Published online May 28, 2026. doi: 10.4329/wjr.v18.i5.118851
Revised: February 12, 2026
Accepted: March 16, 2026
Published online: May 28, 2026
Processing time: 134 Days and 20.7 Hours
Radiation therapy (RT) has advanced substantially since the introduction of the first medical linear accelerator, progressing through successive generations of technological innovation that have improved treatment precision, efficiency, and patient safety. This review provides a comprehensive overview of the evolution of RT technologies-from early linear accelerators to contemporary clinical systems-and examines ongoing research shaping the future of radiotherapy. A comprehensive literature search was conducted using PubMed, Scopus, and Web of Science, covering peer-reviewed publications from the era of the first linear ac
Core Tip: This review outlines the advancement of medical accelerators over time, showing how radiation therapy (RT) has evolved from early treatment machines to modern clinical systems. It focuses on the gradual improvement in treatment accuracy, reliability, and clinical usability. The review highlights how each generation of medical accelerators contributed to better patient care by enabling more precise dose delivery, improved treatment consistency, and safer clinical practice. By presenting this chronological progression in a clear and accessible manner, the article helps readers understand how long-term technological development in medical accelerators has shaped present-day RT and continues to influence ongoing research and future directions.
- Citation: Singh P, Singh MK, Mishra A. Journey through technological advancements in radiation therapy. World J Radiol 2026; 18(5): 118851
- URL: https://www.wjgnet.com/1949-8470/full/v18/i5/118851.htm
- DOI: https://dx.doi.org/10.4329/wjr.v18.i5.118851
Radiotherapy plays a vital role in the care of patients with cancer and forms part of the management of 40% of patients cured of their disease[1]. In the past few decades, thanks to the advancement in engineering, physics and computation, radiotherapy is achieving new milestones in the field of cancer patient care. The advancements in medical accelerators have provided the freedom and opportunity to escalate the dose to increase the tumour control probability and minimise the dose to normal tissues. This advancement includes the improvement in simulation process like helical computed tomography (CT), in on-board imaging like kV, MV, cone beam CT (CBCT) imaging, in treatment planning from two-dimensional (2D) planning to 3D planning with continuous evolution of treatment planning algorithm like Anisotropic Analytical Algorithm, Superposition and convolution, Monte-Carlo etc., and marvellous advancement in the treatment delivery system which henceforth increases the precision and accuracy. Dedicated system were also introduced such as gamma knife, cyber knife etc.[2].
Currently, the precise identification of target volumes for radiotherapy treatment planning relies heavily on integrating advanced imaging techniques. Modalities such as magnetic resonance imaging (MRI) and positron emission tomography (PET) are combined with CT simulation to enhance accuracy. Additionally, image-guided techniques are becoming an essential part of clinical practice, allowing for real-time tumor localization both before and during treatment. This precision is crucial for delivering high-accuracy radiotherapy[3].
A key advancement in this field is adaptive radiotherapy (ART), which enables modifications to treatment plans during the course of therapy. ART accounts for changes in a patient’s anatomy and biological response, ensuring optimal dose delivery throughout the treatment process[4]. The future of radiation oncology will not solely depend on more advanced technology but also on a deeper understanding of tumor biology. In the near future, with the Food and Drug Administration (FDA) approval of PET-linac, biology guided tumor radiotherapy can be delivered[5]. Similarly, the innovation like FLASH therapy can revolutionize the radiotherapy practice and can add a new era to it[6]. This review tries to cover the innovations and technological advancement in medical linear accelerator and radiation therapy (RT) practices for the better tumor control with better sparing of organ at risk (OAR).
The first medical linac, developed and built by metropolitan-vickers used a 3 m long accelerating or ‘corrugated’ waveguide to produce 8 MeV X-rays. Installation of the first clinical linear accelerator began in June 1952 in the Medical Research Council Radiotherapeutic Research Unit at the Hammersmith Hospital, London, United Kingdom. It was handed over for physics and other testing in February 1953 and began treating patients on September 7, although it was not used exclusively for patient treatment[7].
Professors Kaplan and Ginzton, prominent figures in electrical engineering and physics, played a pivotal role in advancing RT with the development of the first medical linear accelerator in the Western Hemisphere, the research group Stanford University, CA, United States had developed a 6 MeV clinical linac which was installed in the Stanford Department of Radiology in 1955. This innovative technology, installed at Stanford-Lane Hospital in San Francisco, became operational in January 1956 and marked a transformative moment in oncological treatment[8]. The inaugural clinical application of this device was for a 2-year-old patient, Gordan Isaacs, diagnosed with retinoblastoma in his remaining left eye following the surgical removal of the right eye due to tumor involvement. The linear accelerator’s unprecedented precision facilitated the targeted destruction of the tumor while preserving the structural integrity of the left eye[9]. Remarkably, normal vision was restored in the treated eye, an outcome that was previously unattainable with earlier, less-focused radiation modalities. This case highlighted the potential of the linear accelerator to revolutionize radiation oncology by achieving therapeutic efficacy while minimizing collateral damage to surrounding healthy tissues. The success of this early application underscored the importance of innovation in medical physics and its direct impact on patient outcomes (Figure 1).
Conventional treatment planning also known as 2D planning is a traditional method, where the treatment is planned and delivered based on two-dimensional imaging (usually X-rays) and fixed beam angles. In this approach, treatment planning is done using X-ray images, and the radiation fields are typically created from two orthogonal views (anterior-posterior and lateral). In 2D planning, the tumor is outlined on the images, and the radiation beams are aimed at the tumor from fixed positions, based on the anatomical landmarks visible on the X-ray. The treatment typically involves multiple radiation beams directed at the tumor from different angles. However, the precision of this method is limited because it doesn't account for the 3D shape and location of the tumor or surrounding structures. The main drawback of 2D planning is its inability to conform the radiation beams to the tumor’s shape, which can result in higher doses being delivered to healthy tissues which are adjacent to the tumor.
3D conformal RT (3D-CRT) is an advanced external beam RT technique that improved the precision of tumor targeting in comparison to conventional 2D radiotherapy. With the help of three-dimensional imaging, typically from CT, MRI, or PET scans, a detailed 3D model of the tumor and surrounding healthy tissues was created. This allows for the precise shaping of radiation beams to conform to the tumor’s geometry, improving dose distribution while reducing exposure to surrounding normal structures. Compared to traditional 2D radiotherapy, which delivers radiation from fixed angles, 3D-CRT optimizes beam arrangement to deliver higher doses to the tumor while minimizing collateral damage. The radiation beams can be shaped using multileaf collimators (MLCs) manually and the beam weightage can be modified to accurately targeting tumors with sparing of OAR which significantly enhances treatment accuracy, making it especially effective for irregularly shaped tumors[10].
It is a revolutionary radiotherapy treatment technique that optimizes dose delivery by modulating beam intensity in a plane perpendicular to its direction with the help of MLC to conform precisely to the tumor shape while minimizing exposure to the healthy tissues. This technique uses the inverse planning algorithm, meaning that the algorithm creates a dose distribution using MLC to meet the user specification. In contrast to the 3D-CRT, the MLCs were shaped by an algorithm whereas in 3D-CRT, the user shapes the MLCs as per requirement. Intensity modulated RT (IMRT) systems, MLCs with 1 cm leaf widths produced fluence distributions using 1 cm × 1 cm beamlets. However, modern MLCs feature narrower leaves, enabling 5 cm × 5 mm beamlets, which enhance precision by allowing a finer resolution of dose modulation. This representation of radiation intensity is referred to as a fluence map, which serves as the foundation for IMRT planning. The goal of IMRT optimization is to generate fluence maps for each beam direction, ensuring an optimal dose distribution that maximizes tumor control while minimizing exposure to surrounding normal tissue[11,12].
From a technical perspective, one major advantage of volumetric modulated arc therapy (VMAT) over IMRT is in overall dose conformity and efficiency. In contrast to IMRT, where multiple fixed-angle beams with individually modulated intensities are used to treat the target volume, VMAT proposes to continuously deliver radiation whilst the gantry rotates around the patient. This dynamic capability to modulate the intensity of the beam, the gantry speed, and the MLC positioning enables VMAT to deliver equivalent or improved dose conformity while using lower numbers of monitor units, thereby minimising unnecessary exposure of healthy tissues to radiation. Moreover, very high dose rates of VMAT reduces overall treatment time relative to IMRT, allowing for better patient experience, especially those who cannot endure lengthy immobilizations. Although IMRT includes several static beam positions, the delivery time is longer overall compared to VMAT, which enables the delivery of the entire dose continuously from a variety of angles[13,14].
Image-guided RV (IGRT) encompasses a range of groundbreaking advancements in radiation oncology designed to address challenges associated with inter- and intra-fractional variations in tumor position. The primary objective of IGRT is to ensure that treatment is administered precisely as planned, using 3D imaging acquired during treatment simulation. These images establish a 3D anatomical reference framework, potentially incorporating motion, for both image-assisted treatment planning and real-time guidance during radiation delivery. In the planning phase, patient-specific 3D anatomy, including the tumor and adjacent OARs, is meticulously mapped to optimize dose distribution. Meanwhile, the image-guided treatment process focuses on aligning the actual tumor position with the planned treatment field by comparing pre-treatment and real-time imaging. This approach helps compensate for positional variations that occur between treatment sessions (interfractional motion) and those arising during a single treatment session (intrafractional motion), thereby enhancing delivery accuracy. The shifting position of normal tissues is often evaluated based on their proximity to the irradiated area in current IGRT methodologies. The integration of multimodal imaging like CBCT throughout the treatment process has become a crucial element, allowing precise localization and visualization of the tumor in both spatial and temporal dimensions. This ensures the accurate execution of a highly conformal treatment plan[15,16].
Stereotactic body RT (SBRT) is a technique that delivers radiation beam radiotherapy to small sized tumors while sparing adjacent tissues at very high precision and dose[17]. While traditional RT consists of repeated treatment cycles over a period of weeks or months with lower-dose sessions (usually 20-35), SBRT allows a high-dose tumor control with significant sparing of the radio-sensitive surrounding healthy tissues by achieving a greatest tumor dose target with exposure to rath era few treatments fractions (usually 1-5)[18]. Advancements in imaging, motion management strategies, and real-time tumor tracking add to the precision of SBRT, which makes it particularly effective for delivering tumor doses for tumors found in mobile organs like the lungs and liver[19]. For patients with early-stage non-small cell lung cancer who are medically inoperable or who choose not to pursue a surgical option, SBRT is the standard of care. Additionally, it has shown significant efficacy in treating both primary and metastatic tumors in the liver, pancreas, kidney, spine, and prostate[20] .Currently, there are various treatment delivery that are capable of delivering this technique which include traditional LINAC gantry like Truebeam-stx (Varian Medical systems, Inc., Paolo Alto, CA, United States) and Versa HD (Elekta, AB, Stockholm, Sweden) and other which are which doesn’t include traditional ones like cyber knife.
Adaptive RT (ART) refers to an advanced radiation treatment technique in which the radiation plan is adapted on a daily basis over the entire treatment course. Whereas classical radiotherapy is delivered according to a fixed treatment plan for the whole treatment course, ART permits treatment alterations based on real-time anatomical and physiological changes in the patient[4]. Such adaptations help to enhance treatment precision, to make sure that the tumor receives the intended dose while limiting radiation to surrounding normal tissue[21]. ART can be further sub-categorized into offline adaptation and online adaptation. Offline ART makes use of imaging data from previous sessions, most frequently MRI or CBCT, to make decisions and make some adaptive adjustments between treatment sessions. In contrast, online ART enables modifications in real-time during the treatment session with sophisticated imaging systems such as MRI-guided RT (MRgRT). This is especially important for tumors in organs subject to motion like the lungs, liver or prostate[22].
Imaging plays a pivotal role in radiotherapy. Radiotherapy mainly consist of five parts which includes simulation, contouring, treatment planning, patient setup verification and response assessment. In the first step, we need to acquire information on patient anatomy, in the early days this used to be done with the help of 2D imaging but only 2D imaging with poor soft tissue information is not enough, and thus the need of 3D imaging arises which is fulfilled by CT (Figure 2).
CT is the 3D imaging technique which is widely acceptable and provides the 3D volumetric information with better resolution. As these images were only used for planning and treatment delivery, the CT machine specifications are quite different from conventional diagnostic CT[23]. In the second step i.e., in contouring, different types of imaging modalities were used to delineate the Target and the OARs like CT, MRI, PET etc., these different imaging serves different purposes for example if we have to delineate in the soft tissue region or region having similar densities MRI is the best option, but to delineate based on the radioactive uptake PET is the best option[24]. In the third step of treatment planning commonly CT images were used, but with the evolution of MRI linac, MRI images were also used for treatment planning[25]. In the fourth step of patient setup verification multiple types of imaging can be used based on machine or site for example MV imaging, room mounted KV X-ray imaging, traditional multi-slice CT scanners integrated ‘on rails’ with gantry linear accelerator and KV or MV CBCT scanner with flat-panel technology[26]. In CBCT technique, multiple 2D images were obtained by cone shaped X-ray beams from a KV (X-ray) or a MV (linear accelerator beam) source while the gantry rotates around the patient. A 3D image set is then reconstructed using those planar images. In final stage of response assessment CT, MRI, PET and single photon emission CT is done. Thus, integration of imaging during the whole process is important.
One of the major challenges in neurosurgery is the treatment of inoperable or deeply located brain tumors, especially those near critical structures like the brainstem and optic nerves. Gamma knife radiosurgery addresses this by delivering highly focused gamma radiation with sub-millimeter precision, minimizing damage to surrounding healthy tissue and reducing complications such as bleeding and infection. This non-invasive alternative to traditional brain surgery has transformed the management of various brain disorders. The first stereotactic Gamma Unit, using Cobalt 60, was installed at the Sophiahemmet Hospital in 1968 and was primarily intended for use in functional brain surgery for the section of deep fibre tracts or nuclei. The lesions were disc shaped and very sharply circumscribed. This apparatus was also used for the irradiation of some tumours and arteriovenous malformations. The results were promising and a second Gamma Unit, with more generally suitable spherical fields of radiation, was constructed and installed at the Karolinska Hospital in Stockholm in 1974[27] (Figure 3).
By the 1980s, third and fourth gamma knife units using 201 Co-60 sources were established in Argentina and England, respectively. In 1987, the fifth gamma knife system was installed at the University of Pittsburgh Medical Center, a milestone in expanding clinical radiosurgery applications[28]. Elekta are mains the sole manufacturer, with its latest model, the gamma knife icon (2015), featuring frameless treatment options, adaptive planning, and real-time motion monitoring. Gamma knife technology has evolved significantly, now integrating MRI, CT, and angiography with advanced treatment planning software for precise tumor localization. Modern systems incorporate a stereotactic coordinate system and an automatic positioning system to align radiation beams with exceptional accuracy[29]. Safety is enhanced with interlock mechanisms and lead shielding to limit radiation exposure to healthy tissues. Today, India hosts more than eight institutions offering gamma knife radiosurgery, increasing national access to this highly precise therapeutic modality
The cyber knife system emerged as a ground breaking alternative to traditional radiosurgery methods like the gamma knife, which required invasive immobilization frames. Conceived by Dr. John R Adler in the late 1980s, cyber knife aimed to deliver precise RT without rigid head frames[30]. Developed in collaboration with Schoderg Radiation Corporation, the first system was installed at Stanford University in 1991. While FDA approval for clinical investigation was granted in 1994, approvals for intracranial tumor treatment and whole-body tumor treatment followed years later.
Since its inception, cyber knife has undergone significant technological advancements. The original model (1994) introduced frameless robotic radiosurgery for intracranial tumors, revolutionizing precision treatments[31]. The G3 (2005) and G4 (2007) models improved imaging and targeting accuracy, enhancing treatment efficiency and patient comfort. By 2009, the VSI model expanded cyber knife’s capabilities to extracranial tumors, incorporating advanced tumor tracking systems. The M6 (2012) introduced multileaf collimation, allowing faster treatments with increased flexibility[32] (Figure 4).
The latest model, cyber knife S7 (2020), integrates advanced imaging with real-time motion synchronization, further improving precision in treating tumors affected by motion, such as those in the lungs and abdomen. Cyber knife’s evolution has led to sub-millimeter accuracy, real-time tumor tracking, Monte Carlo dose calculations, and seamless CT, MRI, and PET integration[33]. The Robo Couch positioning system offers seven degrees of freedom, ensuring precise alignment. These innovations have solidified cyber knife’s role as a leading-edge radiotherapy solution, delivering highly targeted, patient-specific treatments while minimizing damage to surrounding tissues.
Charged particle therapy has emerged as a transformative modality in radiation oncology, leveraging advances in accelerator technology to deliver precision-targeted and biologically potent treatments. From the early use of neutrons to the widespread clinical adoption of protons and the emerging potential of carbon ions, the role of accelerators has been central to the evolution of therapeutic radiation delivery[34,35].
The history of particle therapy begins with neutron radiation, an early application of high linear energy transfer (LET) radiation. Neutrons themselves are uncharged and cannot be accelerated directly; instead, they are generated through nuclear reactions when high-energy protons or deuterons, accelerated by cyclotrons, strike beryllium or lithium targets. The invention of the cyclotron in 1930 by Ernest O Lawrence was a pivotal breakthrough, enabling the production of therapeutic neutron beams. In 1938, the Lawrence Berkeley Laboratory initiated the first clinical neutron therapy trials. Neutron therapy gained clinical traction in the 1970s and 1980s, particularly for treating radioresistant malignancies such as salivary gland carcinomas and soft tissue sarcomas[34].
However, despite its biological advantages, neutron therapy faced significant limitations. The absence of a Bragg peak resulted in suboptimal dose localization and an elevated risk of normal tissue toxicity. The emergence of CT-based planning and photon-based conformal techniques such as IMRT and IGRT further diminished its clinical utility. By the 1990s, most neutron therapy centers had ceased operation, though the modality’s contributions to high-LET radiobiology and accelerator development were foundational[35].
The clinical viability of proton therapy was first articulated by Robert R Wilson in 1946, who proposed that protons could be used therapeutically due to their distinct depth-dose distribution. The Bragg peak characteristic of protons allows for high-dose deposition at a specific depth with minimal exit dose, thereby reducing exposure to surrounding healthy tissue. Initial clinical treatments employed research-grade fixed-field cyclotrons at facilities such as Harvard and Berkeley. These machines, capable of accelerating protons to energies of 70-250 MeV, enabled treatment of deep-seated tumors but were not purpose-built for clinical care[34,36] (Figure 5).
The establishment of the first hospital-based proton therapy center at Loma Linda University Medical Center in 1990 marked a turning point. The facility utilized a synchrotron developed by Fermi National Accelerator Laboratory, integrating rotating gantries and passive scattering techniques into a clinically optimized infrastructure. Subsequent innovations led to the development of compact superconducting cyclotrons and synchrocyclotrons, which have enabled broader implementation of proton therapy in both academic and community settings[36].
The clinical capabilities of proton therapy have expanded through the adoption of pencil beam scanning and intensity-modulated proton therapy, which provide enhanced conformality and treatment versatility. As of 2024, more than 150000 patients have received proton therapy globally, with over 56 centers in operation. Proton therapy has demonstrated particular benefit in pediatric oncology, skull base tumors, and reirradiation cases, where sparing of normal tissues is paramount[34,35].
While proton therapy offers physical precision, carbon ion therapy (CIRT) introduces both physical and biological advantages. Carbon ions are heavier and possess higher charge than protons, resulting in higher LET and a relative biological effectiveness of approximately 2.5-3.0. These characteristics enable superior tumor control, especially in hypoxic and radioresistant cancers. The clinical implementation of carbon ion therapy requires more sophisticated acceleration systems, as heavier particles necessitate higher energy and precise modulation[35,37].
The first clinical facility dedicated to CIRT was established in 1994 at the National Institute of Radiological Sciences in Japan. The Heavy Ion Medical Accelerator in Chiba (HIMAC) employed a dual synchrotron system capable of accelerating carbon ions to energies up to 430 MeV/u. HIMAC demonstrated the feasibility of delivering CIRT with high spatial precision and efficient treatment of deep-seated tumors. The therapy’s steep dose gradients and biologically weighted damage mechanisms facilitated effective hypo-fractionated regimens for a variety of malignancies, including pancreatic cancer, bone sarcomas, and skull base chordomas[37] (Figure 6).
Since HIMAC, additional carbon ion therapy centers have been established in Germany (Heidelberg Ion-Beam Therapy Center), Italy (CNAO), China (SPHIC), and Austria (Med Austron). To date, over 30000 patients have been treated with CIRT. Despite its advantages, the widespread adoption of CIRT has been constrained by the size, complexity, and cost of synchrotron-based systems. However, ongoing research into laser-driven acceleration, superconducting magnets, and multi-ion synchrotrons aims to reduce the economic and infrastructural barriers to expansion[35,37].
Collectively, the advancement of accelerator systems has been fundamental to the success of charged particle therapy. The transition from laboratory-scale cyclotrons to clinically integrated synchrotrons has enabled higher precision, improved treatment outcomes, and expanded accessibility. Modern systems are increasingly incorporating real-time imaging, adaptive planning, and biologically guided treatment protocols. Furthermore, developments in artificial intelligence (AI) and automation promise to further refine treatment planning and delivery[34,37].
In conclusion, the trajectory of charged particle therapy is deeply intertwined with the evolution of accelerator technology. Each modality-neutron, proton, and carbon ion therapy-has contributed uniquely to our understanding of radiation biology and clinical oncology. As the technology continues to advance, the future of RT is poised to become more precise, efficient, and biologically personalized, offering new hope for patients with complex or treatment-resistant cancers.
Integration of imaging modalities in RT has consistently aimed to enhance precision and adaptability, particularly in the visualization and treatment of soft tissues and regions with low electron density. Traditional imaging techniques, such as cone-beam CBCT, face challenges in providing sufficient soft tissue contrast and differentiating tumor margins from healthy tissues. Addressing this limitation, the advent of magnetic resonance-linac offers a significant advancement. MRI, first conceptualized by Lauterbur[38] in 1973, has demonstrated superior soft tissue contrast and the ability to detect subtle physiological changes. This capability makes MRI an invaluable tool in oncology for tumor localization and treatment planning. By integrating MRI with linear accelerator, the magnetic resonance-linac system combines real-time imaging with precise radiation delivery, enabling MRgRT[39]. This innovative approach allows for adaptive treatment planning and improved outcomes, particularly for tumors located in anatomically complex regions[40].
The first clinically active MRgRT device, ViewRay, was installed at the Alvin J. Siteman Cancer Center based at Barnes-Jewish Hospitaland Washington University in St. Louis, United States, and became operational in 2014. This initial system utilized a 0.35 T magnet with three Co-60 heads arranged in a circular gantry[23]. Although effective, subsequent advancements replaced the Co-60 sources with a 6 MV linear accelerator, significantly enhancing its therapeutic precision[41]. Building upon this foundation, the first technical prototype magnetic resonance-LINAC was developed and installed at the University Medical Center Utrecht, The Netherlands, and became operational in May 2017. Elekta’s Unity system, which featured a 1.5 T magnet coupled with a 6 MV linear accelerator, marked a milestone in MRgRT by performing the first human treatments[40,42].
AI is revolutionizing RT, leading to significant advancements in precision, efficiency, and personalized treatment. AI-driven contouring automates the delineation of target volumes and organs at risk, reducing inter-observer variability and enhancing accuracy[43]. Machine learning algorithms optimize dose prediction and distribution, maximizing tumor control probability while minimizing normal tissue complication probability[44] (Figure 7).
AI facilitates real-time ART by enabling treatment plan modification based on daily anatomical variations[45]. In image-guided radiotherapy, AI-powered motion management enhances targeting precision, especially for tumors subject to respiratory or other physiological motion[46]. AI also augments quality assurance by detecting machine deviations, reducing linac downtime, and mitigating treatment errors[47]. Knowledge-based planning utilizes AI to learn from prior treatment data, optimizing plan generation efficiency[48]. Automated treatment planning reduces manual workload and accelerates plan turnaround time. AI-driven automated plan adaptation ensures accurate radiation delivery despite patient-specific anatomical and physiological changes. Furthermore, AI optimizes workflow efficiency, streamlining radiotherapy operations and improving patient through put, ultimately leading to improved patient outcomes.
These advancements translate to enhanced treatment precision through highly accurate dose distributions, reduced treatment planning time due to automation, real-time adaptation of radiation delivery based on anatomical changes, improved machine maintenance and quality assurance via predictive analytics, and standardization with reduced variability in contouring and treatment planning.
Innovation in radiotherapy always craves for increase in tumor control probability with less harmful effect of radiation of normal tissue, to achieve this FLASH radiotherapy is one of the most promising approaches based on the normal tissue sparing effects of ultra-high dose rate (UHDR) irradiation. Although it is still in the research phase and several clinical trials are ongoing, once the potential of FLASH RT is confirmed in clinical trials, this can revolutionize the field of radiotherapy. In FLASH RT the UHDR irradiation with a magnitude higher than the conventional RT is used (≥ 40 Gy/second in FLASH RT vs ≤ 0.03 Gy/second in conventional RT)[49]. Flash radiotherapy can be delivered by different beam categories, including electron beam, photon beams, proton beams and heavier ions. Each type of beam has its characteristics. Firstly, electron beams, which have an excellent ability to control dose distribution, deliver treatment swiftly and stand as a safe and effective treatment modality for skin or superficial tissue tumors such as skin cancer, cutaneous melanoma, and lymphoma[50]. Whereas in comparison to the electron beam, the cost of photon beam equipment technology is notably higher, which has also decreased its adaptability for research and clinical trials, the photon beam exhibit an extraordinary tissue penetration capability, enabling effective penetration into the deep-seated tumor tissues. The next beam category is proton beam, which leverages the Bragg-peak phenomena, by enhancing the accuracy and efficacy by allowing dose escalation while minimising the dose to the near organs. Several research have suggested the superiority of proton over photon in tumor control[50]. But in case of heavy ions, there is still limited researcher who actively does research on heavy ion FLASH RT.
Treating multiple tumors or legions usually comes into the palliative intent category, to ease out the symptoms and relieve the pain. And there are some evidences stating that the ablation of these metastatic tumors through localized RT can increase the overall survival in combination with other therapies. For the ablation of the multiple tumors, the conventional radiation treatment is not sufficient as motion management of tumors, toxicity of normal tissue, etc. plays a vital role, thus a need of innovation or technique arises which can help out or can increase the therapeutic ratio[5].
Then, in 2017, the most revolutionary innovation in radiotherapy came: PET-linac. A PET-linac combines the functional imaging capabilities of PET with the precise radiation delivery of a linac in a single system. This advanced integration aims to enhance the accuracy and efficacy of RT by using real-time biological and metabolic data to guide treatment[51].
RefleXion Medical developed and demonstrated the prototype, RefleXion X1, a system combining PET with linac technology in2017. It is built around a 6 MV flattening-filter-free linear accelerator, which is mounted on an 85 cm O-ring gantry that rotates at 60 RPM. The system features dual 90° arcs of state-of-the-art PET detectors that work in conjunction with a 64-leaf binary MLC, where each leaf transitions at 100 Hz to shape the radiation beam precisely[52].
The system uses two sets of jaws above and below the MLCs, which control the maximum field extent in the superior-inferior direction, offering either 1 cm or 2 cm at the isocenter. To enhance treatment accuracy, the X1 integrates several imaging subsystems, including a kV fan-beam CT scanner for patient setup and a MV detector for quality assurance (Figure 8).
Additionally, the integration of PET enables biologically guided RT (BGRT), where real-time PET imaging helps precisely target metabolically active tumor regions. This is distinct from other treatment techniques like IMRT and SBRT, which rely on different imaging and treatment strategies. In BGRT, the use of PET guidance allows for adaptive therapy during the treatment process. The system delivers radiation axially with the patient couch advancing 2.1 mm between beam stations, in contrast to systems like Tomotherapy, which uses helical delivery. The X1 is capable of performing three treatment modes: IMRT, SBRT, and BGRT. Currently, in year 2020, IMRT and SBRT modes have received the FDA approval for treatment but the BGRT mode is still in the research phase[5,52].
As year of 2023 IAEA data, the global distribution of cancer treatment equipment highlights significant disparities in access to radiotherapy across income groups and geographic regions. High-income countries dominate in the availability of radiotherapy centers and equipment, with 62 out of 75 having RT facilities and a total of 9545 radiotherapy machines. In contrast, low-income countries have only 15 out of 29 countries with radiotherapy facilities, possessing just 40 machines. The disparity extends to middle-income nations, where upper-middle-income countries have 4033 machines, while lower-middle-income countries have only 1616. Regional disparities further illustrate this imbalance. North America has the highest equipment availability, with 11.301 machines per million people, followed by Western Europe (7.090) and Southern and Western Pacific (5.808). Conversely, Middle Africa has the lowest density, with only 0.080 machines per million people, followed by South Asia (0.432) and Southeast Asia (0.677), reflecting limited access to radiotherapy services (Figure 9).
India’s licensed cancer equipment with AERB as of the year 2023 reflects both progress and gaps in radiotherapy infrastructure. The availability of key radiation oncology devices is crucial in addressing the growing cancer burden in the country. According to the provided data, India has a significant number of remote after loading brachytherapy units (381) and medical accelerators (751), which play a central role in delivering effective RT. The presence of 165 CT simulators further strengthens treatment planning capabilities, ensuring accurate dose delivery to patients.
However, the distribution of advanced RT equipment remains a challenge. While medical accelerators are widely available, the number of high-precision devices like cyber knife (13) and gamma knife (7) remains extremely low, limiting access to specialized treatments like stereotactic radiosurgery (SRS). Similarly, the availability of tomotherapy units (36) and intraoperative RT (3) is inadequate compared to the demand. The presence of 156 telecobalt units highlights India's reliance on older RT technology, which is still operational in many centers due to cost-effectiveness and accessibility[53,54].
The overall scenario indicates a growing emphasis on modern radiotherapy equipment, yet accessibility remains uneven across different regions, particularly in rural and economically weaker areas.
The history of radiotherapy reflects a continuous trajectory of innovation aimed at improving tumor control while minimizing toxicity to surrounding normal tissues. The introduction of medical linacs in the 1950s marked a trans
Subsequent decades witnessed significant technological refinement. The emergence of 3D-CRT represented a major step toward anatomically guided dose delivery, which was further advanced by IMRT and VMAT. These techniques enabled highly conformal dose distributions and efficient treatment delivery, particularly for complex tumor geometries. In parallel, advances in imaging modalities-including CT, MRI, and PET-fundamentally transformed radiotherapy planning and verification. The integration of these imaging techniques into clinical workflows led to the development of IGRT and ART, allowing treatment plans to be modified in response to anatomical and biological changes occurring during therapy.
The introduction of SRS and stereotactic body radiotherapy (SBRT) further expanded the precision radiotherapy paradigm by enabling the delivery of ablative doses with sub-millimeter accuracy. These approaches have proven particularly valuable for small, well-defined tumors and lesions located near critical structures. More recently, particle therapy, including proton and CIRT, has gained prominence due to its distinct physical dose characteristics and enhanced radiobiological effectiveness. Although resource-intensive, these modalities offer substantial advantages for selected clinical indications and represent an important frontier in precision radiotherapy.
Currently, AI, machine learning, and automation are redefining radiotherapy practice. AI-driven applications such as automated target and organ-at-risk contouring, dose prediction, plan optimization, and predictive modeling of tumor control probability and normal tissue complication probability are enabling a shift toward adaptive and personalized treatment strategies. These technologies have the potential to reduce inter-operator variability, improve workflow efficiency, and support data-driven clinical decision-making. However, their successful clinical implementation depends on rigorous validation, robust quality assurance frameworks, and transparent model interpretability to ensure patient safety and clinical reliability.
Looking ahead, future radiotherapy is expected to move toward biologically guided and outcome-adaptive treatment paradigms. Integration of radiomics, genomics, and functional imaging with AI-based models may enable real-time personalization of dose prescriptions based on individual tumor biology and treatment response. The development of digital twins and adaptive feedback systems could further refine treatment strategies by continuously learning from patient-specific data. Additionally, advances in automation and remote planning may facilitate knowledge sharing and centralized expertise, offering new opportunities to improve care delivery in resource-limited settings.
Despite these promising developments, significant challenges remain in ensuring equitable access to advanced radiotherapy technologies. Globally, more than 70% of cancer patients are estimated to require radiotherapy at some stage of their treatment, yet access remains severely limited in many low- and middle-income countries. In India, where the cancer burden continues to rise, disparities in infrastructure availability, trained workforce distribution, and access to advanced technologies persist. Addressing these challenges will require coordinated efforts involving government policy, private sector investment, workforce training, and the adoption of cost-effective technological solutions tailored to regional needs.
In conclusion, the progression from early linac-based systems to AI-driven ART underscores radiotherapy’s dual trajectory of rapid technological advancement and enduring responsibility toward equitable, patient-centered care. Future progress must balance innovation with accessibility, ensuring that emerging technologies translate into mean
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