Faculty Bibliography

PURPOSE: Aim of this study was to evaluate the impact of computed tomography (CT)-based simulation and planning on early glottic cancer outcomes and toxicity. METHODS: This is a single-institution retrospective study of 253 patients with T1-2 glottic cancer who underwent radiation therapy (RT) from January 1998-2010. Group A (80%) underwent 2-dimensional RT (2DRT) and group B (20%) 3-dimensional RT (3DRT). 76% of patients in group A and 84% in group B had T1 cancer. The median dose and fraction size were 63 Gy and 2.25 Gy, respectively. RESULTS: With a median follow-up of 83, 93, and 30 months for the whole cohort, group A and B, respectively, the loco-regional control (LRC) was 97.6%. The rate of LRC for T1 disease was 99.5% and for T2 disease 91%. According to the RT modality, rates of LRC were 99.4 and 100% in groups A and B for T1, and 89.8 and 100% for T2. Long-term toxicity was negligible in both groups. Kaplan-Meier Curve showed the 5-year cause-specific survival to be 100%. Chi-square and multivariate analysis tests showed a significant relationship between CT simulation (3DRT) and LRC (p < 0.0001). CONCLUSION: CT-based simulation and planning provided better LRC and less acute side effects compared to 2DRT.

BACKGROUND: Patients with small, low-/intermediate-risk parotid cancers, treated with surgery, and who have the single prognostic factor of close and/or positive margins, constitute an unusual subset. This study evaluates local control and morbidity associated with postoperative radiation therapy for low/intermediate grade parotid cancer in these patients. METHODS: Between 1999 and 2006, 17 patients underwent postoperative radiation therapy at Beth Israel Medical Center for acinic cell carcinoma or low-intermediate-grade mucoepidermoid carcinoma of the parotid with close/positive margins. Pathology, treatment, and follow-up data were retrospectively analyzed for morbidity and local control. Two- and 5-year estimates of survival outcomes were performed followed by an analysis of complications. RESULTS: There were no local failures and no significant long-term complications. CONCLUSIONS: Patients with small, low-risk cancer of the parotid gland have excellent local control and low treatment-related morbidity when receiving postoperative radiation therapy for positive or close margins of resection.

BACKGROUND: We aimed to improve the outcomes for locoregionally advanced nasopharyngeal carcinoma by testing the feasibility and safety of the addition of bevacizumab to chemoradiotherapy. METHODS: We enrolled patients older than 18 years with stage IIB-IVB nasopharyngeal carcinoma from 19 centres in North America and Hong Kong. Treatment consisted of three cycles of bevacizumab (15 mg/kg) and cisplatin (100 mg/m(2)) both given on days 1, 22, and 43 of radiation (70 Gy) with intensity-modulated radiation therapy delivered over 33 days on a daily basis, Monday through Friday. Patients then received three cycles of bevacizumab (15 mg/kg) and cisplatin (80 mg/m(2)), both given on days 64, 85, and 106 after radiation, and three cycles of fluorouracil (1000 mg/m(2) per day), given on days 64-67, 85-88, and 106-109 after radiation. The primary endpoint was the occurrence of treatment-related grade 4 haemorrhage or any grade 5 adverse event in the first year. Analyses were done with all eligible patients who started protocol treatment. The trial is registered at ClinicalTrials.gov, number NCT00408694. FINDINGS: From Dec 13, 2006, to Feb 5, 2009, we enrolled 46 patients, of whom 44 were eligible for analysis. We recorded no grade 3-4 haemorrhages or grade 5 adverse events; nine patients (20%) had a treatment-related grade 1-2 haemorrhage. Nine patients had one or more grade 4 blood or bone marrow-related complication (grade 4 leucopenia was noted in six patients, grade 4 lymphopenia in five, grade 4 neutrophils in five, and grade 4 anaemia in one). One patient had two grade 4 infections with grade 3-4 neutrophils. One patient reported grade 4 tinnitus, one patient reported grade 4 thrombosis, one reported grade 4 radiation mucositis, and two reported grade 4 pharyngolaryngeal pain. With a median follow-up of 2.5 years (IQR 2.1-2.9), the estimated 2 year locoregional progression-free interval was 83.7% (95% CI 72.6-94.9), the 2 year distant metastasis-free interval was 90.8% (82.2-99.5), the 2 year progression-free survival was 74.7% (61.8-87.6), and 2 year overall survival was 90.9% (82.3-99.4). INTERPRETATION: The addition of bevacizumab to standard chemoradiation treatment for patients with nasopharyngeal carcinoma is feasible, and might delay the progression of subclinical distant disease. FUNDING: National Cancer Institute, USA.

European and North American strains of the parasite Toxoplasma gondii belong to three distinct clonal lineages, type I, type II, and type III, which differ in virulence. Understanding the basis of Toxoplasma strain differences and how secreted effectors work to achieve chronic infection is a major goal of current research. Here we show that type I and III infected macrophages, a cell type required for host immunity to Toxoplasma, are alternatively activated, while type II infected macrophages are classically activated. The Toxoplasma rhoptry kinase ROP16, which activates STAT6, is responsible for alternative activation. The Toxoplasma dense granule protein GRA15, which activates NF-kappaB, promotes classical activation by type II parasites. These effectors antagonistically regulate many of the same genes, and mice infected with type II parasites expressing type I ROP16 are protected against Toxoplasma-induced ileitis. Thus, polymorphisms in determinants that modulate macrophage activation influence the ability of Toxoplasma to establish a chronic infection.