tbuckley/cabot-search huggingface dataset:
Identifying patient profiles and mapping treatment journeys of ARPI-treated, taxane-naive patients with metastatic prostate cancer across three countries in a digital patient survey.
Authors: Joe M. O'Sullivan, Reiner Lehmann, Henning Sievert, Stephen Allen, Ernst-Günther Carl, Howard Wolinsky, Andreas Poschenrieder, Osvaldo Mirante, Alicia K. Morgans
Journal: Journal of Clinical Oncology (2024)

56 Background: A fully digital survey of patients with prostate cancer (PCa) was conducted in Germany (DE), the US and the UK to map characteristics, experiences and attitudes. Real-world profiles and treatment journeys, as well as intercountry differences, of taxane-naive patients with metastatic PCa (mPCa) are relatively unknown; data from the survey were leveraged to gain insights into these. Methods: From February 9 to April 10, 2021, DontBePatient Intelligence conducted a survey of patients with PCa. We identified responses from patients with mPCa who were taxane-naive and received at least one androgen receptor pathway inhibitor (ARPI), such as abiraterone or enzalutamide. Demographics, disease characteristics, diagnostic trends and treatments journeys were analyzed, using descriptive and inductive statistics. Results: In total, 458 taxane-naive patients (mean age 68.9 years) had received one ARPI, while 36 had received two. There were differences in time since, mode of, and disease stage at diagnosis between countries (Table). Notably, more US patients were diagnosed through routine screening, yet more had been diagnosed with metastases vs UK/DE. UK patients more frequently reported hospital urologists and oncologists being involved in diagnosis vs DE/US patients. In DE, practice urologists were more frequently reported as being involved vs other specialties throughout the patient journey and these were more involved than in the UK/US. UK patients were more satisfied with radio/brachytherapy and hormone therapy and less satisfied with surgery vs DE/US patients. We uncovered considerable differences in treatment journeys between countries. UK patients had received less surgery vs DE/US patients (9.8% vs 41.5/33.1% patients), driven by less use in 1L. Radio/brachytherapy use was highest in the US (69.4%) and lowest in DE (37.3%), driven by infrequent 1L use in DE. Treatment with bone strengthening agents was less common in the UK (16.4%) vs DE/US (37.3/33.8%). Conclusions: In different countries, taxane-naive patients who received one ARPI have different characteristics at diagnosis and distinct patterns of care. It is important to understand how these differences may affect diagnostic and therapeutic trends to maximally improve patient care in this treatment setting. [Table: see text]
Impact of <sup>18</sup>F-flotufolastat PET on management of patients with recurrent prostate cancer: Data from the SPOTLIGHT study.
Authors: Przemyslaw Twardowski
Journal: Journal of Clinical Oncology (2024)

38 Background: 18 F-Flotufolastat ( 18 F-rhPSMA-7.3) is a newly approved high affinity PSMA-targeting PET radiopharmaceutical for diagnostic imaging in patients with prostate cancer (PCa). SPOTLIGHT (NCT04186845) evaluated 18 F-flotufolastat in patients with recurrent PCa. Here, we report available SPOTLIGHT data to assess the impact of 18 F-flotufolastat on planned treatment after curative-intent primary therapy. Methods: Patients underwent PET 50–70 min after IV administration of 296 MBq 18 F-flotufolastat. The protocol instructed onsite investigators to record patients’ management plans (MP) before and after 18 F-flotufolastat PET. These MP were compared and categorized as: ‘no change’, ‘major change’, ‘other change’, ‘additional information required’ or ‘intended plan not valid’. A ‘major change’ was defined as a change to treatment modality (e.g., salvage radiation therapy [RT] to systemic therapy), while ‘other change’ represented a change within a modality (e.g., modified RT field). Plans categorized as ‘no change’, ‘major change’ or ‘other change’ were considered evaluable. All imaging data were subsequently submitted for blinded image evaluation (BIE) by 3 central readers. Results: Of 389 patients who had 18 F-flotufolastat PET, 97 had sufficient MP data for evaluation. These 97 patients were comparable to the overall population in terms of prior treatment (84% vs 79%, respectively, were post-prostatectomy), Gleason Score (63% vs 60% had Score 7), and median baseline PSA (0.8 vs 1.1 ng/mL). Moreover, BIE data show the detection rate in this subgroup (81/97; 84%) to be equivalent to that in the overall population (322/389; 83%). Most patients, 86/97 (89%) had a change to their MP post-scan. A ‘major change’ was noted for 78 (80%) patients, while 8 (8.2%) had an ‘other change’ (Table). Onsite imaging reads show that both positive and negative 18 F-flotufolastat scans influenced MP. While 88% of revisions occurred after a positive scan, 75% of those whose MP were revised to watchful waiting (WW) had negative scans. All patients with MP revised from salvage therapy to non-curative systemic therapy had distant/extrapelvic 18 F-flotufolastat-avid lesions. Conclusions: 18 F-Flotufolastat located recurrence sites in the majority of patients with recurrent PCa, frequently resulting in major changes to MP. Treatment based on visualization of 18 F-flotufolastat-avid lesions may facilitate optimal targeting of recurrence sites and avoid futile salvage therapy. Future studies of the outcome of such MP changes are warranted. Clinical trial information: NCT04186845 . [Table: see text]
Utility of PSMA PET/CT for imaging ductal carcinoma of the prostate.
Authors: Ahmed M. Mahmoud, Patrick Navin, Miguel Muniz, Fernando Quevedo, Jacob Orme, Jack R. Andrews, Adam McLain Kase, Osama M Mosalem, Alan Haruo Bryce, Irbaz Bin Riaz, Brian J. Burkett, Ayse T. Kendi, Geoffrey Johnson, Praful Ravi, Eugene D. Kwon, Oliver Sartor, Daniel S Childs
Journal: Journal of Clinical Oncology (2024)

49 Background: Ductal carcinoma (DC) is the second most commonly encountered histologic variant of prostate cancer. Previous studies have described its molecular features and aggressive behavior, but few have explored the performance of PSMA PET/CT in the initial staging and follow-up of DC. Methods: To address this gap, we performed a single-institution retrospective analysis using the Mayo Clinic PSMA PET database. All patients receiving a PSMA PET/CT scan in the interval of January 1, 2021, to December 31, 2022, were eligible for inclusion. Cases were filtered and categorized by histology at the time of diagnosis to select for pure DAC and mixed ductal variants. Trained research personnel annotated disease- and treatment-related variables. A board-certified radiologist performed tumor burden segmentation with calculations of SUV max, total lesion SUV mean and volume, and total lesion uptake, and ascribed a miPSMA expression score. Results: We queried 1792 patients from our PSMA PET/CT registry and identified 32 (1.8%) patients with a pathologically confirmed DC, including 8 (25%) patients with pure ductal and 25 (75%) patients with mixed histology. The indication for PSMA PET/CT was biochemical progression or restaging for 29 (91%) patients and initial staging for 3 (9%) patients. The median (IQR) time from prostate cancer diagnosis to PSMA PET scan was 41.6 (11.5-64.7) months, during this time 50% (n= 16) of patients developed CRPC. At the time of the PSMA PET/CT scan, the median age was 70 years, the median (IQR) PSA was 0.5 ng/mL (0.2-2.6). The distribution of metastatic spread and quantitative imaging parameters from PSMA PET are shown in the Table. Conclusions: Despite low PSA at the time of imaging, PSMA PET/CT frequently detected high volume osseous and/or visceral metastases in patients with DC. However, it is noteworthy that more than 50% of patients with DC had a low miPSMA score (0-1). Additional studies are needed to better understand the performance of novel imaging modalities when evaluating variant prostate cancers. [Table: see text]
Glymphatic-stagnated edema induced by traumatic brain injury
Authors: Per Kristian Eide, Geir Ringstad
Journal: Trends in Pharmacological Sciences (2024)

Traumatic brain injury (TBI) outcomes are notably affected by brain edema. A recent report by Hussain et al. unveils a unique form, glymphatic-stagnated brain edema, that stems from impaired glymphatic and lymphatic drainage induced by noradrenergic activation. Consequently, pan-noradrenergic inhibition may emerge as an innovative treatment for TBI-related edema, challenging traditional therapeutic approaches.
Effect of prednisone dosing on mineralocorticoid-related side effects with abiraterone in prostate cancer.
Authors: Maksym Goryachok, Andrew Nicklawsky, Hiba Ahmad, Thomas W. Flaig
Journal: Journal of Clinical Oncology (2024)

67 Background: Abiraterone, a 17a hydroxylase inhibitor, is used for prostate cancer and can lead to mineralocorticoid excess syndrome (e.g. hypertension and hypokalemia). Concurrent prednisone mitigates these effects; however, the optimal prednisone dosage is unclear. This study examines the occurrence of mineralocorticoid side effects from Abiraterone with 5 mg of prednisone daily versus 5 mg twice daily. Methods: Data for 1410 patients treated with abiraterone from 2011 to 2022 were identified from a large academic/community hospital system (Health Data Compass Data Warehouse project). Laboratory measures, clinical parameters, and ICD10 codes were collected from 6 months prior to abiraterone initiation through treatment duration. 348 patients were excluded for missing medication data, discordant prednisone initiation, and use of a second steroid; 1062 patients remained (5 mg daily, N = 555, 10 mg daily, N = 507). Prednisone dose was treated as a time-varying covariate due to dose-switching (N = 122). Hypokalemia and hypertension incidence over 24 weeks after abiraterone initiation was analyzed via time to event frailty cox-proportional hazard models using both CTCAE v5.0 grade and ICD 10 code outcomes. Results: Patients on 5 mg of prednisone twice daily had approximately a 96% longer average time to first event for a combined-endpoint of hypertension and hypokalemia via ICD10 code methodology at any point during the 24 weeks following abiraterone initiation (HR 0.51, CI 0.43 - 0.62, P &lt; 0.001). This trend was durable with individual ICD10 analysis in hypertension (HR 0.52, CI 0.43 - 0.62, P &lt; 0.001) and hypokalemia (HR 0.45, CI 0.30 - 0.66, P = &lt;0.001). Assessing direct clinical measurements via incidentally recorded blood pressure and potassium lab values, the analysis for grade 2/3 hypertension (HR 0.81, CI 0.7-0.93, P = 0.004) and grade 3 hypokalemia (HR 0.46, CI 0.26-0.82, P = 0.008) also showed a corresponding increase in average time to first measure favoring the 5 mg twice daily cohort during the 24-week period. Conclusions: This study shows a significant delay in the development of hypertension and hypokalemia from abiraterone with 5 mg twice daily compared to 5 mg of prednisone daily. This was observed both with ICD10 coding and direct clinical measurements of these events within the EMR. Assessments of other physiologic parameters and survival are ongoing. These findings highlight the impact of prednisone dosing with abiraterone, which may merit additional consideration in specific at-risk patient populations including those with baseline hypertension or cardiovascular risk factors.
Analysis of real-world survival for patients with metastatic castration-sensitive prostate cancer (mCSPC) treated with apalutamide (APA) or abiraterone acetate (ABI) in an oncology database: ROMA study.
Authors: Mehmet Asim Bilen, Ibrahim Khilfeh, Carmine Rossi, Shawn Du, Jill Korsiak, Alvi Rahman, Patrick Lefebvre, Dominic Pilon, Neal D. Shore
Journal: Journal of Clinical Oncology (2024)

58 Background: Androgen receptor signaling inhibitors (ARSI), including APA and ABI plus prednisone, are approved for the treatment of mCSPC. However, studies evaluating survival for these agents in clinical trials or the real-world have not been investigated. This study describes real-world survival among men with mCSPC who initiated APA or ABI in the United States (US). Methods: Data from the Flatiron Metastatic Prostate Cancer (PC) Core Registry Electronic DataMart (1/1/2013–05/31/2023) was used to identify ARSI-naïve patients with chart-confirmed metastasis and without evidence of castration resistance at ARSI initiation. Patients were classified into two treatment cohorts based on the start date for APA or ABI (index date) on/after 9/17/2019. Patients had ≥12 months of clinical data pre-index and were followed from the index date until the earliest of 24 months post-index, end of clinical activity, or end of data availability. Patients’ date of death was obtained by integrating data from electronic medical records, the Social Security Death Index, and or other confirmed sources. Using an intention-to-treat approach, Kaplan-Meier analysis was used to describe the proportion of patients surviving by 24 months post-index. An unadjusted Cox proportional hazards model was used to describe crude differences in survival rates between patients initiating APA and ABI. Results: This study included 242 APA (mean age: 73.0 years; 60.3% White, 13.6% Black) and 607 ABI (mean age: 73.1 years; 57.3% White, 16.8% Black) patients. APA median time on-treatment was 11.4 months over a median observation period of 14.3 months. ABI median time on-treatment was 10.8 months over a median observation of 14.0 months. By 24 months, 85.7% of the APA cohort and 75.9% of the ABI cohort were living (unadjusted hazard ratio=0.60, 95% confidence interval: 0.38, 0.96; p=0.033; Table). Conclusions: In this study, we observed that more ARSI-naïve patients with mCSPC survived by 24 months after initiating APA than those who initiated ABI. While the current study presents unadjusted comparisons, additional causal analyses controlling for confounding variables should be conducted to confirm these initial findings. [Table: see text]
Survival Outcomes of APA as a Starting treatment: Impact in real-world patients with mCSPC (OASIS).
Authors: Benjamin L. Maughan, Suneel Mundle, Mehregan Nematian-Samani, Xiayi Wang, Shawn Du, Yanfang Liu, Lawrence Ivan Karsh
Journal: Journal of Clinical Oncology (2024)

65 Background: Over the last decade,androgen receptor signaling inhibitors (ARSIs; apalutamide [APA], enzalutamide [ENZ], abiraterone acetate + prednisone [AAP]) in combination with androgen-deprivation therapy (ADT) have emerged as more effective life-prolonging treatment options for mCSPC. We examined the impact of ARSI starting therapy in mCSPC on long-term clinical outcomes in real-world clinical practice in the US. Methods: This retrospective, observational cohort study evaluated clinical outcomes in adult patients with mCSPC using the ConcertAI RWD 360 prostate cancer dataset. All patients with newly diagnosed mCSPC from 1 Jan 2018 to 30 Sept 2022 were enrolled and followed up until 31 Mar 2023. Among other outcomes, PSA50 and PSA90 (PSA response defined as a ≥50% and ≥90% decline from baseline, respectively) and undetectable PSA (PSA ≤0.2 ng/mL) were assessed using the Kaplan-Meier method. Relative risks of onset of castration resistance (CR) and death were estimated using multivariate Cox proportional hazard models adjusted for potential confounding factors (age, comorbidities, BMI, baseline PSA). Results: 165 patients with mCSPC started on APA + ADT, 643 started on ENZ + ADT, 1064 on AAP +ADT, 293 on docetaxel (DTX) + ADT, and 543 on ADT alone (Table). A higher proportion of patients initiating APA achieved PSA50, PSA90, or undetectable PSA compared with other treatments. CR-free survival was significantly longer in patients first treated with an ARSI + ADT than those treated with DTX + ADT or ADT alone. Reduced risk of developing CR was observed in patients starting with APA + ADT compared with ADT alone (adjusted hazard ratio [aHR] 0.36, 95% CI 0.19, 0.67; p=0.0016). OS was longer in patients started on ARSIs compared to ADT alone. Patients starting with APA + ADT were observed to have a lower risk of death compared with ENZ + ADT (aHR 0.48, 95% CI 0.23, 0.99; p&lt;0.05) or AAP + ADT (aHR 0.43, 95% CI 0.21, 0.90; p&lt;0.05). Conclusions: ADT alone continues to be used widely despite the availability of newer and more effective life prolonging therapies. Use of APA + ADT as starting treatment for mCSPC demonstrated significantly better clinical outcomes than other ARSIs, DXT + ADT, or ADT alone in real-world clinical practice in the US. [Table: see text]
Updated automated PROMISE assessment: Treatment response evaluation based on PSMA PET/CT.
Authors: Cecil Mayra Benitez, Hannicka Sahlstedt, Johan Brynolfsson, Gholam Reza Berenji, Jesus Eduardo Juarez, Nathanael Kane, Sonny Tsai, Matthew Rettig, Nicholas George Nickols, Sai Duriseti
Journal: Journal of Clinical Oncology (2024)

48 Background: PSMA PETs can track treatment response in patients with prostate cancer. Recent integration of the RECIP framework with PROMISE v2 allows quantitative assessment of PSMA PETs. While useful for assessing differentially responding lesions, manual measurement and tracking is cumbersome and PSA reliance can be misleading. We evaluated an automated AI-enabled platform, aPROMISE, for longitudinal lesion tracking to evaluate treatment response based solely upon tumor volume. Methods: Patients with castration sensitive or resistant disease undergoing 18F-DCFPyL PET/CTs during workup and at ≥3 months after treatment were included. Tracer-avid lesions were identified using the aPROMISE algorithm. Detected lesions were manually approved by an experienced nuclear medicine physician. After lesion identification and approval, the total tumor volume was calculated. The corresponding low-dose CT was auto-segmented, allowing anatomic compartment (prostate/bed, node, bone, or visceral) annotation of 18 F-DCFPyL-avid lesions. Baseline and follow-up PETs were deformably co-registered to automatically match individual lesions if they were in the same anatomic compartment, and had overlap &lt;10 mm center-to-center (&lt;50 mm for rib lesions). Unmatched lesions on follow-up PET were noted as new. Response was assessed as CR (no avidity in follow-up), PR (volume decrease ≥30% without new lesions), SD (volume decrease ≥30% with new lesions), or PD (volume increase ≥20% plus new lesions). Volume changes at the total tumor and individual lesion levels were also assessed independent of RECIP imaging criteria. Results: The automated algorithm assigned the correct RECIP classification in 97% of the 67 cases with 14 as CR, 14 as PR, 20 as SD, and 19 as PD. 1027 of the 1686 lesions identified on baseline PET were seen on follow-up. 673 of the 1700 lesions identified on follow-up PET were new. Conclusions: For response assessment using 18 F-DCFPyL PET/CT and RECIP imaging criteria, the automated algorithm and manual detection achieved the same clinical classifications. Automated approaches may allow more granular lesion analysis The precision and accuracy this automated process is being validated in prospective clinical studies.
Association between SPECT/CT total tumor volume (TTV) and new lesions (NLs) in early cycles of <sup>177</sup>Lu-PSMA-617 (LuPSMA) and progression-free and overall survival (PFS and OS) in men with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Ridvan Arda Demirci, Roman Gulati, Peter Nelson, Heather H. Cheng, Jessica E. Hawley, Todd Yezefski, Michael C. Haffner, Robert Bruce Montgomery, Michael Thomas Schweizer, Evan Y. Yu, Delphine L Chen, Amir Iravani
Journal: Journal of Clinical Oncology (2024)

40 Background: LuPSMA is a newly established treatment in patients with mCRPC, but PSA and survival outcomes vary widely, and predictors of treatment responses are needed. LuPSMA delivers radiation to tumor tissues that can also be imaged with SPECT/CT which provides semiquantitative estimates of TTV and identification of NLs. This study investigates the use of SPECT/CT in early cycles to predict LuPSMA outcomes. Methods: Between June and December 2022, mCRPC patients who initiated the 2 nd cycle of LuPSMA with SPECT/CT 24 hours post-treatment were retrospectively reviewed. We evaluated associations between TTV and the appearance of NLs at the start of the 2 nd or 3 rd cycle with PFS and OS using Cox regression analysis. NLs were classified as non-PSMA-avid with no or low uptake (&lt; liver) with corresponding findings on CT and PSMA-avid (uptake &gt; liver). All analyses were adjusted for change in PSA relative to baseline. Results: Sixty-six mCRPC patients (median age, 73.5) received a median of 4 (IQR: 3-5) cycles of LuPSMA. Median follow-up starting at 2 nd cycle was 26 weeks (IQR: 21-36) with 47/66 (71%) alive at the time of the analysis. A reduction of ≥50% in PSA (PSA50) was noted in 33/66 (50%) patients. Changes in PSA and TTV at 2 nd and 3 rd cycle were apparently concordant in 50/66 (76%) and 42/51 (82%) and were significantly correlated (r= 0.55 and 0.56, both p&lt;0.001). Patients with higher absolute TTV adjusted for PSA change at 2 nd cycle had worse PFS and OS (HR=1.3 and 2.26) with consistent results at 3 rd cycle (Table). NLs were detected in 13/66 (7/13 PSMA-avid, 6/13 non-PSMA-avid) and 7/51 patients (5/7 PSMA-avid, 2/7 non-PSMA-avid) at 2 nd and 3 rd cycle, respectively. Patients with NLs at 2 nd cycle had higher risks of progression and death (HR=4.53 and 6.28). Conclusions: Higher SPECT/CT TTV at 2 nd and 3 rd cycle and detection of NLs at 2 nd cycle were associated with higher risks of progression and death. Although changes in PSA and TTV were correlated, absolute SPECT/CT TTV in early cycles provided a complementary ability to predict outcomes of LuPSMA. [Table: see text]