Prone versus supine free-breathing for right-sided whole breast radiotherapy

Prone setup has been advocated to improve organ sparing in whole breast radiotherapy without impairing breast coverage. We evaluate the dosimetric advantage of prone setup for the right breast and look for predictors of the gain. Right breast cancer patients treated in 2010–2013 who had a dual supine and prone planning were retrospectively identified. A penalty score was computed from the mean absolute dose deviation to heart, lungs, breasts, and tumor bed for each patient's supine and prone plan. Dosimetric advantage of prone was assessed by the reduction of penalty score from supine to prone. The effect of patients' characteristics on the reduction of penalty was analyzed using robust linear regression. A total of 146 patients with right breast dual plans were identified. Prone compared to supine reduced the penalty score in 119 patients (81.5%). Lung doses were reduced by 70.8%, from 4.8 Gy supine to 1.4 Gy prone. Among patient's characteristics, the only significant predictors were the breast volumes, but no cutoff could identify when prone would be less advantageous than supine. Prone was associated with a dosimetric advantage in most patients. It sets a benchmark of achievable lung dose reduction.Trial registration: ClinicalTrials.gov NCT02237469, HUGProne, September 11, 2014, retrospectively registered.

Novel Multifunctional NIR-II Aggregation-Induced Emission Nanoparticles Assisted Intraoperative Identification and Elimination of Residual Tumor

Incomplete tumor resection is the direct cause of the tumor recurrence and metastasis after surgery. Intraoperative accurate detection and elimination of microscopic residual cancer improve surgery outcomes. In this study, a powerful D1-π-A-D2-R type phototheranostic based on aggregation-induced emission (AIE)-active the second near-infrared window (NIR-II) fluorophore is designed and constructed. The prepared theranostic agent, A1 nanoparticles (NPs), simultaneously shows high absolute quantum yield (1.23%), excellent photothermal conversion efficiency (55.3%), high molar absorption coefficient and moderate singlet oxygen generation performance. In vivo experiments indicate that NIR-II fluorescence imaging of A1 NPs precisely detect microscopic residual tumor (2 mm in diameter) in the tumor bed and metastatic lymph nodes. More notably, a novel integrated strategy that achieves complete tumor eradication (no local recurrence and metastasis after surgery) is proposed. In summary, A1 NPs possess superior imaging and treatment performance, and can detect and eliminate residual tumor lesions intraoperatively. This work provides a promising technique for future clinical applications achieving improved surgical outcomes.

Intra-Operative Electron Radiation Therapy (IOERT) Anticipated Boost in Breast Cancer Treatment: An Italian Multicenter Experience

In breast cancer, the use of a boost to the tumor bed can improve local control. The aim of this research is to evaluate the safety and efficacy of the boost with intra-operative electron radiotherapy (IOERT) in patients with early-stage breast cancer undergoing conservative surgery and postoperative whole breast irradiation (WBI). The present retrospective multicenter large data were collected between January 2011 and March 2018 in 8 Italian Radiation Oncology Departments. Acute and late toxicity, objective (obj) and subjective (subj) cosmetic outcomes, in-field local control (LC), out-field LC, disease-free survival (DFS) and overall survival (OS) were evaluated. Overall, 797 patients were enrolled. IOERT-boost was performed in all patients during surgery, followed by WBI. Acute toxicity (≥G2) occurred in 179 patients (22.46%); one patient developed surgical wound infection (G3). No patients reported late toxicity ≥ G2. Obj-cosmetic result was excellent in 45%, good in 35%, fair in 20% and poor in 0% of cases. Subj-cosmetic result was excellent in 10%, good in 20%, fair in 69% and poor in 0.3% of cases. Median follow-up was 57 months (range 12–109 months). At 5 years, in-field LC was 99.2% (95% CI: 98–99.7); out-field LC 98.9% (95% CI: 97.4–99.6); DFS 96.2% (95% CI: 94.2–97.6); OS 98.6% (95% CI: 97.2–99.3). In conclusion, IOERT-boost appears to be safe, providing excellent local control for early-stage breast cancer. The safety and long-term efficacy should encourage use of this treatment, with the potential to reduce local recurrence.

Interstitial high dose rate brachytherapy boost in early-stage breast cancer: deformable image registration for defining target volume

Purpose: optimization of the technique of additional irradiation of the removed tumor bed using high-dose brachytherapy for breast cancer. Material and Methods: the results of treatment of 28 patients diagnosed with breast cancer were analyzed. After surgical treatment and a course of external radiation therapy, all patients underwent additional irradiation of the removed tumor bed using high-dose brachytherapy. The assessment of the operation protocols, the data of the pathomorphological conclusion was carried out, and on the basis of pre- and postoperative CT images, the formation of irradiation fields for high-dose brachytherapy was carried out. Results: After deformable (nonrigid) registration of pre- and postoperative CT images of 28 patients, it was revealed that in 18 women (64.3% of cases) the location of interstitial markers and the primary tumor focus does not match topographically, which can cause incorrect formation of borders irradiation. In 35.7% of cases, radiopaque markers were located on the chest wall (on the pectoralis major muscle) when the primary tumor was located in the breast tissue. In 25% of cases, the markers were located cranial or caudal to the topography of the primary tumor focus. Label migration occurred in 3.6% of cases. In 35.7% of cases, the topography of the primary tumor node and marks completely coincided. Conclusions: The use of deformable (non-rigid) registration of pre- and postoperative CT images is a simpler method to determine the topography of the removed tumor bed, which subsequently leads to a more accurate formation of the clinical volume of irradiation.

Application of a simple device for "attracting" and "trapping" glioma cells in situ

Glioblastoma multiforme (GBM) is the most malignant adult brain tumor. The current adjuvant therapies for GBM are disappointing, which are based on cytotoxicity strategy. Thus, other ways should be explored to improve the curative effect. According to the strong invasive ability of GBM cells, we assume a new treatment strategy for GBM by developing a new cell trap device (CTD) with some kind of "attractive" medium loaded in it to attract and capture the tumor cells. The in vitro experiment showed that Hepatocyte Growth Factor（HGF）presented stronger chemotaxis on C6 and U87 cell line than the Epidermal Growth Factor (EGF) and Fibroblast Growth Factor (FGF). A simple in vitro CTD loaded with HGF was made and in vivo experiments results showed that HGF successfully attracted tumor cells from tumor bed in situ into the CTD. This study proposes the new strategy for GBM treatment of "attract and trap" tumor cells is proved to be feasible.

Giving Oncolytic Viruses a Free Ride: Carrier Cells for Oncolytic Virotherapy

Oncolytic viruses (OVs) are an emerging class of therapeutics which combine multiple mechanisms of action, including direct cancer cell-killing, immunotherapy and gene therapy. A growing number of clinical trials have indicated that OVs have an excellent safety profile and provide some degree of efficacy, but to date only a single OV drug, HSV-1 talimogene laherparepvec (T-Vec), has achieved marketing approval in the US and Europe. An important issue to consider in order to accelerate the clinical advancement of OV agents is the development of an effective delivery system. Currently, the most commonly employed OV delivery route is intratumoral; however, to target metastatic diseases and tumors that cannot be directly accessed, it is of great interest to develop effective approaches for the systemic delivery of OVs, such as the use of carrier cells. In general, the ideal carrier cell should have a tropism towards the tumor microenvironment (TME), and it must be susceptible to OV infection but remain viable long enough to allow migration and finally release of the OV within the tumor bed. Mesenchymal stem cells (MSCs) have been heavily investigated as carrier cells due to their inherent tumor tropism, in spite of some disadvantages in biodistribution. This review focuses on the other promising candidate carrier cells under development and discusses their interaction with specific OVs and future research lines.