K J Cullen

Loyola University Maryland, Baltimore, Maryland, United States

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Publications (76)518.15 Total impact

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    ABSTRACT: While we previously reported a striking racial difference in the prevalence of human papillomavirus (HPV) positive oropharyngeal cancer (OPSCC), less is known about differences in outcomes and trends over time in OPSCC by HPV status and race. We conducted a retrospective analysis of 467 OPSCC patients treated at the University of Maryland Greenebaum Cancer Center between 1992 and 2007, of which 200 had tissue available for HPV16 testing. HPV16 positive patients were significantly more likely to be white, with 45.5% of whites and 15.5% of blacks testing positive for HPV16. There was a significant increase in HPV16 positive OPSCC for all patients over time from 15.6% in 1992-1995 to 43.3% in 2004-2007 (p=.01). From 1992-1995, 33% of white patients were HPV16 positive with no black patients positive. From 2004-2007, 17.7% of black patients and 54% of white patients were HPV16 positive. White and black patients with HPV16 positive tumors had an identical and favorable overall survival (OS)(median 8.1 and 8.1 years, respectively ). However among HPV16 negative patients, whites had an improved OS compared to blacks (median 2.3 vs. 0.9 years, respectively, p = .02) including when analyzed in a multivariable Cox regression model. From 1992 to 2007 the percentage of HPV16 positive OPSCCs increased for white patients and was seen for the first time in black patients. While survival for HPV positive black and white patients was similar and favorable, outcomes for HPV negative patients were poor, with blacks having worse survival even after controlling for baseline characteristics.
    Cancer prevention research (Philadelphia, Pa.). 06/2014;
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    ABSTRACT: Answer questions and earn CME/CNE Human papillomavirus (HPV), one of the most common sexually transmitted diseases worldwide, has an established role in the pathogenesis of genital malignancies such as cervical cancer. The virus has also been implicated in the oncogenesis of nongenital cancers including head and neck malignancies (specifically oropharyngeal cancers) as well as anal cancer. There is less clarity regarding its role in lung and esophageal cancers. Worldwide, the incidence and prevalence of HPV-associated oropharyngeal cancer has been increasing over time. These patients have improved outcomes compared with those with HPV-negative oropharyngeal cancers, and there is continued interest in designing treatments specifically for this HPV-positive subgroup. Clinicians continue to gain an understanding of HPV in anal cancers and the risk factors associated with infection and progression to malignancy. This has potential implications for the eventual screening of high-risk groups. While HPV vaccination is currently approved for the prevention of cervical cancer, it also has potential in the prevention of all HPV-associated malignancies. In this review, current understanding of the role of HPV in nongenital cancers is discussed, as well as future implications for treatment and prevention. CA Cancer J Clin 2013;. © 2012 American Cancer Society.
    CA A Cancer Journal for Clinicians 12/2012; · 153.46 Impact Factor
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    ABSTRACT: Resistance to cisplatin-based chemotherapy is responsible for therapeutic failure of many common human cancers including cancer of head and neck (HNC). Mechanisms underlying cisplatin resistance remain unclear. In this study, we identified neurofilament light polypeptide (NEFL) as a novel hypermethylated gene associated with resistance to cisplatin-based chemotherapy in HNC. Analysis of 14 HNC cell lines revealed that downregulation of NEFL expression significantly correlated with increased resistance to cisplatin. Hypermethylation of NEFL promoter CpG islands was observed in cell lines as examined by bisulfite DNA sequencing and methylation-specific PCR (MSP) and tightly correlated with reduced NEFL mRNA and protein expression. Furthermore, in patient samples with HNC (n = 51) analyzed by quantitative MSP, NEFL promoter hypermethylation was associated with resistance to cisplatin-based chemotherapy [relative risk (RR), 3.045; 95% confidence interval (CI), 1.459-6.355; P = 0.007] and predicted diminished overall and disease-free survival for patients treated with cisplatin-based chemotherapy. Knockdown of NEFL by siRNA in the highly cisplatin-sensitive cell line PCI13 increased (P < 0.01) resistance to cisplatin. In cisplatin-resistant O11 and SCC25cp cells, restored expression of NEFL significantly increased sensitivity to the drug. Furthermore, NEFL physically associated with tuberous sclerosis complex 1 (TSC1), a known inhibitor of the mTOR pathway, and NEFL downregulation led to functional activation of mTOR pathway and consequentially conferred cisplatin resistance. This is the first study to show a role for NEFL in HNC chemoresistance. Our findings suggest that NEFL methylation is a novel mechanism for HNC chemoresistance and may represent a candidate biomarker predictive of chemotherapeutic response and survival in patients with HNC.
    Molecular Cancer Research 02/2012; 10(3):305-15. · 4.35 Impact Factor
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    ABSTRACT: BACKGROUND: We performed a pilot study using Trojan vaccines in patients with advanced squamous cell carcinoma of the head and neck (SCCHN). These vaccines are composed of HLA-I and HLA-II restricted melanoma antigen E (MAGE)-A3 or human papillomavirus (HPV)-16 derived peptides, joined by furin-cleavable linkers, and linked to a "penetrin" peptide sequence derived from HIV-TAT. Thirty-one patients with SCCHN were screened for the trial and 5 were enrolled. METHODS: Enrolled patients were treated with 300 μg of Trojan peptide supplemented with Montanide and granulocyte-macrophage colony-stimulating factor (GM-CSF) at 4-week intervals for up to 4 injections. RESULTS: Following vaccination, peripheral blood mononuclear cells (PBMCs) from 4 of 5 patients recognized both the full Trojan constructs and constituent HLA-II peptides, whereas responses to HLA-I restricted peptides were less pronounced. CONCLUSION: This treatment regimen seems to have acceptable toxicity and elicits measurable systemic immune responses against HLA-II restricted epitopes in a subset of patients with advanced SCCHN. © 2012 Wiley Periodicals, Inc. Head Neck, 2012.
    Head & Neck 01/2012; · 2.83 Impact Factor
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    ABSTRACT: This study analyzed the impact of timing of percutaneous endoscopic gastrostomy (PEG) tube placement on clinical endpoints in patients undergoing concurrent chemoradiation therapy (CRT). In all, 111 patients who underwent CRT for locally advanced squamous cell carcinoma of the head and neck (SCCHN) were retrospectively analyzed to determine the effect of timing of PEG placement on weight loss, hospitalizations, and rates of PEG complications/dependence. Early PEG tube placement was correlated to reductions in weight loss during CRT (p < .001, R = 0.495), hospitalization for nutritional deficits (p = .011, R = 0.262), and magnitude of persistent weight loss at 6 weeks post-CRT (p = .003, R = 0.347). Disease control was the only predictor of PEG dependence. No differences were seen in PEG complication or dependence rates with earlier placement. The results of our series show that patients with locally advanced SCCHN undergoing definitive CRT may derive significant clinical benefit from the early placement of PEG tubes for nutritional supplementation.
    Head & Neck 10/2011; 33(10):1441-7. · 2.83 Impact Factor
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    ABSTRACT: New treatment strategies for locally advanced head and neck squamous cell carcinoma combine induction chemotherapy and chemoradiation. Identifying the predictors of outcome in sequentially treated patients is critical for focusing therapeutic research. In this analysis, the authors evaluated human papillomavirus type 16 (HPV-16) status and the expression levels of a defined set of biomarkers to identify predictors of response to this treatment modality. In total, 114 patients with oropharyngeal cancer (OPC) who were treated on the TAX 324 trial (cisplatin and fluorouracil with or without docetaxel in patients with locally advanced head and neck squamous cell carcinoma) had pretreatment biopsy specimens that were evaluable for HPV-16 DNA and immunohistochemical expression of the following biomarkers: beta-tubulin II (βT-II), glutathione S-transferase (GST-π), p53, and B-cell lymphoma 2 (Bcl-2). Patients were categorized into risk groups based on their HPV status and biomarker expression levels. Patients with high-risk OPC were defined by HPV-negative status and either elevated expression of βT-II or levels of at least 2 of the other 3 adverse markers (elevated GST-π, elevated p53, or low Bcl-2). All other HPV-negative patients were categorized as moderate risk. In total, 55 patients were HPV-positive, and 59 patients were HPV-negative, with 34 were categorized as high risk and 25 categorized as moderate risk. The median survival for HPV-positive patients was not reached. The median survival was 44.2 months for moderate-risk patients (95% confidence interval, 20.9 months to not reached) and 12.1 months for high-risk patients (95% confidence interval, 7.5-19.7 months). The 24-month survival rate was 89% for HPV-positive patients, 67% for moderate-risk patients, and 29% for high-risk patients (P < .0001). The molecular data set in this study readily differentiated between 2 distinct groups of patients with locally advanced, HPV-negative OPC. This risk-stratification strategy may serve as a guide for treatment selection.
    Cancer 08/2011; 118(7):1811-7. · 5.20 Impact Factor
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    ABSTRACT: Glutathione peroxidase 3 (GPx3), a plasma antioxidant enzyme, maintains genomic integrity by inactivating reactive oxygen species (ROS), known DNA-damaging agents and mediators of cancer chemotherapy response. In this study, we demonstrate that loss of GPx3 expression by promoter hypermethylation is frequently observed in a wide spectrum of human malignancies. Furthermore, GPx3 methylation correlates with head and neck cancer (HNC) chemoresistance and may serve as a potential prognostic indicator for HNC patients treated with cisplatin-based chemotherapy. Our findings support the hypothesis that defects in the antioxidant system may contribute to tumorigenesis of a wide spectrum of human malignancies. GPx3 methylation may have implications in chemotherapy response and clinical outcome of HNC patients.
    Cancer letters 06/2011; 309(1):37-45. · 5.02 Impact Factor
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    ABSTRACT: To report the mature data of a prospective Phase II trial designed to evaluate the efficacy of an epidermal growth factor receptor inhibitor cetuximab (CTX) added to the concurrent therapy of weekly paclitaxel/carboplatin (PC) and daily radiation therapy (RT). From 2005 to 2009, a total of 43 patients were enrolled in the study. The median follow-up was 31 months (range, 9-59 months). All patients had Stage III/IV disease at presentation, and 67% had oropharyngeal primaries. The weekly IV dose schedules were CTX 250 mg/m(2) (400 mg/m(2) IV loading dose 1 week before RT), paclitaxel 40 mg/m(2), and carboplatin AUC 2. RT was given at 1.8 Gy per day to 70.2 Gy. Intensity-modulated RT was used in 70% of cases. All patients completed the planned RT dose, 74% without any treatment breaks. The planned CTX and PC cycles were completed in 70% (91% with at least seven of planned nine cycles) and 56% (93% with at least seven of planned eight cycles) of patients, respectively. Toxicity included Grade 3 mucositis (79%), rash (9%), leucopenia (19%), neutropenia (19%), and RT dermatitis (16%). The complete response (CR) rate at the completion of therapy was 84%. The estimated 3-year local regional control rate was 72%. Six patients with an initial CR subsequently experienced a local recurrence, 10 patients experienced distant progression. The median overall survival and disease-free survivals have not been reached. The 3-year actuarial overall survival and disease-free survival were 59% and 58%, respectively. The addition of CTX to weekly PC and daily RT was well tolerated and resulted in encouraging local control and survival rates.
    International journal of radiation oncology, biology, physics 05/2011; 82(5):1845-50. · 4.59 Impact Factor
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    ABSTRACT: PURPOSE: The tumor volume has been established as a significant predictor of outcomes among patients with head-and-neck cancer undergoing radiotherapy alone. The present study attempted to add to the existing data on tumor volume as a prognostic factor among patients undergoing chemoradiotherapy. METHODS AND MATERIALS: A total of 78 patients who had undergone definitive chemoradiotherapy for Stage III-IV squamous cell cancer of the hypopharynx, oropharynx, and larynx were identified. The primary tumor volumes were calculated from the treatment planning computed tomography scans, and these were correlated to the survival and tumor control data obtained from the retrospective analysis. RESULTS: The interval to progression correlated with the primary tumor volume (p = .007). The critical cutoff point for the tumor volume was identified as 35 cm(3), and patients with a tumor volume <35 cm(3) had a significantly better prognosis than those with a tumor volume >35 cm(3) at 5 years (43% vs. 71%, p = .010). Longer survival was also correlated with smaller primary tumor volumes (p = .022). Similarly, patients with a primary tumor volume <35 cm(3) had a better prognosis in terms of both progression-free survival (61% vs. 33%, p = .004) and overall survival (84% vs. 41%, p = < .001). On multivariate analysis, the primary tumor volume was the best predictor of recurrence (hazard ratio 4.7, 95% confidence interval 1.9-11.6; p = .001) and survival (hazard ratio 10.0, 95% confidence interval 2.9-35.1; p = < .001). In contrast, the T stage and N stage were not significant factors. Analysis of variance revealed that tumors with locoregional failure were on average 21.6 cm(3) larger than tumors without locoregional failure (p = .028) and 27.1-cm(3) larger than tumors that recurred as distant metastases (p = .020). CONCLUSION: The results of our study have shown that the primary tumor volume is a significant prognostic factor in patients with advanced cancer of the head and neck undergoing definitive chemoradiotherapy and correlated with the treatment outcomes better than the T or N stage.
    International journal of radiation oncology, biology, physics 05/2011; 82(5):1823-30. · 4.59 Impact Factor
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    ABSTRACT: The association between human papillomavirus (HPV) and overall survival (OS) in oropharynx cancer (OPC) was retrospectively examined in TAX 324, a phase III trial of sequential therapy for locally advanced head and neck cancer. Accrual for TAX 324 was completed in 2003 and data updated through 2008. Pretherapy tumor biopsies were studied by PCR for human papillomavirus type 16 and linked to OS, progression-free survival (PFS) and demographics. Of 264 patients with OPC, 111 (42%) had evaluable biopsies; 56 (50%) were HPV+ and 55 (50%) were HPV-. HPV+ patients were significantly younger (54 versus 58 years, P = 0.02), had T1/T2 primary cancers (49% versus 20%, P = 0.001), and had a performance status of zero (77% versus 49%, P = 0.003). OS and PFS were better for HPV+ patients (OS, hazard ratio = 0.20, P < 0.0001). Local-regional failure was less in HPV+ patients (13% versus 42%, P = 0.0006); at 5 years, 82% of HPV+ patients were alive compared with 35% of HPV- patients (P < 0.0001). HPV+ OPC has a different biology compared with HPV- OPC; 5-year OS, PFS, and local-regional control are unprecedented. These results support the possibility of selectively reducing therapy and long-term morbidity in HPV+ OPC while preserving survival and approaching HPV- disease with more aggressive treatment.
    Annals of Oncology 02/2011; 22(5):1071-7. · 7.38 Impact Factor
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    ABSTRACT: At a minimum follow-up of 2 years, the TAX 324 study showed a significant survival benefit of induction chemotherapy with docetaxel, cisplatin, and fluorouracil (TPF) versus cisplatin and fluorouracil (PF) in locally advanced head and neck cancer. We report the long-term results at 5 years' minimum follow-up. TAX 324 was a randomised, open-label phase 3 trial comparing three cycles of TPF induction chemotherapy (docetaxel 75 mg/m(2), followed by intravenous cisplatin 100 mg/m(2) and fluorouracil 1000 mg/m(2) per day, administered as a continuous 24-h infusion for 4 days) with three cycles of PF (intravenous cisplatin 100 mg/m(2), followed by fluorouracil 1000 mg/m(2) per day as a continuous 24-h infusion for 5 days) in patients with stage III or IV squamous-cell carcinoma of the head or neck. Both regimens were followed by 7 weeks of chemoradiotherapy with concomitant weekly carboplatin. Randomisation was done centrally with the use of a biased-coin minimisation technique. At study entry, patients were stratified according to the site of the primary tumour, nodal status (N0 or N1 vs N2 or N3), and institution. For this long-term analysis, data as of Dec 1, 2008, were gathered retrospectively from patients' medical records. Overall and progression-free survival were the primary endpoints. Tracheostomy and dependence on a gastric feeding tube were used as surrogate measures for treatment-related long-term toxicity. The intention-to-treat analysis included data from all 501 patients (255 TPF, 246 PF); data from the initial analysis in 2005 were used for 61 patients who were lost to follow-up. TAX 324 was registered at ClinicalTrials.gov, NCT00273546. Median follow-up was 72·2 months (95% CI 68·8-75·5). Overall survival was significantly better after treatment with TPF versus PF (hazard ratio [HR] 0·74, 95% CI 0·58-0·94), with an estimated 5-year survival of 52% in patients treated with TPF and 42% in those receiving PF. Median survival was 70·6 months (95% CI 49·0-89·0) in the TPF group versus 34·8 months (22·6-48·0) in the PF group (p=0·014). Progression-free survival was also significantly better in patients treated with TPF (median 38·1 months, 95% CI 19·3-66·1, vs 13·2 months, 10·6-20·7; HR 0·75, 95% CI 0·60-0·94). We detected no significant difference in dependence on gastric feeding tubes and tracheostomies between treatment groups. In the TPF group, three (3%) of 91 patients remained feeding-tube dependent, compared with eight (11%) of 71 patients in the PF group. Six (7%) of 92 patients had tracheostomies in the TPF group, versus eight (11%) of 71 in the PF group. Induction chemotherapy with TPF provides long-term survival benefit compared with PF in locally advanced head and neck cancer. Patients who are candidates for induction chemotherapy should be treated with TPF. Sanofi-Aventis.
    The Lancet Oncology 02/2011; 12(2):153-9. · 25.12 Impact Factor
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    ABSTRACT: TAX 324 was a phase III trial comparing induction chemotherapy (IC) with docetaxel, cisplatin, and fluorouracil (TPF) with cisplatin and fluorouracil (PF) followed by concomitant chemoradiotherapy in locally advanced squamous cell cancer of the head and neck (LASCCHN). This study evaluates a series of tumor markers in pretreatment biopsies from that trial TAX 324 and correlates expression with survival. Pretherapy biopsy specimens were available for 265 of 501 participants. Expression of a series of six markers (p53, thymidylate synthase, glutathione s-transferase pi [GST-pi], Bcl 2, beta tubulin II [betaT-2], and HER2 neu) was evaluated by immunohistochemistry. For patients with low betaT-II expression, median overall survival (OS) was 58.6 months (95% CI, not reached [NR]), compared with 18.2 months for patients with high betaT-II expression (95% CI, 13.11 to 30.06: hazard ratio [HR], 2.39; 95% CI, 1.67 to 3.72; P < .0001). Progression-free survival in patients with low betaT-II expression was 43.2 months (95% CI, 24.4 to NR) versus 9.8 months (95% CI, 7.06 to 18.53) for high betaT-II expression, with a HR of 1.9 (95% CI, 1.43 to 2.77; P < .0001). The predictive value of betaT-II expression was greater in the TPF versus PF arm than in the PF arm. Increased tumor expression of betaT-II is strongly associated with adverse outcome in LASCCHN patients treated with IC, and our data suggest low expression of betaT-II may predict patients most likely to benefit from induction TPF therapy. Further, simple models which combine expression of betaT-II with a carefully defined set of additional immunohistochemical markers may have significant prognostic impact for patients with LASCCHN.
    Journal of Clinical Oncology 11/2009; 27(36):6222-8. · 18.04 Impact Factor
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    ABSTRACT: Bisphosphonate-associated osteonecrosis (BON) is a recently recognized oral complication of bisphosphonate (BP) therapy. Currently, research into the pathogenesis of BON has been hampered by being deficient in studies capable of measuring the level of BP in saliva or at the bone-soft tissue interface. The objective of this current study was to develop a novel bioassay model representative of the oral levels of BPs in patients presenting with or at risk for BON. Zoledronic acid (ZA) injectable was used to develop standardized MTS cell proliferation assay curves at concentrations of 0-10 microM, which were used either in a dilution in normal media, mimicking BP freed from bone or used to "spike" saliva individuals not taking BPs and mimicking BP levels being excreted. This bioassay was then used to estimate BP levels from samples of saliva and bone ex vivo from patients with and without BON. Saliva and bone from patients with existing BON showed levels of BP ranging from 0.4 to 4.6 microM, while patients receiving IV infusion of BP and naïve to BON showed levels in saliva ranging from 0.4 to 5 microM. All control specimens and patients naïve to BP showed levels at 0 microM. Given the fact that BPs are poor candidates for detection using standard methods (HPLC), this bioassay provides us with the ability to estimate clinically relevant concentrations of BP capable of producing apoptosis and the inhibition cell proliferation of oral mucosal cells based on previous studies. Subsequently, apoptosis and the inhibition of proliferation could lead to BON, secondary to the exposure of the bone in the unique microenvironment of the oral cavity.
    Supportive Care in Cancer 09/2009; 17(12):1553-7. · 2.09 Impact Factor
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    ABSTRACT: The burden of squamous cell carcinoma of the head and neck (SCCHN) is greater for blacks than for whites, especially in oropharyngeal cases. We previously showed retrospectively that disease-free survival was significantly greater in white than in black SCCHN patients treated with chemoradiation, the greatest difference occurring in the oropharyngeal subgroup. Oropharyngeal cancer is increasing in incidence and in its association with human papillomavirus (HPV) infection; HPV-positive oropharyngeal cancer patients have significantly better outcomes (versus HPV-negative). These collective data led to the present analyses of overall survival (OS) in our retrospective cohort and of OS and HPV status (tested prospectively in pretreatment biopsy specimens) in the phase 3, multicenter TAX 324 trial of induction chemotherapy followed by concurrent chemoradiation in SCCHN patients. Median OS in the retrospective cohort of 106 white and 95 black SCCHN patients was 52.1 months (white) versus only 23.7 months (black; P = 0.009), due entirely to OS in the subgroup of patients with oropharyngeal cancer--69.4 months (whites) versus 25.2 months (blacks; P = 0.0006); no significant difference by race occurred in survival of non-oropharyngeal SCCHN (P = 0.58). In TAX 324, 196 white patients and 28 black patients could be assessed for HPV status. Median OS was significantly worse for black patients (20.9 months) than for white patients (70.6 months; P = 0.03) and dramatically improved in HPV-positive (not reached) versus HPV-negative (26.6 months, 5.1 hazard ratio) oropharyngeal patients (P < 0.0001), 49% of whom were HPV-16 positive. Overall, HPV positivity was 34% in white versus 4% in black patients (P = 0.0004). Survival was similar for black and white HPV-negative patients (P = 0.56). This is the first prospective assessment of confirmed HPV status in black versus white SCCHN patients. Worse OS for black SCCHN patients was driven by oropharyngeal cancer outcomes, and that for black oropharyngeal cancer patients by a lower prevalence of HPV infection. These findings have important implications for the etiology, prevention, prognosis, and treatment of SCCHN.
    Cancer Prevention Research 07/2009; 2(9):776-81. · 4.89 Impact Factor
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    ABSTRACT: The role of adjuvant neck dissection in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) who obtain complete clinical and radiologic response following definitive chemoradiation treatment is controversial. Patterns of failure among 120 patients with locally advanced SCCHN, all with node-positive disease, treated with concurrent chemoradiation, were analyzed. Ninety-one of the patients achieved a complete response and were observed without undergoing neck dissection. Isolated failure in the neck occurred in 2 patients. The most common site of failure was metastatic disease (17 patients). Six patients had recurrence at the primary only, and 1 experienced failure in the neck and at the primary. Partial responders with resectable disease underwent neck dissection following chemoradiation. This group had worse local control and overall survival compared with complete responders. We recommend observation after definitive chemoradiation for complete responders. Further research is needed to improve outcomes among partial responders.
    Head & Neck 06/2009; 32(1):46-52. · 2.83 Impact Factor
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    ABSTRACT: The purpose of this study was to determine the impact of race on outcome in patients with stage III/IV squamous cell carcinoma of the head and neck (SCCHN) who have completed concurrent chemoradiotherapy. The authors performed a retrospective analysis of 202 patients with stage III/IV SCCHN who were treated at the University of Maryland. Patients received daily radiation to a total dose of 70.2 Gray (Gy) (1.8 Gy/day), concurrently with weekly carboplatin (area under the curve [AUC] = 2) and paclitaxel (45 mg/m(2)) chemotherapy. There were 108 Caucasian (CA) and 94 African American (AA) patients. The median age was 56 years, and 81% were stage IV. The median follow-up was 33 months. The median overall survival (OS) and disease-free survival (DFS) were 33 months and 19 months, respectively. When analyzed by race, the median DFS was 33 months (CA) versus 12 months (AA) (P = .028). The median OS was 44 months (CA) versus 24 months (AA) (P = .071). The 3-year DFS for stage IV AA versus stage IV CA was 29% versus 50% (P = .031). The 3-year DFS for N2 disease in AA versus CA was 32% versus 51% (P = .046). The 3-year DFS for AA versus CA with oropharyngeal tumors was 30% versus 60% (P = .006). This analysis documents the inferior outcome for AA patients. They had inferior DFS and a trend toward worse OS. When stratified by several prognostic variables, the mediocre DFS in the AA patients remains. These data suggest that further investigation into the genetic characteristics of SCCHN in AA patients is warranted.
    Cancer 03/2009; 115(8):1744-52. · 5.20 Impact Factor
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    ABSTRACT: Locally advanced laryngeal and hypopharyngeal cancers (LHC) represent a group of cancers for which surgery, laryngectomy-free survival (LFS), overall survival (OS), and progression-free survival (PFS) are clinically meaningful end points. These outcomes were analyzed in the subgroup of assessable LHC patients enrolled in TAX 324, a phase III trial of sequential therapy comparing docetaxel plus cisplatin and fluorouracil (TPF) against cisplatin and fluorouracil (PF), followed by chemoradiotherapy. Among 501 patients enrolled in TAX 324, 166 had LHC (TPF, n = 90; PF, n = 76). Patient characteristics were similar between subgroups. Median OS for TPF was 59 months [95% confidence interval (CI): 31-not reached] versus 24 months (95% CI: 13-42) for PF [hazard ratio (HR) for death: 0.62; 95% CI: 0.41-0.94; P = 0.024]. Median PFS for TPF was 21 months (95% CI: 12-59) versus 11 months (95% CI: 8-14) for PF (HR: 0.66; 95% CI: 0.45-0.97; P = 0.032). Among operable patients (TPF, n = 67; PF, n = 56), LFS was significantly greater with TPF (HR: 0.59; 95% CI: 0.37-0.95; P = 0.030). Three-year LFS with TPF was 52% versus 32% for PF. Fewer TPF patients had surgery (22% versus 42%; P = 0.030). In locally advanced LHC, sequential therapy with induction TPF significantly improved survival and PFS versus PF. Among operable patients, TPF also significantly improved LFS and PFS. These results support the use of sequential TPF followed by carboplatin chemoradiotherapy as a treatment option for organ preservation or to improve survival in locally advanced LHC.
    Annals of Oncology 02/2009; 20(5):921-7. · 7.38 Impact Factor
  • Fuel and Energy Abstracts 01/2009; 75(3).
  • Ejc Supplements - EJC SUPPL. 01/2009; 7(2):470-471.
  • Fuel and Energy Abstracts 01/2009; 75(3).

Publication Stats

3k Citations
518.15 Total Impact Points

Institutions

  • 2012
    • Loyola University Maryland
      Baltimore, Maryland, United States
  • 2011–2012
    • Indiana University Bloomington
      • Medical Sciences Program
      Bloomington, IN, United States
    • Mount Sinai Medical Center
      New York City, New York, United States
  • 2007–2011
    • University of Maryland Medical Center
      • Department of Radiation Oncology
      Baltimore, Maryland, United States
  • 2006–2011
    • University of Maryland, Baltimore
      • Department of Radiation Oncology
      Baltimore, MD, United States
  • 2003
    • University of Chicago
      • Committee on Cancer Biology
      Chicago, IL, United States
  • 1989–2003
    • Georgetown University
      • • Department of Oncology
      • • Division of Hematology and Oncology
      • • Lombardi Cancer Center
      • • Department of Otolaryngology-Head and Neck Surgery
      United States
    • Baylor College of Medicine
      • Department of Pediatrics
      Houston, TX, United States
    • National Cancer Institute (USA)
      Maryland, United States
    • Breast Cancer Prevention Institute
      Somerville, New Jersey, United States
  • 1998–2002
    • Università di Pisa
      • Department of Clinical and Experimental Medicine
      Pisa, Tuscany, Italy
  • 2000
    • University of Vienna
      • Department of Gynecology
      Vienna, Vienna, Austria
  • 1996
    • Kanazawa University
      Kanazawa, Ishikawa, Japan
  • 1992–1996
    • Rigshospitalet
      • Finsen Laboratory
      København, Capital Region, Denmark
  • 1991
    • Memorial Sloan-Kettering Cancer Center
      New York City, New York, United States