MRI of diffuse large B-cell non-Hodgkin's lymphoma of the head and neck: comparison of Waldeyer's ring and sinonasal lymphoma.

To document the magnetic resonance imaging (MRI) features of diffuse large B-cell lymphoma (DLBCL) in Waldeyer's ring (WR) and the sinonasal (SN) region, and to identify any differences between lymphatic and extra-lymphatic DLBCLs, and predictors of disease beyond the neck. Primary, nodal, and multifocal sites on head and neck MRI were compared between 31 WR and 15 SN DLBCL, and between 27 patients with disease confined to the head and neck and 16 patients with disease beyond the neck, using logistic regression. Compared to SN, WR DLBCLs had significantly smaller primary tumour volumes (p = 0.009), less deep invasion (p = 0.001), and more nodal disease (p = 0.016). Tumour site (WR vs. SN) was an independent predictor of deep invasion (p = 0.007). Nodal and multifocal diseases were predictors of disease beyond the neck (p = 0.027 and 0.011, respectively). Lymphatic WR DLBCLs were less locally aggressive but had greater propensity to nodal spread than extra-lymphatic SN DLBCLs. Nodal and multifocal diseases predicted disease beyond the neck.

Prediction of outcome in cancer patients with febrile neutropenia: a prospective validation of the Multinational Association for Supportive Care in Cancer risk index in a Chinese population and comparison with the Talcott model and artificial neural network.

PURPOSE: We aimed to validate the Multinational Association for Supportive Care in Cancer (MASCC) risk index, and compare it with the Talcott model and artificial neural network (ANN) in predicting the outcome of febrile neutropenia in a Chinese population. METHODS: We prospectively enrolled adult cancer patients who developed febrile neutropenia after chemotherapy and risk classified them according to MASCC score and Talcott model. ANN models were constructed and temporally validated in prospectively collected cohorts. RESULTS: From October 2005 to February 2008, 227 consecutive patients were enrolled. Serious medical complications occurred in 22% of patients and 4% died. The positive predictive value of low risk prediction was 86% (95% CI = 81-90%) for MASCC score ≥ 21, 84% (79-89%) for Talcott model, and 85% (78-93%) for the best ANN model. The sensitivity, specificity, negative predictive value, and misclassification rate were 81%, 60%, 52%, and 24%, respectively, for MASCC score ≥ 21; and 50%, 72%, 33%, and 44%, respectively, for Talcott model; and 84%, 60%, 58%, and 22%, respectively, for ANN model. The area under the receiver-operating characteristic curve was 0.808 (95% CI = 0.717-0.899) for MASCC, 0.573 (0.455-0.691) for Talcott, and 0.737 (0.633-0.841) for ANN model. In the low risk group identified by MASCC score ≥ 21 (70% of all patients), 12.5% developed complications and 1.9% died, compared with 43.3%, and 9.0%, respectively, in the high risk group (p < 0.0001). CONCLUSIONS: The MASCC risk index is prospectively validated in a Chinese population. It demonstrates a better overall performance than the Talcott model and is equivalent to ANN model.

Clinical predictors of response to cetuximab-chemotherapy in metastatic colorectal cancer.

OBJECTIVE: To identify clinical markers to predict which patients with advanced colorectal cancers are likely to benefit from cetuximab-chemotherapy. DESIGN: Retrospective review. SETTING: Oncology unit in a university teaching hospital in Hong Kong. PATIENTS: A total of 102 patients with metastatic colorectal cancer treated with cetuximab-chemotherapy. MAIN OUTCOME MEASURES: Correlation of multiple potential clinical predictive factors with tumour response to cetuximab-chemotherapy. RESULTS: The objective response rates to cetuximab plus chemotherapy were 53% in patients receiving first-line treatment and 17% in previously treated patients. The univariate analysis indicated that fewer prior lines of chemotherapy (odds ratio=0.36; 95% confidence interval, 0.21-0.63; P<0.01) and development of cetuximab-related grade 3 rash (5.52; 1.62-18.76; P<0.01) were associated with significantly higher response rates. Multivariate analysis confirmed the independent predictive value of the number of prior chemotherapy regimens (odds ratio=0.37; 95% confidence interval, 0.20-0.69; P<0.01) and grade 3 rash (4.65; 1.21-19.29; P=0.03). CONCLUSIONS: In this cohort of Chinese patients with advanced colorectal cancer, the presence of grade 3 rash and the number of prior chemotherapy regimens were independent predictors of response to cetuximab-chemotherapy. The utility of these clinical markers in clinical practice should be further evaluated together with established biomarkers.

Hepatitis B virus reactivation in lymphoma patients with prior resolved hepatitis B undergoing anticancer therapy with or without rituximab.

PURPOSE: Reactivation of hepatitis B virus (HBV) infection is a well-recognized complication in cancer patients with chronic HBV (hepatitis B surface antigen [HBsAg] positive) undergoing cytotoxic chemotherapy. In patients who have resolved HBV (HBsAg negative and antibody to hepatitis B core antigen [anti-HBc] +/- antibody to hepatitis B surface antigen [anti-HBs] positive), such incidence has been much less common until recent use of rituximab. In this study on HBsAg-negative/anti-HBc-positive lymphoma patients, the objectives were to determine the HBV reactivation rate in patients treated with rituximab-containing chemotherapy and to compare it with the rate in patients treated without rituximab. PATIENTS AND METHODS: Between January 2003 and December 2006, all patients diagnosed with CD20(+) diffuse large B-cell lymphoma (DLBCL) had HBsAg determined before anticancer therapy. They were treated with either cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) alone or rituximab plus CHOP (R-CHOP). HBsAg-negative patients had anti-HBc determined; serum was stored for anti-HBs and HBV DNA. All patients were observed for HBV reactivation, which was defined as detectable HBV DNA with ALT elevation during and for 6 months after anticancer therapy. RESULTS: Among 104 CD20(+) DLBCL patients, 80 were HBsAg negative. Of the latter, 46 patients (44.2%) were HBsAg negative/anti-HBc positive; 25 of these patients were treated with CHOP, and none had HBV reactivation. In contrast, among the 21 patients treated with R-CHOP, five developed HBV reactivation, including one patient who died of hepatic failure (P = .0148). Exploratory analysis identified male sex, absence of anti-HBs, and use of rituximab to be predictive of HBV reactivation. CONCLUSION: Among HBsAg-negative/anti-HBc-positive DLBCL patients treated with R-CHOP, 25% developed HBV reactivation. Close monitoring until at least 6 months after anticancer therapy is required, with an alternative approach of prophylactic antiviral therapy to prevent this potentially fatal condition.

Small cell neuroendocrine carcinoma of the ethmoid sinuses presenting with generalized seizure and syndrome of inappropriate antidiuretic hormone secretion: a case report and review of literature.

Small cell neuroendocrine carcinoma of the paranasal sinuses is extremely rare. We present a case of small cell neuroendocrine carcinoma of the ethmoid sinuses associated with syndrome of inappropriate antidiuretic hormone secretion that resolved after chemotherapy, followed by a review of the literature.

Malignant cervical lymphadenopathy: diagnostic accuracy of diffusion-weighted MR imaging.

PURPOSE: To prospectively determine the diagnostic accuracy of diffusion-weighted magnetic resonance (MR) imaging for discrimination of malignant neck nodes due to lymphoma, squamous cell carcinoma (SCC), and undifferentiated nasopharyngeal carcinoma (NPC), with histologic findings and imaging criteria as reference standards. MATERIALS AND METHODS: Ethics committee approval and informed consent were obtained. Patients with malignant lymphadenopathy underwent 1.5-T diffusion-weighted MR imaging. A region of interest was drawn around the malignant node on apparent diffusion coefficient (ADC) maps; ADC values were compared (Kruskal-Wallis test). Receiver operating characteristic analysis was employed to investigate whether ADC values could aid in discrimination among malignancies. RESULTS: Forty-three patients (34 men, nine women; mean age, 54 years) with 43 nodes underwent imaging. Mean ADC values for lymphoma (n = 8), NPC (n = 17), and SCC (n = 18) were (0.664 +/- 0.071 [standard deviation]) x 10(-3) mm(2)/sec, (0.802 +/- 0.128) x 10(-3) mm(2)/sec, and (1.057 +/- 0.169) x 10(-3) mm(2)/sec, respectively, with significant differences between SCC and lymphoma or NPC (P < .001) and between NPC and lymphoma (P = .04). To optimize sensitivity and specificity with equal weighting, ADC threshold values for distinguishing between SCC and NPC, between SCC and lymphoma, and between NPC and lymphoma were 0.894 x 10(-3) mm(2)/sec, 0.824 x 10(-3) mm(2)/sec, and 0.694 x 10(-3) mm(2)/sec, respectively. To produce a 100% specificity while sensitivity is maximized, the following ADC threshold values were obtained for prediction of differentiation between malignancies: (a) SCC versus lymphoma, greater than 0.824 x 10(-3) mm(2)/sec (sensitivity, 94%), and lymphoma versus SCC, less than 0.767 x 10(-3) mm(2)/sec (sensitivity 88%); (b) NPC versus SCC, less than 0.764 x 10(-3) mm(2)/sec (sensitivity, 47%), and SCC versus NPC, greater than 1.093 x 10(-3) mm(2)/sec (sensitivity, 39%); (c) NPC versus lymphoma, greater than 0.788 x 10(-3) mm(2)/sec (sensitivity, 53%), and lymphoma versus NPC, no suitable threshold value. CONCLUSION: Diffusion-weighted MR imaging shows significant differences among malignant nodes of SCC, lymphoma, and NPC. ADC threshold values can help distinguish SCC from lymphoma. SUPPLEMENTAL MATERIAL: http://radiology.rsnajnls.org/cgi/content/full/2451061804/DC1.

AKT plays a role in the survival of the tumor cells of extranodal NK/T-cell lymphoma, nasal type.

Phosphorylated AKT has been detected in extranodal NK/T-cell lymphoma, nasal type (ENTL). Either interleukin-2 (IL-2) or interleukin-15 (IL-15) could prevent AKT dephosphorylation and apoptosis in the NK-92 cell line model. IL-15, but not IL-2, was preferentially elevated in patients' serum. AKT and IL-15 may be important in ENTL tumor survival.

Lamivudine for the prevention of hepatitis B virus reactivation in hepatitis B s-antigen seropositive cancer patients undergoing cytotoxic chemotherapy.

PURPOSE: For cancer patients receiving cytotoxic chemotherapy, hepatitis B virus (HBV) reactivation is a well described complication resulting in varying degrees of liver damage. The objectives of this study were to assess the efficacy of the antiviral agent lamivudine in reducing the incidence of HBV reactivation and diminishing morbidity and mortality of cancer patients with chronic HBV infection during chemotherapy. PATIENTS AND METHODS: Two groups were compared in this nonrandomized study. The prophylactic lamivudine group consisted of 65 patients in a phase II study who were treated with lamivudine before and until 8 weeks after discontinuing chemotherapy. The historical controls consisted of 193 consecutive patients who underwent chemotherapy without prophylactic lamivudine. Significant prognosticators for the development of HBV reactivation were determined based on data from the controls. Potential confounding factors were identified between the two groups. The outcomes were compared. RESULTS: In the controls, lymphoma and anthracycline usage were factors identified to be associated with reactivation. The two groups were comparable in most baseline characteristics, although in the prophylactic lamivudine group, there were significantly more patients with lymphoma and receiving anthracyclines. In the prophylactic lamivudine group, there was significantly less HBV reactivation (4.6% v 24.4% in the controls; P <.001), fewer incidences of hepatitis (17.5% v 44.6%; P <.0001) that were less severe (4.8% v 18.7%; P =.0005), and less disruption of chemotherapy (15.4% v 34.6%; P =.0029). The reduction in overall mortality was not statistically different. CONCLUSION: Prophylactic lamivudine significantly reduced the incidence of HBV reactivation and the overall morbidity of cancer patients undergoing chemotherapy.

Non-Hodgkin lymphoma of the larynx: CT and MR imaging findings.

BACKGROUND AND PURPOSE: Non-Hodgkin lymphoma (NHL) of the larynx is a rare tumor. The aim of this study was to report the CT and MR features of laryngeal NHL in four patients to determine if there are any features that might be helpful to distinguish NHL from other laryngeal tumors. METHODS: The CT and MR images of four patients with laryngeal NHL were retrospectively reviewed for tumor volume and distribution, appearance, local invasion, and lymphadenopathy. RESULTS: Tumor volume ranged from 4 to 45 mL(3). Tumor was based in the submucosal (2/4 [50%]), mucosal (1/4 [25%]), or both regions (1/4 [25%]) and was centered in the supraglottis (4/4 [100%]) but also involved the glottis (4/4 [100%]) and subglottis (2/4 [50%]). Laryngeal tumor involved the aryepiglottic folds (4/4 [100%)]), ventricles and false cords (4/4 [100%]), epiglottis (3/4 [75%]), paraglottis (3/4 [75%]), true cords (4/4 [100%]), anterior commissure (4/4 [100%]), and laryngeal cartilage (1/4 [25%]). The tumor extended into the hypopharynx (4/4 [100%]), strap muscles (1/4 [25%]), prevertebral muscles (1/4 [25%]), tongue base (1/4 [25%]), and walls of the oropharynx (1/4 [25%]) and nasopharynx (1/4 [25%]). Bilateral cervical lymphadenopathy with extracapsular tumor spread was present in one patient. CONCLUSION: Laryngeal NHL is a tumor that usually has a large submucosal component centered in the surpaglottis. The tumor extends into the glottis, with less frequent spread to the subglottis, laryngeal cartilage, and strap muscles. Laryngeal NHL also involves the hypopharynx, with large tumors extending superiorly into the tongue base, oropharynx, and nasopharynx. A laryngeal tumor with a large supraglottic submucosal component should alert the ragiologist to the possibility of NHL.

Molecular characterization of circulating EBV DNA in the plasma of nasopharyngeal carcinoma and lymphoma patients.

Despite the increasing clinical applications of circulating EBV DNA analysis as a tumor marker, the molecular nature of these EBV DNA molecules remains unclear. We subjected plasma/serum samples of nasopharyngeal carcinoma and lymphoma patients to DNase digestion and ultracentrifugation and showed that circulating EBV DNA molecules are "naked" DNA fragments instead of being contained inside virions. We further showed that these EBV DNA fragments were relatively short, and 87% of them were shorter than 181 bp. These results provide fundamental information that may improve our understanding of the release of tumor-derived nucleic acids into the blood of cancer patients.

Diagnostic and prognostic implications of circulating cell-free Epstein-Barr virus DNA in natural killer/T-cell lymphoma.

PURPOSE: Natural killer/T-cell (NK/T-cell) lymphoma is a highly aggressive tumor for which no serological tumor marker has yet been established to be useful clinically. We investigated the potential of circulating EBV DNA as a tumor marker for this malignancy. EXPERIMENTAL DESIGN: A real-time quantitative PCR assay was used to measure circulating EBV DNA. RESULTS: Plasma EBV DNA levels were measured in 18 patients with NK/T-cell lymphoma at presentation and during therapy. Plasma EBV DNA was detected in 17 of the 18 patients (median, 659 copies/ml; interquartile range, 181-17,042 copies/ml) but in none of 35 control subjects (p < 0.0001). Serial measurements of plasma EBV DNA levels during therapy showed a close correlation between clinical response and changes in plasma EBV DNA levels. Clinically responding patients showed a fall of plasma EBV DNA levels to low or undetectable levels, whereas those who failed therapy showed a rapid increase in plasma EBV DNA levels. Most importantly, patients with high baseline plasma EBV DNA levels (> or = 600 copies/ml) demonstrated a significantly inferior survival than those with low baseline plasma EBV DNA (< 600 copies/ml; 21% versus 78%; P = 0.024). CONCLUSIONS: Plasma EBV DNA, as measured by real-time quantitative PCR, is a useful tumor marker for diagnosis, disease monitoring, and prediction of outcome in patients with NK/T-cell lymphoma.