Stepwise Cox Proportional Hazards Model Research Articles

Long- and short-term survival following laparoscopic and open pancreaticoduodenectomy for patients with periampullary tumors in Vietnam

BackgroundLaparoscopic pancreaticoduodenectomy (LPD) is a less invasive alternative to the traditional open pancreaticoduodenectomy (OPD) approach used to treat periampullary tumors. However, previous studies examining the advantages of this surgery over OPD have produced mixed results. Here, a retrospective observational approach was used to compare the short- and long-term outcomes of patients with periampullary tumors who underwent LPD or OPD at a single institution in Vietnam. Materials and methodsData were obtained from hospital medical records collected over five years from patients that underwent OPD or LPD. Information on demographics, medical status, tumor characteristics, operative variables, complications, and mortality was examined. Survival curves were constructed and the stepwise multivariate Cox proportional hazard model was used to identify the factors associated with the risk of death following surgery. ResultsEighty-four patients aged 26–80 years were included. Twenty-two patients underwent LPD and 62 received OPD. The operative time for the LPD group was significantly longer than that for the OPD group, and the LPD group was less likely to require a blood transfusion during surgery. While the short- and long-term survival rates did not differ for the procedures, the factors associated with the risk of death following surgery were tumors at the N1 stage and an age >65 years. ConclusionBoth LPD and OPD procedures for treating periampullary tumors exhibited comparable safety profiles, with similar short-term outcomes and long-term survival rates observed. Future studies with a larger sample size should be conducted to further examine the treatment outcomes following these surgical approaches.

Timing of postoperative radiation therapy and survival in resected salivary gland cancers: Long-term results from a single institution.

e18052 Background: Timely administration of postoperative radiation therapy (PORT) impacts oncologic outcomes in resected squamous cell carcinomas of the head and neck. Salivary gland cancers (SGCs) are uncommon, and timing of PORT has not been extensively explored. We aimed to determine if the interval between surgery and PORT impacts outcomes in SGCs. Methods: We retrospectively identified patients with SGCs who underwent curative intent surgical resection followed by adjuvant PORT at our tertiary referral center. Demographic, tumor, and treatment data were collected. Patients with non-oncologic resections and/or delay of > 6 months to radiation start were excluded. Locoregional control (LRC), relapse free survival (RFS), and overall survival (OS) were estimated using the Kaplan Meier method. A multivariate analysis explored the association between demographics, tumor characteristics, and PORT timing with oncologic outcomes using a stepwise Cox proportional hazards model. Results: Between 1/1/1997 and 12/31/2017 180 eligible patients were identified. Patient characteristics are described in Table. The median time to PORT start was 61 (range 8-121) days, 169 (93.9%) of patients received neutron beam PORT. With a median follow up of 8.2 years in surviving patients, the 5-year OS and LRC estimates were 73% and 67%, respectively. In a multivariate analysis, only nodal involvement, histologic grade, and age at diagnosis were associated with OS, while nodal involvement, tumor size, and age at time of diagnosis were associated with LCR and RFS. Time to PORT start or completion was not statistically associated with survival outcomes on multivariate analysis. Conclusions: SGC patients who underwent surgery in our tertiary institution received PORT within a median of 61 days after surgery. With long term follow up, PORT timing in this retrospective series was not associated with worse oncologic outcomes, and support timely administration of PORT with 3 months of surgical resection. Further work is necessary to assess generalizability of these results.[Table: see text]

Post-operative heparin reduces early venous thrombotic complications after orthotopic paediatric liver transplantation.

Despite significant improvements in surgical techniques and medical care, thrombotic complications still represent the primary cause of early graft failure and re-transplantation following paediatric liver transplantation. There is still no standardized approach for thrombosis prevention. The study aimed to evaluate the effectiveness of early intravenous unfractionated heparin started 12 hours postoperatively at 10 UI/kg per hour and used a retrospective "before and after" design to compare the incidence of early thrombotic complications prior to (2002-2010) and after (2011-2016) the introduction of heparin in our institute. From 2002 to 2016, 479 paediatric patients received liver transplantation in our institution with an overall survival rate over one year of 0.91 (95% CI: 0.87-0.94). Of 365 eligible patients, 244 did not receive heparin while 121 did receive heparin. We reported a lower incidence of venous thrombosis (VT) in the group treated with heparin: 2.5% (3/121) vs 7.9% (19/244) (p=0.038). All clinical and laboratory variables considered potential risk factors for VT were studied. By multivariate stepwise Cox proportional hazards models, heparin prophylaxis resulted significantly associated to a reduction in VT (HR=0.29 [95% CI: 0.08-0.97], p=0.045), while age <1 year was found to be an independent risk factor for VT (HR=2.62 [95% CI: 1.11-6.21]; p=0.028). Early postoperative heparin could be considered a valid and safe strategy to prevent early VT after paediatric liver transplantation without a concomitant increase in bleeding. A future randomised control trial is mandatory in order to strengthen this conclusion.

Safety and efficacy of drug-eluting bead transarterial chemoembolization with CalliSpheres® microsphere for hepatocellular carcinoma with portal vein tumor thrombus: a preliminary study.

Objective: To prospectively evaluate the safety and therapeutic effectiveness of drug-eluting beads transcatheter arterial chemoembolization (DEB-TACE) with CalliSpheres® microsphere (CSM) for the treatment of hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT), and to analyze the prognostic factors.Method: Between November 2015 and November 2017, consecutive 58 HCC patients with PVTT who received DEB-TACE with CSM treatment were prospectively enrolled in this study. The demographic characteristics, adverse events (AEs) and treatment response were collected. Overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method. Univariate and multivariate Cox regression analyses were performed to determine the independent factors correlated with OS.Results: The objective response rate (ORR) was 79.3% in terms of tumors and 44.8% in thrombi. The median PFS and OS of patients were 5.0 months and 9.0 months respectively. The cumulative survival rate at 3-, 6-, 9-, 12-, 18- and 24-month were 94.8%, 72.4%, 53.4%, 41.4%, 22.4% and 19.0%, respectively. In a stepwise multivariate Cox proportional hazards model, the higher Child-Pugh classification (HR=2.279; 95%CI, 1.042-4.985, p = 0.039) and tumor burden (p = 0.008) were the significant predictors of poorer OS after adjustment for known risk factors. The most common clinical AEs were postembolization syndrome (PES) and the most prevalent laboratory toxicity was transient liver function damage.Conclusion: DEB-TACE with CSM is safe and well-tolerated in HCC patients with PVTT, and reveals a favorable preliminary clinical outcome. The higher Child-Pugh classification and liver tumor burden are independent prognostic factors associated with poor survival for HCC patients with PVTT treated by DEB-TACE with CSM.

RADT-34. PREDICTIVE FACTORS FOR OVERALL SURVIVAL IN SURGICAL CASES OF GLIOMATOSIS CEREBRI FROM THE NATIONAL CANCER DATABASE

Abstract Gliomatosis Cerebri (GC) is a rare, aggressive, diffusely infiltrating cerebral tumor. Prognostic indicators and management strategies are currently poorly characterized. The National Cancer Database was queried for patients with histologically confirmed GC between 2004 and 2016. Demographic, tumor, and treatment characteristics were collected, including the Charlson/Deyo score, a comorbidity index adapted from the Charleston Comorbidity Index. Allowable values for the Charlson/Deyo score are 0 (no recorded comorbidities), 1, 2, and 3+ (most severe). Factors associated with overall survival were identified via bivariate log-rank tests and multivariate stepwise Cox proportional hazards models. The query returned 108 GC patients. The median age was 60.0 years, males were predominantly affected (63%), and most patients were white (86%). While 12% of cases achieved near/gross total resection and 27% of cases achieved partial resection, most surgeries were for biopsy (61%). Treatments included radiation therapy in 64% and chemotherapy in 63% of patients. The median overall survival was 15.1 (95% confidence interval [CI]=11.1-24.8) months. On bivariate analysis, chemotherapy improved overall survival (p=0.01) while radiation therapy (p=0.07) and extent of resection (p=0.48) did not. On multivariate analysis, older patients (hazard ratio [HR]=1.07, CI=1.03-1.11, p&amp;lt; 0.01) and Charlson/Deyo scores of ≥1 versus 0 (HR=3.47, CI=1.40-8.60, p&amp;lt; 0.01) had significantly increased mortality risk following surgery. In particular, the Charlson/Deyo score is a novel prognostic factor for GC that may guide clinical and surgical decision-making for this rare, rapidly fatal tumor. Further prospective studies are warranted to clarify the effects of chemotherapy versus radiation as treatment modalities for GC.

A Novel Promoter CpG-Based Signature for Long-Term Survival Prediction of Breast Cancer Patients.

DNA methylation has been reported as one of the most critical epigenetic aberrations during the tumorigenesis and development of breast cancer (BC). This study explored a novel promoter CpG-based signature for long-term survival prediction of BC patients. We used The Cancer Genome Atlas (TCGA) data as training set, and results were validated in an independent dataset from Gene Expression Omnibus (GEO). First, the differential methylation CpG sites were screened in TCGA dataset, of which the candidate promoter CpG sites were preliminarily identified with the univariate Cox regression analysis and the least absolute shrinkage and selection operator regression analysis. Second, the signature was constructed with stepwise regression analysis and multivariate Cox proportional hazards model, which was validated with the survival analysis of two cohorts each from TCGA and GEO databases. The 10-year receiver operating characteristic curves of risk score presented an area under the curve of over 0.7 for both cohorts. A nomogram was also constructed and released. Moreover, Gene Set Enrichment Analysis was performed to identify the more active pathways in high-risk patients. The CpG sites–target gene correlations and differential methylation regions were further explored. In conclusion, the promoter CpG-based signature exhibited good prognostic prediction efficacy in the long-term overall survival of BC patients.

Predictive factors for overall survival in surgical cases of gliomatosis cerebri from the National Cancer Database

Gliomatosis Cerebri (GC) is a rare, aggressive, diffusely infiltrating cerebral tumor. Prognostic indicators and management strategies are currently poorly characterized. The National Cancer Database was queried for patients with histologically confirmed GC between 2004 and 2016. Demographic, tumor, and treatment characteristics were collected, including the Charlson/Deyo score, a comorbidity index adapted from the Charleston Comorbidity Index. Allowable values for the Charlson/Deyo score are 0 (no recorded comorbidities), 1, 2, and 3+ (most severe). Factors associated with overall survival were identified via bivariate log-rank tests and multivariate stepwise Cox proportional hazards models. The query returned 108 GC patients. The median age was 60.0 years, males were predominantly affected (63%), and most patients were white (86%). While 12% of cases achieved near/gross total resection and 27% of cases achieved partial resection, most surgeries were for biopsy (61%). Treatments included radiation therapy in 64% and chemotherapy in 63% of patients. The median overall survival was 15.1 (95% confidence interval [CI] = 11.1–24.8) months. On bivariate analysis, chemotherapy improved overall survival (p = 0.01) while radiation therapy (p = 0.07) and extent of resection (p = 0.48) did not. On multivariate analysis, older patients (hazard ratio [HR] = 1.07, CI = 1.03–1.11, p < 0.01) and Charlson/Deyo scores of ≥1 versus 0 (HR = 3.47, CI = 1.40–8.60, p < 0.01) had significantly increased mortality risk following surgery. In particular, the Charlson/Deyo score is a novel prognostic factor for GC that may guide clinical and surgical decision-making for this rare, rapidly fatal tumor. Further prospective studies are warranted to clarify the effects of chemotherapy versus radiation as treatment modalities for GC.

Identification and Validation of an Immunological Expression-Based Prognostic Signature in Breast Cancer.

Background: Emerging evidence suggests that the immune system plays a crucial role in the regulation of the response to therapy and long-term outcomes of patients with breast cancer (BRCA). In this study, we aimed to identify a significant signature based on immune-related genes to predict the prognosis of BRCA patients.Methods: The expression data were downloaded from The Cancer Genome Atlas (TCGA). The immune-related gene list, the transcription factor (TF) gene list, and the immune infiltrate scores of samples in the TCGA database were acquired from the ImmPort database, the Cistrome Cancer database, and the TIMER database, respectively. Univariate Cox regression analysis was utilized to identify prognostic immune-related differentially expressed genes (DEGs) (PIRDEGs) in BRCA. A prognostic immune signature containing 15 PIRDEGs in BRCA was established using the least absolute shrinkage and selection operator (LASSO) model with 1,000 iterations followed by a stepwise Cox proportional hazards model with a training set of 508 samples in TCGA. An independent assessment of the prognostic prediction ability of the signature was conducted using Kaplan–Meier survival analysis with a testing set of 505 samples in TCGA.Results: We identified 466 PIRDEGs and 80 TFs among the DEGs. A gene signature containing 15 PIRDEGs was constructed. Risk scores of BRCA patients were calculated using this model, which showed a high accuracy of prognosis prediction in both the training set and testing set and could be an independent prognostic factor of BRCA patients.Conclusions: Our study revealed that a PIRDEG signature could be a candidate prognostic biomarker for predicting the overall survival (OS) of patients with BRCA.

Outcomes and Predictors of Wound Healing among Patients with Complex Diabetic Foot Wounds Treated with a Dermal Regeneration Template (Integra).

The utility of dermal regeneration templates for treating high-risk diabetic foot wounds is unclear. The authors report wound healing and major amputation outcomes among a cohort of diabetic patients with complex diabetic foot wounds treated in a multidisciplinary setting. All patients with complex diabetic foot wounds treated with a dermal regeneration template (March of 2013 to February of 2019) were captured in a prospective institutional database. Wound severity was classified according to the Society for Vascular Surgery Wound, Ischemia, and foot Infection (WIfI) classification system to determine limb salvage prognosis at baseline. Wound healing and major amputation rates were reported using Kaplan-Meier analyses. A stepwise Cox proportional hazards model was used to identify independent characteristics associated with wound healing. Eighty-five patients with 107 complex diabetic foot wounds were treated (mean age, 61.2 ± 3.3 years; 63.5 percent male and 61.2 percent African American). Most diabetic foot wounds were high-risk (wound, ischemia, and foot infection stage 3 or 4, 93.5 percent), corresponding to a predicted 25 to 50 percent risk of major amputation at 1 year. Dermal regeneration template use resulted in successful wound granulation in 66.7 percent of cases, with a mean time to complete wound healing of 198 ± 18 days. Twelve- and 18-month wound healing rates were 79.0 ± 5.0 percent and 93.0 ± 3.3 percent, respectively. Major amputation was required in 11.2 percent of patients. Independent predictors of poor wound healing included lack of bone involvement, higher WIfI stage, and prior dermal regeneration template failure. Application of a dermal regeneration template to complex diabetic foot wounds at high risk for major amputation results in good wound healing and excellent limb salvage outcomes among diabetic patients treated in a multidisciplinary setting. Therapeutic, IV.

Markers of Poor Prognosis in Patients Requiring Continuous Renal Replacement Therapy After Cardiac Surgery

Acute kidney injury requiring renal replacement therapy after cardiac surgery has an incidence of 2% to 15%, and mortality in affected patients approximates 50%. The authors aimed to study the determinants of poor prognosis in patients receiving continuous renal replacement therapy (CRRT) after cardiac surgery. Retrospective, observational single-center study. Tertiary care, university hospital. Cardiac surgery patients admitted to the intensive care unit (ICU) needing postoperative CRRT between January 1, 2010, and September 31, 2019. Predictors of mortality were examined using groupwide comparisons between ICU survivors versus nonsurvivors and univariate and multivariate Cox proportional hazards models. During the study period, 67 cardiac surgery patients without prior maintenance dialysis required CRRT postoperatively. ICU mortality was 47.7% and 90-day mortality was 58.2%. Only 37.3% of patients were alive at 1 year after surgery. Blood lactate at the start of dialysis was the most significant predictor of ICU and overall mortality. Eighty-seven percent of patients with lactate >3 mmol/L died in the ICU compared with 27.3% of patients with lactate ≤3 mmol/L (p < 0.0001). In patients with lactate exceeding 5.3 mmol/L, ICU mortality was 100%. In a stepwise multivariate Cox proportional hazards model, the association with mortality remained significant for lactate at the start of CRRT (per 1 mmol/L, hazard ratio [HR] 1.19 [95% confidence interval {CI} 1.11-1.28], p < 0.0001), troponin T on the first postoperative morning (per 0.1 µg/L, HR 1.004 [95% CI 1.001-1.008], p = 0.01), and 72-hour fluid balance (per 1000 mL, HR 1.12 [95% CI 1.04-1.21], p = 0.005). Blood lactate at the start of dialysis was the most significant predictor of ICU and overall mortality in patients with CRRT after cardiac surgery.

3:27 PM Abstract No. 301 Drug-eluting beads transcatheter arterial chemoembolization is effective and well-tolerated in hepatocellular carcinoma patients with portal vein tumor thrombus

The aim of this study was to investigate the efficacy and safety of drug-eluting beads transcatheter arterial chemoembolization (DEB-TACE) and prognostic factors in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT). 58 HCC patients with PVTT who received DEB-TACE treatment were included in this retrospective study, and the baseline characteristics were recorded. Treatment response was assessed at 4-6 weeks post treatment according to modified Response Evaluation Criteria in Solid Tumors (mRECIST), Overall survival (OS) was calculated using the Kaplan–Meier method, and adverse events (AEs) were also recorded. Univariate and multivariate Cox regression analyses were used to evaluate the relevant clinical variables in predicting OS. The objective response rate (ORR) was 79.3% in terms of tumors and 44.8% in thrombi. The median PFS and OS of patients were 5.0 months and 9.0 months respectively. The cumulative survival rate at 3-, 6-, 9-, 12-, 18- and 24-month were 94.8%, 72.4%, 53.4%, 41.4%, 22.4% and 19.0%, respectively. In a stepwise multivariate Cox proportional hazards model, the higher Child-Pugh stage (HR = 2.279; 95% CI, 1.042–4.985, P = 0.039) and tumor burden (P = 0.008) were the significant predictors of poorer OS after adjustment for known risk factors. As to AEs, they were mainly transient elevated liver enzymes and postembolization syndrome, all of which were not severe. DEB-TACE is effective and well-tolerated in HCC patients with PVTT. The higher Child-Pugh stage and tumor burden are independent predictors for poorer OS.

How do social determinants of health impact timeliness of chemotherapy and survival in patients with metastatic colon cancer? A 12-year study.

36 Background: Studies have demonstrated disparities in health care driven by socioeconomic factors. Patients with metastatic cancer represent the most vulnerable group of cancer patients. We hypothesized that these factors impact timeliness to chemotherapy in patients with metastatic colon cancer and their treatment outcomes. Methods: We queried the National Cancer Database (NCDB) for patients with metastatic colon cancer (AJCC pathologic stage4) diagnosed from 2004-2016. We selected patients treated with chemotherapy as first line treatment within 90 days of diagnosis. Time to initiation (TTI) was defined as time in days (d) from diagnosis of cancer to initiation of systemic chemotherapy and survival was measured in terms of months (m) from the day of diagnosis. Stepwise negative binomial regression and Cox proportional hazard models were used for analysis. Results: We identified 11,764 patients meeting the eligibility criteria. Median age was 62 (range 18-90) years and included 51% males. Median TTI was 9d (range 1-89) and median overall survival was 24.3m. TTI was significantly associated with race - Caucasian 26.4d (95% CI 25.6-27.1) vs. African American 28.9d (26.9-31.0) p-value=0.021, Median income - ≥ $63,000 23.5d (95% CI 22.4 – 24.5) vs.&lt; $38,000 29.2d (27.3 – 31.0) p-value &lt; 0.0001, Facility type – Community cancer center 23.6d (95% CI 21.6-25.6) vs. Academic/research program 26.5d (95% CI 25.5 – 27.4) p-value=0.014. Factors impacting survival in a multivariate model included time to chemotherapy initiation – 24.7m with TTI ≤ 9d vs. 23.8m with TTI &gt; 9d (p-value &lt;0.0001), type of facility – Academic/research program 26.4m vs. community cancer center 21.3 (p-value &lt;0.0001), age (p-value &lt;0.001), comorbidities (p-value &lt;0.0001) and site of primary. Conclusions: Patients with metastatic cancer are not free from disparities driven by social determinants of health that impact their outcomes. The findings suggest that further studies to identify barriers to healthcare access and continued efforts to improve them are warranted.

Preoperative sterile pyuria as a prognostic biomarker for intravesical recurrence in upper urinary tract urothelial carcinoma.

PurposeTo evaluate if preoperative sterile pyuria can be a prognostic factor for intravesical recurrence (IVR) and overall survival (OS)in patients with upper tract urothelial carcinoma (UTUC) undergoing surgery.Materials and MethodsWe retrospectively reviewed the medical records of patients who were diagnosed with UTUC from October 2003 to December 2016 at Korea University Medical Center. Sterile pyuria was defined as urine containing five or more white blood cells per high-power field in the absence of bacteria in urine culture. We used a stepwise multivariable Cox proportional hazards model to assess the independent effects of the prognostic factors for IVR and OS.ResultsWe investigated a total of 176 patients who were diagnosed with UTUC. Among them, 91 (51.7%) patients had preoperative sterile pyuria. There were no significant differences in the baseline characteristics between the pyuria and non-pyuria groups concerning tumor grade, T stage, tumor multiplicity, and recurrence history. However, there was a significant difference in the IVR between the two groups. In the multivariable analysis, preoperative sterile pyuria, diabetes mellitus, high-grade tumor, and lymphovascular invasion were revealed as independent risk factors for IVR, and only lymphovascular invasion was identified as an independent risk factor for OS.ConclusionsPreoperative sterile pyuria is significantly associated with IVR in patients with UTUC undergoing surgery, but it is not associated with OS. Furthermore, diabetes mellitus, high-grade tumor, and lymphovascular invasion are also independent prognostic factors for these patients.

Acute Undifferentiated Leukemia

Introduction Acute undifferentiated leukemia (AUL) is rare and by definition has neither lymphoid nor myeloid lineage specific markers. Given its rarity, little is known about its incidence, survival, and optimal management. We queried the SEER (Surveillance, Epidemiology, and End Results) registry database to obtain information about the incidence and survival of AUL in comparison to acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Methods We identified patients with microscopically confirmed AUL from the SEER database between 2000 and 2016. Incidence rates of AUL were calculated and age-adjusted according to the 2000 US Standard Population. Annual percentage change was estimated using the weighted least square method to measure trends of AUL over this time period. Survival analysis compared AUL vs AML vs ALL patients who were diagnosed in the same period (patients with a preceding malignancy were excluded). Age, sex, race, ethnicity, year of diagnosis, and use of chemotherapy were compared across the three groups. Overall survival (OS) was estimated using the Kaplan-Meier method and comparisons were made using the log-rank test. All factors with p-values &lt;0.1 in univariate analysis were entered in multivariate stepwise Cox proportional hazard ratio models. Results Between 2000 and 2016, a total of 1888 cases of AUL were diagnosed corresponding to an age-adjusted incidence rate of 1.34 per million person-years. The incidence of AUL has decreased over time, with an estimated annual percentage change of -6.5% (CI: -8.1% to -4.8%), p &lt; 0.0001 (Fig. 1). The incidence increases dramatically in the older age groups. After excluding patients with a previous malignancy, 1444 patients with AUL were analyzed for survival. Table 1 summarizes patient baseline characteristics. Patients with AUL had the highest median age among the three groups (74 years) in comparison to 65 in AML and 12 in ALL. Only 35% of AUL patients were coded as having received chemotherapy (vs no/unknown). On the other hand, 94% of ALL and 71% of AML cases received chemotherapy. Among AUL patients who received chemotherapy, the median OS was 13 months (CI: 11-15), compared to 1 month in patients whose chemotherapy status was labelled as "No/Unknown," HR=3.45 (CI: 3.01-3.95). On multivariate analysis of AUL patients who received chemotherapy, older age was the strongest factor associated with worse survival followed by earlier year of diagnosis (Table 2). We compared the survival of AUL patients who were treated with chemotherapy with survival of ALL and AML patients. Adults (age 18+ years) and children (age &lt;18 years) were analyzed separately. Among adults, AUL patients had the worst prognosis, with a median OS of 9 months (CI: 6-11), compared to 27 months (CI: 26-28) in ALL and 13 months in AML, p &lt;0.0001. In the pediatric population, the median OS was not reached for any of the three groups of leukemias. However, the OS of AUL patients was better than in AML and very similar to ALL. On multivariate analysis (Table 3), in both the adult and pediatric subgroups, older age, non-White race, Hispanic ethnicity, and earlier year of diagnosis were independently associated with worse OS. Male sex was predictive of worse outcomes, but only in the adult subgroup. When AUL was compared to ALL and AML in the multivariate model in the adult subgroup, it had worse outcomes, with 47% and 35% increased risk of death, respectively. By comparison, pediatric AUL had similar outcomes to ALL but better survival than AML. Adjusted survival curves for the three types of leukemias in both adult and pediatric subgroups are shown in Fig. 2. Conclusions We describe the largest series of patients with acute leukemia without lineage defining markers. The incidence of AUL has decreased over time, likely due to better diagnostic tools assigning patients either to the myeloid or lymphoid lineage. The prognosis of AUL is generally poor but has improved over time. We also show that the prognosis of AUL relative to other acute leukemias is different between children and adults. This is probably related to distinct molecular and cytogenetic features. With the introduction of targeted therapies, we foresee further improvements in the prognosis of AUL. Disclosures No relevant conflicts of interest to declare.

Impact of Socioeconomic Factors on Timeliness of First Line Chemotherapy and Survival in Patients with Active Multiple Myeloma

Background Multiple myeloma is a common hematological malignancy. In 2016, there were an estimated 131,392 people living with myeloma in the United States and accounted for 2% of all cancer related deaths. Studies among cancer patients have repeatedly demonstrated that sociodemographic factors impact timeliness of treatment and in turn, survival (Kelly et al. Blood,2016). The treatment options in multiple myeloma are variable and may involve stem cell transplant , chemotherapies and biological therapies. We hypothesized that sociodemographic factors impact the time to initiation of first line chemotherapy in patients with multiple myeloma. We also explored if these factors influenced outcomes. Methods We queried the National Cancer Database for patients with multiple myeloma (ICD-0-3 code 9732) diagnosed from 2004-2016. We excluded patients who were considered for stem cell transplant or other modalites to include only those who received chemotherapy as first line treatment. Active myeloma patients were defined as those who were treated within 3 months (120 days) of diagnosis based on similar methodology in previous studies (Ravindran et al. Blood Cancer J,2016). Time to initiation (TTI) was defined as time in days (d) from diagnosis to initiation of systemic chemotherapy.Survival was measured in terms of months (m) from the day of diagnosis. Stepwise negative binomial regression and Cox proportional hazard models were used for analysis. Results Of 160,900 patients with multiple myeloma, we identified 71,523 patients meeting the eligibility criteria. Median age was 68 (range 21-90) years and 55% were males. Median TTI was 19d (range 0-120d) and median overall survival was 34 months. Even though the TTI increased from 24d (2004) to 27d (2016) this was not significant when other variables were adjusted. The overall median survival improved by 10 months between 2004 and 2012 (28 months to 37 months). Determinants of increased TTI in a multivariate model included African American race (p-value &lt;0.005), not living in Urban area (p-value=0.02), having less comorbidities (p-value&lt;0.0005), being treated at an academic or research program (p-value&lt;0.0005) and are described in Table 1. Factors impacting survival in a multivariate model included year of diagnosis (p-value&lt;0.0005) and age (p-value&lt;0.0005) - positive relation, time to treatment (negative relation, p-value&lt;0.0005-Figure 1), race (Caucasians-32m vs. African Americans-38m, p-value&lt;0.0005), insurance status (Government-28m vs. Private-48m, p-value&lt;0.0005), socioeconomic status (lowest-32m vs. highest-37m, p-value=0.003), comorbidities (lowest-38m vs. highest-15m, p-value&lt;0.0005) , treatment facility (Comprehensive Community Cancer Center-31m vs. Academic Research Program-38m) and are described in Table 2. Conclusion The findings of the present study are twofold. First, while not as pronounced as in other cancer cohorts, disparities do exist in timeliness to chemotherapy initiation. The longer TTI in academic centers is interesting but may reflect a more complicated patient population. Second, shorter time to therapy does not necessarily lead to improved outcome, likely reflecting high risk features not captured by standard assessments. This is similar to other studies in hematological malignancies and supports the proposition that clinical trials should accommodate patients who need urgent therapy to detect treatment effects in high‐risk groups (Olszewski et al. Br J Hem,2018). Disclosures No relevant conflicts of interest to declare.

292O - 90-day mortality in head and neck cancer after concurrent chemoradiotherapy

BackgroundTo predict the 90-day mortality in patients with locally advanced head and neck squamous cell carcinoma (LAHNSCC) after concurrent chemoradiotherapy (CCRT), we propose a predictive scoring system, the Taipei Medical University (TMU)-CCRT Mortality Predictor Scoring System, and validate its accuracy. MethodsThis study extracted data of 16 029 patients with head and neck cancer who completed CCRT from the Taiwan Cancer Registry database (TCRD). Based on the 90-day mortality data after CCRT completion, the patients were divided into 2 groups: 90-day mortality (n = 1 068) and 90-day survival (n = 14 961). Stepwise multivariate Cox proportional hazards model was used to select the significant risk factors. ResultsMultivariate analysis revealed that age ≥ 50 or ≥ 70 years, pneumonia, sepsis, hemiplegia, moderate or severe renal disease, leukemia, and metastatic non-HNSCC solid cancers were significant risk factors affecting the 90-day mortality rate. Next, the risk scores of 0, 1 to 3, 4 to 6, and 7 to 9+ were categorized to indicated very low, low, moderate, and high risks (90-day mortality rate = 3.37%, 5.00%-10.98%, 16.15%-29.13%, and 33.93%-37.50%, respectively). ConclusionsOur TMU-CCRT Mortality Predictor Scoring System can accurately predict the 90-day mortality in CCRT-treated patients with LAHNSCC. Legal entity responsible for the study“Szu-Yuan Wu” without further recourse to the authors. FundingHas not received any funding. DisclosureThe author has declared no conflicts of interest.

Incidence and Risk Factors Associated With Ulcer Recurrence Among Patients With Diabetic Foot Ulcers Treated in a Multidisciplinary Setting

BackgroundRecent studies demonstrate favorable diabetic foot ulcer (DFU) healing outcomes with the implementation of a multidisciplinary team. We aimed to describe the incidence of and risk factors associated with ulcer recurrence after initial complete healing among a cohort of patients with DFU treated in a multidisciplinary setting. MethodsAll patients presenting to our multidisciplinary diabetic limb preservation service from 6/2012-04/2018 were enrolled in a prospective database. The incidence of ulcer recurrence after complete wound healing was assessed per limb using the Kaplan-Meier method, and a stepwise multivariable Cox proportional hazards model was created to identify independent predictors of ulcer recurrence. ResultsA total of 244 patients with 304 affected limbs were included. Ulcer recurrence rates at one and 3 y after healing were 30.6 ± 3.0% and 64.4 ± 5.2%, respectively. Recurrent ulcers were smaller (4.4 ± 1.1 cm2versus 8.2 ± 1.2 cm2; P = 0.04) and had a lower Wound, Ischemia, and foot Infection stage (stage 4: 7.7% versus 22.4%; P < 0.001) than initial ulcers, and wound healing time was significantly reduced (95.0 ± 9.8 versus 131.8 ± 7.0 d; P = 0.004). Independent predictors of ulcer recurrence included abnormal proprioception (HR, 1.57 [95% CI 1.02-4.43]) and younger age (HR 1.02 per year [95% CI 1.01-1.04]). ConclusionsIn this prospective cohort of patients with DFU, time to diagnosis and healing was significantly lower for recurrent ulcers, and downstaging was common. These data suggest that engaging patients with DFU in a multidisciplinary care model with frequent follow-up and focused patient education may serve to decrease DFU morbidity.

P2664Long-term follow-up in a large cohort of survivors after out-of-hospital cardiac arrest: global mortality and comparison with age-specific mortality rate in the general population

Abstract Background Data regarding long-term clinical outcomes after out-of-hospital cardiac arrest (OHCA) are scarce. Purpose To assess long-term mortality rate in OHCA patients, compare it with the general population age-specific mortality rate and identify relevant predictive factors. Methods All consecutive patients admitted to the Acute Cardiac Care Unit after OHCA from August 2007 to January 2019 and surviving until hospital discharge were included. All patients received targeted-temperature management according to our local protocol. Stepwise regression techniques and Cox proportional hazards models were used to investigate clinical variables related to long-term survival. The study population was divided into four quartiles according to their age and their mortality rate was compared with age-specific data from the Spanish National Statistics Institute. Results The final analysis included 201 patients. Mean age was 57.6±14.2 years and 168 (83.6%) were male. The majority of patients experienced witnessed arrests related to shockable rhythms (176, 87.6%). Median time to ROSC was 18 (IQR 12–27) minutes and 14 patients (7.0%) were discharged in a poor neurological condition (CPC 3–4). Thirty-six patients (17.9%) died after a median follow-up of 40.3 months (18.9–69.1). A prognostic multivariate Cox model was developed and is shown in Table 1. Mortality was mainly driven by neurologic (33.%), cardiovascular (30.6%) and oncologic (30.6%) causes. Annual mortality rate per 1000 patients was statistically superior to that in the general population among the first three age quartiles: 18.08 (6.78–48.16) vs 0.64; 29.62 (12.33–71.16) vs 3.30; 63.07 (33.94–117.22) vs 7.77. Nevertheless, no significant differences were observed among the oldest patients, ranging from 68.6 to 90.7 years: 70.93 (43.45–115.78) vs 54.95. Table 1. Cox proportional hazard model Variable Hazard Ratio Std. Err. p value 95% Confidence Interval Time from CA to CPR (per minute) 1.06 0.03 0.06 1.00–1.13 Non-shockable rhythm 2.93 1.11 0.01 1.39–6.16 Poor LVEF at discharge (per %) 1.03 0.01 0.01 1.01–1.06 Age at time of CA (per year) 1.04 0.01 0.01 1.01–1.06 CPC 3–4 at hospital discharge 3.50 1.43 &lt;0.01 1.58–7.78 Figure 1 Conclusions OHCA survivors face significant mortality during follow-up, and its long term prognostic impact may be higher among younger patients. Age at the time of CA, time from CA to CPR, non-shockable rhythm, poor LVEF and poor neurological condition at discharge are independent predictors of long term mortality.

P4155Multiple modality biomarkers predict ischemic heart disease in middle-aged men from the general population during a 21-year follow-up

Abstract Background Ischemic heart disease (IHD) often develops after decades of preceding subclinical coronary atherosclerosis. An early prediction of risk for IHD in a general population would be helpful for preventive decision-making. It is well known that biomarkers including troponine, natriuretic peptides and inflammatory biomarkers are useful prognostic predictors for IHD, their long-term predictive values in a general population for incident IHD have not been studied. Purpose The aim of the study was to investigate the predictive value of multi-modality biomarkers on the incident IHD in a random male sample from the general population followed from the age of 50 to 71 years. Method “The study of Men Born in 1943” is a longitudinal cohort study of men living in the city of Gothenburg in Sweden. All patients underwent a baseline examination in 1993, which included physical examination, questionnaires and blood samples. Because of multifactorial nature of atherosclerosis, a panel of biomarkers representing multiple mechanisms such as high-sensitivity troponine (hs-TNT), interleukin-6 (IL-6), cystatin C, high-sensitivity C-reactive protein (hs-CRP), urat, ferritin, and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) were analyzed from blood samples collected at 50 years of age. Incident IHD was defined as new-onset one of following (myocardial infarction, hospitalized unstable angina and intervention with either percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) during 1993–2014. The impact of biomarkers on incident IHD was studied using univariable, followed by stepwise and multivariable Cox proportional hazards models. Results Among the, 753 patients in the study, 105 patients (13,9%) developed IHD during 21 years of follow up with an event rate per 1000 person years 7.49 and a 95% confidence interval (CI) of 6.19 - 9.07. In Cox proportional hazards model for time to first occurrence of IHD, univariable analyses showed that multi-modality biomarker (CRP &gt;1 mg/ml, NT-proBNP &gt;100 pg/mL, troponin &gt;10 ng/L, IL-6 &gt;8 ng/L) provide most powerful prediction, followed by total cholesterol and fasting plasma glucose. In multivariable Cox proportional hazards model for time to first of IHD, above four-biomarker combination modality remains a most powerful predictor with risk increased by one additional biomarker [Hazard Ratio (95% CI): 1.69 (1.26 - 2.26), p=0.0004], followed by total cholesterol (mmol/L) with risk increased by one [Hazard Ratio (95% CI: 1.31 (1.09 - 1.56), p=0.0031], and fasting plasma glucose (mmol/L) with risk increased by one unit [Hazard Ratio (95% CI): 1.11 (1.01 - 1.22), p=0.038]. Conclusion A multi-modality biomarker strategy can be used to predict increased risk of developing IHD during the following two decades after 50 years, enabling us to identify individuals who might benefit from early intensive risk modification to prevent the development of IHD.

Cytomegalovirus prevention strategies and the risk of BK polyomavirus viremia and nephropathy.

Polyomavirus BK (BKV) is the cause of polyomavirus-associated nephropathy resulting in premature graft loss. There are limited data regarding the role of cytomegalovirus (CMV) infection and its prevention in developing BKV viremia and PVAN. In a prospective study, we analyzed 207 consecutive renal transplant recipients previously enrolled in 2 randomized trials evaluating different CMV prevention regimens with routine screening for BKV and CMV. Of these, 59 received valganciclovir and 100 valacyclovir prophylaxis; 48 patients were managed by preemptive therapy. At 3years, the incidence of BKV viremia and PVAN was 28% and 5%, respectively. CMV DNAemia developed in 55% and CMV disease in 6%. Both BKV viremia (42% vs 23% vs 21%, P=.006) and PVAN (12% vs 2% vs 2%, P=.011) were increased in patients treated with valganciclovir prophylaxis compared to valacyclovir and preemptive therapy. Using multivariate Cox proportional hazard regression, valganciclovir prophylaxis was independent predictor of BKV viremia (hazard ratio [HR]=2.38, P=.002) and PVAN (HR=4.73, P=.026). In contrast, the risk of subsequent BKV viremia was lower in patients with antecedent CMV DNAemia (HR=0.50, P=.018). These data suggest valganciclovir prophylaxis may be associated with increased risk of BKV viremia and PVAN. CMV DNAemia did not represent a risk for BKV.