Design of functionalized magnetic silica multi-core composite nanoparticles for synergistic magnetic hyperthermia/radiotherapy in cancer cells.

Nanomaterials in particular the magnetic nanoparticles (MNPs) offer tremendous potential for cancer treatment due to their unique intrinsic properties. Combining materials with a variety of functional groups, and forming a multifunctional nanosystem to overcome the limitations of monotherapy for cancer treatment has always been a research focus with notable difficulties. Considering the many challenges faced by radiotherapy and hyperthermia, in this study, we designed a rational strategy for magnetic hyperthermia using Fe3O4@SiO2@Sec2@FA nanoparticles as a novel nano-radiosensitizer to simultaneously enhance the therapeutic effects of radiotherapy in the future. Fe3O4@SiO2 core-shell structured nanoparticles were synthesized with an appropriate silica layer thickness to maintain good saturation magnetization. The as-prepared Fe3O4@SiO2@Sec2@FA nanoparticles had the specific absorption rate (SAR)value of 57 W/g, which was below the clinically acceptable alternating magnetic field value of 4.9 × 109 Am-1s-1, indicating good heat generation efficiency (the temperature level ΔT=6-10 °C). Moreover, Folate-modified nanoparticles exhibited approximately 6-fold higher cellular internalization of Hela cells with no obvious cytotoxicity for the Hela and MDA-MB-231 cells, and lower cytotoxicity for the HUVECs in a concentration range of 0-150 µg/mL. In addition, these nanoparticles were modified on the silica surface by L-selenocystine, which could enhance the elimination of tumor cells by producing reactive oxygen species under X-rays, resulting in a novel radiosensitization effect. Therefore, the as-prepared Fe3O4@SiO2@Sec2@FA nanoparticles with good biocompatibility and active targeting would possess synergistic magnetic hyperthermia/radiotherapy effect.

Interobserver variability in target volume delineation in definitive radiotherapy for thoracic esophageal cancer: a multi-center study from China.

PURPOSE: To investigate the interobserver variability (IOV) in target volume delineation of definitive radiotherapy for thoracic esophageal cancer (TEC) among cancer centers in China, and ultimately improve contouring consistency as much as possible to lay the foundation for multi-center prospective studies. METHODS: Sixteen cancer centers throughout China participated in this study. In Phase 1, three suitable cases with upper, middle, and lower TEC were chosen, and participants were asked to contour a group of gross tumor volume (GTV-T), nodal gross tumor volume (GTV-N) and clinical target volume (CTV) for each case based on their routine experience. In Phase 2, the same clinicians were instructed to follow a contouring protocol to re-contour another group of target volume. The variation of the target volume was analyzed and quantified using dice similarity coefficient (DSC). RESULTS: Sixteen clinicians provided routine volumes, whereas ten provided both routine and protocol volumes for each case. The IOV of routine GTV-N was the most striking in all cases, with the smallest DSC of 0.37 (95% CI 0.32-0.42), followed by CTV, whereas GTV-T showed high consistency. After following the protocol, the smallest DSC of GTV-N was improved to 0.64 (95% CI 0.45-0.83, P = 0.005) but the DSC of GTV-T and CTV remained constant in most cases. CONCLUSION: Variability in target volume delineation was observed, but it could be significantly reduced and controlled using mandatory interventions.

Hypofractionated versus conventionally fractionated image-guided volumetric-modulated arc radiotherapy for localized prostate cancer: a phase II randomized trial from China.

PURPOSE: To determine the safety of hypofractionated imaging-guided (IG) volumetric-modulated arc radiotherapy (IG-VMAT; 70 Gy/28 fractions over 5.5 weeks) versus conventionally fractionated regimen (IG-VMAT; 80 Gy/40 fractions over 8 weeks) in Chinese patients with localized prostate cancer. METHOD: In this randomized non-comparative phase II trial, 92 patients with localized prostate cancer were assigned to receive either hypofractionated IG-VMAT (HFRT; 70 Gy/2.5Gy/28f) or conventionally fractionated IG-VMAT (CFRT; 80 Gy/2Gy/40f). Primary endpoint was grade 2 or higher late gastrointestinal (GI) and genitourinary (GU) toxicity at 2 years. The GI/GU toxicity and biochemical relapse-free survival (bRFS) were compared between the two treatment groups. RESULTS: Median follow-up was 26 months. The incidence of grade 2 or higher late GI/GU toxicity was low in both groups; the 5-year cumulative incidence of Radiation Therapy Oncology Group grade 2 or higher GI/GU toxicity at 2 years was 7.6% with HFRT versus 10.3% with CFRT (P = 0.707). Biochemical control was not significantly different between the two groups; the 2-year bRFS was 94.6% for HFRT versus 95.0% for CFRT (P = 0.704). CONCLUSION: Hypofractionated IG-VMAT appears to be equivalent to conventionally fractionated IG-VMAT in terms of toxicity in Chinese patients with localized prostate cancer.

Radiomics of Multiparametric MRI to Predict Biochemical Recurrence of Localized Prostate Cancer After Radiation Therapy.

Background: To identify multiparametric magnetic resonance imaging (mp-MRI)-based radiomics features as prognostic factors in patients with localized prostate cancer after radiotherapy. Methods:From 2011 to 2016, a total of 91 consecutive patients with T1-4N0M0 prostate cancer were identified and divided into two cohorts for an adaptive boosting (Adaboost) model (training cohort: n = 73; test cohort: n = 18). All patients were treated with neoadjuvant endocrine therapy followed by radiotherapy. The optimal feature set, identified through an Inception-Resnet v2 network, consisted of a combination of T1, T2, and diffusion-weighted imaging (DWI) MR series. Through a Wilcoxon sign rank test, a total of 45 distinct signatures were extracted from 1,536 radiomics features and used in our Adaboost model. Results:Among 91 patients, 29 (32%) were classified as biochemical recurrence (BCR) and 62 (68%) as non-BCR. Once trained, the model demonstrated a predictive classification accuracy of 50.0 and 86.1% respectively for BCR and non-BCR groups on our test samples. The overall classification accuracy of the test cohort was 74.1%. The highest classification accuracy was 77.8% between three-fold cross-validation. The areas under the curve (AUC) of receiver operating characteristic curve (ROC) indices for the training and test cohorts were 0.99 and 0.73, respectively. Conclusion:The potential of multiparametric MRI-based radiomics to predict the BCR of localized prostate cancer patients was demonstrated in this manuscript. This analysis provided additional prognostic factors based on routine MR images and holds the potential to contribute to precision medicine and inform treatment management.

Comparison of 3D anatomical dose verification and 2D phantom dose verification of IMRT/VMAT treatments for nasopharyngeal carcinoma.

BACKGROUND: The two-dimensional phantom dose verification (2D-PDV) using hybrid plan and planar dose measurement has been widely used for IMRT treatment QA. Due to the lack of information about the correlations between the verification results and the anatomical structure of patients, it is inadequate in clinical evaluation. A three-dimensional anatomical dose verification (3D-ADV) method was used in this study to evaluate the IMRT/VMAT treatment delivery for nasopharyngeal carcinoma and comparison with 2D-PDV was analyzed. METHODS: Twenty nasopharyngeal carcinoma (NPC) patients treated with IMRT/VMAT were recruited in the study. A 2D ion-chamber array was used for the 2D-PDV in both single-gantry-angle composite (SGAC) and multi-gantry-angle composite (MGAC) verifications. Differences in the gamma pass rate between the 2 verification methods were assessed. Based on measurement of irradiation dose fluence, the 3D dose distribution was reconstructed for 3D-ADV in the above cases. The reconstructed dose homogeneity index (HI), conformity index (CI) of the planning target volume (PTV) were calculated. Gamma pass rate and deviations in the dose-volume histogram (DVH) of each PTV and organ at risk (OAR) were analyzed. RESULTS: In 2D-PDV, the gamma pass rate (3%, 3 mm) of SGAC (99.55% ± 0.83%) was significantly higher than that of MGAC (92.41% ± 7.19%). In 3D-ADV, the gamma pass rates (3%, 3 mm) were 99.75% ± 0.21% in global, 83.82% ± 16.98% to 93.71% ± 6.22% in the PTVs and 45.12% ± 32.78% to 98.08% ± 2.29% in the OARs. The maximum HI increment in PTVnx was 19.34%, while the maximum CI decrement in PTV1 and PTV2 were -32.45% and -6.93%, respectively. Deviations in dose volume of PTVs were all within ±5%. D2% of the brainstem, spinal cord, left/right optic nerves, and the mean doses to the left/right parotid glands maximally increased by 3.5%, 6.03%, 31.13%/26.90% and 4.78%/4.54%, respectively. CONCLUSION: The 2D-PDV and global gamma pass rate might be insufficient to provide an accurate assessment for the complex NPC IMRT operation. In contrast, the 3D-ADV is superior in clinic-related quality assurance offering evaluation of organ specific pass rate and dose-volume deviations.