bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clonal selection of TP53MUT and/or Del (p17) in CLL: Evaluation of 3,373 CLL patients, A real word data story.
Authors: Mpima Sheila , Moehler Thomas , Kanter Sean , Mitrofan Laura 
Published: September 2018

e19004 Background: Del (p17) or TP53MUT are important negative prognostic indicators for CLL patients (pts). Using a large European database we evaluated the influence of chemotherapies on the detection of Del (p17) and TP53MUT in advanced CLL pts requiring CLL-specific therapy. Methods: Anonymized CLL pts-level data collected through a large web-based survey between Oct 2015-2016 in EU5 (France, Germany, Italy, Spain & UK) was used. Mutation testing was recorded at the beginning of each line of therapy. Chi-squared test was used to analyze the association between treatment and/or abnormalities (Del p(17) and TP53MUT). Results: Data of 3,737 CLL pts were analyzed. 33% received ≥2 prior regimens, 38% received 1 prior regimen and 29% are currently in 1L. A switch from negative to positive at 2ndor later line occurred in 68% of pts for Del (17p) and 41% for TP53. 40% of pts bearing a Del (p17) are simultaneously TP53MUT when treated with at least 2 lines of therapy. We compared the treatment regimen of pts that remained negative during the course of treatments with those who switched to Del (17p) or TP53Mut. Analysis showed a strong association (p-value < .0001) between treatment (alkylation agent in combination with an antiCD20 antibody or CYC/FLUD/R) and Del (p17) switch after 2L (total n = 906). Separately, same treatment groups showed lower association (p-value < .0015) with TP53 status change at the end of 2L (total n = 598). Separate ratios have been calculated for each treatment group between pts remaining negative for Del (p17) and TP53, respectively and those who became positive. CYC/FLUD/R treated pts had a 2.2 and 2.7 fold higher ratio of remaining negative versus becoming positive for Del (p17) and TP53MUT, respectively in 2L, when compared to alkylating agent/antiCD20 combination. In addition, there is a high association (p-value < .0001) across the two treatments groups between Del (p17) and TP53MUT for pts with 2L results (n = 868). Conclusions: Analysis shows that patient treated with the 3-drug regimen CYC/FLUD/R had a lower likelihood of undergoing a clonal selection for both Del (17p) and TP53MUT compared to 2-drug regimen including alkylating agent/rituximab combo.
Oligoclonal T cells transiently expand and express TIM3 and LAG3 following CD19 CAR t cell therapy.
Authors: Petersen Christopher Thomas , Jagirdar Neera , Waller Edmund K. 
Published: September 2018

e19017 Background: CAR T therapies targeted towards the CD19 antigen have shown tremendous promise in the treatment of multiple B cell malignancies. However, not all B cell malignancies show the same degree of response; B cell lymphomas such as DLBCL have been more resistant to CAR T-mediated lysis. The reasons for the higher treatment failures and relapse rates in this setting are poorly understood which prompts investigation into the dynamics of T cell responses following CAR T infusion. Methods: Peripheral blood was collected from a single DLBCL patient enrolled on a single-patient compassion-use CAR T cell protocol utilizing a single chain CD19 with 4-1BB co-stimulatory signaling domain (NCT02445248 IND 16130). Blood samples were obtained prior to and on day 1, 8, 17, 24, 31, and 58 post-CAR T infusion. A bone marrow aspirate was collected on day 58. Mononuclear cells were collected by ficoll gradient and cryopreserved. Flow cytometry was performed on thawed samples to identify CAR T cells and surface markers. TCR sequencing was performed using the ImmunoSeq platform on an additional sample from each time point. Results: TCR sequencing revealed distinct waves of oligoclonal T cells within the first two months following CAR T therapy. A population of T cells expressing Vβ 20 appeared early following CAR T infusion and contracted by day 17. Additionally, a population of cells expressing Vβ 27.1 also expanded at the peak of the response (D8), but remained at a high frequency up to two months post-treatment. A third wave of T cells expressing Vβ 7.3 expanded in the blood and marrow on day 58. The expression of TIM3 and LAG3 also changed over time. TIM3 was expressed predominantly in the CD8 compartment while LAG3 expression was limited to the CD4 compartment. Expression of both increased at peak and decreased over time. Low levels of PD-1 expression were detected in contrast to the much higher levels of TIM3. Conclusions: The waves of oligoclonal T cell expansion and dynamic expression of TIM3 and LAG3 provide further insight into the CAR T response and may provide new possible targets for supportive therapies that can enhance the overall response. Clinical trial information: NCT02445248.
Effectiveness of bendamustine in relapse or refractory lymphoma cases: A report from Turkey—The Turkish Oncology Group (TOG) study.
Authors: Karadurmus Nuri , Paydas Semra , Ocal Ramazan , Yildiz Birol , Nayir Erdinc , Dogan Mutlu , Sumbul Ahmet Taner , Surmeli Zeki , Barısta Ibrahim , Ferhanoglu Burhan , Ozgur Gokhan , Erturk Ismail , Ozaydin Sukru , Petekkaya Halil Ibrahim , Uskent Necdet 
Published: September 2018

e19027 Background: Bendamustine is an old conventional agent which is used in the treatment of hodgkin's lymphoma (HL), non-hodgkin's lymphoma (NHL), and chronic lymphocytic leukemia (CLL) patients despite they are relapsed or refractory cases. In our study we wanted to reveal retrospectively the efficacy and side effects of bendamustine in relapse/refractory patients from Turkey. Methods: We included in the study relapse/refractory HL and NHL patients who underwent multiple line chemotherapy. Bendamustine was administered at 90 mg/m² on days 1 and 2, every 3 weeks by 60 minutes infusion. The primary endpoint of the study was to determine the objective response and toxicity. Results: Seventy-five patients (31 female) with a median age of 62.8 years (range 16-89 years) were included in the study. 58 of the patients were NHL (follicular lymphoma:8, diffuse large B-cell lymphoma: 17, mantle cell lymphoma: 11, marginal zone lymphoma: 4, Small lymphocytic lymphoma:11, Others:7) and 17 of them were HL patients. The patients were underwent median three lines chemotherapy (range 1-8) accept autologous stem cell transplantation, 20 patients (HL: 12, NHL:8) were underwent autologous stem cell transplantation. Bendamustine was performed an average of 6 cycles (range 1-38). The objective response rate was 73.3%, complete response rate was 44% (n = 33), partial response rate was 29.3% (n = 22), respectively. The response rate was 65% (11/17) in HL cases, 79% (30/38) in indolent NHL cases and 70% (14/20) in aggressive NHL cases. For median follow-up of 20.7 months, the median overall survival (OS) was 64.9 months, OS rate was 75.5% for 1 year, 67.6% for 2 years and 63.1% for 3 years. The most common side effects associated with treatment were lymphopenia, neutropenia, thrombocytopenia, abdominal pain, fatigue and diarrhea. Side effects which were seen as grade 3 and higher levels: 9.6% lymphopenia, thrombocytopenia 8% and 12% fatigue. Conclusions: Objective response rate of bendamustine with tolerable side effect profile was found to be 73.3% in relapsed / refractory HL and NHL patients as a rescue agent. It appears to be an ideal agent for rescue treatment which had previously received intensive treatment.
Adherence, quality of life, health care resource use, and functional impairment among patients with oral multiple myeloma (MM) treatments.
Authors: Ung Brian , Gupta Shaloo , Parikh Kejal , Liebert Ryan , Abouzaid Safiya , Rosenberg Aaron Seth 
Published: September 2018

e19519 Background: Few studies have assessed the relationship between adherence to prescribed therapies and patient (Pt)-reported outcomes (PRO) in Multiple Myeloma (MM). Pt-reported adherence and its association with quality of life (QoL), healthcare resource use (HRU) and functional impairment among pts on oral MM treatments were assessed. Methods: This was a cross-sectional survey of 118 US adult MM pts identified from the Light Speed Research panel, who were currently on a regimen which included an oral therapy. Pt’s experiences using the Morisky Medication Adherence Scale-4 (MMAS-4), the Work Productivity and Activity Impairment, and the Functional Assessment of Cancer Therapy (FACT)-MM were examined. Higher FACT-MM scores indicated better health-related QoL. Pts were characterized by their MMAS score; score =4 and score ≤3 (max score =4). Pts in each score grouping were summarized based on pt characteristics, treatment history, HRU and PROs. Multivariable analyses estimated the association between MMAS score group and study outcomes. Results: A total of 72 (61%) pts reported a MMAS score = 4 and 46 (39%) pts had a score ≤3. Pts with a score =4 were older (59.2 vs 50.7 years; p<0.001) and were on fewer treatments (1.42 vs 2.13; p<0.001) than with a score ≤3. No differences in race/ethnicity, marital status, income or education level were noted between the two groups. Pts with a score ≤3 had higher levels of absenteeism, impairment while at work (presenteeism), and overall work impairment in descriptive analysis, but only differences in activity impairment (56.5% vs. 39.8%; p=0.015) remained significant in the multivariable analyses. Pts with a score = 4 reported higher FACT-MM scores (106.9 vs 89.2; p<0.001) than pts with a score ≤3, a trend seen in all FACT-MM subscores. More pts with a score ≤3 also reported being overwhelmed or frustrated by having to reschedule MM appointments (64% vs. 26%; p=0.002). Conclusions: Among MM pts on oral treatments, high adherence is associated with improved QoL and a lower level of activity impairment. There may also be a relationship between frustration in managing MM related appointments and levels of adherence.
Allogeneic stem cell transplantation (Allo-SCT) for multiple myeloma (MM): The Mount Sinai experience.
Authors: Afshar Solmaz F. , Galitzeck Zachary , Pineda-Roman Mauricio , Steinberg Amir 
Published: September 2018

e19520 Background: Allo-SCT has been used as a curative treatment for MM, particularly for refractory patients (pts), but outcomes across institutions have shown varying results. In this study, we examined patient-, disease-, and transplant (tx)-related variables in pts of allo-SCT for MM at Mount Sinai. Methods: Adult pts undergoing allo-SCT for MM at Mount Sinai from 2008-2015 were included in this study. Identifying variables were extracted from reports to the CIBMTR. This study was approved by the IRB, and all pts signed informed consent. Our results were compared to the 2011 CIBMTR analysis of allo-SCT for MM pts. Results: 21 pts underwent allo-SCT for MM at a median of 36 months post diagnosis (range, 12-211 mo), while the CIBMTR reported 12 mo. The median age of pts at the time of tx was 53 years (range, 38-62 yrs) with 48% White, and Hispanic, Asian or Black each 14%. Pts had one or more autologous SCT prior to allo-SCT (90%) and the median time between txs was 31.1 mo (range, 0.7-195 mo). Pts were in DS stage III (52%), and the disease was partially responsive (38%) or showed progression (33%). 81% of pts underwent nonmyeloablative/reduced-intensity conditioning, and 86% received GVHD prophylaxis. Still, 38% of pts developed acute GVHD while 19% had chronic GVHD by 1 year post-tx, lower than CIBMTR’s analysis. There was a 52% survival rate at 6 mo post SCT and 29% by year 1, considerably lower than the 46% reported by the CIBMTR. The median time to death was 5 months (range, 1-40 mo), and the main cause was primary disease (37%). At the time of analysis, 2 pts were alive with a maximum survival of 8 years post-tx. Conclusions: The Mount Sinai experience of allo-SCT for MM pts revealed overall suboptimal outcomes during the 2008-2015 study period. Our pts underwent tx much later in the disease course relative to the CIBMTR’s study. Given the noted outcomes, alternative therapies were considered in the last 4 years of our analysis, resulting in half as many allo-SCT for MM pts during the latter time period. For optimal benefit, allo-SCT in selected MM should be performed earlier in the course of disease with improved pt selection. These modifications will be implemented via participation in an upcoming BMT/CTN clinical trial at our institution.
Prognostic value of a 12-gene signature in platinum-based chemotherapy treated SCLC.
Authors: Zhang Jie , Tian Chen , Zhang Henghui , Chen Xiaoling , Han Jindi , Nie Jun , Dai Ling , Hu Weiheng , Tian Guangming , Ma Xiangjuan , Wu Di , Fang Jian 
Published: September 2018

e20011 Background: Small cell lung cancer (SCLC), which accounts for 15-20% of lung cancer, is a highly aggressive neoplasm. Different from non-small cell lung cancer, SCLC is characterized by a high proliferation rate and early metastasis. Only about 25% of patients with limited stage disease will be cured after first-line standard treatment and majority of the patients will relapse after initial sensitivity to the chemotherapy and radiotherapy. The highly complex genetic landscape of SCLC may be the reason for its resistance to conventional therapy but the details are still unclear. Methods: Nine patients with SCLC received platinum-based chemotherapy and/or radiotherapy were included in this study. According to the prognosis, patients were classified into two groups: poor prognosis group (PP group, PFS < 6 months, n = 5) and better prognosis group (BP group, PFS > 24 months, n = 4). Tumor DNA was isolated from pre-treatment paraffin-embedded tumor tissue and subjected to enrichment for a 1.15M size panel cover exon regions from 1,086 genes. Followed by next generation sequencing on an Illumina X10 platform, the captured sequencing data was further processed using bioinformatics analysis to identify somatic mutations, including single nucleotide variants (SNV), short insertions/deletions (indels) and copy number variation (CNV). Changes in tumor DNA were compared with clinical efficiency. Results: We show that the tumor mutation burden in PP group is higher than the BP group (p = 0.06). Using the mutation burden of 12 genes (PTEN, TP53, JAK2, BCL2, CCNE1, EGFR, ROS1, NTRK3, MYC, FGFR1, RANBP2, and CREBBP) as a factor, the PP group can be distinguished from BP group. In addition, TP53 loss is more frequently appeared in the PP group. Conclusions: Our results suggest that high mutation burden status of 12 genes (PTEN, TP53, JAK2, BCL2, CCNE1, EGFR, ROS1, NTRK3, MYC, FGFR1, RANBP2, and CREBBP) might correlate with poor prognosis of small cell lung cancer.
Prognostic value of post treatment PET scan in small cell lung cancer.
Authors: Alsharedi Mohamed Farouq , Chowdhary Aneel A. , Shenouda Mina , Gress Todd W. 
Published: September 2018

e20013 Background: In most lymphomas, improving patient outcome rely on an assessment of response to therapy. Functional imaging with 18-fluoro-deoxyglucose (FDG) positron emission tomography (PET) increases sensitivity and specificity of disease assessment, predicts outcome and directs future therapies. Lately, PET-scan is more utilized in small cell lung cancer (SCLC) both for initial staging and to assess response to therapy. However, limited data in the literature have evaluated the prognostic value of post-therapy response on PET-scan in SCLC. Methods: This is a retrospective chart-review of SCLC patients who received their first-line chemotherapy between January-2007 and December-2013. Inclusion criteria included complete data on age, sex, race, cancer stage, histologic grade, chemotherapy, radiotherapy, and PET images pre- and post-therapy. CR was defined as either 100% drop in FDG uptake on post-therapy PET-scan. Results: Fifty patients met the inclusion criteria, and served as the basis for this study. 46% had Limited Stage Small Cell Lung Cancer (LS-SCLC), and 54% had Extensive stage small cell lung cancer (ES-SCLC). All were treated with platinum-based chemotherapy in addition to concurrently radiation therapy for the LS-SCLC group. Eleven patients out of the whole cohort achieved CR. Using COX regression model, we evaluated the correlation between achieving CR on post-therapy PET-scan and survival outcome. We found that achieving CR was significantly correlated with worse outcome in ES-SCLC group (HR = 2.70; 95%CI: 1.26-5.81; p = 0.01). While, in the whole cohort and LS-SCLC group, P-value was not statistically significant, nevertheless achieving CR indicated unfavorable outcome (HR = 1.18; 95%CI: 0.51-2.69; p = 0.49) and (HR = 1.99; 95%CI: 0.77-5.13; p = 0.15) respectively. Conclusions: Unlike lymphomas, achieving CR on post-therapy PET-scan in SCLC was associated with worse survival outcome. This might indicate that in aggressive small cell lung cancer, despite excellent response to first-line therapy, the prognosis is still dismal. These results suggest that further prospective studies are warranted to identify the prognostic rule of post-therapy PET-scan in SCLC patients particularly those with ES-SCLC.
A meta-analysis of trials of etoposide plus platinum agent versus irinotecan/topotecan plus platinum agent in first-line therapy of extensive stage small cell lung cancer (ES SCLC).
Authors: Ellis Peter Michael , Durocher-Allen Lisa , Vella Emily , Sun Alexander , Ung Yee , Ramchandar Kevin , Darling Gail Elizabeth , Goffin John R. ,   CCO PEBC Lung DST
Published: September 2018

e20019 Background: Etoposide plus a platinum agent (EP) represents the standard treatment of ES SCLC. A trial conducted in Japan demonstrated improved overall survival (OS) for irinotecan and cisplatin (IP), but subsequent trials could not consistently replicate these findings. Genotypic differences may explain these findings. These trials have not undergone systematic analysis. Methods: We conducted a systematic review and metaanalysis of randomized trials (RCT) comparing etoposide plus a platinum agent (EP) with irinotecan (IP) or topotecan (TP) plus a platinum agent. A literature search was undertaken of Cochrane Database, MEDLINE and Embase from 1996 to June 2016 to identify RCTs addressing this question. Data were extracted by one author and checked independently, then synthesized using RevMan software using a random effects model. Outcomes of interest were OS, quality of life (QoL) and toxicity. Results: Three RCTs compared TP and EP. There was no difference in OS (HR 0.97, 95%CI 0.87 – 1.07). Eight RCTs compared IP and EP, although only 7 had data that could be combined. IP significantly improved OS compared with EP (HR 0.84, 95%CI 0.74 – 0.95). The estimated improvement in 12 month OS is 6.4%. There was evidence of statistical heterogeneity. After removal of the trial by Noda et al, there was still a significant improvement in OS (HR 0.88, 95%CI 0.79 – 0.98). IP was associated with less grade 3/4 neutropenia, febrile neutropenia, anemia, thrombocytopenia, but more diarrhea. QoL was assessed in 2 trials and no differences observed. Conclusions: IP results in modest improvements in OS in comparison with EP. IP is associated with less hematological toxicity but more diarrhea and should be considered an acceptable alternative to EP in the first-line treatment of ES SCLC. [Table: see text]
Retrospective analysis to compare the efficacy of oral (O) vs. intravenous (IV) etoposide given in combination with carboplatin for small cell lung cancer (SCLC), extensive disease (ED).
Authors: Mellemgaard Anders , Hersby Ditte Stampe , Chaudhary Farruhk Naheed , Langer Seppo W. 
Published: September 2018

e20020 Background: Approximately two thirds of patients diagnosed with SCLC will have ED at the time of diagnosis. Response rates to chemotherapy are high but median overall survival for patients treated with chemotherapy is only 9 to 10 months. Patients with ED SCLC considered fit for chemotherapy is normally treated with combination chemotherapy including cisplatin or carboplatin, and etoposide or irinotecan. The usual dosing scheme is 3 weeks intervals with the platin administered on day 1 and etoposide given day 1-3 or 1-5. Etoposide is available in as well intravenous as oral formulations. Concerns about the incomplete and variable bioavailability of oral etoposide have been raised. A randomized study of cisplatin with either oral or IV etoposide found no significant difference in treatment outcome but increased rate of severe or life-threatening hematologic toxicity. Methods: The two cancer hospitals serving the Copenhagen area are using carboplatin + etoposide for palliative treatment of SCLC ED. While carboplatin is used identically (AUC5, IV d1), etoposide is given IV by HUH (120mg/m2, IV d1-3) and orally by CUH (200mg/m2 O, d1-3). From the hospital patient database, we identified patients with SCLC, ED treated in 2011-2013. Route of etoposide administration, dose reductions and GCSF use was noted. PFS and OS was calculated from hospital records. Results: 200 SCLC, ED patients received treatment (116 at HUH, 84 at CUH). A non-significant higher proportion of women were treated at HUH while median age was identical. PFS was longer at HUH than CUH (195 vs 140 days), but the OS was identical (235 vs 227 days). Conclusions: The two dosing schemes: O and IV yield similar OS, but longer PFS with the IV schedule. The survival seen is in line with results from randomized trials although the present study includes all patients irrespectible of PS or comorbidity. We have no information on adverse events, quality of life or rates of hospitalization.
Radiation therapy for patients with extensive stage small cell lung cancer: A survey study of medical oncologists.
Authors: Luo Jia , Degnin Catherine , Chen Yiyi , Mitin Timur , Maggiore Ronald John 
Published: September 2018

e20025 Background: National guidelines recommend prophylactic cranial irradiation (PCI) and consideration for thoracic radiation therapy (TRT) for patients with extensive stage small cell lung cancer (ES-SCLC) after chemotherapy. The referral practice patterns among US medical oncologists are unknown. Methods: We developed a survey that was sent to US medical oncologists. The survey evaluated demographics, self-rated knowledge of key TRT studies and approach to radiation oncology referral for ES-SCLC patients regarding TRT and PCI. A predefined knowledge score (KN) (from 0 to 4) was used to characterize self-rated knowledge of existing Jeremic et al and CREST TRT trials with “0” being unaware of the study, “1” being some knowledge, and “2” being knowing trial details. Associations between respondent characteristics and responses were evaluated using Chi-squared or Fisher’s exact tests. Results: 316 complete responses were analyzed. Most respondents had over 10 years of experience (74%; n = 233) and have taken care of more than 10 patients with lung cancer (73%; n = 230), with those treating more patients having higher KN (p = 0.001). 76% (n = 239) of respondents recommended TRT referral after chemotherapy and were more likely to refer if a complete response at metastatic sites had been achieved (p = 0.0001). Higher KN (p = 0.003) was associated with a higher likelihood of TRT referral. 24% (n = 77) did not recommend referral; of these, 84% (n = 65) cited insufficient evidence as their rationale. 75% (n = 237) would obtain brain imaging prior to PCI referral, and 90% (n = 283) supported PCI referral in the absence of brain metastases. Conclusions: Among surveyed US medical oncologists the majority refer patients with ES-SCLC to TRT after chemotherapy. Those physicians who do not refer feel the evidence supporting TRT is insufficient. This is in line with ambiguity reflected in recent ASCO and NCCN consensus guidelines. Most physicians recommend referral for PCI consideration. Additionally, most obtain brain imaging prior to PCI referral, a practice not supported by clinical evidence. These differences in practice patterns support the need for further research to determine the role of TRT and PCI in patients with ES-SCLC.