Significant Decrease In Overall Survival Research Articles

Effectiveness and toxicity of multidisciplinary treatment of head and neck cancer among people with HIV: Real-world evidence from a tertiary cancer center in Brazil.

e24139 Background: The incidence of head and neck squamous cell carcinoma (HNSCC) is rising among people with HIV (PWH). Previous studies have shown an increase in treatment-related toxicities in this population. This study aims to determine the demographics and treatment outcomes in this patient group at a tertiary cancer center in Brazil. Methods: HNSCC patients (pts) with HIV diagnosis treated at our institution between 2009 and 2022 were included. Medical charts were analyzed to extract clinical data. Log rank was used to compare survival estimates and stratified Cox regression model was used for univariate and multivariate analyses. Results: Our search identified 75 pts with HIV among 5956 pts with HNSCC. Median age at cancer diagnosis was 53 years (IQR 49-59.5), 80% were male and 82.7% had a smoking history. Most pts had an oropharynx primary tumor (38.7%) and locally advanced disease (80%), with T3 and T4 tumors in 55 pts (73.3%) and N+ in 48 pts (64.1%). A feeding tube (FT) was placed in 32% of pts before treatment. HIV viral load was detectable in 23 (30.7%) pts and 19 (25.3%) had a CD4 count of fewer than 200 cells/mm³, while 97.3% of the pts were on combination antiretroviral therapy at the time of HNSCC diagnosis. 26 pts were operated with curative intent and 20 pts received adjuvant therapy. In the total population, concurrent cisplatin-based chemoradiation (CCRT) was prescribed to 26 pts (34.7%) and 34 (45.3%) received radiotherapy (RT) alone. 65.4% of the pts in the CCRT group and 20.6% in the RT group were unable to complete treatment as prescribed, mostly due to toxicity. No pts with positive viral load or CD4 < 200 cells/mm³ were able to complete CCRT. Treatment toxicity led to hospitalization in 24% of pts and 7 pts needed FT placement. There were 8 deaths during treatment, 5 in pts with CD4 < 200 cells/mm³. Positive viral load was associated with CCRT interruption (p = 0.03) and a CD4 count of less than 200 cells/mm³ increased the risk of death during treatment (p = 0.02). Median overall survival (OS) was 31.7 months (IQR 14.6-53.7). Multivariate analysis did not show a statistically significant decrease in OS in pts with positive viral load or CD4 < 200 cells/mm³. Factors associated with worse OS on multivariate analysis were FT usage (HR = 2.91; 95% CI: 1.45-5.83) and Eastern Cooperative Oncology Group Performance Status (ECOG-PS) greater than 1 (HR = 3.26; 95% CI: 1.46-7.24). Conclusions: HNSCC treatment in PWH is associated with a high discontinuation rate, even in pts with antiviral therapy. High toxicity rates and deaths during treatment were observed. Positive viral load and low CD4 count were considered contributing factors. ECOG-PS and enteral feeding tube usage were independently associated with worse survival. The development of more tailored strategies in this population is needed to improve outcomes in patients with HNSCC and HIV.

The clustering status of detached gastric cancer cells inhibits anoikis-induced ferroptosis to promote metastatic colonization

Background and purposeFerroptosis is a form of regulated cell death characterized by iron-dependent lipid peroxidation. Its role in cancer metastasis remains unclear. In this study, we aimed to investigate the potential involvement of ferroptosis in gastric cancer (GC) metastasis.MethodsGC cells (AGS, MKN45, HGC27) were used to explore the role of ferroptosis in single and clustered cells with extracellular matrix (ECM) detachment in vitro. We overexpressed glutathione peroxidase 4 (GPX4) to inhibit ferroptosis and assessed the changes in cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). Then tumor tissues from 54 GC patients with and without lymphatic metastasis were collected for immunohistochemical staining to investigate the expression of ferroptosis and EMT markers. Finally, Kaplan–Meier survival curves were used to investigate the relationship between overall survival and expression of GPX4 in 178 GC patients.ResultsDetached single cells had lower viability than adherent cells, but cell clustering improved their survival under matrix-detached conditions. Detached single cells exhibited an induction of iron-dependent reactive oxygen species (ROS) accumulation, glutathione (GSH) depletion, lipid peroxidation, upregulation of ACSL4, TFRC and HO-1, increased iron levels, and changes in mitochondrial morphology. Opposite effects were observed in detached clustered cells, including the upregulation of the ferroptosis suppressors GPX4 and SLC7A11. Overexpression of GPX4 inhibited ferroptosis and promoted GC cell proliferation, migration, invasion, and EMT. Immunohistochemical analysis of tumor tissues from GC patients indicated that lymphatic metastasis was associated with higher potential for ferroptosis inhibition and EMT induction. Finally, Kaplan–Meier survival curves demonstrated a significant decrease in overall survival among GC patients with high GPX4 expression.ConclusionsOur study provides the first evidence that inhibition of ferroptosis is a crucial mechanism promoting GC metastasis. GPX4 may be a valuable prognostic factor for GC patients. These findings suggest that targeting ferroptosis inhibition may be a promising strategy for GC patients with metastatic potential.Trial registration The ethical approval code of this study in Institutional Review Board of Peking Union Medical College Hospital is No: K1447.

Machine learning combining multi-omics data and network algorithms identifies adrenocortical carcinoma prognostic biomarkers.

Background: Rare endocrine cancers such as Adrenocortical Carcinoma (ACC) present a serious diagnostic and prognostication challenge. The knowledge about ACC pathogenesis is incomplete, and patients have limited therapeutic options. Identification of molecular drivers and effective biomarkers is required for timely diagnosis of the disease and stratify patients to offer the most beneficial treatments. In this study we demonstrate how machine learning methods integrating multi-omics data, in combination with system biology tools, can contribute to the identification of new prognostic biomarkers for ACC. Methods: ACC gene expression and DNA methylation datasets were downloaded from the Xena Browser (GDC TCGA Adrenocortical Carcinoma cohort). A highly correlated multi-omics signature discriminating groups of samples was identified with the data integration analysis for biomarker discovery using latent components (DIABLO) method. Additional regulators of the identified signature were discovered using Clarivate CBDD (Computational Biology for Drug Discovery) network propagation and hidden nodes algorithms on a curated network of molecular interactions (MetaBase™). The discriminative power of the multi-omics signature and their regulators was delineated by training a random forest classifier using 55 samples, by employing a 10-fold cross validation with five iterations. The prognostic value of the identified biomarkers was further assessed on an external ACC dataset obtained from GEO (GSE49280) using the Kaplan-Meier estimator method. An optimal prognostic signature was finally derived using the stepwise Akaike Information Criterion (AIC) that allowed categorization of samples into high and low-risk groups. Results: A multi-omics signature including genes, micro RNA's and methylation sites was generated. Systems biology tools identified additional genes regulating the features included in the multi-omics signature. RNA-seq, miRNA-seq and DNA methylation sets of features revealed a high power to classify patients from stages I-II and stages III-IV, outperforming previously identified prognostic biomarkers. Using an independent dataset, associations of the genes included in the signature with Overall Survival (OS) data demonstrated that patients with differential expression levels of 8 genes and 4 micro RNA's showed a statistically significant decrease in OS. We also found an independent prognostic signature for ACC with potential use in clinical practice, combining 9-gene/micro RNA features, that successfully predicted high-risk ACC cancer patients. Conclusion: Machine learning and integrative analysis of multi-omics data, in combination with Clarivate CBDD systems biology tools, identified a set of biomarkers with high prognostic value for ACC disease. Multi-omics data is a promising resource for the identification of drivers and new prognostic biomarkers in rare diseases that could be used in clinical practice.

Elevated serum beta-2 microglobulin level predicts short-term poor prognosis of patients with de novo acute omicron variant COVID-19 infection.

The devastating coronavirus disease of 2019 (COVID-2019) epidemic has been declared a public health emergency, resulting in a worldwide pandemic. The omicron variety is the most common epidemic mutant strain in the globe. Serum beta-2 microglobulin (β2-MG) is associated with endothelial cell injury and has value in monitoring the progression of inflammation in infected individuals. Nonetheless, the potential functions of β2-MG in omicron remain elusive. To investigate the prognostic value of serum β2-MG levels at diagnosis, we retrospectively analyzed a cohort of 240 people with omicron. Over the course of 65 days, all patients were monitored, and death was the primary outcome. Patients were allocated to two groups: those with high and low β2-MG levels. The Kaplan-Meier method was used to examine OS, and the log-rank test was used to compare them. Univariate and multivariate Cox hazard models were used to determine the prognostic significance. Our results revealed that β2-MG was significantly elevated in omicron. β2-MG levels in severe patients were higher than in mild-to-moderate patients, and the difference was statistically significant. Timely, interleukin-6 (IL-6) and interleukin-10 (IL-10) were observed to be significantly increased in individuals exhibiting elevated levels of β2-MG. In addition, patients exhibiting elevated levels of β2-MG demonstrated a statistically significant decrease in overall survival (OS, P < 0.0001). An elevated β2-MG level (≥4.72 mg/l) was found to be an independent, adverse prognostic factor for OS in omicron patients, according to multivariate Cox proportional hazards regression analysis (P = 0.001). Serum β2-MG level at initial diagnosis was significantly correlated with omicron severity and prognosis. Thus, we propose that β2-MG may be an independent poor additional prognostic factor in patients with omicron.

#6715 COGNITIVE IMPAIRMENT IS ASSOCIATED WITH INCREASED MORTALITY IN HEMODIALYSIS PATIENTS

Abstract Background and Aims Patients on dialysis are at substantially higher risk for developing cognitive impairment compared with the general population. At the same time cognitive impairment is a strong and independent risk factor for all-cause mortality. Given that the approaches used to access the prevalence of cognitive disfunction widely vary in different patient populations, their true burden in hemodialysis patients remains poorly understood. The aim of our study was to determine the association between cognitive impairment and overall survival and mortality in patients undergoing hemodialysis treatment. Method A total of 69 chronic hemodialysis patients (47 men and 22 women) were included. The median age of patients was 61 [47-69] years. The median duration of hemodialysis treatment was 32 [21-72] months. The study of cognitive status was conducted using the Montreal Cognitive Assessment (MoCA) questionnaire. The test results are between 0 and 30 points. A score of 26 points or more is considered the norm, less than 26 indicates the presence of cognitive impairment. The end point was a fatal outcome from acute pathology or progression of a chronic disease. The analysis of survival and mortality was evaluated using survival tables, the construction of Kaplan-Mayer curves with the Mantel-Cox log–rank criterion. The risks of the influence of cognitive impairment on mortality were assessed using Cox regression. Results During the 24-month follow-up period, 23 patients died. Structure of mortality over the observation period: acute coronary syndrome – 6 (26 %), COVID-19 – 6 (26 %), acute cerebrovascular accident – 2 (9%), thromboembolic complications – 3 (13%), another causes – 6 (26 %). In patients with cognitive impairment on hemodialysis, the average survival value was 16.33 months ± 1.70 months [CI 95% 12.99-19.66] and 20.48 months±1.32 months [CI 95% 17.88-23.07] in patients without cognitive impairment. According to the Mantel-Cox log-rank criterion, there was a statistically significant decrease in overall survival in patients with cognitive impairment, P = .02. The mortality rate of dialysis patients with cognitive impairment was 51%, without cognitive impairment – 19%. Relative risk of death in the group of patients with cognitive impairment using Cox regression: Hazard ratio (HR) :2.90 [95% CI 1.11-7.37, P = .03]. Conclusion Our results support the notion that cognitive impairment may be an independent predictor of all-cause mortality in hemodialysis patients. There are limitations on the sample size of patients in our study. Further larger-scale observations a large cohort of patients are required.

Determining the optimal interval between neoadjuvant radiochemotherapy and surgery in rectal cancer: a retrospective cohort study.

In locally advanced rectal cancer, the optimal interval between completion of neoadjuvant radiochemotherapy (RT-ChT) and surgical resection remains unclear due to contradictory data on the benefits of extending this interval. Therefore, the aim of this retrospective study was to determine the impact of this interval on outcomes in patients treated for rectal cancer at our center. We retrospectively reviewed 382 consecutive patients treated for stage II/III rectal cancer between October 1, 2012, and December 31, 2017. We evaluated four different cut-off points (56, 63, 70, and 77days) to determine which had the greatest impact on treatment outcomes. The median time between completion of RT-ChT and surgery was 67.2days (range, 28-294). Intervals > 8weeks (56days) were associated with worse therapeutic outcomes. Specifically, an interval ≥ 77days was associated with a significant decrease in overall survival (OS; 84% vs. 70%; p = 0.004), which is why we selected this interval for the comparative analysis. Several outcome variables were significantly better in the short interval (< 77days) group, including margin involvement (5.2% vs. 13.9%; p = 0.01), sphincter preservation (78% vs. 59.3%; p = 0.003), and distant dissemination (22.6% vs. 32.5%; p = 0.04). No significant between-group differences were found in complete/nearly complete response rates (19.2% vs. 24.4%; p = 0.3). Time to surgery was statistically significant on both the univariate and multivariate analyses. Our findings suggest that surgery should not be delayed more than 8weeks (56days) after neoadjuvant treatment. An interval > 8weeks should only be considered in patients who demonstrate a good response to neoadjuvant RT-ChT.

INCIDENCE AND PREDICTIVE FACTORS OF PLATINUM‐ASSOCIATED NEPHROTOXICITY IN PATIENTS WITH LYMPHOID MALIGNANCIES; A 15‐YEAR EXPERIENCE OUTSIDE CLINICAL TRIALS

Introduction: Platinum-based chemotherapy is widely used in patients with lymphoma either in first or successive lines of treatment. However, platinum is well known to be nephrotoxic and could impact in clinical outcomes. Methods: An unicentric retrospective cohort study was carried out including lymphoma patients who received platinum-based chemotherapy between 2007 and 2022. Renal failure (RF) was defined as a decrease in creatinine clearance by 50% or an elevation of plasma creatinine a 50% over the previous level. Patients who received treatment in first line and those who were intended to proceed to cellular therapy were included. Patients on clinical trials were excluded. The final cohort was assessed for incidence of RF and clinical and laboratory variables were evaluated as risk factors. Results: A total of 123 patients were included. Baseline characteristics are summarized in Figure 1A. The incidence of RF was 41.5% (51/123). Median time to RF was 6 days (range: 1–28). RF persisted until data cut-off date in 20/51 (39.2%), and 4/51 (7.8%) patients required dialysis. Following variables: sex, body mass index, diabetes, dyslipidemia, use of anti-CD20 and the type of chemotherapy were not associated to an increased risk of RF. Administration of magnesium supplements and mannitol had no impact on RF. Significant differences were observed between the RF and the no-RF groups in age (58.3 vs. 48.3 years; p < 0.001), hypertension (41.2% vs. 13.9%; p < 0.001), albumin (3.2 vs. 3.7 g/dL; p < 0.001) and hemoglobin (10.9 vs. 12.5 g/dL; p < 0.001). We used the cut-off of 51 years (assessed by the optimal point of the ROC curve) for age to be included in a logistic regression model with categoric predictors. The cut-off values of 3.5 g/dL for albumin and 10 g/dL of hemoglobin were chosen based on a biological basis. These four variables were associated with an increased risk of RF showing univariable odds ratio (OR) of 3.7 (1.7–8) for age, 4.3 (1.8–10.4) for hypertension, 4.3 (2–9.2) for albumin and 4.3 (1.8–10.4) for hemoglobin. A multivariable logistic regression model was built including these variables; having hypertension and hemoglobin <10 remained as significant predictors – OR: 1.8 (1.1–2.9) and 2.8 (1.1–7.6) respectively –, whereas age <51 and albumin kept an OR of 1.9 (0.8–4.9) and 2.3 (0.9–5.5) which resulted non statistically significant. Developing renal failure after platinum treatment was associated with a significant decrease in overall survival (OS); median OS in RF and no-RF groups were: 2.4 versus 6.2 years respectively (Figure 1B, log-rank test: 6.67; p = 0.009). Keywords: late effects in lymphoma survivors, other, risk models No conflicts of interests pertinent to the abstract.

Beta-blocker exposure and survival outcomes in patients with advanced pancreatic ductal adenocarcinoma: a retrospective cohort study (BETAPANC).

Introduction: Preclinical studies have demonstrated the possible role of beta-adrenergic receptors in pancreatic ductal adenocarcinoma (PDAC) tumor invasion and migration. The current study aimed to explore the possible association between survival outcomes and beta-blocker (BB) exposure in patients with advanced PDAC. Methods: This retrospective single-center study included 182 patients with advanced PDAC. Clinical [age, sex, BMI, cardiovascular condition, presence (SBB) or absence (NSBB) of beta-1 selectivity of BB, exposure duration, and multimorbidity], oncological (stage and anticancer treatment regimen), and biological (renal and liver function) data were collected. The endpoints were overall survival (OS) and progression-free survival (PFS). Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for survival outcomes associated with BB exposure were estimated using Cox regression model and propensity score (PS) methods. Results: Forty-one patients (22.5%) were exposed to BB. A total of 104 patients progressed (57.1%) to PDAC and 139 (76.4%) patients died at the end of follow-up (median, 320days; IQR, 438.75days). When compared to the non-exposed group, there was no increase in survival outcomes associated with BB use (OS: HR = 1.38, 95% CI = 0.80-2.39, p = 0.25; PFS: adjusted HR = 0.95, 95% CI = 0.48-1.88, p = 0.88). Similar results were obtained using the PS method. Compared to no BB usage, SBB use was associated with a significant decrease in OS (HR = 1.80, 95% CI = 1.16-2.80, p < 10-2). Conclusion: BB exposure was not associated with improved PDAC survival outcomes. Beta-1-selectivity was not independently associated with any differences.

Association of baseline self-reported fatigue with overall survival after stereotactic body radiation therapy for localized prostate cancer.

Stereotactic Body Radiation Therapy (SBRT) has emerged as a definitive therapy for localized prostate cancer (PCa). However, more data is needed to predict patient prognosis to help guide which patients will benefit most from treatment. The FACIT-Fatigue (FACIT-F) is a well validated, widely used survey for assessing fatigue. However, the role of fatigue in predicting PCa survival has yet to be studied. Herein, we investigate the role of FACIT-F as a baseline predictor for overall survival (OS) in patients undergoing SBRT for localized PCa. A retrospective review was conducted of 1358 patients who received SBRT monotherapy between January 2008 to April 2021 at an academic, tertiary referral center. FACIT-F scores (range 0 to 52) were summed for patients who answered all 13-items on the survey. FACIT-F total scores of ≥35 represented severe fatigue. Patients receiving androgen deprivation therapy were excluded. Differences in fatigue groups were evaluated using chi-squared tests. OS rates were determined using the Kaplan-Meier method and predictors of OS were evaluated using Cox proportional hazard method. Baseline full FACIT-F scores and survival data was available for 891 patients. 5-year OS was 87.6% and 95.2%, respectively, for the severely fatigued and non-fatigued groups. Chi-squared analysis of fatigue groups showed no significant difference in the following categories: D'Amico risk group, age, ethnicity, grade group, T-stage, or PSA density. Severe fatigue was associated with a significant decrease in OS (hazard ratio 2.76; 95%CI 1.55 - 4.89). The Cox proportional hazard model revealed that age and FACIT-F were both statistically significant (p <0.05). Baseline FACIT-F scores are significantly associated with OS. Higher FACIT-F scores, representing less fatigued patients, are associated with an overall survival benefit. These results indicate that the FACIT-F survey could serve as an additional metric for clinicians in determining prognostic factors for patients undergoing SBRT.

CART Therapy or Allogeneic Stem Cell Transplantation in ≥ Third Line Treatment of Large B Cell Lymphoma (LBCL)

Introduction: Allogeneic stem cell transplantation (alloSCT) was the only curative option for younger patients with LBCL (DLBCL, tFL, PMBCL) relapsing or being refractory to second-line therapy including high-dose chemotherapy and autologous SCT. After two commercially available CART products became available many pts are receiving CART third line. We sought to compare data from the EBMT registry focussing on the relative role of both treatment modalities in > third-line treatment of LBCL. Methods: Patients registered with the EBMT database from month 1/2016 to 5/2021 having received either a first alloSCT or commercially available CART therapy (Yescarta® or Kymriah ®) as ≥ third-line therapy of LBCL were analysed. To correct for imbalances in patient characteristics we did multivariate analyses considering only patient with complete information on IPI including LDH. Overall results in these patients and the population at large are identical. Results: We identified 1591 pts fulfilling the inclusion criteria (658 alloSCT, 933 CART); in 453 pts information on IPI and LDH at cell therapy was available (172 alloSCT and 281 CART). Patient groups differed significantly in clinical parameters as median age (50 yrs for alloSCT vs 62 yrs CART), median IPI score at cell therapy (1 in alloSCT and 3 in CART) and elevated LDH at cell therapy. The 1-year estimates for the major endpoints overall survival (OS), progression free survival (PFS), relapse incidence (RI) and non-relapse mortality (NRM) by the strongest prognostic factor LDH are given in the table below. In multivariate analysis, the type of cellular therapy (CART vs alloSCT) (HR 0.71 (95% CI.53-0.96, p=0.0237)) and LDH normal vs elevated (HR 0.58 (95%CI 0.44-077, p=0.00018)) significantly influenced OS, whilst age was not significant. Regarding RI, CART do significantly worse than allo SCT (HR 1.74 (95% 1.26-2.38, P=0.00067)); NRM was significantly lower after CART (HR 0.23 (95%CI 0,12-0.45, p< 0.0001)). Conclusion: Correcting for important confounding factors, pts given CART for ≥ 3rd line treatment of DLBCL still have better OS and PFS than pts treated with alloSCT. While CART therapy causes significantly less TRM, RI is generally higher than after alloSCT. Pts with active lymphoma (LDH >N, high IPI) prior to CART show high RI and a significant decrease in OS. This effect is less strong in allografted pts., Therefore, alloSCT remains a valuable option especially in patients with high-risk disease characterized by elevated LDH and high IPI. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

The Impact of High CMV Viral Load and Refractory CMV Infection on Pediatric HSCT Recipients with Underlying Non-Malignant Disorder.

Hematopoietic stem cell transplantation (HSCT) is a curative therapy for an increasing number of nonmalignant indications. Its use is restricted by severe transplant-related complications, including CMV infection; despite various prophylactic and therapeutic strategies, CMV reactivation has remarkable morbidity and mortality. The analysis included 94 children with nonmalignant disorder who underwent allogeneic HSCT in the Department of Pediatric Hematology, Oncology, and Bone Marrow Transplantation in Wrocław during years 2016–2020. Twenty-seven (29%) children presented with CMV infection, including ten (10/27; 37%) with high level CMV viremia (10,000 copies/mL). Six patients experienced subsequent CMV reactivation. The first-line ganciclovir-based (GCV) treatment was insufficient in 40% (11/27) of children. Overall survival (OS) was significantly lower in children with high CMV viremia compared to those with low levels/no CMV [1yrOS High CMV = 0.80 (95% CI 0.41–0.95) vs. 1yrOS others = 0.96 (95% CI 0.89–0.99)]. Similarly, patients with resistant and recurrent infections had greater risk of death. CMV reactivation at any level relevantly prolonged the hospital stay. CMV reactivation with high viremia load and resistant/recurrent CMV infections lead to a significant decrease in OS in children with nonmalignant disorders treated with HSCT. Our data proves there is an urgent need to introduce an effective anti-CMV prophylaxis in this cohort of patients.

A novel cuproptosis-related gene signature for predicting prognosis in cervical cancer.

Purpose: Cuproptosis, a form of copper-induced cell death, can be a promising therapeutic target for refractory cancers. Hence, we conducted this research to explore the association between cuproptosis and prognosis in cervical cancer (CC). Methods: For constructing a prognostic signature based on cuproptosis-related genes from TCGA database, the least absolute shrinkage and selection operator Cox regression was utilized. The GSE44001 cohort was utilized for validation. Results: A total of nine cuproptosis-related genes showed distinct expression in CC and normal samples in TCGA-GTEx cohort. Two risk groups were identified based on a seven-gene signature. A significant decrease in overall survival was observed in the high-risk group (p < 0.001). The risk score (HR = 2.77, 95% CI = 1.58–4.86) was an autocephalous predictor with a better predictive ability than the clinical stage. Functional analysis indicated that immune activities were suppressed more in the high-risk group than in the low-risk group. A total of 11 candidate compounds targeting the signature were identified. Conclusion: A total of seven cuproptosis-related gene signatures were constructed to predict prognosis and propose a new therapeutic target for patients with CC.

Patterns of neck metastasis and occult neck disease during recurrent laryngeal cancer.

Numerous factors are considered to impact on the rate of complications during salvage total laryngectomy procedures. Neck dissection could be one of these factors. This study analysed the pattern of lymph node metastasis and rate of occult neck disease during salvage total laryngectomy as well as the impact of neck dissection on survival and complication rates. This was a retrospective analysis of a prospectively maintained laryngectomy database in two large tertiary teaching hospitals. The rate of occult neck disease was 11.1 per cent. Most cases with occult neck disease had rT4 disease. Patients with complications, advanced tumour stage and positive margins had a significant decrease in overall survival. Patients receiving elective neck dissection did not have any survival benefit. Positron emission tomography-computed tomography showed a very high specificity and negative predictive value. According to the low risk of occult neck disease when using contemporary imaging techniques as well as the lack of impact on survival, conservative management of the neck should be considered for crT1-T3 recurrence.

Minimally Invasive Surgery for Resectable Adrenocortical Carcinoma: A Nationwide Analysis

IntroductionThe utilization of minimally invasive surgery (MIS) for adrenocortical carcinoma (ACC) remains controversial due to concerns regarding the quality of surgical resection and subsequent oncologic risks. Current guidelines recommend open resections for all cases of suspected ACC independent of size; however, there has been increased adoption of MIS for ACC over time. We sought to determine whether the rise in the utilization of MIS is associated with worse survival outcomes for ACC. MethodsThe National Cancer Database was queried for patients with ACC who underwent surgical resection between 2010 and 2017. Patient selection, oncologic outcomes, and overall survival were compared among patients who received an MIS approach (laparoscopic or robotic) versus an open approach. ResultsA total of 1483 patients underwent ACC resection with 982 (66.2%) patients undergoing an open approach and 501 (33.8%) receiving an MIS operation. The overall utilization of MIS for ACC increased significantly after 2013 (37.7% versus 29.5%, P < 0.01). There was no difference in overall survival between MIS and open resections on univariable (log-rank P = 0.12) analysis. On multivariable analysis, survival was improved in MIS patients versus open resection (Hazard ratio: 0.83, 95% CI: [0.70-0.99]). Notably, survival remained comparable among patients who underwent resection for large ACCs (6-10 cm, log-rank P = 0.66) and giant ACCs (>10 cm, log-rank P = 0.24), irrespective of operative approach. ConclusionsOur findings suggest that in appropriately selected patients with ACC, MIS can be performed safely without a significant decrease in overall survival, independent of size. We recommend consideration of a minimally-invasive approach for adrenal masses despite size >6 cm.

Computed Tomography Assessment of Sarcopenic Myosteatosis for Predicting Overall Survival in Colorectal Carcinoma: Systematic Review.

As the US population ages, cancer incidence and prevalence are projected to increase. In the last decade, there has been an increased interest in the opportunistic use of computed tomography (CT) scan data to predict cancer prognosis and inform treatment based on body composition measures, especially muscle measures for sarcopenia. This article aimed to perform a systematic review of current literature related to CT assessment of muscle attenuation values for myosteatosis in colorectal cancer (CRC) survival prediction. Initial broad search of CT and CRC yielded 4234 results. A more focused search strategy narrowed this to 129 research papers, and 13 articles met the final inclusion criteria. Twelve of 13 studies found a statistically significant decrease in overall survival according to Hounsfield unit (HU)-based sarcopenia, with hazard ratios ranging from 1.36 to 2.94 (mean, 1.78). However, the specific criteria used to define myosteatosis by CT varied widely, with attenuation thresholds ranging from 22.5 to 47.3 HU, often further subdivided by sex and/or body mass index. Current evidence suggests that a strong association between CT-based muscle attenuation values for myosteatosis assessment correlates with overall survival in CRC. However, more research is needed to verify these findings and determine appropriate threshold values for more diverse patient populations. Because CRC patients are staged and followed by CT, the opportunity exists for routine objective myosteatosis assessment in the clinical setting.

Prognostic assessment of tumor markers in lung carcinomas.

Serum tumor markers are molecules that are secreted by tumor cells and may be present in small amounts in the serum of healthy individuals. Their role as prognostic factors in lung cancer remains controversial. To assess the prognostic role of CEA, CA 19-9, CA 15-3, and CA 125 in non-squamous non-small cell lung cancer. A total of 112 patients with non-squamous non-small cell lung cancer from two Oncology Centers were retrospectively analyzed. Tumor marker levels were measured prior to treatment. Data regarding clinical characteristics and overall survival were collected. Median overall survival of all patients was 15.97 months. Pre-treatment elevations of CA 125 and CA 15-3 were associated with shorter overall survival (p=0.004 and p=0.014, respectively). Single CEA and CA 19-9 elevations were not associated with a worse prognosis. Patients with two or more elevated markers had a statistically significant decrease in overall survival (p=0.008). In the multivariate analysis, smoking status and number of positive tumor markers at diagnosis were independently associated with a worse prognosis. High pre-treatment levels of tumor markers were correlated with decreased survival in patients with non-squamous non-small cell lung cancer.

Association between Timing and Duration of Adjuvant Chemotherapy and Colorectal Cancer Survival in Korea, 2011-2014: A Nationwide Study based on the Health Insurance Review and Assessment Service Database.

Background: Population-based analyses of the treatment outcomes of colorectal cancer (CRC) in Asian countries are limited. Therefore, we conducted a nationwide study to assess the relationship between the timing and duration of adjuvant chemotherapy (AC) and survival in patients with CRC in South Korea.Methods: Data on AC from the Health Insurance Review and Assessment Service Database (HIRA) were analyzed, and the survival of patients who underwent curative-intent surgical resection for CRC between 2011 and 2014 was investigated.Results: From the HIRA data, 45,992 patients with stage II-III CRC were identified. Chemotherapy regimens were administered as follows: 10,640 (23.3%) received 5-fluorouracil and leucovorin/capecitabine (FL/CAP), 13,083 (28.7%) received FL/CAP plus oxaliplatin (FOLFOX/CAPOX), 299 (0.7%) received uracil and tegafur/doxifluridine (UFT/D), and 21,570 (47.3%) underwent surgery alone. Patients who did not receive AC had worse survival than those who received AC in both the colon and rectum groups (HR, 1.96, 95% CI, 1.85-2.07 and HR, 2.18, 95% CI, 2.01-2.37, respectively). Regarding patients with stage II-III CRC, AC initiation ≥ 2 months after surgery was associated with a significant decrease in overall survival (OS) (FL/CAP: HR, 1.82; 95% CI, 1.53-2.17 and FOLFOX/CAPOX: HR, 2.92; 95% CI, 2.47-3.45); however, the effects of UFT/D regimens were not statistically significant. For patients with stage II-III colon cancer, AC <3 months had lower OS (FL/CAP: HR, 3.72, 95% CI, 2.80-4.94; FOLFOX/CAPOX: HR, 2.15, 95% CI, 1.87-2.47; and UFT/D: HR, 1.74, 95% CI, 0.56-5.41). In terms of patients with stage II-III rectal cancer, AC <3 months, regardless of chemotherapy regimens, had a significant lower survival (FL/CAP: HR, 1.91, 95% CI, 1.66-2.20; FOLFOX/CAPOX: HR, 2.20, 95% CI, 1.75-2.77; and UFT/D: HR, 3.71, 95% CI, 1.45-9.44).Conclusions: Postoperative time to initiation and duration of AC were associated with survival. Based on our results, initiating AC within 2 months after surgery and administering AC for >3 months can potentially have an OS benefit in patients with stage II-III CRC.

Comparative analysis results of surgical treatment, chemoradiotherapy and chemotherapy with assessment of prognostic factors in cervical esophageal cancer

Aim. To analyze the results of treatment and prognostic factors of survival in patients with cervical esophageal cancer (CEC) who received surgical treatment, chemoradiation therapy and chemotherapy.&#x0D; Materials and methods. The retrospective study included patients with a verified diagnosis of CEC treated at the Petrov National Medicine Research Center of Oncology from 2009 to 2018 and divided into three treatment groups: surgical treatment, chemoradiotherapy and chemotherapy. The endpoints of the study were overall survival (OS) and relapse-free survival (RFS).&#x0D; Results. Ninety-seven patients were included in the study: 48 in the surgical group, 30 in the chemoradiotherapy group and 17 patients in the chemotherapeutic treatment group. The average age of patients was 59.210.4 years. The median OS in the surgical group was 39.1 months, in the chemoradiotherapy group 23.9 months and 8.9 months in the chemotherapy group; the overall 3-year survival rate was 51.0% (95% CI 36.471.7), 44.9% (95% CI 26.974.9) and 26.0% (95% CI 9.968.2), respectively. The overall 5-year survival rate for the surgical group and the chemoradiotherapy group was 40.0% (95% CI 25.862.0), and 44.9% (95% CI 26.974.9), respectively. The presence of coronary heart disease is associated with a significant decrease in OS. The median disease-free survival in the surgical group was 19 months, in the chemoradiotherapy group 11.5 months and 3.4 months in the chemotherapy group; the relapse-free 3-year survival rates were 44.1% (95% CI 30.264.4), 25.0% (95% CI 11.753.4) and 14.3% (95% CI 4.051.5), respectively. The relapse-free 5-year survival rate for the surgical treatment group and the chemoradiotherapy group was 34.6% (95% CI 21.655.3), and 25.0% (95% CI 11.753.4). The presence of peptic ulcer disease was statistically significantly associated with higher overall and RFS regardless of the treatment received.&#x0D; Conclusion. In our study, surgical treatment of the CEC showed better overall and RFS rates compared with chemoradiotherapy. The presence of coronary heart disease and peptic ulcer disease are prognostic factors for overall and RFS.

Siglec-15 promotes progression of clear renal cell carcinoma.

Siglec-15 promotes progression of clear renal cell carcinoma.

OS03.4.A Irradiation of the subventricular and subgranular zone and overall survival in high-grade glioma patients

Abstract BACKGROUND Previous research has shown that neural stem cells (NSCs) in the subventricular zone (SVZ) may support the growth of glioma by recruiting new cells to the tumor. NSCs are located in the SVZ as well as in the subgranular zone (SGZ) of the hippocampus, the two neurogenic niches of the brain. This might indicate that irradiation of the SVZ and SGZ, and thereby damaging NSCs, reduces tumor growth and improves overall survival (OS). However, irradiation may also inhibit the repair capacity of healthy brain tissue by these neurogenic niches. Therefore, we investigated the effects of SVZ and SGZ irradiation dose on OS, in a cohort of high-grade glioma patients. MATERIAL AND METHODS We have retrospectively selected 221 patients (2014–2020) with WHO grade III and IV gliomas that underwent radiotherapy. Next to clinical baseline characteristics, T1 weighted MRI- and CT-images were collected. The SVZ and SGZ regions on the individual T1 images were delineated via non-linear registration of brain atlases. SVZ labels were created in 0.5mm isotropic MNI T1 and T2 templates, while SGZ atlas labels were available via the Hippocampus and Subfields CoBrA atlas. Next, the mean dose from the acquired SVZ and SGZ labels were extracted. The relationship between SVZ doses, SGZ doses and OS were examined using the Cox proportional hazards model and the Kaplan-Meier method (using the Log Rank test for significance). RESULTS For the mean dose in the SVZ, the hazard ratio (HR) was 1.024 per Gy (P = 0.002, [95% confidence interval, 1.009–1.040]) and the mean SGZ dose had a HR of 1.021 per Gy (P&amp;lt; 0.001, [95% confidence interval, 1.012–1.031]). These results were then corrected for the following covariates: sex, age, total intracranial volume and extent of surgery. This resulted in a HR of 1.031 per Gy (P = 0,001, [95% confidence interval, 1.014–1.050]) for the mean SVZ dose, and a HR of 1.025 per Gy (P&amp;lt; 0.001, [95% confidence interval, 1.015–1.036]) for the mean SGZ dose. Patients whose SVZ received greater than the median SVZ dose (= 31.3 Gy) showed a significant decrease in OS compared to patients who received less than the median dose (10.7 months vs 13.5 months median OS, P = 0.001). Patients whose SGZ received greater than the median SGZ dose (= 31.9) showed a significant decrease in OS compared to patients who received less than the median dose (10.7 months vs 15.1 months median OS, P&amp;lt; 0.001). CONCLUSION Here, we present a large cohort of high-grade glioma patients, in which we show a statistically significant decrease in overall survival with increasing radiation dose on the SGZ and SVZ. This correlation suggests that both neurogenic niches might need to be spared during radiotherapy treatment to improve overall survival even in high-grade glioma patients. Modern radiotherapy planning and delivery options are available to implement this.