bluuebunny/crossref_metadata_2025_split huggingface dataset:
LUX-Lung 3: A randomized, open-label, phase III study of afatinib versus pemetrexed and cisplatin as first-line treatment for patients with advanced adenocarcinoma of the lung harboring EGFR-activating mutations.
Authors: Yang James Chih-Hsin , Schuler Martin H. , Yamamoto Nobuyuki , O'Byrne Kenneth John , Hirsh Vera , Mok Tony , Geater Sarayut Lucien , Orlov Sergey V , Tsai Chun-Ming , Boyer Michael J. , Su Wu-Chou , Bennouna Jaafar , Kato Terufumi , Gorbunova Vera , Lee Ki Hyeong , Shah Riyaz N.H. , Massey Dan , Lorence Robert M. , Shahidi Mehdi , Sequist Lecia V. 
Published: February 2017

LBA7500 Background: Afatinib (A) is a selective, orally bioavailable, irreversible ErbB family blocker of EGFR (ErbB1), HER2 (ErbB2), and ErbB4. This global study investigated the efficacy and safety of A compared with pemetrexed/cisplatin (PC) in pts with EGFR mutation positive advanced lung adenocarcinoma. Methods: Following central testing for EGFR mutations (companion diagnostic TheraScreen EGFR RGQ PCR kit), 345 pts (stage IIIB/IV, PS 0–1, chemo-naive) were randomized 2:1 (A: 230; PC: 115) to daily A 40 mg or iv PC (500 mg/m2 + 75 mg/m2 q21 days up to 6 cycles). Primary endpoint was progression-free survival (PFS) by central independent review. Results: Baseline characteristics were balanced in both arms: median age, 61 y; female, 65%; Asian, 72%; never-smoker, 68%; Del19, 49%; L858R, 40%; other mutations, 11%. Treatment with A led to a significantly prolonged PFS vs PC (median 11.1 vs 6.9 mos; HR 0.58 [0.43–0.78]; p=0.0004). In 308 pts with common mutations (Del19/L858R), median PFS was 13.6 vs 6.9 mos, respectively (HR=0.47 [0.34–0.65]; p<0.0001). Objective response rate was significantly higher with A (56% vs 23%; p<0.0001). Significant delay in time to deterioration of cancer-related symptoms of cough (HR=0.60, p=0.0072) and dyspnea (HR=0.68, p=0.0145) was seen with A vs PC. Most common drug-related adverse events (AEs) were diarrhea (95%), rash (62%) and paronychia (57%) with A, and nausea (66%), decreased appetite (53%) and vomiting (42%) with PC. Drug-related AEs led to discontinuation in 8% (A; 1% due to diarrhea) and 12% of pts (PC). Conclusions: LUX-Lung 3 is the largest prospective trial in EGFR mutation positive lung cancer and the first study using pemetrexed/cisplatin as a comparator. Treatment with afatinib significantly prolonged PFS compared to PC, with significant improvements in secondary endpoints. AEs with afatinib were manageable, with a low discontinuation rate. With 4.2 mos PFS improvement in the overall population and 6.7 mos in pts with common mutations, afatinib is a clinically relevant first-line treatment option.
TAILOR: A phase III trial comparing erlotinib with docetaxel as the second-line treatment of NSCLC patients with wild-type (wt) EGFR.
Authors: Garassino Marina Chiara , Martelli Olga , Bettini Anna , Floriani Irene , Copreni Elena , Lauricella Calogero , Ganzinelli Monica , Marabese Mirko , Broggini Massimo , Veronese Silvio , Gherardi Giorgio , Longo Flavia , Fabbri Maria Agnese , Tomirotti Maurizio , Alabiso Oscar , Sarobba Maria Giuseppa , Labianca Roberto , Marsoni Silvia , Farina Gabriella , Scanni Alberto 
Published: February 2017

LBA7501 Background: While the benefit of EGFR tyrosine kinase inhibitors in the treatment of patients with NSCLC harboring EGFR mutations has been widely established, their value in treating patients with wt EGFR is still debated. To assess the role of erlotinib in these patients, we performed an independent multicenter phase III trial (Tarceva Italian Lung Optimization Trial [TAILOR] NCT00637910), comparing erlotinib to docetaxel in second line treatment, having overall (OS) and progression free survival (PFS) as principal and secondary endpoints, respectively. Methods: EGFR and KRAS mutational status were assessed by direct sequencing in all eligible patients; only patients with wt EGFR NSCLC (exons 19 and 21) at progression, and previously treated with a first line platinum-based regimen, were randomized to receive either erlotinib 150 mg daily or docetaxel 75 mg/m2 (3-weekly) or 35 mg/m2 (weekly) until disease progression or unacceptable toxicity occurred. To detect an hazard ratio of 0.67 (2-sided 5% significance level for the log-rank test and a power of 80%), 199 events were required for both OS and PFS evaluation. Results: On the planned analysis date (March 30, 2012), 221 patients had been randomized and 218 were evaluable (docetaxel 110, erlotinib 108; three major violations excluded). At a median follow-up of 20 months, 199 relapses and 157 deaths were recorded. The Kaplan-Meier PFS curves showed a highly significant increase favoring docetaxel (HR 0.70 with 95% CI 0.53-0.94; p = 0.016) over erlotinib regimen. The HR translated into an estimated absolute difference in 6-months PFS of 12% (16% vs 28%). Data concerning toxicity were consistent with the literature. Conclusions: In terms of PFS, our results indicate a clear superiority of docetaxel over erlotinib as second line treatment for patients without EGFR mutations in exons 19 or 21. Analysis of OS will be conducted as far as the planned number of 199 deaths is reached.
Nomogram to predict sentinel lymph node involvement in patients with clinically node-negative breast cancer receiving neoadjuvant chemotherapy.
Authors: Allen Lisa R. , Gadgil Pranjali V. , Bassett Roland , Hunt Kelly , Mittendorf Elizabeth Ann , Yi Min , Babiera Gildy , Kuerer Henry Mark , Ross Merrick I. , Bedrosian Isabelle , Meric-Bernstam Funda , Hwang Rosa F. 
Published: February 2017

150 Background: Sentinel lymph node biopsy (SLNB) has been shown to be an accurate predictor of axillary lymph node involvement in breast cancer patients treated with neoadjuvant chemotherapy (NAC). A predictive model of SLN positivity in clinically node negative patients who completed NAC can assist in preoperative multidisciplinary treatment decision making, such as planning for postmastectomy radiation therapy and breast reconstruction. Methods: We reviewed our prospective database to identifyclinically node negative patients with invasive breast cancer who underwent NAC and SLNB from 1998-2011. Clincopathologic factors including age, tumor location, histology, nuclear grade, tumor size, decrease in tumor size with therapy, multifocality, nodal appearance on preoperative ultrasound, hormone receptor status, and lymphovascular invasion (LVI) were analyzed. A nomogram to predict SLN metastasis was developed using multivariate logistic regression analysis. Results: A total of 836 patients were treated with NAC followed by SLNB. Of these, 160 patients (19.1%) had a positive SLN. All factors were significant predictors of SLN positivity on univariate analysis except tumor location and nodal appearance on preoperative ultrasound. Multivariate analysis showed that young age, invasive lobular histology, tumor size, multifocality, and LVI were independent positive predictors of SLN positivity whereas high grade, response to chemotherapy, and triple negative hormone receptor status were negative predictors. Favorable histologies were strongly associated with a lower rate of SLN positivity but were excluded from the nomogram due to small numbers of patients (N=14). Discrimination of the nomogram to correctly predict SLN positivity was measured using the area under the receiver operating characteristic curve (AUC). The unadjusted AUC was 75.9, while the internally validated 2000 bootstrap sample-adjusted AUC was 74.2. Conclusions: Neoadjuvant chemotherapy is known to decrease the incidence of positive nodes in breast cancer patients. Use of our nomogram preoperatively can assist in decisions regarding multidisciplinary treatment planning.
Tumor characteristics in obese women with breast cancer.
Authors: Chun Jennifer , Refinetti Ana Paula , Schnabel Freya Ruth , Price Alison , Billig Jessica , Cimeno Arielle , Schwartz Shira , Guth Amber , Axelrod Deborah M. ,   The Breast Surgery Section of NYULMC
Published: February 2017

179 Background: Obesity is an established risk factor for postmenopausal breast cancer. Though women with high BMI tend to develop less aggressive molecular subtypes, previous studies have shown that they still have a higher risk of recurrence and worse prognosis. The biological mechanisms for this difference in outcome have yet to be identified. The purpose of this study is to determine the correlation between obesity and tumor characteristics, including Ki67, and Oncotype DX scores in both pre- and post-menopausal women. Methods: The Breast Cancer Database of NYU Langone Medical Center was queried for patients who were newly diagnosed with invasive breast cancer. We looked at the following variables: menopausal status, body mass index (BMI), histology, stage, ER/PR/Her2-neu status, Ki67, and Oncotype DX scores. Obesity was defined as having a BMI (kg/m2) ≥30. We looked at Ki67 as a continuous variable. Oncotype scores were categorized as low (<18), intermediate (18-30), and high (>31). Statistical analyses were performed using Spearman Correlation Coefficients. Results: Out of a total of 648 patients with a median age of 59 years, 153 (24%) women had a BMI≥30. The majority of the obese women had stage I and II (88%) cancers that were ER positive (84%), PR positive (74%), Her2-neu negative (86%), with mean Ki67 of 22%, and low to intermediate Oncotype DX scores (85%). However, when compared with women of BMI <30, there was no correlation between BMI and tumor characteristics, even when stratified by menopausal status. Conclusions: In our cohort, obesity was not correlated with tumor stage, histology, Ki67 and Oncotype DX scores, even after adjusting for menopausal status. There are other factors that may explain the higher risk of recurrence and worse prognosis of breast cancer in obese women, such as insulin resistance, and obesity-related inflammatory cytokines that are independent of breast cancer subtypes and genomics. Treatment-related factors, such as non-compliance and inadequate dosing of chemotherapeutic agents, may also play a role in the worse outcome seen in this population. Further studies are necessary to identify measurable molecular characteristics of breast cancer in obese women that would allow us to predict more aggressive disease.
Factors influencing risk reduction surgery among BRCA mutation carriers: A qualitative analysis.
Authors: Brandt Rachael , Polinsky Cristina , Katz Jessica , Dhamankar Minal , Tucci Rosemarie , Sabol Jennifer L. , McHugh Terri 
Published: February 2017

53 Background: Women known to carry deleterious mutations in BRCA1 and BRCA2 have a substantially increased lifetime risk to develop breast and ovarian cancer. Current risk management options include increased surveillance, chemoprevention and risk reducing surgery. Several studies have quantitatively evaluated the reasoning of high risk women for electing surgical intervention, noting mutation carrier status as a significant, but not sole rationale for this decision. The decision for surgery has also been associated with family cancer history, anxiety, demographics, healthcare setting and prior counseling. More insights regarding factors influencing women’s choice for risk reduction are needed. Methods: To further assess factors influencing the decision to have risk reduction surgery among women in a community hospital system, 129 BRCA mutation carriers in a community-based genetic counseling program were invited to participate in a qualitative study using questionnaires. A thematic analysis was performed by two independent reviewers on open dialogue responses. Results: Of the 59 respondents, 54 completed the question specifically addressing factors regarding the decision on surgery. Of them, 32 opted for mastectomy, salpingo-oophorectomy or both and 22 opted against surgical risk reduction. Themes emerging in support of surgery included: vicarious experience attributable to a strong family history of cancer; desire for control over risk through surgical intervention; high risk perception; co-morbidities; desire for living, regarding longevity and for loved ones; fear of cancer; and skepticism related to cancer detection methods. For women opting against surgery, themes included: co-morbidities; age (too old/young); incomplete childbearing; logistics (scheduling, finances); lack of disease; and skepticism in effectiveness of surgery. Conclusions: While various factors have been studied regarding the association with or probability of women’s decisions for risk reduction surgery, a deeper comprehension of women’s reasoning can be attained through qualitative analysis. This understanding may enhance health care providers’ ability to counsel women regarding this choice.
Esophageal cancer gender disparity.
Authors: Mathieu Luckson Noe , Kanarek Norma , Hooker Craig , Rudin Charles M. , Brock Malcolm 
Published: February 2017

47 Background: Over the past thirty years, esophageal cancer (EC) incidence has been increasing more rapidly than any other solid neoplasm in the Western world. Globally, there is a large male predominance in both esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). The reasons for this gender difference and the possible role of estrogen are unclear. We conducted an analytical epidemiological study to determine if estrogen exposure explains the male predominance in observed esophageal cancer incidence. Methods: We evaluated the SEER cancer incidence and trends from 1975 to 2008 using SEER Stat to calculate the annual percentage change (APC) in each ten-year age group and in EAC and ESCC by gender. Results: Male predominance in incidence rates of EC was most evident in the younger group and those with EAC histology. The rate of increase for EAC incidence in post menopausal females is greater than in any other demographic category. This increasing incidence rate in the post menopausal female was also observed in the ESCC, but to a lesser extent. The APC was negative (-1.5) between 1975-2008 only in the 50-64 age female group. The negative APC in the female 50-64 years age group may be due to the increased use of exogenous hormonal therapy since 1975 for this age group. Interestingly, the APC was positive (increasing) in the 65+ age females. Conclusions: Using age as a proxy for estrogen exposure, our findings suggest a hormonal reason for the observed age-related, declining male to female EC incidence rate ratios. It also confirms gender differences in incidence long observed in EC and suggests that estrogen may serve as a preventative agent against EC. Moreover, this protective role of estrogen may dissipate with time if post menopausal estrogen use is discontinued. We have initiated a subset analysis of the nine individual SEER sites’ database to confirm the above findings by location and plan to further assess the relationship of both endogenous and exogenous estrogen via hormonal therapy use in EC incidence in the Women’s Health Initiative cohort. Our epidemiological observation of gender-age differences warrants translation into a molecular study with the use of sophisticated biomarkers to establish the seemingly protective role of estrogen in esophageal cancer.
Criteria for use of omics-based predictors in NCI-sponsored clinical trials.
Authors: McShane Lisa A. , Conley Barbara A. , Cavenagh Margaret M. , Lively Tracy G. , Eberhard David A. , Williams Paul M. , Bigbee William L. , Mesirov Jill P. , Polley Mei-Yin C. , Kim Kelly Y. , Tricoli James V. 
Published: February 2017

58 Background: High-throughput omics technologies (e.g., genomics, epigenomics, proteomics, metabolomics) offer exciting opportunities for new biological insights into cancer. The IOM report on translational omics defined omics as the study of related sets of biological molecules in a comprehensive fashion. (IOM (Institute of Medicine) 2012. Evolution of Translational Omics: Lessons Learned and the Path Forward. Washington, DC: The National Academic Press.) The promise of omics technologies has proven problematic to translate into clinically useful tests. Difficulty obtaining biospecimens, unrecognized preanalytical influences, and suboptimal assay analytical performance can lead to unreliable results and conflicting reports. Poor reporting of study details and limited access to data and computer code can thwart efforts to replicate published results or to detect flaws in study design and analysis methods. Methods: NCI held an interactive workshop for a wide variety of stakeholders to explore better approaches to omics-based test development and validation. This workshop heavily informed the ideas presented here. Recommendations are stated concisely, then explained. Results: A checklist of items to consider when evaluating the evidence for clinical use of an omics-based predictor, including in a trial where it will guide therapy, is presented. It covers specimen and assay requirements, the predictor model development process, clinical study design and conduct, and regulatory, ethical, and legal issues. The list applies to any trial involving investigational use of an omics test that will alter the clinical management of patients. The criteria also largely apply to situations in which the test will be evaluated retrospectively on specimens collected from patients who were prospectively enrolled on clinical studies. Conclusions: The proposed checklist should serve as a useful guide to investigators planning to submit proposals for NCI-funded studies involving use of an omics-based test. Ideally, this checklist will be consulted in the assay planning and development phases so that the necessary evidence will have been collected in a well-documented fashion by the time definitive evaluation of the test is desired.
Effect of sequential docetaxel followed by mTOR inhibitor temsirolimus on suppression of PI3K overactivation resistance mechanism.
Authors: Huang Chao Hui , Van Veldhuizen Peter J. , Gadashova Ayten , Williamson Stephen K. , Farassati Faris 
Published: February 2017

88 Background: Mammalian target of rapamycin (mTOR) is a downstream regulatory protein of the PI3K/Akt signal transduction pathway. This is a common pathway for a several cell surface receptors including IGFR (Insulin-like Growth Factor Receptor) and EGFR (Epidermal Growth Factor Receptor). The activation of these receptors through PI3K/Akt pathway is essential in cell proliferation, angiogenesis, and anti-apoptosis process. The upregulation of PI3K could be a mechanism of resistance of mTOR inhibitors. Docetaxel (D) is commonly used in the treatment of lung cancer. We demonstrated previously that the sequence of D followed by mTOR inhibitor temsirolimus (T) in lung cancer cell lines (LCCL) had synergistic effect in suppressing cell proliferation compared with T→D. The exact mechanism of this effect is unknown. We studied the expression of mTOR and PI3K in these cell lines treated in different time points to investigate the activity of this pathway when using these sequences of drug treatment. Methods: Adenocarcinoma LCCL H2122 and H1437 were plated and exposed to temsirolimus 1000nM and docetaxel 100nM. The cell viability was measured by optical density (OD) at 24, 48, and 72h. We tested effect of drugs D and T alone as well as the sequence of D treated for 24h followed by addition of T and the reverse in both LCCL. We then prepared cell lysate at 24h, 48h, and 72h time points and studied the expression of phospho mTOR (pmTOR) and PI3K by western blot using antibody obtained from cell signaling. Results: The use of T alone increased the expression of PI3K in both H2122 and H1437 cell lines at 48h time point. The use of D had a variable response: absent in H1437 and present in H2122 at 48 H. The sequence of D→T suppressed the expression of pmTOR and PI3K at 48 and 72 h compared with the opposite sequence of T→D. Conclusions: The combination of D → T is synergistic in suppression of pmTOR and inhibited the overactivation of upstream PI3K in both LCCL compared with opposite sequence. Therefore, the sequential treatment of D followed by T is able to overcome the PI3K overactivation mechanism of resistance in lung cancer cell line when treated with T. This would have implications in the use of these agents in treatment of lung cancer.
The prevalence and burden of cancer symptoms among underserved Chinese American patients.
Authors: Dhingra Lara , Lam Kin Y. , Cheung William , Shao Theresa , Chang Victor Tsu-Shih , Chen Jack , Cheng Sabrina , Li Vanessa , Lam Wan , Chan Selina , Bookbinder Marilyn , Lo Graciete , Portenoy Russell 
Published: February 2017

106 Background: Chinese Americans are the largest Asian subgroup in the U.S., and many are recent immigrants with high rates of cancer, a leading cause of death for this population. Although Chinese American patients frequently present with advanced illness and poorly controlled pain, information on symptom burden in this population is very limited. As part of an ongoing community study to test the effectiveness of a rapid-cycle quality improvement (QI) intervention to enhance symptom management, we evaluated the prevalence and burden of cancer symptoms in a large sample of first-generation, non-English speaking, ethnic Chinese patients. Methods: A consecutive sample of Chinese American patients in two large community-based oncology practices and one hospital-based practice in New York were screened for cancer symptoms. Eligible adults who self-identified as ethnic Chinese, spoke Cantonese or Mandarin as their primary language, and had a history of cancer completed translated instruments assessing symptom prevalence, severity, and distress administered by bilingual research assistants. The study was approved by the IRB at Beth Israel Medical Center in New York. Results: Of 1,018 cancer patients screened to date (62.2% women; M age = 64.0 years (SD = 13.7, range = 23 to 101); 20.6% reported persistent cancer pain for the past month. The most common cancers were breast (34.3%) lung (12.6%), and head and neck (11.8%) and 41.9% were undergoing active treatment. The mean worst pain intensity on a 0-10 numeric scale was 5.5 (SD = 2.2), with 34.4% rating their worst pain as > 6 of 10. Many (84.5%) reported other symptoms, including fatigue (54.4%), dry mouth (52.4%), difficulty sleeping (44.8%), and drowsiness (37.5%). Overall, 32.7% rated their symptoms as “quite a bit” or “very much” distressing, with sleep disturbance (33.1%), lack of appetite (31.3%), and constipation (29.2%) causing the most severe distress. Conclusions: Symptom burden is high among community-dwelling, economically-disadvantaged ethnic Chinese cancer patients. Our ongoing QI intervention may alleviate the high symptom rate in this population and clarify potential patient, provider, and system-related factors that are associated with symptom control outcomes.