Radiotherapy aims to achieve a high tumor control probability while minimizing damage to normal tissues. Personalizing radiotherapy treatments for individual patients, therefore, depends on integrating physical treatment planning with predictive models of tumor control and normal tissue complications. Predictive models could be improved using a wide range of rich data sources, including tumor and normal tissue genomics, radiomics, and dosiomics. Deep learning will drive improvements in classifying normal tissue tolerance, predicting intra-treatment tumor changes, tracking accumulated dose distributions, and quantifying the tumor response to radiotherapy based on imaging. Mechanistic patient-specific computer simulations ('digital twins') could also be used to guide adaptive radiotherapy. Overall, we are entering an era where improved modeling methods will allow the use of newly available data sources to better guide radiotherapy treatments.

To further optimize radiotherapy, a more personalized treatment towards individual patient's risk profiles, dissecting both patient-specific tumor and normal tissue response to multimodality treatments is needed. Novel developments in radiobiology, using in vitro patient-specific complex tissue resembling 3D models and multiomics approaches at a spatial single-cell level, may provide unprecedented insight into the radiation responses of tumors and normal tissue. Here, we describe the necessary team effort, including all disciplines in radiation oncology, to integrate such data into clinical prediction models and link the relatively "big data" from the clinical practice, allowing accurate patient stratification for personalized treatment approaches.

The fusion of cutting-edge imaging technologies with radiation therapy (RT) has catalyzed transformative breakthroughs in cancer treatment in recent decades. It is critical for us to review our achievements and preview into the next phase for future synergy between imaging and RT. This paper serves as a review and preview for fostering collaboration between these two domains in the forthcoming decade. Firstly, it delineates ten prospective directions ranging from technological innovations to leveraging imaging data in RT planning, execution, and preclinical research. Secondly, it presents major directions for infrastructure and team development in facilitating interdisciplinary synergy and clinical translation. We envision a future where seamless integration of imaging technologies into RT will not only meet the demands of RT but also unlock novel functionalities, enhancing accuracy, efficiency, safety, and ultimately, the standard of care for patients worldwide.

Data demonstrates that hypofractionation is increasingly utilized based on evidence-based guidelines. The outdated Medicare fee-for-service approach penalizes radiation oncology (RO) practices from adopting hypofractionation, even as many patients benefit. To address the flawed fee-for-service payment system, which rewards volume over value, ASTRO introduced the Radiation Oncology Case Rate (ROCR) Value-Based Payment Program. ROCR shifts payment for RO services from fee-for-service to payment per patient or per episode. To address disparities, ROCR provides an evidence-based approach through the Health Equity Achievement in Radiation Therapy (HEART) initiative, providing transportation assistance payment for the underserved. Additionally, ROCR allows practices sufficient capital to maintain existing equipment and invest in new technology. This increases patient access to technological advancements allowing for more efficient, targeted, and personalized care with improved patient outcomes at a lower overall cost.

The implementation and early adoption of online adaptive radiotherapy (oART) has required the presence of clinicians, physicists and radiation therapists (RTT) at the treatment console. The impact on each of them is unique to their profession and must be considered for safe and efficient implementation. In the short term future, widespread adoption will depend on the development of innovative workflows, and rethinking of traditional roles and responsibilities may be required. For the future, technologies such as artificial intelligence promise to change the workflow significantly in terms of speed, automation and decision-making. However, overall communication within the team will persist in being one of the most important aspects.

The increasing complexity of radiation therapy treatment presents new potentials for error and suboptimal care. High-performing programs thus not only require adherence to, but also ongoing improvement of, key safety and quality practices. In this article, we review these practices including standardization, risk analysis, peer review, and maintenance of strong safety culture, while also describing recent innovations and promising future directions. We specifically highlight the growing role of artificial intelligence in radiation oncology, both as a tool to deliver safe, high-quality care and as a potential new source of safety challenges.

With more treatment options in oncology lead to better outcomes and more favorable side effect profiles, patients are living longer-with higher quality of life-than ever, with a growing survivor population. As the needs of patients and providers evolve, and technology advances, cancer care is subject to change. This review explores the myriad of changes in the current oncology landscape with a focus on the patient perspective and patient-centered care.

Telemedicine allows providers and patients to communicate without being in the same room through video platforms or telephone. Like the increased use of telework for businesses, telemedicine exploded during the pandemic. While many workplaces and clinics have returned to some level of in-person interactions, the convenience and comfort have given telemedicine staying power. Patients can be seen from the comfort of their homes; family members can join from the same or a different location. Driving, obtaining childcare, or taking time off from work is unnecessary. Pediatric patients' parents can pull them into the conversation at appropriate times and avoid the awkwardness of having them leave for portions of the discussion. Because virtual visits are more efficient for everyone, they can often be scheduled sooner than an in-person visit. While not every visit can be done without the patient physically with the provider, many can. This is particularly true for cancer patients, who often have several visits with multiple providers. For immunocompromised patients, there is an added benefit of avoiding exposure from travel and a hospital visit. Oncology and radiation oncology practices have widely adopted telemedicine. While legal and logistical barriers exist in some areas of the world, these are sure to be resolved to make this medicine feasible for all in the modern era.

Radiation oncology caregivers worldwide are dedicated to advancing cancer treatment with the ultimate goal of eradicating the disease. Recognizing the inherent complexity of cancer treatment using hypo-fractionation radiotherapy (HFRT), these caregivers are committed to exploring avenues for progress and providing personalized care to each patient. Strong teams and effective workflows are an essential component to implementing safe HFRT. Every patient presents unique challenges, and as a united team of clinical and administrative professionals, radiation oncology care teams strive to drive advancements and streamline complexities in their field, guided by continuous technological innovation.

There has long existed a substantial disparity in access to radiotherapy globally. This issue has only been exacerbated as the growing disparity of cancer incidence between high-income countries (HIC) and low and middle-income countries (LMICs) widens, with a pronounced increase in cancer cases in LMICs. Even within HICs, iniquities within local communities may lead to a lack of access to care. Due to these trends, it is imperative to find solutions to narrow global disparities. This requires the engagement of a diverse cohort of stakeholders, including working professionals, non-governmental organizations, nonprofits, professional societies, academic and training institutions, and industry. This review brings together a diverse group of experts to highlight critical areas that could help reduce the current global disparities in radiation oncology. Advancements in technology and treatment, such as artificial intelligence, brachytherapy, hypofractionation, and digital networks, in combination with implementation science and novel funding mechanisms, offer means for increasing access to care and education globally. Common themes across sections reveal how utilizing these new innovations and strengthening collaborative efforts among stakeholders can help improve access to care globally while setting the framework for the next generation of innovations.

Treating radioresistant and bulky tumors is challenging due to their inherent resistance to standard therapies and their large size. GRID and lattice spatially fractionated radiation therapy (simply referred to GRID RT and LRT) offer promising techniques to tackle these issues. Both approaches deliver radiation in a grid-like or lattice pattern, creating high-dose peaks surrounded by low-dose valleys. This pattern enables the destruction of significant portions of the tumor while sparing healthy tissue. GRID RT uses a 2-dimensional pattern of high-dose peaks (15-20 Gy), while LRT delivers a three-dimensional array of high-dose vertices (10-20 Gy) spaced 2-5 cm apart. These techniques are beneficial for treating a variety of cancers, including soft tissue sarcomas, osteosarcomas, renal cell carcinoma, melanoma, gastrointestinal stromal tumors (GISTs), pancreatic cancer, glioblastoma, and hepatocellular carcinoma. The specific grid and lattice patterns must be carefully tailored for each cancer type to maximize the peak-to-valley dose ratio while protecting critical organs and minimizing collateral damage. For gynecologic cancers, the treatment plan should align with the international consensus guidelines, incorporating concurrent chemotherapy for optimal outcomes. Despite the challenges of precise dosimetry and patient selection, GRID RT and LRT can be cost-effective using existing radiation equipment, including particle therapy systems, to deliver targeted high-dose radiation peaks. This phased approach of partial high-dose induction radiation therapy with standard fractionated radiation therapy maximizes immune modulation and tumor control while reducing toxicity. Comprehensive treatment plans using these advanced techniques offer a valuable framework for radiation oncologists, ensuring safe and effective delivery of therapy for radioresistant and bulky tumors. Further clinical trials data and standardized guidelines will refine these strategies, helping expand access to innovative cancer treatments.

Spatially fractionated radiation therapy (SFRT), also known as the GRID and LATTICE radiotherapy (GRT, LRT), the concept of treating tumors by delivering a spatially modulated dose with highly non-uniform dose distributions, is a treatment modality of growing interest in radiation oncology, physics, and radiation biology. Clinical experience in SFRT has suggested that GRID and LATTICE therapy can achieve a high response and low toxicity in the treatment of refractory and bulky tumors. Limited initially to GRID therapy using block collimators, advanced, and versatile multi-leaf collimators, volumetric modulated arc technologies and particle therapy have since increased the capabilities and individualization of SFRT and expanded the clinical investigation of SFRT to various dosing regimens, multiple malignancies, tumor types and sites. As a 3D modulation approach outgrown from traditional 2D GRID, LATTICE therapy aims to reconfigure the traditional SFRT as spatial modulation of the radiation is confined solely to the tumor volume. The distinctively different beam geometries used in LATTICE therapy have led to appreciable variations in dose-volume distributions, compared to GRID therapy. The clinical relevance of the variations in dose-volume distribution between LATTICE and traditional GRID therapies is a crucial factor in determining their adoption in clinical practice. In this Point-Counterpoint contribution, the authors debate the pros and cons of GRID and LATTICE therapy. Both modalities have been used in clinics and their applicability and optimal use have been discussed in this article.

A large proportion of cancer patients present with unresectable bulky disease at baseline or following treatment failure. The data available in the literature suggest that the vast majority of these patients do not benefit from available standard therapies. Therefore the clinical outcomes are poor; patients are desperate and usually relegated to palliative or best supportive care as the only options. Large tumor masses are usually hypoxic, resistant to radiation and systemic therapy, with extensive regional infiltration of the surrounding critical organs, the presence of which makes it impossible to deliver a radical dose of radiation. Promising data in terms of improved therapeutic ratio where such complex tumors are concerned can be seen with the use of new emerging unconventional radiotherapy techniques known as spatially fractionated radiotherapies (SFRT). One of them is PATHY, or PArtial Tumor irradiation targeting HYpoxic segment, which is characterized by a very short treatment course offering a large spectrum of therapeutic benefits in terms of the symptom relief, quality of life, local tumor control, neoadjuvant and immunomodulatory effects.

Radiation treatment has been the cornerstone in cancer management. However, long term treatment-related morbidity always accompanies tumor control which has significant impact on quality of life of the patient who has survived the cancer. Spatially fractionated radiation has the potential to achieve both cure and to avoid dreaded long term sequelae. The first ever randomized study of mini-beam radiation treatment (MBRT) of canine brain tumor has clearly shown the ability to achieve this goal. Dogs have gyrencephalic brains functionally akin to human brain. We here report long term follow-up and final outcome of the dogs, revealing both tumor control and side effects on normal brain. The results augur potential for conducting human studies with MBRT.

FLASH radiotherapy (RT) is emerging as a potentially revolutionary advancement in cancer treatment, offering the potential to deliver RT at ultra-high dose rates (>40 Gy/s) while significantly reducing damage to healthy tissues. Democratizing FLASH RT by making this cutting-edge approach more accessible and affordable for healthcare systems worldwide would have a substantial impact in global health. Here, we review recent developments in FLASH RT and present perspective on further developments that could facilitate the democratizing of FLASH RT. These include upgrading and validating current technologies that can deliver and measure the FLASH radiation dose with high accuracy and precision, establishing a deeper mechanistic understanding of the FLASH effect, and optimizing dose delivery conditions and parameters for different types of tumors and normal tissues, such as the dose rate, dose fractionation, and beam quality for high efficacy. Furthermore, we examine the potential for democratizing FLASH radioimmunotherapy leveraging evidence that FLASH RT can make the tumor microenvironment more immunogenic, and parallel developments in nanomedicine or use of smart radiotherapy biomaterials for combining RT and immunotherapy. We conclude that the democratization of FLASH radiotherapy represents a major opportunity for concerted cross-disciplinary research collaborations with potential for tremendous impact in reducing radiotherapy disparities and extending the cancer moonshot globally.

The "FLASH effect" is an increased therapeutic index, that is, reduced normal tissue toxicity for a given degree of anti-cancer efficacy, produced by ultra-rapid irradiation delivered on time scales orders of magnitude shorter than currently conventional in the clinic for the same doses. This phenomenon has been observed in numerous preclinical in vivo tumor and normal tissue models. While the underlying biological mechanism(s) remain to be elucidated, a path to clinical implementation of FLASH can be paved by addressing several critical translational questions. Technological questions pertinent to each beam type (eg, electron, proton, photon) also dictate the logical progression of experimentation required to move forward in safe and decisive clinical trials. Here we review the available preclinical data pertaining to these questions and how they may inform strategies for FLASH cancer therapy clinical trials.