Michael J Kelley

Duke University, Durham, North Carolina, United States

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Publications (105)888.07 Total impact

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    ABSTRACT: BACKGROUND Adjuvant chemotherapy after surgical resection improves outcomes for patients with early-stage non-small cell lung cancer (NSCLC). To the authors' knowledge, there are no published prospective trials to date of adjuvant chemotherapy after surgical resection administered exclusively in older patients. In the current study, the authors sought to evaluate the efficacy of adjuvant chemotherapy in older patients in a Veterans Health Administration cohort. METHODS Patients who underwent surgical resection for American Joint Committee on Cancer stages IB to III NSCLC between 2001 and 2011 were analyzed. Data regarding patient demographics and comorbidities, tumor characteristics, and primary treatment were collected. Patients were divided into 2 groups based on age at diagnosis: those aged <70 years and those aged 70 years. The primary exposure was use of adjuvant chemotherapy. A Cox proportional hazards model was used to estimate the significance of patient characteristics. Survival curves were estimated using the Kaplan-Meier method and group comparisons were performed using the log-rank test. RESULTSThe analysis included 7593 patients who underwent surgical resection for stage IB to stage III NSCLC. Among these, 2897 patients (38%) were aged 70 years. The percentage of older patients who received adjuvant chemotherapy was approximately one-half that of younger patients who did so (15.3% vs 31.6%; P<.0001). Carboplatin-based doublets were used most often in all patients (64.6%). Both younger patients (hazard ratio, 0.79; 95% confidence interval, 0.72-0.86) and older patients (hazard ratio, 0.81; 95% confidence interval, 0.71-0.92) were found to have a lower risk of death with receipt of adjuvant chemotherapy. CONCLUSIONS Older patients derive a similar magnitude of benefit from adjuvant chemotherapy as younger patients and therefore adjuvant chemotherapy should not be withheld based on age alone. Cancer 2015;121:2578-2585. (c) 2015 American Cancer Society. Older patients with early-stage non-small cell lung cancer derive a similar magnitude of benefit from adjuvant chemotherapy as younger patients. Adjuvant chemotherapy should not be withheld based on patient age alone.
    No preview · Article · Apr 2015 · Cancer
  • Jason Zhu · Tian Zhang · Radhika Shah · Arif H Kamal · Michael J Kelley
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    ABSTRACT: Quality improvement measures are uniformly applied to all oncology providers, regardless of their roles. Little is known about differences in adherence to these measures between oncology fellows, advance practice providers (APP), and attending physicians. We investigated conformance across Quality Oncology Practice Initiative (QOPI) measures for oncology fellows, advance practice providers, and attending physicians at the Durham Veterans Affairs Medical Center (DVAMC). Using data collected from the Spring 2012 and 2013 QOPI cycles, we abstracted charts of patients and separated them based on their primary provider. Descriptive statistics and the chi-square test were calculated for each QOPI measure between fellows, advanced practice providers (APPs), and attending physicians. A total of 169 patients were reviewed. Of these, 31 patients had a fellow, 39 had an APP, and 99 had an attending as their primary oncology provider. Fellows and attending physicians performed similarly on 90 of 94 QOPI metrics. High-performing metrics included several core QOPI measures including documenting consent for chemotherapy, recommending adjuvant chemotherapy when appropriate, and prescribing serotonin antagonists when prescribing emetogenic chemotherapies. Low-performing metrics included documentation of treatment summary and taking action to address problems with emotional well-being by the second office visit. Attendings documented the plan for oral chemotherapy more often (92 vs. 63 %, P = 0.049). However, after the chart audit, we found that fellows actually documented the plan for oral chemotherapy 88 % of the time (p = 0.73). APPs and attendings performed similarly on 88 of 90 QOPI measures. The quality of oncology care tends to be similar between attendings and fellows overall; some of the significant differences do not remain significant after a second manual chart review, highlighting that the use of manual data collection for QOPI analysis is an imperfect system, and there may be significant inter-observer variability.
    No preview · Article · Feb 2015 · Journal of Cancer Education
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    ABSTRACT: The optimal chemotherapy regimen to use with radiotherapy in stage III non-small-cell lung cancer is unknown. Here, we compare the outcome of patents treated within the Veterans Health Administration with either etoposide-cisplatin (EP) or carboplatin-paclitaxel (CP). We identified patients treated with EP and CP with concurrent radiotherapy from 2001 to 2010. Survival rates were compared using Cox proportional hazards regression models with adjustments for confounding provided by propensity score methods and an instrumental variables analysis. Comorbidities and treatment complications were identified through administrative data. A total of 1,842 patients were included; EP was used in 27% (n = 499). Treatment with EP was not associated with a survival advantage in a Cox proportional hazards model (hazard ratio [HR], 0.97; 95% CI, 0.85 to 1.10), a propensity score matched cohort (HR, 1.07; 95% CI, 0.91 to 1.24), or a propensity score adjusted model (HR, 0.97; 95% CI, 0.85 to 1.10). In an instrumental variables analysis, there was no survival advantage for patients treated in centers where EP was used more than 50% of the time as compared with centers where EP was used in less than 10% of the patients (HR, 1.07; 95% CI, 0.90 to 1.26). Patients treated with EP, compared with patients treated with CP, had more hospitalizations (2.4 v 1.7 hospitalizations, respectively; P < .001), outpatient visits (17.6 v 12.6 visits, respectively; P < .001), infectious complications (47.3% v 39.4%, respectively; P = .0022), acute kidney disease/dehydration (30.5% v 21.2%, respectively; P < .001), and mucositis/esophagitis (18.6% v 14.4%, respectively; P = .0246). After accounting for prognostic variables, patients treated with EP versus CP had similar overall survival, but EP was associated with increased morbidity. © 2014 by American Society of Clinical Oncology.
    No preview · Article · Nov 2014 · Journal of Clinical Oncology
  • A. Ganti · C. Williams · A. Gajra · M.J. Kelley

    No preview · Article · Nov 2014 · International journal of radiation oncology, biology, physics
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    ABSTRACT: Background: Bevacizumab is associated with an increased risk of arterial thromboembolism (ATE); however, its effect on venous thromboembolism (VTE) remains controversial. Scant data exist on the factors that increase the risk of ATE/VTE in patients with prostate cancer. The authors investigated the association of bevacizumab treatment and clinical factors with ATE/VTE risk in patients who were treated on Cancer and Leukemia Group B (CALGB) trial 90401. Methods: Patients with metastatic, castration-resistant prostate cancer were randomized to receive docetaxel and prednisone with or without bevacizumab once every 21 days. Cycle-to-event Cox regression models were used to investigate the association of bevacizumab with the incidence of grade 3 or greater (≥ 3) ATE and VTE. Age, prior ATE/VTE, baseline antiplatelet/anticoagulant use, and VTE risk score (based on leukocyte count, hemoglobin, platelet count, body mass index, and tumor location) were evaluated in univariate and multivariable analyses. Results: Of 1008 randomized patients, the odds of experiencing grade ≥ 3 ATE were significantly greater in those who received bevacizumab compared with those who received placebo (odds ratio, 2.79; P = .02), whereas an opposite trend was noted for grade ≥ 3 VTE (odds ratio, 0.60; P = .08). In the multivariable analysis, bevacizumab treatment (hazard ratio [HR], 3.00; P = .01) and age (HR, 1.06; P = .02) were significantly associated with the risk of ATE; whereas age (HR, 1.05; P = .01) and VTE risk score (HR, 1.83; P = .03) were significantly associated with the risk of VTE. Conclusions: Bevacizumab was significantly associated with a greater risk of ATE in patients with metastatic, castration-resistant prostate cancer, but it was not significantly associated with the risk of VTE. Understanding clinical factors that increase the risk for experiencing ATE/VTE is essential to mitigate the risks and reduce the burden of these prevalent complications in cancer care.
    No preview · Article · Nov 2014 · Cancer
  • Isaac M Lipkus · Rochelle Schwartz-Bloom · Michael J Kelley · Wei Pan
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    ABSTRACT: Introduction: Many young smokers underestimate their risk for becoming addicted to cigarettes. We explored whether informing light college smokers (i.e., fewer than 5 cigarettes/day) of their genetic predisposition to nicotine dependence influenced their perceived risks and worry about becoming addicted, their ability to quit (i.e., self-efficacy), their desire to quit, and smoking cessation. Methods: College smokers (n = 142) received educational materials on mechanisms and consequences of nicotine addiction and were offered genetic susceptibility testing for nicotine dependence. Participants who accepted testing were randomized to receive feedback or no feedback (i.e., control). Tested participants learned they were above or not above average genetic risk for nicotine dependence. All participants responded to questions about perceived risks and worry about becoming addicted, efficacy to quit, and desire to quit. Cessation was assessed during a 1-month follow-up. Results: Efficacy beliefs, worry about becoming addicted, and desire to quit did not differ by study condition or feedback. Perceived risk for becoming addicted was highest among tested participants informed they were above average risk for nicotine dependence. Overall, self-reported 30- but not 7-day quit rate was higher among participants who underwent genetic testing compared with control participants. Conclusions: This pilot study is the first to show that among light college smokers, receipt of genetic susceptibility feedback to nicotine dependence potentially curbs smoking without producing detrimental effects.
    No preview · Article · Aug 2014 · Nicotine & Tobacco Research
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    ABSTRACT: Chordoma is a rare bone cancer that is believed to originate from notochordal remnants. We previously identified germline T duplication as a major susceptibility mechanism in several chordoma families. Recently, a common genetic variant in T (rs2305089) was significantly associated with the risk of sporadic chordoma. We sequenced all T exons in 24 familial cases and 54 unaffected family members from eight chordoma families (three with T duplications), 103 sporadic cases, and 160 unrelated controls. We also measured T copy number variation in all sporadic cases. We confirmed the association between the previously reported variant rs2305089 and risk of familial [odds ratio (OR) = 2.6, 95 % confidence interval (CI) = 0.93, 7.25, P = 0.067] and sporadic chordoma (OR = 2.85, 95 % CI = 1.89, 4.29, P < 0.0001). We also identified a second common variant, rs1056048, that was strongly associated with chordoma in families (OR = 4.14, 95 % CI = 1.43, 11.92, P = 0.0086). Among sporadic cases, another common variant (rs3816300) was significantly associated with risk when jointly analyzed with rs2305089. The association with rs3816300 was significantly stronger in cases with early age onset. In addition, we identified three rare variants that were only observed among sporadic chordoma cases, all of which have potential functional relevance based on in silico predictions. Finally, we did not observe T duplication in any sporadic chordoma case. Our findings further highlight the importance of the T gene in the pathogenesis of both familial and sporadic chordoma and suggest a complex susceptibility related to T.
    Full-text · Article · Jul 2014 · Human Genetics
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    ABSTRACT: Given the growing interest in the cancer burden in persons living with HIV/AIDS, we examined the validity of data sources for cancer diagnoses (cancer registry versus International Classification of Diseases, Ninth Revision [ICD-9 codes]) and compared the association between HIV status and cancer risk using each data source in the Veterans Aging Cohort Study (VACS), a prospective cohort of HIV-infected and uninfected veterans from 1996 to 2008. We reviewed charts to confirm potential incident cancers at four VACS sites. In the entire cohort, we calculated cancer-type-specific age-, sex-, race/ethnicity-, and calendar-period-standardized incidence rates and incidence rate ratios (IRR) (HIV-infected versus uninfected). We calculated standardized incidence ratios (SIR) to compare VACS and Surveillance, Epidemiology, and End Results rates. Compared to chart review, both Veterans Affairs Central Cancer Registry (VACCR) and ICD-9 diagnoses had approximately 90% sensitivity; however, VACCR had higher positive predictive value (96% versus 63%). There were 6,010 VACCR and 13,386 ICD-9 incident cancers among 116,072 veterans. Although ICD-9 rates tended to be double VACCR rates, most IRRs were in the same direction and of similar magnitude, regardless of data source. Using either source, all cancers combined, most viral-infection-related cancers, lung cancer, melanoma, and leukemia had significantly elevated IRRs. Using ICD-9, eight additional IRRs were significantly elevated, most likely due to false positive diagnoses. Most ICD-9 SIRs were significantly elevated and all were higher than the corresponding VACCR SIR. ICD-9 may be used with caution for estimating IRRs, but should be avoided when estimating incidence or SIRs. Elevated cancer risk based on VACCR diagnoses among HIV-infected veterans was consistent with other studies.
    No preview · Article · Jul 2014 · Journal of AIDS & Clinical Research
  • Christina D Williams · Ajeet Gajra · Apar K Ganti · Michael J Kelley
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    ABSTRACT: Despite clinical trials demonstrating improved survival with adjuvant chemotherapy (AC) for patients with American Joint Committee on Cancer stages I to III non-small cell lung cancer (NSCLC), it is unclear whether this survival benefit extends to broader populations. The current study evaluated patterns of AC use and examined the impact of AC on survival. A retrospective analysis was conducted of patients in the Veterans Affairs Central Cancer Registry diagnosed with stages IB to IIIA NSCLC between 2001 and 2008. Descriptive statistics were used to examine patterns of AC use over an 8-year time period. Cox proportional hazards regression analyses were used to estimate hazards ratios (HR) and 95% confidence intervals (95% CIs) to compare mortality risk among patients treated with and without AC. Among 14,306 patients with stages IB to IIIA NSCLC, 4929 underwent surgery and 22% of these received AC. The percentages of patients diagnosed in 2001 through 2003, 2004 through 2005, and 2006 through 2008 receiving AC were 7.0%, 29.8%, and 29.5%, respectively. There was no survival benefit with AC noted for patients diagnosed between 2001 and 2003, but AC was associated with improved survival for the period between 2004 and 2005 (HR, 0.78; 95% CI, 0.67-0.91) and 2006 through 2008 (HR, 0.79; 95% CI, 0.69-0.91). Of those patients receiving AC, 89% received platinum-doublet chemotherapy. Carboplatin remained the most common agent, although cisplatin use reached 43% in the period between 2006 and 2008. The HR for cisplatin relative to carboplatin was 0.96 (95% CI, 0.80-1.15). There was a significant increase in the use of AC between 2001 and 2008 and AC was associated with an improvement in overall survival. Cancer 2014. © 2014 American Cancer Society.
    No preview · Article · Jul 2014 · Cancer
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    ABSTRACT: Object: Chordoma cells can generate solid-like tumors in xenograft models that express some molecular characteristics of the parent tumor, including positivity for brachyury and cytokeratins. However, there is a dearth of molecular markers that relate to chordoma tumor growth, as well as the cell lines needed to advance treatment. The objective in this study was to isolate a novel primary chordoma cell source and analyze the characteristics of tumor growth in a mouse xenograft model for comparison with the established U-CH1 and U-CH2b cell lines. Methods: Primary cells from a sacral chordoma, called "DVC-4," were cultured alongside U-CH1 and U-CH2b cells for more than 20 passages and characterized for expression of CD24 and brachyury. While brachyury is believed essential for driving tumor formation, CD24 is associated with healthy nucleus pulposus cells. Each cell type was subcutaneously implanted in NOD/SCID/IL2Rγ(null) mice. The percentage of solid tumors formed, time to maximum tumor size, and immunostaining scores for CD24 and brachyury (intensity scores of 0-3, heterogeneity scores of 0-1) were reported and evaluated to test differences across groups. Results: The DVC-4 cells retained chordoma-like morphology in culture and exhibited CD24 and brachyury expression profiles in vitro that were similar to those for U-CH1 and U-CH2b. Both U-CH1 and DVC-4 cells grew tumors at rates that were faster than those for U-CH2b cells. Gross tumor developed at nearly every site (95%) injected with U-CH1 and at most sites (75%) injected with DVC-4. In contrast, U-CH2b cells produced grossly visible tumors in less than 50% of injected sites. Brachyury staining was similar among tumors derived from all 3 cell types and was intensely positive (scores of 2-3) in a majority of tissue sections. In contrast, differences in the pattern and intensity of staining for CD24 were noted among the 3 types of cell-derived tumors (p < 0.05, chi-square test), with evidence of intense and uniform staining in a majority of U-CH1 tumor sections (score of 3) and more than half of the DVC-4 tumor sections (scores of 2-3). In contrast, a majority of sections from U-CH2b cells stained modestly for CD24 (scores of 1-2) with a predominantly heterogeneous staining pattern. Conclusions: This is the first report on xenografts generated from U-CH2b cells in which a low tumorigenicity was discovered despite evidence of chordoma-like characteristics in vitro. For tumors derived from a primary chordoma cell and U-CH1 cell line, similarly intense staining for CD24 was observed, which may correspond to their similar potential to grow tumors. In contrast, U-CH2b tumors stained less intensely for CD24. These results emphasize that many markers, including CD24, may be useful in distinguishing among chordoma cell types and their tumorigenicity in vivo.
    Full-text · Article · Jun 2014 · Journal of Neurosurgery Spine
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    ABSTRACT: Providing smokers feedback using epigenetic markers of lung cancer risk has yet to be tested as a strategy to motivate smoking cessation. Epigenetic modification of Rb-p16 (p16) due to tobacco exposure is associated with increased risk of developing lung cancer. This study examined the acceptance of testing for methylated p16 and the understanding of test results in smokers at risk for development of lung cancer. Thirty-five current smokers with airways obstruction viewed an educational presentation regarding p16 function followed by testing for the presence of methylated p16 in sputum. Participants were offered smoking cessation assistance and asked to complete surveys at the time of enrolment regarding their understanding of the educational material, perception of risk associated with smoking and desire to quit. Participants were notified of their test result and follow-up surveys were administered 2 and 10 weeks after notification of their test result. Twenty per cent of participants had methylated p16. Participants showed high degree of understanding of educational materials regarding the function and risk associated with p16 methylation. Sixty-seven per cent and 57% of participants with low-risk and high-risk test results, respectively, reported that the information was more likely to motivate them to quit smoking. Smoking cessation rates were similar between methylated and non-methylated participants. Testing for an epigenetic marker of lung cancer risk is accepted and understood by active smokers. A low-risk test result does not decrease motivation to stop smoking. NCT01038492.
    Full-text · Article · May 2014
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    ABSTRACT: While platinum-based doublet chemotherapy is standard of care for patients presenting with metastatic non-small-cell lung cancer, the optimal platinum agent (cisplatin versus carboplatin) is unclear. We therefore compared survival and toxicity among persons receiving these agents at Department of Veterans Affairs hospitals. We used the Veterans Affairs Central Cancer Registry to identify veterans presented between 2001 and 2008 with metastatic non-small-cell lung cancer, then selected those receiving initial platinum doublet chemotherapy. We compared survival between those receiving cisplatin and carboplatin using multivariable Cox proportional hazards models and propensity score analyses to adjust for imbalances in demographics and clinical characteristics. We identified 4352 eligible persons; 4061 (93%) received carboplatin. Patients treated with cisplatin were younger (median age 61 versus 63, p < 0.01) and had less comorbidities (summary comorbidity score > 2, 7.7% versus 12.8%, p = 0.01) and higher eGFR (87 versus 84 mL/min/1.73 m). Median survival was similar for persons receiving cisplatin and carboplatin (8.1 versus 7.5 months, p = 0.54). In an adjusted survival analyses, the use of cisplatin was not associated with a better survival (hazard ratio 0.98, 95% confidence interval 0.84-1.14, p = 0.79). We performed subgroup analysis defined by histology and second agent, the hazard ratio for mortality ranged spanned 1 and none of these approached statistical significance (all p values > 0.20). Cisplatin-treated patients were more likely to have more hospitalization (1.7 versus 1.3, p < 0.01) and outpatient visits (11 versus 9.6, p < 0.01). Cisplatin-treated patient had more subsequent encounters for infection (41.6% versus 34.3%, p < 0.01) and acute kidney injury/dehydration (29.2% versus 15.5%, p < 0.01) CONCLUSIONS:: Patients receiving cisplatin and carboplatin-based doublets did not have significantly different survival, but cisplatin use was associated with an increase morbidity and healthcare use.
    No preview · Article · Mar 2014 · Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer

  • No preview · Article · Aug 2013 · Cancer Research
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    ABSTRACT: Chordoma is a rare, slow growing malignant tumor arising from remnants of the fetal notochord. Surgery is the first choice for chordoma treatment, followed by radiotherapy, although postoperative complications remain significant. Recurrence of the disease occurs frequently due to the anatomy of the tumor location and violation of the tumor margins at the initial surgery. Currently, there are no effective drugs available for patients with chordoma. Due to the rarity of the disease, there is limited opportunity to test agents in clinical trials and no concerted effort to develop agents for chordoma in the pharmaceutical industry. To rapidly and efficiently identify small molecules that inhibit chordoma cell growth, we screened the NCGC Pharmaceutical Collection (NPC) containing approximately 2,800 clinically approved and investigational drugs at 15 different concentrations in chordoma cell lines, U-CH1 and U-CH2. We identified a group of drugs including bortezomib, 17-AAG, digitoxin, staurosporine, digoxin, rubitecan and trimetrexate that inhibited chordoma cell growth, with potencies from 10 to 370 nM in U-CH1 cells, but less potent in U-CH2 cells. Most of these drugs also induced caspase 3/7 activity with a similar rank order as the cytotoxic effect on U-CH1 cells. Cantharidin, digoxin, digitoxin, staurosporine and bortezomib showed similar inhibitory effect on cell lines and three primary chordoma cell cultures. The combination treatment of bortezomib with topoisomerase I and II inhibitors increased the therapeutic potency in U-CH2 and patient-derived primary cultures. Our results provide information useful for repurposing currently approved drugs for chordoma and potential approach of combination therapy.
    Full-text · Article · May 2013 · Cancer biology & therapy
  • Ryan D Nipp · Michael J Kelley · Christina D Williams · Arif H Kamal
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    ABSTRACT: A growing set of quality measures is being implemented to evaluate all components of cancer care, from diagnosis through the end of life. We investigated the Quality Oncology Practice Initiative (QOPI) quality measures portfolio. Additionally, we explored the effect of quality measure type on conformance. We performed QOPI data collections twice per year from fall 2007 through fall 2010 and spring 2012, using chart review of the Durham Veterans Administration outpatient oncology clinic. We categorized QOPI measures as nontreatment-related supportive care (NTSC), treatment-related supportive care (TSC), diagnostic, or therapeutic. Descriptive statistics and χ(2) were used to compare longitudinal conformance. The majority of QOPI measures in spring 2012 assess processes of chemotherapy treatment (therapeutic, 54.3%; TSC, 8.7%) or diagnostic modalities (19.6%). Measures targeting NTSC are few (17.4%) but increased from three measures in fall 2007 to eight measures in spring 2012. During those 5 years, average conformance to NTSC, TSC, diagnostic, and therapeutic measures was 71.4%, 86.1%, 89.3%, and 75.4%, respectively (P < .001). Within the NTSC measures, emotional well-being and constipation assessment were least documented (41.0% and 46.3%, respectively). In spring 2012, NTSC measure conformance (75.8%) remained significantly lower than diagnostic measure conformance (91.5%; P < .001). Most QOPI quality measures assess diagnosis or treatment processes of care and not supportive care. Aggregate conformance to the NTSC measures was lower than that of other categories. The differential conformance demonstrates the necessity of standardized documentation methods and quality improvement efforts that remain commensurate with the increasing portfolio of supportive care measures.
    No preview · Article · May 2013 · Journal of Oncology Practice
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    ABSTRACT: PURPOSEIt is unclear why racial differences exist in the frequency of surgery for lung cancer treatment. Comorbidity is an important consideration in selection of patients for lung cancer treatment, including surgery. To assess whether comorbidity contributes to the observed racial differences, we evaluated racial differences in the prevalence of comorbidity and their impact on receipt of surgery. PATIENTS AND METHODSA total of 1,314 patients (1,135 white, 179 black) in the Veterans Health Administration diagnosed with early-stage non-small-cell lung cancer in 2007 were included. The effect of comorbidity on surgery was determined by using generalized linear models with a logit link accounting for patient clustering within Veterans Administration Medical Centers.ResultsCompared with whites, blacks had greater prevalence of hypertension, liver disease, renal disease, illicit drug abuse, and poor performance status, but lower prevalence of respiratory disease. The impact of most individual comorbidities on receipt of surgery was similar between blacks and whites, and comorbidity did not influence the race-surgery association in a multivariable analysis. The proportion of blacks not receiving surgery as well as refusing surgery was greater than that among whites. CONCLUSION Blacks had a greater prevalence of several comorbid conditions and poor performance status; however, the overall comorbidity score did not differ by race. In general, the effect of comorbidity on receipt of surgery was similar in blacks and whites. Racial differences in comorbidity do not fully explain why blacks undergo lung cancer surgery less often than whites.
    No preview · Article · Dec 2012 · Journal of Clinical Oncology
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    ABSTRACT: Introduction: We sought to determine the efficacy of using both irinotecan- and etoposide-containing regimens sequentially for patients with untreated limited-stage small-cell lung cancer. Methods: Patients with untreated, measurable, limited-stage small-cell lung cancer with performance status 0 to 2, and adequate organ function were eligible. Treatment consisted of induction with cisplatin 30 mg/m and irinotecan 65 mg/m intravenously on day 1 and 8, every 21 days for two cycles. Beginning day 43, daily chest irradiation to 70 Gy was administered concurrently with carboplatin area under curve 5 on day 1, and etoposide 100 mg/m on days 1 to 3, every 21 days for three cycles. The primary objective was to differentiate between 45% and 60% 2-year survival. Results: Two induction cycles were delivered to 72 of 75 eligible patients (96%) and all planned treatment was delivered to 59 patients (79%). Cisplatin and irinotecan induction chemotherapy resulted in complete responses in 7% and partial responses in 64% (response rate 71%, 95% confidence interval [CI], 59%-81%). The best response to all therapy included 88% complete or partial responses (95% CI, 78%-94%). With median follow-up of 57 months, the median progression-free survival and overall survival are 12.6 (95% CI, 9.4-14.7) and 18.1 months (15.8-22.9), respectively. The 1- and 2-year survival was 69% and 31%, respectively. Frequent (>20%) grade 3 and 4 toxicities were neutropenia in 84%, hemoglobin in 36%, platelets in 51%, esophagitis in 22%, and dehydration in 24%. There were no fatal toxicities. Conclusions: This treatment regimen of irinotecan-cisplatin induction chemotherapy followed by 70 Gy concurrent radiation and etoposide-carboplatin had tolerable toxicity but did not meet the preplanned 2-year survival target for further development.
    No preview · Article · Nov 2012 · Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer
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    ABSTRACT: Approximately 40,000 incident cancer cases are reported in the Veterans Affairs Central Cancer Registry (VACCR) annually (approximately 3% of U.S. cancer cases). Our objective was to provide the first comprehensive description of cancer incidence as reported in VACCR. Data were obtained from VACCR for incident cancers diagnosed in VA. Analyses focused on 2007 data. Cancer incidence among VA patients was compared to the general U.S. cancer population. In 2007, 97.5% of VA cancers were diagnosed among men. Approximately 78.5% of newly diagnosed patients were White, 19.0% Black, and 2.5% were another race. Median age at diagnosis was 66 years. The geographic distribution of cancer patients in VA aligns that of VA users. The most commonly diagnosed cancers were similar between VA and the U.S. male cancer population. The five most frequently diagnosed cancers among VA cancer patients were: prostate (31.8%), lung/bronchus (18.8%), colon/rectum (8.6%), urinary bladder (3.6%), and skin melanomas (3.4%). VA patients were diagnosed at an earlier stage of disease for the three most commonly diagnosed cancers--lung/bronchus, colon/rectum, and prostate--compared to the U.S. male cancer population. Registry data indicate that incident cancers in VA in 2007 approximately mirrored those observed among U.S. men.
    No preview · Article · Jun 2012 · Military medicine
  • Christina D. Williams · Dawn Provenzale · Michael Kelley

    No preview · Article · Sep 2011 · Cancer Epidemiology Biomarkers & Prevention
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    ABSTRACT: We have generated 3 mouse lines, each with a different mutation in the nonmuscle myosin II-A gene, Myh9 (R702C, D1424N, and E1841K). Each line develops MYH9-related disease similar to that found in human patients. R702C mutant human cDNA fused with green fluorescent protein was introduced into the first coding exon of Myh9, and D1424N and E1841K mutations were introduced directly into the corresponding exons. Homozygous R702C mice die at embryonic day 10.5-11.5, whereas homozygous D1424N and E1841K mice are viable. All heterozygous and homozygous mutant mice show macrothrombocytopenia with prolonged bleeding times, a defect in clot retraction, and increased extramedullary megakaryocytes. Studies of cultured megakaryocytes and live-cell imaging of megakaryocytes in the BM show that heterozygous R702C megakaryocytes form fewer and shorter proplatelets with less branching and larger buds. The results indicate that disrupted proplatelet formation contributes to the macrothrombocytopenia in mice and most probably in humans. We also observed premature cataract formation, kidney abnormalities, including albuminuria, focal segmental glomerulosclerosis and progressive kidney disease, and mild hearing loss. Our results show that heterozygous mice with mutations in the myosin motor or filament-forming domain manifest similar hematologic, eye, and kidney phenotypes to humans with MYH9-related disease.
    Full-text · Article · Sep 2011 · Blood

Publication Stats

4k Citations
888.07 Total Impact Points


  • 2000-2015
    • Duke University
      • Department of Medicine
      Durham, North Carolina, United States
  • 2000-2014
    • Duke University Medical Center
      • Department of Medicine
      Durham, North Carolina, United States
  • 2010
    • Durham University
      Durham, England, United Kingdom
  • 2009
    • Catholic University of Louvain
      • Institute of Experimental and Clinical Research (IREC)
      Walloon Region, Belgium
  • 2005
    • Columbia University
      New York, New York, United States
  • 1992-1999
    • National Cancer Institute (USA)
      • Laboratory of Cellular and Molecular Biology
      베서스다, Maryland, United States
  • 1995
    • NCI-Frederick
      Фредерик, Maryland, United States