bluuebunny/crossref_metadata_2025_split huggingface dataset:
Longitudinal changes in physical activity of head and neck squamous cell carcinoma patients.
Authors: Jolly Shruti , Peterson Lisa A , Rozek Laura S , Chepeha Douglas Brian , Prince Mark E , McLean Scott A , Ward Brent , Bradford Carol Rossier , Helman Joseph , Stanley Jeffrey , Worden Francis , Eisbruch Avraham , Wolf Gregory T. ,   University of Michigan Head and Neck SPORE
Published: March 2020

9607 Background: Head and neck cancer (HNCa) treatment results in unfavorable changes in physical function, body composition and quality of life. The ability of these patients to perform physical activity after cancer treatment has not been previously evaluated. To develop clinical models that will guide the care of HNCa survivors, it is important to characterize these physical activity changes. Methods: From 2008 to 2011, as part of an institutional Head and Neck SPORE longitudinal epidemiology project, health survey data including the Physical Activity Scale in the Elderly (PASE) was collected at baseline, 6 months and annually thereafter. The PASE score assesses the hours doing leisure time physical activity, walking, occupational, and household chores over a typical 7-day period. During follow up, subjects deceased, were lost to follow-up, or refused survey completion. Paired t-test was used to compare the mean PASE score at various endpoints from baseline. Results: 294 HNCa patients completed the survey at baseline. Following a mean follow-up of 25.7 (+/-11.9) months, 66%(n=193), 73%(n=215) and 42%(n=124) of patients completed the assessment at 6-months, 1-year and 2-years respectively. Majority (97%) of the HNCa patients had oropharynx, oral cavity or larynx cancer, which were treated by chemoradiation (36%), surgery followed by chemoradiation (23%) or surgery alone (20%). Results of the PASE score revealed the lowest levels of physical activity at baseline with steady statistically significant improvement at each subsequent timepoint (p<0.05). Stratifying by treatment modality, the difference between baseline and 1-year PASE score was significant only for chemoradiation patients (p<0.05). Conclusions: Baseline cancer burden appeared to have the most impact on physical activity levels in HNCa patients. In patients who completed the survey, the levels of physical activity improved longitudinally over time and are most notable for patients treated by chemoradiotherapy. Therefore, the most benefit of a physical activity intervention would be either during or immediately following treatment.
Effect of abiraterone acetate (AA) on patient-reported pain in metastatic castration-resistant prostate cancer (mCRPC) post-docetaxel: Results of longitudinal sensitivity analyses.
Authors: Hao Yanni , Cleeland Charles S. , Gagnon Dennis , Espindle Derek , Molina Arturo , Basch Ethan M. 
Published: March 2020

9618 Background: The COU-AA-301 phase 3 trial showed that AA + prednisone (P) improved overall survival in mCRPC patients (pts) post-docetaxel. Compared with P alone, AA + P also had significant benefits on patient-reported pain. Here we describe post hoc sensitivity analyses of pain data from that trial, using different methods to compensate for the potential impact of missing data. Methods: Pts with mCRPC progressing after docetaxel-based chemotherapy were randomized 2:1 to AA + P or placebo + P. Pain intensity and interference of pain with daily activities were assessed with the Brief Pain Inventory-Short Form (BPI-SF) questionnaire at baseline, Day 15 of Cycle 1, and Day 1 of each 28-day treatment cycle thereafter until treatment discontinuation. The effect of treatment on BPI-SF scores was analyzed using repeated measure mixed-effects (RMM) models, piecewise linear mixed-effects (PWLME) models, and joint mixed-effects and log time-to-dropout (JMEL) models. RMM and PWMLE models assumed missing data (due to death, study dropout, or administrative issues) to be missing at random, the JMEL model to be missing not at random. Model results were compared between treatment arms. Results: 797 pts were randomized to AA + P, and 398 to P only. RMM model estimates suggested statistically significant (p < 0.05) differences in change from baseline for pain intensity and pain interference scores in favor of AA + P at the majority of study visits through cycle 11. PWLME models yielded significantly smaller areas under the curve (AUCs) for AA + P vs P for pain intensity (p = 0.0031) and pain interference (p = 0.0006); smaller AUCs reflect better pain outcomes. Results using JMEL models were nearly identical to those with PWLME models, with AUCs for AA + P significantly smaller than for P alone for pain intensity (p = 0.0031) and pain interference (p = 0.0007). Conclusions: Using various modeling methods that assess the impact of missing data, AA + P showed superior patterns of pain outcomes over time compared with P only in mCRPC pts refractory to docetaxel. These results support the previously reported pain benefits of AA + P over P alone from the same trial. Clinical trial information: NCT00638690.
Differential effects of bevacizumab on the risk of hand-foot syndrome associated with cytotoxic chemotherapy: An updated meta-analysis.
Authors: Gopal Arun , Flores Ronald A. , Lacouture Mario E. , Wu Shenhong 
Published: March 2020

9622 Background: Hand-foot syndrome (HFS) is a dose-limiting toxicity of many chemotherapeutic agents. In a prior meta-analysis of published randomized-controlled clinical trials (RCTs) we showed that the risk of HFS increased significantly with the use of bevacizumab, an angiogenesis inhibitor that is widely used for the treatment of many cancers. In this study, we have included more recent trials and updated our findings. Methods: Databases from PUBMED, Cochrane Database, and abstracts presented at the American Society of Clinical Oncology until December, 2012 were searched for the identification of relevant studies. Eligible studies included prospective RCTs in which the addition of bevacizumab to chemotherapy was compared directly to chemotherapy alone in cancer patients. Relative risk (RR), and 95% confidence interval (CI) were calculated using a fixed- or random-effects model based on the heterogeneity of the studies. Results: A total of eight RCTs including 8,150 patients (bevacizumab 4211, control 3939) with a variety of tumors were analyzed. The summary incidence of HFS was 14.3% (95% CI: 4.8-36.0%). The addition of bevacizumab to chemotherapy did not significantly increase the risk of developing all-grade (RR: 1.17, 95% CI: 0.90-1.51, P=0.240) and high-grade HFS (RR: 1.50, 95% CI: 0.92-2.47, P=0.11) as opposed to chemotherapy alone. The risk of HFS did not vary significantly with tumor types (P=0.21) and bevacizumab dose (P=0.28). However, the risk of HFS varied significantly with concurrent chemotherapeutic agents (P=0.004). Bevacizumab significantly increased the risk for 5-FU based agents (RR 1.2, 95% CI 1.08-1.33, P=0.001) but decreased the risk for non-5-FU based agents (RR 0.63, 95% CI: 0.41-0.96, P=0.03). Conclusions: Bevacizumab may enhance or reduce the risk of HFS depending on particular chemotherapeutic agents used in cancer patients. These findings are of importance to direct supportive care efforts.
Antibiotic prescribing in primary care for end-of-life cancer patients.
Authors: Gao Wei , Spicer James F. , Higginson Irene 
Published: March 2020

9627 Background: There is ongoing debate on whether it is appropriate to administer anti-infection medications to patients approaching end of life. Population-based epidemiologic data on current antibiotic prescribing status is needed to shed lights on this issue. Methods: A population-based retrospective cohort study, based on data extracted from the General Practice Research Database (GPRD). Patients (N=29,810) with one of five major cancers (lung, colorectal, breast, prostate, head and neck), and who died in 2000-2008 were included for this analysis. Prescriptions of antibiotics(BNF codes: 5.1.1-5.1.13) for individual patients in the last 3 months of life were reviewed and analysed. The outcome was with (1) or without (0) antibiotic prescriptions. A Generalized Estimating Equation (GEE) logistic regression model was used to assess for the associations between outcome and explanatory variables. Results: Overall, 26.8% of patients(95%CI: 26.3-27.3%) had been prescribed antibiotics. There was an increasing trend in antibiotic prescribing for end-of-life cancer patients, rising from 23.2%(21.5-24.9%) in 2000 to 29.5%(28.0-31.0%) in 2008 (p<0.001). Patients with the following characteristics were more likely to be prescribed antibiotics(p<0.001): being younger(<70:ORs 1.14-1.27) vs 80+, male gender(OR: 1.10; 1.03-1.18), lung & head & neck cancer(ORs:1.50-2.00) vs colorectal cancer, higher co-morbidity score(ORs vs 0-3:1.02-1.19), smoking(OR vs non-smoking 1.17;1.07-1.27), living in Northern Ireland(OR:1.43; 1.17-1.75) and Scotland(ORs: 1.23; 1.03 to 1.47) vs London. No difference by whether they drank alcohol or social economic status. Conclusions: Antibiotic prescribing at the end of life was common and increasing over the years. Further studies need to investigate clinical conditions associated with antibiotic prescribing to inform clinical practices and end of life care policy.
A prospective multicenter, single blinded, randomized phase III trial to compare the efficacy of ramosetron, aprepitant and dexamethasone with ondansetron, aprepitant, and dexamethasone for preventing chemotherapy-induced nausea and vomiting: KCSG PC10-21.
Authors: Kim Hyo Jung , Song Eun-Kee , Kim Jun Suk , Ahn Jin Seok , Yun Hwan Jung , Cho Yo Han , Park Keon Uk , Kim Si-Young , Jang JoungSoon , Kim Sang-We , Lee Hyun Woo , Lee Se Ryeon , Kim Yang Soo , Lee Soon-Nam , Ko Yoon-Ho , Kim Hwa Jung , Kang Jin Hyoung , Shin Sang Won ,   Korean Cancer Study Group
Published: March 2020

9633 Background: Combination of aprepitant, 5-HT3 receptor antagonist and steroid improve complete response (CR) of chemotherapy induced nausea and vomiting (CINV). But until now, there was no information whether ramosetron is as effective as other 5-HT3receptor antagonists for the combination regimen. Therefore, we compared a ramosetron, aprepitant and dexamethasone (RAD) with ondansetron, aprepitant and dexamethasone (OAD) to establish the non-inferiority of RAD in controlling highly emetogenic chemotherapy induced nausea and vomiting. Methods: A total of 334 patients with malignant disease who were scheduled to receive highly emetogenic chemotherapy were randomized to RAD or OAD. Aprepitant (125 mg day 1; 80 mg day 2, 3) and dexamethasone (12 mg day 1; 8 mg day 2-4) were administered to both group. Intravenous ramosetron (0.3mg day 1) or ondansetron (16mg day1) was given to RAD or OAD, respectively. Patients recorded vomiting and nausea (VAS score) on the diary. The primary end point was CR (no vomiting or retching and no rescue medication) rate in the acute period (chemotherapy day 1). The non-inferiority margin was defined as -15% differences. Results: 299 patients (RAD 143, OAD 156) were eligible for the efficacy analyses of modified intention-to-treat. Median age and sex were 60 (IQR 52 – 66) and 61 (51.5 – 68, p=0.54), 90 Male/66 Female and 114 Male/29 Female (p<0.0001) in RAD and OAD, respectively. There were no significant differences between two groups on the other baseline characteristics. The CR rates of RAD vs OAD were 84.6% vs 77.6% (95% C.I. -0.4 – 14.5%) at acute period, 69.5% vs 62.6% (-2.1 – 16.0%) at delayed period (days 2-5), and 66.7% vs 58.1% (-0.6 – 17.8%) at overall period. Median nausea score at acute period were 4 (IQR 2 – 5) and 3 (2-5, p=0.14) in RAD and OAD, respectively. There were no grade 3 or 4 toxicities. Conclusions: RAD regimen is as effective and tolerable as OAD antiemetic combination for the prevention of CINV in patients receiving highly emetogenic chemotherapy. Ramosetron could be considered as one of the best partners for aprepitant. Clinical trial information: NCT01536691.
A randomized study of ganetespib, a heat shock protein 90 inhibitor, in combination with docetaxel versus docetaxel alone for second-line therapy of lung adenocarcinoma (GALAXY-1).
Authors: Ramalingam Suresh S. , Goss Glenwood D. , Andric Zoran Gojko , Bondarenko Igor , Zaric Bojan , Ceric Timur , Poddubskaya Elena Vladimir , Ciuleanu Tudor-Eliade , Spicer James F. , Felip Enriqueta , Hirsh Vera , Manegold Christian , Rosell Rafael , Khuri Fadlo Raja , Vukovic Vojislav M. , Teofilovici Florentina , El-Hariry Iman , Guo Wei , Bahcall Safi R. , Fennell Dean 
Published: March 2020

CRA8007 The full, final text of this abstract will be available at abstract.asco.org at 7:30 AM (EDT) on Monday, June, 3, 2013, and in the Annual Meeting Proceedings online supplement to the June 20, 2013, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Monday edition of ASCO Daily News.
Radiosensitization of HER2-positive breast cancer cell lines with trastuzumab.
Authors: Demirci Alanyali Senem , Bozkurt Emir , Alanyali Hilmi , Karaca Burcak , Uslu Ruchan 
Published: March 2020

e11501 Background: HER2 is a member of the human epidermal growth factor (EGF) receptor family that is blocked by a monoclonal antibody, Trastuzumab (Herceptin). In daily clinical practice, Trastuzumab is being used concurrently with radiotherapy (RT) in breast cancer patients. Administration of Trastuzumab with RT appear to be safe in regard to cardiac morbidity and mortality in patients with relatively modest follow-up duration (less than 5 years). In this study we aimed to determine the possible interactions between RT and Trastuzumab in HER2 positive breast cancer cell line MDA-MB-453. Methods: MDA-MB-453 cells were treated with increased dose of Trastuzumab (10 – 200 µg/mL, 72 hours) and irradiation (0-8 Gy, 4 Gy/min, 48 hours). XTT (Roche) viability assay was used to measure the cytotoxicity of Trastuzumab, and trypan blue method was used to measure the cytotoxicity of irradiation. The sensitization of MDA-MB-453 cell lines was done by IC50 of Trastuzumab with 24 hours treatment followed by 6 and 8 Gy irradiation. Results: Cytotoxicity was increased in a dose and time dependent manner by Trastuzumab and irradiation treatment in MDA-MB-453 cell lines. IC50 values of Trastuzumab and irradiation were found to be 167 µg/mL and 8 Gy, at 48 hours, respectively.Cells were pretreated with IC25 and IC50 doses of Trastuzumab for 24 hours and then irradiated with 6 and 8 Gy doses. The cell viability at 24 and 48 hours were significantly decreased (p=0.0012) compared to single exposures (Trastuzumab or irradiation), indicating that Trastuzumab sensitizes HER2 positive breast cancer cells to irradiation. Conclusions: This preliminary study showed the sensitization effect of Trastuzumab to irradiation in HER2 positive breast cancer cells. Further studies are warranted for the optimal dosing and normal tissue toxicity of this combination.
AQP5 variant associated with prognosis in patients with early breast cancer.
Authors: Park Ho Yong , Lee Soo Jung , Chae Yee Soo , Kim Jong Gwang , Kang Byung Woog , Lee Yoo Jin , Jeong Ji Yun , Park Ji-young 
Published: March 2020

e11505 Background: Our previous study showed the association of AQP5 expression with unfavorable prognosis in patients with early breast cancer (EBC). In addition, we analyzed the prognostic impact of polymorphisms of AQP5 gene in the chromosomal region 12q13 on breast cancer. Methods: The genomic DNA was extracted from paraffin-embedded tumor-free tissue from 609 early breast cancer (EBC) patients underwent curative surgery and then genotyped for 3 polymorphisms (rs3736309, rs1964676, and rs74091167) using the Sequenom Mass array system. Results: The median age of patients was 49 years (range 23-79). 106 (18.2%) patients underwent breast conserving surgery and adjuvant chemotherapy was given to 562 (92.3%) patients. Among enrolled subjects, 447 (73.3%) were hormone-responsive, 94 (15.3%) for HER2 overexpressed, and 98 (16.1%) for triple negative EBC. Among the 3 polymorphisms, AQP5 rs74091167 was significantly associated with disease-free survival (DFS) and distant disease-free survival (DDFS) in a dominant model (P < 0.001 and P = 0.021, respectively). Moreover, multivariate survival analysis revealed that the GG genotype of AQP5 rs74091167 was significantly associated with better DFS (HR = 0.377; 95% CI 0.179-0.793; P = 0.010) when compared with the combine GC/CC genotype adjusted to clinicopathological variables. However, no difference in AQP5 rs74091167 polymorphism was observed based on patient and tumor characteristics. Conclusions: AQP5 rs74091167 variant can be considered as a prognostic marker in patients with EBC after curative operation. In the future, functional relevance of this variant needs to be clarified.
Tolerability and cardiac safety of neo/adjuvant trastuzumab-based chemotherapy regimens for HER2+ breast cancer: A single institution experience.
Authors: Jitawatanarat Potjana , Kossoff Ellen , Riebandt Grazyna , Levine Ellis Glenn , O'Connor Tracey L. , Chittawatanarat Kaweesak , Ngamphaiboon Nuttapong 
Published: March 2020

e11508 Background: Docetaxel/carboplatin/trastuzumab (H) (TCaH) and doxorubicin/cyclophosphamide/paclitaxel/H (AC-TH) and its variants are recommended by standard guidelines for neoadjuvant and adjuvant treatments for HER2+ breast cancer. Docetaxel/cyclophosphamide/H (TCyH) has also been used in clinical practice. Tolerability and cardiac safety among these regimens have not been well described. Methods: We retrospectively reviewed HER2+ early stage breast cancer who received neo/adjuvant H at RPCI between 2004-2011. Acute toxicities of different regimens (AC-TH and its variants, TCaH, TCyH) were evaluated. Cardiac events were defined as symptomatic congestive heart failure (CHF) and/or asymptomatic decline of ejection fraction (EF) that resulted in holding H. Results: 177 patients were identified (AC-TH=114, TCaH=39, TCyH=24). Patients who received AC-TH were younger, had less comorbidity, including cardiac history, and received less GCSF support. AC-TH regimens were associated with more febrile neutropenia (FN), grade 3-4 neutropenia, and dose delay (Table). Overall cardiac events were observed in 18% (anthracyclines 14% vs non-anthracyclines 9%; p=0.346). Termination of H was not significantly different between patients treated with anthracyclines (4%) vs non-anthracyclines (2%), nor was the CHF rate (4% vs 6%). Median absolute EF decline was also similar (5% vs 4%). After adjustment for age ≥65, cardiac history, baseline EF <55%, and Charlson Comorbidity Index, patients treated with anthracyclines showed a trend toward increased cardiac events (OR 4.53, 95% CI 0.99-20.5; p=0.05) in multivariate analysis. Conclusions: Although physician selection of patients for trastuzumab directed therapy lessens overall toxicity, the acute toxicity and cardiac event rate among those considered the most fit remains considerable when an anthracycline is introduced. [Table: see text]
Bond oracle HER2 IHC assay for identifying low to intermediate HER2-expressing breast cancer.
Authors: Reid Victoria Ann , Schwartz Mark W. , Kumar Sonia , White Yvonne Alexandra , Mazanet Rosemary 
Published: March 2020

e11509 Background: HER2 targeted therapies are effective treatment for breast tumors that overexpress the HER2 protein to a high level (IHC score of 3+) or have amplification of the HER2 gene (HER2/CEP17 >2). However, the majority of breast tumors exhibit low to intermediate expression of HER2 (IHC 1+ and 2+), for which there are limited treatment options. A new cancer vaccine candidate, E75 or nelipepimut-S, offers prevention of reoccurrence in these patients by generating a specific immune response to a HER2 peptide. To date, no companion diagnostic test is validated to differentiate HER2 at these levels of expression. The BOND Oracle HER2 IHC assay (Leica Biosystems) is being validated to reliably identify IHC HER2 1+ and 2+ cases by correlating to independent analytical measures of HER2 expression. Methods: Quantitative PCR was used to determine HER2 DNA copy number and mRNA expression in eight breast cancer cell lines spanning HER2 IHC scores of 0 to 3+ and 45 formalin fixed, paraffin embedded (FFPE) invasive breast tumor samples. HER2 receptor load was determined for the eight cell lines by flow cytometry. Data was correlated to HER2 expression levels as determined by manual interpretation using the BOND Oracle HER2 IHC assay. Results: Previous testing by Leica Biosystems (Table) demonstrates the relationship between HER2 receptor load, HER2 copy number, and HER2 IHC status on four assay control breast cancer cell lines. Preliminary results also show that HER2 mRNA expression correlates with IHC staining with the BOND Oracle HER2 IHC Assay in FFPE breast cancer tissue samples. Conclusions: Improving the discrimination of HER2 protein expression (IHC 1+, 2+) using the Bond Oracle HER2 IHC assay in breast cancer tumors will identify patients for new treatments in development such as E75. [Table: see text]
Association of NBS1 expression with improved pathologic complete response rate in HER2-overexpressing breast cancer.
Authors: Sen Fatma , Yavuz Ekrem , Yegen Gulcin , Karanlik Hasan , Tuzlali Sitki , Aydiner Adnan 
Published: March 2020

e11534 Background: Our aim was to investigate potential correlation between expression levels of Nijmegen breakage syndrome1 (NBS1) protein and phosphatidylinositol-3 kinase (PI3K) and pathologic complete response (pCR) rate to neoadjuvant treatment in locally advanced HER2+ breast cancer. We also assess possible association between NBS1 and PI3K expressions. Methods: Totally 42 patients (median age 49 years), received neoadjuvant treatment due to locally advanced HER2+ breast cancer, were included. Immunohistochemical analyses were performed on paraffin sections, obtained during initial diagnosis. Paraffin sections were stained with anti-NBS1 (P95-NBS1 antibody, Y112, ab32074) and anti-PI3K (PI3-Kinase p85 alpha+gamma antibody, ab741369) antibodies to determine positivity of related proteins. Results: NBS1 protein loss was detected in 19 (%45) patients whereas p85 loss was shown in 25 (%60). There was no initial clinicopathologic variable predicting pCR. Fifteen of 30 patients, received neoadjuvant trastuzumab, had pCR, whereas only 1 of 12 patients, not received trastuzumab, achieved pCR (P = 0.012). p85 loss did not predict treatment response, however NBS1 protein expression positively correlated with increased response rate to neoadjuvant treatment (P = 0.007). Conclusions: NBS1 protein expression associates with increased pCR rate in HER2+ breast cancer. However, P85 positivity did not associate with pCR rate or NBS1 overexpression.