Three-year Survival Research Articles

Levels of cardiac biomarkers and three-year survival rate in hospitalized patients with heart failure and community-acquired pneumonia

Aim. To evaluate the impact of community-acquired pneumonia (CAP) on the levels of cardiac biomarkers and long-term survival rate in patients with heart failure (HF).Material and methods. The prospective observational single-center study included 132 patients (73 men, 59 women); mean age — 72,3±12,1 years, consecutively hospitalized at Clinical Hospital № 4 of the I. M. Sechenov First Moscow State Medical University with decompensated heart failure in the period from March 2018 to December 2019. The main (n=40) and comparison group (n=92) included patients with and without clinical and CT signs of CAP, respectively.Results. Patients with HF and CAP and HF without CAP were comparable in sex, age, and severity of HF. CAP in most patients met the criteria for non-severe pneumonia (average CURB-65 score — 1,55±0,73). The levels of N-terminal probrain natriuretic peptide (NT-proBNP) in patients with HF with CAP (1188,9 [439; 2493] pg/ml) were insignificantly higher than in patients with HF without CAP (839,6 [413; 1900]) pg/ml (p>0,05). A similar pattern was noted for the soluble growth stimulation expressed gene 2 (sST2) (30,85 [12,8; 59,6] ng/ml vs 22,8 [15,2; 44,7] ng/ml, p>0,05). The haptoglobin level in patients with CAP was significantly lower (732 [315; 1312] ng/l), compared to the group without CAP (1270 [902; 2022] ng/l, p=0,0022). No differences in the concentrations of galectin-3, copeptin and hepcidin were detected. The one-year mortality rate of patients who underwent CAP was 27,3%, and without CAP — 7,2% (p<0,001), while the three-year mortality rate was 44,9% and 21,4%, respectively (p=0,0004). Elevated levels of NT-proBNP and sST2, along with age over 75 years and left ventricular ejection fraction <40%, are additional factors of poor prognosis in patients with HF and CAP.Conclusion. CAP in patients with HF does not have a significant effect on most cardiac biomarkers, but significantly worsens the prognosis. Independent factors of unfavorable prognosis in patients with HF and CAP are age over 75 years, left ventricular ejection fraction <40%, increased NT-proBNP and sST2 levels.

Oncologic Outcomes of Salvage Surgery in Recurrent Oral Tongue Squamous Cell Carcinoma.

This study aimed to determine the oncologic outcomes and identify prognostic factors in patients undergoing salvage glossectomy for recurrent oral tongue squamous cell carcinoma (OTSCC). A retrospective chart review was conducted encompassing all patients who underwent salvage oral glossectomy out of 259 individuals undergoing oral glossectomy at a tertiary academic center. Inclusion criteria comprised patients who met the following conditions: 1) biopsy-proven oral tongue recurrence, 2) salvage glossectomy performed with curative intent, 3) availability of imaging records, and 4) comprehensive documentation. Cases involving base of tongue tumors and second primaries were excluded from the analysis. Categorical data were expressed as proportions, and continuous data as medians/quartiles. Univariate analysis used Fisher's exact test for categorical variables and Student's t-test for continuous ones. Survival analysis employed Kaplan-Meier estimates and the log-rank test. High-risk histopathological risk factors were significantly more common with recurrence compared to initial presentation. The mean locoregional disease-free interval was 35 months.Kaplan-Meier estimates for one- and three-year disease-free survival (DFS) were 62.7% and 33.4%, while disease-specific survival (DSS) rates were 73% and 38.9%, respectively.Recurrent T-stage was a predictor for DFS, while margin status was a strong predictor for both LR control (p = 0.024) and DSS (p = 0.030), as was perineural invasion (p = 0.001 and p = 0.030). Alcohol use was associated with worse overall survival (p = 0.024).In contrast to other reports, nodal status was not a predictor in this series. Upon recurrence, histopathological analysis unveils detrimental changes in tumor biology, which significantly influence disease control. Notably, consistent with findings from other studies, factors, such as recurrent T-stage, presence of perineural invasion, and, most importantly, margin status, play pivotal roles in determining oncologic outcomes. Consequently, the imperative for aggressive salvage surgery becomes evident in achieving sufficient disease control. This underscores the necessity for proactive management strategies aimed at addressing these factors to enhance patient outcomes.

Three-Year Overall Survival Outcomes and Correlative Analyses in Patients With NSCLC and High (50%–89%) Versus Very High (≥90%) Programmed Death-Ligand 1 Expression Treated With First-Line Pembrolizumab or Cemiplimab

IntroductionResponses to first-line programmed cell death protein 1 inhibition vary among patients with metastatic NSCLC and a programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) greater than or equal to 50%. We previously reported improved clinical outcomes to first-line programmed cell death protein 1 inhibition in patients with metastatic NSCLC with a PD-L1 TPS of greater than or equal to 90% versus 50% to 89% in a pilot study. Here, we report the three-year survival with first-line pembrolizumab and cemiplimab in two large independent cohorts of patients with PD-L1 TPS greater than or equal to 90% versus 50% to 89% and characterize genomic and immunophenotypic differences between these PD-L1 expression groups, which were largely unknown. MethodsWe analyzed three-year outcomes of the following two independent cohorts: (1) a multicenter cohort of patients from four academic centers in the United States treated with pembrolizumab and (2) EMPOWER-Lung 1, randomized, phase III trial comparing first-line cemiplimab with chemotherapy. Tumor genomic profiling and multiplexed immunofluorescence were performed to evaluate genomic and immunophenotypic correlates of very high PD-L1 expression. ResultsAt three years of follow-up, progression-free survival (hazard ratio [HR], 0.69; p < 0.001) and overall survival (HR, 0.70; p < 0.01) to first-line commercial pembrolizumab were significantly improved in patients with a PD-L1 TPS greater than or equal to 90% versus 50% to 89%. In the EMPOWER-Lung 1, patients assigned to the cemiplimab arm with a PD-L1 TPS greater than or equal to 90% also had significant improvements in progression-free survival (HR, 0.53; p < 0.0001) and overall survival (HR, 0.63; p = 0.007) compared with those with a PD-L1 of 50% to 89%. Tumor genomic profiling of 553 NSCLC samples revealed that mutations in STK11 and SMARCA4 were significantly more frequent in tumors with a PD-L1 TPS of 50% to 89% compared with those with a PD-L1 TPS greater than or equal to 90% (Q < 0.15), whereas BRCA2 was enriched in NSCLC samples with a PD-L1 TPS greater than or equal to 90% (Q < 0.15). Multiplexed immunofluorescence on 93 NSCLC samples identified higher intratumoral CD8+PD1+ T cells (p = 0.02) in tumors with PD-L1 TPS greater than or equal to 90% versus 50% to 89%. ConclusionPembrolizumab and cemiplimab were found to have long-term survival benefit and favorable genomic and immunophenotypic profile in patients with advanced NSCLC with PD-L1 TPS greater than or equal to 90% compared with TPS 50% to 89%.

Stereotactic Radiation for Ultra-Central Non-Small Cell Lung Cancer: A Safety and Efficacy Trial (SUNSET)

The use of stereotactic body radiotherapy (SBRT) for tumors in close proximity to the central mediastinal structures has been associated with a high risk of toxicity. This study (BLINDED FOR REVIEW) aimed to determine the maximally tolerated dose (MTD) of SBRT for ultra-central (UC) non-small cell lung carcinoma (NSCLC), using a time-to-event continual reassessment methodology (TITE-CRM). Patients with T1-3N0M0 (≤ 6 cm) NSCLC were eligible. The MTD was defined as the dose of radiotherapy associated with a ≤ 30% rate of grade (G) 3-5 pre-specified treatment-related toxicity occurring within 2 years of treatment. The starting dose level was 60 Gy in 8 daily fractions. The dose-maximum hotspot was limited to 120% and within the planning tumor volume (PTV); tumors with endobronchial invasion were excluded. This primary analysis occurred two years after completion of accrual. Between March 2018 and April 2021, 30 patients were enrolled at 5 institutions. The median age was 73 years (range: 65-87) and 17 (57%) were female. PTV was abutting proximal bronchial tree in 19 (63%), esophagus 5 (17%), pulmonary vein 1 (3.3%) and pulmonary artery 14 (47%). All patients received 60 Gy in 8 fractions. The median follow-up was 37 months (range: 8.9-51). Two patients (6.7%) experienced G3-5 adverse events related to treatment: 1 patient with G3 dyspnea and 1 G5 pneumonia; the latter had CT findings consistent with a background of interstitial lung disease. Three-year overall survival was 72.5% (95% confidence interval [CI]: 52.3-85.3%), progression-free survival 66.1% (95% CI: 46.1-80.2%), local control 89.6% (95% CI: 71.2-96.5%), regional control 96.4% (95% CI: 77.2-99.5%) and distant control 85.9% (95% CI: 66.7-94.5%). Quality of life scores declined numerically over time, but the decreases were not clinically or statistically significant. 60 Gy in 8 fractions, planned and delivered with only a moderate hotspot, has a favorable adverse event rate within the pre-specified acceptability criteria, and results in excellent control for UC tumors.

Perioperative and oncological outcomes following robotic en bloc multivisceral resection for colorectal cancer.

As multidisciplinary treatment strategies for colorectal cancer have improved, aggressive surgical resection has become commonplace. Multivisceral and extended resections offer curative-intent resection with significant survival benefit. However, limited data exist regarding the feasibility and oncological efficacy of performing extended resection via a minimally invasive approach. The aim of this study was to determine the perioperative and long-term outcomes following robotic extended resection for colorectal cancer. We describe the population of patients undergoing robotic multivisceral resection for colorectal cancer at our single institution. We evaluated perioperative details and investigated short- and long-term outcomes, using the Kaplan-Meier method to analyse overall and recurrence-free survival. Among the 86 patients most tumours were T3 (47%) or T4 (47%) lesions in the rectum (78%). Most resections involved the anterior compartment (72%): bladder (n = 13), seminal vesicle/vas deferens (n = 27), ureter (n = 6), prostate (n = 15) and uterus/vagina/adnexa (n = 27). Three cases required conversion to open surgery; 10 patients had grade 3 complications. The median hospital stay was 4 days. Resections were R0 (>1 mm) in 78 and R1 (0 to ≤1 mm) in 8, with none being R2. The average nodal yield was 26 and 48 (55.8%) were pN0. Three-year overall survival was 88% and median progression-free survival was 19.4 months. Local recurrence was 6.1% and distant recurrence was 26.1% at 3 years. Performance of multivisceral and extended resection on the robotic platform allows patients the benefit of minimally invasive surgery while achieving oncologically sound resection of colorectal cancer.

Liver regeneration after portal and hepatic vein embolization improves overall survival compared with portal vein embolization alone: mid-term survival analysis of the multicentre DRAGON 0 cohort.

The purpose of this study was to compare 3-year overall survival after simultaneous portal (PVE) and hepatic vein (HVE) embolization versus PVE alone in patients undergoing liver resection for primary and secondary cancers of the liver. In this multicentre retrospective study, all DRAGON 0 centres provided 3-year follow-up data for all patients who had PVE/HVE or PVE, and were included in DRAGON 0 between 2016 and 2019. Kaplan-Meier analysis was undertaken to assess 3-year overall and recurrence/progression-free survival. Factors affecting survival were evaluated using univariable and multivariable Cox regression analyses. In total, 199 patients were included from 7 centres, of whom 39 underwent PVE/HVE and 160 PVE alone. Groups differed in median age (P = 0.008). As reported previously, PVE/HVE resulted in a significantly higher resection rate than PVE alone (92 versus 68%; P = 0.007). Three-year overall survival was significantly higher in the PVE/HVE group (median survival not reached after 36 months versus 20 months after PVE; P = 0.004). Univariable and multivariable analyses identified PVE/HVE as an independent predictor of survival (univariable HR 0.46, 95% c.i. 0.27 to 0.76; P = 0.003). Overall survival after PVE/HVE is substantially longer than that after PVE alone in patients with primary and secondary liver tumours.

Clinical Outcomes of Renal Transplant Recipients Undergoing Percutaneous Coronary Intervention

Clinical outcomes of patients with renal transplant (RT) undergoing percutaneous coronary intervention (PCI) remain poorly elucidated. Between 2014 and 2021, data were analysed for the following three groups of patients undergoing PCI enrolled in a multicentre Australian registry: (1) RT recipients (n=226), (2) patients on dialysis (n=992), and (3) chronic kidney disease (CKD) patients (estimated glomerular filtration rate [eGFR], 30‒60 mL/min per 1.73 m2) without previous RT (n=15,534). Primary outcome was 30-day major adverse cardiac and cerebrovascular events (MACCEs)-composite of mortality, myocardial infarction, stent thrombosis, target vessel revascularisation, and stroke. RT recipients were younger than dialysis and patients with CKD (61±10 vs 68±12 vs 78±8.2 years, p<0.001). Patients with RT less frequently had severe left ventricular dysfunction compared with dialysis and CKD groups (6.7% vs 14% and 8.5%); however more, often presented with acute coronary syndrome (58% vs 52% and 48%), especially STEMI (all p<0.001). Patients with RT and CKD had lower rates of 30-day MACCE (4.4% and 6.8% vs 11.6%, p<0.001) than the dialysis group. Three-year survival was similar between RT and CKD groups, however was lower in the dialysis group (80% and 83% vs 60%, p<0.001). After adjustment, dialysis was an independent predictor of 30-day MACCE (odds ratio [OR] 1.90, 95% confidence interval [CI] 1.44‒2.50, p<0.001), however RT was not (OR 0.91, CI 0.42‒1.96, p=0.802). Both RT (hazard ratio [HR] 2.07, CI 1.46‒2.95, p<0.001) and dialysis (HR 1.35, CI 1.02‒1.80, p=0.036) heightened the hazard of long-term mortality. RT recipients have more favourable clinical outcomes following PCI compared with patients on dialysis. However, despite having similar short-term outcomes to patients with CKD, the hazard of long-term mortality is significantly greater for RT recipients.

Siewert II esophagogastric junction adenocarcinoma: Still searching for the right treatment transabdominal or transthoracic surgical approaches?

To date, the discussion is still ongoing whether the Siewert II adenocarcinoma of the esophagogastric junction (AEG) should be resected either by thoracoabdominal esophagectomy or gastrectomy with resection of the distal esophagus by transhiatal extension. The aim of our study was to compare the oncological and perioperative outcomes of the transthoracic approach (TTA) and the transabdominal approach (TAA). Searches of electronic databases identifying studies from Cochrane, PubMed and Google Scholar were performed. Randomised and non-randomised studies comparing TTA and TAA approaches for surgical treatment of AEG Siewert type II were included. The Newcastle-Ottawa and Jada scales were used to evaluate methodological quality. The risk of bias was assessed using the Rob v2 and Robins-I tools. Meta-analyses were conducted for the outcomes. We included 17 trials (2 randomised controlled trials and 15 cohorts) involving 15297 patients. Longer three-year overall survival, five-year overall survival and R0 resection rates were observed in the TTA group. However, TTA had greater morbidity and pulmonary complications. Transthoracic approach appears to be preferable for selected Siewert II tumours. This may lead to higher survival rates and better R0 resection rate. Well-designed studies are needed to confirm the results of this systematic review.

Microwave coagulation for liver metastases.

Microwave coagulation for liver metastases.

Evaluation of bacterial contamination and medium-term oncological outcomes of intracorporeal anastomosis for colon cancer: A propensity score matching analysis.

Although intracorporeal anastomosis (IA) for colon cancer requires longer operative time than extracorporeal anastomosis (EA), its short-term postoperative results, such as early recovery of bowel movement, have been reported to be equal or better. As IA requires opening the intestinal tract in the abdominal cavity under pneumoperitoneum, there are concerns about intraperitoneal bacterial infection and recurrence of peritoneal dissemination due to the spread of bacteria and tumor cells. However, intraperitoneal bacterial contamination and medium-term oncological outcomes have not been clarified. To clarify the effects of bacterial and tumor cell contamination of the intra-abdominal cavity in IA. Of 127 patients who underwent laparoscopic colon resection for colon cancer from April 2015 to December 2020, 75 underwent EA (EA group), and 52 underwent IA (IA group). After propensity score matching, the primary endpoint was 3-year disease-free survival rates, and secondary endpoints were 3-year overall survival rates, type of recurrence, surgical site infection (SSI) incidence, number of days on antibiotics, and postoperative biological responses. Three-year disease-free survival rates did not significantly differ between the IA and EA groups (87.2% and 82.7%, respectively, P = 0.4473). The 3-year overall survival rates also did not significantly differ between the IA and EA groups (94.7% and 94.7%, respectively; P = 0.9891). There was no difference in the type of recurrence between the two groups. In addition, there were no significant differences in SSI incidence or the number of days on antibiotics; however, postoperative biological responses, such as the white blood cell count (10200 vs 8650/mm3, P = 0.0068), C-reactive protein (6.8 vs 4.5 mg/dL, P = 0.0011), and body temperature (37.7 vs 37.5 °C, P = 0.0079), were significantly higher in the IA group. IA is an anastomotic technique that should be widely performed because its risk of intraperitoneal bacterial contamination and medium-term oncological outcomes are comparable to those of EA.

Correlation between Ki-67 or Profilin-1 Expression Levels, Clinicopathological Characteristics and Postoperative Prognosis in Patients with Bladder Cancer.

Bladder cancer is the most common malignancy of the urinary system, and the search for new and reliable biomarkers has important clinical significance for the personalized treatment of bladder cancer. This study aims to explore the correlation between nuclear proliferation antigen (Ki-67) or Profilin-1 (PFN1) levels, clinicopathological characteristics, and postoperative prognosis in patients with bladder cancer. Patients with bladder cancer who underwent transurethral resection of bladder cancer tumor in The Fourth Affiliated Hospital of Soochow University, hospital from January 2019 to January 2021 were selected as the study group (n = 60), and patients with benign lesions of bladder cancer during the same period were selected as the control group (n = 60). The expression of Ki-67 and PFN1 in tumor and bladder tissues of the two groups was analyzed. Ki-67 recorded the patient's pathological parameters and calculated the patient's postoperative prognosis. The correlation between Ki-67 and PFN1 expression levels, pathological parameters, and postoperative prognosis was analyzed. The positive expression rates of Ki-67 and PFN1 in the study group were 63.33% and 73.33%, respectively, which were significantly higher than the positive expression rates in the control group (χ2 = 14.803, 17.757, p < 0.001). The positive expression rates of Ki-67 and PFN1 were related to histological grade, clinical stage, infiltration, and lymph node metastasis, and the differences were statistically significant (p < 0.05). Bladder cancer patients with non muscle-invasive bladder cancer (NMIBC), high-grade histological grade, Ta~T1 clinical stage, invasive, and lymph node metastasis have a higher Ki-67 positive expression rate than bladder cancer patients with muscle-invasive bladder cancer (MIBC), low-grade histological grade, T2~T4, non-invasive, and no lymph node metastasis. The high expression level of Ki-67 has little relationship with gender, age, tumor diameter, and vascular invasion (p > 0.05). The survival time and three-year survival rate of the Ki-67 positive expression group were significantly lower than those of the Ki-67 negative expression group (p < 0.05). The survival time and three-year survival rate of the PFN1 positive expression group were significantly lower than those of the PFN1 negative expression group (p < 0.05). The positive expression rates of Ki-67 and PFN1 in bladder tumor tissue are significantly higher than those in bladder tissue, and pathological pattern, histological grade, clinical stage, infiltration, and lymph node metastasis are related to the positive expression rates of Ki-67 and PFN1, and different genders, ages, tumors diameter and vascular invasion are not related to the positive expression rates of Ki-67 and PFN1. The survival time and three-year survival rates of bladder cancer patients with Ki-67 positive and PFN1 positive expression are shorter.

Long-Term Survival and Immune Response Dynamics in Melanoma Patients Undergoing TAPCells-Based Vaccination Therapy.

Cancer vaccines present a promising avenue for treating immune checkpoint blockers (ICBs)-refractory patients, fostering immune responses to modulate the tumor microenvironment. We revisit a phase I/II trial using Tumor Antigen-Presenting Cells (TAPCells) (NCT06152367), an autologous antigen-presenting cell vaccine loaded with heat-shocked allogeneic melanoma cell lysates. Initial findings showcased TAPCells inducing lysate-specific delayed-type hypersensitivity (DTH) reactions, correlating with prolonged survival. Here, we extend our analysis over 15 years, categorizing patients into short-term (<36 months) and long-term (≥36 months) survivors, exploring novel associations between clinical outcomes and demographic, genetic, and immunologic parameters. Notably, DTHpos patients exhibit a 53.1% three-year survival compared to 16.1% in DTHneg patients. Extended remissions are observed in long-term survivors, particularly DTHpos/M1cneg patients. Younger age, stage III disease, and moderate immune events also benefit short-term survivors. Immunomarkers like increased C-type lectin domain family 2 member D on CD4+ T cells and elevated interleukin-17A were detected in long-term survivors. In contrast, toll-like receptor-4 D229G polymorphism and reduced CD32 on B cells are associated with reduced survival. TAPCells achieved stable long remissions in 35.2% of patients, especially M1cneg/DTHpos cases. Conclusions: Our study underscores the potential of vaccine-induced immune responses in melanoma, emphasizing the identification of emerging biological markers and clinical parameters for predicting long-term remission.

Randomized, Double-Blind Phase III Study of Pazopanib Versus Placebo in Patients With Metastatic Renal Cell Carcinoma Who Have No Evidence of Disease After Metastasectomy: ECOG-ACRIN E2810.

Patients with no evidence of disease (NED) after metastasectomy for renal cell carcinoma are at high risk of recurrence. Pazopanib is an inhibitor of vascular endothelial growth factor receptor and other kinases that improves progression-free survival in patients with metastatic RCC (mRCC). We conducted a randomized, double-blind, placebo-controlled multicenter study to test whether pazopanib would improve disease-free survival (DFS) in patients with mRCC rendered NED after metastasectomy. Patients with NED after metastasectomy were randomly assigned 1:1 to receive pazopanib 800 mg once daily versus placebo for 52 weeks. The study was designed to observe an improvement in DFS from 25% to 45% with pazopanib at 3 years, corresponding to 42% reduction in the DFS event rate. From August 2012 to July 2017, 129 patients were enrolled. The study was unblinded after 83 DFS events (92% information). The study did not meet its primary end point. An updated analysis at 60.5-month median follow-up from random assignment (95% CI, 59.3 to 71.0) showed that the 3-year DFS was 27.4% (95% CI, 17.9 to 41.7) for pazopanib and 21.9% (95% CI, 13.3 to 36.2) for placebo. Hazard ratio (HR) for DFS was 0.90 ([95% CI, 0.60 to 1.34]; Pone-sided = .29) in favor of pazopanib. Three-year overall survival (OS) was 81.9% (95% CI, 72.7 to 92.2) for pazopanib and 91.4% (95% CI, 84.4 to 98.9) for placebo. The HR for OS was 2.55 (95% CI, 1.23 to 5.27) in favor of placebo (Ptwo-sided = .012). Health-related quality-of-life measures deteriorated in the pazopanib group during the treatment period. Pazopanib did not improve DFS as the primary end point compared with blinded placebo in patients with mRCC with NED after metastasectomy. In addition, there was a concerning trend favoring placebo in OS.

Three-year survival of breast cancer patients attending a one-stop breast care clinic nested within a primary care health facility in sub-Saharan Africa-Zambia.

In Zambia, women with breast symptoms travel through multiple levels of the healthcare system before obtaining a definitive diagnosis. To eradicate this critical barrier to care, we nested a novel breast specialty service platform inside a large public-sector primary healthcare facility in Lusaka, Zambia to offer clinical breast examination, breast ultrasound, and ultrasound-guided core needle biopsy in a one-stop format, tightly linked to referral for treatment. The objective of the study was to determine the life expectancy and survival outcomes of a prospective cohort of women diagnosed with breast cancer who were attended to and followed up at the clinic. The effect of breast cancer stage on prognosis was determined by estimating stage-specific crude survival using the Kaplan-Meier method. Survival analysis was used to estimate mean lifespan according to age and stage at diagnosis. We enrolled 302 women with histologically confirmed breast cancer. The overall 3-year survival was 73%. An increase in patients presenting with early breast cancer and improvements in their survival were observed. Women with early-stage breast cancer had a lifespan similar to the general population, while loss of life expectancy was significant at more advanced stages of disease. Our findings suggest that implementing efficient breast care services at the primary care level can avert a substantial proportion of breast cancer-related deaths. The mitigating factor appears to be stage of disease at the time of diagnosis, the cause of which is multifactorial, with the most influential being delays in the referral process.

Abstract 7319: Glycemic traits and colorectal cancer survival in a cohort of South Korean patients: A Mendelian randomization analysis

Abstract Background: Clinical diabetic traits have been reported to be associated with increased colorectal cancer risk (CRC) in observational studies. Using the Mendelian randomization (MR) analysis method, we examined the causal association between glycemic traits, such as fasting glucose (FG), fasting insulin (FI), and glycosylated hemoglobin A1c (HbA1c), and survival in a cohort of CRC patients. Methods: We conducted a two-sample MR analysis among a cohort of patients with locally advanced CRC at Seoul National University Hospital. Single-nucleotide polymorphisms robustly associated (P&amp;lt;5 × 10−8) with the three glycemic traits were obtained from the Meta-Analyses of Glucose and Insulin-related traits Consortium, Asian Genetic Epidemiology Network, and Korea Biobank Array. Three-year and five-year overall survival (OS) and progression-free survival (PFS) were used as outcomes. Survival analysis was conducted using subgroup analysis by cancer stage and subsite in a multivariate Cox proportional hazards model adjusted for age and sex to examine whether glycemic traits affected survival. Results: A total of 509 patients were included in our final analysis. MR analysis showed that HbA1c levels were associated with poor three-year OS (β=4.20, P=0.02). Sensitivity analyses did not show evidence of any violations of the MR assumptions. In the cancer subgroup analysis of the Cox proportional hazards model, pooled hazard ratios for FG were significantly associated with poor three-year OS and PFS regardless of cancer stage. FI was not significantly associated with any three-year survival endpoints. Among stage III patients, three glycemic traits were significantly associated with both five-year OS and PFS. Location-specific subgroup analysis showed a significant association between three glycemic traits and five-year PFS in patients with left-sided colon cancer. FG was associated with poor three-year survival for colon cancer but not rectal cancer. Conclusions: Our results suggest that FG and HbA1c could be used to predict prognosis in CRC patients. Lifestyle and/or pharmacological interventions targeting glycemic traits could help improve survival for CRC patients. Citation Format: So Yon Jun, Sooyoung Cho, Min Jung Kim, Ji Won Park, Seung Yong Jeong, Aesun Shin. Glycemic traits and colorectal cancer survival in a cohort of South Korean patients: A Mendelian randomization analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7319.

Abstract 6750: Validation of a platform to develop new dendritic cell vaccines for cancer immunotherapy

Abstract Osteosarcoma is the most common malignant form of bone cancer that generally causes patients to die of pulmonary metastasis. If detected before the tumor has metastasized, osteosarcoma has a 75% survival at 5 years after the conventional therapy with surgery and chemotherapy. However, most osteosarcomas are high-grade tumors that grow quickly and spread before being detected, lowering patient survival to 20%. Our unique protocol using the human platelet lysate PLTMax® allows establishing tumor cell lines without genetically modifying cells and with minimal genetic drift. The use of PLTMax® and allogeneic tumor cell cultures has proven to be a major advantage for the generation of large amounts of rich tumor antigen libraries for dendritic cell (DC) vaccines. This protocol was used in an autologous dendritic cell/allogeneic tumor lysate vaccine developed at the Mayo Clinic and licensed to Mill Creek Life Sciences (MCLS) to treat newly diagnosed glioblastoma (GBM), which normally has a poor survival rate at only 2%. The technology was used in a phase I clinical trial (MC1272) performed at the Mayo Clinic. The clinical outcomes proved over a 10 time increase in survival rate of patients that received the DC vaccine after the conventional therapy, providing over 20% three-year survival rate. Our technology differs from other clinically used DC vaccines in three primary ways: a) Highly efficient cell line establishment: The unique method for generating tumor cell lines uses Mill Creek Life Sciences’ PLTMax®, a media supplement derived from human platelets. PLTMax® more closely mimics the native microenvironment of tumors and is used to reduce genetic drift and senescence. b) High genetic fidelity: GBM tumor cells expanded via PLTMax® maintain genetic fidelity and TAA expression—a feat that has not been previously achieved by any other GBM cell culture method. c) Reduction of treatment delays and inclusion of all patients that qualify for treatment: Because we will use allogeneic tumor cell lines, we will be able to avoid delays in treatment caused by the time required to culture autologous tumor cell lines, and all patients may receive treatment without exclusion. Through our preliminary work we transferred the technology from a labor-intensive, small-scale approach, to an automated scalable system. Our ultimate goal is to apply this strategy to not only osteosarcoma, but also several other tumor types to validate it as a platform. Like osteosarcoma, there are other therapy-refractory cancers that we believe can benefit from the use of our platform technology, through the use of DC vaccines that offer an immune response against a wider panel of tumor antigens. Citation Format: Vanesa Alonso-Camino, William Mirsch. Validation of a platform to develop new dendritic cell vaccines for cancer immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6750.

Development and Methodological Validation of a Modified Staging System for de Novo Metastatic Breast Cancer

Validation of a new method for prognostication of de novo metastatic breast cancer (dnMBC) to better reflect the heterogenecity of the disease. To perform external methodological validation of the Plichta staging system, a novel prognostic system for de novo metastatic breast cancer (dnMBC). This retrospective cohort study used a multicenter, nationwide, population-based Danish Breast Cancer Group database to validate the new method. Participants were patients with dnMBC diagnosed between 2010 and 2019. Data were analyzed from April to June 2023. A recursive partitioning analysis (RPA) was performed, as demonstrated by Plichta and colleagues, to group patients with similar overall survival (OS) based on clinical factors. The main outcome was to group patients into 4 prognostic groups based on 3-year OS as stage IVa, greater than 70%; stage IVb, 50% to 70%; stage IVc, 25% to less than 50%; or stage IVd, less than 25%. Bootstrapping was applied for 1000 iterations, with final stage assignments based on the most commonly occurring assignment. A total of 1859 women were included with a median (IQR) age of 69 (57-77) years. With a median potential follow-up of 89.9 (95% CI, 86.4-95.1) months and a median OS of 31.7 (95% CI, 29.5-34.1) months, the RPA stratified patients into 10 groups, with organ sites, estrogen receptor status, and human epidermal growth factor receptor 2 status as the key clinical factors. Three-year survival rates ranged from 62% (95% CI, 56%-69%) to 8% (95% CI, 3%-21%), which were further combined into 3 stage groups: IVb, 59.4% (95% CI, 56.2%-62.8%); IVc, 39.4% (95% CI, 36.2%-43.0%); and IVd, 15.4% (95% CI, 11.2%-21.3%) (P < .001). Following bootstrapping, an IVa group emerged, resulting in 4 stage groups with separate 3-year OS rates identified as IVa, 75.8% (95% CI, 67.8%-84.7%); IVb, 58.8% (95% CI, 55.5%-62.3%); IVc, 39.2% (95% CI, 35.8%-43.0%); and IVd, 14.4% (95% CI, 10.8%-19.4%) (P < .001). These findings provide external and independent validation of the methods applied in the novel Plichta staging system for dnMBC. This could guide future revisions of the current American Joint Committee on Cancer staging guidelines and may be incorporated as a stratification factor in clinical trials.

Comparative Analysis of the Outcomes of Laparoscopic Right Hemicolectomy with D2 and D3 Lymphadenectomy in the Treatment of Patients with Right Colon Cancer

Introduction. The standard volume of removed groups of lymph nodes for right colon cancer (RCC) has not been determined. According to Japanese clinical guidelines, it is necessary to perform D3 lymphadenectomy in all cases, except stage I, while according to European and Russian clinical guidelines, the standard scope of surgical intervention includes only D2 lymphadenectomy. There are no long-term results regarding differences between D2 and D3 lymph node dissection in RCC; therefore, it is relevant to conduct studies to improve the long-term results of treatment of patients with RCC.Aim: to comparatively evaluate the results of treatment of patients with RCC who underwent laparoscopic right hemicolectomy at A. Tsyb Medical Radiological Research Center.Materials and methods. Conducted from 2018 to 2023, the study included 174 patients with stage I–III RCC: in 106 patients, laparoscopic right hemicolectomy with D2 lymph node dissection was performed, in 68 patients — with D3 lymph node dissection. When assessing the homogeneity and comparability of the groups, according to input parameters, such as clinical stage, gender, age, body mass index and tumor location, their heterogeneity was noted, which did not allow a direct comparative assessment of both groups. To eliminate heterogeneity and adequately select groups, a pseudorandomization technique was used, after which the groups (n = 68) became statistically comparable in all main clinical parameters.Results. Statistically significant differences were obtained in the median duration of surgical intervention, which was longer in the group of patients with D3 lymph node dissection — 150 (60–393) and 213 (70–390) minutes (p &lt; 0.001), and in the median time of flatus passage — 2 (1–4) and 3 (1–9) days, respectively (p = 0.042). Postoperative complications in accordance with the Clavien — Dindo classification occurred in 16 (23.5 %) patients in the group with D2 and in 15 patients (22.1 %) in the group with D3 lymph node dissection (p = 0.999); III–V grade complications were noted in 2 (2.9 %) cases in each group (p = 0.999). Postoperative hospital stay was 6 days for patients in both groups (p = 0.369). During pathomorphological assessment of the removed specimen, the median number of examined lymph nodes was significantly higher in the group with D3 lymph node dissection: 14 (1–52) and 19 (3–59) lymph nodes, respectively (p &lt; 0.001). Involvement of apical lymph nodes (groups 203, 213, 223) was noted in 2 (3 %) patients. In the group with D2 lymph node dissection, distant metastases were recorded twice as often as in the group with D3 lymph node dissection — in 8 (11.8 %) and 4 (5.9 %) patients, respectively (p = 0.365). Local recurrence was not established in any case. The three-year overall and disease-free survival rates were 94.8 ± 3.0 and 100 % (p = 0.149) and 80.5 ± 5.8 and 88.7 ± 5.8 % (p = 0.177), respectively.Conclusions. The experience of using total mesocolonectomy with D3 lymph node dissection for RCC indicates the safety of this surgical intervention in comparison with traditional surgical techniques, while we did not obtain statistically significant differences in patient survival. To definitively determine the role of D3 lymph node dissection in the treatment of patients with RCC, large multicenter randomized studies are certainly needed.

Integrating molecular subtype and CD8+ T cells infiltration to predict treatment response and survival in muscle-invasive bladder cancer

BackgroundLuminal and Basal are the primary intrinsic subtypes of muscle-invasive bladder cancer (MIBC). The presence of CD8+ T cells infiltration holds significant immunological relevance, potentially influencing the efficacy of antitumor responses. This study aims to synergize the influence of molecular subtypes and CD8+ T cells infiltration in MIBC.MethodsThis study included 889 patients with MIBC from Zhongshan Hospital, The Cancer Genome Atlas, IMvigor210 and NCT03179943 cohorts. We classified the patients into four distinct groups, based on the interplay of molecular subtypes and CD8+ T cells and probed into the clinical implications of these subgroups in MIBC.ResultsAmong patients with Luminal-CD8+Thigh tumors, the confluence of elevated tumor mutational burden and PD-L1 expression correlated with a heightened potential for positive responses to immunotherapy. In contrast, patients featured by Luminal-CD8+Tlow displayed a proclivity for deriving clinical advantages from innovative targeted interventions. The Basal-CD8+Tlow subgroup exhibited the least favorable three-year overall survival outcome, whereas their Basal-CD8+Thigh counterparts exhibited a heightened responsiveness to chemotherapy.ConclusionsWe emphasized the significant role of immune-molecular subtypes in shaping therapeutic approaches for MIBC. This insight establishes a foundation to refine the process of selecting subtype-specific treatments, thereby advancing personalized interventions for patients.

Glycemic traits and colorectal cancer survival in a cohort of South Korean patients: A Mendelian randomization analysis.

Clinical diabetic traits have been reported to be associated with increased colorectal cancer (CRC) risk in observational studies. Using the Mendelian randomization (MR) analysis method, we examined the causal association between glycemic traits, such as fasting glucose (FG), fasting insulin (FI), and glycosylated hemoglobin A1c (HbA1c), and survival in a cohort of CRC patients. We conducted a two-sample MR analysis among a cohort of patients with locally advanced CRC at Seoul National University Hospital. Single-nucleotide polymorphisms robustly associated (p < 5 × 10-8 ) with the three glycemic traits were obtained from the Meta-Analyses of Glucose and Insulin-related traits Consortium, Asian Genetic Epidemiology Network, and Korea Biobank Array. Three-year and 5-year overall survival (OS) and progression-free survival (PFS) were used as outcomes. Survival analysis was conducted using subgroup analysis by cancer stage and subsite in a multivariate Cox proportional hazards model adjusted for age and sex to examine whether glycemic traits affected survival. A total of 509 patients were included in our final analysis. MR analysis showed that HbA1c levels were associated with poor 3-year OS (β = 4.20, p = 0.02). Sensitivity analyses did not show evidence of any violations of the MR assumptions. In the cancer subgroup analysis of the Cox proportional hazards model, pooled hazard ratios for FG were significantly associated with poor 3-year OS and PFS regardless of cancer stage. FI was not significantly associated with any 3-year survival endpoints. Among Stage III patients, three glycemic traits were significantly associated with both 5-year OS and PFS. Location-specific subgroup analysis showed a significant association between three glycemic traits and 5-year PFS in patients with left-sided colon cancer. FG was associated with poor 3-year survival for colon cancer but not rectal cancer. Our results suggest that FG and HbA1c could be used to predict prognosis in CRC patients. Lifestyle and/or pharmacological interventions targeting glycemic traits could help improve survival for CRC patients.