High-Dose Radiation Offers Hope for People with Inoperable Pancreatic Cancer

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A patient in a linear accelerator at Memorial Sloan Kettering with radiation therapist Derek Fogelson.

Radiation therapist Derek Fogelson with a patient in 2019. A new MSK study suggests that in certain patients, high doses of radiation could control pancreatic cancer as well as surgery.

Pancreatic cancer has proven very difficult to treat compared with more common cancers. Despite decades of research, the prospects remain bleak for those diagnosed, with a survival rate of 10% at five years for all stages combined.

One reason pancreatic cancer is especially challenging is that surgery is often not possible. The disease is usually diagnosed only after it has moved into surrounding tissue, if not other parts of the body. Even if the cancer has not spread outside the pancreas, the tumor is often adjacent to or wrapped around major blood vessels. This makes surgery difficult, with a high risk of leaving cancer cells behind. But keeping pancreatic cancer in check with other treatments — such as chemotherapy or radiation — has largely been ineffective.

In recent years, Memorial Sloan Kettering radiation oncologists have investigated using high-dose radiation for some pancreatic cancer patients who cannot have surgery. Now, they have published results in JAMA Oncology suggesting this approach could have success rates similar to surgery. Radiation oncologist Marsha Reyngold discusses the meaning of these results and what a difference the treatment could make for patients.

Why Is Pancreatic Cancer So Hard to Treat?
Learn why pancreatic cancer has long foiled effective treatments — and why this could soon change.

How does this high-dose radiation differ from conventional radiation treatments?

In the past, radiation oncologists could not feel confident about delivering large radiation doses safely to the pancreas. It’s very hard to avoid damaging the stomach and intestines, which are nearby. But MSK specialists have the expertise to deliver the treatment without harming normal tissue.

We measure radiation doses in units called grays. Standard treatment for a pancreatic tumor would typically be 45 to 50 grays given in 25 sessions — or more recently, with the advent of the stereotactic technique, 25 to 33 grays given in five sessions. At MSK, we’ve been giving 67.5 grays in 15 sessions or 75 grays in 25 sessions. Although each individual dose may be slightly smaller compared with the five-session treatment course, the cumulative biological dose is high enough to control the tumor. Breaking the treatment into many sessions helps to selectively spare nearby tissue and organs.

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What did the new study show about the effectiveness of this high-dose approach?

The higher-dose approach has about the same success rate as what is seen in patients who are eligible for surgery. The team, led by radiation oncologist Christopher Crane and me, looked at 119 MSK patients with stage III pancreatic cancer who were not eligible for surgery. The patients all received chemotherapy, followed by radiation of either 75 grays over 25 sessions or 67.5 grays over 15 sessions. We followed this group for at least two years after treatment and saw that 38% were still alive. The survival rate for this patient group — people with inoperable tumors — is usually around 25% or less.

I should be clear that this study does not represent a direct comparison. We didn’t split a patient group into two subgroups in which one received high-dose radiation and one received surgery. It is more that we are reporting our outcomes and putting them in context of all the historical data of the people who’ve been treated with surgery. It would be difficult to do a trial in which people are randomly assigned into either a surgery group or a radiation group. For each case of pancreatic cancer, there are individual anatomical and clinical differences that make someone more suited for either surgery or radiation.

I am now collaborating with MSK surgeon Alice Wei on a study that will do a more direct comparison with surgical patients. Looking at people receiving either treatment at the same institution where all other aspects are equal should give us more solid evidence.

The higher-dose approach has about the same success rate as what is seen in patients who are eligible for surgery.
Marsha Reyngold radiation oncologist
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What advantages does MSK offer that makes this high-dose radiation possible?

Most other places don’t offer this type of therapy. Many institutions use precise radiation techniques, but the doses are lower and not as effective. A critical part of our success is being able to control and account for the movement of nearby organs from one treatment to the next. For example, air in the bowel or stomach can affect the position of multiple organs. Our doctors can look at CT scans and tell the difference between random, temporary motion and a more consistent shifting in position that requires a change in the treatment plan.

Also, we now can treat select patients on our new magnetic resonance (MR)-guided radiation machine. This allows improved ability to see the tumor with real-time tracking of changes in its position and shape. This technology also lets our doctors make real-time adjustments to the radiation plan, allowing for even more precise radiation delivery. Patients can get the high-dose radiation condensed into even fewer treatments.

We carefully evaluate pancreatic cancer patients to see whether this high-dose therapy will be the best approach. Even if we think other radiation methods are more appropriate, patients benefit from our high level of expertise. We treat a large number of people with this disease. Each year, about 200 patients receive radiation therapy for pancreatic cancer at MSK, with about half receiving the high-dose therapy.

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Could this treatment replace surgery for a large percentage of people with pancreatic cancer?

For most patients who qualify, surgery is the recommended treatment and will likely continue to be. In fact, we are conducting a clinical trial in which high-dose radiation is used to shrink the pancreatic tumor away from blood vessels so that more people can be eligible for surgery.

However, the biggest group to benefit from the high-dose radiation approach will be those who are not eligible for surgery. We think we are extending the lives of most of these patients and possibly buying time for when a clinical trial may offer them another treatment option.

We also believe there’s going to be a small number of patients who are actually cured. That number was practically nonexistent before. We think it’s probably on the order of 20% who can be permanently cured. Of course, pancreatic cancer remains a very difficult disease, so we continue to look for ways to improve treatment.

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