Juneko E. Grilley-Olson

University of North Carolina at Chapel Hill, North Carolina, United States

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Publications (11)71.38 Total impact

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    ABSTRACT: Platinum plus etoposide is the standard therapy for extensive-stage small cell lung cancer (ES-SCLC) and is associated with significant myelosuppression. We hypothesized that the combination of carboplatin and nanoparticle albumin-bound paclitaxel (nab-paclitaxel) would be better tolerated. We investigated carboplatin with nab-paclitaxel on every-3-week and weekly schedules. This noncomparative randomized phase II trial used a two-stage design. The primary objective was objective response rate, and secondary objectives were progression-free survival, overall survival, and toxicity. Patients with ES-SCLC and an Eastern Cooperative Oncology Group performance status ≤2 and no prior chemotherapy were randomized in a 1:1 ratio to arm A (carboplatin area under the curve [AUC] of 6 on day 1 and nab-paclitaxel of 300 mg/m(2) on day 1 every 3 weeks) or arm B (carboplatin AUC of 6 on day 1 and nab-paclitaxel 100 mg/m(2) on days 1, 8, and 15 every 21 days). Response was assessed after every two cycles. Patients required frequent dose reductions, treatment delays, and omission of the weekly therapy. The trial was closed because of slow accrual. Carboplatin and nab-paclitaxel demonstrated activity in ES-SCLC but required frequent dose adjustments. ©AlphaMed Press; the data published online to support this summary is the property of the authors.
    The Oncologist 01/2015; 20(2). DOI:10.1634/theoncologist.2014-0327 · 4.54 Impact Factor
  • Cancer Research 10/2014; 74(19 Supplement):CT205-CT205. DOI:10.1158/1538-7445.AM2014-CT205 · 9.28 Impact Factor
  • Cancer Research 10/2014; 74(19 Supplement):5598-5598. DOI:10.1158/1538-7445.AM2014-5598 · 9.28 Impact Factor
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    ABSTRACT: Objectives: Platinum-based chemotherapy with bevacizumab is a standard therapy for patients with stage IIIB/IV non-small cell lung cancer (NSCLC) with non-squamous (NS) histology. Mechanisms of resistance to bevacizumab include increased VEGF signaling or activation of VEGF receptors. Pazopanib is a multi-targeted VEGF receptor tyrosine kinase with single agent activity in NSCLC. Materials and methods: Stage IIIB/IV patients with adequate organ function, who progressed on a bevacizumab containing therapy were eligible if it had been <= 8 weeks since the last bevacizumab treatment. The primary end-point was disease control rate (DCR), defined as partial or complete response, or stable disease for >= 12 weeks. Patients were assessed radiographically every 2 cycles (6 weeks). A Simon 2-stage design was used, and if in the first stage <= 4 of 17 patients experienced disease control the trial was to have been stopped for futility. An unplanned analysis was performed after 15 patients were evaluable secondary to slow accrual. Results: Between December 2010 and November 2013, 15 patients were treated on trial. The median age was 61 years (range 39-74), and all patients had stage IV disease. Of the 15 patients, 4 discontinued therapy prior to cycle 2 evaluation due to adverse events (n = 3) and medical illness (n = 1), 5 patients had progressive disease, 4 patients had stable disease for <12 weeks, and 2 patients had stable disease for >= 12 weeks. No responses were observed. The DCR observed was 13% (2115), and the trial did not meet the criteria to proceed to the second stage. Episodes of grade 3 treatment related toxicities observed included: increased ALT (n = 2), increased AST (n = 1), anorexia (n = 3), fatigue (n=3), hypertension (n=1), infection (n = 1), mucositis (n = 2), nausea (n = 3), pericardial effusion (n = 1), and vomiting (n=1). Conclusion: Pazopanib has limited activity in NSCLC-NS in patients who have experienced disease progression on bevacizumab.
    Lung cancer (Amsterdam, Netherlands) 08/2014; 86(2). DOI:10.1016/j.lungcan.2014.08.011 · 3.74 Impact Factor
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    ABSTRACT: Background Brain metastases are one of the most malignant complications of lung cancer and constitute a significant cause of cancer related morbidity and mortality worldwide. Recent years of investigation suggested a role of LKB1 in NSCLC development and progression, in synergy with KRAS alteration. In this study, we systematically analyzed how LKB1 and KRAS alteration, measured by mutation, gene expression (GE) and copy number (CN), are associated with brain metastasis in NSCLC. Materials and Methods Patients treated at University of North Carolina Hospital from 1990 to 2009 with NSCLC provided frozen, surgically extracted tumors for analysis. GE was measured using Agilent 44,000 custom-designed arrays, CN was assessed by Affymetrix GeneChip Human Mapping 250 K Sty Array or the Genome-Wide Human SNP Array 6.0 and gene mutation was detected using ABI sequencing. Integrated analysis was conducted to assess the relationship between these genetic markers and brain metastasis. A model was proposed for brain metastasis prediction using these genetic measurements. Results 17 of the 174 patients developed brain metastasis. LKB1 wild type tumors had significantly higher LKB1 CN (p < 0.001) and GE (p = 0.002) than the LKB1 mutant group. KRAS wild type tumors had significantly lower KRAS GE (p < 0.001) and lower CN, although the latter failed to be significant (p = 0.295). Lower LKB1 CN (p = 0.039) and KRAS mutation (p = 0.007) were significantly associated with more brain metastasis. The predictive model based on nodal (N) stage, patient age, LKB1 CN and KRAS mutation had a good prediction accuracy, with area under the ROC curve of 0.832 (p < 0.001). Conclusion LKB1 CN in combination with KRAS mutation predicted brain metastasis in NSCLC.
    Lung Cancer 08/2014; 86(2). DOI:10.1016/j.lungcan.2014.08.013 · 3.74 Impact Factor
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    ABSTRACT: Cisplatin is a widely used antineoplastic. One of the major complications of cisplatin use is dose-limiting nephrotoxicity. There are many strategies to prevent this toxicity, including the use of mannitol as a nephroprotectant in combination with hydration. We aimed to evaluate the rates of cisplatin-induced nephrotoxicity in cancer patients receiving single-agent cisplatin with and without mannitol. This single-center retrospective analysis was a quasi experiment created by the national mannitol shortage. Data were collected on adult cancer patients receiving single-agent cisplatin as an outpatient from January 2011 to September 2012. The primary outcome was acute kidney injury (AKI). We evaluated 143 patients who received single-agent cisplatin; 97.2% of patients had head and neck cancer as their primary malignancy. Patients who did not receive mannitol were more likely to develop nephrotoxicity: odds ratio [OR] = 2.646 (95% CI = 1.008, 6.944; P = 0.048). Patients who received the 100 mg/m(2) dosing and patients who had a history of hypertension also had a higher likelihood of developing nephrotoxicity: OR = 11.494 (95% CI = 4.149, 32.258; P < 0.0001) and OR = 3.219 (95% CI = 1.228, 8.439; P = 0.017), respectively. When limited quantities of mannitol are available, it should preferentially be given to patients at particularly high risk of nephrotoxicity. Our analysis suggests that those patients receiving the dosing schedule of 100 mg/m(2) cisplatin every 3 weeks and those with hypertension are at the greatest risk of nephrotoxicity and would benefit from the addition of mannitol.
    Annals of Pharmacotherapy 04/2014; 48(7). DOI:10.1177/1060028014533303 · 2.92 Impact Factor
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    ABSTRACT: BACKGROUND: The purpose of this study was to determine whether indeterminate pulmonary nodules (IPNs) at staging are predictive of lung metastasis, primary lung carcinoma, or survival in patients with advanced head and neck squamous cell carcinoma (HNSCC). METHODS: One hundred ten patients with IPN at staging who had follow-up imaging and 100 patients without IPN were identified from an HNSCC database. The primary endpoints were lung progression-free survival (PFS) and overall survival (OS). RESULTS: Two-year lung PFS for the IPN and No-IPN cohorts were 66% versus 61% (p = .92) and the OS for these cohorts were 71% versus 68% (p = .77). Within the IPN cohort, level IV/V lymph node involvement (odds ratio = 4.34; p = .03), hypopharynx primary (odds ratio = 21.5; p = .005), and race (odds ratio = 9.29; p = .001) were independent predictors of developing lung malignancy. CONCLUSION: IPNs at staging in patients with HNSCC do not affect prognosis and should neither influence initial treatment planning nor the frequency of posttreatment surveillance. © 2013 Wiley Periodicals, Inc. Head Neck, 2013.
    Head & Neck 03/2014; 36(3). DOI:10.1002/hed.23294 · 3.01 Impact Factor
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    ABSTRACT: Recently, the management of head and neck squamous cell carcinoma (HNSCC) has focused considerable attention on biomarkers, which may influence outcomes. Tests for human papilloma infection, including direct assessment of the virus as well as an associated tumour suppressor gene p16, are considered reproducible. Tumours from familial melanoma syndromes have suggested that nuclear localisation of p16 might have a further role in risk stratification. We hypothesised p16 staining that considered nuclear localisation might be informative for predicting outcomes in a broader set of HNSCC tumours not limited to the oropharynx, human papilloma virus (HPV) status or by smoking status. Patients treated for HNSCC from 2002 to 2006 at UNC (University of North Carolina at Chapel Hill) hospitals that had banked tissue available were eligible for this study. Tissue microarrays (TMA) were generated in triplicate. Immunohistochemical (IHC) staining for p16 was performed and scored separately for nuclear and cytoplasmic staining. Human papilloma virus staining was also carried out using monoclonal antibody E6H4. p16 expression, HPV status and other clinical features were correlated with progression-free (PFS) and overall survival (OS). A total of 135 patients had sufficient sample for this analysis. Median age at diagnosis was 57 years (range 20-82), with 68.9% males, 8.9% never smokers and 32.6% never drinkers. Three-year OS rate and PFS rate was 63.0% and 54.1%, respectively. Based on the p16 staining score, patients were divided into three groups: high nuclear, high cytoplasmic staining group (HN), low nuclear, low cytoplasmic staining group (LS) and high cytoplasmic, low nuclear staining group (HC). The HN and the LS groups had significantly better OS than the HC group with hazard ratios of 0.10 and 0.37, respectively, after controlling for other factors, including HPV status. These two groups also had significantly better PFS than the HC staining group. This finding was consistent for sites outside the oropharynx and did not require adjustment for smoking status. Different p16 protein localisation suggested different survival outcomes in a manner that does not require limiting the biomarker to the oropharynx and does not require assessment of smoking status.
    British Journal of Cancer 06/2012; 107(3):482-90. DOI:10.1038/bjc.2012.264 · 4.82 Impact Factor
  • Cancer Research 06/2012; 72(8 Supplement):1744-1744. DOI:10.1158/1538-7445.AM2012-1744 · 9.28 Impact Factor
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    ABSTRACT: Context.-Precise subtype diagnosis of non-small cell lung carcinoma is increasingly relevant, based on the availability of subtype-specific therapies, such as bevacizumab and pemetrexed, and based on the subtype-specific prealence of activating epidermal growth factor receptor mutations. Objectives.-To establish a baseline measure of interobserver reproducibility for non-small cell lung carcinoma diagnoses with hematoxylin-eosin for the current 2004 World Health Organization classification, to estimate interobserver reproducibility for the therapeutically relevant squamous/nonsquamous subsets, and to examine characteristics that improve interobserver reproducibility. Design.-Primary, resected lung cancer specimens were converted to digital (virtual) slides. Based on a single hematoxylin-eosin virtual slide, pathologists were asked to assign a diagnosis using the 2004 World Health Organization classification. Kappa statistics were calculated for each pathologist-pair for each slide and were summarized by classification scheme, pulmonary pathology expertise, diagnostic confidence, and neoplastic grade. Results.-The 12 pulmonary pathology experts and the 12 community pathologists each independently diagnosed 48 to 96 single hematoxylin-eosin digital slides derived from 96 cases of non-small cell lung carcinoma resection. Overall agreement improved with simplification from the comprehensive 44 World Health Organization diagnoses (κ  =  0.25) to their 10 major header subtypes (κ  =  0.48) and improved again with simplification into the therapeutically relevant squamous/nonsquamous dichotomy (κ  =  0.55). Multivariate analysis showed that higher diagnostic agreement was associated with better differentiation, better slide quality, higher diagnostic confidence, similar years of pathology experience, and pulmonary pathology expertise. Conclusions.-These data define the baseline diagnostic agreement for hematoxylin-eosin diagnosis of non-small cell lung carcinoma, allowing future studies to test for improved diagnostic agreement with reflex ancillary tests.
    Archives of pathology & laboratory medicine 05/2012; 137(1). DOI:10.5858/arpa.2012-0033-OA · 2.88 Impact Factor
  • Thomas E Stinchcombe, Juneko E Grilley-Olson, Mark A Socinski
    Journal of Clinical Oncology 03/2010; 28(11):1810-2. DOI:10.1200/JCO.2009.27.1247 · 17.88 Impact Factor