Risk Factor For Worse Survival Research Articles

Initial balloon versus surgical valvuloplasty in children with isolated congenital aortic stenosis: Influence on timing of aortic valve replacement

ObjectiveTo evaluate the influence of initial intervention on the long-term outcomes in congenital aortic stenosis. MethodsTwo hundred forty-three children underwent initial intervention between 1997 and 2022, by surgical valvuloplasty in 92 (32% neonates, 36% infants) and balloon valvuloplasty in 151 (27% neonates, 30% infants). Twenty-eight patients (11.5%) had associated mitral valve stenosis. Competing risk analysis for death, alive after initial intervention, or alive after aortic valve replacement (AVR) was performed and factors influencing survival or AVR examined. ResultsThere were 9 early deaths (3.7%). During a median follow-up of 13.5 years (range, 1.5-26.7), 98 patients had reintervention on the aortic valve (40.3%), whereas 145 had AVR (59.6%) at a median age of 14.0 years (interquartile range, 9.0-17.0), which was by Ross procedure in 130 (89.6%). Of the 12 late deaths, 3 were perioperative and 9 occurred as outpatients. There were no perioperative or late deaths after AVR. AVR occurred earlier in patients who had initial balloon (12.0 years [interquartile range, 5.0-14.5]) rather than surgical (18.5 years [interquartile range, 15.5-21.5]) valvuloplasty (P < .05). Actuarial survival in the cohort was 91.3% at 25 years, with no difference between the 2 initial interventions. Critical aortic stenosis, mitral stenosis, and initial intervention as a neonate were independent risk factors for worse survival. ConclusionsWe demonstrate excellent early and late survival in patients with congenital aortic stenosis after initial balloon or surgical valvuloplasty. Whilst children who had balloon valvuloplasty had AVR earlier than those who had initial surgical valvuloplasty, patient factors had a greater influence on survival than choice of initial intervention.

Hispanic/Latino Ethnicity is an Independent Predictor of Worse Survival for Gastric Cancer in a Multicenter Safety-Net Patient Population.

Various population-based studies have shown Hispanic/Latino ethnicity is a risk factor for worse survival in patients with gastric cancer linked to disparate access to care. We aimed to address whether Hispanic patients treated within safety-net hospital systems continue to experience this survival deficit compared to non-Hispanic patients. We performed a retrospective cohort study comparing survival between Hispanic and non-Hispanic patients diagnosed with gastric adenocarcinoma between January 1, 2016 to December 31, 2020 within Los Angeles County's safety-net hospital system. Gastric cancer-specific survival was compared between the two cohorts using the Kaplan-Meier estimate and Cox proportional-hazards regression model. 448 patients who received care from five medical centers were included. 348 (77.7%) patients self-identified as Hispanic and 100 (22.3%) as non-Hispanic. Mean follow-up time was 2.0 years (median 0.91 years, IQR, 0.34-2.5 years). Hispanic patients were found to be diagnosed at a younger age (55.6 vs 60.7 years, p <0.01), demonstrate higher state area deprivation index (6.4 vs 5.0, p <0.01), and present with metastatic disease (59.8% vs 45%, p =0.04). After adjusting social and oncologic variables, Hispanic ethnicity remained an independent risk factor for worse survival (HR 1.56, [95% CI 1.06-2.28], p = 0.02). Hispanic patients treated within a large, multi-center safety-net hospital system experience worse survival compared to non-Hispanic patients. This suggests ethnic disparities exist within safety-net hospital systems, independent of known clinicopathologic factors. Improving outcomes for Hispanic patients with gastric cancer requires future efforts aimed at defining and addressing these unidentified barriers to care.

Surgical management of giant cell arteritis of the proximal aorta

ObjectiveGiant cell arteritis (GCA) may present as proximal aortic pathology requiring surgical intervention. We present our experience with surgical management of GCA in patients presenting with proximal aortic disease. MethodsFrom January 1993 to May 2020, 184 adult patients were diagnosed with GCA on histopathology after undergoing cardiac surgery. Survival was estimated with Kaplan-Meier method. Reoperation rates were estimated with cumulative incidence accounting for competing risks of death. ResultsThe most common indication for surgery was ascending aortic aneurysm (n = 179, 97.3%). Stroke occurred in 6 (3.3%), pneumonia in 8 (4.4%), and dialysis in 3 (1.6%) patients. Multivariable analysis found advanced age (hazard ratio [HR], 1.054; 95% confidence interval [CI], 1.026-1.082, P < .001), recent heart failure (HR, 1.890; 95% CI, 1.016-3.516, P = .04), peripheral vascular disease (HR, 2.229; 95% CI, 1.458-3.624, P < .001), and cerebrovascular disease (HR, 1.762; 95% CI, 1.035-3.000, P = .03) as predictors of late mortality. Median follow-up was 13.7 years, and 30-day mortality was 1.5%. Nineteen patients underwent 24 aortic reinterventions including aortic arch reconstruction (n = 4), descending thoracic aorta aneurysm repair (n = 8), thoracoabdominal aortic aneurysm repair (n = 11), and pseudoaneurysm repair (n = 1). Rate of reintervention on the aorta was 3.9% (95% CI, 1.9%-8.1%), 7.1% (95% CI, 4.1%-12.3%), 12.8% (95% CI, 8.3%-19.6%), and 12.8% (95% CI, 8.3%-19.6%) at 1, 5, 10, and 15 years, respectively. ConclusionsSurgery in patients with GCA can be performed with acceptable early and late outcomes. Advancing age, heart failure, peripheral vascular disease, and cerebrovascular disease are risk factors for worse survival. Postoperative surveillance is important as need for aortic reintervention is not uncommon.

Prognostic significance of the aspartate aminotransferase to lymphocyte ratio index in patients with acute myocardial infarction.

This study aimed to investigate the clinical value and prognostic significance of the alanine aspartate aminotransferase-to-lymphocyte ratio index (ALRI) in patients diagnosed with acute myocardial infarction (AMI). Clinical indices of patients with AMI were collected from the Medical Information Mark for Intensive Care (MIMIC) III database and Wuhan Sixth Hospital. Cox regression analysis was used to explore whether ALRI was a risk factor for a worse prognosis in patients with AMI, and a nomogram including ALRI was created to estimate its predictive performance for 28-day mortality. Based on clinical data from the MIMIC-III database, we found that a high ALRI was closely associated with a variety of clinical parameters. It was an important risk factor for 28-day survival in patients with AMI (HR = 5.816). ALRI had a high predictive power for worse 28-day survival in patients with AMI(area under the curve [AUC] = 0.754). Additionally, we used clinical data from the Wuhan Sixth Hospital to verify the predictive power of ALRI in patients with AMI, and a high level of ALRI remained an independent risk factor for worse survival in patients with AMI (HR = 4.969). The AMI nomogram, including ALRI, displayed a good predictive performance for 28-day mortality in both the MIMIC-III (AUC = 0.826) and Wuhan Sixth Hospital cohorts (AUC = 0.795). The ALRI is closely related to the survival outcomes of patients with newly diagnosed AMI, indicating that it could serve as a novel biomarker for risk stratification such patients.

An epidemiological and clinicopathological study of type 1 vs. type 2 morphological subtypes of papillary renal cell carcinoma– results from a nation-wide study covering 50 years in Iceland

IntroductionPapillary renal cell carcinoma (pRCC) is the second most common histology of renal cell carcinoma (RCC), accounting for 10–15% of cases. Traditionally, pRCC is divided into type 1 and type 2, although this division is currently debated as a prognostic factor of survival. Our aim was to investigate the epidemiology and survival of the pRCC subtypes in a whole nation cohort of patients during a 50-year period.Materials and methodsA Population based retrospective study including consecutive cases of RCC in Iceland from 1971–2020. Comparisons were made between histological classifications of RCC, with emphasis on pRCC subtypes (type 1 vs. 2) for outcome estimation. Changes in RCC incidence were analyzed in 5-year intervals after age standardization. The Kaplan–Meier method and Cox regression were used for outcome analysis.ResultsA total of 1.725 cases were identified, with 74.4%, 2.1% and 9.2% having clear cell (ccRCC), chromophobe (chRCC), and pRCC, respectively. The age standardized incidence (ASI) of pRCC was 1.97/100.000 for males and 0.5/100.000 for females, and the proportion of pRCC increased from 3.7% to 11.5% between the first and last intervals of the study (p < 0.001). Age standardized cancer specific mortality (ASCSM) of pRCC was 0.6/100.000 and 0.19/100.000 for males and females, respectively. The annual average increase in ASI was 3.6% for type 1 pRCC, but the ASI for type 2 pRCC and ASCSM for both subtypes did not change significantly. Male to female ratio was 4.4 for type 1 pRCC and 2.3 for type 2. The average tumor size for type 1 and 2 was 58.8 and 73.7 mm, respectively. Metastasis at diagnosis was found in 8.7% in the type 1 pRCC, compared to 30.0% of patients with type 2 pRCC (p < 0.001). Estimated 5-year cancer-specific survival (CSS) were 94.4%, 80.7%, and 69.3% for chRCC, pRCC and ccRCC, respectively (p < 0.001). For the pRCC subtypes, type 1 was associated with better 5-year CSS than type 2 (86.3% vs. 66.0%, p < 0.001), although this difference was not significant after adjusting for cancer stage and grading.ConclusionspRCC histology was slightly less common in Iceland than in other countries. Males are more than three times more likely to be diagnosed with pRCC, compared to other RCC histologies. The subtype of pRCC was not found to be an independent risk factor for worse survival, and as suggested by the most recent WHO Classification of Urinary Tumors, grade and TNM-stage seem to be the most important factors for estimation of survival for pRCC patients.

O VALOR DO ÍNDICE NUTRICIONAL PROGNÓSTICO PRÉ-OPERATÓRIO NO CÂNCER GÁSTRICO APÓS RESSECÇÃO CURATIVA

ABSTRACT BACKGROUND: Predicting short- and long-term outcomes of oncological therapies is crucial for developing effective treatment strategies. Malnutrition and the host immune status significantly affect outcomes in major surgeries. AIMS: To assess the value of preoperative prognostic nutritional index (PNI) in predicting outcomes in gastric cancer patients. METHODS: A retrospective cohort analysis was conducted on patients undergoing curative-intent surgery for gastric adenocarcinoma between 2009 and 2020. PNI was calculated as follows: PNI=(10 x albumin [g/dL])+(0.005 x lymphocytes [nº/mm3]). The optimal cutoff value was determined by the receiver operating characteristic curve (PNI cutoff=52), and patients were grouped into low and high PNI. RESULTS: Of the 529 patients included, 315 (59.5%) were classified as a low-PNI group (PNI&lt;52) and 214 (40.5%) as a high-PNI group (PNI≥52). Older age (p=0.050), male sex (p=0.003), American Society of Anesthesiologists score (ASA) III/IV (p=0.001), lower hemoglobin level (p&lt;0.001), lower body mass index (p=0.001), higher neutrophil-lymphocyte ratio (p&lt;0.001), D1 lymphadenectomy, advanced pT stage, pN+ and more advanced pTNM stage were related to low-PNI patient. Furthermore, 30-day (1.4 vs. 4.8%; p=0.036) and 90-day (3.3 vs. 10.5%; p=0.002) mortality rates were higher in low-PNI compared to high-PNI group. Disease-free and overall survival were worse in low-PNI patients compared to high-PNI (p&lt;0.001 for both). ASA III/IV score, low-PNI, pT3/T4, and pN+ were independent risk factors for worse survival. CONCLUSIONS: Preoperative PNI can predict short- and long-term outcomes of patients with gastric cancer after curative gastrectomy. Low PNI is an independent factor related to worse disease-free and overall survival.

Copy-number-gain of telomerase reverse transcriptase (hTERT) is associated with an unfavorable prognosis in esophageal adenocarcinoma

Esophageal adenocarcinoma exhibits one of the highest mortality rates among all cancer entities. Multimodal therapy strategies have improved patients’ survival significantly. However, patients in early stages are currently limited to receiving only local therapies, even though some patients within this group showcase short survival periods. Until now, there has been no widely established clinically used biomarker to detect these high-risk patients. Telomerase reverse transcriptase (TERT), a gene encoding a crucial subunit of the telomerase enzyme, plays a significant role in establishing cancer cell immortality and is under suspicion for its potential contribution to tumor progression. Therefore, we aimed to evaluate the clinical relevance of the TERT amplification status. We included 643 patients with esophageal adenocarcinoma, who underwent Ivor-Lewis esophagectomy at the University Hospital of Cologne. The TERT amplification status was characterized using fluorescence in situ hybridization. Clinicopathological values and patients’ overall survival were compared between patients with and without TERT amplification. Further sub-cohort analyses were conducted for patients with pT1N0-3 tumor stage. Eighty-One patients (12.6%) exhibited TERT amplification. Patients with amplified TERT showed significantly worse overall survival (median OS: 22.6 vs. 36.8 months, p = 0.009). Interestingly, TERT amplification could be characterized as an independent risk factor for worse overall survival in multivariate analysis in patients with pT1N0-3 tumor stage (HR = 2.440, 95% CI 1.095–5.440, p = 0.029). In this study, we describe the TERT amplification status as an independent risk factor for worse survival in patients diagnosed with esophageal adenocarcinoma at pT1N0-3 tumor stage, encompassing cases involving tumor infiltration of the lamina propria, muscularis mucosae, and/or submucosa. Based on our findings, we put forth the proposition that evaluating the TERT amplification status may serve as a valuable tool in identifying a specific subgroup of patients, namely those with TERT amplification and pT1N0-3 tumor-stage esophageal adenocarcinoma. The patients of this subgroup could potentially benefit from enhanced follow-up protocols, more aggressive treatment approaches, or possible targeted TERT inhibition therapies, all aimed at improving their overall clinical outcomes.

Immunosuppression is a risk factor for worse survival and disease‐specific death in cutaneous squamous cell carcinoma

AbstractBackgroundPrevious literature on cutaneous squamous cell carcinoma (cSCC) suggests that the incidence, rate of metastasis, and tumour severity of cSCC are higher in immunosuppressed patients than in immunocompetent patients. However, current literature lacks an extensive comparison of cSCC clinical characteristics and outcomes in immunosuppressed patients.ObjectivesWe compared cSCC tumour characteristics and disease‐related outcomes to help guide the clinical management of immunosuppressed patients.MethodsWe conducted a retrospective review of histopathologic and clinical data from 935 cSCC cases (19.5% immunosuppressed) from the Mayo Clinic.ResultsImmunosuppression was associated with younger age (69.3 vs. 74.8 years old, p &lt; 0.0001), male gender (78.6% vs. 67.2%, p = 0.003), and higher grade cSCC tumour characterized by moderate or poor differentiation (25.7% vs. 15.8%, p = 0.009; 9.2% vs. 7.2%, p = 0.009, respectively). No significant differences were found in other tumour characteristics, including clinical tumour dimension, Brigham and Women's Hospital tumour staging or cumulative risk of metastasis and recurrence. Immunosuppressed patients had an increased risk of disease‐specific death on univariate analysis (hazard ratio [HR] [95% confidence interval, CI] 2.05 [1.13–3.74], p = 0.0128). Overall survival in the immunosuppressed population was worse (adjusted HR [95% CI] 1.83 [1.42–2.35], p &lt; 0.001) and, notably, solid organ transplant recipients had the lowest overall survival when stratifying immunosuppressed patients by immunosuppression type (HR [95% CI] 1.62 [1.17–2.24], p &lt; 0.0001).ConclusionsIn our study, immunosuppression status was predictive of poor differentiation of tumours and a reduction in overall and cSCC‐specific survival. Current staging systems for cSCC do not include immunosuppression as a risk factor and incorporating immune status may be beneficial for accurate risk stratification.

Low Skeletal Muscle as a Risk Factor for Worse Survival in Nonmetastatic Renal Cell Carcinoma with Venous Tumor Thrombus.

Renal cell carcinoma (RCC) with tumor thrombosis often requires nephrectomy and tumor thrombectomy. As an extensive and potentially morbid operation, patient preoperative functional reserve and body composition is an important consideration. Sarcopenia is a risk factor for increased postoperative complications, systemic therapy toxicity, and death solid organ tumors, including RCC. The influence of sarcopenia in RCC patients with tumor thrombus is not well defined. This study evaluates the prognostic ability of sarcopenia regarding surgical outcomes and complications in patients undergoing surgery for RCC with tumor thrombus. We retrospectively analyzed patients with nonmetastatic RCC and tumor thrombus undergoing radical nephrectomy and tumor thrombectomy. Skeletal muscle index (SMI; cm2/m2) was measured on preoperative CT/MRI. Sarcopenia was defined using body mass index- and sex-stratified thresholds optimally fit via a receiver-operating characteristic analysis for survival. Associations between preoperative sarcopenia and overall (OS), cancer-specific survival (CSS), and 90-day major complications were determined using multivariable analysis. 115 patients were analyzed, with median (IQR) age and body mass index of 69 (56-72) and 28.6 kg/m2 (23.6-32.9), respectively. 96 (83.4%) of the cohort had ccRCC. Sarcopenia was associated with shorter median OS (P=.0017) and CSS (P = .0019) in Kaplan-Meier analysis. In multivariable analysis, preoperative sarcopenia was prognostic of shorter OS (HR = 3.38, 95% confidence interval [CI] 1.61-7.09) and CSS (HR=5.15, 95% CI 1.46-18.18). Notably, 1 unit increases in SMI were associated with improved OS (HR = 0.97, 95% CI 0.94-0.999) but not CSS (HR=0.95, 95% CI 0.90-1.01). No significant relationship between preoperative sarcopenia and 90-day major surgical complications was observed in this cohort (HR=2.04, 95% CI 0.65-6.42). Preoperative sarcopenia was associated with decreased OS and CSS in patients surgically managed for nonmetastatic RCC and VTT, however, was not predictive of 90-day major postoperative complications. Body composition analysis has prognostic utility for patients with nonmetastatic RCC and venous tumor thrombus undergoing surgery.

Specific Subtypes of Carcinoma-Associated Fibroblasts Are Correlated with Worse Survival in Resectable Pancreatic Ductal Adenocarcinoma

The pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancer entities. Effective therapy options are still lacking. The tumor microenvironment possibly bears further treatment possibilities. This study aimed to describe the expression patterns of four established carcinoma-associated fibroblast (CAFs) markers and their correlation in PDAC tissue samples. This project included 321 patients with PDAC who underwent surgery with a curative intent in one of the PANCALYZE study centers. Immunohistochemical stainings for FAP, PDGFR, periostin, and SMA were performed. The expression patterns of each marker were divided into low- and high-expressing CAFs and correlated with patients' survival. Tumors showing SMAhigh-, PeriostinhighSMAhigh-, or PeriostinhighSMAlowPDGFRlowFAPhigh-positive CAFs demonstrated significantly worse survival. Additionally, a high expression of SMA in PDAC tissue samples was shown to be an independent risk factor for worse survival. This project identified three subgroups of PDAC with different expression patterns of CAF markers which showed significantly worse survival. This could be the base for the further characterization of the fibroblast subgroups in PDAC and contribute to the development of new targeted therapy options against CAFs.

Inflammation and Fibrosis in Patients with Non-Cirrhotic Hepatitis B Virus-Associated Hepatocellular Carcinoma: Impact on Prognosis after Hepatectomy and Mechanisms Involved.

Background: We investigated whether the degree of inflammation and fibrosis in para-carcinoma tissue can predict prognosis of patients with non-cirrhotic hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) after hepatectomy. We also explored the mechanisms through which inflammation and fibrosis might affect prognosis. Methods: Clinicopathological data were retrospectively analyzed from 293 patients with non-cirrhotic HBV-associated HCC who were treated at our institution by curative resection from 2012 to 2017. Based on the Scheuer score system, patients were classified into those showing mild or moderate-to-severe inflammation and fibrosis. Rates of overall and recurrence-free survival were compared between the groups using Kaplan-Meier curves, and survival predictors were identified using Cox regression. Using tumor and para-tumor tissues from independent samples of patients with non-cirrhotic HBV-associated HCC who were treated at our institution by curative resection from 2018 to 2019, we performed next-generation sequencing and time-of-flight cytometry (CyTOF) to examine the influence of inflammation and fibrosis on gene expression and immune cell infiltration. Results: In the analysis of the 293 patients, those with mild inflammation and fibrosis showed significantly better overall and recurrence-free survival than those with moderate-to-severe inflammation and fibrosis. Multivariate Cox regression confirmed that moderate-to-severe inflammation and fibrosis were independent risk factors for worse survival. RNA sequencing and CyTOF showed that more severe inflammation and fibrosis were associated with stronger invasion and migration by hepatocytes. In cancerous tissues, the biological processes of cell proliferation were upregulated, the signaling pathways promoting tumor growth were activated, the proportion of Th17 cells promoting tumor progression was increased, and CD8+ T cells expressed higher levels of PD-L1. In para-cancerous tissues, biological processes of immune response and cell chemotaxis were downregulated, and the proportion of tumor-killing immune cells was decreased. Conclusion: Worse inflammation and fibrosis in non-cirrhotic HBV-associated HCC is associated with worse prognosis, which may reflect more aggressive tumor behavior and an immunosuppressed, pro-metastatic tumor microenvironment.

Risk Factors Associated With Recurrence and Death in Patients With Tall Cell Papillary Thyroid Cancer

Tall cell morphology (TCM) is a rare and aggressive variant of papillary thyroid carcinoma (PTC) that has been associated with poor outcomes; however, the risk factors for worse survival are not well characterized. To identify prognostic factors associated with cancer recurrence and death in patients with PTC-TCM. All patients treated for PTC-TCM at a single tertiary-level academic health care institution from January 1, 1997, through July 31, 2018, were included. Tall cell variant (TCV) was defined as PTC with TCM of 30% or more; and tall cell features (TCF) was defined as PTC with TCM of less than 30%. Patients with other coexisting histologic findings and/or nonsurgical management were excluded. Clinicopathologic features associated with worse outcomes were identified using Kaplan-Meier and Cox proportional-hazards model. Data were analyzed from March 1, 2018, to August 15, 2018. Locoregional recurrence-free survival (LRRFS), distant recurrence-free survival (DRFS), and overall survival (OS) after surgery. A total of 365 patients (median [range] age, 51.8 [15.9-91.6] years; 242 [66.3%] female) with PTC-TCM (TCV, 32%; TCF, 68%) were evaluable. Total thyroidectomy was performed in 336 (92%) patients; 19 (5.2%) received radiotherapy; and 15 (4.1%) received radioactive iodine. Clinical features were pT3 or T4, 65%; node-positive, 53%; and positive surgical margins, 24%. LRRFS at 1-, 3-, 5-, and 10-year was 95%, 87%, 82%, and 73%, respectively. On multivariable analysis, male sex and age were not independent predictors of inferior 5-year LRRFS, whereas positive surgical margins (HR, 3.5; 95% CI, 2.0-6.3), positive lymph nodes (HR, 2.8; 95% CI, 1.4-5.8), and primary tumor size of 3 cm or more (HR, 3.3; 95% CI, 1.4-7.8) were strongly associated with worse LRRFS. Age 55 years or older (HR, 3.2; 95% CI, 1.5-7.0), male sex (HR 4.5; 95% CI, 2.1-10.0), positive surgical margins (HR, 2.7; 95% CI, 1.2-6.0), nodal positivity (HR, 3.1; 95% CI, 1.3-7.7), tumor diameter of 1.5 cm or more (HR, 20.6; 95% CI, 2.8-152.1), and TCV vs TCF (HR, 3.1; 95% CI, 1.5-6.7) were associated with worse DRFS. Male sex (HR, 3.1; 95% 1.4-6.8) and tumor diameter of 1.5 cm or more (HR, 2.8; 95% CI, 1.0-7.4) were associated with worse OS. A findings-based nomogram was constructed to predict 10-year LRRFS (C index, 0.8). This retrospective cohort study found that in patients with PTC-TCM, positive surgical margins, node positive disease, and tumor size of 3 cm or more were risk factors for worse LRRFS. Intensified locoregional therapy, including adjuvant radiation, may be considered for treating these patients.

Abstract PD4-08: Breast cancer clinical subtypes in brain metastases patients from a prospective registry of advanced breast cancer, GEICAM/2014-03 (RegistEM)

Abstract Background: The incidence of breast cancer brain metastases (BCBM) is estimated to be around 5-15%, but necropsies show a much higher incidence (30-50%). Frecuency of BCBM has gradually increase likely as a result from advances in systemic treatment that allow more patients to live long enough to develop BCBM. In general, outcome for patients with BCBM is poor, with 1-year survival of approximately 20%, but some patient and tumor characteristics are associated with improved behaviour. The RegistEM study is a non-interventional cohort study providing prospective data from around 1,867 advanced breast cancer (ABC) patients (pts.). This study offers a unique opportunity to assess the incidence, potential risk factors, and outcomes for patients with BCBM. Methods: In this analysis (cut-off date 26/April/2021 and ongoing database), we describe the features of 218 pts. with BCBM included in the RegistEM study, which represent the 11% of current total number of pts. in the study. BC clinical subtypes are based on the most recent tumor lesion (distant metastasis or primary BC). The most frequent therapies by BC subtypes are detailed in the table below. At the database cut-off date, death had been reported in 74% pts with BCBM. Results: All pts. were female, 97% caucasian, and at ABC diagnosis, 66% were postmenopausal and their median age was 55 years. The subtype distribution was: Luminal (ER+/HER2-) 41%, HER2+ 35%, Triple Negative (TN) 19%, unknown 5%. Eighty pts. (37%) had BM at diagnosis of ABC, and in 17 of them BM was the only site of relapse. The median time from diagnosis of primary BC to BM at initial diagnosis of ABC was 34 months (mo), being shorter for TN (18 mo). In patients without BM at diagnosis of ABC, the median time from ABC diagnosis to onset of BM for de novo metastatic disease was: Luminal 27 mo, HER2+ 28 mo, TN 10 mo; while for EBC disease was: Luminal 18 mo, HER2+ 14 mo, TN 10 mo. De novo metastatic BC was associated with longer time to BM appearance (HR:0.527, CI 95%: 0.358-0.776) while TN subtype with shorter time (HR:4.122, CI 95%: 2.318-7.329) compared to Luminal subtype. The median survival from the onset of BM, according to BC subtype was: Luminal 6 mo, HER2 11 mo and TN 4 mo. Risk factors for worse survival were: BM at ABC (HR:1.677, CI 95%:1.169-2.406) and TN subtype (HR:3.631, CI 95%: 2.353-5.603) compared to Luminal subtype. Conclusions: TN breast cancer is associated with a shorter time to brain metastases and poorer outcome than other breast cancer subtype. Patients with de novo metastatic BC develop metastases later than patients with metastatic recurrence after primary BC. New treatment approach to avoid the onset of brain metastases in patients with ABC warrants further research. Luminaln=90 (41%)HER2+n=77 (35%)Triple Negativen=41 (19%)HRHER2+-Any+–First BC diagnosis, nEBC (stages I-III)ULABC or de novo metastatic65. 2555. 2227. 14Only CNS metastases at ABC diagnosis584Number of line (L)1L2L3L1L2L3L1L2L3Ln877158745936352515Type of therapy, nET/BT26167443---ET239531----CT/BT/ET58-15-----CT/BT10924014211331CT/ET623------CT172635321222214BT1693811---Most frequent therapies by mechanism of action, nAI/CDK4/6i 20SERD 12CT single agent 12AI single agent 11CT + antiangiogenic 9CT single agent 24SERD +/- CDK4/6i 8AI + CDK4/6i 7CT + antiangiogenic 7CT single agent 27CT combination 8SERD +/- CDK4/6i 6CT + dual anti-HER2 blockade 46CT + anti-HER2 blockade single agent 7Anti-HER2 single agent 35CT + anti-HER2 blockade single agent 12CT + anti-HER2 blockade single agent 18Anti-HER2 blockade single agent 9CT combination 12CT + antiangiogenic 12CT single agent 10CT single agent 16CT combination 6CT + antiangiogenic 4CT single agent 9CT combination 5Median Treatment duration, months (range)7 (0-31)6 (0-41)4 (0-16)12 (0-43)5 (0-47)3 (0-17)5 (0-18)3 (0-7)2 (0-6)TTP in months, median (range)8 (2-35)--12 (3-46)--6 (2-19)--Death, n635139Abbreviations: HR=hormone receptor; HER2=human epidermal growth factor receptor 2; BC=breast cancer; EBC=early breast cancer; ULABC=unresectable locally advanced breast cancer; ET=endrocrine therapy; BT=biological therapy; CT=chemotherapy; TTP=time to progression; AI=aromatase inhibitor; SERD=selective estrogen receptor degrader; CDK4/6i=cyclin dependent kinases 4 and 6 inhibitor Citation Format: Sara López-Tarruella, Ángel Guerrero-Zotano, César A Rodríguez, Josefina Cruz, María Hernández, Encarna Adrover, Álvaro Rodríguez-Lescure, Catalina Falo, Purificación Martínez, Ana Miguel, Raquel Andrés, Silvia Antolín, J. Ignacio Chacón, Jose Luis Alonso Romero, Rafael Villanueva Vázquez, Ana Isabel Ballesteros García, María Galán Gramaje, Diego Malón Jiménez, Silvia Varela Ferreiro, Diana Moreno Muñoz, Ruth Campo, María José Escudero, Susana Bezares, Federico Rojo, Isabel Alvarez. Breast cancer clinical subtypes in brain metastases patients from a prospective registry of advanced breast cancer, GEICAM/2014-03 (RegistEM) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD4-08.

Vimentin immunoexpression and its prognostic activity in colon cancer among Caucasian patients.

IntroductionIt is generally accepted that colon cancer is the most commonly diagnosed gastrointestinal cancer and a major public health problem. As revealed by studies, the clinical outcomes of patients, especially those with lymph node-positive status, are still unsatisfactory.AimThe current study investigated the expression of vimentin protein in colon adenocarcinoma samples from proximal and distal parts of the colon to assess its prognostic significance by correlating its immunohistochemical expression with the clinicopathological variables and survival of Caucasian patients.Material and methodsTo investigate the clinicopathological and prognostic roles of vimentin expression, the immunohistochemical analysis was performed in colon cancer tumour samples and adjacent non- pathological mucosa. As revealed, the level of vimentin immunohistochemical reactivity correlated with the grade of the histological differentiation (H [2.97] = 37.949; p < 0.001).ResultsThe Kaplan-Meier survival analysis showed that the overall survival rate in the group of patients with low vimentin immunoreactivity was significantly greater than that for patients with a moderate or strong level of vimentin protein expression. Multivariate analysis demonstrated that the grade of tumour differentiation (HR = 2.150; 95% CI: 1.380–3.349, p = 0.001) and vimentin expression (HR = 3.901; 95% CI: 2.436–6.247, p < 0.001) were independent risk factors for worse survival.

The prognostic activity of transforming acidic coiled-coil 3 (TACC3) immunohistochemical expression in colon adenocarcinoma patients.

IntroductionColorectal cancer is most common in developed countries. Each year, more than one million people develop colon cancer, and nearly 70,000 people die from the disease. Although medicine has made great strides in the treatment of colorectal cancer, the prognosis of patients is still poor. It is difficult to find the main cause of colon cancer, so it is necessary to introduce new methods that will accurately diagnose the cause of this malignancy.Material and methodsParaffin-embedded colon adenocarcinoma samples (n = 97) were assessed immunohistochemically for TACC3 protein. Connections between TACC3 immunoexpression and clinicopathological factors, including the 5-year overall survival (OS), were evaluated.ResultsImmunohistochemical expression of TACC3 protein in colon adenocarcinoma samples and non-pathological samples of colon tissue was described as weak, moderate, or strong. As demonstrated, the level of the TACC3 immunohistochemical reactivity was not correlated with demographic factors including gender and age, and clinicopathological factors. The average survival time for all the patients was 36.8 months (95% CI: 33.134–40.536). A multivariate analysis demonstrated that the grade of tumour differentiation (HR = 2.740; 95% CI: 1.864–4.027, p < 0.001) and TACC3 immunoexpression in healthy tissues (HR = 1.700; 95% CI: 1.073–2.694) were independent risk factors for worse survival of patients.ConclusionsThe high level of TACC3 immunoexpression in cancerous tissue was not associated with malignancy-related clinicopathological factors and 5-year overall survival of patients.

Early implementation of a perioperative nutrition support pathway for patients undergoing esophagectomy for esophageal cancer.

BackgroundUnintentional weight loss and malnutrition are associated with poorer prognosis in patients with cancer. Risk of cancer‐associated malnutrition is highest among patients with esophageal cancer (EC) and has been repeatedly shown to be an independent risk factor for worse survival in these patients. Implementation of nutrition protocols may reduce postoperative weight loss and enhance recovery in these patients.MethodsWe retrospectively identified all patients who underwent Ivor Lewis esophagectomy for EC from January 2015 to August 2019 from a prospectively collected institutional database. Patients who underwent surgery after the implementation of this protocol (September 2017–August 2019) were compared with patients who underwent resection before protocol implementation (January 2015–July 2017). Patients undergoing surgery during the month of protocol initiation were excluded.ResultsOf the 404 patients included in our study, 217 were in the preprotocol group, and 187 were in the postprotocol group. Compared with the preprotocol group, there were significant reductions in length of hospital stay (p < 0.001), time to diet initiation (p < 0.001), time to feeding tube removal (p = 0.012), and postoperative weight loss (p = 0.002) in the postprotocol group. There was no significant difference in the incidence of postoperative complications, 30‐day readmission, or mortality rates between groups.ConclusionsResults of the present study suggest a standardized perioperative nutrition protocol may prevent unintentional weight loss and improve postoperative outcomes in patients with EC undergoing resection.

Clinicopathological Features and Outcomes of EBV Positive and Negative DLBCL: A Study from the Grupo De Estudio Latinoamericano De Linfoproliferativos (GELL)

Introduction: Studies conducted in the pre-rituximab era found EBV positive diffuse large B-cell lymphoma (EBV+ DLBCL) as a disctinct entity carrying a dismal prognosis when compared with EBV negative (EBV-) DLBCL cases. However, studies evaluating this disparity in the rituximab era are lacking. Therefore, we aim to investigate the clinicopathological features and outcomes patterns among EBV+ and EBV- DLBCL managed in the modern era.Methods: We retrospectively analyzed patients 18 years and older diagnosed with DLBCL between 2006 to 2020. Seven centers from the Grupo de Estudio Latinoamericano de Linfoproliferativos (GELL) participated in the study. Hematopathologists at each participating institution reviewed the pathological samples to confirm the diagnosis of EBV+ or EBV- DLBCL, not otherwise specified (NOS). EBV infection was confirmed with a positive EBER test ≥1%. The primary endpoint was overall survival (OS), defined as the time from the date of diagnosis until death from any cause or last follow up. The secondary endpoint was progression-free survival (PFS) defined as the time from diagnosis until death, progression, or last follow up. OS and PFS probabilities were computed with the Kaplan-Meier method and compared using the log-rank test. We used Cox regression analysis to evaluate the proportional hazard ratios (HRs) of each score for our study outcomes. Outcomes with a p-value <0.05 were considered statistically significant.Results: A total of 119 patients with EBV+ DLBCL, NOS and 122 patients with EBV- DLBCL, NOS were included in this analysis. The median age at diagnosis was 58 years (range 19-86 years) with an slight female (53%) predominance. Most cases (68%) had advanced stage (III/IV) at diagnosis. EBV+ DLBCL patients had higher-risk clinical features compared with EBV- DBCL: 34% presented ECOG performance status ≥2 (vs 18%, p=0.010), 45% had poor risk R-IPI score (vs 29%, p=0.03), 47% had high and high-intermediate risk NCCN IPI score (vs 40%, p=0.002). Germinal center B-cell was the most common phenotype in both groups (46% each); non-germinal center was more common in EBV+ (44%) than EBV- (34%). All patients received either R-CHOP (95%) or R-EPOCH (5%) as first-line treatment. The overall response rate was 91% for EBV- DLBCL (complete response, CR 81%) compared to 74% for EBV+ DLBCL (CR 65%, p=0.015). With a median follow-up of 60 months, the 5-year OS rates for EBV+ and EBV- DLBCL were 64% and 75% (p=0.062; Fig 1A), respectively; whereas the 5-year PFS rates for EBV+ and EBV- DLBCL were 53% and 68% (p=0.031; Fig 1B), respectively. In the univariate analysis, ECOG ≥2, extranodal involvement >1, elevated serum lactate dehydrogenase (LDH), and serum albumin <3.5 g/dL were statistically significant for OS (Table 1). On the other hand, EBV+ status, ECOG performance status ≥2, extranodal involvement >1, elevated serum LDH, and serum albumin <3.5 g/dL were significant predictors for PFS. In the multivariate analysis, no variable was statistically significant for OS or PFS (Table 1).Conclusions: In this large cohort of Latin American patients with EBV+ DLBCL, we found poor clinical features in EBV+ compared to EBV-DLBCL cases. Although shorter PFS was found in EBV+ DLBCL cases, in the multivariate analysis we could not identify EBV status as an independent risk factor for worse survival. Our results suggest that in the rituximab era, there has been an improvement on the survival outcomes of EBV+ DLBCL, NOS patients managed with chemoimmunotherapy. We are currently validating our findings in a prospective cohort of DLBCL patients and to improve clinical decision-making in those deemed at high-risk for early mortality and relapse. [Display omitted] DisclosuresRamirez-Ibarguen: Asofarma: Consultancy; MSD: Consultancy; Abbvie: Speakers Bureau; Astra Zeneca: Speakers Bureau; Janssen: Speakers Bureau; Roche: Speakers Bureau; Takeda: Consultancy, Speakers Bureau. Perini: Janssen: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau; Astra Zeneca: Honoraria, Speakers Bureau; MSD: Honoraria, Speakers Bureau. Oliver: Abbvie: Other: conference support and fees ; Roche: Other: conference support and fees . Castillo: Abbvie: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Janssen: Consultancy; Roche: Consultancy; TG Therapeutics: Research Funding.

Extended intensive care correlates with worsening of surgical outcome after elective abdominal aortic reconstruction

The aim of this study was to evaluate the impact of extended postoperative intensive care on short- and long-term patient outcome after elective abdominal aortic surgery and to assess the risk factors for patient survival after extended intensive care unit (ICU) treatment. The data of 231 patients that underwent open or endovascular abdominal aortic surgery were retrospectively analysed with regard to extended postoperative intensive care, defined as ICU treatment for more than 24 consecutive hours. Pre- and intraoperative factors were evaluated. The endpoints of the study were postoperative complications, mortality, and long-term follow-up. Univariate and multivariate Cox proportional regression analyses were performed to identify risk factors of worse overall survival. Extended postoperative intensive care was needed in 84 patients (63 after open and 21 after endovascular surgery). The period of ICU treatment was similar in both groups. Only the wound complications (31.8% vs. 9.5%, P=0.0498; OR 4.42 [0.94-20.84]) and the rate of acute kidney injury (82.5% vs. 57.1%, P=0.0352; OR 3.55 [1.20-0.46]) were more frequent after open surgery, whereas brief reactive psychosis (38.1% vs. 14.3%, P=0.0281; OR 0.27 [0.09-0.84]) was more frequent after endovascular surgery. ICU stay of ≥8 days correlated with significantly lower survival rates compared to a shorter ICU stay (P=0.0034), independent of open or endovascular techniques. Other multivariate risk factors for worse survival were the absence of preoperative aspirin medication, a Body Mass Index (BMI) of <25, chronic renal insufficiency, and coronary artery disease. Endovascular therapy was a positive predictive factor of short ICU stay of ≤3 days. The outcome after extended intensive care following elective aortic surgery is strongly dependent on the length of ICU stay.

Survival trends of older adult patients with diffuse large B-cell lymphoma: A National Cancer Database analysis.

7542 Background: 60-70% of patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) can be cured with R-CHOP or R-CHOP-like immunochemotherapy. However, patients ≥80 years of age were either excluded or underrepresented in modern DLBCL trials, and their outcomes are understudied. The aim of this study is to define the survival trends and risk factors for inferior survival in older adult patients with DLBCL. Methods: Patients with newly diagnosed DLBCL were identified from the National Cancer Database (2004-2017, representing the rituximab era). Clinical characteristics, treatment, and outcomes were compared between patients ages ≥ 80, 65-79, and &lt; 65 years. The Kaplan-Meier method and Cox proportional hazards model were used for survival analysis. Results: A total of 231,756 patients with newly diagnosed DLBCL were identified; 46,250 (20%) were ≥80 years, 87,702 (38%) were 65-79 years, and 97,904 (42%) were &lt; 65 years. Patients ≥80 years were more likely to have a higher Charlson-Deyo Comorbidity Index score (CDS) (CDS ≥2, 12% vs 11% vs 8%, p = 0.001), less likely to receive systemic chemotherapy (63% vs 83% vs 89%, p &lt; 0.001), and more likely to receive treatment at a non-academic center (71% vs 65% vs 48%, p &lt; 0.001), compared to patients 65-79 and &lt; 65 years, respectively. Median overall survival (OS) was significantly worse for patients ≥80 years compared to patients 65-79 years (11.6 vs 61.0 months, p = 0.001) and patients &lt; 65 years (11.6 vs 178.1 months, p = 0.001). During the study period, the median OS had only minimally improved for patients ≥80 years (10.6 months in 2004-2007 vs 11.5 months in 2008-2011 vs 12.3 months in 2012-2016, p = 0.006). In contrast, the OS improvement appears more meaningful in patients 65-79 years (median in months: 51 vs 61.2 vs 65.9, p = &lt; 0.001) and patients &lt; 65 years (median in years: 14.6 vs 11.3 vs not reached, p &lt; 0.001) in the prespecified intervals (2004-07, 2008-11, and 2012-16). In multivariate analysis, the most substantial risk factor for worse survival in patients ≥80 years was not receiving systemic therapy (hazard ratio [HR] = 3.26, 95%CI = 3.01-3.54, p = 0.001). Other risk factors associated with worse survival included high-risk IPI score (HR = 2.16, 95%CI = 1.96-2.39, p = 0.001), CDS score ≥2 (HR = 1.56, 95%CI = 1.40-1.73, p = 0.001), male sex (HR = 1.16, 95%CI = 1.09-1.24, p = 0.001), B symptoms at diagnosis (HR = 1.16, 95%CI = 1.08-1.25, p = 0.001), and treatment at a non-academic center (HR = 1.1, 95%CI = 1.01-1.20, p = 0.001). Conclusions: Patients ≥ 80 years of age with DLBCL have a significantly inferior survival which has not meaningfully improved in recent years. More than 1/3 of patients ≥ 80 years did not receive systemic therapy. Older adult patients with DLBCL should be assessed for fitness for chemotherapy using validated geriatric assessment tools. Novel therapeutic strategies with favorable safety profiles are urgently needed for this expanding patient population.

Women survive longer than men undergoing cytoreductive surgery and HIPEC for appendiceal cancer.

BackgroundWe hypothesize that women undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis from appendiceal cancer will have a survival advantage compared to men.MethodsThe National Cancer Database (NCDB) public user file (2004–2014) was used to select patients with PC undergoing CRS and HIPEC from appendiceal cancer. Univariate and multivariable analyses were performed.Results1,190 patients with PC from appendiceal cancer underwent HIPEC and CRS. OS was significantly longer for women than for men, with mean and median OS being 73.8 months and 98.2 months for women vs 58.7 months and 82.5 months for men, respectively (p = 0.0032). On multivariable analysis, male sex (HR: 1.444, 95% CI: 1.141–1.827, p = 0.0022) and increasing age (HR: 1.017, 95% CI: 1.006–1.027, p = 0.0017) were both found to be independent risk factors for worse OS.ConclusionWomen undergoing CRS and HIPEC for PC from appendiceal origin live longer than men undergoing the same treatment. Increasing age was also found to be independent risk factors for worse survival