tbuckley/cabot-search huggingface dataset:
Comorbidity in clinical trial patients with advanced or metastatic non-small cell lung cancer (NSCLC).
Authors: Maxim Kosov, Akhil Kumar, Maxim Belotserkovskiy
Journal: Journal of Clinical Oncology (2016)

e20606 Background: Co-morbid conditions can have an impact on the natural course of lung cancer, as well as on treatment efficacy and safety outcomes. It is important to understand the difference in co-morbidity between clinical trial patients and the general population in order to remain vigilant for an altered safety and efficacy in the post-approval setting. We did a retrospective review of the prevalence of co-morbidity in patients with advanced or metastatic NSCLC enrolled in clinical trials conducted by PSI-CRO over a decade. Methods: A retrospective review of the prevalence of co-morbidities in NSCLC patients enrolled in clinical trials conducted by PSI-CRO from 2005 to 2015 was done. A total of 8 clinical studies involving 1,355 patients were identified. Results: The median age was 60 years with 30% of patients being 65 or older. More than two-thirds (72%) were men. About one-fifth (19%) had ECOG PS of 0 with remaining four-fifths (81%) having PS of 1. Only a small subset (9%) did not have any co-morbid conditions while more than three-quarters (77%) presented with at least 2 comorbidities. The most common comorbidities were hypertension (41%), coronary artery disease (24%), and chronic obstructive pulmonary disease (COPD) (13%). Only 1.4% of patients had malignancies in the past, which could be explained by their routine exclusion from clinical trials. Also the prevalence of diabetes mellitus (2.7%) and neurologic diseases (4%) is noted to be small. Conclusions: The prevalence of hypertension and cardiovascular co-morbidity in patients with advanced or metastatic NSCLC enrolled in clinical trial is in line with that in general population. In contrast, the prevalence of COPD, diabetes, neurologic diseases, and previous malignancies was significantly lower. The differences in prevalence in some of the co-morbidities might be explained by the restrictive inclusion criteria as well as a resulting lower PS leading to ineligibility for clinical trials. Our findings suggest that with certain co-morbidities, difference exists between the general population and those enrolled in clinical trials. This may have a potential impact on post-approval drug efficacy and safety outcomes.
Serous ovarian and primary peritoneal cancers: A comparative analysis of clinico-pathological features, molecular subtypes and treatment outcome.
Authors: Bo Gao, Kristina Lindemann, Lyndal Anderson, Sian Fereday, Jillian Hung, Kathryn Alsop, Richard Tothill, Val Gebski, Catherine Kennedy, Rosemary L Balleine, Paul R. Harnett, David Bowtell, Anna deFazio
Journal: Journal of Clinical Oncology (2016)

5553 Background: Primary peritoneal cancer is rare and usually considered as a variant of advanced ovarian cancer, but questions remain concerning its underlying biology, prognosis and optimal management. Gene expression profiling in epithelia ovarian cancer has identified molecular subtypes with different survival and may improve our understanding of this disease. Methods: Clinico-pathological and treatment data on stage III/IV serous primary peritoneal (N = 112) and ovarian (N = 369) cancers were obtained from the Australian Ovarian Cancer Study (AOCS). Survival curves were plotted with the Kaplan-Meier method and the log rank test was used to compare survival. Cox proportional hazards models were fitted to obtain hazard ratios and 95% confidence intervals. Molecular subtype was determined by gene expression profiling on the Affymetrix U133 plus2 arrays (GSE9891). Results: Compared with advanced serous ovarian cancer, primary peritoneal cancer patients were older (mean age 65.5 vs. 60.2 years, p < 0.001), more often treated with neoadjuvant chemotherapy (38.4% vs. 11.4%, p < 0.001) and fewer patients were completed resected upfront (14.5% vs 23.2%, p = 0.109). They had significantly shorter progression-free (11.6 vs. 13.6 months, p = 0.007) and overall survival (31.7 vs. 39.8 months, p = 0.012). Multivariate analysis indicated residual disease and neoadjuvant chemotherapy were the main contributing factors to inferior survival. A higher proportion of advanced primary peritoneal tumors were classified as C1 (high stromal response) subtype (70.6% vs. 30.5%, p= 0.026). Patients with a C1 tumor subtype, regardless of their classification as primary peritoneal or ovarian cancer, had a much lower complete surgical debulking rate compared to the cohort of advanced stage serous cancer patients (5.4% and 23.1%). Conclusions: The inferior survival ofprimary peritoneal cancer patients may be attributable to the less favorable complete surgical resection rates and more frequent treatment with neoadjuvant chemotherapy. Different biology characterized by stroma fibrosis may cause these differences in treatment and clinical outcome.
Ten-year survival after randomized comparison of imatinib (IM) 400 mg vs. IM 800 mg vs. IM + IFN vs. IM + Ara C vs. IM after IFN in chronic myeloid leukemia (CML).
Authors: Ruediger Hehlmann, Michael Lauseker, Susanne Saussele, Markus Pfirrmann, Andreas Neubauer, Stefan W. Krause, Dieter K. Hossfeld, Christoph Nerl, Gabriela M. Baerlocher, Dominik Heim, Hans-Jochem Kolb, Ulrike Proetel, Katharina Kohlbrenner, Alois Gratwohl, Andreas Burchert, Astghik Voskanyan, Sebastien Ly Rinaldetti, Andreas Hochhaus, Joerg Hasford
Journal: Journal of Clinical Oncology (2017)

7049 Background: It is unclear whether IM 400 mg is the optimum choice for the successful treatment of CML. Treatment optimization was therefore attempted. Methods: From July 2002 to March 2012, 1551 newly diagnosed patients in chronic phase (CP) were randomized into a 5-arm study to analyze 2 IM doses and 3 combinations. 1536 patients were evaluable, 400 for IM 400 mg, 420 for IM 800 mg, 430 for IM + Interferon (IFN), 158 for IM + Ara C and 128 for IM after IFN. Recruitment to the latter two arms was stopped after a pilot phase. Results: 10-year overall survival (OS) of all patients was 82%, 10-year progression free survival (PFS) 80%. 10-year OS was 80% with IM 400 mg, 79% with IM 800 mg, 84% with IM + IFN, 84% with IM + Ara C and 79% with IM after IFN. The differences were not significant. 10-year PFS was 80% with IM 400mg, 77% with IM 800mg, 83% with IM + IFN, 82% with IM + Ara C and 75% with IM after IFN. The differences were not significant either. Survival with any treatment was not significantly different from IM 400mg at any risk level by any risk score (Euro Sokal, EUTOS, ELTS). 87 patients progressed to blast crisis (BC). The 10-year cumulative incidence of BC was 5.8% (95% CI: 4.7%; 7.1%) equally distributed across treatment arms. Most BC occurred in the first 2 years. Median survival after BC was 7.9 months across treatment arms. 275 patients have died, 23 after stem cell transplantation in first CP. Two thirds of deaths were unrelated to CML. Incidence of death due to CML by competing risk analysis with death unrelated to CML as competing risk was not different between the 5-treatment arms. 10-year relative survival probability was 92% when compared to matched general population data. Patients reaching the cytogenetic or molecular response landmarks according to European LeukemiaNet criteria ( &lt; 10% BCR-ABL IS at 3 months, &lt; 1% BCR-ABL IS or complete cytogenetic remission at 6 months, &lt; 0.1% BCR-ABL IS (MMR) at 12 months) had a significantly better survival than those not reaching the landmarks regardless of therapy. Conclusions: In conclusion, outcome of CML is currently more determined by prognostic markers than by choice of therapy. IM400 mg remains an excellent choice for initial therapy of CP-CML. Clinical trial information: NCT00055874.
Features associated with long-term survival in metastatic breast cancer.
Authors: Natalie Klar, Margaret Q. Rosenzweig, Brenda Diergaarde, Adam Brufsky
Journal: Journal of Clinical Oncology (2018)

e13074 Background: 5-10% of women with metastatic breast cancer (MBC) survive ≥5 years. Predictors of long-term survival are not clearly elucidated. We used data from 122 long-term MBC survivors (≥5-year survival from date of MBC dx) and 191 short-term MBC survivors (≤2-year survival from date from MBC dx) to identify clinico-pathologic and socioeconomic features associated with MBC survival. Methods: Women initially diagnosed with breast cancer (BC) in or after 1999, and diagnosed with MBC at Magee Women’s Cancer Program of UPMC were included (N = 313). Data abstracted from medical records included: stage at initial BC diagnosis, body mass index (BMI), Charlson Comorbidity Index (CCI), age, menopausal status, tumor receptor status at initial BC diagnosis, site of initial metastases, time between initial diagnosis and MBC, household income, race, employment status, and partner status. Differences between groups were assessed using t-tests and Chi-square or Fisher’s exact tests. Odds ratios and 95% confidence intervals were calculated using multivariate logistic regression models. Results: Long-term survivors were significantly (P < 0.05) younger, and had more ER positive, PR positive, and Her2 positive disease, lower CCI, lower rates of visceral metastases, higher household income, and positive partner status than short-term survivors. Long-term term survivors were also significantly more often diagnosed with de novo MBC compared to short-term survivors; less often with early-stage BC. The association with long-term survival remained significant after adjustment for age, tumor receptor status, and CCI, 3.0 (1.6-5.4). Time interval between initial diagnosis and MBC, BMI, menopausal status, race, and employment status were not associated with survival. Conclusions: Diagnosis of de novo MBC, ER- and/or Her2-positive primary tumor, higher household income, and having a partner are associated with long-term survival after diagnosis of MBC.
Is the Pediatric End-stage Liver Disease Score Truly a Detriment to Pediatric Liver Allocation?
Authors: Nadim Mahmud, Melissa M. Gadsden, David S. Goldberg
Journal: JAMA Pediatrics (2018)

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Abstract 15920: Atrial Fibrillation is Associated With Higher Rates of Dementia in Patients Anticoagulated With Warfarin
Authors: Kevin G Graves, Heidi T May, Victoria Jacobs, Tami L Bair, Brian G Crandall, Michael Cutler, Charles Mallender, Jeffrey S Osborn, J P Weiss, John D Day, T J Bunch
Journal: Circulation (2016)

Introduction: Patients with atrial fibrillation (AF) are at higher risk for developing dementia, particularly those exposed to broad fluctuations in anticoagulant therapy. Warfarin is a common ther...
Long-term cancer survivors: Satisfaction with medical care and information received during the diagnosis and treatment of cancer.
Authors: Alejandro Gallego, Beatriz Martinez, Enrique Espinosa, Ismael Ghanem, Leticia Ruiz-Gimenez, Tania Garcia, Teresa Gonzalez, Beatriz Castelo, Pilar Zamora, Andres Redondo, Jaime Feliu
Journal: Journal of Clinical Oncology (2017)

e21573 Background: Long-term survival rates for many types of cancer have substantially improved in past decades. A specific medical office was started up two years ago at our institution for the follow-up and comprehensive care of this population. Long-term cancer survivors were surveyed to know how they perceive medical care and information received during the diagnosis and treatment of cancer. Methods: A 54-item questionnaire was developed based on QLACS (Quality of Life in Adult Cancer Survivors). 286 patients completed the questionnaire from January 2015 to December 2016. All of them were disease-free and without any antitumour therapy for at least two years. The information was collected in a database and processed with SPSS 18. Results: Median age at the time of diagnosis was 56 years. Colorectal and breast carcinomas accounted for 54% of all cases and 61% of patients had been diagnosed in early stages of disease. Median time from cancer diagnosis to questionnaire completion was 104 months (range 29-444 months). Sixty-seven per cent of patients were satisfied with the information received by their oncologist about their cancer, although information provided about other health issues was less satisfactory. Twenty-eight per cent reported that the oncologist never made recommendations about healthy lifestyle. In fact, only 8 patients (2.8%) made dietary modifications, all regular alcohol drinkers (31.1%) maintained their daily intake and 73 patients (25.5%) gained 5 kg over their recommended weight. Anxiety/depression symptoms were reported by 30% of the best informed patients about cancer treatment and 52% of the worst informed. Only 12.4% of long-term cancer survivors of our study consulted their family doctor during the last year, while 75.4% visited their oncologist. Finally, the medical care of the oncologist was satisfactory for 235 patients (83.2%), receiving an overall score of 8.7 on a 0 to 10 scale. Conclusions: Most long-term cancer survivors feel satisfied with the medical care received, but the information provided about other health aspects should be improved. Furthermore, although they rely on their family doctors, most prefer being followed-up by their oncologist.
Survival outcomes of sustained MR4.5 in patients with chronic myeloid leukemia (CML) treated with various tyrosine kinase inhibitors (TKI).
Authors: Boyu Hu, Hagop M. Kantarjian, Farhad Ravandi, Gautam Borthakur, Tapan M. Kadia, Alessandra Ferrajoli, William G. Wierda, Guillermo Garcia-Manero, Naval Guastad Daver, Naveen Pemmaraju, Sara Dellasala, Sherry Pierce, Elias Jabbour, Jorge E. Cortes
Journal: Journal of Clinical Oncology (2016)

7057 Background: TKI discontinuation for CML pts may be considered for those who achieve the deepest molecular responses as qualified by MR4.5 and complete molecular response for ≥ 2 years (susMR4.5). We describe the cumulative incidence of susMR4.5, the long term impact of susMR4.5 and baseline characteristics of those pts. Methods: 522 pts treated with TKI in prospective clinical trials followed at our institution for ≥ 2 years between 2000 and 2015 were analyzed for time to susMR4.5, long term impact of susMR4.5 after achieving complete cytogenetic response for ≥ 2 years (susCCyR) as measured by event-free survival (EFS), transformation-free survival (TFS) and overall survival (OS), and their baseline characteristics. Results: Among pts analyzed, 65 (12%) were treated with Imatinib 400mg (IM400), 183 (35%) with Imatinib 800mg (IM800), 121 (23%) with Nilotinib (NILO), 113 (22%) with Dasatinib (DASA) and 40 (8%) with Ponatinib (PONA). After a median follow-up of 106.9 mo (range 17.0-177.9), 311 (60%) pts achieved susMR4.5 with a median time to susMR4.5 of 17.6 mo (range 2.7-107.8). The incidence of susMR4.5 for IM400, IM800, DASA, NILO and PONA was 25 (38%), 120 (66%), 73 (65%), 75 (62%) and 18 (45%), respectively. IM400 was statistically inferior to IM800, DASA and NILO at achieving susMR4.5 (p = < 0.001). In the 418 pts attaining susCCyR, there was no difference in EFS, TFS and OS between pts who also achieved susMR4.5 and pts with only MR4.5 (p = 0.369, p = 0.468, p = 0.129). There was improved EFS and TFS between susMR4.5 pts and pts who never reached MR4.5 (p = < 0.001, p = < 0.001) with a trend towards improved OS (p = 0.08). Older age corresponds to susMR4.5 (p = 0.003) while other baseline characteristics such as race, sex, Sokal score and initial stage at diagnosis had no correlation. Conclusions: In pts who achieve susCCyR, attaining susMR4.5 and MR4.5 had equal long term outcomes, but not achieving MR4.5 was worse for EFS and TFS with a trend towards worse OS. Attaining susMR4.5 depended on initial frontline TKI choice as higher potency TKIs (IM800, DASA and NILO) was superior to IM400. Older age was the only predictive baseline characteristic for pts achieving susMR4.5.
Abstract 19005: Identifying the Focal Points of Cardiac Research From Publication Records
Authors: Maggie P Lam, Vidya Venkatraman, Tevfik U Dincer, Edward Lau, Jennifer E Van Eyk, Peipei Ping
Journal: Circulation (2015)

Introduction: The human heart expresses ~10,000 genes, but only a subset is most relevant to cardiac disease and medicine. To maximize the impact of new technological developments to cardiac research, it is imperative that valuable resources be allocated such that genes that are most relevant to the cardiac community are prioritized, e.g., to ensure high-quality research reagents on these genes are available and to promote biocuration efforts to annotate their functions. Hypothesis: A relatively small number of genes concern the majority of cardiac research efforts, and can be identified from the analysis of publicly available literature records. Method: We developed a novel data science method to analyze over one million peer-reviewed cardiac-related publications and the cardiac genes referenced to these articles. We then derived a metric to measure gene importance to cardiac research based on the normalized semantic distance between the gene and articles on various cardiac diseases to which it is referenced. The cardiac genes with the least semantic distance to cardiac publications were retrieved. Results: We identified 50 of the most highly investigated genes in the heart, accounting for ~15% of all cardiac research, and constructed gene networks from their publication records and functional annotations. The analysis also allowed us to visualize several major clusters of cardiac research focuses, surrounding the contractile machinery, ion channels, BNP signaling, and PKA signaling. In addition, we identified ~50 proximal genes which are functionally related to critical cardiac processes but currently under-studied, and which we predict will become important research targets in the near future. Conclusion: We demonstrate here a big data-driven approach to catalogue and predict the focus and trend of cardiac research.
OS5.1 Molecular subgroups of low- and high-grade gliomas diagnosed in the first year of life
Authors: A Guerreiro Stücklin, S Ryall, K Fukuoka, M Zapotocky, A Lassaletta, A Arnoldo, Y Zhong, P Kowalski, C Li, M Grotzer, M Taylor, U Tabori, C Hawkins
Journal: Neuro-Oncology (2018)

CNS tumours are the most common malignancies in infants. The majority of tumours diagnosed in the first year of life are gliomas. Though considered benign, low-grade gliomas (LGG) diagnosed in infancy have a worse outcome, whereas high-grade gliomas (HGG) have a better outcome than their counterparts in older children. We sought to determine the genetic drivers and clinical factors that impact outcome of this understudied patient population. Multi-institutional retrospective study of patients diagnosed with gliomas (WHO I-IV) in the first year of life. Clinical information and samples were collected for 171 patients diagnosed between 1985 and 2017. Histopathology was centrally reviewed and whenever sufficient tissue was available DNA and RNA extracted for molecular studies. Tier 1 of molecular studies consisted of clinically available tools, including a Nanostring panel detecting known glioma-associated fusions and ddPCR for BRAFV600E and H3K27M. Selected negative cases were then further profiled in tier 2 by RNA sequencing, SNP array and/or methylation array. Novel oncofusions were further validated. Ten-year overall survival for LGG and HGG in the entire cohort was 77% and 35%, respectively. Midline diencephalic tumours were predominantly low-grade (optic pathway gliomas, OPG), comprising 98% of all diencephalic tumours and 47% of all LGG. Molecular analysis of OPG revealed high frequency of BRAF alterations, with 44% carrying a BRAFV600E mutation and 36% a BRAF-KIAA1549 fusion. OPG were associated with a markedly worse outcome when compared with LGGs at other locations (10-year overall survival of 63% vs 92%), suggesting that these patients respond poorly to conventional treatment and should be prioritized for targeted therapies. Strikingly, hemispheric tumours (35% of all LGG and 82.4% of all LGG and HGG, respectively) were found to have recurrent alterations shared between LGG and HGG, most notably novel gene fusions involving the ALK oncogene. Additionally, NTRK, FGFR, MET and novel fusions involving ROS1 were found predominantly in hemispheric tumours, particularly in HGG. iNHA cells transduced with CCDC88A-ALK fusion and implanted intracranially in NSG mice were tumorigenic in vivo with a short latency and 100% penetrance. Gliomas in infants have a distinct molecular profile and clinical course. Whereas diencephalic tumours are predominantly low-grade and driven by BRAF alterations, recurrent alterations involving NTRK/ALK/ROS1, FGFR and MET are found in HGG and a subset of these alterations are shared with LGG hemispheric tumours. Our study characterizes a critically understudied patient population and reveals a high frequency of targetable alterations, supporting routine molecular studies and the use of targeted inhibitors in future clinical trials.