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2.  The Impact of Radiographic Retropharyngeal Adenopathy in Oropharyngeal Cancer 
Cancer  2013;119(17):3162-3169.
We carried out this study to define the incidence of radiographic retropharyngeal lymph node (RPLN) involvement in oropharyngeal cancer (OPC) and its impact on clinical outcomes, which have not been well established to date.
Our departmental database was queried for patients irradiated for OPC from 2001–2007. Analyzable patients were those with imaging data available for review to determine radiographic RPLN status. Demographic, clinical, and outcomes data were retrieved and analyzed.
The cohort consisted of 981 patients. Median follow up was 69 months. The base of tongue (47%) and tonsil (46%) were the most common primary sites. The majority of patients had T1-2 primaries (64%) and 94% stage 3-4B disease. IMRT was used in 77%, and systemic therapy was delivered to 58%. The incidence of radiographic RPLN involvement was 10% and highest for pharyngeal wall (23%) and lowest for base of tongue tumors (6%). RPLN adenopathy correlated with a number of patient and tumor factors. RPLN involvement was associated with poorer 5-year outcomes on univariate analysis (p <.001 for all): local control (79% vs. 92%), nodal control (80% vs. 93%), recurrence-free (51% vs. 81%), distant metastases-free (66% vs. 89%), and overall survival (52% vs. 82%), and maintained significance for local control (p=.023), recurrence-free (p=.001), distant metastases-free (p=.003), and overall survival (p=.001) on multivariate analysis.
In this cohort of nearly 1000 patients investigating radiographic RPLN adenopathy in OPC, RPLN involvement was observed in 10% of patients and portends a negative influence on disease recurrence, distant relapse, and survival.
PMCID: PMC3775996  PMID: 23733178
Oropharyngeal cancer; retropharyngeal lymph nodes; incidence; radiation therapy; survival
3.  Prospective Assessment of an Atlas-Based Intervention Combined With Real-Time Software Feedback in Contouring Lymph Node Levels and Organs-at-Risk in the Head and Neck: Quantitative Assessment of Conformance to Expert Delineation 
Practical radiation oncology  2013;3(3):186193-.
A number of studies have previously assessed the role of teaching interventions to improve organ-at-risk (OAR) delineation. We present a preliminary study demonstrating the benefit of a combined atlas and real time software based-feedback intervention to aid in contouring of OARs in the head and neck.
Methods and Materials
The study consisted of a baseline evaluation, a real-time feedback intervention, atlas presentation, and a follow-up evaluation. At baseline evaluation, 8 resident observers contoured 26 organs-at-risk on a computed tomography scan without intervention or aid. They then received feedback comparing their contours both statistically and graphically to a set of atlas-based expert contours. Additionally, they received access to an atlas to contour these structures. The resident observers were then asked to contour the same 26 organs-at-risk on a separate computed tomography scan with atlas access. In addition, 6 experts (5 radiation oncologists specializing in the head and neck, and 1 neuroradiologist) contoured the 26 organs-at-risk on both scans. A STAPLE composite of the expert contours was used as a gold-standard set for analysis of organs-at-risk contouring.
Of the 8 resident observers who initially participated in the study, 7 completed both phases of the study. Dice Similarity Coefficients (DSCs) were calculated for each user-drawn structure relative to the expert STAPLE composite for each structure. Mean DSC across all structures increased between Phase 1 and Phase 2 for each resident observer demonstrating a statistically significant improvement in overall OAR-contouring ability (p < 0.01). Additionally, intervention improved contouring in 16/26 delineated organs-at-risk across resident observers at a statistically significant level (p ≤ 0.05), including all otic structures and suprahyoid lymph node levels of the head and neck.
Our data suggest that a combined atlas and real-time feedback-based educational intervention detectably improves contouring of OARs in the head and neck.
PMCID: PMC3706296  PMID: 23853674
4.  Clinical Implications of PET-Negative Residual CT Masses after Chemotherapy for Diffuse Large B-Cell Lymphoma 
Leukemia & lymphoma  2013;54(12):10.3109/10428194.2013.784967.
Response to primary treatment in diffuse large B cell lymphoma (DLBCL) is highly predictive of long-term outcome. We evaluated the value of computed tomography (CT) findings relative to positron emission tomography (PET) findings, after the completion of chemotherapy; we retrospectively reviewed records from 491 patients with DLBCL at MD Anderson in 2001-2007; 22 patients were excluded for uncertain pathology and 169 for having received consolidative radiation, leaving 300 patients for the current analysis (median age, 61 years; 53% men, 47% women; 27% stage I-II, 73% stage III-IV; 73% completed 6-8 cycles of doxorubicin-based therapy). Factors associated with outcome on univariate analysis were response according to PET/CT and CT (P<0.0001 for OS, DSS, and PFS); number of chemotherapy cycles received (P<0.0001 OS, P<0.0001 DSS, P<0.002 PFS); the combined presence of Ki-67 >50%, PET SUV ≥13, and bulky (>5 cm) disease (P=0.005 OS, P=0.001 DSS, P=0.001 PFS); and International Prognostic Index (IPI) score (P=0.003 OS, P=0.005 DSS, P=0.003 PFS). On multivariate analysis, PET/CT-negative, CT residual mass (>2 cm) significantly influenced OS, DSS and PFS (P<0.0001). The presence of a residual mass >2 cm on CT, coupled with negative findings on PET/CT, has prognostic value in DLBCL.
PMCID: PMC3827734  PMID: 23488661
5.  Adipose tissue dysfunction tracks disease progression in two Huntington's disease mouse models 
Human Molecular Genetics  2009;18(6):1006-1016.
In addition to the hallmark neurological manifestations of Huntington's disease (HD), weight loss with metabolic dysfunction is often observed in the later stages of disease progression and is associated with poor prognosis. The mechanism for weight loss in HD is unknown. Using two mouse models of HD, the R6/2 transgenic and CAG140 knock-in mouse strains, we demonstrate that adipose tissue dysfunction is detectable at early ages and becomes more pronounced as the disease progresses. Adipocytes acquire a ‘de-differentiated’ phenotype characterized by impaired expression of fat storage genes. In addition, HD mice exhibit reduced levels of leptin and adiponectin, adipose tissue-derived hormones that regulate food intake and glucose metabolism. Importantly, some of these changes occur prior to weight loss and development of some of the characteristic neurological symptoms. We demonstrate that impaired gene expression and lipid accumulation in adipocytes can be recapitulated by expression of an inducible mutant huntingtin transgene in an adipocyte cell line and that mutant huntingtin inhibits transcriptional activity of the PGC-1α co-activator in adipocytes, which may contribute to aberrant gene expression. Thus, our findings indicate that mutant huntingtin has direct detrimental effects in cell types other than neurons. The results also indicate that circulating adipose-tissue-derived hormones may be accessible markers for HD prognosis and progression and suggest that adipose tissue may be a useful therapeutic target to improve standard of life for HD patients.
PMCID: PMC2649017  PMID: 19124532

Results 1-5 (5)