Faculty Bibliography

PURPOSE: To evaluate the impact of radiation therapy (RT) on the long-term outcomes and pattern of failure for T1-2 glottic cancer. MATERIALS AND METHODS: This is a single-institution, retrospective study. From January (1997 to 2010), 253 patients with early glottic cancer underwent RT by 2-dimensional or 3-dimensional RT with Co or linear accelerator. Appropriate daily bolus was applied with linear accelerator-based RT to avoid under dosage of the anterior commissure. RESULTS: A total of 253 patients with T1-T2 glottic cancer were treated with definitive RT. The median age was 65 and males made up 87% of the population. T1 was 77% of the population. The median dose and fraction size were 63 and 2.25 Gy, respectively. After a median follow-up of 83 months, the locoregional control (LRC) for the whole cohort was 98%. Specifically, LRCs for T1 (195 patients) and T2 (58 patients) were 99.5% and 91%, respectively. Kaplan-Meier curve shows the 5-year cause-specific survival to be 100%. CONCLUSIONS: Single-modality RT provides an excellent and effective treatment for T1-T2 glottic cancer with remarkable functional preservation and 5-year LRC of 98% with negligible long-term toxicity.

In this Review, we summarise recent published work on the use of intraoperative radiotherapy to treat common tumour sites in the primary or recurrent setting. Techniques, radiobiology, and the physics of intraoperative radiotherapy are also explored. Disease sites discussed in this Review include head and neck cancer, breast cancer, sarcoma, gastrointestinal cancer, genitourinary cancer, gynaecological cancer, thoracic cancer, and palliative applications.

OBJECTIVES: Radiation induced cranial nerve palsy (RICNP) involving the lower cranial nerves (CNs) is a serious complication of head and neck radiotherapy (RT). Recommendations for delineating the lower CNs on RT planning studies do not exist. The aim of the current study is to develop a standardized methodology for contouring CNs IX-XII, which would help in establishing RT limiting doses for organs at risk (OAR). METHODS: Using anatomic texts, radiologic data, and guidance from experts in head and neck anatomy, we developed step-by-step instructions for delineating CNs IX-XII on computed tomography (CT) imaging. These structures were then contoured on five consecutive patients who underwent definitive RT for locally-advanced head and neck cancer (LAHNC). RT doses delivered to the lower CNs were calculated. RESULTS: We successfully developed a contouring atlas for CNs IX-XII. The median total dose to the planning target volume (PTV) was 70Gy (range: 66-70Gy). The median CN (IX-XI) and (XII) volumes were 10c.c (range: 8-12c.c) and 8c.c (range: 7-10c.c), respectively. The median V50, V60, V66, and V70 of the CN (IX-XI) and (XII) volumes were (85, 77, 71, 65) and (88, 80, 74, 64) respectively. The median maximal dose to the CN (IX-XI) and (XII) were 72Gy (range: 66-77) and 71Gy (range: 64-78), respectively. CONCLUSIONS: We have generated simple instructions for delineating the lower CNs on RT planning imaging. Further analyses to explore the relationship between lower CN dosing and the risk of RICNP are recommended in order to establish limiting doses for these OARs.

Toxoplasma gondii transmission between intermediate hosts is dependent on the ingestion of walled cysts formed during the chronic phase of infection. Immediately following consumption, the parasite must ensure survival of the host by preventing adverse inflammatory responses and/or by limiting its own replication. Since the Toxoplasma secreted effectors rhoptry 16 kinase (ROP16) and dense granule 15 (GRA15) activate the JAK-STAT3/6 and NF-kappaB signaling pathways, respectively, we explored whether a particular combination of these effectors impacted intestinal inflammation and parasite survival in vivo. Here we report that expression of the STAT-activating version of ROP16 in the type II strain (strain II+ROP16I) promotes host resistance to oral infection only in the context of endogenous GRA15 expression. Protection was characterized by a lower intestinal parasite burden and dampened inflammation. Host resistance to the II+ROP16I strain occurred independently of STAT6 and the T cell coinhibitory receptors B7-DC and B7-H1, two receptors that are upregulated by ROP16. In addition, coexpression of ROP16 and GRA15 enhanced parasite susceptibility within tumor necrosis factor alpha/gamma interferon-stimulated macrophages in a STAT3/6-independent manner. Transcriptional profiling of infected STAT3- and STAT6-deficient macrophages and parasitized Peyer's patches from mice orally challenged with strain II+ROP16I suggested that ROP16 activated STAT5 to modulate host gene expression. Consistent with this supposition, the ROP16 kinase induced the sustained phosphorylation and nuclear localization of STAT5 in Toxoplasma-infected cells. In summary, only the combined expression of both GRA15 and ROP16 promoted host resistance to acute oral infection, and Toxoplasma may possibly target the STAT5 signaling pathway to generate protective immunity in the gut.

OBJECTIVES/HYPOTHESIS: To report the long-term outcomes of radiation therapy (RT), and the impact of fractionation size and RT duration on HIV patients with Benign Lymphoepithelial Cysts (BLEC) of the parotid glands. METHODS: From January 2000 to 2011, 30 patients were eligible for our single institution retrospective study. Both parotids were treated with 24 Gy via RT. The median age at RT, HIV diagnosis, and duration of HIV seropositive was 45 years (28-64), 38 years (23-53), and 11 years (6-35), respectively. Patients were stratified into two groups. Group A and B received 2Gyx12 and 1.5Gyx16, respectively. RESULTS: After a median follow-up of 66 months (12-141), the overall response (OvR) was 93% of the patients. Specifically, complete response (CR) and partial response (PR) were 80% and 13%, respectively. In group A, 100% had CR. Treatment failure was 7% and all were in group B, which was mainly due to poor compliance. A Chi-square test showed significant relationship between OvR and RT duration (P <0.001), and a positive trend between CR and fraction size of 2 Gy (P = 0.053). All acute toxicities were grade