tbuckley/cabot-search huggingface dataset:
Effect of JAK2 SNP rs2274472 on outcome for mCRC patients treated with first-line FOLFIRI and bevacizumab: Data from FIRE-3 trial.
Authors: Martin D. Berger, Sebastian Stintzing, Volker Heinemann, Dongyun Yang, Shu Cao, Yan Ning, Satoshi Okazaki, Yuji Miyamoto, Mitsukuni Suenaga, Marta Schirripa, Roel Gopez, Diana L. Hanna, Wu Zhang, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2017)

595 Background: The Jak2 (Janus kinase 2) / Stat5a (signal transduction and activators of transcription 5a) pathway plays a key role in regulating cell survival, proliferation and immune function. JAK2 is a non-receptor tyrosine kinase which is stimulated by a variety of cytokines. Moreover the JAK2 / STAT5 axis is activated by hypoxia and involved in regulating angiogenesis. We therefore hypothesize that variations in the JAK2 gene may predict outcome in patients with metastatic colorectal cancer (mCRC) treated with first-line FOLFIRI and bevacizumab (bev). Methods: Theimpact of 2 functional SNPs within the JAK2 and STAT5a genes on outcome was evaluated in 295 pts with mCRC treated with first-line FOLFIRI / bev in the randomized phase III FIRE-3 trial. 227 pts receiving FOLFIRI and cetuximab (FIRE-3) served as a negative control. Genomic DNA was extracted from formalin fixed paraffin embedded tissue and the SNPs were analyzed by PCR-based direct sequencing. Results: Baseline characteristics in the FOLFIRI / bev arm were as follows: female:male ratio = 1/3:2/3; median age = 65y (31-76) andmedian PFS/OS = 10.1/24.2 months. The JAK2 rs2274472 SNP showed significant association with progression-free survival (PFS). C allele carriers had a shorter median PFS compared to those with a T/T genotype (9.9 vs 11.7 months) in both univariate (HR 1.30, 95% CI 1.00-1.69, p = 0.045) and multivariate analysis (HR 1.39, 95% CI 1.06-1.83, p = 0.018). However, this association could not be observed in patients treated with FOLFIRI and cetuximab. Here, patients harboring any C allele and T/T genotype carriers showed an equal median PFS (10.0 vs 9.9 months, HR 1.00, 95% CI 0.75-1.33, p = 1.00). Conclusions: Our results provide the first evidence that the JAK2 polymorphism rs2274472 might serve as a predictive marker in pts with mCRC treated with FOLFIRI and bev in the first line setting. Targeting the JAK2 / STAT5A axis might be a promising approach to further enlarge our treatment options against mCRC and to overcome resistance to anti-angiogenic therapy.
Prevention of lymphedema in women with breast cancer (BC): Results of CALGB (Alliance) 70305.
Authors: Electra D. Paskett, Jennifer Le-Rademacher, Jill Oliveri, Heshan Liu, Drew K. Seisler, Jeffrey Sloan, Jane M. Armer, Michelle Joy Naughton, Karen Hock, Michael A. Schwartz, Gary Walter Unzeitig, Gilbert D. A. Padula, Stephen S. Grubbs, Lisa Yee, Lisa Bailey, Shawna C. Willey, Thomas Dean Sunnenberg, Lisa L. Baddi, Gini F. Fleming
Journal: Journal of Clinical Oncology (2017)

104 Background: Lymphedema (LE), a side effect of BC treatment, affects 8%–56% of women. The study tested the effectiveness of an education only vs education + exercise intervention on LE incidence in a group randomized trial (NCT00376597) of 38 cooperative group sites. Methods: Newly diagnosed women with stage I-III BC were consented and arm circumference and range of motion were measured pre-surgery. After surgery, patients (pts) were enrolled based on the randomization assignment of their treating institution, stratified by their type of node dissection (sentinel or axillary), and received either: education only: its causes, signs, symptoms and risk reduction strategies, or education + personalized exercise instruction from a physical therapist, with elastic compression garments to wear during heavy arm use and air travel. Pts completed surveys and arm measurements at baseline (BL), 12 and 18 months with the LE endpoint defined as ≥ 10% difference in limb volume at any time from BL to 18 months or physician diagnosis of LE. Cochran-Mantel-Haenszel (CMH) tests were used to compare the LE-free rate between arms, adjusted for type of biopsy. Logistic regression assessed predictors of LE. Results: 568 pts were enrolled, 45% in education only, and 55% in education + exercise, with 554 (98%) included in the analyses. Pts were on average 57.7 years, White (83%), non-Hispanic (92%) and married (62%). 47% only had sentinel node dissection, 35% had mastectomy, and 37% had chemotherapy. The LE-free rate was 58% in education only vs 55% in education + exercise (CMH p = 0.73). Predictors of LE included surgery type (lumpectomy vs mastectomy, OR = 2.22, p &lt; 0.001) and chemotherapy (no vs yes, OR = 1.73, p = 0.02), after adjusting for BMI and type of node dissection. Only one-third wore the sleeve at least 75% of the time and only 50% did LE exercises at least weekly. Conclusions: There was no difference by intervention arm in LE incidence by 18 months. Poor adherence in the education + exercise arm may have been a factor. Additional analyses will assess quality of life, body image and knowledge about LE by arm. Further research is needed to effectively prevent LE in pts after BC surgery. Research Support: UL1TR001409; U10CA037447, UG1CA189823 Clinical trial information: NCT00376597.
Ponatinib Exerts Multiple Effects on Vascular Endothelial Cells: Possible Mechanisms and Explanations for the Adverse Vascular Events Seen in CML Patients Treated with Ponatinib
Authors: Emir Hadzijusufovic, Rudolf Kirchmair, Markus Theurl, Susanne Gamperl, Daniela Lener, Clemens Gutmann, Ursula Stanzl, Andrijana Kirsch, Sasa Frank, Peter Valent
Journal: Blood (2016)
Elderly Head and Neck Cancer (ELAN) study: Personalized treatment according to geriatric assessment in patients age 70 or older: First prospective trials in patients with squamous cell cancer of the head and neck (SCCHN) unsuitable for surgery.
Authors: Joel Guigay, Herve Le Caer, Cecile Mertens, Cecile Ortholan, Emmanuel Blot, Yungan Tao, Frederic Peyrade, Yoann Pointreau, Pierre Guillet, Cedrik Lafond, Karen Benezery, Sophie Renard-Oldrini, Julia Villa, Georges Garnier, Marc Alfonsi, Naima Lezghed, Nadejda Vintonenko, Dominique Schwob, Perrine Capolino, Anne Auperin
Journal: Journal of Clinical Oncology (2014)

TPS6099 Background: 30% of SCCHN occur in patients (pts) >= 70y and the main challenges in these pts are to cope with the treatment benefit/risk ratio and the tumor related symptoms. However, these pts are usually not included in trials. We developed a large prospective clinical program planed to enroll 448 pts in 3 distinct trials to improve the multidisciplinary management of elderly SCCHN pts. The main objectives of this study are to demonstrate that a geriatric evaluation is feasible in daily practice for SCCHN pts and to set new standards of care in this population. Methods: To be included in one of the three trials, SCCHN pts aged 70 or over, not suitable for surgery, must first be enrolled in ELAN-ONCOVAL study where they are classified as fit or unfit, using a geriatric evaluation applicable to the daily practice. Comprehensive Geriatric Assessment is optional. In curative situation, unfit pts are proposed to be enrolled in the randomized non-inferiority ELAN-RT trial, comparing standard radiotherapy (RT, 70Gy, 35 fractions, 7 weeks) and hypofractionated split course schedule (30 Gy in 10 fractions, 2 weeks stop, 25 Gy in 10 fractions, total 6 weeks). Main endpoint is the rate of patients alive with local control 6 months after end of RT. 202 pts are planned to be randomized. In first line treatment of recurrent and/or metastatic (R/M) pts: - Fit pts are proposed to be enrolled in the 2-stage phase II ELAN-FIT trial, which evaluates the cetuximab-carboplatin-5FU (EXTREME) combination in terms of efficacy (objective response at 12 weeks) and safety assessed by lack of grade>=3 toxicity and lack of loss of independence. Enrollment of 82 pts is planned. - Unfit pts are proposed to be enrolled in the efficacy randomized phase III ELAN-UNFIT trial, that compares two monotherapies (cetuximab 500 mg/m² every 2 weeks versus weekly methotrexate 40 mg/m²) in terms of failure free survival (failures are progression, treatment stop, loss >= 2 points in Activities in Daily Living scale or death). 164 pts are planned to be randomized. Inclusions started on June 2013. At now 23 centers are opened. Grants: INCa PAIR Clinical trial information: NCT01884623; NCT01864850; NCT01864772.
A video-based, personalized web page (VBPWP) as a complement to clinical trial (CT) patient management.
Authors: Hannah Mills, Rana R. McKay, Lillian Werner, Susanna J. Jacobus, Amanda Fredericks Pace, Judith Prisby, Meghara K. Walsh, Atish Dipankar Choudhury, Toni K. Choueiri, Mark Pomerantz, Christopher Sweeney, Laura Polacek, Mary-Ellen Taplin
Journal: Journal of Clinical Oncology (2017)

266 Background: Most advances in the diagnosis and treatment (T x ) of patients (pts) with genitourinary (GU) cancers are the result of pt involvement in CTs. There is a clear need to identify ways to improve CT processes for pts and research teams (RTs). The goal of this project is to assess the use of a VBPWP to improve pt compliance, safety, CT quality, and RT efficiency in GU CTs of oral agents. Methods: This is an unblinded, randomized trial using a VBPWP as an intervention (INT) for pts with advanced non-metastatic (M0) or metastatic (M1) GU cancers. Pts consented but not yet started on CTs of oral agents are randomized 2:1 to the INT or control arm. The INT includes videos of provider-pt encounters and educational videos related to dosing and adverse events (AEs). Target accrual is 99 pts. The primary end point is number of cumulative pt violations (PVs) over 4 cycles (4Cs) of INT. PVs are defined as improper dosing, non-compliance, and failure to report AEs or hospitalizations. Herein we report an early pooled analysis of pts who completed 4Cs. Results: 90 pts enrolled (61 M1, 67 prostate, 22 kidney). 58 pts completed ≥ 4Cs. 58% (n = 33) of pts had ≥ 1 PV on study (Table). Despite RT instructions, overall, 7%, 9%, and 3% of pts failed to return pill bottles or report AEs, missed a dose of T x on 3 occasions, or took a wrong dose, respectively. Median total score of the Functional Assessment of Chronic Illness Therapy T x Satisfaction-Pt Satisfaction (FACIT-TS-PS) measure was 72 (n = 45) at baseline (BL) and did not significantly change after 4Cs (73, n = 48). Scores of 73 indicate high levels of pt satisfaction. The Perceived Stress Scale (PSS) 10-Item indicated pt stress levels were highest at BL (score = 28) and improved after 1C of T x (score = 24). Scores ≥ 20 indicate high stress. Stress levels did not significantly change after 4Cs. Conclusions: Longer follow up is needed to compare outcomes between pts randomized to the video INT compared to the control arm. Data show that the majority had ≥ 1 PV. This suggests the need to improve education for CT pts. The use of a VBPWP as a complement to standard CT pt education is feasible and may have the potential to increase pt safety and CT quality. [Table: see text]
Mir-31-3p as a predictive biomarker of cetuximab effects in a post hoc analysis of new EPOC phase III trial.
Authors: Pierre Laurent-Puig, John A. Bridgewater, John Neil Primrose, Sian Alexandra Pugh, Gareth Thomas, Karwan Moutasim, Francis Rousseau, Karine Fontaine, Celine Vazart, Virginie Decaulne, Anne Leclair, Berengere Genin, Sandrine Imbeaud, Francois Liebaert, Raphaële Thiébaut
Journal: Journal of Clinical Oncology (2014)

3523 Background: miR31-3p expression level has been associated with progression free survival (PFS) in KRAS wild type metastatic colorectal cancer (mCRC) patients treated with anti-epidermal growth factor receptors (EGFRs). In this study we evaluated its predictive value on PFS in the new EPOC trial by measuring its expression in primary tumors and liver metastases. Methods: miR31-3p expression was determined by RT-QPCR in 125 formalin-fixed and paraffin-embedded (FFPE) primary tumor samples from patients. There were 63 patients (control arm) who received oxaliplatin or irinotecan-based chemotherapy and 62 received the above plus cetuximab. Correlations between miRNA expression and survival were performed using an adjusted Cox model. Liver metastasis were available for 58 of the 125 patients and comparison was done using a Pearson correlation on log2 transformed miR31-3p expression value. Results: A significant association was found between PFS and miR31-3p expression in the cetuximab arm (p=0.035; HR=1.2, CI95% CI [0.98 – 1.48]), and not in the control arm (p=0.36; HR=0.96, CI95% [0.75 – 1.23]).A predictive model was developed dichotomizing patients with high or low risk of progression. In the cetuximab arm PFS was significantly shorter in patients with high expression than in patients with low expression (p=0.033). In all patients with high miR31-3p expression, PFS was significantly shorter in the cetuximab treated arm than in the control arm (p=0.0177, median PFS: 49.6 and 64.9 weeks respectively), in all patients with low miR31-3p expression, PFS was not different between cetuximab and control arm. Study of miR-31-3p expression in primary tumor and matching metastasis showed a correlation in the control arm (p=0.00004) but not in the cetuximab arm (p=0.55). Conclusions: We demonstrated for the first time that miR31-3p expression is predictive of cetuximab effects and replicated association of its expression with PFS in patients receiving cetuximab. Furthermore miR31-3p allowed identification of a subgroup of patients in which cetuximab with chemotherapy had a detrimental effect on PFS. Eventually the correlation of miR31-3p expression in metastases and primary tumors in the control arm, but not in the cetuximab arm, suggests cetuximab has an effect on miR31-3p expression, supporting its involvement in the EGFR pathway.
New medicinal products for chronic heart failure: advances in clinical trial design and efficacy assessment
Authors: Martin R. Cowie, Gerasimos S. Filippatos, Maria de los Angeles Alonso Garcia, Stefan D. Anker, Anna Baczynska, Daniel M. Bloomfield, Maria Borentain, Karsten Bruins Slot, Maureen Cronin, Pieter A. Doevendans, Amany El‐Gazayerly, Claudio Gimpelewicz, Narimon Honarpour, Salim Janmohamed, Heidi Janssen, Albert M. Kim, Dominik Lautsch, Ian Laws, Martin Lefkowitz, Jose Lopez‐Sendon, Alexander R. Lyon, Fady I. Malik, John J.V. McMurray, Marco Metra, Santiago Figueroa Perez, Marc A. Pfeffer, Stuart J. Pocock, Piotr Ponikowski, Krishna Prasad, Isabelle Richard‐Lordereau, Lothar Roessig, Giuseppe M.C. Rosano, Warren Sherman, Wendy Gattis Stough, Karl Swedberg, Benoit Tyl, Faiez Zannad, Caroline Boulton, Pieter De Graeff
Journal: European Journal of Heart Failure (2017)
A phase I clinical trial of autologous, anti-CD19 gene targeted T cells for adults with B cell acute lymphoblastic leukemia (B-ALL).
Authors: Marco L. Davila, Isabelle Riviere, Xiuyan Wang, Shirley Bartido, Jolanta Stefanski, Clare Taylor, Malgorzata Olszewska, Oriana Borquez-Ojeda, Jinrong Qu, Teresa Wasielewska, Mark G. Frattini, Michel Sadelain, Renier J. Brentjens
Journal: Journal of Clinical Oncology (2012)

TPS2619 Background: Complete remission (CR) rates for B-ALL in adults is high (&gt;80%), but overall survival remains low (approximately 30%). Patients with relapsed disease have a very poor prognosis with a median survival measured in months. Therefore, there is a dire need for novel therapies for adults with relapsed or minimal residual B-ALL. To this end we have developed a novel T cell therapy for B cell malignancies using patient derived T cells genetically modified to express the 19-28z chimeric antigen receptor (CAR), an artificial T cell receptor specific to the CD19 antigen expressed on most B cell tumors. Human T cells retrovirally modified to express the 19-28z CAR successfully targets and eradicates B cell tumors in vitro and systemic human B cell cancers in mice. We have recently published the results of our initial Phase I clinical trial experience (Brentjens, Rivière et al., Blood 2011) utilizing this technology in adults with chronic lymphocytic leukemia. These results suggest clinical activity and demonstrate a persistence of 19-28z+ T cells that is inversely associated with tumor burden. These studies suggest that 19-28z+ T cells may be particularly effective in relapsed B-ALL because these tumors retain a degree of chemotherapy sensitivity, which will allow the infusion of T cells after salvage chemotherapy when patients have low tumor burdens. To our knowledge, this is the first clinical trial using autologous CD19 targeted T cells in adults with B-ALL. Methods: We are enrolling patients to a Phase I T cell dose escalation trial (NCT01044069). Adults with CD19+ B-ALL classified as a CR, relapsed, or refractory are eligible for enrollment. After patients are enrolled they are leukapheresed to obtain peripheral blood T cells, which are then retrovirally transduced to express the 19-28z CAR and expanded in our GMP gene transfer facility. Enrolled patients with relapsed or refractory B-ALL undergo a cycle of re-induction chemotherapy and conditioning cyclophosphamide followed by infusion of autologous 19-28z+ T cells. To date, 11 patients have been enrolled and 2 patients have been infused with 19-28z+ T cells.
Presence of 18q loss of heterozygosity (LOH) and disease-free and overall survival in stage II colon cancer: CALGB Protocol 9581
Authors: M. M. Bertagnolli, D. Niedzwiecki, M. Hall, S. D. Jewell, R. J. Mayer, R. M. Goldberg, T. A. Colacchio, R. S. Warren, M. Redston
Journal: Journal of Clinical Oncology (2009)

4012 Background: LOH at 18q is associated with poorer overall survival in patients with colon cancer; however available studies are retrospective and vary in analysis methods. We recently completed an 18qLOH assay method validation study, and after standardizing technique, this prospective study investigated the role of 18qLOH among patients with low-risk stage II colon cancer. Methods: In Cancer and Leukemia Group B (CALGB) protocol 9581, we randomized 1738 stage II patients to post-operative treatment with a 500 mg loading dose of monoclonal antibody 17–1A followed by four infusions of 100 mg every 28 days or observation. The primary endpoint was overall survival (OS); disease free survival (DFS) was a secondary endpoint. Status of 18qLOH was assessed in patients with available tissue and interpretable PCR results. Patients were excluded if their tumors were uninformative for 18qLOH or if their tumors displayed microsatellite instability. Results: We report 18qLOH data on 156 patients. Patient characteristics including treatment, age, gender, performance status, site and grade of tumor, were similar between all patients enrolled and the subset of patients with tumor samples analyzed. The DFS and OS for treated and observed patients were no different (5-yr DFS: 0.81 and 0.80, p= 0.96; 5-yr OS: 0.88 and 0.86, p=0.44 at a median of 6.8 yrs of follow-up) and the data were pooled across the study's arms. Of the tumors examined, 101 (65%) were positive for 18qLOH. A significantly lower proportion of patients with 18qLOH-positive tumors had proximal tumors (46.5% vs 65.5%; p=0.02). Significantly decreased DFS and OS were observed in patients with 18qLOH-positive tumors. Five-year DFS among patients with 18qLOH-positive tumors was 0.78 vs 0.93 among patients with 18qLOH-negative tumors [HR 0.39; 95% CI (0.16, 0.94); logrank p=0.03 based on 33 events]. Five-year OS among patients with 18qLOH-positive tumors was 0.85 vs 0.98 among patients with 18qLOH-negative tumors [HR 0.25; 95% CI (0.07, 0.83); logrank p=0.01 based on 24 events]. Conclusions LOH at 18q was prognostic for DFS and OS among patients with available tissue for analysis after resection of low-risk stage II colon cancer who were not treated with chemotherapy in the adjuvant setting. [Table: see text]
Intermittent maintenance treatment with bevacizumab in patients with metastatic colorectal cancer: A single centre experience.
Authors: Eleonora Cerchiaro, Michela Squadroni, Maria Grazia Sauta, Maria Bonomi, Federica Brena, Cristina Ripa, Rosalba Barile, Piermario Salvini, Giovanni Luca Ceresoli, Giordano D. Beretta
Journal: Journal of Clinical Oncology (2017)

776 Background: The main objective of care in patients with metastatic colorectal cancer (mCRC) is survival prolongation preserving the quality of life (QoL). Optimal duration of chemotherapy after induction treatment is still a matter of debate, such as the treatment strategies that could be adopted (intermittent versus continuous maintenance chemotherapy). Methods: In this monoinstitutional retrospective study we evaluated 70 patients (pts) diagnosed with mCRC with stable or responsive disease after chemotherapy with Bevacizumab (12 courses of FOLFIRI-Bevacizumab) as first or second-line treatment. We observed three groups: group A (20pts): maintenance therapy with de Gramont-Bevacizumab 2 months on/2 months off until disease progression (intermittent strategy); group B (30 pts): no maintenance treatment; group C (20 pts): induction treatment exclusively as first line followed by continuous maintenance with de Gramont-Bevacizumab. Results: Median progression free survival (PFS) was 21 months in Group A (range: 10-51 months), 9 months in Group B (range 6.6-12.9 months), 11 months in groups C (range 10.4-13.3 months), the difference resulted significant among group in favor of intermittent strategy (p = 0.006). Median OS was 60.6 months (range: 35.6-96.2 months) in group A, 27.2 months (range 19.5-39.9 months) in group B and 23.6 months in group C (range: 19.1-31 months); p = 0.0011. The most frequent adverse events of all grades were: hypertension, neutropenia, thrombocytopenia, diarrhea, asthenia. No toxic death was observed. Adverse events (AEs) of all grades were more frequent in group C (15% Grade 3-4), comparing with Group A and B (10% Grade 3-4 AEs) Conclusions: According to our retrospective analysis, intermittent maintenance treatment with chemotherapy and Bevacizumab appears to be a feasible strategy in pts with stable or responsive disease. PFS and OS resulted longer in patients treated with intermittent strategy comparing with other groups. The study has at least three bias: selection of patients, small sample size and retrospective nature, however we can conclude that intermittent strategy could improve patients outcome with an acceptable toxicity profile.