Free Survival Research Articles

Evaluation of Treatments with Radiotherapy Alone and Radiotherapy Plus Chemo-immunotherapy in Patients with Primary Liver Cancer based on Blood Biomarkers.

It is critical to assess primary liver cancer patients likely to benefit from radiotherapy (RT) or RT plus chemo-immunotherapy. Many potential peripheral biomarkers from blood samples have been proposed for clinical application. Therefore, the aim of this study was to evaluate treatments with radiotherapy alone and radiotherapy plus chemo-immunotherapy in patients with unresectable primary liver cancer based on blood biomarkers. From January, 2017, to February, 2022, 63 unresectable primary liver cancer patients receiving radiotherapy alone (RT, n = 21) or radiotherapy plus chemo-immunotherapy (RT plus C/IT, n = 42) were included in this study. We compared the clinical outcomes and adverse effects of these two groups. Also, distant metastasis-free survival (DMFS), overall survival (OS), and progress- free survival (PFS) were retrospectively analyzed. Finally, univariable and multivariable Cox analyses were used to explore the prognostic role of blood biochemical biomarkers. In this study, 1, 2, and 3 years of OS after RT treatment were 63.9%, 27.0%, and 13.5%, and after RT plus C/IT were 68.2%, 37.0%, and 24.7%, respectively (p = 0.617). Compared with baseline, white blood cells (WBC) and lymphocytes were significantly decreased after RT (p = 0.002 and p = 0.001, respectively) or RT plus C/IT therapy (p = 0.135 and p<0.001, respectively). In multivariable Cox regression analyses, higher lymphocyte counts before RT (pre-Lymphocyte) were associated with better OS and PFS (HR=0.439, p = 0.023; HR=0.539, p = 0.053; respectively), and higher lymphocyte counts before RT (pre- Platelets) were a poor prognostic factor associated with DMFS (HR=1.013, p = 0.040). Importantly, OS and PFS were significantly better for patients (pre-Lymphocyte ≥1.10 x 109/L) (p = 0.006; p = 0.066, respectively). The DMFS was significantly better for patients (pre-platelets < 233.5 ×109/L) (p<0.001). Our evaluation of blood biomarkers before and after radiotherapy or plus chem-immunotherapy for primary liver cancer revealed a potential marker for clinics to decide on precise treatment strategies.

Abstract A049: Peritoneal tumor DNA as a prognostic biomarker in locally advanced gastroesophageal cancer: A pilot prospective cohort study

Abstract Background: Gastroesophageal cancers commonly spread to the peritoneum. Peritoneal disease significantly alters patient prognosis and treatment-intent. Currently, peritoneal lavage cytology (PLC) is the method of choice for detecting peritoneal micro-metastasis within the peritoneum. Despite its pervasive use, PLC has a variable sensitivity of 10% - 80% in detecting peritoneal micro-metastasis in gastroesophageal cancers. Peritoneal tumor DNA (ptDNA) is tumor-derived DNA detectable in peritoneal lavage fluid. ptDNA-positivity may indicate peritoneal micro- metastasis and may be more sensitive than PLC in staging the peritoneum and predicting disease- free survival (DFS) and overall survival (OS). We aimed to develop and test a tumor-informed platform for ptDNA detection and validate its sensitivity and specificity against PLC. Methods: For this pilot study, peritoneal lavage fluid were collected at staging laparoscopy from 15 patients with gastroesophageal cancer. Cytology and peritoneal metastases (where clinically detectable) were confirmed by histopathology. A tumor-informed ptDNA testing was performed via whole-genome sequencing of tumor tissue and buffy coat to identify somatic variants for each patients, followed by tracking of up to 96 variants in each patient’s peritoneal fluid. Results: 5 out of 15 patients were either cytology positive or had macroscopic peritoneal disease and ptDNA was detectable in all 5 cases. Additionally, out of the 10 cytology-negative patients without macroscopic peritoneal disease, ptDNA positivity was detected in 6 patients prior to commencing neoadjuvant chemotherapy or surgery. Two of these 6 patients demonstrated radiological evidence of recurrence at 15- and 18-months follow-up respectively. Interestingly, one patient with macroscopic peritoneal disease tested negative for cytology. In this case, peritoneal lavage was carried out to the upper two abdominal quadrants only, and the pelvic deposit of disease was detected after the lavage had been completed. Despite a negative cytology result, ptDNA was detected using the same fluid sample, suggesting a higher sensitivity compared to PLC. Conclusions: This pilot study demonstrates that a tumor-informed ptDNA detection platform is feasible and potentially more sensitive than PLC in gastroesophageal cancer. To further validate the clinical utility of ptDNA we are proceeding to a multi-center prospective cohort study. Citation Format: Zexi Allan, Yuxuan Wang, Jeanne Tie, Niall Tebbutt, Nicholas Clemons, Nickolas Papadopoulos, Kenneth Kinzler, Bert Vogelstein, David SH Liu. Peritoneal tumor DNA as a prognostic biomarker in locally advanced gastroesophageal cancer: A pilot prospective cohort study [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A049.

Follow-up on patients with initial negative mpMRI target and systematic biopsy for PI-RADS ≥ 3 lesions - an EAU-YAU study enhancing prostate cancer detection.

To investigate the detection and predictors of prostate cancer (PCA) and clinically significant prostate cancer (csPCA) in patients with positive multiparametric MRI (mpMRI) followed by a negative MRI - guided target biopsy (TB) and systematic biopsy (SB). This retrospective multicenter study included 694 patients from 10 tertiary referral centers with an initial positive mpMRI (PI-RADS ≥ 3) and negative results on both MRI-TB and SB. Patients were classified into three groups based on follow-up: Group 1 (prostate re-biopsy without new mpMRI), Group 2 (standardized second prostate mpMRI and subsequent re-biopsy), and Group 3 (follow-up with mpMRIs and biopsy based on clinical and radiological triggers). The primary outcomes were the detection of any PCA and csPCA during follow up. Study groups were compared according to their probability of PCA and csPCA assessed with the ERSPC-MRI risk calculator. Statistical analysis included Kaplan - Meier analysis, Cox regression, and multivariable analysis for the detection of (cs)PCa. The overall detection of PCA and csPCA was 26.8% and 19.3%, respectively, with varying rates in different PI-RADS groups. Group 3 had the highest 2-year and 5-year PCA-free survival (94 and 84%) and csPCA - free survival (96 and 86%). Multivariable analysis revealed a significantly higher risk of PCA and csPCA in Group 1 and 2 compared to Group 3 (p < 0.01). Clinical and radiological predictors for PCA and csPCA included higher age, prostate volume, PI-RADS score, the presence of atypical small acinar proliferation (ASAP), and a smaller number of TB and SB performed during the initial biopsy. Study limitations, include the retrospective design and reliance on clinical and radiological triggers for follow-up decisions. Patients with positive mpMRI but negative TB and SB results exhibit varying rates of PCA and csPCA depending on the follow up scheme. Tailored follow-up strategies are essential for optimal management in this clinical scenario.

SGSM2 in Uveal Melanoma: Implications for Survival, Immune Infiltration, and Drug Sensitivity.

The abnormal expression of small G protein signaling modulator 2 (SGSM2) is related to the occurrence of thyroid cancer and breast cancer. However, the role of SGSM2 in uveal melanoma (UVM) is unclear. To elucidate this ambiguity, our study utilized bioinformatics analysis and experimental validation. The expression of SGSM2 was detected in UVM cell lines through quantitative real-- time PCR (qRT-PCR). We utilized the Cancer Genome Atlas (TCGA) database to assess the relationship between SGSM2 expression and clinical characteristics, as well as its prognostic significance in UVM. Furthermore, the study examined potential regulatory networks involving SGSM2 in relation to immune infiltration, immune checkpoint genes, microsatellite instability (MSI), and drug sensitivity in UVM. The study also examined SGSM2 expression in UVM single-cell sequencing data. SGSM2 was highly expressed in UVM cell lines. Moreover, elevated levels of SGSM2 in UVM patients were significantly linked to poorer overall survival (OS) (p < 0.001), progress- free survival (PFS) (p < 0.001), and disease-specific survival (DSS) (p < 0.001). Additionally, SGSM2 expression was identified as an independent prognostic factor in UVM patients (p < 0.001). SGSM2 was associated with several pathways, including the calcium signaling pathway, natural killer cell-mediated cytotoxicity, cell adhesion molecules (CAMs), and others. The study revealed that SGSM2 expression in UVM is linked to immune infiltration, immune checkpoint genes, and MSI. Additionally, a significant inverse correlation was observed between SGSM2 expression and the compounds GSK690693, TL-2-105, PHA-793887, Tubastatin A, and SB52334 in UVM patients. SGSM2 may not only serve as an important indicator for prognostic assessment. Still, it may also be a key target for the development of new therapeutic approaches, providing new perspectives on the treatment of UVM patients.

Esophagogastric cancer surgery characteristics and outcomes in bariatric patients, compared with non-bariatric patients.

The association between bariatric surgery and esophagogastric cancer (EGC) is debated. This study aimed to assess EGC characteristics and surgery outcomes comparing bariatric and non-bariatric patients. Single-center retrospective analysis of prospective EGC surgery database. EGC-surgery was performed in 269 patients, classified as bariatric (N.=10, 3.3%), and non-bariatric (N.=259, 96.6%) groups. Non-bariatric group was sub-classified into body mass index (BMI) <35 kg/m2 (N.=244) and >35 kg/m2 (N.=15). BMI was 35.3±5.6 vs. 25.7±16.1 and 37.8±8.7 kg/m2 in bariatric vs. non-bariatric-BMI <35 and >35, respectively (P<0.001). Bariatric patients were significantly younger (56.75±11 vs. 71±10 and 68.38±8.2 years; P<0.001). They tended to have lower rates of diabetes mellitus (30% vs. 43.9% and 73.3%; P=0.05) and significantly lower hypertension rates (50%, vs.86.5% and 93.3%, P<0.004). Bariatric procedures were performed 11.3 years (IQR 5.5-16.5) prior to EGC-surgery. Tumor characteristics were statistically comparable except a significantly higher number of positive LN in the bariatric group (6.9±13.6 vs. 2.7±4.9 and 1.9±4.8; P=0.006), and more bariatric patients received adjuvant treatment (P=0.035). Postoperative major complication rates (0% vs. 25.8%, and 33.3%; P=0.14) and length of hospital stay (14.1±15.3, vs. 23±28.5, and 21±18 days; P=0.59) were comparable. There was no significant difference in Disease- free survival (P=0.42) or overall survival (P=0.48) between patient-groups. Bariatric patients were diagnosed with EGC at a younger age, and tended to have worse nodal involvement. Although outcomes were comparable, clinical and endoscopic surveillance seem important as EGC can occur 10 years or earlier than in non-bariatric patients.

Left ventricular end-systolic and diastolic elastance as predictors of cardiac events in patients who underwent mitral valve surgery for severe mitral regurgitation

Abstract Background/Introduction In severe mitral regurgitation (MR), the prognostic significance of left ventricular ejection fraction (LVEF) and LV dimensions is well-established. However, the assessment of diastolic function in this patient presents a notable challenge, and its impact on postoperative outcomes remains unclear. Purpose This study was designed to explore the potential of LV end-systolic (Ees) and diastolic elastance (Eed) as novel predictors for cardiac events following surgery. Methods A retrospective cohort study was performed on 199 patients (53% male, average age 60 years, mean LVEF 60.0%) with severe MR and undergoing surgery. Preoperative Ees and Eed were calculated using established formulas: Ees = (systolic blood pressure x 0.9) / LV end-systolic volume, and Eed = left atrial pressure / stroke volume, with left atrial pressure estimated from mitral Doppler flow parameters as SBP – (4 x peak MR velocity²). The primary outcome was defined as either cardiac death or hospitalization due to heart failure. Results Average values for Ees and Eed were 2.61 (IQR: 1.67-3.20) and 0.32 (IQR: 0.05-0.57), respectively. Univariate analysis indicated Ees (HR: 1.24, 95% CI: 0.99-1.57, p = 0.066) and Eed (HR: 5.93, 95% CI: 2.87-12.26) as potential predictors. Adjusting for age, LVEF, and LV dimensions, Eed remained an independent predictor of cardiac events (HR: 5.89, 95% CI: 2.81-12.28). Stratifying Eed at a threshold of 0.31—identified as best sum of sensitivity and specificity—revealed that Eed &amp;gt; 0.31 were associated with a 3.9-fold increase in cardiac events compared to those with Eed ≤ 0.31 (p = 0.008). (Fig.) Conclusions The assessment of Eed is a straightforward and readily available parameter in routine clinical practice. Our findings advocate for the inclusion of preoperative Eed evaluation as an independent prognostic indicator for patients undergoing surgery for severe MR.Event free survival by Eed

The impact of HER2-low status on pathological complete response and disease-free survival in early-stage breast cancer

BackgroundThe HER-2 status of breast cancer (BC) has been classified as negative or positive for a long time. Given the efficacy of novel anti-HER2-targeted antibody drug conjugates (ADCs) in HER2-low BC, a distinct subgroup of HER2-low tumors has emerged within BC. The biology and prognostic impact of HER2-low expression are not yet well defined, and inconsistent results were reported. This study aims to evaluate the impact of low HER-2 status on the response to neoadjuvant chemotherapy (NACT) and disease- free survival (DFS) rates.MethodsWe retrospectively analyzed BC patients treated with NACT from 2017 to 2023 in two cancer centers. HER2-negative patients were included. HER-2 low status was defined by IHC + 1 or + 2/ISH non-amplified, and HER2-zero was defined by IHC 0. Pathological complete response (pCR) rates and DFS between HER2-low and HER2-zero populations were compared.Results170 patients were identified. 122 (72%) of these patients were HER2- zero BC, whereas 48 (28%) were HER2-low BC. Overall, pCR was achieved in 35 (20.5%) patients. Of these, pCR was observed in 30 patients (44.6%) from the HER2- zero group, compared to 5 patients (10.4%) from the HER2-low group (p = 0.046), but significance was lost in multivariate analysis. Among the hormone receptor (HR) positive subtype, pCR was achieved 19.8% of HER2-zero tumors and 7.5% of HER2-low tumors (p = 0.08). For HR-negative subtype 34.1% HER2-zero tumors had pCR and 25% of the HER2-low tumors had pCR (p = 0.614). There was no association between DFS and HER2-low status.ConclusionsOur study indicates that HER2-low status had no impact on pCR or DFS.

Echocardiographic parameters for weaning from Extracorporeal Membrane Oxygenation - the role of longitudinal function and cardiac time intervals.

Limited data exist on echocardiographic predictors of weaning from veno-arterial extracorporeal membrane oxygenation (V-A ECMO). We aimed to test the performance of different echocardiographic indices to predict weaning from V-A ECMO. and free survival after weaning. Observational study including patients with cardiogenic shock submitted to V-AECMO. Echocardiography was performed after V-AECMO placement and daily during the weaning trial to assess cardiac recovery. Echocardiography data after V-A ECMO implantation and during the last weaning-trial before V-A ECMO removal were analyzed. Besides traditional parameters, total isovolumic time (t-IVT, a left ventricular performance index) and mitral annular plane systolic excursion (MAPSE) were also tested.76 patients were included. A greater ventricular velocity-time integral (LVOT VTI) at baseline was associated with a 5-fold increase in weaning success (p < 0.001) as MAPSE lateral >6.15 mm (p 0.001) did. TAPSE and S' at tricuspid annulus showed an analogous association. During the weaning trial t-IVT, LVEF, MAPSE, LVOT VTI and TAPSE all improved significantly (p <0.001 for all). At regression analysis t-IVT <14.4second/minute (<0.001), LVOT VTI >12.3cm (p <0.001), MAPSE >8.9mm (p < 0.001), TAPSE> 16mm (<0.001) and E/e' <15.5 (p 0.001) were associated with weaning success and free survival after weaning. LVEF did not predict the weaning success and survival at any time-point (p 0.230). Longitudinal function, t-IVT and native ejection, measured with LVOT VTI, are reliable parameters to predict weaning success in V-A ECMO whereas the LVEF, although dynamically changing during weaning trial, it is not.

Expression of human epidermal growth factor receptor 2 (HER2) in colorectal cancer and its correlation with clinicopathological characteristic among Jordanian patients

Abstract Introduction/Objective Human epidermal growth factor receptor 2 (HER2/neu) is a well-established therapeutic target in breast and gastric cancers. Currently HER2 expression is being considered in other solid tumors including colorectal cancer (CRC). We aimed to investigate HER2 expression in CRC among Jordanians and its association with clinicopathological variables. Methods/Case Report Formalin-fixed, paraffin-embedded tissue blocks of 69 CRC cases were retrieved with their clinicopathological data. Tissue microarray (TMA) were constructed and immunostained using anti-HER2/neu 4B5 monoclonal antibody (Ventana, Tucson, AZ). HER2 scoring was performed by two experienced pathologists using the HERACLES criteria (HER2 positivity: cases of (3+) in ≥10% of cells and FISH-positive equivocal cases). Fisher’s exact/Chi-square test was used to investigate the association between HER2 s and clinicopathological data such as age, gender, histological differentiation, node and metastasis (NM) stage, and tumor site. Survival analysis was evaluated using Kaplan–Meier curves. Results (if a Case Study enter NA) Any degree (score) of HER2/neu expression was seen in 43.5 % of the cases. In 25 (36.2%), 4 (5.8%) and 1 (1.5%) the HER2 score was 1+, 2+ and 3+ respectively. The rest of the cases, 39 (56.5%) were scored as 0. Two of the four cases with a score (2+) required ISH testing to confirm amplification which was not performed. No significant association was found between HER2/neu expression and clinicopathological parameters or with survival. However, survival analysis showed that combined 2+/ 3+ group tend to have worse overall (OS) and event -free survival than the (0/1+) group. Conclusion The prevalence of HER2 overexpression in CRC is low among Jordanian patients, with only 1.5% of the study sample exhibiting definite HER2 overexpression. This rate is lower than the 3-5% rate reported in general, however the small sample size and lack of FISH confirmation might have contributed to this low rate. There was a trend towards worse OS and EFS in HER2 positive cases

Long-term survival can be achieved in a significant fraction of older patients with core binding factor acute myeloid leukemia treated with intensive chemotherapy.

Acute Myeloid Leukemia is mainly a disease of the elderly: however, the knowledge on the outcomes of treatment in core binding factor AML (CBFAML) in older population, is limited. We retrospectively collected data on 229 patients with CBF- AML followed long-term in the last two decades. A 5-year overall survival (OS) of 44.2% (95%CI, 39.9-47.5) and a 5-year event - free survival (EFS) of 32.9% (95%CI, 25.5-40.1) was observed. In a subgroup of >70-year patients who completed intensive therapy (induction + >3 courses of consolidation including autologous stem cell transplant: 10 patients) the median EFS was 11.8 months (95%CI, 9.4 - 15.2) and OS was 40.0% (95%CI, 36.4 - 44.1) at 5yr. In univariate analysis, age >70 (hazard ratio (HR) 1.78, [95%CI, 1.15 - 2.54], p=.008), failure to achieve remission following induction (HR, 8.96 [95%CI, 5.5 - 13.8], p=<.0001), no consolidation therapy (HR, 0.75 [95%CI, 0.47 - 1.84], p=.04) and less than 3 cycles of consolidation (HR, 1.48 [95%CI, 0.75 - 3.2], p=.0004), predicted poorer EFS. Our study shows that intensive therapy, in selected older CBF-AML patients, leads to longer survival. Achieving a CR seems to be the most important first step and at least 3 cycles of consolidation, an important second one. The analysis suggests that these patients should not be excluded from studies with intensive therapies.

Effectiveness of Atherectomy and Drug-Coated Balloon Angioplasty in Femoropopliteal Disease: A Comprehensive Outcome Study.

Atherectomy has been reintroduced for debulking calcified atheroma to enhance the efficacy of drug-coated balloons (DCBs); however, its efficacy in severe calcification and related outcomes have not been fully evaluated. This study aimed to evaluate the outcomes of atherectomy and DCB angioplasty for treating femoropopliteal occlusive disease (FPOD). From 2014 to July 2022, 85 limbs in 76 patients with FPOD underwent atherectomy with DCB angioplasty. We evaluated the efficacy of this procedure using primary patency (PP) and clinically driven target lesion revascularization (CD-TLR)-free survival. PP was defined as the duration of uninterrupted patency without occlusion or a peak systolic velocity ratio more than 2.5 at the target lesion. Lesion calcification was evaluated according to Peripheral Arterial Calcium Scoring System, and Grade 4 was classified as severe. Seventy-one (84%) cases were male, and 56 limbs (66%) were treated for claudication. Rotational and directional atherectomies were performed in 62 (73%) and 23 limbs, respectively. The improvement in the median ankle-brachial index was 0.36 (interquartile range, 0.25-0.48). Median follow-up duration was 19.4 months. The overall PP and CD-TLR-free survival rates were 77% and 93% at 1 year and 64% and 83% at 2 years, respectively. On multivariable analysis, female sex (adjusted hazard ratio [aHR], 3.77; 95% confidence interval (CI), 1.30-10.87, P=0.014), dialysis (aHR, 4.35; 95% CI, 1.33-13.22, P=0.015), and severe calcification (aHR, 2.42; 95% CI, 1.07-5.46, P=0.033) were independent risk factors for poor PP. Dialysis (aHR, 11.07; 95% CI, 3.72-32.92, P<0.001) and severe calcification (aHR, 3.19; 95% CI, 1.15-8.84, P=0.026) were identified as independent risk factors for CD-TLR. Atherectomy with DCB angioplasty for FPOD did not work well in female patients, patients with lesions with severe calcification, and patients undergoing dialysis. Therefore, careful monitoring of these patients is crucial for patency loss and the requirement for revascularization. Additionally, for these patients requiring revascularization, surgical bypass may be appropriate for suitable candidates; whereas more proactive conservative management may be justified for claudicants.

Early and repetitive novel-tracer PET-guided stereotactic body radiotherapy for nodal oligorecurrent prostate cancer after definitive first-line therapy.

Prostate-specific membrane antigen (PSMA) positron-emission tomography (PET) imaging can detect prostate cancer (PCa) nodal oligorecurrences (NOR) at very low prostate-specific antigen (PSA) levels. Prospective studies on oligorecurrent (OR) PCa have been hampered by either dated diagnostics or inhomogeneous cohorts and/or treatment approaches. We hypothesized that early and-if necessary and feasible-repetitive PSMA-PET-based metastasis-directed therapy (MDT) using stereotactic body radiotherapy (SBRT) would improve freedom from palliative (systemic) therapy at low toxicity. This study is aretrospective analysis of patients treated for OR PCa after definitive first-line therapy using PSMA-PET/CT-based SBRT. Endpoints were biochemical progression-free survival (bPFS), SBRT-free survival (SBRT-FS), androgen deprivation therapy (ADT)-free survival (ADT-FS), and toxicity. Atotal of 67patients and 248 metastases (211 nodal) were treated. Patients on concurrent ADT were excluded. Median PSA at inclusion was 2.175 ng/ml. bPFS, SBRT-FS, and ADT-FS for multiple-course SBRT were 9.5, 19.5, and 35.0 months, respectively; 32patients had ≥ 1course of SBRT. Median PSA nadir was 0.585 ng/ml. There was no ≥ grade2 toxicity. Modern-tracer PET/CT-based early and repetitive focal SBRT yields promising results with regard to bPFS, SBRT-FS, and ADT-FS with low toxicity. The ability of this approach to postpone initiation of palliative treatment with low toxicity should be re-evaluated prospectively.

Abstract C162: Prespecified interim analysis of the DARolutamide ObservationaL (DAROL) study in Black/African American patients with nonmetastatic castration-resistant prostate cancer (nmCRPC)

Abstract Introduction: Black/African American (B/AA) men are disproportionately affected by prostate cancer, having higher incidence and mortality rates compared with other ethnic/racial populations. Darolutamide (DARO) is a structurally distinct and highly potent androgen receptor inhibitor with low blood–brain barrier penetration and limited potential for drug–drug interactions. In ARAMIS (NCT02200614; phase 3), DARO significantly improved metastasis- free survival (MFS) by ∼2 years and reduced the risk of death by 31% vs placebo in patients with nmCRPC, with favorable tolerability. The DAROL study (NCT04122976) is assessing the real- world safety and effectiveness of DARO in patients with nmCRPC. Here we report a subgroup analysis of B/AA patients from the prespecified third interim analysis (IA3). Methods: DAROL is an ongoing, global, open-label, single-arm, non-interventional study in patients aged ≥18 years with nmCRPC for whom the decision to be treated with DARO was decided pre-enrollment. The primary endpoint is safety, including incidence and severity of treatment-emergent adverse events (TEAEs). Secondary endpoints include MFS, overall survival (OS), prostate-specific antigen (PSA) progression, and PSA response. IA3 was conducted when 550 patients completed ≥6 months of treatment (data cut-off July 17, 2023). Results: Of 550 patients, 199 (36%)/191 (35%)/152 (28%)/8 (2%) were from Europe/North America/Asia Pacific/Latin America, respectively. All 23 B/AA patients were from North America and represented 12% of this cohort. At baseline, PSA levels (median 4.2 ng/mL vs 4.0 ng/mL) and PSA doubling time (median 5.9 months vs 5.3 months) were similar in the B/AA and overall DAROL population, whereas B/AA patients were generally younger than the overall population (median 74 [range 49–94] vs 79 [range 29–98] years, respectively) with proportionately fewer patients aged ≥75 yrs (12 [52%] vs 387 [70%]), fewer B/AA patients (33%) had a Gleason score ≥8 vs the overall population (53%), and proportionally more B/AA patients (94%) had ECOG PS 0 vs the overall population (64%). Consistent with the DAROL IA3 overall population, DARO showed a favorable safety profile in the B/AA subgroup, and TEAEs were mostly grade 1/2. In the DAROL IA3 overall population, the proportion of patients who achieved a 90% reduction in PSA from baseline was 54%, while MFS and OS rates at 2 years were 78% and 88%, respectively. Effectiveness and safety outcomes for the B/AA subgroup will be presented. Conclusion: Findings from the DAROL IA3 B/AA subgroup were similar to the overall population and consistent with the favorable efficacy and safety profile of DARO observed in the ARAMIS B/AA subgroup and overall population. Citation Format: Evan Y. Yu, Christopher Pieczonka, Hiroyoshi Suzuki, Alberto Briganti, Murilo Luz, Declan Murphy, Patrick Adorjan, Mercedeh Ghadessi, Frank Verholen, Andrew J. Armstrong. Prespecified interim analysis of the DARolutamide ObservationaL (DAROL) study in Black/African American patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C162.

Incidence and Prognostic Significance of Silent Coronary Disease in Asymptomatic Patients with Severe Aortic Stenosis.

Background and Objectives: The aim of this study was to estimate the prevalence of silent coronary artery disease (CAD) in asymptomatic patients with severe aortic stenosis (AS) and assess long-term prognosis in terms of major adverse cardiovascular event (MACE)-free survival. Materials and Methods: This was a prospective study conducted at the Clinic for Cardiac Surgery, University Clinical Center of Serbia, in asymptomatic patients with severe AS, normal LVEF and stress test without signs of myocardial ischemia. Adverse cardiovascular events (cardiac death, myocardial infarction and any hospitalization due to heart disease) was monitored during one year of follow up. Results: A total of 116 asymptomatic patients with severe AS were included in the study. The average age was 67.3 ± 9.6 years, and 56.9% of patients were men. The most common cause of AS was degenerative valvular disease (83.5%). The incidence of significant CAD was 30 out of 116 patients (25.9%). The median Society for Thoracic Surgeons (STS) predicted risk of mortality score was 1.62% (25th to 75th percentile: 1.15-2.76%). The overall mean gradient across aortic valve (Pmean) was 52.30 mmHg ± 12.16, and the mean indexed AVA (AVAi) was 0.37 ± 0.09 cm2/m2. The mean LVEF was 68.40% ± 8.01%. Early surgery for aortic valve replacement was performed in 55 patients (55.2%), while 52 (44.8%) patients received conservative treatment. Twenty-two patients (42.3%) in the conservative treatment group underwent surgery during follow up. There were a total of 44 (37.9%) patients with MACE during one year of follow up. Univariate Cox regression analyses identified the following significant risk factors for MACE-free survival: presence of CAD and early conservative treatment (p = 0.004), age (p = 0.003), diabetes mellitus (p = 0.016) and STS score (p = 0.039). According to multivariate analysis, the presence of CAD with early conservative treatment was the most important predictor of MACE-free survival in asymptomatic patients with severe aortic stenosis (p ≤ 0.001). Conclusions: Early surgery for aortic valve replacement in asymptomatic patients with severe AS and concomitant CAD is beneficial for long-term survival.

Multicenter randomized controlled trial to assess the effectiveness of PASSEO-LUX DCB® drug coated balloon compared to plain balloon angioplasty of arteriovenous fistulae for hemodialysis: Two-years results.

To compare primary patency after angioplasty with drug-coated balloon (DCB)-Passeo-18Lux, BIOTRONIK versus uncoated balloon in dysfunctional peripheral vascular access (PVA) for hemodialysis. A total of 133 patients from four hospitals were randomized to receive DCB or plain old balloon angioplasty (POBA) after satisfactory treatment (residual stenosis <30%) with high pressure balloon (HPB). The primary endpoint was clinical patency of PVA 2 years after angioplasty. Secondary endpoints included the relationship between the location of stenosis and patency and also, other covariates. Mortality at 2 years was compared between both groups. Patency measured in days after angioplasty was higher in fistulae dilated with DCB than HPB. Kaplan-Meier survival curves showed the next percent of success (free time restenosis) after DCB versus POBA at 6 months-77.1% versus 58.2% (160.41-143.72 days until restenosis), 12 months-51.4% versus 44.3% (274.1-237.23), 18 months-38.6% versus 38% (350.74-305.18), and 24 months-37.1% versus 30.4% (419.04-369.1). At 6 months, this difference was statistically significant (p = 0.018), but not at 12 (p = 0.225), 18 (p = 0.471), or 24 months (p = 0.236). Mortality was similar in both groups. DCB angioplasty resulted in superior target lesion primary patency (TLPP)-free survival at 6 months of follow-up. No significant improvements in TLPP-free survival long term were observed. Mortality observed at 1 and 2 years was similar in DCB and POBA: there was no significant difference, and a safety study demonstrated no difference between the two groups (complications and mortality): DCB is safe to use in stenosis treatment in patients who are PVA carriers. Level Ia, therapeutic study, RCT. EBM ratings will be based on a scale of 1-5.

Long-term oncological outcomes after radical prostatectomy in a non-university teaching hospital

The evaluation of oncological outcomes after radical prostatectomy (RP) is a major component of quality control in prostate cancer (PCa) centres. To evaluate the oncological outcomes after RP in a non-university teaching hospital and compare them with other high-volume PCa centres. This study included 1,161 patients after RP who were divided into two risk groups. Low-risk: localised PCa (pT2) and prostate-specific antigen (PSA)≤ 20 ng/ml, Gleason score (GS) 6-7b and pN0. High-risk: locally advanced PCa (≥pT3a) and/or PSA >20 ng/ml and/or GS≥ 8 and/or pN1. Risk groups and clinicopathological features were correlated to biochemical recurrence (BCR)-free survival, cancer-specific survival (CSS) und overall survival (OS). The 10-year BCR-free survival, CSS und OS were 68.4%, 47.0% and 100% in the low-risk group and 87.4%, 89.0% and 73.9% in the high-risk group, respectively; the outcomes between risk groups were statistically significant (p<0.05). A multivariate Cox regression analysis was performed. GS was the most significant prognostic factor for CSS (p=0.00001) und BCR-free survival (p=0.00036). Nodal involvement (pN1) was strongly associated with CSS (p=0.00004). Age was the most important factor for overall survival in the high-risk group (p=0.0011). RP could be a curative treatment option for advanced PCa in selected cases. GS is the most important prognostic factor. Good oncological outcomes can also be achieved in non-university teaching hospitals.

Comparing right- versus left-first implantation in off-pump sequential double-lung transplantation: an observational cohort study.

Historically, the perfusion-guided sequence suggests to first transplant the side with lowest lung perfusion. This sequence is thought to limit right ventricular afterload and prevent acute heart failure after first pneumonectomy. As a paradigm shift, we adopted the right-first implantation sequence, irrespective of lung perfusion. The right donor lung generally accommodates a larger proportion of the cardiac output. We hypothesized that the right-first sequence reduces the likelihood of oedema formation in the firstly transplanted graft during second-lung implantation. Our objective was to compare the perfusion-guided and right-first sequence for intraoperative extracorporeal membrane oxygenation (ECMO) need and primary graft dysfunction (PGD). A retrospective single-centre cohort study (2008-2021) including double-lung transplant cases (N = 696) started without ECMO was performed. Primary end-points were intraoperative ECMO cannulation and PGD grade 3 (PGD3) at 72 h. Secondary end-points were patient and chronic lung allograft dysfunction-free survival. In cases with native left lung perfusion ≤50% propensity score adjusted comparison of the perfusion-guided and right-first sequence was performed. When left lung perfusion was ≤50%, right-first implantation was done in 219 and left-first in 189 cases. Intraoperative escalation to ECMO support was observed in 10.96% of right-first versus 19.05% of left-first cases (odds ratio 0.448; 95% confidence interval 0.229-0.0.878; P = 0.0193). PGD3 at 72 h was observed in 8.02% of right-first versus 15.64% of left-first cases (0.566; 0.263-1.217; P = 0.1452). Right-first implantation did not affect patient or chronic lung allograft dysfunction-free survival. The right-first implantation sequence in off-pump double-lung transplantation reduces need for intraoperative ECMO cannulation with a trend towards less PGD grade 3.

Totally endoscopic coronary artery bypass grafting: experience in 1500 patients.

Totally endoscopic coronary artery bypass grafting (TECAB) is a minimally invasive approach to achieve surgical revascularization through a minimally invasive approach. Still, data regarding non-robotic TECAB are limited. This report presents the results of a TECAB technique using long-shafted instruments, defined as Endo-CABG, from a single-centre experience in 1500 consecutive patients. One thousand and five hundred patients underwent Endo-CABG between January 2016 and February 2023. Data were collected retrospectively, and patients were followed up for 1 year. The primary outcome of this study was major adverse cardiac and cerebrovascular events (MACCE)-free survival. Secondary efficacy outcomes were graft failure and mortality. Furthermore, we analysed factors influencing long-term freedom from MACCE and all-cause mortality. The mean age was 68 [61-75] years, of which 193 (12.87%) were octogenarians. Multivessel disease was present in 1409 (93.93%) patients, and the mean EuroSCORE II was 1.64 [1.09-2.92] %. All patients underwent full arterial revascularization with bilateral internal mammary grafting in 88.47%. Graft failure occurred in 1.80% of cases after 1 year (n = 27). Thirty-day mortality was 1.73% (n = 26), 1-year survival was 94.7% (95% CI: 93.5-95.9%; n = 26) and 1-year MACCE-free survival was 91.7% (95% CI: 90.2-93.2%). Age, left ventricular ejection fraction, arterial hypertension and urgency were significantly associated with 1-year MACCE-free survival. Endo-CABG appears to be a safe procedure, achieves surgical revascularization and provides good outcomes regarding graft failure and MACCE at 1 year, while age, left ventricular ejection fraction, arterial hypertension and urgency were associated with 1-year outcomes.

Decreased Expression of CD247 and CD4 Immune Marker Predicts Poor Prognosis in Triple Negative Breast Cancer.

Triple negative breast cancer (TNBC) is an aggressive from of breast cancer and is associated with poor prognosis. Tumor microenvironment of breast cancer consists of a wide range of cell types, including tumor-infiltrating lymphocytes (TILs). Accumulating evidence indicate that TILs play a crucial role in cancer progression and resistance to standard chemotherapy. We used online computational tools to evaluate the prognostic significance of CD247 and CD4 in TNBC. TNBC patients with lower expression of CD247 and CD4 have much shorter relapse- free survival and overall survival than the patients with higher expression of these genes. CD247 and CD4 expression show a strong positive correlation with tumor-infiltrating dendritic cells, B-cells, CD4+, CD8+, and neutrophils. We've concluded that low levels of CD247 and CD4 may stop immune cells from entering the area around the tumor, which stops cancer cells from being killed and gives the patient a bad outlook. These findings suggest that CD247 and CD4 may be useful biomarkers or as a target to understand the progression of TNBC. Our findings also suggest that CD247 and CD4 targeted therapeutics should be explored in detail, and could be a potentially used as atreatment strategy for TNBC.

Polyploid cancer cells reveal signatures of chemotherapy resistance.

Therapeutic resistance in cancer significantly contributes to mortality, with many patients eventually experiencing recurrence after initial treatment responses. Recent studies have identified therapy-resistant large polyploid cancer cells in patient tissues, particularly in late-stage prostate cancer, linking them to advanced disease and relapse. Here, we analyzed bone marrow aspirates from 44 advanced prostate cancer patients and found the presence of circulating tumor cells with increased genomic content (CTC-IGC) was significantly associated with poorer progression-free survival. Single cell copy number profiling of CTC-IGC displayed clonal origins with typical CTCs, suggesting complete polyploidization. Induced polyploid cancer cells from PC3 and MDA-MB-231 cell lines treated with docetaxel or cisplatin were examined through single cell DNA sequencing, RNA sequencing, and protein immunofluorescence. Novel RNA and protein markers, including HOMER1, TNFRSF9, and LRP1, were identified as linked to chemotherapy resistance. These markers were also present in a subset of patient CTCs and associated with recurrence in public gene expression data. This study highlights the prognostic significance of large polyploid tumor cells, their role in chemotherapy resistance, and their expression of markers tied to cancer relapse, offering new potential avenues for therapeutic development.