tbuckley/cabot-search huggingface dataset:
Correlation between mutation clearance and clinical response in elderly patients with acute myeloid leukemia (AML) treated with azacitidine and pracinostat.
Authors: Koichi Takahashi, Yasmin Abaza, Ehab L. Atallah, Bruno C. Medeiros, Sam Khal, Martha Lucia Arellano, Mrinal Patnaik, Richard Ghalie, Guillermo Garcia-Manero
Journal: Journal of Clinical Oncology (2017)

7034 Background: In a phase II study in 50 elderly patients (pts) with AML who were not eligible for intensive chemotherapy, treatment with pracinostat + azacitidine (AZA) was well tolerated, led to 42% complete remission (CR) rate and a median overall survival (OS) of 19.1 months (Blood 2016: 128;100). Here we investigate the impact of somatic mutations and their clearance on disease response and patient outcomes. Methods: 88 samples from 41 study pts were sequenced. All 41 pts were analyzed pre-treatment, and a median of 3 longitudinal samples were analyzed from 19 pts between Cycle 2 and 9. Mutations were assayed by SureSelect targeted capture exon sequencing (Agilent) of 295 genes that are recurrently mutated in hematologic malignancies. Longitudinal mutation clearance was analyzed by plotting variant allele frequency (VAF). Results: At baseline, 96 mutations in 28 genes were detected in 38 pts, with the most frequent being in SRSF2 (27%), DNMT3A (20%), IDH2 (17%), RUNX1 (17%), and TET2(17%). Mutations associated with CR rate and OS are indicated in the Table. A CR was achieved in 10/19 pts that had longitudinal sequencing analysis and at the time of CR, 9 (90%) had persistently detectable mutations in their bone marrow. In 7 of them, continued exposure to pracinostat + AZA lowered the VAF or cleared residual mutations. In 2 pts, relapsed samples showed re-expansion of the founder clone. Conclusions: Mutations in NPM1, and DNA methylation pathway were associated with a better response to pracinostat + AZA, while TP53 mutation was associated with a poor response. Persistent mutation at the time of CR suggests residual preleukemic clonal hematopoiesis in this elderly population. Benefit of prolonged exposure to pracinostat + AZA was also confirmed at molecular level where continued decline of mutation VAF was seen after achieving CR. Clinical trial information: NCT01912274. [Table: see text]
Abstract 12769: Antiepileptic Medication and the Risk for Sudden Cardiac Death Caused by an Acute Coronary Event
Authors: Eeva K Hookana, Hanna Ansakorpi, Kari S Kaikkonen, M Juhani Junttila, Marja-Leena Kortelainen, Heikki V Huikuri
Journal: Circulation (2013)

Introduction: Epilepsy is associated with an increased prevalence of sudden cardiac death (SCD). It is not well known, if this association is caused by the disease itself or by the use of antiepileptic medication, many of which have influence on the cardiac ion channel functions. We studied the role of antiepileptic drugs as a triggering factor of SCD in a large case-control study. Methods: The FinGesture study population was derived from autopsies of victims of SCD caused by an acute coronary event in Northern Finland during 1998-2007. The use of medication was compared between victims of SCD and survivors of an acute coronary event in a case-control study including a consecutive series of victims of SCD (n=2674, mean age 62.8±12.3y) verified at medico-legal autopsy and consecutive series of patients surviving an acute myocardial infarction (AMI; n=1120, mean age 65.5±12.0y). The medication history was obtained from autopsy/hospital records and interviews with relatives of SCD victims and AMI patients. R...
Impact on treatment adherence, side effects control, patients QoL, and rehospitalization rate through new management of oral chemotherapy.
Authors: Ida Pavese, Thierry Collon, Yasmine Chait, Amine Cherait, Laurence Bisseux, Besma MBarek, Carole Miette, Jocelyne Imbeau, Ida Iurisci
Journal: Journal of Clinical Oncology (2018)

e18533 Background: In our oncology department, serving an under-privileged suburban area north-east of Paris, the patient’s population treated with oral chemotherapy increased steadily during the last 4 years (+25%). In 2017, we changed our organization for outpatients with oral chemotherapy in order to improve their safety and QoL, to detect and rapidly treat toxicity, to control adherence and reduce the hospitalization rate. Methods: We organized a platform to manage the prescription and delivery of oral drugs, the patients’ information and education, the patients’ treatment adherence (20%) and the toxicity in order to guarantee quality of therapy, outcomes, patients’ quality of life and prevent the re-hospitalisations, considered as a hall- mark of poor-quality care. 25 oral molecules, sequentially or in association with IV drugs and prescribed until disease progression, were our therapeutic arsenal. The platform team is composed of two oncologists, a pharmacologist and two nurses who are now authorized by the French Health Authority to prescribe drugs or evaluation tests in a new and very specific context with strict rules. The platform is coordinated with general medical doctors and pharmacies. The nurses follow the out patients in oral chemotherapy by weekly telephone calls by submitting them the toxicity related drug questionnaire, the PRO and the QoL EORTC questionnaire. Our patients are not sufficiently equipped with tablets or smartphones to rely on these to communicate with us and we use a telephone number and mail address. While the platform is low tech, it also has a low care cost. Results: Since June 2017 to January 2018 we treated 227 patients (177 Treatments per OS and 50 IV+ per OS). Median age was 64 years, 75 patients were more than 70 years old, 106 M and 121 F. The median treatment lasted 10 weeks. Thanks to the new organisation, we control the patient adherence and QoL, reduced toxicity degree (23%), treatment interruption (-15%) and re-hospitalization rates (10%). Conclusions: This organization permits a good quality follow up of patients in oral therapy with low cost and low-tech resources.
Neurofibromatosis type 1 and risk of late outcomes after a primary tumor: A report from the Childhood Cancer Survivor Study.
Authors: Peter de Blank, Nan Li, Nicole J. Ullrich, Michael J. Fisher, Smita Bhatia, Yutaka Yasui, Charles A. Sklar, Wendy M. Leisenring, Rebecca M. Howell, Kevin C. Oeffinger, Kristina K. Hardy, Mehmet Fatih Okcu, Todd M. Gibson, Leslie L. Robison, Gregory T. Armstrong, Kevin R. Krull
Journal: Journal of Clinical Oncology (2018)

10563 Background: It is not known whether survivors of childhood cancer with neurofibromatosis type 1 (NF1) are at increased risk for poor long-term health outcomes. Methods: 1,936 > 5yr survivors of childhood cancer diagnosed between 1970-1999 (176 with NF1 and 1,760 non-NF1 survivors matched on diagnosis and diagnosis era) and 5,051 siblings were compared on self-reported chronic medical conditions (CTCAE v 4.0) and cognitive impairment (defined as > 90th percentile of siblings on the CCSS Neurocognitive Questionnaire) using logistic and Poisson regression to adjust for age at survey, age at diagnosis, sex, race, CNS radiation and other treatment exposures. Results: Among survivors with NF1, CNS astrocytoma was the most common primary tumor (n = 142, 78%). Compared to non-NF1 survivors, NF1 survivors were more likely to report a serious health condition (grade 3-4; RR[95% CI] 2.2[1.9-2.6]) and multiple chronic conditions (grade 2-4, 1.9[1.6-2.2]). Specific health risks (grade 1-5) are shown below. Curiously, diabetes and abnormal thyroid were less common in NF1 survivors compared to non-NF1 survivors and siblings. Survivors with NF1 were more likely to report impaired organization (OR 1.9 [1.0-3.4]), task completion (1.7 [1.1-2.8]) and learning/memory (1.6 [1.3-1.8]). NF1 survivors were less likely to attend college (0.4 [0.2-0.7]) and be employed (0.6 [0.4-0.9]). Conclusions: NF1 impacts risk of health/cognitive outcomes in adult survivors of childhood cancer. Further research should investigate the underlying mechanisms of these risks. Condition RR [95%CI] vs nonNF1 survivor vs Sibling Diabetes 0.14 [0.07-0.27] 0.22 [0.12-0.43] Abnormal Thyroid 0.25 [0.19-0.33] 0.54 [0.41-0.73] Speech Deficit 0.38 [0.18-0.81] 0.64 [0.30-1.35] Hearing Loss 0.57 [0.48-0.68] 1.24 [1.05-1.4] Hyperlipidemia 0.69 [0.57-0.83] 1.71 [1.42-2.06] Osteoporosis/Osteopenia 1.25 [1.05-1.49] 14.9 [12.4-17.9] Epilepsy 1.71 [1.51-1.95] 7.99 [7.06-9.05] GI Disease 1.79 [1.57-2.05] 2.80 [2.47-3.18] Sensory impairment 1.89 [1.69-2.11] 1.66 [1.49-1.84] Motor impairment 2.05 [1.84-2.29] 4.87 [4.41-5.38] Heart Disease 2.07 [1.71-2.50] 1.05 [0.88-1.25] Vision Loss 2.06 [1.81-2.35] 6.26 [5.53-7.09]
Pharmacological interaction and side effects in oncohaematology: a retrospective observational study.
Authors: Elena Tenti, Andrea Casadei Gardini, Cristina Papayannidis, Giovanni Marconi, Giorgia Simonetti, Sarah Parisi, Stefania Paolini, Chiara Sartor, Emanuela Ottaviani, Claudia Venturi, Maria Chiara Fontana, Antonella Padella, Viviana Guadagnuolo, Nicoletta Testoni, Carmen Baldazzi, Francesco Brera, Giovanni Martinelli
Journal: Journal of Clinical Oncology (2016)

e18235 Background: Patients affected by oncohaematology pathology follow multiple therapies that can contribute to the drug interactions resulting in change in pharmacokinetics or pharmacodynamics of chemotherapy and then increase or decrease the efficacy of the drugs. Knowledge on the interactions between drugs used in chemotherapy protocols are supported by numerous publications, but most of knowledge in this field is derived from clinical trials that revealed a limited number of interactions due to the controlled nature of these trials.To optimize the therapy was performed a retrospective analysis to get information on possible interactions between molecules used in chemotherapeutic protocol (or those of conditioning for transplantation bone marrow) and other drugs taken by patients. Methods: Were evaluated therapies used for multiple myeloma disease, hodgkin's / non-Hodgkin's lymphoma disease, and leukemia syndrome myelodysplastic prescribed between Oct 2014 and Jun 2015 and were analyzed all possible drug interactions consulting UpToDate and Micromedex programs, Stockley's data and the drugs sheets. Results: Were analyzed 91 patients for a total of 72 preconditioning cycles for autologous hematopoietic stem cells and 362 cycles of chemotherapy; were detected 166 clinically relevant interaction given by the combination of thalidomide and dexamethasone (59.6%), cyclophosphamide and allopurinol (28.3%), cisplatin and rituximab (6.7%),cyclophosphamide and cyclosporine (5.4%). Were detected also 107 moderate interactions given by the combination of bortezomib and azole antifungals (31.8%), cyclophosphamide and ondansetron (24.3%), desametasone and ondansetron( 15.9%), prednisone and antifungals (13%),methotrexate and ciclosporin (7.5%) and methotrexate and inhibitor proton pump (7.5%). During the observational period were recorded 31 adverse drug reactions (ADRs). Conclusions: Data from these studies indicate that more than half of the patients in treatment is potentially exposed to at least one adverse reaction caused by drug interactions
Clinical trials in children and adolescents with systemic lupus erythematosus: methodological aspects, regulatory landscape and future opportunities
Authors: Hermine I Brunner, Alberto Martini, Daniel J Lovell, Nicolino Ruperto
Journal: Annals of the Rheumatic Diseases (2018)

Childhood-onset systemic lupus erythematosus (cSLE) is rare in many regions of the world, including Europe. Access to approved medications for cSLE is currently limited, among others, due to a lack of high-quality evidence from clinical trials. The objectives of the study were to evaluate the current regulatory framework regarding medication approvals, delineate barriers to clinical trial conduct, and strategies to improve access to new medications for cSLE. Relevant methodological and regulatory aspects, epidemiological data, study designs and outcome measures are reviewed, and the results of a survey among Paediatric Rheumatology International Trials Organisation/Pediatric Rheumatology Collaborative Study Group investigators are presented. Laws and regulations in the USA and Europe necessitate that novel medicines are studied in paediatric populations, if similar or the same diseases in adults have been found to benefit from them. Regulatory agencies consider cSLE the paediatric form of SLE in adults. For medicines that have been found safe and effective in adult SLE, paediatric extrapolation strategies can limit the number and complexity of studies needed to support the labelling of these medicines for use in cSLE. In this setting, specialised research networks, validated outcome measures, stakeholder input, study designs as well as statistical methods successfully used in other uncommon diseases will help improve study efficiency in an effort to enhance the speed with which new drugs for cSLE can be studied. Open-label pharmacokinetic-pharmacodynamic studies are preferred by paediatric rheumatologists over double-blind parallel designs for cSLE trials. Appropriate infrastructure, outcome measures and sufficient numbers of patients are available for the testing of new medicines for children with cSLE.
Efficacy and safety of apatinib in refractory unresectable and metastatic cholangiocarcinoma: A retrospective analysis.
Authors: Haibo Mou, Qinfen Xie, Lan Fang Yu, Qin Liao, Yu Yang, Yingfang Wu
Journal: Journal of Clinical Oncology (2018)

e16123 Background: Biliary tract cancers (BTCs) are invasive adenocarcinomas associated with poor prognosis. And there is no standard regimen for unresectable and metastatic BTC patients who failed to first-line gemcitabine-containing chemotherapy. Apatinib, VEGFR-2 inhibitor, has been proved to be effective and safe in patients with advanced gastric cancer after second-line chemotherapy, and also showed promising results in non-small cell lung cancer, hepatocellular carcinoma and sarcoma etc. In this study, we aimed to explore the efficacy and safety of apatinib in salvage treatment for advanced BTCs after failure of chemotherapy. Methods: Between June 2016 and December 2017, BTC patients who received apatinib alone in daily dose of 500 mg for at least four weeks were enrolled. Dose reduction to 250 mg was allowed. The objective response rate (ORR) was evaluated based on RECIST version 1.1 and the safety profile was determined according to NCI-CTC4.0. Results: The median follow up time was 13 months (1-17 months). The cutoff date for data analysis was 27 January 2018. Twenty-one patients were enrolled, 16 men and 5 women with a median age of 61 years (38–75 years). The primary cancer sites were: 12 (57%) intrahepatic cholangiocarcinoma, 5 (24%) gallbladder, and 4 (19%) extrahepatic cholangiocarcinoma. Three patients (14%) (2 of them were gallbladder cancer) achieved partial response (PR) and 12 (57%) achieved stable disease (SD). Thus, the cancer control rate was 71%. Median progression-free survival (PFS) was 2.8 months (95% CI 0.85-8.03 months), and the median overall survival (OS) was 8.8 months (95% CI 2.85-14.7 months). The most common grade 3 or 4 treatment-related adverse events were hypertension (14.2%, 3/21), hand-foot syndrome (23.8%, 5/21), proteinuria(9.5%, 2/21), fatigue (9.5%, 1/21), hyperbilirubinemia (4.7%, 1/21), and diarrhea (4.7%, 1/21). 8 patients experienced dose reductions and there was no treatment-related death. Conclusions: Apatinib exhibits promising activity and manageable toxicity for the pretreated patients with advanced biliary tract cancers. Prospective large sample size trials are needed for further investigation.
Re-irradiation for relapsed paediatric ependymoma.
Authors: Louise Janet Murray, Cynthia Hawkins, Michael Taylor, Ute Katharina Bartels, Annie Huang, Abhaya Kulkarni, Vijay Ramaswamy, Eric Bouffet, Uri Tabori, Normand Laperriere
Journal: Journal of Clinical Oncology (2016)

10565 Background: Re-irradiation (re-RT) is increasingly adopted in relapsed ependymoma. In the setting of local relapse without dissemination, there is variation in whether focal or craniospinal (CSRT) re-RT is used. Indications for, and outcomes from, re-RT in one centre were investigated. Methods: Retrospective chart review for paediatric patients (pts) re-irradiated for recurrent ependymoma. Results: Of 71 pts initially irradiated focally (54-59.4Gy) for localised ependymoma between 1998 and 2015, 27 relapsed and received re-RT. In the setting of isolated local relapse, 12 pts received focal re-RT (54-59.4Gy), 2 received single fraction stereotactic radiosurgery (15-24Gy), and 4 received CSRT (36Gy to whole CNS, 54-59.4Gy local boost). A further 9 pts received CSRT for metastatic recurrence (36Gy to CNS, 54-59.4Gy boosts). Median time to re-RT was 25.2 months (range 5.4-141.0) and median age at re-RT was 9.7 years (range 2.4-22.3). Re-RT was preceded by surgery in 22 pts. Re-RT was well tolerated with no acute severe toxicities. Table 1 shows survival outcomes from date of re-RT. At 3 years, in pts with isolated local relapse, all CSRT re-RT pts were alive, compared to 78% of focal re-RT pts. In addition, at 3 years, in pts with local relapse, 75% of CSRT re-RT pts were progression free, compared to 36% of focal re-RT pts. As expected, as numbers were small and follow-up for CSRT short, differences were not statistically significant. A second course of re-RT was delivered in 7 pts (focal in 2, CSRT in 5). There were 4 cases of radionecrosis. Of 15 surviving pts, 5 have endocrinopathies. There was a wide range in intellectual function in re-RT pts, ranging from pts with severe developmental delay to pts achieving top academic grades. Conclusions: Re-irradiation in relapsed ependymoma is well tolerated. The excellent survival in pts who received CSRT re-RT for isolated local relapse is encouraging. Re-RT outcomes. Re-RT type and indication (n) Median follow-up (months) Median overall survival (months) 3 year overall survival Median progression free survival (months) 3 year progression free survival Focal, local relapse (14) 67.6 56.9 77.9% 15.8 35.7% CSRT, local relapse (4) 32.2 Not reached 100% Not reached 75.0% CSRT, metastatic relapse (9) 21.5 25.4 30.0% 13.6 0%
Risk of CNS adverse events (CNS-AEs) for patients with non-small cell lung cancer (NSCLC) and melanoma brain metastases (BM) treated with CNS radiation (CNS-RT) and immune checkpoint inhibitors (CPIs).
Authors: Michael Edward Devitt, Ralph Sumner Abraham, Jacobi Hines, Bethany J Horton, Camilo E. Fadul, James Mitchell Larner, Jason Sheehan, Richard Delmar Hall, Ryan D. Gentzler
Journal: Journal of Clinical Oncology (2018)

2010 Background: CPIs are widely used in the treatment of both metastatic melanoma and NSCLC. BM frequently occur and are treated with CNS-RT. Since both CNS-RT and CPIs can cause neuro-inflammation, we tested the hypothesis that concomitant treatment with CPIs and CNS-RT results in an increased risk of CNS-AEs. Methods: We identified patients with melanoma and NSCLC with BM treated with CNS-RT and seen at our institution between 2014 and 2016. Concomitant treatment with CPIs and CNS-RT was defined as administration of CPIs within 3 months before or after CNS-RT. CNS-AEs were defined as new or worsening edema on brain MRI without disease progression, new or worsening neurological deficit, or need to start or increase corticosteroids. A generalized linear model incorporated significant variables from a univariate analysis to model the incidence of CNS-AEs. Variables considered included the use of CPIs within 3 months of CNS-RT, cancer type, type of CNS-RT (gamma knife [GKRS] versus whole brain radiation therapy [WBRT]), number of metastases, and maximum metastasis size. Results: We identified 213 cases of CNS-RT (NSCLC 167 [78%], GKRS 147 [69%], WBRT 63 [30%], median 2 BM [1 to > 20], median 17 mm max diameter [2 mm-74 mm]). Patients were 52% female with median age 61 (range 21-87), and ECOG 0-2 in 93% at time of CNS-RT. CNS-AEs occurred in 40 (19%) cases. Receipt of CPIs within 3 months of CNS-RT was the only factor associated with an increased risk of CNS-AEs (odds ratio 3.9, 95% CI 1.6-9.2, p-value 0.002). The rates of CNS-AEs were 11 of 28 (39%) in cases which received CPIs within 3 months of CNS-RT and 29 of 184 (16%) in cases which did not. The characteristics of the 11 cases with CPI exposure and CNS-AEs were: 73% underwent GKRS, 45% were NSCLC, 18% received CTLA4 alone, 55% PD-(L)1 alone, 27% combined CTLA4/PD-1, and 55% had a neuro deficit as part of their CNS-AE. Conclusions: This retrospective analysis demonstrates that the use of CPIs within 3 months of CNS-RT is associated with an increased risk of CNS-AEs. CNS-RT modality, cancer type, and metastasis size or number were not associated with an increased risk of CNS-AEs.
Opinions of palliative care physicians regarding renaming the specialty supportive care.
Authors: Anna Marie Sorensen, Kirsten Wentlandt, Monika K. Krzyzanowska, Gary Rodin, Lisa W Le, Camilla Zimmermann
Journal: Journal of Clinical Oncology (2016)

10126 Background: It has been suggested that the name “palliative care” poses a barrier to referral to palliative care, particularly early in the disease course. Although studies have reported that oncologists believe they would refer earlier to a service called “supportive care”, the opinions of palliative care physicians are unknown. We conducted a survey of Canadian palliative care physicians to solicit their opinions on this subject. Methods: Practicing palliative care physicians identified by the Canadian Society of Palliative Care Physicians were sent a survey by mail and email. Multivariate linear regression using stepwise selection was performed to determine factors associated with the degree to which physicians agreed with the statement “The specialty of palliative care should be renamed supportive care” (entry p ≤ 0.1). Results: The response rate for the survey was 71% (531/747). Forty percent (205/514) of physicians disagreed, 31.5% (162/514) were neutral, and 28.5% (147/514) agreed that the specialty of palliative care should be renamed supportive care. Further, 57.1% (301/527) agreed that patients have a negative perception of the term palliative care; 41.6% (220/528) agreed that patients would feel more comfortable with early referral if palliative care were renamed supportive care; and 37.5% (198/528) agreed that this would be the case for referring physicians. Physicians who agreed that palliative care should be renamed were more likely be older (p < 0.01), female (p < 0.01), to practice palliative care as a smaller proportion of their clinical time (p < 0.0001) and to agree that patients have a negative perception of the term palliative care (p < 0.0001). Conclusions: A substantial minority of practicing Canadian palliative care physicians believe that palliative care should be renamed supportive care. Rebranding and/or renaming of palliative care should be considered to encourage and destigmatize early referral.