tbuckley/cabot-search huggingface dataset:
Clinicopathologic features and survival outcomes of secondary diffuse large b-cell lymphoma after a primary solid malignancy: SEER propensity-matched analysis.
Authors: Muhammad Saad Hamid, Raji Shameem, Philip Pancari, Chethan Ramamurthy, Pooja Ghatalia, Patricia Lamont Kropf
Journal: Journal of Clinical Oncology (2016)

e19022 Background: Outcomes of secondary DLBCL (sDLBCL) in patients with a prior diagnosis of a solid malignancy compared to de novo DLBCL (dnDLBCL) are not well understood. We sought to determine factors that may affect outcome through analysis of data from a large nationwide cancer registry. Methods: The Surveillance Epidemiology and End Results (SEER) database (2001-2012) was used to detect DLBCL (ICD-O-3 code: 9680/3) adult cases. The variable “First Malignant Primary Indicator” was used to differentiate between dnDLBCL and sDLBCL cases. For inclusion, a sDLBCL case was required to have a prior solid malignancy diagnosed after a latency period ≥ 60 months (mo). Overall survival (OS) was calculated using the cox regression model to determine the impact of sDLBCL on survival, after adjusting for age, race, gender, stage, and radiation use using 1:2 propensity score matching. Chi square test was utilized to ascertain for any significant difference between dnDLBCL and sDLBCL cases. Results: Overall, 52694 patients were included: 2764 (5.2%) sDLBCL and 49930 (94.80%) dnDLBCL cases. Primary malignancies including breast (126 mo) and endometrial (178 mo) had a latency period of greater than 10 years. Median age at diagnosis was 78 (25-99) years for sDLBCL and 65 (18-99) years for dnDLBCL. Stage III and IV was more frequent in sDLBCL (87.5%) compared to (47.8%) in dnDLBCL (p < 0.01.) The relative incidence of sDLBCL compared to dnDLBCL was greater for males (59.5% vs. 53.4%, p < 0.01), age ≥ 65 years (87.5% vs. 52.0%, p < 0.01), extra-nodal involvement (37.9% vs.34.1%, p < 0.01). In sDLBCL cases radiation was given less (21.4% vs. 18.7%, p < 0.01). Compared to dnDLBCL (33 mo), sDLBCL (24 mo) had worse median OS (HR: 1.134, 95% CI: 1.067 – 1.214, p < 0.01). Conclusions: We have demonstrated significant differences in gender, age, stage at initial diagnosis, and rates of extra-nodal involvement between sDLBCL and dnDLBCL cases. OS was worse in sDLBCL as compared to de novo DLBCL in a propensity matched cohort. This may be due to differences in treatment approaches.
Fluoroquinolone prophylaxis for the prevention of central line-associated bloodstream infection in autologous stem cell transplant.
Authors: Matthew Ziegler, Cheryl Gilmar, Daniel Jeffrey Landsburg, David Pegues, Colleen Kucharczuk, Theresa Gorman, Kristen Bink, Amy Moore, Rebecca Fitzpatrick, Edward A. Stadtmauer, Patricia Mangan, Kelly Kraus, Jennifer Han
Journal: Journal of Clinical Oncology (2017)

e19508 Background: Patients (Pts) undergoing stem cell transplant (SCT) for the treatment of hematologic malignancy are at increased risk for central line-associated bloodstream infection (CLABSI). Use of prophylactic antibiotics to prevent CLABSI in autologous SCT (autoSCT) is of unclear benefit. We aimed to evaluate the impact of levofloxacin prophylaxis on reducing CLABSI in autoSCT. Methods: Pts undergoing autoSCT at the University of Pennsylvania received levofloxacin prophylaxis during a 6-month intervention period from 1/13/2016 - 7/12/2016. Levofloxacin was administered from autoSCT until day 13, absolute neutrophil count &gt; 500/mm 3 , or febrile neutropenia. Outcomes were compared to a retrospective cohort who underwent autoSCT, but did not receive routine antibacterial prophylaxis during the previous year (1/13/2015 – 1/12/2016). The primary endpoint was incidence of CLABSI assessed using Cox proportional hazards regression. Results: A total of 243 pts underwent autoSCT, with 69 receiving levofloxacin prophylaxis during the intervention period. Median age was 59 yrs, 74% had multiple myeloma, and 58% received melphalan 200mg/m 2 . Median duration of neutropenia was 6 days. CLABSI rate was reduced from 18.4% during the baseline period to 7.3% during the intervention period ( P= 0.03). There were no significant differences in characteristics between the baseline and intervention groups except for liver disease (1% versus 5%, P= 0.03). On multivariable analysis, levofloxacin prophylaxis was associated with a significant reduction in CLABSI incidence (HR 0.33; 95% CI 0.12-0.88; P= 0.02), as was underlying multiple myeloma (HR 0.38; 95% CI 0.20-0.74; P= 0.004) and liver disease (HR 4.31; 95% CI 0.99-18.8; P= 0.05). There was also a reduction in neutropenic (NTP) fever (OR 0.21; 95% CI 0.11-0.38; P&lt; 0.001) and a trend toward reduction in ICU transfer for sepsis (OR 0.13; 95% CI 0.01-1.39; P= 0.08) in patients receiving levofloxacin prophylaxis. There were no significant differences in rates of secondary BSIs, C. difficileinfection, or mortality. Conclusions: Levofloxacin prophylaxis was effective in reducing CLABSI and NTP fever in patients undergoing autoSCT.
Clinical outcomes of adolescents and young adults (AYA) with advanced solid tumors participating in phase I trials.
Authors: Raghav Sundar, Terri Patricia McVeigh, Ann Petruckevitch, Nikolaos Diamantis, Joo Ern Ang, Maxime Chenard-Poirier, Dearbhaile Catherine Collins, Joline Si Jing Lim, Malaka Ameratunga, Khurum Hayat Khan, Stanley B. Kaye, Udai Banerji, Juanita Suzanne Lopez, Johann S. De Bono, Winette T.A. Van Der Graaf
Journal: Journal of Clinical Oncology (2017)

10536 Background: AYA cancer patients are relatively under-represented in clinical trials, with no published data regarding their outcomes in phase I studies. Trials utilizing novel therapeutic agents are often considered in these patients, due to their tendency to have good organ reserve, and ability to tolerate additional lines of therapy. This study describes the experience of AYA patients with advanced solid tumors treated in a specialized drug development unit. Methods: Patient characteristics and clinical outcomes of AYA patients (defined as age 15 to 39 years at time of initial cancer diagnosis) treated at the Drug Development Unit, Royal Marsden Hospital, United Kingdom, between 2002 and 2016, were captured and analyzed from case and trial records. Results: From a database of 2631 patients treated on phase I trials, 219 AYA patients (8%) were identified. Major tumor types included gynaecological cancer (24%), sarcoma (18%), gastrointestinal (16%) and breast cancer (11%). Patients had a median of 3 previous lines of systemic chemotherapy (range 0 – 6), and 19% participated in 2 or more phase I studies. Twenty (9%) had a known hereditary cancer syndrome (most commonly BRCA), 27% had a family history (FH) of cancer, 15% no FH and 49% no FH documented. Molecular characterization of tumors (n = 45) identified mutations most commonly in p53 (33%) , PI3KCA (18%) and KRAS (9%) . Major trial categories included DNA damage repair (16%), PI3K (16%) and anti-angiogenesis (15%) agents. Grade 3/4 toxicities were experienced in 25% of patients (10% hematological). Of the 214 evaluable patients, objective response rate was 12%, with clinical benefit rate at 6 months of 22%. Median progression free survival was 2.3 months (95% CI: 1.9 to 2.8), median OS was 7.6 months (95% CI: 6.3 to 9.5), and 2-year OS was 11%. Of patients with responses, 35% were matched to phase I trials based on germline or somatic genetic aberrations. Conclusions: A sub-group of AYA patients with advanced solid tumors derive considerable benefit from participating in trials involving novel therapeutics. Future research must focus on predictive biomarkers and molecular profiling to identify those that would benefit from novel therapies.
The impact of positive SWOG treatment trials on population survival.
Authors: Joseph M. Unger, Michael Leo LeBlanc, Charles David Blanke
Journal: Journal of Clinical Oncology (2017)

6513 Background: Recently, tremendous prominence has been given to the investigation of the impact of different research processes as part of the Cancer Moonshot. More than half a century ago, the National Cancer Institute (NCI) established a network of publicly-funded cancer cooperative research groups to systematically advance the science of clinical trial research and the evaluation of new treatments for efficacy and safety. Our objective was to examine the extent to which positive NCI-sponsored cancer treatment trials have benefited cancer patients in the U.S. population. Methods: We used study data from SWOG, an NCI-sponsored Network cooperative research group. We identified all treatment trials over SWOG’s 60-year history (1956-2016) for which the new experimental therapy provided a statistically significant improvement in overall survival. We assumed the new, proven treatments from these trials established new standards for care in the treatment community. Twenty-three treatment trials were identified from a variety of difference cancer types. We estimated population life-years gained from the trials through 2015 by mapping the impact of the new treatments onto the U.S. cancer population, using an area-under-the-survival-curve approach that combined trial-specific hazard function and hazard ratio results with SEER and life-table data. Calculations were age-adjusted. Dollar return on investment was estimated as the ratio of total investment by the National Cancer Institute in the SWOG treatment trial program divided by the estimate of life-years gained. Results: In total, 12,361 patients were enrolled to the 23 positive trials from 1965-2012. We estimated that 3.34 million years of life were gained through 2015. Estimates were greater than 2 million life years gained under 95% of model simulations. The dollar return on investment was $125 per life year gained. Conclusions: SWOG treatment trials have had a substantial impact on population survival for cancer patients over 60 years. The National Cancer Institute’s investment in its cancer cooperative group research program has provided exceptional value and benefit to the American public.
A phase 1/2 study of durvalumab (DURVA) in combination with lenalidomide (LEN) with or without dexamethasone (DEX) in patients (pts) with newly diagnosed multiple myeloma (NDMM).
Authors: Sagar Lonial, Albert Oriol, Maria-Victoria Mateos, Paula Rodriguez-Otero, Nizar J. Bahlis, William Bensinger, Kimmo Porkka, Niels Van De Donk, Wai Yiu, Carl Di Casoli, Annette L. Ervin-Haynes, Mohamed H. Zaki, Annette Vangsted
Journal: Journal of Clinical Oncology (2017)

TPS8055 Background: LEN + DEX (Rd) is approved for pts with newly diagnosed MM, including those who are transplant non-eligible (TNE). DURVA is a monoclonal antibody to programmed death ligand 1 (PD-L1) that blocks PD-L1 binding to programmed death-1 (PD-1). Preclinical studies showed anti-MM immune responses with PD-1/PD-L1 blockade that were enhanced with LEN (Görgün et al, 2015). Here, we present a phase 1/2, multicenter, open-label trial in progress (MEDI4736-MM-002) designed to evaluate DURVA in combination with LEN ± DEX in a target population of pts who are TNE and/or with high-risk NDMM. Methods: Enrollment of up to 138 pts from the US, Canada, and Europe is planned to determine the recommended dose of DURVA (primary endpoint) with LEN ± DEX for the treatment (Tx) of NDMM. Key secondary endpoints include safety, response outcomes, pharmacokinetics, progression-free survival, and overall survival. Pts with previously untreated MM with ≥ 1 of the following will be included: 1 of the CRAB criteria or clonal bone marrow plasma cells ≥ 60% and an Eastern Cooperative Oncology Group performance status of ≤ 2. Pts with a history of primary immunodeficiency will be excluded. Each independent cohort (A, B, C) will enroll 6 pts in parallel in the dose-finding phase (Table). Dose-limiting toxicities will be evaluated during the first cycle of Tx. The optimal regimen will be determined from the dose-finding phase and a parallel dose-expansion phase of up to 40 pts per cohort. Tx will continue until progressive disease or unacceptable toxicity. To date, 15 pts have enrolled. Clinical trial information: NCT02685826. [Table: see text]
Clinico-epidemiologic characteristics and patterns of care in Merkel cell carcinoma: Data from a single-institution series.
Authors: Michael Del Rosario, Eric Anderson, Yani Lu, Stephanie Farrell, Steven C. Plaxe, Constantin Dasanu
Journal: Journal of Clinical Oncology (2017)

e21049 Background: Merkel cell carcinoma (MCC) is associated with increased sun exposure. There is an average of 348 days of sunshine per year in our geographic area. Methods: With the IRB approval, we performed a retrospective chart review of all consecutive MCC patients seen at our institution between 2006-2017. Clinico-epidemiologic data such as age, gender, race, stage, tumor size, stage at presentation, and disease course were collected. Therapy and survival were analyzed. Using the surveillance, epidemiology, and end results program (SEER), we identified 4,256 patients with MCC from the years 2006-2013. We compared our data with the SEER findings . Statistical analysis: Chi-square and Fishers’ exact tests were used to assess the significance of associations in large and small populations, respectively. Survival analyses were performed using the Cox proportional hazards. Results: We identified 40 patients with MCC (n = 40) with a median age of 77. Compared to SEER data, our population was entirely Caucasian (100% vs. 95%; p = 0.11) and male predominant (75% vs. 63%; p = 0.11). The patients in our cohort were diagnosed more often with TNM stage I (50% vs. 39%; p = 0.00003) and found to have more often a primary tumor size &lt; 2cm (58% vs. 34%; p &lt; 0.01). Our patients were more frequently treated with lymph node dissection (70% vs. 63%, p = 0.002) and radiation therapy (60% vs. 50%; p = 0.24). Conclusions: Compared to the general population, MCC patients treated at our institution had similar mean age at diagnosis, gender and racial distribution and radiation treatment frequency (all p-values &gt; 0.05). However, our patient population was significantly more likely to be diagnosed at stage I disease, have a primary tumor size less than 2 cm and receive lymph node dissection. Final statistical analysis, including survival analysis, and significance are to be discussed.
Factors predicting organ response in light chain amyloidosis (AL).
Authors: Surbhi Sidana, Nidhi Tandon, Angela Dispenzieri, Morie A. Gertz, Francis Buadi, Martha Lacy, David Dingli, Amie L. Fonder, Suzanne R. Hayman, Miriam A. Hobbs, Wilson I. Gonsalves, Yi Lisa Hwa, Prashant Kapoor, Robert A. Kyle, Nelson Leung, Ronald S. Go, John Anthony Lust, Stephen J. Russell, S. Vincent Rajkumar, Shaji Kumar
Journal: Journal of Clinical Oncology (2017)

8048 Background: Organ response (OR) in AL is often delayed and difficult to predict early. Methods: We retrospectively analyzed 1308 patients (pts) with newly diagnosed AL from 2006 – 2015 to determine factors which could predict for OR. Results: Median age was 64 years (yr) and Mayo Stage was: 1 (22%); 2 (23%); 3 (25%); 4 (31%). Organ involvement was: cardiac (74%, n=932); renal (59%, n=738), liver (16%, n=205); gut (24%, n=310) and autonomic (12%, n=152). 59% (n=765) had &gt; 1 organ involved, including 43% (n=567) with &gt; 1 critical organ (heart, kidney, liver) involved. Treatment was: ASCT based (28%, n=330, N=1186), bortezomib based (24%, n=281), alkylator based (33%, n=392), others (5%, n=54) and none (10%). In evaluable pts, VGPR or better rates were: 53% at 6 months (m) (N=625), 72% at 12 m (N=465) and 57% overall (N=688). Table 1 lists OR at various time points. Complete OR in all involved critical organs was seen in: 51% (n=308, N=600), partial response (at least 1 OR when &gt;1 organ involved) in 12% (n=73) and none in 37% (n=219). Complete OR was associated with better overall survival (OS) than partial or no OR (median OS: not reached vs 42 m vs 29 m; P &lt;0.0001). In multivariate model the following variables at baseline or 1 yr mark were predictive of complete OR: lower Mayo Stage (p=0.01), fewer critical organs involved (p=0.007), higher baseline GFR (p=0.03), female sex (Complete OR 60% vs 47%; p=0.04) and VGPR at 1 yr (Complete OR 70% vs. 36%; p &lt;0.0001). Other factors included in the model were age (p=0.9), bilirubin (p=0.1) and transplant (p=0.2). All aforementioned factors were significant in univariate analysis. Conclusions: Achievement of response in all involved critical organs is associated with better survival in AL pts than partial or no OR. Various baseline factors and VGPR at 1 yr can predict for achieving complete OR, with 70% pts who achieve VGPR at 1 yr having a complete OR. [Table: see text]
OS6.2 Identifying molecular subtypes of non-enhancing glioma using MRI perfusion and diffusion parameters
Authors: S Koene, F Incekara, S van der Voort, A Vincent, M van den Bent, G Lycklama à Nijeholt, R Nandoe Tewari, M Smits
Journal: Neuro-Oncology (2018)

According to the 2016 WHO classification low grade glioma can be classified into three groups based on molecular profile. A non-invasive method to identify these molecular profiles has yet to be established. There is evidence MRI perfusion and diffusion imaging might aid in the differentiation of the molecular profiles. Our aim is to identify MR imaging parameters to distinguish molecular profiles of non-enhancing glioma. 96 patients with non-enhancing, presumed low grade glioma were included. Patients were included if a pre-operative MRI-scan was available including at least T2w/FLAIR, dynamic susceptibility contrast perfusion and diffusion imaging and if the molecular status - 1p/19q co-deletion status and IDH mutation - was known. Tumors were segmented semi-automatically. Imaging parameters such as relative Cerebral Blood Volume (rCBV) and Apparent Diffusion Coefficient (ADC) were derived using IB Neuro. Tumors were divided into three clinically relevant molecular subgroups; 1p/19q co-deletion with IDH mutation (n=39), IDH-mutation without co-deletion (n=37), and IDH-wildtype without co-deletion (n=20). Kruskall-Wallace test showed significant differences for rCBV (Median, 75th and 85th percentile) and ADC (Median, 15th and 25th percentile) values between the three groups (p<0.05). Post-hoc analysis showed that IDH-mutated tumors without co-deletion had a significantly lower rCBV compared to the 1p/19q-codeleted tumors and the IDH-wildtype tumors (Median rCBV 0.67, 0.98 and 1.02 respectively p<0.05). Also, IDH-mutated, non-codeleted tumors have a significantly higher ADC compared to the two other groups (Median ADC 1.52 versus 1.27 and 1.17 p<0.05). No significant differences were found between 1p/19q co-deleted tumors and IDH-wildtype tumors in ADC or rCBV. Multinomial regression analysis (with age, tumor location and median rCBV/ADC ratio) showed an accurate prediction of the molecular profile of 79.2%. IDH-mutated, non-codeleted tumors had a significantly lower rCBV and significantly higher ADC compared to IDH-wildtype and 1p/19q co-deleted tumors. These results suggest that MRI perfusion and diffusion parameters are promising to determine mutation status of non-contrast enhancing low grade glioma.
TCT-72 A Prospective Evaluation for Hypoattenuated Leaflet Thickening Following Transcatheter Aortic Valve Replacement
Authors: Liang Tang, John Lesser, Mario Goessl, Marcus Burns, Lynelle Schneider, Hiroki Niikura, Dawn Witt, Ross Garberich, Paul Sorajja
Journal: Journal of the American College of Cardiology (2018)
Abstract 16450: The 99th Percentile of High-Sensitivity Assayed Troponin I is Associated With a High Risk of Death in Patients With Acute Chest Pain
Authors: Nils A Sörensen, Johannes T Neumann, Francisco M Ojeda, Tjark F Schwemer, Renate B Schnabel, Thomas Renné, Tanja Zeller, Mahir Karakas, Stefan Blankenberg, Dirk Westermann
Journal: Circulation (2016)

Background: The use of high-sensitivity assayed troponin allows measuring troponin concentrations far below the 99th percentile and enables rapid procedures to rule out acute myocardial infarction (AMI) with lower troponin cut-offs. Objective: To compare follow-up events of patients with acute onset chest pain and ruled out AMI by either a recently published “rapid algorithm” using a high-sensitivity cardiac troponin I (hs-TnI) cut-off of 6 ng/L at 0h and 1h or the 99th percentile of that assay (27ng/L) at 0h and 3h (“standard of care”). Methods: Hs-TnI was measured in 1,216 patients presenting to the chest pain unit of a German tertiary care center on admission (0h), after 1h and 3h. Patients with ST-elevation AMI were excluded. Follow-up was performed at 30 days, 6, 12 and 24 months. Overall mortality and cardiac rehospitalization were assessed. Results: The median follow-up time was 525 days. Patients ruled out by the “rapid algorithm” showed less cardiac rehospitalizations after 24 months (18.8% vs 23...
Patterns of recurrence in primary central nervous system lymphoma: Mechanistic inferences.
Authors: Prakash Ambady, Rochelle Fu, Cymon Kersch, Jenny Firkins, Nancy Diane Doolittle, Edward A. Neuwelt
Journal: Journal of Clinical Oncology (2016)

e19051 Background: Primary central nervous system lymphoma (PCNSL) is a highly chemo-sensitive tumor. High response rates can be achieved with first-line high dose methotrexate (HD-MTX) based regimens, yet most relapse within 2 years after complete response (CR). Although recurrences are generally believed to be from the same clone as the initial tumor, very little is understood about the mechanism of PCNSL recurrences. Recognizing patterns of recurrence is key for early detection and may provide valuable insight into potential recurrence mechanisms and guide therapies to extend CR duration. Methods: IRB approval was obtained to retrospectively review patients with CD20+ PCNSL treated with high dose methotrexate (HD-MTX) based chemotherapy after blood brain barrier disruption (BBBD). Patients with measurable disease at presentation who progressed after CR were included. Pattern and location of first recurrence were identified. Results: 128 patients were treated with HD-MTX/BBBD, 75 attained CR, 40 subsequently progressed and met inclusion criteria. At recurrence, new enhancement was noted in a spatially distinct site in 34 of 40 (85%). Only 6/40 (15%) of recurrences were contiguous to the initial lesion. Conclusions: Our results suggest that unlike gliomas, the majority of PCNSL recur at spatially distinct anatomical locations within, and in few cases outside, the CNS. Recurrence distal from the site of initial disease after CR suggests that seeding from potentially dormant CNS, ocular or systemic lesions may play a significant role. Muldoon et al (2011) previously described occult CNS disease outside the enhancing lesions in animal models, while Jahnke et al (2006) demonstrated persistent systemic monoclonal B-cells in blood and bone marrow of patients in CR. Prolonged duration of response seen with maintenance rituximab therapy after CR (Ney and Abrey, 2009) may be due its effects on these occult sites. Maintenance immunotherapy is being evaluated in a randomized trial. Site of recurrence after CR (n=40). Distant 34 (85%) Different lobe 18 Systemic / Non CNS 6 Ocular 3 Same lobe but distinct site 3 Corpus callosum 2 Leptomeningeal 2 Local 6 (15%) Corpus callosum 3 Cerebellum/ Posterior fossa 2 sub-ependymal 1