tbuckley/cabot-search huggingface dataset:
Efficacy and safety of methadone in the treatment of pain in palliative care patients with cancer: The EQUIMETH2 national, randomized, open, phase III study.
Authors: Philippe Poulain, Marie Pierre Berleur, Shimsi Lefki, Daniele Lefebvre Kunt, Eric Serra, Gisele Chvetzoff, Alain Derniaux, Flora Tremellat, Marilène Filbet, Anna Simon, Bich Dang Vu, Cyril Guillaume
Journal: Journal of Clinical Oncology (2016)

212 Background: Methadone is used more and more as a second-line treatment for refractory cancer pain in palliative care patients. Methods: The study aimed to compare the effect of two methadone titration methods (Stop and Go vs progressive titration) in 146 palliative care cancer patients with pain inadequately relieved or intolerant to level 3 opioids. The primary endpoint was the rate of success/failure at Day 4 defined by pain relief (reduction of at least two points of the numerical scale (0 - 10) AND a pain score &lt; 5 for 2 consecutive days) AND no overdose (Rudkin scale ≥ 3 AND respiratory rate &lt; 8/min). Results: Pain was nociceptive in 16% and mixed in 84%. 85% of the patients had breakthrough pain. Half received oxycodone, 1/5 fentanyl, 1/5 morphine and &lt; 10% hydromorphone. Reasons for switching were lack of efficacy isolated (56%), or with intolerance to previous opioid (38%). More than 2/3 of the patients reached a pain score &lt; 5 for two days at D4, adequate pain relief was obtained in 80% of the patients (median of 3 days in both groups (p = 0.12)) and lasted until D56. The rate of success/failure was about 40% at D4 with no difference between the two methods. Overdoses defined as respiratory rate &lt; 8/min were observed in 13.2% patients throughout the study with no difference between groups. 9 required naloxone. The two methods were equally considered easy by about 60% of the clinicians. Conclusions: Methadone is an effective and sustainable second-line alternative opioid in the treatment of cancer pain in palliative care patients inadequately relieved or intolerant to level 3 opioids. The two methods of titration of methadone are comparable in terms of efficacy, safety and ease of use.
OTX2 Activity at Distal Regulatory Elements Shapes the Chromatin Landscape of Group 3 Medulloblastoma
Authors: Gaylor Boulay, Mary E. Awad, Nicolo Riggi, Tenley C. Archer, Sowmya Iyer, Wannaporn E. Boonseng, Nikki E. Rossetti, Beverly Naigles, Shruthi Rengarajan, Angela Volorio, James C. Kim, Jill P. Mesirov, Pablo Tamayo, Scott L. Pomeroy, Martin J. Aryee, Miguel N. Rivera
Journal: Cancer Discovery (2017)

Medulloblastoma is the most frequent malignant pediatric brain tumor and is divided into at least four subgroups known as WNT, SHH, Group 3, and Group 4. Here, we characterized gene regulation mechanisms in the most aggressive subtype, Group 3 tumors, through genome-wide chromatin and expression profiling. Our results show that most active distal sites in these tumors are occupied by the transcription factor OTX2. Highly active OTX2-bound enhancers are often arranged as clusters of adjacent peaks and are also bound by the transcription factor NEUROD1. These sites are responsive to OTX2 and NEUROD1 knockdown and could also be generated de novo upon ectopic OTX2 expression in primary cells, showing that OTX2 cooperates with NEUROD1 and plays a major role in maintaining and possibly establishing regulatory elements as a pioneer factor. Among OTX2 target genes, we identified the kinase NEK2, whose knockdown and pharmacologic inhibition decreased cell viability. Our studies thus show that OTX2 controls the regulatory landscape of Group 3 medulloblastoma through cooperative activity at enhancer elements and contributes to the expression of critical target genes.Significance: The gene regulation mechanisms that drive medulloblastoma are not well understood. Using chromatin profiling, we find that the transcription factor OTX2 acts as a pioneer factor and, in cooperation with NEUROD1, controls the Group 3 medulloblastoma active enhancer landscape. OTX2 itself or its target genes, including the mitotic kinase NEK2, represent attractive targets for future therapies. Cancer Discov; 7(3); 288-301. ©2017 AACR.This article is highlighted in the In This Issue feature, p. 235.
P08.49 The value of neurocognitive testing in multimodal response assessment in patients with glioblastoma multiforme
Authors: A. Tinchon, B. Calabek, B. Andreas, U. Riedlberger, G. Minear, B. Reinhard, G. Liegl, E. Freydl, F. Marhold, S. Oberndorfer
Journal: Neuro-Oncology (2016)

approximately 15 months following standard of care therapy.However, 10 % survival at 5 years was observed in a randomized phase III study.At GBM recurrence, the addition of bevacizumab (BEV), a humanized monoclonal antibody against circulating vascular endothelial growth factor (VEGF), resulted in a 3-4 month prolongation of progression-free survival (PFS) without improving overall survival (OS).A 45-year-old female who underwent surgery for left fronto-temporal WHO grade II astrocytoma associated with epilepsy in 2005, 125I seed implantation at disease progression in 2009 and seed explantation 9 months later, was diagnosed with MGMT methylated GBM on the occasion of partial tumor resection in 2010 followed by radiotherapy plus concomitant and adjuvant temozolomide (TMZ) chemotherapy, which was stopped after 4 months due to resection of a left temporal tumor cyst and recurrent cyst within 1 month.TMZ treatment causing prolonged thrombocytopenia was discontinued after 1 additional cycle.Immediately after this cycle, the patient experienced left median cerebral artery stroke resulting in right hemianopia, Broca's aphasia and severe hemiparesis of the right side.Three months later, BEV 10 mg/kg i.v.q14d was initiated, shortly interrupted for abdominal herniotomy in 2012, and continued for 3 years.Since 2014, concurrent low molecular weight heparin was given because of right lower limb deep venous thrombosis suspicion.Whereas GBM progression had not been detected for 2 years during anti-VEGF therapy, methionine PET MRI 6 months after BEV discontinuation revealed left temporal tumor recurrence.Rechallenge with BEV was initiated and the patient remained in stable clinical and radiographical condition for 10 months until now.This case highlights the utility of sequential BEV treatment in a patient being at high risk to develop chemotherapy-induced myelotoxicity.Long-term survival (> 3 years after diagnosis) in GBM has been attributed to patient-derived rather than tumor-derived factors.To our knowledge, this is the first description of effective long-term monotherapy with BEV for GBM and ongoing therapeutic response to single-agent BEV rechallenge in a patient with recurrent secondary GBM.
CBIO-22. SELECTIVE INHIBITION OF HDAC6 AFFECTS CILIOGENESIS AND PREVENTS GLIOBLASTOMA GROWTH
Authors: Lan Hoang-Minh, Loic Deleyrolle, Nariaki Nakamura, Brent Reynolds, Matthew Sarkisian
Journal: Neuro-Oncology (2016)

Histone deacetylases (HDACs) are critical regulators of gene expression and have been exploited in the treatment of cancers; however, pan-HDAC inhibitors can lead to off-target effects and toxicity. HDAC6-selective inhibitors have recently garnered interest as they alter the acetylation of non-histone regulatory proteins implicated in tumor-related processes. One critical function of HDAC6 is to regulate cell cycle progression by triggering the retraction of cells’ primary cilium before entering mitosis. We previously reported that cilia are routinely detected in GBM biopsies and that the majority of GBM patient-derived cells can give rise to ciliated progeny. Our preliminary data suggest that cilia persist in all phases of the cell cycle except mitosis. Since recent reports suggest HDAC6 is often overexpressed in GBM biopsies, we hypothesized that inhibiting HDAC6 will slow GBM growth by disrupting ciliogenesis. OBJECTIVE: To determine the relationship between HDAC6, primary cilia, and GBM cell proliferation. We treated patient GBM-derived cells with vehicle or ACY-1215, a selective HDAC6 inhibitor, and measured cell viability, cell cycle phase distribution, ciliogenesis, and proliferative abilities of control and KIF3A (an essential regulator of ciliogenesis)/cilia-depleted GBM cell lines. HDAC6 was expressed in both patient cell lines that we examined. ACY-1215 treatment significantly reduced GBM cell proliferation, increased the number of cells in the G2/M phases, decreased cell viability in a dose-dependent manner (IC50 ~500nM), and increased apoptotic cell death. Surprisingly, ACY-1215 exposure significantly decreased or increased the percentage of ciliated GBM cells, depending on the cell line and time point analyzed post treatment. Notably, ACY-1215 did not affect the viability of GBM cells that lack cilia following the knockout of KIF3A. Selective HDAC6 inhibition slows GBM growth by affecting cell cycle progression and cell survival in a KIF3A/cilia-dependent manner. Future studies will focus on elucidating the molecular mechanisms underlying these effects.
RTHP-07. IMPACT OF RADIOTHERAPY AND GROSS-TOTAL RESECTION FOR EPENDYMOMA IN YOUNG CHILDREN: A POPULATION-BASED STUDY
Authors: Christina Snider, Kailin Yang, Stephen Mack, John Suh, Samuel Chao, Erin Murphy
Journal: Neuro-Oncology (2016)

Recent genomic characterization of pediatric ependymomas revealed a unique balanced genetic profile without recurrent mutations, predominantly associated with children under 3 years of age. We analyzed the prognostic factors and treatment outcomes of 493 patients between ages 0 and 3 with diagnosis of ependymoma identified from the Surveillance, Epidemiology, and End Results registry (1973-2013). The impact of treatment on overall survival (OS) was assessed by Log-rank test and multivariate Cox proportional hazard modeling. Radiation therapy (RT) was delivered to 51.9% of patients, and gross-total resection (GTR) was performed in 51.0% of patients. Tumor histology was WHO grade II (9391 ependymoma) in 62.1% of patients and grade III (9392 anaplastic ependymoma) in 37.9% of patients. OS at 10 years was 48.6% with median follow up 8.4 years. WHO grade was not predictive of OS, with 47.2% and 51.4% survival at 10 years for grade II and III (p=0.340), respectively. Extent of resection was significant to survival, as the OS at 10 years with GTR was 61.0%, while OS for patients with STR and biopsy was 38.7% and 35.2%, respectively (p<0.001). RT significantly benefitted OS for both grade II and III. 10 year OS for grade II was 50.8% with RT and 43.4% without RT (p=0.024); 10 year OS for grade III was 66.8% with RT and 35.5% without RT (p=0.001). Multivariate analysis showed significantly improved OS with RT (HR 0.566, 95% CI 0.412-0.777, p<0.001) and GTR (HR 0.460, 95% CI 0.321-0.660, p<0.001). Outcomes of ependymomas in patients of ages 0-3 are significantly improved with RT and GTR. However, given the poor OS for this patient population and unique genetic profile, future prospective studies with genomic profiling should be performed to evaluate for additional prognostic factors.
Moving Forward With Accountable Care Organizations
Authors: Carrie H. Colla, Elliott S. Fisher
Journal: JAMA Internal Medicine (2017)

K. John McConnell, PhD; Stephanie Renfro, MS; Benjamin K. S. Chan, MS; Thomas H. A. Meath, MPH; Aaron Mendelson, BA; Deborah Cohen, PhD; Jeanette Waxmonsky, PhD; Dennis McCarty, PhD; Neal Wallace, PhD; Richard C. Lindrooth, PhD
A Single Microarray Assay for Simultaneous Diagnosis of t(15;17), t(8;21), Inv(16)/t(16;16), NPM1 Type A/B/D Mutation, CEBPA Double Mutation, and Aberrant Expression of BAALC or EVI1 in AML/APL Patients
Authors: Erik H. van Beers, Leonie de Best, Martin H. van Vliet, Jaap Brand, Pia Burgmer, Linda de Quartel, Belinda Dumee, Astrid Provoost, Peter Valk, Lars Bullinger, Peter J van der Spek, Henk E Vietor, Hartmut Doehner, Bob Lowenberg
Journal: Blood (2011)
Structural Analysis of a BAX-BIM SAHB Complex Reveals a Novel BH3 Interaction Site on BAX for Therapeutic Activation of Apoptosis
Authors: Evripidis Gavathiotis, Motoshi Suzuki, Marguerite L. Davis, Kenneth Pitter, Gregory H. Bird, Samuel G. Katz, Ho-Chou Tu, Hyungjin Kim, Emily Cheng, Nico Tjandra, Loren D. Walensky
Journal: Blood (2008)
Phase II study of MKC-1 in patients with metastatic or resistant epithelial ovarian cancer or advanced endometrial cancer
Authors: C. Elser, H. Hirte, L. Kaizer, H. Mackay, S. Bindra, L. Tinker, K. MacAlpine, L. Wang, C. Sidor, A. Oza
Journal: Journal of Clinical Oncology (2009)

5577 Background: MKC-1 is a novel oral cell cycle inhibitor with preclinical activity in xenograft models of human ovarian and endometrial cancers. MKC-1 also reduces pAKT, an attractive target in endometrial cancer due to frequent PTEN mutations. Methods: The objective of this phase II study is to assess the efficacy of MKC-1 in 2 patient (pt) populations: metastatic or recurrent platinum-resistant ovarian cancer (EOC) and advanced endometrial cancer (EC). Three prior lines of treatment were allowed in both groups. A two arm, parallel group multicenter 2-stage design was used. The primary endpoint was tumor response by RECIST or CA-125. MKC-1 125 mg/m 2 was administered orally twice daily for 14 days in 28-day cycles. Results: Accrual to stage one is complete with 21 pts in each arm. 19 pts with EOC (median age 56 yrs, range 31–71) and 9 patients with EC (median 63 range 50–74) were available for efficacy. A total of 66 cycles (EOC/EC: 39/27cycles) median 2 per patient (range 1–8) were delivered. 11/4 pts had prior adjuvant CT, 14/10 had prior systemic CT for advanced disease, and 2/6 received prior radiation. In pts with EOC, 7 pts have stable disease (SD), 12 progressive disease (PD), 2 remain on study. Median time to progression is 1.8 months. In pts with EC 4 pts had SD, 5 PD, 6 remain on study. Toxicity data are available in 28 pts (17/11). Most common adverse events (AE) possibly related to MKC-1 were fatigue, nausea, elevated ALT or AST, urine discoloration, anemia, anorexia, elevated AP and gastrointestinal disorder in 55%, 39%, 36%, 24%, 23%, 21%, 21%, and 21 % of cycles respectively. The only possibly related grade 3+ AEs were neutropenia, leucopenia and hyponatremia in 9 %, 3 %, and 2% of cycles. Conclusions: MKC-1 was well tolerated in both patient populations. Single agent MKC-1 has insufficient activity in platinum resistant EOC to warrant further investigation. Updated clinical data for both patient groups will be presented at the meeting. [Table: see text]
Intratumoral immune reaction: A novel paradigm for cancer.
Authors: J. Galon, B. Mlecnik, A. Kirilovsky, G. Bindea, M. Tosolini, W. Fridman, F. Pages
Journal: Journal of Clinical Oncology (2011)

471 Background: To date the anatomic extent of tumor (TNM classifications) has been by far the most important factors to predict the prognosis of cancer patients. However, the impact of immune responses and tumor escape on patient prognosis in human cancer is poorly understood. Methods: We analyzed large retrospective cohorts of colorectal cancer patients. Results: We showed that tumors from human colorectal cancer with a high density of infiltrating memory and effector memory T-cells (T-EM) are less likely to disseminate to lymphovascular and perineural structures and to regional lymph-nodes (New Engl J Med, 2005). We showed that the combination of immune parameters associating the nature, the density, the functional orientation and the location of immune cells within the tumor was essential to accurately define the impact of the local host immune reaction on patients prognosis (Science, 2006). We proposed to define these immune criteria as “immune contexture.” Analysis of patients with early-stage colorectal cancer confirmed the major role of cyotoxic effector T cells in predicting the prognosis of the patients (J Clin Oncol, 2009). Investigation of the primary tumor microenvironment allowed us to uncover the association of favorable outcomes with efficient coordination of the intratumoral immune response. We described four major immune coordination profiles within primary tumors depending on the balance between tumor escape and immune coordination. Recent advances analyzing mechanisms responsible for lymphocytic infiltration will be discussed. Conclusions: The density and the immune-cell location within the tumor have a prognostic value that is superior of those of the TNM classifications. Tumor invasion is statistically dependent on the host-immune reaction. No significant financial relationships to disclose.
Poly-therapy with EGFR, STAT3 and Src-YAP1 signaling pathway inhibition; A breakthrough for EGFR mutant NSCLC
Authors: N. Karachaliou, I. Chaib, X. Cai, X. Li, A.F. Cardona, G. López-Vivanco, A. Vergnenegre, J.M. Sanchez Torres, M. Provencio, F. de Marinis, E. Carecereny, N. Reguart, R. García Campelo, S. Viteri, M.A. Molina Vila, C. Zhou, P. Cao, P. Ma, T. Bivona, R. Rosell
Journal: Annals of Oncology (2016)
Expanded Proliferation Centers (PCs) Identify a Histological Subtype of Chronic Lymphocytic Leukemia (“Accelerated” CLL) with Adverse Clinical Outcome.
Authors: Eva Gine, Antonio Martinez, Neus Villamor, Armando Lopez-Guillermo, Mireia Camós, Daniel Martinez, Jordi Esteve, Xavier Calvo, Ana Muntañola, Pau Abrisqueta, Emili Montserrat, Elias Campo, Francesc Bosch
Journal: Blood (2009)
Toxicity of targeted therapy in elderly patients
Authors: L. Stocchi, M. Famtini, G. Drudi, E. Barzotti, C. Ridolfi, S. Nicoletti, V. Arcangeli, F. Drudi, M. Nicolini, A. Polselli, C. Santelmo, E. Tamburini, L. Gianni, D. Tassinari
Journal: Annals of Oncology (2016)
Estimating the percentage of patients with advanced melanoma achieving long-term survival with pembrolizumab (Pembro) treatment in KEYNOTE-006
Authors: C. Blank, J. Ma, J.J. Grob, J. Larkin, B. Neyns, C. McNeil, M. Lotem, E. Richtig, G. Masucci, T. Petrella, A. Ribas, J. Wang, N. Ibrahim, K.M. Anderson, A. Arance
Journal: Annals of Oncology (2016)
A successful case of switching treatment from crizotinib to alectinib after the onset of crizotinib-induced ILD
Authors: Chihiro Konishi, Nobuko Matsuura, Genju Koh, Shizuka Matsumoto, Kiyoaki Uryu, Satoshi Minamino, Mika Kusanagi, Yosie Iwasaki, Hiromasa Harada
Journal: Annals of Oncology (2016)
Quality of life during rehabilitation: Rectal cancer patient and partner experiences with altered bowel function.
Authors: J. Boucher, B. Piperdi, D. Lundquist
Journal: Journal of Clinical Oncology (2011)

468 Background: In 2010, the American Cancer Society has estimated rectal cancer affects over 39,670 adult patients in the United States. Five-year disease-free survival for rectal cancer patients with stage II/III disease ranges from 60-70%. Current gaps exist regarding long-term effects after treatment including altered bowel function and health-related quality of life (HR-QOL) concerns from rectal cancer patient and partners' perspectives both individually and together during rehabilitation and as cancer survivors. The purpose of this study was to: (1) describe the experiences of adult rectal cancer patients and their partners during rehabilitation from cancer treatment, including long- term effects; (2) examine health-related quality of life (HR-QOL) issues for rectal cancer patients and their partners including well-being and coping during their rehabilitation and as survivors. Methods: A qualitative descriptive study for a planned sample of 20 adult rectal cancer patients, stage II/III, and their partners from an academic health science hospital and cancer center has been conducted. Twelve patients and their partners have currently completed face to face semi-structured interviews. Patient participants were at least 6 months to 5 years post treatment. Qualitative descriptive design used purposive sampling to obtain broad information on rectal cancer patients' and partners' perspectives for content analysis. Results: Preliminary findings have revealed unexpected difficulties; chronic bowel function alterations; symptom unpredictability; nutrition intolerances; patient/partner adjustments; social concerns in going places, reactions by friends, work and financial strains; and, acceptance in living with it or chronic life changes as survivors. Partners acknowledged their own needs for information and support to assist their spouse or significant other. Further rich, thick descriptions will be presented in presentation of findings for 20 patient and partner responses. Conclusions: Survivorship follow-up regarding these concerns should be emphasized for rectal cancer patients and their partners to formalize interventions for study to enhance HR-QOL well-being. No significant financial relationships to disclose.
Treatment patterns for locoregional esophageal carcinoma according to race/ethnicity, histology, and insurance.
Authors: D. D. Cox, S. Fedewa, A. Chen, K. S. Virgo, E. M. Ward
Journal: Journal of Clinical Oncology (2011)

128 Background: Esophageal carcinoma (EC) is a disease with a poor prognosis. There has been a rise in incidence of EC in many western countries, including the United States. African Americans (AA) have a higher mortality rate from EC than any other ethnic group in the U.S. We investigated if there were differences in treatment and clinical characteristics in AA patients with locoregional EC compared to whites. Methods: We used the National Cancer Data Base (NCDB), a national hospital-based cancer of registry to study 20,056 adults diagnosed with locoregional EC from 2004-2007. Treatment and outcome data were obtained from the NCDB. Multivariate log binomial models were used to estimate relative risk ratios (RR) and 95% confidence intervals (CI) of receiving surgery, surgery plus systemic treatment vs. surgery alone, and margin status among patients undergoing surgery. Results: Compared to whites, AA were younger, more likely to have proximal tumors and squamous cell carcinoma, and to be uninsured. AA patients had a lower likelihood of surgery compared to whites (RR = 0.71, 95% CI = 0.66-0.77). Patients who were uninsured, Medicaid insured or younger Medicare patients had a lower likelihood of surgery. Other important predictors of surgical treatment included age, tumor location, size and histology type. Facility level factors impacted surgical treatment as well. Among patients receiving surgery, there were no differences in receipt of systemic treatment by race/ethnicity and insurance status. Younger Medicare patients and uninsured patients were more likely to have positive margins while there was no difference by race/ethnicity. Conclusions: AA patients were less likely than whites with locoregional EC to receive surgery, however, there were no treatment disparities among AA receiving surgery. Tumor characteristics, patient, provider and/or institutional factors that may influence lower receipt of surgical treatment and survival among AA should be further explored. No significant financial relationships to disclose.
Deferasirox Reduces Serum TNF-α but Impairs Renal Function in Patients with Thalassemia Major after 12 Months of Therapy
Authors: Ersi Voskaridou, Eleni Plata, Dimitrios Christoulas, Charoula Xirakia, Eleni Stoupa, Konstantinos Varvagiannis, Antonios Bilalis, Athanasios Papatheodorou, Panagiotis Tsaftaridis, Evangelos Terpos
Journal: Blood (2008)
Intensified chemotherapy for metastatic pancreatic cancer: interim analysis of a large retrospective pan-European database and real life evaluation
Authors: S. Krug, G. Beyer, M.A. Javed, N. Le, A. Vinci, R.D. Morgan, R. Hubner, J.W. Valle, H. Wong, S. Chowdhury, Y. Ting Ma, D. Palmer, P. Maisonneuve, A. Neesse, M. Sund, M. Schober
Journal: Annals of Oncology (2016)
Allogeneic Hematopoietic Cell Transplantation Can Cure Some Patients with Acute Leukemia in Relapse or Primary Induction Failure: A CIBMTR Study.
Authors: Michel Duval, Wensheng He, John P. Klein, Martin S. Tallman, John F. DiPersio, Donald W. Bunjes, Daniel J. Weisdorf
Journal: Blood (2009)
CD38 Gene Polymorphisms Contribute to Genetic Predisposition to B-Cell Chronic Lymphocytic Leukemia.
Authors: Krzysztof Jamroziak, Zofia Szemraj, Olga Grzybowska-Izydorczyk, Janusz Szemraj, Barbara Cebula, Ewa Balcerczak, Ewa Wawrzyniak, Marek Mirowski, Tadeusz Robak
Journal: Blood (2007)