A review of prognostic and predictive biomarkers in breast cancer.

Breast cancer (BC) is a common cancer all over the world that affects women. BC is one of the leading causes of cancer mortality in women, which today has decreased with the advancement of technology and new diagnostic and therapeutic methods. BCs are histologically divided into in situ and invasive carcinoma, and both of them can be divided into ductal and lobular. The main function after the diagnosis of invasive breast cancer is which patient should use chemotherapy, which patient should receive adjuvant therapy, and which should not. If the decision is for adjuvant therapy, the next challenge is to identify the most appropriate treatment or combination of treatments for a particular patient. Addressing the first challenge can be helped by prognostic biomarkers, while addressing the second challenge can be done by predictive biomarkers. Among the molecular markers related to BC, ER, PR, HER2, and the Mib1/Ki-67 proliferation index are the most significant ones and are tightly confirmed in the standard care of all primary, recurrent, and metastatic BC patients. CEA and CA-15-3 antigens are the most valuable markers of serum tumors in BC patients. Determining the series of these markers helps monitor response to the treatment and early detection of recurrence or metastasis. miRNAs have been demonstrated to be intricate in mammary gland growth, proliferation, and formation of BC known to be incriminated in BC biology. By combining established prognostic factors with valid prognostic/predicted biomarkers, we can start the journey to personalized treatment for every recently diagnosed BC patient.

Modeling and optimization of respiratory-gated partial breast irradiation with proton beams - A Monte Carlo study.

The selection of a suitable duty factor (DF) remains a major challenge in respiratory-gated treatments. Therefore, this study aims at presenting a new methodology for fast optimizing the gating window width (duty factor (DF)) in respiratory-gated proton partial breast irradiation (PBI). To do so, GATE Monte Carlo simulations were performed for various target sizes and locations in supine and prone positions. Three different duty factors of 20, 25, and 33% were considered. Sparing factors (SF) for four organs-at-risk (OARs) were then assessed. The weighted-sum method was employed to search for an optimal DF. The results indicate that an SF higher than unity was obtained for all plans. The SF also depends on the target size/location and the patient positioning. By increasing the DF, SF monotonically decreases. Optimal DF was found to be 25% and 20% for shallow-/laterally- and medially-located targets, respectively. It can be concluded that for PBI using multiple passively scattered proton fields with large hinge angles, the respiratory-gated treatment addresses the intrafractional target motion and the extent of its impact remains patient specific.

Target motion management in breast cancer radiation therapy.

BACKGROUND: Over the last two decades, breast cancer remains the main cause of cancer deaths in women. To treat this type of cancer, radiation therapy (RT) has proved to be efficient. RT for breast cancer is, however, challenged by intrafractional motion caused by respiration. The problem is more severe for the left-sided breast cancer due to the proximity to the heart as an organ-at-risk. While particle therapy results in superior dose characteristics than conventional RT, due to the physics of particle interactions in the body, particle therapy is more sensitive to target motion. CONCLUSIONS: This review highlights current and emerging strategies for the management of intrafractional target motion in breast cancer treatment with an emphasis on particle therapy, as a modern RT technique. There are major challenges associated with transferring real-time motion monitoring technologies from photon to particles beams. Surface imaging would be the dominant imaging modality for real-time intrafractional motion monitoring for breast cancer. The magnetic resonance imaging (MRI) guidance and ultra high dose rate (FLASH)-RT seem to be state-of-the-art approaches to deal with 4D RT for breast cancer.

Evaluation of the organs at risk doses for lung tumors in gated and conventional radiotherapy.

PURPOSE: The purpose of this study was to evaluate the organs at risk (OARs) doses for lung tumors in gated radiotherapy (RT) compared to conventional RT using the four-dimensional extended cardiac-torso (4D-XCAT) digital phantom in a simulation study. MATERIALS AND METHODS: 4D-XCAT digital phantom was used to create 32 digital phantom datasets of different tumor diameters of 3 and 4 cm, and motion ranges (MRs) of 2, 2.5, 3, and 3.5 cm and each tumor was placed in four different lung locations (right lower lobe, right upper lobe, left lower lobe, and left upper lobe). XCAT raw binary images were converted to the digital imaging and communication in medicine format using an in-house MATLAB-based program and were imported to treatment planning system (TPS). For each dataset, gated and conventional treatment plans were prepared using Planning Computerized RadioTherapy-three dimensional (PCRT-3D) TPS with superposition computational algorithm. Dose differences between gated and conventional plans were evaluated and compared (as a function of 3D motion and tumor volume and its location) with respect to the dose-volume histograms of different organs-at-risk. RESULTS: There are statistically significant differences in dosimetric parameters among gated and conventional RT, especially for the tumors near the diaphragm (P < 0.05). The maximum reduction in the mean dose of the lung, heart, and liver were 6.11 Gy, 1.51 Gy, and 10.49 Gy, respectively, using gated RT. CONCLUSIONS: Dosimetric comparison between gated and conventional RT showed that gated RT provides relevant dosimetric improvements to lung normal tissue and the other OARs, especially for the tumors near the diaphragm. In addition, dosimetric differences between gated and conventional RT did generally increase with increasing tumor motion and decreasing tumor volume.

Evaluation of normal lung tissue complication probability in gated and conventional radiotherapy using the 4D XCAT digital phantom.

PURPOSE: The present study was conducted to investigate normal lung tissue complication probability in gated and conventional radiotherapy (RT) as a function of diaphragm motion, lesion size, and its location using 4D-XCAT digital phantom in a simulation study. MATERIALS AND METHODS: Different time series of 3D-CT images were generated using the 4D-XCAT digital phantom. The binary data obtained from this phantom were then converted to the digital imaging and communication in medicine (DICOM) format using an in-house MATLAB-based program to be compatible with our treatment planning system (TPS). The 3D-TPS with superposition computational algorithm was used to generate conventional and gated plans. Treatment plans were generated for 36 different XCAT phantom configurations. These included four diaphragm motions of 20, 25, 30 and 35 mm, three lesion sizes of 3, 4, and 5 cm in diameter and each tumor was placed in four different lung locations (right lower lobe, right upper lobe, left lower lobe and left upper lobe). The complication of normal lung tissue was assessed in terms of mean lung dose (MLD), the lung volume receiving ≥20 Gy (V20), and normal tissue complication probability (NTCP). RESULTS: The results showed that the gated RT yields superior outcomes in terms of normal tissue complication compared to the conventional RT. For all cases, the gated radiation therapy technique reduced the mean dose, V20, and NTCP of lung tissue by up to 5.53 Gy, 13.38%, and 23.89%, respectively. CONCLUSIONS: The results of this study showed that the gated RT provides significant advantages in terms of the normal lung tissue complication, compared to the conventional RT, especially for the lesions near the diaphragm.

Radiation dose to neonates undergoing X-ray imaging in special care baby units in Iran.

Radiographic imaging has a significant role in the timely diagnosis of the diseases of neonates in intensive care units. The estimation of the dose received by the infants undergoing radiographic examination is of great importance, due to greater more radiosensitivity and longer life expectancy of the neonates and premature babies. In this study, the values of entrance skin dose (ESD), dose area products (DAPs), energy imparted (EI), whole-body dose, effective dose and risk of childhood cancer were estimated using three methods including direct method [using thermoluminescence dosimetry (TLD) chips], indirect method (using tube output) and Monte Carlo (MC) method (using MCNP4C code). In the first step, the ESD of the neonates was directly measured using TLD-100 chips. Fifty neonates, mostly premature, with different weights and gestational ages in five hospitals mostly suffering from respiratory distress syndrome and pneumonia were involved in this study. In the second step, the values of ESD to neonates were indirectly obtained from the tube output in different imaging techniques. The imaging room, incubator, neonates and other components were then simulated in order to obtain the ESD values using the MCNP4C code. Finally, the values of ESD assessed by the three methods were used for calculation of DAP, EI, whole-body dose, effective dose and risk of childhood cancer. The results indicate that the mean ESD per radiograph estimated by the direct, indirect and MC methods are 56.6±4.1, 50.1±3.1 and 54.5±3.3 µGy, respectively. The mean risk of childhood cancer estimated in this study varied between 4.21×10(-7) and 2.72×10(-6).