tbuckley/cabot-search huggingface dataset:
Multicenter phase II trial to investigate safety and efficacy of an adjuvant therapy with gemcitabine and cetuximab in patients with R0 or R1 resected pancreatic cancer.
Authors: H. Fensterer, C. Schade-Brittinger, H. Mueller, B. Schupfner, J. Fass, U. Lindig, U. Settmacher, M. P. Ebert, M. Kornmann, R. Hofheinz, E. Endlicher, C. Brendel, P. J. Barth, D. K. Bartsch, T. M. Gress
Journal: Journal of Clinical Oncology (2011)

4039 Background: Chemotherapy with gemcitabine is the standard adjuvant or additional treatment in R0- or R1-resected pancreatic cancer. Adding cetuximab is suggested to improve the outcome of these patients. Methods: This was a prospective, open-label, multi-centre, non-randomized phase II study in patients (pts) with R0- or R1-resected ductal adenocarcinoma of the pancreas within 8 weeks after surgery. The pts received gemcitabine 1 g/m2 on days 1,8 and 15 every 4 weeks for 6 cycles. Cetuximab was given weekly at a dose of 250 mg/m2 (initial dose: 400 mg/m2) for 24 weeks. We analyzed K-Ras point mutations in codons 12 and 13 by direct DNA sequencing after microdissection from paraffin-embedded tissue. The primary study objective was to determine the disease-free survival (DFS) rate at 18 months after registration and to demonstrate at a one-sided level of α=5% that this rate is >35%, the unsatisfactory rate achievable with standard treatment. Secondary endpoints included overall survival (OS) and toxicity. The planned sample size was 73 to power with 80% an 18-month DFS rate of 50%. Results: Between 10/06 and 11/08, 76 pts were enrolled. Of these pts, 42 were male (55.3%), median age was 64.0 years, 68 (89.5%) had an ECOG-status of 1 or 2. 65 pts. (85.5%) were T3-stage, 17 (22.4%) were R1-resected and 47/68 (69.1%) had a K-Ras mutation. 73 pts received at least one dose of cetuximab and constitute the first set for efficacy analysis: Median DFS was 11.9 months, the DFS rate at 18 months was 33.5%, failing to demonstrate superiority over 35% as hypothesized (p=0.602). Median OS (95% CI) was 21.5 (16.9 – 28.2) months. Grade 3/4 toxicities per pt were: leucocytes (11.0%), platelets (8.2%), skin toxicity (6.9%) and allergic reaction (6.9%). Conclusions: Addition of cetuximab to gemcitabine does not seem to improve DFS in the adjuvant situation over gemcitabine alone.
Developing an eHealth intervention for cancer symptom management for rural residents.
Authors: Stephanie Gilbertson-White, Chi Yeung, Keri Nace Mercer, Dorota Bartoczszyk, Todd Papke
Journal: Journal of Clinical Oncology (2016)

207 Background: A disproportionate number of late-stage cancer diagnoses occur in rural residents. Paradoxically this population, with an increased need for palliative care, has minimal access to these services. As smartphone and high-speed internet connectivity reaches near universal penetrance across the country, eHealth technologies have the potential to address this palliative care access gap. Oncology Associated Symptoms and Individualized Strategies (OASIS) web-app was developed to provide tailored cancer symptom self-management support and address this gap. Methods: A two-phased, mixed-methods design was used to: (1) assess stakeholder needs and opinions on the role of eHealth technologies to manage cancer symptoms; and (2) beta test a symptom self-management web-app. Adult patients with advanced cancer and clinic staff from two rural cancer clinics were recruited. A descriptive qualitative approach was used to analyze the patient interviews and staff focus groups. Themes related to symptom management needs and the role of technology were identified. OASIS was developed to address the themes found in phase 1. OASIS consists of 57 self-management strategies for 15 cancer symptoms and a visual symptom/strategy tracker for patients to monitor their symptoms and improve their self-management skills. Results: n = 15 patients were interviewed and n = 11 staff participated in focus groups. Themes identified were “fatalistic acceptance”, “teaching self how to manage symptoms”, and “balancing information needs”. To address these themes OASIS was developed and beta-tested with n = 10 rural residents with advanced cancer. 100% of participants were able to access OASIS via their home internet connection, 80% understood how to use the web-app after one 15 min teaching session, and 50% requested access to the web-app for family to help them with their symptoms. Conclusions: Patients and staff in rural communities have significant cancer symptom management needs and are interested in using eHealth technologies to address these needs. OASIS was found to be accessible, user friendly, easily navigated, and visually appealing. Future research is needed to evaluate the feasibility and acceptability as well as the efficacy of OASIS.
Correlation between miRNA (miR) and gene expression profiles (GEP) and response to neoadjuvant chemotherapy (NT) in patients with locally advanced and inflammatory breast cancer (BC).
Authors: Sierra Mi Li, Xiwei Wu, Paul Henry Frankel, Harry Gao, Guihua Sun, Femke De Snoo, John Rossi, Emily Wang, Paul Roepman, Yun Yen, Justine Peeters, Lisette Stork, George Somlo
Journal: Journal of Clinical Oncology (2012)

10545 Background: GEP may predict for pathologic complete response (pCR). Correlation between miRs, GEP, and pCR may reveal novel targets. Methods: Patients (pts) with HER2- BC were randomized to receive docetaxel, doxorubicin, cyclophosphamide (TAC, arm A) or A and C given every 2 weeks x 4, followed by carboplatin and nab-paclitaxel (arm B). Pts with HER2+ BC received NT per arm B, with trastuzumab added (arm C). Core biopsies were snap-frozen prior to NT, and RNA extracted for gene array analysis (Agilent 44K microarray) and deep sequence miRNA analysis (Solexa/Illumina platform). HER2 testing by IHC [3+] or FISH and/or gene array was carried out (Blueprint). MiRs were measured in 72 of 119 enrolled pts. Of 882 miRNAs reported by Solexa sequencing, 487 were assessed (observed at raw counts &gt; 10 in at least 3 pts). TargetScan was used to obtain miRNA targets and negative correlation between miR and mRNA expression was applied. Results: In 44 HER2- cases, we found 17 miRs differentially expressed between pts who achieved pCR vs. pts who did not (&lt; pCR), 13 with predicted targets by TargetScan (TS). We found 28 canonical pathways (including Embryonic Cell, EGF signaling, Estrogen-dependent signaling) affected by the identified miRs, and inclusive of 74 target mRNAs identified (Agilent) and correlating with pCR. The top overexpressed miRs are 31 [gene targets: FZD4]; 18a [IGF1, ALDH5A1]; 19a [PIK3R, IGF1]) and 3 lowest expressors are miR-190b [MMP1]; 29c [FOS, WNT5B]; 342-3p [BMP7]. Among the 28 HER2+ cases there were 14 miRNAs differentially expressed between BCs with pCR vs &lt;pCR, and 8 had predicted targets from TS. We found 10 canonical pathways (including p53, HER-2, PTEN) affected by miRs, which included 44 target mRNAs (Agilent) correlating with pCR. The most overexpressed miRs are miR-708 [gene target: RRM2B; 193a-p5 [BMPR1B, RPRM] ; 92b [CCNE2, DKK2]. The lowest expressors are: miR-30a [FZD1, SMAD1, TP63]; miR-450-5p [FOXO1, WINT5A, ERBB2]; miR-497 [PIK3R1, FGFR1, FOXO1]. Conclusions: Combined assessment of miRNA and gene expression patterns is feasible, and may yield information leading to individualized and improved NT.
Survival advantage associated with palliative oophorectomy in patients with metastatic colorectal cancer (CRC) to the ovaries (mCRC-O): A single institution retrospective analysis.
Authors: B. George, Y. You, C. Viswanathan, S. Wen, V. Baladandayuthapani, M. J. Overman, B. K. Kee, S. Kopetz, C. Eng, C. R. Garrett
Journal: Journal of Clinical Oncology (2011)

539 Background: The ovaries are an uncommon site for secondary spread from metastatic CRC. We hypothesize that palliative oophorectomy improves survival among patients with mCRC-O. Methods: We undertook a single institution IRB-approved (DR-09-623) retrospective evaluation of women with mCRC-O from 2001-2008; 110 pts with ovarian metastases and follow-up information for survival analysis were identified out of 3,776 female pts with CRC (2.9%). Survival data was calculated from the date of diagnosis of ovarian metastases (by pathology or radiology) to date of death. Results: Median age of patients was 49 years (range 19-82); median duration of follow-up was 49 months. Twenty patients were identified from 1,758 female patients with CRC seen at our institution from 2001-2004 (1.1%) and ninety patients identified from 2,018 female CRC patients from 2005-2008 (4.5%). KRAS mutation was present in the primary tumor in 23 of 43 (54%). Sixteen evaluable patients who received systemic chemotherapy with mCRC-O and other sites of metastatic disease were identified; five (31%) had a mixed radiographic response (progression in the ovarian metastases with disease response in other sites of metastases). Seventy-one (64.5%) patients had metastatic disease at the time of initial presentation; 39 (35.5%) had completely resected stage II or III CRC with mCRC-O occurring at a later date. 86 (78.2%) underwent unilateral or bilateral oophorectomy for treatment of their disease. Patients who had metastatic disease at presentation and underwent oophorectomy had a median survival of 39.4 months versus 18.2 months for those with ovarian metastases left in situ (p &lt; 0.0001); patients who developed ovarian relapse after prior colectomy and subsequently underwent oophorectomy had a median survival of 50 months versus 12 months for those patients who did not (p = 0.001). Patients with mCRC-O and peritoneal metastases had a significantly worse survival (p = 0.003). Conclusions: This single institution retrospective data analysis suggests that women with colorectal cancer metastatic to the ovaries may derive a survival benefit from palliative oophorectomy. No significant financial relationships to disclose.
Documentation of code status at an outpatient academic cancer center: A marker of discussing end-of-life preferences.
Authors: Anjana Ranganathan, Deborah Reardon, Tracey L. Evans
Journal: Journal of Clinical Oncology (2012)

307 Background: Documentation of a patient’s code status preference is becoming an increasingly emphasized part of medical care. Hospitals are adopting protocols that encourage code status documentation at the time of admission; however, this requires patients to consider end of life care at a time of acute illness with a practitioner with whom they have little familiarity. We sought to assess the proportion of patients with a documented code status preference in the electronic medical records (EMR) of our outpatient oncology clinics. Methods: The EMR for all patients seen at the Abramson Cancer Center in the months of March, April, and May 2012 were reviewed for the presence of a documented code status and the specific code status designation. The query was limited to patients seen by a medical oncologist and to patients with at least five outpatient visits occurring during or prior to the month being studied. Demographic information regarding patient age, race, religion, medical comorbidities, and oncologic diagnosis including stage were also recorded. Results: A median of 2,071 patients who have had at least five prior visits were seen per month by staff medical oncologists. Of these patients, a median of 49 patients (2%) had a documented code status recorded in the EMR. Patients seen by the thoracic medical oncology group were more likely to have a documented code status (17% vs. &lt;1%); however, these results were not statistically significant (p=0.3173), likely due to extremely small numbers of documentation. Given the low numbers of code status documentation, we were unable to detect an association with any other demographic factor. Conclusions: At our institution, only a small minority of patients with an oncologic diagnosis has documentation of code status in the readily available EMR. This initial analysis emphasizes the need for a larger effort targeted at increasing documentation of code status in the outpatient setting where patients have a longitudinal relationship with their care provider.
Comparison of quality of life between voice-rehabilitated and nonrehabilitated laryngectomees in a developing world community.
Authors: B. T. Varghese, A. Mathew, P. Sebastian
Journal: Journal of Clinical Oncology (2010)

5598 Background: We present a prospective and crossoverstudy of overall quality of life (QOL) and morbidity related to voice restoration in laryngectomees. Methods: EORTC quality of life questionnaire (QLQ–C30 and QLQ- H&N-35) was distributed among all the consenting patients alive after laryngectomy from January 2008 to October 2009. In patients who had secondary voice rehabilitation, postrehabilitation QOL scores were collected separately. Comparison of QOL between the rehabilitated and nonrehabilitated cohorts was done and a crossover study of prerehabilitation and post rehabilitation scores were done in the second cohort. Results: One hundred and thirteen patients were studied. Table show the QOL comparisons that had statistical significance at 5% level. Conclusions: QOL scores were significantly higher among voice-rehabilitated patients although it was accompanied by significant immediate and long-term morbidity and a cost implication to the patient. Significance of mean scores between rehabilitated and nonrehabilitated group Scale Mean score P value* Rehabilitated (N = 52) Not rehabilitated (N = 61) Functional scales Physical functioning (PF2) 85.9 76.69 0.0001 Role functioning (RF2) 87.18 80.33 0.01 Emotional functioning (EF) 86.22 73.45 0.0001 Social functioning (SF) 84.29 67.76 0.0001 Symptom scales/items Fatigue (FA) 19.44 28.42 0.01 Pain (PA) 15.38 18.58 0.0001 Financial difficulties (FI) 52.56 68.31 0.02 QLQ-H&N35 symptom scales/items Pain (HNPA) 8.97 13.11 0.03 Speech problems (HNSP) 53.53 70.58 0.0001 Trouble with social contact (HNSC) 16.39 27.95 0.0001 Felt ill (HNFI) 16.03 31.15 0.01 Weight loss (HNWL) 30.77 52.46 0.02 After rehabilitation** Before rehabilitation** Physical functioning (PF2) 91.48 82.22 0.03 Nutritional supplements (HNNU) 88.24 47.06 0.02 Feeding tube (HNFE) 11.76 35.29 0.05 * Mann-Whitney U test, only statisticaly significant scales are provided. Significance of mean scores between before and after rehabilitated group. ** n = 18; Wilcoxon test is used for related samples and only statistically significant scales are provided. No significant financial relationships to disclose.
Impact of adjuvant aromatase inhibitors on bone mineral density in breast cancer patients
Authors: C. N. Lai, P. D. Correa, A. Alhasso
Journal: Journal of Clinical Oncology (2009)

e11616 Aims: It is well known that aromatase inhibitors (AI) are associated with significant reduction in bone mineral density (BMD) through suppression of estrogen production. This effect has been confirmed in several studies. It is considered important that we evaluate our patients and assess their baseline BMD in the adjuvant setting in relation to the use of AIs. Methods: 122 patients on adjuvant AI were evaluated retrospectively. AIs were used either as upfront, early switch or extended adjuvant therapy. BMD (T score for hip and lumbar spine) was evaluated using DEXA scanning at baseline and annually thereafter. Risk factors for osteoporosis were assessed prior to each scan. Results: Mean baseline T scores for lumbar spine and hip were - 0.95 and - 0.79 respectively. The corresponding T scores after 1 year of treatment were -1.06 and -0.92 respectively. This represents 10.6% and 17.4% reduction in T scores for the spine and hip. 24 patients (19.7%) required anti osteoporosis therapy on the basis of their baseline T Score and they were predominantly osteoporotic. 77 patients had chemotherapy as well and had a more significant reduction in their T scores (29% reduction at the hips) in comparison to non chemotherapy patients. Patients on upfront AIs had lower baseline mean T scores (- 0.932 at hip and - 1.119 at L- Spine) and at follow up (- 1.066 at hip and -1.165 at L spine) in comparison to those on the switch approach (baseline: - 0.666 hip, - 0.816 spine; follow up: - 0.809 hip, - 0.974 spine) Conclusions: AIs are associated with decreased BMD particularly for patients who had chemotherapy. Normal T scores at baseline are reassuring and in the absence of other risk factors probably do not require further scanning. Those with low T scores (&lt;-1.5) will require continued follow up, however, the optimal scanning interval is not yet fully established and longer follow up is required. No significant financial relationships to disclose.
Effect of transplantation of pro-angiogenic monocytes to pancreatic cancer-bearing mice on resistance to chemotherapy/radiotherapy.
Authors: Y. Mizukami, T. Kawamoto, Y. Sugiyama, J. Sasajima, K. Koizumi, K. Moriichi, M. Fujiya, N. Bardeesy, D. C. Chung, Y. Kohgo
Journal: Journal of Clinical Oncology (2011)

212 Background: Hypoxic tumors are usually resistant to conventional chemotherapy and radiotherapies, which typically target actively dividing cells. The tumor vasculatures are unorganized and lack adequate pericyte coverage, which compromises delivery of drugs to tumors. How best to normalize the aberrant tumor vasculature to maximize anticancer drug delivery comprises an area of intensive investigation. Methods: We tested out hypothesize that bone marrow (BM) cells may be able to restore appropriate vessel function in tumor vasculature using nude mice bearing pancreatic cancer xenografts and genetically engineered mice that develop pancreatic adenocarcinoma. Results: Culturing BM mononuclear cells with endothelial growth medium resulted in the early outgrowth of spindle-shaped attached monocytic cells expressing CD11b/CXCR4 with a significant vessel stabilizing activity. Intravenous administration of these cultured pro- angiogenic cells into mice bearing pancreatic cancer significantly reduced areas of hypoxia without enhancing tumor growth. The resulting vasculature structurally mimicked normal vessels with intensive pericyte coverage. Consistent with a marked reduction in gene expressions involved in drug resistance such as MDR1 and ABCG2 in monocytes-injected tumors, a combination of the transplantation and chemotherapeutic agents reduced tumor size and significantly increased areas of necrosis as compared to chemotherapy alone. Conclusions: Our findings offer an alternate approach to improve delivery and efficacy of anticancer drugs to hypoxic tumors through a remodeling of the abnormal tumor vessels. No significant financial relationships to disclose.
Induction chemotherapy with carboplatin (C), paclitaxel (P) and gemcitabine (G) in unresectable stage IIIA or IIIB non-small cell lung cancer (NSCLC). A phase I-II study
Authors: G. Novello, G. L. Banna, N. Restuccia, P. G. Vigneri, S. Saita, M. D’Arrigo, L. M. Pasetto, C. Buscarino, F. Ferraù
Journal: Journal of Clinical Oncology (2008)

7592 Background: The addition of G to doublet chemotherapy with C and P has demonstrated improvement in overall response rate in stage IIIB and stage IV NSCLC with increased hematologic toxicity. Aim of the study was to evaluate safety and efficacy of a triplet induction (ind) chemotherapy followed by concomitant (conc) chemo-radiotherapy with CPG in clinically unresectable stage IIIA or IIIB NSCLC patients (pts) suitable for radical radiation treatment. Methods: In a phase I-II study, pts with histologically confirmed NSCLC, aged 18- 75, ECOG PS 0–1, adequate organ function, no prior chemotherapy, received 3 cycles of CPGind at two dose levels (see table). Pts with responding or stable disease received CPGcon (C AUC 2 day 1, P 40 mg/m2 day 1, G 225 mg/m2 day 4, every 7 days). Surgery was allowed for stage IIIA disease responsive to CPGind. Results: Nineteen pts were treated, 16 were evaluable for toxicity and response, 12 males and 4 females, median age 56 (range, 39–74), PS 0/1 (11/5 pts), stage IIIA/IIIB (9/7 pts). Dose limiting toxicities (DLTs) are reported in the table. No toxic death and febrile neutropenia were observed. Seven out of 8 assessable pts did not complete CPGcon, mainly due to grade 3 mucositis (7 pts) and haematological toxicity (5 pts). Following CPGind, 12 pts (75%) had a partial response, 3 stable disease, 1 pt disease progression. Four out of 8 assessable pts (50%) with stage IIIA disease underwent surgery. Conclusions: CPGind is feasible at the first dose level, although associated with significant haematological toxicity, and produces high response and resectability rates. It is unlikely to be followed by CPGcon, so it should be considered for future studies in unresectable stage IIIA disease Dose levels and DLTs Dose level Pts DLTs Grade 3 DLT Grade 4 DLT Level 1 11 5 neutropenia (3 pts), thrombocytopenia (1 pt), anemia (1 pt) acute myocardial infarction (1 pt), neutropenia (1 pt) C AUC5 d1 P 175 mg/m2 d1 G 800 mg/m2 d1,8 (q21) Level 2 5 3 AST/ALT (1 pt), asthenia (1 pt), neutropenia (1 pt) - C AUC6 d1 P 200 mg/m2 d1 G 1,000 mg/m2 d1,8(q21) No significant financial relationships to disclose.
Association between ursodeoxycholic acid therapy and prolonged transplant-free survival among patients with primary biliary cholangitis a number needed to treat analysis
Authors: Maren H Harms, Annarosa Floreani, Douglas Thorburn, George N Dalekos, Harry L Janssen, Christophe Corpechot, Pietro Invernizzi, Marlyn J Mayo, Pier Maria Battezzati, Henk R van Buuren, Willem J Lammers, Albert Pares, Frederik Nevens, Andrew Mason, Kris Kowdley, Cyriel Y Ponsioen, Tony Bruns, Keith D Lindor, Xavier Verhelst, Gideon M Hirschfield, Nicholas F LaRusso, Bettina E Hansen, Adriaan J van der Meer
Journal: Hepatology (2016)
Study of VH3-21 in a Large Cohort of Chronic Lymphocytic Leukemia Patients Reveals Evidence for Antigen Selection and Confirms Its Predictive Value for Early Disease Progression.
Authors: Emanuela M. Ghia, Laura Z. Rassenti, George F. Widhopf, Donna S. Neuberg, Michael J. Keating, William G. Wierda, John G. Gribben, Jennifer R. Brown, Ian W. Flinn, Kanti R. Rai, John C. Byrd, Neil E. Kay, Andrew W. Greaves, Thomas J. Kipps
Journal: Blood (2006)