Adverse Prognostic Indicator Research Articles

Rare triple-negative breast cancers (TNBC): An NCDB analysis.

e19253 Background: The literature on rare triple negative breast cancer (TNBC) histology types is sparse; herein we present the clinical demographic and treatment patterns as well as overall survival (OS) for rare (< 10%) types of breast cancers that typically present as TNBCs: Medullary carcinoma (MedC), Adenoid cystic carcinoma (ACC), and Metaplastic breast cancer (MetC). Methods: Records of patients with a confirmed diagnosis of MedC, ACC, and MetC between 2010 and 2016 in the National Cancer Database (NCDB) were analyzed. Patients with an unknown stage were excluded. Univariate analyses and multivariable Cox-regression models were performed in SAS v. 9.4. Results: A total of 8,479 records were analyzed. MetC was the most commonly diagnosed histologic type in our cohort with 6,867 (81%) patients versus 255 (3.0%) MedC patients and 1,357 (16%) ACC patients. MedC presented earlier in life, with a median age of 53 years versus 62 years for ACC patients, and 63 years for MetC patients. The proportion of TNBC varied by histology type for MedC (70.4%), ACC (77.0%), and MetC (79.0 %). Patients with ACC were less likely to receive radiotherapy (52.4%) and chemotherapy (12.9%) compared to MedC (61.2%, 74.5%) and MetC (49.7%, 68.6%) respectively. On Cox multivariate regression, age ≥60 (HR 4.7), stage ≥3 [compared to patients with stage 0&1] (HR 5.7), and not receiving radiotherapy (HR 2.0) or chemotherapy (HR 1.25) conferred worse overall survival for MedC. Similarly, among patients with ACC, age ≥60 (HR 3.5), stage ≥3 (HR 5.3), and lymph node involvement (HR 4.8) were adverse prognostic indicators as well as not receiving radiation therapy (HR 1.47). Among MetC, lung metastasis (HR 2.6), stage ≥3 (HR 4.5), but also not receiving chemotherapy (HR 1.8) or radiation therapy (HR 1.47) was associated with worse survival outcomes. All p-values for cox regression is <0.0001. The 5-year OS was 92.6% for patients with MedC, 92.0% for ACC patients, 69.3% for MetC patients; all p-values <0.0001. Conclusions: This analysis describes rare types of TNBCs: MedC (most common), ACC, and MetC. We noted heterogeneity among these 3 rare types of TNBC, with the worst 5-year OS noted for MetC. Poor prognostic factors for MetC include advanced stage, lung metastasis, older age, and not receiving chemotherapy or radiation therapy. Future research focusing on rare subtypes of breast cancer is desirable and would potentially inform the optimal management of these breast carcinomas.

Predictors of Renal Complications in Children With Hematotoxic Snakebite

To study the predictors of renal complications following hematotoxic snakebite in children. This comparative study was conducted in the pediatric ward of a tertiary-care centre among 364 consecutively children admitted with hematotoxic snakebite between January 2016 and December 2017. Clinical and laboratory indicators were compared between children who developed acute kidney injury and those who did not. Acute kidney injury was seen in 139 children (38.2%), majority being stage 2 (55, 39.5%). 59 children (16.2%) developed permanent renal damage and 16 (4.4%) died due to envenomation. Acute tubular necrosis was the most common (25, 39.1%) histopathological change. Receiving anti-snake venom more than one hour after bite was the most significant adverse prognostic indicator, both for renal complications and mortality.

Influence of Hyperglycemia on Treatment Outcomes of Oral Cavity Squamous Cell Carcinoma

The present study investigated the association between perioperative hyperglycemia and the treatment and survival outcomes of patients with oral cavity squamous cell carcinoma (OSCC). From 2004 to 2016, 385 patients with OSCC were enrolled and stratified into normoglycemic (<180mg/dL) and hyperglycemic (≥180mg/dL) groups. The clinicopathologic characteristics and treatment outcomes of OSCC were subsequently analyzed. Of the 385 patients, 61 (15.8%) were in the hyperglycemic group. Hyperglycemia was significantly associated with pT stage, pN stage, overall pathologic stage, extranodal extension, albumin level, and tumor depth (P=.004, P=.042, P=.008, P=.001, P=.004, and P=.011, respectively). Patients with hyperglycemia also required a longer hospital stay (P=.003). The 5-year overall survival and disease-specific survival were poorer in the hyperglycemic group than in the normoglycemic group (P=.001 and P=.002, respectively). Multivariate analysis revealed that hyperglycemia is a significant adverse prognostic indicator for OSCC (hazard ratio, 1.709; 95% confidence interval, 1.003 to 2.912; P=.049). Hyperglycemia is associated with more advanced disease and poorer survival rates in patients with OSCC. It correlates with adverse clinicopathologic characteristics and longer hospital stay. Screening for hyperglycemia and maintenance of normal glycemic status during the treatment course is imperative in the treatment of OSCC.

Efficacy and safety of 225Ac-PSMA-617 targeted alpha therapy in metastatic castration-resistant Prostate Cancer patients.

Rationale: Despite the success of several standards of care treatment options in metastatic castration-resistant prostate cancer (mCRPC), a significant number of patients attain therapeutic resistance and eventually develop disease progression. Managing these patients are currently challenging. Hence, there is an unmet need for further efficient therapeutic options that induce anti-tumor activity and improve survival. The objective of this study was to assess the safety and therapeutic efficacy of 225Ac-PSMA-617 targeted alpha therapy (TAT) in mCRPC patients in real-world conditions.Methods: In this prospective study, we recruited patients with mCRPC who either were refractory to 177Lu-PSMA-617 radioligand therapy (RLT) or did not receive previous 177Lu-PSMA-617 RLT. Patients were treated with 225Ac-PSMA-617 TAT (100 KBq/Kg body weight) at 8-weekly intervals. The primary endpoint included the assessment of biochemical response by measuring the serum prostate-specific antigen (PSA) response rate as per the prostate cancer working group criteria (PCWG3). Secondary endpoints comprised the estimation of overall survival (OS), progression-free survival (PFS), molecular tumor response assessment (PERCIST 1 criteria), disease control rate (DCR), toxicity according to CTCAE v5.0, and clinical response evaluation.Results: A total of 28 patients were recruited for this cohort study among whom 15 (54%) received prior 177Lu-PSMA-617 RLT and the remaining 13 (46%) patients were 177Lu-PSMA-617 RLT naïve. The mean age was 69.7 years (range: 46-87 years). All patients, except one, had extensive skeletal metastases on baseline 68Ga-PSMA-11 PET/CT scan; one patient had lymph node dominant disease and advanced primary prostatic tumor. The mean activity administered was 26.5 ± 12 MBq (range: 9.25 - 62.9 MBq) [715.5 ± 327 µCi, range: 250 - 1700 µCi] with a median of 3 cycles (range: 1 - 7 cycles). At 8th week of post first cycle of 225Ac-PSMA-617 therapy (initial follow-up) and the end of the follow-up, >50% decline in PSA was observed in 25% and 39%, respectively. The median PFS and OS were 12 months (95% CI: 9 - 13 months) and 17 months (95% CI: 16 months - upper limit not reached), respectively. Molecular tumor response by PERCIST 1 criteria could be conducted in 22/28 (78.6%) patients, which revealed complete response in 2/22 (9%), partial response in 10/22 (45.4%) patients, 2/22 (9%) with stable disease, and 8/22 (36%) with progressive diseases. The disease control rate, according to the biochemical and molecular tumor response criteria, was 82% and 63.6%, respectively. Multivariate analysis revealed PSA progression as adverse prognostic indicator of OS, and any PSA decline as a good prognostic indicator of PFS. There was no Grade III/IV toxicity noted in this series. The most common side-effect was transient fatigue (50%) followed by grade I/II xerostomia (29%).Conclusion: 225Ac-PSMA-617 TAT showed promising disease control rate, even when all other therapeutic options were exhausted, with low treatment-related toxicities.

Clinical outcome of whole‐body gamma‐knife combined with pemetrexed concurrent chemoradiotherapy in elderly patients with locally advanced lung adenocarcinoma

AbstractObjectiveCurrently, concurrent chemoradiotherapy has become the standard treatment for locally advanced non‐small cell lung cancer, but it is often difficult for elderly patients to tolerate. In this study, we evaluated the curative effect, acute radiation reaction, and clinical application of stereotactic radiotherapy with whole‐body gamma‐knife combined with pemetrexed treatment in elderly patients with locally advanced lung adenocarcinoma.MethodsA total of 37 elderly patients with lung adenocarcinoma from Hubei Provincial Armed Police Corps Hospital from 2 January 2013 to 30 December 2015, who were treated with stereotactic radiotherapy with super‐gamma‐knife, were included in the study. The radiotherapy plan was made according to the patient's physical condition, tumor location and size, and therapeutic purpose. A dose of 3.5–5 Gy was administered by 50–70% isodose curve, with a total dose range of peripheral irradiation 35–45 Gy. In the same period, pemetrexed was administered at 500 mg/m2, the first day of chemotherapy (d1), intravenous drip, with 21 days as one cycle, and the number of cycles was more than two.ResultsThe median follow‐up duration was 18 months, and the 1‐, 2‐, and 3‐year follow‐up rates were 86.49% (32/37), 59.46% (33/37), and 21.62% (8/37), respectively. There were no missing cases. After 2–3 months of treatment, computed tomography showed that 13 patients (35.14%) had complete remission, 22 patients (59.46%) had partial remission, one patient (2.70%) achieved a stable status, and one patient (2.70%) still had progression, and the total response rate was 94.59%. The 1‐year local control rate was 67.57%. The 1‐, 2‐, and 3‐year overall survival rates were 86.49%, 45.45%, and 25.00%, respectively. The median overall survival time was 17.0 months (95% CI 14.5–21.3 months); the progression‐free survival time was 12.0 months (95% CI 11.6–12.8 months). Multivariate analysis showed that lymph node stage N ≥2 and radiotherapy biological effective dose &lt;60 Gy were the adverse prognostic indicators of overall survival (P = 0.016 and P = 0.032, respectively). The 1‐year local control rate and median survival time were 62.50% and 71.43%, and 19 and 17 months in the gross tumor volume ≥120 cm3 subgroup and gross tumor volume &lt;120 cm3 subgroup, respectively. There was no significant statistical difference (P = 0.061 and P = 0.400, respectively). The incidence rates of grade 3–4 neutropenia and thrombocytopenia were 10.81% (4/37) and 5.41% (2/37), respectively, during the period of concurrent chemoradiotherapy. The incidence of grade 2 radiation‐induced pneumonitis and esophagitis was 13.51% and 16.22%, respectively. No grade &gt;2 acute or late lung and esophagus toxicity was observed.ConclusionsIn elderly patients with lung adenocarcinoma, stereotactic body radiotherapy with super‐gamma‐knife combined with pemetrexed treatment is safe and definitive, with mild adverse effects.

The Predictive Value of Pre-/Postneoadjuvant Chemoradiotherapy MRI Characteristics for Patient Outcomes in Locally Advanced Rectal Cancer

This study aimed to investigate the predictive value of pre-/postneoadjuvant chemoradiotherapy (nCRT) magnetic resonance imaging (MRI) characteristics for the long-term survival outcomes in patients with locally advanced rectal cancer (LARC). We retrospectively evaluated pre- and post-nCRT MRI and clinicopathologic characteristics of LARC patients. The 3-year disease-free survival (DFS) was estimated using the Kaplan-Meier product-limit method. Associations between MRI variabilities and survival outcomes were assessed using Cox proportional hazards model. In total, 171 LARC patients (112 men and 59 women) with a median age of 55 years (range, 27-82 years) treated with nCRT were evaluated. The median follow-up was 47.6 months, and the 3-, 4-, and 5-year DFS in the overall cohort was 76.6%, 74.5%, and 73.7%, respectively. MRI assessment of extramural venous invasion (mrEMVI) positivity was a significant independent adverse factor of long-term survival (hazard ratio [HR] = 2.589, 95% confidence interval [CI] = 1.398-4.794, p = 0.002) on multivariate analysis. Patients with positive mrEMVI had significantly lower 3-year DFS than those with negative mrEMVI (52.6 months vs 65.1 months; p = 0.003). Moreover, the tumor regression grade on MRI (mrTRG) also significantly correlated with survival outcomes in patients with LARC. Patients with partial response on post-nCRT MRI (mrPR) showed short DFS than those with complete response (mrCR; HR = 4.914, 95% CI = 1.176-20.533, p = 0.029). The 3-year DFS of mrCR and mrPR patients were 74.3 months and 58.9 months, respectively (p = 0.011). The pre-/post-nCRT MRI characteristics may be used to long-term survival stratification in LARC patients. mrEMVI positivity was an independent adverse prognostic indicator for 3-year DFS. Further, mrTRG may also be a predictive factor for the prognosis of LARC patients. The pre-/post-nCRT MR imaging may offer more information for providing individualized treatment.

C-Reactive Protein to Albumin Ratio in Colorectal Cancer: A Meta-Analysis of Prognostic Value.

Background:The relationship between pretreatment C-reactive protein to albumin ratio (CAR) and colorectal cancer (CRC) prognosis has been extensively studied in various tumors. However, little is known on CAR and its association with prognosis in CRC. This study aims to investigate the prognostic value of pretreatment CAR in CRC.Methods:We conducted a systematic search of MEDLINE, EMBASE, and Cochrane Library databases for eligible studies evaluating the associations of CAR with survival and/or clinicopathology of CRC. Overall survival (OS), disease-free survival (DFS), relapse-free survival (RFS), and clinicopathological features were synthesized and compared.Results:Nine studies including 3431 patients were analyzed in this meta-analysis. Pooled results showed that elevated pretreatment CAR was associated with poor OS (pooled hazards ratio [HR]: 2.18, 95% confidence interval [CI]: 1.70-2.78, P < .001) and DFS/RFS (pooled HR: 2.36, 95% CI: 1.40-3.98, P < .001). Moreover, elevated pretreatment CARs were correlated with male patients, large tumor diameter, late III-IV tumor node metastasis stage tumors, high serum carcinoembryonic antigen and carbohydrate antigen 19-9, and presence of lymphatic invasion and venous invasion.Conclusion:Elevated pretreatment CAR could be an adverse prognostic indicator in patients with CRC.

Serum γ-Glutamyltransferase as a Prognostic Biomarker in Metastatic Castration-resistant Prostate Cancer Treated With Enzalutamide.

Serum γ-glutamyltransferase (GGT) is reportedly associated with survival and therapeutic response in various malignancies; however, as far as we are aware its impact on metastatic castration-resistant prostate cancer (mCRPC) has never been assessed. Fifty consecutive men with mCRPC receiving enzalutamide at a single cancer center were retrospectively evaluated. The primary endpoint was overall survival (OS) and the secondary endpoints were prostate-specific antigen (PSA) response, maximal PSA change, and PSA progression-free survival (PSA-PFS). Multivariable analysis demonstrated that elevation of GGT (≥40 U/l) was significantly and independently associated with shorter OS (hazard ratio(HR)=3.61; p=0.004), as were lower hemoglobin (HR=6.04; p<0.001) and higher PSA (HR=4.38; p=0.009). Elevated GGT was also associated with poorer PSA response, maximal PSA change, and shorter PSA-PFS. Elevated GGT was an adverse prognostic indicator in men with mCRPC receiving enzalutamide. External validations would improve the generality of our findings.

Does race predict survival for women with invasive breast cancer?

Black women with breast cancer have lower survival rates and higher recurrence rates in comparison with white women. This study compared treatment and survival outcomes for black and white women at a highly specialized tertiary care cancer center. An institutional review board-approved, retrospective institutional database review was performed to identify all black women treated for invasive breast cancer between 2005 and 2010. Women with a prior history of breast cancer, stage IV cancer, or bilateral breast cancer were excluded. White women had similar exclusion criteria applied and were then matched to black women 1:1 by age and diagnosis year. Clinicopathologic and treatment variables were compared by race. Kaplan-Meier methodology was used to estimate overall survival (OS) and disease-free survival (DFS); a multivariable analysis was conducted with Cox regression models. The study group consisted of 1332 women (666 black). The median tumor size was larger in black women (1.6 vs 1.3cm; P<.001). Black women had more nodal disease (41.1% vs 32%; P<.001) and had tumors that were more frequently an estrogen receptor-negative (32.9% vs 15%; P<.001), progesterone receptor-negative (47.1% vs 30.2%; P<.001), or triple-negative (TN) subtype (24% vs 8.9%; P<.001) in comparison with white women. Black women also had inferior DFS and OS; race was not an independent prognostic indicator in the multivariable analysis. Black women had more advanced disease and adverse prognostic indicators at diagnosis, but race was not an independent predictor of outcome. Black women were significantly more likely to have TN breast cancer. Further research is necessary to understand the differences in tumor biology associated with race.

Tracheo-bronchial adenoid cystic carcinoma: A retrospective study.

Adenoid cystic carcinoma (ACC) of the trachea and bronchus is rare, representing 1% of all respiratory tract cancers. We presented our experiences in treating tracheal-bronchial ACC and the results of long-term surveillance. We conducted a retrospective study of treating tracheo-bronchial ACC. From 2009 to 2014, 42 patients presented to our department. All of them received surgical resection andadjunctive therapy. R0 resections were achieved in 33 patients, whereas 15 patients whose lesions spread outside the tracheo-bronchial lumens. Nine patients had R1 resections followed by radiation and chemotherapy. The 5 year survival rate of R1 resection group showed no difference compared to the R0 resection group, but the 5 year disease-free survival rate showed difference in extra-lumenal invasion (ELI) and non-ELI group (P=0.0357<0.05), although no difference was seen in the overall survival rate in these two groups. ACC of the trachea and bronchus is a rare and low-to-moderate grademalignant tumor. When the R0 resection is over risky or may cause mortal complication, the R1 resection with adjunctive therapy is acceptable for patients to obtain a promising prognosis, whereas pathological ELI is an adverse prognostic indicator.

Prognostic significance of nuclear Yes-associated protein 1 in patients with nonsmall cell lung cancer: A systematic review and meta-analysis.

Background:Nuclear Yes-associated protein 1 (YAP1) has often been regarded as an adverse prognostic indicator in various tumors. Recent studies have associated YAP1 with unfavorable prognosis in nonsmall cell lung cancer (NSCLC). However, due to small sample sizes, the prognostic value of nuclear YAP1 in NSCLC patients is not well understood. In the present study, we evaluated the prognostic role of nuclear YAP1 in NSCLC patients via a systematic review and meta-analysis.Methods:We searched the PubMed, EMBASE, Cochrane, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang Databases for papers investigating the prognostic significance of nuclear YAP1 expression in NSCLC patients. Hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were calculated with reference to overall survival (OS) and progression-free survival (PFS) of NSCLC patients to provide synthesized estimates of the effects of nuclear YAP1 expression.Results:Among 414 cases, higher nuclear YAP1 expression presented as a predictive factor of poorer OS (HR = 1.52; 95% CI: 1.11–2.08; P = .01; I2 = 0.0%) and decreased PFS (HR = 2.11; 95% CI: 1.52–2.93; P < .001; I2 = 44.2%) in NSCLC patients. Subgroup analysis revealed shortened OS (HR = 1.63; 95% CI: 1.14–2.34; P = .007; I2 = 0.0%) and worse PFS (HR = 2.25; 95% CI: 1.53–3.30; P < .001; I2 = 0.0%) in patients from Asia with higher nuclear YAP1 expression. Prognosis was also worse in patients with III–IV stage cancer (PFSHR = 2.09; 95% CI: 1.45–3.01; P < .001; I2 = 58.1%) and in patients treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) (OS HR = 1.59; 95% CI: 1.00–2.51; P = .048; I2 = 15.5%, and PFS HR = 2.35, 95% CI: 1.62–3.42; P < .001; I2 = 0.0%).Conclusion:High expression of nuclear YAP1 was associated with shorter survival outcome in patients with NSCLC.

Liver resection for ruptured hepatocellular carcinoma – a propensity matched analysis

Background: Ruptured hepatocellular carcinoma (HCC) are considered to have worse prognosis compared to non-ruptured. Factors implicated include advanced disease, cirrhosis and peritoneal seeding. We aimed to assess the effect of rupture as a potential adverse prognostic indicator among patients with HCC that undergo resection. Methods: Retrospective observational study among HCC patients that underwent resection in a single UK center between 2005 and 2015. Patients with ruptured HCC (group A) were matched with non-ruptured HCC (group B) using a propensity score. Covariates included age, cirrhosis, size, multifocality, vascular invasion, extrahepatic disease, AFP, background liver function and type of resection. Results: Fifteen subjects in group A (7 female, mean age: 56.9) underwent hepatectomy (7 major hepatectomy, 8 minor) and were matched with an equal number from group B. Mean follow up for group A was 45 and for group B 39 months. 27% of patients had moderate fibrosis, 23% severe fibrosis and 13% had cirrhosis confirmed by histology. The 3-year and 5-year survival for ruptured and non-ruptured HCC were 83% and 59% vs. 84% and 84%, respectively for group A and B. There was no difference in the overall survival (78.3 vs 99 months, p= 0.347) or disease-free survival (60.8 vs 38.4 months, p= 0.397) between the two groups. Conclusion: In this propensity-matched comparative study, rupture was not found to be a prognostic factor for patients with HCC who underwent liver resection.

The Novel Berbamine Derivative, Cbbm, Downregulates c-Myc to Block Diffuse Large B-Cell Lymphoma Cell Maintenance

▪Diffuse large B-cell lymphoma (DLBCL), is one of the most common lymphoma subtypes worldwide, and represents 30% of non-Hodgkin lymphoma (NHL). The current DLBCL chemotherapy R-CHOP regimen is limited by lack of specificity and toxicity to normal hematopoietic cells. Identification of a targeted therapeutic approach is an unmet need for the disease. Through translocations, amplifications or overexpression, c-Myc is dysregulated in many human cancers, including DLBCL. Aberrant overexpression of c-Myc promotes tumorigenesis by activating target genes critical for cell proliferation/survival. In our preliminary study, c-Myc protein levels in 119 cases of newly diagnosed DLBCL were evaluated by immunohistochemistry. We found that c-Myc levels were evident (>30% positive cells) in 40.52% (47/116) and high (>80% positive cells) in 6.90% (8/116) of patients. We also observed that relative to c-Myc negative cases, c-Myc positive cases (>30% positive cells) were associated with adverse prognostic indicators including high international prognostic index (IPI) score (≥60 years old group) (p=0.033), high Ki-67 index (p=0.002), high central nervous system involvement (p=0.003) and low complete response rate (p=0.028), confirming that c-Myc plays a critical role in DLBCL pathogenesis.Currently, c-Myc is considered to be an “undrugable” oncoprotein. Chemotherapeutic agents do not affect c-Myc activity. Our previous work in T-cell lymphoma (Cancer Cell, 32:115-128) demonstrated that berbamine, a natural bis-benzylisoquinoline alkaloid, effectively reduced N-Methyl-N-Nitrosourea (MNU)-induced lymphoma burden by disrupting the Ca 2+ /calmodulin-dependent protein kinase II (CaMKII)γ/c-Myc axis. We also showed that CaMKIIγ stabilizes c-Myc by phosphorylating it at the serine 62 residue (Ser62). We created the berbamine derivative 4-chlorobenzoyl berbamine (CBBM) (Fig.1), and evaluated its efficacy in vitro using DLBCL cell lines (n=5) which expressed high levels of c-Myc. The IC50 of CBBM was an order of magnitude lower than that of berbamine across a panel of DLBCL cell lines: the IC50 (μmol/L) of CBBM vs. berbamine in these cells were OCI-Ly3 (1.39±0.04 vs 12.20±0.71), OCI-Ly10 (2.56±0.04 vs 23.66±0.53), U2932 (3.89±0.07 vs 17.78±0.29), SU-DHL 16 (1.82±0.05 vs 17.56±0.71) and Pfeiffer (3.73±0.06 vs 26.16±0.56). CBBM also induced apoptosis in a dose-dependent manner in these cell lines while sparing normal hematopoietic cells from healthy donors (n=2). As an example, CBBM treatment dose-dependently induced apoptosis on OCI-Ly3 cells (vehicle control was 4.43±0.06%, 4 μmol/L CBBM was 24.43±0.72% and 6 μmol/L CBBM was 75.43±0.25%, vehicle control vs CBBM at 4 μmol/L, p<0.001). Conversely, more than 85% of normal hematopoietic cells from mobilized healthy donor peripheral blood were still viable after exposure of CBBM at 10 μmol/L, which is a lethal dose for DLBCL lines. Moreover, CBBM treatment significantly reduced cycling of DLBCL cells (SG2M fractions: vehicle control 68.11±0.40%, CBBM 4 μmol/L 38.36±0.34%, p<0.001). Mechanistically, exposure of DLBCL lines (n=5) to CBBM decreased c-Myc protein levels in a dose-dependent manner. We also validated the reduction of PD-L1 expression, a reported c-Myc target through immunoblots. The proteasome inhibitor MG132 prevented CBBM-induced c-Myc protein degradation, indicating that reduced c-Myc after CBBM treatment is related to downregulation of protein stability. Importantly, we also explored the effect of CBBM on the CaMKIIγ/c-Myc axis. CBBM treatment reduced phospho-c-Myc (Ser62) levels in all the lines. We observed CBBM-mediated inhibitory effects (IC50 of five lines) was correlated with the basal level of CaMKIIγ (R2 = -0.8269, p=0.0323) (Fig.2). Beyond targeting c-Myc, CBBM also exhibited immune modulator potency including downregulation of autocrine interleukin 10 (IL10) level assayed by ELISA, leading to reduction of the downstream JAK2/STAT3 levels. Currently, we are in the process of testing CBBM in vivo effects using an OCI-Ly3 xenograft model. Although the overall survival result is pending, following 4 weeks of CBBM treatment (1 g/kg, i.g.), tumors from animals receiving drug treatment show decreased c-Myc expression levels relative to that of vehicle treated animals. Collectively, our results support further evaluation of CBBM as a promising compound to treat c-Myc associated DLBCL. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Ring Chromosome 8 as a sole abnormality: An adverse prognostic indicator in Acute Myeloid Leukemia?

Ring Chromosome 8 as a sole abnormality: An adverse prognostic indicator in Acute Myeloid Leukemia?

Does tumour SUVmax predict adverse prognostic features in patients with pancreatic cancer?

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease with poor long term outcomes. The majority of indicators associated with early recurrence and poor survival are obtained post-operatively which limit their clinical utility. The aim of this study was to investigate whether tumour SUVmax obtained on 18FDG PET/CT is associated with adverse prognostic indicators in patients with PDAC. Methods: We identified patients diagnosed with PDAC from a clinical trial database investigating the role of 18FDG PET/CT in patients with suspected pancreatic cancer (PETPANC trial-ISRCTN73852054). Single variable linear and logistic regression models were fitted to examine the association of tumour SUVmax with: tumour size, differentiation, baseline CA 19.9, presence of lymph nodes and distant metastasis using Wilcoxon and Pearson χ2 tests in addition to fisher's exact test. Results: 257 patients with PDAC were identified from the trial registry. The Pearson's correlation test showed no association between tumour size (n = 249) and CA 19.9 (n = 163) with tumour SUVmax (r = 0.138 and 0.024 respectively). Single variable logistic regression analysis showed that tumour SUVmax had a statistically significant effect on the presence of distant metastasis [OR 1.07 (95% CI 1.00–1.15); p = 0.044)] but not for the presence of positive lymph nodes (p = 0.472). Single variable linear regression showed that the degree of histological differentiation did not have an impact on tumour SUVmax (p = 0.596). Conclusions: Pancreatic tumour SUVmax is associated with the presence of distant metastasis but was not associated with lymph node positivity nor the degree of histological differentiation.

Liver resection for ruptured hepatocellular carcinoma – A propensity matched analysis

Introduction: Ruptured hepatocellular carcinoma (HCC) is rare in the Western world and robust data regarding standardised treatment is lacking. This study evaluates treatment strategies and the effect of rupture as a potential adverse prognostic indicator among patients with HCC that undergo resection. Method: A retrospective review of patients presenting with ruptured HCC between 2005 and 2015 in a tertiary centre. Patients who underwent resection for ruptured HCC (group A) were identified and these subjects were matched with non-ruptured HCC (group B) patients using a propensity score based on logistic regression analysis. Results: A cohort of 34 patients (27 male:7 female) was identified. Definitive management with surgical resection, TACE (transarterial chemoembolisation) and TAE (transarterial embolisation) were associated with median survivals of 104 (95% CI:37.6-170.4), 48 (95% CI:0-118.6) and 0.5 (95% CI: < 000.5-1.3) month respectively. There was no difference in the mean overall survival between group A (78.3 months) and group B (99 months, p=0.347) or mean disease-free survival (60.8 vs 38.4 months, p=0.397). Conclusions: In selected patients with ruptured HCC, liver resection is associated with the most favourable outcome. Rupture is not a prognostic factor for patients with HCC who undergo resection.

Outcome and prognostic factors in metastatic urothelial carcinoma patients receiving second-line chemotherapy: an analysis of real-world clinical practice data in Japan.

The objective of the present study was to investigate the survival outcome and prognostic factors of metastatic urothelial carcinoma patients treated with second-line systemic chemotherapy in real-world clinical practice. Overall, 114 patients with metastatic urothelial carcinoma undergoing second-line systemic chemotherapy were included in this retrospective analysis. The dominant second-line chemotherapy was a paclitaxel-based combination regimen (60%, 68/114). We assessed the progression-free survival and overall survival times using the Kaplan-Meier method. The Cox proportional hazards model was applied to identify the factors affecting overall survival. The median progression-free survival and overall survival times were 4 and 9 months, respectively. In the multivariate analysis, an Eastern Cooperative Oncology Group performance status score greater than 0 at presentation, C-reactive protein level ≧1 mg/dl and poor response to prior chemotherapy were adverse prognostic indicators. Patients with 0, 1, 2 and 3 of those risk factors had a median overall survival of 17, 12, 7 and 3 months, respectively. The Eastern Cooperative Oncology Group performance status at presentation, C-reactive protein level and response to prior chemotherapy were prognostic factors for metastatic urothelial carcinoma patients undergoing second-line chemotherapy. In the future, this information might help guide the choice of salvage treatment, such as second-line chemotherapy or immune checkpoint inhibitors, after the failure of first-line chemotherapy.

Prognostic factors in men receiving androgen deprivation therapy (ADT) for recurrent prostate cancer: Using absolute PSA and PSA doubling time (DT) to guide timing of ADT initiation.

129 Background: ADT is the first-line treatment for men experiencing recurrence after undergoing radical therapy for prostate cancer. However, timing of ADT initiation is controversial and there are limited data on prognostic factors in patients starting ADT. Methods: We identified consecutive men who underwent radical prostatectomy (RP) for localized prostate cancer at our institution between 1987 and 2007 and who subsequently received salvage ADT. Early progression on ADT was defined as development of metastatic disease within 2yrs of initiation. The primary outcomes of interest were cancer-specific (CSS) and overall survival (OS). Results: A total of 2418 men were included. Median age at RP was 64yrs and median follow-up was 13.9yrs. 48% and 20% of men had pathologic Gleason scores of 7 and 8-10 respectively. The median PSA was 2.6ng/ml, while 385 men (16%) had metastatic disease at receipt of ADT. Overall, 1060 men (44%) developed clinical metastases, with 625 (59%) of these doing so within 2yrs of starting ADT. On multivariable analysis, longer PSA DT before ADT was associated with lower odds of early progression on ADT (DT 3-9mths, OR = 0.19; DT ≥9mths, OR = 0.10, both p &lt; 0.001). 10- and 20-year CSS were 89% and 70%, and 10- and 20-year OS were 82% and 40% respectively. Independent predictors of lower CSS included metastatic disease at time of ADT (HR = 2.60), PSA at ADT of 5-50ng/ml (HR = 2.68) and &gt; 50ng/ml (HR = 4.33, all p &lt; 0.001), while longer PSA DT was associated with higher CSS (DT 3-9mths, HR = 0.54; DT ≥9mths, HR = 0.45, both p &lt; 0.001). PSA at ADT of 5-50ng/ml (HR = 3.10) and &gt; 50ng/ml (HR = 5.20, both p &lt; 0.001) were independent predictors of OS. Conclusions: PSA DT &lt; 3mths and absolute PSA at ADT initiation of ≥ 5ng/ml are adverse prognostic indicators in men receiving salvage ADT for relapse after RP. For patients with these features, their risk of early progression and death should be part of a discussion about the timing of ADT and consideration given to more aggressive treatment strategies. Conversely, men with biochemical relapse who have longer DT and PSA &lt; 5ng/ml are at lower risk and could make an informed decision to defer ADT initiation.

Neonatal Seizures in Iraq: Cause and Outcome.

During a daily neonatology practice, seizures are a continuous challenge as a common neurological disease with a wide range of underlying etiologies, and considerable risks of morbidity and mortality. This study aimed to clarify the rate, etiological factors and outcomes of neonatal seizures, and a possible foresight of neonatal death in Iraq. A prospective cohort study was conducted in neonates with seizures admitted to 3 major neonatology centers in Baghdad, Iraq, from 1st of December 2017 till the end of May 2018. Both term and preterm neonates affected by seizures were recruited with a total number of 203 patients. Perinatal asphyxia (n = 81; 39.90%), infection (n = 77; 37.93%), and metabolic abnormalities (n = 52; 25.62%) were most common causes for seizures. Death occurred in 66 neonates (32.51%), with higher mortality rates found in preterm neonates. Six adverse prognostic indicators were shown to be significant: positive pressure resuscitation, mechanical ventilation, perinatal asphyxia, infection, gestational age (preterm babies), and low birth weight (< 2,500 g). Neonatal seizures may be the first manifestation of neurological insults, and they are most commonly caused by perinatal asphyxia, followed by infection, and metabolic disturbances. Prevention of neonatal seizures is much more important than the treatment of them for the reduction of neonatal mortality. The effective strategies should therefore be proper medical care and management for mothers and neonates before, during and after delivery to prevent neonatal infections, perinatal asphyxia, low birth weight, prematurity, metabolic abnormalities, and other risk factors of neonatal seizures.

Extracorporeal membrane oxygenation in pediatric cardiac surgery: A retrospective review of trends and outcomes in Scotland.

Introduction:Around 3.2%–8.4% of patients receive venoarterial (VA) extracorporeal membrane oxygenation (ECMO) support after pediatric cardiac surgery. The desired outcome is “bridge-to-recovery” in most cases. There is no universally agreed protocol, and given the associated costs and complications rates, the decisions as of when and when not to institute VA ECMO are largely empirical.Methods:A retrospective review of the ECMO database at the Scottish Pediatric Cardiac Services (SPCS) was undertaken. Inclusion criterion encompassed all children (<16 years of age) who were supported with VA ECMO following cardiac surgery between January 2011 and October 2016. The timing of ECMO support was divided into three distinct phases: “endofcase” or intheatre ECMO for patients unable to effectively wean from cardiopulmonary bypass (CPB), ECMO for cardiopulmonary resuscitation (“ECPR”), and Intensive Care Unit ECMO for “failing maximal medial therapy” following cardiac surgery. The patients were analyzed to identify survival rates, adverse prognostic indicators, and complication rates.Results:We identified 66 patients who met the inclusion criterion. 30day survival rate was 45% and survival rate to hospital discharge was 44% (the difference represents one patient). On followup (median: 960 days, range: 42–2010 days), all survivors to hospital discharge were alive at review date. “End-of-case” ECMO showed a trend toward better survival of the three subcategories (“end of case,” ECPR, and ECMO for “failing maximal medical therapy” survival rates were 47%, 41%, and 37.5%, respectively, P = 0.807). The poorest survival rates were in the younger children (<6 months, P = 0.502), patients who had prolonged CPB (P = 0.314) and aortic crossclamp times (P = 0.146), and longer duration of ECMO (>10 days, P = 0.177).Conclusions:Allcomers VA ECMO following pediatric cardiac surgery had survival to discharge rate of 44%. Elective “end-of-case” ECMO carries better survival rates and therefore ECMO instituted early maybe advantageous. Prolonged ECMO support has a direct correlation with mortality.