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Focal to bilateral tonic–clonic seizures in newly diagnosed focal epilepsy
Agashe, Shruti , Cascino, Gregory, Devinsky, Orrin , Barnard, Sarah , Gidal, Barry E. , Abou‐Khalil, Bassel , Fox, Jonah , Pellinen, Jacob , Project, the Human Epilepsy, Gidal, Barry , Fox, Jonah , Pellinen, Jacob , French, Jacqueline , Devinsky, Orrin , Barnard, Sarah , Agashe, Shruti H , Holmes, Manisha , Klein, Pavel , French, Jacqueline A. , Project, the Human Epilepsy

Epilepsia | February 20, 2025 | Volume: 66 | Issue: 4 | Pages: No page available

10.1111/epi.18324 | PMID 39973623 Get It

AbstractPresence of focal to bilateral tonic–clonic seizures (FBTCS) in focal epilepsy is associated with increased morbidity and mortality. Risk factors for FBTCS are poorly understood, and little is known regarding FBTCS recurrence after treatment initiation. This study aimed to investigate factors related to FBTCS in newly diagnosed focal epilepsy and their recurrence after starting antiseizure medications (ASMs) in the Human Epilepsy Project (HEP) cohort. HEP was an international, prospective cohort study that enrolled people with newly diagnosed focal epilepsy within 4 months of treatment initiation and followed them for up to 6 years. Baseline characteristics, treatment choices, and seizure outcomes were collected. Descriptive and inferential statistical analysis was conducted to assess the differences between study participants who had FBTCS and those who never experienced FBTCS. A total of 443 participants were included in this analysis; 77% (n = 342) had FBTCS at some point prior to or within the study period. In participants with FBTCS, regardless of initial seizure type, diagnosis was mostly made after FBTCS (335/342, 98%). After treatment initiation, FBTCS did not recur in 57% (n = 194/342) of cases. A higher number of total pretreatment seizures (median = 16 vs. 11, p = .048, Mann–Whitney U‐test), predominantly focal aware seizures (FAS) or focal impaired awareness seizures (FIAS; median = 15 vs. 10, p = .049, Mann Whitney U‐test), was associated with no recurrence in FBTCS after treatment initiation. Of 108 participants without FBTCS prior to treatment, only seven (6%) developed FBTCS after treatment initiation. There was no significant difference in choice of initial ASM class (levetiracetam vs. sodium channel blockers) between participants who experienced FBTCS and those who did not. This study highlights the significance of FBTCS among individuals with newly diagnosed focal epilepsy. The majority of participants who experienced FBTCS were diagnosed with epilepsy after experiencing their first FBTCS despite preceding FAS/FIAS. The more frequent FAS/FIAS in participants whose FBTCS resolved may be a characteristic of their epilepsy.
Artificial Intelligence ECG Diastolic Dysfunction and Survival in Cardiac Intensive Care Unit Patients
Jentzer, Jacob C. , Lee, Eunjung , Attia, Zachi I. , Kane, Garvan C. , López-Jiménez, Francisco , Noseworthy, Peter A. , Friedman, Paul A. , Oh, Jae K. , Attia, Zachi I , Hillerson, Dustin , Lopez-Jimenez, Francisco , Noseworthy, Peter A , Friedman, Paul A , Oh, Jae K. , Jentzer, Jacob C

Journal of the American Heart Association | February 19, 2025 | Volume: 14 | Issue: 5 | Pages: No page available

10.1161/jaha.124.037839 | PMID 39968804 Get It

Background Left ventricular diastolic dysfunction (LVDD) predicts mortality in patients in cardiac intensive care units. An artificial intelligence enhanced ECG (AIECG) algorithm can predict LVDD and mortality in general populations but has not been examined in cardiac intensive care units. Methods This historical cohort study included consecutive adults admitted to Mayo Clinic cardiac intensive care unit from 2007 to 2018 with an admission AIECG. The AIECG assigned the LVDD grade (0–3). Medial mitral E/e' ratio >15 on transthoracic echocardiogram (TTE) defined elevated filling pressures. In‐hospital and 1‐year mortality was evaluated, before and after multivariable adjustment. Results We included 11 868 patients (median age 69.5 years, 37.7% female); 48% had heart failure and 44% had acute coronary syndromes. AIECG LVDD grade was 0 (normal), 33%; 1, 7%; 2, 39%; and 3, 21%. In‐hospital and 1‐year mortality increased in each higher AIECG LVDD grade. After adjustment, each higher AIECG LVDD grade was associated with higher in‐hospital (adjusted odds ratio [OR], 1.22 [95% CI, 1.13–1.32]) and 1‐year mortality (adjusted hazard ratio [HR], 1.23 [95% CI, 1.19–1.29]); this persisted after adjustment for TTE measurements. Patients with grade 2 or 3 LVDD by AIECG and medial mitral E/e' ratio >15 by TTE had the highest in‐hospital (adjusted OR, 2.54 [95% CI, 1.69–3.88]) and 1‐year (adjusted HR, 2.03 [95% CI, 1.65–2.48]) mortality, whereas patients meeting either of these criteria had similar, elevated mortality. Conclusions The AIECG LVDD grade was strongly associated with in‐hospital and 1‐year mortality in patients in cardiac intensive care units, even after adjusting for clinical variables and TTE measurements. Patients with concordant AIECG and TTE for elevated filling pressures were at highest risk.
Large language models (LLMs) for inferring genomic characteristics and facilitating genomic literacy in prostate cancer (PCa) patients.
Naqvi, Syed Arsalan Ahmed , Ayub, Umair , Khoury, Peter R., Ravichandar, Deepak B, Witte, Owen H., Orme, Jacob J. , Khan, Muhammad Ali , Khoury, Peter R., Witte, Owen H., Childs, Daniel S. , Zakharia, Yousef , Singh, Parminder Pal , Bryce, Alan H. , Riaz, Irbaz Bin

Journal of Clinical Oncology | February 18, 2025 | Volume: 43 | Issue: 5_suppl | Pages: 261-261

10.1200/jco.2025.43.5_suppl.261 Get It

261 Background: Clinicians use next-generation sequencing (NGS) to tailor targeted treatments for PCa patients. However, the results are often available in unstructured formats and are saturated with technical jargon, making them inaccessible for patients. Therefore, we aimed to assess the efficacy of LLMs to accurately extract genomic characteristics from unstructured reports and generate patient-friendly summaries for ease of variant interpretation in PCa patients. Methods: This retrospective study included patients with PCa who underwent NGS from 2023-2024. The GPT4 model was utilized using structured zero-shot prompts to extract genomic characteristics from unstructured reports in a non-decomposed manner. Prompt development was conducted iteratively using a 2% random sample of the dataset. Genomic characteristics ascertained by LLM were assessed against held out vendor-curated test dataset for evaluation. Performance was assessed using weighted evaluation metrics (precision, recall, and F1-score). Additionally, the extracted variables were organized using rule-based criterion and presented as a separate prompt to GPT4 to generate summaries for interpretation at the level of each biologically relevant variant. Mean Flesch-Kincaid scores and Vocd-D statistic with standard deviations were computed to assess readability and lexical diversity of LLM-generated variant interpretation summaries. Results: A total of 331 patients (370 NGS reports) were included in the study. Evaluation on the held-out test dataset (Table) showed that the weighted average precision ranged from 80% for extracting tumor mutational burden to 100% for extracting the CtDNA fraction from unstructured reports. The weighted average recall ranged from 85% for extracting CtDNA tumor fraction to 99% for ascertaining variant/alteration. The weighted average F1-scores varied from 0.83 for extracting tumor mutational burden to 1.0 for extracting specimen site from NGS reports. The mean Flesch-Kincaid score was 8.29 ± 1 indicating average/standard readability ease. The mean Vocd-D statistic was 7.55 ± 1 indicating focused summaries, however, with limited lexical diversity. Conclusions: This study suggests that large language models can effectively extract genomic characteristics from unstructured reports and can potentially improve genomic literacy among prostate cancer patients by providing easy-to-interpret variant summaries. However, targeted prompting may be required to increase lexical diversity for improved engagement. Performance across different genomic characteristics. Category Precision Recall F1-Score Altered gene 0.86 0.97 0.89 Variant/alteration type 0.98 0.99 0.98 Variant allele fraction 0.96 0.96 0.96 Test name/type 1 0.99 1 Specimen site 1 0.99 1 Tumor mutational burden 0.8 0.93 0.83 CtDNA tumor fraction 1 0.85 0.92 MSI status 0.99 0.97 0.98
Olanzapine for managing side effects from tyrosine-kinase inhibitors.
Koch, Regina M. , Muniz, Miguel, Peskey, Candy S , Jatoi, Aminah , Ruddy, Kathryn J. , Orme, Jacob J. , Pagliaro, Lance C. , Quevedo, Fernando , Costello, Brian A. , Spychalla, Megan, Heath, Elisabeth I. , D’Andre, Stacy D. , Loprinzi, Charles L. , Zakharia, Yousef , Singh, Parminder Pal , Riaz, Irbaz Bin , Cathcart-Rake, Elizabeth , Childs, Daniel S.

Journal of Clinical Oncology | February 18, 2025 | Volume: 43 | Issue: 5_suppl | Pages: 524-524

10.1200/jco.2025.43.5_suppl.524 Get It

524 Background: Antiangiogenic tyrosine kinase inhibitors (TKIs) play a key role in treating renal cell carcinoma and other solid organ malignancies, but TKIs cause bothersome side effects that frequently necessitate dose reductions or treatment holds. Olanzapine has been useful for palliating symptoms from classical chemotherapies and advanced cancer, but its effect on TKI-related symptoms is largely unknown. This retrospective study aimed to estimate the efficacy of olanzapine for TKI-induced nausea, vomiting, anorexia, weight loss, and insomnia. Methods: All patients prescribed olanzapine with lenvatinib, cabozantinib, axitinib, or tivozanib at Mayo Clinic between January 1, 2018, and June 30, 2024 were assessed for inclusion. For baseline symptom assessment, clinical care team notes documenting the presence or absence of symptoms and indication(s) for starting olanzapine were reviewed. For response assessment, clinical notes and patient portal messages from the first three months after starting olanzapine were evaluated for qualitative descriptions of change in symptom burden. Relevant data were extracted as direct quotations, which were reviewed by the research team and categorized as “improved,” “worsened,” “stable,” or “missing data.” Each symptom domain was analyzed independently when olanzapine was prescribed for multiple interrelated symptoms. Results: A total of 60 patients who received olanzapine for the treatment of TKI-related adverse effects were included. The most common documented indication for olanzapine was nausea without vomiting (n=35), followed by anorexia (n=25), nausea with vomiting (n=16), weight loss (n=16), and insomnia (n=11). In 32 cases (53%), olanzapine was prescribed for multiple, simultaneous symptoms. Response rates for each symptom domain are shown in the table. In addition, prior to olanzapine, 34 patients (57%) had documented weight loss. Following olanzapine, 50% (n=17) gained weight (median increase: 6.1 kg; range: 2.0 - 10.7 kg), 26% (n=9) stabilized their weight (±1 kg), and 24% (n=8) continued to lose weight. Clinicians utilized a TKI dose reduction within one week of olanzapine initiation in 5 cases (8.3%), and 3 of these patients could resume the higher dose of TKI after starting olanzapine. Only 4 patients (7%) discontinued olanzapine within 3 months due to perceived side effects. Conclusions: Olanzapine appears to be effective in treating TKI-induced nausea, vomiting, anorexia, insomnia, and weight loss. Prospective randomized placebo-controlled studies are needed to confirm these findings. Improvedn (%) Worsened n (%) Stablen (%) Missing Datan (%) Nausea without emesis 32 (84) 3 (8) 1 (3) 2 (5) Nausea with emesis 13 (93) 0 (0) 0 (0) 1 (7) Anorexia 26 (74) 2 (6) 4 (11) 3 (9) Insomnia 11 (85) 0 (0) 2 (15) 0 (0)
Clinical efficacy of enfortumab vedotin-pembrolizumab (EV-P) in locally advanced (LA) or metastatic urothelial carcinoma (mUC): A real-world retrospective study.
Jain, Prateek , Naqvi, Syed Arsalan Ahmed , Anjum, Muhammad Umair , Afzal, Muhammad Umar, Yum, Ji-Eun Irene, Warraich, Kainat , Jajja, Salman Ayub, Swati, Fnu, Tripathi, Nikita , Orme, Jacob J. , Tyson, Mark D. , Yu, Nathan Y. , Jain, Prateek, Khan, Muhammad Ali , Afzal, Muhammad Umar, Childs, Daniel S. , Zakharia, Yousef , Riaz, Irbaz Bin , Singh, Parminder Pal

Journal of Clinical Oncology | February 18, 2025 | Volume: 43 | Issue: 5_suppl | Pages: 745-745

10.1200/jco.2025.43.5_suppl.745 Get It

745 Background: The combination of EV-P therapy has recently been approved as first-line (1L) therapy for patients with LA/mUC based on the results of the EV-302 trial. Herein, we report the updated results from a cohort of patients with LA/mUC who received EV-P in real world clinical setting. Methods: This retrospective study included patients with LA/mUC (07/2022-08/2024) at the Mayo Clinic who completed at least one cycle of EV-P. The best overall response (BOR) was evaluated using radiographic imaging and was adjudicated as complete response (CR), partial response (PR), stable disease (SD), mixed response (MR), or progressive disease (PD). The median progression-free survival (PFS), defined as the time from treatment initiation to disease progression or death, was estimated using the Kaplan-Meier method. Patients who had not experienced disease progression by their last follow-up were censored for the PFS analysis. Results: A total of 120 patients were included; 79 (65.8%) were males, 41 (34.1%) females, 109 (91%) White, and 119 (99%) were non-Hispanic/Latino. The median age was 72 years (IQR: 65-77). Of these, only 22 (18.3%) had locally advanced disease while the remaining had mUC; 62 (51.6%) had lower tract urothelial carcinoma (LUTC), 36 (30%) had upper tract urothelial carcinoma (UTUC). The median follow-up time was 7.1 months (IQR: 4.93-9.26). In terms of BOR, 56 patients (46.6%) experienced PR, 34 (28.3%) CR, 12 (10%) PD, 7 (5.8%) MR, and 8 (6.6%) experienced SD. 3 (2.5%) patients were not evaluable. The BOR across subgroups, LA and mUC, including LUTC and UTUC, is summarized in the table. Among the responders, the median number of treatment cycles to first response was 3 (IQR: 2.25–4). Within the follow-up, 28 patients (23.3%) experienced eventual radiographic disease progression; death was observed in 25 patients (20.8%). The median PFS was 12.7 months (95% CI: 9.8-NE), and OS was 25.1 months (16.3-NE). Conclusions: In real world setting, the combination of EV-P in LA/mUC demonstrated clinical efficacy compatible with the findings from the EV-302 trial. Our results showed comparable efficacy with EV-P in both UTUC and LUTC, highlighting it's broad therapeutic potential. However, clinical data at longer follow-up is required to fully evaluate overall survival and the durability of response. mUC LA Overall LUTC UTUC Total patients 98 62 36 22 BOR CR 23 (23.4%) 13 (20.9%) 10 (28.5%) 11 (50%) PR 49 (52.6%) 31 (50%) 18 (50%) 7 (31.8%) SD 6 (6.4%) 2 (3.2%) 4 (11.4%) 2 (9.0%) PD 10 (10.7%) 9 (15.5%) 1 (2.8%) 2 (9.0%) MR 7 (7.5%) 5 (8.6%) 2 (5.7%) 0 (0%)
Real-world outcomes of nadofaragene firadenovec in BCG-unresponsive non-muscle invasive bladder cancer.
Moyer, Jacob A. , Durant, Adri , Nguyen, Mimi Thi, Mi, Lanyu , Zganjar, Andrew , Shah, Paras , Boorjian, Stephen A. , Tyson, Mark D. , Nguyen, Mimi, Lyon, Timothy D.

Journal of Clinical Oncology | February 18, 2025 | Volume: 43 | Issue: 5_suppl | Pages: 716-716

10.1200/jco.2025.43.5_suppl.716 Get It

716 Background: Nadofaragene firadenovec is an FDA-approved gene therapy for Bacillus Calmette-Guérin (BCG) unresponsive non-muscle invasive bladder cancer (NMIBC) with promising clinical trial results. However, real-world post-marketing efficacy or safety data remain lacking. We evaluated complete response rates and safety in a multisite experience. Methods: Per IRB protocol, we analyzed patients treated with nadofaragene firadenovec for BCG-unresponsive NMIBC across three Mayo Clinic sites. Outcomes included complete response (CR), high-grade recurrence-free survival (HGRFS), cystectomy-free survival (CFS), overall survival (OS), and adverse events (AEs). CR and HGRFS were reported for patients with carcinoma in situ (CIS) and patients with Ta/T1 without CIS respectively. Failure to retain was defined as any medication loss, including leakage around the catheter or early voiding. Results: Between November 2023 and October 2024, 45 patients were treated with nadofaragene firadenovec for BCG-unresponsive NMIBC. Fifteen patients with follow-up less than 6 months and one patient with extensive metastatic disease identified one week after first instillation were excluded from efficacy analysis. Our efficacy-evaluable population of 29 patients with median follow-up of 8.2 months is summarized in the Table. CR/HGRFS at 3 and 6 months was 72% and 62% respectively. CFS was 94% and OS was 100% at 6 months. Three patients experienced disease progression during follow-up: one to T1, another to T2, and a third with metastases to the abdomen and lungs. A separate patient developed a metachronous upper tract urothelial carcinoma (pT2) without bladder recurrence. Bladder spasms (62%) and failure to retain (31%) were the most common AEs. Most AEs were low-grade, although four (9%) patients had grade 3 events (fatigue, fever, and dizziness). No grade 4-5 AEs were reported. Conclusions: Early real-world data demonstrates encouraging clinical complete response rates in patients with BCG-unresponsive NMIBC and a favorable safety profile. Further investigation with larger cohorts and longer follow-up is warranted. Evaluable patients (N=29) CIS cohort (N=15) Ta/T1 only cohort (N=14) Prior pembrolizumab (N=9) Prior intravesical chemotherapy (N=16) Age, years 72 (67-77) 74 (69-77) 71 (67-77) 69 (67-78) 73 (67-81) Elixhauser Index 5 (4-6) 5 (4-7) 5 (4-6) 5 (3-5) 5 (3-6) Prior BCG instillations 12 (10-14) 12 (12-15) 11 (8-13) 12 (12-12) 12 (11-13) Prior intravesical chemotherapy among recipients 6 (6-11) 6 (6-10) 6 (6-11) 10 (7-12) 6 (6-11) Prior pembrolizumab doses among recipients 7 (4-8) 8 (7-8) 4 (4-4) 7 (4-8) 8 (5-8) Follow-up, months 8.2 (6.9-9.5) 7.6 (6.9-9.5) 8.5 (6.9-9.4) 9.1 (8.0-10.1) 8.6 (6.7-9.9) 3-month CR/HGRFS 72% [53-87] 73% [45-92] 71% [42-92] 67% [30-93] 56% [30-80] 6-month CR/HGRFS 62% [42-79] 67% [38-88] 57% [29-82] 44% [14-79] 44% [20-70] Data are median (IQR) or % [95% CI].
Utility of post-treatment SPECT/CT for identifying disease progression in patients with mCRPC treated with 177 Lu-PSMA-617.
Muniz, Miguel, Sartor, Alton Oliver, Orme, Jacob J. , Koch, Regina M. , Kase, Adam M. , Kendi, Ayşe Tuba Karagülle, Bilgin, Gokce Belge , Nikanpour, Yalda , Kwon, Eugene D., Quevedo, Fernando , Riaz, Irbaz Bin , Thorpe, Matthew , Johnson, Geoffrey B. , Childs, Daniel S.

Journal of Clinical Oncology | February 18, 2025 | Volume: 43 | Issue: 5_suppl | Pages: 114-114

10.1200/jco.2025.43.5_suppl.114 Get It

114 Background: Oncologists have traditionally relied upon serial assessments of PSA and periodic imaging (i.e., every 2 to 3 cycles) to monitor treatment response. Early identification of disease progression allows for faster transitions to alternative therapies that might be more effective. In this study, we evaluated the utility of post-treatment SPECT/CT for earlier detection of treatment failure in patients receiving Lutetium-177–PSMA-617 (LuPSMA). Methods: We queried an IRB-approved registry including all patients starting LuPSMA at Mayo Clinic, MN, in the interval of March 2022 to March 2023. Those receiving fewer than 2 cycles of treatment and missing SPECT/CT data were excluded. We reviewed clinical notes to document the date and reason(s) for treatment discontinuation. The assembled cohort consists of patients stopping LuPSMA for progressive disease ([PD], categorized as biochemical, radiographic, or both). Results of the prior SPECT/CT imaging reports were reviewed. At our institution SPECT/CT images are typically acquired on the day after each infusion. Metrics collected from the radiology reports included: new foci of PSMA localization since the prior PSMA PET or SPECT/CT, suspicion for new non-PSMA avid disease, and a visual determination of PSMA-avid tumor volume. Results: A total of 256 patients received an initial cycle of LuPSMA. SPECT/CT imaging data for at least 2 consecutive treatment cycles was available for 68 patients who developed PD after a median (IQR) of 3 (2-4) cycles. There were 55 patients (81%) with both biochemical and radiographic evidence of PD, 7 (10%) with biochemical only progression, and 6 (9%) with radiographic only progression. The most used imaging modality for response assessment was PSMA PET/CT (n=46, 67%), followed by conventional imaging (n=9, 13%), and choline PET/CT (n=5, 7%). The median time between most recent post-therapy SPECT/CT and determination of PD was 39 days. The prior SPECT/CT had detected new foci of PSMA avid disease in 12 (18%) cases and new non-PSMA avid disease in 5 (7%) cases. Two patients had both new PSMA-avid and non-PSMA avid lesions. The most common sites of new PSMA-avid disease on SPECT/CT were bone (n=10) and liver (n=2). A total of 20 (29%) patients had visually increased tumor volume on SPECT/CT, 9 (45%) of which had no new lesions. In total, 24 of 68 patients (35%) had early detection of treatment futility detected by SPECT/CT. At a median (IQR) follow-up time of 8 (6.4-12) mo, the median OS [95% CI] was similar for patients with PD detected on SPECT/CT (7.8 [6.6 – 9] mo) compared to those without clear evidence of PD on SPECT/CT(8.4 [6.4-10.3] mo, p=0.885). Conclusions: Post-treatment SPECT/CT imaging may complement traditional forms of response assessment and provide an earlier warning of treatment failure through identification of new PSMA-avid lesions, non-PSMA avid disease, and increased tumor volume.
Outcomes for 177 Lu-PSMA-617 with and without concurrent use of ARPIs in patients with mCRPC.
Muniz, Miguel, Sartor, Alton Oliver, Orme, Jacob J. , Koch, Regina M. , Quevedo, Fernando , Kase, Adam M. , Naqvi, Syed Arsalan Ahmed , Andrews, Jack R. , Bilgin, Gokce Belge , Kwon, Eugene D., Riaz, Irbaz Bin , Thorpe, Matthew , Kendi, A. Tuba , Johnson, Geoffrey B. , Childs, Daniel S.

Journal of Clinical Oncology | February 18, 2025 | Volume: 43 | Issue: 5_suppl | Pages: 112-112

10.1200/jco.2025.43.5_suppl.112 Get It

112 Background: We now have more than a decade of experience using Androgen Receptor Pathway Inhibitors (ARPIs) across various disease states of prostate cancer, and the safety of their combination with Lutetium-177–PSMA-617 has been demonstrated in VISION and other large randomized clinical trials. However, real-world data on treatment patterns and outcomes involving combination therapies with 177 Lu-PSMA-617 remain limited. Methods: For this analysis, we utilized the Mayo Clinic Rochester radiopharmaceutical database, a prospectively maintained retrospective database containing all patients who received 177 Lu-PSMA-617 at our institution. We focused on patients who started treatment from March 2022 to March 2023. Patients receiving an ARPI (abiraterone acetate, enzalutamide, apalutamide, or darolutamide) during the course of 177 Lu-PSMA-617 treatment were identified, inclusive of patients who continued using an ARPI prescribed as a prior line of treatment and those who started (i.e., switched) to a new ARPI. Baseline clinicopathologic and imaging characteristics were abstracted and compared using the Mann-Whitney U and Chi-square tests. Best PSA response during treatment was reported as a percent decline from baseline. Survival was calculated from the date of the first cycle of 177 Lu-PSMA-617. PSA50 response and overall survival (OS) outcomes for the two groups (concurrent use of ARPI vs. 177 Lu-PSMA-617 alone) were compared using the Chi-square test and Kaplan-Meier method, respectively. A multivariate Cox regression analysis was performed, including established prognostic factors. Results: An ARPI was prescribed to 106 of the 256 patients (41.4%) starting 177 Lu-PSMA-617 in the interval of March 2022 to March 2023. With regards to baseline characteristics, those receiving an ARPI concurrently with 177 Lu-PSMA-617 had a lower PSA (3.4 vs 29.7 ng/mL, p < 0.001) and a lower frequency of bone (77.4% vs. 87.4%, p = 0.035) and visceral metastases (18.9 vs 34%, p = 0.008) at start of treatment. Median follow-up for the overall cohort (IQR) was 19.1 months (8.7 – 23.6). Patients receiving an ARPI plus 177 Lu-PSMA-617, as compared to 177 Lu-PSMA-617 alone, were more likely to complete all 6 planned doses of treatment (63.2% vs. 48.7%, p < 0.001), though the PSA50 response rate was similar (49.1% vs 47.3%, p = 0.786). Median OS [95% CI] for the overall cohort was 21.3 [16.7 – 25.9] months and significantly longer for those receiving ARPI with 177 Lu-PSMA-617 (NR [NE – NE]) as compared to 177 Lu-PSMA-617 alone (15.3 mo [11.6 – 19.1], p < 0.001). However, on multivariate analysis including known prognostic variables, use of ARPI was not independently associated with improved survival (HR = 1.03 [CI: 0.68 to 1.55], p = 0.891). Conclusions: Patients receiving an ARPI with 177 Lu-PSMA-617 were more likely to complete all 6 cycles of treatment, but no clear differences in survival were observed on multivariate analysis.
Inferring ECOG performance status (PS) using large language models in patients with advanced prostate cancer.
Raina, Ammad, Muniz, Miguel, Anjum, Muhammad Umair , Ayub, Umair , Naqvi, Syed Arsalan Ahmed , Jajja, Salman Ayub, Yum, Ji-Eun Irene, Yu, Nathan Y. , Abdul‐Muhsin, Haidar , Sartor, Alton Oliver, Orme, Jacob J. , Zhou, Ben , Singh, Parminder Pal , Zakharia, Yousef , Childs, Daniel S. , Riaz, Irbaz Bin

Journal of Clinical Oncology | February 18, 2025 | Volume: 43 | Issue: 5_suppl | Pages: 136-136

10.1200/jco.2025.43.5_suppl.136 Get It

136 Background: The ECOG performance status (PS) is a critical measure for evaluating functional capacity and determining clinical trial eligibility in patients with advanced prostate cancer. We aim to assess the capability of large language models (LLMs) to accurately infer ECOG PS from unstructured oncology notes. Methods: This retrospective study included patients with metastatic castration-resistant prostate cancer (mCRPC) receiving Lutetium-177–PSMA-617 ( 177 Lu) at the Mayo Clinic (2022-2023). Baseline ECOG PS scores were manually curated by a trained clinician from clinical notes recorded within four weeks prior to 177 Lu initiation. Structured zero-shot prompts were then used to prompt GPT-4 to infer ECOG PS scores from unstructured oncology notes. Total dataset was randomly sampled to prompt development (20%) and held-out test set (80%). Three experimental setups were employed to assess model performance: (i) utilizing unmasked clinical notes, (ii) clinical notes with only numerical ECOG PS scores masked while retaining narrative descriptive/assessment by oncologist of ECOG score, and (iii) clinical notes with both numerical scores and narrative ECOG descriptors masked. Final performance was assessed using evaluation metrics (precision, recall, F1 score) on the held-out test set. Results: A total of 240 patients (n: 50 prompt development; n: 190 test set) were included in the analysis. The median age was 70 (IQR: 66-76); a majority of patients were White (n: 229; 95%) and non-Hispanic (n: 233; 97%). The most prevalent ECOG PS score was 0 (n: 140; 58%), followed by 1 (n: 88; 37%), and 2 (n: 12; 5%). The performance was numerically higher when using unmasked notes (weighted average precision: 0.89; recall: 0.89; F1: 0.89), compared to using notes with masked scores only (weighted average precision: 0.76; recall: 0.79; F1: 0.75) and notes with both scores and narrative masked (weighted average precision: 0.57; recall: 0.53; F1: 0.48). Metrics by each ECOG PS score is outlined (Table). Conclusions: Large language models demonstrate significant potential in precisely extracting ECOG performance status from unstructured oncology notes, offering valuable support for treatment decision-making and clinical trial enrollment. However, model performance declines as reliance on implicit reporting within clinical notes increases. Future efforts focusing on prediction of ECOG using a series of notes over time will be the next step. ECOG Unmasked oncology notes ECOG Score masked only ECOG Score + ECOG narrative marked Precision Recall F1 Score Precision Recall F1 Score Precision Recall F1 Score 0 0.89 0.92 0.91 0.75 0.93 0.83 0.59 0.74 0.66 1 0.88 0.86 0.87 0.76 0.74 0.75 0.19 0.47 0.27 2 1.00 0.82 0.90 0.78 0.33 0.47 0.78 0.16 0.26
Sociodemographic predictors of the late-stage diagnosis in patients with prostate cancer: A retrospective cohort study.
Afzal, M. , Raina, Ammad, Riaz, Zaryab Bin, Warraich, Kainat , Sartor, Alton Oliver, Orme, Jacob J. , Abdul‐Muhsin, Haidar , Kase, Adam M. , Moore, Cassandra N., Agarwal, Neeraj , Cobran, Ewan K. , Khan, Muhammad Ali , Bryce, Alan H. , Singh, Parminder Pal , Childs, Daniel S. , Agarwal, Neeraj , Zakharia, Yousef , Riaz, Irbaz Bin

Journal of Clinical Oncology | February 18, 2025 | Volume: 43 | Issue: 5_suppl | Pages: 132-132

10.1200/jco.2025.43.5_suppl.132 Get It

132 Background: Distant metastasis at the time of prostate cancer (PCa) diagnosis is associated with increased morbidity and mortality. This study aimed to assess the impact of sociodemographic characteristics on distant metastasis at the time of PCa diagnosis. Methods: The Surveillance Epidemiology and End Results (SEER) database (2000-2021), including PCa patients from 17 registries, was queried. Patients with late-stage diagnosis (LSD) were defined as those who were initially diagnosed with stage IV disease, indicating distant metastasis. Sociodemographic predictors included race, ethnicity, age, marital status, residential status, and median household income. Multicollinearity was assessed using variance inflation factors (VIF). Univariable logistic regression was performed to identify significant predictors of LSD, which were further analyzed in multivariable logistic regression using a maximum likelihood estimation approach. Odds ratios with 95% confidence intervals (CI) were computed with a p-value of <0.05 indicating a statistically significant association. Results: Of the 1,089,736 PCa patients diagnosed, 64,983 (6%) had an LSD. The majority were white (80%), non-Hispanic/Latino (HL) (91%), aged ≥65 years (60%), married (75%), residents in metropolitan areas (88%), and had an annual house income of ≥$70,000 (70%). Multivariable logistic regression identified Black (OR: 1.24; 95%CI: 1.22-1.27), Asian or Pacific Islander (1.35; 1.30-1.40), and American Indian/Alaska Native (1.70; 1.53-1.89) to have higher odds of LSD compared to White patients (Table). In addition, HL ethnicity compared to non-HL (OR: 1.45; 95% CI: 1.42-1.49), age ≥65 compared to <65 (1.68; 1.65-1.71), unmarried status compared to married (1.88; 1.85-1.91), residency in non-metropolitan areas compared to metropolitan (1.10; 1.07-1.12), and household income <$70,000 compared to ≥$70,000 (1.03; 1.01-1.05) had a significant association with LSD. Conclusions: Older, non-White (Black, Asian/Pacific Islander, American Indian/Alaska Native), Hispanic/Latino, unmarried men, residents of non-metropolitan areas, or those with lower annual household incomes have higher odds of late-stage diagnosis. Interventions targeting early detection in these at-risk groups may improve prostate cancer outcomes in the US. Variable Odds Ratio (95% CI) p-value Race (Black vs White) 1.24 (1.22-1.27) <0.01 Race (Asian or Pacific Islander vs White) 1.35 (1.31-1.40) <0.01 Race (American Indian/Alaska Native vs White) 1.70 (1.53-1.89) <0.01 Ethnicity (Hispanic/Latino vs non-/Hispanic/Latino) 1.45 (1.42-1.49) <0.01 Age (≥65 vs <65) 1.68 (1.65-1.71) <0.01 Marital status (unmarried vs married) 1.88 (1.85-1.91) <0.01 Residence status (non-metropolitan vs metropolitan) 1.10 (1.07-1.12) <0.01 Household income (<$70,000 vs ≥$70,000) 1.03 (1.01-1.05) <0.01