tbuckley/cabot-search huggingface dataset:
Burden of oral mucositis and/or esophagitis in patients undergoing radiation treatment for head and neck cancer or non-small cell lung cancer
Authors: V.-L. Montserrat, S. Sonis, G. Oster
Journal: Journal of Clinical Oncology (2004)

8104 Background: To assess risk factors for and consequences of oral mucositis (OM) and/or esophagitis (E) in patients undergoing radiation treatment (RT) for head and neck cancer (HNC) or nonsmall cell lung cancer (NSCLC). Methods: Subjects were aged >18 years and had received RT for HNC (n=450) or NSCLC (n=310). Information on highest grade of OM/E, and potential risk factors for and consequences of OM/E, were collected via chart review. Chi-square statistics and ANOVA were used to assess the relationship between the highest grade of OM/E and age, gender, weight, tobacco use, tumor location, RT type (standard, hyperfractionated, accelerated) and cumulative dose, and timing of any chemotherapy (CT). Techniques of logistic regression were used to examine the independent contribution of OM/E to breaks/delays in treatment, receipt of feeding tubes/total parenteral nutrition, placement of indwelling IV lines, chemotherapy dose reduction, and hospitalization. Results: Mean age of HNC patients was 60 years. Most received standard RT (mean cumulative dose, 63,000 cGy); more than one-half did not receive CT. Most patients (83%) developed OM/E (mild 19%; moderate 35%; severe 29%). Patients with OM/E were younger than those without (p<0.01), and more likely to have naso/oropharyngeal tumors (p=0.013), mean cumulative RT dose >50,000 cGy (p<0.001), and concomitant CT (p<0.01). Patients with OM/E were about 4-fold more likely to have unplanned RT breaks (adjusted odds ratio=3.8 [95% CI=1.7, 8.5]) and >3 times as likely to be hospitalized (3.5 [1.3, 9.5]). Findings for NSCLC patients were similar. Those with OM/E had more unplanned breaks in RT (adjusted odds ratio 2.2 [1.0, 4.6]) and CT (2.7 [1.3, 5.7]) and were more likely to have indwelling lines (2.7 [1.2, 4.9]). Conclusions: OM/E is a frequent complication of RT in patients with HNC and NSCLC. Tumor location, radiation type and dose, and concomitant CT are risk factors for OM/E. Patients with OM/E are at significantly higher risk of hospitalization and unplanned breaks/delays in RT and CT. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Clinical Assistance Programs/payments to hospital Amgen
Feasibility of docetaxel, epirubicin, and capecitabine (TEX) plus pegfilgrastim as neoadjuvant treatment for primary breast cancer: A pilot stud
Authors: C. Wenzel, D. Hussian, R. Bartsch, U. Pluschnig, G. J. Locker, M. Gnant, R. Jakesz, C. C. Zielinski, G. G. Steger
Journal: Journal of Clinical Oncology (2004)

714 Background: Preoperative chemotherapy in patients with primary breast cancer treated with anthracyclines and taxanes results in high response rates, allowing breast conserving surgery in patients primarily not suitable for this procedure. Capecitabine, as a well tolerated, highly effective, and convenient alternative to parental 5-FU, plays potentially a key role in the treatment of patients with advanced breast cancer. A current phase II study demonstrated that TEX regimen has substantially activity as first-line treatment in patients with metastatic breast cancer and impressive activity in patients with locally advanced breast cancer, of whom approximately 30% achieved a pathological complete response. However 51% of the patients developed grade 3/4 neutropenia and febrile neutropenia occurred in 16%. Methods: Based on these results we are conducting a pilot trial adding capecitabine to epirubicin and taxotere in patients with primary breast cancer. Oral capecitabine, 1000 mg/m2, is administered twice daily on days 1–14 of each 3-week treatment cycle. Epirubicin, 75 mg/m2, and docetaxel, 75 mg/m2, is administered as a short i.v. infusion and a 1-hour infusion on day 1 of each treatment cycle, respectively. As primary prophylaxis to prevent neutropenia pegfilgrastim 6 mg s.c. on day 2 of each cycle is applied. Conclusions: Aim of this study is the concern about the concomitant application of a G-CSF to continuous chemotherapy and therefore to evaluate the feasibility and toxicity of this therapy regimen. Toxicity and efficacy data will be presented at ASCO meeting 2004. No significant financial relationships to disclose.
A phase II, multicenter, randomized, double-blind, placebo-controlled trial of ganitumab or placebo in combination with carboplatin/paclitaxel as front-line therapy for optimally debulked primary ovarian cancer: The TRIO14 trial.
Authors: Gottfried E. Konecny, Paul Haluska, Fritz Janicke, Jalid Sehouli, Matthias W. Beckmann, Gabriele Feisel, Martin Pölcher, Lynda Roman, Achim Rody, Beth Karlan, Isabelle Laure Ray-Coquard, Diane M. Provencher, Noa Ben-Baruch, Paul H. Cottu, Hsiao-Wang Chen, Chen Wang, Judy Dering, Sylvie Jacod, Vincent Houe, Dennis J. Slamon
Journal: Journal of Clinical Oncology (2014)

5529 Background: IGF signaling has been implicated in the pathogenesis and progression of ovarian cancer (OC). Ganitumab (GAN; AMG 479) is an investigational, fully human, monoclonal antibody inhibitor of IGF1R. We explored the efficacy and safety of adding GAN to carboplatin and paclitaxel (CP) front line chemotherapy in patients with optimally debulked (<1 cm) FIGO stage III and IV (positive pleural cytology only) ovarian epithelial (including fallopian tube and primary peritoneal) cancer. Methods: Patients were randomized in a 1:1 fashion to receive CP (C AUC6/ P 175 mg/m2 q3w) plus GAN (18 mg/kg q3w) or placebo (PLB) for 6 cycles followed by 6 additional cycles of single agent GAN (18 mg/kg q3w) or PLB. The primary endpoint was PFS. Secondary objectives were: Overall survival (OS), safety, quality of life (QOL FACT-O), and to explore the relationship between PFS and molecular OC subtypes (gene expression) or IGFR1 signaling (phospho-proteins). Results: 170 patients were enrolled. Median age was 58 yrs (range 18-77); ECOG PS 0/1/2, 41%/53%/6%. 165 patients were assessable for toxicity; most frequent grade 3/4 adverse events for CP+GAN vs. CP+PLB were neutropenia (42% vs. 38%), thrombocytopenia (23% vs. 13%), hyperglycemia (3.4% vs. 1.3%) and skin rash (3.4% vs. 0%). The median PFS estimates were 15.7 mos (CP+GAN) vs. 16.7 mos (CP+PLB); HR (PFS): 1.22 (95% CI:0.81-1.82); median OS not yet reached. Self-reported QOL showed no difference between treatment arms. Correlative biomarker studies in 116 patients are ongoing and will be presented. Conclusions: PC+GAN was well tolerated in this population, however, the addition of GAN did not prolong PFS with respect to PC in unselected OC patients. Clinical trial information: NCT00718523.
Are WHO “best buys” for non-communicable diseases effective in low-income and lower-middle-income countries? A systematic review
Authors: Luke N Allen, Jessie Pullar, Kremlin Wickramasinghe, Julianne Williams, Charlie Foster, Nia Roberts, Bente Mikkelsen, Cherian Varghese, Nick Townsend
Journal: The Lancet Global Health (2017)

BackgroundThe central plank of the global strategy to combat non-communicable diseases (NCDs) is a cluster of highly cost-effective interventions that WHO has dubbed "best buys". These 24 interventions promoted by WHO include tobacco taxation, salt reduction, cervical screening, and aspirin. Although the greatest burden of NCDs is in low-income and lower-middle income countries, evidence for most of the best buys comes from high-income countries. We did a systematic review to assess evidence for the effectiveness of best buys in low-income and lower-middle-income countries (LLMICs), where the need for effective NCD interventions is greatest.MethodsUsing a registered protocol (PROSPERO: 42016039051) and following PRISMA guidelines, we searched 13 major databases for studies that quantified the effectiveness of the 24 interventions as defined in the 2013–20 Global Action Plan on NCDs. We included studies that were undertaken in 83 countries defined by the World Bank as LLMICs, published between Jan 1, 1990, and Feb 5, 2015. We accepted interrupted time-series designs as well as trials that compared interventions with usual health care. Two reviewers independently screened papers using a piloted form. We used study-specific Newcastle-Ottawa and Cochrane tools to assess risk of bias and adopted a narrative approach to data synthesis. Primary outcomes were NCD-related mortality, morbidity, and risk-factor prevalence.FindingsOur search returned 2672 records after duplicate removal and we included 36 studies in the final review, of which 26 had been done in India. 19 of the 36 studies reported on tobacco-related best buys, two pertained to diet and physical activity, four were on cardiovascular medication, and 11 on cancer interventions. Only four "best buys" had two or more studies that showed that the intervention was effective: group smoking reduction programmes, smoking bans in public places, cervical cancer screening, and hepatitis B immunisation. There was no evidence for the effectiveness of any best-buy interventions in 74 of the 83 LLMICs (89%).InterpretationThere is an urgent need to evaluate whether established NCD-prevention policies from high-income countries are effective in low-income settings. Our exact following of the wording of the WHO best buy definitions might have excluded some relevant studies; however, our review was comprehensive in scope and had a very robust search strategy.FundingWorld Health Organization.
Letrozole efficacy is related to human aromatase CYP19 single nucleotide polymorphisms (SNPs) in metastatic breast cancer patients
Authors: B. Lloveras, M. Monzo, R. Colomer, A. Llombart, M. Ramos, J. I. Mayordomo, D. Fuster, E. Alba
Journal: Journal of Clinical Oncology (2004)

507 Background: We have previously reported a prospective cohort study of patients with ER+ and/or PR+ metastatic breast cancer treated with the aromatase inhibitor letrozole (SABCS 2001), in which the efficacy of letrozole, measured with time to treatment progression (TTP), correlated with the levels of circulating HER2 ECD. We have now evaluated in tumor tissue samples whether SNPs of the CYP19 aromatase gene had a predictive value. CYP19 is located on chromosome 15q and encodes a steroid aromatase that catalyzes the conversion of C19 androgens to estrogens. Methods: PCR allelic discrimination (ABI prism 7700 sequence detector) was used to examine SNPs in DNA obtained from 67 breast cancer patients accrued from 04/1999 to 11/2000. Two regions of the aromatase CYP19 gene were examined, one localized in the 3' untranslated region (UTR) and one in the intronic region. Presence of wild-type gene (WT) or SNPs was recorded. All patients in the study had documented disease progression and had been treated previously with a SERM. Sixty-five patients are evaluable for efficacy. Results: Median age was 62 years, median number of metastatic sites was 2. Percentage of cases with SNP variation of CYP19 UTR was 46% and of CYP19 intronic region was 63%, respectively. Time to treatment progression was longer in patients with SNPs of CYP19 UTR when compared with CYP19 UTR WT (525 vs. 196 days, p=0.02). This relationship was not observed for CYP19 intronic region (459 vs 510 days, p=0.9). Conclusions: In hormone receptor-positive metastatic breast cancer patients treated with the aromatase inhibitor letrozole, the presence of single nucleotide polymorphisms on the 3'UTR of the CYP19 aromatase gene is associated with improved treatment efficacy, and may help in selecting patients for letrozole therapy. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis
Thalidomide (Thal) tolerance in patients treated with transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC)
Authors: A. Goldenberg, M. Volm, H. Hochster, F. Muggia, R. Rosen, L. Teperman, G. Morgan, J. Schwartz, M. Sung, S. Wadler
Journal: Journal of Clinical Oncology (2004)

4255 Background: Most HCCs are hypervascular and appropriate for treatments that target tumor angiogenesis. Tumor vascularity may be mechanically disrupted by TACE yet biologic disruption is preferable. As Thal has anti-angiogenic properties we studied the combination of Thal and TACE in patients with HCC. Thal's tolerance in patients (pt) with a variety of illnesses is not well-established. We therefore reviewed Thal's tolerability in pts with liver disease and HCC undergoing Adriamycin (Adria) Lipiodol (Lip) TACE. Methods: 56 pts with HCC have been enrolled. All pts had total bili < 3, and transaminases ≤ 5 X nl. Thal was initiated at a dose(ds) of 200 mg/d and ds escalations or decreases were permitted as tolerated. After 28 days Thal was discontinued and pts underwent a Adria Lip collagen TACE after which Thal was restarted. Results: The mean pt age was 58.4 yrs. The m/f ratio was 46/10. All pts had hepatitis B or C, or alcoholic liver disease. 15 pts recieved liver transplants. 8 pts were removed from study for Thal toxicity (tox). 4, 1 and 3 of the 8 pts were withdrawn for grade (gr) II-III neurologic (neuro), gr I gastrointestinal (gastro) and gr ≥ III other Thal toxs, respectively. 42 pts have undergone TACE. 24 pts remained on 200 mg/d and 18 pts were ds escalated to 250–500 mg/d prior to TACE. There were 42 Thal ds increases and 32 ds reductions. The first post TACE ds was reduced for TACE related constitutional tox in 8 pts. 13 of 18 pts ds escalated prior to TACE required ds reductions after TACE. There were more ds reductions due to Thal tox after TACE then before it (28 vs 4, p = 0.0002), and more pts were reduced to ≤ 150 mg/d as a result of Thal tox after TACE then prior to it. (19 vs 5 p = 0.0007). 47.1 %, 3.7 % and 18.8 % of ds reductions were prompted by constitutional, gastro and neuro Thal tox, respectively. 41.5%, 45.2% and 13.2% of the ds reductions resulted from gr I, II and III Thal toxs. Conclusions: 1.0 Initial Thal ds of 200 mg/d are tolerable in HCC pts with minimal liver dysfunction. 2.0 Ds escalations > 200 mg often result in subsequent ds reductions. 3.0 Ds reductions are more frequent after TACE when some pts may tolerate only 50–150 mg/d. No significant financial relationships to disclose.
Multiple Roles of APC and its Therapeutic Implications in Colorectal Cancer
Authors: Lu Zhang, Jerry W. Shay
Journal: JNCI Journal of the National Cancer Institute (2016)

Adenomatous polyposis coli (APC) is widely accepted as a tumor suppressor gene highly mutated in colorectal cancers (CRC). Mutation and inactivation of this gene is a key and early event almost uniquely observed in colorectal tumorigenesis. Alterations in the APC gene generate truncated gene products, leading to activation of the Wnt signaling pathway and deregulation of multiple other cellular processes. It has been a mystery why most patients with CRC retain a truncated APC protein, but accumulating evidence suggest that these C terminally truncated APC proteins may have gain of function properties beyond the well-established loss of tumor suppressive function. Here, we will review the evidence for both the loss of function and the gain of function of APC truncations and how together they contribute to CRC initiation and progression.
PCBP1 and NCOA4 regulate erythroid iron storage and heme biosynthesis
Authors: Moon-Suhn Ryu, Deliang Zhang, Olga Protchenko, Minoo Shakoury-Elizeh, Caroline C. Philpott
Journal: Journal of Clinical Investigation (2017)

Developing erythrocytes take up exceptionally large amounts of iron, which must be transferred to mitochondria for incorporation into heme. This massive iron flux must be precisely controlled to permit the coordinated synthesis of heme and hemoglobin while avoiding the toxic effects of chemically reactive iron. In cultured animal cells, iron chaperones poly rC–binding protein 1 (PCBP1) and PCBP2 deliver iron to ferritin, the sole cytosolic iron storage protein, and nuclear receptor coactivator 4 (NCOA4) mediates the autophagic turnover of ferritin. The roles of PCBP, ferritin, and NCOA4 in erythroid development remain unclear. Here, we show that PCBP1, NCOA4, and ferritin are critical for murine red cell development. Using a cultured cell model of erythroid differentiation, depletion of PCBP1 or NCOA4 impaired iron trafficking through ferritin, which resulted in reduced heme synthesis, reduced hemoglobin formation, and perturbation of erythroid regulatory systems. Mice lacking Pcbp1 exhibited microcytic anemia and activation of compensatory erythropoiesis via the regulators erythropoietin and erythroferrone. Ex vivo differentiation of erythroid precursors from Pcbp1-deficient mice confirmed defects in ferritin iron flux and heme synthesis. These studies demonstrate the importance of ferritin for the vectorial transfer of imported iron to mitochondria in developing red cells and of PCBP1 and NCOA4 in mediating iron flux through ferritin.
Lirex: A Package for Identification of Long Inverted Repeats in Genomes
Authors: Yong Wang, Jiao-Mei Huang
Journal: Genomics Proteomics & Bioinformatics (2017)

Long inverted repeats (LIRs) are evolutionarily and functionally important structures in genomes because of their involvement in RNA interference, DNA recombination, and gene duplication. Identification of LIRs is highly complicated when mismatches and indels between the repeats are permitted. Long inverted repeat explorer (Lirex) was developed and introduced in this report. Written in Java, Lirex provides a user-friendly interface and allows users to specify LIR searching criteria, such as length of the region, as well as pattern and size of the repeats. Recombinogenic LIRs can be selected on the basis of mismatch rate and internal spacer size from identified LIRs. Lirex, as a cross-platform tool to identify LIRs in a genome, may assist in designing following experiments to explore the function of LIRs. Our tool can identify more LIRs than other LIR searching tools. Lirex is publicly available at http://124.16.219.129/Lirex.
Can a web-based tracking and feedback tool improve breast cancer care at safety-net hospitals?
Authors: Nina A. Bickell, Maria Castaldi, Ajay Shah, Alan Sickles, Theophilus Lewis, Shalini Arora, Kevin Clarke, Peter J Pappas, Margaret Kemeny, Anitha Srinivasan, Rebeca Franco, Kezhen Fei, Michael Parides, Ann Scheck McAlearney
Journal: Journal of Clinical Oncology (2017)

107 Background: System failures, a cause of underuse in which doctors order care, patients don’t refuse but care doesn’t ensue, tend to happen more at safety net hospitals (SNH). Tracking &amp; follow-up approaches that close referral loops in SNHs may reduce underuse. In a randomized trial, we tested a Tracking &amp; Feedback (T&amp;F) tool to reduce underuse of adjuvant breast cancer treatment. Methods: We recruited 5 community &amp; 5 municipal SNHs that serve a large proportion of minorities in the NYC metropolitan area. We implemented rapid case ascertainment, a T&amp;F tool and trained point persons at each site to determine if women with newly operated stage 1-3 breast cancer, connected with the oncologist since such connections are associated with getting treated. The tool created a daily “to do” reminder for point persons to ascertain if patients were seen by the oncologist. Point persons then relayed this information to surgeons to follow through as they deemed necessary. Underuse includes: no RT after lumpectomy or mastectomy with &gt; 4 positive nodes; no chemo for HR- and no hormonal therapy for HR+ tumors &gt; 1cm; no trastuzumab for Her2+ tumors. We interviewed key informants about tool usefulness. We conducted intention to treat and pre-post analyses to assess tool and implementation effectiveness, respectively. Results: Pre-intervention, despite randomizing hospitals, intervention (INT) hospitals had fewer whites (4% vs 14%; p = 0.0005), poorer follow-up approaches (0.68 vs 0.80; p = 0.07), less Medicaid &amp; uninsured patients (36% vs 62%; p &lt; .0001) and more underuse (28% vs 15%; p = 0.002) compared to control (CNTL) hospitals; comorbidities and stage were similar. The RCT found no difference in underuse rates (9% at INT &amp; 11% at CNTL hospitals; p = 0.8). Because randomization did not result in equivalent distributions, we modeled pre- (N = 403) and post (N = 191) populations controlling for time period and clustering &amp; found that hospitals with better follow-up (OR = 0.82; 95% CI: 0.71-0.96) had less underuse. In settings with poor follow-up &amp; tracking approaches, key informants found the tool useful. Conclusions: While the RCT findings were negative, they suggest a T&amp;F tool may help reduce underuse in SNHs with poor follow-up capabilities. Clinical trial information: NCT01544374.
Quality and Safety in Health Care, Part XXVII
Authors: Jay A. Harolds
Journal: Clinical Nuclear Medicine (2017)

This article discusses some of the most recent research and future directions of the Adult Cardiac Surgery Database of the Society of Thoracic Surgeons. In addition to numerous articles on short-term outcomes from cardiac surgery on adults, there are new initiatives of the Adult Cardiac Surgery Database which will allow long-term outcome analysis and better estimation for each patient on the likely value of the procedure to that individual.
Irinotecan, carboplatin, and imatinib in extensive stage small cell lung cancer: A phase II trial of the Minnie Pearl Cancer Research Network
Authors: E. L. Raefsky, J. D. Hainsworth, D. Rinaldi, M. Schreeder, D. R. Spigel, H. A. Burris, D. A. Yardley, D. S. Thompson, F. A. Greco
Journal: Journal of Clinical Oncology (2004)

7300 Background: Small cell carcinoma of the lung expresses c-kit (CD117 staining) in approximately 70–80% of patients. However, it remains unknown if c-kit is activated and essential to the neoplastic process. Methods: This study was designed to assess the toxicity and the response rate in extensive stage small cell lung cancer to imatinib 600mg po daily plus concurrent chemotherapy with carboplatin (AUC=4) on day 1 and irinotecan 60mg/m2 on days 1, 8, and 15 at 4-week intervals for 4 courses. Imatinib was planned for 2 years in responding and stable patients. Results: Thirty-four patients of the required 60 patients have been entered and thus far 25 are evaluable for response. The grade 3 toxicity of the combined regimen included neutropenia (20%), thrombocytopenia (3%), anemia (6%), nausea/vomiting (26%), diarrhea (20%), and fatigue (23%). Grade 4 toxicity was rare (6% neutropenia). One patient was hospitalized with neutropenia/fever (3%) and there were no treatment-related deaths. There were no unexpected severe toxicities observed. 21 of 25 patients responded to treatment (84%) with 20 partial responses (80%) and 1 complete response (4%). The minimum follow-up is 2 months (range 2–14 months). Correlations of response to treatment, response duration and survival with the presence and degree of CD117 staining will be evaluated. Conclusions: This regimen is relatively well tolerated and active, with no unexpected severe toxicity. Further follow-up of these patients and other comparative studies may help clarify the role of imatinib. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis; Pfizer-Pharmacia