tbuckley/cabot-search huggingface dataset:
A novel cardiovascular disease risk score for prediction of atherosclerotic disease events in men with prostate cancer.
Authors: Nickolas Stabellini, Min Choon Tan, Jennifer Cullen, Neal L Weintraub, John Shanahan, Neeraj Agarwal, Sagar A. Patel, Alberto J. Montero, Avirup Guha
Journal: Journal of Clinical Oncology (2024)

314 Background: Prostate cancer patients (PC) face an elevated risk of both developing atherosclerotic cardiovascular disease (ASCVD). The American College of Cardiology Pooled Cohort Equations (PCE) for ASCVD predictions may lack accuracy. Methods: Males ≥18 years, diagnosed with PC between 2005-2012 at a hybrid academic-community practice were included. Using XGBoost algorithm we developed using a training subset of the cohort (50% train + 25% test), ranked 33 covariates (including demographic, treatment-related and social determinants of health (SDOH) information) for ASCVD prediction using SHAP (Shapley additive explanations) values. The top 10 predictors were transformed in a predictive equation using logistic regression models. This equation was tested in the cohort validation subset (25%), and subsequently compared to the PCE risk score. Results: We included 1,506 patients, with a median age of 67 (IQR 60-74) years, 13.8% had advanced stage disease (TNM III-IV), 1.5% had high risk PC (Gleason 8-10), and 20.5% received androgen deprivation therapy (ADT). Of those, 10.4% had a 10-year ASCVD risk. The PCE had an area under the curve (AUC)=0.61 and underestimated ASCVD in 0.9% (mean risk=20.1% [95% CI 17.2-23.0] vs. mean predicted risk=19.2% [95% CI 18.6-19.8]). The equation pooled from the top-10 predictors of the ML algorithm (C-index=0.78 [95% CI 0.75-0.81]) achieved an AUC=0.71 (Table). Conclusions: Conventional PCE tend to underestimate ASCVD risk in males with PC. A cancer-specific model inclusive of SDOH exhibits good performance for predicting ASCVD risk in this population. [Table: see text]
Patterns of concurrent chemotherapy selection in US patients undergoing trimodality therapy for muscle-invasive bladder cancer.
Authors: Eryn Callihan, Elizabeth Molina Kuna, Tyler P. Robin, Corbin J. Eule, Simon P. Kim, Thomas W. Flaig
Journal: Journal of Clinical Oncology (2024)

554 Background: Trimodality therapy (TMT) consists of concurrent chemoradiation following maximal transurethral resection of the bladder tumor for muscle-invasive bladder cancer (MIBC). Current TMT treatment guidelines allow for several different radiosensitizing chemotherapy regimens, however there is limited data on existing use patterns. Methods: Using data from CancerLinQ Discovery, 71,499 patients with a bladder tumor diagnosed between 2000-2022 were included. Patients with documented radiation to “bladder” or “pelvis” with no known metastatic disease and a documented chemotherapy regimen started within a 30-day window of radiation, were included in the final analyses (n=233). Chemotherapy regimens included cisplatin, gemcitabine, 5FU+ mitomycin, taxanes, and other. Through bivariate analyses, patient characteristics and TMT treatment patterns were characterized. Results: The most commonly utilized TMT chemotherapy regimen was cisplatin alone (42.5%) followed by gemcitabine (19.3%), 5FU+ mitomycin (15.8%), taxanes (12.5%) and other (9.9%). These data demonstrated a significant relationship between age at diagnosis and chosen TMT regimen (p=0.017). Patients &lt;65 were more likely to receive cisplatin (27.3%), 5FU mitomycin (29.7%) or other (30.4%) while patients 85+ were more likely to receive gemcitabine (28.9%). Patients more frequently received cisplatin alone prior to 2017 (before 2011: 28.3% vs. 2011-2016: 53.5% vs. 2017-2022:18.2%, p-value &lt;.001), with a trend towards more gemcitabine use in the most recent period between 2017-2022 (51.1% vs. before 2011: 20.0% vs 2011-2016: 28.9%, p-value &lt;.001). Additionally, there was less taxane use over time (before 2011: 37.9% vs. 2011-2016: 55.2% vs 2017-2022: 6.9%, p-value &lt;.001). Finally, the association between TMT regimen and Charlson Comorbidity Index (CCI) trended toward significance—those treated with cisplatin alone were most likely to have a CCI of 0 (62.6%, p-value = 0.081) while patients receiving gemcitabine alone or 5FU + mitomycin were more likely to have a CCI of 1+ (gemcitabine alone: 51.1%, 5FU + mitomycin 51.4%, p-value = 0.081). Conclusions: There remains wide variation in the use of chemotherapy regimens in TMT with cisplatin monotherapy as the most utilized radiosensitizing agent overall. Since 2000, there has been a shift away from taxane therapy and increased gemcitabine use. Patients with lower CCI had a trend to more frequently receive cisplatin and older patients more frequently received gemcitabine. Further investigations are needed to better characterize patient characteristics as well as toxicity and survival by drug regimen to better help inform treatment guidelines.
De novo financial toxicity in patients with prostate cancer following radical prostatectomy and its impact on health-related quality of life.
Authors: Thilo Westhofen, Alexander Buchner, Lennert Eismann, Severin Rodler, Armin Becker, Christian G. Stief, Alexander Kretschmer
Journal: Journal of Clinical Oncology (2024)

318 Background: Financial toxicity (FT), a patient-reported outcome measure (PROM) is defined as the detrimental impact of financial burden caused by a cancer diagnosis on a patient’s well-being. FT is common among cancer patients, yet little is known about FT following radical prostatectomy (RP) for prostate cancer in countries with universal health coverage. We aimed to assess de novo FT and its impact on health-related quality of life (HRQOL) in a large prospective cohort of patients undergoing RP with a systematic follow-up of up to 10 yrs. Methods: 2254 consecutive patients who underwent RP at a large tertiary care center were analyzed. PROMs were prospectively assessed preoperatively, postoperatively at 3mo, then annually until a maximum follow-up of 120mo, applying the validated EORTC QLQ-C30- and the prostate cancer-specific QLQ-PR25 questionnaires. FT was assessed by the “financial toxicity subscale” (FTS) of the EORTC QLQ-C30. Based on previous reports, meaningful FT was defined as FTS ≥ 17. Multivariable regression analysis was used to identify predictors for the development of de novo FT. Separate modeling of longitudinal HRQOL was performed for patients with de novo FT (FT-cohort) and without FT (no-FT-cohort). General HRQOL was assessed by the global health status domain (GHS) of the EORTC QLQ-C30. Results: 298 patients reporting FT prior RP were excluded from further analysis. 20.3% (n=397) of the included patients reported de novo FT within 12 months after RP with a mean FTS-score of 47.3 (SD 21.9). Baseline clinicopathological characteristics did not differ between the FT-cohort and the no-FT-cohort (p-range .060-.173). Multivariable logistic regression analysis revealed subsequent therapies following RP (OR 1.981, 95%CI 1.11-3.53, p=.020), low preoperative emotional functioning (OR 0.990, 95%CI 0.92-0.99, p=.031) and low preoperative social functioning (OR 0.990, 95%CI 0.98-0.99, p=.035) to independently predict development of de novo FT after RP. In longitudinal analysis, significantly worse general HRQOL was observed for patients with de novo FT postoperatively and up to 48mo after RP (p-value each &lt; .001). In the longer term, both cohorts reported no significant difference in general HRQOL up to 10yrs post RP (p-range: .90 - .91). Conclusions: The current study provides prospective data from a unique contemporary patient cohort, which reveals independent predictors for de novo FT in prostate cancer patients following RP. Furthermore, it displays the natural course of general HRQOL for patients who develop de novo FT.
PRECISION 1: A phase 2, multicenter, open-label basket trial of <i>nab</i>-sirolimus for malignant solid tumors harboring pathogenic inactivating alterations in <i>TSC1</i> and <i>TSC2</i>.
Authors: Gopa Iyer, David J. Kwiatkowski, Li Ding, Anita N. Schmid, Willis H. Navarro, Jordi Rodon Ahnert
Journal: Journal of Clinical Oncology (2024)

TPS526 Background: According to SEER data, patients in the USA with advanced genitourinary (GU) cancers such as bladder and kidney cancers have low 5-year survival rates of 8.3% and 17.8%, respectively. This underscores the need for more efficacious treatments. Tumor growth and disease progression may be facilitated by aberrant activation of the mTOR pathway in some GU cancers. The tumor suppressor genes TSC1 and TSC2 are critical negative regulators of the mTOR pathway, and their inactivation may result in tumor growth. Inactivating TSC1 and TSC2 alterations have been observed in GU cancers with combined frequencies of up to 9.6% in bladder, 5.8% in kidney, and 0.7% in prostate cancers. nab-Sirolimus, approved in the USA for patients with advanced malignant perivascular epithelioid cell tumor (PEComa), is an albumin-bound mTOR inhibitor (mTORi) that inhibits the mTOR pathway via suppression of the mTORC1 complex. Clinically, in an exploratory analysis of AMPECT (NCT02494570), a pivotal trial of nab-sirolimus in advanced malignant PEComa, 8/9 (89%) and 1/5 (20%) patients with inactivating alterations in TSC2 and TSC1, respectively, had a confirmed response. Most treatment-related adverse events in AMPECT were grade 1/2 (none were grade ≥4) and were consistent with mTORi-class adverse events. Based on the clinical observations from AMPECT and the underlying mechanism of action of nab-sirolimus, the PRECISION 1 trial was designed to assess the safety and efficacy of nab-sirolimus in a tumor-agnostic study of patients with advanced cancers harboring TSC1 or TSC2 inactivating alterations. Enrollment is open to patients with bladder, kidney, and prostate cancers with TSC1 or TSC2 inactivating alterations. Methods: In PRECISION 1 (NCT05103358), eligible patients are ≥12 years old and mTORi-naïve, have advanced malignant solid tumors with TSC1 or TSC2 inactivating alterations identified using next-generation sequencing (NGS) in tumor tissue or liquid biopsy (confirmed by central review of NGS reports), and they have received appropriate standard treatments, per investigator. nab-Sirolimus 100 mg/m 2 will be given intravenously over 30 min on days 1 and 8 of each 21-day cycle. The primary endpoint is overall response rate per independent radiographic review (IRR) using Response Evaluation Criteria in Solid Tumors v1.1. Other endpoints include duration of response, time to response, progression-free survival by IRR, overall survival, patient-reported quality of life, and safety. Enrollment began in March 2022. Collaboration with leading NGS vendors will expedite the identification of patients with qualifying TSC1 and TSC2 alterations; ongoing study access is facilitated through a just-in-time approach to trial location activation. Clinical trial information: NCT05103358 .
Pharmacodynamics and gene expression analysis of patients with renal cell carcinoma treated with combination nivolumab and TPST-1120 in a phase I clinical trial (NCT03829436).
Authors: Bruno R. Bastos, Nathan Standifer, Rohan Garje, Sam H. Whiting
Journal: Journal of Clinical Oncology (2024)

438 Background: TPST-1120 is a first-in-class, oral inhibitor of peroxisome proliferator-activated receptor (PPAR-α), a fatty-acid ligand-activated transcriptional factor that controls the expression of multiple genes involved in fatty acid oxidation (FAO), angiogenesis and inflammation. In a phase 1 open-label trial, TPST-1120 was administered as a single agent and in combination with nivolumab in multiple tumor types. Among the tumor types treated, 4 patients in the combination arm had Renal Cell Carcinoma (RCC). 2 of the patients experienced clinical and radiographic response confirmed by RECIST. On this study, we plan to further study the pharmacodynamic and radiographic changes in these patients with RCC to further understand signals to identify patients who may benefit from this treatment. Methods: Mutational analysis of ctDNA was assessed using the PredicineCARE assay (Predicine Inc.), and lipid analysis was performed by tandem mass spectrometry. Gene Expression changes were quantified using the nCounter PanCancer Iune Profiling Panel (Nanostring Inc.) supplemented with 30 PPAR-α target genes. The radiographic Analysis was performed with CT chest-abdomen-pelvis and response evaluated using RECIST criteria. Results: RCC patients with PR (2/4) confirmed by RECIST exhibit greater reductions in 6 PPAR-α regulated genes. They had an early increase in thrombospondin (TSP-1) level due to PPAR-α inhibition. An increase in long-chain fatty chain fatty acids was seen including circulating FFA, lysophosphorylcholine (LPC) or lysophosphorylethanolaine (LPE). They also had great reductions in 6 PPAR-α regulated genes including ACAD8, ACSL3, CPT2, FABP1, FABP3, HADHB. Conclusions: There is a paucity of treatment options for patients with stage IV RCC post anti-PD1 and anti-VEGF therapies. Novel therapies on this clinical scenario are needed. On this abstract we showed radiographic and pharmacodynamic data on patients with RCC who achieved a clinical partial response by RECIST on the phase I clinical trial TPST1120-001. The trial explored the se of a PPAR-α inhibitor in combination with Nivolumab. The pharmacodynamic data indicates that there is fatty acid oxidation perturbation and immune gene expression changes as potential biomarkers of clinical benefit. PI3K pathway or IDH mutations may indicating a signal that RCC patients may benefit from this combination therapy. Larger studies in the future may be designed to further explore the use of this combination in patients with RCC. Clinical trial information: NCT03829436 .
Comparative outcomes of radical nephroureterectomy and kidney-sparing surgery in the treatment of high-grade upper tract urothelial carcinoma.
Authors: Helen Gao, Kyle Moore, Jennifer Delgado, Anirudh Kulkarni, Benjamin Lichtbroun, Kevin J. Chua, John Pfail, Vignesh T. Packiam, David Golombos, Thomas L. Jang, Saum Ghodoussipour
Journal: Journal of Clinical Oncology (2024)

607 Background: Patients with upper tract urothelial carcinoma (UTUC) can be managed with either radical nephroureterectomy (RNU) or kidney sparing surgery (KSS) depending on the pathology and patient specific characteristics. Due to the rarity of this disease, high-level evidence is lacking with regard to clinical and oncologic outcomes after surgery. This study aims to compare outcomes of RNU with KSS for patients with high-grade (HG) UTUC. Methods: We retrospectively reviewed patients with &gt;1 year follow-up who were treated for HG UTUC at our institution from 2015-2021. Oncologic and clinical outcomes were recorded. Procedure-related burdens, including total number of procedures under anesthesia, anesthesia time, and days hospitalized were collected. Results: 65 patients were analyzed, with 46 patients treated via RNU and 19 treated via KSS. There were no differences in the ASA or CCI between patients in the two groups. The 5-year overall survival (OS) was 65.2% (95% CI, 52.8%-80.5%) for RNU and 44.4% (95% CI, 26.5%-74.5%) for KSS. The 3-year metastasis-free survival was 78.3% for RNU and 78.9% for KSS. The 3-year recurrence-free survival, including recurrences in the bladder, was 47.8% (95% CI, 35.4%-64.7%) for RNU and 43.8% (95% CI, 25.1%-76.3%) for KSS. A decline of GFR &lt;10 2 years after surgery occurred in 97.1% of patients treated with RNU and 100.0% of those treated with KSS. The total number of procedures under anesthesia was higher for KSS than RNU at 3.4 +/- 1.7 vs 2.1 +/- 1.7, respectively (p = 0.0155). The total number of TURBTs for KSS and RNU was similar at 0.6 +/- 0.7 vs 1.1 +/- 1.7, respectively (p = 0.9538). The total number of days hospitalized for KSS was similar to RNU at 5.5 +/- 4.3 vs 6.8 +/- 4.6, respectively (p = 0.3579). The total anesthesia time for KSS was 400 +/- 218 min and was 474 +/- 185 min for RNU (p = 0.2561). Conclusions: There were similar oncologic and clinical outcomes in patients with HG UTUC treated with either KSS or RNU. Patients treated with KSS saw a higher procedural load. There was a trend towards lower OS for patients treated with KSS but this was not statistically significant, likely due to the small sample size. Larger datasets are needed to further evaluate outcome and treatment burdens of RNU vs KSS as treatment options for patients with HG UTUC. [Table: see text]
Effect of neutrophil to lymphocyte ratio (NLR) on outcomes with immune checkpoint inhibitors (ICIs) in patients (pts) with metastatic urothelial carcinoma (mUC) in real-world setting.
Authors: David Lynn, Scott Dawsey, Ubenthira Patgunarajah, Nikhil Pramod, Wei Wei, Charbel Hobeika, Monica Nair, Kimberly Maroli, Allison Martin, Moshe Chaim Ornstein, Christopher Eing Wee, Timothy D. Gilligan, Amanda Nizam, Amanda Bonham, Omar Y. Mian, Paul G. Pavicic, C. Marcela Diaz-Montero, Shilpa Gupta
Journal: Journal of Clinical Oncology (2024)

678 Background: Elevated inflammatory biomarkers like the neutrophil to lymphocyte ratio (NLR) has been associated with poor prognosis in several cancers, including UC but there is limited evidence on its role as a prognostic biomarker in patients (pts) with mUC treated with ICIs. We studied the effect of baseline (pre-treatment) NLR on outcomes with ICI in mUC pts in our large cohort of patients with mUC treated with ICIs. Methods: We identified 335 adult pts with mUC at the Cleveland Clinic treated who received &gt;/= 2 cycles of ICI with pembrolizumab (P) or atezolizumab (A) between 2015 and 2023. Patient characteristics including age, sex, race, primary site (bladder vs upper tract UC (UTUC)), tumor histology and pre-ICI treatment NLR values were collected and divided into four quartiles: (NLR &lt;2.7, 2.7-4.0, 4.0-7.1, and &gt;7.1). Impact of NLR on overall survival (OS) and progression free survival (PFS) post ICI start date was studied. OS and PFS were estimated using the Kaplan Meier method and compared by log rank test. Results: Of the 335 pts, NLR values were available for 320 pts. Median age was 73 yrs (35-95) and 76% pts were males. 247 pts (74%) received P and 88 (26%) received A. We found that in the 320 patients with available NLR values, the highest quartile values of NLR &gt;/= 7.1 was significantly associated with worse OS (p=0.01). We did not find a statistically significant impact of NLR on PFS (p=0.06). (Table). Conclusions: In our large real-world cohort of pts with mUC receiving ICI, we report the effect of baseline NLR on outcomes with ICI and that NLR &gt;/=7.1 was associated with significantly worse OS. Further validation studies are warranted to risk-stratify pts with mUC planned for ICI treatment. [Table: see text]
Utilization of patient-reported outcomes to assess adherence to relugolix when combined with radiation therapy.
Authors: Kelly Gaudian, Min Ji Koh, Min Jung Koh, Ryan Collins, Zoya Zwart, Malika Danner, Alan Zwart, Marilyn Ayoob, Thomas M. Yung, Mark Fallick, Deepak Kumar, Michael Carrasquilla, Paul Denis Leger, Nancy Ann Dawson, Simeng Suy, Sean P. Collins
Journal: Journal of Clinical Oncology (2024)

319 Background: Injectable GnRH receptor agonists have been shown to improve cancer control when combined with radiotherapy (RT). Relugolix is an oral GnRH receptor antagonist that achieves rapid testosterone suppression. Non-adherence to oral medications due to poor social support or bothersome side effects may increase the risk of cancer recurrence. This prospective study sought to evaluate early testosterone suppression and relugolix drug adherence when combined with RT. Utilization of patient-reported outcomes (PROs) to evaluate oral medication adherence and guide intervention may improve appropriate utilization of oral medications. This study focuses on the use of the Simplified Medication Adherence Questionnaire (SMAQ) as a tool to assess relugolix adherence. Methods: Relugolix was initiated at least 2 months prior to questionnaire administration. Adherence was assessed using the SMAQ. Total testosterone levels were obtained at the time of SMAQ administration. Castration was defined as serum testosterone ≤ 50 ng/dL. Poor drug adherence was delineated as failure to reach castration or non-adherence per the SMAQ (any non-adherence answer, missed &gt;2 doses in last week or since last visit). To compare the demographic and clinical characteristics of patients who adhered to treatment versus who did not, t-test, Wilcoxon rank sum test, Chi-square test, and Fisher’s exact test were used. A p-value &lt;0.05 determined statistical significance. Results: Between May 2021 and June 2023, 92 men were treated at Georgetown with relugolix and RT per an institutional protocol. The median age was 73 years, and 32% of patients were non-white. Patients initiated relugolix at a median of 5 months prior to the SMAQ (2-24 months). 97% of patients achieved castration (≤ 50 ng/dL) at the time of the SMAQ. 96% of men reported always taking relugolix at the appropriate time. 3% discontinued medication due to bothersome side effects, 18% reported forgetting to take the medication, and 2% reported missing a dose during the weekend. 99% and 97% did not miss a dose more than 2 times in the last week and since the last visit, respectively. Overall patient-reported drug adherence was 73%. Conclusions: Relugolix allows for high rates of castration and drug adherence when combined with RT. Monitoring drug adherence during treatment allows for prompt detection of non-adherence and timely intervention. Future studies should focus on how to optimally incorporate this questionnaire into patient management. [Table: see text]
Lenvatinib plus everolimus (LenEve) in patients with pre-treated advanced renal cell carcinoma (mRCC): Real world evidence (Relevance).
Authors: Philipp Ivanyi, Hendik Eggers, Ramona Stelmach, Martin Boegemann, Arne Strauß, Christian Thomas, Johannes Landmesser, Mario W Kramer, Stefanie Zschaebitz
Journal: Journal of Clinical Oncology (2024)

437 Background: The therapeutic armamentarium in mRCC underwent a rapid change during the recent past. LenEve, proved to be effective as subsequent treatment in mRCC in clinical trials.Here, we evaluate efficacy and safety in mRCC patients in a real-world setting. Methods: mRCC patients who started LenEve treatment between 08/2016 and 12/2021 at 6 tertiary German centers were retrospectively analyzed. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR), were evaluated per local investigator. Subgroup analyses by risk scores, previous therapies and initial dosing were performed. Results: Eighty-one patients were assessed: Median age was 61 years (range 42-80), 81.5% were males, ECOG score was 0 to 1 in 80.2%. Synchronous metastases were found in 39.5% of patients. The median number of treatment lines prior to LenEve was 3. Median treatment duration with LenEve was 6.1 months (range 0.2-29.2). The ORR, DCR, median OS and PFS was 28.4%, 61.7%, 11.3 months (95% CI 8.7-13.9) and 6.5 months (95% CI 5.4-7.6), respectively. Across patients with 0-2 compared to ≥3 previous therapeutic lines median PFS, OS and ORR were similar, as well as for patients with or without previous immunotherapy. Safety was manageable, with 6.2% of patients discontinuing treatment due to treatment related adverse events. Conclusions: High efficacy in second- and later-line in a heavily pre-treated real-world cohort of mRCC patients was demonstrated by LenEve, regardless of treatment line, IMDC risk group, initial dosing or previous treatment with immunotherapy.