Thomas E Keane

Medical University of South Carolina, Charleston, South Carolina, United States

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Publications (101)228.61 Total impact

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    ABSTRACT: A need remains for new therapeutic approaches for men with advanced prostate cancer, particularly earlier in the disease course.
    European Urology 06/2014; 67(2). DOI:10.1016/j.eururo.2014.06.011 · 13.94 Impact Factor
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    ABSTRACT: Prostate cancer is often associated with metastases to bone and/or soft tissue. The progression to metastatic castrate-resistant prostate cancer is a seminal event in disease progression affecting treatment decisions. A multidisciplinary group was convened to review the currently available imaging guidelines for metastatic disease in prostate cancer and found no consensus on eligibility criteria, type of imaging modality, and the frequency of scanning for detecting metastatic disease. The aim of this review was to present the recommendations from the group to identify optimal strategies for early identification of metastases in patients with prostate cancer.
    Urology 03/2014; 83(3). DOI:10.1016/j.urology.2013.10.026 · 2.19 Impact Factor
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    ABSTRACT: Prostate cancer (PCa) is one of the most common cancers diagnosed in men in the United States, and approximately 20% to 30% of men treated for localized PCa will fail therapy and develop advanced PCa More drugs have been approved for the treatment of advanced PCa in the past three years than in the past three decades, and each drug has its own mechanism of action and, often, unique monitoring requirements Since the treatment landscape for men with advanced PCa is undergoing significant expansion, the roles of both oncologists and urologists are shifting, and the decision for the urologist to treat versus refer requires early assessment to identify which patients are candidates for these novel treatments and the monitoring of patients for tolerability, response, and potential side effects Given these rapid changes, the authors of this review met in January 2013 and again in April 2013 to discuss the current challenges facing urologists in adopting these new treatments into their own practices Here, we provide a brief overview of advanced PCa medical therapies approved in the past decade, the necessary monitoring procedures and early detection methods needed to safely and effectively manage patients receiving these therapies, and our recommendations for applying these new therapies within different models of urology practice such that urologists can remain an integral component of their patient's care once he has transitioned into advanced Pca
    BJU International 02/2014; 115(2). DOI:10.1111/bju.12665 · 3.53 Impact Factor
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    Thomas E Keane ·

    World Journal of Urology 11/2013; 31(6). DOI:10.1007/s00345-013-1209-x · 2.67 Impact Factor
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    ABSTRACT: This was a phase I study to find the maximum tolerable dose (MTD) of weekly docetaxel combined with high-dose intensity-modulated radiotherapy (IMRT) and androgen deprivation therapy (ADT). Men with localized high-risk prostate cancer (HRPC) were treated with weekly docetaxel at 10 to 30 mg/m(2) concurrent with IMRT of 77.4 Gy to the prostate and 45 Gy to the seminal vesicles. ADT consisted of a gonadotropin-releasing hormone agonist (GnRHa) and bicalutamide beginning 2 months before and during chemoradiation. GnRHa was continued for 24 months. Nineteen patients were enrolled. No dose-limiting toxicity (DLT) was seen with docetaxel doses up to 25 mg/m(2). At the 30 mg/m(2) level, 2 of 4 patients experienced DLTs of both grade 3 fatigue and dyspepsia. At 41 months' median follow-up, 2 patients had died-1 from metastatic prostate cancer and the other from heart failure. Two other patients experienced biochemical failure. One patient with bladder invasion at diagnosis experienced late grade 2 urinary hesitancy 9 months after completion of radiotherapy, requiring short-term intermittent catheterization. All patients had erectile dysfunction, but no late toxicities worse than grade 2 were identified. Weekly docetaxel may be combined with high-dose IMRT and long-term ADT up to a MTD of 25 mg/m(2). Acute toxicities and long-term side effects of this regimen were acceptable. Future studies evaluating the efficacy of docetaxel, ADT, and IMRT for localized HRPC should use a weekly dose of 25 mg/m(2) when limiting the irradiated volume to the prostate and seminal vesicles.
    Clinical Genitourinary Cancer 11/2013; 12(2). DOI:10.1016/j.clgc.2013.11.019 · 2.32 Impact Factor
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    ABSTRACT: Escape of prostate cancer (PCa) cells from ionizing radiation-induced (IR-induced) killing leads to disease progression and cancer relapse. The influence of sphingolipids, such as ceramide and its metabolite sphingosine 1-phosphate, on signal transduction pathways under cell stress is important to survival adaptation responses. In this study, we demonstrate that ceramide-deacylating enzyme acid ceramidase (AC) was preferentially upregulated in irradiated PCa cells. Radiation-induced AC gene transactivation by activator protein 1 (AP-1) binding on the proximal promoter was sensitive to inhibition of de novo ceramide biosynthesis, as demonstrated by promoter reporter and ChIP-qPCR analyses. Our data indicate that a protective feedback mechanism mitigates the apoptotic effect of IR-induced ceramide generation. We found that deregulation of c-Jun induced marked radiosensitization in vivo and in vitro, which was rescued by ectopic AC overexpression. AC overexpression in PCa clonogens that survived a fractionated 80-Gy IR course was associated with increased radioresistance and proliferation, suggesting a role for AC in radiotherapy failure and relapse. Immunohistochemical analysis of human PCa tissues revealed higher levels of AC after radiotherapy failure than those in therapy-naive PCa, prostatic intraepithelial neoplasia, or benign tissues. Addition of an AC inhibitor to an animal model of xenograft irradiation produced radiosensitization and prevention of relapse. These data indicate that AC is a potentially tractable target for adjuvant radiotherapy.
    The Journal of clinical investigation 10/2013; 123(10):4344-4358. DOI:10.1172/JCI64791 · 13.22 Impact Factor
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    ABSTRACT: Introduction: In this prospective study of localized prostate cancer patients and their partners, we analyzed how partner issues evolve over time, focusing on satisfaction with care, influence of cancer treatment, and its impact on relationship with patient, cancer worry, and personal activities. Aims: Our study aims were twofold: (i) to determine whether the impact of treatment on patients and partners moderate over time and (ii) if receiving surgery (i.e., radical prostatectomy) influences partner issues more than other treatments. Methods: Patients newly diagnosed with localized prostate cancer and their female partners were recruited from three states to complete surveys by mail at three time points over 12 months. Main outcome measures: The four primary outcomes assessed in the partner analysis included satisfaction with treatment, cancer worry, and the influence of cancer and its treatment on their relationship (both general relationship and sexual relationship). Results: This analysis included 88 patient-partner pairs. At 6 months, partners reported that cancer had a negative impact on their sexual relationship (39%--somewhat negative and 12%--very negative). At 12 months, this proportion increased substantially (42%--somewhat negative and 29%--very negative). Partners were significantly more likely to report that their sexual relationship was worse when the patient reported having surgery (P = 0.0045, odds ratio = 9.8025, 95% confidence interval 2.076-46.296). A minority of partners reported significant negative impacts in other areas involving their personal activities (16% at 6 months and 25% at 12 months) or work life (6% at 6 months, which increased to 12% at 12 months). Conclusion: From partners' perspectives, prostate cancer therapy has negative impact on sexual relationships and appears to worsen over time.
    Journal of Sexual Medicine 09/2013; 10(12). DOI:10.1111/jsm.12295 · 3.15 Impact Factor
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    ABSTRACT: Informal care plays an important role in the overall care for people with cancer. This study estimates lost productivity and informal caregiving and associated costs among partner caregivers of localized prostate cancer patients within 1 year after diagnosis. We applied data from the Family and Cancer Therapy Selection study, a three-wave self-administered survey among patients diagnosed with localized prostate cancer and their partner caregivers in multiple clinics in the USA. Time spent was measured by the sum of working hours lost, informal caregiving hours performed, and hours spent on household chores. The national median income for women 55 years or older was used to calculate costs associated with the time spent using the opportunity cost method. Descriptive and bivariate analyses were conducted. The average working hours decreased from 14.0 h/week (SD = 17.6) to 10.9 h/week (SD = 15.9), without a significant change in responsibility/intensity at work. The mean annual time spent on informal caregiving and household chores was 65.9 h/year (SD = 172.4) and 76.2 h/year (SD = 193.3), respectively. The mean annual economic burden among partner caregivers was US$6,063 (range US$571-US$47,105) in 2009 dollars accounted for by a mean of 276.2 h (range 26-2,146) in the study sample. The time spent on informal caregiving and household chores varied by patient and caregiver characteristics. Pilot estimates on non-medical economic burden among partner caregivers (spouses) during the initial phase of the treatment provide important information for comprehensive estimation of disease burden and can be used in cost-effectiveness analyses of prostate cancer interventions.
    Supportive Care in Cancer 08/2013; 21(12). DOI:10.1007/s00520-013-1931-3 · 2.36 Impact Factor
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    ABSTRACT: Purpose: To preliminarily evaluate the potential for an improvement in diagnostic performance by a combined interpretation of In-111 capromab pendetide single photon emission computed tomography (SPECT) including computed tomography (CT) image fusion with magnetic resonance diffusion-weighted imaging (MR-DWI) for identifying prostate cancer in pelvic lymph nodes thru correlation with histopathology. Materials and methods: This institutional approved, retrospective study identified patients with available histopathology of lymph nodes removed at the time of radical prostatectomy and who had undergone staging with In-111 capromab pendetide SPECT-CT and/or pelvic MRI (including DWI). The performance of In-111 capromab pendetide SPECT for identifying malignant lymph nodes was assessed. Subsequently, a combined reading of In-111 capromab pendetide SPECT and prostate MRI with DWI was performed and the performance assessed. Results: 18 patients underwent In-111 capromab pendetide SPECT-CT. Of these, 12 patients had also undergone imaging with MR-DWI. In-111 capromab pendetide SPECT-CT had a sensitivity of 40.0% and specificity of 96.7% for identification of malignant lymph nodes. However, In-111 capromab pendetide SPECT-CT combined with MRI with DWI had a sensitivity of 88.9% and specificity of 98.5%. Conclusions: The addition of MR-DWI to the interpretation of In-111 capromab pendetide SPECT-CT may increase the sensitivity for detecting malignant lymph nodes in prostate cancer. Future prospective evaluation of combined In-111 capromab pendetide SPECT-CT and MR-DWI is indicated and may improve clinical evaluation of nodal disease in prostate cancer.
    World Journal of Urology 04/2013; 31(6). DOI:10.1007/s00345-013-1079-2 · 2.67 Impact Factor

  • The Journal of Urology 04/2013; 189(4):e903-e904. DOI:10.1016/j.juro.2013.02.2113 · 4.47 Impact Factor
  • Uzair B Chaudhary · Nitin Verma · Thomas Keane · Vinay Gudena ·
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    ABSTRACT: Background: The objectives of the current study were to evaluate the safety and efficacy of gemcitabine and irinotecan (Irinogem) in patients with metastatic bladder cancer. Irinotecan and gemcitabine are newer-generation chemotherapeutic agents with different mechanisms of action, nonoverlapping toxicity profiles, and synergistic activity in vitro. Methods: Sixteen patients have been enrolled, of which 13 are evaluable for response. The median age is 68.5 years (range, 52 to 82 y). According to the Bajorin prognostic model for metastatic bladder cancer, 8 patients were classified as "low risk" and 8 as "intermediate risk." Gemcitabine 1000 mg/m and irinotecan 100 mg/m were administered on days 1 and 8 of each 3-week cycle. All patients had histologically proven transitional cell cancer of the bladder with bidimensionally measurable disease. All but 2 patients were chemotherapy naive at enrollment. Results: The median number of cycles administered was 4. Among the 13 patients evaluable for efficacy, objective radiographic response was documented in 8 patients (2 complete and 6 partial responses), 4 had stable disease, and 1 progressed on therapy. Median progression-free survival was 8.78 months (95% confidence interval, 5.98-15.38) and median overall survival was 13.51 months (95% confidence interval, 8.02-21.93). Toxicity evaluated in all 16 patients was modest: 2 episodes of febrile neutropenia, grades 3 to 4 neutropenia in 4 patients, grades 3 to 4 diarrhea in 2 patients, grades 3 to 4 fatigue in 1 patient, grades 3 to 4 nausea/vomiting in 2 patients, grades 3 to 4 neurological toxicity in 1 patient, and no grades 3 to 4 thrombocytopenia. No toxic deaths were noted. One patient discontinued therapy due to grade 4 fatigue, 1 due to stroke, 1 due to grade 4 colitis, 1 due to progressive disease, and 1 declined to participate in the trial after receiving the first cycle of therapy. Conclusions: The results of the current study suggested that the combination of Irinogem was an effective treatment for patients with metastatic bladder cancer, with manageable toxicities. The study was closed early due to delays in accrual and loss of funding. Hence, the study lacks adequate power to make definite conclusions. Further studies in multi-institutional setting in patients with normal and compromised renal function are warranted.
    American journal of clinical oncology 12/2012; 37(2). DOI:10.1097/COC.0b013e318271b306 · 3.06 Impact Factor
  • Sandip M. Prasad · Thomas Keane · Charles L. Bennett ·

    Urology 09/2012; 80(3):563-563. DOI:10.1016/j.urology.2012.02.086 · 2.19 Impact Factor
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    ABSTRACT: To explore an alternative approach to quantifying the burden of side effects at 1 year after treatment for prostate cancer among both patients and their partners. We analyzed data from 75 couples in the Family and Cancer Therapy Selection study. Paired patients and family members were independently asked about their willingness to pay (WTP) for a hypothetical new treatment that cures prostate cancer without side effects if they could reconsider their treatment decision by indicating the maximum amount they would be willing to pay given 11 separate "bids" ranging from $0 to $1500 per month. Descriptive and regression analyses were conducted for patients and family members controlling for sociodemographic characteristics and health status; Spearman correlations were also examined. Among 75 couples analyzed, the income-adjusted mean WTP estimates per month were $400.8 (standard error [SE] $54.3) for patients and $650.2 (SE 72.2) for family members. The WTP between patients and family members was correlated (Pearson ρ 0.30; P = 0.01). After adjusting for covariates, the adjusted mean WTP per month was $588.1 (SE 65.77) for patients and $819.4 (SE 74.33) for family members. Wanting to avoid side effects at baseline predicted higher WTP for patients (P = 0.010). Experiencing sexual side effects was predictive of higher WTP for family members (P = 0.047). Fairly high WTP amounts for a hypothetical treatment without side effects suggests that patients and their partners are experiencing important burdens 1 year after treatment. The higher amounts partners are willing to pay and the correlation with sexual side effects suggest that they are perceptive of significant treatment burdens.
    Value in Health 07/2012; 15(5):716-23. DOI:10.1016/j.jval.2012.03.003 · 3.28 Impact Factor
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    ABSTRACT: Our study aims at understanding the timing and nature of mitochondrial deoxyribonucleic acid (mtDNA) alterations in urothelial cell carcinoma (UCC) and their detection in urine sediments. The entire 16.5 kb mitochondrial genome was sequenced in matched normal lymphocytes, tumor and urine sediments from 31 UCC patients and compared to different clinical stages and histological grades. The mtDNA content index was examined in all the specimens. Sixty-five percent (20/31) of the patients harbored at least 1 somatic mtDNA mutation. A total of 25 somatic mtDNA mutations were detected, which were more frequent in the respiratory complex coding regions (Complex I, III, IV and V) of the mtDNA and significantly affected respiratory Complex III compared to the other complexes (p = 0.021-0.039). Compared to Stage Ta, mtDNA mutation was higher in Stage T1 and significantly higher in Stage T2 (p = 0.01) patients. MtDNA mutation was also significantly higher (p = 0.04) in Stage T2 compared to Stage T1 patients. Ninety percent (18/20) of the patients harboring mtDNA mutation in the tumor also had mutation in their urine sediments. Eighty percent (20/25) of the tumor-associated mtDNA mutations was detectable in the urine sediments. Compared to the normal lymphocytes, the mtDNA content increased significantly in the tumor (p = 0.0013) and corresponding urine sediments (p = 0.0025) in 19/25 (76%) patients analyzed. Our results indicate that mtDNA alterations occur frequently in progressive stages of UCC patients and are readily detectable in the urine sediments. MtDNA mutations appear to provide a promising tool for developing early detection and monitoring strategies for UCC patients.
    International Journal of Cancer 07/2012; 131(1):158-64. DOI:10.1002/ijc.26357 · 5.09 Impact Factor

  • Cancer Research 06/2012; 72(8 Supplement):2111-2111. DOI:10.1158/1538-7445.AM2012-2111 · 9.33 Impact Factor
  • F Schröder · E.D. Crawford · K Axcrona · H Payne · T.E. Keane ·
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    ABSTRACT: Since Huggins and Hodges demonstrated the responsiveness of prostate cancer to androgen deprivation therapy (ADT), androgen-suppressing strategies have formed the cornerstone of management of advanced prostate cancer. Approaches to ADT have included orchidectomy, oestrogens, luteinizing hormone-releasing hormone (LHRH) agonists, anti-androgens and more recently the gonadotrophin-releasing hormone antagonists. The most extensively studied antagonist, degarelix, avoids the testosterone surge and clinical flare associated with LHRH agonists, offering more rapid PSA and testosterone suppression, improved testosterone control and improved PSA progression-free survival compared with agonists. The clinical profile of degarelix appears to make it a particularly suitable therapeutic option for certain subgroups of patients, including those with metastatic disease, high baseline PSA (>20 ng/mL) and highly symptomatic disease. As well as forming the mainstay of treatment for advanced prostate cancer, ADT is increasingly used in earlier disease stages. While data from clinical trials support the use of ADT neoadjuvant/adjuvant to radiotherapy for locally advanced or high-risk localized prostate cancer, it remains to be established whether specific ADT classes/agents provide particular benefits in this clinical setting.
    BJU International 06/2012; 109 Suppl 6(6):1-12. DOI:10.1111/j.1464-410X.2012.11215.x · 3.53 Impact Factor
  • Sandip M Prasad · Thomas E Keane · Charles L Bennett ·

    Urology 05/2012; 80(1):168. DOI:10.1016/j.urology.2012.01.069 · 2.19 Impact Factor
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    ABSTRACT: We wanted to investigate vitamin D in low-risk prostate cancer. The objective of the study was to determine whether vitamin D(3) supplementation at 4000 IU/d for 1 yr is safe and would result in a decrease in serum levels of prostate-specific antigen (PSA) or in the rate of progression. In this open-label clinical trial (Investigational New Drug 77,839), subjects were followed up until repeat biopsy. All subjects were enrolled through the Medical University of South Carolina and the Ralph H. Johnson Veterans Affairs Medical Center, both in Charleston, SC. All subjects had a diagnosis of low-risk prostate cancer. Fifty-two subjects were enrolled in the study, 48 completed 1 yr of supplementation, and 44 could be analyzed for both safety and efficacy objectives. The intervention included vitamin D(3) soft gels (4000 IU). Adverse events were monitored throughout the study. PSA serum levels were measured at entry and every 2 months for 1 yr. Biopsy procedures were performed before enrollment (for eligibility) and after 1 yr of supplementation. No adverse events associated with vitamin D(3) supplementation were observed. No significant changes in PSA levels were observed. However, 24 of 44 subjects (55%) showed a decrease in the number of positive cores or decrease in Gleason score; five subjects (11%) showed no change; 15 subjects (34%) showed an increase in the number of positive cores or Gleason score. Patients with low-risk prostate cancer under active surveillance may benefit from vitamin D(3) supplementation at 4000 IU/d.
    The Journal of Clinical Endocrinology and Metabolism 04/2012; 97(7):2315-24. DOI:10.1210/jc.2012-1451 · 6.21 Impact Factor
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    ABSTRACT: What's known on the subject? and What does the study add? Penile cancer is a rare malignancy with limited evidence to support most treatment recommendations. No randomised controlled trials have been published and few recommendations are available for guiding management. However, evidence-based guidelines are currently available through the European Association of Urology. This review provides the reader with the most up-to-date information on diagnosis and management of all stages of squamous cell carcinoma of the penis. It provides a rapid review and study guide for this rare disease.
    BJU International 11/2011; 108(9):1378-92. DOI:10.1111/j.1464-410X.2011.10647.x · 3.53 Impact Factor

Publication Stats

2k Citations
228.61 Total Impact Points


  • 2004-2014
    • Medical University of South Carolina
      • • Department of Pathology and Laboratory Medicine (College of Medicine)
      • • Department of Urology
      • • Department of Biochemistry and Molecular Biology (College of Medicine)
      • • Department of Medicine
      Charleston, South Carolina, United States
  • 2013
    • Charleston School of Law
      Charleston, South Carolina, United States
  • 2012
    • Iowa State University
      • Department of Animal Science
      Ames, Iowa, United States
  • 2010
    • VA Puget Sound Health Care System
      Washington, Washington, D.C., United States
  • 2008
    • Charleston Area Medical Center
      Charleston, West Virginia, United States
  • 1995-2008
    • Emory University
      • • Department of Urology
      • • Department of Surgery
      Atlanta, Georgia, United States