tbuckley/cabot-search huggingface dataset:
A nine-gene predictor of therapy response in adult Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph+ ALL)
Authors: Z. Zuo, D. M. Jones, D. A. Thomas, S. O'Brien, F. Ravandi, H. M. Kantarjian, L. J. Medeiros, R. Luthra, S. S. Chen
Journal: Journal of Clinical Oncology (2009)

7014 Background: Ph+ ALL in adults shows a poor response to therapy and high frequency of relapse. This study utilized a meta-analysis of previous genome-wide gene expression studies to define and validate a nine-gene predictor of outcome in Ph+ ALL patients. Methods: Normalized gene expression data from previously published studies of 672 ALL patients were analyzed to identify genes associated with therapy response. Expression of the selected genes was assessed using Applied Biosystems low density reverse transcription quantitative PCR (RT-qPCR) arrays in bone marrow (BM) samples from 27 adult Ph+ ALL patients treated with standard chemotherapy plus a tyrosine kinase inhibitor. Therapy responses were defined at the molecular level by monitoring BCR/ABL1 levels, and categorized into 3 groups: optimal, persistent and relapse. Median follow up was 6 months (range 4–15). Median disease-free survival among the optimal and relapse groups were 12 and 5 months respectively (p = 0.002). There was no statistical difference in age, initial peripheral blood white cell and BM blast counts, and initial normalized BCR/ABL1 levels between groups. Differentially expressed genes were selected using the significance analysis of microarrays (SAM). Hierarchical clustering and principal component analysis were applied to assess the correlation between gene expression pattern and therapy response. A predictive model was built using support vector machines. Differences in survival among groups were compared by Kaplan-Meier analysis. Results: Data mining and pathway analysis of the published data identified 46 genes in 7 pathways potentially associated with therapy response (p &lt; 0.001). RT-qPCR results from a 15 case training set, 5 in each outcome group, identified 9 genes that classified the cases with 100% accuracy. Validation using an additional 12 cases showed 91.7% prediction accuracy (ROC error = 0.056). Compared with the initial diagnostic samples, gene expression pattern in relapsed samples shifted to that resembling the persistent group. Conclusions: Using data-trimming of whole genome expression studies, we defined and validated a nine-gene signature that is an independent predictive marker for therapy response in adult Ph+ ALL patients. No significant financial relationships to disclose.
Safety and antiemetic effect of palonosetron for chemoradiation therpy of esophageal cancer.
Authors: Yasushi Ichikawa, Ayumu Goto, Noritoshi Kobayashi, Motohiko Tokuhisa, Takashi Ishikawa, Hirochika Makino, Takashi Kosaka, Hirotoshi Akiyama, Chikara Kunisaki, Shin Maeda, Itaru Endo
Journal: Journal of Clinical Oncology (2014)

e20695 Background: With esophageal cancer (EC), chemotherapy or chemo-radiation therapy is important not only for curative intent but for palliative intent treatment. Cisplatin is one of the key drugs of combination chemotherapy for esophageal cancer and is one of the most highly emetic drugs. In some guideline, palonosetron is recommended as an antiemetic drug for moderate emetic chemotherapy combined with dexamethasone and is preferred for highly emetic chemotherapy combined with aprepitant. There was no data of effect of palonosetron of cehemo or chemo-radiation therapy using 5FU and cisplatin (FP) for EC. Aim of this study is to investigate safety and antiemetic effect of palonosetron combined with aprepitant and dexamethasone for FP+radiation therapy of EC. Methods: Single arm phase 2 trial was conducted. 30 chemo and radiation therapy naïve patients of esophageal cancer were enrolled. FP schedule was as below; Cisplatin 70 mg/m2 was administered by slow drip infusion on days 1 and 5-FU 700 mg/m2/day was administered by continuous infusion for 24 h on days 1–5. Radiation was performed 1.8-2.0 Gy on day 1-5. Antiemetic treatment was performed as below; palonosetron 0.75 mg/body on day 1 by IV, aprepitant 125 mg/body on day 1 and 80 mg/body on day 2, 3 per OS and dexamethasone 13.2 mg/body on day 1 and 6.6 mg/body on day 2-5 by IV. Primary endopoint was complete response rate (CR) of acute phase (0-24 hrs) and delayed phase (24-120 hrs). Antiemetic effect was evaluated by a questionnaire answered by each patient. Adverse events were evaluated by CTCAE ver. 4. Results: Enrolled 30 patients were 4 (13.3%) of females and 26 (86.7%) of males. Seven (23.3%) were chemotherapy only and 23 (76.6%) were chemoradiation therapy. Alcohol consumption was No; 8 (26.7%), rarely, sometimes; 1 (3.3%) and everyday; 21 (70%). CC of acute phase was 96.7%, CC of late phase was 86.7%, and then CC of overall was 86.7%. Total control (TC) of early phase was 96.7%, TC of late phase was 73.3% and TC of over all was 73.3%. There was no severe adverse event relating to palonosetron. Conclusions: Palonosetron combined with aprepitant and dexamethasone showed very good antiemetic effect in both of early and late phase of chemo and chemoradiation therapy of EC. Clinical trial information: 000005017.
NRAS mutation: A potential biomarker of clinical response to immune-based therapies in metastatic melanoma (MM).
Authors: Douglas Buckner Johnson, Christine Marie Lovly, Marisa Flavin, Gregory Dan Ayers, Zhiguo Zhao, Wade Thomas Iams, Anthony John Iafrate, Elizabeth Gates Berry, Charles R Terry, Ryan J. Sullivan, Richard D. Carvajal, Jeffrey Alan Sosman
Journal: Journal of Clinical Oncology (2013)

9019 Background: NRAS mutant (mut) MM comprises a distinct, molecularly defined cohort of this disease that appears to have a poor prognosis compared to other genetic subsets. In contrast to BRAF mut MM, there are no effective small molecule inhibitors specifically targeting NRAS. Immune based therapy (IT) has become a mainstay in MM treatment, especially in BRAF wild type (WT) patients (pts). Biomarkers to predict which pts will benefit from IT have not been validated. The goal of this study was to evaluate whether genetic subtype (specifically NRAS) has a role in predicting benefit from IT in BRAF WT MM. Methods: We identified 173 pts from 3 institutions who underwent clinical genotyping (exome or PCR based) for NRAS and BRAF mutation from 1/09 – 8/12 and were treated with IT (defined as IL-2, ipilimumab (ipi), or anti-PD-1 (nivolumab, MK3475)/ PD-L1 (MPDL3280A)). Only BRAF WT pts were included. Primary endpoints were response rate (RR) and clinical benefit rate (CBR), defined as RR + stable disease lasting &gt;24 wks to IT (best response as assessed by treating clinicians in any line of IT). Secondary endpoints were overall survival (OS) and progression-free survival (PFS) from first line IT. Results: Of the 173 pts, 59 had NRAS mut MM compared to 114 WT/WT (no mutation in NRAS or BRAF). Improved clinical outcomes were seen in the NRAS mut compared to WT/WT cohort in terms of RR (32% vs. 18%, p=0.042), and CBR (49% vs. 30%, p=0.012). Improvements in PFS and OS did not reach statistical significance. By specific IT, NRAS mutation predicted benefit compared to WT/WT for anti-PD-1/PD-L1 (RR 78% vs. 19%, p=0.002; CBR 78% vs. 29%, p=0.013, n=30) and ipi (RR 18% vs. 12%, p=0.315; CBR 41% vs. 22%, p=0.018, n=137). No significant differences were observed with IL-2 (RR 33% vs. 28%, p=0.730; CBR 33% vs. 39%, p=0.741, n=33). Conclusions: This study demonstrates that pts with NRAS mut MM achieve increased clinical benefit from IT compared to pts with BRAF/NRAS WT MM. A larger, prospective analysis is necessary to validate and expand on these results, including those with BRAF mut and KIT mut MM. However, our data suggest that NRAS mutation status may be a biomarker of response to IT in MM and that molecularly targeted immunotherapy may be feasible.
Arsenic trioxide, ascorbic acid, filgrastim and erythropoietin for the treatment of myelodysplastic syndromes
Authors: N. Khera, H. Miske, R. K. Shadduck, J. M. Rossetti, J. Lister
Journal: Journal of Clinical Oncology (2007)

17519 Background: Arsenic trioxide (ATO) has been reported to have activity when used as monotherapy for the myelodysplastic syndromes (MDS). Herein we report the results of MDS patients treated with ATO as a differentiating agent coupled with ascorbic acid and cytokine pharmacotherapy. Methods: Nine patients with MDS, regardless of IPSS category and prior treatment, were enrolled in this study. Patients with the proliferative variant of CMML and those with significant cardiac dysfunction or a prolonged QT interval were excluded. They received ATO and ascorbic acid combined with growth factors. All patients received induction therapy with ATO at 0.25 mg/kg IV infusion daily x 5 for one week, followed by twice weekly for seven weeks. Responders were eligible for one consolidation cycle of twice weekly ATO for eight weeks. Four patients received one cycle of consolidation. G-CSF 300 mcg was given thrice weekly and EPO 40,000 units twice weekly. Ascorbic acid 1 gm was given intravenously 30 minutes after each dose of ATO. Response to treatment was assessed using the International Working Group (IWG) criteria for MDS. Results: Median age of patients was 69.5 years (range = 56 to 83 years). IPSS scores were: Int-1 = 5, Int-2 = 2, High = 2. Patients had received prior therapy with azacitidine (n = 8), cytokines (n = 4), and transfusions alone (n = 1). The overall response rate was 56% (5/9): partial response (PR) = 2, hematologic improvement (HI) = 3. Platelet responses were seen in 44% of patients (4/9). Four patients had stable disease (44%). The average duration of response for PR and HI was 122 days and 70 days, respectively. The overall median duration of HI was 3.5 months (range = 0.6 to 4.1 months). There were no cytogenetic responses noted in four evaluable patients. Four patients died during the study. Two patients died due to disease related illness and two due to complications of their comorbid conditions. No treatment related mortality was seen. Conclusions: Arsenic trioxide in combination with ascorbic acid and cytokines has activity in patients with MDS. Larger studies are necessary to establish the efficacy of this regimen earlier in the treatment schema of MDS. No significant financial relationships to disclose.
Association of IGF2 DMR0 hypomethylation in esophageal squamous cell carcinoma with poor prognosis.
Authors: Yoshifumi Baba, Masayuki Watanabe, Asuka Murata, Hironobu Shigaki, Shiro Iwagami, Takatsugu Ishimoto, Hideo Baba
Journal: Journal of Clinical Oncology (2013)

11065 Background: The insulin-like growth factor 2 gene (IGF2) is normally imprinted. Loss of imprinting (LOI) of IGF2 in humans is associated with an increased risk of cancer and is controlled by CpG-rich regions known as differentially methylated regions (DMRs). Specifically, the methylation level at IGF2 DMR0 is correlated with IGF2 LOI and is a suggested surrogate marker for IGF2 LOI. A relationship between IGF2 DMR0 hypomethylation and poor prognosis has been shown in colorectal cancer. However, no study has examined the relationships among the IGF2 DMR0 methylation level, LOI, and clinical outcome in esophageal squamous cell carcinoma (ESCC). Methods: The IGF2 imprinting status was screened using ApaI polymorphism, and IGF2 protein expression was evaluated by immunohistochemistry with 30 ESCC tissue specimens. For survival analysis, IGF2 DMR0 methylation was measured using a bisulfite-pyrosequencing assay with 216 ESCC tissue specimens. The Cox proportional hazards model was used to calculate mortality hazard ratios (HR) adjusted for clinical, epidemiologic, and pathological variables.The term “prognostic marker” is used throughout this article according to the REMARK Guidelines. Results: Twelve (40%) of 30 cases were informative (i.e., heterozygous for ApaI), and 5 (42%) of 12 informative cases displayed IGF2 LOI. IGF2 LOI cases exhibited lower DMR0 methylation levels (mean, 23%) than IGF2 non-LOI cases (37%). The IGF2 DMR0 methylation level was significantly associated with IGF2 protein expression. Among 202 patients eligible for survival analysis, IGF2 DMR0 hypomethylation was significantly associated with higher cancer-specific mortality (log-rank P=0.013; univariate HR=2.03, 95% confidence interval: 1.14–3.58, P=0.017; multivariate HR=2.34, 95% CI: 1.29-4.22, P=0.0054). Conclusions: The IGF2 DMR0 methylation level in ESCC was associated with IGF2 LOI and IGF2 protein expression. In addition, IGF2 DMR0 hypomethylation was associated with a shorter survival time, suggesting its potential role as a prognostic biomarker.
Health insurance and pancreatic cancer.
Authors: Cameron Schlegel, Liping Du, Yu Shyr, Martin Whiteside, Alexander A. Parikh
Journal: Journal of Clinical Oncology (2017)

247 Background: Health insurance disparities affect the treatment and outcomes of many cancers and include differences in screening, surgical therapy and receipt of adjuvant therapy. The purpose of this study is to better identify the effect of health insurance on surgical therapy and overall survival (OS) in pancreatic adenocarcinoma (PDAC). Methods: 4564 patients diagnosed with PDAC between 2004 and 2013 from the Tennessee Cancer Registry were stratified into 5 groups: Private, Medicare, Military, Medicaid, and uninsured. Univariate analysis and multivariable (MV) logistic regression models were used to test the association of insurance with receipt of surgical therapy, adjuvant therapy, OS and cost. Results: Uninsured and Medicaid patients were more often black and presented with later stage disease. In patients with stage 1 and 2 disease, R0 resection rates, lymph node positivity and overall cost were similar across insurance groups. By MV analysis, Medicare and Military insurance patients were more likely to be resected (OR 2.52 and 3.30 respectively) with a trend for private insurance (OR 2.19) compared to the uninsured and Medicaid. There was no difference in the use of adjuvant chemotherapy (ACT). By Cox-proportional hazards regression, OS in resected patients amongst different insurance groups and race were similar (Table). Factors associated with decreased OS survival included increasing age, stage, lymph node status, and grade while the use of ACT, but not chemoradiation (ACRT), was associated with improved OS. Conclusions: Uninsured and Medicaid patients with PDAC present with later stage disease and are less likely to undergo resection. The use of adjuvant chemotherapy, OS and cost, however, are similar among insurance types. These results are in contrast to other cancers, suggesting that disparities in health insurance may play a smaller role in more aggressive cancers without effective screening. [Table: see text]
Endoscopic submucosal dissection using a pocket-creation method: a modified technique of endoscopic submucosal tunnel dissection
Authors: Yuyong Tan, Deliang Liu, Jirong Huo
Journal: Endoscopy (2017)

We read with great interest the article by Miura et al. [1] entitled "Duodenal endoscopic submucosal dissection is feasible using the pocket-creation method." In this article, the authors described a novel endoscopic method for removal of nonampullary duodenal lesions, which they called endoscopic submucosal dissection (ESD) using a pocket-creation method (PCM). This new technique has several advantages over conventional duodenal ESD, including a lower rate of perforation and use in difficult locations such as duodenal angles.
Multicenter, phase II study of bendamustine in refractory or relapsed T-cell lymphoma: The BENTLY trial.
Authors: Remy Gressin, Gandhi Laurent Damaj, Kamal Bouabdallah, Guillaume Cartron, B Choufi, Emmanuel Gyan, Arnaud Jaccard, Sophie Park, Jean-Marc Schiano De Colella, Laurent Voillat, Bertrand Joly, Steven Le Gouill, Alain Saad, Laurence Sanhes, Marie-Pierre Moles-Moreau, Michael Bubenheim, Marie C. Bene, Antoine Martin, Jean pierre Marolleau, Thierry Lamy
Journal: Journal of Clinical Oncology (2012)

8026 Background: T-cell lymphomas have a poor prognosis with few options of effective treatment. This study determined the efficacy and safety of bendamustine as a single agent in the treatment of refractory or relapsed T-cell lymphomas. Methods: Patients with histologically confirmed peripheral T-cell lymphoma (PTCL) or cutaneous T-cell lymphoma (CTCL), who had previously received at least one line of chemotherapy were selected. Bendamustine was administered IV at the dosage of 120 mg/m 2 on days 1 and 2 every 3 weeks, for 6 cycles. Treatment response was assessed using the IWC for non-Hodgkin's lymphoma. The primary end point was overall response rate (ORR). Secondary end points were duration of response (DoR), progression-free survival (PFS), and overall survival (OS), NCT00959686. Results: Twenty two female and 38 male were included. The median age was 66 years with more 1/4 of them &gt; 75. Histology was predominantly angio-immunoblastic lymphadenopathy (n=32) and PTCL-nos (n=23). The median previous line of chemotherapy was 1 (1-3). Nearly one half (45%) of the patients was refractory to the last previous chemotherapy and the median duration of the best previous response was 6.6 (1.5-67) months. The disease was disseminated in the majority of case (87%) and the international prognostic index (IPI) was high (3–5) in 68% of the patients. Twenty patients (33%) received less than 3 cycles of bendamustine. The major reason for early discontinuation was disease progression. In the Intent-To-Treat (ITT) population, the best ORR was 50%, including complete response (CR) in 28% and partial response (PR) in 22 %. Bendamustine showed a consistency in the efficacy as a function of major disease characteristics. The median values for DoR, PFS and OS were 3.5, 4 and 6 months respectively. The most frequent grade 3/4 AEs were neutropenia (30%), thrombocytopenia (24%) and infections (20%). Conclusions: Bendamustine is active in high risk refractory and relapsed T-cell lymphoma with manageable toxicity.
Toxicity and survival in older versus younger esophageal cancer (EC) patients (pts) treated with neoadjuvant chemoradiotherapy (nCRT).
Authors: Rishi Jain, Jia-Llon Yee, Talha Shaikh, Cherry Au, Elizabeth Handorf, Joshua E. Meyer, Efrat Dotan
Journal: Journal of Clinical Oncology (2017)

204 Background: Trimodality therapy (TMT) for EC is associated with significant toxicity. Limited data are available on the safety of nCRT in vulnerable populations such as older pts. We evaluated the associations between age and toxicity as well as survival in pts treated with nCRT as part of TMT. Methods: A retrospective review of pts with EC treated with nCRT as part of TMT at an academic cancer center between 2002-2014 was conducted. We assessed the impact of age (&lt;65 versus ≥65) on chemotherapy dose reduction/interruption (DRI), hospitalizations (H), and toxicity including grade 3/4 (G3+T), and composite number of any grade non-hematologic (NHT) or hematologic (HT) toxicity. Relapse free (RFS) and overall survival (OS) were assessed with the Kaplan-Meier (KM) method. Univariate (UVA) and multivariate regression analyses (MVA) were performed. Results: 125 pts were identified. The median age was 63 (range 35-80) with 46% of patients ≥65.There were increased co-morbidities in older pts and more active smokers in younger group. Otherwise,baseline characteristics were well balanced. In UVA, advanced age was associated with increased HT, and a trend towards increased G3+T (table 1). After adjusting for covariates in MVA, no differences in toxicity were noted between older and younger pts. There were no differences in RFS or OS between groups (table).Conclusions: Our study demonstrates similar rates of toxicity and outcomes among older and younger EC patients treated with nCRT as part of TMT. Advanced age alone should not be a barrier to nCRT. [Table: see text]
Shifting revenue from drug sales to cognitive services: Impact on physician prescribing behavior.
Authors: Bruce A. Feinberg, Joseph Cooper, Winston Wong, Daniel Winn, Tim Olson, Ram Swarup Trehan, Jeffrey A. Scott
Journal: Journal of Clinical Oncology (2013)

6629 Background: Extensive literature has cited fee-for-service physician reimbursement methodology as a critical driver of resource utilization constituting overtesting, overtreatment, and an impediment to bending the cost curve in cancer care. CareFirst BlueCross BlueShield (CFBCBS) partnered with Cardinal Health Specialty Solutions to launch the first cancer clinical pathway in the US in Aug 2008. Physician participation was voluntary and reimbursement remained fee-for-service. Due to its early success with regard to savings and physician participation and compliance, an oncology medical home (MH) program was piloted in Jan 2011 offering a new physician reimbursement model, which shifted the source of revenue from margin on drug sales to cognitive services. This would allow physicians to focus on optimal patient (pt) care without the financial incentive to prescribe chemotherapy (chemo). We analyzed physician behavior modification after this change in reimbursement structure 1 year after implementation of the MH program. Methods: Practices that participated in the first pathways program were eligible to join the MH program. Claims data from CFBCBS were collected from Apr 2010 to Mar 2012. New and established pt visits, chemo administrations (admins) per pt and per practice, and % generic drug use were compared for year +1 versus year -1 of the MH program. Results: Fourteen practices (31 physicians, 478 pts) joined the MH program. In year +1, new pt visits increased by 2.7%, visits per established pt increased 1%, chemo admins per pt increased by 3%, and the percentage of regimens utilizing all generic drugs increased by 3.9%. Conclusions: Switching financial incentives from drug administration toward cognitive services did not significantly alter physician behavior with regard to the type or frequency of chemo admins or the frequency of pt visits. Whether this is because the physicians were mature pathways participants, influenced by brand-name prescription drug detailing, following National Comprehensive Cancer Network guidelines, or influenced by cognitive dissonance is speculative. Assumptions regarding fee-for-service reimbursement may not be applicable to chemo and will be further studied.