Secondary cancer risk from modern external-beam radiotherapy of prostate cancer patients: Impact of fractionation and dose distribution.

Modern radiotherapy (RT) uses altered fractionation, long beam-on time and image-guided procedure. This study aimed to compare secondary cancer risk (SCR) associated with primary field, scatter/leakage radiations and image-guided procedure in prostate treatment using intensity-modulated RT (IMRT), CyberKnife stereotactic body RT (CK-SBRT) in relative to 3-dimensional conformal RT (3D-CRT). Prostate plans were generated for 3D-CRT, IMRT (39 fractions of 2 Gy), and CK-SBRT (five fractions of 7.25 Gy). Excess absolute risk (EAR) was calculated for organs in the primary field using Schneider's mechanistic model and concept of organ equivalent dose (OED) to account for dose inhomogeneity. Doses from image-guided procedure and scatter/leakage radiations were determined by phantom measurements. The results showed that hypofractionation relative to conventional fractionation yielded lower SCR for organs in primary field (p ≤ 0.0001). SCR was further modulated by dose-volume distribution. For organs near the field edge, like the rectum and pelvic bone, CK-SBRT plan rendered better risk profiles than IMRT and 3D-CRT because of the absence of volume peak in high dose region (relative risk [RR]: 0.65, 0.22, respectively, p ≤ 0.0004). CK-SBRT and IMRT generated more scatter/leakage and imaging doses than 3D-CRT (p ≤ 0.0002). But primary field was the major contributor to SCR. EAR estimates (risk contributions, primary field: scatter/leakage radiations: imaging procedure) were 7.1 excess cases per 104 person-year (PY; 3.64:2.25:1) for CK-SBRT, 9.93 (7.32:2.33:1) for IMRT and 8.24 (15.99:2.35:1) for 3D-CRT (p ≤ 0.0002). We conclude that modern RT added more but small SCR from scatter/leakage and imaging doses. The primary field is a major contributor of risk which can be mitigated by the use of hypofractionation.

MALAT1 Decreases the Sensitivity of Head and Neck Squamous Cell Carcinoma Cells to Radiation and Cisplatin.

BACKGROUND/AIM: Two-thirds of head and neck squamous cell carcinoma (HNSCC) patients present with locally advanced (LA) stages and have a poor survival rate. The aim of this study was to investigate the roles of the long non-coding RNAs MALAT1 on radiation and cisplatin sensitivity of HNSCC cells. MATERIALS AND METHODS: Clonogenic, cell viability, and apoptosis assays were performed in cells following MALAT1 knockdown using CRISPR/Cas9 system. RESULTS: MALAT1 was overexpressed in HNSCC cell lines as compared to a non-tumorigenic cell line. The number of colonies formed after radiation was significantly reduced in MALAT1 knockdown cells. The IC50 value of cisplatin in MALAT1 knockdown cells was lower than that of the control cells. MALAT1 knockdown resulted in cell cycle arrest at G2/M phase, DNA damage and apoptotic cell death. CONCLUSION: MALAT1 knockdown enhanced the sensitivity of HNSCC cells to radiation and cisplatin partly through the induction of G2/M cell cycle arrest resulting in DNA damage and apoptosis.