What Is Adaptive Radiotherapy and How Does It Work? Pros and Cons

Adaptive radiotherapy (ART) is a sophisticated evolution of traditional radiation therapy, designed to enhance treatment precision by dynamically adjusting radiation plans in response to real-time anatomical and physiological changes within the patient. This personalized approach aims to maximize tumor destruction while minimizing damage to healthy tissues, marking a significant advancement in oncology.

What Is Adaptive Radiotherapy?

Adaptive radiotherapy (ART) represents a refined approach to cancer treatment, fundamentally altering radiation delivery by adapting treatment plans to the dynamic anatomical and physiological shifts within a patient’s body during therapy. Unlike conventional radiation therapy, which employs a static, pre-determined plan, ART embraces the body’s inherent variability. Through frequent imaging, such as CBCT, MRI, or PET, specialists meticulously visualize changes like tumor shrinkage, organ movement, or weight loss. By comparing these real-time images with initial planning scans, they can precisely modify the radiation dose. This meticulous process ensures that the radiation is delivered with optimal accuracy, maximizing tumor targeting while minimizing exposure to healthy tissues.

How Does Adaptive Radiotherapy Work?

Adaptive radiotherapy (ART) employs continuous monitoring and adjustment to maintain optimal radiation targeting. Advanced imaging like CBCT, MRI, and PET visualize changes in tumor and patient anatomy. Before or between sessions, scans are compared to initial plans, and the radiation oncology team analyzes discrepancies. Adjustments, made in real-time or between sessions, may involve modifying dose, beam angles, or target volume. This personalized approach ensures precise tumor targeting and minimizes healthy tissue exposure, optimizing treatment effectiveness and reducing side effects.

What Are the Main Types of Adaptive Radiotherapy?

Adaptive radiotherapy (ART) encompasses several distinct approaches, each tailored to address different aspects of anatomical and physiological changes during cancer treatment. The primary classifications are offline, online, and the conceptually advanced real-time ART. Offline ART involves acquiring imaging scans and subsequently modifying the treatment plan between radiation therapy sessions. This method is particularly useful for addressing gradual anatomical changes that occur over the course of treatment, such as tumor shrinkage or weight loss. Online ART, in contrast, entails adjusting the treatment plan immediately before radiation delivery, while the patient is positioned on the treatment table. This approach is designed to account for inter-fractional variations, which are changes that occur between treatment sessions, allowing for immediate adaptation to daily anatomical shifts.

Offline Adaptive Radiotherapy

Offline adaptive radiotherapy (ART) involves a process where treatment plans are adjusted between radiation therapy sessions, guided by periodic imaging assessments. This approach typically utilizes sophisticated imaging modalities such as cone-beam computed tomography (CBCT), magnetic resonance imaging (MRI), or positron emission tomography (PET) to obtain detailed images of the patient’s anatomy. These images are crucial for evaluating changes in tumor dimensions, shape, and location, as well as alterations in the position and configuration of organs at risk (OARs) and the overall body.

Aristophanous et al. (2024), published in International Journal of Radiation Oncology,Biology,Physics developed a LINAC-based adaptive radiation therapy (ART) workflow for head and neck cancer, using automated image tracking (AWARE). In a study of 46 patients, ART significantly reduced doses to submandibular glands (-219.2 cGy), parotids (-68.2 cGy), and the oral cavity (-238.7 cGy) (p < 10⁻⁵ to 0.001). Xerostomia risk also significantly decreased (p = 0.008). Volume reductions (ΔV) were observed in GTVs and normal tissues. Candidate ART triggers were identified: parotid ΔV ≥ 7%, neck ΔV ≥ 2%, and nodal GTV ΔV ≥ 29%.

Online Adaptive Radiotherapy

Online adaptive radiotherapy (ART) modifies treatment plans immediately before delivery, using on-couch imaging like CBCT, MRI, or PET to visualize the patient’s anatomy. Advanced software and AI facilitate rapid plan adjustments to accommodate daily anatomical variations. Some systems offer real-time monitoring for immediate corrections during delivery. This approach enables highly personalized treatment, minimizing tumor underdosing and healthy tissue exposure.

Real-Time Adaptive Radiotherapy

Real-time adaptive radiotherapy (ART) adjusts treatment parameters continuously during radiation delivery, addressing intra-fractional variations. It requires sophisticated imaging and algorithms for immediate beam adjustments based on real-time anatomical changes. Though largely conceptual, it promises enhanced precision and minimized side effects by accommodating subtle movements during treatment.

Khouya et al. (2023), published in Cancers, analyzed the dosimetric effects of intrafractional CTV deformations in online adaptive radiotherapy (oART) for bladder cancer (9 patients). The study found that in half of the treatment series, extending adaptation time beyond 10 minutes by an additional 5 minutes necessitated a 1.9 ± 0.24 mm increase in PTV margin to maintain equivalent uniform dose within the CTV. The EUDCTV per fraction decreased by -4.4 ± 0.9% of the prescribed dose per minute in treatment series with steeper time dependency. The study highlights the importance of minimizing adaptation time in oART to maintain precision.

4D Adaptive Radiotherapy

4D Adaptive Radiotherapy (4D-ART) is a sophisticated approach that integrates the time dimension into radiation therapy to manage tumor and organ motion. Utilizing 4D imaging techniques like 4D-CT and 4D-MRI, it captures and quantifies motion patterns, enabling dynamic treatment planning. This is particularly vital for cancers in areas affected by respiratory movement or variable organ filling, such as lung, abdominal, and pelvic cancers. By synchronizing the radiation beam with motion and allowing for real-time adjustments, 4D-ART enhances treatment precision, reduces exposure to healthy tissues, and minimizes side effects. This advanced method ultimately aims to improve tumor control and overall patient outcomes.

Paulson et al. (2020) in Clinical and Translational Radiation Oncology successfully implemented 4D-MRI driven MR-guided online adaptive radiotherapy (MRgOART) with ATP and ATS workflows for free-breathing abdominal SBRT on a 1.5 T MR-Linac. In a study of eleven patients, 50% of treatments used ATS. Mean daily adaptive plan secondary dose calculation and ArcCheck 3D Gamma passing rates were high (97.5% and 99.3%, respectively). Median overall treatment times were 46 min (ATP) and 62 min (ATS).

Dynamic Adaptive Radiotherapy

Dynamic adaptive radiotherapy (ART) continuously adjusts treatment delivery based on real-time changes in patient anatomy and tumor characteristics. Using imaging like CBCT, MRI, or PET, it creates a “living” picture for immediate detection of changes. AI and advanced software rapidly process this information to adjust the radiation beam, ensuring optimal targeting and minimizing healthy tissue exposure. This dynamic, personalized approach enhances precision and effectiveness.

Kim and Phillips (2016) in Medical Physics presented DART, a stochastic control framework for radiotherapy that aims to maximize tumor control by adapting to tumor response uncertainty. In a phantom study comparing DART to conventional IMRT (60 Gy in 30 fractions for NSCLC), DART achieved average relative tumor dose increases of 102.0%-125.2% (dependent on replanning frequency). DART also showed potential for reducing average relative maximum doses to the cord (84%-102.4%) and esophagus (99.8%-106.9%), mean doses to the heart (66.9%-85.6%) and lungs (58.2%-78.8%), and D05 to unspecified tissue (85.2%-94.0%). The authors concluded that DART, using CBCT for midtreatment monitoring, could potentially improve tumor control and reduce OAR dose compared to nonadaptive IMRT, especially for parallel organs with mean or dose-volume constraints.

Read OncoDaily’s Special Article About Image-Guided Radiation Therapy

What Types of Cancer Are Treated with Adaptive Radiotherapy?

Adaptive radiotherapy (ART) excels in treating cancers where anatomical shifts during therapy pose challenges. Lung cancers, with their susceptibility to respiratory motion, benefit from ART’s precision, especially when coupled with 4D imaging. Gastrointestinal malignancies, like pancreatic, liver, and rectal cancers, see improved outcomes due to ART’s ability to adapt to daily organ variations. Prostate cancer treatment is enhanced by ART, which addresses bladder and rectal volume changes. Gynecologic cancers, including cervical and bladder cancers, also respond well to ART’s capacity to adjust for anatomical shifts. Essentially, ART’s adaptability makes it particularly valuable for cancers where target or organ movement significantly affects radiation delivery.

What to Expect During Adaptive Radiotherapy?

Patients undergoing adaptive radiotherapy (ART) should anticipate a personalized treatment journey that begins with comprehensive initial imaging to establish a baseline plan. Throughout the therapy, immobilization techniques are employed to ensure consistent patient positioning. During each session, or at scheduled intervals, additional imaging scans are conducted to monitor anatomical and tumor changes. If significant variations are detected, the treatment plan is dynamically adjusted, potentially modifying the radiation dose, beam angles, or target volume. The frequency of these adjustments depends on the cancer type and the rate of anatomical changes.

Pros and Cons of Adaptive Radiotherapy

Adaptive radiotherapy (ART) offers several advantages over traditional radiation therapy, primarily stemming from its ability to personalize treatment based on real-time anatomical and tumor changes. A significant benefit is the enhanced precision in delivering radiation, which allows for higher doses to the tumor while minimizing exposure to healthy tissues. This can lead to improved tumor control and reduced side effects. Furthermore, ART’s adaptability is crucial in treating cancers where anatomical changes are common, such as lung, gastrointestinal, and gynecologic cancers, ensuring that the treatment remains effective throughout the course.

However, ART also has drawbacks. It requires advanced imaging technologies and sophisticated treatment planning software, which can be expensive and may not be available in all treatment centers. The process of frequent imaging and plan adjustments can also increase treatment time, potentially causing patient discomfort and logistical challenges. Additionally, the need for highly trained personnel to operate these systems and interpret the data adds to the complexity and cost of ART.

Who Is a Good Candidate for Adaptive Radiotherapy?

Ideal candidates for adaptive radiotherapy (ART) often include patients whose tumors are located in close proximity to critical structures, as ART’s enhanced precision can minimize radiation exposure to these sensitive areas. This is particularly relevant in cases involving tumors near the spinal cord, heart, or major blood vessels. Additionally, patients with tumors prone to significant changes in size, shape, or position during treatment are well-suited for ART. Lung cancer patients, for instance, benefit from ART’s ability to account for respiratory motion, while those with gastrointestinal cancers can benefit from adjustments made for daily organ filling variations. Lastly, patients with gynecological cancers, like cervical or bladder cancer, who can experience significant daily changes in organ volume, are also excellent candidates.

ART enhances lung cancer radiotherapy accuracy, allowing higher doses without organ damage. Patient-specific respiratory margins are used, with ITV favored despite larger volumes. Respiratory imaging reduces motion artifacts. Adaptive management of interfraction shifts reduces errors, except when nodes are involved. Treatment response adaptations improve efficacy. Respiratory motion is stable, minimizing adaptive correction impact on margins. This summary is based on research by Sonke et al., published in Seminars in Radiation Oncology in 2010.

Innovations in Adaptive Radiotherapy

Recent innovations in adaptive radiotherapy (ART) are significantly enhancing its precision and effectiveness, primarily through the integration of artificial intelligence (AI), real-time tumor tracking, and the development of more precise imaging techniques.

Sibolt et al. (2021) assessed a new CBCT/AI-based oART system (Ethos) for pelvic cancers. Preclinical tests showed comparable plan quality and good AI segmentation (minor edits < 25% of cases), with adapted plans being better in 88%. The first 5 clinical cases (bladder, rectum, sarcoma) had a median 17.6-min adaptation time. Bladder patients saw a 42% median PTV reduction, potentially lowering bowel dose (V45Gy by 24-30%). The authors found this oART solution feasible for pelvic sites, allowing timely adaptation and potentially reducing toxicity, particularly in bladder cancer.

Written by Aren Karapetyan, MD