Advances of Radiation Therapy in Rectal Cancer and Beyond: Q+A with Lisa Kachnic, MD
The field of radiation oncology is experiencing a jolt of innovation. Improved methods to deliver precision radiation with less side effects, and new technologies, such as artificial intelligence-guided adaptive radiotherapy, have the potential to significantly impact patient care.
“Over the past 30 years, we've had major developments in imaging, surgical techniques, systemic therapy, and radiation delivery, which altogether has created a more personalized treatment approach for individuals with cancer,” says Lisa Kachnic, MD, chair of the Department of Radiation Oncology at Columbia University Vagelos College of Physicians and Surgeons.
In rectal cancer, depending on the stage of the disease, the treatment approach is often surgery, chemotherapy, and radiation therapy. But with the introduction of newer techniques and delivery methods of radiotherapy, patients now have more enhanced radiation options.
Dr. Kachnic, also the associate director of cancer network strategy at the Herbert Irving Comprehensive Cancer Center (HICCC), is a leading gastrointestinal radiation oncologist who has pioneered approaches to optimize radiotherapy delivery particularly in rectal and anal cancer. Her current research into the efficacy of AI-driven radiotherapy approaches, also referred to as adaptive radiation therapy, is an exciting new frontier in precision cancer medicine.
Dr. Kachnic and collaborators in the Department of Radiation Oncology at Columbia University and NewYork-Presbyterian are working on installing a new radiation delivery machine called Ethos, which will be the first of its kind in the Northeast that uses AI to efficiently fine-tune a patient’s daily radiation treatment. This technique, known as on-board adaptive radiation, has the potential to reduce treatment side effects as well increase the radiation dose to the tumor which may allow for improved cancer outcomes.
“It is very exciting,” says Dr. Kachnic. “We have set up a dedicated adaptive research team at Columbia, including members of our medical and physics faculty Drs. Christine Chen, Olga Dona Lemus, David Horowitz and Michelle Savacool, as well as our new vice chair of physics, Dr. Michael Price, who will be joining us in April. Our resident physicians are also actively involved with this research, preparing them to be leaders in this new frontier in cancer care." The team has recently received funding from Varian Medical Systems, Inc. to conduct this important work.
Dr. Kachnic talks to HICCC News about the state of rectal cancer treatment and the overall changing landscape of radiation oncology.
What are the different types of colorectal cancer?
The majority of colon and rectal cancers are adenocarcinomas—this means they originate in the lining of the intestines and can grow into a polyp, and some of these polyps can develop into cancer. Polyps are generally removed during routine colonoscopies, hopefully before they develop into a cancer, which is why March—Colorectal Cancer Awareness Month—is a good reminder for folks to obtain their screenings at the age of 45 and above, or sooner if they have a family history of colorectal cancer. Importantly, the American Cancer Society recently recommended starting screening for colorectal cancer at age 45, and starting screening at this age can help save more lives. There are also less common types of colon and rectal cancers, such as lymphomas, gastrointestinal stromal tumors, sarcomas, small cell or carcinoid tumors, and melanomas.
How has the field of radiation oncology made strides in treating rectal cancer?
The role of radiation for the treatment of rectal cancers has changed dramatically over the past 30 years. Our treatment approach for patients has become much more personalized. For example, we now give radiation with chemotherapy before a patient gets surgery, and that gives the surgeon the best chance of taking the tumor out and removing all cancer cells, and also helps to prevent the tumor from coming back locally. Back when I trained, we used to deliver the radiation after the surgery, but we now know from clinical trials that pre-operative radiation is associated with decreased side effects, more tumor shrinkage, a better chance for avoiding a colostomy surgery, and improved local control, as compared to post-operative radiation. The U.S. cancer research bases are also developing trials to assess whether we can omit surgery in select patients who appear to have no MRI-screened residual tumor following chemotherapy and radiation.
We've also refined the way we deliver radiation. When I trained, it used to be a very “boxy” technique where you give the same dose that you give to the tumor to the normal surrounding tissues, and this often resulted in side effects. However, over the last two decades, we deliver the radiation much more conformally. With a technique, known as intensity modulated radiation therapy or IMRT, we focus the radiation on the patient’s tumor and minimize the radiation dose that goes to the normal surrounding organs, which for rectal cancer, consists of the female or male genitalia, the bladder, the hips, and the small bowel. There are also imaging devices on our radiation delivery machines, including CTs, that allow us to make sure that the tumor is treated with precision. The combination of conformal radiation delivery and on-board imaging allows for decreased side effects and in some cancers, improved treatment outcomes, as compared to the older radiation delivery techniques.
Artificial intelligence (AI) has been abuzz not just in cancer research and treatment but in many different sectors. Tell us how Columbia Radiation Oncology is diving into AI and what does that mean?
For rectal cancer, we generally deliver five to six weeks of daily radiation, Monday through Friday, combined with an oral chemotherapy agent to make the radiation more effective in eradicating the cancer. Before starting the radiation, we perform a planning session where the patient receives a CT scan in the same position that they're going to be treated. We then work closely with our physics staff over several days to develop an individualized radiation plan that maximizes the radiation delivery to the tumor and minimizes radiation to the normal tissues. But when the patient is under treatment for these five to six weeks, they, nor their cancers, are static. Patients may lose weight and tumors hopefully shrink. In addition, the normal organs around the tumor, especially the bowel surrounding the tumor, can move. So that initial plan we develop a week or two before the patient even starts the treatment might need a little bit of tweaking. However, the time it takes to re-plan with our current tools (days to weeks) and the inconvenience for the patient, often makes this difficult to accomplish. This is where AI comes in.
Adaptive radiation therapy, driven by AI, is a promising new treatment technique where we are able to adapt a patient's treatment in real-time while they're actually lying on the treatment machine. This may allow reducing the radiation dose to the normal surrounding tissues. If the normal organ moves closer to the tumor, we can adjust our plan to avoid the organ, and if the organ moves further away from the tumor or the tumor shrinks, we may be able to increase the dose the tumor. Columbia and our NewYork-Presbyterian partners are currently installing a new radiation accelerator machine called Ethos, which will be the first of its kind in the Northeast that uses artificial intelligence to efficiently perform daily adaptive re-planning and treatment.
What other new research or treatment advances are you excited about?
In rectal and other cancers, we are conducting clinical trials at Columbia focused on reducing the time it takes to deliver radiation. For rectal cancer, we are about to enroll our first patient onto the SHORT trial. I and a colleague from Virginia Mason Cancer Institute developed a study to reduce the time it takes to give neoadjuvant chemo-radiation therapy before surgery for select patients with intermediate risk rectal cancer. The radiation will be delivered over one week instead of the current 5.5 weeks, and the duration of chemotherapy using a novel agent in combination with oxaliplatin, is also shorter in duration. Dr. Eileen Connelly has been leading a clinical trial at Columbia assessing the role of intraoperative radiation for select women with early breast cancer. Instead of the four to six weeks of daily radiation therapy, we deliver one dose of radiation at the time of the lumpectomy surgery, by directly administering the radiation into the surgery bed. It's amazing, and so convenient for our patients. My colleague, Dr. David Horowitz, uses this same techniques to deliver radiation at the time of surgery for select abdominal and pelvic tumors, including rectal cancers, when the surgeon is having difficulty in obtaining clear margins. This one dose ‘boost’ of radiation can help to eradicate any small amount of tumor that may be remaining.
A totally new paradigm of radiation delivery that I’m really excited about is called FLASH radiotherapy. This could be a really big game changer for the future of our field. Today we typically deliver small, daily doses of radiation over five to eight weeks, depending on the type of cancer. Side effects, if they occur, are cumulative over that course of radiation, and then once radiation is completed, they usually resolve, although there is always a small chance of residual effects. FLASH is just what it sounds like. We deliver a very large dose of radiation over a fraction of a second. Our pre-clinical research shows that FLASH radiation delivery provides the same tumor cure as our standard longer radiation courses, but with virtually no side effects. And this finding has been demonstrated in every normal tissue studied. Drs. Simon Cheng, Cheng-Chia Wu and Oscar Padilla from our department are currently testing FLASH in cell and mouse studies. Moreover, our radiation research core facility at the Radiological Research Accelerator Facility (RARAF), led by Dr. David Brenner, is one of the few places in the country that have the equipment to perform FLASH, really enabling this important research.
What challenges remain in treating rectal cancer with radiotherapy?
Oncology management is moving towards more personalized risk-stratified treatment, and the current challenge is when to give radiation. For years, we've delivered pre-operative radiation for all patients with stage II and III rectal cancer, but we are uncertain if all patients receive the same benefit. Are there subgroups with better risk cancers that we can safely omit radiation, as well as patients treated with chemotherapy and radiation for whom surgery can be avoided? Our current clinical trials are focused on finding the optimal therapeutic combination (surgery, chemotherapy, and radiation) for each subset of patients. Hopefully, future clinical trial data will help guide oncologists to make more personalized treatment decisions.
Are there patient initiatives the Department of Radiation Oncology is working on?
Our exceptional NYP nursing staff have been working on both English and non-English speaking educational tools regarding radiation side effects for our adult patients, while Dr. Cheng-Chia Wu is developing a children’s educational book intended to educate pediatric patients and their families about radiation planning and delivery. I've also had the privilege to mentor one of my senior residents, Dr. Oscar Padilla, in the development of his funded study to assess barriers in radiation clinical trial enrollment for non-English speaking patients. In the United States, there is a very low rate of under-represented patient accrual onto cancer studies. As such, understanding the cause is critical, so that we may create effective tools to better educate on the importance of clinical trials.
In the spring of 2020 when New York City became an epicenter of the pandemic, how did that impact radiation oncology at Columbia?
Radiation oncology, and all of our oncology practices at Columbia and NYP, didn’t have an opportunity for a pause. We all had to buckle down and work together as a team to create safe systems so that we could continue to treat our patients. Last spring, my resident physicians, advanced providers, and administrative team began calling every patient the night before their appointments or treatments to make sure that they were not experiencing any COVID-19 symptoms or had any exposures. We then participated in daily early morning and late night team Zoom huddles to make important patient decisions, such as which patients needed quarantine and urgent COVID testing, and how were we going to safely treat patients that tested positive. Luckily, very few patients and team members were diagnosed with COVID, which meant that the systems and protocols we put in place were effective.
The pandemic really provided us with a unique opportunity to become stronger as a department, and much more efficient in our practice. New workflows, remote working capabilities, and telehealth were all quickly implemented and streamlined in the interest of social distancing. Importantly, telehealth visits are here to stay. We are able to virtually provide radiation oncology expertise to patients from both near and far, and moreover, our entire team of multi-disciplinary experts (radiation, medical oncology, surgery) can participate in the same telehealth visit.