Dholaria, Bhagirathbhai R

Abstract Background Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening systemic inflammatory condition. Due to rarity of the cases, it presents difficulties in diagnosis and management. Survival remains poor despite aggressive chemotherapy. Objective Patient outcomes varied markedly despite standardize therapy. Reliable prognostic disease markers may help to tailor intensity of therapy and predict long term outcomes. We attempt to look for variables associated with difference in mortality within 30 days of diagnosis. Methods We performed a retrospective search on mayo clinic patient database for the patients with the diagnosis of HLH from 2005 to 2015. HLH-04 criteria were used to select the study population. Patients were divided in two groups based on survival after the diagnosis. We analyzed different clinical and laboratory parameters to detect difference between the patients expired within 30 days of diagnosis and who survived longer than 30 days. Baseline Characteristics: Demographics: 40 patients were included in the analysis who met HLH- 04 criteria. Mean age was 49 years, 40% (16/40) were female and 60% (24/40) were male. Underlying HLH etiology was malignancy 37% (15/40), infection 20% (8/40), rheumatological 17% (7/40), idiopathic 20% (8/40). Two patients were peripartum and one with Kikuchi syndrome. EBV DNA PCR were positive in 32% (13/40) of patients. Table 1 show clinical and laboratory characteristics according to HLH-04 criteria. Treatment: Steroids were used in 92% (37/40), etoposide was used in 55% (22/40), and HLH 04 protocol (Etoposide/dexamethasone/cyclosporine) was used in 40% (16/40) of the patients. IVIG was used in 13% with underlying rheumatological process. Mean follow up was 57 weeks (0.1 to 336 weeks) for the whole group. Total 40% (16/40) died within 30 days of diagnosis. Results Risk of 30-days mortality was significantly higher in the patients with ferritin >5000 mcg/L at the time of diagnosis and age > 55 years. Out of total 40 patients, 54% (12/22) died in ferritin >5000mcg/L group and 22% (4/18) died in ferritin < 5000 mcg/L group within 30 days. (p-0.03) Death rate within 30 days was 65% (11/17) with age > 55 years and 22% (5/23) with age < 55 years at the time of diagnosis of HLH. (p-0.05) No difference between the groups in terms of gender, EBV positivity, underlying etiology and etoposide use was found in 30 days mortality. Table 2 summarizes the findings. Discussion HLH is a complex disorder with significant heterogeneity in terms of underlying etiology and response to treatments. Diagnosis is based on a set of clinical and investigational parameters. Most commonly used criteria are HLH-04. Treatment involves rapid immunosuppression with steroids, chemotherapy and calcineurin inhibitors. Previous retrospective studies have pointed out different risk factors associated with poor survival, which are malignancy, hypoalbuminemia, elevated creatinine and bilirubin. Ours is a relatively small retrospective analysis, but it shows significant prognostic value to elevated ferritin (>5000 mcg/L) at the time of diagnosis and age > 55 years. Survival remains poor in high risk patients despite aggressive therapy. Biological agents (IL1 and IL6 blockage) may provide new realm of therapy with tolerable toxicity profile. Conclusion Elevated ferritin at the time of diagnosis and older age are associated with significant risk of 30 day mortality in HLH. These factors can be incorporated in future clinical trials to choose different treatment pathways. Table. Clinical and laboratory characteristics according to HLH- 04 criteria Clinical/laboratory manifestation Presence of HLH 04 criteria (%) Fever > 38.5C 36/40 90 Splenomegaly 30/40 75 Hemoglobin < 9g/dl 22/40 55 ANC < 1000/microL 14/40 35 Platelets < 100, 000/microL 31/40 77 Triglyceride > 265 mg/dl 22/40 55 Ferritin > 500 mcg/L 36/40 90 Fibrinogen <150 mg/dl 12/38 31 sIL2- R > 1000u/ml 13/14 92 Low NK - cell activity 13/15 86 Presence of hemophagocytosis 33/39 84 Table 2. Difference in clinical variables based on survival after the diagnosis of HLH Survival < 30 days Survival > 30 days P value Age (years) 62 40 0.0004 Median time to start treatment (weeks) 40.7 8.6 0.23 Baseline ferritin (mcg/L) 32866 10667 0.01 Peak ferritin (mcg/L) 45870 29894 0.26 Albumin (g/dL) 2.3 2.6 0.41 LDH (U/L) 1271 720 0.51 Bilirubin (mg/dL) 8.9 4.5 0.14 Triglyceride (mg/dl) 260 276 0.70 Disclosures No relevant conflicts of interest to declare.

e20599 Background: The anti-PD-1 antibodies nivolumab and pembrolizumab have demonstrated improved overall survival (OS) and progression free survival (PFS) in a subset of patients with metastatic or locally advanced lung cancer (LC). To date, no blood biomarkers have been identified to predict clinical outcome to anti-PD-1 agents. Methods: A retrospective analysis of 52 patients with advanced LC and treated with anti-PD-1 antibodies in a single institution was performed. White blood cell count (WBC), absolute neutrophil count (ANC), absolute lymphocyte count (ALC), absolute neutrophil to absolute lymphocyte count ratio (ANC/ALC), absolute eosinophil count (AEC), and platelet counts at baseline before start of anti-PD-1 antibody were assessed. Kaplan–Meier and Cox regression analysis were done. Results: 48 patients were treated with nivolumab (92.3%) and 4 patients with pembrolizumab (7.7%). Median follow up was 13.6 months and median OS was 26 months. Higher baseline ANC and ANC/ALC ratio significantly correlated with worse clinical outcomes. Patients with baseline ANC > 6060/mm3 had a significantly increased risk of death [hazard ratio (HR) = 2.46; 95% CI 1.12–5.42, P = 0.025] and of progression on anti-PD-1 antibody [HR = 2.41; 95% CI 1.25–4.64, P = 0.009] compared with patients with ANC ≤6060/mm3. Similarly, patients with baseline ANC/ALC ratio ≥ 4.59 had a significantly increased risk of death [HR = 2.41; 95% CI 1.11–5.24, P = 0.027] and of progression on anti-PD-1 antibody [HR = 2.08; 95% CI 1.10–3.95, P = 0.027] compared with patients with ANC/ALC < 4.59. One year survival rate in patients who had ANC < 3390/mm3, ANC 3390-6060/mm3 and ANC > 6060/mm3 were 86.5%, 76.9% and 48.1% respectively. Conclusions: Increased baseline ANC and ANC/ALC were associated with poor PFS and OS in LC patients treated with anti-PD-1 antibodies. Although these findings need to be validated in a large sample size, our data suggested that baseline ANC and ANC/ALC ratio might help the risk stratification and assist treatment strategies. The potential predictive value of peripheral blood biomarkers for clinical outcomes to anti-PD-1 antibody should be further investigated in a prospective study.

Abstract Background Treatment of non‐small‐cell lung cancer (NSCLC) has been rapidly advancing over the last decade. Academic centers are considered equipped with better expertise. NSCLC outcome trends in novel therapeutic era and impact of initial treatment at academic centers have not been reported. Methods The National Cancer Database (NCDB) was used to identify NSCLC incident cases from 2004 to 2013. Overall survival (OS) was plotted by year of diagnosis and type of initial treatment center, accounting for several factors available in NCDB. Results A total of 1 150 722 NSCLC patients were included and separated by initial treatment center type (academic: 31.5%; nonacademic: 68.5%). Median follow‐up and OS for all patients were 11.8 months (range: 0‐133.6 months) and 13.1 months (95% CI: 13.08‐13.17), respectively. Median OS improved significantly for those diagnosed in 2010‐2013 (14.8 months [95% CI: 14.7‐14.9]) as compared to 2004‐2009 (12.4 months [95% CI: 12.3‐12.5]) ( P < 0.001). Treatment at academic centers was associated with improved OS (multivariate HR for OS = 0.929 [95% CI: 0.92‐0.94], P < 0.0010). Four‐year OS for academic and nonacademic cohorts was 28.5%% and 22.1%, respectively ( P < 0.001), and the difference was more pronounced in stage I to III NSCLC. Conclusion In this largest analysis, thus far, NSCLC survival has improved over time, and type of initial treatment center significantly influences survival. Identifying and removing barriers to obtaining initial treatment of NSCLC at academic medical centers could improve OS.

232 Background: Screening for distress in cancer patients (pts) is recommended by several national guidelines. High distress scores are associated with increased depression. We established universal depression screening and investigated its impact on cancer patient management. Methods: Patient Health Questionnaire (PHQ9) was administered to newly diagnosed cancer patients prior to receiving their first non-oral antineoplastic agent. Patient demographics, disease characteristics, chronic medication load, antidepressant use, treatment interruptions, weight change, referral and adherence to psychiatry were recorded. Pts with high (> 9) and low (< 4) PHQ9 scores were compared using Chi-square and Wilcoxon rank-sum tests. Results: Screening was performed in 1,190 consecutive pts over an 18 month period at Mayo Clinic. Responses were received from 1055 (89%) pts, of which 144 had high score (PHQ-H). These were compared with 99 randomly selected low score (PHQ-L) pts. The 243 pts (median age 65; range 18-92 years) in the final analysis included: 53.5% females, 90% Caucasians, 74% married and 77% living with others. Diagnosis was solid organ cancer in 81% and metastatic disease in 54% patients, and 13% were on antidepressants for preexisting depression. PHQ-H were more likely to be on antidepressants than PHQ-L (19% vs. 3%; p = 0.0002), be referred to psychiatry (69% vs. 12%; p < 0.0001), attend psychiatry appointment (45% vs. 12%; p < 0.0001) and require behavioral therapy (50% vs 8%; p = 0.0065). PHQ-H did not have a significantly increased antidepressant use, treatment interruptions (p = 0.5) or weight change (p = 0.4). Race, gender, chronic medication load, marital status, living situation, metastatic disease and type of cancer were not significantly different between PHQ-H and PHQ-L. Conclusions: We implemented a universal depression screening and management plan for cancer pts and noted that previously being on antidepressants was associated with higher patient distress. Higher score led to more frequent behavioral therapy, possibly preventing non-compliance or need for increased psychotropic medications. Our model identifies cancer pts with depression and implements an effective management plan for their care.