tbuckley/cabot-search huggingface dataset:
Associations between genetic polymorphisms and survival in patients with advanced non-small cell lung cancer (NSCLC) treated with paclitaxel-based therapy
Authors: C. Lu, Y. Ye, J. Clague, J. Y. Chang, S. M. Lippman, D. J. Stewart, M. Spitz, X. Wu
Journal: Journal of Clinical Oncology (2008)

11107 Background: Germline genetic variants such as single nucleotide polymorphisms (SNPs) in genes involved in pathways related to drug transport and metabolism, cell cycle control, DNA repair, and apoptosis have been associated with clinical outcome in cancer patents. Paclitaxel is widely used in the treatment of advanced NSCLC. To test the hypothesis that common SNPs relevant to paclitaxel transport, metabolism, and cytotoxicity may affect clinical outcome, we explored the associations of SNPs in candidate genes involved in these pathways with survival in patients with advanced NSCLC who received paclitaxel-based therapy. Methods: 211 stage IIIB and IV NSCLC cases enrolled in a molecular epidemiology study who received first-line paclitaxel-based therapy were genotyped for 16 common polymorphisms in 11 selected genes involved in pathways which may influence paclitaxel transport, metabolism, and cytotoxicity. The SNPs included: MDR1 exon 26 C3435T, MDR1 exon 21 G2677A/T, p53 intron 3, p53 intron 6, p53 exon 4 R72P, FAS -670, FASL -834, p21 exon 2 S31R, CYP2C8, ERBB2 I655V, STK15 exon 4 F31I, STK15 exon 4 I57V, CCND1 exon 4 G870A, CDK4 promoter, CDK6 3’UTR, p27 5’UTR. Results: Patient characteristics: 59% male, 27% stage IIIB, 73% stage IV, 22% never smokers, median survival 12.5 months. Adjusting for age, gender, stage, performance status, weight loss, and smoking pack-years, patients with the MDR1 exon 26 variant genotype (C/T + T/T) had significantly better survival compared to patients with the wildtype genotype (P=0.044). The median survival time was 15.0 months for patients with the variant genotype and 9.6 months for those with the wildtype. Patients with the CYP2C8 variant genotype had significantly poorer survival compared to patients with the wildtype genotype (P=0.032). The median survival time was 11.8 months for patients with the variant genotype and 13.4 months for those with the wildtype. No significant associations with survival were observed with the other SNPs. Conclusions: SNPs in genes involved in drug transport and metabolism pathways may have prognostic importance in NSCLC patients treated with paclitaxel. Further studies are warranted. Supported by RO1 CA55769 and CA111646. No significant financial relationships to disclose.
Patients with Early T-Cell Precursor (ETP) Acute Lymphoblastic Leukemia (ALL) Have High Levels of Minimal Residual Disease (MRD) at the End of induction—A Children's Oncology Group (COG) Study.
Authors: Brent Wood, Stuart Winter, Kimberly Dunsmore, Elizabeth Raetz, Michael J. Borowitz, Meenakshi Devidas, Naomi J. Winick, William L. Carroll, Stephen P Hunger, Mignon L. Loh
Journal: Blood (2009)
LR11 Is a Novel Surface Marker for Normal Leukocytes and Leukemia Cells
Authors: Masahiro Takeuchi, Chikako Ohwada, Shio Sakai, Yusuke Takeda, Daijiro Abe, Naomi Shimizu, Emiko Sakaida, Takeharu Kawaguchi, Kohei Takubo, Hiroyuki Ebinuma, Isamu Fukamachi, Koutaro Yokote, Atsushi Iwama, Wolfgang J Schneider, Hideaki Bujo, Chiaki Nakaseko
Journal: Blood (2010)
Impact of neoadjuvant hormonal therapy (HT) on quality of life (QL) of patients treated with interstitial brachitherapy (IB) for localized prostate cancer (LPC):
Authors: O. Caffo, F. Valduga, G. Fellin, A. Bolner, F. Coccarelli, C. Divan, S. Mussari, F. Ziglio, M. Frisinghelli, E. Galligioni
Journal: Journal of Clinical Oncology (2005)

4744 Background: When IB is planned as definitive treatment for LPC, HT is frequently prescribed to shrink the tumor mass and improve treatment outcomes. IB may produce per se a negative impact on patients’ (pts) QL, which can further be worsened by pretreatment HT. Methods: From May 2000 to May 2004, a consecutive series of 177 pts has received IB in our institution as definitive treatment for LPC. Among these pts, 100 have received HT as neoadjuvant treatment. All pts were requested to self fill a QL questionnaire a week before, one month and then yearly after IB. The questionnaire, previously validated and used in a retrospective study (Br J Urol. 1996;78:557), identifies 7 QL subascales: physical (PHY) and psychological well-being (PSY), relational life (REL), physical autonomy (POW), rectal (REC), urinary (URI) and sexual functioning (SEX). QL was assessed based on the differences between the means subscales score values, before and after IB. The pts were stratified according to the use of HT and the differences were evaluated by ANOVA analysis and General Linear Model (GLM) Univariate procedure. Results: To date we have evaluated data from 154 pts (HT yes/no 86/68). Before IB no differences were observed between yesHT and noHT pts, excepting for sexual functioning: more noHT pts had regular sexual activity than yesHT (p = 0.03) and among sexually active pts, those not receiving HT experienced less sexual impairment (p = 0.02). Comparing the pre and post-IB subscales scores in the noHT group, we observed a statistically significant difference in REC, URI and SEX scales, while in yesHT group the differences were significant in REC and URI scales only. At GLM Univariate procedure, the influence of HT on SEX was greater than IB. Conclusions: Comparing pre- and post-IB QL data, it appears, that HT before IB may negatively affect, as expected, only sexual functioning, which may further be influenced by IB. By the time of the meeting, data concerning the yearly follow-up will be available and presented. No significant financial relationships to disclose.
Design of a phase II randomized, open-label trial of DN24-02, an autologous cellular immunotherapy targeting HER2/neu, in patients with surgically resected urothelial cancer at high risk of recurrence.
Authors: Dean F. Bajorin, Padmanee Sharma, Robert Brownell Sims, Andrew Sandler, Seth P. Lerner
Journal: Journal of Clinical Oncology (2012)

TPS4673 Background: Despite surgical resection and the use of (neo)adjuvant chemotherapy, up to 50% of patients with invasive urothelial carcinoma will have disease recurrence and eventually die of metastatic disease. New approaches are needed for these patients. Approximately 50% of patients with high-risk pathologic features have evidence of HER2 expression in the primary tumor or involved lymph nodes. DN24-02 is an autologous cellular immunotherapy targeting HER2, which is based on Dendreon’s Antigen Delivery Cassette technology – the same platform used for sipuleucel-T (an FDA-approved treatment for asymptomatic or minimally symptomatic metastatic castrate-resistant prostate cancer). Each dose of DN24-02 is manufactured by culture of peripheral blood mononuclear cells obtained by leukapheresis with a recombinant antigen that comprises components of the intra- and extracellular domains of the HER2 antigen linked to GM-CSF. A product similar to DN24-02 has shown evidence of safety and immune response in phase I studies. Objectives: The primary objective is to determine whether DN24-02, given as adjuvant therapy following surgical resection, can prolong survival compared to standard of care (SOC). Secondary objectives are to evaluate disease-free survival, safety, and immune responses to DN24-02. Methods: Eligible patients will have undergone surgical resection of a primary urothelial cancer, with either ≥pT2 or pN+ staging, and HER2 expression ≥1+ by IHC based on pathologic review. Approximately 180 patients will be randomized (1:1) to receive three IV infusions of DN24-02 as adjuvant therapy approximately every 2 weeks, or SOC. Stratification will include 1) neoadjuvant chemotherapy vs surgery alone; and 2) positive (pN+) vs negative lymph node involvement (pN0). Other adjuvant chemotherapy will not be allowed. Patients can be treated per SOC if there is disease recurrence. Patients will be monitored for evidence of recurrence by imaging, and followed for survival. Cellular and serological immune responses will be assessed at baseline and post-DN24-02 therapy.
Expression of estrogen receptor (ER) beta isoforms and Its correlation with DNA methylation in human epithelial ovarian cancer
Authors: F. Suzuki, J. Akahira, I. Miura, S. Nagase, T. Takano, H. Niikura, T. Suzuki, K. Ito, S. Hayashi, H. Sasano, N. Yaegashi
Journal: Journal of Clinical Oncology (2008)

11063 Background: Ovarian cancer is one of the leading causes of death from gynecological tumors in women. Several lines of evidence suggest that estrogens may play an important role in ovarian carcinogenesis, through binding with their receptors, ERα and ERβ. Two novel estrogen receptor β (ERβ) isoforms that diverge in their 5’-untranslated regions, ERβ mRNA (0K-1) and ERβ mRNA (0N-1), have recently been identified. This finding indicates that transcription of the human ERβ gene occurs from at least two different promoters, i.e., promoter 0K and promoter 0N. The purpose of this study was to study the expression of ERβ isoforms in primary cultures of normal human ovarian surface epithelial cells (OSE), a panel of ovarian cancer cell lines and in normal human ovarian tissues and ovarian cancer tissues; and to examine whether methylation of the two ERβ promoters is involved in regulation of ERβ gene expression or not. Methods: The expression of ERβ isoforms and the methylation status was evaluated in 8 OSE cells, 15 ovarian cancer cell lines, 6 normal, and 57 ovarian cancer tissues. Using quantitative real-time PCR techniques, mRNA expression levels of ERβ1, ERβ2 (ERβcx), ERβ3, ERβ4 and ERβ5 were evaluated. The methylation status of two ERβ promoters were confirmed by direct bisulfate sequencing. Results: ERβ1, ERβ2 and ERβ4 were significantly lower in ovarian cancer cell lines than OSE cells (p<0.01). In contrast, ERβ5 were significantly higher in ovarian cancer cell lines than OSE cells (p<0.01). Promoter 0N was unmethylated in OSE, but was extensively methylated in ovarian cancer cell lines. In contrast, promoter 0K was unmethylated in both normal and malignant ovarian epithelial cells. Correlation was detected between promoter 0N hypermethylation and loss of ERβ mRNA expression in ovarian cancer cell lines. These findings were also detected in ovarian cancer tissues. Conclusions: Decreased level of ERβ mRNA is considered to be associated with ovarian tumorigenesis, and that DNA methylation is an important mechanism for ERβ gene silencing in ovarian cancer. No significant financial relationships to disclose.
Assessing distress in patients with gastrointestinal tumors during radiotherapy.
Authors: Laeticia Hollant, Megan Paige Single, Katherine Gaines, Bridget Smart, Jacob Habboush, Tasneem Kaleem, Katherine S. Tzou, Stephen Ko, Heather Biers, Atiya Day, Robert Clell Miller
Journal: Journal of Clinical Oncology (2016)

524 Background: Psychosocial distress during radiotherapy (RT) for gastrointestinal tumors is poorly characterized. Since 2012, patients receiving RT in our clinic have been prospectively screened for causes of distress. The results of our screening were reviewed in order to elucidate concerns of GI cancer patients and to delineate patterns within patient reported distress (PRD). Methods: Patients treated with RT at our institution receive a 30 question PRD survey that also includes a linear analog measure of overall distress at the start and during RT. The PRD survey asks patients to rate forms of distress on a scale of 1 to 5 (5 being the most distressed). The survey also asks patients to rate overall distress according to the National Comprehensive Cancer Network (NCCN) Distress Thermometer on a scale 0 to 10. The reported results were retrospectively reviewed in patients receiving definitive RT for GI cancers from 04/02/2012 to 08/05/2015. Results: PRD surveys were completed by 113 patients, 55 (48.7%) male and 58 (51.3%) female. Median age was 65 years (range 28 to 93). The most common tumor histology was adenocarcinoma, 67 (59.3%). 105 patients (93.0%) received chemotherapy and 66 (58.4%) underwent surgery. Overall, NCCN distress thermometer results ranged from 0 to 10, with a median of 4.3. The mean distress scores for the top five complaints ranged from 1.27 to 2.63. Top distresses were “How will I feel during treatment” (2.63), “Fatigue” (2.45), “Pain that affects daily functioning” (2.35), “Out of pocket medical costs” (2.31), and “Sleep difficulties” (2.31). The least concerning complaints were “Housing during treatment” (1.27), “A loved one relying on me for their physical care” (1.30), “Spirituality” (1.33),“Family communication about my illness”(1.37), and “Transportation” (1.38). Conclusions: Patients’ major concerns were aligned with daily quality of life, such as fatigue, pain and insomnia. Highest reported distress was linked with the process of RT and side effects associated with treatment. Medical expenses were also perceived as a burden. Medical providers should identify psychosocial stressors during RT in order to effectively communicate and provide resources to improve quality of life.
A multicenter phase II study on the feasibility and efficacy of neoadjuvant chemotherapy for locally advanced rectal cancer.
Authors: Saori Goto, Suguru Hasegawa, Takuya Matsumoto, Koya Hida, Junichiro Kawamura, Satoshi Yamanokuchi, Takashi Yamaguchi, Ryo Matsusue, Yoshio Kadokawa, Shigeru Kato, Dai Manaka, Ryuta Nishitai, Akinari Nomura, Akiyoshi Kanazawa, Kenji Kawada, Takahisa Kyogoku, Yoshiharu Sakai
Journal: Journal of Clinical Oncology (2016)

730 Background: The aim of this prospective multi-center phase II study was to evaluate the feasibility and efficacy of neoadjuvant chemotherapy (NAC) for locally advanced rectal cancer (LARC). Methods: Patients with LARC (cStage II–III) were included; those with cT4b tumor were excluded. Six cycles of mFOLFOX6 plus either bevacizumab (bev) or cetuximab (cet), depending on KRAS status, were administered before surgery. Primary endpoint was R0 resection rate. Secondary endpoints included completion rate of NAC, response rate, postoperative complications, pathological complete response (CR) rate, overall and disease-free survival, and quality of life. Results: Sixty patients from 7 institutes were enrolled. mFOLFOX6 was administered with bev to 40 patients who had wild-type KRAS and with cet to 20 patients who had K-RAS mutations. Completion rate of NAC was 88.4% and overall response rate was 81.7%. Sphincter-preserving surgery and abdominoperineal resection were performed in 43 and 17 patients, respectively. Median operation time was 335 min and median blood loss was 40 g. R0 resection rate was 98.3% and pathological CR rate was 16.7%. Overall postoperative complication rate ( ≥ grade 2) was 21.7%, including anastomotic leakage (11.6%), surgical site infection (6.7%), and urinary dysfunction (3.3%). There were no significant differences between patients with wild-type KRAS and those with KRAS mutations in response rate, postoperative complication rate, and pathological CR rate. Conclusions: NAC was a feasible and promising treatment option for LARC. Clinical trial information: UMIN000005654.
Expression of Adam28 as a prognostic biomarker of survival in patients with early-stage non-small cell lung cancer.
Authors: Y. Zhang, X. Zhang, Y. L. Wu, G. Zhang, H. Cheng, S. Dong
Journal: Journal of Clinical Oncology (2011)

10600 Background: The Adam (a disintegrin and metalloproteinase) family could modulate key cell signaling pathways via the shedding of membrane-associated proteins. Overexpression of Adam28 is involved in cell proliferation and progression in various carcinomas. This study was aimed to evaluate Adam28 expression to serve as prognostic marker in non-small cell lung cancer (NSCLC). Methods: 100 lung cancer tumor tissues and 53 adjacent tissues from patients with stage Ι – IIIa were obtained between 2004 and 2006 in Guangdong Lung Cancer Institute. All of them were pathologically assessed and analyzed with expression profile microarray. Then we conducted the real-time quantitative PCR (qPCR) for validation on the expression level of Adam28 in cancer tissues. Disease free survival was plotted using the Kaplan-Meier method, univariate and multivariate analyses were performed for factors affecting survival of patients. Results: Microarray data demonstrated significantly increased expression of Adam28 in cancer tissues (P<0.001), and confirned by qPCR. Mean value of qPCR was considered as the cut-off point. The expression of Adam28 is significantly correlated with T staging and histology. Patients whose tumors displayed high-level Adam28 showed a significantly shorter mean recurrence time of 39.6 vs 53.4 months (P=0.017). Similarly,N status, clinical stage and performance status (PS) were significant prognostic markers in univariate Cox survival analysis (P-value of 0.1 was adopted as the limit for entering into multivariate survival analysis).Importantly, Adam28 expression (P=0.029) together with N status (P=0.036) and PS (P=0.024) proved to be independent prognostic parameters in multivariate analysis. Conclusions: Our results suggest that Adam28 expression is significantly increased in NSCLC and provides additional prognostic information for survival of surgically treated NSCLC patients. We further hypothesize that high-level expression of Adam28 could relate to an enhanced propensity of tumor cells for survival, proliferation and migration, which calls for further investigation.
Determination of dihydropyrimidine dehydrogenase (DPYD) gene single-nucleotide polymorphism (SNP) in Mexican patients with locally advanced esophageal carcinoma.
Authors: Erika Ruiz-Garcia, Alicia Lopez-Yañez, German Caderillo-Ruiz, Connie Zuratzi Deneken, Consuelo Diaz, MaryTere Herrera, Jesus Zamora Moreno, Horacio Noe López-Basave, Jaime G. De La Garza, Abelardo Meneses-Garcia, Horacio Astudillo
Journal: Journal of Clinical Oncology (2015)

93 Background: Fluoropyrimidines as 5-fluorouracil (5-FU) and its prodrug capecitabine are chemotherapeutic drugs commonly used in the treatment of gastrointestinal cancer. Patients with deficiency of dihydropyrimidine dehydrogenase enzyme (DPD), which interfere with the pyrimidine metabolism, could be at risk toxicity (mild, severe or lethal) because 80-90% of the administered 5-FU is catabolized by DPD. Methods: Retrospectively, we analyzed the initial paraffin embedded tissue block of 72 Mexican patients with locally advanced esophageal cancer, DPD activity was evaluated through the detection of the seven most relevant DPYD SNPs (IVS14 + 1G&gt;A; 85T&gt;C/85T&gt;T; 2657G&gt;A; 2921A&gt;T; 1679T&gt;G; 2846A&gt;T; and 496A&gt;G). Results: We found that 20.83% (15/72) of our patients had three different polymorphisms: 9.72% (7/72) were positive for SNP 496A&gt;G in heterozygous patients and 4.16% (3/72) in homozygous patients; 4.16% (3/72) were positive for SNP 2657G&gt;A in heterozygous patients; 2.77% (2/72) were positive for SNPs 85T&gt;C and 85T&gt;T in heterozygous patients. The rest of patients 79.10% (57/72) were negative to these SNPs. Conclusions: This is the first study in Mexican population, determining DPYD SNPs. We found that frequency of SNP 85T&gt;C and 85T&gt;T is similar as Oriental race (2-3%), but contrast with Caucasians (0.19%). The SNP 2657G&gt;A whose allelic frequency is unknown, in Mexicans is about 4%; meanwhile, for SNP 496A&gt;G which Caucasian prevalence was reported 0.8%, in our Mexican sample was very high (14%). None of our patients even those with toxicity grade 3-4, were positive to the SNP associated to high toxicity (IVS14 + 1G&gt;A). Because of this heterogeneity, know we are sequencing the complete gen.
Evaluating the quality of supportive oncology using patient-reported survey data.
Authors: Anne M. Walling, Sydney Morss Dy, Jennifer Malin, Jennifer W. Mack, Benjamin Kim, Karl Lorenz, Diana M. Tisnado
Journal: Journal of Clinical Oncology (2012)

42 Background: Quality indicators for supportive oncology care are critical for measuring and monitoring improvement in domains such as symptom management and communication. Patient-reported outcome (PRO) data may complement medical record documentation in assessing quality of care patients receive and perceive. To evaluate how PRO data may be used in quality indicators for key supportive oncology domains, we conducted a study using patient-reported data from a national cohort study, the Cancer Care Outcomes Research and Surveillance Consortium initiative. Methods: We analyzed patient survey responses with utilization and outcomes data from 4,174 patients diagnosed with lung or colorectal cancer of any tumor stage between 2003 and 2005, which included a variety of validated PRO instruments administered within approximately five months of diagnosis. We defined existing supportive oncology indicators addressing symptom management and end-of-life discussions, primarily from Cancer Quality-ASSIST and the American Society of Clinical Oncology Quality Oncology Practice Initiative, that could be feasibly obtained from the survey data, with adaptations as needed. For example, all patients were asked whether they had pain; for pain screening, a survey item asked patients who reported pain whether a provider knew about the patient’s pain, and for treatment, the survey asked patients whether the provider provided help for the pain. Results: See Table. Conclusions: In summary, quality of care for symptom management as measured by patient-reported survey data was highest for pain screening and treatment, and lowest for fatigue treatment and significant depressive symptoms. Quality was much lower for end-of-life discussions. Patient-reported outcome data can provide a valuable, patient-centered perspective on the quality of supportive oncology care. [Table: see text]
Phase III double-blinded, randomized trial to evaluate the use of black cohosh in the treatment of hot flashes: A North Central Cancer Treatment Group study
Authors: B. A. Pockaj, J. Gallagher, C. L. Loprinzi, P. J. Stella, D. L. Barton, J. A. Sloan, R. Rao, T. R. Fitch, K. M. Rowland, P. J. Novotny
Journal: Journal of Clinical Oncology (2005)

8013 Background: Hot flashes can cause significant morbidity in post-menopausal women and women undergoing or finished with breast cancer treatment. Based on initial pilot data suggesting black cohosh could be efficacious in the treatment of hot flashes, a phase III trial was initiated. Methods: A double-blind, randomized, cross-over methodology with two 4 week periods, was used to study the efficacy of black cohosh (1 capsule, Cimicifuga racemosa 20 mg BID) for the treatment of hot flashes in women. Participants kept a daily hot flash diary during a baseline week and then during an 8-week cross-over treatment period. Treatment effectiveness was measured using the mean daily numbers of hot flashes and the hot flash scores; the latter measured by assigning points (1–4, for mild to very severe) to each hot flash based on severity and then adding the points for a given time period. The study design provided 80% power to detect a moderate effect size difference (1/2 standard deviation) in the hot flash scores between the two treatment groups. Results: 132 patients were randomized between 10/31/03 - 3/4/04. Data on 80% of patients have been analyzed and are reported here. Toxicity was minimal and not different by treatment group with 83% of patients receiving black cohosh and 76% of patients receiving placebo reporting no adverse events. Patients receiving black cohosh reported a mean decrease in hot flash score (comparing the fourth treatment week to the baseline week) of 20% compared to 27% for patients on placebo (p=0.53). Mean hot flash frequency was reduced 17% on black cohosh and 26% on placebo (p=0.36). Patient treatment preferences were measured after completion of both treatment periods by ascertaining which treatment period, if any, the patient’s preferred: 34% of patients preferred the black cohosh treatment, 38% preferred placebo, and 28% did not prefer either treatment. Conclusion: This trial failed to provide any evidence that black cohosh reduced hot flashes more than the placebo did. No significant financial relationships to disclose.