New challenges in high-energy particle radiobiology
31 Jan 2014-British Journal of Radiology (British Institute of Radiology)-Vol. 87, Iss: 1035, pp 20130626-20130626
TL;DR: Particle radiobiology is now entering into a new phase, where beyond RBE, the tissue response is considered, and these results may open new applications for both cancer therapy and protection in deep space.
Abstract: Densely ionizing radiation has always been a main topic in radiobiology. In fact, α-particles and neutrons are sources of radiation exposure for the general population and workers in nuclear power plants. More recently, high-energy protons and heavy ions attracted a large interest for two applications: hadrontherapy in oncology and space radiation protection in manned space missions. For many years, studies concentrated on measurements of the relative biological effectiveness (RBE) of the energetic particles for different end points, especially cell killing (for radiotherapy) and carcinogenesis (for late effects). Although more recently, it has been shown that densely ionizing radiation elicits signalling pathways quite distinct from those involved in the cell and tissue response to photons. The response of the microenvironment to charged particles is therefore under scrutiny, and both the damage in the target and non-target tissues are relevant. The role of individual susceptibility in therapy and risk is obviously a major topic in radiation research in general, and for ion radiobiology as well. Particle radiobiology is therefore now entering into a new phase, where beyond RBE, the tissue response is considered. These results may open new applications for both cancer therapy and protection in deep space.
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TL;DR: This Review focuses on how mechanistic processes might be targeted to improve the outcome of radiotherapy at the individual patient level, and would seem a more productive avenue of treatment than simply trying to increase the radiation dose delivered to the tumour.
Abstract: The past 20 years have seen dramatic changes in the delivery of radiation therapy, but the impact of radiobiology on the clinic has been far less substantial. A major consideration in the use of radiotherapy has been on how best to exploit differences between the tumour and host tissue characteristics, which in the past has been achieved empirically by radiation-dose fractionation. New advances are uncovering some of the mechanistic processes that underlie this success story. In this Review, we focus on how these processes might be targeted to improve the outcome of radiotherapy at the individual patient level. This approach would seem a more productive avenue of treatment than simply trying to increase the radiation dose delivered to the tumour.
372 citations
TL;DR: Several randomized trials of charged-particle therapies that are ongoing are reviewed, with results that will enable selective delivery to patients who are most likely to benefit from them and aspects related to radiobiology, including the immune response and hypoxia, which will need to be taken into consideration in future randomized trials to fully exploit the potential of charged particles.
Abstract: Radiotherapy with high-energy charged particles has become an attractive therapeutic option for patients with several tumour types because this approach better spares healthy tissue from radiation than conventional photon therapy. The cost associated with the delivery of charged particles, however, is higher than that of even the most elaborate photon-delivery technologies. Reliable evidence of the relative cost-effectiveness of both modalities can only come from the results of randomized clinical trials. Thus, the hurdles that currently limit direct comparisons of these two approaches in clinical trials, especially those related to insurance coverage, should be removed. Herein, we review several randomized trials of charged-particle therapies that are ongoing, with results that will enable selective delivery to patients who are most likely to benefit from them. We also discuss aspects related to radiobiology, including the immune response and hypoxia, which will need to be taken into consideration in future randomized trials to fully exploit the potential of charged particles.
309 citations
TL;DR: Research in applied nuclear physics, including nuclear interactions, dosimetry, image guidance, range verification, novel accelerators and beam delivery technologies, can significantly improve the clinical outcome in particle therapy.
Abstract: Charged particle therapy has been largely driven and influenced by nuclear physics. The increase in energy deposition density along the ion path in the body allows reducing the dose to normal tissues during radiotherapy compared to photons. Clinical results of particle therapy support the physical rationale for this treatment, but the method remains controversial because of the high cost and of the lack of comparative clinical trials proving the benefit compared to x-rays. Research in applied nuclear physics, including nuclear interactions, dosimetry, image guidance, range verification, novel accelerators and beam delivery technologies, can significantly improve the clinical outcome in particle therapy. Measurements of fragmentation cross-sections, including those for the production of positron-emitting fragments, and attenuation curves are needed for tuning Monte Carlo codes, whose use in clinical environments is rapidly increasing thanks to fast calculation methods. Existing cross sections and codes are indeed not very accurate in the energy and target regions of interest for particle therapy. These measurements are especially urgent for new ions to be used in therapy, such as helium. Furthermore, nuclear physics hardware developments are frequently finding applications in ion therapy due to similar requirements concerning sensors and real-time data processing. In this review we will briefly describe the physics bases, and concentrate on the open issues.
220 citations
TL;DR: A comprehensive review of the studies of carbon ion radiotherapy for almost every type of malignancy, including intracranial malignancies, head and neck malignANCs, primary and metastatic lung cancers, tumors of the gastrointestinal tract, prostate and genitourinary cancers, sarcomas, cutaneous malIGNancies, breast cancer, gynecologic malignations, and pediatric cancers is provided.
Abstract: Radiation therapy is one of the most widely used therapies for malignancies. The therapeutic use of heavy ions, such as carbon, has gained significant interest due to advantageous physical and radiobiologic properties compared to photon based therapy. By taking advantage of these unique properties, carbon ion radiotherapy may allow dose escalation to tumors while reducing radiation dose to adjacent normal tissues. There are currently 13 centers treating with carbon ion radiotherapy, with many of these centers publishing promising safety and efficacy data from the first cohorts of patients treated. To date, carbon ion radiotherapy has been studied for almost every type of malignancy, including intracranial malignancies, head and neck malignancies, primary and metastatic lung cancers, tumors of the gastrointestinal tract, prostate and genitourinary cancers, sarcomas, cutaneous malignancies, breast cancer, gynecologic malignancies, and pediatric cancers. Additionally, carbon ion radiotherapy has been studied extensively in the setting of recurrent disease. We aim to provide a comprehensive review of the studies of each of these disease sites, with a focus on the current trials using carbon ion radiotherapy.
113 citations
Cites background from "New challenges in high-energy parti..."
...In addition, higher doses per fraction have been shown to increase the immune response following radiation, and most patients treated with CIRT are treated with a hypofractionated regimen (110, 112)....
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TL;DR: An overview of progress and typical yields from intense laser-plasma acceleration of ions is presented, and pulse energy scaling of maximum ion energies and typical differential spectra obtained over the past two decades provide guidance for continued advancement of laser-driven energetic ion sources and their meaningful applications.
Abstract: An overview of progress and typical yields from intense laser-plasma acceleration of ions is presented. The evolution of laser-driven ion acceleration at relativistic intensities ushers prospects for improved functionality and diverse applications which can represent a varied assortment of ion beam requirements. This mandates the development of the integrated laser-driven ion accelerator system, the multiple components of which are described. Relevant high field laser-plasma science and design of controlled optimum pulsed laser irradiation on target are dominant single shot (pulse) considerations with aspects that are appropriate to the emerging petawatt era. The pulse energy scaling of maximum ion energies and typical differential spectra obtained over the past two decades provide guidance for continued advancement of laser-driven energetic ion sources and their meaningful applications.
107 citations
References
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TL;DR: It is now becoming clear that the tumour microenvironment, which is largely orchestrated by inflammatory cells, is an indispensable participant in the neoplastic process, fostering proliferation, survival and migration.
Abstract: Recent data have expanded the concept that inflammation is a critical component of tumour progression. Many cancers arise from sites of infection, chronic irritation and inflammation. It is now becoming clear that the tumour microenvironment, which is largely orchestrated by inflammatory cells, is an indispensable participant in the neoplastic process, fostering proliferation, survival and migration. In addition, tumour cells have co-opted some of the signalling molecules of the innate immune system, such as selectins, chemokines and their receptors for invasion, migration and metastasis. These insights are fostering new anti-inflammatory therapeutic approaches to cancer development.
12,395 citations
01 Jul 1959
TL;DR: Recommendations are presented which represent concepts and practices evolved from recent discussions at formal and informal meetings of the Commission and its Committees.
Abstract: The International Commission on Radiological Protection has been functioning since 1928 when it was established, under the name of International X- ray and Radium Protection Commission, by the Second International Congress of Radiology held in Stockholm, Sweden. It assumed the present name and organizational form in 1950 in order to cover more effectively the rapidly expanding field of radiation protection. Recommendations are presented which represent concepts and practices evolved from recent discussions at formal and informal meetings of the Commission and its Committees. (auth)
6,166 citations
Journal Article•
5,934 citations
TL;DR: None of four chemotherapy regimens offered a significant advantage over the others in the treatment of advanced non-small-cell lung cancer.
Abstract: Background We conducted a randomized study to determine whether any of three chemotherapy regimens was superior to cisplatin and paclitaxel in patients with advanced non–small-cell lung cancer. Methods A total of 1207 patients with advanced non–small-cell lung cancer were randomly assigned to a reference regimen of cisplatin and paclitaxel or to one of three experimental regimens: cisplatin and gemcitabine, cisplatin and docetaxel, or carboplatin and paclitaxel. Results The response rate for all 1155 eligible patients was 19 percent, with a median survival of 7.9 months (95 percent confidence interval, 7.3 to 8.5), a 1-year survival rate of 33 percent (95 percent confidence interval, 30 to 36 percent), and a 2-year survival rate of 11 percent (95 percent confidence interval, 8 to 12 percent). The response rate and survival did not differ significantly between patients assigned to receive cisplatin and paclitaxel and those assigned to receive any of the three experimental regimens. Treatment with cisplatin...
4,781 citations
01 Jan 2002
TL;DR: The response rate for all 1155 eligible pa-tients was 19 percent, with a median survival of 79 months (95 percent confidence interval, 73 to 85), a1-year survival rate of 33 percent, and a 2-year surviv-al rate of 11 percent.
Abstract: The response rate for all 1155 eligible pa-tients was 19 percent, with a median survival of 79months (95 percent confidence interval, 73 to 85), a1-year survival rate of 33 percent (95 percent confi-dence interval, 30 to 36 percent), and a 2-year surviv-al rate of 11 percent (95 percent confidence interval,8 to 12 percent) The response rate and survival didnot differ significantly between patients assigned toreceive cisplatin and paclitaxel and those assigned toreceive any of the three experimental regimens Treat-ment with cisplatin and gemcitabine was associatedwith a significantly longer time to the progression ofdisease than was treatment with cisplatin and pacli-taxel but was more likely to cause grade 3, 4, or 5 re-nal toxicity (in 9 percent of patients, vs 3 percent ofthose treated with cisplatin plus paclitaxel) Patientswith a performance status of 2 had a significantlylower rate of survival than did those with a perform-ance status of 0 or 1
3,839 citations