tbuckley/cabot-search huggingface dataset:
The prognostic value of ductal adenocarcinoma of the prostate in patients with advanced prostate cancer treated with abiraterone acetate.
Authors: Yifu Shi, Xinyuan Wei, Fengnian Zhao, Jinge Zhao, Pengfei Shen, Ni Chen, Hao Zeng
Journal: Journal of Clinical Oncology (2024)

167 Background: Previous studies have indicated that ductal adenocarcinoma of the prostate (DA) is associated with adverse prognosis in patients with localized prostate cancer (PCa). However, the clinical significance of DA in advanced PCa remains largely ambiguous. This study endeavors to investigate the relationship between the existence of DA in prostate biopsy specimens and treatment outcomes among patients with advanced PCa receiving abiraterone acetate (AA) therapy. Methods: We retrospectively analyzed data from 440 patients with advanced PCa who received AA at either the metastatic hormone-sensitive (mHSPC, N=123) or castration-resistant PCa (mCRPC, N=317) stage. The presence of DA and its proportion was evaluated based on prostate biopsy specimens. Kaplan-Meier curves and COX regression were used to evaluate the predictive significance of DA on AA efficacy, including PSA response, PSA progression-free survival (PSA-PFS), and radiographic progression-free survival (rPFS). Results: In aggregate, DA was detected in 35/440 (8.0%) patients, with 13/440 (3.0%) and 22/440 (5.0%) men harboring DA&lt;5% and ≥5%, respectively, in the total tumors. The overall PSA response rate in the entire cohort was 302/440 (68.6%), and it was comparable for people with and without DA, with both groups having a response rate of 68.6%. Of note, compared with patients without DA, men with DA have significantly longer median PSA-PFS (mPSA-PFS, 12.1- vs. 25.0-Mo, P=0.005) and median rPFS (mrPFS, 19.8 vs. 38.2-Mo, P=0.034). Subgroup analysis based on DA proportion further revealed that in comparison with PCa without DA, DA≥5% was an indicator of favorable PSA-PFS (HR, 95%CI: 0.28, 0.14-0.56, p&lt;0.001) and rPFS (HR, 95%CI: 0.35, 0.18-0.72, p=0.004), while DA&lt;5% was not. In multivariate COX regression analysis, after adjusting by clinicopathological factors, including mCRPC/mHSPC stage, ISUP grading, metastatic burden, pain score and pretreatment hemoglobin, alkaline phosphatase, and lactate dehydrogenase, DA≥5% was still independently associated with better therapeutic efficacy of AA treatment (PSA-PFS: HR, 95%CI: 0.36, 0.17-0.74, p&lt;0.001; rPFS: HR, 95%CI: 0.47, 0.23-0.96, p=0.040). Conclusions: A DA proportion ≥5% in the tumor is related to improved treatment efficacy for individuals with advanced PCa receiving AA. Thus, in the pathological diagnosis of PCa, it is necessary to routinely report the presence and proportion of DA in order to aid with treatment decision-making.
Role of tumor mutational burden (TMB) and microsatellite instability (MSI) in patients (pts) with advanced urothelial carcinoma (aUC) treated with immune checkpoint inhibitor (ICI).
Authors: Dimitra Rafailia Bakaloudi, Rafee Talukder, Dimitrios Makrakis, Leonidas Nikolaos Diamantopoulos, Ubenthira Patgunarajah, Vinay Mathew Thomas, Tanya Jindal, Jason R Brown, Marija Miletic, Jeffrey Johnson, Gavin Hui, Lucia Alonso Buznego, Rafael Morales-Barrera, David Humberto Marmolejo Castañeda, Charles B Nguyen, Pedro C. Barata, Tyler F. Stewart, Shilpa Gupta, Petros Grivas, Ali Raza Khaki
Journal: Journal of Clinical Oncology (2024)

654 Background: MSI and TMB correlate with ICI efficacy. We assessed the association between TMB and MSI with outcomes in pts with aUC treated with anti-PD1/L1 in a ‘real-world’ cohort. We hypothesize that pts with high TMB and MSI-high (H) have better outcomes with ICI. Methods: In this retrospective study we included pts from 13 sites treated with ICI for aUC. We calculated overall response rate (ORR), median overall and progression-free survival (mOS, mPFS) using KM method from ICI start. TMB and MSI were assessed by NGS. TMB was analyzed as dichotomous (≥10 vs &lt;10 mut/Mb) and continuous variable. The analysis was stratified by therapy line (1L/upfront, 2+L). Multivariable models were adjusted by Khaki factors for 1L/upfront and Bellmunt factors for 2+L. We separately analyzed pts on maintenance avelumab (mAV). MSI is reported with descriptive statistics only. Results: 342 pts were treated with ICI 1L/upfront or 2+L (69% pure UC, median age at ICI start 69, 77% men, 90% White, 16% upper tract primary, 12% liver metastases [mets], 78% ECOG PS 0-1). Median f/u from ICI start was 34 months (mo). ORR was 36% (95%CI 26-46%) in pts with TMB≥10 vs 30% (95%CI 23-36%) with TMB&lt;10 (OR=1.4 [95%CI 0.8-2.5] p=0.3). ORR was 75% (6/8) in pts with MSI-H and 30% (60/200) with MSI stable (MSI-S). mPFS was similar between TMB≥10 and &lt;10 groups (6 vs 4 mo; HR=0.88 [95%CI 0.61-1.26] p=0.48) and between MSI-H and MSI-S (5 mo). mOS was numerically longer (not significant) in pts with TMB≥10 vs TMB&lt;10: 25 vs 21 mo; (HR=0.7 [95%CI 0.50-1.09] p=0.12) and with MSI-H and MSI-S (NR and 20 mo). A significant association was found between TMB (continuous variable) and OS (HR=0.97 [95%CI 0.95-0.99] p=0.01). TMB analyses by therapy line are shown in Table. In the 1L/upfront setting (N=144), ORR 71% (5/7) vs 33% (45/135), mPFS 5 and 4 mo, mOS NR and 22 mo for MSI-H and MSI-S, respectively. Pts on mAV (n=77) were 77% men, 92% White, 16% upper primary, 13% liver mets, 84% ECOG PS 0-1 with median f/u 15 mo from avelumab start; mOS was NR for MSI-H and 24 mo for MSI-S; mPFS was 4 mo for both groups. Of 3 pts on mAV with MSI-H: 1 CR, 2 SD; of 58 pts with MSI-S: 4CR, 4PR, 24 SD, 21 PD, 5 unknown. Conclusions: MSI-H had numerically higher ORR and higher TMB was associated with longer OS with ICI, but further validation is needed. Limitations: retrospective design, small sample size for MSI-H cases, lack of randomization and central scan review, selection/confounding. [Table: see text]
Outcomes in patients (pts) with advanced urothelial carcinoma (aUC) treated with enfortumab vedotin (EV) after switch maintenance avelumab (MAv) in the UNITE study.
Authors: Amanda Nizam, Tanya Jindal, Cindy Y. Jiang, Omar Alhalabi, Dimitra Rafailia Bakaloudi, Rafee Talukder, Matthew P. Davidsohn, Charles B Nguyen, Eugene Oh, Amy K Taylor, Emily Lemke, Deepak Kilari, Christopher J. Hoimes, Hamid Emamekhoo, Shilpa Gupta, Joaquim Bellmunt, Petros Grivas, Matthew T Campbell, Ajjai Shivaram Alva, Vadim S Koshkin
Journal: Journal of Clinical Oncology (2024)

537 Background: MAv is approved in pts with aUC without progression (PD) on 1L platinum-based therapy (PBT). As pts in the pivotal EV trials had not received MAv after PBT, data on outcomes with EV post-MAv are limited. We examined outcomes with EV post-MAv in the multicenter retrospective UNITE study. We hypothesized that outcomes would be similar to published EV data. Methods: Pts who received sequential PBT, MAv, then EV monotherapy were included. Investigator-assessed observed response rate (ORR) was assessed for evaluable pts with scans after ≥ 1 cycle EV using χ 2 test and logistic regression. Progression-free and overall survival (PFS, OS) were measured from EV start and assessed using ΚΜ method and Cox proportional hazards model. Results: Among 633 pts at 16 US sites, 49 received PBT and MAv then EV. Median age 72; 63% men; 96% Caucasian; 82% ECOG PS 0/1, 71% lower tract tumor; 65% pure urothelial histology; 71% visceral or bone mets; 33% Bellmunt score (BS) 2-3. In terms of PBT, 67% had cisplatin-based (cis); 26% carboplatin-based (carbo); 6% both cis- and carbo-based therapy. Best response to PBT was CR/PR/SD for 12% / 59% / 29% pts, respectively. Median time from PBT start to EV start was 8.5 months (mo) (3.9-21.2). Median follow up from EV start was 8.5 mo (95%CI 6.7-15.0). ORR to EV was 54%; median PFS and OS were 7.0 mo (95%CI 5.8-13.3) and 13.3 mo (95%CI 10.8-NR). Median PFS2 measured from PBT start until PD after starting EV or death was 17.5 mo (95%CI 15.2-22.5). Median OS from PBT start was 22.5 mo (95%CI 18.6-NR); 29% of pts remained on EV at data cutoff; 43% received subsequent therapy (Tx) after EV with median time to next therapy 6.4 mo (1.8-15.9). Outcomes did not differ among subgroups, except for improved PFS and OS in pts with BS 0-1 vs BS 2-3 (Table). Conclusions: Pts with aUC treated with EV after MAv had outcomes consistent with data for EV in PBT- and checkpoint inhibitor-refractory aUC. These data support the use of EV as third-line Tx after progression on MAv but should be validated in larger cohorts. [Table: see text]
Key parameters that influence surgical strategy in localised kidney cancer.
Authors: Maksym Pikul, Axel Heidenreich, Eduard Stakhovsky, Sofiya Semko, David A. Pfister, Oleg Voylenko, Pia Paffenholz, Oleksii Kononenko, Iuriy Vitruk, Oleksandr Stakhovskyi
Journal: Journal of Clinical Oncology (2024)

423 Background: The goal of this studywas to select the key factors affecting choice between radical nephrectomy (RN) and partial nephrectomy (PN) for patients with localized RCC based on clinical and nephrometry data. Methods: A special retrospective cohort study was conducted in National Cancer Institute of Ukraine, which results were further validated on patient dataset in urological department of University Clinic of Cologne. The Institutional Review Boards and the local ethics committees of both high-volume centres approved the study. The main nephrometry parameters of tumor location in the kidney were analysed according to the R.E.N.A.L nephrometry score. The remaining functional parenchymal volume (RFPV) was calculated using the special formula. To determine the relationship between the risk of RN or PN, the multivariate predictive modelling method containing 12 parameters was used (Artificial Neural Networks [ANN]). Data validation based on referential centre experience using ROC-curve analysis to detect clinical applicability of the null hypothesis was performed. Results: Based on the analysis, for polary and laterally located tumors, the risk of RN was conditioned only by RFPV. The average critical value of RFPV for polar lesions was X6 crit = 58% (in X6 &lt; X6 crit , RN was predicted); for lateral tumors - X6 crit = 67% (in X6 &lt; X6 crit , RN was predicted). For medial location, the risk of RN only depended on the tumor size. Average critical value of the tumor size in the medial location was X7 crit = 38 mm (in X7 &gt; X7 crit , RN was predicted). Based on the ROC curve comparison, there were no statistically significant differences between the AUC Lin_12 and AUC MLP_3 (p = 0.12); thus, the reduced amount of the factor indicators from 12 to 3 did not worsen the model predictive qualities. Designed during primary analysis hypothesis was successfully validated in a referent centre on the cohort of 300 patients. Out of the cohort - 14 (4.6%) patients experienced false positive/negative outcome, which resulted in a radical/partial nephrectomy out of the hypothesis margins. Predictive model is characterized by high sensitivity (95.2%) and specificity (95.4%) in selecting patients for partial nephrectomy. Conclusions: For the polar and lateral tumor locations, the functioning parenchymal volumes of over 58 and 67% respectively serve as PN indications. However, for the medial lesions, the primary PN indication is a tumor size less than 38 mm.
Demographic and prognostic factors in papillary transitional cell carcinoma: An analysis of the National Cancer Database.
Authors: Sankalp Vinayak, Maya Samuel, Emily Han, Peter T. Silberstein, Beau Hsia, Robert Hu
Journal: Journal of Clinical Oncology (2024)

541 Background: Transitional cell carcinomas account for the majority of bladder cancers, with the papillary subtype comprising most of these cases. The role of race in bladder cancers has been investigated in the past, but there have been no studies that collectively investigated the role of different demographic factors in survival and mortality in papillary transitional cell carcinoma (PTCC). This study analyzes the effects of demographic factors on overall mortality (OM) in patients with PTCC. Methods: A retrospective cohort analysis was conducted using National Cancer Database data from 2004-2019, including 12,300 patients with histologically confirmed PTCC (ICD-O-3=8130). Sex, race (Black, White, and Other), insurance status, and median household income quartile (based on 2016-2020 American Community Survey data) were examined. Kaplan-Meier curves were used to calculate 2, 5, and 10 year survival (2-5-10 YS). Multivariable Cox regression was used to calculate hazard ratios (HR) to identify independent prognostic factors. Statistical significance was set at α=0.05. Results: Females had higher 2-5-10 YS and decreased OM compared to males (HR=0.85, P&lt;.001). White patient survival was higher at 2 years compared to Black patients, but Black patient survival was higher at 5 and 10 years. There was no significant difference in OM between Black and White patients (HR=1.07, P=0.260). Patients of other races had higher 2-5-10 YS and decreased OM compared to White (HR=0.85, P=0.023) and Black patients (HR=0.80, P=0.011). Patients on Medicaid had lower 2-5-10 YS and increased OM compared to patients on private insurance (HR=1.19, P=0.036). Patients on Medicaid had higher 2-5-10 YS than patients on Medicare, but no significant difference in OM (HR=0.87, P=0.091). Patients on private insurance (HR=0.70, P&lt;.001) and Medicare (HR=0.73, P=0.003) had decreased OM compared to uninsured patients. Patients in the fourth income quartile had decreased OM compared to patients in the first (HR=0.82, P&lt;.001), second (HR=0.87, P&lt;.001), and third quartiles (HR=0.90, P=0.003). Conclusions: Male sex, uninsured status, and lower income were associated with increased OM. Black patients and White patients had increased OM compared to patients of other races. Future research should investigate the reasons for these disparities and how to minimize them. [Table: see text]
Intravesical recombinant BCG followed by perioperative chemo-immunotherapy for patients with muscle-invasive bladder cancer (MIBC): A multicenter, single arm phase 2 trial (SAKK 06/19).
Authors: Richard Cathomas, Martin Spahn, Stefanie Hayoz, Sabrina Chiquet, Martina Schneider, Cyrill A. Rentsch, Sacha Rothschild, Ulf Petrausch
Journal: Journal of Clinical Oncology (2024)

TPS707 Background: The integration of immune checkpoint inhibitors (ICI) in the perioperative setting of localized muscle-invasive bladder cancer (MIBC) is extensively investigated and several results from phase 2 trials have been published. While promising, the pathological complete remission rate (pCR, ypT0 ypN0) achieved with ICI-containing regimens appears similar to cisplatin-based chemotherapy alone. Further improvement is needed. Intravesical BCG has successfully been used for decades for non-muscle invasive bladder cancer (NMIBC) in patients (pts) with carcinoma in situ (CIS) and as adjuvant treatment for high-risk papillary tumors. Intravesical BCG induces a local inflammation leading to induction of the innate immune system, probably followed by a tumor-specific adaptive immune response. Recently, a novel recombinant BCG vaccine (VPM1002BC) has been developed and a clinical study in BCG-refractory NMIBC (SAKK 06/14, Eur Urol Oncol. 2022 Apr;5(2):195-202.) has demonstrated good safety with low local toxicity and promising efficacy. We hypothesize that induction therapy with intravesical VPM1002BC improves the efficacy of systemic perioperative chemo-immunotherapy in pts with operable MIBC. Methods: SAKK 06/19 is an open-label single arm phase II trial for pts with operable pT2 or cT2-T4a cN0-1 MIBC without contraindication for cisplatin. Prior intravesical BCG is excluded as are pts unable to keep BCG instillation for less than 1 hour. Intravesical VPM1002BC is administered weekly for 3 instillations. Atezolizumab (atezo) 1200mg is given on day 1 and then every 3 weeks (q3w) for four times. Chemotherapy with cisplatin (70mg/m2 day 1) and gemcitabine (1000mg/m2 day 1 &amp; 8) q3w is started on day 22 and given for four cycles followed by radical cystectomy and lymphadenctomy. Atezo is continued after surgery for 13 cycles in case of residual muscle invasive disease (≥ypT2) or positive lymph nodes (ypN+) only. pCR at cystectomy is the primary endpoint. A total of 46 pts is needed (including 15% dropout rate) using Simon’s minimax two-stage design with type I error 5%, power 80%, a null hypothesis of ≤35% pCR and an alternative hypothesis of ≥55% pCR. Secondary endpoints include pathological response rate (&lt;ypT2N0), event-free survival, recurrence-free survival, overall survival, feasibility and toxicity. An interim safety analysis will be performed after the first 12 pts have completed neoadjuvant treatment specifically assessing toxicity possibly associated with intravesical BCG application. An interim efficacy analysis will be performed after the first 21 pts have undergone surgery. Accrual to the study is currently ongoing (NCT04630730). Clinical trial information: NCT04630730 .
Retrospective study assessing the use of angiotensin converting enzyme inhibitors or angiotensin receptor blockers to reduce toxicity from tyrosine kinase inhibitors in metastatic renal cell carcinoma.
Authors: Theodore Joseph Miller, Ashok Maddukuri, Michael Elias, Megan Wheelden, Naman Trivedi, Junjia Zhu, Monika Joshi
Journal: Journal of Clinical Oncology (2024)

411 Background: The main toxicities associated with tyrosine-kinase inhibitors (TKIs) in the treatment of renal cell carcinoma (RCC) are proteinuria and hypertension. Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have established reno-protective and anti-hypertensive effects and can help with toxicity in mRCC. We hypothesize that use of ACEIs/ARBs is an effective method to decrease the degree of proteinuria and hypertension in patients treated with TKIs for metastatic/advanced renal cell carcinoma (mRCC). Methods: Single Institution retrospective study; mRCC patients (pts) who received TKI and ACEIs/ARBs and had urine protein measurements available at baseline and at 4-6 wk follow up post ACEs/ARBs were included in the analysis. Primary endpoints included improvement in grade of proteinuria and BP in mRCC pts on TKI treatment at baseline and with addition of ACEIs/ARBs. Secondary endpoints included number of dose interruptions (DI), BUN and creatinine changes. Paired statistical tests were used to compare the selected outcome variables between baseline and post ACE/ARB measures: for example, nonparametric Wilcoxon Signed-rank test for paired quantitative data and McNemar test for paired binary data. Results: Out of 71 screened patients between 2020-2023, N of 22 mRCC (N=22, 72.7% male, 77.3% white; 9% Hispanic; N=14 for TKI+ immunotherapy; N=8 TKI alone) pts were selected. ACEIs/ARBs treatment was associated with significantly reduced levels of proteinuria at 4–6wk follow-up. At baseline vs. follow-up, pts were found to have significantly lower proteinuria overall after ACEI/ARBs (p=0.0147), and 45.4% of pts had clinically insignificant proteinuria vs. 22.7% at baseline. Additionally, DI rates for TKI were significantly lower for pts placed on ACEIs/ARBs, with an 81% chance that pts with prior DI would not experience similar event in the follow-up period (p=0.003). Reductions in BP, creatinine, and TKI dosing were seen but not statistically significant (p&gt;0.05 for all measures). Conclusions: In our small study, degree of proteinuria was notably reduced with administration of ACEIs/ARBs. Further findings show fewer DI of TKIs with ACEIs/ARBs use. Our findings suggest a potential role for ACEIs/ARBs in managing toxicity in patients undergoing TKI based therapy for mRCC. Future studies are needed to evaluate the use of ACE/ARB from the time of initiation of TKI based therapy to reduce the toxicities and improve the adherence to mRCC treatment which may result in better outcomes.
The prognostic value of circulating miRNAs in patients with localized/locally advanced prostate cancer after radical prostatectomy and radiotherapy.
Authors: Ahmed H. Zedan, Torben Hansen, Jonna Skov Madsen, Palle Jörn Sloth Osther
Journal: Journal of Clinical Oncology (2024)

184 Background: The outcome after curative intended management of local prostate cancer (PC) is promising. However, there is still a risk of biochemical relapse (BR) after either radical prostatectomy (RP) or radiotherapy (RT). MicroRNAs (miRNAs) have showed encouraging results as alternative biomarkers in different settings of PCa. The aim of this study was to investigate the prognostic value of circulating miRNAs after management of local PCa. Methods: In total 107 newly diagnosed patients with local or locally advanced PCa were included in the study. The cohort was divided into an interventional group with 59 patients (RP (39 patients) or RT (20 patients)) and an observational group with 48 patients (active surveillance (AS)). Both baseline samples at time of diagnosis and follow-up samples six months after treatment were collected. The relative expression of four miRNAs (miRNA-21, -93, -125b, and miRNA-221) was assessed in plasma using real-time polymerase chain reaction. Results: In the interventional cohort, the decrease in miRNA-125b after RT was significantly associated with a longer time to biochemical recurrence (BR) (HR= 0.17, p=0.03), and a higher level of miRNA-125b at baseline samples showed a tendency to higher risk for BR in the same population (HR= 2.82, p=0.09). On the other hand, lower levels of miRNA-221 at both baseline and follow-up samples tended to be associated with lower risk of BR in patients managed by RT (HR=0.14, p=0.07, and HR=0.13, p=0.07, respectively). None of these four miRNAs was associated with a significant risk of progression in patients managed by AS. Conclusions: Both baseline and the dynamics of miRNA-125b was informative as to the risk of BR in patients with PCa treated by RP. Validation in independent cohorts is called for.