Advancing the Future of Personalized Cancer Care
Advocacy We sat down with radiation oncology specialist Jadranka Dragovic, M.D. of Henry Ford Cottage and Susan Burke, president of the Association of Pediatric Hematology Nurses, to discuss the promise and challenges of radiation therapy.
What are the benefits of radiation therapy?
Jadranka Dragovic: Radiation therapy is one of several major forms of cancer treatment, in addition to surgery and systemic therapy, such as chemotherapy or immunotherapy. It kills cancer cells by damaging their DNA and preventing them from multiplying. The benefits of radiation for cancer treatment became apparent very soon upon discovery of X-rays by Roentgen in 1895 (it was noted that repeated exposures of skin to X-rays led to severe tissue damage and it was concluded that any physical agent capable of doing so much damage to normal tissues might be able to damage cancerous growths). Radiation is presently used in about two out of three patients with cancer. It is a non-invasive curative treatment for patients with cancer that has not spread (metastasized). Radiation therapy can be used to treat cancer almost anywhere in the body, and it is often part of a treatment plan that includes chemotherapy or surgery. It is also an excellent palliative treatment for patients whose tumor has spread from the site of original growth to a secondary site cancer, and to relieve pain and other symptoms caused by cancer, significantly improving the patient’s quality of life.
Susan Burke: The treatment of both adult and pediatric cancers frequently encompasses a multi-modal approach (i.e., using surgery, radiation therapy, chemotherapy, stem cell transplant, and/or immunotherapy). By incorporating different treatment approaches into the plan of care, survival rates for many cancers have significantly improved.
Radiation therapy uses high energy x-rays to kill cancer cells. Recent advances in imaging and computer technology have made radiation therapy a more precise medicine, by ensuring more directed therapy to the cancer while sparing surrounding healthy tissue. These techniques reduce overall side effects while maintaining good treatment outcomes.
Radiation therapy plays a different role in treatment depending on the type and extent of cancer. In some adult cancers, radiation therapy is the primary curative treatment. In other cancers, radiation is given as adjunctive therapy (a treatment that is given either before or after the primary treatment). When used before surgery, radiation therapy can shrink the tumor size to make surgery more successful. When used after surgery or chemotherapy, radiation therapy can eliminate any residual cancer cells. In the pediatric setting, multi-modal therapy is considered the standard practice with radiation therapy often part of that approach – for example, a child with high risk neuroblastoma will receive chemotherapy, surgery, stem cell transplant, radiation therapy, and immunotherapy. This combination approach has resulted in significant improvements in survival rates for children with high risk disease.
Radiation therapy is a key treatment strategy in patients for whom cure is not possible, where the primary goal is to control symptoms such as debilitating pain or shortness of breath. This is often a difficult time for the patient and family as they shift their goals from trying to cure cancer at all costs to focusing on controlling cancer and symptoms to allow for a peaceful death. Short course radiation has been instrumental in assisting patients to achieve these goals.
In rare situations, radiation may be used in a more emergent setting when a patient may have cancer compressing the spinal cord or cancer pushing on the airway making it difficult to breathe. Emergent radiation aimed at reducing the size of the tumor and its compression on vital organ structures has helped reduce life-threatening or debilitating complications. The radiation oncology nurse is an important member of the multidisciplinary radiation oncology team and works closely with the team to develop an individualized plan of care for the patient. The nurse plays a key role in the provision of patient/family education, starting from the point of referral through completion of the treatment. They guide the patient/family through the process, anticipating potential side effects and providing management strategies when side effects occur. As advancements are made in the field of radiation oncology, it is important that nurses seek opportunities to expand their knowledge and skill related to newer treatment modalities.
How has radiation oncology advanced in the last five years?
Jadranka Dragovic: Radiation therapy has greatly benefited from rapid technological growth in computer and imaging technology in the past few decades. These advancements have allowed for greater precision of treatment and accurate targeting of tumors with radiation therapy, along with safe delivery of higher doses of radiation to the tumor, while sparing normal tissues. New techniques to deliver radiation therapy include intensity modulated radiation therapy, and millimeter-focused stereotactic body radiation therapy or stereotactic radiosurgery through utilization of advanced imaging. For example, the Henry Ford Cancer Institute pioneered stereotactic spine radiosurgery to safely deliver higher doses of radiation to areas near the sensitive spinal cord area. Another exciting example is stereotactic radiation for patients with inoperable early stage lung cancer, now accepted as standard treatment with excellent cure rates and quality of life.
Susan Burke: Radiation therapy continues to evolve due to advancements in medical imaging and computer technology, resulting in more sophisticated radiation delivery methods. The development of these new and improved delivery systems has allowed for more precise targeting of the cancer, safe delivery of higher and more focused doses of radiation therapy, while reducing exposure to surrounding healthy tissue. This is especially important in pediatric oncology as the child’s body continues to develop and mature, placing the child at significant lifetime risk for developing late side effects of therapy. A landmark study of childhood cancer survivors demonstrated that about two-thirds of all survivors will develop at least one chronic health condition in their lifetime. An example of a late side effect from radiation therapy might be hypothyroidism (low thyroid hormone) secondary to radiation involving the head and neck region. If this develops, these patients will need to be on lifelong thyroid hormone replacement. Patients who receive radiation involving the chest region will have an increased risk of developing heart or lung problems later in life. By reducing exposure of these vital organ structures to radiation through more precise techniques, childhood cancer survivors will hopefully face a healthier future.
Intensity-Modulated Radiation Therapy (IMRT) is one type of precision therapy. IMRT uses a CT or MRI derived 3-D image of the malignant tumor during the treatment planning. Using this computer image, computer controlled linear accelerators deliver a radiation dose that conforms more precisely to the shape of the tumor, and allows the radiation oncology team to modulate (control) the intensity of the radiation dose in a specific radiation field.
Image Guided Radiation Therapy (IGRT) uses frequent imaging during a course of radiation therapy for the purpose of providing precise and accurate dosing. This technique is used to treat tumors that are prone to movement such as the lungs, liver and prostate gland, as well as tumors located close to critical organs and tissues. It is often used in conjunction with other types of radiation therapy such as IMRT, proton beam therapy, or stereotactic radiotherapy. In IGRT, imaging is performed immediately prior to dose delivery and/or may occur during delivery of the dose. Specialized computer software compares the images obtained during the initial radiation planning with the new images, allowing the physician to make any necessary adjustments to either the patient’s position and/or radiation beams.
These are a few of the techniques being used today that allow for more defined sculpting of the radiation dose and allow the treatment to be more specifically tailored to the individual tumor and its specific characteristics. These techniques have allowed for the safe delivery of higher and more effective radiation doses while reducing the side effects when compared to conventional techniques.
What are immunotherapy-radiotherapy combinations and how do they work?
Jadranka Dragovic: Combination immunotherapy approaches involving radiation, chemotherapy and T-cell modulation has been extensively studied in animal models, but has only recently become a reality for humans. This is a very exiting area of investigation with recent data suggesting that radiation therapy may activate the immune system. The combination of radiation therapy and immune therapies may have the potential to improve both local control and control of metastatic tumor. Research has shown that radiation-induced damage of cancer cells may lead to the release of signal molecules that attract the immune cells to the tumor microenvironment. This works by increasing the number of cells eliminated by the immune system. The synergistic effect of radiotherapy and immunotherapy may also explain the so called “abscopal effect,” whereby ionizing radiation can inhibit distant tumors deposits even after localized radiation therapy. This is a field still in evolving in the clinical setting, with much promise for the future.
Susan Burke: Immunotherapy-radiotherapy treatment combines a drug or compound geared at targeting a specific type of cancer cell with some form of radioactive material. This tagged compound is administered to the patient, absorbed by tumor cells, which are then killed by the attached radiation. The benefit of this type of therapy is that it destroys the tumor cells while protecting normal, healthy tissue. It is generally well tolerated and may spare the individual from systemic toxicities (side effects) of other types of cancer treatments.
An example is MIBG therapy, which is used to treat neuroblastoma, a childhood cancer. Metaiodobenzylguanidine (MIBG) is a compound that is absorbed by certain types of nerve tissue, including neuroblastoma cells. It can be combined with radioactive iodine (I-131) and administered via an intravenous infusion to deliver targeted radiation to the neuroblastoma cells. I-131 MIBG has been well tolerated with the primary side effect being bone marrow suppression (low blood counts). A large study showed that 30-40 percent of children with relapsed neuroblastoma respond to MIBG therapy, making it one of the most active treatments for relapsed disease. While it doesn’t cure neuroblastoma alone, I-131 MIBG provides control of disease and possibly a prolonged period of disease stabilization.
What are the advantages of joining a clinical trial?
Jadranka Dragovic: Without clinical trials, there can be little to no progress in cancer treatment. Clinical trials offer patients the opportunity to be treated with novel strategies that are not yet available as standard care. Clinical trials may, for example, test a new treatment by comparing it to a standard approach of care. In certain cases, participation in a clinical trial may provide a potential benefit from the intervention itself or from other aspects of study participation, such as access to research nurses. Patients who participate in clinical trials help future patients and scientific progress.
Susan Burke: A clinical trial is when a group of cancer specialists try to improve treatment for a type of cancer by making a change to the current best treatment. This change can be adding a new medicine, a new type of treatment (e.g., radiation therapy, immunotherapy, targeted agent), or changing the order or timing of anti-cancer medicines. The decision to participate in a clinical trial is very personal and can be impacted by many factors. Decisions about participating in clinical trials happen under stressful circumstances - as the patient and family have either just learned of the cancer diagnosis or experienced a recurrence. Providing time for the patient and family to absorb the information is critical to their decision-making ability. Ensuring open and honest communication about the risks and benefits of the clinical trial, and addressing any concerns is essential. I believe it is important to share with the patient and family what we have learned from previous clinical trials and how that has influenced both current treatments as well as patient outcomes. Nurses play a key role in the informed consent process and should be involved early on in discussions with patients and families. This provides the nurse an opportunity to reinforce and clarify the information presented, acting as a liaison between the patient/family and physician. In addition, the nurse plays a critical role in monitoring for side effects, providing ongoing patient/family education and support, and ensuring adherence to the medications and requirements of the clinical trial.
What we have observed in pediatric oncology is that most children and teens diagnosed with cancer participate in a clinical trial; largely as a result of their participation, cure rates for childhood cancer have increased to approximately 80 percent. In my clinical role, I frequently ask patients and families why they chose to enroll on a clinical trial. The primary reason given is the strong belief that they or their child will directly benefit from participation. Another common response that I receive is “because my child is now benefitting from other children’s participation in previous trials”. Inherent in their decision is an opportunity to “pay it forward” to children and families who will face similar decisions in the future. They also believe that the information gathered from the clinical trial will add to the scientific body of knowledge and guide future care. Data has shown that adolescents and young adults (AYA) are more likely to enroll on a clinical trial when treated at a pediatric oncology center compared to adult centers, and superior outcomes have been observed when adolescents and young adults with Acute Lymphoblastic Leukemia were treated on pediatric versus adult treatment protocols.
Curative options for patients with multiply recurrent disease are often limited. Participating in early phase clinical trials, designed to learn more about how new medications are delivered safely, provides similar benefits.
It is important that patients who participate in clinical trials also understand the risks as well as the benefits. Some of the risks may include:
Patients may not benefit from the new approach being tested by the clinical trial
New approach may have side effects or risks that were not anticipated
New approach being studied isn’t always better than the standard of care
Cost of participating in a clinical trial may not always be covered by health insurance or through the trial.
In your opinion what do you think has been the biggest breakthrough for oncologists when focusing on patient care?
Jadranka Dragovic: Precision medicine is, perhaps, the biggest breakthrough in care for cancer patients. Using precision medicine, cancer experts can tailor medical treatment to the individual patient with the help of genetic testing, and sometimes with a biopsy (a test in which a small sample of a tumor is taken for analysis). The cancer team then looks for specific mutations that indicate whether the cancer will respond well to a particular treatment. Precision, and personalized care, also extends into the field of radiation oncology, as we focus care to the individual patient’s unique tumor target, anatomy, and internal motion. At the Henry Ford Cancer Institute we are delivering precise radiation through the use of the world’s first ViewRay MRLinac, which allows us to use real-time MRI imaging to track the patient’s exact target motion during treatment itself. This enables us to modify and adapt the radiation plan in order to maximize the radiation dose to the cancer and minimize dose to normal tissue structures.
Susan Burke: There is so much excitement in the cancer world today as researchers and clinicians continue to develop a better understanding of cancer biology. Researchers have developed new ways to harness the power of the immune system to kill cancer cells. We now have 2 immuno-therapies that can be used in the treatment of relapsed B-cell acute lymphoblastic leukemia (ALL). ALL is the most common type of childhood cancer. These new therapies, blinatumomab and CAR T-Cell therapy, act by targeting CD19, an antigen expressed on the surface of the B-cell, a type of white blood cell. Researchers also have identified genetic mutations in some types of cancer and developed medicines that target these mutations. Two different types of leukemias that occur in children and adolescents, B-cell ALL and chronic myelogenous leukemia (CML), can have a rearrangement of the same two chromosomes. The rearranged chromosomes result in the cell being permanently turned “on” to continuously make new copies of itself resulting in cancer. There are medicines (imatinib, dasatinib) used to treat these types of leukemia that specifically target the rearranged chromosomes. The use of these medicines has dramatically increased the likelihood of cure of these diseases.
Pediatric oncology teams are in the early stages of incorporating treatments targeted against these genetic mutations (specific genetic changes in the cell that caused it to turn into a cancer cell). There is new hope on the horizon. A recently opened clinical trial, Pediatric Molecular Analysis for Therapy Choice (Pediatric MATCH), is conducted jointly between the National Cancer Institute (NCI) and the Children’s Oncology Group (COG). In patients with recurrent or progressive solid tumors, the tumor cells will be tested to identify their genetic mutation. Medicines that are known to affect the specific mutation will be recommended. Two patients with the same type of cancer may have different genetic changes, requiring different targeted medicines to control the cancer growth. As we expand the use of personalized medicine in pediatric oncology, we have great hope that treatments will continue to increase cancer survival rates while reducing the long-term sequelae of childhood cancer therapies.
I think it is critical that we acknowledge the impact that advances in supportive care have had on the patient’s tolerance of treatment, quality of life, and overall survival. Preventing and minimizing side effects of treatment are extremely important to the well-being of the patient and can influence a patient’s decision to continue therapy. Advances in supportive care include improved understanding of how to minimize bothersome symptoms such as nausea or vomiting as well as the burden of uncontrolled symptoms on patient’s lives. Additionally, new antimicrobial agents have dramatically improved the ability to treat previously deadly infections. Today, I am caring for patients with invasive fungal infections who previously would have died from this complication of therapy. These advances are made through ultimate teamwork – collaboration between disciplines has led to the use of new aggressive surgical techniques, more effective antifungal therapy, growth factor support, and hyperbaric oxygen therapy to bring hope to a previously hopeless complication of cancer therapy. It takes a multidisciplinary team working together to see this type of success – something that is incorporated into all facets of pediatric oncology care.