461
Background: Understanding the specific tumor characteristics associated with detectable ctDNA in the blood of patients with renal cell carcinoma (RCC) is critical to informing future studies ...seeking to establish the clinical utility of such testing. We characterized pathological and clinical characteristics associated with ctDNA detected preoperatively in patients with renal masses suspicious of RCC. Methods: Using our single institution prospectively maintained database, we identified consecutive patients who underwent partial or radical nephrectomy for non-metastatic suspected RCC (stages cT1b-cT3) during 2022-2023. Included were patients who had undergone tumor-informed ctDNA testing using the commercial Signatera assay (Natera). Baseline characteristics, pathology results, imaging study results, and oncological treatment and follow-up data were collected from the electronic medical records. ctDNA results were collected through the Natera portal. Study findings were reported using descriptive statistics. A p-value of <0.05 was considered statistically significant. R programming language version 4.3 was used for all statistical analyses. Results: A total of 54 patients with a median age of 63 years (IQR 51-71) were included in the study. Twenty-one (39%) were women. The median follow-up time was 4 months (range: 1-21 months). Among the 54 patients, 27 (50%) had detectable ctDNA pre-operatively Post-operative results were available for 33 patients, and 3 (9%) had detectable tDNA (of those 2 had Inferior vena cava involvement). The first patient developed metastatic disease. The two other patients are receiving adjuvant immunotherapy. Analysis of 50 patients with solely malignant RCC revealed that patients with detectable versus undetectable ctDNA were older 67 vs. 54 years (p=0.03), had a higher pathological stage (p= 0.002), larger tumors (7.2 vs. 4.7 cm, p = 0.004), and higher pathological grade (grade 3-4 vs. grade 1-2; p=0.035) (Table 1). All the patients with renal vein or inferior vena cava involvement had detectable ctDNA (n=8). Conclusions: In our cohort, preoperative ctDNA was detectable in 50% of patients with suspected clinically localized RCC. Detectable ctDNA preoperatively correlated with clinically relevant features. The ability of preoperative ctDNA to predict recurrence and survival in patients with clinically localized RCC warrants further evaluation. Table: see text
Second-generation androgen receptor axis-targeting (ARAT) agents have become a standard treatment for patients with advanced prostate cancer (PC), however much remains unknown about the potential ...cardiovascular toxicities.
We performed a systematic search of PubMed, Embase, Web of Science, and Cochrane library for randomized controlled trials of patients receiving ARAT agents for PC from inception to March 2023. The odds ratios (ORs) of all-grade and high-grade cardiovascular adverse events (CVAEs) for patients treated with and without ARAT agents were pooled for meta-analysis. Subgroup analyses based on PC type and treatment regimen were conducted.
A total of 15 double-blind placebo-controlled phase 3 trials comprising 15,842 patients were included. In addition to hot flush and hypertension of any degree of severity, inclusion of ARAT agents was associated with a significantly higher risk of acute myocardial infarction (OR: 1.96, 95% CI: 1.05-3.68, P = .04), myocardial infarction (OR: 2.44, 95% CI: 1.27-4.66, P = .007) and angina pectoris (OR: 2.00, 95% CI: 1.00-4.02, P = .05). With regard to individual ARAT agents, enzalutamide was associated with a significantly higher risk of acute myocardial infarction (OR: 3.11, 95% CI: 1.17-8.28, P = .02), coronary artery disease (OR: 8.33, 95% CI: 1.54-44.95, P = .01), and high-grade hypertension (OR: 4.94, 95% CI: 1.11-22.06, P = .04), while abiraterone and apalutamide were associated with a significantly higher risk of angina pectoris (OR: 5.48, 95% CI: 1.23-24.33, P = .03) and myocardial infarction (OR: 7.00, 95% CI: 1.60-30.62, P = .01), respectively.
The inclusion of ARAT agents was associated with a significantly higher risk of several CVAEs. Clinicians should remain vigilant, both in pre-treatment screening and monitoring for clinical symptoms and signs, when considering ARAT agent particularly for patients with pre-existing risk factors.
To comprehensively investigate the risk of CVAEs associated with ARAT agents, we conducted an updated meta-analysis of 15 phase 3 RCTs involving 15,842 patients. The inclusion of ARAT agents was significantly associated with an increased risk of various CVAEs, including all- and high-grade hypertension, acute myocardial infarction, myocardial infarction, angina pectoris and coronary artery disease.
Background
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) remain the frontline standard of care for patients with EGFR-mutant non-small cell lung cancer. An updated ...toxicity profile of EGFR-TKIs proves valuable in guiding clinical decision making.
Objective
This study comprehensively assessed the risk of EGFR-TKI-related adverse events (AEs) involving different systems/organs.
Methods
We systematically searched PubMed, Embase, Web of Science, and Cochrane library for phase III randomized controlled trials comparing EGFR-TKI monotherapy with placebo or chemotherapy in patients with non-small cell lung cancer. The odds ratio (OR) of all-grade and high-grade adverse events (AEs) including dermatologic, gastrointestinal, hematologic, hepatic, and respiratory events was pooled for a meta-analysis. Subgroup analyses based on the control arm (placebo or chemotherapy) and individual EGFR-TKIs (erlotinib, gefitinib, afatinib, dacomitinib, and osimertinib) were conducted.
Results
Thirty-four randomized controlled trials comprising 15,887 patients were included. The pooled OR showed EGFR-TKIs were associated with a significantly increased risk of all-grade dermatologic AEs including paronychia, pruritus, rash, skin exfoliation, and skin fissures, gastrointestinal AEs including abdominal pain, diarrhea, dyspepsia, mouth ulceration, and stomatitis, hepatic AEs including elevated alanine aminotransferase and aspartate aminotransferase, and respiratory AEs including epistaxis, interstitial lung disease and rhinorrhea. Furthermore, a significantly increased risk of high-grade rash (OR 7.83, 95% confidence interval CI 5.11, 12.00), diarrhea (OR 2.10, 95% CI 1.44, 3.05), elevated alanine aminotransferase (OR 3.93, 95% CI 1.71, 9.03), elevated aspartate aminotransferase (OR 3.22, 95% CI 1.05, 9.92) and interstitial lung disease (OR 2.35, 95% CI 1.38, 4.01) was observed in patients receiving EGFR-TKIs. When stratified by individual EGFR-TKIs, gefitinib showed a significant association with all-grade and high-grade hepatotoxicity and interstitial lung disease.
Conclusions
Epidermal growth factor receptor tyrosine kinase inhibitors were associated with a significantly increased risk of various types of AEs. Clinicians should be vigilant about the risks of these EGFR-TKI-related AEs, particularly for severe hepatotoxicity and interstitial lung disease, to facilitate early detection and proper management.
To compare active with passive voiding trials on the rate of passing a trial of void and discharge rates with catheter in women who have undergone midurethral sling for treatment of stress urinary ...incontinence (SUI).
MEDLINE, EMBASE, and ClinicalTrials.gov were searched through February 24, 2023.
Our population included women undergoing midurethral sling, with or without anterior or posterior repair, for treatment of SUI. Our two primary outcomes were rate of passing voiding trial and rate of discharge with a catheter. Our secondary outcome was the rate of delayed postoperative urinary retention, when a patient initially passes a trial of void but then subsequently presents in retention.
Abstracts were doubly screened; full-text articles were doubly screened; and accepted articles were doubly extracted. In single-arm studies evaluating either passive or active voiding trial, random-effects meta-analyses of pooled proportions were used to assess outcomes. Of 3,033 abstracts screened, 238 full-text articles were assessed, and 26 met inclusion criteria. Ten studies including 1,370 patients reported active trial of void. Sixteen studies including 3,643 patients reported passive trial of void. We included five randomized controlled trials, five comparative retrospective studies, five prospective single group studies, and 11 retrospective single group studies. Five of the studies included patients with a concomitant anterior or posterior colporrhaphy. On proportional meta-analysis, the active trial of void group was less likely to pass the voiding trial (81.0%, 95% CI, 0.76-0.87% vs 89.0%, 95% CI, 0.84-0.9%3, P =.029) with high heterogeneity ( I2 =93.0%). Furthermore, there were more discharges with catheter in active trial of void compared with passive trial of void (19.0%, 95% CI, 0.14-0.24% vs 7.0%, 95% CI, 0.05-0.10%, P <.01). The rates of delayed postoperative urinary retention were low and not different between groups (0.6%, 95% CI, 0.00-0.02% vs 0.2%, 95% CI, 0.00-0.01%, P =.366) with low heterogeneity ( I2 =0%). Sling revisions were statistically lower in the active trial of void group (0.5%, 95% CI, 0.00-0.01% vs 1.5%, 95% CI, 0.01-0.02%, P =.035) with low heterogeneity ( I2 =10.4%).
Passive trial of void had higher passing rates and lower discharge with catheter than active trial of void. Rates of most complications were low and similar between both groups, although passive trial of void had higher sling revisions.
PROSPERO, CRD42022341318.
ctDNA has been gaining popularity in directing and personalizing treatment modalities in solid cancers. The lethality and high recurrence rates witnessed in specific subgroups of patients post ...radical cystectomy calls for better treatment optimization. We seek to characterize the changes of ctDNA in a cohort of patients who underwent robotic assisted radical cystectomy (RARC) in predicting metastasis free survival.
Our single institution prospectively maintained database identified consecutive patients who underwent robotic radical cystectomy between;November 2021 to March 2023, included were patients who had a ctDNA (Natera™) performed before and after radical cystectomy. Baseline characteristics, pathology results, imaging study results and oncological treatment follow-ups were collected from electronic medical charts. ctDNA information was collected through Natera™ portal. Study findings were reported using descriptive statistics. Kaplan-Mayer survival analysis was performed to detect metastasis free survival (MFS). A p-value of <0.05 was considered statistically significant. R programming language version 4.3 was used for all statistical analyses.
A total of;65 patients were included in the study, all patients underwent RARC with intracorporal diversion. The median age was 70 (IQR 64-77).;Twelve patients (19%) were females the median follow-up time was 9;months (IQR 5-12). A total of 16 patients (25%) received neoadjuvant therapy, the pre-cystectomy and post-cystectomy clinical and pathological stage comparison did not differ between upfront RARC to the neoadjuvant arm (p=0.6 and p=0.8, respectively). MFS divided according to pre-cystectomy and post-cystectomy ctDNA status showed;better MFS both to negative status; before RARC and if converted to negative after RARC (Figure 1). Subgroup analysis of patients stratified according to pre-cystectomy ctDNA status showed that patients with positive ctDNA result had higher pT stage, lymph node involvement, and variant histology (Table 1). Subgroup analysis of patients with positive ctDNA status prior to RARC with or without neoadjuvant treatment didn't show difference between the groups (p=0.45).
Pre-cystectomy ctDNA status appears to be a predictor for disease recurrence and progression to metastatic disease. Patients who converted to negative ctDNA status after RARC appear to have similar MFS as patients with negative precystectomy ctDNA, while those who convert to positive ctDNA status after RARC fare as poorly as those who were positive before RARC. Neoadjuvant treatment didn't improve MFS (however the study was underpowered to detect a difference).;ctDNA should be considered in the future for treatment guidance. Longer follow up-time and larger cohorts are necessary to validate our initial results.
Introduction
The combination of sequential intravesical gemcitabine and docetaxel (Gem/Doce) chemotherapy has been considered a feasible option for BCG (Bacillus Calmette-Guérin) treatment in ...non-muscle invasive bladder cancer (NMIBC), gaining popularity during BCG shortage period. We seek to determine the efficacy of the treatment by comparing Gem/Doce induction alone vs induction with maintenance, and to evaluate the treatment outcomes of two different dosage protocols.
Methods
A bi-center retrospective analysis of consecutive patients treated with Gem/Doce for NMIBC between 2018 and 2023 was performed. Baseline characteristics, risk group stratification (AUA 2020 guidelines), pathological, and surveillance reports were collected. Kaplan–Meier survival analysis was performed to detect Recurrence-free survival (RFS).
Results
Overall, 83 patients (68 males, 15 females) with a median age of 73 (IQR 66–79), and a median follow-up time of 18 months (IQR 9–25), were included. Forty-one had an intermediate-risk disease (49%) and 42 had a high-risk disease (51%). Thirty-seven patients (45%) had a recurrence; 19 (23%) had a high-grade recurrence. RFS of Gem/Doce induction-only vs induction + maintenance was at 6 months 88% vs 100%, at 12 months 71% vs 97%, at 18 months 57% vs 91%, and at 24 months 31% vs 87%, respectively (log-rank, p < 0.0001). Patients who received 2 g Gemcitabine with Docetaxel had better RFS for all-grade recurrences (log-rank, p = 0.017). However, no difference was found for high-grade recurrences.
Conclusion
Gem/Doce induction with maintenance resulted in significantly better RFS than induction-only. Combining 2 g gemcitabine with docetaxel resulted in better RFS for all-grade but not for high-grade recurrences. Further prospective trials are necessary to validate our results.
Background
Robotic-assisted radical cystectomy (RARC) offers decreased blood loss during surgery, shorter hospital length of stay, and lower risk for thromboembolic events without hindering ...oncological outcomes. Cutaneous ureterostomies (UCS) are a seldom utilized diversion that can be a suitable alternative for a selected group of patients with competing co-morbidities and limited life expectancy.
Objective
To describe operative and perioperative characteristics as well as oncological outcomes for patients that underwent RARC + UCS.
Methods
Patients that underwent RARC + UCS during 2013–2023 in 3 centers (EU = 2, US = 1) were identified in a prospectively maintained database. Baseline characteristics, pathological, and oncological outcomes were analyzed. Descriptive statistics and survival analysis were performed using R language version 4.3.1.
Results
Sixty-nine patients were included. The median age was 77 years (IQR 70–80) and the median follow-up time was 11 months (IQR 4–20). Ten patients were ASA 4 (14.5%). Nine patients underwent palliative cystectomy (13%). The median operation time was 241 min (IQR 202–290), and the median hospital stay was 8 days (IQR 6–11). The 30-day complication rate was 55.1% (grade ≥ 3a was 14.4%), and the 30-day readmission rate was 17.4%. Eleven patients developed metastatic recurrence (15.9%), and 14 patients (20.2%) died during the follow-up period. Overall survival at 6, 12, and 24 months was 84%, 81%, and 73%, respectively.
Conclusions
RARC + UCS may offer lower complication and readmission rates without the need to perform enteric anastomosis, it can be considered in a selected group of patients with competing co-morbidities, or limited life expectancy. Larger prospective studies are necessary to validate these results.
Purpose
Stress-induced adrenergic signaling can suppress the immune system. In animal models, pharmacological beta-blockade stimulates CD8 + T-cell activity and improves clinical activity of immune ...checkpoint blockade (ICB) in inhibiting tumor growth. Herein, we investigated the effect of BB on clinical outcomes of patients receiving ICB in advanced solid tumors.
Methods
We retrospectively evaluated patients with solid tumors treated with ICB at our institution from January 1, 2011 to April 28, 2017. The primary clinical outcome was disease control. Secondary clinical outcomes were overall survival (OS), and duration of therapy (DoT). The primary predictor was use of BB. Association between disease control status and BB use was assessed in univariable and multivariable logistic regression. OS was calculated using hazard ratios of BB-recipient patients vs. BB non-recipient patients via Cox proportional hazards regression models. All tests were two-sided at a significance level of 0.05.
Results
Of 339 identified patients receiving ICB, 109 (32%) also received BB. In covariate-adjusted analysis, odds of disease control were significantly higher among BB recipients compared to BB-non-recipients (2.79; 1.54–5.03;
P
= 0.001). While we did not observe significant association of OS with the use of BB overall, significant association with better OS was observed for the urothelial carcinoma cohort (HR: 0.24; 0.09, 0.62;
P
= 0.0031).
Conclusions
Concurrent use of BB may enhance the clinical activity of ICB and influence overall survival, particularly in patients with urothelial carcinoma. Our findings warrant further investigation to understand the interaction of beta adrenergic signaling and antitumor immune activity and explore a combination strategy.
Abstract only
482
Background: Despite the widespread use of immune checkpoint inhibitors (ICIs), patterns of disease progression (POD) are poorly characterized. We aim to define these characteristics ...in patients (pts) with advanced urothelial carcinoma (UC) and renal cell carcinoma (RCC) treated with ICIs. Methods: We retrospectively reviewed charts of pts with advanced UC and RCC who received at least 2 ICI doses at our institution from 12/1/10 – 10/31/18. Demographics, medical history, ICI course, toxicity, and outcomes were recorded. Characteristics at the time of radiographic POD including location of metastases (mets), symptoms (sx), and hospitalization details were collected. Fisher’s exact test was used to study differences in pts with and without hospitalization at POD. Results: Of the 71 pts identified (UC N=53; RCC N=18), 59 pts had POD. At POD, 19 (32.2%) pts had new sites of disease involvement, while the remaining pts (N=40, 67.8%) had progression only at previously known sites of disease. Fourty-six (78.0%) pts had sx at POD: 1 sx (N=19, 32.2%), 2 sx (N=13, 22.0%), 3+ sx (N=14, 23.7%). Pain was the most common sx at POD (N=32, 54.2%), followed by loss of energy (N=18, 30.5%), and loss of appetite (N=14, 23.7%). Twenty-five (42.4%) pts were hospitalized at POD, most commonly for sepsis (N=8, 32%). No clinical factors were identified to predict for pts being hospitalized at POD. Conclusions: In our review of GU cancer patients on ICIs, a large proportion of pts reported clinical sx at POD, pain being the most frequent. Furthermore, a substantial number of pts were hospitalized at POD, most commonly for sepsis. Thus, further studies are warranted to confirm these findings, and potentially identify strategies to optimize patients’ quality-of-life and reduce rates of hospitalizations at the time of POD on ICIs.
