tbuckley/cabot-search huggingface dataset:
Cytoreductive nephrectomy in patients with metastatic renal cell carcinoma treated with immunotherapy: A systematic review and meta-analysis.
Authors: Fengnian Zhao, Junru Chen, Haoyang Liu, Hao Zeng
Journal: Journal of Clinical Oncology (2024)

427 Background: lmmunotherapy is changing the treatment of patients with metastatic renal cell carcinoma (mRCC). In recent years, many immune checkpoint inhibitors (ICls) have been introduced, and ICl-combination therapies have changed the treatment landscape for patients with mRCC. However, the role of cytoreductive nephrectomy (CN) in patients with mRCC receiving ICls is not clear. We aimed to assess the role of ICl-combination therapies in patients receiving /not receiving CN. Methods: PubMed, Embase, and Cochrane Library databases were searched for English-language clinical trials, cohort studies, and case-control studies evaluating OS in patients with mRCC who underwent /did not undergo CN (end-of-search date: 1 April 2023). The hazard ratio [HR] and 95% confidence interval [CI] for OS obtained by multivariate analysis were extracted and aggregated. Meta-analysis was performed using Review manager 5.4.1, and p&lt;0.05 was defined as a statistical significance. Results: Eleven studies met the eligibility criteria. Receiving CN+ICI combination therapy was associated with significantly better OS than patients receiving ICI combination therapy alone (HR: 0.56，95% CI: 0.46-0.69, P &lt; 0.001). In subgroup analyses, thinking about the number of lines for immunotherapy, CN provided OS benefit when immunotherapy was used as either first-line (HR: 0.54, 95% CI: 0.41-0.70, P &lt; 0.001) or non-first-line treatment (HR: 0.59, 95% CI: 0.44-0.81, P = 0.001). In terms of tumor pathologic type, CN also provided OS benefit no matter the pathologic type was only clear cell renal cell carcinoma (ccRCC) (HR: 0.52, 95% CI: 0.28-0.95, P = 0.03) or not (HR: 0.54, 95% CI: 0.39-0.75, P &lt; 0.001). For the choice of drugs, CN provided OS benefits with nivolumab/nivolumab + ipilimumab (HR: 0.50, 95% CI: 0.32-0.79, P = 0.003) or immunotherapy combined with tyrosine kinase inhibitors (HR: 0.59, 95% CI: 0.48-0.73, P &lt; 0.001). About the timing of CN, CN also provided OS benefit when performing before immunotherapy (HR: 0.63, 95% CI: 0.54-0.73, P &lt; 0.001) or no strictly restricted (HR: 0.49, 95% CI: 0.33-0.74, P = 0.0007). Conclusions: CN brings good effect on OS in mRCC patients treated with ICI-combination therapies. In ICI-combination therapy era, the role of CN still deserves attention.
Patients with prostate cancer consider clinical trial options significantly earlier in their journey compared to patients with other solid tumors.
Authors: Liat Edry-Botzer, Yelena Lapidot, Hanna Katz, Tzvia Bader, Avital Gaziel
Journal: Journal of Clinical Oncology (2024)

305 Background: A common misconception is that oncology clinical trials (CT) are a last resort for those who have exhausted treatments or are in advanced stages. This is reflected in the patient (pt) population seeking CT and the greater focus on CT tailored to progressive, refractory, or recurrent diseases. Due to effective screening and its natural progression, prostate cancer (PC) is discovered relatively early, compared to other cancers. Effective, sophisticated non-systemic approaches for treatment are also available in the clinical and also within CT for this cancer. In this study, using real-world pt data, we explored whether those differences impact the way PC pts digitally search for CT. Methods: Leal Health, an AI-based platform, matches cancer pts to CT using pt-reported questionnaires to create individual clinical profiles. These profiles include disease status, stage, biomarkers, treatment history, diversity, and demographics. We analyzed a cohort of 35,671 pt profiles, comparing different clinical and non-clinical parameters between PC pts and those with other solid tumors (bladder, CRC, lung, breast). Results: Leal's data revealed a significantly greater proportion of newly diagnosed PC pts who actively pursued CT, in comparison to individuals diagnosed with other solid tumors (49% vs. 32%, p&lt;0.0001). Additionally, there were significantly fewer available PC trials for newly diagnosed pts compared to relapsed/refractory cases (p&lt;0.0001). The increase in matched trials was 1.61-fold for relapsed/refractory PC pts (p&lt;0.0001) and 2.08-fold for pts with other solid tumors (p&lt;0.0001). A stratified analysis showed that male gender is not a dominant driver for the difference. PC pts were often diagnosed at earlier stages with better performance status compared to other cancer types (p&lt;0.001 for both comparisons). 51% of newly diagnosed PC pts were at stage 1, compared to only 35% of other solid tumors cancer types were. Furthermore, 12% of newly diagnosed PC cases had metastatic disease compared to 26% for other solid tumors. Conclusions: Our research highlights a shift in the traditional pt decision-making, with PC pts showing proactive interest in CT much earlier in their journey compared to other cancers. Male gender alone does not account for this significant difference, which is primarily linked to PC type. While more research is needed, immediate implications and opportunities arise. For example, the significant representation of newly diagnosed PC pts in the digital space represents an opportunity to introduce CT options to pts through this channel and invest in research and trial designs for those pt populations who are not adhering to the traditional standard of care approach before exploring CTs.
Immune-related adverse events (irAEs) and the association with clinical outcomes in advanced genitourinary cancers treated with immunotherapy: A systematic review and meta-analysis.
Authors: Yaowen Zhang, Junru Chen, Guangxi Sun, Xingming Zhang, Hao Zeng
Journal: Journal of Clinical Oncology (2024)

431 Background: The approval of several immune checkpoint inhibitors (ICIs) for the treatment of advanced genitourinary cancers has resulted in a significant revolution in the management of urological tumors. This study investigated the profile of the irAEs and evaluated the association between irAEs and clinical outcomes in the patients with advanced genitourinary cancers treated with ICIs. Methods: We conducted a comprehensive search of online databases up to April 2023 to identify eligible studies. We extracted the type, grade, and frequency of irAEs, the hazard ratios(HRs) and corresponding 95% confidence intervals (95%CIs) for overall survival (OS) and progression-free survival (PFS), raw data or the odds ratios (ORs) and corresponding 95% confidence intervals (95%CIs) for objective response rate (ORR) and disease control rate (DCR). RevMan5.3 software was used to calculate pooled results. Results: A total of 21 studies with 4779 patients were included. Of those, 13 studies investigated renal cell carcinoma (RCC), 6 studies investigated urothelial carcinoma (UC), and 2 investigated mixed population with RCC or UC. The pooled overall incidence was 29.0% (95%CI: 28.0%-30.0%) for any-grade irAEs in RCC and UC and 13.0% (95%CI: 11.0%-14.0%) for grade ≥3 irAEs. Furthermore, the HRs for OS and PFS in advanced genitourinary cancer patients with versus without irAEs were 0.45 (95%CI: 0.40-0.51, p &lt; 0.001) and 0.41 (95%CI: 0.31-0.55, p &lt; 0.001), respectively. The ORs for overall ORR and DCR in advanced genitourinary cancer patients with irAEs versus without irAEs were 3.65 (95%CI: 3.03-4.39, p &lt; 0.001) and 4.19 (95%CI: 2.94-5.97, p &lt; 0.001), respectively. In the subgroup analysis, we also observed a positive association between the occurrence of irAEs and improved treatment outcomes in UC and RCC, respectively. Specifically, patients with skin irAEs showed a better OS, patients with skin irAEs and thyroid disfunction were associated with better PFS. Conclusions: Our study provides a comprehensive overview of irAEs in advanced genitourinary cancers treated with immunotherapy. Our findings suggest that the occurrence of irAEs could be a favorable prognostic factor for advanced genitourinary cancer patients treated with ICIs.
Extended follow-up report of a randomized phase II trial comparing gemcitabine and cisplatin with or without berzosertib in patients with advanced urothelial carcinoma.
Authors: Mamta Parikh, Sumanta Kumar Pal, Paul Henry Frankel, Christopher Ruel, Amir Mortazavi, Matthew I. Milowsky, Ulka N. Vaishampayan, Yung Lyou, Peng Wang, Rahul Atul Parikh, Benjamin A. Teply, Robert Dreicer, Hamid Emamekhoo, Dror Dror Michaelson, Christopher J. Hoimes, Tian Zhang, Sandy Srinivas, William Y. Kim, Glenn Liu, Primo N Lara
Journal: Journal of Clinical Oncology (2024)

614 Background: Gemcitabine with cisplatin (GC) remains a frontline treatment option for patients (pts) with metastatic urothelial cancer (mUC). Preclinical synergy has been noted when combining cisplatin with berzosertib, a selective ATR inhibitor. This trial sought to determine the effect of addition of berzosertib to GC on clinical outcomes in mUC; here we present final study results with extended follow-up. Methods: This open-label, randomized study enrolled pts with confirmed mUC, no prior cytotoxic therapy for metastatic disease, &gt; 12 months since perioperative chemotherapy and eligible for cisplatin based on standard criteria. Pts were randomized to receive either GC plus berzosertib (Arm A) or GC alone (Arm B). In Arm A, cisplatin 60 mg/m 2 IV was given on D1, gemcitabine 875 mg/m 2 IV on D1 &amp; 8, and berzosertib 90 mg/m 2 IV on D2 &amp; 9 of a 21-day cycle. In Arm B, cisplatin 70 mg/m 2 IV was given on Day 1 (D1) and gemcitabine 1000 mg/m 2 IV on D1 &amp; 8 of a 21-day cycle. The primary endpoint of the study was progression-free survival (PFS), with secondary endpoints including response rate (RR), overall survival (OS) and toxicity. Results: A total of 87 pts (median age 67; M:F 68:19) were randomized, 46 pts to Arm A and 41 pts to Arm B. With a median follow-up of 37.7 months (95% CI: 28.3, 39.3), median PFS in Arm A was 6.2 month and 7.1 months in Arm B (HR: 1.3 [95% CI: 0.8-2.2], p=0.1). RR was 54% in Arm A and 63% in Arm B. Median OS was 10.9 months in Arm A and 19.8 months in Arm B (HR: 1.2 [95% CI: 0.7-2.1], p=0.2). Common &gt; Grade 3 adverse events included anemia (Arm A: 57%, Arm B: 24%), neutropenia (Arm A: 36.9%, Arm B: 26.8%), thrombocytopenia (Arm A: 58.7%, Arm B: 39%). Conclusions: With &gt;18 months of extended follow-up, there remained no PFS or OS benefit with the addition of berzosertib to GC, compared to GC alone in a biomarker unselected population. Myelosuppression was common despite reduced dosing of cisplatin and gemcitabine suggesting that combining ATR inhibition with platinum-based chemotherapy may not be feasible in pts with mUC. Clinical trial information: NCT02567409 .
Pulsed electromagnetic field therapy's effect on bladder cancer cell line HT-1376.
Authors: Maxwell Sandberg, Wyatt Whitman, Christina Ross, Matvey Tsivian, Stephen Walker
Journal: Journal of Clinical Oncology (2024)

666 Background: Pulsed electromagnetic field therapy (PEMF) is a magnetic waveform energy that can be targeted for delivery to cells and/or patients. It is noninvasive, and to date no reported negative side effects exist. Recently, its use as a therapeutic for cancer has come into focus. However, to our knowledge, no study has examined the effect of PEMF on bladder cancer at the cellular level. In this study, we sought to examine how PEMF altered a bladder cancer cell line (HT-1376) at the genomic level. Methods: HT-1376 cells were cultured, and cells were plated into either a control plate (no PEMF) or experimental plate (PEMF). The experimental cells were subjected to PEMF which had an oscillating magnetic field ranging from 1.5 MilliTesla (mT) to 16 mT at 30 Hertz, 1 hour each day for 3 total days. RNA was isolated from both control and experimental cell plates on day 3 and assayed on whole genome microarrays. Day 3 control samples from HT-1376 were compared to day 3 PEMF treated cells. Results were analyzed using Ingenuity Pathway Analysis. Results: Data from genomic analysis revealed that many cancer-related pathways were altered after treatment with PEMF in HT-1376. Relevant cancer pathways downregulated after PEMF treatment in HT-1376 cells compared to controls were the PIK3/AKT pathway (p=8.1e-61), neuroinflammation signaling pathway (p=2.3e-60), and external growth factor pathway (p=4.8e-35). Upregulated pathways after PEMF treatment relative to controls were the p53 signaling pathway (p=1.1e-06), endocannabinoid cancer inhibition pathway (p=1.1e-38), and the T-cell exhaustion signaling pathway (p=3.7e-22). The table also lists cancer relevant genes up and downregulated after PEMF treatment. Conclusions: PEMF appears to alter the tumor profile of bladder cancer cell line HT-1376. Key pathways implicated in cancer pathogenesis were altered after treatment. Further, after treating HT-1376 bladder cancer cells with PEMF for 3 days, significant alterations in gene expression occurred. This has widespread implications for prognosis, management, and treatment of bladder cancer. Ultimately, PEMF may represent an exciting new non-invasive therapeutic in bladder cancer, which necessitates further research.[Table: see text]
Racial differences and predictors of outcomes in testicular cancer based on the National Cancer Database (NCDB).
Authors: Eun-mi Yu, Hongkun Wang, Jeanny B. Aragon-Ching
Journal: Journal of Clinical Oncology (2024)

503 Background: The incidence of testicular cancer in the U.S. is highest in white (W) men and lower in black (B), Hispanic (H) and Asian-American men, with reports of increasing trends in Hispanic men with worse outcomes (Li et al., BMC Cancer 2020). We aim to verify the emerging ethnicity variations in a large database. Methods: Using the NCDB database with patient-level data extraction from 2004 to 2020, we sought to identify the incidence, demographics, regional differences, treatment, and outcomes in men who are Hispanic versus non-Hispanic White (NHW) and other races with testicular cancer diagnoses (non-seminoma, NS; seminoma, S) with differences in treatment patterns from different institution types, insurance across regions. Results: There were 81571 pts in all with 46979 S pts W and 34592 NS pts W vs 1754 S pts B and 1106 NS pts B with 5396 S pts H and 5609 NS pts H with other races/unknown for the rest. More S patients were treated at comprehensive community cancer programs (17%) compared to NS pts (6.1%). The majority of patients had Charlson-Deyo Score of 0 (92.7% of S pts and 93.7% of NS pts), had private insurance (74.1% S pts, 69.1% NS pts), though incidence appeared to be similar except for a slight drop in 2020 at 5.9% compared to 6.6% during years 2018 to 2019. Most were diagnosed with Stage I (29.6%) and Stage II and III (16.3%) though it was unknown/missing for 54%. Overall survival (OS) was better for S compared to NS in all pts (p&lt;0.0001), and in stages II &amp; III (p&lt;0.001). OS was better for W vs B (p&lt;0.0001), NHW vs H (p&lt;0.0001), and with differences in Charlson-Deyo score (p &lt;0.0001), facility type (p=0.008) and insurance status (p &lt;0.0001). OS p-values are from Log-rank tests. Conclusions: Our analysis reveals some differences in survival trends with better survival in seminoma compared to non-seminoma, though Blacks and Hispanics have worse outcomes compared to Whites and Non-Hispanic Whites. This highlights the need for targeted efforts to bridge gaps in care.
Effect of dipeptidyl protease 4 (DPP4) inhibitors on progression-free survival in patients with metastatic renal cell carcinoma: A single-center retrospective analysis.
Authors: Soham Ali, Kathryn Fortune, Jack Masur, Paul Vincent Viscuse, Michael Edward Devitt, Robert Dreicer, William Paul Skelton
Journal: Journal of Clinical Oncology (2024)

426 Background: Dipeptidyl peptidase IV (DPP4) is a cell surface receptor with exopeptidase activity that is expressed on most cell types, and possesses numerous substrates including growth factors, chemokines, and vasoactive peptides. These effects have implicated DPP4 in tumor growth and metastasis. Prior SEER-Medicare and retrospective studies have suggested an association between DPP4 inhibition and increases in both progression-free survival (PFS) and overall survival (OS) in patients with colorectal and lung cancers. Similar studies have shown no associated OS benefit from DPP4 inhibition in breast or pancreatic cancers, and increased OS but not PFS in prostate cancer. However, no studies to date have explored the impact of DPP4 inhibitors (DPP4i) in renal cell carcinoma (RCC). Thus, in this study we present a first-time analysis examining the impact of DPP4i use on PFS in patients with metastatic RCC and type 2 diabetes mellitus. Methods: We performed a single-center retrospective analysis of patients with diabetes and metastatic RCC at University of Virginia. The control group included patients who were on metformin, a sulfonylurea or SGLT2 inhibitor during treatment for metastatic RCC, while the study group included those who were taking a DPP4i with or without metformin and other diabetes medications during treatment. The primary and secondary endpoints of this study were PFS and OS, respectively. Results: Fifty-nine patients were eligible for the study, 11 of whom were taking a DPP4i with or without other diabetic medications during RCC treatment, while 48 were taking metformin with or without other non-DPP4i medications. Cancer progression occurred in 81.8% of patients in the DPP4i group compared to 66.7% of patients in the control group with an odds ratio of 1.58 (95% CI: 0.672-3.71), p = 0.57. No statistically significant difference on PFS (HR: 1.60; 95% CI: 0.75-3.43; p = 0.24) or OS (HR of death: 0.73; 95% CI: 0.27-1.97; p = 0.52) was found in this study. Conclusions: This retrospective study explored the effect of DPP4i on outcomes in patients with metastatic RCC and diabetes. While DPP4i have been shown in previous SEER-Medicare and retrospective studies to have favorable effects on PFS and OS in certain cancers such as colorectal and lung, the results of this study suggest that DPP4i do not confer clinical benefit in patients with RCC, similar to pancreatic and breast cancers. Given the small sample size in this study, larger studies are warranted to better elucidate the effect of DPP4i in metastatic RCC as well as the mechanisms underlying differential tumor response to these agents.
Analysis of neoadjuvant immunotherapy and chemotherapy for muscle-invasive bladder cancer in a national registry.
Authors: Matthew Nicholas Klein, Vincent Eric Xu, Olivia French Gordon, Ryan Michael Antar, Michael Joseph Whalen
Journal: Journal of Clinical Oncology (2024)

611 Background: Neoadjuvant immunotherapy (NIO) is an exciting new treatment option for muscle-invasive bladder cancer (MIBC). Early-phase trials are encouraging however increased evidence is needed to support its use over Neoadjuvant chemotherapy (NAC). In this study, we sought to assess factors associated with NIO use in MIBC and survival outcomes. Methods: The National Cancer Database was used to identify 8,267 patients between 2006 and 2019. Patients were included based on urothelial bladder cancer diagnosis, clinical staging (T2-4N0-3M0), and receipt of NIO or NAC prior to radical cystectomy. NAC and NIO patient groups with similar clinical and demographic characteristics were defined using a 1:1 propensity score matching method. Categorical and continuous were assessed with chi-square test and independent sample T-test, respectively. Survival outcomes were compared using Kaplan-Meier analyses. Results: Mean age at diagnosis was significantly higher in NIO patients (70.5 years, SD 8.93) compared to NAC patients (65.64 years, SD 8.99) (p&lt;.001). NIO patients were associated with higher Charlson-Dayo scores (p=.028), high income (p=.027), treatment at an academic facility (p&lt;.001), and at a facility greater than 30 miles away (p=.002) when compared to NAC patients. In the matched analysis, these characteristics were all similar. NAC use was associated with increased rates of T down-staging to pT0-1 compared to NIO (47/118, 39.8% vs 20/109, 18.3%; p&lt;0.001). Conversely, NIO use was associated with increased rates of T up-staging to pT3-4 compared to NAC (38/109, 34.9% vs 23/118, 19.5%; p=0.009). Kaplan-Meier analysis demonstrated no difference in overall survival when comparing patients who received NIO and NAC (p=.477). Conclusions: In this study use of NIO was associated with older and more comorbid patients compared to NAC. We found NIO less effective at achieving pathologic down-staging than NAC. Furthermore, increased rates of pathologic up-staging were observed with NIO use compared to NAC. These findings suggest the clinical benefit of neoadjuvant immunotherapy remains unclear. [Table: see text]
Preliminary efficacy and safety results from ReBirth: A phase II study of risk-based bladder-sparing therapy for MIBC.
Authors: Yijun Shen, Xiaolin Lu, Xuejun Ma, Wei Liu, Dingwei Ye
Journal: Journal of Clinical Oncology (2024)

615 Background: Trimodal therapy (TMT) has achieved long-term survival and persistent oncologic control in selected MIBC patients, however, tailored treatment using biomarkers based on chemotherapy plus PD-1 inhibitor responses is currently absent. Furthermore, the safety and efficacy of hypo-fractionated radiation in combination with PD-1 inhibitors and concurrent chemotherapy is worth exploring. Methods: This is a two-stage, single-arm, phase II trial recruiting cT2-4aN0-1M0 MIBC pts. Based on results of cystoscopy, urine cytology, imaging and MRD detection after first stage (Tislelizumab (T) 200 mg on D1, Cisplatin (C) 70 mg/m 2 on D1 and Gemcitabine (G) 1000 mg/m 2 on D1 and D8 Q3W for 3-4 cycles), pts achieving cCR (cT0, cTa) are treated with T, while the other pts receive T and chemoradiotherapy (whole bladder 44Gy/16 fractionation combined with C as radiosensitizer). 1-year BIDFS rate is the primary endpoint. Secondary endpoints include 2-year MFS rate, 2-year BIDFS rate and safety. Tissue and urine samples will be obtained for genetic profiling and biomarker research. Results: The preliminary efficacy and safety are reported this time. As of September 20, 2023 (median follow up: 258 (49-415) days, 25 pts with a median age of 64 (36-77) years were enrolled and 96% are male. 19 pts with cT2 (57.14%), cT3 (33.33%) and cT4 (9.52%) tumors were evaluable. 2 pts were assessed as N1. 14/19 pts (73.68%) achieved cCR and maintained a sustained response. Based on positive urine cytology and MRD, 5 pts were classified as non-cCR (2 pts in cT3N0M0, 2 pts in cT4N0M0 and 1 pt in cT2N0M0). Due to RC (2 pts achieving ypT0N0 and 1 pt achieving ypT2N0) and incomplete treatment cycles, 6 pts were excluded from the efficacy analysis set. BFS rate at 1 yr is evaluated in 6 pts (2 pts received hypo-fractionated on the second stage) and the rate is 100%. TRAEs were found in 19 of 25 pts (76%). The grade 3-4 TRAEs observed (8%) was adrenal cortical insufficiency and immuno-therapy related colonitis. Hematological AEs (32%), renal insufficiency (24%), pruritus (20%), and fatigue (20%) are the most common AEs. During hypo-fractionated radiation, no new safety signs were discovered. Conclusions: The preliminary findings indicate a potential efficacy and manageable toxicity during the two-stage treatment. Enrollment is still ongoing, and long-term efficacy will be proved. Clinical trial information: NCT05531123 .