tbuckley/cabot-search huggingface dataset:
Role of microbiota and Toll-like receptors in progression of esophageal adenocarcinoma (EAC) in a rat reflux model.
Authors: Lori A Kelly, Ali H Zaidi, Mark Barlek, Rachael Kreft, Ashten Omstead, Juliann Kosovec, Yoshihiro Komatsu, Blair A Jobe
Journal: Journal of Clinical Oncology (2015)

28 Background: The discovery of the link between H. pylori and gastric cancer may be the most direct proof that bacterial signaling and host response can result in carcinogenesis. Accumulating evidence supports that activation of the Toll-like receptor (TLR) signaling pathway by microbes is associated with the development of GI malignancies. Using the modified Levrat model of gastroduodenojejunal reflux which mimics the physiological and molecular sequence of human EAC in the rat, this study profiles the expression of genes central to TLR-mediated signal transduction as well as characterizes the esophageal microbiome across the spectrum of EAC development. Methods: Modified Levrat’s surgery induced chronic acid reflux in Sprague-Dawley’s with harvest of esophagus 40 weeks post-surgery. Macordissection of normal adjacent epithelium, Barrett’s esophagus (BE), dysplasia and EAC tumor was performed followed by RNA/DNA isolation. Five samples per group were selected for gene expression profiling on the Qiagen TLR Signaling Pathway PCR Array as well as microbiome analysis by IBIS technology. Validation of IBIS was performed by fluorescence in situ hybridization (FISH). Results: Gene expression analysis identified TLRs 1-3 and 6, 7, 9 as significantly upregulated in EAC compared to normal esophagus. TLR 1 and 5 were significantly upregulated in dysplasia. TLR 1 was significantly upregulated in BE and normal adjacent epithelium. Thirty seven genes involved in the TLR signaling pathway were dysregulated in EAC, 30 in dysplasia, 21 in BE and 23 in normal adjacent. IBIS analysis revealed a prevalence of E. coli in BE and EAC which was validated by FISH. Conclusions: Toll-like receptor (TLR) signaling pathway responses to E. coli may participate in the development of EAC. E. coli may be a potential risk factor for EAC requiring further clinical validation.
The pattern of complementary and alternative medicine use by cancer patients in Saudi Arabia.
Authors: A. R. Jazieh, R. Al Sudairy, O. A. M. Abulkhair, A. Alaskar, F. Al Safi, N. Sheblaq, H. Tamim
Journal: Journal of Clinical Oncology (2011)

e13011 Background: The use of complementary and alternative therapy (CAM) is common among cancer patients. However, the issue is not well studied among our patient population. Our study aimed at determining the patterns of CAM use among cancer patients in Saudi Arabia. Methods: Cross sectional study using interview-administered questionnaire was conducted on cancer patients seen at the Oncology Department, King Abdulaziz Medical City in Riyadh. Patients were asked about the use of CAM including dietary supplement (DS) and non DS remedies. Univariate and multivariate analyses were conducted to identify predicting factors for CAM use. Results: 453 adult patients were enrolled in the study with median age of 53.5 years (14.7–94.6), and female/male 271/182 (59.8/40.2%). 410 patients (90.5%) used some type of CAM remedy.399 patients (88%) used non DS remedy mainly of religious nature including reciting Quran (74.8%), prayer (16%), supplication (13%) and others (3.7%). 386 patients (85%) used DS including: Zamzam water (59.8%), honey (54%), black seed (36%), water with Quran recited on it (30%) and others. 90% of patients used CAM as cancer treatment and the rest for various reasons such as symptoms control or supportive treatment. Only 18% of the patients discussed CAM use with their physicians compared to 68% discussing it with the religious scholar (Sheikh). The univariate analysis revealed that only female gender is a predictor of CAM use which remain significant in a multivariate analysis in addition to current employment as shown in the table. Conclusions: The use of complementary therapies among Saudi cancer patients is very prevalent with predominance of interventions of religious background, reflecting the influence of religion on people lives especially when faced by a life threatening illness. Multiple regression analysis for the use of CAM (DS and non-DS). Characteristics Odds ratio 95% CI P value Dietary supplements Gender 2.05 1.09-3.86 0.03 Current employment 2.30 1.01-5.22 0.05 Nondietary supplements Gender 2.60 1.38-4.90 0.0030 Current employment 3.00 1.26-7.14 0.01
Reflecting time dependency in hazard rates to analyse the cost-effectiveness of letrozole or anastrozole versus tamoxifen as adjuvant therapies for early breast cancer in hormone receptor-positive (HR+) postmenopausal women: The U.S. perspective
Authors: J. Karnon, N. Mody-Patel, S. Kaura
Journal: Journal of Clinical Oncology (2008)

596 Background: The BIG 1–98 and ATAC randomized controlled trials demonstrated that, in postmenopausal women with hormone receptor-positive (HR+) early breast cancer, initial adjuvant therapy for 5 years with the aromatase inhibitors (AIs) letrozole (LET) or anastrozole (ANA) is superior to tamoxifen (TAM). The table shows the difference in early effects of the 2 AIs. This study shows the cost-effectiveness of 5 years of initial adjuvant therapy with LET or ANA versus 5 years TAM in a postmenopausal HR+ population. Methods: Clinical trial data from BIG-198 and ATAC populated a Markov model to estimate the incremental cost per quality-adjusted life year (QALY) gained of the AIs compared to TAM. Variable annual hazard ratios for time to recurrence over the 5 year treatment period were applied to a pooled set of variable annual hazard rates for TAM. Probabilities of breast cancer event type and adverse events (AEs) (end. cancer, fractures, stroke, VTEs, and bleeding) were based on published results of the clinical trials and U.S. studies. Costs of breast cancer and AE care, and QALY weights were taken from published studies. Incremental costs and QALYs were estimated over the lifetime of HR+ women aged 60 yrs, discounted at 5% annually. Results: LET increases QALYs by 0.22 per patient compared with TAM while ANA patients gain 0.18 QALYs. Mean incremental cost per QALY gained for the AIs compared to TAM were $37,328 for LET and $40,531 for ANA. Probabilistic sensitivity analysis demonstrated that LET and ANA have around a 70% probability of being cost-effective at a QALY value of $50,000. Conclusions: Adjuvant treatment of postmenopausal HR+ women with LET or ANA for 5 years is a cost-effective use of U.S. health care resources compared with TAM. Based on an indirect comparison of mean values, LET is more cost-effective than ANA, with a higher predicted increment in quality adjusted survival. Early Effects in the ATAC and BIG-198 Trials ATAC (No. of events at 2.5 years) BIG 1–98 (No. of events at 2 years) ANA TAM Prevented (% reduction) LET TAM Prevented (% reduction) Recurrences 196 236 40 (-17%) 117 168 51 (- 30%) Distant recurrences 133 143 10 (-7%) 87 125 38 (-30%) Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis Novartis Novartis
Phase II clinical trial of bortezomib and bevacizumab combination in recurrent glioblastoma.
Authors: D. A. Bota, Z. Eroglu, D. A. Reardon, B. D. Fu, J. Norfleet, A. Desjardins, M. E. Linskey, K. Peters, H. S. Friedman, J. J. Vredenburgh
Journal: Journal of Clinical Oncology (2011)

2056 Background: The only approved 2nd-line treatment for glioblastoma is Bevacizumab (Avastin), with estimated 6-month progression-free survival (PFS) rate of 42.6% and overall survival (OS) of 9.2 months. Laboratory data show Bortezomib (Velcade) is an effective agent in glioma models. We evaluated the combination of Avastin and Velcade in patients with recurrent GBM in a phase II, 2 center, open-label trial. Methods: Eligible patients were over 18 years of age, with WHO grade 4 glioma, Karnofsky score 70%. Bevacizumab was given 15 mg/kg IV every 3 weeks, and Bortezomib was given on days 1, 4, 8, 11, 22, 25, 29, and 32 of a 42 day cycle, at 1.7 mg/m2 for patients on non-enzyme-inducing antiepileptic drugs (EIAED) and 2.5 mg/m2 for patients on EIAED. Primary end points were 6-month PFS; secondary endpoints were toxicity, PFS, OS and radiographic response. Results: There were a total of 61 patients enrolled, 32 patients on non-EIAEDs, and 29 patients on EIADs. Median age was 55.2. Six-month PFS was 40.6% for patients on non-EIAEDs, and 24.1% for patients on EIAEDs (p=0.17). Eleven patients are still alive; median OS was 9.1 months, with 8.8 months for non-EIAED patients, and 9.6 months for EIAED patients (p = 0.9). Of the patients on non-EIAEDs, best radiographic response included 11 patients (34.4%) with partial response, 13 with stable disease (40.6%), and 8 with progressive disease. Of patients on EIAEDs, 3 patients (10.3%) had a partial response, 18 (62.1%) with stable disease, and 6 with progression. On comparison of partial response rates between the 2 groups, p=0.03 was obtained. Most frequent grade 3 non-hematologic toxicities included fatigue (15.9%), sensory neuropathy (10.2%), diarrhea (9%), and thrombosis (8%). There were 2 episodes of grade 4 hyponatremia and 1 episode of epistaxis from a nasal septal ulcer. 14 patients eventually had to be taken off of Velcade and continued Avastin alone, due to sensory neuropathy. Conclusions: Bevacizumab and Bortezomib appear to be an effective treatment for recurrent malignant gliomas with a moderate toxicity profile. However, this phase II clinical study suggests that the combination is not superior to single-agent Bevacizumab and that the response may be blunted in the presence of EIAEDs.
The changing pattern of risk factors and disease characteristics of breast cancer in Turkey: A cross-sectional study of a Turkish oncology group (BREASTTURK).
Authors: H. Akbulut, M. K. Altundag, P. Saip, H. S. Coskun, C. Camci, M. Ozkan, S. Paydas, N. Zengin, G. Alco, M. Aliustaoglu, G. Basaran, D. Yamac, I. Yucel, E. Goker, E. Yaman, A. Isikdogan, Y. Y. Ozisik, E. Topuz, M. Ozdogan, F. Icli
Journal: Journal of Clinical Oncology (2011)

e12007 Background: Breast cancer is the most common cancer among women in Turkey. The risk factors and characteristics of breast cancer patients have not been widely studied in Turkish population. In this observational study we planned to define the disease characteristics and the role of risk factors of patients with early breast cancer in Turkey. We present the results of the interim analysis of an ongoing study of Turkish Oncology Group. Methods: This is a nation-wide cross-sectional study of patients with early breast cancer. A total of 3.000 patients with newly diagnosed breast cancer at the 35 centers between March 2008 and March 2011 were planned to be included in the study. In this report we present the results of 2350 patients whom records were available at the time of analysis. Results: The median age was 49 years (range: 22 - 86). The 47% of the patients were post-menopausal and 53% pre-menopausal. The median age at menarche (13 years) and at menopause (48 years), the rate of smoking (12.1% current), alcohol (1.7%), hormonal contraception use (14.5%) were similar to the general female population. Among the studied environmental risk factors, the ratio of use of computerized tomography of abdomen/chest during adolescent period was worrisome in this cohort of breast cancer patients (15.4%). Likewise, the ratio of important stress (death of child/husband/parent) within past 10 years was enormously high (28.4%). The history of previous breast cancer was 0.6% and the family history of breast cancer 19.9%. The major histologic type was invasive ductal cancer (82.9%). The rate of axillary negative patients was 59.1% and T1 tumors 45.1%. ER positivity was 71.7% and c-erbB-2 overexpression 19.7%. Conclusions: Although it is needed to be clarified, the very high rate of history of use of computerized tomography during adolescent period in this study underlines the possible role of diagnostic radiation exposure during childhood in carcinogenesis. Likewise, important stress within 10 years of diagnosis seems to be an important risk factor. We believe that the breast cancer awareness campaigns have changed the disease characteristics of patients with breast cancer in Turkey.
The role of myeloid derived suppressor cells in cholangiocarcinoma: A potential target for therapy.
Authors: Richard Francis Dunne, Nathania Figueroa, Brian Belt, Jennifer Findeis-Hosey, Michael Lunt, Jian Ye, Loralee McMahon, Andrea Baran, Andrew Shubin, Marcus Smith Noel, Mohamedtaki Abdulaziz Tejani, Aram F. Hezel, David Linehan
Journal: Journal of Clinical Oncology (2016)

273 Background: Cholangiocarcinoma (CC) is a highly lethal malignancy with a poor 5 year overall survival in the advanced setting. Benefits of treating CC with chemotherapy are limited and no FDA approved targeted therapies currently exist. CC is associated with a desmoplastic reaction comprised of extracellular matrix, fibroblasts and inflammatory leukocytes. Myeloid-derived suppressor cells (MDSC) are the predominant tumor infiltrating leukocytes in several cancers, but little is known about their role in CC. MDSCs are derived from a monocytic (M-MDSC) or granulocytic (G-MDSC) origin and infiltrate the tumor microenvironment (TME) where they suppress anti-tumor immunity and play a crucial role in tumor growth, chemoresistance and metastasis. Here, we characterize the prevalence and prognostic significance of MDSC in CC. Methods: A de-identified human CC clinical database (n = 220) with linked tumor tissue was collected under an IRB approved protocol. Total white blood cell count and percent monocytes (a surrogate marker for M-MDSC prevalence in peripheral circulation) before starting therapy were collected and correlated with overall survival in patients with unresectable CC. Immunohistochemistry for myeloid cell markers (CD33, CD11b, CD14, CCR2, and CD15) was performed on formalin-fixed paraffin embedded human CC and normal liver sections. Staining was scored by a pathologist or quantified with digital imaging software. Results: Analysis of chemotherapy naive blood specimens revealed that an increase in monocyte percentage inversely correlated with survival in patients with unresectable CC (p = 0.0117). Statistical significance was more pronounced in patients with intrahepatic CC (p = 0.0091) compared to other disease sites. There was an increased level of M-MDSC and G-MDSC in CC compared to normal liver tissue and all 22 tested CC samples stained positively for MDSC markers within the tumor stroma. Conclusions: The prevalence of circulating monocytes correlates negatively with prognosis and MDSCs infiltrate the TME in unresectable CC. Therefore, targeting MDSC is an attractive therapeutic strategy and future studies aim to fully characterize the TME and block MDSC recruitment in a mouse model of CC.
Indication for adjuvant chemotherapy in early breast cancer based on a 21-gene profile: Initial experience in Mexico.
Authors: R. Gerson, F. Alban, A. Villalobos, A. Serrano
Journal: Journal of Clinical Oncology (2011)

e11009 Background: Breast cancer (BC) is most frequent among Mexican women. Since prognosis varies in early stages, a high percentage of patients are overtreated with chemotherapy. A 21-gene profile (Oncotype-DX) predicts recurrence risk in ER+, lymph node negative BC. Objective: To correlate clinical-biological characteristics of early BC in relation 21-gene profile recurrence score groups. Methods: BC stages I-IIA, with prior surgery, ER+, PR+, HER2 negative were included. The 21-gene profile (Genomic Health, Inc. California) was determined in the paraffin-blocks from primary tumor. Three groups were analyzed: low < 18, intermediate 18 - 30, > 30 high. Results: Retrospective analysis of 36 women, mean age 51.5 + 12.6 yrs. Median follow-time 12 mos (1 – 39). All patients (pts) received adjuvant endocrine therapy. Conclusions: 14% of patients had high recurrence score. They showed higher Ki-67 and lower ER expression than the low and intermediate recurrence risk groups. More time for follow-up is needed to evaluate the impact of the 21-gene profile upon recurrence. Low risk N= pts (%) Intermediate risk N= pts (%) High risk N= pts (%) P value No. pts 23 (63.9) 8 (22.2) 5 (13.9) Age (yrs) 51.6 51.6 49 NS Tumor size (mm) 12.9 16.1 18 NS CS I CS IIA 20 (87) 3 (13) 5 (62.5) 3 (37.5) 4 (80) 1(20) NS Ductal Lobular Mucinous 20 2 1 7 1 0 5 0 0 Ki-67 (%) 10.1 21.1 32.5 0.007 ER (%) 85.3 85.4 56.9 0.005 PR (%) 76 55.3 81 NS P53 + Negative Unknown 17 4 2 7 0 1 4 0 1 NS CD31 8.7 10.3 10.7 NS HER2 (RT-PCR) 9.1 9 8.3 0.084 ER (RT-PCR) 10.1 9.6 8.9 0.070 PR (RT-PCR) 7.7 7.5 7.3 NS 21-gene profile score 12.6 23.1 47.2 0.000 Follow-up time (mos) 14.2 11.1 7.8 NS Adjuvant chemotherapy 0/23 4/8 5/5 Recurrence/death 0 0 0
A 5-year review of an educational program focused on meeting the needs of patients with advanced breast cancer.
Authors: Ivy A. Ahmed, Allison Harvey, Marni Amsellem
Journal: Journal of Clinical Oncology (2012)

87 Background: Women living with advanced breast cancer have distinct often unmet needs, even compared to other women with breast cancer. For the past five years, the Cancer Support Community has been committed to delivering Frankly Speaking About Cancer: Advanced Breast Cancer, a comprehensive psychosocial education program created for women with metastatic breast cancer and their families. The program’s clinically facilitated evidence-based education workshops have reached 2,690 attendees since its inception in 2006. The workshop provides valuable information about current treatments, clinical trials, side-effect management, and social and emotional challenges of an advanced breast cancer diagnosis. Workshop outcomes are analyzed annually, informing program content and ensuring the program is meeting the needs of those served. As the program enters its sixth year, data were consolidated across years to investigate how the program has been meeting the needs of these women and their loved ones. Methods: 1,827 workshop attendees since the program’s beginning have completed evaluations (68% response rate) which included assessing levels of pre- and post-workshop knowledge about advanced breast cancer, patient-provider communication, and general workshop feedback. Results: 64.9% of respondents were survivors, 78.5% were Caucasian, and the average age was 56. Most workshop respondents (89.6%) reported gaining a high or very high level of knowledge about advanced breast cancer, with significant increases compared with pre-workshop levels (p &lt;.01). Most reported intent to increase communication with their clinical team following the workshop. A majority reported feeling better equipped to ask questions to their health care team (92.1%), and discuss the possibility of clinical trials with their healthcare team (77.7%). Furthermore, 90% of attendees felt confident that after the workshop they could speak knowledgably about side effects of cancer treatment with their doctor, a key issue in regards to quality of life. Conclusions: Taken together, the data indicate the continued relevance of this program for those affected by advanced breast cancer.
Transfusion utilization at the end of life.
Authors: Lauren S. Prescott, Alaina J. Brown, Charlotte C. Sun, Charles F. Levenback, Lois M. Ramondetta, Diane C. Bodurka
Journal: Journal of Clinical Oncology (2014)

303 Background: Both the AMA’s Consortium for Performance Improvement and the Joint Commission have identified blood transfusions as one of the top 5 treatments that are over-utilized. We sought to quantify packed red blood cell transfusion (PRBT) utilization among ovarian cancer (OCa) pts in the last 6 months of life and identify risk factors for PRBT. Methods: We performed a retrospective cohort study of deceased OCa pts treated at our institution in their last 6 months of life from 2007-2011. Pts who underwent emergent procedures for bleeding were excluded. Demographic and end of life-interventions were compared between transfusion and non-transfusion groups using chi-squared and univariate analysis. End-of-life interventions included anti-cancer treatment (chemotherapy radiation, or hormonal therapy), invasive procedure or abdominal surgery, as well as aggressive end-of-life care as defined by the NQF. Results: Of the 182 pts who met inclusion criteria, 59.9% received a PRBT in the last 6 months of life. Of those pts, 54.1% received a PRBT in the last 30 days of life. Mean hgb level at which pts were transfused was 8.4 ± 0.9 g/dL. Pts received a combined total of 436 units of PRBC. The majority of pts received 1 transfusion (n=50, range 1-16). Mean number of total units transfused was 4 (range 1-25). The most common indication for PRBT was hgb &lt; 9 g/dL (61.1%), followed by symptomatic anemia (21.9%). There was no difference in PRBT rate between pts who received medical interventions in the last 6 months of life v. those who did not. Specifically, transfusion rate was not correlated with: anti-cancer treatments (93.2% v. 92.7%, OR 0.93; 95% CI (0.29, 2.96)), invasive procedures (82.2% v. 81.7%, OR 0.96; CI (0.45,2.08)), abdominal surgery (11.0% v. 11.0%, OR 1.01; 95% CI(0.39,2.59)), or aggressive end-of-life care (46.6% v. 56.9%, OR 1.51; 95% CI (0.83,2.74)). Conclusions: The majority of our pts received a PRBT in the last 6 months of life. We did not identify significant differences in clinical interventions between pts who received a PRBT and those who did not. Based on our analysis, transfusion practices in terminally ill OCa pts should be reevaluated. Creation of transfusion guidelines for cancer pts could potentially result in better utilization of blood bank resources.
Is adjuvant chemotherapy useful in lobular breast cancer (LBC)?
Authors: X. Liem, M. Baranzelli, N. Penel, S. Giard, J. Bonneterre
Journal: Journal of Clinical Oncology (2011)

e11540 Background: Neoadjuvant chemotherapy rarely induces a complete pathological response in LBC. Nevertheless, adjuvant chemotherapy is used in lobular as well as in other tumor types. Methods: We performed a retrospective analysis in 299 patients (pts) treated with the same adjuvant chemotherapy regimen (FEC100) between November 1999 and October 2002. All the 79 lobular carcinomas have been reviewed by the same expert pathologist with e cadherine immunohistochemistry as well as the 299 clinical files. The description of the study population (lobular and non-lobular cancer pts) was based on classical methods, the comparison using the exact Fisher test. Overall survival (OS), Local relapse free survival (LRFS) and distant relapse free survival (DRFS) were calculated using the Kaplan Meyer method and comparisons the Log rank and Cox methods. A Cox model analysis was performed to analyze the predictive value of the lobular subtype on OS, LRFS and DRFS taking into account the confounders which differed between the 2 groups. Results: The 79 lobular cancer pts were significantly older (p=.0004) with less frequent grade III tumors (p=.02) and bigger tumors (p=.0001). They were more often treated with mastectomy (p=.0001). OS at 10 years was 73.2 % for pts with lobular tumors and 82.7% for the other ones (HR:1.59 [0.90-2.8], p=.10). There was no significant difference in LRFS (p=.54) nor on DRFS (p=.16). After adjustment on the 3 confounders (age, grade and size), no statistical difference was observed between lobular and non lobular types. Conclusions: This single-center study suggests that the outcome of LBC pts treated with adjuvant chemotherapy is similar to the outcome of other pts. Nevertheless, this result could be explained by the limited number of pts (a posteriori power of the study was 0.63). Regarding the absence of literature data and the impossibility to run a randomized clinical trial, we can’t deny adjuvant chemotherapy in pts with lobular cancer.