tbuckley/cabot-search huggingface dataset:
Low-Intensity Transcranial Current Stimulation in Psychiatry
Authors: Noah S. Philip, Brent G. Nelson, Flavio Frohlich, Kelvin O. Lim, Alik S. Widge, Linda L. Carpenter
Journal: American Journal of Psychiatry (2017)

Neurostimulation is rapidly emerging as an important treatment modality for psychiatric disorders. One of the fastest-growing and least-regulated approaches to noninvasive therapeutic stimulation involves the application of weak electrical currents. Widespread enthusiasm for low-intensity transcranial electrical current stimulation (tCS) is reflected by the recent surge in direct-to-consumer device marketing, do-it-yourself enthusiasm, and an escalating number of clinical trials. In the wake of this rapid growth, clinicians may lack sufficient information about tCS to inform their clinical practices. Interpretation of tCS clinical trial data is aided by familiarity with basic neurophysiological principles, potential mechanisms of action of tCS, and the complicated regulatory history governing tCS devices. A growing literature includes randomized controlled trials of tCS for major depression, schizophrenia, cognitive disorders, and substance use disorders. The relative ease of use and abundant access to tCS may represent a broad-reaching and important advance for future mental health care. Evidence supports application of one type of tCS, transcranial direct current stimulation (tDCS), for major depression. However, tDCS devices do not have regulatory approval for treating medical disorders, evidence is largely inconclusive for other therapeutic areas, and their use is associated with some physical and psychiatric risks. One unexpected finding to arise from this review is that the use of cranial electrotherapy stimulation devices-the only category of tCS devices cleared for use in psychiatric disorders-is supported by low-quality evidence.
Prognostic value of methlylenetetrahydrofolate reductase (MTHFR), thymidylate synthase (TS) promoter, and p53 codon 72 variants and survival in advanced non-small cell lung cancer (NSCLC).
Authors: T. Franchina, N. Ferlazzo, F. Colonese, E. Alafaci, A. D' Aquino, G. Ferraro, C. Garipoli, C. Maisano, M. Picciotto, M. Currò, R. Ientile, V. Adamo
Journal: Journal of Clinical Oncology (2011)

e21161 Background: Folate plays an important role as a cofactor of enzymes involved in DNA synthesis and in the regulation of gene expression through methylation. Hypometylation of the p53 tumor suppressor gene has been described in folate depletion. p53 codon 72 polymorphism influencing the function of the protein is thought to be linked with an increased risk of lung cancer. Since MTHFR 677 and 1298 SNP and TS promoter polymorphisms are involved in folate metabolism, DNA methylation and DNA repair we tested their expression and interaction with p53 codon72 polymorphism in patients (pts) with locally advanced and metastatic NSCLC and compared with patients’overall survival (OS). Methods: Genomic DNA was isolated from peripheral blood lymphocytes of 50 pts, using Puregene Genomic DNA Purification System. Pts (36 M/14 F) median age was 61.5 (range 45-84).Median OS was 21,2 months. Genotyping for MTHFR polymorphism was carried out by DG-DGGE(double gradient-denaturing gradient gel electrophoresis), for p53 codon 72 (Arg/Pro) with the use of fluorogenic allele-specific oligonucleotide TaqMan probes on a 7900HT Fast Real-Time PCR System and for TS Promoter Polymorphisms with PCR and subsequent electrophoresis on 3% agarose gel. Products of 214 bp, 242 bp, or both, depending on the TS promoter genotype, were observed. TS tandem repeats and SNPs were combined. Patient’s overall survival were compared with MTHFR, TS and/or p53 codon 72.A multivariate analysis was performed. Results: We have recorded no significant correlations between survival data and the expression of MTHFR 677 and 1298 SNPs, TS tandem repeats, and p53 codon 72 polymorphisms, considered separately. However, the combined MTHFR CT677/AC1298 genotype was significantly associated with longer survival (34,5 months p<0,05) also in association of TS genotype homozygous for triple repeats (3R/3R), (29,5 months p<0,05). Conclusions: Although preliminary, these data support the role of MTHFR and TS genotypes as prognostic marker in NSCLC patients, where gene-gene interactions between the genotypes may occur. Further studies are needed to confirm these findings.
In Vivo Bioluminescence Imaging (BLI) and Sequential 18F]FHBG microPET Imaging Studies of Human T Cell (huT) Trafficking, Expansion and Xenogeneic Graft-Versus-Host-Disease (XGVHD) Following Different Routes of T Cell Administration.
Authors: Bruno Nervi, Michael P. Rettig, Julie K. Ritchey, Hanlin L. Wang, Gerhard Bauer, Jon Walker, Julie L. Prior, David Piwnica-Worms, Jan A. Nolta, John F. DiPersio
Journal: Blood (2006)
Side effects associated with the use of dexamethasone for prophylaxis of delayed emesis after moderately emetogenic chemotherapy
Authors: J. L. Vardy, K. Chiew, J. Galica, I. F. Tannock
Journal: Journal of Clinical Oncology (2005)

8017 Background: The role of dexamethasone to reduce delayed emesis following highly emetogenic chemotherapy is proven, but there is less evidence of benefit after mild-moderately emetogenic regimens. Here, we develop and evaluate a Dexamethasone Symptom Questionnaire [DSQ] to assess the side effects of dexamethasone in the week after patients receive moderately emetogenic chemotherapy. Methods: After optimization with a focus group, 60 patients receiving oral dexamethasone for delayed prophylaxis of emesis after adjuvant chemotherapy for breast cancer completed and then evaluated the DSQ. Results: Patients reported that the DSQ was worded clearly and addressed items important to them. Patients receiving dexamethasone reported moderate-severe problems with insomnia (45%), indigestion/epigastric discomfort (27%), agitation (25%), increased appetite (18%), weight gain (17%) and acne (15%) in the week following chemotherapy. (See table) Conclusions: The side effects of dexamethasone may outweigh its benefits when used with moderately emetogenic chemotherapy as prophylaxis for delayed nausea and vomiting. A randomized, double-blind crossover trial is underway to determine the effect of dexamethasone on nausea and vomiting, and the impact of side-effects of dexamethasone and of nausea and vomiting, on quality of life. No significant financial relationships to disclose.
Comparative effectiveness of primary tumor resection in metastatic colon cancer: An instrumental variable analysis.
Authors: Zeinab Alawadi, Uma Phatak, Chung-Yuan Hu, Christina Edwards Bailey, Lillian Kao, Y. Nancy You, George J. Chang
Journal: Journal of Clinical Oncology (2015)

674 Background: Although the safety of chemotherapy without primary tumor resection (PTR) has been established, questions remain regarding potential survival benefit with PTR. The purpose of this study was to compare mortality with and without PTR among patients with unresectable metastatic colon cancer using nationwide hospital based cancer registry data. Methods: An observational study was conducted of patients with stage 4 colon cancer identified from the National Cancer Data Base (2003-2005). Patients who underwent metastectomy were excluded. Patient, treatment, and hospital data were analyzed. Multivariate Cox regression stratified by receipt of chemotherapy was performed to compare survival with and without PTR. To account for treatment selection bias, Propensity Score Weighting (PSW) and Instrumental Variable (IV) analyses, using hospital-level PTR rate as the instrument, were performed. In order to account for the potential bias associated with early comorbidity or disease burden associated deaths (survivor treatment bias), 1 year landmark analysis was performed. Results: A total of 14,399 patients met inclusion criteria and 6,735 patients were eligible for landmark analysis. PTR was performed in 38.2% of the total cohort and 73.8% of those at landmark. Using multivariate Cox regression analysis, PTR was associated with a significant reduction in mortality (HR 0.39; 95% CI, 0.38-0.41). This effect persisted with PSW (HR 0.4; 95% CI, 0.38-0.43). However, IV analysis showed a much smaller effect, (RR 0.88; 95% CI, 0.83-0.93). While a smaller benefit was seen on landmark analysis using multivariate Cox regression (HR 0.6; 95% CI, 0.55-0.64) and PSW (HR 0.59; 95% CI, 0.54-0.64), IV analysis showed no improvement in survival with PTR (RR 0.97; 95% CI, 0.87-1.06). Stratification by chemotherapy did not alter the results. Conclusions: Among patients with stage IV colon cancer, PTR offered no survival benefit over systemic chemotherapy alone when the IV method was applied at the 1 year landmark. Subject to selection and survivor treatment bias, standard regression analysis may overestimate the benefit of PTR. Future study should focus on identifying patients most likely to benefit from PTR.
Collaborating with Ontario cancer centers to ensure coordinated access to safe, evidence-based, high-quality IMRT treatment.
Authors: Elizabeth Murray, Kate Bak, Eric Gutierrez, Padraig Richard Warde
Journal: Journal of Clinical Oncology (2013)

187 Background: In 2007, CCO identified variability in access to Intensity Modulated Radiation Therapy (IMRT) across the province. To ensure access to this technology, a three-year IMRT implementation Project was started in 2008, focusing on the development of: disease site guidelines and targets, cost-effectiveness analyses, a provincial quality assurance program, disease and discipline specific communities of practice and knowledge-sharing platforms. Methods: Needs assessments were conducted to identify educational and training needs in all disciplines. Systematic reviews were undertaken to establish disease site specific IMRT indications, set targets and conduct cost effective analyses. Educational courses and hands on expert-based coaching, were made available and a provincial IMRT quality assurance program was established. Results: The needs assessments identified a strong interest in educational and coaching opportunities. IMRT indication guidelines were developed for 10 disease sites and utilization targets were set for 6 disease sites. Results from two cost effectiveness analyses confirmed IMRT as a standard of care over 3D Conformal Radiation Therapy. 11 cancer centres received IMRT expert-based coaching, which included hands on-training, site visits, and educational support. Knowledge sharing and educational opportunities were provided to over 949 radiation therapists, oncologists and physicists. 13 cancer centres participated in external IMRT quality assurance testing for head and neck and prostate cancer. IMRT utilization has increased without affecting wait times or patient safety with no increase in incidents during this time period. All six disease sites have me their targets for 2012/13. Conclusions: IMRT knowledge and expertise across the province has grown along with a dramatic increase in the percentage of patients being treated for curative intent receiving IMRT. This jurisdictional implementation project was successful in making this treatment available to all Ontarians who would benefit. The lessons learned from this experience may be useful in the future rollout of other new technologies in Ontario and in other health care settings.
<i>PIK3CA</i> as a predictor of the clinical efficacy for epirubicin plus docetaxel neoadjuvant chemotherapy in breast cancer.
Authors: Xi Ru Li, Yan Jun Zhang, Mei Liu, Yi Qiong Zheng, Hui Yi Yang
Journal: Journal of Clinical Oncology (2012)

113 Background: PIK3CAgene mutations are the most common activating mutations in human breast cancer (BC). Its association with the resistance to herceptin in HER2-positive BC was reported, but whether it’s related to the efficacy of neoadjuvant chemotherapy is unknown. Methods: We reviewed records of 108 patients with BC treated with epirubicin plus docetaxel neoadjuvant chemotherapy between June 2005 and April 2011. 92 patients’ clinical and pathologic objective response data were collected. FFPE tumor biopsies obtained at the time of diagnoses (and before treatment) were collected. EGFR, KRAS, BRAF, PIK3CA mutations and HER2, PTEN, EGFR mRNA expression were analyzed by liquidchip technology. Chi-square test and Fisher’s exact test were used in statistical analysis. A p value less than 0.05 was considered statistically significant. Results: No mutation was detected in EGFR, KRAS and BRAF. The mutation rate of PIK3CA was 35.1% (38/108), and mutation rates of E542K, E545K, H1047L and H1047R were 3.7, 10.2, 3.7 and 17.6% respectively. More PIK3CA mutations were detected in HER2 high expression tumors (p=0.018). No correlation was found between PIK3CA mutations and PTEN, EGFR expression. Clinical response (CR+PR, 63/92) was associated with PIK3CA mutations (p=0.002). However, PIK3CA mutations rate between pathologic complete release (pCR, 7/92) and non-pCR group was not significantly different (p=0.422). Conclusions: PIK3CA mutation may predict better clinical response in BC patients treated with epirubicin plus docetaxel neoadjuvant chemotherapy. More studies are needed to validate these results and the correlation between PIK3CA mutations and pCR.
Prognostic impact of baseline serum C-reactive protein in metastatic renal cell carcinoma treated with sunitinib.
Authors: Vano Yann-Alexandre, Benoit Beuselinck, Pascal Wolter, Corine Teghom, Debruyne Philip, Alexandra Karadimou, Evelyne Lerut, Paridaens Robert, Patrick Schöffski, Stephane Oudard
Journal: Journal of Clinical Oncology (2013)

425 Background: The aim of our study was to determine whether baseline serum C-reactive protein (CRP) level could predict outcome of patients with metastatic renal cell carcinoma (mRCC) receiving sunitinib in first-line setting. Methods: We reviewed the charts of 187 consecutive patients in three hospitals in Belgium and France who started sunitinib as first targeted treatment between 2005 and 2012. Data were collected from each individual patient file on known prognostic factors for mRCC and anatomical location of metastatic sites, response rate, progression free survival (PFS), and overall survival (OS). Results: 187 eligible patients were identified by retrospective chart review. Median PFS was 26 months in the group with baseline CRP within normal limits (≤5 mg/l) versus 8 months in the group with elevated baseline CRP (&gt;5 mg/l) (p &lt; 0.0001). Median OS was 50 versus 12 months respectively (p &lt; 0.0001). In the group with normal baseline CRP, 69% of patients experienced a partial response (PR) compared to 31% of patients in the group with elevated baseline CRP (p &lt; 0.0001). On multivariate analysis, taking into account baseline neutrophil count, platelet count, ECOG PS, serum lactate dehydrogenase (LDH) activity, hemoglobin levels, corrected serum calcium levels, interval between initial diagnosis of RCC and start of systemic therapy &lt;/≥12 months, presence/absence of liver metastases or bone metastases and prior nephrectomy, baseline serum CRP-level was found to be an independent variable associated with poor PFS (p = 0.01) and OS (p &lt; 0.0001). Conclusions: Baseline serum CRP level is an independent parameter correlated with ORR, PFS and OS in mRCC patients treated with sunitinib in first-line. [Table: see text]
Matched pair analysis of sequential short course radiotherapy and FOLFOX chemotherapy as preoperative therapy for rectal cancer compared to neoadjuvant long course chemoradiotherapy.
Authors: Fady Youssef, Stephanie Subasic Markovina, Shariq S. Khwaja, Todd A. DeWees, Steven R. Hunt, Benjamin R. Tan, Robert J. Myerson, Parag J. Parikh, Jeffrey R. Olsen
Journal: Journal of Clinical Oncology (2015)

665 Background: A recently completed institutional phase II trial evaluated near-total neoadjuvant therapy (nTNT) for locally advanced rectal cancer using short course radiotherapy (SCRT) followed by four cycles of FOLFOX prior to total mesorectal excision (TME). A matched pair analysis is presented to compare clinical outcomes for nTNT with conventional chemoradiotherapy (CRT), TME, and postoperative chemotherapy (CT) for patients treated at our institution. Methods: 80 patients with cT3-4N0-2M0-1 rectal adenocarcinoma planned for resection of all tumor enrolled on a phase II study of preoperative SCRT (25 Gy to the involved mesorectum, 20 Gy to elective nodes, in 5 fractions) followed by four cycles of mFOLFOX6 before TME, with 6-8 cycles of adjuvant FOLFOX suggested. 69 patients with cM0 disease comprised the study cohort for this analysis. Patients treated with conventional CRT, followed by TME and adjuvant CT (63% ≥4 cycles adjuvant FOLFOX) were identified and matched 2:1 for exact cTNM stage. Kaplan-Meier with log-rank analysis was used to compare local control (LC), distant metastasis free survival (DMFS), disease free survival (DFS), and overall survival (OS), and two-tailed Mann-Whitney and Chi-squared tests used to compare cohort characteristics. Results: Median follow-up was 26 and 49 months for the study and control groups, respectively. Median age (57 vs. 55 years, p = 0.98) and distance from the anorectal ring (6 vs. 5 cm, p = 0.16) were similar for study and control groups, respectively. Pathologic complete response (pCR) and T-downstaging rates were 30% vs. 23% (p = 0.26) and 75% vs 50% (p = 0.001) in the study and match cohort, respectively. Actuarial 2-year LC (97% vs. 98%, p = 0.69) and OS (100% vs. 95% at 2 years, p = 0.57) were similar between the study and control groups, respectively. Two-year DMFS (94% vs. 80%, p = 0.016) and DFS (94% vs. 80%, p = 0.027) were significantly better in the study cohort. Conclusions: Controlling for institutional bias, exact cTNM stage, and tumor location, nTNT resulted in increased T-downstaging, superior DMFS and DFS, and similar LC and OS compared to conventional CRT.
Chemosensitivity and clinical characteristics of pancreatic malignancies in <i>BRCA </i>mutation carriers.
Authors: Talia Golan, Zaheer Kanji, Ron Epelbaum, Nicholas Devaud, Efrat Dagan, Spring Holter, Dan Aderka, Bella Kaufman, Ruth Gershoni-Baruch, Malcolm J. Moore, Eitan Friedman, Steven Gallinger
Journal: Journal of Clinical Oncology (2013)

278 Background: Somatic inactivation of genes involved in homologous recombination (HR) may confer increased sensitivity to poly (ADP-ribose)- polymerase (PARP) inhibition and DNA cross-linking agents (eg. mitomycin C, platinum-based chemotherapy). Studies in BRCA associated ovarian cancer have demonstrated favorable outcomes with platinum based treatments. The role of BRCA mutations in pancreatic cancer outcome is understudied. In this study, the clinical features and therapeutic responses of BRCA 1/2 mutation carriers with pancreatic malignancies are reported. Methods: Patients with BRCA1/2 -associated pancreatic ductal adenocarcinoma (PDAC) diagnosed between January 1994-June 2012 were identified from clinical databases at three participating institutions. Demographic, clinical, and therapeutic response data were collected and analyzed using non-parametric models. Progression-free (PFS) and overall survival (OS) were analyzed. Results: Overall, 63 patients with PDAC and a BRCA1 (n=17), BRCA2 (n=43) or both (n=1) mutations were included. Mean age at diagnosis was 60.2 (range 33-83), 37 (58.7%) were male, 48 (76.2%) were Jewish, 26 (41.3%) were smokers, 55 (87.3%) had a family history of malignancy of which 18 (32.7%) had a history of PDAC. Twenty-five (39.7%) patients underwent a primary resection, and 30 (47.6%) had stage IV disease at presentation. PFS on platinum-based first-line chemotherapy in 12 metastatic BRCA positive cases (median: 90 days) was not statistically different than that of non-platinum chemotherapy treated carriers (n=18, median: 92 days) (p= 0.6412). Two patients with advanced disease were down-staged from unresectable to resectable using combination gemcitabine/cisplatin therapy. One of these is disease free at 50 months after surgery. Median OS for all 51 patients (excluding patients receiving experimental treatments) was 14.02 months (9.48-18.2). Conclusions: The natural history of BRCA associated PDAC appears similar to non-carriers. The role of platinum agents in these individuals remains unclear as data are not mature, however, to date, no difference in median PFS was observed. Surgical downstaging may be possible in a subset of these patients.
Pharmacogenetic variants and outcomes after hematopoietic cell transplantation.
Authors: B. Thyagarajan, P. Jacobson, S. Jackson, S. Basu, D. J. Weisdorf, M. Gross, M. Arora
Journal: Journal of Clinical Oncology (2011)

6601 Background: Allogeneic hematopoietic cell transplants (HCT) is potentially curative in patients with otherwise fatal malignancies. However, one third of patients experience recurrence of primary malignancy (disease relapse) and up to 50% die within the first year after HCT from treatment-related causes (transplant related mortality or TRM). Differential systemic drug kinetics, transport and repair of tissue damage, controlled by polymorphisms in chemotherapy and/or immunosuppressant related genes, could explain the differences in toxicity (TRM) or efficacy (disease relapse). Methods: We evaluated the association between single nucleotide polymorphisms (SNPs) and insertion/ deletion polymorphisms in the drug related pathways (n=118) with TRM at one year and disease relapse in a cohort of 467 recipient-donor pairs who underwent allogeneic HCT for treatment of hematologic malignancies at the University of Minnesota between 1998 and 2007. We used a Fine and Gray proportional hazards model adjusted for competing risks to evaluate the association between the genetic variants and time to the study outcomes. Results: After adjustment for age at transplant, donor type, race, conditioning regimen, disease status at time of transplant and diagnosis, one recipient SNP, rs4574536 in the heat shock protein, HSPA4 gene, and one donor SNP, rs2179591 in the nuclear receptor co-activator, NCOA3 gene were associated with decreased risk of TRM at one year (p= 0.01). Polymorphisms in heat shock proteins, which include one recipient SNP, rs6002182 in the HSP40 gene, and one donor SNP, rs8005905 in HSP90AA1 gene were associated with increased risk of TRM at one year (p≤0.01). Polymorphisms in the solute transporter membrane proteins, included one recipient SNP, rs4149056, in the SLCO1B1 gene and one donor SNP, rs138328, in the SLC25A17 gene were associated with increased risk of disease relapse (p=0.01). Conclusions: These findings provide evidence that genetic variants in pharmacogenetic pathways in both recipients and donors can influence the outcome of patients undergoing allogeneic HCT and if confirmed, could guide drug therapy during HCT.