tbuckley/cabot-search huggingface dataset:
Population-based analysis of a novel prognostic model for metastatic castration-resistant prostate cancer (mCRPC) patients (pts) treated with abiraterone acetate (AA).
Authors: Arun Azad, Renee Lester, Raya Leibowitz-Amit, Anthony M. Joshua, Daniel Yick Chin Heng, Bernhard J. Eigl, Kim N. Chi
Journal: Journal of Clinical Oncology (2014)

5078 Background: A prognostic model for predicting overall survival (OS) in mCRPC pts commencing AA was recently developed from a post-hoc analysis of the COU-AA-301 trial. The model consists of 6 pre-treatment risk factors (RF): ECOG performance status (PS) ≥2, presence of visceral metastases, time from start of androgen deprivation therapy (ADT) to start of AA ≤36 months (mos), low albumin (≤40g/L), high ALP (>160 IU/L) and high LDH (>250 IU/L). Our aim was to evaluate this model in a population-based cohort. Methods: Three Canadian cancer registries were used to identify mCRPC pts treated with AA. OS was estimated by the Kaplan-Meier method and compared by log-rank. Multivariate analysis was performed with the Cox proportional hazard regression model. Results: In post-docetaxel pts (n=286), 21%, 50% and 28% were classified into good (0-1 RF), intermediate (2-3 RF) and poor (4-6 RF) prognosis (prog) groups respectively based on the COU-AA-301 model. Median OS was significantly longer for good prog pts (23.9 mos) compared to intermediate (16.2 mos) and poor prog pts (8.0 mos) (Table). ECOG PS (p<0.001), LDH (p=0.040), albumin (p=0.003), visceral metastases (p<0.001) and time from start of ADT to start of AA (p=0.037) were confirmed as independent prognostic factors. In docetaxel-naïve pts (n=138), 31%, 50% and 19% were classified into good, intermediate and poor prog groups respectively. Median OS was significantly longer for good prog pts (36.9 mos) compared to intermediate (13.3 mos) and poor prog pts (7.3 mos) (Table). Conclusions: In a population-based setting, our data validate the COU-AA-301 model as a tool for prognostic stratification of both docetaxel-experienced and –naïve mCRPC pts treated with AA. This model can be used to predict outcomes for individual pts and to assist in selection of pts for clinical trials based on expected prognosis. Prognostic group Post-docetaxel pts Docetaxel-naïve pts HR (95% CI) P (log-rank) HR (95% CI) P (log-rank) Good (0-1 RF) Reference - Reference - Intermediate (2-3 RF) 2.02* (1.30, 3.12) 0.001 4.70* (2.06, 10.74) <0.001 Poor (4-6 RF) 4.41* (2.79, 6.97) <0.001 12.19* (4.77, 31.11) <0.001 *Versus good prog group.
Use of pharmacogenomic modeling in pancreatic cancer for prediction of chemotherapy response and resistance.
Authors: Kenneth H. Yu, Vineet Sangar, Mark Ricigliano, Manuel Hidalgo, Ghassan K. Abou-Alfa, Maeve Aine Lowery, Leonard Saltz, Joseph F. Crotty, Kristen Gary, Jing Yin, Eun Yong Choi, Eileen Mary O'Reilly
Journal: Journal of Clinical Oncology (2013)

4017 Background: Pancreatic adenocarcinoma (PDAC) is uniformly lethal and is the 4th leading cause of cancer mortality. Despite this, modern cytotoxics (C) can induce tumor responses and extend life. Xenograft models have shown that pharmacogenomic (PGx) modeling of C can predict efficacy. Chemo-sensitivity and gene expression profiling of circulating tumor and invasive cells (CTICs) isolated from peripheral blood may predict tumor response, progression and resistance. Methods: A prospective MSKCC study has completed planned accrual of 50 patients. 10 mL of peripheral blood is collected from patients with unresectable PDAC prior to C and at disease progression. Clinical data is prospectively collected. CTICs are isolated (Vita-Cap, Vitatex Inc.), total RNA is extracted and gene-expression analysis is performed. PGx models for twelve chemotherapy drug combinations used in PDAC were created from the GI50 data obtained from the NCI-60 cell lines (CellPath Therapeutics, Inc., Baltimore, MD). Expression data were normalized through GCRMA then probed to identify expression differences between patients with short v long TTP and within patients at baseline v at time of progression. The analysis was performed at the pathway and individual gene level. Results: CTICs were isolated, and gene expression and chemo-sensitivity patterns were obtained in all 50 patients prior to initiating C and in 20 patients at 1st line disease progression. Preliminary analysis demonstrates clinical benefit for patients treated with C predicted to be effective versus ineffective (TTP 7.3 mo v 3.7 mo, p=0.017, HR 0.30). Changes in chemo-sensitivity patterns were evident at disease progression, reflecting treatment resistance. Pathway analysis revealed that E2F1 and NFκB pathways are associated with prognosis, PLC and RB1 pathways become disrupted with disease progression. Conclusions: Isolation and gene expression profiling of CTICs can be performed reliably in unresectable PDAC. Preliminary analysis suggests that C profiling can predict response. Repeat PGx profiling identifies key pathways associated with treatment resistance. Clinical trial information: NCT01474564.
Therapeutic efficacy of combination therapy with intra-arterial 5-fluorouracil and systemic pegylated interferon α-2b for advanced hepatocellular carcinoma.
Authors: Kazuhiro Kasai
Journal: Journal of Clinical Oncology (2015)

400 Background: The prognosis of advanced hepatocellular carcinoma (HCC) remains poor, particularly among patients with portal vein tumor thrombosis (PVTT). This study evaluated the efficacy of combined hepatic arterial infusion chemotherapy of 5-fluorouracil (5-FU) and systemic pegylated interferon (PEG-IFN) α-2b in patients with advanced HCC. Methods: Subjects comprised 59 HCC patients with PVTT treated using subcutaneous administration of PEG-IFNα-2b (50-100 mg on day 1 of every week, for 4 weeks) and intra-arterial infusion of 5-FU (250 mg/day for 5 h on days 1-5 of every week, for 4 weeks). One treatment cycle lasted 4 weeks. Response to treatment was evaluated according to the Response Evaluation Criteria in Solid Tumors. The current therapy was discontinued in patients with progressive disease (PD). For responses other than PD, treatment was repeated for ³1 cycle. The primary efficacy endpoint was the objective early response rate. Secondary efficacy endpoints were progression-free survival (PFS) and overall survival (OS). Results: Objective early response rate was 73.0%. Cumulative PFS rates were 67.4% at 6 months, 30.2% at 12 months, 25.9% at 18 months and 20.7% at 24 months. Median PFS was 9.7 months. Cumulative survival rates were 82.4% at 6 months, 73.6% at 12 months, 52.8% at 24 months, and 44.0% at 36 months. Median survival time was 29.9 months. Prognostic factors affecting patient survival were analyzed by examining 21 potential parameters. Univariate analysis revealed two significant prognostic factors related to survival: PVTT grade (P=0.038); and therapeutic effect (P&lt;0.001). All adverse reactions were controllable by temporary suspension of treatment. Serious complications and treatment-related deaths were not observed. Conclusions: Although a prospective randomized controlled trial using a larger population of patients with advanced HCC is needed to evaluate combination therapy with 5-FU and PEG-IFNα-2b, this new combination therapy may be useful for patients with advanced HCC.
A phase II study of cetuximab (cet) and mFOLFOX6 in metastatic colorectal cancer (mCRC) (JACCRO CC-05).
Authors: Tatsuro Yamaguchi, Akihito Tsuji, Yu Sunakawa, Masato Nakamura, Mitsugu Kochi, Tadamichi Denda, Ken Shimada, Satoshi Tani, Akinori Takagane, Masahito Kotaka, Hidekazu Kuramochi, Junichi Koike, Kaoru Furushima, Yutaka Yonemura, Yuji Negoro, Yasutaka Takinishi, Masahiro Takeuchi, Wataru Ichikawa, Masashi Fujii, Toshifusa Nakajima
Journal: Journal of Clinical Oncology (2014)

611 Background: FOLFOX4 combined with cet for mCRC patients (pts) with KRAS wild tumor demonstrated the prolonged progression-free survival (PFS) with higher response rate (RR) in the OPUS study. To evaluate the clinical efficacy and safety of the cet plus mFOLFOX6, we conducted a multi-center phase II study of Japanese pts. Methods: In this trial, pts with KRAS wild type tumor and receiving no prior chemotherapy for mCRC were treated with cet (initial dose 400, and 250 mg/m 2 weekly) followed by mFOLFOX6 (oxaliplatin 85mg/m 2 , l-leucovorin 200 mg/m 2 , fluorouracil, as 400mg/m 2 intravenous bolus then 2,400mg/m 2 46-hour continuous infusion). The treatment was repeated every 2 weeks. The primary endpoint was RR evaluated by the external review board according to RECIST v1.1. Secondary endpoints included PFS, OS, % chronological change at the base line and safety. Results: A total of 57 pts were enrolled from August 2010 to September 2011. The median age was 60 years, 65% of pts were male, and ECOG PS 0 was observed in 91% of pts. All pts had EGFR-expressing disease. The median treatment courses were 21 (cet) and 10 (FOLFOX). The RR was 66.7% (95%CI, 53.4 to 77.7). Complete remission was observed in 5 cases (9.3%). The median PFS was 11.1 months (95%CI, 8.0 to 14.7). The early tumor shrinkage (ETS; over 20% regression at 8 weeks) was observed in 80% of pts, and the PFS for pts with ETS was statistically significantly prolonged as compared with pts without ETS (median PFS, 11.5 vs. 3.7 months, respectively; p = 0.0002). The OS was not reached at the time of median follow-up (19.2 months). Grade 3 or worse adverse events were neutropenia (48.2%), leucopenia (22.2%), rash acneform (20.4%), and peripheral neuropathy (18.5%). Conclusions: The first-line cet+mFOLFOX6 has an acceptable safety profile and demonstrates advantages in response rate for pts with KRAS wild tumor. The first-line cet+mFOLFOX6 should be considered as one of the recommended treatment regimens for pts with KRAS wild tumor. Update survival data will be presented. Clinical trial information: UMIN000004197.
Loss of EBV-Specific CD4+T Cells during Progression to EBV-Related AIDS Non-Hodgkin Lymphoma: Restoration by Highly Active Antiretroviral Therapy (HAART).
Authors: Erwan R. Piriou, Christine Jansen, Karel van Dort, Iris De Cuyper, Nening M. Nanlohy, Joep M. Lange, Frank Miedema, Marinus H.J. Van Oers, Debbie van Baarle
Journal: Blood (2004)
Optimizing discharge teaching process to increase the efficiency and effectiveness of the follow-up call.
Authors: Laurie Kaufman, Gina Aranzamendez, Beverly A Hayes, Kavita Pathak, Duke Rohe, Valerie Haywood
Journal: Journal of Clinical Oncology (2016)

226 Background: Patients undergoing complex oncologic operations are at high risk for perioperative complications associated with adverse effects on quality of life, costs and overall outcomes. Complications within 30 days of discharge are most commonly identified during first 48-72 hours post-discharge. Telephone follow-up can provide a safety net and is part of a larger discharge teaching process. Initial review of the current follow up processes underscored many variations. An interdisciplinary team was tasked to optimize discharge processes across the continuum of care which leads to a more efficient follow-up call encounter. Methods: Working with in and outpatient frontline staff from focus group teams, pre and post implementation work flow processes were captured. Inefficiencies were used for a redesign session to develop a standard discharge teaching guide and patient checklist. A database was used for data collection of measures for issues and complications encountered by patients. Storyboards were used to communicate the project progression to those working within the processes being redesigned. Results: A 42% reduction in inefficiencies of overall discharge teaching process was obtained with the largest decrease during the post discharge phase. The number of patients contacted during follow-up calls increased by 12%: discussions were longer and documentation took less time (excluding outliers). 46% of the issues were handled by the Clinical Nurse Leaders: all other medium/high issues were handed off to primary team. The time spent for follow-up calls increased, therefore, increasing direct labor cost. The rate of complications and severity decreased during the implementation phase. Effects on the readmission rates remains to be seen and patient satisfaction scores are showing a positive trend. Conclusions: Involving content experts to assess the discharge teaching process identified a worklist of inefficiencies. Using these to optimize the process, a discharge teaching guide and patient checklist were developed. Inefficiencies were reduced and process made more effective with an increased percent of patients contacted during the follow-up call.
Indoleamine 2,3-dioxygenase activity and clinical outcome following induction chemotherapy and concurrent chemoradiation in stage III non-small cell lung cancer.
Authors: B. C. Creelan, G. Bepler, S. Antonia, T. Garrett, H. H. Soliman
Journal: Journal of Clinical Oncology (2011)

10538 Background: Indoleamine 2,3-dioxygenase (IDO) has recently been proposed as an inducible promoter of tumor-related immunosuppression through the metabolism of tryptophan into kynurenine. Our objective was to prospectively correlate IDO activity with response type and survival in non-small cell lung cancer (NSCLC) patients treated with combined modality therapy. Methods: This is a companion study to a single-arm phase II trial of first-line induction gemcitabine and carboplatin followed by concurrent paclitaxel and carboplatin with 74 Gy thoracic radiation in stage III NSCLC. Serum kynurenine and tryptophan levels were drawn at baseline, post-induction, and post-concurrent treatment. Imaging studies were repeated 8 weeks after therapy. Kynurenine to tryptophan ratio (kyn/trp) was used as a surrogate for IDO activity. Kyn/trp was tested by analysis of variance and log-rank for relationships to clinical outcomes. Results: Characteristics of 28 participants: 13 females; median age 62. Median overall survival (OS) was 18.8 months (mo), and median progression-free survival (PFS) was 11.5 mo. Mean kyn/trp at baseline (4.25) increased after induction (5.04, p = 0.09) and chemoradiation (6.11, p = 0.04). Association of post-treatment increase in kyn/trp with radiologic response type was not statistically significant (p = 0.21). No significant correlation was found between post-chemoradiation kyn/trp and PFS (HR 0.97, 95% CI 0.84 - 1.12, p=0.68) or OS (HR 0.96, 95% CI 0.83 - 1.10, p = 0.51). Post-induction chemotherapy increase in kyn/trp was significantly related to worse OS (HR 1.25, 95% CI 1.01 - 1.56, p= 0.04). Conclusions: In this exploratory study, kyn/trp ratio increased during chemoradiation for NSCLC, possibly due to therapy-related inflammation inducing IDO activity within tumors. Increased IDO activity following chemotherapy may be a means for tumors to maintain immune suppression, and NSCLC may be a potential area for the application of IDO inhibitors.
Contribution of environment and genetics to oxidative stress in pancreatic cancer (PC) patients (pts).
Authors: B. A. Hocevar, E. G. Chiorean, L. Kamendulis, S. M. Perkins, E. L. Johnston, J. DeWitt, L. Li, J. E. Klaunig
Journal: Journal of Clinical Oncology (2011)

211 Background: Several risk factors have been identified as contributors to PC development, including tobacco and alcohol use, and exposure to environmental chemicals. A common denominator of these risk factors is the ability to induce oxidative stress/damage. An individual's genetic makeup may also contribute to oxidative stress, as oxidative stress/damage genes exhibit single nucleotide polymorphisms (SNPs), which can alter protein expression or activity. The goal of this study was to (1) determine if increased oxidative stress/damage is observed in PC pts and (2) to assess the contribution of environmental and genetic factors to oxidative stress/damage parameters. Methods: An oxidative stress/damage profile was generated from blood samples of newly diagnosed PC pts (n=20), from non-cohabiting genetic relatives (n=20) and/or from non-genetic relatives living in the same household (n=20). This profile consisted of measurement of total antioxidant capacity (Trolox equivalent antioxidant capacity, TEAC), direct and oxidative DNA damage (COMET), and malondialdehyde (MDA) levels. Expression of SNPs in selected oxidative stress/response genes was also evaluated. Environmental and dietary/lifestyle information was collected using a detailed questionnaire. Results: PC pts, when compared to healthy nonrelated but cohabitating relatives, displayed a significant increase in direct DNA damage (p=0.002), while oxidative DNA damage, TEAC and MDA levels were similar. When comparing PC pts to healthy genetic relatives, increased levels of TEAC, direct and oxidative DNA damage approached or were statistically significant (p = 0.061, 0.002, and 0.062 respectively). Analysis of 26 selected SNPs in oxidative stress/ damage genes in the PC pts vs healthy controls revealed that expression of CYP2A6 (L160H), rs1801272, and TNF (-308G&gt;A), rs1800629, approached statistical significance (p=0.05 and 0.20 respectively). Conclusions: Increased oxidative DNA damage observed in PC pts vs healthy related, but non-cohabitating relatives, suggests that environmental exposures contribute to oxidative stress. In combination with a specific genetic background, environmental influences may increase the risk of PC. No significant financial relationships to disclose.
HER2Δ16 expression in HER2-positive breast cancer.
Authors: Jocelyn Torres De Yao, Danyu Sun, Donna Galehouse, Scott Shorten, Nairmeen Awad Haller, Esther Hoogland Rehmus
Journal: Journal of Clinical Oncology (2014)

31 Background: HER2Δ16 isoform was detected in breast cancer and showed similar increased transforming activity to somatic mutation or deletion activated rat HER2 oncogene with 89% of HER2-positive breast cancer with this mutation developing local lymph node positive disease progression. This is the first study characterizing and determining the prevalence of HER2Δ16 isoform in patients from a NAPBC-accredited cancer center. Methods: 95 HER2-positive breast cancer tissue samples from 2002 to 2008 were obtained from Akron General Medical Center. Total RNA from cancer cells were isolated and RT-PCR was performed using primers to amplify the wild-type HER2 and HER2Δ16 isoform. DNA products from RT-PCR were then loaded in agarose gel electrophoresis with the HER2Δ16 isoform band being shorter compared to the wild type HER2. Results: Preliminary results from our ongoing study showed 39% (12 of 31) of our HER2 samples has HER2Δ16 isoform. Out of the 12 HER2Δ16 isoform samples, 17% are Stage I, 50% are Stage II, 25% are Stage III, and 8% are Stage IV breast cancer at diagnosis. Patient age ranges from 34 to 87, with 50% of the HER2Δ16 isoform patients having lymph–node positive disease at the time of diagnosis. This is in contrast to patients with HER2 wild type for which 26% (5 of 19) are diagnosed with Stage I disease and 42% have lymph node positive disease at the time of diagnosis. Conclusions: Transgenic mice that overexpressed rat HER2 oncogene with small extracellular domain deletion promoted transforming activity of this protein. HER2Δ16 isoform is detected in 39% of HER2 positive breast cancer based on our preliminary results with 50% having lymph node–positive breast cancer on initial diagnosis. Immunohistochemistry and FISH could not distinguish the wild type HER2 from the HER2Δ16 isoform. Further study is recommended for possible prognosticating utility of HER2Δ16 isoform in breast cancer.
Preclinical Development of LNA Antimir-155 (MRG-106) in Acute Myeloid Leukemia
Authors: Nina C. Zitzer, Parvathi Ranganathan, Brent A Dickinson, Aimee L Jackson, David M Rodman, Carlo M. Croce, Guido Marcucci, Ramiro Garzon
Journal: Blood (2015)
A multi-center study of 349 pancreatic mucinous cystic neoplasms: Preoperative risk factors for adenocarcinoma.
Authors: Lauren McLendon Postlewait, Cecilia G. Ethun, Nipun B. Merchant, Alexander A. Parikh, Kamran Idrees, William G. Hawkins, Ryan C. Fields, Sharon M. Weber, Clifford Suhyun Cho, Robert C. G. Martin, Charles Raben Scoggins, David J. Bentrem, Hong Jin Kim, Syed A. Ahmad, Daniel Erik Abbott, David A. Kooby, Shishir Kumar Maithel
Journal: Journal of Clinical Oncology (2016)

231 Background: Pancreatic mucinous cystic neoplasms (MCN) are defined by presence of ovarian stroma per WHO 2000 classification. Given their malignant potential, current guidelines recommend resection. However, there are limited data on preoperative risk factors for adenocarcinoma (AC) and high grade dysplasia (HGD) occurring in an MCN. Methods: MCN resections from 2000-2014 at the 8 institutions of the Central Pancreas Consortium were included. Patients with and without AC/HGD were compared. Primary aims were to determine preoperative risk factors for AC/HGD in an MCN and to assess outcomes of MCN-associated AC. Results: Of 1667 resections for pancreatic cystic lesions, 349 pts (21%) had an MCN with 52 (15%) having MCN-associated AC/HGD. Male gender (29 vs 8%; p&lt;0.001), head/neck location (39 vs 13%; p&lt;0.001), increased MCN size (7.2 vs 4.6 cm; p=0.004), radiographic presence of a solid component/mural nodule (54 vs 20%; p&lt;0.001), and duct dilation (43 vs 12%; p&lt;0.001) were associated with AC/HGD compared to benign MCN. All persisted as independent predictors of MCN-associated AC/HGD (Table). AC/HGD was not associated with presence of radiographic septations or preoperative cyst fluid analysis (CEA, amylase, or mucin). Median CA19-9 for patients with AC/HGD was 210 vs 15 U/ml for those without (p=0.001). In the 44 pts with AC, 41 (93%) had lymph nodes harvested with nodal metastases in only 14 (34%). Median FU for pts with AC was 27 mos. AC recurred in 12 pts (27%) with a 3-yr RFS of 59%. OS for pts with MCN-associated AC was 64% at 3 yrs. Conclusions: Adenocarcinoma or high grade dysplasia is present in 15% of resected pancreatic mucinous cystic neoplasms. Pre-operative factors associated with AC/HGD in an MCN include male gender, head/neck location, larger MCN, solid component/mural nodule, and duct dilation on imaging. MCN-associated AC appears to have decreased LN involvement and increased RFS and OS compared to typical pancreatic ductal adenocarcinoma. [Table: see text]