tbuckley/cabot-search huggingface dataset:
Abstract 14575: Implantable Cardiac Defibrillator in the Setting of Tetralogy of Fallot: Long-Term Follow-Up of a French National Multicenter Retrospective Registry
Authors: Abdeslam Bouzeman, Maxime De Guillebon, Guillaume Duthoit, Magalie Ladouceur, Raphael Martins, Laurent Fauchier, Denis Amet, Pascal Defaye, Jean-Baptiste Gourraud, Jean-Marc Sellal, Pierre Mondoly, Fabien Lalombarda, Frederic Anselme, Linda Koutbi, Nathalie Elbaz, Franck Halimi, Anne Messali, Amel Mathiron, Jean-Benoit Thambo, Laurence Iserin, Nicolas Combes, Eloi Marijon
Journal: Circulation (2015)

Background: Tetralogy of Fallot (TOF) is the most frequent form of congenital heart disease managed by EP physicians for potential ICD. However, few studies have reported long-term outcomes of TOF patients with ICD. Methods: Between 2005 and 2014, all TOF patients with ICD in 17 French centers were enrolled in a specific evaluation aiming to determine characteristics at implantation as well as outcomes (overall mortality, appropriate ICD therapies, and device-related complications). Results: Overall 78 patients (45±13 years, 64% males) were enrolled. A majority of patients were implanted in the setting of secondary prevention (73%), whereas the remaining (27%) in primary prevention. Among the latest group, known risk factors for sudden cardiac death were: severe pulmonary regurgitation (30%,) prior palliative shunt (50%), syncope with unknown origin (25%), inducible ventricular tachycardia (45%), QRS duration ≥180ms (18%), non-sustained ventricular tachycardia (25%), and documented sustained supra ventricular tachycardia (45%).Overall, patients implanted in the setting of primary prevention presented with a mean of 3.1±1.4 risk factors. After a mean follow-up of 4.9±3.8 years, 35 patients (45%) experienced at least one appropriate therapy (25% in the primary prevention group compared to 53% in the secondary prevention group), giving annual-incidences of 6.9% (95%CI 0.14-13.7) and 21.3% (12.4-30.3) respectively (P=0,01). The mean time between ICD implantation and the first appropriate therapy was 2.2±3.2 years, without significant differences between primary and secondary prevention. Overall, ≥one ICD-related complication occurred in 30 patients (38%), including inappropriate shock (n=9), major pocket hematoma (n=1), lead dysfunction (n=12), infection (n=4), shoulder algodystrophia (n=2), device failure or dislodgement needing reintervention (n=2). Eventually, four patients were transplanted (5%), and six patients (8%) died during the course of follow-up. Conclusions: Considering relatively long-term follow-up, patients with TOF and ICDs experience high rates of appropriate ICD therapies, in both primary and secondary prevention. Major ICD-related complications remain, however, high.
Integrated, structured reporting and diagnosis of localized prostate cancer.
Authors: Hans Hofstraat, Ralf Hoffmann, Marco Janssen, Maud de Klerk, Marc Loos, Frederik Jaederling, Olof Akre
Journal: Journal of Clinical Oncology (2017)

e16573 Background: To date 80-90% of men with primary prostate cancer are diagnosed with localized disease with a wide range of risks of future tumor progression. To optimize the balance between tumor removal and preserved continence and erectile function, it is essential to integrate all available information on tumor location, tumor characteristics, and baseline clinical data. Methods: We have developed a cloud-web-based technology allowing flexible access to the clinical data with close integration to the existing IT-environment like the hospital information management systems. The system allows the systematic and structured reporting of medical data generated by the involved disciplines of urology, laboratory, radiology, pathology, and (radiation) oncology, and patient reported health status and outcomes. Results: By use of the developed data integration platform we have collected diagnostic data of a prostate cancer case example scheduled for a multi-disciplinary primary treatment decision. The data comprises the patient health conditions, laboratory measures, multi-parametric MRI, localization information of MRI/US fusion guided biopsies, histo-pathology outcomes of prostate biopsy specimen, and patient reported outcomes on urinary and sexual function status. The collected data was presented in a visually integrated way and was used to discuss in a multi-disciplinary team, with the consistencies or discordances of findings across the various medical domains involved. Based on the discussion a primary treatment decision was concluded for this patient. Conclusions: The developed IT system to integrate heterogeneous medical data was successfully tested in a multi-disciplinary clinical setting. All required clinical variables to provide an informed primary treatment decision for a patient with primary localized prostate cancer was available in the system for discussion during the multi-disciplinary team (MDT) meeting and was presented in a clear visual way to support the interactive discussions between MDT members representing different clinical specialties.
Cancer-related distress and cost of care concerns among gastric cancer patients.
Authors: Linda S. House, Melissa F Miller, Alexandra K Zaleta, Jamese Johnson, Crystal Shereen Denlinger, Joanne S Buzaglo
Journal: Journal of Clinical Oncology (2017)

e15583 Background: Individuals with gastric cancer (GC) are at risk for significant physical, psychological, and financial burden related to their illness and cost of care. This study characterizes cancer-related distress and concerns among survivors of GC and related cancers and the support survivors receive from their health care team for these concerns. Methods: Of 110 GC survivors enrolled in the Cancer Support Community’s online Cancer Experience Registry, 30 (43% stomach, 37% esophageal, 20% GIST) rated their level of concern (0 = not at all; 4 = very seriously) about psychological, emotional, physical and practical concerns (27 items). Risk for clinically significant distress was identified via a 4-item subscale (α = 0.86, cutoff score = 6.) Participants also completed the Impact of Events (IES) intrusion subscale and questions about their healthcare team’s involvement in addressing concerns. Results: Participant median age was 61 years; median time since diagnosis was 3 years. 23% experienced recurrence; 37% had metastatic disease.The highest ranked concerns (rated moderately to very seriously) included: eating and nutrition (62%); fatigue (62%); health insurance or money worries (59%); worry about the future (59%); feeling sad or depressed (50%); changes or disruptions to work, school, or home life (48%); sleep problems (48%); and worry about family (48%). Half of respondents (50%) were at risk for clinically significant emotional distress; 39% reported intrusive thoughts about the cost of cancer care. Fewer than half indicated their health care team asked about emotional distress (43%), lifestyle (43%), work (40%), finances (37%), or family (33%). Participants wished for more help with emotions related to cancer (57%), long-term side effects (55%), and financial advice/assistance (52%). Conclusions: Substantial proportions of gastric cancer survivors express concern about physical symptoms, emotional distress, and financial burden, yet many report they are not counseled about these concerns. Efforts are needed to reduce distress and the financial burden associated with gastric cancer to reduce their potential impact on quality of life, treatment adherence, and other illness outcomes.
Apatinib to enhance antitumor activity of gefitinib in non-small cell lung cancer.
Authors: Fang Li, Tengjiao Zhu, Xiang Zhu, Jiadong Wang, Li Liang
Journal: Journal of Clinical Oncology (2017)

e20086 Background: Gefitinib, an oral EGFR-TKI, is recommended as the first-line therapy for non-small cell lung cancer (NSCLC) patients with EGFR mutations. Apatinib is an oral TKI against VEGFR-2 and is effective as third- or later-line treatment in advanced NSCLC. EGFR and VEGF/VEGFR pathways are interrelated. We conducted this study to explore the effect of gefitinib plus apatinib therapy in NSCLC and the possible mechanism. Methods: Cell viability assay was performed on 4 NSCLC cell lines (A549, H1975, H1650 and HCC827) to determine IC 50 of gefitinib, apatinib and their combination for growth inhibition. The nude mice were injected i.h. with H1975 cells to establish EGFR mutated NSCLC xenograft tumor. Tumor volume was recorded every three days. Immunohistochemistry for Ki67 and PCNA expression was performed to detect tumor cell proliferation in mice. In addition, the expression levels of key proteins were detected by immunohistochemistry and western blot, respectively. Results: The H1975 cells were the most susceptible to the combination of gefitinib and apatinib, with lowest IC 50 value of 0.44 ± 0.09, compared with other cells. In H1975 xenograft model, gefitinib plus apatinib showed markedly higher inhibiting effect on tumor volume than both gefitinib and apatinib mono-therapy. Moreover, the expressions of both Ki67 and PCNA significantly decreased in mice after combined therapy than either gefitinib or apatinib alone, indicating that the combined therapy was superior to mono-therapy of gefitinib or apatinib in suppressing cell proliferation in mice. Additionally, there was an obviously higher expression of EGFR, pho-EGFR, VEGFR, pho-VEGFR, VEGFA, p-mTOR, t-mTOR, p-AKT, t-AKT, p-Erk, and t-Erk in mice treated with gefitinib plus apatinib than mono-therapy. Furthermore, the much stronger inhibitory effect on angiogenesis of gefitinib plus apatinib therapy was revealed, as more expression of CD31 than both gefitinib and apatinib mono-therapy. Conclusions: Apatinib significantly potentiated the antitumor effect of gefitinib in NSCLC both in vivo and vitro. These findings support a great therapeutic potential role for the combination of apatinib and EGFR-TKI in the treatment of NSCLC in clinic.
A rare manifestation: Primary mediastinal large-b cell lymphoma.
Authors: Erden Atilla, Pinar Ataca, Osman Ilhan, Onder Arslan, Gunhan Gurman, Muhit Ozcan
Journal: Journal of Clinical Oncology (2016)

e19071 Background: Primary Mediastinal Large B-Cell Lymphoma (PMLBL) is a rare subtype of diffuse large B-cell lymphoma occurs mostly in young adult group with bulky disease. Herein, our aim is to present PMLBL cases followed in our clinic. Methods: We retrospectively evaluated 11 patients diagnosed as PMLBL from January 2006 to March 2015 in Ankara University Department of Hematology, Turkey. Results: The median age at diagnosis was 29,4 (range, 19-71), female to male ratio:6/5. 9 of the patients (82%) were aged < 35. Except a patient who presented with pericardial and pleural involvement- stage IV disease, 90.9% patients (n = 10) had stage I or II disease. 81.8% patients (n = 9) had ECOG performance score < 3 with IPI < 3. 10 patients (90.9%) had symptomatic bulky lesion at diagnosis. We administered R-CHOP (rituximab, cyclophosphamide, vincristine,prednisolone) protocol to all patients and 4 patients (36.3%) received radiotherapy. The patients are followed by control PET for residual disease. The median follow-up period was 21.3 months (range, 3.9-103.5 months). Overall response rate was 90.9%. 1 patients relapsed at 18th months of diagnosis and received 2 courses of salvage regimen (ICE) and underwent autologous stem cell transplantation. He is followed in complete remission. Conclusions: We demonstrated our 11 PMLBL patients, succesfully treated with R-CHOP regimen. Radiotherapy should be evaluated up to patients status.
Stereotactic body radiotherapy (SBRT) for inoperable hepatocellular carcinoma: A retrospective analysis.
Authors: Nikesh Hanumanthappa, Vikram maiya Manoor, Premitha R, Dr.Radheshyam Naik, Pichandi Anchineyan, Kumara Swamy
Journal: Journal of Clinical Oncology (2016)

e15618 Background: Hepatocellular Carcinoma (HCC) amenable to radical surgery at presentation, comprise of one third of the patients, while majority of them are inoperable and metastatic. The options of palliative treatment are also limited at this stage. We report the survival of inoperable HCC patients, treated with SBRT using Robotic arm Radiosurgery. Methods: We reviewed the clinical data of patients with inoperable HCC who underwent SBRT using Robotic arm Radiosurgery technique from September 2009 to December 2015. The clinical data was obtained from patients’ case records. Data analysis was carried out using SPSS software (version 20). Survival was calculated using Kaplan-meier method. Results: A total of 15 patients who were treated on alternate days with SBRT using Robotic arm Radiosurgery technique in the study period were included. There were 14 male and 1 female patients. Median age at presentation was 67 years (range:42-82 years). Of the 15 patients, 11(73.3%) had stage IV disease and 4(26.7%) were stage III. Seven (46.7%) patients underwent prior treatment with systemic chemotherapy with or without radiofrequency ablation (RFA). All patients belonged to child pugh class A. The median size of the lesion was 8.8 cm (3.3-18cm). The median dose of SBRT given was 24 Gy (range:18-36 Gy) and median number of fractions was 3 (2-6), with a median prescription isodose of 75% (65-84%). All patients received sorafenib during and after SBRT. The median overall survival after completion of SBRT was 1 month. Two patients with tumour size of 3.3 cm and 7.6 cm were alive with progressive disease at last follow up (3 and 1 years respectively). On univariate analysis, factors such as age and tumour size did not have a significant impact on overall survival. Conclusions: SBRT may be considered as a feasible option in inoperable and advanced HCC in a select group of patients. Tumour size is important for predicting outcomes which has not been clearly shown in our study due to small sample size. Prospective evaluation with better selection of patients is proposed.
Abstract MP06: Statins and the Risk of Diabetes Type II in Children Ages 8 to 20 with and without Dyslipidemia
Authors: Nina Joyce, Justin Zachariah, Charles Eaton, Amal trivedi, Gregory Wellenius
Journal: Circulation (2016)

Introduction: There is increasing evidence of a causal association between statin use and type II diabetes mellitus (T2DM) in adults. However the risk of incident T2DM in children treated with statins is unknown, and a recent study demonstrating a protective effect of familial hypercholesterolemia suggests there may be heterogeneity of effect by the presence of genetic dyslipdemia. We estimated the association between statin use and the risk of T2DM in a commercially insured population ages 8 to 20 from 2004 to 2013 with and without a diagnosis of dyslipidemia. Methods: New users of statins with a minimum 75 percent of days covered (PDC) in the first year of use were matched to up to 10 non-users using year-specific propensity scores within a 0.01 caliper. The outcome was defined as incident T2DM more than 12 months after the match date to address possible confounding by indication and allow for a biologically plausible level of cumulative exposure. Cox proportional hazard models were used to estimate the relative hazards for T2DM among statin users and non-users. Time was defined from the end of the 12 month latency period to either the outcome or censoring. Sensitivity analyses varied the width of this exclusionary window, as well as PDC to test the robustness of our results to study assumptions. Results: There were a total of 13,443,478 patients who met eligibility criteria, 755 (0.1%) of whom were started on statins and met the minimum PDC. Of these, 748 (98%) were matched with no significant difference in the year-specific match rate. Statin use was associated with an increased risk of T2DM in children without dyslipidemia diagnosis (HR 2.75, 95%CI 1.20-6.30, p=0.01), but not in children with a recorded diagnosis of dyslipidemia (HR 1.01, 95%CI 0.59-1.70, p=0.98). The results were robust to variations in the latency period and PDC (figure). Conclusion: Statin use was associated with increased risk of new onset T2DM in children without a dyslipidemia diagnosis, but not in children with a diagnosis of dyslipidemia.
Single institution retrospective review of patients with primary CNS lymphoma (PCNSL).
Authors: Andrew Thomas Johnson, Zohra Nooruddin, Gentry Teng King, Henning Helmut Schade, Manali K. Kamdar, Brad M. Haverkos, Douglas Edward Ney
Journal: Journal of Clinical Oncology (2016)

e19078 Background: Primary central nervous system lymphomas (PCNSL) are a rare type of b cell lymphoma, confined to the CNS, the majority of which are Diffuse Large B-Cell Lymphomas (DLBCL). Despite advances in therapy, the prognosis remains poor. Chemotherapy regimens include a HD-MTX backbone with or without other agents. Methods: We retrospectively reviewed the medical records of patients with a diagnosis of PCNSL that were diagnosed and treated at the University of Colorado Hospital from 1995 to 2015. Results: A total number of 70 patients were identified. Median age was 64 years old (29-86) and 55% were male. 67% of patients had a KPS > 70 at diagnosis. 18 % of patients were immunosuppressed and included in the survival analysis. 16% of patients underwent initial radiation therapy. Median PFS and OS for all patients was 9.4 months (95% CI 6-22) and 14.9 months (95% CI 8-35) respectively. At diagnosis, KPS < 70 and elevated CSF protein were associated with a trend toward worse OS. Of the 70 patients identified, 42 were initially treated with a HD-MTX based regimen with or without rituximab. Patients initially treated with a HD-MTX based regimen without rituximab (N = 13) had a median overall survival of 14.5 months. The median OS of patients initially treated with HD-MTX and rituximab (N = 23) has not been reached and favors the addition of rituximab (HR 0.25, 95% CI 0.06-0.49). 17 of 23 patients treated with the combination of HD-MTX and rituximab were treated with R-MPV, none of which went on to autologous stem cell transplant (ASCT). Patients treated with R-MPV had a 2 yr OS of 72% (95%CI 41-87) with a median follow up of 41 months. Conclusions: In this consecutive series of 70 patients with PCNSL from a single institution over a 20 year period KPS < 70 and elevated CSF protein were associated with a trend toward worse OS. Our analyses showed a clear trend toward improved OS in patients who received rituximab and HD- MTX as compared to patients treated with regimens without rituximab. The 17 patients treated with R-MPV alone without ASCT had a 2 yr OS of 72%. Further studies comparing the outcomes of patients treated with R-MPV with or without ASCT are warranted. ABC versus GC subtyping and the effect on outcomes is ongoing.
Drivers of phase-based costs in patients with multiple myeloma.
Authors: Abdalla Aly, Zoe Clancy, Brian Ung, Amit Agarwal, Ruchit Shah
Journal: Journal of Clinical Oncology (2018)

e20022 Background: Patients with multiple myeloma (MM) are living longer, compared to other cancers. This analysis characterized the drivers of MM cost by phases of care along the patient journey. Methods: Newly diagnosed patients (≥18 years) with MM were matched to non-MM controls using Optum™ Clinformatics™ Data Mart from 2007-2016. Index date was the first MM diagnosis date for cases and first claim date after 12 months of continuous enrollment for controls. Propensity scores, index dates, and death dates were used to match cases with controls. Post matching, non-MM patients were assigned the MM index date of the matched MM case. The follow up time for each patient was parsed into 4 phases: 3 months prior to diagnosis (pre-diagnosis), first 6 months after (initial), last 12 months before death (terminal), and any remaining time between initial and terminal phases (continuation). Results: 12,452 MM cases were matched to 49,798 non-MM controls. The mean (median) follow up time spent in the continuation phase for cases and controls was 23.9 (17.5) and 23.9 (18.0) months, respectively. In all phases, the major cost drivers for cases and controls were outpatient, inpatient, followed by pharmacy costs. Outpatient costs contribution (% of total costs) was 44.5%, 52.6%, 50.9%, and 41.7% for MM cases and 44.1%, 45.3%, 40.0%, and 41.7% for non-MM controls during the pre-diagnosis, initial, continuation, and terminal phase, respectively. Inpatient costs (% of total costs) was 34.5%, 27.5%, 21.6%, and 40.0% for MM cases and 30.6%, 27.2%, 34.6%, and 46.6% for non-MM controls during the pre-diagnosis, initial, continuation, and terminal phase, respectively. Pharmacy costs contribution (% of total costs) was 9.6%, 13.9%, 21.5%, and 10.7% for MM cases and 12.6%, 13.8%, 11%, and 6.6% for non-MM controls during the pre-diagnosis, initial, continuation, and terminal phase, respectively. Conclusions: With better survival, patients with MM will spend more time in the continuation phase. Pharmacy costs were the smallest contributor of total healthcare costs while outpatient and inpatient costs were the major drivers of total costs throughout the course of the disease.
Association of genetic variations in genes implicated in the axis with outcome in patients (pts) with metastatic colorectal cancer (mCRC) treated with cetuximab plus chemotherapy.
Authors: Yuji Miyamoto, Sebastian Stintzing, Volker Heinemann, Wu Zhang, Shu Cao, Satoshi Okazaki, Martin D. Berger, Mitsukuni Suenaga, Marta Schirripa, Shivani Soni, Satoshi Matsusaka, Yan Ning, Dongyun Yang, Roel Gopez, Elizabeth Melendez, Diana L. Hanna, Afsaneh Barzi, Hideo Baba, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2017)

3585 Background: Accumulating evidence suggests that right- and left-sided CRCs have different prognoses and different sensitivities to EGFR inhibitors in several phase3 trials. These differences might be related to different embryological origins, which are reflected in different molecular profiles of tumors. LEFTY, Nodal and ACVR2B, which are TGF-betasuperfamily, are key regulators of left-right axis during embryogenesis; these expressions control sidedness. Our aim was to evaluate whether SNPs in these genes are associated with clinical outcomes in mCRC pts enrolled in the FIRE3 trial. Methods: Genomic DNA was obtained from mCRC pts receiving cetuximab plus FOLFIRI as first-line treatment and analyzed by using PCR-based direct sequencing. Four functional SNPs in 4 genes ( LEFTY1, LEFTY2, Nodal, and ACVR2B) were tested in 305 pts in FIRE3 trial cetuximab cohort (NCT00433927). Main characteristics were the following: male/female = 207/98; median age = 64; RAS-wildtype/mutant = 195/95; median PFS = 9.6 months; median OS = 26.5 months, median follow-up time = 41.8 months. Results: In patients with left sided tumor ( N= 237), LEFTY2 rs3007716 G/G variants ( N= 14) showed shorter PFS than any A variants ( N= 222) in univariate (8.0 months (M) vs. 10.3 M, HR = 2.24, 95%CI = 1.27-3.94, P &lt; 0.01) and multivariate analyses (HR = 2.12, 95%CI = 1.20-3.75, P &lt; 0.01). Nodal rs1904589 T/T ( N= 36) showed longer OS than any C variants ( N= 196) in univariate analysis (50.1 m vs. 29.8 M, HR = 0.61, 95% = 0.37-1.01, P = 0.048) and multivariate analyses (HR = 0.59, 95%CI = 0.35-0.99, P = 0.046). In patients with right sided tumors ( N= 58), ACVR2B rs2268753 C/C ( N= 12) showed shorter PFS than any T variants ( N= 43) in univariate analysis (3.7 m vs. 7.7 M, HR = 1.93, 95% = 0.99-3.77, P = 0.038) and multivariate analysis (HR = 2.24, 95%CI = 1.12-4.51, P = 0.023). Conclusions: Our study showed for the first time that genetic variations in sidedness related genes are associated with PFS and OS in patients receiving cetuximab based chemotherapy, which may dependent on location.