ARTICLE IN PRESS JID: YSONC [mUS5Gb;August 3, 2019;14:5] Seminars in Oncology xxx (xxxx) xxx Contents lists available at ScienceDirect Seminars in Oncology journal homepage: www.elsevier.com/locate/seminoncol Technological evolution of radiation treatment: Implications for clinical applications Roberto Pacelli a,* , Mara Caroprese a , Giuseppe Palma b , Caterina Oliviero c , Stefania Clemente c , Laura Cella b , Manuel Conson a a Department of Advanced Biomedical Sciences, University “Federico II”, Napoli, Italy b Institute of Biostructures and Bioimages, National Research Council, Napoli, Italy c University Hospital “Federico II”, Napoli, Italy a r t i c l e i n f o Article history: Received 20 June 2019 Accepted 17 July 2019 Available online xxx Keywords: Radiation therapy IMRT Stereotactic radiotherapy Particle beam therapy a b s t r a c t The contemporary approach to the management of a cancer patient requires an “ab initio” involvement of different medical domains in order to correctly design an individual patient’s pathway toward cure. With new therapeutic tools in every medical field developing faster than ever before the patient care outcomes can be achieved if all surgical, drug, and radiation options are considered in the design of the appropriate therapeutic strategy for a given patient. Radiation therapy (RT) is a clinical discipline in which experts from different fields continuously in- teract in order to manage the multistep process of the radiation treatment. RT is found to be an ap- propriate intervention for diverse indications in about 50% of cancer patients during the course of their disease. Technologies are essential in dealing with the complexity of RT treatments and for driving the increasingly sophisticated RT approaches becoming available for the treatment of Cancer. High confor- mal techniques, namely intensity modulated or volumetric modulated arc techniques, ablative techniques (Stereotactic Radiotherapy and Stereotactic Radiosurgery), particle therapy (proton or carbon ion ther- apy) allow for success in treating irregularly shaped or critically located targets and for the sharpness of the dose fall-off outside the target. The advanced on-board imaging, including real-time position man- agement systems, makes possible image-guided radiation treatment that results in substantial margin reduction and, in select cases, implementation of an adaptive approach. The therapeutic gains of mod- ern RT are also due in part to the enhanced anticancer activity obtained by coadministering RT with chemotherapy, targeted molecules, and currently immune checkpoints inhibitors. These main clinically relevant steps forward in Radiation Oncology represent a change of gear in the field that may have a profound impact on the management of cancer patients. © 2019 Elsevier Inc. All rights reserved. Background Radiation therapy (RT) is the oldest nonsurgical anticancer modality. Ionizing radiation (IR), the single most effective agent capable of interfering with cell replication, commonly finds a clinical application in about 50% of patients with a diagnosis Abbreviations: Ablative radiotherapy (SRT, SRS); BTV, biological target volume; HCT, high conformal techniques; IMRT, intensity modulated radiotherapy; FFF beams, flattening filter free beams; LINAC, linear accelerator; MLCs, multileaf col- limators; NTCP, normal tissue complication probabilities; OARs, organs at risk; RBE, relative biological effectiveness; 3D-CRT, three-dimensional conformal RT; TPSs, treatment planning systems; TCP, tumor control probabilities; NTCP, normal tissue complication probability; VMAT, volumetric-modulated arc therapy. * Corresponding author. Department of Advanced Biomedical Sciences, University “Federico II”, Edificio 10, Via S. Pansini, 5, 80131 Napoli, Italy. E-mail address: roberto.pacelli@unina.it (R. Pacelli). of cancer [1]. The nonspecificity of IR for cancer cells has been historically mitigated by using devices to focus the beams and by delivery strategies such as fractionation [2,3]. This discipline requires competences embracing several cultural backgrounds to be interconnected. Different professionals are required to manage the complexity of the multistep process of a radiation treatment. Administration of a physical agent such as IR is intrinsically linked to machines (eg, linear accelerators), thus technologies are essen- tial for radiation oncologists. Technological advances in external beam radiotherapy with photons or charged particles as well as in brachytherapy led to high precision in dose delivery [4]. The main technological improvements in photon external beam radiotherapy regard linear accelerator (LINAC) equipment, target definition, and treatment planning systems (TPSs). The state of the art of LINAC equipment includes high performance multileaf collimators (MLCs), availability of flattening filter free beams and advanced https://doi.org/10.1053/j.seminoncol.2019.07.004 0093-7754/© 2019 Elsevier Inc. All rights reserved.