October: Breast

Timing is everything: When and how do we check to see if radiation treatment for breast cancer is working?

Sawyer Badiuk, MSc and Melissa Evans, BSc
October 14, 2020

Breast cancer can start in the milk ducts (ductal cancers) or sometimes in the glands (lobular cancer) responsible for making breast milk.  Although this is where the cancer originates, it may not stop there. If breast cancer is not controlled early, it will continue to grow and spread to other areas of the body. Since every breast cancer patient is different and will respond differently to treatment, physicians are faced with the task of finding the optimal therapies for each individual patient. Moreover, with so many available treatment options, each with their own strengths and weaknesses, it is critical for physicians to know if a patient is responding to effective treatment. This article discusses one of the first investigations of high-dose radiation therapy treatment in a clinical setting using comprehensive medical imaging. They used a magnetic resonance imaging (MRI) technique to assess the response of breast cancer to treatment and determine a suitable timeline to perform imaging.

Healthy breast cells naturally divide at a steady rate. Breast cancer starts to develop when these cells abruptly change and begin to grow out of control. This can then form into an abnormal clump of cells called a tumour. Tumour cells can travel to other nearby organs or parts of the body through the blood and lymphatic vessels. This spread of cancer cells to distant areas is called metastasis and this coincides to the stage of breast cancer – how much the cancer has grown and where it has spread.

Treatment for breast cancer typically involves a combination of local and systemic treatments. Local treatments target the tumour, such as surgery and radiation therapy. Systemic treatments treat the cancer with drugs that can reach cancer cells in almost all areas of the body, including chemotherapy, hormone therapy, and immunotherapy. With each type of treatment comes different strengths and weaknesses. In common clinical practice, combinations of treatments are used to treat the entire cancer. Radiation therapy is often used before surgery to shrink the tumour or after surgery to reduce the risk of recurrence.

Radiation is a type of energy and radiation treatment is the delivery of this energy to the body. When radiation passes through the body the damage can stop cancer cells from being able to divide and grow. However, as radiation travels to the cancer, it can also damage normal, healthy cells. Therefore, it is key that the radiation is focused on the cancerous tissue and spares healthy tissue. Conventionally radiation therapy is delivered over weeks, but in more recent years, high-dose radiation therapy has become increasingly popular. This technique involves delivering large amounts of focused radiation to the tumour in only a few visits.

With radiation, it is important for physicians to see that the body has properly responded to treatment prior to proceeding or assessing the next step of surgery. This means that physicians must find the optimal window to check how breast cancer radiation treatments are going. If they check too early, patients may still be in early stages of treatment response and it may appear as they are not responding. On the other end, if they check too late, the doctor can lose valuable time and be a burden to the patient if a treatment is not working as intended.

One-way physicians can see how patients are responding to treatment uses medical imaging. Medical imaging can help show the inner workings of the body and differentiate between different tissue types, such as bone, muscle, and fat. In patients with cancer, being able to see if the tumour is growing or shrinking could allow for better treatments decisions to be made on a patient-by-patient basis.

A team at Lawson Health Research Institute in London, Ontario, studied when to use medical imaging after high-dose radiation therapy in breast cancer patients using comprehensive imaging methods. At the time this research was conducted, Matthew Mouawad, a doctoral candidate at Western University, was working under the supervision of Dr. Stewart Gaede, the Chief Medical Physicist at the London Regional Cancer Program (LCRP) and Dr. Neil Gelman, an imaging scientist at St. Joseph’s Hospital in London, Ontario. In their work, they use a high-dose radiation therapy technique called stereotactic ablative radiotherapy (SABR) that uses precisely targeted radiation in a few high-dose treatments. To assess the response of the cancer to the radiation they used  MRI technology with a dynamic contrast enhancement.

Dynamic contrast enhancement requires the injection of a dye called a contrast agent that helps differentiate tissue types, making them easier for physicians to see on the image. A series of images were taken after the contrast was injected into the blood vessels and had time to collect in the tissues. With this, they were able to look at the integrity of tiny blood vessels and if there was damage to tissues from the radiation. This is important because damage to tiny blood vessels (called capillaries) from radiation plays a key role in decreasing the number of cancer cells or size of the tumour. When these capillaries are damaged, it blocks off blood flow to the tumour which means nutrients cannot get in to feed the cancerous cells.

The study involved three groups of patients with early stage breast cancer. All three groups received radiation treatment to their breasts prior to surgery to remove the cancerous portions of their breasts. Radiation performed prior to surgery helps to shrink the tumour.

The first goal of the study was to confirm that MRI showed the expected response between a high-dose radiation treatment (delivered in one visit) and a normal radiation treatment (delivered over three visits). The second goal was to find the best time to image the breast after radiation treatment to measure the response of the tumour.

As seen in the diagram, two of the three groups had a large amount of radiation delivered in one visit. The third group received a slightly lower amount of radiation in three separate visits. Overall, the total amount of radiation delivered was different between the groups, though the different delivery schedules generate similar effects on tumour cell killing and differing effects with healthy tissue sparing. When a large amount of radiation was delivered, enough damage was caused, such that some normal cells won’t have enough time to repair. When a lower amount of radiation was delivered over several visits, the healthy cells have time to repair. The effect is similar to running. If you have just started running for the first time and run 15 kilometers at once you are going to be really sore. If instead you run five kilometers three times in one week, there is time to recover between each run and you may be less sore after each session.

Choosing the right time to image radiation response is challenging. Similar to the benefit of detecting cancer early, the sooner physicians know if a treatment is working, the better. However, imaging too early is not helpful – normal tissue cells may still be repairing, and physicians won’t be able to tell if the patient is responding. In this study, MRI was performed before and after the radiation was delivered. Shown in the diagram, groups that received a large radiation dose in one visit were imaged either 1 week or 2.5 weeks after treatment. Whereas, the group that received a slightly lower amount of radiation in three separate visits was imaged only 2.5 weeks after treatment.

Figure 1: The study contained 3 groups of patients that received high-dose radiation therapy treatment, followed by  dynamic contrast enhanced MRI 1 week or 2.5 weeks post-treatment.

As one of the first studies to investigate high-dose radiation therapy in a clinical setting using comprehensive imaging, MRI was able to show the response of the tumours and surrounding normal tissue to radiation. It was confirmed that the lower amount of radiation delivered in three separate visits had a similar or better tumour response over the large amount of radiation delivered in one visit. This ensured physicians could trust that these images could show a good representation of the response. Imaging at 2.5 weeks was found to be a better time point for observing the tumour response for a large amount of radiation delivered in one visit. These findings demonstrate that MRI has the potential to be used in clinical workflow to improve breast cancer patient care.

To read more about this paper go to https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6993055/

Original Article:
Mouawad, M., Biernaski, H., Brackstone, M., Lock, M., Yaremko, B., Shmuilovich, O., Kornecki, A., Ben Nachum, I., Muscedere, G., Lynn, K., Prato, F. S., Thompson, R. T., Gaede, S., & Gelman, N. (2020). DCE-MRI assessment of response to neoadjuvant SABR in early stage breast cancer: Comparisons of single versus three fraction schemes and two different imaging time delays post-SABR. Clin Transl Radiat Oncol, 21, 25-31. https://doi.org/10.1016/j.ctro.2019.12.004