A Century of Fractionated Radiotherapy: How Mathematical Oncology Can Break the Rules.

Radiotherapy is involved in 50% of all cancer treatments and 40% of cancer cures. Most of these treatments are delivered in fractions of equal doses of radiation (Fractional Equivalent Dosing (FED)) in days to weeks. This treatment paradigm has remained unchanged in the past century and does not account for the development of radioresistance during treatment. Even if under-optimized, deviating from a century of successful therapy delivered in FED can be difficult. One way of exploring the infinite space of fraction size and scheduling to identify optimal fractionation schedules is through mathematical oncology simulations that allow for in silico evaluation. This review article explores the evidence that current fractionation promotes the development of radioresistance, summarizes mathematical solutions to account for radioresistance, both in the curative and non-curative setting, and reviews current clinical data investigating non-FED fractionated radiotherapy.

MR-guided radiotherapy for prostate cancer: state of the art and future perspectives.

Advances in radiotherapy technology have increased precision of treatment delivery and in some tumour types, improved cure rates and decreased side effects. A new generation of radiotherapy machines, hybrids of an MRI scanner and a linear accelerator, has the potential to further transform the practice of radiation therapy in some cancers. Facilitating superior image quality and the ability to change the dose distribution online on a daily basis (termed "daily adaptive replanning"), MRI-guided radiotherapy machines allow for new possibilities including increasing dose, for hard to treat cancers, and more selective sparing of healthy tissues, where toxicity reduction is the key priority.These machines have already been used to treat most types of cancer, although experience is still in its infancy. This review summarises the potential and current evidence for MRI-guided radiotherapy, with a predominant focus on prostate cancer. Current advantages and disadvantages are discussed including a realistic appraisal of the likely potential to improve patient outcomes. In addition, horizon scanning for near-term possibilities for research and development will hopefully delineate the potential role for this technology over the next decade.

Magnetic resonance linear accelerator technology and adaptive radiation therapy: An overview for clinicians.

Radiation therapy (RT) continues to play an important role in the treatment of cancer. Adaptive RT (ART) is a novel method through which RT treatments are evolving. With the ART approach, computed tomography or magnetic resonance (MR) images are obtained as part of the treatment delivery process. This enables the adaptation of the irradiated volume to account for changes in organ and/or tumor position, movement, size, or shape that may occur over the course of treatment. The advantages and challenges of ART maybe somewhat abstract to oncologists and clinicians outside of the specialty of radiation oncology. ART is positioned to affect many different types of cancer. There is a wide spectrum of hypothesized benefits, from small toxicity improvements to meaningful gains in overall survival. The use and application of this novel technology should be understood by the oncologic community at large, such that it can be appropriately contextualized within the landscape of cancer therapies. Likewise, the need to test these advances is pressing. MR-guided ART (MRgART) is an emerging, extended modality of ART that expands upon and further advances the capabilities of ART. MRgART presents unique opportunities to iteratively improve adaptive image guidance. However, although the MRgART adaptive process advances ART to previously unattained levels, it can be more expensive, time-consuming, and complex. In this review, the authors present an overview for clinicians describing the process of ART and specifically MRgART.

Moving Forward in the Next Decade: Radiation Oncology Sciences for Patient-Centered Cancer Care.

In a time of rapid advances in science and technology, the opportunities for radiation oncology are undergoing transformational change. The linkage between and understanding of the physical dose and induced biological perturbations are opening entirely new areas of application. The ability to define anatomic extent of disease and the elucidation of the biology of metastases has brought a key role for radiation oncology for treating metastatic disease. That radiation can stimulate and suppress subpopulations of the immune response makes radiation a key participant in cancer immunotherapy. Targeted radiopharmaceutical therapy delivers radiation systemically with radionuclides and carrier molecules selected for their physical, chemical, and biochemical properties. Radiation oncology usage of "big data" and machine learning and artificial intelligence adds the opportunity to markedly change the workflow for clinical practice while physically targeting and adapting radiation fields in real time. Future precision targeting requires multidimensional understanding of the imaging, underlying biology, and anatomical relationship among tissues for radiation as spatial and temporal "focused biology." Other means of energy delivery are available as are agents that can be activated by radiation with increasing ability to target treatments. With broad applicability of radiation in cancer treatment, radiation therapy is a necessity for effective cancer care, opening a career path for global health serving the medically underserved in geographically isolated populations as a substantial societal contribution addressing health disparities. Understanding risk and mitigation of radiation injury make it an important discipline for and beyond cancer care including energy policy, space exploration, national security, and global partnerships.

Contemporary radiotherapy: present and future.

Oncology care is increasingly a multidisciplinary endeavour, and radiation therapy continues to have a key role across the disease spectrum in nearly every cancer. However, the field of radiation oncology is still one of the most poorly understood of the cancer disciplines. In this Review, we attempt to summarise and contextualise developments within the field of radiation oncology for the non-radiation oncologist. We discuss advancements in treatment technologies and imaging, followed by an overview of the interplay with advancements in systemic therapy and surgical techniques. Finally, we review new frontiers in radiation oncology, including advances within the metastatic disease continuum, reirradiation, and emerging types of radiation therapy.

Artificial intelligence in brachytherapy: a summary of recent developments.

Artificial intelligence (AI) applications, in the form of machine learning and deep learning, are being incorporated into practice in various aspects of medicine, including radiation oncology. Ample evidence from recent publications explores its utility and future use in external beam radiotherapy. However, the discussion on its role in brachytherapy is sparse. This article summarizes available current literature and discusses potential uses of AI in brachytherapy, including future directions. AI has been applied for brachytherapy procedures during almost all steps, starting from decision-making till treatment completion. AI use has led to improvement in efficiency and accuracy by reducing the human errors and saving time in certain aspects. Apart from direct use in brachytherapy, AI also contributes to contemporary advancements in radiology and associated sciences that can affect brachytherapy decisions and treatment. There is a renewal of interest in brachytherapy as a technique in recent years, contributed largely by the understanding that contemporary advances such as intensity modulated radiotherapy and stereotactic external beam radiotherapy cannot match the geometric gains and conformality of brachytherapy, and the integrated efforts of international brachytherapy societies to promote brachytherapy training and awareness. Use of AI technologies may consolidate it further by reducing human effort and time. Prospective validation over larger studies and incorporation of AI technologies for a larger patient population would help improve the efficiency and acceptance of brachytherapy. The enthusiasm favoring AI needs to be balanced against the short duration and quantum of experience with AI in limited patient subsets, need for constant learning and re-learning to train the AI algorithms, and the inevitability of humans having to take responsibility for the correctness and safety of treatments.

No Longer a Match: Trends in Radiation Oncology National Resident Matching Program (NRMP) Data from 2010-2020 and Comparison Across Specialties.

PURPOSE: To report trends in the number and types of applicants and matched trainees to radiation oncology in comparison to other specialties participating in the National Resident Matching Program (NRMP) between 2010 and 2020. METHODS AND MATERIALS: Data from the NRMP and Electronic Residency Application System (ERAS) were obtained for 18 medical specialties between 2010 and 2020. We assessed the numbers and types of applicants and matched trainees relative to available positions in the NRMP and Supplemental Offer and Acceptance Program (SOAP). RESULTS: In the 2020 NRMP, 122 US MD senior graduates preferentially ranked radiation oncology, a significant decrease from a median of 187 between 2010 to 2019 (interquartile range [IQR], 170-192; P < .001). Across all 18 specialties, radiation oncology experienced the greatest declines in the 2020 NRMP cycle relative to 2010 to 2019, in both the number of ERAS applicants from the United States and Canada (-31%) and the percentage of positions filled by US MD or DO senior graduates (-28%). Of 189 available positions, 81% (n = 154) filled in the NRMP prior to the SOAP, of which 65% (n = 122) were "matched" by US MD senior graduates who preferentially ranked radiation oncology as their top choice of specialty, representing a significant decrease from a median of 92% between 2010 to 2019 (IQR, 88%-94%; P = .002). The percentages of radiation oncology programs and positions unfilled in the NRMP prior to the SOAP were significantly increased in 2020 compared with 2010 to 2019 (programs: 29% vs 8% [IQR, 5%-8%; P < .001]; positions: 19% vs 4% [IQR, 2%-4%; P <.001]). Despite >99% (n = 127 of 128) of US MD or DO senior applicants preferring radiation oncology successfully matching to a radiation oncology position in the 2020 NRMP, 16 of 35 remaining unfilled positions were filled via the SOAP. Radiation oncology was the top user of the SOAP across all specialties participating in the 2020 NRMP, filling 15% of total positions versus a median of 0.9% (IQR, 0.3%-2.3%; P <.001). CONCLUSIONS: The supply of radiation oncology residency positions now far exceeds demand by graduating US medical students. Efforts to nullify a market correction revealed by medical student behavior via continued reliance on the SOAP to fill historical levels of training positions may not be in the best of interest of trainees, individual programs, or the specialty as a whole.

Current status and developments of German curriculum-based residency training programmes in radiation oncology.

PURPOSE: The current status of German residency training in the field of radiation oncology is provided and compared to programmes in other countries. In particular, we present the DEGRO-Academy within the international context. METHODS: Certified courses from 2018 and 2019 were systematically assigned to the DEGRO-Curriculum, retrospectively for 2018 and prospectively for 2019. In addition, questionnaires of course evaluations were provided, answered by course participants and collected centrally. RESULTS: Our data reveal a clear increase in curriculum coverage by certified courses from 57.6% in 2018 to 77.5% in 2019. The analyses enable potential improvements in German curriculum-based education. Specific topics of the DEGRO-Curriculum are still underrepresented, while others decreased in representation between 2018 and 2019. It was found that several topics in the DEGRO-Curriculum require more attention because of a low DEGRO-curriculum coverage. Evaluation results of certified courses improved significantly with a median grade of 1.62 in 2018 to 1.47 in 2019 (p = 0.0319). CONCLUSION: The increase of curriculum coverage and the simultaneous improvement of course evaluations are promising with respect to educational standards in Germany. Additionally, the early integration of radiation oncology into medical education is a prerequisite for resident training because of rising demands on quality control and increasing patient numbers. This intensified focus is a requirement for continued high standards and quality of curriculum-based education in radiation oncology both in Germany and other countries.

Insights into the theranostic value of precision medicine on advanced radiotherapy to breast cancer.

Breast cancer is the most common cancer in women worldwide. "Breast cancer" encompasses a broad spectrum of diseases (i.e., subtypes) with significant epidemiological, clinical, and biological heterogeneity. Each of these subtypes has a different natural history and prognostic profile. Although tumour staging (TNM classification) still provides valuable information in the overall management of breast cancer, the current reality is that clinicians must consider other biological and molecular factors that directly influence treatment decision-making, including extent of surgery, indication for chemotherapy, hormonal therapy, and even radiotherapy (and treatment volumes). The management of breast cancer has changed radically in the last 15 years due to significant advances in our understanding of these tumours. While these changes have been extremely positive in terms of surgical and systemic management, they have also created significant uncertainties concerning integration of local and locoregional radiotherapy into the therapeutic scheme. In parallel, radiotherapy itself has also experienced major advances. Beyond the evident technological advances, new radiobiological concepts have emerged, and genomic data and other patient-specific factors must now be integrated into individualized treatment approaches. In this context, "precision medicine" seeks to provide an answer to these open questions and uncertainties. Although precision medicine has been much discussed in the last five years or so, the concept remains somewhat ambiguous, and it often appear to be used as a "catch-all" term. The present review aims to clarify the meaning of this term and, more importantly, to critically evaluate the role and impact of precision medicine on breast cancer radiotherapy. Finally, we will discuss the current and future of precision medicine in radiotherapy.

Optimal Radiotherapy Dose in Anal Cancer: Trends in Prescription Dose and Association with Survival.

PURPOSE: Definitive chemoradiotherapy represents a standard of care treatment for localized anal cancer. National Comprehensive Cancer Network guidelines recommend radiotherapy (RT) doses of ≥ 45 Gy and escalation to 50.4-59 Gy for advanced disease. Per RTOG 0529, 50.4 Gy was prescribed for early-stage disease (cT1-2N0), and 54 Gy for locally advanced cancers (cT3-T4 and/or node positive). We assessed patterns of care and overall survival (OS) with respect to the RT dose. METHODS: The National Cancer Database identified patients with non-metastatic anal squamous cell carcinoma from 2004 to 2015 treated with chemoradiotherapy. Patients were stratified by RT dose: 40-< 45, 45-< 50, 50-54, and > 54-60 Gy. Crude and adjusted hazard ratios (HR) were computed using Cox regression modeling. RESULTS: A total of 10,524 patients were identified with a median follow-up of 40.7 months. The most commonly prescribed RT dose was 54 Gy. On multivariate analysis, RT doses of 40-< 45 Gy were associated with worse OS vs. 50-54 Gy (HR 1.68 [1.40-2.03], P < 0.0001). There was no significant difference in OS for patients who received 45-< 50 or > 54-60 Gy compared with 50-54 Gy. For early-stage disease, there was no significant association between RT dose and OS. For locally advanced disease, 45-< 54 Gy was associated with worse survival vs. 54 Gy (HR 1.18 [1.04-1.34], P = 0.009), but no significant difference was detected comparing > 54-60 Gy vs. 54 Gy (HR 1.08 [0.97-1.22], P = 0.166). CONCLUSIONS: For patients with localized anal cancer, RT doses of ≥ 45 Gy were associated with improved OS. For locally advanced disease, 54 Gy but not > 54 Gy was associated with improved OS.

Prostate-Specific Membrane Antigen-Targeted Radiopharmaceuticals in Diagnosis and Therapy of Prostate Cancer: Current Status and Future Perspectives.

Prostate cancer is the most common cancer to affect men in the United States and the second most common cancer in men worldwide. Prostate-specific membrane antigen (PSMA)-based positron emission tomography (PET) imaging has become increasingly popular as a novel molecular imaging technique capable of improving the clinical management of patients with prostate cancer. To date, several 68Ga and 18F-labeled PSMA-targeted molecules have shown promising results in imaging patients with recurrent prostate cancer using PET/computed tomography (PET/CT). Studies of involving PSMA-targeted radiopharmaceuticals also suggest a higher sensitivity and specificity, along with an improved detection rate over conventional imaging (CT scan and methylene diphosphonate bone scintigraphy) and 11C/18F-choline PET/CT. In addition, PSMA-617 and PSMA I&T ligands can be labeled with α- and ß-emitters (e.g., 225Ac, 90Y, and 177Lu) and serve as a theranostic tool for patients with metastatic prostate cancer. While the clinical impact of such concept remains to be verified, the preliminary results of PSMA molecular radiotherapy are very encouraging. Herein, we highlighted the current status of development and future perspectives of PSMA-targeted radiopharmaceuticals and their clinical applications.