tbuckley/cabot-search huggingface dataset:
Hospital challenges faced by frail patients with ovarian cancer and the adverse outcomes: A nationwide study.
Authors: Nataly Ortega Yaguachi, Saad Javaid, Kelly Frasier, Vivian Li, Julia Vinagolu-Baur, Evadne Rodriguez, Olivia Del Castillo, Raquel Batista, Kenlee Jonas, Laura Palma
Journal: Journal of Clinical Oncology (2024)

5572 Background: Ovarian cancer is a leading cause of gynecological cancer-related deaths and one of the most common causes of cancer-related fatalities among women. Frailty has been identified as a predictor of unfavorable outcomes for cancer patients, but there is limited research on its impact on individuals with ovarian cancer. We examined the effects of Frailty in hospitalized ovarian cancer patients and the associated outcomes. Methods: National Inpatient Sample (NIS) 2020 was used to identify the patients with a primary diagnosis of ovarian cancer (local/regional and advanced metastatic) and was stratified into patients with and without Frailty. The primary outcome was mortality, and secondary outcomes included length of stay, the total cost of hospitalization, and other in-hospital adverse outcomes. Multivariate logistic regression analysis was used to calculate the outcomes after adjusting for confounding variables. Results: A total of 19790 patients were hospitalized with a primary diagnosis of Ovarian cancer, among which 3215 (16.24%) patients had the concurrent diagnosis of Frailty. The mean age of patients with and without Frailty was 65.76 (+/-13.10) and 60 (+/-14.45),p&lt;0.001, respectively. After adjusting for confounding variables, Frailty was associated with an increased risk of mortality in patients with ovarian cancer (OR=3.01(1.83-4.95); p&lt;0.001). Patients with Frailty were also at risk of increased length of stay (+3.80 Days (3.09-4.50; p&lt;0.001) and total cost of hospitalization (+ $ 34662 (22973-46351); p&lt;0.001). Frail patients also had an increased likelihood of Acute respiratory failure (OR=1.72 (1.22-2.42); p=0.002), Acute kidney injury (OR=2.40 (1.88-3.05); p&lt;0.001), Sepsis (OR=4.97 (3.19-7.75); p&lt;0.001), ICU admission (OR=2.23 (1.44-3.45); p&lt;0.001), Pneumonia (OR=2.63 (1.69-4.10); p&lt;0.001), total parenteral nutrition (OR=14.20 (7.80-25.83); p&lt;0.001) and Intubation (OR=2.11 (1.21-3.69); p=0.008). However, there was no difference in the risk of noninvasive mechanical ventilation (OR=2.07 (0.95-4.52); p=0.48) or enteral feeding (OR=32.73 (0.63-1696); p=0.08). Conclusions: Frailty in ovarian cancer patients is considered an independent predictor of mortality. It is also associated with increased healthcare resource utilization and adverse in-hospital outcomes.[Table: see text]
Clinical characteristics and outcomes of veterans with metastatic hormone-sensitive prostate cancer (mHSPC) based on volume of disease and site of metastases.
Authors: Kaitlin Stackable, Carley Pickett, Forest Riekhof, Nicholas Fedele, Priya Baxi, Kara Ingram, Krishny Karunanandaa, Srinivas Govindan, Nina Cheranda, Rohan Agarwal, Martin W. Schoen
Journal: Journal of Clinical Oncology (2024)

e17083 Background: Metastatic hormone-sensitive prostate cancer (mHSPC) is categorized by volume of disease and high tumor volume is associated with worse outcomes. Assessment of volume of disease and site of metastases at diagnosis may help risk stratify patients with mHSPC. This study describes patient characteristics and survival in U.S. veterans treated for mHSPC. Methods: Veterans were identified with initial diagnosis of SEER stage ‘distant’ prostate cancer. All veterans had androgen deprivation therapy (ADT) initiated within 4 months of diagnosis and followed until September 2023. Veterans treated with ADT alone during 2018, ADT+docetaxel (DOC) from 7/2016-6/2021 or androgen receptor pathway inhibitors (ARPIs) abiraterone, enzalutamide, apalutamide, and darolutamide from 7/2017-6/2021 were included if initiated within 4 months after ADT. Veterans were categorized as high or low volume of disease by chart review. If patients had more than one site of metastasis, they were categorized as follows: any liver, any lung, any high volume bone. Age, PSA, and body mass index (BMI) were collected at diagnosis and compared by ANOVA or Kruskal-Wallis with Bonferroni correction for multiple comparisons. Results: 1520 veterans were identified with 886 high volume bone metastases, 154 lung metastases, 70 liver metastases, and 410 low volume patients. Mean age of patients was 72.3 years (SD 0.4) with median PSA of 103.2 ng/mL and mean BMI of 27.4. There was no difference in mean age between high volume and low volume (72.3 vs. 72.5 years, p=0.28), however median PSA was higher in high volume (152.0 vs. 48.8 ng/mL, p&lt;0.001) and median BMI was lower in high volume (26.5 vs. 27.5, p=0.002). High volume metastasis was associated with shorter survival (31.2 vs. 56.3 months, p&lt;0.001). For site of metastases, there was no difference in age between location (p=0.365), PSA was higher in liver, lung, and high volume bone compared to low volume while for BMI, only liver metastasis was associated with significantly lower BMI. Liver metastasis was associated with shorter survival compared to low volume, high volume bone, and lung metastasis (all p&lt;0.001 by log-rank). Conclusions: High volume disease and liver metastases were associated with shorter survival in veterans with mHSPC. Presence of liver metastasis was independently associated with decreased overall survival compared to high volume bone or lung metastases. Volume of disease and location of metastases may provide information for prognostication in mHSPC. [Table: see text]
Dynamic androgen receptor alterations (ARa) ctDNA profiles and clinical outcomes in metastatic prostate cancer (mPC).
Authors: Chinmay Jani, Eli Tran, Nicole Zhang, Jill Tsai, Leslie A Bucheit, Elizabeth Pan, Justine Panian, Rana R. McKay
Journal: Journal of Clinical Oncology (2024)

5069 Background: The AR plays a pivotal role in PC pathogenesis and ARa, including ligand binding domain mutations and amplifications, can evolve under the selective pressure of androgen deprivation therapy and androgen receptor signaling inhibitors (ARSi). Next-generation sequencing of circulating tumor DNA (ctDNA) enables non-invasive, longitudinal monitoring of AR dynamics in patients (pts) undergoing systemic therapies. This study aims to explore the dynamic changes in ctDNA profiles, particularly focusing on the AR gene and its association with clinical outcomes. Methods: We utilized GuardantINFORM, a clinical-genomics database containing de-identified ctDNA test results and commercial payer-claims data. Eligible pts had a diagnosis of mPC and underwent ctDNA testing pre (within 3 months prior to initiation) and post (within 3 months of discontinuation prior to initiating subsequent treatment) ARSi, poly ADP‐ribose polymerase inhibitors (PARPi), and taxane chemotherapy. The primary endpoint was to characterize changes in molecular alterations pre- and post-therapy. Secondary endpoints included overall survival (OS), time to treatment discontinuation (TTD), and time to next treatment (TTNT) for pts receiving with ctDNA testing within 3 months prior to 1L ARSI for mCRPC. Results: From a database of 21,682 pts with PC, 145 had ctDNA collected pre/post ARSI, 54 pre/post PARPi, and 115 pre/post taxane chemotherapy. We observed increased ARa across the three treatment groups (%pre/%post): ARSi (17/35), PARPi (39/43), and taxanes (44/58) (Table). In the ARSi group, most common (%pre/%post) ARa included AR amplifications (11/23), AR T878A (5/9), AR L702H (2/6) and AR H875Y (0.7/1.4). In the PARPi group, the most prevalent (%pre/%post) ARa comprised AR amplifications (24/32), AR L720H (15/15), AR T878A (11/9) and AR F877L (2/6). In the taxane group, notable (%pre/%post) ARa consisted of AR amplifications (33/44), AR L702H (4/10), AR H875Y (3/9) and AR T878A (7/8). 1294 pts had ctDNA testing prior to 1L ARSi for mCRPC and were included in the outcomes analysis. Pts with ARa showed worse TTD (2.8 vs 4.3, p&lt;0.0001), TTNT (6.9 vs 4.8, p&lt;0.0001) and (OS (15.3 vs 49.3, p&lt;0.0001). Conclusions: Our study elucidates evolving changes in AR in mPC using ctDNA profiling. We observed an increase in ARa following ARSi, PARPi, and taxane treatment in mPC. Furthermore, our findings highlight associations between ARa and clinical outcomes, emphasizing the potential for personalized treatment strategies in mPC pts based on molecular profiling. [Table: see text]
Treatment outcomes for patients with Ga68-PSMA-PET prostate cancer (PC) with or without conventional imaging correlates.
Authors: Wadih Issa, Maureen Aliru, Damla Gunenc, Song Zhang, Qinhan Zhou, Qian Qin, Jue Wang, Waddah Arafat, Kevin Dale Courtney, Daniel X. Yang, Neil B Desai, Aurelie Garant, Raquibul Hannan, Jeffrey A. Cadeddu, Kris Gaston, Solomon L. Woldu, Vitaly Margulis, Yair Lotan, Andrew Zhuang Wang, Tian Zhang
Journal: Journal of Clinical Oncology (2024)

5078 Background: The high sensitivity of PSMA PET/CT in pts with PC has created a new advanced disease space (PSMA+/CT-) with stage migration. Treatment outcomes and optimal management remain largely unstudied for these pts. Methods: Pts with metastatic castration sensitive PC identified during standard of care PMSA PET/CT imaging (Ga68 gozetotide/PSMA-11) were reviewed retrospectively at UTSW and stratified by whether a CT lesion correlates to a PSMA avid lesion (SUVmax &gt;2.5): PSMA+/CT- vs PSMA+/CT+ groups. The primary objective was PSA Progression Free Survival (PFS) and time to castration resistance (TTCR) between cohorts. The secondary objective was TTCR in pts with PSMA+/CT- disease based on exposure to androgen deprivation therapy (ADT) alone or with AR-targeted therapy (ARTT intensification). Cohorts were compared using a two-sample t-test or a chi-square test; survival analysis was conducted using Kaplan-Meier and Cox proportional hazards regression. Results: Overall,135 pts were included; of whom 122 received ADT (PSMA+/CT- [n=73] vs PSMA+/CT+ [n=49]) and 13 PMSA+/CT- pts received localized treatment only. PSMA+/CT- and PSMA+/CT+ pts had comparable median age at diagnosis and similar racial distribution. The median follow-up was 19 months. In pts who received ADT, the PSMA+/CT- group had a lower median PSA (1.3 vs 14 ng/ml, P=0.0002), a lower rate of de-novo metastatic disease (30% vs 55%, p=0.0082) and ADT+ ARTT use (59% vs 88%, p=0.0006) compared to the PMSA+/CT+ group. Median therapy duration was similar. In pts receiving ADT, the median PSA PFS in the PSMA+/CT- group was not reached (NR) versus 37 months in the PSMA+/CT+ group. After adjusting for known prognostic factors, PSMA+/CT- lesions were significantly associated with a better PSA PFS and TTCR (Table). In pts with PMSA+/CT- receiving ADT alone (n=30) vs ADT+ARTT (n=43), only 1 patient progressed to castration resistance. After adjusting for prognostic factors, pts with PSMA+CT- disease who received ADT had a better PSA PFS [HR 0.1 (0.02-0.45)] compared to those who received localized therapy only (n=13). Conclusions: Pts with PSMA+CT- PC vs pts with PSMA+/CT+ PC have better prognosis and outcomes, with low rates of PSA progression and castration resistance. Localized therapy alone is likely insufficient for these pts, and ARTT intensification to improve longer term outcomes needs prospective studies through ongoing trials. [Table: see text]
Prognostic validation of a digital pathology-based multi-modal artificial intelligence (MMAI) biomarker in patients with metastatic hormone-sensitive prostate cancer (mHSPC) from the CHAARTED trial (ECOG-ACRIN EA3805).
Authors: Mark Christopher Markowski, Yi Ren, Danielle Croucher, Trevor Joseph Royce, Rikiya Yamashita, Meghan Tierney, Huei-Chung Huang, Tamara Todorovic, Emmalyn Chen, Michael Anthony Carducci, Yu-Hui Chen, Glenn Liu, Charles Parker, Andre Esteva, Felix Y Feng, Gerhardt Attard, Christopher Sweeney
Journal: Journal of Clinical Oncology (2024)

5077 Background: The ArteraAI MMAI prognostic biomarker leverages histopathology images and clinical data to risk stratify patients (pts) with localized prostate cancer. This study aimed to validate the MMAI biomarker in mHSPC. Methods: The validation cohort included a subset of pts from the CHAARTED phase III randomized trial with known age at diagnosis, baseline PSA, T-stage, and available histopathology images. Baseline characteristics were compared to examine the balance between included and excluded patients. Using the existing MMAI model, scores were generated, and prognostic ability was evaluated for overall survival (OS) in Cox proportional hazard model. Four defined prognostic groups based on tumor volume (high (HV) vs. low (LV)) and metastatic stage at diagnosis (M1 vs. M0) were included: 1. M0LV, 2. M0HV, 3. M1LV, 4. M1HV. These clinical groups were evaluated using multivariable analysis (MVA) which included MMAI risk group and treatment. Results: A subset of the CHAARTED patient population had evaluable digital histopathological images, allowing inclusion in this study (N=456/790, 57.7%), of which 370 (81.1%) were classified as MMAI-high and 86 (18.9%) as MMAI-intermediate/low risk. Data were available from 394/456 pts for classification into M0LV (N=57), M0HV (N=29), M1LV (N=66), or M1HV (N=242). MMAI-high proportion among groups were 56.1%, 69.0%, 86.4% and 92.6%, respectively. Median follow-up of the censored patients was 4.1 (IQR: 3.3-5.0) yrs. The estimated 5-yr OS across MMAI high, intermediate, and low groups was 39%, 58%, 83%, respectively (log rank p=&lt;0.001). On MVA, the MMAI-high risk group model associated with OS (HR: 1.77 (95% CI: 1.10-2.84) p=0.02) adjusting for treatment arm, volume status, and stage at diagnosis (Table 1). When compared to M0LV, HV subgroups were also associated with OS on MVA. Conclusions: The ArteraAI MMAI model was found to be prognostic for OS among men with mHSPC in CHAARTED. This effect persisted when controlling for treatment, metastatic burden, and metastatic status at diagnosis. On MVA, M0HV and M1HV also maintained prognostic value. This analysis is exploratory in nature, to be followed by development of a model optimized for advanced prostate cancer.[Table: see text]
Rectal spacer in radiotherapy for prostate cancer: Correlation of spacer symmetry to rectal dosimetry.
Authors: Tomer Charas, Yossi Ben Dor, Veronique Bakouche, Salem Billan
Journal: Journal of Clinical Oncology (2024)

e17102 Background: Rectal spacers are used to temporarily position the anterior rectal wall away from the prostate during radiotherapy for prostate cancer, and to limit the exposure of the rectum to excessive radiation. These spacers use different insertion techniques and filling materials. Our study aims to compare and correlate the symmetry and rectal dosimetry in patients implanted with either the balloon spacer (BioProtect Balloon Implant System) or a gel spacer (SpaceOAR). Methods: A qualitative model utilizing measurements of prostate-rectal interspace from axial computed tomography scans was applied to assess 62 T1c-T4 prostate cancer patients (28 balloon, 34 gel spacer) undergoing SBRT (5/6 fractions, 36-40 Gy) or IMRT (20/28 fractions, 60-70 Gy). Spacer symmetry at midgland, 1 cm superior or inferior to midgland was scored as ‘S’. Asymmetrical placement (1 or 2cm lateral left or right) was scored as 1 or 2. Axial slices with no spacer was scored as 0. A total symmetry score (SYM) was evaluated by using a scoring of SYM-S indicating spacer symmetry in all 3 slices and scores ranging 1-to-4 representing increasing spacer asymmetry. SYM score was then evaluated relatively to rectal dosimetry at V60%-V100%. Results: For balloon and gel spacers, symmetrical distribution at midline, at 1 cm inferior and superior to midgland was observed in 16 (57.1%) and 18 (52.9%) patients, 16 (57.1%) and 15 (44.1%) patients, 10 (35.7%) and 12 (35.3%) patients, respectively. The balloon was not visible in 3 (10.7%) superior slices compared to 3 (8.8%) inferior and 6 (17.6%) superior gel spacer slices, receiving score 0. The mean rectal dose for the balloon spacer compared to the gel spacer was 9.8 and 12.9 for V60%, 5.6 and 7.9 for V70%, 3.1 and 4.5 for V80%, 1.5 and 2.0 for V90% and 0.12 and 0.17 for 100% respectively. The study results show that as the spacers became more asymmetric, the rectal dose-volume at V60%-V100% increased. Conclusions: The balloon provides a better symmetrical distribution and lower dose to the rectum compared to the gel. The potential advantages of the balloon should be further evaluated in a prospective setting.
Oncogenic alteration rates, race, and prostate cancer specific mortality in Veterans with metastatic prostate cancer undergoing somatic tumor next generation sequencing.
Authors: Luca Faustino Valle, Jiannong Li, Heena Desai, Ryan Hausler, Candace Haroldsen, Michael J. Kelley, Timothy Rebbeck, Brent S. Rose, Matthew Rettig, Nicholas George Nickols, Isla Garraway, Kosj Yamoah, Kara Noelle Maxwell
Journal: Journal of Clinical Oncology (2024)

5017 Background: National guidelines recommend next generation sequencing (NGS) of tumors from patients diagnosed with metastatic prostate cancer (PCa) to identify potential actionable alterations. We sought to determine associations between alteration frequencies of PCa-related genes and pathways, self-identified race, and PCa specific mortality (PCSM) in Veterans. Methods: This comprehensive retrospective cohort study evaluated the association of somatic alterations with race in Veterans with metastatic PCa who obtained NGS through the Veterans Affairs National Precision Oncology Program. NGS data was linked to clinicopathologic and social determinants of health (SDOH) data elements. Multivariate logistic regression permitted associations between race and genomic alteration frequencies, adjusted for specimen tested and clinical and SDOH co-variates. Cox proportional hazards models permitted associations of race, alteration frequencies, and PCSM, stratified by genomic alteration frequencies and adjusting for race, clinicopathologic features, and SDOH. Results: 5015 Veterans with metastatic PCa and self-identified race/ethnicity as non-Hispanic Black (NHB, n=1784) and non-Hispanic White (NHW, n= 3231) were included. NGS was conducted on primary tumors (n= 2359), metastases (n = 1011), and cfDNA (n = 1644). NHB Veterans were younger, had higher PSA at PCa diagnoses, were less likely to report Agent Orange exposure, and resided in more deprived neighborhoods. Upon adjusting for tissue sequenced and clinicopathologic variables, NHB race/ethnicity was significantly associated with a higher rate of genomic alterations in immunotherapy targets, SPOP and BRAF(p&lt;0.05 for all) .Furthermore , NHB race/ethnicity was significantly associated with lower rates of genomic alterations in the AKT/PI3K pathway, AR axis ,and tumor suppressor genes including TP53and PTEN(p&lt;0.05 for all). While alterations in TP53 (HR 1.5 [1.1-2.0], p=0.007), and tumor suppressor pathways (HR 1.3 [1.0-1.8], p=0.04) conferred a significantly higher risk of PCSM in all men on adjusted analysis, race was not independently associated with PCSM. Conclusions: In this diverse cohort of Veterans undergoing NGS for metastatic PCa in the equal access VA healthcare system, we observed significant differences in alteration rates of several oncogenic genes/pathways by race. While alterations in tumor suppressor genes were significantly associated with PCSM, race was not. Thus, there remains a critical need for integrating personalized approaches to patient selection for metastatic PCa treatments in order to improve disease-specific outcomes across diverse populations.
Randomized PROSTATE-IQ trial to reduce ADT treatment burden for patients with biochemical recurrence after prostatectomy.
Authors: Karen E. Hoffman, Marisa Kollmeier, Paul L. Nguyen
Journal: Journal of Clinical Oncology (2024)

TPS5130 Background: Men with PSA recurrence of prostate cancer after prostatectomy often receive Androgen Deprviation Therapy (ADT) with salvage radiation therapy to the prostate resection bed. Traditional ADT improves cancer control; however, it also causes fatigue, sexual dysfunction, hot flashes, cognitive changes, metabolic dysregulation, body composition changes, and negatively impacts men’s quality of life. Methods: The PROSTATE-IQ trial is a randomized multi-center clinical trial that is investigating ways to reduce the adverse effects of ADT treatment. First, the trial uses intrinsic cancer properties assessed by ArteraAI and clinical-pathologic variables to personalize the intensity of Androgen Axis Therapy (AAT). Those with low ArteraAI score are assigned to the Artera Low Cohort and those with either high ArteraAI score, PSA &gt;0.5 ng/ml or nodal involvement are assigned to the Higher-risk Cohort. Second, the trial randomizes men between traditional ADT and apalutamide-based therapy. We hypothesize that the apalutamide-based therapy will reduce the adverse effects of treatment and thereby improve quality of life. 220 men in the Artera Low Cohort are being randomized between 6 months of ADT vs. 6 months of apalutamide monotherapy. 220 men in the Higher-risk Cohort are being randomized between 24 months of ADT (winning arm of RADICALS-HD trial) vs. 6 months of apalutamide and ADT (winning arm of FORMULA 509 trial). We hypothesize that the apalutamide-based treatments will reduce fatigue and boost activity, sleep, and cognitive function. Patients wear an activity and sleep tracker, undergo cognitive assessments, and complete validated fatigue, leisure activity, and mental health questionnaires. We will compare fatigue, activity, sleep, mental health, body composition, metabolic dysregulation, quality of life, and cancer control between treatment arms. This trial will be impactful because it is the first to use the validated ArteraAI test to personalize intensity of androgen axis therapy and because it will reduce the adverse effects of treatment and improve quality of life for prostate cancer survivors treated with salvage radiation and androgen axis therapy.