in combination with standard radiotherapy given over approximately 5 weeks. Ifosfamide will be administered on Days 1 - 5 of all 3 cycles. The phase II participants will receive the combination with ifosfamide at the RP2D determined during phase I. The primary objective of the phase II portion is to determine the percent necrosis and pathologic complete response (pCR) at the time of resection. These endpoints will be summarized by proportions along with the associated 2-sided exact 95% CIs. Assuming the true pCR rate is 25%, enrolling 20 patients will result in a 90% CI for estimating the pCR (10%, 45%). The trial has begun accrual and is soon to open at multiple sites. Clinical trial information: NCT05813327 .
Sleep apnea and glymphatic dysfunction as a mediator of executive dysfunction and neurodegenerative risk in cancer related cognitive impairment (CRCI).
Authors: Sophie Kushman, Alique Gabrielle Topalian, Rhonna Shatz
Journal: Journal of Clinical Oncology (2024)

12091 Background: Cancer survivors often experience cognitive changes, formally known as Cancer-Related Cognitive Impairment (CRCI), during or after treatment. CRCI commonly consists of executive dysfunction, which includes impairments in short-term memory, sustained attention/inhibitory control, cognitive flexibility, processing speed, and top-down processing. CRCI may be impacted by comorbidities and can increase neurodegenerative disease risk. Sleep disorders and disruptions (SDs) impair executive function in the general population. SDs may contribute to CRCI by impeding progression to deep sleep stages associated with enhanced glymphatic flow (GF) and clearance of inflammatory byproducts, leading to ventriculomegaly (VM- enlarged ventricles). VM is associated with cognitive impairment in other disorders, such as normal pressure hydrocephalus. Using data from the University of Cincinnati Cancer Cognitive Registry, we investigated relationships between the incidence and type of SD in CRCI, SDs and executive dysfunction, and evidence of altered GF in SD as measured by Evans Indices (EIs). SDs are known to be prevalent in CRCI patients. We hypothesize that evidence of impaired GF as measured by EIs will be present and associated with SDs and executive dysfunction. Identifying modifiable contributors to CRCI and their mechanisms of action are critical steps towards increasing quality of life in survivors. Methods: 174 patients referred for CRCI between 10/2021-10/2023 underwent assessments for CRCI and sleep hygiene with a cognitive battery, subjective questionnaires, and nocturnal polysomnography. Retrospective data gathered from Epic was entered into a REDCap registry. MRIs were analyzed in McKesson to calculate EIs. Results: Our data demonstrated the presence of SDs in 84% of patients and obstructive sleep apnea in 45%. Measures of apnea severity (apnea-hypopnea index-AHI) and GF (EIs) inversely correlated with executive function scores. This implicates sleep-related GF as a potential mediator of CRCI. Conclusions: CRCI and accompanying increased neurodegenerative risk may be the result of restricted cerebral spinal fluid exchange due to SDs in conjunction with systemic inflammation from cancer and its treatment. Sleep assessments should be routine in CRCI evaluations. Longitudinal assessments will help determine the relationship of SDs and their treatment to the course of CRCI and risk of neurodegenerative disease.
Real world effectiveness of immunotherapy combined with anti-angiogenic therapy in patients with anthracycline-resistant soft tissue sarcomas.
Authors: Mengye He, Suzhen Xu, Xiaoting Wang, Xiaochen Zhang, Peng Shen
Journal: Journal of Clinical Oncology (2024)

e23543 Background: Soft tissue sarcomas are a heterogeneous group of malignant tumors of mesenchymal origin with more than 50 histologic subtypes. They have distinct molecular, genetic and clinical features and account for 1% of adult malignancies, the most common being liposarcoma, undifferentiated pleomorphic sarcoma and leiomyosarcoma. Immune checkpoint inhibitors (ICIs) have limited efficacy in sarcomas compared to other solid tumors; however, they have shown some activity in certain subtypes. The use of immunotherapy in sarcoma faces many challenges due to tumor heterogeneity, scarcity of therapeutic antibodies and chimeric antigen receptors to target antigens in sarcoma subtypes. However, combining ICIs with other therapies seems to improve the therapeutic efficacy to some extent. Antiangiogenic targeted therapy has been recommended by major guidelines as the treatment of choice for second-line soft tissue sarcomas. However, there are limited results from large clinical studies on whether immunotherapy combined with antiangiogenic therapy improves the efficacy. Methods: In this real-world single-center retrospective cohort study conducted at the First Affiliated Hospital of Zhejiang University School of Medicine, the efficacy of immunotherapy combined with antivascular therapy was assessed by progression-free survival (PFS) and overall survival (OS). Safety was assessed using the Common Terminology Criteria for Adverse Events version 5.0. Results: In this study, we enrolled a total of 21 eligible patients, of which 6 were liposarcoma, 4 were leiomyosarcoma, 4 were rhabdomyosarcoma, and 7 were other types. The immunotherapy used in all patients was anti-PD-1 antibody, with bevacizumab as the antivascular therapy drug in four of them and antiangiogenic tyrosine kinase inhibitors in the others. 12(57%) patients had received one-line therapy, 9 (43%) had received ≥ second-line therapy. Median progression-free survival (mPFS) was 5.5 months and median overall survival (mOS) 16.1 months in the total population. mPFS was significantly longer in 2 nd -line V.S. ≥3 rd -line patients (9.6 months V.S. 3.1 months, P = 0.0007), with a tendency to be prolonged mOS in 2 nd -line treatment (16.1 months V.S. 9.3 months), but with no statistically significant difference. The most common grade ≥3 adverse events were hypertension, hand-foot syndrome, and abnormal thyroid function. Conclusions: This study confirms that immunotherapy combined with antiangiogenic therapy is effective and tolerable in anthracycline-resistant soft tissue sarcomas in the real world.It is possible that use in the second line may lead to better efficacy than use in multiple lines, and more clinical studies are expected.
An update on SOC-1882: A phase 2 study using talimogene laherparepvec, nivolumab, and trabectedin for advanced leiomyosarcoma.
Authors: Sant P. Chawla, Neal Shiv Chawla, Nadezhda Omelchenko, Samantha Jeffrey, Anmol Dia Agarwal, Victoria Chua, Ania Moradkhani, Doris V. Quon, Erlinda Maria Gordon
Journal: Journal of Clinical Oncology (2024)

e23570 Background: Intratumoral injection of Talimogene Laherparepvec (TVEC) has a local oncolytic effect and evokes a cytotoxic immune response. The combination of Trabectedin (T) and Nivolumab (N) is a safe and effective therapy in soft tissue sarcoma (STS). Here, we report an update on an ongoing Phase 2 study that aims to determine the efficacy and safety of adding TVEC to the combination of T and N in advanced leiomyosarcoma (LMS). Objectives: Primary: To assess progression-free survival (PFS). Secondary: (1) To evaluate the best overall response, (2) PFS rate at 6 and 9 months, (3) Overall survival (OS) rate at 6, 9, and 12 months, (4) Incidence of conversion from unresectable to the resectable tumor, and (5) Incidence of treatment-related adverse events (TRAEs). Patients and Methods: Eligible patients included patients ≥ 18 years of age with locally advanced unresectable or metastatic LMS, measurable disease by RECIST v1.1, and at least one accessible tumor for TVEC intratumoral injection. N (3 mg/kg q2 weeks), T (1.2 mg/m2 q3 weeks), and TVEC (1x10 8 PFU/ml q 2 weeks depending on tumor size) were administered. A starting dose of TVEC (1x10 6 PFU/ml) was initially given, followed by a total dose of 1x10 8 PFU/ml q 2 weeks depending on tumor size) three weeks later. Results: Efficacy: Per protocol, there were 17 evaluable subjects (Modified Intention to Treat [mITT] patients who had completed at least one treatment cycle and had a follow-up CT scan). The median number of prior lines of therapy was 4 (range 1-9). The disease control rate (PR+SD) was 94% with 1 PR, and 15 SD. The median PFS was 8.0 months (95% CI:4.8-11.28) with a 6-month PFS rate of 71%; median OS 19.2 months (95% CI:12.7- 25.7); 6-month OS rate, 82%. Safety: 22 patients (Intention to treat [ITT] who had received at least one-time drug administration) were evaluated for safety analysis. The &gt; Grade 3 TRAEs include anemia (n = 3), thrombocytopenia (n = 3), neutropenia (n = 1), increased ALT (n = 1), increased GGT (n = 1), decreased LVEF (n = 1), dehydration (n = 1), hyponatremia (n = 1). There were no new safety signals noted in this study. Conclusions: Taken together, the data confirms our previous report that (1) the combination regimen using Talimogene laherparepvec, Nivolumab &amp; Trabectedin may be more effective and treatment for previously treated patients with advanced leiomyosarcoma with manageable toxicity, and (2) The best responders are patients with HR+ uterine LMS. Clinical trial information: NCT03886311 .
Epidemiology of undifferentiated sarcomas: A rare entity.
Authors: Hassan Ali, Sivaguha Yadunath Prabhakaran, Hafiz Muhammad Ajmal Saleem, Rajesh Thirumaran, Krishna Desai
Journal: Journal of Clinical Oncology (2024)

e23571 Background: Undifferentiated Sarcomas (USar), previously known as malignant fibrous histiocytomas, are a group of rare and diverse malignant tumors of mesenchymal origin with a prevalence of 0.08-1 per 100,000. These are aggressive tumors with often high-grade morphology. The diagnosis is made by exclusion of other sarcoma entities upon bone marrow biopsy (criteria listed below). Undifferentiated sarcomas are of four major types, i.e. Pleomorphic, Epithelioid, spindle and round cells. The exact etiology of these sarcomas remains obscure, although many signaling pathways with various genetic alterations may be implicated in their development. The goal of this epidemiologic study is to assist in better understanding of this lesser known aggressive malignancy. Methods: The data was collected from Surveillance, Epidemiology and End Result database Research Plus Data, 17 Registries, Nov 2022 Sub (2000-2020). We extracted undifferentiated sarcoma cases diagnosed between 0-90 years of age, using the ICD Code 8805/3. The analysis was stratified age, gender, race, &amp; primary site labeled. The analysis was further completed by comparing survival using the Log-rank test (GraphPad Prism). Results: A total of 1680 cases of USar were identified, which were diagnosed between 2000 and 2020. Median age of diagnosis was 59.5 years. 50.54% were males and 49.46% were females. Of these cases, ~64.05% were Caucasians, ~15.18% Hispanics, ~10.48% Asians or Pacific Islanders, ~9.35% Black, and &lt; 1% were Alaskan natives/American Indian and Non-Hispanics of unknown race. Further survival curves were compared based on gender, race and organ system. The average months of survival (MoS) based on gender showed no statistical significance (p value 0.6077). MoS calculated for Whites (28), Blacks (16), Asian &amp; Pacific islanders (1), Alaskan natives &amp; American-Indians (15), &amp; Hispanics (21) (p value &lt; 0.0001). MoS based on involved organ system were compared for: head/face/neck (18), GI tract (10), respiratory tract (4), heart/mediastinum/pleura (9), skin &amp; soft tissue (51), bone (32), breast (30), GU (19), CNS (26), gynecological tract (12) and male reproductive system (29) (p &lt; 0.0001). Conclusions: Undifferentiated Sarcoma accounts for less than 1% of all adult tumors. Only 1680 cases were found in the past twenty years, rendering it one of the rarest seen malignancies. Of the reported data, USar was most commonly observed in Caucasians. Comparing the survival curves also showed that there was no difference in survival based on gender. The highest MoS was seen in undifferentiated sarcomas of skin and soft tissues while respiratory tract tumors had the lowest average survival time. More research and analysis is warranted to understand this lesser known malignancy given its extremely low incidence.
Retrospective analysis of peripheral neuropathy in blood cancer survivors evaluated for cellular therapy.
Authors: Elizabeth S Hile, Chao Xu, Desirae R Feierabend, Abby Cha, Rachel Neuhold, Abby McIntire, Phuong Phi, Ryan David Nipp, Adam Steven Asch, George Basil Selby
Journal: Journal of Clinical Oncology (2024)

12087 Background: Blood cancer survivors (BCS) sustain peripheral neuromotor decline from toxic therapies but also aging, diabetes and cancer. Peripheral neuropathy (PN) threatens balance and quality of life, and pre-existing nerve deficits raise future PN risk. The evaluation for cellular therapies is an opportunity to identify functional deficits and optimize their management before additional toxic exposures or disease progression. PN is often diagnosed by paresthesias, but toe strength and sensory deficits also impact balance. We aim to quantify the prevalence of these 3 PN manifestations and walking difficulty in BCS evaluated at our center for possible cellular therapies and compare BCS with and without paresthesias. Methods: We retrospectively analyzed clinical data from 5 years of physical therapy (PT) evaluations during the medical assessment for cellular therapy. As count (%) or mean ± SD we described foot paresthesias [Functional Assessment of Cancer Therapy (FACT) Item NTX2], hallux extension weakness (Medical Research Council Grade ≤4 either side), hallux vibration deficit (biothesiometer ≥24.7 V), and reported trouble walking (FACT An6). We then dichotomized the cohort by NTX2 and compared groups with Chi-square, Fisher’s exact or Wilcoxon rank sum tests. Results: 598 (87.6%) of 683 BCS evaluated by PT had FACT data (79.1% White, 5.5% Latinos); 1 in 2 BCS reported paresthesias, 71.2% as moderate-severe. See table for group comparisons. Race (p=.654) &amp; ethnicity (p=.608) were n.s. 506 BCS with FACT (84.6%) had both strength and sensory data; we found ≥ 1 hallux deficit in 396 (78.3%), more commonly with paresthesias (86.3% vs. 69.5%, p&lt;.001). Conclusions: At cellular therapy evaluation, 1 in 2 BCS reported foot paresthesias, and 3 in 4 had strength or sensory hallux deficit. Regardless of the cause, these deficits could contribute to the trouble walking reported by 44%. BCS with paresthesias were older and had more myeloma, diabetes, chemotherapy, hallux deficits, and trouble walking. But trouble walking and hallux deficits were also common without paresthesias. Research is needed to quantify hallux-gait relationships in BCS, and to establish the highest-value rehabilitative approaches to improve strength and walking before further toxic exposures. [Table: see text]
Comparing emergency department and oncology urgent care for non-emergent acute care.
Authors: Arthur S. Hong, Sadaf Charania, Angela F. Bazzell, D. Mark Courtney, John W. Sweetenham, Ethan A. Halm
Journal: Journal of Clinical Oncology (2024)

e23107 Background: Adults with cancer often visit the emergency department (ED) during treatment for commonly anticipated issues (e.g. pain, nausea). Some providers have created oncology urgent care clinics (OUCC) to manage these non-emergent issues. Evidence suggests that they are associated with lower ED use. Little is known about the care delivered at OUCCs, and how it compares to ED care. We compared visits from our OUCC to ED visits at our comprehensive cancer center. Methods: We studiedvisits from Jan 1 – June 30, 2023. To limit selection bias, we excluded ED visits if patients were referred by an outpatient clinician, including phone triage. Triage nurses document a validated Emergency Severity Index (ESI, version 4) as part of usual care in the ED, but not the OUCC. The ESI ranks high-severity (level 1 – “patient dying”; 2 – “shouldn’t wait”) to lower-severity (level 5), with the three lower levels distinguished by vital signs and clinical resources needed to stabilize a patient. Two clinicians reviewed OUCC visits and recorded ESIs. We assessed inter-rater reliability of OUCC ESI coding. We used multivariate, mixed-effects methods (visits clustered to patient) to model two outcomes: care escalation (OUCC to ED/inpatient; ED to inpatient) and length of stay (LOS). We excluded visits with ESI at the extremes (1 and 5). We adjusted for sex, age, comorbidities, cancer type and stage, date/time of arrival, and ESI. We then used marginal effects methods to report adjusted outcomes, stratified by ESI. Results: We analyzed 904 OUCC visits (580 patients) and 4,115 ED visits (2,866 patients). Over half (55.5%) of ED arrivals occurred after business hours. Median patient age was 67 (IQR 57 - 74), 48% were female, and 58% non-Hispanic white. Cancer types included 18% hematologic, 17% GI/colorectal, 12% breast, and 7% lung; 11% were advanced-stage. Unweighted inter-rater reliability for ESI was high for a subset of 164 OUCC visits (k = 0.81, 95% CI: 0.72 - 0.89). Although OUCC had a sizable portion of level 2 visits, ED had significantly higher severity. At each ESI level, adjusted rates of care escalation were significantly higher for ED than OUCC (overall aOR 5.6, 95% CI: 4.4 - 7.2), and LOS was longer for ED than OUCC (5.2 hours longer, 95% CI 4.8 – 5.6). Conclusions: The severity of OUCC visits was high, though patient self-referred ED visit severity was higher. OUCC may be more efficient than the ED for managing non-emergency care in this population. Future work should further investigate the quality of care delivered at each site, including cost of care. [Table: see text]