Revolution in Cancer Care: Artificial Intelligence and Adaptive Radiotherapy Dr. Vinitha Reddy

Abstract
In recent years, significant strides have been made in the field of cancer treatment, largely attributed to the emergence of personalized medicine and precision cancer care. This paradigm shift represents a ground breaking approach that tailors medical interventions to the unique genetic makeup of individual patients. This abstract delves into the concept of precision cancer care within the framework of personalized medicine and its profound impact on advancing cancer treatment. Recent advancements in radiation oncology technology have led to improved dose distributions and reduced toxicity in specific tumor locations. As a result of these advancements, there is a greater potential for improving local tumor control and increasing cure rates. Strict immobilization, good quality imaging, efficient motion management techniques precise and accurate treatment delivery systems, skill and expertise of the clinicians and staff – all contribute to an efficient radiotherapy department. Moreover, precision cancer care transcends the realm of treatment initiation. It facilitates the monitoring of a patient’s cancer over time, allowing for real-time adjustments to the treatment strategy as the cancer’s genetic profile evolves. This adaptability ensures that patients receive therapies that remain effective even in the face of cancer’s attempts to evade treatment. Additional clinical trials are necessary to demonstrate the benefits of advanced technologies before they are adopted for widespread use.
Keywords: Precision Cancer Care, Adaptive Treatment Strategies, Radiotherapy, Adaptive Therapy, Artificial Intelligence
Conflict of Interest: None declared
Source of Support: None declared

Introduction
Radiotherapy forms an integral part of cancer care. It works by damaging the DNA of cancer cells, thereby causing tumor shrinkage. During this process, radiation also affects the normal tissues. The Ethos radiotherapy machine is a revolution in cancer care. It utilizes advanced imaging and radiation technology to deliver more precise and personalized treatment. With its ability to adapt to changes in the patient’s anatomy and tumor size, the Ethos machine offers a new level of flexibility and accuracy in cancer treatment.

Precision Care in Cancer Treatment
Precision Medicine is the practice of the day. It is the tailoring of treatment to suit specific characteristics of the disease and the patient. Though the applicability of precision medicine is evolving in many diseases; oncology has been leading largely because of our immense knowledge of the role of genetic mutations in the development and progression of cancer.
The research conducted in the past two decades has increased our understanding of the biology of cancer, in particular cancer genomics, and in our ability to translate this ever-increasing knowledge for the benefit of patients.
Different cancers are characterized by different genetic alterations or mutations, and this provides the basis for precision cancer medicine. For example, 5 percent of non-small cell lung cancers – the most common form of lung cancer are driven by alterations in a gene called anaplastic lymphoma receptor tyrosine kinase (ALK). Many patients with ALK-positive non-small cell lung cancer benefit from drugs that block ALK, such as crizotinib and ceritinib. Other factors, in

¹Consultant Radiation Oncologist, American Oncology Institute, Hyderabad.
Corresponding author: Dr. Vinitha Reddy,Consultant Radiation Oncologist, American Oncology Institute, Hyderabad.
Email:drvinitha@americanoncology.com

including a patient’s disease presentation, gender, lifestyle, and exposure to potential cancer-causing agents like cigarette smoke could be considered in precision medicine.
The treatment of each patient can be focused on drugs most likely to benefit him or her, sparing the patient the cost and potential harmful side effects from drugs that are unlikely to be beneficial. For example, drugs targeted to the HER2 protein are offered only to the 20 percent of breast cancer patients who have a disease that tests positive for high levels of HER2. As our ability to analyze and integrate patient characteristics increases, we can expect faster and broader implementation of precision medicine across the spectrum of cancer care, from cancer prevention and early detection to treatment of late-stage disease.

Radiation Oncology has a High Potential to Showcase the Efficacy of Precision Medicine in Oncology.^[1]
Radiotherapy forms an integral part of cancer care. It works by damaging the DNA of cancer cells, thereby causing tumor shrinkage. During this process, radiation also affects the normal tissues. The accurate targeting of tumors with maximal sparing of normal tissues has been the foremost goal of radiotherapy practice.
Technological advances and clinical research over the past few decades have given radiation oncologists the capability to personalize treatments for accurate delivery of radiation doses based on anatomical variations and clinical parameters. Eradication of gross and microscopic tumors with preservation of health-related quality of life can be achieved in most patients.
Developments in imaging technology coupled with advances in computer technology have fundamentally changed the processes of tumor targeting and radiation therapy planning.
The ability to display anatomical information in an infinite selection of views has led to the emergence of three-dimensional conformal radiotherapy (3D-CRT); a modality in which the volume treated conforms closely to the shape of the tumor volume.
During the past two decades, the leap in radiotherapy technology has been overwhelming. The use of this technology in radiotherapy practice has made a tremendous difference in the cure rates and a significant impact on the quality of life of the patients surviving.

Technologies in Radiation Therapy
Intensity-modulated Radiation Therapy (IMRT)
IMRT is an advanced form of three-dimensional conformal radiotherapy. Variable radiation intensity is generated across each beam, which is further subdivided into multiple beam lets, each with an individual intensity.^[2] The use of several beams can build up a highly conformal dose distribution, allowing precise shaping of dose to a curved target and thus further sparing the normal tissues. The non-uniform intensity of the radiation beams and computerized inverse planning are the key features of IMRT planning. It is of value for target volumes with concave or complex shapes with proximity to radiosensitive normal structures.^[3]

Image Guided Radiation Therapy (IGRT)
IGRT is one of the most advanced innovations in cancer technology available. Uncertainty in the patient’s position in the treatment unit is one of the many factors that may contribute to differences between the planned dose distribution and the delivered dose distribution. IGRT refers to the use of advanced imaging (2D and 3D) to make sure that the positioning of the tumor will match the highly conformal dose delivery.^[4] Tumors can move during treatment because of breathing and other movement within the body. IGRT allows doctors to locate and track the tumor during treatment. With this technology, we can deliver precise radiation treatment to tumors that shift because of breathing and movement of the bladder and bowels.

Helical Tomo Therapy
Helical Tomo Therapy represents a novel and innovative means of delivering radiotherapy. The helical Tomo Therapy unit is essentially a hybrid between a linear accelerator and a helical CT scanner and hence radiation is delivered slice by slice, for the purpose of delivering intensity-modulated radiation therapy (IMRT).^[5] Helical Tomo Therapy, with its unique design and features, has the potential to provide improvements in radiotherapy precision, thereby allowing dose escalation and possible reductions in overall treatment time.

Volumetric Modulated Arc Therapy (VMAT)
VMAT is a relatively new IMRT method that combines rotational (or arc) delivery and MLC-based IMRT.^[6] VMAT makes use of the same fundamental methods (intensity modulation, inverse planning) as IMRT, but is different in the constraints that the rotational IMRT delivery places onto the plan optimization strategies that are used.^[6] One important advantage of current VMAT delivery techniques is that often the VMAT delivery for a single arc, or even for a multiple arc plan, can be much faster than that for fixed field IMRT.

Stereotactic Radiotherapy
Stereotactic radiotherapy is a specialized type of external beam radiation therapy where focused radiationbeams are used to target a well-defined tumor. It relies on detailed imaging, computerized three-dimensional treatment planning, and precise treatment set-up to deliver the radiation dose with extreme accuracy.^[7]
Stereotactic radiosurgery (SRS) denotes stereotactic treatment to the brain or spine while stereotactic body radiation therapy (SBRT) or stereotactic ablative radiotherapy (SABR) involves treatment of tumors within the body, excluding the brain or spine.^[7] This treatment does not involve surgery. Stereotactic radiotherapy is generally used to treat small tumors with great accuracy and is commonly used to treat benign tumors like Pituitary adenomas, acoustic neuromas,etc., and small metastatic tumors in the brain, lung, and liver.

Particle Therapy
Charged Particle therapy is an emerging development in radiotherapy. Particle radiotherapy, mainly using protons and carbon ions, provides physical characteristics allowing for a volume conformal irradiation and a reduction of the integral dose to normal tissue.^[8] Carbon ion therapy additionally features an increased biological effectiveness resulting in peculiar molecular effects.

Brachytherapy
Brachytherapy is the administration of radiation therapy by placing radioactive sources adjacent to or into tumors or body cavities. With this mode of therapy, a high radiation dose can be delivered locally to the tumor with rapid dose fall-off in the surrounding normal tissues, with the use of radionuclides such as cesium-137, iridium-192, gold-198, iodine-125, and palladium-103.^[9]

Currently, the image-based treatment planning of gynecological brachytherapy takes full advantage of modern imaging techniques (CT, MRI).^[9] It visualizes the tumor, the applicators, and the organs at risk and prescribes the doses accurately to pre-defined volumes and with dose–volume F constraints. The use of advanced techniques of radiation requires meticulous immobilization and image guidance techniques as tighter margins are given around the tumor. This ensures a sharp dose falls off of the dose and thus spares the normal tissues from receiving high doses. Techniques like respiratory gating and breath-hold are used when organ motion has to be accounted for.

Adaptive therapy and Artificial Intelligence
During the course of radiotherapy, there are changes that might happen in a patient’s body, be it because of tumor response weight loss, or internal organ motion. It is necessary to adapt radiotherapy treatments to such changes. Adaptive treatment has so far required re-planning between treatment sessions, which was time-consuming.^[10]

Adaptive Radiation with Ethos
Varian Adaptive Intelligence solution uses artificial intelligence and machine learning to create contours and generates adapted plans within minutes, while the patient is on the treatment couch.^[10] Thus it guides the physician to choose a suitable plan to deliver and completes treatment within 15 minutes.
It helps see changes in a patient’s anatomy with diagnostic clarity and adapt the treatment plan within minutes.
Ethos therapy integrates multi-modal diagnostic quality images at the point of treatment on the treatment console.^[10] By providing a current and detailed view of patient anatomy, Ethos therapy gives clinicians confidence that adapted plans are based on quality imaging. During each treatment, we can visualize a patient’s anatomy on that particular day with the help of iCBCT images and the expected 3D dose distribution to the target and organs at risk facilitating simplified decision-making guided by AI. Ethos therapy mitigates the complexity of adaptive planning and makes decision-making quicker.
During initial planning, Ethos therapy quickly produces several customized plans, showing the possible radiation dose distributions. Each day, the clinician selects the plan – that meets his or her intent- original or adapted and executes the treatment. This capability ensures that the patient is receiving the intended dose and improves understanding of the treatment progress.

Challenges in Radiotherapy and Ways to Address Them
Radiation oncologists encounter some challenges while treating tumors in parts of the body that move during treatment. Tumor motion during treatment due to respiration or any other reason increases the risk of missing the target. As the delivery of the radiation dose becomes more and more precise, the movements of organs and tumors have a significant effect on the efficacy of the treatment. This is particularly specific for tumors in the chest, owing to their movement during respiration. Though the movement is significant with tumors located in the chest; tumors in the larynx, abdomen (liver), and in the pelvis (prostate and bladder), also move during treatment.
With the advent of respiratory-gated radiotherapy, tumor motion can now be taken into account. Monitoring of breathing movements in real-time and synchronization of the treatment beam with the respiratory cycle is now possible. It is now possible to choose the phase of respiration (inspiration or expiration) during which the tumor can be irradiated. This ensures that the tumor is always encompassed in the radiation beam, but the exposure of critical organs is minimized.
The introduction of new and advanced technologies raises questions about cost, efficacy, and ethics. The increased capital and operating costs and the economic burden of increased QA are a challenge.^[12] Stereotactic radiosurgery, SBRT, proton, and other charged particle therapies using single or hypo-fractionation regimens have the advantage of saving time but require well-qualified personnel and excellent QA/QC programs as there is little chance of adjustment once the treatment has been initiated.^[11]
The major challenges for using advanced equipment and techniques are appropriate human resources, qualified and trained staff for the accurate delivery of high therapeutic radiation doses; infrastructure requirements capable of handling this technology most efficiently and effectively; knowledge of types and stages of cancers to be treated; development of commissioning and QA/QC protocols; and institutional resources and clinical backup to deal with increased downtime for the more complex technologies.^[12]

Conclusion
The remarkable progress in the field of cancer treatment, fueled by the principles of personalized medicine and precision cancer care, presents a promising shift towards more effective and tailored interventions. As exemplified by recent advancements in radiation oncology, the integration of cutting-edge technologies like the Ethos radiotherapy machine showcases the potential to enhance treatment accuracy and patient outcomes.
Precision cancer care, guided by the intricate genetic and molecular understanding of individual cancers, has revolutionized treatment strategies. The ability to select therapies based on the unique genetic characteristics of a patient’s cancer not only maximizes treatment effectiveness but also minimizes unnecessary side effects. This approach transcends the initial treatment phase, enabling real-time adjustments to therapy as the cancer’s genetic profile evolves, thereby maintaining treatment efficacy.
As the trajectory of cancer treatment continues to evolve, the principles of precision medicine and personalized care remain at the forefront. The ongoing collaboration between clinical expertise, technological innovation, and research endeavors promises to reshape the landscape of cancer care, providing patients with more effective, efficient, and tailored treatment options. With a commitment to addressing challenges and optimizing resources, the field is poised to unlock even greater potential in advancing cancer treatment, ultimately offering renewed hope to individuals facing this complex disease.

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