tbuckley/cabot-search huggingface dataset:
Race and decisional conflict about genetic testing in patients with advanced prostate cancer.
Authors: JP P Purtell, Avery Ralston, Courtney M Rose, Kyle McElyea, Farhan Ibrahim, Alexandra Thompson, Sunita Ghosh, Clara Hwang
Journal: Journal of Clinical Oncology (2024)

5062 Background: Guideline recommended genetic testing in advanced prostate cancer (PC) is underutilized and not always accepted by patients (pts). We assessed attitudes and decisional conflict (DC) surrounding genetic testing associated with subsequent test completion, and differences between white and nonwhite pts. Methods: Eligibility for this prospective single institution study included pts with N1 or M1 PC who had not yet completed genetic testing. Upon informed consent, pts were given a 24-question survey using a Likert scale of 0 (strongly agree) to 4 (strongly disagree) to assess attitudes toward genetic testing including a validated assessment of DC. DC and DC subscores (range 0-100, with 100 being highest DC) were calculated from subsets of survey responses. Self-identified race was obtained from the EMR. Two-group comparisons between white and nonwhite pts, and between those who completed genetic testing and who did not, were conducted with SAS v9.4 software using Fisher’s exact test for categorical variables and Wilcoxon rank sum test for Likert scale survey questions and DC score variables. Results: Of 42 enrolled pts (21 white, 17 black, 1 Asian, 3 declined), 22 (52.4%) completed genetic testing. Compared to white pts, nonwhite pts expressed more concern about test result privacy (mean = 1.72 v 2.95, p = 0.002), test results being used for non-healthcare purposes (1.78 v 3.00, p = 0.003), and trying unproven treatments (1.72 v 2.67, p = 0.01). Nonwhite pts felt more external pressure in decision-making compared to white pts (0.67 v 0.29, p = 0.04). No significant differences were appreciated in completion of testing, DC, or any subscore between racial groups. Compared to pts who did not complete testing, those who completed testing were more likely to report they knew which options were available (0.73. v 1.25, p = 0.05), knew the benefits of each option (0.77 v 1.30, p = 0.04), knew the risk and side effects of each option (0.95 v 1.50, p = 0.05), were clear about which benefits matter most to themselves (0.73 v 1.37, p = 0.02), and were clear about the best choice for themselves (0.73 v 1.35, p = 0.02). DC (28.59 v 18.11, p = 0.03) was higher in pts who did not complete testing, along with uncertainty (31.25 v 19.32, p = 0.02) and informed (31.25 v 20.45, p = 0.03) subscores. No differences were seen in values clarity, support, or effective decision subscores. Conclusions: In our study, nonwhite pts expressed greater concern about privacy, data misuse, and trying unproven treatments. Those who did not complete testing had more DC with greater uncertainty about knowledge and decision making. These findings will help direct targeted interventions to increase knowledge, trust, and decisional certainty about genetic testing in pts with advanced PC. Ongoing studies will assess the impact of these interventions on rates of testing completion at our institution.
The BEV1L study: Do real-world outcomes associated with the addition of bevacizumab to first-line chemotherapy in patients with ovarian cancer reinforce clinical trial findings?
Authors: Linda R. Duska, Jonathan Lim, Tirza Areli Calderón Boyle, Mark Guinter, Siobhan Halloran, John Hartman, Jeanne M. Schilder, Jean A. Hurteau, Amanda Golembesky
Journal: Journal of Clinical Oncology (2024)

5563 Background: Data from the GOG-0218 (NCT00262847) and ICON7 (NCT00483782) trials suggest that adding bevacizumab (bev) to first-line (1L) chemotherapy (CT) for treatment of stage III/IV ovarian cancer (OC) improves progression-free survival (PFS) among the overall population, but an improvement in overall survival (OS) may be limited to patients (pts) with high-risk clinical factors. Real-world (rw) evidence assessing the impact of adding bev to 1L CT may help identify subgroups of pts who may benefit from 1L CT alone vs CT + bev. Methods: This retrospective study included pts from the US nationwide Flatiron Health electronic health record–derived deidentified database who were diagnosed with stage III/IV epithelial OC on/after 1/1/2016 and initiated 1L CT ± bev on/after 1/1/2017. Pts with high-risk clinical factors were defined as those with stage IV disease or stage III disease with either visible residual disease or no evidence of surgery. Rw endpoints included time to next treatment (rwTTNT), rwPFS, and rwOS. Kaplan-Meier methods were used to estimate unadjusted median outcomes, indexed to 1L start date. Results: Among 1752 pts, median age was 68 years (IQR, 60–75 years), and median follow-up time was 18.5 months (IQR, 8.0–36.6 months). Among pts with high-risk clinical factors, median rwTTNT was significantly longer with 1L CT + bev than with CT alone; no differences were seen with median rwPFS, although a trend toward longer rwOS was observed with 1L CT + bev vs with CT alone (Table). Among pts without high-risk clinical factors, no significant differences were observed in median estimates of rwTTNT, rwPFS, or rwOS between pts receiving 1L CT + bev and pts receiving CT alone. Conclusions: This rw study provides support for findings from ICON7 and GOG-0218, suggesting that the benefit of adding bev to 1L CT may be limited to pts with high-risk clinical factors. [Table: see text]
Post chemotherapy retroperitoneal lymph node dissection (PC-RPLND) for metastatic pure seminoma.
Authors: Axel Heidenreich, Siamak Daneshmand, Yu Che, David A. Pfister, Pia Paffenholz, Alireza Ghoreifi, Stefanie Zschaebitz, Marcus Hentrich, Sophia Thy, Peter Albers, Clint Cary, Axel Gerdtsson, Anders Kjellman, Helene F. S. Negaard
Journal: Journal of Clinical Oncology (2024)

5037 Background: Surgical resection of post-chemotherapy residual masses for metastatic seminoma is discussed controversially with regard to oncological and functional outcome. Furthermore, the role of FDG-PET/CT to detect vital seminoma is still unclear. It is the aim of this study is to report the outcomes of patients with pure seminoma who underwent PC-RPLND. Methods: In this retrospective multi-institutional study, pure seminoma patients whounderwent PC-RPLND for marker negative, FDG-PET/CT positive residual masses &gt; 3cm or marker negative retroperitoneal relapse following first line chemotherapy between 2000 and 2023 were included. Patients with residual masses and negative FDG-PET/CT, inadequate systemic chemotherapy, insufficient clinical data, positive markers, or with residual or relapsing masses following salvage chemotherapy were excluded. Perioperative and long-term outcomes were reviewed. Results: 109 patients were included. All patients received first-line cisplatin-based chemotherapy. Clinical features of the patients are presented in the table. 92.6% of PC-RPLNDs were performed via an open transperitoneal approach. 61 (55.9%) and 48 (44.1%) pts underwent unilateral and a full bilateral resection, resp. Adjunctive surgery was performed in 46 (42%) pts, the most common of which were ureteral resection/repair in 16 (15%) pts, and vascular resection/repair in 14 (13%) pts. Median (IQR) blood loss and length of hospital stay were 550 (300 – 5800) mL and 4 (2 – 18) days, resp. Clavien - Dindo complications ≥ 3a developed in 11 (10.1%) pts. Final pathology revealed necrosis/fibrosis in 75 (69%) and seminoma in 34 (31%). FDG-PET/CT for residual masses &gt; 3cm showed a positive predictive value of only 20%. Except for marker negative progression (p&lt;0.001), no reliable clinicopathologic parameters were identified to predict presence of viable seminoma. With a median (IQR) follow-up of 56 (2 – 164) months, 15 (14%) patients relapsed (12 with lymph node, 3 with visceral/skeletal metastases). 3 (3%) patients died of disease. Conclusions: One third of patients with progressive or &gt; 3cm FDG-PET-CT positive residual retroperitoneal masses following first-line chemotherapy for metastatic seminoma may have viable tumor. FDG-PET/CT has a poor positive predictive value and might be omitted as staging procedure. In selected cases, PC-RPLND may be a valuable option if performed in high-volume centers with expertise in testicular cancer management.[Table: see text]
Utilization patterns and outcomes of radiotherapy for patients with germ cell tumor relapsing with brain metastases, with a focus on stereotactic radiosurgery.
Authors: Chengcheng Gui, Samuel A Funt, Yao Yu, Melissa Zinovoy, Linda Chen, Yoshiya Yamada, Luke R. G. Pike, Darren R. Feldman, Brandon S. Imber
Journal: Journal of Clinical Oncology (2024)

5032 Background: Brain metastases (BM) from germ cell tumors (GCT) are a poor-prognostic feature. Nonetheless, many patients (pts) relapsing with BM achieve long-term disease control. Radiotherapy (RT) is a key component of GCT BM management, alongside salvage chemotherapy (CT), but minimal data are available to guide its use. Outcomes of stereotactic radiosurgery (SRS) alone, without whole brain RT (WBRT), are seldom reported. We describe treatment patterns and outcomes of pts with GCT who received RT for BM relapse. Methods: Male pts with extracranial GCT who received RT for BM relapse between 2005 and 2023 were included. Four subgroups were defined based on incorporation of RT into the broader BM treatment strategy: RT without concurrent salvage CT (Group 1), RT with salvage conventional-dose CT (CDCT) (Group 2), RT with high-dose CT (HDCT) (Group 3), and salvage RT for progressing BM initially treated with CT alone (Group 4). RT approach included WBRT and SRS. Primary outcomes were overall survival (OS) and intracranial progression (IP) from RT completion. Local progression (LP) after SRS was also assessed. Associations with outcomes were modeled with Cox regression and competing risk regression, accounting for death. Results: Sixty pts were included. Median age at BM diagnosis was 28 years. Median follow-up among those alive was 87 months. At 3 years after RT, OS was 39%, and IP was 44%. Groups 1, 2, 3, and 4 included 20, 17, 13, and 10 pts, respectively. Groups were not significantly associated with other baseline features, including RT approach. Outcomes by Group are reported (Table). OS was not significantly different in any Group. There was a trend for worse IP in Group 4, compared with all other groups (HR 2.2, 95% CI 0.99-5.1, p = 0.05). WBRT and SRS alone were used in 32 and 27 pts, respectively. RT approach was not significantly associated with other baseline features. Outcomes by RT approach are reported (Table). OS and IP were not significantly different. Among 53 BM treated with SRS, LP was 8% at 3 years. Among 27 pts treated with SRS, ≥ 2 BM (13 pts) predicted increased risk of death (HR 4.9, 95% CI 1.5-16, p = 0.01) and IP (HR 3.6, 95% CI 1.2-11, p = 0.02). This was not observed after WBRT. Conclusions: We found heterogeneous patterns of RT use for BM relapse: RT alone, RT with CDCT, RT with HDCT, and salvage RT after initial CT alone. Long-term survival and intracranial control are achievable with each strategy and with both WBRT and SRS. This analysis includes the largest reported series of GCT BM treated with SRS; local control after SRS is excellent, but caution is advised for pts with multiple BM, given elevated risk of IP and death. [Table: see text]
Cabozantinib tolerability in metastatic renal cell carcinoma: A meta-analysis.
Authors: Hafsa Farooq, Anna Andrzejczyk, Amna Farooq, Shenhong Wu
Journal: Journal of Clinical Oncology (2024)

e16546 Background: Cabozantinib, an oral multiple receptor-tyrosine kinase inhibitor, has been used as a single agent or in combination with immunotherapy in the treatment of metastatic renal cell carcinoma, and is associated with discontinuation due to adverse events. We conducted a meta-analysis of clinical trials to evaluate the tolerability of cabozantinib in this setting. Methods: A systematic literature search (from January 2014 to January 2024) was conducted to identify clinical trials of cabozantinib in metastatic renal cell carcinoma. Eligible studies included clinical trials with single‐agent cabozantinib or in combination with chemotherapy/immunotherapy in metastatic renal cell carcinoma reporting treatment discontinuation due to adverse events. Incidence, relative risk and 95% confidence intervals (CI) were calculated by a fixed or random effects model. Results: A total of 2,993 patients from 14 studies were included in the meta‐analysis (cabozantinib group n = 1532, control n = 1404). The summary discontinuation rate for cabozantinib due to adverse events was 13.3% (95% CI: 9.6-18.3%). There was no significant difference between cabozantinib as a single agent and in combination with other agents (P=0.52). No significant difference was identified between clear cell and non-clear cell RCC (P=0.25). When compared with controls, cabozantinib overall has similar discontinuation rate due to adverse events (RR: 0.79, 95% CI: 0.43-1.44, P=0.44). However, cabozantinib has significantly lower discontinuation rate as compared to sunitinib (OR: 0.57, 95% CI: 0.39-0.84, P=0.004). Conclusions: The tolerability of cabozantinib is comparable to other therapies overall, and it may be better tolerated than sunitinib in the treatment of advanced renal cell carcinoma.
Systematic literature review and network meta-analysis of first-line therapies for locally advanced/metastatic urothelial carcinoma.
Authors: Lisa Bloudek, Shirley Huang, Phoebe Wright, Vanessa Shih, Ryan Dillon, Anna Martirosyan, Rajshree Pandey, Troy Williams, Nancy N. Chang
Journal: Journal of Clinical Oncology (2024)

e16547 Background: Platinum-based chemotherapy (PBC) has been the standard of care for first-line (1L) locally advanced/metastatic urothelial carcinoma (la/mUC). This systematic literature review (SLR) and network meta-analysis (NMA) analyzed the latest 1L clinical trial data to assess the comparative efficacy of the novel regimen enfortumab vedotin in combination with pembrolizumab (EV+P) against PBC and other approved and investigational 1L regimens for patients with la/mUC. Methods: English language publications (1/2000-10/2023) and congress presentations (1/2015-10/2023) of Phase 2 and 3 clinical trials assessing efficacy and safety of 1L therapies in la/mUC were identified in the SLR. Studies were categorized as: mixed eligibility (cisplatin [cis]-eligible and -ineligible), cis-eligible, and cis-ineligible. An NMA assessed comparative efficacy of EV+P to guideline-recommended therapies and emerging therapies with demonstrated survival benefit. 1L switch maintenance therapies were not included due to differences in study design. Comparative efficacy for overall survival (OS) was assessed under a Bayesian framework assuming constant hazard ratio (HR). Results: The SLR identified 69 unique studies, 2 of which demonstrated survival benefit over PBC (EV-302 and CheckMate-901 substudy). Across all mixed eligibility studies, median OS for PBC ranged from 12.1-16.1 months. Five studies were included in the NMA (3 mixed eligibility, 4 cis-eligible, 3 cis-ineligible). NMA results for the mixed eligibility network showed that EV+P improved OS over all comparator regimens (HR 0.47-0.51; Table). In the cis-eligible network, EV+P subgroup analysis showed improved OS over nivolumab+PBC (HR 0.68 [95% CI 0.47, 0.98]) and PBC (HR 0.53 [95% CI 0.39, 0.72]) and numerically improved OS over ddMVAC (HR 0.76 [95% CI 0.48, 1.20]). In the cis-ineligible network, EV+P subgroup analysis showed improved OS over all comparator regimens (HR range 0.43-0.52). Limitations include few studies contributing to the networks and heterogeneity in patient populations. Conclusions: EV+P is the only regimen shown to improve survival compared with PBC regardless of cisplatin eligibility. This indirect comparison suggests that EV+P has a favorable survival benefit compared with other approved and investigational 1L regimens in patients with previously untreated la/mUC. [Table: see text]
Hospital related outcomes of acute kidney injury in patients with bladder cancer: A nationwide inpatient study.
Authors: Julia Vinagolu-Baur, Saad Javaid, Kelly Frasier, Vivian Li, Nataly Ortega Yaguachi, Evadne Rodriguez, Olivia Del Castillo, Raquel Batista, Kenlee Jonas, Laura Palma
Journal: Journal of Clinical Oncology (2024)

e16624 Background: Bladder cancer is the most common urinary tract cancer and is associated with a high risk of acute kidney injury(AKI). However, there is a lack of Nationwide data on bladder cancer concerning acute kidney injury. We studied the impact of AKI on bladder cancer and the predictors of these adverse outcomes. Methods: The National Inpatient Sample for the years 2017-2020 was employed to identify patients with a primary diagnosis of bladder cancer (local/regional and advanced metastatic), and they were stratified into two cohorts with and without acute kidney injury (AKI). We calculated mortality as the primary outcome and other factors such as hospital stay, cost, sepsis, and respiratory failure as secondary outcomes using multivariate regression analysis after adjusting for confounding factors. Results: A total of 102485 patients had Bladder cancer, among which 30345 had AKI. The mean age of patients with and without AKI was 74.02 vs 71.36 years, respectively (p&lt;0.004). After adjusting for confounding variables, patients with AKI had higher odds of mortality (OR=2.7(2.06-3.54); p&lt;0.001). Length of stay and total hospitalization cost was also significantly increased in patients with concurrent AKI (+2.5 days(2.25-2.76) and + $ 25924(21831-30017); p&lt;0.001, respectively). Similarly, bladder cancer patients with AKI had an increased likelihood of Fluid and electrolyte disorders (OR=3.99(3.70-4.30); p&lt;0.001), Acute respiratory failure (OR=3.65(3.09-4.32); p&lt;0.001), Cardiac arrest (OR=4.32(2.62-7.10);p&lt;0.001), Sepsis (OR=6.52(5.38-7.92);p &lt;0.001), Intensive care unit admission (OR=3.19(2.73-3.73);p&lt;0.001), Invasive mechanical ventilation (OR=3.35(2.76-4.07); p&lt;0.001), Vasopressor use (OR=2.83(2.07-3.86);p&lt;0.001), Pneumonia (OR=2.04(1.61-2.57); p&lt;0.001) and constipation (OR=1.91(1.70-2.15), p&lt;0.001). Conclusions: Our study concluded that AKI in bladder cancer patients was associated with more than twofold increased odds of mortality. The presence of AKI also leads to increased length of stay in the hospitals and increased healthcare resource utilization. Careful evaluation and prompt intervention in acute kidney injury patients can significantly improve outcomes and reduce mortality rates in individuals with bladder cancer. These proactive measures enhance patient survival and improve the quality of life with treatment. [Table: see text]
Nimotuzumab plus concurrent chemoradiotherapy for locally advanced cervical squamous cell carcinoma: The randomized, phase 3 CC3 study.
Authors: Jun jie Wang, Ping Jiang, Ang Qu, Lichun Wei, Lijuan Zou, Xiaofan Li, Chunyan Wang, Xiaoge Sun, Li Ding, Xiangkun Yuan, Huijun Cheng, Dehua Wu, Rong Cai, Rutie Yin, Jidong Zhang, Hui Qiu, Tiejun Wang, Kun Gao, Yanhong Zhuo, Yun Yan Zhang
Journal: Journal of Clinical Oncology (2024)

5514 Background: Cervical cancer is the fourth common malignancy in women, with a 5-year overall survival rate of 24%-76.1%. At present, there are few studies on targeted drugs combined with concurrent chemoradiotherapy (CCRT) for locally advanced cervical cancer (LACC) and the survival results were not satisfactory. This CC3 study is the first randomized, controlled, multicenter phase 3 trial of EGFR combined with CCRT for advanced cervical cancer, aims to evaluate the efficacy and safety of nimotuzumab (humanized EGFR) in combination with CCRT for LACC. (NCT04678791). Methods: All patients with locally advanced cervical squamous cell carcinoma were randomized (1:1) to receive nimotuzumab (400mg, iv, weekly, for 6 weeks) combined with CCRT (cisplatin: 40 mg/m 2 , weekly, for 6 weeks; IMRT/VMAT: 45-50.4 Gy/25-28f; high-dose rate brachytherapy: 30-40 Gy, in 8 weeks) or CCRT alone. The primary endpoint was 3-year progression free survival (PFS) per RECIST 1.1. The secondary endpoints were 3-year overall survival (OS), objective response rate (ORR), complete response (CR) rate per RECIST v1.1, and safety per CTCAE v5.0. Results: Totally 286 patients were enrolled. 142 patients in the Nimo group (nimotuzumab combined with CCRT) and 144 in the CCRT group (CCRT alone). The baseline characteristics were balanced between the two groups. The 1-year PFS rate of the Nimo group was longer than that of CCRT group (96.1% vs. 92.1%, P=0.506). There was no significant difference in the risk ratio between the two groups (HR=0.76, 95% CI: 0.33-1.72, P=0.507), the 3-year PFS and 3-year OS were not reached. A total of 62 (43.99%) patients achieved partial response (PR) and 57 (40.14%) achieved CR in the Nimo group, 50 (34.72%) and 57 (39.58%) in the CCRT group, respectively. The ORR was 83.80% vs. 74.31% (P=0.049). The most common AEs were graded 1-2 as reported before. Follow-up is ongoing. Conclusions: Nimotuzumab combined with CCRT showed significant ORR improvement, longer trend in PFS and good safety in the treatment of LACC patients. Clinical trial information: NCT04678791 . [Table: see text]