Citations

239 Background: In part, TMB guides therapeutic decisions on the use of immune checkpoint inhibitors (ICIs) in aPC. Most patients (pts) with aPC do not have high TMB (TMB-H) at the time of initial assessment. However, TMB changes over time (from treatment pressure) as pts progress through lines of therapy (LOT) has not been extensively explored in aPC. We describe real world data on changes to blood TMB (bTMB) in pts with aPC exposed to several LOT. Methods: Genomic results from pts with aPC who had ≥1 ctDNA test(s) with TMB analyzed (Guardant360, Guardant Health, Inc) as part of clinical care from Oct 2020 – Jun 2022 were retrospectively queried. Clinical factors were extracted from test requisition forms; pts from Mayo Clinic had additional factors, including intervening treatment, extracted from medical records. High bTMB (TMB-H) was defined as ≥13.4 mut/Mb, as previously reported. Proportions were compared using Fisher’s Exact Test. Results: 316 patients with a median age of 72 (range: 44-91) were analyzed. Initial median TMB for the entire cohort was 8.18 mut/Mb (range: 0.01-268.3). On subsequent test, TMB decreased in 122(40%), increased in 173(55%), of whom 29 (17%) became TMB-H; 21 (7%) had unchanged TMB. Median time between tests was 182 days (range: 21-578). 101 patients with 262 tests and a median age of 71 years (range: 46-87) were clinically annotated in the Mayo cohort of whom 58 had >2 consecutive TMB scores: 25 (43%) had TMB increase, of whom 4 (16%) became TMB-H, 23 (40%) had TMB decrease, 10 (17%) had dynamic changes with increases and decreases. Numeric but not statistically significant differences in clinical factors were observed between groups (p>0.05). Conclusions: In this real world cohort, variation in TMB is seen with increasing LOT. Importantly, nearly 1 in 5 patients with increasing tumor mutational burden develop TMB-H, which may be a clinically actionable finding as these pts become eligible for ICI. Findings underscore the importance of repeat genetic testing with time and LOT. [Table: see text]

192 Background: In the setting of disease progression of metastatic castrate resistant prostate cancer (mCRPC) on docetaxel, abiraterone acetate (AA) and enzalutamide are two commonly used second line therapies with data demonstrating survival benefits. Less is known about patient specific factors that contribute to success with these therapies. The objective of this study is to improve patient selection for post-docetaxel second generation hormone therapy (AA or enzalutamide) by evaluating whether overall metastatic burden is associated with treatment response in this setting. Methods: By retrospective chart review, patients with mCRPC treated with AA or enzalutamide following docetaxel failure (defined as PSA rise and radiographic progression) were identified. Patients were categorized into low volume and high volume metastatic disease based on the number of pre-treatment metastatic lesions; where low volume disease describes patients with ≤ 5 metastatic lesions (e.g. oligometastatic disease), and high volume disease represents patients with > 5 individual lesions. The primary endpoint was cancer-specific mortality and the secondary endpoint was radiographic progression free survival. Median follow-up time was 29.5 months. Results: 75 patients were identified and included in our analysis: 39 with high volume metastatic disease, and 36 with low volume metastatic disease. Baseline characteristics of age and pre-treatment ECOG were not statistically different between these groups. Pre-treatment high-volume disease burden was significantly associated with increased risk of radiographic disease progression (HR 4.21, 95%CI 1.97-8.99, p < 0.0001) and cancer specific mortality (HR 5.84, 95% CI 1.58-21.53, p = 0.0026) during treatment with second generation androgen deprivation therapy. Conclusions: High volume metastatic disease burden is associated with significantly increased cancer specific mortality and decreased progression free survival for patients on second line therapy with AA or enzalutamide following docetaxel treatment failure.

189 Background: The objective of this study is to evaluate the prognostic value of early PSA decline following initiation of second-generation hormone therapy (2nd HT), namely abiraterone acetate or enzalutamide, in the post-chemotherapy setting in patients with metastatic castrate-resistant prostate cancer (mCRPC). Methods: We retrospectively identified 75 m-CRPC patients treated with 2nd HT following docetaxel failure (defined as PSA rise and radiographic progression). Patients were categorized into two groups based on first PSA within 3 months after initiation of therapy: PSA reduction ≥ 50% (Group A) and PSA reduction < 50% (Group B). The primary endpoint was cancer-specific mortality and the secondary endpoint was radiographic progression free survival. Results: There were 75 patients (52 in group A, 23 in group B) in the analytic cohort. Baseline clinical and demographic characteristics, including median age, primary Gleason score risk group, median pre-treatment PSA, disease burden, site of metastases, and pre-treatment ECOG score were not statistically different between the two groups. PSA reduction ≥50% was significantly associated with decreased risk of radiographic disease progression (HR 0.41, 95%CI 0.21-0.80, p = 0.0113) as well as decreased risk of cancer-specific mortality (HR 0.29, 95%CI 0.09-0.87, p = 0.0325). Conclusions: PSA reduction ≥50% within 3 months of starting 2nd HT for patients with mCRPC who have failed first-line docetaxel is associated with significantly improved 3-year cancer-specific mortality and progression free survival. Our data supports the use of PSA as an early prognosticating marker for patient outcomes on this second line therapy. [Table: see text]

125 Background: Assessments of financial toxicity among patients with metastatic prostate cancer are lacking. We sought to describe the prevalence and severity of financial toxicity, identify coping mechanisms, and assess characteristics that may be protective of financial toxicity among such patients at our institution. Methods: All patients evaluated in the advanced prostate cancer clinic at Mayo Clinic, Rochester, MN, were approached to complete a survey between February and May 2022. The survey consisted of three parts: 1) demographic, cancer, and treatment characteristics; 2) a coping mechanism questionnaire; and 3) The Comprehensive Score for Financial Toxicity (COST-FACIT) questionnaire. COST-FACIT scores range from 0-44, with lower scores signifying higher financial toxicity. Patients were defined as having either high (COST-FACIT score >24) or low (COST-FACIT score ≤24) financial toxicity. Coping mechanisms were compared between patients with low and high financial toxicity using Fisher’s exact test. Multivariable linear regression was used to evaluate patient characteristics associated with high COST-FACIT scores. Results: Of the 786 patients approached, 417 (53.1%) completed the survey and 281 met inclusion criteria. The median COST-FACIT score was 30 (IQR 24-36). On multivariable analysis, characteristics associated with lower financial toxicity included older age, (estimate:0.36, 95%CI 0.21-0.52), applying for patient assistance programs (estimate:4.42, 95%CI 1.72-7.11), and an annual income of at least $100,000 (estimate:7.81, 95%CI 0.97,14.66). Patients with high financial toxicity were more likely to decrease spending on basic goods (34.6% vs. 2.5%, p<0.001) and leisure activities (61.5% vs. 16.9%, p>0.001), as well as use savings (61.5% vs. 16.9%, p<0.001) to pay for their treatment. However, few patients stopped or partially filled their prostate cancer treatments due to cost. Conclusions: In this cross-sectional study of patients with metastatic prostate cancer, older age, higher income, and applying for patient assistance programs were associated with lower financial toxicity. Greater self-reported financial toxicity was associated with decreased spending on basic goods, leisure activities, and tapping into savings. On rare occasion they delayed or skipped treatment. These findings are important to inform treatment shared decision-making and supportive interventions to mitigate financial toxicity in metastatic prostate cancer.

Abstract Aims Iron deficiency is common in pulmonary hypertension, but its clinical significance and optimal definition remain unclear. Methods and results Phenotypic data for 1028 patients enrolled in the Redefining Pulmonary Hypertension through Pulmonary Vascular Disease Phenomics study were analyzed. Iron deficiency was defined using the conventional heart failure definition and also based upon optimal cut-points associated with impaired peak oxygen consumption (peakVO2), 6-min walk test distance, and 36-Item Short Form Survey (SF-36) scores. The relationships between iron deficiency and cardiac and pulmonary vascular function and structure and outcomes were assessed. The heart failure definition of iron deficiency endorsed by pulmonary hypertension guidelines did not identify patients with reduced peakVO2, 6-min walk test, and SF-36 (P &gt; 0.208 for all), but defining iron deficiency as transferrin saturation (TSAT) &lt;21% did. Compared to those with TSAT ≥21%, patients with TSAT &lt;21% demonstrated lower peakVO2 [absolute difference: −1.89 (−2.73 to −1.04) mL/kg/min], 6-min walk test distance [absolute difference: −34 (−51 to −17) m], and SF-36 physical component score [absolute difference: −2.5 (−1.3 to −3.8)] after adjusting for age, sex, and hemoglobin (all P &lt; 0.001). Patients with a TSAT &lt;21% had more right ventricular remodeling on cardiac magnetic resonance but similar pulmonary vascular resistance on catheterization. Transferrin saturation &lt;21% was also associated with increased mortality risk (hazard ratio 1.63, 95% confidence interval 1.13–2.34; P = 0.009) after adjusting for sex, age, hemoglobin, and N-terminal pro-B-type natriuretic peptide. Conclusion The definition of iron deficiency in the 2022 European Society of Cardiology (ESC)/European Respiratory Society (ERS) pulmonary hypertension guidelines does not identify patients with lower exercise capacity or functional status, while a definition of TSAT &lt;21% identifies patients with lower exercise capacity, worse functional status, right heart remodeling, and adverse clinical outcomes.

Background: Metabolic syndrome (MS) is rapidly growing as risk factor for HCC. Liver resection for HCC in patients with MS is associated with increased postoperative risks. There are no data on factors associated with postoperative complications. Aims: The aim was to identify risk factors and develop and validate a model for postoperative major morbidity after liver resection for HCC in patients with MS, using a large multicentric Western cohort. Materials and Methods: The univariable logistic regression analysis was applied to select predictive factors for 90 days major morbidity. The model was built on the multivariable regression and presented as a nomogram. Performance was evaluated by internal validation through the bootstrap method. The predictive discrimination was assessed through the concordance index. Results: A total of 1087 patients were gathered from 24 centers between 2001 and 2021. Four hundred and eighty-four patients (45.2%) were obese. Most liver resections were performed using an open approach (59.1%), and 743 (68.3%) underwent minor hepatectomies. Three hundred and seventy-six patients (34.6%) developed postoperative complications, with 13.8% major morbidity and 2.9% mortality rates. Seven hundred and thirteen patients had complete data and were included in the prediction model. The model identified obesity, diabetes, ischemic heart disease, portal hypertension, open approach, major hepatectomy, and changes in the nontumoral parenchyma as risk factors for major morbidity. The model demonstrated an AUC of 72.8% (95% CI: 67.2%–78.2%) (https://childb.shinyapps.io/NomogramMajorMorbidity90days/). Conclusions: Patients undergoing liver resection for HCC and MS are at high risk of postoperative major complications and death. Careful patient selection, considering baseline characteristics, liver function, and type of surgery, is key to achieving optimal outcomes.

Abstract We utilized CD11a, an integrin up-regulated on effector and memory CD8+ T cells, as a biomarker to identify, measure, and monitor endogenous tumor-reactive cytotoxic lymphocytes (CTLs) in two mouse tumor models and in melanoma patients. CD11ahigh CD8+ T cells were detected in primary and metastatic tumor sites after tumor cell injection, as well as in spontaneous murine breast cancer tissues. In the peripheral blood of melanoma patients, tumor antigen-specific T cells were detected within the population of CD11ahigh CD8+ T cells that express high levels of PD-1. Infusion of lethally irradiated tumor cells failed to stimulate the expansion of CD11ahigh CD8+ T cells, suggesting that the access of tumor cells to target tissues is required to induce CD11ahigh CD8+ T cell responses. Phenotypic analysis revealed that the CD11ahigh CD8+ T cells detected in our studies were proliferating (Ki67+) activated T cells (CD62L-, CD69+). Although CD11ahigh CD8+ T cells were differentiated effector cells with CTL effector functions, they were typically unable to control tumor growth in our mouse models, possibly due to high expression of PD-1. Our results demonstrate that CD11a can be used as a biomarker to identify and track endogenous tumor-reactive CTLs.