bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of ONC201 and bortezomib on apoptosis in non-Hodgkin's lymphoma (NHL) xenografts.
Authors: Talekar Mala Kiran , Hall Junior , Wertheim Gerald B , Martinez Daniel , Allen Joshua E. , Grupp Stephan A. 
Published: September 2018

e19016 Background: Our group has previously shown preclinical in vitro efficacy of novel small molecule, ONC201 across several pediatric NHL cell lines (Talekar et al, 2015) as a monoagent as well as in combination with chemotherapy agents, significantly cytarabine and bortezomib. We investigated the preclinical efficacy of ONC201 and bortezomib combination in vivo in a NHL mouse xenograft model. Methods: Burkitt’s lymphoma cell line (Ramos) transduced with lentiviral GFP was utilized to establish subcutaneous flank xenografts in 5-7 week(wk) old immunodeficient SCID mice [NOD.Cg- Prkdcscid Il2rgtm1Wjl/SzJ]. All tumors were established by Day 10, detected by bioluminescent imaging and were serially imaged x1/wk. Mice were studied in 4 treatment arms (7 mice per arm) as tabulated in the table. Results: Mice in Arms 1, 2 & 3 had continued tumor growth and were humanely euthanized during Wk 3- 4 of treatment when the tumor volume reached the maximum allowable size per the approved institutional IACUC protocol. Mice in Arm 4 showed gross tumor necrosis and had to be euthanized in Wk 4. Upon treatment initiation, 2 mice in each arm were sacrificed at 48 and 72 hours respectively and tumor samples harvested for histology and IHC analysis (TRAIL and CHOP/GADD). Histological analysis revealed that the control group had predominantly viable tumor cells at both 48 & 72 H. The monoagent groups showed minimal cell death with bortezomib alone and modest cell death with ONC201 as monoagent in clustered regions. In contrast, the combination group showed: i) extensive global tumor necrosis with nuclear debris on H&E, ii) prominent TRAIL induction by IHC analysis, and, iii) significant apoptotic cell death accompanied by CHOP /GADD overexpression indicating potential ER stress. Induction of these pharmacodynamic markers in Arm 4 were evident at 48H and more prominent at the 72H. Conclusions: ONC201 effectively synergizes with bortezomib to cause apoptotic tumor cell death in pediatric NHL murine xenograft and merits further investigation. [Table: see text]
Prognostic value of the absolute lymphocyte to monocyte (ALC/AMC) ratio on overall survival among patients with mantle cell lymphoma.
Authors: Goy Andre , Feldman Tatyana , Leslie Lori Ann , Skarbnik Alan P. , Wu Tommy , Hansen Eric , Arunajadai Srikesh , Protomastro Ewelina , Valentinetti Marisa , Smith Judy , Choi Kelly 
Published: September 2018

e19030 Background: The peripheral blood absolute lymphocyte-to-monocyte ratio (ALC/AMC) is prognostic of overall survival (OS) in Hodgkin Lymphoma, Diffuse Large B-cell Lymphoma, and several solid tumors. Lymphocyte and monocytes have been suggested to be surrogate biomarkers of immune homeostasis and tumor microenvironment, respectively. We sought to determine if the post-induction therapy ALC/AMC is prognostic in mantle cell lymphoma. Methods: A retrospective review was conducted of 96 consecutive mantle cell lymphoma patients (pts) with available data treated at the John Theurer Cancer Center (n=77) and 4 Regional Cancer Care Associate practices (n=19) by 24 physicians between Aug 2005 and Dec 2015 (90% cases after 2009). Cases were identified via the COTA database which extracts and organizes relevant data from the electronic health records. Peripheral blood counts (to calculate the ALC/AMC) were determined approximately 30 days following completion of initial therapy or immediately prior to stem cell mobilization in those pts undergoing first line transplant. All analyses were performed using the R statistical language. Results: 67 pts had ALC/AMC less than 2 and 29 pts had ALC/AMC greater than or equal to 2. The cohorts (<2 vs >2) had similar median ages (64 vs 68; p=0.18), ethnicities (p=0.38), stage distributions (including 87% vs 79% stage IV disease; p=0.51), elevated beta-2-microglobulin (p=1), elevated LDH (p=1) and MIPI scores (including 19% vs 41% high risk; p=0.13). ALC/AMC was <2 in 10 of 13 (77%) transplanted pts and 57 of 83 (69%) non-transplanted pts (p=0.57). With a median follow-up of 43 months, the median OS has not been reached in either cohort; the 5-year survival rates were higher among pts with ALC/AMC greater than or equal to 2 (90% vs 68%; log-rank p<0.05). Similar ALC/AMC 5-year survival trends were noted when sub-setting to the 25 pts with high risk MIPI scores (72% vs 45%; p=0.07). Conclusions: An elevated ALC/AMC >2, following induction therapy, is associated with improved overall survival in MCL. Novel maintenance programs, including targeting the microenvironment or immune response, might be appropriate among pts with low ratios.
Diffuse large B-cell lymphoma in very elderly patients older than 80 years: A multicenter retrospective analysis of clinical characteristics, treatment patterns, and outcome—KCSG LY16-01.
Authors: Choi Jung Hye , Yuh Young Jin , Kim Tae Min , Kang Hye Jin , Kwon Jung Hye , Kim Seok-Hyun , Nam Seung-Hyun , Shim Hyeok , Lee Soon-Nam , Lee Soonil , Chong So Young , Han Jaejoon , Park Byeong Bae , Koh Sung Ae , Sun Der-Sheng , Kim Hyo Jung , Yi Jun Ho , Jin Jong-Youl , Jung Yun Hwa 
Published: September 2018

e19031 Background: Treatment strategy for elderly patients older than 80 years with diffuse large B cell lymphoma (DLBCL) has not been established because of treatment intolerability and lack of the data. Methods: This multicenter retrospective study was conducted to investigate clinical characteristics, treatment patterns and outcome of patients older than 80 years at the diagnosis of DLBCL from 19 institutions in Korea between 2005 and 2016. Results: A total of 194 patients were identified (men: women 93:101). Median age was 83.3 years (range 80.1-95.7). 114 (59.3%) patients had an age-adjusted international prognostic index (aaIPI) score of 2-3 and 48 (24.7%) had Charlson index with a score 4 or more. R-CHOP was given in 124 (63.9%) cases, R-CVP in 13 cases, other chemotherapy in 17 cases, radiation alone in 9 cases, and surgery alone in 2 cases. 29 (14.9%) patients did not receive any treatment. The median cycle of chemotherapy was three (range 1-10). Only 43 patients completed planed cycles of treatment. The overall response rate of 105 evaluable patients was 91.4% (CR 41.9%, PR 49.5%). 29 patients died due to treatment-related toxicity (TRT) such as pneumonia and sepsis. 13 patients died due to TRT just after 1st cycle. Median overall survival was 14.0 months. Main causes of death were disease progression (30.8%) and treatment-related toxicities (27.1%). In multivariate analyses, overall survival was affected by aaIPI, hypoalbuminemia, elevated creatinine, and treatment. Conclusions: Age itself should not be a contraindication to treatment. However, since elderly patients show higher TRT due to infection, careful monitoring and dose modification of chemotherapeutic agents would be needed.
Hepatosplenic T-cell lymphoma (HSTL): A SEER data analysis.
Authors: Master Samip R. , Koshy Nebu V. , Mills Glenn Morris , Mansour Richard P. , Shi Runhua 
Published: September 2018

e19035 Background: HSTL is a very rare neoplasm accounting for less than one percent of non- Hodgkin lymphomas. The most common presentation of the patient with HSTL is marked hepatosplenomegaly and thrombocytopenia without lymphadenopathy. We performed SEER data analysis for the patients with HSTL to investigate the socio-economic factors and survival outcomes for this rare disease. Methods: Data from 92 adult patients registered in the SEER data with diagnosis of HSTL, between year 1998-2012 and follow up through 2013 were analyzed. Impact of patient demographics (sex, age, and race, year of diagnosis, family income, education, unemployment) and treatment characteristics (delivery of radiotherapy and tumor directed surgery) on survival were evaluated via univariate analysis. Results: The mean age of diagnosis 40.4 ± 18 years (see table). The education, income and employment are zip code level based on 2000 census data. The annual income is cost of living adjusted median family income. The education is the percentage of people in patient’s zip code with college education. The median survival was 13 months. Out of the factors analyzed only surgery and radiation affected survival. The median survival for the patient who got tumor specific surgery was 20 months , compared to 8 months for those who did not get tumor specific surgery(p = 0.04). Conclusions: HSTL is more common in younger population with majority of patient less than 64 years of age. Also, it is more common in males. Age, sex, race, income, employment, education and year of diagnosis do not affect survival. Unfortunately, SEER database does not have details about chemotherapy or bone marrow transplant. Previous literature in form of case reports and case series has suggested splenectomy for management of HSTL. Our data suggest that pts who underwent tumor specific surgery had improved outcomes. [Table: see text]
Clinicopathological presentation of extranodal lymphomas of head and neck: A single institution experience over the last decade.
Authors: Gill Amitoj , Cisak Kamila Izabela , Gosain Rahul , Perez Cesar Augusto 
Published: September 2018

e19042 Background: Non-Hodgkin’s lymphoma can have an extranodal presentation in about 33% of cases. Up to one third of these extranodal lymphomas (ENL) develop in the head and neck region. We looked at the clinicopathological presentation of ENL diagnosed at an academic institution. Methods: All patients with ENL of head and neck diagnosed between 2008 and 2016 at a single institution were included. Analysis was done for histologic subtype of lymphoma, primary site, immunohistochemical profile (Bcl-2,Bcl-6 and Ki67) and prognostic factors. Results: A total of 68 patients were included of which 41 (60%) were females and 27 (40%) were males. Median age at diagnosis was 64 (range 26 to 92) and a large number of the patients were Caucasian (74%). Diffuse Large B-Cell Lymphoma (DLBCL) was most commonly seen followed by Marginal Zone B Cell Lymphoma (MZBCL). The most common site of presentation was Tonsils/Waldeyer's ring (21%) followed by Nasopharynx (15%) and Orbital/Periorbital areas (15%). Among the patients with indolent Lymphomas (non-DLBCL), most presented with stage I (per Ann Arbor staging) at diagnosis (60%). On the other hand, stage III was the most common stage at diagnosis for the patients with DLBCL (30%). Higher Bcl-6 expression (52%) was noted in DLBCL with majority (81%) having a Ki67 expression of more than 30%. The 2-year overall survival for the DLBCL subgroup was 77% (95% CI 0.61 - 0.93). A high Neutrophil to Lymphocyte ratio (NLR) was associated with worse overall survival in patients with DLBCL. Conclusions: MZBCL was the most common indolent ENL of the head and neck, but DLBCL was the most common type of all ENL of the head and neck. NLR was associated with worse outcomes in patients with DLBCL. [Table: see text]
Bloodless tandem autologous stem cell transplant for multiple myeloma in Jehovah's Witness patients.
Authors: Rafiullah Fnu , Mott Sarah L , Schultz Allyson , Tricot Guido J. 
Published: September 2018

e19523 Background:, Cases of Jehovah’s Witnesses (JW) who undergo, and survive, autologous and allogeneic stem cell transplant(SCT) are increasingly reported. Tandem autologous stem cell transplantation(ASCT) for multiple myeloma has not been previously reported in JW. We are describing the first reports of four JW patients who successfully underwent tandem bloodless ASCT for multiple myeloma. Methods:, We retrospectively studied the outcome of four JW patients who underwent tandem ASCT from November 2000 to January 2017. . The bleeding complications, number and cost of transfusion of blood products were compared with last 100 consecutive tandem autologous transplants done from November 2014 till January 2017. Results:,There were 4 JW patients and 59 non-JW patients. Among 4 JW patients 3 were male and 1 was female. Among 59 non-JW 24(40.7%) were female and 35 (59.3%) were female. Median age was 60-years (range 54–66) and 59-years (range 36–71) for JW and non-JW patients, respectively. At Day+30 one JW patient had grade III pulmonary hemorrhage and Non-JW patients had no grade III or higher bleeding problems .The median number of CD34 cells transfused was 7.48 millions cells/kg in non-JW patients while it was 9.44 millions/kg in JW patients. Complete Remission(CR) was achieved in 33(59%) after 1st tandem and 35(81.4%) after the second tandem transplant in Non-JW patients as compared to 100% CR rate in JW patients . The median number of platelet transfusions in non-JW patients was 2(range 0—21) and PRBC units was 1(range 0—7) at day+30 . Total cost of PRBC and platelet transfusions for the 59 non-JW patients was ~ 192,374 dollars (average 1923.74$/transplant). This excludes the supply costs and management of transfusion reactions costs. Conclusions: 1) Tandem autologous transplant for multiple myeloma in JW population is practical and largely safe. 2) Blood products are expensive and can be further minimized based on the JW patient data
Treatment patterns and survival among patients with extensive disease small cell lung cancer (ED-SCLC).
Authors: Danese Mark D. , Gleeson Michelle L. , Lubeck Deborah P. , Korytowsky Beata , Bobiak Sarah 
Published: September 2018

e20026 Background: There has been little change to the ED-SCLC treatment landscape in the past 30 years. Patients with ED-SCLC have limited treatment options after recurrence and poor overall survival (OS). Prior work has described OS in patients with ED-SCLC but did not report OS beyond first-line (1L) therapy. Methods: This study used linked data from the Surveillance, Epidemiology, and End Results program and Medicare claims. Patients aged ≥66 years with a first primary, pathologically confirmed ED-SCLC diagnosis between 01/01/2007 and 12/31/2011 and who had Medicare Parts A and B coverage were included. Patients were followed from diagnosis until death, end of follow-up, second primary cancer diagnosis, or switch to managed care coverage. OS from ED-SCLC diagnosis and from initiation of 1L and second-line (2L) outpatient chemotherapy were estimated. Cox proportional hazards models were used to identify factors associated with OS from diagnosis. Results: Of 5498 patients with ED-SCLC (mean age: 75 years [range: 66, 98]) included in this study, 49% were male, 86% were white, 40% had ≥1 indicator of mobility limitations, and 23% lived in an area with high poverty (≥20%). Median OS for all patients was 4.7 months (untreated [n = 2484]: 1.3 months; treated with outpatient chemotherapy within 90 days of diagnosis [n = 3014]: 8.3 months). Among all patients, factors associated with shorter OS included older age, male sex, ≥1 indicator of mobility limitations, and residence in a high poverty area. In the 3014 patients who received 1L outpatient chemotherapy (86% platinum/etoposide; 4% platinum/irinotecan; 10% other), median OS from initiation of 1L therapy was 7.9 months overall (platinum/etoposide: 8.0 months; platinum/irinotecan: 7.8 months; other: 6.4 months). A total of 1162 patients received 2L chemotherapy (38% topotecan monotherapy; 28% platinum regimens; 34% other). Median OS from initiation of 2L therapy was 4.4 months overall (topotecan: 4.0 months; platinum regimens: 6.4 months; other: 3.7 months). Conclusions: OS was poor in this cohort of real-world patients with ED-SCLC especially in those not treated with outpatient chemotherapy. These findings underscore the need for new treatments for this population.
Risk stratification of lung cancer patients at initial presentation: A retrospective cohort study.
Authors: Lavoie Jean-Michel , Ho Cheryl , Sun Sophie 
Published: September 2018

e20062 Background: Early detection and treatment of non-small cell lung cancer (NSCLC) has been shown to improve survival. Current screening guidelines focus on at-risk populations, overlooking a significant proportion of patients (pts) who will develop NSCLC. There is a need for further risk stratification in this group. Methods: A retrospective cohort analysis was conducted on pts referred to the BC Cancer Agency – Vancouver Centre for NSCLC. Records were reviewed for the date of first abnormal imaging and 6 clinical factors (CF) noted by the referring clinician at initial presentation. CFs were: ECOG PS > 2, new-onset dyspnea > MRC 3, chest pain, hemoptysis, weight loss > 10% and systemic symptoms (seizure, bone pain, or paraneoplastic syndrome). Individuals meeting current low-dose CT screening criteria (age 55-74, 30 pack-year smoking history within the last 15 years) were also identified. Results: 435 cases were identified from Jan 1 to Dec 31, 2013; 308 had sufficient information to be included for analysis. Median age: 69; smoking history: 69%; stage: I = 5%, II = 9%, III = 26%, IV = 60%. Multivariate analysis identified 4 of 6 CF were associated with worse overall survival (OS, p < 0.05); hemoptysis and weight loss were not significant predictors and were not retained for analysis. Cases were stratified based by the number of CFs. Pts with no CF had significantly improved OS (median 30.5 mo) compared to those with 1 (12.1 mo), 2 (8.1 mo) or 3-4 (2.5 mo; p < 0.001 for all comparisons) CF. Screening criteria were met for 94 pts (31%). For the other 214 pts (69%), number of CF was 0 = 29%, 1 = 29%, 2 = 33%, 3-4 = 9%. OS was similar whether or not pts were eligible for screening. In the subset of ineligible pts, CFs retained their predictive value (p < 0.05). Conclusions: Four clinical factors predict poor outcomes in pts presenting with abnormal imaging suspicious for NSCLC. In this population, 31% of patients would have been eligible for low-dose CT screening. An additional 49% of patients with abnormal imaging had at least one CF identifiable upon initial contact with a healthcare provider. Determination of key clinical factors may assist in risk stratification of pts ineligible for screening who warrant further investigation for lung cancer.
Safety and clinical activity of first-line durvalumab in advanced NSCLC: Updated results from a Phase 1/2 study.
Authors: Antonia Scott Joseph , Brahmer Julie R. , Balmanoukian Ani Sarkis , Kim Dong-Wan , Kim Sang-We , Ahn Myung-Ju , Jamal Rahima , Jaeger Dirk , Ott Patrick Alexander , Ascierto Paolo Antonio , Gregorc Vanesa , Goldman Jonathan Wade , Blakely Collin M. , Jin Xiaoping , Antal Joyce , Gupta Ashok Kumar , Segal Neil Howard 
Published: September 2018

e20504 Background: Single-agent durvalumab demonstrated manageable safety and encouraging clinical activity in advanced squamous and non-squamous NSCLC in preliminary analyses from the Phase 1/2 1108 study (NCT01693562). Here we present updated safety data and clinical activity in NSCLC pts with no prior treatment for advanced disease. Methods: In this Phase 1/2 dose-escalation and expansion study, pts with Stage IIIB/IV NSCLC, ECOG PS 0–1, and availability of a fresh tumor biopsy and/or archival tumor tissue for PD-L1 testing received durvalumab 10 mg/kg every 2 weeks for up to 12 months, with retreatment permitted for those progressing after 12 months of therapy. Tumor PD-L1 expression was assessed using the Ventana PD-L1 (SP263) Assay (PD-L1 high: ≥25% of tumor cells with membrane staining). Results: As of 24 October 2016, 59 pts (63% ECOG PS 1, 49% squamous) received first-line durvalumab. Median duration of follow-up was 17.3 (1.0–36.8) mos. Safety profile was consistent with the overall (N = 304, ≥0 prior lines of therapy) NSCLC cohort. All-grade treatment-related adverse events (AEs) were reported in 56%; the most common were fatigue (15%), diarrhea (13%), and decreased appetite (10%). 7% had a treatment-related AE leading to discontinuation of durvalumab, including diarrhea in 2 pts. Grade ≥3 treatment-related AEs (all n = 1) occurred in 10%; 1 pt died due to drug-related pneumonia. 49 pts had high PD-L1 expression and 9 pts had low/negative PD-L1 expression; data are not summarized for the latter group due to the small number of pts. For the PD-L1 high subpopulation, confirmed ORR (investigator-assessed RECIST v1.1) was 28.6% (95% CI 16.6–43.3) and disease control rate (stable disease ≥24 weeks) was 42.9% (95% CI 28.8–57.8); median PFS was 4.0 months (95% CI 2.3–9.1), median OS was 21.0 months (95% CI 14.5–not estimable), and 12-month OS rate was 72% (95% CI 56–83). Response rates were similar and durable regardless of histology. Conclusions: Consistent with prior data, durvalumab had a tolerable safety profile in advanced treatment-naïve NSCLC. Clinical activity was seen in PD-L1 high pts, with encouraging OS. Clinical trial information: NCT01693562.
Efficacy and safety of crizotinib in patients with anaplastic lymphoma kinase-positive stage IV non-small cell lung cancer.
Authors: Mohi El.Din Ahmed M. , Rasmy Ayman Ahamd 
Published: September 2018

e20516 Background: Crizotinib is an oral small-molecule tyrosine kinase inhibitor targeting ALK, MET, and ROS1 tyrosine kinases. It was first approved by the Food and Drug Administration (FDA) in 2011 for treatment of patients in late-stage (locally advanced or metastatic) non-small cell lung cancer (NSCLC) with abnormal anaplastic lymphoma kinase (ALK) gene as detected by an FDA-approved test, as it confers improved progression-free survival comparison with chemotherapy. Methods: This is a retrospective chart review study of patients with stage IV ALK-positive NSCLC who attended the medical oncology department of Kuwait Cancer Control Centre (Kuwait) and King Fahad Specialist Hospital (Saudi Arabia) between January 2013 and May 2016. The efficacy and safety of crizotinib (250 mg orally, twice daily, with or without food.) were evaluated based on overall survival (OS), progression-free survival (PFS), Objective response rate (ORR), time to objective response, duration of response, and dose reduction or cessation because of crizotinib toxicity. Results: Twenty-three patients were involved in this study with a median age of 55.5 years and male-to-female ratio of 2.4:1 The median OS from initiation of crizotinib has not been reached; 1-year overall survival was 71.2%. Crizotinib treatment demonstrated median PFS of 9.6 months (95% CI, 3.0-24.1 months). The ORR was 70.9%. Complete response was achieved in 4.2% of patients, and partial response was achieved in 66.7% of patients. The most frequently reported adverse effects of crizotinib (Grade 1 / 2) were muscle ache, fatigue, nausea, vomiting, diarrhea, constipation, edema, elevated transaminases, bradycardia, and vision disorders. Grade 3 / 4 diarrhea was reported in 12.5% of patients. The proportion of patients who required dose reduction because of Crizotinib-induced bradycardia was 8.3% of patients. Conclusions: Crizotinib appears to be a very favorable option for treating patients with stage IV ALK-positive NSCLC. Crizotinib showed a very tolerable toxicity profile.