tbuckley/cabot-search huggingface dataset:
Independent blinded validation of an AI-based digital histology classifier for prostate cancer recurrence and metastasis risk prediction.
Authors: Magdalena Fay, Ross Liao, Zaeem M Lone, Chandana A. Reddy, Hassan Muhammad, Chensu Xie, Parag Jain, Wei Huang, Hirak S Basu, Jane Nguyen, Sujit S. Nair, Dimple Chakravarty, Sean R. Williamson, Shilpa Gupta, Christopher Weight, Rajat Roy, George Wilding, Ashutosh K. Tewari, Eric A. Klein, Omar Y. Mian
Journal: Journal of Clinical Oncology (2024)

5098 Background: Artificial intelligence (AI) tools which identify pathology features from digitized whole slide images (WSI) of prostate cancer (CaP) generate data to predict risk of disease recurrence and metastasis. PathomIQ and ISMMS have developed an AI-enabled prognostic test, PATHOMIQ_PRAD, which predicts risk of biochemical recurrence (BCR) and distant metastasis (DM) using WSIs. The objective of this study was to evaluate the clinical validity of PATHOMIQ_PRAD using a retrospective clinical cohort at Cleveland Clinic. We also compared the test's performance to Decipher, an established genomic risk classifier. Methods: We conducted a retrospective PATHOMIQ_PRAD analysis of CaP WSIs of patients who underwent prostatectomy at Cleveland Clinic from 2009-2022 and did not receive any adjuvant therapy before BCR. 263 patients in the cohort received definitive treatment with radical prostatectomy and had a median follow-up of 50 months. Of these patients, 65 patients had BCR, and 14 patients developed DM as of last follow up. WSIs were de-identified, anonymized, and patient outcomes were blinded during the study. Patients were stratified into high-risk and low-risk categories based on pre-determined thresholds for PATHOMIQ_PRAD scores (0.45 for BCR and 0.55 for DM). The Kaplan-Meier method with log-rank was used to compare biochemical recurrence-free survival (BCRFS) and metastasis-free survival (MFS). Multivariable Cox proportional hazards regression was used to identify factors associated with BCR. Results: The rate of BCRFS and MFS were associated with both PATHOMIQ_PRAD score (BCR: &gt;0.45 vs. &lt;0.45, p&lt;0.0001; DM: &gt;0.55 vs. &lt;0.55, p&lt;0.0001) and Decipher score (BCR: &gt;0.6 vs. &lt;0.6, p=0.0009; DM: &gt;0.6 vs. &lt;0.6, p=0.0095). All 14 patients who had DM during the follow up time had a high PATHOMIQ_PRAD score. Univariate analysis shows that PATHOMIQ_PRAD reliably identifies patients at risk of BCR (HR: 4.19, p&lt; 0.0001), and had comparable prognostic performance to Decipher (HR: 2.83, p=0.0013). Multivariate analysis (Table) shows that there was an increased risk of BCR in both the high-risk PATHOMIQ_PRAD (HR: 3.58, p=0.0005) and Decipher (HR: 2.20, p=0.0159) groups relative to the low-risk groups, which suggests that combining the two tests may further improve risk stratification. Conclusions: These results show that PATHOMIQ_PRAD continues to demonstrate clinical validity in predicting risk of BCR and DM with favorable performance compared to a commonly used genomic classifier. PATHOMIQ_PRAD may identify patients for early treatment intensification, as well as inform clinical trial patient selection. [Table: see text]
Real-world treatment patterns with lutetium-177-PSMA-617 (<sup>177</sup>-Lu-PSMA) in patients with metastatic castrate-resistant prostate cancer (mCRPC).
Authors: Sami Dwabe, Omid Yazdanpanah, Brian Warnecke, David Joseph Benjamin, Arash Rezazadeh, Nataliya Mar
Journal: Journal of Clinical Oncology (2024)

e17064 Background: The VISION study demonstrated improved outcomes with up to 6 doses of 177 -Lu-PSMA plus standard-of-care (SOC) therapy versus SOC alone in pre-treated mCRPC patients, which led to its regulatory approval on 03/23/22. This is our real-world experience with 177 -Lu-PSMA at the University of California, Irvine and Hoag Hospital. Methods: This is a retrospective analysis of 22 patients with mCRPC treated with 177 -Lu-PSMA at the University of California, Irvine and Hoag Hospital since 03/23/2022. Baseline demographic, pathologic, and genomic characteristics of all patients who received 177 -Lu-PSMA (along with their outcomes) were analyzed. Results: Selected baseline characteristics of the study population are included in the table, which contrast treatment responders and non-responders. At the time of this analysis, 22.7% (5/22) of patients completed all 6 planned cycles of 177 -Lu-PSMA, 40.9% (9/22) discontinued early due to disease progression, 18.2% (4/22) are still receiving therapy, 9.1% (2/22) stopped treatment due to toxicity, and 9.1% (2/22) discontinued for other reasons. PSA reduction by at least 50% (PSA50) was achieved in 59.1% (13/22) of patients, 27.3% (6/22) achieved &lt; PSA50, and 3/22 (13.6%) had no PSA response at all. In PSA responders, the median time to PSA nadir was 11.7 weeks [range: 2.3 - 38.0], while the median time to second PSA rise above nadir was 6.0 weeks [range, 4.0 – 22.3]. Treatment related toxicities occurred in 54.5% (12/22) of patients, including 22.7% with dry mouth, 22.7% with fatigue, and 13.6% with nausea. Conclusions: This dataset highlightsreal-world treatment patterns with 177 -Lu-PSMA, which is an active and well-tolerated therapy. Despite initial response, some patients appear to have quick PSA progression, which led to early treatment discontinuation. We set out to evaluate if there were any baseline characteristics predictive of response among our patients. Ultimately, our data did not show any factors predictive of response to therapy. Given its financial toxicity, further studies identifying which patients are most likely to respond to 177 -Lu-PSMA are indicated. [Table: see text]
Rezvilutamide (REZ) plus docetaxel (DOC) in patients (pts) with chemo-naïve metastatic castration-resistant prostate cancer (mCRPC) after progression on abiraterone (ABI).
Authors: Zhenhua Liu, Qiang Wei, Ping Feng, Shusuan Jiang, Hong Luo, Hong Liao, Dexin Yu, Zhiwen Chen, Dahong Zhang, Tao Dai, Zeng Li, Zhiqiang Zhang, Hong Bai, Feng Liu, Wenliang Wang, Jiaqin Lin, Yike Wang
Journal: Journal of Clinical Oncology (2024)

5059 Background: Despite DOC is recommended for chemo-naïve mCRPC pts previously treated with novel hormone therapy, prognosis remains unfavorable. Herein we report the safety, PK, and preliminary efficacy of addition of REZ (a novel androgen receptor inhibitor) to DOC in chemo-naïve mCRPC pts who had progressed after ABI. Methods: This was a multicenter, 2-part, phase 2 study. Part 1 included a 3 + 3 dose escalation phase and a dose expansion phase. Eligible pts were enrolled to receive REZ (160/240 mg, PO, QD) plus DOC (75 mg/m 2 , IV, D1, Q3W, up to 10 cycles [C]), followed by REZ monotherapy (240 mg, PO, QD). REZ was given continuously staring from C1D2. DOC was concurrent with prednisone (5 mg, PO, BID). Both dose levels of REZ were selected to be expanded. Primary endpoint of part 1 was safety. Results: As of Aug 31, 2023, 36 pts were enrolled (18 with REZ 160 mg plus DOC and 18 with REZ 240 mg plus DOC). In the REZ 160 mg plus DOC and REZ 240 mg plus DOC groups, rate of pts with ECOG PS of 1 was 83.3% and 61.1%, rate of pts with Gleason score ≥ 8 was 88.9% and 72.2%, rate of pts with &gt;10 bone metastases was 66.7% and 44.4%, and median baseline prostate-specific antigen (PSA) level was 81.7 ng/mL (range: 2.7-5993.0) and 144.0 ng/mL (2.9-3720.0). No DLTs were reported. Treatment-related adverse events of grade ≥ 3 occurred in 32 (88.9%) pts (14 [77.8%] pts with REZ 160 mg plus DOC, and 18 [100.0%] pts with REZ 240 mg plus DOC), with the most common being decreased neutrophil count, decreased white blood cell count, and anemia. C2/C1 ratio of AUC 0-24h and C max of DOC was 0.73 and 0.78 when combined with REZ 160 mg, while that was 0.58 and 0.68 when combined with REZ 240 mg, which indicated influence of CYP3A strong inducer REZ on CYP3A4 substrate DOC with stronger impact at REZ 240 mg. Rate of PSA response at week 12 was 75.0%, time to PSA progression was 10.5 mo (95% CI, 5.6-11.3), and radiological PFS was 13.8 mo (95% CI, 5.7-19.6) with REZ 160 mg plus DOC, while that with REZ 240 mg plus DOC was 60.0%, 14.1 mo (95% CI, 4.1-21.4), and 8.5 mo (95% CI, 5.6-not reached) (Table). Conclusions: REZ plus DOC was well tolerated with promising efficacy in chemo-naïve mCRPC pts who had progressed after ABI. Clinical trial information: NCT04603833 . [Table: see text]
Prognostic reclassification and survival outcomes in intermediate- and poor-risk nonseminomatous germ cell tumors (NSGCT).
Authors: Kunal Naishadh Jobanputra, Gagan Prakash, Amandeep Arora, Bhagyashri Jadhav, Mahendra Pal, Akash Pawar, Sayak Dey, Ganesh Bakshi, Vedang Murthy, Priyamvada Maitre, Nandini Sharrel Menon, Minit Jalan Shah, Santosh Menon, Palak Popat, Aparna Ringe-Katdare, Nilesh Sable, Archi Agrawal, Vanita Noronha, Kumar Prabhash, Amit Joshi
Journal: Journal of Clinical Oncology (2024)

5033 Background: Intermediate and poor-risk nonseminomatous germ cell tumors (NSGCT) form a large group of patients with varying prognosis. There is a need to revisit the existing International Germ Cell Cancer Collaborative Group (IGCCCG) classification to identify the ‘poorest subset’ of patients. Methods: We retrospectively analysed the outcomes of consecutive patients with intermediate and poor-risk NSGCT who were diagnosed between 2015 to 2021 at our centre and had received first-line chemotherapy. Overall survival (OS) and relapse-free survival (RFS) were calculated by Kaplan-Meier analysis. A multivariate risk factor model was constructed out of the prognostic factors for OS and RFS. Concordance statistic (c-statistic) was computed and compared between the proposed model and IGCCCG classification and boot-strap sampling was used to evaluate this comparison. Results: A total of 360 patients were included, having a median age of 29 (IQR: 24-34) years, with 149 in the intermediate-risk and 211 in the poor-risk according to the IGCCCG classification. Most of the patients had testis as the primary site of the tumor (336 patients, 93.3%). Median follow-up was 58.0 months (95%CI 50.7-65.3). The 5-year OS was 84.4% (95%CI 78.5-90.8) in the intermediate-risk versus 55.3% (95%CI 48.4-63.1) in the poor-risk (p &lt; 0.001). RFS at 5 years was 76.8% (95%CI 70.0-84.3) in the intermediate-risk and 46.2% (95%CI 39.7-53.9) in the poor-risk (p &lt; 0.001). Age above 35 years, baseline alpha-fetoprotein (AFP) &gt;10,000 ng/mL, presence of liver and brain metastasis were identified to be poor prognostic risk factors for OS, while lung metastasis in addition to the above factors was prognostic for RFS by multivariate analysis. The multivariate model using the above four risk factors for OS had a higher c-statistic (0.668) than the existing IGCCCG classification (0.632) with an improvement of 0.036 (Table). This model also showed a similar improvement in c-statistic over IGCCCG classification for RFS (0.659 vs 0.625). Conclusions: The proposed model showed better discriminatory ability than the existing IGCCCG classification. This emphasizes the need to revise the risk stratification to identify the ‘very-high risk’ subset of patients for potential treatment intensification.[Table: see text]
Evaluation of tumor gene expression profile and Gleason score in patients with metastatic prostate cancer.
Authors: Carla Simone Moreira Freitas, Thais Almeida Marques da Silva, Fabiana Rocha Silva, Aleida Nazareth Soares
Journal: Journal of Clinical Oncology (2024)

e17065 Background: The Gleason Score (GS) is a fundamental prognostic indicator in prostate adenocarcinoma. Despite this significant clinical relevance, the determinants underlying disease aggressiveness in relation to GS remain largely unknown. To explore gene expression profiles among patients diagnosed with metastatic prostate adenocarcinoma, considering GS variation. Methods: This study is prospective in nature and was approved by CONEP-SCBH-CAAE 42638620.3.0000.5138. The study included 30 patients with histologically confirmed metastatic prostate adenocarcinoma who had not undergone any treatment. Patients were stratified into two distinct cohorts based on GS: low GS (GS &lt;8) and high GS (GS ≥ 8). This design allowed for a more in-depth analysis of the associations between gene expression profiles and GS variations in the context of metastatic prostate adenocarcinoma. Results: The data show that 26.7% of patients (n=8) had a GS lower than 8, while 73.3% (n=22) had a GS equal to or greater than 8. In patients with a GS lower than 8, genetic profile analysis revealed that the ATM gene was expressed in three patients and the BRCA2 and TP53 genes were detected in one patient (n=1 for each gene). In relation to patients with GS equal to or greater than 8, the TP53 gene was expressed in 7 patients; the BRCA2, CHECK2, FANCL, RAD51C and RAD54L genes were expressed in only one patient (n=1 for each gene). These results indicate a more prominent expression of TP53 in patients with high GS, suggesting a relationship between the expression of this gene and the aggressiveness of metastatic prostate cancer with GS ≥8. In the sample, no positivity was observed for the BRCA1, CDK12, CHECK1, PALB2, PPP2R2A, RAD51B and RAD51D genes. Conclusions: The results show that metastatic prostate cancer patients with GS ≥8 exhibit elevated TP53 gene expression. The current sample of 30 patients provides preliminary insight, but the statistical robustness of these associations could be improved with a larger cohort. Carrying out subsequent studies with a broader sample will allow for a more reliable validation of the observed trends, contributing to a more comprehensive understanding of the associations between the analyzed variables and gene expression in patients with metastatic prostate carcinoma. Therefore, the interpretation of the results presented must be carried out with caution, considering the need for a more substantial sample size to verify and consolidate possible associations identified. Clinical trial information: CAAE42638620.3.0000.5138.
Long-term survival outcomes for hormonal therapy in premenopausal patients with clinical stage I endometrial cancer.
Authors: Yukio Suzuki, Yongmei Huang, Laura J Havrilesky, Stephanie V. Blank, Elena B. Elkin, Alexander Melamed, Jennifer S. Ferris, Haruya Saji, Etsuko Miyagi, Chung Yin Kong, Evan R. Myers, Jason Dennis Wright
Journal: Journal of Clinical Oncology (2024)

5508 Background: As the number of young women with early-stage endometrial cancer is increasing, there is growing interest in use of progesterone-based therapy to allow fertility preservation. To date, there is a paucity of data on the safety and long-term outcomes of progesterone therapy. The objective of our study was to determine the safety and long-term outcomes of hormonal therapy for clinical stage I endometrial cancer in premenopausal women. Methods: The National Cancer Database was used to identify patients 18-49 years of age with clinical stage I, grade 1-2, endometrioid endometrial cancer diagnosed from 2004-2020. Primary treatment was defined as hysterectomy or hormonal therapy. Trends in the use of hormonal therapy were examined. A multivariable regression model was developed to examine the association between hormonal therapy and demographic factors. After propensity score matching, survival was compared between patients treated primarily with hormonal therapy and with primary hysterectomy. Results: A total of 15,849 patients, including 14,662 (92.5%) treated with primary hysterectomy and 1,187 (7.5%) who received primary hormonal therapy were identified. The use of hormonal treatment increased from 5.2% in 2004 to 13.8% in 2020 (P&lt;0.0001). In a multivariable model, younger age, more recent year of diagnosis, non-White race, lower tumor grade, and earlier stage were associated with use of hormonal therapy (P&lt;0.05 for all). After propensity score balancing, 5-year survival was 98.5% (95% CI, 97.3-99.2%) for hysterectomy and 96.8% (95% CI, 95.3-97.8%) for hormonal therapy (HR=1.84; 95% CI 1.06-3.21). Among patients &lt;40 years of age, there was no difference in survival between hysterectomy and hormonal therapy (HR=1.00; 95% CI, 0.50-2.00). However, for patients age 40-49, hormonal therapy was associated with a significantly increased risk of death (HR=4.94; 95% CI, 1.89-12.91). There was no statistically significant difference in outcomes for hormonal therapy compared to hysterectomy in sub-set analyses stratified by grade (1 or 2) or stage (1A or 1B). Conclusions: The use of fertility-preserving hormonal therapy among reproductive age patients with early-stage endometrial cancer has increased over time. Among women age 40-49, hormonal therapy is associated with decreased survival. [Table: see text]
Kidney outcomes in patients with bladder cancer: Insights from real-world data—A National Inpatient Sample (NIS) study, 2020.
Authors: Manasawee Tanariyakul, Sakditad Saowapa, Natchaya Polpichai, Chalothorn Wannaphut, Pitchaporn Yingchoncharoen, Jerapas Thongpiya, Pharit Siladech, Diego Alonso Olavarria Bernal, Nattanicha Chaisrimaneepan, Thitiya Sirisinha Dejthevaporn, Phuuwadith Wattanachayakul
Journal: Journal of Clinical Oncology (2024)

e16622 Background: Bladder cancer constitutes a notable etiological factor in kidney disease, precipitating acute kidney injuries (AKI) through mechanisms such as post-renal obstruction, with the potential for progression to chronic kidney disease (CKD) over time. The objective of this study is to systematically evaluate the correlation between bladder cancer and the manifestation of acute or chronic kidney disease across various stages, with a focus on hospitalized patients undergoing treatment for bladder cancer. Methods: The 2020 United States National Inpatient Sample (NIS) database was subjected to analysis in this study. We focused on adult patients (≥18 years) with a primary discharge diagnosis of bladder cancer, specifically those who were hospitalized for cancer and presented with a diagnosis of acute kidney injury or diverse stages of chronic kidney disease, as identified through pertinent ICD-10 CM codes. Utilizing survey multivariable logistic and linear regression analysis, we calculated adjusted odds ratios (ORs) to assess the outcomes of interest. A p-value of &lt;0.05 was deemed statistically significant in this analytical framework. Results: In 2020, 81,995 eligible patients were identified, with 75.62% being male. The ethnic distribution was 81% Caucasian, 8% Black, 5% Mexican American, and 2% Asian. Using a multivariable regression model adjusting for patient and hospital-level factors, bladder cancer showed a significant association with acute kidney injury (OR 1.92, 95% CI: 1.85-2.00, P &lt; 0.001) and all stages of chronic kidney disease (OR 1.66, 95% CI: 1.58-1.74, P &lt; 0.001). Further analysis revealed no significant association with early CKD stages 1 and 2 (P = 0.25 and 0.26), but a notable association with increased risk for CKD stages 3 and 4 (OR 1.45, 95% CI: 1.37-1.52, P &lt; 0.001) and (OR 1.69, 95% CI: 1.56-1.83, P &lt; 0.001), respectively. Intriguingly, bladder cancer displayed a negative association with CKD stage 5 (OR 0.76, 95% CI: 0.63-0.78, P &lt; 0.001). Conclusions: In summary, our study reveals that bladder cancer in hospitalized cancer patients is linked to increased risks of acute kidney injury (AKI), CKD stages 3 and 4, and a decreased risk of CKD stage 5. Vigilant kidney function monitoring is crucial during cancer hospitalization, given the elevated risk of worsening function. Proactive interventions are necessary to address kidney-related complications. Further longitudinal cohort studies are warranted to enhance our understanding and devise strategies to reduce the risk of CKD in individuals with bladder cancer.
Bacillus Calmette-Guerin (BCG) utilization and treatment (Tx) patterns in Chinese patients (pts) with non-muscle invasive bladder cancer (NMIBC): Results from a national urologist survey.
Authors: Wang He, Suili Zhuang, Zhenhua Liu, Lifang Jia, Huirong Mao, Jian Huang
Journal: Journal of Clinical Oncology (2024)

e16587 Background: China has the highest annual incidence (&gt;85,694 new cases) and mortality (&gt;39,393 deaths) from bladder cancer of any country; NMIBC is the most common subtype and is associated with a high risk of recurrence and progression. While intravesical BCG following transurethral resection (TURBT) is effective for NMIBC, there are limited real-world data on patient characteristics, BCG use and factors informing Tx decisions in China. Methods: We performed a cross-sectional, questionnaire-based survey of 300 urologists with experience of administering BCG for NMIBC from 13 cities and 10 provinces across China. Here, we summarized patient characteristics, urologists’ approach to risk assessment, BCG use and Tx patterns. Net Importance Score (NIS) was defined as the percentage of urologists who stated a factor was important (6–7 on a scale from 0–7) minus those who did not (1–4/7). Results: Pts with NMIBC had a median age of 59.6 years, 73% were male, 33% had a low annual household income (≤100,000 CNY [~13,700 USD]), 19% had a family history of cancer and the most common TNM stage was T1 (48%). The most common risk assessments (following the NCCN guidelines) were low- or intermediate-risk (both 35% of pts), followed by high risk (26%) and highest risk (4%). Urologists rated tumor stage and grade as the two most important factors for evaluating pt risk level. For pre-treated pts, the most common prior therapy was TURBT (87.1%). Among newly diagnosed pts and pts with recurrent NMIBC, 24% and 32% received BCG, respectively (overall 27%). BCG was most commonly monotherapy and at a dose of 120mg in both newly diagnosed (98% monotherapy/72% 120mg) and recurrent (96% monotherapy/74% 120mg) settings. Most urologists gave a schedule of induction (85%; BCG weekly, duration 6–8 weeks) followed by intensive Tx (65–69%; BCG Q2W, 6–8 weeks), and then maintenance (54%-68%;monthly; ≤1 year), depending on risk level. Compared with chemotherapy, 88% of responders agreed that BCG was more effective in preventing recurrence. The most important factors for choosing BCG were recurrence frequency and risk level and TNM stage (Table); 89% and 88% of urologists responded that limited BCG supply and pricing were important factors in continuing BCG. Post BCG, the most popular subsequent Tx was radical/partial cystectomy (35%) and intravesical chemotherapy (22%) although 15% of responders indicated they would extend BCG. Conclusions: These descriptive survey data provide important insights into real-world BCG utilization and factors influencing BCG use in NMIBC in China. [Table: see text]