tbuckley/cabot-search huggingface dataset:
Outcomes in pediatric CML in a developing country: Beyond the disease biology.
Authors: Ranga Raman Ganta, Sadashivudu Gundeti, Srividya Nasaka, Vijay Gandhi Linga, Ravi Sankar Arigela, Rajesh Kota, Krishnamani Iyer Kalpathi, Muralidhar Gullipalli, Ashok Kumar Pillai, Ramu Kandula, Joseph Stalin Bala, Lakshmi S. Maddali, Raghunadharao Digumarti
Journal: Journal of Clinical Oncology (2014)

e21005 Background: About 25% of adult patients on Imatinib for chronic myeloid leukemia (CML) did not take the drug as prescribed, and ended up taking less than 90% of their doses. This had an adverse effect on their cytogenetic and molecular responses, and might ultimately affect long-term outcomes according to Smith et al in 2010. CML in children is rare and accounts for only 5% of all leukemias. Data on Imatinib compliance and outcomes is scarce in this age. We attempted to correlate the compliance and outcome data in our pediatric CML patients. Methods: Hospital records of pediatric CML patients (age ≤18 years) from January 2010 to December 2012, were retrospectively analyzed for drug compliance, possible reasons for noncompliance and cytogenetic responses (CyR) at 6 months. All children received free Imatinib under an international patient assistance program (GIPAP). Compliance was defined as ≥ 90% adherence to specified treatment duration. Results: Out of sixty children, 12 were excluded (No compliance data for 4 and no response evaluation in 8 children). The median age was 14.5 years (range 5-18) with a male preponderance (M:F- 1.85:1). Sokal scores were low, intermediate and high in 29%, 55%, 16% children respectively. Only 58% of children were compliant. At the end of 6 months, complete cytogenetic response (CCyR) was achieved in 78.5% of compliant as compared to only 5% among the non compliant children. Majority of the noncompliant children had only a partial response (80%), while 15% had nil cytogenetic response. Reasons for non compliance were financial constraints to even come to the hospital [36%], ignorance of the parents [24%], intolerance to Imatinib [15%], false sense of well being after partial treatment [10%], and unknown reasons [15%]. Conclusions: Majority of the noncompliant children had only partial cytogenetic response at the end of six months. We conclude that compliance is a major modifiable factor influencing the outcome in pediatric CML patients in developing countries like India. A little extra effort from the health care provider and parents can successfully overcome this often neglected factor. Outcome Compliant n=28 Noncompliant n=20 P value CCyR 22 1 <0.0001 PCyR 4 16 <0.0001 NilCyR 0 3 0.08 PD 2 [ T351I +ve] 0 0.33
The NeuroDev Study: Phenotypic and Genetic Characterization of Neurodevelopmental Disorders in Kenya and South Africa
Authors: Victoria de Menil, Michelle Hoogenhout, Patricia Kipkemoi, Dorcas Kamuya, Emma Eastman, Alice Galvin, Katini Mwangasha, Jantina de Vries, Symon M. Kariuki, Serini Murugasen, Paul Mwangi, Ilina Singh, Dan J. Stein, Amina Abubakar, Charles R. Newton, Kirsten A. Donald, Elise Robinson
Journal: Neuron (2019)
Impact of the analysis of retrospective data in cervical tumors in South America.
Authors: Angel Gabriel D'Annunzio, Cecilia Heredia, Raul Sanchez, Matias Chacon, Federico Esteso, Victoria Costanzo, Jose Carmona, Nestor Tappari, Marcos Ortiz, Walter Cattaneo
Journal: Journal of Clinical Oncology (2014)

e17526 Background: Cervical cancer is one of the most damaging tumors in some regions of SouthAmerica. Standard treatment according NCCN and ESMO for locally advanced disease is concurrent radiation and platinum based chemo regimen. Cultural and logistics issues have been described as barriers to optimize treatment delivery. Objectives: To review retrospective data of consecutive cervical cancer patients in a single central hospital of an extensive area in the north of Argentina and to identify potential deficits in the treatment that impact in outcome of patients. Methods: data from consecutive patients with histologic diagnosis of cervical carcinoma were analyzed. A single public institution was involved in the treatment of a heterogeneous group of patients in terms of education level, distance to hospital and possibility to stay in the city for the radiation treatment. Weekly cisplatinum and concurrent radiation therapy and sequential brachytherapy were planned. Demographics, stage and treatment were analyzed trying to focus in the time delayed between initial diagnosis, external radiation and brachytherapy. Results: between February 2011 and December 2013, 72 female patients were included. Median age was 49 years old (27-80). Stage IIB and IIIB were 57% and 26% respectively. Median time from diagnosis to start radiation was 140 days (20-951). All the patients received concurrent cisplatinum and radiation without significant interruption. The median delayed from the end of external radiation and the start of brachytherapy was 14.7 weeks (1.3-96). Local recurrence was observed in 19 (33%) of 57 evaluable patients. Thirty four patients (48%) were treated during 2013. Multiple factors (social, logistics, distance) were involved in the inappropriate timing of treatment, and threaten the chances of cure. Conclusions: This retrospective analysis of cervical cancer in an epidemic region of the country showed the great delayed between initial diagnosis and the treatment has a relevant impact in the outcome of this population. This data modifies the current approach to cervical cancer moving to more education, prevention and to improve logistics in terms of radiation delivery.
In vitro chemoresponse in metachronous pairs of ovarian cancers.
Authors: Heather J. Dalton, James Fiorica, Robert P. Edwards, Ivor Benjamin, Rodney Paul Rocconi, Fernando O Recio, John L. Lovecchio, Matthew O. Burrell, Mark S. Shahin, Edward C. Grendys, Dakun Wang, Tianhua Wang, Bradley J. Monk
Journal: Journal of Clinical Oncology (2014)

e16520 Background: Intrinsic or acquired resistance to first-line platinum/taxane therapy remains a challenge in treating epithelial ovarian cancer (EOC). A chemoresponse assay has demonstrated clinical potential to aid effective therapy selection in both primary and recurrent EOC. This study explores potential changes in chemoresponse between primary and recurrent tumors and further explores clinical application of the assay. Methods: 242 EOC patients with chemoresponse testing of paired primary and recurrent tumors against up to 7 common EOC therapies, including first-line (carboplatin, cisplatin, paclitaxel, docetaxel) and recurrent (doxorubicin, gemcitabine, topotecan) therapies, were examined in the study. An increase in the chemoresponse assay area under the dose response curve (AUC) indicates an increase in resistance. Change in AUC between primary and recurrent tumors was assessed by paired t-test. Results: A significant increase in AUC from primary to recurrent was identified in 3 of 4 commonly utilized first-line therapies [cisplatin (p=0.012), paclitaxel (p<0.001), docetaxel (p<0.001)] and trended for carboplatin (p=0.105), while no significant difference was observed in 2 of 3 recurrent therapies [gemcitabine (p=0.946) and topotecan (p=0.770)]. Further, when time elapsed between occurences was <17 months (median PFS for EOC), no difference was observed for any recurrent therapies, and a significant increase in AUC was observed in only 2 of the 4 first-line therapies. Comparatively, when ≥17 months, all 7 therapies showed a significant increase. Conclusions: Results from a chemoresponse assay suggest a general increase in resistance to chemotherapy between primary and recurrent EOC tumors, which is more pronounced for first-line therapies and with increased time elapsed between occurrences. The results reported herein suggest that chemoresponse assay results are likely most applicable when the tumor sample is obtained just prior to the chemotherapy administration for which the assay results are being considered. However, if a tumor sample is unobtainable at recurrence, assay results obtained within the prior 17 months may provide utility in therapy selection, particularly for therapies not previously administered.
Long-term follow-up of the CESS 81 and CESS 86 Ewing sarcoma trials.
Authors: Herbert Juergens, Christiane Hoffmann, Uta Dirksen, Michael Paulussen, Andreas Ranft
Journal: Journal of Clinical Oncology (2014)

10529 Background: Since 1980 patients with Ewing sarcoma have been treated according to consecutive protocols (CESS) of the German Society of Pediatric Oncology and Hematology (GPOH)(supported by Deutsche Krebshilfe). Post treatment surveillance also includes long term follow-up (supported by BMBF/DLR 01ER0807). The observation time now covers a period of more than 30 years. Methods: 673 patients (pts) entered into the CESS 81 (n=183) (1980-1985) and CESS 86 (n=490) (1985-1992) Ewing sarcoma trials were analyzed. 375 pts (59%) were male, 278 (41%) female. 549 pts (82 %) had localized, 124 (18%) metastatic disease. Primary tumor location was lower extremity in 37%, pelvis in 26%, other axial sites in 29%, and upper extremity in 8%. The median age at diagnosis was 14.8 years (range 0.7 - 41.4). The median age of survivors at last time of observation was 28.9 years (range 8.8 - 63.3). Median follow-up time of survivors was 15.5 years (range 0.3 - 30.6). Data were retrospectively analyzed with descriptive statistics and survival analyses, and complemented by questionnaire information. Results: 315 pts (47%) were alive at last follow-up, 358 pts (53%) have died. The cause of death was DOD in 318 pts (89%), DOC in 31 pts (9%), and death of other cause in 9 pts (2%). Events were observed in 361 pts: local relapse in 19%, distant relapse in 64%, combined relapse in 13%, and secondary malignancies in 4%. Self-reported late morbidity was available from 128 of 315 survivors: 19.5% cardiac and 6.2% renal abnormalities. In 5 pts (3.9%) secondary amputation was reported. The analysis of late functional outcome is ongoing. 10-year event-free survival (EFS) was 0.49 (SE=0.02) in localized, and 0.21 (SE=0.04) in metastatic disease. 10-year overall survival (OS) was 0.54 (SE=0.02) in localized, and 0.23 (SE=0.04) in metastatic disease. Conclusions: Long-term observation is crucial in pediatric cancer survivors. Nearly half of patients of the earliest phase III Ewing sarcoma trials are long-term survivors. Approx. 90% of patients with recurrence died from disease. Patient-related outcome scores are currently investigated in a long-term observation study for inclusion into long-term follow-up guidelines and to better predict the long-term quality of survivorness.
Association of high volume center with survival for glioblastoma patients: Results from a prospective population-based registry (PERNO).
Authors: Alba Ariela Brandes, Enrico Franceschi, Alicia Tosoni, Luigi Cavanna, Maria Michiara, Anna Pisanello, Roberta Depenni, Benedetta Urbini, Marina Faedi, Norina Marcello, Claudio Dazzi, Antonella Valentini, Roberto D'Alessandro, Giovanni Frezza, Federica Bertolini, Stefania Bartolini, Silvio Cavuto, Mario Ermani, Agostino Baruzzi
Journal: Journal of Clinical Oncology (2014)

2048 Background: The Project of Emilia Romagna in Neuro-Oncology (PERNO) is a prospective registry and it was created to evaluate the incidence and treatment of primary brain tumors (PBTs) in this italian region. In this network, as a subproject, a population-based prospective study was conducted to assess the survival outcome of glioblastoma (GBM) patients, and correlations with potential prognostic factors. Methods: Based on the data from this registry, from January 1st 2009 to December 31st 2010, a prospective study was made of the treatment efficacy and outcome in newly diagnosed GBM patients £70 years treated with the worldwide accepted standard treatment according to the EORTC 22981/26981) /NCIC CE.3 trial (temozolomide concomitant with and adjuvant to radiotherapy - RT/TMZ). Results: 267 GBM patients were enrolled, 139 patients were £70 years and received RT/TMZ, achieving a median overall survival (OS) of 16.4 months (95%CI: 14.0–18.5). At multivariate analysis, OS was significantly correlated with KPS (HR=0.458, 95%CI: 0.248-0.847, p=0.0127), MGMT methylation status (HR=0.612, 95%CI: 0.388-0.966, p=0.0350) and if treatment was received in the high volume center (HR=0.569, 95%CI: 0.328-0.986, p=0.0446). Median overall survival was 24.1 months for patients treated in the referral high volume center and 15.9 months in other centers (HR: 0.533, 95% CI: 0.328 – 0.866, p=0.0110), with no significant differences in KPS and MGMT methylation status among the centers. Conclusions: For the first time in the field of neuro-oncology, we have investigated the impact of center volume and expertise in post-surgical treatment, as a variable that may influence the outcome of GBM patients < 70 years and treated with RT/TMZ. Our findings may have depended on several factors, such as expertise in neuroradiology interpretation as well as the management of adverse events, and the use of third line treatments or the best supportive care. The amount of OS improvement supports further investigation of center volume and expertise as a prognostic factor.
Dynamic Personalized Assessment of Outcome in Patients with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia
Authors: Koji Sasaki, Elias J. Jabbour, Farhad Ravandi, Nicholas J Short, Guillermo Garcia-Manero, Naval G. Daver, Tapan M. Kadia, Marina Y. Konopleva, Nitin Jain, Ghayas C. Issa, Victoria Jeanis, Joie Alvarez, Maria Khouri, Patrice Nasnas, Rebecca E. Garris, William G. Wierda, Philip A. Thompson, Naveen Pemmaraju, Jorge E. Cortes, Susan M. O'Brien, Hagop M. Kantarjian
Journal: Blood (2018)
A Phase 1 Study of Two Investigational Agents, ACTR087, an Autologous T Cell Product Expressing an Antibody-Coupled T Cell Receptor, in Combination with SEA-BCMA, a Novel Non-Fucosylated Monoclonal Antibody, in Subjects with Relapsed or Refractory Multiple Myeloma
Authors: Don M. Benson, Houston Holmes, Parameswaran Hari, Jessica Sachs, Ben Exter, Ann Ranger, Tooba Cheema, Iga Sienczylo, Megan M. O'Meara, Django Sussman, Luke P. Akard
Journal: Blood (2018)
Abstract 14848: Meta-analysis of the Effects of Carvedilol vs Metoprolol on All-cause Mortality and Hospitalizations in Patients With Heart Failure
Authors: Alexandros Briasoulis, Sagar Mallikethi-Reddy, Shikha Sharma, Rajeev Sudhakar, Luis Afonso
Journal: Circulation (2015)

Introduction: Long-term treatment with appropriate doses of carvedilol or metoprolol is currently recommended for patients with Heart Failure with reduced Ejection Fraction (HFrEF) to decrease the risk of death, hospitalizations and patients’ symptoms. It remains unclear if the b-blockers used in HFrEF patients are equal or carvedilol is superior to metoprolol types. Methods: We performed a meta-analysis of the comparative effects of carvedilol vs metoprolol tartrate and succinate on all-cause mortality or/and hospitalization. We conducted an EMBASE and MEDLINE search for prospective controlled trials and cohort studies of patients with HFrEF who were received to treatment with carvedilol vs. metoprolol. Results: We identified 4 prospective controlled and 6 cohort studies with 30943 that received carvedilol and 69925 patients on metoprolol types (tartrate and succinate) with an average follow up duration of 36.4 months. All-cause mortality was reduced in prospective studies with carvdedilol vs metoprolol tartrate. Neither all-cause mortality nor hospitalizations were significantly different between carvedilol and metoprolol succinate in the cohort studies. Conclusion: In patients with HFrEF carvedilol and metoprolol succinate have similar effectiveness in reducing all-cause mortality.
<i>KRAS</i> screening for clinically important mutants via a multiplex allele-specific PCR assay for exons 2, 3, and 4.
Authors: Garrett Larson, Craig Stephens, Stephanie H. Astrow, Jack Hsiang, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2014)

e14569 Background: The selection of chemotherapies is guided by the analysis of molecular targets in solid tumors for well-known somatic mutations identified in microdissected formalin-fixed and paraffin embedded tissue. In colon and lung cancers, the identification of tumor-associated RAS activating mutations is used to determine anti-EGFR therapeutic eligibility. Historically patients possessing KRAS exon 2 mutations (codons 12/13) show poor clinical response to anti-EGFR therapies such as cetuximab and panitumumab. The identification of new tumor-associated mutations in codons 61, 117 and 146 result in increased levels of guanosine triphosphate-bound RAS proteins and also predict anti-EGFR resistance. A study by Douillard, et al. (NEJM 369:1023) has linked these newly classified mutations with clinical outcomes and The European Medicines Agency supports the addition of these clinically important mutants in any comprehensive KRAS screening strategy prior to administration of tyrosine kinase inhibitors (TKI). Methods: We have expanded our existing KRAS mutation assay by utilizing multiplex ARMS chemistries which now permits the screening of these additional mutations with minimal sample consumption. This assay represents a significant improvement over existing commercial assays which only identify mutations in codons 12 and 13. Results: An analysis of specimens previously reported as wild type based on exon 2 KRAS coverage identified approximately 15% of these samples harbored Exon 3 and 4 mutations based on the expanded coverage assay. Conclusions: These mutations in codons 61 (6/10 mutations) and 146 (4/10 mutations) were identified in tumor specimens and were verified by Sanger sequencing, confirming that the expanded assay identifies additional patients who are unlikely to respond to EGFR-targeted therapies in colon cancer.
MGP Interacts with BMP-4 and BMP-2 and Supports Normal and Malignant Hematopoietic Stem/Progenitor Cells
Authors: Aya Yokoi, Kana Kuronuma, Tomoya Fukuoka, Chie Goto, Miki Matsuo, Eri Adachi, Naoko Okada, Hikaru Tsutsumi, Mirano Kajitani, Natsumi Hasegawa, Shigetaka Asano, Mitsuhiro Ito
Journal: Blood (2018)
Genomic Biomarkers Predict Response/Resistance to Lenalidomide in Non-Del(5q) Myelodysplastic Syndromes
Authors: Yazan F. Madanat, Mikkael A. Sekeres, Sudipto Mukherjee, Cassandra M. Hirsch, Yihong Guan, Yasunobu Nagata, Vera Adema, Metis Hasipek, Aaron T. Gerds, Hetty E. Carraway, Anjali S. Advani, Bartlomiej P. Przychodzen, Valeria Santini, Jaroslaw P. Maciejewski, Babal K. Jha, Aziz Nazha
Journal: Blood (2018)
Oxidized Mitochondrial DNA Is a Catalyst and Biomarker of Pyroptotic Cell Death in Myelodysplastic Syndromes
Authors: Grace A Ward, Kathy L McGraw, Amy F McLemore, Farnoosh Abbas-Aghababazadeh, Hsin-An Hou, Thu Le Trinh, Nicole D. Vincelette, Benjamin S. Meyer, Alexis H Onimus, Alexandra Calescibetta, Erika A Eksioglu, Sheng Wei, Alan F. List
Journal: Blood (2018)
Impact of underestimation of risk on treatment duration and recurrence in GIST patients.
Authors: Annie Guérin, Anthony Paul Conley, Medha Sasane, Alexander R. Macalalad, Qing Huang, Frances Annelies Schwiep, Christopher Hunt Keir, Eric Qiong Wu
Journal: Journal of Clinical Oncology (2014)

10545 Background: Adjuvant imatinib therapy has been shown to reduce risk of recurrence and improve survival in gastrointestinal stromal tumor (GIST) patients (pts) who had complete tumor resection. Though different tools are available, the revised NIH criteria are most widely used to assess recurrence risk and help determine treatment duration. This study analyzed the impact of risk under-estimation on under-treatment and recurrence in GIST pts. Methods: An online questionnaire was used to collect chart data on 506 pts with primary resectable KIT+ GIST from 109 US oncologists. By comparing the risk of recurrence evaluated by NIH criteria based on primary tumor characteristics vs. physicians’ assessment noted in pts’ charts, pts’ recurrence risks were categorized as underestimated, consistent, or overestimated. Under-treatment was defined for high risk pts as <36 months of planned adjuvant imatinib therapy (NCCN Guidelines). The impact of underestimated risk on under-treatment and recurrence were analyzed using GEE logistic and Cox proportional hazard regression models, adjusting for potential confounding factors. Results: Risk of recurrence was underestimated in 37.5% of pts (53.4% consistent; 9.1% over-estimated). Among the 65.8% of pts who were at high risk (NIH criteria), 50.8% had their risk underestimated. Pts with intermediate tumor size, intermediate mitotic count, and non-gastric primary tumor were the most likely to have their risk underestimated; 46.8% of underestimated pts had a tumor >5-10cm, 64.7% had a mitotic count 6-10/50 HPF, and 70.0% had non-gastric tumor. High risk pts who had their risk underestimated (vs. not underestimated) were more likely to be under-treated (OR=2.26, p=.001). Among all GIST pts, those with underestimated risk (vs. not underestimated) had a significantly higher hazard of recurrence (hazard ratio=1.81, p=.028). Conclusions: Underestimation was found to lead to under-treatment in high risk pts and an overall higher risk of recurrence. Given the high proportion of pts with underestimated risk, these findings suggest that with more consistent and systematic approaches to assess risk, overall recurrence-free survival could be improved in GIST patients.
A Phase I/II, Open-Label, Multicentre 2-Part Study to Assess the Safety, Tolerability, Pharmacokinetics, and Efficacy of AZD2811 Nanoparticle As Monotherapy or in Combination in Treatment-Naïve or Relapsed/Refractory Acute Myeloid Leukaemia/Myelodysplastic Syndrome Patients Not Eligible for Intensive Induction Therapy
Authors: William B. Donnellan, Ehab L. Atallah, Adam S. Asch, Manish R Patel, Julie Charlton, Alexander MacDonald, Elena Young, Elizabeth Sainsbury, Donald Strickland, Suzanne Jones, Philip Overend, Carrie A. Adelman, Jon Travers, Simon Smith, J. Elizabeth Pease, Wolfram Brugger
Journal: Blood (2018)