bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictive factors for plasma cell disorders in African American patients: A community practice perspective.
Authors: Tun Nay Min , Joseph Gardith , Soe Aye Min 
Published: March 2020

e19508 Background: African Americans have over two-fold higher incidence of multiple myeloma (MM) compared to other ethnic groups in the United States. Screening tests for MM are most often done when patients present with features suggestive of anemia, renal impairment, hypercalcemia, hypergammaglobulinemia or lytic bone disease, although MM may present with other manifestations. We carried out a retrospective study to investigate the potential clinical variables predictive of plasma cell disorders (PCD) in African American population. Methods: We reviewed the charts of African American patients who had serum protein electrophoresis, immunofixation and serum free light chain levels from 2007 to 2012. We defined traditional triggers for MM workup as hemoglobin (Hb) < 11 g/dL, serum creatinine (Cr) > 1.3 mg/dL, corrected serum calcium (Ca) > 10.5 mg/dL, albumin to globulin ratio (A:G ratio) < 1, and osteopenia or lytic lesion on DEXA scan/X-ray. PCD was defined as monocloncal gammopathy of unknown significance (MGUS), smoldering MM, MM, light chain MGUS or light chain only MM. Results: 254 patients were eligible. Mean and range of age, Cr, Ca, A:G ratio, Hb, total white blood cell, absolute neutrophil and platelet counts were 60 years (21 - 95), 1.05 mg/dL (0.49 - 9.6), 9.5 mg/dL (8.5 - 11), 1.07 (0.31 - 3.08), 11.7 g/dL (5.7 - 16.5), 6 x 103/mm3 (1.9 - 26), 3675 x 103/mm3 (192 - 11765) and 237 x 103/mm3 (22 - 1262), respectively. Twelve (13%) out of 92 patients without traditional trigger variables had PCD. In contrast, 50 (31%) out of 162 patients with trigger variables had PCD (composed of 48% MGUS, 8% smoldering MM, 14% MM, 25% light chain MGUS and 2% light chain only MM). There is a significant association between the presence of trigger variables and PCD (χ2= 9.16, p = .002). The number of trigger variables is positively correlated with the likelihood of a PCD (Spearman’s rho = .22, p < .001). So is increasing age (Spearman’s rho = .29, p < .001) in patients with trigger variables. However, age is not predictive of PCD in patients without trigger variables (rho = .1, p = .34). Conclusions: The number of traditional trigger variables and increasing age (especially over 50 years) are predictive of PCD in African American population.
Use of a mathematical model of serum-free light chain decline to identify a kinetic predictive marker of survival in patients with newly diagnosed multiple myeloma treated with bortezomib plus dexamethasone and autologous stem cell transplantation.
Authors: Mael Heiblig , Florence Lachenal , Colomban Olivier , Karlin Lionel , You Benoit 
Published: March 2020

e19515 Background: According to 2011 International Myeloma Working Group recommandations, serum-free light chain (sFLC) assessment is indicated in non secretory Multiple Myeloma (MM). sFLC monitoring is now routinely used for diagnosis and early response treatment assessment but its actual prognosis values regarding survival is not clear. Based on mathematical modeling, this study aimed at evaluate the predictive value on progression free survival (PFS) of modeled sFLC kinetics during frontline treatment. Methods: Model-based analysis of sFLC kinetics from 28 newly diagnosed MM patients treated at a single institution with 4 cycles of bortezomib and dexamethasone plus autologous stem cell transplantation (ASCT). MONOLIX program was used to fit Box-Cox transformed [sFLC] concentration-time profiles to the equation : [sFLC(t) = [sFLC1*exp(-KDEC1*t)]+[sFLC2*exp(-KDEC2*t)]+[sFLC3*exp(KPROD*t)] ] where KDEC1 and KDEC2 represent the decline rates of sFLC while KPROD is the involved light chain production rate observed after the end of the decrease. The predictive values of the modeled kinetic parameters , regarding PFS were tested using logistic regression, and survival analysis. Results: Median PFS was 17.9 months . Three modeled kinetic parameters categorized by their medians had strong predictive values regarding PFS using univariate tests: sFLC decline rate KDEC1 (median PFS = 38.6 months if KDEC1 ≥ median vs 14 months if KDEC1 < median, P=0.01); light chain production rate KPROD (median PFS = 24.9 months if KPROD < median vs 7.8 months if KPROD ≥ median, p=0.01); and initial SFLC production slope sFLC3 (median PFS = 24.9 months if sFLC3 < median vs 14 months if sFLC3 ≥ median, p=0.03). The same kinetic model for M-protein decline was not significant (p=0.53). Using multivariate analysis, the only remaining significant predictive factor of PFS was: KDEC1 (HR, 0.11; 95% CI 0.01-0.88; P=0.04). Conclusions: The modeled kinetic parameter of sFLC decline KDEC1, may be easily used as an early predictor of survival after frontline ASCT in MM. Validation in larger studies is warranted.
Prothrombotic profile in multiple myeloma: Response to treatment and associated thrombotic complications: A prospective observational study.
Authors: Panda Dipanjan , Sharma Atul , Raina Vinod , Kumar Lalit , Saxena Renu , Thulkar Sanjay 
Published: March 2020

e19531 Background: Venous thromboembolism (VTE) is a major complication of Multiple myeloma. The exact cause of thrombosis, role of anti myeloma drugs especially immunomodulators and steroids and the relation of thrombosis with alteration of thrombotic profile is not clear. While some available data is suggestive of low incidence of VTE in Asian population, true incidence and risk factors of VTE in Indian population is not known.So the present study was undertaken to have an evaluation of prothrombotic factors in Indian population. Methods: A prospective observational study was conducted from July 2008 to November 2009 at All India Institute of Medical Sciences (AIIMS), New Delhi, India. Thirty patients of newly diagnosed myeloma were recruited and were treated with thalidomide and dexamethasone for 4 months. Prothrombotic profile including protein Cand S, activated protein C resistance, plasma fibrinogen, factor VII and von Willebrand factor level was measured and Doppler study was done at baseline and after 4 months. Statistical analysis was done using SPSS 15 software. Frequency distribution, mean, median, range, standard deviation, Inter Quartile Range were calculated. To find out difference between pre and post treatment, Macnemar chi-square test (for proportion) and paired t test (mean) were done. Results: At the base line 4 patients (13%) had low protein C, 3 (10 %) had low protein S and 2 patients (6%) had high factor VIII. Post induction therapy 7 patients showed low protein C, 1 had low protein S and 1 had high factor VIII value. Rest of the factors was within normal limit both at baseline and post treatment in other patients. During the study period 2 subjects developed DVT. While one had low protein S, other patient had low protein C and low anti thrombin III which was done to find out the cause of DVT. Conclusions: Incidence of DVT in our patients seems to be less than western published data. Although thrombotic factors abnormalities are present in myeloma patients but the relation of coagulation factor abnormalities and development of DVT require further study. A larger prospective trial may be required to get a clear picture.
Gemcitabine and plasmacytic non-Hodgkin lymphoma response.
Authors: Jajeh Ahmad 
Published: March 2020

e19537 Background: Lymphomas are highly sensitive to chemotherapy. Gemcitabine is an active agent in non-Hodgkin lymphomas NHL. It is a diflourinated analogue of deoxycytadine which acts as antimetabolite. It is cell cycle specific and blocks cells in the G1/S interface. Gemcitabine is a better substrate for transport into cells. Active phosphorylated form is more readly and is excreted more slowly than other drugs. It inhibit DNA synthesis via depletion of cellular deoxynucleotide pools and by way of masked DNA chain termination. Gemcitabine seem to work it best on indolent and plasmacytoid low grade and intermediate NHL. Gemcitabine is also an active agent in Hodgkin lymphoma, Diffuse large B Cell NHL and T cell lymphomas. Methods: Retrospective reviews of patients with B cell NHL treated with gemcitabine as a single agent or in combination was carried out in one single institution over the last 13 years. Reveiw of biopsy reports and histology with immunostaining and flowcytometry done. This include CD20, CD10, BCL2, BCL6, MUM1, CD5, and cyclin D1. Clinical correlation with outcome CR, PR and Overall survival was done. Results: Forty patients with B cell lymphoproliferative disorders NHL were identified; five with mantle cell, ten with marginal zone and plasmacytoid morphology, fifteen with Diffuse Large B Cell Lymphoma DLBCLand ten with other low grade morphology. No correlation with germinal type versus post germinal (activated type) found in term of response. Plasmacytoid/ marginal zone type and mantle cell seem to have the best significant durable response when compared to DLBCL and other low grade NHL. Of note most patients received gemcitabine after failure to rituximab-CHOP and as salvage therapy in post second- and third-line failure. Conclusions: Gemcitabine may have more durable activity if used as a first-line combination therapy. Larger group of patients analysis needed to see if this agent has more activities in germinal than activated type of DLBCL. Plasmacytoid NHL seem to have more rapid and durable respone in our analysis.
Two rare presentations and treatments of Ewing's sarcoma: A need for a standard treatment approach.
Authors: Ayyanar Kanyalakshmi , Narayan Nitya , Moeller Karen , Gump William , Moriarty Thomas , Silverman Craig I. , Balasa Vinod , Bertolone Salvatore J. 
Published: March 2020

e21000 Background: We describe two Caucasian boys with rare presentations of non-metastatic Ewings sarcoma (ES) with atypical primary sites. One was extradural but FISH negative for 22q11.2. Another was intradural but extramedullary, and FISH positive. Literature search showed few publications which describe such cases, and there is currently no standard of care. Methods: MG, an 11 year old male, presented with a frontal skull mass, with an intracranial epidural extension of about 5 mm. Biopsy confirmed ES. MG was treated with Vincristine, Doxorubicin, and Cyclophosphamide, alternating with Ifosfamide and Etoposide every 2 weeks, for 6 weeks. He underwent tumor excision for local control with good response. Chemotherapy continued, completing 14 cycles total. He is in remission 15 months after completion. AH, a 13 year old male, presented with lower back pain and paraesthesias of feet. MRI revealed an intradural, extra-medullary L1-L3 mass. Intra-operatively, all visible tumor peeled off readily, except for the L2 nerve root. The tumor was FISH positive for EWSR1. He was treated with the same regimen as MG for 6 cycles. Local control was done with radiation. He then continued chemotherapy, completing a total of 14 cycles. MRI scans 3 months later revealed enhancing intradural lesions along the spinal cord (involving C5, T5 and T8) and two lesions along the cerebellum. He was started on cyclophosphamide and topotecan and has completed 8 cycles without disease progression. Results: MG was diagnosed based solely on histo-pathological diagnosis. While MG’s lesion was extra-osseus in nature, more unusual presentations demonstrate the importance of molecular diagnostic techniques. AH was diagnosed based on chromosomal analysis. Progression is presumably from microscopic residual disease in intradural space that invaded CSF. He is presently on salvage chemotherapy. Nine months after relapse, disease is stable, with plans to minimize disease and consolidate. Conclusions: Intradural tumors tend to progress rapidly, maybe more so than extradural tumors. Future suggestions include developing a standard approach that will improve both treatment of Ewing’s sarcoma and prognostic outcomes for rare initial presentations.
Outcome of leiomyosarcoma of bone: A single center experience.
Authors: Rajendra Rajeev , Pollack Seth , Rodler Eve T. , Conrad Ernest U. , Davidson Darin J , Chai Xiaoyu , Jones Robin Lewis 
Published: March 2020

e21502 Background: Leiomyosarcoma (LMS) of bone is a very rare sarcoma subtype. These tumors are managed akin to osteosarcoma, with neoadjuvant chemotherapy followed by surgery. The precise role of chemotherapy remains to be defined. Methods: Patients treated with primary bone LMS at the University of Washington between 2002 and 2012 were included. Patients with high grade tumors were treated with neoadjuvant chemotherapy and surgery; whereas those with low grade tumors were treated with surgical resection alone. Chemotherapy consisted of doxorubicin and ifosfamide x 2 cycles. Treatment details included: initial treatment (surgery versus chemo), surgical and pathological margins, and timing of chemotherapy. Follow-up data included: time to local recurrence, time to metastasis, time to last follow up if alive, or time to death. Results: Ten patients were identified, 4 male and 6 female. Median age at diagnosis: 52 years (range 29 - 91). The primary site was the distal femur in 5 patients, and the hemipelvis, acetabulum, proximal femur, distal clavicle and mid-shaft of femur in 1 patient each. Median tumor size at diagnosis was 8 cm. Five were high-grade tumors; 3 were intermediate and 2 were low grade. Four of 10 patients received neoadjuvant chemotherapy, with the following histological response; 70%, 30%, 15% and <5%. None of these patients had a dimensional radiological response to chemotherapy. Of the patients treated with surgery alone, one developed a local recurrence and another developed metastatic disease. Of the patients treated with chemotherapy and surgery, 1 died from an unrelated cause. Median follow-up was 9 months (range 0 - 83). Median DFS was 9 months (range 0 - 83). OS has not yet been reached. Conclusions: Surgical resection remains the mainstay of management of LMS of bone. The role of neoadjuvant chemotherapy requires further evaluation. Larger collaborative studies and biomarker analyses are essential to evaluate optimal treatment strategies for this rare disease.
Tumor characteristics and treatment (trt) patterns following disease recurrence in gastrointestinal stromal tumor (GIST) patients (pts) who received adjuvant imatinib (IM) as primary trt: A retrospective chart extract-based approach.
Authors: Gauthier Geneviève , Sasane Medha , Guérin Annie , Schwiep Frances Annelies , Keir Christopher Hunt , Magestro Matt , Wu Eric Q. , Conley Anthony Paul 
Published: March 2020

e21514 Background: Though adjuvant IM trt is associated with a reduced risk of GIST recurrence, little is known about tumor characteristics and trt patterns at the time of recurrence. The study describes tumor characteristics and trt patterns in pts with recurrent disease after completing treatment with adjuvant imatinib for resectable disease. Methods: An online tool was developed to collect clinical information for 410 pts treated with adjuvant IM for ≥6 months for primary resectable KIT+GIST, discontinued, had a recurrence following discontiuation, and then restarted IM or initiated sunitinib. Data were collected at two specific time points: primary diagnosis and disease recurrence. Results: Pts were, on average, 60.2 years of age, mostly male, and Caucasian. At primary diagnosis, most pts had intermediate/high risk profiles based on Fletcher score. Pts received adjuvant IM for a median of 360 days for primary GIST before discontinuing trt; the first recurrence occurred 281 days after IM discontinuation. At the time of recurrence, most patients had a multifocal (62%), unresectable (45%) or metastatic (40%) tumor and did not have a surgery (80%). Most patients had intermediate/high risk profiles at recurrence. 23% of pts had a recurrence outside the gastrointestinal (GI) system (39% of pts initiated on sunitinib; 19% of those who restarted IM, p=<.001). 93% had recurrence inside the GI (85% of pts initiated on sunitinib; 95% of those who restarted IM; p=.002).The majoritiy of patients were restarted on IM (with surgery:74% without surgery:77%), with a 400mg dose (with surgery:79% without surgery: 63%). Conclusions: At the time of recurrence, most pts had high risk, unresectable/mestatstic multifocal tumor and re-started IM 400mg. [Table: see text]
FDG PET/MR for therapy response assessment in sarcoma.
Authors: Richter Stephan , Beuthien-Baumann Bettina , Kotzerke Joerg , Laniado Michael , van den Hoff Joerg , Ehninger Gerhard , Schuler Markus Kajo , Platzek Ivan 
Published: March 2020

e21518 Background: Magnetic resonance imaging is the preferred modality for local staging of sarcoma. Positron emission tomography (PET) allows for the evaluation of tissue metabolism. Recently, PET and MR can be performed as a combined examination on a single scanner. The aim of this pilot study was to evaluate the agreement of PET and MR regarding therapy response in patients who received PET/MR for sarcoma staging and assess the diagnostic value of PET/MR in contrast to standalone MR. Methods: Thirteen patients with soft tissue sarcoma (7 m, 6 f, mean age 50 y, age range 18-80 y) received FDG PET MR on to occasions to assess therapy response. Average time between the two scans was 47 d (21-98 d). Average time between tracer injection and the beginning of the PET scan was 70 min (58-106 min). 4.5 MBq 18F-FDG /kg body weight were applied before the examination (252-331 MBq 18F-FDG /patient, 289 MBq on average). Image evaluation was performed separately by a radiologist and a nuclear medicine physician, respectively, who were blinded for other imaging procedures or clinical data. On MR images therapy response was determined according to the RECIST criteria. PET data evaluation included the calculation of mean an maximum SUV (=standardized uptake value) and metabolic volume. In this case, an increase or decrease of 30% or more of the base value was considered a progressive disease or positive response, respectively. Agreement of PET and MR regarding response was evaluated using Cohen's kappa. Results: The primary tumor showed increased FDG uptake in all patients. Response assessment based on RECIST and SUVmean differed in six of 13 cases (k=0,25). Assessment based on RECIST and metabolic volume showed slightly better agreement (k=0,35). Assessment based on RECIST and SUVmax differed in x cases (k=0,34). Conclusions: Sarcoma therapy response based on morphologic MR imaging and PET parameters yield differing results in many cases. FDG positive sarcoma may show a decrease of metabolic parameters on PET scans, while they appear largely unchanged on MR scans. Due to additional information about tumor metabolism provided by PET, PET/MR is a promising modality for sarcoma imaging. Further studies are necessary to evaluate the prognostic significance of PET findings in sarcoma patients.
Comparison of traditional Chinese medicine (TCM) herbal mixture LQ and paclitaxel on the phase of cancer cell cycle blockage and cancer cell invasion.
Authors: Hoffman Robert M. , Wu Chengyu , Yano Shuya , Zhang Lei 
Published: March 2020

e22014 Background: Although Traditional Chinese Medicine (TCM) has been used to treat cancer for thousands of years, the mechanisms of action are either poorly understood or unknown. In the present report, we use state-of-the-art technology to investigate the anti-cancer mechanism of the TCM herbal mixture LQ. Methods: Fluorescence ubiquitination-based cell cycle indicator (FUCCI) was used to monitor cell cycle arrest HeLa cells after LQ treatment. FUCCI-HeLa cells were cultured in two dimensional (2D) monolayer, Matrigel and 3D Gelfoam. Changes of cell cycle status were observed using the Olympus FV1000 confocal imaging system whereby cycling cells fluoresce green and quiescent cells red. Paclitaxel (Taxol) was used as the positive control. Results: Paclitaxel induced a G2/M cell cycle block. In contrast, LQ blocked FUCCI-HeLa cells in the G0/G1 phase of the cell cycle in all 3 culture models. In monolayer culture, the paclitaxel positive control had approximately 45% of the cells in G2/M phase. In contrast, the LQ-treated cells were mostly in the G0/G1 phase (>90%). In Matrigel culture, HeLa cells formed spheres. The spheres in the paclitaxel control group had 40% of the cells in G2/M phase, but only 15% in LQ-treated cultures. In 3D Gelfoam culture, cells grew along the structures of the Gelform. The paclitaxel positive control culture had approximately 45% of cells in G2/M phase. In contrast, the cells in LQ-treated culture were mostly in G0/G1 phase (>80%). The cells in pacilitaxel control group invaded to 250~300 µm deep in the Gelfoam, but only 150~200 µm deep in LQ-treated culture. Conclusions: The anti-cancer mechanism of TCM herbal mixture LQ involves cancer cell cycle arrest at G0/G1 and inhibition of cancer cell invasion.
Circulating tumor cells (CTCs) and epithelial mesenchymal transition (EMT) in primary breast cancer.
Authors: Karaba Marian , Mego Michal , Minarik Gabriel , Benca Juraj , Sedlackova Tatiana , Manasova Denisa , Sieberova Gabriela , Hlavata Zuzana , Jurik Andrej , Minarik Tomas , Macuch Jan , Gronesova Paulina , Oravcova Eva , Svabova Veronika , Sufliarsky Jozef , Pechan Juraj , Reuben James M. , Mardiak Jozef 
Published: March 2020

e22023 Background: CTCs are prognostic in breast cancer (BC) patients and represent a heterogeneous population of cells with different phenotypes and biological value. EMT gives rise to cells with stem cell-like properties with increased chemotherapy resistance and may be responsible for under detection of CTCs by currently approved assays. The aim of this study was to characterize CTCs based on the expression of epithelial and mesenchymal markers in non-metastatic BC patients. Methods: This prospective ongoing study included 124 patients (pts) with non-metastatic BC enrolled from March 2012 to December 2012. CTCs were detected before surgery (124 pts), before 1st cycle (28 pts) and before 2nd cycle (23 pts) of adjuvant therapy. Isolated peripheral blood mononuclear cells (PBMC) were depleted of hematopoietic cells using RossetteSep kit negative selection with anti-CD45 antibody. RNA extracted from CD45-depleted (CD45-) PBMC was interrogated for expression of EMT-inducing transcription factors (TWIST1, SNAIL1, SLUG, ZEB1) and epithelial (CK19) gene transcripts by qRT-PCR. Expressions of gene transcripts in CD45- PBMC of patients were compared to those of CD45- PBMC of 60 healthy donors. Results: CTCs were detected in 26.6% pts before surgery, in 21.4% pts before 1st cycle and in 43.5% of pts before 2nd cycle of adjuvant therapy. Before surgery, CTCs exhibiting only epithelial makers were present in 12.9% pts, whereas CTCs with only EMT markers were observed in 12.1% of pts and CTCs coepressing both markers were detected in 1.6% pts. There was a trend for higher CTC positivity in high grade, triple negative tumors and in the presence of lymphovascular invasion. We detected CTCs with only an EMT phenotype more often in pts with N+ than in N0 disease (20.4% vs. 10.2%; p = 0.03) and in pts after 1stcycle of adjuvant chemotherapy compared to before surgery (30.4% vs. 12.1%; p = 0.03). There was no association between epithelial CTCs and analyzed clinico-pathological variables. Conclusions: Our data suggest that CTCs with EMT phenotype are involved in tumor dissemination and treatment resistance, and support the role of EMT in cancer pathogenesis. Moreover, these results underlay the concept of CTCs heterogeneity.