bluuebunny/crossref_metadata_2025_split huggingface dataset:
KRAS gene mutation status and sensitivity to pemetrexed: A retrospective analysis.
Authors: Kamdar Manali K. , Parent Teresa , Walker Paul R. 
Published: March 2020

e19154 Background: KRAS is the most frequently mutated oncogene (25%) in lung adenocarcinoma. KRAS mutations are a negative prognostic factor for survival. Recent phase II trial with a MEK inhibitor has shown promising efficacy albeit at the cost of higher adverse events. Preclinical work by Moran et al showed that antifolate therapies like pemetrexed decrease KRAS gene expression in KRAS wild type and KRAS mutant but do not do so in KRAS mutant amplified cells. Targeted therapies for EGFR, ALK and ROS1 have increased the survival for lung adenocarcinoma expressing these actionable targets. No therapies are yet approved for KRAS mutant subsets. Hence therapeutic strategies that target this cohort represent an unmet medical need. Methods: We reviewed data from patients (pts) in our thoracic oncology clinic with stage IIIB and stage IV lung adenocarcinoma with KRAS mutation positive tumours who received pemetrexed either during induction or maintenance therapy. Pt characteristics including age, sex, race, smoking history, KRAS mutation subtype and overall survival were analyzed. Results: Between April 2010 and October 2012 we treated 154 pts with stage IIIB and stage IV lung adenocarcinoma. Of these 154 pts we found 34 patients with KRAS mutation positive tumours. 10 pts out of 34 pts with KRAS mutation positive tumours received pemetrexed during induction or maintenance therapy and were analyzed further. Median age 63. 60% females. 90% Caucasians. 90% were smokers. KRAS 12C mutation was found in 2 pts, KRAS 12V in 4, KRAS 12A in 3 and KRAS 13A in 1 pt. 4(40%) patients died. Median overall survival (OS) in the KRAS 12C, 12V, 12A and 13A was 14, 9.5, 10 and 12 months respectively. Conclusions: The median OS in published series is 15.4, 14, 8 and 7 months in the KRAS 12C, 12V, 12A and 13A cohorts respectively (Rosell et al). Our analysis found that pts with KRAS 12C, 12A and 13A mutation had a survival advantage with pemetrexed therapy as compared to pts with KRAS 12V mutation. Thus this retrospective study supports the concept that KRAS mutation status affects sensitivity to antifolate therapy (pemetrexed).
Comorbidity: Usage of, and survival after chemotherapy for advanced lung cancer.
Authors: Mellemgaard Anders , Bredin Philomena , Iachina Maria , Green Anders , Krasnik Mark , Jakobsen Erik , Lüchtenborg Margreet , Møller Henrik 
Published: March 2020

e19157 Background: Comorbidity may influence prognosis in lung cancer, affect performance status (PS) of patients as well as complicate treatment. The present study examines usage and outcome of chemotherapy (CT) for advanced-stage lung cancer, and focuses on the role of comorbidity. Methods: Patients with advanced-stage lung cancer were identified in the Danish Lung Cancer Registry. A total of 22,999 patients with non-resectable, advanced-stage lung cancer were identified. Data on stage, PS, Charlson comorbidity score (ChS), age, histology and type of first treatment (if any) were avaliable. First treatment was categorized as chemotherapy (n=7,346), chemo-radiotherapy (2,636), radiotherapy (n=4,155) or no therapy (n=8,862). Survival was examined separately for 0-1 year and 1-5 years, and further distinction was made between metastatic and non-metastatic lung cancer. Data are presented for the subgroup of patients receiving chemotherapy as first treatment only. All estimates are derived from logistic regression model adjusting for the effect of performance status, pulmonary function and histological type, except for usage where models included same variables plus stage. Results: Use of chemotherapy was less frequent for more comorbid patients (OR 0.86, 0.64, 0.56 for Charlson score 1, 2, 3+ respectively compared to no comorbidity). Older patients and men were less likely to receive CT. For patients receiving CT as first treatment for non-metastatic lung cancer, survival in the first year was slightly worse for those with co-morbidity (HR 0-1year, non metastatic =0.91, 0.92, 0.87 for ChS 1,2,3+ respectively). For 1-5years and for metastatic lung cancer no correlation between comorbidity and survival was noted. In contrast, PS and sex was strongly associated with survival. Conclusions: With increasing co morbidity, chemotherapy was used less often. Comorbidity is not an important prognostic factor in advanced lung cancer treated with chemotherapy. However, sex and especially performance status remain as strong prognostic factors in this patient group.
Clinical predictive model for brain metastasis at presentation in patients with non-small-cell lung cancer (NSCLC).
Authors: Acevedo-Gadea Carlos Rodrigo , Trinkaus Kathryn , Govindan Ramaswamy , Morgensztern Daniel 
Published: March 2020

e19158 Background: There is limited data on the prevalence of brain metastases at presentation in NSCLC. Between 1988 and 1997, the Surveillance, Epidemiology, and End Results (SEER) database recorded the use of brain radiation in patients with lung cancer. We developed a predictive clinical model for brain metastases (BM) at presentation based on the use of brain radiation (BRT), which may be used as a surrogate since it is not indicated in NSCLC patients without BM. Methods: Patients with NSCLC diagnosed between 1988-1997, aged 21 or older were subdivided according to radiation data into none or indicated (given, refused or unknown if administrated). Since the database records only initial therapy, patients with indication for radiotherapy were assumed to have had early brain metastases. Frequencies and odds Ratio (OR) were calculated for each demographic factor and the most significant were included in the predictive model. Results: Among the 131,456 patients evaluated, 10,963 (8.4%) had BRT indicated. The most significant predictors in multivariate analysis were age > 60 (HR 0.5; 95% CI 0.46-0.54), non-squamous histology (HR 0.53; 95% CI 0.48-0.59), size > 5 cm (HR 1.27; 95% CI 1.16-1.39), grades III-IV (HR 2.04; 95% CI 1.82-2.27) and N2-3 involvement (HR 2.55; 95% CI 2.34-2.78). The 40,963 patients with known status of all 5 factors were used in the predictive model. The frequency of BM for patients with zero, 1, 2, 3, 4 and 5 factors were 0.7%, 1.8%, 4.7%, 8.9%, 13.7% and 20.2% respectively. Conclusions: Despite the limitations of this study, including indication for BRT as a surrogate for BM, older data and possible bias in the use of brain imaging according to demographic factors, our findings showed that the risk of BM at presentation may be stratified with the use of 5 clinical factors. These results may be used as a baseline for studies on clinical and molecular determinants of BM.
Third-line therapy and beyond for patients with advanced/metastatic non-small cell lung cancer (NSCLC).
Authors: Corral Jaime Jesus , Gonzalez de la Peña Miriam , Alonso Miriam , Sanchez Gastaldo Amparo , Mediano Maria Dolores , Amerigo Marta , Robles Carlos Enrique 
Published: March 2020

e19160 Background: Lung cancer is the leading cause of cancer-related deaths globally, with a 15% 5-year survival rate. Platinum-based chemotherapy constitutes the main treatment modality, with a median overall survival (OS) of approximately 10–12 months. The current National Comprehensive Cancer Network (NCCN) guidelines recommend several options for first-line and second-line therapies but endorse only erlotinib/gefitinib as third-line therapy in unselected patients, as well as crizotinib in ALK-positive selected patients.The paucity of approved agents for third-line therapy and beyond for patients with non-small cell lung cancer (NSCLC) constitutes an important unmet medical need. Methods: Retrospective analysis of 22 patients with advanced/metastatic NSCLC in progression after a minimum of 3 lines of therapy. Results: Between January 2009 and October 2012, 22 patients were analysed. Median age at diagnosis was 62 years old. 15% of patients were never smokers and 72.7% had non squamous NSCLC histology. Stage at diagnosis resulted: 6 (27.3%) stage IIIA, 3 (13.6%) stage IIIB and 13 (59.1%) stage IV. 3 (13.6%) patients were EGFR mutation carriers and 1(1%) patient had ALK translocation. Third line therapy options resulted a clinical trial (27.3%), erlotinib (22.7%), paclitaxel/gemcitabine (13.6%), docetaxel (9.1%) and crizotinib (4.5%). Estimated median progression-free survival (PFS) between first and second line therapy was 5.3 months; PFS between second and third line resulted 4.4 months. Median PFS and overall survival (OS) beyond third line treatment has not been reached yet. Conclusions: Currently, erlotinib/gefitinib and crizotinib, which target EGFR and ALK, are the only recommended agents for third-line therapy in patients with advanced/metastatic NSCLC. Real-world clinical practice reveals a variety of chemotherapeutic agents used in this setting. Additional systemic and/or targeted therapeutic under development, with complementary biomarker analysis, should be the key in identifying those patients most likely to benefit from newer agents.
Effect of LIM domain only (LMO2) protein expression on survival in multiple myeloma patients.
Authors: Kelkitli Engin , Atay Memis Hilmi , Yildiz Levent , Turgut Mehmet 
Published: March 2020

e19500 Background: Better understanding of the biology of myeloma paved the way for new treatments that target myeloma cells which are playing a critical role in the pathogenesis of the disease and microenvironments of the bone marrow. LMO2 (LIM domain only 2) is located on 11p13 and belongs to a family of 4 genes encoding LIM only proteins, that are transcription regulators that control cell fate in normal hematopoiesis. LMO2 has been identified as a novel oncogene associated with carcinogenesis and better prognosis in several malignant tumors such as pancreatic, prostate cancer. We examined if LMO2 protein expression can predict the outcome in MM patients. Methods: Forty-one patients were enrolled with MM admitted to our hospital. Immunohistochemistry on bone marrow biopsy material for LMO2 protein was performed in our hospital pathology laboratory, and staining in greater than 30% of plasma cells was assigned positive score. Results: Of the 41 patients , 21 were male and 20 were female. The mean age was 62±11. The demographic characteristics of patients are shown in the table. Thirty patients had LMO2 protein expression in bone marrow samples whereas in eleven patients LMO2 protein expression was not detected. LMO2 negativity were more frequent in patients with type of lambdaM protein (P=0.04). The risk of death was increased in the patients with LMO2 protein expression compared with patients who had no LMO2 protein expression. While overall survival was %100 in the patients with no LMO2 protein expression, it was %76.7 in the patients with LMO2 protein expression (according to Kaplan Meier test, long rank p=0.04). Conclusions: We report that the no LMO2 protein expression is correlated with improved overall survival in the MM patients. This method is simple, inexpensive, and effective. We suggest that the expression of LMO2 should be tested in a larger series of MM patients. [Table: see text]
Rituximab and dose-adjusted EPOCH (R-EPOCH) for treatment of aggressive B-cell non-Hodgkin lymphomas: A developing country perspective.
Authors: Jain Hasmukh , Shet Tanuja , Sridhar Epari , Menon Hari , Dangi Uma Bhaskar , Bagal Bhausaheb Pandurang , Gujral Sumeet , Laskar Siddharth , Rangarajan Venkatesh , Sengar Manju 
Published: March 2020

e19503 Background: Biological heterogeneity of diffuse large B-cell lymphomas (DLBL) is reflected in variable outcomes with R-CHOP. Clinicopathological features like high IPI, underlying acquired immunodeficiency, non-germinal center phenotype, primary mediastinal B-cell histology and Bcl-2 positivity correlate with adverse biology. Effect of adverse biological attributes is also reflected in outcomes B-cell lymphoma intermediate between diffuse large cell B-cell and Burkitt’s lymphomas (BCLU) and Burkitt’s lymphoma in elderly and HIV-positive individuals with low CD4 counts. Given the promising efficacy of R- EPOCH in poor-risk DLBL we used it in therapy of aggressive B-cell NHL. Methods: From May 2010 to December 2012 patients with de-novo aggressive B-cell lymphomas with adverse clinicopathological features (DLBL with multiple extranodal sites, high IPI, primary mediastinal B-cell lymphoma, BCLU, Burkitt’s lymphoma in elderly or in HIV-positive individuals) were treated with R-EPOCH. Demography,stage, bulk of disease, IPI, CD4 counts, grade 3/4 toxicities and death were recorded. Responses were evaluated at mid and end of therapy. Overall and progression-free survivals were calculated. Immunohistochemistry was used to classify the germinal center and non-germinal center phenotype. Results: 33 patients (males-21, female-12) were treated with median of 6 cycles (range 3-6) of R-EPOCH. Histologicalsubtypes distribution was- DLBL-16, BL-8, BCLU-5, and PMBL-4. Sixty percent of DLBL were non-germinal center type and bcl-2 positive. Median age was 33 years (range 15-73 years). More than 2/3 of patients had stage 3/4 bulky disease with high IPI. Twelve patients were HIV positive with median CD4 count of 173/µL (range 43-359/µL). Complete responses were seen in 66.7% at interim evaluation and in 90% at the end of therapy. At a median follow up of 8 months, 1- year overall survival and progression- free survival were 72.5% and 90% respectively. Two patients died due to therapyand grade 3/4 toxicities were seen in 10% patients. Conclusions: R-EPOCH regimen is efficacious in patients with poor-risk aggressive B-cell NHL however longer follow-up is needed.
Biologic variations of plasma cells in the bone marrow of smoldering multiple myeloma (SMM) and multiple myeloma (MM) patients: Multiple biopsies in the same patient.
Authors: Manasanch Elisabet E. , Korde Neha , Yuan Constance , Kwok Mary , Tageja Nishant , Bhutani Manisha , Flanders Aaron W. , Zingone Adriana , Costello Rene , Tembhare Prashant , Mulquin Marcia , Zuchlinski Diamond , Maric Irina , Calvo Katherine R. , Steinberg Seth M. , Roschewski Mark J. , Landgren Ola , Braylan Raul , Stetler-Stevenson Maryalice 
Published: March 2020

e19506 Background: The European Myeloma Network has reported that plasma cell (PC) enumeration by flow cytometry (FC) varies depending on quality of aspirate pull and field biopsied. We conducted a prospective study to evaluate PC site variation content in the core biopsy (CB), PC viability (V) and proportion of monoclonal PCs based on immunophenotypic characteristics, anticoagulant use, and aspirate (A) pull sequence in SMM and MM treatment-naïve patients. Methods: Untreated SMM (n=5) and MM (n=5) patients underwent bilateral bone marrow (BM) A and CB. Bilateral first-pull A were anticoagulated with ethylenediaminetetraacetic acid (EDTA). The second-pull A were anticoagulated with heparin. CB were performed after obtaining all A. The first pull A was sent for morphology and FC evaluation, and the second-pull for FC. CB infiltration by PC was assessed by CD138 immunohistochemistry (IHC). Analysis of PC by FC used CD markers: 19, 45, 20, 38, 138, 27, 28, 19, 81, 126, 200 and 117. V was measured by FC using 7-amino-actinomycin D exclusion. We used the two-tailed Wilcoxon signed rank test to determine the significance of the difference between paired values. Results: The mean difference in estimated percentage of PC infiltration between the right and left CB was 0.033 +/- 0.017 (p=0.25). Phenotypic analysis of PCs by FC showed similar expression of CD markers. PC V was significantly lower in samples anticoagulated with EDTA when compared to heparin (p<0.005), suggesting that the latter is superior for PC analysis. Of importance, the fraction of abnormal PCs determined by FC did not differ significantly between the two sides, use of EDTA/heparin or order of A pull (p>0.05). Conclusions: Based on IHC and FC, our results suggest that in untreated patients with SMM or MM there are no major differences in the estimated number or immunophenotypic characteristics and distribution of PC in marrow samples obtained from two distant bone sites. These observations have implications for current diagnostic and treatment of MM and its precursor disease. More advanced molecular profiling may find biological variation in bone marrow tumor PC extracted from different locations.
Results of upfront therapy for marginal zone lymphoma (MZL).
Authors: Cabanillas Fernando , Ortega Jose Luis , Rivera-Rodriguez Noridza , Rodriguez Blanca , Pardo Wandaly Ibis , Pavia Orestes Antonio , Bruno Margarita , Santiago Karen J. 
Published: March 2020

e19510 Background: MZL is an indolent NHL composed of 3 subtypes: extranodal (MALT), splenic marginal zone (SMZL) and nodal marginal zone (NML). While MALT usually presents with early stage, the others frequently present with advanced disease. Early stage MALT is usually treated with XRT or antibiotics with ~85-90% failure free survival (FFS) and overall survival (OS), while for SMZL watch and wait or splenectomy (Spl) have been the mainstay of therapy. Spl leads to improvement but rarely to CR. 5 yr FFS and OS with Spl have been 45% and 80%. At 10 yrs FFS and OS are 22% and 62%. NML is usually managed with watch and wait. The 5 yr FFS and OS for NML have been 30% and 60%. Watch and wait and Spl are used in part because advanced MZL is considered incurable. Rituximab (R) as well fludarabine (F) are active in this disorder but traditionally are given after relapse. Methods: Instead of watch and wait or Spl, we have used upfront chemo with curative intent for SMZL and NML as well as for advanced MALT. For early stage MALT we used either XRT alone or antibiotics. We hereby report on 44 pts with MZL of which 31 were MALT, 9 SMZL, 4 NMZL. For the purpose of analysis we divided the pts in 2 groups. Group 1 consists of 22 early stage MALT who were all treated with either XRT (N=17) or antibiotics +/- surgery (N=5). Group 2 consists of 22 cases who were treated with chemo alone. This group is made up of 9 MALT (4 advanced stage, 3 early stage but with transformation, 2 early stage but in whom XRT was contraindicated), 9 advanced stage SMZL, 4 NML. Chemo for group 2 consisted of F, mitoxantrone, dexamethasone, rituximab (FND-R) (N=14) or R-CHOP (N=8). Maintenance R was used in 70% of group 2. Results: Of the whole group, 100% were CR and only 2 relapsed at 70 and 75 months; both relapses were stage I MALT and had received XRT only. Both were salvaged with FND-R and remain NED 27 and 39 months from relapse. At 10 yrs, FFS was 80% and OS=100%. None of the 22 in group 2 have relapsed. The long-term toxicity has been acceptable. Conclusions: The excellent FFS and OS using upfront chemotherapy in group 2, suggests that this disorder is curable and our results should be confirmed in a prospective trial. For those with early stage MALT, XRT alone +/- antibiotics and when necessary salvage with FND-R, should be tested.
Post-transplant lymphoproliferative disorder (PTLD) after liver transplantation: Report of 16 cases from a single center.
Authors: Ulusakarya Ayhan , Delmas Marsalet Beatrice , Misra Srimanta , Cucherousset Nahla , Ichai Philippe , Haydar Mazen , Almohamad Watek , Gumus Yusuf , Bessaoud Hamid , Innominato Pasquale , Goldschmidt Emma , Samuel Didier , Guettier Catherine , Machover David , Turhan Ali , Morere Jean-Francois 
Published: March 2020

e19513 Background: PTLD is a rare complication of organ transplantation, but it can jeopardize the transplantation outcome. Methods: Paul Brousse University Hospital is the largest liver transplantation center in France. We retrospectively analyzed data from all of the patients who experienced PTLD and treated in our hematology/oncology department in the last 10 years. Results: 16 cases of PTLD occurred after various intervals following the liver transplant without correlation with the type of underlying liver disease or immunosuppressive treatment. Overall, the patients had poor general health (ECOG 3-4: 69%), renal and/or hepatic failure (75%), and cytopenia (63%). PTLD were often of high grade (81%), B phenotype (94%), stage IV (75%), with high LDH (88%). The most frequent disease sites were liver (63%), subdiaphragmatic lymphadenopathy (69%), and extranodal (69%). After a reduction in the immunosuppressive treatment, the patients received their initial chemotherapy mostly with a combination of prednisolone, cyclophosphamide, vincristine, and rituximab. As soon as their general condition improved, R-CHOP was given as the standard regimen. All patients experienced severe and frequent complications during chemotherapy. Two patients had liver transplant rejection, lethal in one case. Six patients died: 4 of progression or relapse of PTLD, one after 4th liver transplantation, one of leukoencephalitis. Complete remission was obtained in 81% of patients. Ten patients (63%) are alive in complete remission after a median follow up of 6.5 years. Conclusions: Despite the clinical complexity of these patients, PTLD can be treated utilizing common lymphoma chemotherapy with treatment accommodations to poor ECOG, liver and renal dysfunctions.
Impact of bone marrow fibrosis (BMF) at diagnosis in patients with multiple myeloma (MM).
Authors: Preet Mohan , Liu Jinli , Axiotis Constantine A , Braverman Albert S , Sidhu Gurinder Singh 
Published: March 2020

e19522 Background: BMF is known to occur in a minority of myeloma patients, but its incidence in American patients of African origin is not known. The impact of BMT on presenting clinical and laboratory findings, and its relationship to genetic variants has not been defined. Methods: Kings County Hospital is located in the East Flatbush section of Brooklyn, New York, where the population is mainly of African-Caribbean origin. Records and bone marrow specimens of myeloma patients who presented from 2000 through 2010 were reviewed. Degree of fibrosis was graded according to World Health Organization criteria: mild, moderate and severe. Results: Records of 113 patients were reviewed, 110 (97%) 97 of whom were African American or Caribbean; 62 (55%) were female and 51 (45%) male. Their ages ranged from 38 to 89 (median 65). Of the 27 patients with BMF (24%), 17 (63%) were female. Mild, moderate and severe BMF were present in 14 (52%), 7 (26%) and 6 (22%) patients respectively. Presentation calcium and creatinine levels were normal in all patients. Hemoglobin levels were similar (median 9.6 G/dl) in patients without BMF and in those with mild and moderate grades, the median level was 7.5 G/dl in those with severe BMF. Immunoglobulin G, A and D levels (67, 20 and 1) were similar in patients with and without BMF, but lambda light chain expression was greater in the BMF patients: 41 vs 24%. Cytogenetic data (CGD) was available in 46 patients; and abnormal in 10 (22%). All patients with abnormalities of chromosomal number were hyperdiploid. Of the 27 BMF patients CG data was available in 17, and was abnormal in 2 (12%). FISH results were normal in 23 of 25 patients, and in all of those with BMF. The fraction of the BMF and non BMF patients surviving after median follow up periods of 828 and 885 days were similar. Conclusions: BMF in this population was 24%, and severe in 5%. Female preponderance is a characteristic of MM patients of African origin, and was more marked in those with BMF. The BMF patients were characterized by more severe anemia and greater lambda light chain expression.