bluuebunny/crossref_metadata_2025_split huggingface dataset:
Number of cycles of chemotherapy in patients with advanced non-small cell lung caner: Efficacy and relationship with histology.
Authors: Richardet Eduardo , Richardet Martin Eduardo , Castagneris Nicolas , Cortes Matias Nicolas , Laura Perelli , Molina Matias 
Published: March 2020

e18125 Background: Platinum based regimens are standard first-line treatment in patients with advanced non mall cell lung cancer. We intend to evaluate their effectiveness according to the number of cycles administered, and investigate whether histology is a predictor of benefit from a greater number of infusions. Methods: 124 patients with stage IV NSCLC were evaluated retrospectively. They were divided according to whether they made 4 or 6 cycles of chemotherapy. The schemes used were: Cisplatin / Gemcitabine and Carboplatin / Paclitaxel, at standard doses. We studied the efficacy in both groups according to the most common histologies (adenocarcinoma and squamous cell carcinoma). PFS (progression-free survival) and OS (overall survival) were calculated by the Kaplan-Meier curves and compared by the Log Rank Test. Results: Those who underwent 4 cycles had a PFS of 7.77 months and OS of 12.2 months vs. 8.64 and 10.8 months those who received 6 cycles (p = 0.47, p = 0.76). Within the subgroup with squamous histology (n = 43), PFS and OS were 7.38 and 13.38 months respectively in the group that received 4 cycles vs. 7.97 and 9.76 months in those receiving 6 (p = 0.70, p = 0.32 ). Within adenocarcinoma histology (n = 81), those who received 4 cycle, has a PFS of 8.17 months and they lived 11.56 month, vs 8.96 and 10.79 months for those receiving 6 cycles (p = 0.29, p = 0.88) Conclusions: In our population, a greater number of cycles showed no advantages in terms of progression-free survival or overall survival. Histology is not a predictive factor for deciding how many chemotherapy cycles administer.
Predictors of early discontinuation of chemotherapy (EDC) in patients (pts) age 65 or older with stage IV non-small cell lung cancer (NSCLC).
Authors: Gajra Ajeet , Tew William P. , Hardt Molly , Mohile Supriya Gupta , Owusu Cynthia , Klepin Heidi D. , Gross Cary P. , Lichtman Stuart M. , Katheria Vani , Hurria Arti ,   on behalf of the Cancer and Aging Research Group (CARG)
Published: March 2020

e18133 Background: NSCLC accounts for the highest cancer related mortality. Older pts suffer higher chemotherapy (chemo) toxicity (tox). Inability to complete a planned chemo course is associated with poor outcome. We studied factors associated with EDC (defined as chemo duration of ≤ 6 weeks) in pts ≥ age 65 with stage IV NSCLC. Methods: We conducted a subset analysis of pts with stage IV NSCLC (n=100) enrolled in a multi-site prospective study (n=500) which identified predictors of chemo tox in pts age > 65 (Hurria et al, JCO 2011). Bivariate analysis and multivariate logistic regression were utilized to identify factors associated with EDC among pts with stage IV NSCLC including: sociodemographics, chemo factors (1st vs. 2nd + line; single vs doublet), labs (hemoglobin [Hb], liver function, creatinine clearance, albumin) and geriatric assessment (GA) variables (functional status, comorbidity, social support, psychological, cognitive and nutritional status). Results: Of the 100 pts (median age 73, range 65-89) with stage IV NSCLC, 33 had EDC. Of these 67% was for disease progression, 15% tox and 15% for both progression and tox. Majority received 1st line (58%) and doublet chemo (67%). In bivariate analysis (p values <0.01 for all), pts with EDC were more likely to receive single agent (52% vs. 24%) and 2nd + line chemo (70% vs 28%)and have lower mean Hb (11.3 vs 12.7 g/dl) and albumin levels (3.4 vs 4.0 g/dl). GA variables associated with EDC include poorer physical function [lower score on Medical Outcomes Study physical health (MOS physical), MD rated Karnofsky performance status (KPS), self rated KPS, and MOS social activity, and need assistance with instrumental activities of daily living; p<0.01 for each variable]. On multivariate analysis, factors independently associated with EDC include 2nd + line chemo (OR=5.93; 95%CI = 2.25-15.61) and lower MOS physical score of <70 (OR= 4.19; 95% CI= 1.56-11.29). Conclusions: In older pts with NSCLC, factors associated with chemo duration of < 6 weeks include 2nd+ line chemo and poor physical function best assessed by MOS physical in this cohort. These simple factors may help the practicing oncologist identify older pts with NSCLC at greatest risk for EDC.
KRAS mutations and outcomes for patients with stage IV NSCLC treated with frontline platinum/pemetrexed based chemotherapy.
Authors: Levy Benjamin , Seetharamu Nagashree , Richardson Stacie , Becker Daniel Jacob , Choi Walter , Evans Andrew , Bhora Faiz Y. , Connery Cliff P. , Grossbard Michael L. , Chachoua Abraham 
Published: March 2020

e18139 Background: KRAS mutations are the most common driver mutation indentified in NSCLC, occurring in 20 - 30% of adenocarcinomas. While several studies suggest KRAS predicts for lack of response to TKI therapy, few data exist regarding its association with outcomes for patients treated with cytotoxic chemotherapy. This study explores the association between KRAS mutations and outcomes (RR, PFS) in a cohort of patients treated with frontline platinum/pemetrexed (PPm) based therapy. Methods: In this retrospective chart review, we evaluated RR and PFS for 16 KRAS + EGFR – pts treated with carboplatin (AUC 5-6) or Cisplatin 75mg/m2 and (Pm)pemetrexed (500 mg/m2) +/- (B)bevacizumab 15mg/kg. For comparators, we identified 19 KRAS - EGFR - patients treated with the same regimen. Maintenance therapy with Pm or Pm+B was given at the discretion of the treating physician. KRAS and EGFR mutational status were assessed by RT-PCR on tumor tissue collected at first diagnosis. RR was assessed using RECIST criteria. Kaplan-Meier estimates for PFS were evaluating using log rank test. Fisher exact test was used to assess the association between KRAS mutation status and response rate. Results: The groups were similar in age (KRAS + mean 61 vs. 60; p=0.87), gender (62% vs. 57% F; p= 0.9), ECOG 2 (0 vs. 10%,p=0.47), smoking hx (93% vs. 94% current/former smokers, p=0.7), brain mets (0% vs. 18% p=0.22), mean number induction cycles (4 in each, p=0.6), cisplatin and bevacizumab use (12% vs 10%, p > 0.1;10% vs. 40%, p=0.10). Pm maintenance was used in 31% KRAS+ (5/16) and 26% KRAS-(5/19) (p=0.79). P+B maintenance was used in 12% (2/16) and 5% (1/19) (p=0.70). RR was 56% in the KRAS + (9/16) vs. 36% KRAS- (7/19) respectively (p=0.3). There was a statistically significant improvement in PFS in the KRAS + group (10.3 mos vs. 5.7 mos, p =0.03). Conclusions: In this small retrospective review, KRAS mutations appeared to be associated with a non-significant improvement in RR and significant improvement in PFS for patients treated with frontline PPm based therapy. Future prospective studies should investigate and validate the predictive value of KRAS for this cytotoxic regimen. [Table: see text]
GGCP041/09: A Galician study of second-line erlotinib in patients with advanced non-squamous non-small cell lung cancer (nsNSCLC).
Authors: Vazquez Estevez Sergio , Villanueva Silva Maria Jose , Firvida Perez Jose Luis , Lazaro Quintela Martin , Varela Ferreiro Silvia , Huidobro Vence Gerardo , Fernandez Calvo Ovidio , Campos Balea Begona , Casal Rubio Joaquin , Areses Manrique Carmen ,   Galician Lung Cancer Group
Published: March 2020

e18146 Background: Efficacy of oral erlotinib has been conclusively established in 2nd line setting (BR.21 and TRUST studies) and the outcomes are similar to those provided by other approved chemotherapeutical agents (TITAN study). Higher responses rates have been found in p with Asian ethnicity, adenocarcinoma, women and never smokers, where predictive EGFR mutations occur more frequently; even though erlotinib has a significant effect on survival in all subgroups of patients. This observational study evaluates the efficacy of 2nd line erlotinib in unselected p with nsNSCLC in 4 Galician institutions. Methods: Unselected p with advanced nsNSCLC were treated with 150 mg/day of erlotinib as 2nd line therapy until unacceptable toxicity or progressive disease. EGFR mutational status was retrospectively tested when feasible, and serum carcinoembryonic antigen (CEA) monitored during the treatment period. Results: Baseline characteristics of 45 p included at the time of this analysis: mean age of 61.7 yrs. (range: 38-83); 80% male; 73.3% adenocarcinoma; 71.1% stage IV; 7/69/24% PS ECOG 0/1/2; 29/33/38 % never/current/former smokers. EGFR activating mutation testing was performed in 24 p (53%) and 2 positive cases were found (8%), both with metastatic adenocarcinoma (stage IV). The median PFS was 3.3 (95% CI: 1.6-5.1) and the median OS 10 months (95% CI: 7.5-12.5). Among p without EGFR mutations, erlotinib conferred a median OS of 8.1 months (95% CI: 1.4-14.9). Out of 31 p evaluable, radiologic response was achieved in 7 p (22.6%), for an overall disease control rate of 45.2 %. No unexpected toxicities were reported: 60 % of p experienced cutaneous toxicity (6.6 % grade ¾), 22.2% asthenia (4.4% grade ¾) and 17.8% diarrhea (2.2% grade ¾). Only 3 p discontinued due to adverse events. Conclusions: This study confirms the efficacy and safety of 2nd line erlotinib in a clinical practice scenario and the outcomes in p with non-squamous NSCLC are equivalent to those reported with the chemotherapy for salvage therapy. Moreover, the absence of mutations does not preclude the benefit from the drug. Updated data of the study will be presented.
A single-institution experience with the hyper-CVAD regimen in aggressive NHL.
Authors: Younas Mariam , Gregory Stephanie A. , Jajeh Ahmad , Larson Melissa L. , Al-Rifai Taha 
Published: March 2020

e18510 Background: Hyper-CVAD (± rituximab) is a chemotherapy regimen designed as a treatment for aggressive hematological malignancies. It consists of 8 cycles. Cycle 1, 3, 5, 7 (3-4 weeks/cycle) includes cyclophosphamide 300mg/m2 IV over 2 hours (hrs) every 12 hrs for 6 doses on day 1-3 + Mesna 600mg/m2 per day continuous IV on days 1-3 to start 1 hr before cyclophosphamide till 12 hrs after completion of cyclophosphamide + vincristine 2mg IV on days 4 and 11 + doxorubicin 50mg/m2 IV over 24 hrs on Day 4 + dexamethasone 40mg daily orally on days 1-4 and days 11-14. Cycle 2, 4, 6, 8 (3-4 weeks/cycle) consist of high dose methotrexate (MTX) (200mg/m2) IV over 2 hrs followed by 800mg/m2 continuous IV infusion over 22 hrs on day 1 + cytarabine 3gm/m2 (1gm/m2 for patient age over 60 years old) IV over 2 hrs every 12 hrs for doses on days 2 and 3 + leucovorin 50mg IV every 6 hrs starting 12 hrs after completion of MTX till MTX level < 0.05µM. Hyper-CVAD is a short intensified regimen given over eight months compared to known therapy for ALL and Burkitt lymphoma. Methods: Retrospective review of all cases of acute lymphoblastic leukemia/lymphoma and Burkitt’s lymphoma between 2000 and 2012 was done. It included all patients and evaluated response to therapy including Hyper-CVAD. Results: A total of 79 patients with aggressive acute lymphoblastic leukemia/lymphoma and Burkitt’s NHL were analyzed. Mean age 39 years (range 15-75 years). All patients were admitted at least twice with febrile neutropenia. Prolonged cytopenias were observed in more than 50% of patients. Conclusions: Hyper-CVAD is an intense regimen that produces high rates of clinical remission in less than 8 months of therapy compared to established regimen for aggressive hematological malignancies. [Table: see text]
Gastrointestinal tract NK/t cell lymphoma: Clinical features, management, and prognosis of 47 patients.
Authors: Jiang Ming , Zou Li qun 
Published: March 2020

e18514 Background: The gastrointestinal tract is the most common primary sites of extranodal lymphomas, while gastrointestinal NK/T cell lymphomas (GINKT) are relatively rare. So far, the researches on this disease are few and the number of cases is small. In this article, we examined the clinical features andprognostic conditions of GINKT. Methods: A retrospective analysis was carried out on clinical data from 47 cases of confirmed GINKT. Results: Patients had a median age of 37 years. 35 cases were men (74.5%) and 12 cases were women (25.5%). The common clinical manifestations included fever (78.7%), abdominal pain (76.6%). Seventeen cases have intestinal perforation (36.2%). All patients showed ulcerative lesions, the most common site of involvement was the colon (27/47; 57.4%), followed by the jejunoileum and ileocecum (14/47; 29.8%). The median survival was 2.83(95% CI, 0.27–29) months. The log-rank univariate analysis showed older than 60 years, perforation, increased LDH level, high ECOG and NKIPI score, without chemotherapy, without surgery before perforation, late stage according to Musshoff or Lugano stage system had relatively poor prognoses. Cox multivariate analysis shown that age, perforation, B syndrome, stage according to Lugano system and surgery were independent prognostic risk factor for GINKT. Conclusions: GINKT is a rare type of lymphoma, is prone to perforation, hemorrhage and other complications, the prognosis is very poor. Lugano staging is a relatively suitable staging system. Surgery before Perforation is a key therapy factor which affected prognosis. Although values of chemotherapy and radiotherapy are unclear, combination therapy maybe is necessary.
Outcome in different molecular subtypes of diffuse large B-cell lymphoma: Indian experience.
Authors: Prakash Gaurav , Sharma Atul , Raina Vinod , Kumar Lalit , Sharma Mehar C 
Published: March 2020

e18518 Background: DLBCL has emerged as a heterogeneous disease and gene expression profiling has divided it into distinct molecular subtypes of Germinal center B-Cell (GCB) and Non-GCB- cell origin. These subtypes are reported to vary in the treatment responses and outcome. Methods: We analysed 97 consecutive patients of DLBCL who had satisfactory paraffin block of baseline biopsy. After reviewing diagnosis of DLBCL, sequential immunohistochemical staining with CD10, bcl6 and MUM1 was performed in all the cases. Using these markers the cases were sub-classified into GCB and non-GCB types as per Hans’ algorithm. Baseline presentation, stage, international prognostic score and treatment outcome were recorded. Survival was assessed by Kaplan-Meier survival curves and results were compared using log-rank test. Results: Thirty-three (34%) patients were classified in GCB group while 64(66%) patients in non-GCB group. Median age in both the groups was 50 years. High IPI score2-5 (GCB-34%, non GCB-72%;p 0.005) and stage 3,4 (GCB-39%,nonGCB-61%;p 0.04) were higher in non-GCB group. All the patients were treated with 6-8 cycles of CHOP based regimen and involved field radiotherapy wherever required. Complete remission rate (GCB-52%, nonGCB-27%; p0.02) was higher in GCB group. Three year overall survival, 75% and 63 %( p0.04), and event free survival was 63% and 43 %( p0.02) in GCB and non GCB subtypes, respectively. There was no difference in between two groups for performance status, LDH level and age. Conclusions: In our study, GCB-DLBCL patients had better response rate, EFS and OS in comparison to non GCB subtype. There were higher number of patients with advanced stage and high IPI score in non-GCB subtype which might have contributed to the poorer outcome.
Central nervous system lymphoma: Prognostic factors.
Authors: Huelves Miriam , Millán Isabel , Cantos Blanca , Doger de Speville Bernard Gaston , Ibeas Patricia , Lopez-Gonzalez Ana , Mendez Miriam , Sánchez Antonio , Maximiano Constanza , Provencio Mariano 
Published: March 2020

e18521 Background: CNSL constitute less than 2% of all the NHL and 3% of the tumors of the CNS. We studied the prognostic factors of these patients. Methods: This is a retrospective study, we analyzed data from 21 patients, diagnosed on the last 20 years. We used the test of Chi-square corrected by Yachts and Fisher's exact test for qualitative variables and the contrast t of Student and the contrast not parametric U of Mann-Whitney for quantitative variables. The curves of survival were estimated by Kaplan-Meier's method. Results: 62% were males, with a median age of 53.4 years (range 31-72), and the 90.5% were HIV negative. The most frequent histological type (52.4 %) was the Diffuse Large B-cells Lymphoma. Most of them, 75%, were treated with High dose-Metotrexate (HD-MTX). Patients treated with other schedules obtained less disease free survival (DFS) and overall survival (OS). Many prognostic factors were analyzed, but only high LDH values at diagnosis was associated to worse prognostic (p=0.021). The OS and DFS at the first year were 88.2 % and 67.7 % respectively. Conclusions: The best results were obtained in patients treated with HD–MTX. Because of difficult management of these patients, we believe they must be treated in reference centers.
Preclinical development of an anti-CD30/anti-CD16A bispecific tetravalent TandAb antibody for the treatment of Hodgkin lymphoma.
Authors: Knackmuss Stefan , Reusch Uwe , Burkhardt Carmen , Fucek Ivica , Le Gall Fabrice , Pauels Hans-Gerd , Little Melvyn , Zhukovsky Eugene 
Published: March 2020

e18532 Background: CD30 is a validated tumor target that is expressed on both Hodgkin’s Lymphoma cells and some activated immune cells. To improve antibody-based therapies targeting CD30, Affimed developed an NK cell-recruiting bispecific antibody. Methods: To enhance the recruitment and activation of NK cells for tumor cell lysis, we isolated a human antibody that is highly specific for the A isoform of FcgRIII (CD16A). Its variable domain (Fv) was used to construct a tetravalent bispecific TandAb, consisting of four Fvs linked in tandem, with two binding sites for both the CD16A on NK cell and the CD30 target cell antigens. The resulting anti-CD30/anti-CD16A bispecific tetravalent TandAb AFM13 was compared to both an anti-CD30/anti-CD16A bispecific diabody and an Fc-enhanced anti-CD30 IgG in binding and cytotoxicity assays in vitro. Pharmacokinetics and safety of the TandAb were investigated in Cynomolgus monkeys. Results: AFM13 is retained longer on NK cells than either the anti-CD30 IgG or the bispecific diabody due to its bivalency for CD16A; it binds both CD16A alleles (158F, 158V) equally well indicating the potential for broader patient response than that achieved with current therapeutic mAbs. AFM13 did not induce systemic activation of NK cells. It displays higher potency (EC50) and higher efficacy (maximal lysis) than either the anti-VD30 IgGs or the bispecific diabody in a cytotoxicity assay. The cytotoxic activity of AFM13 is unaffected by physiological concentrations of polyclonal IgG, whereas that of anti-CD30 IgGs is dramatically reduced. Cynomolgus monkeys were identified as the only relevant species for toxicity testing. Pharmacokinetics studies reveal AFM13 half-lives of up to 22.9 h after repeated dosing. MTD was not reached in a single dose escalation study ranging to 100 mg/kg maximum. A 28 days toxicity study, with dosing up to 10 mg/kg every other day, revealed an excellent safety profile. No signs of immunotoxicity or systemic cytokine release were observed. Conclusions: AFM13 may be a more effective treatment for Hodgkin’s Lymphoma that is refractory to treatment with anti-CD30 IgGs and is under evaluation in a Phase I clinical trial.
Clinical significance of nuclear kappa B and chemokine receptor CXCR4 expression in patients with diffuse large B-cell lymphoma.
Authors: Kang Byung Woog , Kim Jong Gwang , Chae Yee Soo , Lee Soo Jung , Sohn Sang Kyun , Moon Joon Ho , Choi Jun Young , Lee Yoo Jin , Baek Jin Ho 
Published: March 2020

e18533 Background: This study investigated the activation of nuclear factor kB (NFkB) and the chemokine receptor CXCR4 co-expression in patients with diffuse large B-cell lymphoma (DLBCL) who received rituximab-based therapy. Methods: Seventy patients with DLBCL and treated with rituximab-CHOP (RCHOP) were included. Tissue microarray blocks were created from 70 cases of DLBCL. Sections were stained with antibodies to IKKα, p-IkB, p50, p52, and CXCR4. To classify cases of DLBCL into GCB (germinal center B-cell-like) and non-GCB, additional immunohistochemical expression of CD10, bcl-6, or MUM1 has been used in this study. A numeric intensity score of 0-3 was assigned each case. Negative was scored if 0/+1 and positive was scored if 2+/3+. Results: The median age was 66.5 years (range, 17-87) and 58.6% were male. Twenty-seven patients (38.6%) had stage III and IV at diagnosis. Twenty-three patients (32.9%) were categorized as high or high-intermediate risk according to their IPI. The overall incidence of BM involvement was 5.7%. Positive expression for NFkB and CXCR4 were more than 80%. In NFkB and CXCR4 status, there are no significant difference between GCB and non-GCB. High NFkB expression is associated with CXCR4 expression and they are co-expressed in about two thirds of patients. With a median follow-up duration of 28.7 months (range, 0.1-76.1), the 5-year overall survival (OS) and event-free survival (EFS) rate was 67.4% and 79.8%, respectively. Neither NFkB nor CXCR4 were associated with DLBCL outcomes. Conclusions: In concolusion, none of the NFkB and CXCR4 expression profiles investigated in this study was found to be an independent prognostic marker for Korean patients with DLBCL. However, further studies on a larger scale are warranted to clarify the role of NFkB and CXCR4 as a prognostic marker.
What is the significance of CCR5 status in HIV-associated non-Nodgkin lymphoma (NHL)?
Authors: Zaia John , Gaal Karl , Palmer Joycelynne , Li Shirley , Simpson Jennifer , Forman Stephen J. , Krishnan Amrita Y. 
Published: March 2020

e18542 Background: The chemokine receptor CCR5 is a co-receptor for HIV. Carriers of the delta 32 gene (D32) mutation who lack CCR5 are protected from HIV infection by the R5 variant of the virus. Heterozygotes have slower progression to AIDS. For HIV NHL patients, the effects of the presence of the gene mutation are unclear. Methods: 93samples obtained from the ASCR (AIDS and Cancer Specimen Resource ) tissue bank of patients with HIV NHL were assayed for the presence of the mutation. We then studied if there was an association with the mutation and subtype of diffuse large cell lymphoma (DLBCL) (germinal center GC vs non GC), EBV status, or cell activation markers. Date of NHL diagnosis was from 1989 to 2005. Samples predating 1996 were characterized as pre HAART (highly active antiretroviral therapy) and all others post HAART. Results: There were 87 DLBCL, 3 plasmablastic lymphoma, 2 plasmacytoma and 1 anaplastic large cell T-cell subtype. Of the DLBCL, 48 were GC subtype and 39 were non GC subtype. GC subtype was 8.3 % (4/48) heterozygous for the D32. Non GCB subtype was 10.3 % (4/29) heterozygous. There was no difference in the percent heterozygosity for D32 pre or post HAART (14.8% vs 11.1%). The pre HAART specimens had greater EBV+ (44% vs 29% P=0.16) and more frequent BLIMP(B lymphocyte induced maturation protein) positivity ( 27% vs 17%. P=0.39) ). CCR5 heterozygous mutants were less often BLIMP positive (10% vs 21.4% P=0.68) and more often overexpressed p53 by immunostain (40% vs 23.9% P=0.47) compared to wild type CCR5. There was no correlation between EBV status and the presence of the mutation (36.3% vs 33.3%). Conclusions: CCR5 gene mutation status did not influence the subtype of DLCL. but the differences seen in BLIMP expression may have implications. Additional larger studies are needed to bear out suggested but statistically non-significant trends. BLIMP is a known repressor of p53. The overexpression of p53 and decreased BLIMP seen in CCR5 heterozygotes suggests alternate oncogenic pathways may be operative compared to wild type CCR5 lymphoma patients. Our ongoing clinical trial of HIV NHL pts undergoing transplant is assessing CCR5 status to see if there is a correlation with disease free and overall survival.