Novel image-guided marker aimed at organ-preserving therapies for prostate cancer.

OBJECTIVE: We developed fiducial imaging-guidance markers for the prostate with less imaging artifacts than currently commercially available markers. The aim of this study was to evaluate the imaging artifacts and potential usefulness and safety of these novel fiducial imaging markers in preclinical experiments. METHODS: We selected specific metal materials and a shape that can minimize artifacts in line with a license we obtained for a metal with a gold-platinum (Au-Pt) alloy composition that maximized artifact-free MRI images. Both phantom and canine prostate tests were conducted in order to evaluate the imaging artifacts for three imaging modalities, MRI, CT and ultrasound, and the risk of migration of the markers from the site of insertion to elsewhere, as well as crushing. RESULTS: The newly developed Au-Pt material had less imaging artifacts in the MRI, CT and ultrasound imaging modalities in comparison with current commercially available fiducial markers made from gold materials only. The Au-Pt markers had sufficient strength and durability and were considered to be potentially clinically useful and safe markers. CONCLUSION: The developed Au-Pt markers could be potential tools for accurate lesion-targeted, organ-preserving therapies such as lesion-targeted focal therapy and active surveillance in addition to conventional radiation therapies.

External radiotherapy for breast cancer in the elderly.

BACKGROUND: Breast cancer is the most common malignancy amongst elderly women and the main cause of mortality. A specific management for elderly woman is not clear because clinical trials are usually not customized for this subset of patients. AIMS: The aim of this paper is to provide an overview of the available information on the main issues in the field of breast cancer radiotherapy in the elderly population. MATERIALS AND METHODS: Authors discuss on different radiation treatments for breast cancer in the elderly, based on the data of the literature with a focus on new strategy: hypo-fractionation, accelerated partial breast irradiation, and the utility of a dose boost. DISCUSSION: The treatment of breast cancer is not standardized in the elderly. The optimal management in this population often requires complex multidisciplinary supportive care due to multiple comorbidities to optimize their cancer care. CONCLUSIONS: New options such as APBI or HyRT regimens should be taken into consideration and offered as a breach of duty to the elderly population. Furthermore, they should be extensively investigated through randomized clinical trials.

Evaluation of Diaphragm Position Variations During Proton Therapy for Pediatric Patients With Neuroblastoma.

Background To evaluate the respiratory-induced intrafractional diaphragm motion and interfractional diaphragm displacement in pediatric patients with neuroblastoma (NBL). Materials and methods Ten pediatric patients with a mean age of 4.5 years (range: 1.8-8.7 years) with abdominal NBL treated with proton therapy (PT) have been evaluated. Intrafractional motion and interfractional displacement have been analyzed by using cine radiography and orthogonal X-ray images, respectively. In each case, the cranio-caudal positions of the diaphragm have been measured as an index. This study has investigated the possible correlations between intrafractional diaphragm motion and height. Additionally, interfractional displacement and its time trend during the treatment course have been analyzed. Results The average right and left diaphragm intrafractional motions of 8.3 mm (range: 4.4-11.5 mm) and 6.4 mm (range: 2.2-11.8 mm) were observed, respectively; however, no significant correlation has been observed with height. An interfractional displacement of 5 mm or more has been observed in 20 out of 152 fractions (13%). The average absolute value of the interfractional displacement was 2.5 mm (range: 0-8.6 mm). Interfractional displacement did not show a peculiar tendency throughout the treatment period. Conclusions It was suggested that respiratory-induced diaphragm position variation in children varies greatly among individuals, and accurately estimating it based on height is difficult. Thus, these individual evaluations are considered indispensable.

Trends and distribution of external radiation therapy facilities in Japan based on Survey of Medical Institutions from the Ministry of Health, Labour and Welfare.

This study aimed to explore the distribution of external radiation therapy (RT) facilities, the status of related device installations and the adoption of high-precision RT using Survey of Medical Institutions from the Ministry of Health, Labour and Welfare in Japan. Analysis, categorized by the hospital size and prefecture, provides specific insights into the trends in treatment facility healthcare capabilities. Data on the number of RT facilities, high-precision RT facilities, RT devices and treatment planning systems (TPS) categorized by the number of beds and prefecture from 1996 to 2020 were analyzed. In addition, the study examined the correlation between the high-precision implementation rate and the number of TPSs or radiation oncologists and other medical staff. High-precision RT exceeded 95% in large facilities (800+ beds) but remained <50% in medium-sized facilities (300-499 beds). In a prefecture-by-prefecture analysis, calculation of the maximum-minimum ratio of RT facilities per million population and per 30 km2 revealed a disparity of 3.7 and 73.1 times in the population ratio and the density ratio, respectively. Although a correlation was found between the number of TPSs per RT device or the number of medical physicists per million population and the rate of high-precision RT implementation, no correlation was found among other professions. Detailed analysis based on the hospital size and prefecture provided more specific information on the medical functions of RT facilities in Japan. These findings can potentially contribute to the future development of RT, including the standardization of treatment techniques and optimal resource allocation.

Role of brachytherapy in post-operative cervical cancer patients with risk factors other than positive stump.

OBJECTIVE: This study aimed to determine the effectiveness of brachytherapy in post-operative cervical cancer patients with risk factors other than positive stump, and to identify the candidates most likely to benefit. METHODS: Newly diagnosed, non-metastatic cervical cancer patients treated in our hospital between January 2012 and November 2015 were retrospectively reviewed. Early stage patients receiving radical surgery and needing adjuvant external radiotherapy were included, but those with positive stump were excluded. All patients received external radiotherapy. They were divided into two groups: one group received vaginal brachytherapy and the other did not. The 5-year local-regional recurrence free survival (LRRFS) and overall survival (OS) rates in the two groups were compared. RESULTS: Two hundred and twenty-five patients were included in this study; while 99 received brachytherapy, 126 did not. The brachytherapy group had significantly superior 5-year LRRFS (87.7% vs. 72.5%, p = 0.004), but did not show a significant overall survival benefit (78.4% vs. 75.3%, p = 0.055). In multivariate analysis, brachytherapy, pathological type, high-risk factors, duration of radiotherapy, and transfusion were independent prognostic factors for 5-year LRRFS. In stratified analysis, the brachytherapy group showed superior LRRFS in those meeting Sedlis criteria (p = 0.017). CONCLUSION: The combination of external beam radiation therapy and brachytherapy can improve LRRFS in post-operative cervical cancer patients with risk factors other than positive stump. Therefore, brachytherapy should be considered for these patients.

Solving the volumetric modulated arc therapy (VMAT) problem using a sequential convex programming method.

The volumetric modulated arc therapy (VMAT) problem is highly non-convex and much more difficult than the fixed-field intensity modulated radiotherapy optimization problem. To solve it efficiently, we propose a sequential convex programming algorithm that solves a sequence of convex optimization problems. Beginning by optimizing the aperture weights of many (72) evenly distributed beams using the beam's eye view of the target from each direction as the initial aperture shape, the search space is constrained to allowing the leaves to move within a pre-defined step-size. A convex approximation problem is introduced and solved to optimize the leaf positions and the aperture weights within the search space. The algorithm is equipped with both local and global search strategies, whereby a global search is followed by a local search: a large step-size results in a global search with a less accurate convex approximation, followed by a small step-size local search with an accurate convex approximation. The performance of the proposed algorithm is tested on three patients with three different disease sites (paraspinal, prostate and oligometastasis). The algorithm generates VMAT plans comparable to the ideal 72-beam fluence map optimized plans (i.e. IMRT plans before leaf sequencing) in 14 iterations and 36 mins on average. The algorithm is also tested on a small down-sampled prostate case for which we could computationally afford to obtain the ground-truth by solving the non-convex mixed-integer optimization problem exactly. This general algorithm is able to produce results essentially equivalent to the ground-truth but 12 times faster. The algorithm is also scalable and can handle real clinical cases, whereas the ground-truth solution using mixed-integer optimization can only be obtained for highly down-sampled cases.

Development of a standardized mucositis and osteoradionecrosis animal model using external radiation.

OBJECTIVES: Although the side effects of radiation therapy vary from mucositis to osteomyelitis depending on the dose of radiation therapy, to date, an experimental animal model has not yet been proposed. The aim of this study was to develop an animal model for assessing complications of irradiated bone, especially to quantify the dose of radiation needed to develop a rat model. MATERIALS AND METHODS: Sixteen Sprague-Dawley rats aged seven weeks with a mean weight of 267.59 g were used. Atraumatic extraction of a right mandibular first molar was performed. At one week after the extraction, the rats were randomized into four groups and received a single dose of external radiation administered to the right lower jaw at a level of 14, 16, 18, or 20 Gy, respectively. Clinical alopecia with body weight changes were compared and bony volumetric analysis with micro-computed tomography (CT), histologic analysis with H&E were performed. RESULTS: The progression of the skin alopecia was different depending on the irradiation dose. Micro-CT parameters including bone volume, bone volume/tissue volume, bone mineral density, and trabecular spaces, showed no significant differences. The progression of osteoradionecrosis (ORN) along with that of inflammation, fibrosis, and bone resorption, was found with increased osteoclast or fibrosis in the radiated group. As the radiation dose increases, osteoclast numbers begin to decrease and osteoclast tends to increase. Osteoclasts respond more sensitively to the radiation dose, and osteoblasts are degraded at doses above 18 Gy. CONCLUSION: A standardized animal model clinically comparable to ORN of the jaw is a valuable tool that can be used to examine the pathophysiology of the disease and trial any potential treatment modalities. We present a methodology for the use of an experimental rat model that incorporates a guideline regarding radiation dose.

CYTOGENETIC DAMAGES IN LUNG CANCER PATIENTS TREATED BY EXTERNAL RADIATION THERAPY. / TsYTOGENETYChNI POShKODZhENNIa U KhVORYKh NA RAK LEGENI PRY DYSTANTsIY̆NIY̆ PROMENEVIY̆ TERAPIÏ.

OBJECTIVE: to estimate the chromosome type aberrations outcome in lung cancer patients during radiation therapy course depending on radiation energy. MATERIALS AND METHODS: Chromosome aberrations were studied in 16 lung cancer patients examined before treat- ment in the middle and at the end of external gamma-radiotherapy 60Со on ROCUS-AM and megavolt therapy on lin- ear accelerator Clinac 600C. RESULTS: The radiation-induced chromosome aberrations outcome in lung cancer patients during radiotherapy with different irradiation sources was studied. The over-spontaneous excess of chromosome type aberrations in cancer patients before treatment was shown. The similar and different features of cytogenetic damage accumulation dur- ing radiation therapy regarding to radiation type was displayed. The cytogenetic damage frequency raised during the course of therapeutic exposure in both studied groups. At the same time, the growth rate depended on the irra- diation regimen and was higher for patients undergoing 60Co gamma-therapy. The different range of cells with unsta- ble chromosome aberrations from the beginning to the end of the radiation therapy course was displayed. In the middle of the course the number of aberrations per aberrant cell was similar - 1-5 damages for gamma therapy, 1-4 damages for megavoltage therapy. At the end of treatment the maximum of 10 aberrations per aberrant cell for ROCUS-AM and in 5 aberrations per aberrant cell for linear accelerator was observed. During radiotherapy the distri- butions of radiation-induced chromosome aberrations was found to be over-dispersed according to Poisson statis- tic in both patients' groups. CONCLUSIONS: The study of chromosome type aberration revealed the particularities of cytogenetic damages out- come during radiotherapy course depending on the irradiation source used. The more pronounced genotoxic effect in blood lymphocytes of lung cancer patients due to gamma-irradiation with ROCUS-AM was demonstra- ted despite the higher radiation energy used on a linear accelerator. Therefore, in radiation treatment effects estimation it is necessary to take into account not only the radiation quality and energy, but also the source, regimen and pre-radiotherapy procedures. The data obtained can contribute to the assessment of the conse- quences of local fractionated irradiation and to the development of a reference biodosimetry system in radia- tion therapy.