microRNA expression pattern as an ancillary prognostic signature for radiotherapy.

BACKGROUND: In view of the limited knowledge of plasma biomarkers relating to cancer resistance to radiotherapy, we have set up screening, training and testing stages to investigate the microRNAs (miRNAs) expression profile in plasma to predict between the poor responsive and responsive groups after 6 months of radiotherapy. METHODS: Plasma was collected prior to and after radiotherapy, and the microRNA profiles were analyzed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) arrays. Candidate miRNAs were validated by single qRT-PCR assays from the training and testing set. The classifier for ancillary prognosis was developed by multiple logistic regression analysis to correlate the ratios of miRNAs expression levels with clinical data. RESULTS: We revealed that eight miRNAs expressions had significant changes after radiotherapy and the expression levels of miR-374a-5p, miR-342-5p and miR-519d-3p showed significant differences between the responsive and poor responsive groups in the pre-radiotherapy samples. The Kaplan-Meier curve analysis also showed that low miR-342-5p and miR-519d-3p expressions were associated with worse prognosis. Our results revealed two miRNA classifiers from the pre- and post-radiotherapy samples to predict radiotherapy response with area under curve values of 0.8923 and 0.9405. CONCLUSIONS: The expression levels of miR-374a-5p, miR-342-5p and miR-519d-3p in plasma are associated with radiotherapy responses. Two miRNA classifiers could be developed as a potential non-invasive ancillary tool for predicting patient response to radiotherapy.

EGFR mutations are associated with favorable intracranial response and progression-free survival following brain irradiation in non-small cell lung cancer patients with brain metastases.

BACKGROUND: The presence of epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) is associated with increased radiosensitivity in vitro. However, the results from clinical studies regarding the radiosensitivity in NSCLC with mutant EGFR are inconclusive. We retrospectively analyzed our NSCLC patients who had been regularly followed up by imaging studies after irradiation for brain metastases, and investigated the impact of EGFR mutations on radiotherapy (RT). METHODS: Forty-three patients with brain metastases treated with RT, together with EGFR mutation status, demographics, smoking history, performance status, recursive partitioning analysis (RPA) class, tumor characteristics, and treatment modalities, were included. Radiological images were taken at 1 to 3 months after RT, and 3 to 6 months thereafter. Radiographic response was evaluated by RECIST criteria version 1.1 according to the intracranial images before and after RT. Log-rank test and Cox regression model were used to correlate EGFR mutation status and other clinical features with intracranial radiological progression-free survival (RPFS) and overall survival (OS). RESULTS: The median follow-up duration was 15 months. Patients with mutant EGFR had higher response rates to brain RT than those with wild-type EGFR (80% vs. 46%; p = 0.037). Logistic regression analysis showed that EGFR mutation status is the only predictor for treatment response (p = 0.032). The median intracranial RPFS was 18 months (95% CI = 8.33-27.68 months). In Cox regression analysis, mutant EGFR (p = 0.025) and lower RPA class (p = 0.026) were associated with longer intracranial RPFS. EGFR mutation status (p = 0.061) and performance status (p = 0.076) had a trend to predict OS. CONCLUSIONS: Mutant EGFR in NSCLC patients is an independent prognostic factor for better treatment response and longer intracranial RPFS following RT for brain metastases.

Effect of regression of enlarged neck lymph nodes on radiation doses received by parotid glands during intensity-modulated radiotherapy for head and neck cancer.

OBJECTIVES: The regression of enlarged neck lymph nodes during intensity-modulated radiotherapy (IMRT) may increase actual radiation doses to the parotid glands of patients with head-and-neck cancer. We investigated the changes in the lymph nodes volume during IMRT and the effect of these changes to the parotid gland doses. METHODS: Ten head and neck cancer patients with enlarged neck lymph nodes were enrolled in this study. Computed tomography (CT) imaging was repeated to evaluate the change in lymph nodes volume after initial 45 Gy, and the second part of IMRT (21 Gy) was then replanned to reflect the change of nodal tumor volume. The dosimetric benefit of parotid sparing with replanning was compared with that of no replanning. RESULTS: The enlarged neck lymph nodes in all patients pushed the parotid glands outward in pretreatment CT images. After 45 Gy of IMRT, nodal regression caused the parotid glands to shift inward into the high-dose area. When compared with those without replanning, we found modification of IMRT plan after 45 Gy significantly reduced radiation dose to parotid glands (mean reduction of 2.95 +/- 1.10 Gy to the left and 3.23 +/- 1.37 Gy to the right, respectively; P < 0.001). CONCLUSIONS: Excessive parotid gland doses secondary to the regression of enlarged neck nodes could be mitigated by replanning after 45 Gy. However, recontouring of large lymph nodes that regress during therapy has a risk of under-dosing extracapsular extension of lymph node metastases. Therefore, recontouring should be done with extreme caution.