bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radiosensitization of androgen receptor (AR)-positive triple-negative breast cancer (TNBC) cells using seviteronel (SEVI), a selective CYP17 lyase and AR inhibitor.
Authors: Speers Corey Wayne , Chandler Benjamin , Zhao Shuang , Liu Meilan , Wilder-Romans Kari , Olsen Eric , Nyati Shyam , Rae James M. , Hayes Daniel F. , Spratt Daniel Eidelberg , Wahl Daniel Richard , Feng Felix Yi-Chung , Pierce Lori J. 
Published: September 2018

e12102 Background: Increased rates of locoregional recurrence have been observed in TNBC despite chemotherapy and radiation (RT). A novel radiosensitizer screen nominated the AR as a promising target for treatment of radioresistant breast cancer, including TNBC. We assessed in vitro activity of SEVI (VT-464), a selective CYP17 lyase and AR inhibitor, as a potential radiosensitizer in AR+ TNBC model. Methods: Clonogenic survival assays were used to determine the intrinsic RT sensitivity of 21 breast cancer cell (BCC) lines. IC50 values were determined for 130 clinically available compounds and correlation coefficients were calculated using IC50 values and SF-2Gy. Gene expression was measured using RNA Seq or qRT-PCR and protein expression was measured using RPPA arrays. AR function was assessed using functional inhibition with SEVI in MDA-MB-453, ACC-460, SUM-185 (all three AR+ TNBC), MDA-MB-231 (AR- TNBC), and T47D (AR- ER+) BCC lines. Double-stranded DNA (dsDNA) break repair was assessed with γH2AX foci counting. Results: Our novel radiosensitizer screen identified the activity of bicalutamide, an AR antagonist, in RT-resistant BCC lines (R2 = 0.46, p-value < 0.01). Heterogeneity in AR expression was identified in human BCC lines. There was a strong correlation between AR RNA expression and protein expression across all BC intrinsic subtypes. AR inhibition using SEVI induced radiation sensitivity in vitro with an enhancement ratio (ER) of 1.24-1.62 in three different AR+ TNBC lines. No such radiosensitization was seen in AR(-) TNBC or ER+, AR(-) BCC lines. Radiosensitization was at least partially dependent on impaired dsDNA break repair with significant delays in dsDNA break repair at 16 and 24 hours in all AR+ TNBC lines examined (p-value < 0.01). Conclusions: Our results implicate the AR as a mediator of radioresistance in breast cancer and support the rationale for developing seviteronel as a novel radiosensitizing agent in AR+ TNBC.
Evaluation of antiangiogenic therapy with bevacizumab in addition to neoadjuvant chemotherapy in the treatment of locally advanced breast cancer.
Authors: McCammack Erin , Birhiray Reumu 
Published: September 2018

e12115 Background: Anti-angiogenic therapy improves outcomes in cancer therapy; we hypothesized an improved outcome with the addition of bevacizumab to dose dense neoadjuvant chemotherapy (ddNAC) in the treatment of locally advanced breast cancer (LABC). Methods: We added bevacizumab to ddNAC in the pre-operative management of LABC. Eligible subjects signed an informed consent, had biopsy and radiographically confirmed stage II-III LABC and absence of major organ malfunction. ddNAC was comprised of docetaxel 35mg/M2 intravenous (IV) on days 1 and 8, capecitabine 800mg/M2 by mouth two times a day on days 1-14 and bevacizumab 15mg/kg IV repeated every 21 days for 4 cycles, followed with doxorubicin 60 mg/M2 and cyclophosphamide 600mg/M2IV with peg-filgrastim 6mg given subcutaneously on day 1, every 14 days for 4 cycles (TX/ddAC). Subsequently, subjects underwent surgery and adjuvant radiation and/or hormonal therapy as clinically indicated. The primary objective was the pathologic complete response rate (pCR). As a secondary end point, we compared the rates of pCR with our prior study of the same chemotherapy regimen without bevacizumab (n = 52). Lastly, we evaluated the safety and tolerability of the regimen. Results: 34 subjects were enrolled and 31 completed the study. Using a modified intent to treat analysis, pCR with residual in-situ carcinoma (pCRinv) was 3/31 (9.7%), total pCR 8/31 (25.8%), and residual invasive carcinoma 20/31 (64.5%). In comparison, our prior study results, presented at the 2006 San Antonio Breast Cancer Symposium, showed a pCRinv7/52 (13.5%), total pCR 27/52 (52%), and rate of residual invasive carcinoma of 25/52 (48%). Observed toxicities included hand/foot syndrome, alopecia, nausea/vomiting, mucositis, neutropenia, febrile neutropenia, nail changes and hyperlacrimation. There was one treatment related death. Conclusions: The addition of bevacizumab to chemotherapy (TX/ddAC) did not improve the observed rates of pCR. However, the role of capecitabine in the neoadjuvant setting needs to be explored further. Moreover a post hoc analysis of the efficacy of the regimen in LABC subtypes is ongoing, with biologic correlates.
Pathological complete response in HER2 positive breast cancer treated with trastuzumab and chemotherapy: Predictive factors report.
Authors: Gasol Cudós Ariadna , Morales Serafin , Novell Alvarez Anna , Serrate Lopez Anna , Velasco Sanchez Ana , Salud Salvia Antonieta 
Published: September 2018

e12133 Background: Achieving a pathological complete response (pCR) in HER2 positive disease is a surrogate of survival. Several factors were studied in order to predict pCR, but only negative estrogen receptor is correlated to pCR. Methods: 168 patients (March 2002-December 2016) with neoadjuvant trastuzumab-based treatment were retrospectively analyzed in order to find if common clinicopathological factors, HER2 expression and immune infiltrates could correlate with pCR. Results: Median age was 55 years (29-86), median tumor size of 39mm and 53% of tumors had initial nodal involvement. 45% of patients were estrogen and 71% progesterone receptor negative and median ki67 expression was of 43%. Otherwise HER2 expression was analyzed by immunohistochemistry, FISH amplification and mRNA expression; we also determined the presence of immune infiltrates stromal and intratumoral L45 lymphocytes, PD1 and PD-L1. A 38% pCR rate was found in whole population. In the univariate model we found and association with pCR and: estrogen receptor negative (p = 0.003; OR 2.5), high HER2 expression by mRNA in tissue > 3.9 (p = 0.012; OR 8.4), stromal L45 expression > 35% (p = 0.001; OR 5.3), stromal PD1 expression > 10 (p = 0.004; OR 4.5). The most powerful factor associated with pCR is HER2 mRNA expression > 3.9, with 82% of pCR rate in those tumors; followed of L45 stromal expression > 35%, with 76% of pCR rate. Conclusions: Factors related to pCR are mostly estrogen receptor negative and high HER2 expression by mRNA and high L45 stromal infiltrates. With those variables, we could design a predictive model in order to perform the best neoadjuvant treatment to increase the pCR rate.
Real-world effectiveness of fulvestrant monotherapy as first hormonal therapy in metastatic breast cancer patients.
Authors: Olufade Temitope O , Skinner Karen E , Di Santo Nicola , Shenolikar Rahul A. , Walker Mark Stephen , Schwartzberg Lee Steven 
Published: September 2018

e12537 Background: Fulvestrant is a selective estrogen receptor degrader approved as monotherapy for postmenopausal women with estrogen-receptor-positive metastatic breast cancer (MBC) who progress following anti-estrogen therapy. The recent Phase 3 FALCON study for hormone therapy (HT) naïve women showed increased median progression-free survival (PFS) (16.6 months) in fulvestrant treated patients (pts) compared with anastrozole (13.8 months), but real-world data are lacking. This study examined the real-world effectiveness of fulvestrant monotherapy as first (L1) or second line (L2) treatment after MBC diagnosis. Methods: This was a retrospective medical record review from 10 US community oncology practices. Female pts initiated fulvestrant monotherapy as the first HT after MBC diagnosis, administered as L1 or as L2 treatment following L1 chemotherapy. Fulvestrant was initiated between 1/1/2011 and 12/31/2015. Pts were classified as HT naïve; and HT relapse status: early relapse (≤12 months of adjuvant HT completion), late relapse (>12 months). Time to first chemotherapy (TTC), PFS, and overall survival (OS) were evaluated using Kaplan-Meier analyses. Results: The study included 121 pts: mean (SD) age 65.7 (11.4) years, 81.8% Caucasian, 94.2% postmenopausal/undocumented, and 92.0% HER2-/undocumented. Overall, 15.7% were de novo metastatic and 86.0% initiated fulvestrant in L1. At the start of fulvestrant, 40.5% had visceral metastasis. The study results (Table 1) suggest better outcomes (TTC, PFS, OS) in HT naïve and late relapse pts, than early relapse pts. Conclusions: First line fulvestrant in the real-world setting demonstrates comparable PFS benefit to clinical trial results and appeared successful in delaying chemotherapy initiation in HT naïve and late relapse pts. This finding supports the use of fulvestrant monotherapy as the first hormonal therapy in a metastatic setting. [Table: see text]
Can 8 week 18F-FDG PET/CT predict clinical response in evaluation of bone metastases in breast cancer?
Authors: Azad Gurdip Kaur , Cousin Francois , Swampillai Angela , Taylor Benjamin P , Sandri Ines , Harries Mark , Mansi Janine , Cook Gary J. R. 
Published: September 2018

e12539 Background: 18F-FDG (fluorodeoxyglucose) PET/CT scan is widely used for staging and response assessment of metastatic breast cancer. However, the role of early treatment response assessment of bone metastases remains undefined and the optimal method not yet determined. Our hypothesis was that early 18F-FDG PET/CT can predict subsequent clinical response and our aim was to compare early 8 week 18F-FDG PET/CT with clinical response assessment up to 12 weeks in bone metastases following endocrine treatment. Methods: Eighteen patients starting endocrine treatment for de novo or progressive bone metastases were prospectively recruited. 18F-FDG PET/CT scans were performed before and 8 weeks after treatment. Percentage change in maximum SUV (SUVmax) from the same ≤ 5 index lesions was measured. Clinical response up to 12 weeks, (combination of CT/bone scintigraphy, patient symptoms, Ca-15.3), assessed by an oncologist blinded to PET imaging findings was used as a reference standard. Results: In the 4 patients with progressive disease (PD); SUVmax increased ( > 25%) in 2/20 (10%) and was stable in 15/20 (75%) lesions. Clinically, 2/4 (50%) patients had stable symptoms and 2/4 (50%) worsening bone pain at 8 and 12 weeks. Ca-153 increased ( > 40%) in 3/4 (75%) patients. Conventional imaging at 12 weeks showed PD in all 4 patients. In the 7 patients with clinical partial response (PR); SUVmax decreased ( < 25%) in 23/35 (66%) and remained stable in 10/35 (29%) lesions. Ca-153 decreased ( > 80%) in 4/7 (57%) patients. Clinically, symptoms remained stable or improved in 6/7 (86%) patients at 8 and 12 weeks. Conventional scanning at 3 months showed either PR (n = 3) or SD (n = 4). In the 7 patients with stable disease (SD); SUVmax remained unchanged in 15/27 (56%) and decreased in 12/27 (44%) lesions. Ca-153 showed minimal changes in 6/7 (86%) patients. Conventional scans showed SD in all 7 patients. Conclusions: Our data show that although 18F-FDG PET/CT is reliable at predicting PR or SD, it has poorer predictive ability for clinical PD in bone metastases at 8 weeks. Intra-patient heterogeneity of response between lesions is a common observation. Clinical trial information: 12/LO/1801.
Treatment patterns in metastatic triple-negative breast cancer (mTNBC).
Authors: Jiang Shan , Hill Kala , Varghese Della , Waldeck Adrian Reg , Botteman Marc 
Published: September 2018

e12589 Background: Real-world treatment patterns have not been extensively described in mTNBC. There is no generally accepted standard of care (SoC) in mTNBC or consensus regarding the use of multidrug regimens. We assessed drug-utilization patterns in commercially-insured US patients (pts) with mTNBC. Methods: Adult females with ≥1 breast cancer and ≥1 distant secondary malignant neoplasm diagnosis codes (2011-2015) were identified from the IMS LifeLink claims database. mTNBC status was approximated via receipt of any chemotherapy (chemo) post-metastatic diagnosis (mDx) in absence of pre-/post-mDx hormone replacement therapy/contraceptives or trastuzumab usage. First regimen (FR) was defined as the first chemo agent used post-mDx; chemo agents started ≤30 days of this first agent were counted as combination (combo) FR. Second regimen (SR) was defined as the chemo agent following FR by >30 days, or the same agent if there was a ≥90-day gap after FR. Kaplan-Meier survival curves were used to estimate time to SR initiation. Predictors of FR combo therapy and SR initiation were identified via logistic and Cox proportional hazard (CPH) regressions, respectively. Results: 2,949 pts received FR (median age: 53 years). Progression to SR occurred in 54% and 68% of pts at 12 and 36 months post-FR initiation, respectively. Median (95% CI) time between FR and SR was 81 (75-87) days. 39% and 27% of pts in FR and SR received combo therapy. Patients with age <55, surgery, no radiation, or more comorbidities during the pre-metastatic period were more likely to receive combo FR (Table). Pts with no surgery, more comorbidities, or combo FR, were more likely to start SR. Conclusions: There is no generally accepted SOC in mTNBC.Over half of mTNBC pts do not receive combo therapy and a majority progress to a SR within 1 year. [Table: see text]
Modified Glasgow prognostic score in a North American population of metastatic lung cancer patients: Baseline characteristics from the SNAP trial.
Authors: Stroud Chipman Robert Geoffrey , Walker Paul R. , Cherukuri Sulochana Devi , Sharma Nitika , Cherry Cindy , Parent Teresa , Hardin Jessica 
Published: September 2018

e13072 Background: There is a growing body of evidence that implicates inflammation as a mechanism of disease progression and reduced survival in patients with advanced cancer (Laird B et al. Oncologist 2013;18:1050-5.). Specifically, elevated c-reactive protein (CRP) levels have been associated with a severe symptom burden including pain, dyspnea, fatigue, nausea/vomiting, impaired quality of life, and inferior overall survival (Laird B et al. Oncologist 2013;18:1050-5.). The Modified Glasgow Prognostic Score (mGPS) is a composite inflammatory score based on CRP and serum albumin with proven prognostic value in patients with advanced lung cancer (Simmons CP et al. Lung Cancer 2015;88:304-309.). There is a significant body of evidence supporting the use of the mGPS in both Europe and Asia but the significance of the mGPS in a North American population has not been completely elucidated. We present preliminary data from a group of patients from Eastern North Carolina. Methods: Serum albumin and CRP were drawn at baseline and patients were followed for clinical course and overall survival. Patients with a dx of cancer were included regardless of stage. Clinicopathological features were abstracted from the chart and compared to a similar population from Europe (Simmons CP et al. Lung Cancer 2015;88:304-309.). Statistical comparisons were done by chi-squared test. Results: Two-hundred and twenty seven patients were eligible. Of these, 110 had either stage IV NSCLC (N= 97) or extensive stage small cell lung cancer (n=13). Median CRP was 21.9 mg/L (0.01 - 329.5). Median serum albumin was 3.4 g/dl (2.3-4.6). The number of patients with mGPS of 0, 1, and 2 were 27 (24.5%), 37 (33.6%) and 46 (41.8%), respectively. As compared to the population from Europe, the chi squared statistic was 10.1229 (p = 0.0063). There was no significant association between mGPS and race (p = 0.2277) or gender (p=0.0607). Conclusions: Lung cancer patients in Eastern North Carolina possess a strikingly poor inflammatory signature with significant implications for quality of life and survival. [Table: see text]
Patterns of head and neck cancer incidence, mortality, and survival in the U.S. Hispanic population.
Authors: Oh Melissa S. , Jiang Renjian , Liu Yuan , Zhu Xiting , Saba Nabil F. , Henriquez Oswaldo A. 
Published: September 2018

e13084 Background: To compare the incidence, mortality, and survival of head and neck cancer (HNCA) in the U.S. Hispanic population to other racial/ethnic groups. Methods: Using the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program, we compared the incidence and mortality of cancer of the oral cavity, pharynx, and larynx between the U.S. Hispanic population versus other racial and ethnic subgroups, as well as the annual percent change between 2000-2013. A comparative analysis for different groups stratified by age and sex was performed. Survival analysis was performed using Kaplan-Meier estimate and logistic regression analysis. Results: The incidence of oral cavity, pharyngeal, and laryngeal cancers were significantly lower in Hispanics compared to Non-Hispanics (p < 0.05). The incidence of laryngeal cancer decreased significantly at a rate of 2.5% annually (p < 0.05), while incidence of oral cavity and pharyngeal cancers remained unchanged in U.S. Hispanics. The mortality rate for oral cavity, pharyngeal, and laryngeal cancers in the U.S. Hispanic population were 1.4 per 100,000, 1.1 per 100,000, and 1.2 per 100,000 respectively. Mortality rates in Hispanics were significantly lower compared to Non-Hispanics (p < 0.05). Non-Hispanics Blacks had the highest HNCA-related mortality among all the compared groups. The mortality of HNCA was significantly declining annually in the U.S. Hispanic population (p < 0.05). Conclusions: The incidence and mortality of HNCA in the U.S. Hispanic population appears to be declining and is significantly lower compared to Non-Hispanics.
A multicenter, 3-arm, open-label, phase IIa clinical trial to evaluate the safety and efficacy of tanibirumab (VEGFR2 mAb), in patients with recurrent glioblastoma (GBM).
Authors: Cher Lawrence , Nowak Anna K. , Iatropoulos George , Lee Weon Sup , Lee Seon Young , Shim Sang Ryeol , Yoo Jin San 
Published: September 2018

e13522 Background: Treatment of recurrent GBM remains a challenge. The VEGF signal transduction pathway is upregulated in GBM. We evaluated Tanibirumab, a mAb to VEGFR2, in an open-label, dose-escalation, 3-arm, Phase 2a clinical trial. Primary and secondary endpoints were determining safety and efficacy (6-month PFS, ORR, DCR and OS). Methods: Eligibility criteria included age ≥19 yrs at 1st or 2nd recurrence of GBM, measurable disease, KPS≥80, and no prior bevacizumab. Patients were enrolled in 3 arms: Arm 1 (8mg/kg d1,8,15/q28 days); Arm 2 (12mg/kg d1,8,15/q28 days) and Arm 3 (12mg/kg weekly). Response evaluation with MRI (RANO criteria) including DCE, was performed every 2 cycles. Results: 12 patients were enrolled over 10 months from 2 sites: 3 patients each in Arms 1 & 2; 6 in Arm 3. The median age was 50 years and 8 were male. 6 patients had second recurrence. At 1st infusion, 8 out of 12 were on baseline corticosteroids. 10 patients have progressed. No dose limiting toxicities (DLT) were observed. Cutaneous hemangiomas (CH) were frequent (83% of patients) and all G2 or less. No drug-related G3 or 4 AEs were observed. All SAEs were unrelated to the study drug apart from G2 bleeding haemangioma and G2 cerebral haemorrhage. Expected AEs with anti-angiogenic drugs (hypertension; impaired wound healing) were not observed. Among 12 patients allocated to Arm 1, 2 and 3, no objective radiological responses were observed. 3 patients demonstrated stable disease (SD); 2 patients had SD beyond 4 cycles and are still receiving treatment at weeks 45 (Arm 1) & 20 (3). This was correlated with the highest expression of VEGFR2 using immunohistochemistry on archival tumour and blood vessels. Only 2 patients needed to initiate or increase corticosteroids for control of tumor edema while on treatment. Current data are immature to determine time to event efficacy endpoints (PFS,OS). Conclusions: Tanibirumab can be safely administered to patients with recurrent GBM, with CH being common. SD was seen in 2 patients up to 10+ months, with some indication that VEGFR2 expression may be a response biomarker. Clinical trial information: NCT03033524.
Nivolumab for patients with recurrent glioblastoma progressing on bevacizumab: A retrospective case series.
Authors: Chamberlain Marc C. , Kim Bryan T. 
Published: September 2018

e13538 Objective: A single institution retrospective evaluation of nivolumab following disease progression on bevacizumab in adults with recurrent glioblastoma (GBM) with an objective of determining progression free survival (PFS). Background: There is no accepted therapy for recurrent GBM after failure of bevacizumab. Methods: 16 adults, ages 52-72 years (median 62), with recurrent GBM were treated. All patients had previously been treated with surgery, concurrent radiotherapy and temozolomide, and post-radiotherapy temozolomide. Bevacizumab (with or without lomustine) was administered to all patients at first recurrence. Patients were treated with nivolumab only (3mg/kg) once every 2 weeks at second recurrence. One cycle of nivolumab was defined as 2 treatments. Neurological evaluation was performed bi-weekly and neuroradiographic assessment every 4 weeks. Results: A total of 37 treatment cycles (median 2) were administered of nivolumab in which there were 14 Grade 2 adverse events (AEs) and Grade 3 AEs in 2 patients. No Grade 4 or 5 AEs were seen. Following 1 month of nivolumab, 7 patients’ demonstrated progressive disease and discontinued therapy. No patient demonstrated a response though 9 patients demonstrated neuroradiographic stable response. Survival in the entire cohort ranged from 2 - 6 months with a median of 3.5 months (CI: 2.8, 4.2). Median and 6-month PFS at 6 months was 2.0 months (range 1-5 months; CI: 1.3, 2.7) and 0% respectively. Conclusions: Nivolumab salvage therapy demonstrated no survival advantage in patients with recurrent bevacizumab refractory GBM emphasizing a continued unmet need in neuro-oncology.