tbuckley/cabot-search huggingface dataset:
Effectiveness of trastuzumab in first-line HER2+ metastatic breast cancer after failure in adjuvant setting: A controlled cohort study.
Authors: Eva Negri, Alberto Zambelli, Matteo Franchi, Marta Rossi, Martina Bonifazi, Giovanni Corrao, Antonella Zambon, Lorenzo Moja, Carlo Zocchetti, Carlo La Vecchia
Journal: Journal of Clinical Oncology (2014)

e11571 Background: The evidence supporting the use of trastuzumab (T) in metastatic setting comes from studies that included (almost) only patients who never received prior T. We investigated the effectiveness of T as first line therapy for metastatic breast cancer (mBC) in women already treated with T in the adjuvant setting. Methods: Using record linkage of 4 admistrative healthcare databases of Lombardy, Italy, we identified 2046 women treated with T for early BC in 2006-2009, 96 of whom developed a metastasis and were retreated with T in first line for mBC (treatment group). We compared overall survival (OS) of these women with that of 197 women treated with T in first line for mBC, who were treated with therapies other than T for early disease (control group). We computed Kaplan-Meier 2-year OS, and used a proportional hazard model to estimate the hazard ratio (HR) of death of the intervention group as compared to the control group. Results: Two-year OS was 60.0% in the treatment group and 59.5% in the control group. The HR of death of the treatment group compared to the control group, adjusted by age and metastatic site, was 0.80 (95% Confidence Interval 0.50-1.28). Conclusions: Given the unavailability of data from randomized clinical trials, our data provide suggestive evidence that the outcome of women receiving first line T treatment for mBC after T-failure in adjuvant setting is comparable to that of women not exposed to T for early BC.
A phase 1b/II study of cancer stemness inhibitor napabucasin in combination with gemcitabine (gem) &amp; nab-paclitaxel (nabptx) in metastatic pancreatic adenocarcinoma (mpdac) patients (pts)
Authors: T. Bekaii-Saab, A. Starodub, B. El-Rayes, B. O’Neil, S. Shahda, K. Ciombor, A. Noonan, W. Hanna, A. Sehdev, W. Shaib, S. Mikhail, A. Neki, C. Oh, Y.Z. Li, W. Li, L. Borodyansky, C.J. Li
Journal: Annals of Oncology (2017)
Support ventilation versus conventional oxygen [1] (multiple letters)
Authors: Gad Cotter, Zvi Vered, Isaac Shpirer, J. Masip, A. J. Betbesé, J. Páez, F. Vecilla, Catherine Kelly, David E. Newby, Nicholas A. Boon, Neil J. Douglas, Stefano Nava, Annalisa Carlucci
Journal: The Lancet (2001)
Outpatient Stem Cell Mobilization with Intermediate-Dose Cyclophosphamide Is a Safe and Effective Procedure
Authors: Alessandra Pompa, Anna Ines Gregorini, Francesca Guidotti, Maria Cecilia Goldaniga, Francesca Gaia Rossi, Riccardo Marcolin, Luca Baldini, Agostino Cortelezzi
Journal: Blood (2016)
The effect of anti-thymocyte globulin on outcomes of reduced intensity conditioning for acute myelogenous leukemia.
Authors: Patrick Alan Hagen, John Wagner, Todd E. DeFor, Michelle Dolan, Mukta Arora, Erica D. Warlick, Daniel Jordan Weisdorf, Claudio G. Brunstein
Journal: Journal of Clinical Oncology (2014)

7034 Background: Antithymocyte globulin (ATG) has been administered to patients considered high risk for graft rejection and graft-versus-host disease (GVHD), such as those receiving HLA-mismatched allografts. If the benefits on engraftment and GVHD are offset by increased risk of relapse, delayed T-cell recovery, and increased infections remains controversial. Methods: We retrospectively studied the effect of ATG in 144 acute myelogenous leukemia (AML) patients undergoing nonmyeloablative umbilical cord blood transplantation (UCB) or HLA-matched sibling peripheral stem cell transplantation (PBSC). GVHD prophylaxis consisted almost universally of Cyclosporine and Mycophenolate mofetil. ATG was administered to a subgroup of patients who had not received immunosuppressive chemotherapy in the months (UCB = 3 months; PBSC = 6 months) prior to transplantation and considered high risk for graft rejection. Results: There were no significant differences between study groups in regards to disease status at treatment, disease risk, cytomegalovirus serostatus, and cytogenetic risk. ATG treated patients had significantly more infections between 46-180 days post-transplantation. The risk of treatment related mortality was 30 vs 20% (p=.45), in particular infection related death at 1 year was 21 vs. 10% (p=.12) for ATG and non-ATG recipients respectively. The cumulative incidences of acute and chronic GVHD were lower, but not statistically significant, in ATG treated patients. The cumulative incidence of relapse at 2 years was also lower (p=.09) in ATG treated patients. Outcomes were not influenced by donor type. Conclusions: The lower risk of relapse with ATG likely reflects our indication for ATG, possibly selecting patients with a less aggressive phenotype and longer pre-transplant remission. Regardless, ATG did not adversely influence risk of relapse. The lower, but not statistically significant reduction in the risk of GVHD in the ATG treated patients may reflect the limited number of events in our patients. In summary, we showed that when administering ATG in the non-myeloablative setting according to our institutional criteria in AML patients there was no adverse effect on outcomes.
Beyond first-line non-anthracycline-based chemotherapy for extranodal NK/T-cell lymphoma: clinical outcome and current perspectives on salvage therapy for patients after first relapse and progression of disease
Authors: S.H. Lim, J.Y. Hong, S.T. Lim, H. Hong, J. Arnoud, W. Zhao, D.H. Yoon, T. Tang, J. Cho, S. Park, Y.H. Ko, S.J. Kim, C. Suh, T. Lin, W.S. Kim
Journal: Annals of Oncology (2017)
Pegylated liposomal formulation of doxorubicin overcomes drug resistance in a genetically engineered mouse model of breast cancer
Authors: András Füredi, Kornélia Szebényi, Szilárd Tóth, Mihály Cserepes, Lilla Hámori, Veronika Nagy, Edina Karai, Péter Vajdovich, Tímea Imre, Pál Szabó, Dávid Szüts, József Tóvári, Gergely Szakács
Journal: Journal of Controlled Release (2017)
Effort to Relax School Lunch Guidelines
Authors: Jeff Lyon
Journal: JAMA (2017)

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Nrf2 Mutagenic Activation Drives Hepatocarcinogenesis
Authors: Hoang Kieu Chi Ngo, Do-Hee Kim, Young-Nam Cha, Hye-Kyung Na, Young-Joon Surh
Journal: Cancer Research (2017)

Nrf2, a master regulator of oxidative stress, is considered a prominent target for prevention of hepatocellular carcinoma (HCC), one of the leading causes of cancer-related deaths worldwide. Here we report that Nrf2-deficient mice resisted diethylnitrosamine (DEN)-induced hepatocarcinogenesis without affecting P450-mediated metabolic activation of DEN. Nrf2 expression, nuclear translocation, and transcriptional activity were enhanced in liver tumors. Overactivated Nrf2 was required for hepatoma growth in DEN-induced HCC. Following DEN treatment, Nrf2 genetic disruption reduced expression of pentose phosphate pathway-related enzymes, the depletion of which has been associated with an amelioration of HCC incidence. Conversely, enhanced Nrf2 activity was attributable to alterations in the ability to bind its endogenous inhibitor Keap1. Our findings provide a mechanistic rationale for Nrf2 blockade to prevent and possibly treat liver cancer. Cancer Res; 77(18); 4797-808. ©2017 AACR.
Early Low Level Hemolysis Is Associated with Subsequent Device Thrombosis and Ischemic Stroke during Continuous Flow Left Ventricular Assist Device Support By the Heart Mate II
Authors: Omar Saeed, Sabarivinoth Rangasamy, Mohammad Algodi, Morayma Reyes Gil, Snehal R Patel, Daniel J Goldstein, Henny H Billett, Ulrich P Jorde
Journal: Blood (2016)
Fosaprepitant use in children and adolescents at Memorial Sloan Kettering Cancer Center.
Authors: Dazhi Liu, Krisoula Horiates, Sherry Mathew, Melissa Pozotrigo, Jennifer Thackray, Michelle Kussin, Shirley Qiong Yan, Brian M. Seyboth, Shakeel Modak
Journal: Journal of Clinical Oncology (2017)

10575 Background: Recent NCCN guidelines recommend the addition of a neurokinin-1(NK1) receptor antagonist (e.g. fosaprepitant) to the serotonin 5-hydroxytryptamine type 3 (5-HT3) receptor antagonist-corticosteroid combination for controlling both acute and delayed chemotherapy induced nausea and vomiting(CINV) associated with high emetogenic chemotherapy (HEC) in adults. Fosaprepitant is bioequivalent to aprepitant and could offer benefits to patients who are unable to tolerate oral antiemetics. However, little is known about the efficacy and safety of fosaprepitant in children. Methods: This retrospective chart review included all pediatric patients less than 18 years of age who received fosaprepitant at Memorial Sloan Kettering Cancer Center from July 2011 to November 2016. Results: Thirty-one patient charts representing a total of 105 doses of fosaprepitant were reviewed. Median age was 15 (range 2-17) years. Fifty-one doses (49%) were administered for primary prophylaxis for 11 patients; 40 doses (38%) for 12 patients who had a history of severe CINV and 14 doses (13%) as rescue for CINV in 10 patients after chemotherapy. Seventy-eight of the 101 chemotherapy cycles were highly emetogenic including 39 containing cisplatin. In the first two groups, patients did not have any episodes of vomiting in 97% and 88% of chemotherapy cycles respectively after fosaprepitant therapy. Seven of 12 patients receiving fosaprepitant for &gt; 3 episodes of breakthrough vomiting within 24 hours had no vomiting episodes during the first 24 hours post fosaprepitant administration. No fosaprepitant-related side effects were reported. Conclusions: Fosaprepitant appears to be safe and tolerable in children with cancer in whom it may provide benefit as prophylaxis and treatment of CINV. However a phase III study is warranted to formally study its role in pediatrics.
Internet based double-blind cross-over clinical trial to test efficacy of high dose isoflavone soy in controlling breast cancer survivor hot flashes
Authors: W. C. Dooley, C. Hendricks, Y. Gusev, L. Shockney
Journal: Journal of Clinical Oncology (2006)

636 Background: Severe hot flashes are common after completion of allopathic breast cancer treatment. Hot flashes are rare in the Orient where high isoflavone soy diets are common. Methods: We enrolled breast cancer survivors experiencing hot flashes after the completion of surgery, radiation and chemotherapy into a 16 week double blind cross-over casein placebo controlled trial of a 160 mg isoflavone soy dietary supplement. Hot flash frequency, severity, and time of day, exercise time and patient journaling was recorded by an internet diary placed on a HIPPA compliant server with password access. Results: Of 168 patients enrolled, 117 actually participated in taking supplementation and completing internet diaries giving adequate data for analysis. Of this group 13 patients dropped out of study for failure to finish all dietary supplements throughout the study period. The hot flash data during the last 4 weeks on each supplement was compared to determine benefit. There was no statistical difference in hot flash frequency, intensity or duration between either supplement independent of exercise level. Interestingly, 82% of patients reported a decrease in hot flashes in the first 4 weeks of study independent of which supplement they were randomized to receive. The journal entries report during this “induction” period that the majority of patients had identified emotional or dietary or other triggers for their hot flashes. The avoidance of the triggers seemed to substantially reduce their reported menopausal symptoms. Conclusions: High dose soy isoflavone dietary supplementation is ineffective in reducing breast cancer survivor hot flashes. Journaling may have a benefit in allowing survivors to find their individual triggers for the most severe hot flashes. Internet patient data entry provides a unique and highly compliant tool for obtaining direct patient reporting in survivorship clinical trials. [Table: see text]
Correlation of PD-L1 expression with EGFR, KRAS, or ALK alterations and with survival of non-small cell lung cancer (NSCLC) treated with EGFR-TKIs: A meta-analysis of published trials.
Authors: Dianhe Li, Xiaoxia Zhu, Na Li, Yiyi Li
Journal: Journal of Clinical Oncology (2016)

e20576 Background: Pre-clinical data demonstrate that PD-L1 expression could be modulated by some driven genes. However, these associations and the utility of PD-L1 in advanced NSCLC patients undergoing EGFR-TKIs therapy have been inconsistent in clinical observations. Methods: A systematic review of Medline, EMBASE, Cochrane and meeting abstracts through October 2015 identified publications exploring PD-L1 expression combined with driven genes status or with EGFR-TKIs therapy. Pooled HRs for survival outcomes and ORs or RRs for dichotomous data with 95% CI were calculated. A random-effects model was used if there were heterogeneity between studies; otherwise, a fixed-effects model was used. Results: Ten studies were identified, including eight studies focused on EGFR status, five on KRAS status, four on ALK alterations, and three on EGFR-TKIs therapy. KRAS-mutant tumors were more likely to be PD-L1 positive than KRAS-wild type tumors (51% vs 36%; OR 1.69; 95% CI 1.01-2.84; p = 0.045). In contrast, PD-L1 expression did not differ by the status of EGFR (OR 0.86; 95% CI 0.43-1.73; p = 0.675) or ALK (OR 1.02; 95% CI 0.44-2.37; p = 0.954). There was significant heterogeneity in studies especially in PD-L1 positivity assessment criteria. When setting 5% as the cut-off for PD-L1 positivity and minimizing the impact of special histological type, positive PD-L1 expression was significantly correlated with the presence of EGFR mutations (OR 2.00; 95% CI 1.36-2.95; p < 0.001). In 209 EGFR mutant NSCLC patients treated with EGFR-TKIs, positive PD-L1 expression was statistically significantly associated with reduction in the risk of death (HR 0.49; 95% CI 0.29-0.83; p = 0.007) and progression (HR 0.57; 95% CI 0.32-1.00; p = 0.051), whereas no significant benefit was observed in unselected NSCLC patients received EGFR TKIs. Conclusions: NSCLC with KRAS mutations showed a trend for higher frequency of positive PD-L1 expression. PD-L1 positivity was predictive of survival benefit from EGFR-TKIs in EGFR mutant NSCLC patients. Our findings may help in the design of future clinical trials in advanced NSCLC patients.
ATTITUDES OF PHYSICIANS TOWARD WITHHOLDING AND WITHDRAWAL OF LIFE-SUSTAINING TREATMENTS IN ASIAN INTENSIVE CARE UNITS
Authors: J Phua, GM Joynt, M Nishimura, Y Deng, SN Myatra, YH Chan, NG Binh, CC Tan, MO Faruq, Y Arabi, B Wahjuprajitno, SF Liu, Smr Hashemian, W Kashif, D Staworn, Jem Palo, Y Koh
Journal: Intensive Care Medicine (2014)
Audit of Percutaneous Endoscopic Gastrostomy
Authors: M Ahmed, M O'Boyle, M Saba, K Walsh
Journal: Endoscopy (2006)

Background: Percutaneous endoscopic gastrostomy (PEG) is now the preferred method for long term enteral feeding. Concerns have been expressed about it's overall safety. The objective of this study was to assess the indication, complications, and 30-day mortality rate following insertion of a PEG tube.
An exploratory analysis of the R250W polymorphism in the KLK2 gene as a prognostic marker in prostate cancer
Authors: Manish Kohli, Paul Rothberg, Allison Constantino, Changyong Feng, Edward Messing, Deepak Sahasrabudhe
Journal: Clinical Cancer Research (2007)

PR-7  Background: A strong association of KLK2 gene expression with prostate cancer risk has been previously reported. KLK2 gene single nucleotide polymorphism (SNP) in exon 5 (rs198977; c.748C>T) results in R250W in the hKLK2 protein product. The Trp (W) allele has been shown to be enzymatically inactive and also associated with the development of prostate cancer (OR: 2.13). We hypothesize that presence of the Trp allele (CT/TT genotypes) in prostate cancer cases will result in shorter survival periods.  Methods: DNA was extracted from peripheral blood of prostate cancer patients after obtaining informed consent. The rs 198977 SNP was genotyped using a homogeneous nucleobase quenching assay. CT and TT genotypes were grouped together for data analysis. Clinico-pathological data was collected from medical records. Biochemical recurrence free survival (bRFS) in patients experiencing a rising PSA after primary prostate therapy was calculated in months from time of first diagnosis to PSA failure.  Results: One hundred and eighty two prostate cancer patients were genotyped (98% European ancestry). The overall distribution of the CC, CT and TT genotype was 48%, 44% and 8% respectively. Gleason score (GS) morphology was available on 169 of 182 patients. The distribution of high (8-10), moderate (5-7) and low GS (2-4) among the CC and CT/TT genotype groups was 14/82 (17%); 61 (74%) and 7 (9%) compared to 22/87 (25%); 64 (74%) and 1 (1%) respectively (significant p-value=0.03 only for low GS distribution). After a study mean follow up period of 85.4 months (SD: 69 months) 87/182 patients have experienced PSA relapse. The mean bRFS for high GS (8-10) group is 28.7 months (SD: 22.8 months) compared to 47.4 months (SD: 40 months) for moderate/low GS (≤7) (p-value= 0.01 two-sample t-test). The mean bRFS for patients with a CT/TT genotype was 39.6 months (SD: 38 months) compared to 58.1 months (SD: 49 months) for the CC group (p-value=0.06, two-sample t-test).  Conclusions: This exploratory analysis in a population of prostate cancer patients with a predominantly common ancestry investigates a prognostic role for a KLK2 SNP previously found associated with increased risk for cancer development. The Trp allele was found less likely to be associated with low GS morphology in the cancer cohort and more likely to have a shorter bRFS. Further studies are needed to confirm and extend these pilot findings for the R250W polymorphism as a genomic classifier for prognosis in larger prostate cancer cohorts.
PDK1-mediated IKKβ phosphorylation activates NF-κB signaling
Authors: Hiroshi Tanaka, Naoya Fujita, Takashi Tsuruo
Journal: Cancer Research (2006)

4837   The IκB kinase (IKK)/NF-κB and phosphatidylinositol-3-OH kinase (PI3K)/3-phosphoinositide-dependent protein kinase-1 (PDK1)/Akt pathways regulate various cellular functions, especially cell survival. These two pathways are often activated in many tumors and are thought to be associated with tumor progression. However, the crosstalk between them remains unclear. Here we show that PDK1 can activate IKK/NF-κB signaling in addition to Akt signaling to promote cell survival. Screening kinases that could modulate NF-κB activity revealed that expression of an upstream Akt kinase PDK1 upregulates NF-κB transcriptional activity. We found that PDK1 directly phosphorylates IKKβ at the Ser 181  residue in the activation loop, leading to NF-κB nuclear translocation and NF-κB-dependent anti-apoptotic gene expression. IKKα is not required for PDK1-mediated NF-κB activation because NF-κB activation was observed in  IKK α -/-  MEF cells as in wild-type MEF cells. Akt, which was previously reported to activate IKKα, did not participate in the PDK1-dependent IKKβ or NF-κB activation. The siRNA-me diated  PDK1  gene silencing attenuated NF-κB activity and increased TRAIL-mediated cytotoxicity. Moreover, expression of constitutively active IKKβ (CA-IKKβ) overcame the PDK1 siRNA-mediated susceptibility to TRAIL. These results indicate that PDK1 is a critical regulator of cell survival by modulating the IKK/NF-κB pathway in addition to the Akt pathway. Therefore, PDK1 would be a promising and an attractive target for cancer chemotherapy.
Feasibility of next-generation sequencing (NGS) for squamous non-small cell lung cancer (NSCLC): Implications for the NCI LungMAP study.
Authors: Adrian G. Sacher, Lynette M. Sholl, Stacy L. Mach, Bruce E. Johnson, Peter S. Hammerman, Pasi A. Janne, Geoffrey R. Oxnard
Journal: Journal of Clinical Oncology (2015)

8096 Background: While potentially targetable genomic alterations have been identified in squamous NSCLC, none have yet been translated into effective therapy. The NCI LungMAP study was designed to match patients (pts) with advanced squamous NSCLC to genotype selected treatment using targeted NGS. We studied a large cohort of consecutive pts with squamous NSCLC to gauge the feasibility of NGS for clinical trial arm allocation. Methods: All patients presenting to the Dana-Farber Cancer Institute are offered targeted NGS of existing biopsy samples under an institutional protocol (#11-104). This internally developed NGS assay sequences over 300 genomic targets of interest with a mean overall target coverage of 200x. All squamous NSCLC pts seen at our institution during the study period were identified from an institutional database. The rate of test utilization, assay failure, and detected genomic alterations were studied. Results: 174 pts with squamous NSCLC presented to our institution from 7/1/2013-11/18/2014. Of these, 100 consented to targeted NGS. Median age was 65, 89% and 11% were heavy versus light/never smokers, 66% were stage IIIB/IV. The majority of patients underwent core biopsy (52 core, 30 resection, 14 FNA, 3 cytology) Targeted NGS was successful in 74 patients, pending in 12 patients and failed in 13 patients due to insufficient tissue (5 FNA/cytology, 8 core). The mutational rates for each target of the LungMAP study were as follows: PIK3CA mutation 12% (9), CCND1-2 amplification 16% (12), CDK4 amplification 3% (2), FGFR1-4 amplification 24% (18), FGFR1-4 mutation 7% (5) and MET amplification 3% (2). Of these, 12% (9) pts had multiple targets detected. 18% (6/33) of these amplification events were high level (ploidy estimate > 5 copies). Conclusions: NGS in a real-world squamous NSCLC cohort is feasible and yields a high rate (51% pts) of potentially targetable genetic alterations. The majority of amplification events are low-level (2-5 copies) which may be challenging to therapeutically target. Our findings support the use of targeted NGS as a tool to facilitate trial enrollment in studies such as the NCI LungMap and Match studies.