Negative Prognostic Factor For Overall Survival Research Articles

Liposomal irinotecan pre-emptive dose reduction in patients with pancreatic ductal adenocarcinoma: 667 patients' experience within a population-based study.

Background:Liposomal irinotecan (nal-IRI) plus 5-fluorouracil and leucovorin (5-FU/LV) is currently the standard second-line treatment for patients with pancreatic ductal adenocarcinoma (PDAC) after previous failed gemcitabine-based therapy. This population-based study aimed to evaluate the efficacy and safety of nal-IRI + 5-FU/LV and the association of pre-emptive nal-IRI dosing with treatment outcomes in patients with PDAC.Methods:We retrospectively enrolled a total of 667 consecutive patients with PDAC who received nal-IRI plus 5-FU/LV treatment between August 2018 and November 2020 at 9 medical centers in Taiwan. Patients were allocated into groups according to pre-emptive nal-IRI dosing (⩾75%, 50–74%, <50%) for comparison of treatment efficacy and safety.Results:The median overall survival (OS) and time to treatment failure (TTF) were 5.9 months [95% confidence interval (CI), 5.3–6.5] and 2.8 months (95% CI, 2.6–3.0), respectively. The median OS was 6.5 months (95% CI, 5.7–6.7), 5.0 months (95% CI, 3.4–6.5), and 4.1 months (95% CI, 2.7–5.6), respectively, among the ⩾75%, 50–74%, and <50% pre-emptive nal-IRI dosing groups, whereas the median TTF of the three groups was 3.0 months (95% CI, 2.6–3.4), 2.6 months (95% CI, 2.3–2.9), and 1.9 months (95% CI, 1.6–2.2), respectively. Pre-emptive nal-IRI dosing <50% was an independent negative prognostic factor for OS and TTF in multivariate analyses. The most common severe adverse events were neutropenia (22.9%), anemia (21.1%), and hypokalemia (15.4%). Patients in the <50% pre-emptive nal-IRI dosing group had a significantly lower incidence of neutropenia and non-neutropenic infection than those in the other groups.Conclusion:Our results support the use of nal-IRI + 5-FU/LV as standard clinical practice for treating patients with PDAC based on this large population-based study. Our findings encourage physicians to provide adequate doses of nal-IRI in order to achieve better outcomes without compromising safety profiles.

PTBP1 Genetic Variants Affect the Clinical Response to Androgen-deprivation Therapy in Patients With Prostate Cancer.

Heterogeneous nuclear ribonucleoproteins (hnRNPs) contribute to multiple cellular functions including RNA splicing, stabilization, transcriptional and translational regulation, and signal transduction. However, the prognostic importance of genetic variants of hnRNP genes in clinical outcomes of prostate cancer remains to be elucidated. We studied the association of 78 germline single-nucleotide polymorphisms (SNPs) in 23 hnRNP genes with the overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS) in 630 patients with prostate cancer receiving androgen-deprivation therapy (ADT). PTBP1 rs10420407 was the most significant SNP (false discovery rate q=0.003) and carriers of the A allele exhibited poor OS, CSS, and PFS. Multivariate Cox analysis confirmed PTBP1 rs10420407 A allele was an independent negative prognostic factor for OS and PFS. Expression quantitative trait loci analysis showed that the rs10420407 A allele had a trend towards increased PTBP1 mRNA expression, and higher expression was correlated with prostate cancer aggressiveness and poor patient prognosis. Meta-analysis of 16 independent studies further indicated a tumorigenic effect of PTBP1, with a higher expression in prostate cancers than in adjacent normal tissues (p<0.001). Our data suggest that PTBP1 rs10420407 may influence patient response to ADT, and PTBP1 may be involved in the pathogenesis of prostate cancer progression.

NCOG-58. IMPACT OF TIME FROM PRESENTATION TO TREATMENT INITIATION ON CLINICAL OUTCOMES IN CENTRAL NERVOUS SYSTEM LYMPHOMA

Abstract OBJECTIVE To examine impact of time from presentation to treatment initiation (TPT) on clinical outcomes in a cohort of patients with central nervous system lymphoma (CNSL). INTRODUCTION Earlier work in our population found that multifocal disease, cerebrospinal fluid (CSF) sampling, and use of immunomodulatory therapies were associated with longer TPT in CNSL, but impact on clinical outcomes was not assessed. METHODS We retrospectively reviewed records of patients who were diagnosed with CNSL from 2010-2018 and treated at Columbia University Irving Medical Center (CUIMC). Regression models were applied to examine the impact of age, gender, response to methotrexate (MTX), use of radiation, and TPT &amp;gt;/= 30 days on survival 1 year from diagnosis (one-year survival), overall survival (OS), and functional independence (FI, defined as Karnofsky Performance Status (KPS) &amp;gt; 70). RESULTS There were sixty-nine patients (51% men; median age at diagnosis 70 years, range 21-90). Median TPT was 24 days (range 7-372). TPT was &amp;lt; 30 days in 59 (85%) and &amp;gt;/= 30 days in 10 (15%). One-year survival was 77%, and FI rate was 78%. Negative prognostic factors for OS were age &amp;gt; 65 years (HR 5.34, CI 1.20-24.30, p=0.03) and absence of complete response to MTX (HR 2.40, CI 0.87-6.69, p=0.09). Only complete response to MTX predicted both FI (OR 4.71, CI 1.17-19.02, p=0.03) and one-year survival (OR 6.77, CI 1.98-23.13, p=0.002). Notably, OS was numerically improved among patients with TPT &amp;gt;/= 30 days vs. &amp;lt; 30 days (HR 0.31, p=0.27), though this did not meet statistical significance. CONCLUSIONS Longer TPT has been associated with worse outcomes in systemic lymphoma, but such a correlation has not always been observed in brain cancers such as glioblastoma. We found no negative impact of longer TPT on survival or FI.

Analysis of reliability of different risk classifications for assessment of relapses of gastrointestinal stromal tumors (GIST) — the impact of primary tumor genotyping

Background. Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Radical surgery is the primary treatment for GIST. Unfortunately, 40–50% of patients relapse, mainly due to hepatic and peritoneal metastases. Currently, the treatment of choice for locally advanced, inoperable or metastatic GIST is the use of tyrosine kinase inhibitors, including imatinib. GISTs are a group of tumors with various morphological, pathological and molecular features as well as different clinical courses, therefore their biological course is difficult to determine. Nevertheless, we currently have 5 classifications that assess the risk of relapse after surgery. The aim of this study was to analyze prognostic factors with regard to the risk of recurrence and overall survival, and to compare the clinical reliability of the recurrence risk classifications developed so far with an attempt to present a new classification including the genotype of primary GIST. Patients and methods. The material consisted of a group of 697 patients with primary GIST treated with the intention to cure, collected prospectively as part of the GIST clinical registry, Department of Melanoma and Soft Tissue and Bone Sarcomas, Maria Sklodowska-Curie National Research Institute of Oncology in Warsaw. All patients were classified based on 5 existing recurrence risk classifications. Univariate and multivariate analysis were performed for disease-free survival (DFS) and overall survival (OS). The relationships of the following factors with DFS and OS were assessed: sex, age, primary tumor mutational status, primary tumor location, primary tumor size, number of mitoses/50 HPF, surgical margins and the presence of tumor rupture. The next analysis concerned the comparison of the accuracy of existing recurrence risk classifications. The analysis was performed using ROC curves and a new classification model was proposed including mutation analysis as well as factors such as gender and age for selected existing recurrence risk assessment models. Results. Univariate and multivariate analyses showed statistical significance of variables such as male sex (P = 0.02), mitotic index 5–10/50 HPF and &gt; 10/50 HPF (P &lt; 0.001), primary tumor size 5–10 cm and &gt; 10 cm (P &lt; 0.001), primary tumor location outside of the stomach (P &lt; 0.001), R1 surgery (P &lt; 0.001), tumor rupture (P &lt; 0.001), and the presence of mutations in the KIT gene exon 11 including deletion 557–558 and the KIT gene exon 9 (P = 0.009) as negative prognostic factors affecting disease recurrence. Five-year disease-free survival rate was 57.3%. Median DFS was 76 months. Negative prognostic factors for OS are: age &lt; 40 (P = 0.045), mitotic index 5–10/50 and &gt; 10/50 HPF (P &lt; 0.001), primary tumor size 5–10 cm and &gt; 10 cm (P &lt; 0.001), R1 surgery and tumor rupture (P &lt; 0.001). All existing recurrence risk classifications showed prognostic value for assessing differences in DFS and OS, no significant differences were found between individual recurrence risk classifications. In addition, the reliability of all these classifications was improved by adding gender, age and mutation status. The value added of mutation status for better risk assessment was most significant when used in intermediate risk groups according to different classifications (P &lt; 0.01). Conclusion. All current GIST recurrence risk classifications allow for reliable assessment of recurrence risk. Mutations involving deletions (557–558) in the KIT gene exon 11 are most often present in the group at high risk of recurrence. Patients with confirmed mutations in the PDGFRA gene exon 18 and wild-type genotype have a favorable prognostic effect. The reliability of existing classifications for assessing the risk of relapse after GIST resection can be improved by adding mutation status, especially in groups at intermediate risk of relapse, which should facilitate therapeutic decisions in the context of adjuvant therapy.

Association between carbonic anhydrase 9 expression and poor prognosis in sinonasal squamous cell carcinoma

ObjectivesCarbonic anhydrase 9 (CA9), as a member of the carbonic anhydrase enzyme family, was an endogenous marker of hypoxia. Previous studies suggested CA9 expression was correlated with poor prognosis in multiple types of malignancies. Therefore, this study was to evaluate the role of CA9 in sinonasal squamous cell carcinoma (SNSCC) and to determine whether this biomarker was associated with patient clinicopathologic characteristics and prognosis. MethodsWe assessed 63 patients diagnosed with SNSCC in 2013–2017 who underwent curative surgery. Tumor specimens was immunohistochemically analyzed for CA9 expression. The expression levels of CA9 was evaluated in relation to clinicopathological factors and prognosis. ResultsPositive expression of CA9 was observed in 21 (33.3%) patients and was significantly correlated with local recurrence (p = 0.016), overall survival (OS) (p = 0.003) and disease-free survival (DFS) (p = 0.002). In Cox's multivariate analysis, CA9 expression was an independent negative prognostic factor for OS (p = 0.048) and DFS (p = 0.019). ConclusionsOur findings demonstrated that CA9 overexpression could be used as an independent prognostic biomarker and therapeutic target in SNSCC.

Excessive vitamin B6 during treatment is related to poor prognosis of patients with nasopharyngeal carcinoma: A U-shaped distribution suggests low dose supplement

Several studies explored the association of vitamin B6 intake with the risk of cancers. However, it is unclear whether different doses of vitamin B6 have distinct effects on the prognosis of nasopharyngeal carcinoma (NPC) patients. This study investigated the relationship between different doses of B6 intake and the prognosis of NPC patients. This retrospective cohort analysis included 792 newly diagnosed NPC patients with a median follow-up of 62.05 months. Restricted cubic spline and maximally selected rank statistics were performed to determine the cut-off value of vitamin B6 during treatment (VB6DT). Kaplan-Meier method and log-rank tests were performed to analyze survival outcomes. A multivariable Cox proportional hazard model was performed to determine the independent prognostic factors. NPC patients were divided into three groups according to the cut-off value of VB6DT: non-users (0mg/d), VB6DT>8.6mg/d, and VB6DT≤8.6mg/d. Patients with VB6DT>8.6mg/d had significantly lower 5-year overall survival (OS) (83.5% vs. 90.8%, p=0.006), distant metastasis-free survival (DMFS) (83.5% vs. 91.0%, p=0.004), and progression-free survival (PFS) (73.7% vs. 81.7%, p=0.011) and slightly but not significantly lower 5-year local recurrence-free survival (LRFS) (87.7% vs. 90.7%, p=0.214) than the non-users. Patients with VB6DT≤8.6mg/d had slightly but not significantly better 5-year OS (93.3% vs. 90.8%, p=0.283) than the non-users, while all other primary endpoints were similar (p>0.50). Multivariable analyses confirmed that VB6DT>8.6mg/d was an independent negative prognostic factor of OS (p=0.010), DMFS (p=0.017), and PFS (p=0.030) but not of LRFS (p=0.428). Excessive VB6DT higher than the cut-off value is an independent negative prognostic factor for NPC patients. Additionally, low dose intake improved OS only slightly but not significantly.

Prognostic value of tissue-infiltrating immune cells in tumor microenvironment of follicular lymphoma: A meta-analysis

BackgroundThe follicular lymphoma (FL) microenvironment is composed of follicular dendritic cells (FDCs), tumor-infiltrating CD4/CD8+ T cells (TILs), follicular regulatory T (Treg) cells, lymphoma-associated macrophages (LAMs), and immune checkpoint–related immune cells, all of which are relevant in the prognosis of FL, but their results remain controversial. Therefore, we performed this systematic review to explore the relationship between the FL microenvironment and prognosis. MethodsRelevant studies were identified from PubMed, EMBASE and the Cochrane Library. Twenty-three trials involving 3336 patients with FL were included for analysis. ResultsThis meta-analysis confirmed the unfavorable prognostic role of high CD21+/CD23+ FDC density in overall survival (OS) and progression-free survival (PFS). CD8+ or granzyme B+ TILs instead of CD4+ TILs are indicators for good OS. FoxP3+ Treg cells was not associated with prognosis, and even in subgroup analysis neither the number of cells nor the infiltration pattern had predictive value. A high degree of CD68+ macrophage infiltration was a negative prognostic factor for OS, but was associated with good prognosis in the rituximab-era subgroup. Although there was no correlation between PD1-positive immune cells and prognosis, subtypes with the follicular helper T (TFH) or exhausted T cell (TEX) phenotype tended to influence prognosis. The HR in the short time to transformation (TTT) analyses suggested that high CD68+ LAM numbers, diffuse pattern of FOXP3+ Treg cells and PD1+ cells, and high PD-L1 cell numbers are adverse factors leading to early transformation. ConclusionsMultiple tissue-infiltratingimmune cells in microenvironment play critical and different roles in FL prognosis.

Prognostic value of neuron-specific enolase for small cell lung cancer: a systematic review and meta-analysis

BackgroundNeuron-specific enolase (NSE) has become a widely used and easily attainable laboratory assay of small cell lung cancer (SCLC). However, the prognostic value of NSE for SCLC patients remains controversial. The aim of the study was to evaluate the correlation between elevated serum NSE before therapy and survival of SCLC patients.MethodsWe performed a systematic review and meta-analysis. A systematic literature search was conducted in PubMed, Embase, and the Cochrane Central Register from the inception dates to December 2019. Eligible articles were included according to inclusion and exclusion criteria; then, data extraction and quality assessment were performed. The primary outcome was overall survival (OS), and the secondary endpoint was progression-free survival (PFS).ResultsWe identified 18 studies comprising 2981 patients. Pooled results revealed that elevated NSE was associated with worse OS (HR = 1.78, 95% CI 1.55–2.06, p < 0.001) and PFS (HR = 1.50, 95% CI 1.16–1.93, p = 0.002). In subgroup analysis, elevated NSE did not predict worse OS in patients who received only chemotherapy (HR 1.22, 95% CI 0.96–1.55, p = 0.10) or part of whom received surgical resection before chemotherapy and radiotherapy (HR = 2.16, 95% CI 0.82–5.69, p = 0.12).ConclusionElevated serum NSE before any therapy of SCLC patients may be a negative prognostic factor for OS and PFS. The prognostic value of NSE for OS was particularly observed in patients treated by standard management.

Minimally invasive surgery is feasible after preoperative chemotherapy for stage IV gastric cancer.

AimTo elucidate the safety and feasibility of minimally invasive surgery (MIS) as conversion surgery after chemotherapy for stage IV gastric cancer, we compared the background characteristics and clinical courses of patients who underwent open conversion surgery (open group) versus MIS (MIS group).MethodsWe included 94 consecutive patients with stage IV gastric cancer who received chemotherapy followed by conversion surgery gastric resection from January 2011 to October 2019 at the Osaka International Cancer Institute in this analysis.ResultsThe open group included more patients who had macroscopic peritoneal metastasis and required splenectomy. However, other background characteristics, including preoperative chemotherapy duration, were comparable. The MIS group had significantly longer operative time (266 vs 339 minutes, P = .0039) and less operative blood loss (520 vs 10 mL, P < .0001). The incidence of postoperative complication of Clavien‐Dindo grade II or higher was non‐significantly lower (24.5% vs 9.8%, P = .058) and length of postoperative hospital stay was significantly shorter in the MIS group (12 vs 8 days, P < .0001). Even though the open group included more patients with more advanced (ypT4a or higher, or N3) disease, the MIS group had better recurrence free survival and overall survival (OS). Multivariate analysis revealed that N status (hazard ratio [HR], 4.39; 95% confidence interval [CI], 2.18‐12.26; P < .0001) and T status (2.11; 1.05‐4.36; P = .036) were independent prognostic factors for OS. MIS was not a negative prognostic factor for OS (HR, 0.44; 95% CI, 0.15‐1.10; P = .081).ConclusionMIS can be safely performed as conversion surgery following chemotherapy for stage IV gastric cancer.

Circulating tumor DNA is prognostic and potentially predictive of eryaspase efficacy in patients with advanced pancreatic adenocarcinoma.

4617 Background: Eryaspase is composed of L-asparaginase encapsulated in erythrocytes. It has demonstrated significant efficacy in combination with chemotherapy in a randomized phase 2 trial in second-line in patients with advanced pancreatic adenocarcinoma. We assessed, in this study, the prognostic and predictive value of circulating tumor DNA (ctDNA) in plasma samples of patients included in the eryaspase phase 2 trial. Methods: Samples prospectively collected pre-treatment at each 28-day cycle were centrally analyzed by next-generation sequencing (BPER method). Prognostic values of baseline ctDNA and ctDNA early changes between day 0 and 28 were assessed in both arms combined on objective response rate (ORR), progression free survival (PFS) and overall survival (OS). We conducted interaction test between ctDNA positivity and treatment arm, and the predictive value of ctDNA for eryaspase efficacy was investigated. Results: Patients with at least one available plasma sample have been included (n = 122/141). The presence of ctDNA at baseline was identified in 68% (77/113) of patients and was an independent negative prognostic factor for OS (4.6 vs 8.8 months; p = 0.0025) and PFS (1.6 vs 3.3 months; p = 0.00043). Early change in ctDNA levels was assessed by separating patients into three categories (one without detectable ctDNA, and two according to radio median value between day 0 and day 28) that were significantly correlated with ORR, PFS and OS. A significant interaction was observed between the presence of ctDNA and eryaspase efficacy. In patients with ctDNA detectable at baseline, eryaspase was associated with better PFS (HR = 0.53; 95% CI: 0.3-0.94) and OS (HR = 0.52; 95% CI: 0.29-0.91). Conclusions: We confirm from a prospective randomized trial that 1/ the presence of ctDNA at baseline is a major prognostic factor, 2/ the early change of ctDNA correlates with treatment outcome and 3/ the ctDNA could be a predictive biomarker of eryaspase efficacy. Clinical trial information: NCT02195180 .

CCL2 Expression in Tumor Cells and Tumor-Infiltrating Immune Cells Shows Divergent Prognostic Potential for Bladder Cancer Patients Depending on Lymph Node Stage

Bladder cancer (BCa) is the ninth most commonly diagnosed cancer worldwide. Although there are several well-established molecular and immunological classifications, markers for tumor cells and immune cells that are associated with prognosis are still needed. The chemokine CC motif ligand 2 (CCL2) could be such a marker. We analyzed the expression of CCL2 by immunohistochemistry (IHC) in 168 muscle invasive BCa samples using a tissue microarray. Application of a single cut-off for the staining status of tumor cells (TCs; positive vs. negative) and immune cells (ICs; ≤6% of ICs vs. >6% of ICs) revealed 57 cases (33.9%) and 70 cases (41.7%) with CCL2-positive TCs or ICs, respectively. IHC results were correlated with clinicopathological and survival data. Positive CCL2 staining in TCs was associated with shorter overall survival (OS), disease-specific survival (DSS), and relapse-free survival (RFS) (p = 0.004, p = 0.036, and p = 0.047; log rank test) and appeared to be an independent prognostic factor for OS (RR = 1.70; p = 0.007; multivariate Cox’s regression analysis). In contrast, positive CCL2 staining in the ICs was associated with longer OS, DSS, and RFS (p = 0.032, p = 0.001, and p = 0.001; log rank test) and appeared to be an independent prognostic factor for DSS (RR = 1.77; p = 0.031; multivariate Cox’s regression analysis). Most interestingly, after separating the patients according to their lymph node status (N0 vs. N1+2), CCL2 staining in the ICs was differentially associated with prognosis. In the N0 group, CCL2 positivity in the ICs was a positive independent prognostic factor for OS (RR = 1.99; p = 0.014), DSS (RR = 3.17; p = 0.002), and RFS (RR = 3.10; p = 0.002), whereas in the N1+2 group, CCL2 positivity was a negative independent factor for OS (RR = 3.44; p = 0.019)) and RFS (RR = 4.47; p = 0.010; all multivariate Cox’s regression analyses). In summary, CCL2 positivity in TCs is a negative prognostic factor for OS, and CCL2 can mark ICs that are differentially associated with prognosis depending on the nodal stage of BCa patients. Therefore, CCL2 staining of TCs and ICs is suggested as a prognostic biomarker for BCa patients.

Increased CD44 Expression and MEK Activity Predict Worse Prognosis in Gastric Adenocarcinoma Patients Undergoing Gastrectomy

PurposeWe have shown that activation of the receptor tyrosine kinase (RTK)-RAS pathway in gastric adenocarcinoma (GA) promotes acquisition of cancer stem-like cell (CSC) phenotypes including metastasis and chemotherapy resistance. Here, we evaluated the prognostic value of the CSC marker CD44 and the RTK-RAS activation marker phosphorylated MEK (p-MEK) in patients with resectable GA. MethodsCD44 and p-MEK were measured in tumors from GA patients who underwent curative-intent gastrectomy at Fujian Medical University Union Hospital (FMUUH, n = 134) and Memorial Sloan Kettering Cancer Center (MSKCC, n = 56). Overall survival (OS) was estimated by the Kaplan-Meier method, and multivariate analysis was performed by Cox proportional hazards regression modeling. ResultsDespite multiple significant differences in clinicopathologic characteristics between the FMUUH and MSKCC cohorts, high CD44 and high p-MEK expression were both independent negative prognostic factors for OS on univariate analysis in both cohorts (p < 0.05). Both factors were also significant on multivariate analysis when the cohorts were combined (p ≤ 0.003). On subgroup analysis, the 5-year OS of patients with both high CD44 and high p-MEK was 39.5–41.6% compared with 55.4–66.4% for patients with low CD44. High CD44 expression was associated with more advanced TNM stage in the FMUUH cohort and larger tumor size and undifferentiated histology in the MSKCC cohort. High p-MEK was associated with undifferentiated histology in the FMUUH cohort and larger tumor size in the MSKCC cohort. ConclusionsIncreased CD44 and p-MEK expression are predictive of worse OS in GA patients. Thus, targeting the RTK-RAS pathway may benefit patients with CD44-positive, RAS-activated GA by inhibiting metastasis and reversing chemotherapy resistance.

Treatment outcome and prognostic factors of Korean patients with chronic lymphocytic leukemia: a multicenter retrospective study.

Background/AimsCompared with Western countries, chronic lymphocytic leukemia (CLL) rarely occurs in Asia and has different clinical characteristics. Thus, we aimed to evaluate the clinical characteristics, treatment outcomes, and prognostic significance of Korean patients with CLL.MethodsWe retrospectively analyzed 90 patients with CLL who had received chemotherapy at 6 centers in Korea between 2000 and 2012.ResultsCompared with Western patients with CLL, Korean patients with CLL express lambda (42.0%) and atypical markers such as CD22 and FMC7 (76.7% and 40.0%, respectively) more frequently. First-line chemotherapy regimens included chlorambucil (n = 43), fludarabine and cyclophosphamide (FC) (n = 20), fludarabine (n = 13), rituximab-FC (n = 4). The remaining patients were treated with other various regimens (n = 10). The 5-year overall survival (OS) and progression-free survival (PFS) rates were 79.3% and 28.1%, respectively. Multivariate analyses showed that hyperleukocytosis (≥ 100 × 103/μL), extranodal involvement, and the Binet C stage were significant negative prognostic factors for OS (hazard ratio [HR] 4.75, p = 0.039; HR 21.6, p = 0.002; and HR 4.35, p = 0.034, respectively). Cytogenetic abnormalities including complex karyotypes (≥ 3), del(11q), and del(17) had a significantly adverse impact on both OS and PFS (p < 0.001 and p = 0.010, respectively).ConclusionsInitial hyperleukocytosis, extranodal involvement, complex karyotype, del(17) and del(11q) need to be considered in the risk stratification system for CLL.

Establishment and Validation of a Nomogram for Nasopharyngeal Carcinoma Patients Concerning the Prognostic Effect of Parotid Lymph Node Metastases.

PurposeThe prognosis of nasopharyngeal carcinoma (NPC) patients with parotid lymph node (PLN) metastasis remains unclear. This study was performed to investigate the prognostic significance and optimal staging category of PLN metastasis and develop a nomogram for estimating individual risk. Materials and MethodsClinical data of 7,084 non-metastatic NPC patients were retrospectively reviewed. Overall survival (OS) was the primary endpoint. A nomogram was established based on the Cox proportional hazards regression model. The accuracy and calibration ability of this nomogram was evaluated by C-index and calibration curves with bootstrap validation. ResultTotally, 164/7,084 NPC patients (2.3%) presented with PLNs. Multivariate analyses showed that PLN metastasis was a negative prognostic factor for OS, progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRFS). Patients with PLN metastasis had a worse prognosis than N3 disease. Five independent prognostic factors were included in the nomogram, which showed a C-index of 0.743. The calibration curves for probability of 3- and 5-year OS indicated satisfactory agreement between nomogram-based prediction and actual observation. All results were confirmed in the validation cohort. ConclusionNPC patient with PLN metastasis had poorer survival outcome (OS, PFS, DMFS, and LRFS) than N3 disease. We developed a nomogram to provide individual prediction of OS for patients with PLN metastasis.

Clinical Analysis of 15 Cases of Gallbladder Neuroendocrine Carcinoma and Comparison with Gallbladder Adenocarcinoma Using a Propensity Score Matching.

PurposeThis study aimed to investigate the clinicopathological features and prognosis of gallbladder neuroendocrine carcinoma (GB-NEC).Patients and MethodsFifteen patients with GB-NEC and 171 patients with gallbladder adenocarcinoma (GB-ADC) treated in two tertiary medical centers between 2009 and 2015 were included. The clinicopathological features and prognostic risk factors of GB-NEC were analyzed retrospectively. A propensity score matching in a 1:2 ratio was used to compare the prognosis of GB-NEC and GB-ADC.ResultsFor patients with GB-NEC, the median age of patients was 58.4 years (range 26–75), with a M:F ratio of 7:8. Based on 2010 WHO classification, ten cases were pathologically confirmed as NECs and five cases as MANECs. For TNM staging, eleven patients were stage III or above; while for Nevin staging, seven patients were stage IV or above. The 1-, 2-, and 3-year overall survival (OS) of GB-NEC were 60.0%, 38.8% and 31.1%, respectively, and the median survival time was 20.4 months. Patients with lymph node metastasis had significantly shorter survival than those without (OS: 10.4 vs 26.0 months, p<0.05). Accordingly, patients of Nevin stage III had better OS than those of Nevin stage IV (p<0.05), but other potential risk factors including gender, age, clinical symptoms, TNM stage, histopathologic subtype and treatment showed no significance. After the propensity score matching, the baseline variables had no significant difference between 15 patients with GB-NEC and 30 patients with GB-ADC, survival analysis showed GB-NEC had worse prognosis (3-year overall survival rate: 31.1% vs 63.8%, p<0.01).ConclusionNevin staging helps classify patients of GB-NEC with different prognosis and the lymph node metastasis is a strong negative prognostic factor for OS. The propensity score analysis revealed even with the similar stage and treatment, GB-NEC still had worse OS than GB-ADC.

High Preoperative Plasma Fibrinogen Independently Predicts a Poor Prognosis in Patients with Nonmetastatic RCC.

Background: This study aims to determine the relationship between preoperative plasma fibrinogen levels and the prognosis of patients with nonmetastatic renal cell carcinoma (RCC), including overall survival (OS), cancer-specific survival (CSS) and progression-free survival (PFS).Methods: We retrospectively analysed the clinical data and prognostic information of 1194 nonmetastatic RCC patients who received radical nephrectomy or nephron-sparing surgery between 2005 and 2015 at our institution. Serum was collected for fibrinogen detection in the week prior to curative operation, and prognostic information was regularly collected by specially trained personnel. The cut-off value of the preoperative plasma fibrinogen level was defined by receiver operating characteristic (ROC) analysis. The chi-square test was used to analyse the association between preoperative fibrinogen level and clinical characteristics. Kaplan-Meier analysis was used to calculate survival curves, and significant differences were determined by the log-rank test. Other significant prognostic factors were evaluated by the Cox multivariate proportional hazard model.Results: The median follow-up period after radical or partial nephrectomy was 42.4 months (ranging from 0.433 to 146.37 months). The optimal preoperative plasma fibrinogen concentration was 3.975 g/L. The preoperative fibrinogen level was significantly associated with age, pathological T stage, sarcomatoid differentiation, necrosis and vein tumour thrombus (all p<0.05). High plasma fibrinogen levels were related to poor prognosis in terms of OS (p<0.001), CSS (p<0.001) and PFS (p<0.001). Multivariate analysis showed that the preoperative fibrinogen level remained an independent prognostic factor for OS (HR: 3.22, 95%CI: 1.87-5.55, p<0.001), CSS (HR: 4.12, 95%: 2.15-7.89, p<0.001) and PFS (HR: 3.137, 95%CI: 2.17-4.53, p<0.001).Conclusions: High preoperative plasma fibrinogen level is an independent negative prognostic factor for OS, CSS and PFS in patients with non-metastatic RCC. Preoperative plasma fibrinogen could be an ideal indicator for evaluating the outcomes of postoperative patients with nonmetastatic RCC.

Skeletal muscle mass is an imaging biomarker for decreased survival in patients with oropharyngeal squamous cell carcinoma.

Low skeletal muscle mass (SMM) and sarcopenic obesity (co-presence of low SMM and obesity) are emerging prognosticators in oncology, but the prevalence and prognostic value in oropharyngeal squamous cell carcinoma (OPSCC) is not yet known. Patients with OPSCC, curative treatment intention and pre-treatment diagnostic imaging of the head and neck area were included. Patients with unknown HPV-status, palliative treatment intention or unavailable imaging were excluded, Relevant demographic and clinical characteristics were collected between 2009 and 2016. Patients were stratified into a low-, intermediate-, and high-risk group according to HPV-status, amount of pack-years, tumor and nodal stage. SMM was radiologically measured and cutoff values were determined by optimal stratification. The prognostic value of low SMM and sarcopenic obesity for overall survival (OS) and disease-free survival (DFS) was determined by Cox regression analysis and Kaplan Meier survival curves. In 216 patients, low SMM and sarcopenic obesity were present in 140 (64.8%) and 13 (6.0%) patients, respectively. On multivariate analysis, stratification into a high-risk group (HPV-negative status with ≥10-pack-years or T4-stage) was a prognostic factor for OS and DFS (HR 2.93, p<0.01) (HR 4.66, p<0.01). Of specific interest, sarcopenic obesity was a strong negative prognostic factor for OS and DFS (HR 4.42, p<0.01 and (HR 3.90, p<0.05), independent from other well-known prognostic factors such as HPV-status. Low skeletal muscle mass is highly prevalent in OPSCC patients. Sarcopenic obesity is a novel pretreatment prognosticator for OS and DFS in OPSCC and should therefore be considered in clinical decision making.

Clinical Significance of Additional Cytogenetic Abnormalities (ACA) at Disease Progression in Patients with High-Risk Myelodysplastic Syndrome (MDS) Treated with Azacitidine

Background: Although cytogenetic abnormalities at diagnosis are recognized as one of the most important prognostic factors in MDS patients, their cytogenetic findings are not stable and ACA are sometimes acquired in their clinical courses. We recently described that ACA acquisition at relapse was found in 40% and associated with the lower second complete remission (CR) rate and the inferior overall survival (OS) rate in adult patients with acute myeloid leukemia (AML) and Philadelphia chromosome-negative acute lymphoblastic leukemia (Ph-negative ALL). However, this clinical impact of ACA acquisition has not been elucidated in high-risk MDS patients during azacitidine treatment. So, we conducted this retrospective study to address this unsolved issue. Patients and methods: Of the 63 patients who were diagnosed as high-risk MDS according to French-American-British classification and were treated with azacitidine between 2012 and 2019, 34 whose cytogenetic data both at diagnosis and disease progression were available were included in this study. Treatment response to azacitidine was evaluated based on international working group response criteria for myelodysplasia. Cytogenetic changes between the time of diagnosis and disease progression were classified into four groups: (1) no change, (2) ACA was acquired at time of disease progression, (3) cytogenetic abnormalities observed at diagnosis were reduced or had disappeared at the time of disease progression, and (4) cytogenetic abnormalities observed at diagnosis were reduced or had disappeared, and completely different ACA was acquired at the time of disease progression. In this study, groups 2 and 4 were defined as those with ACA acquisition. OS was defined as the interval from the date of disease progression to the date of death. Fisher's exact test was used to compare binary variables. OS was estimated with the Kaplan-Meier method and compared using the log-rank test. The Cox proportional hazard model was used for multivariate analysis of prognostic factors. The potential factors evaluated in this analysis were age, gender, blast count in bone marrow (&lt; or =&gt; 10%), karyotype (complex or not), revised international prognostic scoring sysytem (high/high-intermediate or not), and response to azacitidine (CR/partial remission or not). Values of p &lt; 0.05 were considered to indicate statistical significance. Results: Of the 34 patients included in this study, 25 were male and 9 were female, and the median age was 66 years (range, 38-78 years). According to the definition described above regarding cytogenetic changes between the time of diagnosis and disease progression, 11 (32%), 14 (41%), 0 (0%), and 9 (26%) patients were categorized into group 1, 2, 3, and 4, respectively; thus, 23 patients (67%) acquired ACA at disease progression with a higher incidence in comparison with that of AML and Ph-negative ALL patients. In univariate analysis, only complex karyotype at treatment initiation was extracted as a significant predisposing factor for ACA acquisition at disease progression (100% vs. 47.6%, respectively; p = 0.002). Among 14 patients (nine and five in patients with and without ACA acquisition, respectively) received chemotherapy after disease progression, only two (14.3%) achieved CR (one and one, respectively). Although the OS rates after disease progression were not significantly different between patients with and without ACA acquisition (19.3% vs. 32.0% at one year, respectively; p = 0.256), in multivariate analysis, only ACA acquisition was identified as a negative prognostic factor of OS after disease progression (hazard ratio: 3.21, p = 0.043). Conclusion: These findings suggested that ACA acquisition at disease progression is frequently observed in high-risk MDS patients treated with azacitidine, especially in those harboring complex karyotype, and is associated with poor prognosis even after azacitidine failure, just like AML and Ph-negative ALL. As clinical impacts of ACA acquisition are common among multiple hematologic malignancies, to clarify the biological basis of ACA acquisition might contribute to the development of novel therapeutic strategies. Disclosures Handa: Ono: Research Funding.

Analysis of Perioperative Platelet Indices and Their Prognostic Value in Head and Neck Cancer Patients Treated with Surgery and Postoperative Radiotherapy: A Retrospective Cohort Study.

Objectives: Activated platelets might play an important role in tumor progression. Mean platelet volume (MPV) has been used as a surrogate marker for platelet activation, and therefore its value as a marker of tumor prognosis has attracted recent attention. In this study, we aimed to critically evaluate the prognostic significance of the perioperative platelet count (COP), MPV and the MPV/COP ratio in head and neck cancer patients. Additionally, we explored the individual postoperative trajectory of these indices and their association with overall survival (OS) and disease-free survival (DFS). Methods: We retrospectively evaluated 122 head and neck squamous cell carcinoma patients receiving surgery with curative intent followed by postoperative radiotherapy. Platelet indices were measured preoperatively and on days 1 and 7 postoperatively. OS and DFS were analyzed using Kaplan–Meier estimators, the log-rank test and uni and multivariable Cox models. Cutoffs to dichotomize patients for Kaplan–Meier curves and log-rank tests were empirically chosen at the respective median. The median follow-up was 8.8 years. Results: The adjusted preoperative COP, MPV and MPV/COP ratio were not associated with disease outcome. A low postoperative COP and a high MPV/COP ratio on the first postoperative day were independently associated with worse OS and DFS. In comparison to the preoperative measurements, patients whose COP increased by day 1 post-op showed a better OS (hazard ratio (HR) per 50 G/L increase: 0.73, 95% confidence interval (CI): 0.58–0.93, p = 0.013) and DFS (HR per 50 G/L increase: 0.74, 95% CI: 0.58–0.94, p = 0.018) in multivariable analysis. Conclusions: Our results suggest that a low postoperative COP and a high MPV/COP ratio represent a negative prognostic factor for OS and DFS. Notably, patients with an increase in COP by day 1 post-op when compared to their preoperative value showed a significantly better OS and DFS.

557P - Loss of CDX-2 expression is an independent poor prognostic biomarker in colorectal cancer

BackgroundLoss of caudal-type homeobox transcription factor-2 (CDX-2) expression in colorectal cancers (CRC) has recently been proposed as a predictive biomarker for response to chemotherapy and also prognosis. However, the data on relationship between alterations in CDX-2 expression and clinicopathological variables remain limited. We herein aimed to investigate the clinicopathological factors and prognostic implications associated with loss of CDX-2 expression in CRC patients. MethodsImmunohistochemistry for CDX-2 expression was performed on formalin-fixed, paraffin-embedded tissue samples from 427 patients with CRC. Correlation between CDX-2 expression and clinicopathological characteristics were evaluated. Univariate and multivariate survival analyses were performed to reveal the prognostic value of loss of CDX-2 expression. ResultsOf 427 patients, 85% were stage I-III. Seventy six percent had left-sided primary tumors. Deficient mismatch repair (dMMR) was found in 12%. CDX-2-negative expression was identified in 18 out of 427 (4.2%) patients. Loss of CDX-2 expression was more commonly found in patient with right-sided tumors rather than left-sided tumors (9.4% vs 2.8% respectively, p=0.005) and dMMR compared to proficient MMR (11.5% vs 3.3% respectively, p=0.006). There was no association between CDX-2 expression and sex, stage, histologic subtype, tumor differentiation and lymphovascular/perineural invasion. By univariate analysis, patients with CDX-2 loss of expression had significantly worse overall survival (OS) and disease free survival (DFS) than those with CDX-2 positive expression (median OS 1.6 vs 11.6 months (mo), p<0.001; median DFS 1.33mo vs NR, p=0.003). By multivariate analysis, loss of CDX-2 expression remained a negative prognostic factor for OS (hazard ratio 2.32; 95%CI 1.25-4.28, p=0.007). ConclusionsLoss of CDX-2 expression was associated with right-sided tumor and dMMR status. Moreover, loss of CDX-2 expression is a poor prognostic factor for OS, even among patients with dMMR tumors. Legal entity responsible for the studyThe authors. FundingFaculty of Medicine Siriraj Hospital. DisclosureAll authors have declared no conflicts of interest.