Periodontal pathogens are a risk factor of oral cavity squamous cell carcinoma, independent of tobacco and alcohol and human papillomavirus

Over the past decade, there has been a change in the epidemiology of oral cavity squamous cell cancer (OC-SCC). Many new cases of OC-SCC lack the recognized risk factors of smoking, alcohol and human papilloma virus. The aim of this study was to determine if the oral microbiome may be associated with OC-SCC in nonsmoking HPV negative patients. We compared the oral microbiome of HPV-negative nonsmoker OC-SCC(n = 18), premalignant lesions(PML) (n = 8) and normal control patients (n = 12). Their oral microbiome was sampled by oral wash and defined by 16S rRNA gene sequencing. We report that the periodontal pathogens Fusobacterium, Prevotella, Alloprevotella were enriched while commensal Streptococcus depleted in OC-SCC. Based on the four genera plus a marker genus Veillonella for PML, we classified the oral microbiome into two types. Gene/pathway analysis revealed a progressive increase of genes encoding HSP90 and ligands for TLRs 1, 2 and 4 along the controls→PML → OC-SCC progression sequence. Our findings suggest an association between periodontal pathogens and OC-SCC in non smoking HPV negative patients

Central nervous system involvement in T-cell lymphoma: A single center experience

Barriere de l'Étoile [model]; From 1784 to 1789 Ledoux was engaged by Calonne and the Ferme to build a new tax-wall around Paris, together with attendant boulevards and toll-gates or barrières. These latter buildings Ledoux conceived as monumental entries to the city, for which he adopted simplified geometric forms and manipulated scale and classical elements to produce bold, imaginative designs; 40 were proposed, in many variations of a few prototypes, and they were built very rapidly--almost all being completed in the four years before the Revolution--amid heated controversy and despite Ledoux's own dismissal from the work in 1789. The barrières, long a target of press criticism for their monumental scale and distorted motifs, were not unexpectedly the first recipients of that violence against monuments later called vandalism, and only four survived the 19th century: the Barrière d'Enfer, Barrière du Trône, Rotonde de la Villette and Rotonde de Monceau. Source: Grove Art Online; http://www.groveart.com/ (accessed 12/2/2007

Definition of bulky disease in early stage Hodgkin lymphoma in computed tomography era: prognostic significance of measurements in the coronal and transverse planes

Disease bulk is an important prognostic factor in early stage Hodgkin lymphoma, but its definition is unclear in the computed tomography-era. This retrospective analysis investigated the prognostic significance of bulky disease measured in transverse and coronal planes on computed tomography imaging. Early stage Hodgkin lymphoma patients (n=185) treated with chemotherapy with or without radiotherapy from 2000-2010 were included. The longest diameter of the largest lymph node mass was measured in transverse and coronal axes on pre-treatment imaging. The optimal cutoff for disease bulk was maximal diameter greater than 7 cm measured in either the transverse or coronal plane. Thirty patients with maximal transverse diameter ≤7 cm were found to have bulk in coronal axis. The 4-year overall survival was 96.5% (CI 93.3%, 100%) and 4-year relapse-free survival was 86.8% (CI 81.9%, 92.1%) for all patients. Relapse free survival at 4-years for bulky patients was 80.5% (CI 73%, 88.9%) compared to 94.4% (CI 89.1%, 100%) for non-bulky, Cox HR 4.21 (CI 1.43, 12.38), P = 0.004. In bulky patients, relapse free survival was not impacted in patients treated with chemoradiotherapy; however, was significantly inferior in patients treated with chemotherapy alone. In an independent validation cohort of 38 patients treated with chemotherapy alone, patients with bulky disease had an inferior relapse-free survival (at 4-years, 71.1% (CI 52.1%, 97%) versus 94.1% (CI 83.6%, 100%), Cox HR 5.27 (CI 0.62, 45.16), P = 0.09). Presence of bulky disease on multidimensional computed tomography imaging is a significant prognostic factor in early stage Hodgkin lymphoma. Coronal reformations may be included for routine Hodgkin lymphoma staging evaluation. In future, our definition of disease bulk may have utility in identifying patients who are most appropriate for chemotherapy-alone

Prognostic Value of FDG PET/CT before Allogeneic and Autologous Stem Cell Transplantation for Aggressive Lymphoma

PURPOSE: To determine the prognostic value of performing fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) before allogeneic and autologous stem cell transplantation (SCT) in patients with aggressive lymphoma. MATERIALS AND METHODS: A HIPAA-compliant retrospective review was performed under institutional review board waiver. Patients with aggressive lymphoma underwent allogeneic or autologous SCT between January 2005 and December 2010. FDG PET/CT was performed within the 3 months prior to transplantation. PET/CT images were evaluated for lesions with FDG avidity greater than that of the background liver. The relationship between pretransplantation PET and progression-free survival (PFS), disease-specific survival (DSS), and overall survival (OS) was assessed with Kaplan-Meier curves and a corresponding log-rank test for categorical variables and Cox regression for continuous variables. RESULTS: A total of 175 patients were identified, of whom 73 underwent FDG PET/CT before allogeneic SCT and 102 underwent FDG PET/CT before autologous SCT. Before allogeneic SCT, 23 of 73 patients (32%) had FDG-avid lesions, and before autologous SCT, 11 of 102 patients (11%) had FDG-avid lesions. For allogeneic SCT, the 2-year PFS estimate was 68% (95% confidence interval [CI]: 56%, 82%) in patients without FDG-avid lesions, but only 35% (95% CI: 20%, 61%) for patients with FDG-avid lesions (P = .014). For autologous SCT, the 2-year PFS was 72% (95% CI: 64%, 82%) in patients without FDG-avid lesions, but only 18% (95% CI: 5%, 64%) for patients with FDG-avid lesions (P < .0001). Similar differences were seen in OS and DSS. The risk for posttransplantation recurrence correlated with higher lesional maximum standardized uptake values: for PFS, P < .0001 to P = .01; for DSS, P < .0001 to P = .002; and for OS, P < .0001 to P = .015. CONCLUSION: Performing FDG PET/CT before SCT in patients with aggressive lymphoma has prognostic value. For patients with aggressive lymphomas, the presence of FDG-avid lesions at PET/CT performed before allogeneic and autologous SCT indicates a lower likelihood of SCT success. (©) RSNA, 201

Oral Microbiome in Nonsmoker Patients with Oral Cavity Squamous Cell Carcinoma, Defined by Metagenomic Shotgun Sequencing

Objectives: Smoking is the commonest cause of oral cavity squamous cell carcinoma (OC-SCC), but the etiology of OC-SCC in nonsmokers is unknown. Our primary goal was to use metagenomic shotgun sequencing (MSS) to define the taxonomic composition and functional potential of oral metagenome in nonsmokers with OC-SCC. Methods: We conducted a case&ndash;control study with 42 OC-SCC case and 45 control nonsmokers. MSS was performed on DNA extracted from mouthwash samples. Taxonomic analysis and pathway analysis were done using MetaPhlAn2 and HUMAnN2, respectively. Statistical difference was determined using the Mann&ndash;Whitney test controlling false discovery rate. Results: There was no significant difference in age, sex, race, or alcohol consumption between OC-SCC and control patients. There was a significant difference in beta diversity between OC-SCC and controls. At the phylum level, Bacteroidetes and Synergistetes were overly represented in OC-SCC while Actinobacteria and Firmicutes were overly represented in controls. At the genus level, Fusobacterium was overly represented in OC-SCC compared with controls, while Corynebacterium, Streptococcus, Actinomyces, Cryptobacterium, and Selenomonas were overly represented in controls. Bacterial pathway analysis identified overrepresentation in OC-SCC of pathways related to metabolism of flavin, biotin, thiamin, heme, sugars, fatty acids, peptidoglycans, and tRNA and overrepresentation of nucleotides and essential amino acids in controls. Conclusions: The oral microbiome in nonsmoker patients with OC-SCC is significantly different from that of nonsmoker control patients in taxonomic compositions and functional potentials. Our study&rsquo;s MSS findings matched with previous 16S-based methods in taxonomic differentiation but varied greatly in functional differentiation of microbiomes in OC-SCC and controls

Central nervous system involvement in T-cell lymphoma: A single center experience

BACKGROUND: We characterized the incidence of central nervous system (CNS) involvement, risk factors and outcome in a large single institution dataset of peripheral T cell lymphoma (PTCL). METHODS: Retrospective review of the PTCL database at Memorial Sloan Kettering Cancer Center. We identified 231 patients with any subtype of PTCL between 1994–2011 with a minimum 6 months of follow-up or an event defined as relapse or death. RESULTS: Histologies included peripheral T cell lymphoma – no not otherwise specified (PTCL-NOS) (31.6%), angioimmunoblastic (16.9%), anaplastic large cell lymphoma (ALCL), ALK- (12.1%), ALCL, ALK+ (6.1%), extranodal NK/T-cell lymphoma (7.4%), adult T-cell leukemia/lymphoma (ATLL) (7.4%), and transformed mycosis fungoides (8.7%). 17 patients had CNS disease (7%). Fifteen had CNS involvement with PTCL and two had diffuse large B cell lymphoma and glioblastoma. Median time to CNS involvement was 3.44 months (0.16 to 103.1). CNS prophylaxis was given to 24 patients (primarily intrathecal methotrexate). Rates of CNS involvement were not different in patients who received prophylaxis. Univariate analysis identified stage III-IV, bone marrow involvement, >1 extranodal site and ATLL as risk factors for CNS disease. On multivariate analysis, >1 extranodal site and international prognostic index (IPI) ≥ 3 were predictive for CNS involvement. The median survival of patients with CNS involvement was 2.63 months (0.10 to 75). CONCLUSIONS: Despite high relapse rates, PTCL, except ATLL, carries a low risk of CNS involvement. Prognosis with CNS involvement is poor and risk factors include: >1 extra nodal site and IPI ≥ 3

Prospective Study of 3′-Deoxy-3′- 18

PURPOSE: Current clinical and imaging tools remain suboptimal for early assessment of prognosis and treatment response in aggressive lymphomas. Positron emission tomography (PET) with (18)F-fluorothymidine (FLT) can be used to measure tumor cell proliferation and treatment response. In a prospective study in patients with advanced stage B-cell lymphoma we investigated the prognostic and predictive value of FLT PET in comparison to standard imaging with FDG PET and clinical outcome. PATIENTS AND METHODS: 65 patients were treated with an induction/consolidation regimen consisting of four cycles of R-CHOP-14 followed by 3 cycles of ICE. FLT PET was performed at baseline and at interim (iPET) after 1–2 cycles of therapy. FDG PET was performed at baseline, after cycle 4, and at the end of therapy. The relationship between PET findings, progression free survival (PFS) and overall survival (OS) was investigated. RESULTS: With a median follow-up of 51 months, PFS and OS were 71% and 86% respectively. FLT iPET, analyzed visually, using a 5-point score, or semi-quantitatively, using SUV and ΔSUV, predicted both PFS and OS (p<0.01 for all parameters). Residual FLT SUVmax on iPET was associated with an inferior PFS (HR: 1.26, p=0.001) and OS (HR: 1.27, p=0.002). Using FDG PET, findings in the end of treatment scan were better predictors of PFS and OS than findings on interim scan. Baseline PET imaging parameters, including SUV, proliferative or metabolic tumor volume, did not correlate with outcome. CONCLUSION: FLT PET after 1–2 cycles of chemotherapy predicts PFS and OS, and a negative FLT iPET may potentially help design risk-adapted therapies in patients with aggressive lymphomas. In contrast, the positive predictive value of FLT iPET remains too low to justify changes in patient management