Independent Predictor Of Shorter Survival Research Articles

Early-onset dysphagia predicts short survival in multiple system atrophy.

The prognostic impact of dysphagia in multiple system atrophy (MSA) remains controversial. This study aimed to investigate the relationship between dysphagia severity and survival in MSA and to elucidate whether this impact differs between MSA-cerebellar ataxia (MSA-C) and MSA-parkinsonism (MSA-P). This retrospective study included 297 patients with MSA: 251 met criteria for clinically established MSA and 46 for clinically probable MSA. Among them, 171 had MSA-C and 126 had MSA-P. We evaluated symptomatic dysphagia within 3years of onset and quantified dysphagia severity using the Hyodo score (0 to 12) through fibreoptic endoscopic evaluation of swallowing (FEES) and clinical features, including autonomic dysfunction and vocal cord paralysis. Patients were followed up until death or tracheostomy, and survival factors were analysed using the log-rank test and multivariate Cox proportional hazards model. Ninety patients developed symptomatic dysphagia within 3years of onset, and 75 were evaluated for dysphagia severity using FEES. Survival from onset was shorter in patients with dysphagia within 3years compared to those without (median: 4.2years vs. 7.3years; p < 0.001). Symptomatic dysphagia within 3years of onset was an independent predictor of shorter survival in the multivariate Cox analysis. While the Hyodo score was higher in MSA-P than in MSA-C patients (p = 0.048), the Hyodo score was associated with survival in both MSA-C and MSA-P patients (log-rank p < 0.001 and p = 0.046, respectively). Symptomatic dysphagia within 3years of onset predicts shorter survival in MSA-C and MSA-P patients.

The involvement of brain regions associated with lower KPS and shorter survival time predicts a poor prognosis in glioma.

Isocitrate dehydrogenase-wildtype glioblastoma (IDH-wildtype GBM) and IDH-mutant astrocytoma have distinct biological behaviors and clinical outcomes. The location of brain tumors is closely associated not only with clinical symptoms and prognosis but also with key molecular alterations such as IDH. Therefore, we hypothesize that the key brain regions influencing the prognosis of glioblastoma and astrocytoma are likely to differ. This study aims to (1) identify specific regions that are associated with the Karnofsky Performance Scale (KPS) or overall survival (OS) in IDH-wildtype GBM and IDH-mutant astrocytoma and (2) test whether the involvement of these regions could act as a prognostic indicator. A total of 111 patients with IDH-wildtype GBM and 78 patients with IDH-mutant astrocytoma from the Cancer Imaging Archive database were included in the study. Voxel-based lesion-symptom mapping (VLSM) was used to identify key brain areas for lower KPS and shorter OS. Next, we analyzed the structural and cognitive dysfunction associated with these regions. The survival analysis was carried out using Kaplan-Meier survival curves. Another 72 GBM patients and 48 astrocytoma patients from Harbin Medical University Cancer Hospital were used as a validation cohort. Tumors located in the insular cortex, parahippocampal gyrus, and middle and superior temporal gyrus of the left hemisphere tended to lead to lower KPS and shorter OS in IDH-wildtype GBM. The regions that were significantly correlated with lower KPS in IDH-mutant astrocytoma included the subcallosal cortex and cingulate gyrus. These regions were associated with diverse structural and cognitive impairments. The involvement of these regions was an independent predictor for shorter survival in both GBM and astrocytoma. This study identified the specific regions that were significantly associated with OS or KPS in glioma. The results may help neurosurgeons evaluate patient survival before surgery and understand the pathogenic mechanisms of glioma in depth.

Higher Prevalence of Chronic Kidney Disease in Myelodysplastic Syndromes Patients Compared to Age- Adjusted General Population - Results from the Polish Adult Leukemia Group (PALG) Registry

Introduction Chronic comorbidities that are common in the elderly population can have a significant impact on the clinical course, the choice of treatment, and survival of myelodysplastic syndromes (MDS) patients. No studies have focused on the coexistence of two diseases that are common in the elderly population, chronic kidney disease (CKD) and MDS, so the epidemiological data and clinical implications of both diseases occurring together are unknown. Aims Primary objective: to assess the prevalence of CKD in patients with MDS in comparison to the age-adjusted general population. Secondary objective: to evaluate the impact of CKD on clinical course in MDS patients. Methods This was a prospective analysis using clinical and laboratory data from MDS patients who were registered in the Polish Adult Leukemia Group (PALG) Registry from 2010 to 2023. Data have been provided by 28 hematologic centers. CKD was defined as an eGFR &amp;lt; 60 mL/min/1.73m², disregarding albuminuria since urinalysis results were not recorded in the database. The stages of CKD were classified based on eGFR according to the NKF KDOQI National Kidney Foundation Kidney Disease Outcome Quality Initiative guidelines, and eGFR was calculated using CKD-EPI equation. For comparison of the prevalence of CKD in MDS subjects aged ≥60 years to the general population, we used data from the PolSenior 2 study (covering the years 2018-2019). Data were age and sex standardized using demographic tables from Statistics Poland (https:// demografia.stat.gov.pl/bazademografia/Tables.aspx). Median survival time was calculated using Kaplan-Meier estimator. Multivariate analysis was performed using Cox regression. Results Overall, data (including eGFR) were available for 1813 MDS patients. Median age at diagnosis was 71 years [IQR 64 - 78]. and 55.3% patients were male. Sixty percent of the patients were diagnosed as IPPS lower risk. At the time of MDS diagnosis, CKD was detected in 479 patients (26.4%). Among patients aged ≥ 60, the crude rate of CKD was 30.3%. The standardized rate of CKD in the general population aged ≥ 60 years was significantly lower than in the similarly aged MDS group, with rates of 13.2% [CI 12.3-14.1] and 25.5% [CI 22.9-28.4]; p&amp;lt;0.001, respectively. (Figure 1) Patients with CKD were significantly older (median 78 yo) than those without CKD (median 68 yo; p&amp;lt;0.001), and more likely to have diabetes (33.2% vs 19.7%; p&amp;lt;0.001), and to have coincidence of another malignancy (21.6%) than those without CKD (14.9%; p=0.001). Median hemoglobin concentration was significantly lower in the CKD group (8.9 g/dL) than in the non-CKD group (9.4 g/dL; p &amp;lt; 0.05). Subjects with decreased eGFR were more likely to be dependent on RBC transfusion (56.5%) than subjects with eGFR ≥ 60 ml/min per 1.73m 2 (48.9%; p=0.0008). Median survival of patients with eGFR ≥ 60 ml/min per 1.73m 2 was 2.5 y [CI 1.0-6.1] vs 1.4 y [CI 0.6-4.2] for CKD. In multivariate analysis we found that CKD stage, age ≥ 65, higher IPSS score, high-risk IPSS cytogenetics and ECOG &amp;gt;1 were independent predictors of shorter survival. (Figure 2). Conclusions Myelodysplastic syndrome (MDS) subjects are more likely to have chronic kidney disease (CKD) than the general population. The presence of CKD in MDS patients is associated with worse overall survival and higher RBC transfusion requirement.

A novel prognostic model for oligometastatic renal cell carcinoma: COMPARZ study post-hoc analysis.

e16521 Background: International metastatic renal cell carcinoma database consortium (IMDC) is the most commonly used prognostic model for metastatic renal cell carcinoma (mRCC), however, its clinical application has been limited due to the cumbersome design and vague recommendation of treatment decisions for patients in the IMDC intermediate risk group. Previous studies indicated the favorable prognosis of oligometastatic RCC, but the definition of oligometastasis has not been clarified. This study aims to construct a new prognostic model of oligometastatic RCC based on the COMPARZ study cohort. Methods: Patients from the COMPARZ study (which was a randomized phase III non-inferiority study comparing pazopanib and sunitinib in advanced RCC or mRCC patients). Patients (N=1038) were divided into two cohorts for models construction respectively, Cohort A (n=293) with primary kidney tumor; Cohort B (n=745) without primary kidney tumor. Multivariate Cox regression analysis was performed to identify the independent prognostic risk factors for each model with overall survival (OS) as primary endpoint. Uno’s C-statistics was utilized to compare the novel risk model with IMDC risk. These models were then used to examine and stratify the patients in IMDC intermediate risk group. Results: In Cohort A, four risk factors were identified independent predictors for short survival. Patients were segregated into the oligo group and the non-oligo group. The concordance index (C-index) for Model A and IMDC risk model was 0.63 (95%CI: 0.59-0.67) and 0.65 (95%CI: 0.61-0.69), respectively (p=0.389). In Cohort B, three risk factors were identified as independent predictors of short survival. Patients were also divided into the oligo group and the non-oligo group. The C-index between Model B and IMDC risk model was 0.62 (95%CI: 0.59-0.64) and 0.61 (95%CI: 0.58-0.64), respectively (p=0.650). For Model A, mOS for non-oligo group was 13.4 months vs NR in oligo group (3y OS: 25.3 vs 51.8%), while for model B, mOS was 18.5 vs NR respectively (3y OS: 24.3 vs 57.5%). With the novel prognostic models, patients in the IMDC intermediate risk group could be further stratified into oligo group (mOS: NR; 3y OS: 55.6%) that had a better outcome than patients in non-oligo group (mOS: 19.2 month; 3y OS: 24.9%; p&lt;0.001). Conclusions: Compared with the current IMDC model, the novel prognostic models of oligometastatic mRCC could well distinguish patients into favorable and poor prognostic groups with fewer risk factors and comparable predictive power. Meanwhile, the novel models can better stratify the IMDC intermediate risk group into oligo and non-oligo groups with significantly different OS outcomes, and is more conductive to the comprehensive treatment of patients with mRCC.

The flail-arm syndrome: the influence of phenotypic features

Objective: The flail-arm syndrome (FAS), one of the Amyotrophic lateral sclerosis (ALS) phenotypes, is characterized by slow progression and predominantly lower motor neuron (LMN) involvement with proximal upper limb (UL) weakness. We aim to characterize the clinical features, progression and survival of FAS associated with distal or proximal onset and presence or absence of upper motor neuron signs (UMN) signs at diagnosis. Methods: Data from 704 ALS patients was analyzed. Of the 190 patients with UL onset; 134 were excluded as not respecting the published criteria for FAS. The included patients were divided into four groups according to distal/proximal onset and presence/absence of UMN signs. Results: 56 FAS patients (8% of the population), median age at onset 59.9 years (Q1/Q3, 50.3–68.1), 75% men, were studied. Distal onset with UMN signs occurred in 37.5%, distal onset without UMN signs in 28.6%, proximal onset with UMN signs in 8.9% and proximal onset without UMN signs in 25%. Age of onset, sex, fasciculations at onset, diagnostic delay, progression rate, time to respiratory involvement and survival were similar among the four groups. Sex ratio was more balanced in patients with UMN signs (p = 0.032) and survival was shorter (69.5 months, 95% CI: 55.4–110.4 vs 152.6 months, 95% CI: 69.0–177.3; p = 0.035). The Cox regression identified rate of progression (p < 0.001) and UMN signs (p = 0.003) as independent predictors of shorter survival. Conclusions: Distal or proximal onset had no influence on clinical characteristics and prognosis but UMN signs at diagnosis are a negative prognostic predictor.

Clinical course and prognosis of patients with lung cancer who develop anticancer therapy-related pneumonitis.

Pneumonitis can be triggered by anti-cancer therapies: cytotoxic chemotherapy, tyrosine kinase inhibitors, and immune checkpoint inhibitors. There are few treatment options for patients who develop such pneumonitis and their treatment including chemotherapy is generally difficult thus would limit patient's prognosis. In this study, we investigated the clinical course of patients with lung cancer who developed anti-cancer therapy-related pneumonitis. We retrospectively examined data of patients who had developed pneumonitis triggered by anti-cancer agents and required hospitalization from January 2014 to March 2019 and analyzed their subsequent clinical course and prognosis. The median age of the 58 study patients was 68years and 82.8% were men. The median interval between first receiving the responsible agent and drug-induced pneumonitis was 7.4weeks. Approximately 38% of patients were subsequently able to receive some anti-cancer therapy. The median post-pneumonitis overall survival (OS) from commencement of anti-cancer treatment was 13.2months. No significant differences were found in survival time between treatment agents. However, patients who received some anticancer therapy after pneumonitis had significantly longer survival times than those did not (HR = 4.11, p = 0.0003) and patients who took longer to develop pneumonitis had a longer survival (HR = 2.28, p = 0.0148). Multivariate analysis revealed that short interval to onset and no post-pneumonitis anticancer therapy were independent predictors of short survival. Although patients who developed pneumonitis had relatively short survival times, the interval between initial therapy and pneumonitis had survival impact. Survival can be prolonged by administering further cancer treatment after resolution of pneumonitis.

A Preclinical Trial and Molecularly Annotated Patient Cohort Identify Predictive Biomarkers in Homologous Recombination–deficient Pancreatic Cancer

Pancreatic ductal adenocarcinoma (PDAC) arising in patients with a germline BRCA1 or BRCA2 (gBRCA) mutation may be sensitive to platinum and PARP inhibitors (PARPi). However, treatment stratification based on gBRCA mutational status alone is associated with heterogeneous responses. We performed a seven-arm preclinical trial consisting of 471 mice, representing 12 unique PDAC patient-derived xenografts, of which nine were gBRCA mutated. From 179 patients whose PDAC was whole-genome and transcriptome sequenced, we identified 21 cases with homologous recombination deficiency (HRD), and investigated prognostic biomarkers. We found that biallelic inactivation of BRCA1/BRCA2 is associated with genomic hallmarks of HRD and required for cisplatin and talazoparib (PARPi) sensitivity. However, HRD genomic hallmarks persisted in xenografts despite the emergence of therapy resistance, indicating the presence of a genomic scar. We identified tumor polyploidy and a low Ki67 index as predictors of poor cisplatin and talazoparib response. In patients with HRD PDAC, tumor polyploidy and a basal-like transcriptomic subtype were independent predictors of shorter survival. To facilitate clinical assignment of transcriptomic subtype, we developed a novel pragmatic two-marker assay (GATA6:KRT17). In summary, we propose a predictive and prognostic model of gBRCA-mutated PDAC on the basis of HRD genomic hallmarks, Ki67 index, tumor ploidy, and transcriptomic subtype.

Diagnostic delay and outcome in immunocompetent patients with primary central nervous system lymphoma in Spain: a multicentric study.

To assess the management of immunocompetent patients with primary central nervous system lymphomas (PCNSL) in Spain. Retrospective analysis of 327 immunocompetent patients with histologically confirmed PCNSL diagnosed between 2005 and 2014 in 27 Spanish hospitals. Median age was 64years (range: 19-84; 33% ≥ 70years), 54% were men, and 59% had a performance status (PS) ≥ 2 at diagnosis. Median delay to diagnosis was 47days (IQR 24-81). Diagnostic delay > 47days was associated with PS ≥ 2 (OR 1.99; 95% CI 1.13-3.50; p = 0.016) and treatment with corticosteroids (OR 2.47; 95% CI 1.14-5.40; p = 0.023), and it did not improve over the years. Patients treated with corticosteroids (62%) had a higher risk of additional biopsies (11.7% vs 4.0%, p = 0.04) but corticosteroids withdrawal before surgery did not reduce this risk and increased the diagnostic delay (64 vs 40days, p = 0.04). Median overall survival (OS) was 8.9months [95% CI 5.9-11.7] for the whole series, including 52 (16%) patients that were not treated, and 14.1months (95%CI 7.7-20.5) for the 240 (73.4%) patients that received high-dose methotrexate (HD-MTX)-based chemotherapy. Median OS was shorter in patients ≥ 70years (4.1 vs. 13.4months; p < 0.0001). Multivariate analysis identified age ≥ 65years, PS ≥ 2, no treatment, and cognitive/psychiatric symptoms at diagnosis as independent predictors of short survival. Corticosteroids withdrawal before surgery does not decrease the risk of a negative biopsy but delays diagnosis. In this community-based study, only 73.4% of patients could receive HD-MTX-based chemotherapy and OS remains poor, particularly in elderly patients ≥ 70years.

Circulating Tumor Cells are an Independent Predictor of Shorter Survival in Patients Undergoing Resection for Pancreatic and Periampullary Adenocarcinoma.

We evaluated the prognostic impact of circulating tumor cells (CTCs) for patients with presumed resectable pancreatic and periampullary cancers. Initial treatment decisions for this group are currently taken without a reliable prognostic marker. The CellSearch system allows standardized CTC-testing and has shown excellent specificity and prognostic value in other applications. Preoperative blood samples from 242 patients between September 2009 and December 2014 were analyzed. One hundred seventy-nine patients underwent tumor resection, of whom 30 with stage-I tumors and duodenal cancer were assigned to the low-risk group, and the others to the high-risk group. Further 33 had advanced disease, 30 benign histology. Observation ended in December 2016. Cancer-specific survival (CSS) and disease-free survival (DFS) were calculated by log-rank and Cox regression. CTCs (CTC-positive; ≥1 CTC/7.5 mL) were detected in 6.8% (10/147) of the high-risk patients and 6.2% (2/33) with advanced disease. No CTCs (CTC-negative) were detected in the low-risk patients or benign disease. In high-risk patients, median CSS for CTC-positive versus CTC-negative was 8.1 versus 20.0 months (P < 0.0001), and DFS 4.0 versus 10.5 months (P < 0.001). Median CSS in advanced disease was 7.7 months. Univariate hazard ratio (HR) of CTC-positivity was 3.4 (P < 0.001). In multivariable analysis, CTC-status remained independent (HR: 2.4, P = 0.009) when corrected for histological type (HR: 2.7, P = 0.030), nodal status (HR: 1.7, P = 0.016), and vascular infiltration (HR: 1.7, P = 0.001). Patients testing CTC-positive preoperatively showed a detrimental outcome despite successful tumor resections. Although the low CTC-rate seems a limiting factor, results indicate high specificity. Thus, preoperative analysis of CTCs by this test may guide treatment decisions and warrants further testing in clinical trials.

Relationship between SHP-1 gene methylation and STAT3 phosphorylation and prognosis in patients with myelodysplastic syndrome

Objective: To assess the methylation level of SHP-1 promoter region and the effects on the phosphorylation of the Signal Transducers and Activators of Transcription 3 (STAT3) protein in bone marrow specimen of patients with myelodysplastic syndrome (MDS), and to explore the relationship of SHP-1 methylation and prognosis of the patients. Method: Bone marrow specimens of 93 patients with MDS were collected from the General Hospital of Tianjin Medical University from September 2010 to June 2014. The enrolled subjects included 54 males and 39 females and they were divided into the low-risk group (IPSS score:0-1.0, median: 0.5) and the high-risk group (IPSS score: 1.5-3.0, median: 2.5) according to the International Prognostic Score System (IPSS). The methylation level of SHP-1 was detected by methylation-specific polymerase chain reaction, and the level of p-STAT3 was detected using Western blot. Results: In the high-risk group, 64.44% (29/45) of the patients had methylation in the SHP-1 promoter region, which was significantly higher than the low-risk group 22.92% (11/48). Therefore, SHP-1 methylation was frequently presented in the patients of the high-risk group. Similarly, 66.67% (30/45) of the patients in the high-risk group had positive STAT3 phosphorylation status, whereas only 20.83% (10/48) were tested positive in the low-risk group. In addition, correlation analysis also revealed that the SHP-1 methylation rate was positively correlated with the positive rate of STAT3 phosphorylation (r=0.57,P<0.001). Conclusions: SHP-1 methylation is significantly correlated with the risk of MDS patients. It may be used as an independent predictor of shorter survival in patients of the high-risk group. The increased level of SHP-1 methylation will lead to the uncontrolled activation of the downstream JAK/STAT3 pathway, which in turn can cause further positive feedback to amplify the carcinogenic signal.

Impact of Fibroblast-Derived SPARC on Invasiveness of Colorectal Cancer Cells.

Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein modulating cell-matrix interactions and was found up-regulated in tumor stroma. To explore the effect of high stromal SPARC on colorectal cancer (CRC) cell behavior and clinical outcome, this study determined SPARC expression in patients suffering from stage II and III CRC using a publicly available mRNA data set and immunohistochemistry of tissue microarray sections. Moreover, in vitro co-culture models using CRC cell lines together with colon-associated fibroblasts were established to determine the effect of fibroblast-derived SPARC on cancer cells. In 466 patient samples, high SPARC mRNA was associated with a shorter disease-free survival. In 99 patients of the tissue microarray cohort, high stromal SPARC in the primary tumor was an independent predictor of shorter survival in patients with relapse (27 cases; HR = 4574, p = 0.004). In CRC cell lines, SPARC suppressed phosphorylation of focal adhesion kinase and stimulated cell migration. Colon-associated fibroblasts increased migration velocity by 30% and doubled track-length in SPARC-dependent manner. In a 3D co-culture system, fibroblast-derived SPARC enhanced tumor cell invasion. Taken together, stromal SPARC had a pro-metastatic impact in vitro and was a characteristic of aggressive tumors with poor prognosis in CRC patients.

P-078 - Preoperative neutrophil to lymphocyte ratio as a prognostic factor for patients with colorectal cancer

Introduction: This study aimed to determine the role of the neutrophil to lymphocyte ratio (NLR) as a prognostic marker for patients with colorectal cancer (CRC) undergoing curative resection. Management of CRC and postsurgical treatment is usually arranged using the TNM staging system, but there are still prognostic variations among patients at the same TNM stage. Recent studies showed correlations between the inflammatory response and clinical outcomes in various cancers. The NLR reflected a systematic inflammatory response with some evidence suggesting that an elevated preoperative NLR is associated with poorer survival in patients with CRC. Methods: One hundred seventy eight patients with CRC, undergoing surgical resection in Surgical Departement Generaly Hospital Studenica Kraljevo- Serbia, between 2010. and 2015. were included in our retrospective analysis. Patients separated into two groups according to a cut-off value for NLR. Patient data included age, gender, localisation and differentiation of tumor, TNM stage, survival rate were analyzed for correlation with the NLR. Results: Using ROC curve analysis, we determined a cut-off NLR value of 2.1 in order to best detect differences in patient survival between our groups. The average length of survival in patients that had NLR≤2.1 was 7.3 months (72.7±12) and within these patients, the median of survival had not been reached. Patients with NLR > 2.1 had an average length of survival of 60 months (60.11±3.4) and median of survival was 70.0. The log-rank test showed that there was a statistically significant difference (P = .041) of survival between patients that had NLR ≤ 2.1 compared with those who had NLR > 2.1. Also, the log-rank test showed that advanced pathologic TNM stage (P = .000), pathologic nodal stage (P = .007) were predictive of shorter survival. Conclusion: High pre-treatment levels of NLR is a significant independent predictor of shorter survival in patients with colorectal cancer. This parameter is a simple, cheap, easily accessible laboratory value for identifying patients with poorer prognosis.

The Impact of Neutrophil to Lymphocytic Ratio (NLR) as a Predictor of Treatment Outcomes in Rectal Carcinomas: A Retrospective Cohort Study

Background and aim: The prognostic role of neutrophil to lymphocyte ratio (NLR) has been shown in many solid tumors included in a recent meta-analysis of one hundred studies. We aimed to evaluate the prognostic value of neutrophil to lymphocyte ratio in treatment outcomes; response and survival of patients with different stages of rectal cancers. Patients and methods: All patients with pathologically confirmed cancer rectum presented to our department during the period from January 2012 to the end of 2014 were included in this retrospective study, these recruited patients were evaluated through their files to determine different objectives of our study. Results: The median overall survival was 31 ± 4.676 months while disease free survival was 40 ± 2.346 for the whole study group; neutrophil to lymphocyte ratio was negatively correlated with overall survival with r = –0.743, P disease free survival with r = –0.717, P total number of lymph nodes dissected ratio with r = +0.254, P = 0.028. Roc curve was used to find the accurate cut point of NLR for these patients and was found to be of 4.5. Conclusion: Elevated pre-treatment NLR is an independent predictor of shorter survival in patients with rectal cancer. This parameter is a simple, easily accessible laboratory test for identifying patients with poorer prognosis.

Pelvic exenterations for primary rectal cancer: Analysis from a 10-year national prospective database.

AIMTo identify short-term and oncologic outcomes of pelvic exenterations (PE) for locally advanced primary rectal cancer (LAPRC) in patients included in a national prospective database.METHODSFew studies report on PE in patients with LAPRC. For this study, we included PE for LAPRC performed between 2006 and 2017, as available, from the Rectal Cancer Registry of the Spanish Association of Surgeons [Asociación Española de Cirujanos (AEC)]. Primary endpoints included procedure-associated complications, 5-year local recurrence (LR), disease-free survival (DFS) and overall survival (OS). A propensity-matched comparison with patients who underwent non-exenterative surgery for low rectal cancers was performed as a secondary endpoint.RESULTSEight-two patients were included. The mean age was 61.8 ± 11.5 years. More than half of the patients experienced at least one complication. Surgical site infections were the most common complication (abdominal wound 18.3%, perineal closure 19.4%). Thirty-three multivisceral resections were performed, including two hepatectomies and four metastasectomies. The long-term outcomes of the 64 patients operated on before 2013 were assessed. The five-year LR was 15.6%, the distant recurrence rate was 21.9%, and OS was 67.2%, with a mean survival of 43.8 mo. R+ve resection increased LR [hazard ratio (HR) = 5.58, 95%CI: 1.04-30.07, P = 0.04]. The quality of the mesorectum was associated with DFS. Perioperative complications were independent predictors of shorter survival (HR = 3.53, 95%CI: 1.12-10.94, P = 0.03). In the propensity-matched analysis, PE was associated with better quality of the specimen and tended to achieve lower LR with similar OS.CONCLUSIONPE is an extensive procedure, justified if disease-free margins can be obtained. Further studies should define indications, accreditation policy, and quality of life in LAPRC.

Does Race Impact Survival in Multiple Myeloma?

Purpose:Multiple myeloma (MM), a cancer involving abnormal antibody production from plasma cells, accounts for approximately 1.8% of all new cancer cases in the US. The International Staging System (ISS) for MM classifies patients with serum beta2 microglobulin < 3.5mg/l and serum albumin ≥3.5g/dl as having stage I disease, patients with serum beta2 microglobulin ≥ 5.5 mg/l as having stage III disease, and all others as having stage II disease. The median survival by stage at time of diagnosis is 62 months, 45 months, and 29 months, respectively, for stages I, II, and III.The median age at time of diagnosis of MM is 69 years, with approximately 62% of all patients being at least 65 years old at time of diagnosis. There is a 2-fold increase in MM incidence amongst blacks as compared to whites in both the male and female population. This study was conducted to further characterize our MM patient population and to potentially identify racial and gender impact on mortality.Methods:A retrospective chart review of all patients in our geographic region diagnosed with MM between 2012 and 2017 was conducted using the Louisiana Tumor Registry Board database. Clinical data abstraction included epidemiology, laboratory, and pathologic data at time of diagnosis, and time to autologous stem cell transplant and death, if applicable. We performed chi-square analysis, linear regression, and survival analysis to compare survival outcomes between groups.Results:Chart review data was available for 184 of the 243 patients diagnosed with MM between 2012-2017, including 89 (47.6%) males and 98 females (52.4%), and 90 (48.1%) whites and 88 (47.1%) blacks. Females were significantly older than males (66.1 vs 62.6 years, p=0.037) at time of diagnosis yet whites were not significantly older compared to blacks (65.1 vs. 63.9 years, p=0.498). Among the 108 patients with documented stage of disease, 17 (15.7%) patients were diagnosed with stage I MM compared to 40 patients (37.0%) diagnosed at stage II and 51 (47.2%) diagnosed at stage III. With regards to stage, there was no significant difference between race or sex in our population. When adjusted for gender and age at diagnosis, race was a significant predictor of survival time with survival being 6.45 months shorter for black patients with MM compared to whites with the disease. (95% CI, 1.1 to 11.8; p = 0.019)Conclusion:Our data suggest that race exists as an independent predictor of shorter survival in our black patient population with MM. Additional studies investigating the biologic diversity of this disease are warranted to explain this racial disparity. DisclosuresNo relevant conflicts of interest to declare.

Clinicopathological and prognostic significance of Ras association and pleckstrin homology domains 1 (RAPH1) in breast cancer.

Ras association and pleckstrin homology domains 1 (RAPH1) is involved in cytoskeleton regulation and re-epithelialisation in invasive carcinoma and, therefore, may play a key role in carcinogenesis and metastasis. We, herein, investigated the biological and clinical significance of RAPH1 in breast cancer using large annotated cohorts. The clinicopathological and prognostic significance of RAPH1 was assessed at the genomic and transcriptomic levels using The Cancer Genome Atlas (TCGA) dataset (n = 1039) and the results were validated using the Molecular taxonomy of breast cancer international consortium (METABRIC) cohort (n = 1980). RAPH1 protein expression was evaluated by immunohistochemistry in a large, well-characterised cohort of early-stage breast cancer (n = 1040). In both the TCGA and METABRIC cohorts, RAPH1 mRNA expression and RAPH1 copy number alteration were strongly correlated. RAPH1 mRNA overexpression was significantly correlated with high expression of adhesion and EMT markers including CDH1, TGFβ1 and CD44. RAPH1 mRNA overexpression was a significant predictor of a poor prognosis (Hazard ratio 3.88; p = 0.049). High RAPH1 protein expression was associated with higher grade tumours with high proliferation index, triple negative phenotype and high E-cadherin expression. High RAPH1 protein expression was an independent predictor of shorter survival (Hazard ratio 4.37; p = 0.037). High RAPH1 expression is correlated with aggressive breast cancer phenotypes and provides independent prognostic value in invasive breast cancer.

Germline mutations in PPFIBP2 are associated with lethal prostate cancer.

Few genes have germline mutations which predispose men to more aggressive prostate cancer (PCa). This study evaluated the contribution of germline loss of function (LOF) variants in PPFIBP2 to risk of lethal PCa. A case-case study of 1414 PCa patients with lethal PCa and low-risk localized PCa was performed. Germline DNA samples from these patients were sequenced for PPFIBP2. Mutation carrier rates and association with lethal PCa were analyzed using the Fisher exact test, logistic regression, and Kaplan-Meier survival analysis. In the entire study population, eight patients, all of European ancestry, were identified as carrying PPFIBP2 pathogenic or likely pathogenic mutations. Seven (1.52%) of 462 lethal PCa patients were carriers compared with only one (0.12%) carrier in 810 low-risk PCa patients, P = 0.0029. The estimated Odds Ratio (OR) of carrying PPFIBP2 mutation for lethal PCa was 13.8 in European American population. The PPFIBP2 loss-of-function mutation carrier rate in lethal PCa cases was also higher than in 33 370 non-Finnish European individuals from the Exome Aggregation Consortium (ExAC) (carrier rate of 0.17%, P = 1.92 × 10-5 ) and in 498 men with localized PCa from The Cancer Genome Atlas cohort (TCGA) cohort (carrier rate of 0%, P = 0.0058). Survival analysis in European American lethal cases revealed PPFIBP2 mutation status as an independent predictor of shorter survival after adjusting for age at diagnosis, PSA at diagnosis, and genetic background (hazard ratio = 2.62, P = 0.034). While larger studies are needed, germline mutations in a novel gene, PPFIBP2, differentiated risk for lethal PCa from low-risk cases and were associated with shorter survival times after diagnosis.

The prognostic value of fragmented QRS in patients undergoing transcatheter aortic valve implantation

BackgroundAlthough transcatheter aortic valve implantation (TAVI) can successfully correct aortic narrowing, pre-existing pathophysiological alterations in the left ventricle are still a concern in terms of long-term mortality. This study aimed to examine the predictive role of fQRS morphology on long-term prognosis in patients undergoing TAVI due to severe aortic stenosis. MethodsA total of 117 patients undergoing TAVI due to severe aortic stenosis were included in this retrospective cohort study. Patients were assigned into two groups based on the presence (n = 36) or absence (n = 81) of fQRS. Predictors of long-term survival were estimated. ResultsIn-hospital mortality was higher in fQRS group (5.5% vs. 1.2%, p = 0.0224). In the long-term, fQRS (OR: 3.06, 95% CI 1.29–7.27, p: 0.01), LVEF <50% (OR: 2.54, 95% CI 1.07–6.02, p: 0.03) and presence of atrial fibrillation (OR: 2.42, 95% CI 1.05–5.60, p: 0.03) emerged as significant independent predictors of short survival. ConclusionPresence of fQRS on ECG, an indirect indicator of myocardial fibrosis, seems to have the potential to be used as a prognostic marker after TAVI procedure. Large prospective studies are warranted.

Palliative chemotherapy outcomes in patients with ECOG-PS higher than 1.

PurposeAlthough patients with incurable disease and Eastern Cooperative Oncology Group performance status (ECOG-PS ≥ 2) are underrepresented in clinical trials, they are frequently offered palliative chemotherapy (pCT) in daily clinical practice in order to improve symptoms and quality of life. In this case-control retrospective analysis, our goal was to identify factors associated with poorer survival and lack of benefit of pCT in this population.Patients and methodsWe evaluated 2,514 patients who died between August 2011 and July 2012 in an academic cancer care institution and its hospice. A total of 301 patients with solid tumours and ECOG-PS ≥ 2 at prescription of pCT were selected for this case-control retrospective analysis. Cases were defined as patients who survived less than 90 days after the first cycle of first line pCT, and controls were those who had a longer survival.Results142 cases and 159 controls were included. Cases were more likely to experience grade ≥ 3 toxicity (43% versus 28%; p = 0.005), die of toxicity (16% versus 6%; p < 0.001) and not be offered best supportive care (BSC) only (47% versus 71%; p < 0.001). Median overall survival was 204 among controls and 34 days in cases (hazard ratio = 0.177; 95%, confidence interval = 0.015–0.033, p < 0.001). Logistic regression analysis identified ECOG-PS > 2 (odds ratio (OR) = 2.3, p = 0.044) and serum creatinine (sCr) > 1 mg/dL (OR = 11.2, p < 0.001) as independent predictors of 90-day mortality.ConclusionsThe independent predictors of short survival (less than 3 months) after initiation of pCT in this population were ECOG-PS > 2 and elevated sCr. Therefore, patient selection is crucial, as pCT may be deleterious in ECOG-PS ≥ 2 pts.

Clinical and biological roles of Kelch-like family member 7 in breast cancer: a marker of poor prognosis

The functions of many proteins are tightly regulated with a complex array of cellular functions including ubiquitination. In cancer cells, aberrant ubiquitination may promote the activity of oncogenic pathways with subsequent tumour progression. Kelch-like family member 7 (KLHL7) is involved in the regulation of ubiquitination and may play a role in breast cancer (BC). Present study aims to evaluate the biological and clinical usefulness of KLHL7 in BC utilising large well-characterised cohorts with long-term follow-up. The relationships between KLHL7 gene copy number alteration (CNA) and mRNA expression and clinicopathological variables and clinical outcomes were evaluated in 1980 patients from the METABRIC BC cohort. Prognostic significance of KLHL7 mRNA was validated using the Breast Cancer Gene-Expression Miner v4.0 datasets (n = 5206). KLHL7 protein expression was assessed using immunohistochemistry in a large annotated series of early-stage BC (n = 917) with long-term follow-up. KLHL7 CNA was significantly correlated with its mRNA expression. KLHL7 mRNA expression was higher in luminal B and basal-like molecular subtypes and in higher grade tumours. Increased KLHL7 protein expression was significantly correlated with features of aggressive phenotype including lymphovascular invasion, high histological grade, hormonal receptor negativity, high PIK3CA and p53 expression. Outcome analysis showed that high KLHL7 expression is an independent predictor of shorter survival (p = 0.0011). KLHL7 appears to play an important role in BC progression. High KLHL7 protein expression identified a subgroup of BC with aggressive behaviour and provided independent prognostic information.