bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reacquisition of RAI uptake in RAI-refractory metastatic thyroid cancers by pretreatment with the MEK inhibitor selumetinib.
Authors: Ho Alan Loh , Leboeuf Rebecca , Grewal Ravinder K. , Sherman Eric Jeffrey , Deandreis Desiree , Pentlow Keith S. , Tuttle Robert Michael , Fury Matthew G. , Ricarte-Filho Julio Cezar M. , Pfister David G. , Larson Steven M. , Fagin James A. 
Published: March 2020

5509^ Background: Therapies for radioactive iodine (RAI)-refractory thyroid cancers of follicular origin (TC-FCO) are desperately needed. TC-FCO mouse models show that blocking mitogen-activated protein kinase (MAPK) signaling with a MAP kinase kinase 1/2 (MEK1/2) inhibitor increases sodium iodide symporter expression and iodine incorporation. This 20 patient (pt) pilot study aimed to evaluate if the MEK1/2 inhibitor selumetinib (AZD6244, ARRY-142866) can reverse RAI-refractoriness in TC-FCO pts (NCT00970359). Methods: RAI-refractory TC-FCO disease was defined as: 1) non-RAI-avid lesion/s on a diagnostic or post-therapy RAI scan, 2) RAI-avid lesion/s that was stable or increased in size after RAI therapy, or 3) fluorodeoxyglucose (FDG)-avid lesion/s by positron emission tomography (PET) scan. rhTSH-stimulated lesional dosimetry with 124I PET was performed prior to and after 4 weeks of treatment with selumetinib (75 mg orally bid). If the second 124I PET scan predicted a lesional RAI dose of > 2000 cGy, therapeutic RAI was administered while on the drug. Primary endpoints were to evaluate changes in tumor iodine uptake and RECIST response after RAI therapy; changes in serum thyroglobulin (TG) after RAI was a secondary endpoint. Results: 24 pts were enrolled, 22 eligible, and 20 evaluable. For the 20 evaluable pts, median age was 61 (range 44-77 yrs), 11 were men. 19 pts had tumors analyzed for BRAF and N-,K- RAS mutations. 8 pts had BRAF mutant (MUT), 11 BRAF wild-type (WT) tumors; 1 pt to be analyzed. Selumetinib increased 124I uptake in 12 of the 20 pts (4 of 8 BRAF MUT; 8 of the 12 other pts). The 8 of those 12 pts achieving sufficient iodine avidity to warrant RAI therapy included all 5 pts known to be NRAS MUT to date and 1 BRAF MUT pt. Of the 7 pts who have received RAI, 5 had partial responses (PRs); 2 stable disease (SD). Mean percent reduction in TG in this group (pre- vs 2 months post- RAI) was 91%. No > grade 2 CTCAE toxicities attributable to selumetinib were observed. 1 pt was diagnosed with myelodysplastic syndrome > 51 weeks after RAI (unrelated to selumetinib). Conclusions: Selumetinib can enhance iodine uptake in a subset of RAI-refractory TC-FCO and may be particularly effective for RAS MUT tumors.
Acetylated tubulin and risk of nodal metastases in squamous cell carcinoma of the head and neck (SCCHN).
Authors: Saba Nabil F. , Magliocca Kelly R. , Kim Sungjin , Muller Susan , Chen Zhengjia , Eggers Carrie , Phelan Vanessa H , Kono Scott A. , Owonikoko Taofeek Kunle , Ramalingam Suresh S , Grist William , Chen Amy Y. , Beitler Jonathan Jay , Shin Dong M , Marcus Adam , Khuri Fadlo Raja 
Published: March 2020

5560 Background: We previously established that AT expression predicts for response to chemotherapy in SCCHN (Saba et al, AACR 2010 meeting abstr 3744). We wanted to further examine the relation of AT expression and nodal metastases in SCCHN. Methods: We assessed AT expression in archival tissue specimens from primary SCCHN cases with (50 cases) and without (53 cases) lymph node metastases (NM) using standard immunohistochemistry (IHC). Clinical characteristics of patients were retrieved from the department of pathology under the guidelines of the institutional review board (IRB). IHC staining for AT was scored based on intensity and percentage of tumor cells stained: 0 = no staining, 1+ = weak, 2+ = moderate, 3+ = moderate to high, 4+ = high and a weighted index (WI) was calculated as percent stain x stain intensity. Wilcoxon two-sample test and Kruskal-Wallis test were used to estimate the relationships of the WI with nodal metastasis, node status, primary tumor location, grade, and stage. Log-rank test was used to examine the difference in OS and DFS among four groups based on quartiles of the WI. A Cox proportional hazard model was employed to estimate the adjusted effect of WI on OS and DFS. Results: A higher AT expression was associated with nodal metastasis (p=0.0155) and higher stage (p=0.0311). A lower AT expression was associated with oral cavity primary (p=0.0107). After adjusting for age, gender, race, and smoking status, a lower AT expression was significantly associated with better DFS in the subset of patients with NM by multivariate analysis (HR=1.008; 95% CI=1.002- 1.014; p=0.0123). Among patients with no NM there was a marginally significant difference in OS among four different groups based on quartiles of AT expression (p=0.0765). Conclusions: High AT expression is associated with nodal metastases in SCCHN and may be a marker of poor prognosis in patients with node positive disease. The value of AT as a prognostic marker in SCCHN needs to be better defined. This work is supported by a SPORE CDP Grant P50 CA128613-03 to NFS.
P16 and cyclin D1 (CYD1) as prognostic markers in hypopharyngeal (HSC) and oropharyngeal squamous cell carcinoma (OSC).
Authors: Ang Siok Hoon , Haaland Benjamin , Thu Minn Minn Myint , Krishna Sai Sakktee , Chen Wallace , Hwang Siok Gek Jacqueline , Tan Puay Hoon , Tai Wai Meng David , Tan Eng Huat , Lim Wan-Teck , Ang Mei-Kim 
Published: March 2020

5580 Background: In head and neck cancer (HNC), dysregulation of cell cycle proteins p16 and CYD1 are common. Variable associations of p16 over- and under- expression and CYD1 overexpression with overall survival (OS) have been described in different HNC sites. We evaluated the relationship of p16 and CYD1 expression with clinical characteristics and OS in OSC and HSC. Methods: p16 and CYD1 expression was evaluated by immunohistochemistry in 77 HSC and 103 OSC patients (pts) and recorded as p16N (0% tumor cells stained), p16L (5-69%) and p16H (≥70%), CYD1-(<10%) and CYD1+ (≥10%). OS between groups was evaluated by Kaplan-Meier method and compared by log rank test. Hazard ratio (HR) for death was estimated using multivariable Cox models. Results: Pts were predominantly Chinese (83.6% v 85.4%) with locally advanced HNC (91.4% v 92.2%). Compared to OSC, HSC pts were older (median age 67 v 61 yrs), more likely male (89.3% v 74.0%), current or ex-smokers (83.3% v 63.6%) with higher comorbidity-age combined risk score (ageCCI), less likely p16H (6.5% v 30.1%)(all p<0.001) and had similar CYD+. p16H pts were younger (median age 58 (p16H) v 65 (p16L) v 66 (p16N) yrs, p=0.002), more likely non-smoker (51.4% v 23.4% v 13% p<0.001) with lowest ageCCI (p<0.001). Clinical characteristics did not differ by CYD1 status. At median f/u of 50mths, median OS was 33 mths. Median OS was poor in HSC compared to OSC (23.9 v 72.1, p<0.001). Multivariate analysis showed associations of N2/N3 disease (HR 1.57, p=0.036), ageCCI (HR 1.22 per 1 pt increase, p<0.001), p16 (p16H: ref; p16L: HR 2.34, p=0.045; p16N: HR 2.74, p=0.013) and CYD1+ (HR 1.94, p=0.015) with death, independent of gender, smoking and site. Association of p16 with OS was seen mainly in OSC (median OS p16H: not reached (NR), p16L: 62, p16N: 22 mths, p<0.001) compared with median OS (HSC) (27 v 28 v 21, p=0.609). Similarly the association of CYD1 with OS was mainly in OSC (median OS CYD1-: NR v 23 mths, p<0.001 v HSC: 25 v 25 mths, p=0.19). Conclusions: In OSC, p16 expression correlates with OS, with p16N associated with worst OS. CYD1 has an independent association with OS. Poorer OS in HSC may be due to adverse clinical characteristics. Assessment of p16 and CYD1 status in HSC did not predict for OS.
Characterization of the overall survival benefit in ENCORE 301, a randomized placebo-controlled phase II study of exemestane with and without entinostat in ER+ postmenopausal women with metastatic breast cancer.
Authors: Klein Pamela , Ordentlich Peter , McCulloch William , Cruickshank Scott , Rees Miranda , Yardley Denise Aysel 
Published: March 2020

567 Background: Histone deacetylase inhibitors (HDACi) prevent the emergence of drug tolerant clones and sensitize cells to a variety of anti-cancer therapies. We previously reported ENCORE 301, a randomized placebo controlled phase 2 study comparing exemestane with (EE) and without (EP) the HDACi entinostat met its primary endpoint of prolonging progression free survival (PFS) (4.3 months vs 2.3 months) and extending overall survival (OS) benefit (26.9 vs 19.8 months). In order to characterize and better understand the OS benefit, exploratory analyses were conducted. Methods: Hazard ratios (HR) for treatment were estimated from the Cox proportional hazards model, with EP serving as the reference treatment in the calculations. Inferential comparisons between treatment groups were made using the log-rank test. Results: Analysis of OS across multiple subsets of interest demonstrated a consistent benefit in EE group versus EP. Sensitivity analysis of baseline characteristics potentially impacting OS did not identify any factors that influenced the effect of EE on OS. Examination of treatments received during follow-up after discontinuation of EE and EP demonstrated balance between treatment group for patients receiving chemotherapy (48% EE: 44% EP), hormone therapy (37% EE: 35% EP), bisphosphonates (2% EE; 0% EP), radiation (6% EE; 5%EP), and surgery (0% EE: 2% EP). Compared to EP, OS was longer in EE group for patients whose first subsequent treatment was a hormone therapy (EE median not reached vs EP median 20.5 months; HR 0.65 [95% CI 0.26, 1.58]) or chemotherapy (EE median 26.9 months vs EP median 17.6 months; HR 0.51 [95% CI 0.25, 1.04]). Updated PFS and OS data will also be presented along with correlation analysis of PFS and OS. Conclusions: Analyses of baseline characteristics, subsequent treatment and subsets of prognostic factors in ENCORE 301 did not identify any contributing factors that account for the extended OS benefit in the EE treatment group. Long lasting effects of entinostat on progenitor cells, emergence of drug tolerant cells and or priming to subsequent therapies cannot be ruled out.
Treatment pattern by hormone receptors and HER2 status in patients with metastatic breast cancer in the United Kingdom, Germany, France, Spain, and Italy (EU-5): Results from a physician survey.
Authors: DeKoven Mitch , Bonthapally Vijayveer , Lee Won Chan , Pathak Prathamesh , Jiao Xiaolong , Ray Saurabh 
Published: March 2020

570 Background: The differences in country-specific treatment patterns across Europe for Stage IV metastatic breast cancer (mBC) patients have not been extensively studied. This study compared treatment choices, by biomarker status, between various lines of therapy (LOT) in clinical practice in the EU-5 countries among newly diagnosed stage IV mBC patients. Methods: The IMS LifeLink Oncology Analyzer (OA) database, based upon practicing oncologist surveys, was used to identify mBC patients aged ≥21 and surveyed between July 2008 – June 2010. The database encompasses over 100,000 unique patients per year, treated by nearly 3,000 physicians, including nearly 60,000 patients and 800 physicians in the EU5. Results: A total of 152,311 mBC patients were included in the study. In Italy, 30.8% of HER2+/HR+ patients received chemotherapy following mBC diagnosis, as compared to only 8.6% in France. The majority of these patients in France received chemotherapy plus a HER2 targeted therapy (58.2%) as their first treatment. For HER2+/ HR- patients, chemotherapy plus a HER2 targeted therapy was provided to the majority of the patients in France (70.8%), with the UK providing this regimen to the fewest patients with this biomarker status (44.9%). Monotherapy hormonal regimens were given as a first LOT for HER2-/HR+ patients (UK 64.7%, Spain 52.8%). Triple negative patients received chemotherapy (UK 84.1% as compared to France 57.3%) or chemotherapy plus bevacizumab (France 36.6% as compared to UK 0.9%) as a first treatment. Conclusions: Thisstudy confirmed that chemotherapy combined with HER2-targeted therapy was the most frequent initial treatment option for HER2+ patients, while the vast majority of ER/PR+ patients were initially treated by hormonal therapy, suggesting that a personalized medicine approach has been accepted in the EU-5. However, the use of HER2-targeted therapy and bevacizumab greatly varied; while they were most frequently used in France, they were least frequently opted for in the UK. Also, fewer treatment options existed for triple negative patients and patients with HER2+ disease following trastuzumab treatment.
An international study of multitrial data investigating quality of life and symptoms as prognostic factors for survival in different cancer sites.
Authors: Quinten Chantal , Zikos Efstathios , Sprangers Miriam , Greimel Eva , Martinelli Francesca , Reeve Bryce B. , Ringash Jolie , Gotay Carolyn , Maringwa John T , Coens Corneel , Ediebah Divine Ewane , King Madeleine , Osoba David , Cleeland Charles S. , Flechtner Henning , Schmucker-Von Koch Jospeh , Taphoorn Martin J. B. , Weis Joachim , Bjordal Kristin , Bottomley Andrew 
Published: March 2020

6002 Background: The prognostic value for survival of HRQOL data derived from self-report questionnaires, has been well documented in cancer research. The objective of this study was to examine the prognostic value of HRQOL parameters for different cancer sites using one standardized and validated patient self-assessment tool. Methods: A total of 11 different cancer sites, pooled from 30 European Organisation for Research and Treatment of Cancer (EORTC) Randomized Controlled Trials (RCTs), were selected for this study. For each cancer site, univariate and multivariate Cox proportional hazard modeling was used to assess the prognostic value (p<0.05) of 15 HRQOL parameters, assessed with the EORTC QLQ-C30 at baseline before randomization, for overall survival. Models were adjusted for the parameters age, gender, distant metastasis, World Health Organization performance status and stratified by clinical study. Results: A total of 7,417 patients completed the EORTC QLQ-C30 before randomization. For brain cancer cognitive functioning (CF) (hazard ratio (HR) =0.95; p<.0001) was prognostic. For breast cancer nausea and vomiting (NV) (HR=1.17; p=0.0011) was a prognostic indicator. For colorectal cancer physical functioning (PF) (HR=0.93; p<.0001), NV (HR=1.07; p<.0001), and appetite loss (AP) (HR=1.07; p<.0001) predicted survival. For esophageal cancer PF (HR=0.88; p=0.0072) and for head and neck cancer NV (HR=1.14; p=0.0097) were prognostic. For lung cancer PF (HR=0.94; p=0.0006) and pain (HR=1.08; p<0.0001), for melanoma dyspnea (HR=1.06; p<.0001), for ovarian cancer NV (HR=1.2; p<.0001), for pancreatic cancer global QOL (HR=0.83; p=0.0073), for prostate cancer role functioning (RF) (HR=0.96; p=0.006) and AP (HR=1.07; p<.0001), and for testis cancer RF (HR=0.81; p=0.0144) were predictors of survival. Conclusions: Our findings show that different HRQOL parameters provide prognostic information for survival for patients with different tumor sites and that no single HRQOL scale can predict survival in all cancer patients. Thus, each cancer site needs careful examination and no single QOL paramenter can predict survival in all cancer diseases.
Refused versus recommended adjuvant chemotherapy in the United States: A reason for concern.
Authors: Habermann Elizabeth Butzer , Abraham Anasooya A , Zhu Yanrong , Markin Abraham , Rothenberger David A. , Kuntz Karen M , Vickers Selwyn M. , Al-Refaie Waddah B. 
Published: March 2020

6016 Background: We designed this study to identify factors driving treatment recommendations and refusal in surgically treated patients with gastrointestinal (GI) cancers eligible for adjuvant chemotherapy. Methods: Using the 2001-2008 California Cancer Registry (CCR), we constructed a cohort of 22,469 patients surgically treated for three GI cancers and eligible for adjuvant chemotherapy (stage III colon cancer in patients < 80 years, Ib-IVM0 gastric cancer, or nonmetastatic resected pancreatic adenocarcinoma). Information on chemotherapy receipt, recommendation, and refusal was utilized to construct our outcome measures. Multivariate logistic regression models identified predictors of recommendation and refusal of adjuvant chemotherapy across three GI cancer sites, adjusting for potential confounders. Results: Of those eligible for adjuvant therapy, only 61.4% were recommended treatment and 54.3% received it. Refusal rate was 3.5%. Persons who were older, black, publicly insured or uninsured, or with gastric cancers were less likely to have adjuvant chemotherapy recommended. Yet, older, Medicaid-insured, and those treated for gastric cancer were more likely to refuse adjuvant therapies. Women were as likely as men to be recommended adjuvant therapies but more likely to refuse them (Table). Conclusions: Many patients eligible for adjuvant chemotherapy after GI cancer surgery have not been so advised. Striking variations exist between recipients of treatment recommendations versus those who refuse them. These results demonstrate a wide implementation gap between the recommendations arising from cancer clinical trials versus actual clinical practice. [Table: see text]
Endocrine therapy use among Medicaid-insured breast cancer survivors with hormone receptor-positive tumors.
Authors: Kohler Racquel Elizabeth , Wheeler Stephanie B. , Reeder-Hayes Katherine Elizabeth , Goyal Ravi K. , Lich Kristen Hassmiller , Smith Timothy , Melvin Cathy , Moore Alexis , Muss Hyman Bernard 
Published: March 2020

6017 Background: Estrogen receptor positive (ER+) and progesterone receptor positive (PR+) cancers account for the majority of breast cancer diagnoses and deaths. Among women with ER+ or PR+ breast cancers, endocrine therapy (ET) is the cornerstone of adjuvant therapy and reduces 5-year risk of recurrence by as much as 40%. Observational studies in Medicare and privately-insured populations suggest that ET is underutilized. We sought to characterize ET use in a low-income Medicaid-insured population in North Carolina. Methods: We used Medicaid claims data matched to NC Central Cancer Registry records for women ages 18-64 diagnosed with in situ, stage I or II breast cancer from 2003-2007. We excluded dual eligibles and included only cases enrolled in Medicaid for at least 12 of the 15 months following the index diagnosis. We defined our outcome as receipt of any ET medication (tamoxifen, letrozole, exemestane, or anastroxole) in prescription claims during the 15-month period post-diagnosis, among women with ER+ or PR+ disease. In multivariate logistic regressions, independent variables included age, race, tumor characteristics, receipt of other breast cancer treatments, co-morbidity, rural/urban residence, reason for Medicaid eligibility, involvement in the Breast and Cervical Cancer Control Program (BCCCP), patient-centered medical home enrollment, and diagnosis year. Results: Of the 269 women who met inclusion/exclusion criteria and were ER+ or PR+, only 45% filled a prescription for ET during the study period. In multivariate analyses, being involved in the CDC-affiliated BCCCP was significantly associated with higher likelihood of receipt of guideline-recommended endocrine therapy (Marginal Effect: 0.299, p<0.01), but other independent variables were not significantly correlated with receipt of ET. Conclusions: Results suggest that ET is substantially underutilized in this low-income, vulnerable population and that intervention efforts to improve ET use may be important. Qualitative research is needed to understand the more nuanced, behavioral reasons for ET underuse, which may be related to symptom burden, cost, and patient-provider communication.
Neoadjuvant bevacizumab (B) and trastuzumab (T) in combination with weekly paclitaxel (P) as neoadjuvant treatment in HER2-positive breast cancer: Results from a phase II trial (AVANTHER).
Authors: Fernandez Abad Maria , Calvo Isabel , Martinez Noelia , Herrero Mercedes , Quijano Yolanda , Duran Hipolito , Garcia Aranda Mariola , Suárez Ana , López-Ríos Fernando , Perez Diego , Perea Sofia , Hidalgo Manuel , García-Estevez Laura 
Published: March 2020

602 Background: B in combination with T has showed meaningful activity in patients (pts) with metastatic HER2-positive breast cancer. AVANTHER is a Phase II trial of preoperative systemic therapy combining B with T and P in a weekly regimen in HER2 positive breast cancer to assess safety and efficacy of the combination. Methods: Pts with centrally-confirmed HER2-positive (IHC 3+ or FISH positive) breast cancer (stage II or III including locally advanced) received neoadjuvant chemotherapy (NC) with weekly P (80mg/m2/week) for 12 weeks in combination with weekly T (4mg/kg loading dose and 2 mg/kg maintenance) and B (15mg/kg every 3 weeks) for 4 cycles. After surgery all pts received T (1 year) and liposomal doxorubicin plus cyclophosphamide every 3 weeks (4 cycles); primary endpoint was rate of pathological complete response (pCR) in breast and axilla. For all patients, a tissue sample at baseline as well as at surgery was collected for biomarker analyses. Results: A total of 44 pts have been enrolled. Median tumor size: 3.9 cm. Seven (19.4%) pts had stage IIA; 17 (47.2%) stage IIB; 8 (22.2%) stage IIIA and 4 (11.1%) stage IIIB. Twenty-one (58.3%) pts had both positive-hormonal receptors and 10 (27.8%) were hormone receptor negative. Eight (22.2%) pts had sentinel biopsy before NC, being negative in 6 (16.7%) cases. Data from surgery (only from 36 pts): pCR was achieved in 16 (44.4%) pts. Safety and tolerability were good, with rare adverse events of grade ≥3 [1 (2.8%) episode of severe hypertension]. Conclusions: These data show that the combination of P with T and B without an anthracycline for 12 weeks is very effective as NC in HER2 positive breast cancer pts with a high rate of pCR and minimal side effects.