tbuckley/cabot-search huggingface dataset:
Risk factors and a model to predict toxicity-related treatment discontinuation in patients with metastatic renal cell carcinoma treated with VEGF-targeted therapy: Results from the International Metastatic RCC Database Consortium.
Authors: Marina Dusevic Kaymakcalan, Wanling Xie, Laurence Albiges, Scott A. North, Christian K. Kollmannsberger, Martin Smoragiewicz, Nils Kroeger, Connor Wells, Sun Young Rha, Jae-Lyun Lee, Andre Poisl Fay, Daniel Yick Chin Heng, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2015)

464 Background: VEGF targeted therapy (VEGF-TT) are standard in advanced metastatic renal cell carcinoma (mRCC), however, toxicities that can lead to drug discontinuation can have a significant impact on patient (pt) outcomes. We aimed to identify risk factors for toxicity and develop the first model to predict toxicity-related treatment discontinuation (TrRD) in mRCC pts treated with VEGF-TT. Methods: Baseline characteristics and treatment outcome data were collected on 936 mRCC pts on first-line VEGF-TT from 7 IMDC institutions. TrTD was analyzed using a competing risk regression model for treatment discontinuation. Results: Median follow up was 23 months. Treatment discontinuation occurred in 833 pts (89%), of which 198 (23.8%) were related to drug toxicity. Sunitinib was the most common VEGF-TT (77%) in our series followed by sorafenib (18.4%). Median time on therapy was 7.1 months in all pts and 4.4 months for pts with TrTD. Most common toxicities leading to TrTD included fatigue, diarrhea and mucositis. On multivariate analysis, significant adverse predictors for TrTD (p&lt;0.05) were: age (≥60 years), baseline glomerular filtration rate (GFR) &lt;30 cc/min, number of metastatic sites (&gt;1), and baseline sodium level (&lt;LLN). A model was developed using the number of patient risk factors to predict the risk of TrTD (Table). Conclusions: In the largest series reported to date, age, GFR, number of metastatic sites, and baseline sodium level were found to be independent risk factors that predict toxicity-related treatment discontinuation in mRCC pts treated with VEGF-TT. Based on the number of risk factors present, we built the first model to predict treatment-related drug discontinuation. This model can be used for treatment and frequency of monitoring considerations in clinical practice. [Table: see text]
Histologic review of second-line permetrexed treatment in patients with non-small cell lung cancer (NSCLC).
Authors: S. Virani, M. Almubarak, J. S. Rogers
Journal: Journal of Clinical Oncology (2011)

e18071 Background: NSCLC accounts for approximately 85% of lung cancers. It is subdivided into adenocarcinoma (including bronchoalveolar), squamous cell carcinoma (SCC), and large cell histologies. Chemotherapy is indicated for advanced disease based on histology. Upfront combination chemotherapy with platinum plus microtubule agent or gemcitabine is recommended for SCC. For non-squamous cell, carboplatin-paclitaxel-bevacizumab or cisplatin-permetrexed combinations are recommended based on superior efficacy in Phase II/III trials. Analyses of Phase III studies also suggest that permetrexed is effective when used in non-squamous NSCLC as maintenance therapy and as a second-line agent. However, the data is scant. We present histology based review of previously treated NSCLC patients who received permetrexed upon progression. Methods: Charts were reviewed for 49 consecutive previously treated NSCLC patients who upon progression had received permetrexed at West Virginia University between Sept. 2004 and Dec. 2010. Tumor histology, stage, performance status, prior therapies, permetrexed details (number of cycles, clinical and radiologic response) and survival data were reviewed. Results: The median age was 64 (47 % males, 53% females). Most patients (96%) had good performance status (ECOG 0-1). 63% had received at least 2 prior therapies including a tyrosine kinase inhibitor. Histological distribution was as follows: adenocarcinoma (AD) 47%, squamous cell (SCC) 20%, large cell (LG) 2%, not specified (NOS) 31%. Initial RECIST response (after 2 cycles) showed differential efficacy based on histology; AD - response rate (RR) 18%, stable disease (SD) 55%, progressive disease (PD) 27%, SCC - SD 22%, PD 78%, LG - PD 100% (1 patient), NOS - RR 9%, SD 55%, PD36%. Mean time-to-progression were as follows: AD 5.7 months (Range 1.1 to 28.7), SCC 1.4 months (Range 1.3 to 1.9) and NOS 7.6 months (Range 1.1 to 20.2). Data was insufficient to perform survival analysis. Conclusions: Permetrexed has superior efficacy when used in patients with non-squamous NSCLC who have previously been treated with chemotherapy. It was not effective in squamous cell histology, therefore alternative therapies should be considered.
Oral HDAC Inhibitor HBI8000 in Japanese Patients with Non-Hodgkin Lymphoma (NHL): Phase I Safety and Efficacy Results
Authors: Makoto Onizuka, Kiyoshi Ando, Makoto Yoshimitsu, Takashi Ishida, S Yoshida, Ilseung Choi, Michihiro Hidaka, Yasushi Takamatsu, Midori Nagashima, Akira Miyazato, Joachim P Schupp, Alain Rolland, Mireille Gillings, Gloria T. Lee, Kensei Tobinai
Journal: Blood (2016)
ALK rearrangement in a selected population of advanced non-small cell lung cancer patients: FISH and inmunohistochemistry diagnostic methods, prevalence, and clinical outcomes.
Authors: P. Martinez, J. Hernandez-Losa, J. Castellvi, N. Tallada, S. Cedres, M. A. Montero, V. Rodriguez-Freixinos, I. Nuñez, G. Argiles, N. Mulet-Margalef, D. Torrejon, S. Ramon y Cajal, E. Felip
Journal: Journal of Clinical Oncology (2011)

7566 Background: ALK rearrangement represents a novel molecular target in a subset of non small cell lung cancers (NSCLC). Our aim is to explore fluorescence in situ hibridation (FISH) and inmunohistochemistry (IHC) as diagnostic methods, prevalence and clinical outcomes of ALK rearrangement patients in a selected population of NSCLC. Methods: patients with NSCLC previously screened for EGFR mutation at our institution bettween June 2006 and January 2010 were selected. ALK rearrangement was identified by using FISH and the value of IHC (D5F3 monoclonal antibody-mAb) was explored. For IHC ALK protein expression positivity was defined as tumor-specific staining of any intensity in ≥10% of the tumor cells. Results: 92 patients were identified. Data is available for 71 patients: median age was 61 years (range 36-83), 80% were adenocarcinomas, 7% squamous and 13% NOS carcinomas. 51% patients were female. All were caucasian. 32% of the patients were never smokers and 30% former smokers. 6 (8.5%) patients were ALK rearranged positive by FISH, 9 (12.7%) were EGFR mutant, and 56 (78.8%) were wild type (WT/WT) for both ALK and EGFR. ALK rearrangements and EGFR mutations were mutually exclusive. ALK rearranged patients tend to be younger than EGFR mutated or WT/WT patients (median age of 53, 59 and 62 years, respectively). Patients with ALK positive tumors were predominantly never smokers (67%) and adenocarcinomas (83.4%) with equal distribution for sex. ALK positive and EGFR mutant patients have a better survival than WT/WT patients (p=0.003 and p=0.03). All patients with ALK FISH negative tumors were negative for ALK IHC. Out of 6 patients positive for ALK FISH, 4 were also positive for ALK IHC, 1 negative and in the other there was not enough tissue to perform the analysis. Conclusions: The prevalence of ALK rearrangement is 8.5% in a caucasian selected population of NSCLC. ALK positive patients have different clinical features and a better prognostic than EGFR WT and ALK negative patients. IHC with D5F3 mAb against ALK is a promising method for detecting ALK rearranged NSCLC patients.
Randomized controlled trials (RCTs) in the era of molecular oncology: Methodology, biomarkers, and endpoints.
Authors: A. Kay, J. Higgins, A. G. Day, R. M. Meyer, C. M. Booth
Journal: Journal of Clinical Oncology (2011)

6049 Background: We previously reported the metrics of RCTs testing systemic therapies for patients with breast, colorectal (CRC) and non-small cell lung cancer (NSCLC) and published in major journals between 1975–2004 (Booth JCO 2008). To evaluate principles associated with RCTs in the era of targeted therapies (TT), we have repeated a similar analysis of RCTs published 2005-2009. Methods: A search for phase III systemic therapy RCTs published in JCO, JNCI, NEJM, Lancet, JAMA 2005-2009 was performed. Details related to trial design, endpoints and results were captured. Trials were classified as TT if they involved any non-hormonal targeted agent. We also extracted data regarding biomarker use, including integral biomarkers (defined as tests used to determine eligibility, stratification, or allocation). Descriptive statistics were used to analyze trends over time. Results: 137 eligible RCTs were evaluated (50% breast, 23% CRC, 26% NSCLC). Compared with 1995-2004, the number (17 to 27 per year) and size (median sample size 446 to 722, p<0.001) of RCTs increased. The proportion of RCTs evaluating TT increased from 4% to 29% (p<0.001). There was also an increase in the proportion of trials sponsored by industry (57% to 78%, p=0.001). A greater proportion of contemporary trials use a time-to-event primary endpoint (75% to 90%, p=0.001); among these, there was a decrease in use of overall survival (66 to 41%, p<0.001). RCTs of TT were more likely to be conducted in the palliative setting (88% vs 43%, p<0.001), involve patients with NSCLC (43% vs 23%, p=0.023), and be sponsored by industry (95% vs 71%, p=0.001) than RCTs without TT. Biomarkers were included in 58% of RCTs (63% of TT trials vs 57% of non-TT trials, p=0.57). Integral biomarkers were included in 36% of RCTs (45% of TT trials vs 32% of non-TT trials, p=0.17). Among the 49 RCTs with integral biomarkers, 40 (82%) used HER2 and/or ER/PR. Conclusions: RCTs published in 2005-2009 are larger, more likely to evaluate targeted therapies, use a time-to-event endpoint, and be sponsored by industry. Biomarkers may be increasingly used, but the most common use relates to traditional use of ER/PR and evolving use of HER2 in breast cancer RCTs.
Epidermal ADAM17 maintains the skin barrier by regulating EGFR ligand-dependent terminal keratinocyte differentiation
Authors: Claus-Werner Franzke, Cristina Cobzaru, Antigoni Triantafyllopoulou, Stefanie Löffek, Keisuke Horiuchi, David W. Threadgill, Thomas Kurz, Nico van Rooijen, Leena Bruckner-Tuderman, Carl P. Blobel
Journal: The Journal of Experimental Medicine (2012)
A multicenter randomized phase III trial of customized chemotherapy versus standard of care for first-line treatment of elderly patients with advanced non-small cell lung cancer (EPIC).
Authors: George R. Simon, Silvia Novello, Tiziana Vavala, Tom Stinchcombe, Vanesa Gregorc, Gregory Alan Otterson, Barbara Jennifer Gitlitz, Robert M. Langdon, Rodolfo Bordoni, Rita Axelrod, David R. Gandara, Giorgio Scagliotti
Journal: Journal of Clinical Oncology (2012)

TPS7619 Background: Personalizing therapy based on an individual patient’s molecular profile is a potentially promising approach to optimize efficacy with the available agents. Optimizing efficacy in the elderly is particularly relevant owing to their increased propensity to suffer therapy-induced toxicity. In this proposal we will attempt to demonstrate optimization of therapy in good performance EGFR mutation negative elderly patients by taking in to consideration the histology of the tumor, the ERCC1 (marker of platinum resistance), RRM1 (for gemcitabine resistance) and TS (for pemetrexed resistance) status. Methods: Untreated advanced stage NSCLC patients age &gt;70 years with measurable disease will be enrolled. Patients will be randomized in a 2:1 randomization to experimental arm (A) or standard arm (B). In arm A, treatment with single or dual-agent chemotherapy will be selected based on histology, ERCC1 (E), RRM1(R) and TS (T) expression at the RNA level. The cut off for high (+, therefore resistant) or low (-, therefore sensitive) expression have been previously defined. Patients with squamousNSCLC who are E-R+ will be treated with single agent carboplatin, E+R- with gemcitabine, E-R- with carboplatin and gemcitabine and E+R+ with docetaxel or vinorelbine. In non-squamous NSCLC patients E-T+ will be treated with carboplatin, E+T- withpemetrexed, E-T- with carboplatin and pemetrexed, E+T+R- with gemcitabine and E+T+R+ with docetaxel or vinorelbine. In arm B treatment with single or dual-agent chemotherapy will be at the discretion of the care provider, i.e., standard of care. The primary endpoint of the trial is overall survival (OS). The secondary endpoint is progression-free survival (PFS). The tertiary endpoint is disease response. Treatment will continue to maximum of 6 cycles if tolerated or until disease progression. A sample size of 453 patients will give us 90% power to detect a three-month improvement in median survival (8 to 11 months; corresponding to a HR of 0.73) with the log rank test at a significance level of 5%(1-sided) allowing for a 10% failure rate in gene analyses.
Prognostic impact of pancreatic intraepithelial neoplasia (PanIN)-III accompanying chronic pancreatitis in patients who underwent R0 resection for pancreatic adenocarcinoma.
Authors: In kyeom Hwang, Bong Kyun Kang, Yoon Suk Lee, Jaihwan Kim, Jin-Hyeok Hwang
Journal: Journal of Clinical Oncology (2014)

246 Background: The clinical significance of pancreatic intraepithelial neoplasia (PanIN)-III, known as carcinoma in situ of pancreatic ductal adenocarcinoma (PDAC), remains unclear yet. Recent research showed inflammation enhanced early cellular invasion of PanIN-III by facilitating epithelial to mesenchymal transition (EMT), even before frank malignancy in experimental model. Therefore we decided to investigate whether PanIN-III accompanying chronic pancreatitis (CP) might have an important prognostic impact in patient who underwent curative resection for PDAC. Methods: Medical records of 199 PDAC patients with R0 resection were reviewed. Presence and grade of PanIN and CP in resected specimen were determined based on College of American Pathologists protocol. Overall survival (OS) and disease free survival (DFS) were analyzed according to PanIN-III and CP. Results: CP was observed in 19.6% (39/199) of resected specimen and PanIN-III in 21.1% (42/199). In the group with CP, PanIN-III was associated with poor prognosis in univariate analysis (16.6 months vs. 32.0 months, P=0.001 for OS and 7.5 months vs. 15.1 months, p=0.012 for DFS), whereas PanIN-III was not a prognostic factor in the group without CP. When we divided into two groups [PanIN-III accompanying CP (n=12) vs. the others (n=187)], it showed that median DFS and OS were significantly shorter in PanIN-III and CP group than those of the others (7.5 months and 16.6 months vs. 12.4 months and 26.0 months, p=0.017 and p=0.003, respectively). In multivariate analysis, PanIN-III accompanying CP remained a statistically significant poor prognostic factor (HR: 2.06; 95% CI: 1.008 to 4.221; p=0.048 for OS, HR: 2.6; 95% CI: 1.267 to 5.462; P=0.009 for DFS using Cox proportional hazard ratio). Conclusions: PanIN-III accompanying CP might influence on poor long-term outcomes in patients who underwent R0 resection for PDAC. Therefore, it would support that chronic inflammation could enhance the dissemination of carcinoma in situ.
Pluripotency genes expression in glioma-initiating stem cells and clinical outcome.
Authors: L. Karayan-Tapon, C. Villalva, U. Cortes, C. Marquant, M. Wager, N. Sorel, J. Guilhot, J. Tourani, A. Bennaceur, J. Chomel, A. Turhan
Journal: Journal of Clinical Oncology (2011)

e12509 Background: Accurate prognostic markers are required for patients with glioblastoma multiforme. Recent studies have demonstrated a relationship between the expression of stem cell-associated genes and relapses in glioblastoma, suggesting a key role of tumor stem cells in this process. The aim of this study was to identified tumor stem cell-associated markers in glioblastoma by monitoring pluripotency and stemness-related genes expression and to evaluate their potential prognostic value. Methods: By using TaqMan Low Density Array (TLDA), a highly specific and sensitive gene expression technology, the pluripotency genes expression profiles were analysed in glioblastoma-derived neurospheres from 11 patients undergoing surgery. After enrichment of the tumor-initiating stem cell population, gene expression profiling was performed and compared to human embryonic stem cells (hES). Following hierarchical clustering, differentially expressed genes were assessed in neurospheres and further confirmed in an independent cohort of 30 patients with glioblastoma. Results: Hierarchical clustering analyses revealed 8 differentially expressed genes in neurospheres and primary tumors, among which COL1A1 and IFITM1 with the highest expression levels. Considering COL1A1 and IFITM1 expression and clinical data (overall survival), Kaplan-Meier survival analysis clearly demonstrated that COL1A1 and IFITM1 overexpression were associated with a longer survival (10.5 months versus 17.5 months, p<10-3). Conclusions: COL1A1 and IFITM1 pluripotency genes could be used for stratifying patients with glioblastoma into subgroups for risk of recurrence at diagnosis, as well as for prognostic and therapeutic evolution.
The anatomic location of pancreatic cancer as a prognostic factor for inpatient complications.
Authors: Shuang Yin Zhang, Shuang Qin Zhang, Jimmy Jing Jiang, Bassel F. El-Rayes
Journal: Journal of Clinical Oncology (2015)

247 Background: Patients with cancer in the head of the pancreas (HP) have a higher frequency of biliary stents, which are associated with complications requiring hospitalization. We hypothesized that hospitalized patients with cancers of the HP have a higher incidence of morbidity and mortality as compared to patients with cancer in the body (B) or tail (T). The primary aim of this study was to investigate whether anatomic location of pancreatic primary lesions is associated with complications and mortality in hospitalized patients. Methods: The Nationwide Inpatient Sample (NIS) database was queried to identify all non-surgical hospital admissions for patients with a diagnosis of pancreatic cancer (PC) for 2011. Based on ICD-9 diagnosis codes, patients were divided into three groups: H, B, and T. Patient demographics, comorbidities, medical complications, and hospitalization outcomes were compared among these 3 groups by univariate analysis. Two sample independent t-tests were used to compare all linear variables, and Chi-squared tests were used to compare categorical data. Results: In total, 4,910 patient admissions were analyzed, of which 3,590 had H, 519 B, and 801 T. No difference was observed in the mean age for all three cohorts (67-68 years). Length of hospitalization for each cohort averaged 6 days. Patient with pancreatic cancer of tail had statistically significant higher incidence of pneumonia (H 4.7%, B 6.2%, T 9.1%, p&lt;0.001), deep venous thrombosis (H 5.5%, B 10.6%, T 13.5%, p&lt;0.001), pulmonary embolic (H 3.3%, B 6.9%, T 9.4%, p&lt;0.001), cerebral vascular events (H 0.7%, B 1.5%, T 2.9%, p&lt; 0.001), ileus (H 6.0%, B 8.1%, T 10%, p&lt;0.001), encephalopathy (H 2.0%, B 1.7%, T 3.5%, p=0.02), acute renal failure (H 13%, B 9.1%, T 15%, p= 0.005), and in-hospital mortality (H 5.3%, B 6.9%, T 8.9%, p&lt;0.001). Conclusions: In this study, pancreatic cancer of the tail correlates with higher incidences of in-hospital complications and mortality. This suggest that the impact of biliary stents on outcome of hospitalized patients with PC may be limited. Anatomic location of pancreatic malignancy may also be utilized as prognostic factor in management of inpatient PC patients.
A Novel Method of Using Molecular Profiling in Myelodysplastic Syndromes to Predict Patient-Specific Potential Therapeutics
Authors: Christopher R. Cogle, Gaurav Trikha, Peter P. Sayeski, Shireen Vali, Ansu Kumar, Neeraj Kumar Singh, Prashant R Nair, Deepak Anil Lala, Kabya Basu, Taher Abbasi, Maher Albitar
Journal: Blood (2014)
Long-term efficacy of stereotactic body radiotherapy for localized prostate cancer: A multi-institutional pooled analysis.
Authors: Patrick Kupelian, Alan J. Katz, Debra Freeman, Irving D. Kaplan, Donald B. Fuller, Giampaolo Bolzicco, Sean P. Collins, Robert Meier, Jason Wang, Christopher R. King
Journal: Journal of Clinical Oncology (2013)

9 Background: The purpose of this study is to report biochemical relapse-free survival (bRFS) rates for a group of localized prostate cancer patients from a pooled multi-institutional dataset with at least 5 years follow-up after stereotactic body radiotherapy (SBRT). Methods: The outcome data from 1101 patients treated with SBRT between 2003 and 2011 were pooled from 8 institutions. A subset of 135 cases had a minimum 5 years follow-up. All 135 cases had clinical stage T1 or T2A disease. The distribution by Gleason score (GS) was &lt;6 in 80% and 7 in 20%. The median pretreatment PSA (iPSA) level was 5.1 ng/ml (range: 0.1-27.8). The distribution by risk was 77% low, 21% intermediate, and 2% high risk. The median dose was 36.25 Gy (35-40 Gy range) delivered either with 4 or 5 fractions. The prescribed dose groups were as follows: 35 Gy in 42%, 36.25 Gy in 47%, and &gt;38 Gy in 11%. Androgen deprivation therapy was given to 21% of patients. Biochemical relapse, defined as a rise &gt; 2 ng/ml above nadir, was determined in a total of 4 failures. Results: The median follow-up for all 135 cases was 60 months (range 60 to 72). For all patients, the bRFS rate at 5 years was 97%. The 5-year actuarial bRFS rates for GS &lt; 6, and Gleason score 7 were 98%, and 92%, respectively (p=0.15). The 5-year actuarial bRFS rates for low versus intermediate/high-risk patients were 99% and 93%, respectively (p=0.11). The 5-year actuarial bRFS rates for patients receiving 35 Gy versus &gt;36.25 Gy were 93% and 100%. No difference in bRFS was observed with the use of androgen deprivation (p=0.78). Multivariate analysis showed only GS to be an independent predictor of relapse (p=0.03); iPSA (p=0.10) and radiation dose (0.97) were not. Conclusions: In a relatively large cohort of localized prostate cancer patients treated with SBRT, long follow-up period (&gt;5 years), excellent efficacy was demonstrated with 97% of patients being free from relapse. For low and intermediate risk cases, these results compare favorably with other modalities with similar follow-up periods. Although a trend for worse outcome was seen with total radiation doses of 35 Gy, this was not confirmed on multivariate analysis.