Level Ib CTV delineation in nasopharyngeal carcinoma based on lymph node distribution and topographic anatomy.

BACKGROUND AND PURPOSE: To analyze the distribution pattern of lymph nodes (LNs) metastasis of level Ib in nasopharyngeal cancer (NPC) and propose shrinkage of clinical target volume (CTV) boundaries to avoid unnecessary radiation for some space with very low-risk of involvement. MATERIALS AND METHODS: Pretreatment images of pathologically proven NPC patients were reviewed and those with positive level Ib LN metastasis was enrolled. The geometric center of each level Ib LN in the neck was marked on a template CT. The spatial relationship of nodes with key structures in level Ib was analyzed. Modified level Ib CTV according to the 2013 International CTV consensus was proposed based on the LN distribution pattern. A PlanIQ Feasibility DVH module was implemented to evaluate the feasibility analysis of the best possible sparing of organs at risk (OAR) with modified Ib CTV. RESULTS: A total of 1518 NPC patients were reviewed and 54 with positive level Ib nodes were enrolled. Four sub-level anatomical regions were defined within the gross area of level Ib. Of 106 positive nodes identified, none, one, 88, and 17 were found in the intraglandular (IG), medial mandibular (MM), supra perivascular (SP), and infra perivascular (IP) sub-level, respectively. This study proposes sparing the IG and MM sub-level and including the area within a specified distance from the submandibular gland (11 mm for SP, 17 mm for IP) for CTV coverage. Compared with planning based on CTV-consensus, planning based on CTV-proposed results in a significantly reduced CTV volume, and mean dose (Dmean) of both the ipsilateral SMG and bilateral SLG. CONCLUSIONS: Based on detailed analysis of the relationship between positive node distribution and several important anatomical structures, modified level Ib CTV for prophylactic irradiation was proposed to reduce the dose of OAR irradiation.

Effects of lysophosphatidic acid and its receptors LPA⠓ on radiation pneumonitis.

Radiation pneumonitis (RP) is a serious complication of radiation therapy for thoracic tumors. Lysophosphatidic acid (LPA) and its receptors LPA⅓ were reported to participate in the processes of inflammation. We tested the hypothesis that LPA and its receptors LPA⅓, take part in the pathogenesis of RP. In our study, irradiation increased LPA levels in the lung and expression of LPA⅓. To further determine the role of LPA⅓, we performed pharmacological knockout of LPA⅓ by a specific antagonist, VPC-12249. On day 60 post-irradiation, RP was significantly alleviated in a dose-dependent manner in mice treated with VPC-12249, as shown by H&E staining, malondialdehyde (MDA, an indicator of oxidative damage) assay in lung, and concentrations of proinflammatory and profibrotic cytokines in plasma, including IL-1ß, TNF-α, and TGF-ß1. Additionally, VPC-12249 administration decreased the phosphorylation of IκB-α (the initial event that activates the NF-κB signal way), and expression of TGF-ß1, CTGF, and α-SMA mRNA. Our findings suggest that LPA and LPA⅓ may play a pivotal role in RP, and LPA-LPA⅓ may serve as novel therapeutic targets for the treatment of RP.