Background and Summary: The management of endometrial cancer, in an ever-older population with considerable comorbidity, remains a challenge for gynecological and radiation oncologists. Key Message: ...The present paper reviews literature data on treatment options for endometrial cancer patients unfit for surgery.
Hadrontherapy is an innovative radiation therapy modality for which one of the main key advantages is the target conformality allowed by the physical properties of ion species. However, in order to ...maximise the exploitation of its potentialities, online monitoring is required in order to assert the treatment quality, namely monitoring devices relying on the detection of secondary radiations. Herein is presented a method based on Monte Carlo simulations to optimise a multi-slit collimated camera employing time-of-flight selection of prompt-gamma rays to be used in a clinical scenario. In addition, an analytical tool is developed based on the Monte Carlo data to predict the expected precision for a given geometrical configuration. Such a method follows the clinical workflow requirements to simultaneously have a solution that is relatively accurate and fast. Two different camera designs are proposed, considering different endpoints based on the trade-off between camera detection efficiency and spatial resolution to be used in a proton therapy treatment with active dose delivery and assuming a homogeneous target.
Abstract Purpose Hadrons, i.e. particles that are heavier than electrons, are playing an increasingly important role in radiation oncology. Due to the high investment costs for the necessary ...infrastructure, this option is only available in specialized centers. Methods This article describes some of the physical properties that make hadrons attractive for external beam radiation therapy (EBRT), but also some of the challenges that need to be considered. Results The importance of linear energy transfer for biological effects is discussed. Conclusions In addition to the use of charged particles, the importance of neutrons for radiotherapy is also highlighted, in particular the properties of boron neutron capture therapy (BNCT), which open up completely new possibilities for the further development of EBRT.
Abstract Nanomedicine is proposed as a novel strategy to improve the performance of radiotherapy. High-Z nanoparticles are known to enhance the effects of ionizing radiation. Recently, multimodal ...nanoparticles such as gadolinium-based nanoagents were proposed to amplify the effects of x-rays and g-rays and to improve MRI diagnosis. For tumors sited in sensitive tissues, childhood cases and radioresistant cancers, hadrontherapy is considered superior to x-rays and g-rays. Hadrontherapy, based on fast ion radiation, has the advantage of avoiding damage to the tissues behind the tumor; however, the damage caused in front of the tumor is its major limitation. Here, we demonstrate that multimodal gadolinium-based nanoparticles amplify cell death with fast ions used as radiation. Molecular scale experiments give insights into the mechanisms underlying the amplification of radiation effects. This proof-of-concept opens up novel perspectives for multimodal nanomedicine in hadrontherapy, ultimately reducing negative radiation effects in healthy tissues in front of the tumor. From the Clinical Editor Gadolinium-chelating polysiloxane nanoparticles were previously reported to amplify the anti-tumor effects of x-rays and g-rays and to serve as MRI contrast agents. Fast ion radiation-based hadrontherapy avoids damage to the tissues behind the tumor, with a major limitation of tissue damage in front of the tumor. This study demonstrates a potential role for the above nanoagents in optimizing hadrontherapy with preventive effects in healthy tissue and amplified cell death in the tumor.
Pancreatic ductal adenocarcinoma (PDAC) is one of the major causes of death in the Western world, and it is estimated to become the second leading cause of tumour-related mortality in the next 10 ...years. Among pancreatic cancers, ductal adenocarcinomas are by far the most common, characterised by a challenging diagnosis due to the lack of initial and pathognomonic clinical signs. In this scenario, non-metastatic locally advanced pancreatic cancer (LAPC) accounts for a large proportion of all new pancreatic ductal adenocarcinoma diagnoses. There is no consensus on a common definition of LAPC. Still, it usually includes tumours that are not resectable due to vascular involvement. As of today, treatment is limited, and the prognosis is very unfavourable. Curative-intent surgery remains the gold-standard even if often jeopardized by vascular involvement. Continuing progress in our understanding of LAPC genetics and immunology will permit the development of different treatments, targeted or combined, including radiation therapy, hadrontherapy, targeted immunotherapies or new chemotherapies. A multidisciplinary approach combining various fields of expertise is essential in aiming to limit disease progression as well as patient outcome. Using a narrative literature review approach, the manuscript explores the most up-to-date knowledge concerning locally advanced pancreatic ductal adenocarcinoma management.
Purpose: A study is presented of the irradiation of cancerous cervical cell line HeLa loaded with a platinum salt, betamethasone and deoxyglucose. The presence of the platinum increases the ...free-radical concentration and augments the cell death rate, whereas betamethasone or deoxyglucose induces radiosensitization by the alteration of metabolic pathways. Two by two combinations of these chemicals are made to investigate the possible benefit when two radiosensitizers are present. A model is proposed to understand the results of the presence of two modifying agents on the dose effects.
Materials and methods: The cells were incubated for 6 h in the presence of the following molecules: dichloro terpyridine platinum, concentration C = 350 μM, betamethasone and deoxyglucose with concentrations of C = 0.2 μM and C = 6 mM, respectively. The cells were subsequently irradiated by carbon C
6+
ion 290 MeV/amu up to a dose of 2.5 Gy, under atmospheric conditions.
Results: The presence of the platinum salt or bethamethasone augments the cell death rate. The combination of betamethasone with the platinum salt also increases the cell death rate, but less than for the platinum salt alone. The explanation is that any radiosensitizer also behaves as a scavenger of free radicals. This dual behavior should be considered in any optimization of the design of radiosensitizers when different ionizing particles are used.
TERA Foundation has proposed and designed hadrontherapy facilities based on novel linacs, i.e. high gradient linacs which accelerate either protons or light ions. The overall length of the linac, and ...therefore its cost, is almost inversely proportional to the average accelerating gradient. With the scope of studying the limiting factors for high gradient operation and to optimize the linac design, TERA, in collaboration with the CLIC Structure Development Group, has conducted a series of high gradient experiments. The main goals were to study the high gradient behavior and to evaluate the maximum gradient reached in 3 and 5.7 GHz structures to direct the design of medical accelerators based on high gradient linacs. This paper summarizes the results of the high power tests of 3.0 and 5.7 GHz single-cell cavities.
The manuscript summarizes and discusses the various versions of a radiation damage biophysical model, implemented as a Monte Carlo simulation code, originally developed for chromosome aberrations and ...subsequently extended to cell death. This extended version has been called BIANCA (BIophysical ANalysis of Cell death and chromosome Aberrations). According to the basic assumptions, complex double-strand breaks (called “Cluster Lesions”, or CLs) produce independent chromosome free-ends, mis-rejoining within a threshold distance d (or un-rejoining) leads to chromosome aberrations, and “lethal aberrations” (i.e., dicentrics plus rings plus large deletions) lead to clonogenic cell death. The mean number of CLs per Gy and per cell is an adjustable parameter. While in BIANCA the threshold distance d was the second parameter, in a subsequent version, called BIANCA II, d has been fixed as the mean distance between two adjacent interphase chromosome territories, and a new parameter, f, has been introduced to represent the chromosome free-end un-rejoining probability. Simulated dose-response curves for chromosome aberrations and cell survival obtained by the various model versions were compared with literature experimental data. Such comparisons provided indications on some open questions, including the role of energy deposition clustering at the nm and the µm level, the probability for a chromosome free-end to remain un-rejoined, and the relationship between chromosome aberrations and cell death. Although both BIANCA and BIANCA II provided cell survival curves in general agreement with human and hamster fibroblast survival data, BIANCA II allowed for a better reproduction of dicentrics, rings and deletions considered separately. Furthermore, the approach adopted in BIANCA II for d is more consistent with estimates reported in the literature. After testing against aberration and survival data, BIANCA II was applied to investigate the depth-dependence of the radiation effectiveness for a proton SOBP used to treat eye melanoma in Catania, Italy. The survival of AG01522 cells at different depths was reproduced, and the survival of V79 cells was predicted. For both cell lines, the simulations also predicted yields of chromosome aberrations, some of which can be regarded as indicators of the risk to normal tissues.
•The evolution of a model of chromosome aberrations and cell death was discussed.•Both DSB complexity and DSB proximity play a role in chromosome aberration induction.•DSB clusters at the kilo-base-pair scale may be an example of such complex DSBs.•For some cells, clonogenic death can be explained by dicentrics, rings and large deletions.•The distal increase in biological effectiveness was quantified for a therapeutic proton SOBP.
Various definitions are currently in use to describe high-risk prostate cancer. This variety in definitions is important for patient counseling, since predicted outcomes depend on which ...classification is applied to identify patient’s prostate cancer risk category. Historically, strategies for the treatment of localized high-risk prostate cancer comprise local approaches such as surgery and radiotherapy, as well as systemic approaches such as hormonal therapy. Nevertheless, since high-risk prostate cancer patients remain the group with higher-risk of treatment failure and mortality rates, nowadays, novel treatment strategies, comprising hypofractionated-radiotherapy, second-generation antiandrogens, and hadrontherapy, are being explored in order to improve their long-term oncological outcomes. This narrative review aims to report the current management of high-risk prostate cancer and to explore the future perspectives in this clinical setting.
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