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Expert Shares Obstacles With Neoadjuvant Chemo in GEJ and Esophageal Cancers

Greg Kennelty
Published: Thursday, Jul 28, 2016

David Ilson, MD

David Ilson, MD

According to recent findings, pre-operative chemotherapy administered to patients with esophageal cancer may not have a particularly significant benefit for those who are undergoing resection, says David Ilson, MD, PhD. However, researchers globally debate whether chemotherapy alone or combined with radiation therapy is the optimal treatment for patients, specifically in tumors of the esophagus and junction versus the esophagus and stomach. 

In an interview with OncLive, Ilson, a medical oncologist at Memorial Sloan Kettering Cancer Center, discusses pre-operative chemotherapy alone versus chemotherapy plus radiation therapy for the treatment of patients with esophageal and gastroesophageal (GE)-junction cancers, and how recent data points to the latter being the better choice.

OncLive: Can you tell us about your recent studies into adjuvant chemotherapy plus surgery in esophageal and GE-junction cancers?

Ilson: I recently presented a review on recent literature from a pre-operative treatment in esophageal and GE-junction cancers. It's pretty clear that these cancers, including gastric cancers, benefit from a combination of adjuvant chemotherapy plus surgery. Whether that chemotherapy is given before surgery, which is done typically in Europe and the United States, or surgery first and then chemotherapy after the surgery as it's done in Japan, there's evidence that combining chemotherapy with surgery offers a benefit.

What's been debated is whether or not there's an additional role for adding radiation therapy. That topic came up in a recent lecture about the role of the optimal treatment of pre-operative therapy for esophageal and GE-junction cancers. There are two approaches: some favor chemotherapy alone, whereas in the United States we're more convinced that radiation needs to be combined with chemotherapy, particularly in tumors of the esophagus and the junction between the esophagus and the stomach.

What I did was go back and look at older studies and compare them to data from two very large recent trials looking at chemotherapy alone. What's clear from these studies is that giving chemotherapy alone as a pre-operative treatment does improve survival, but you also have to worry about good surgical outcomes with these diseases. In order to cure a patient, you have got to get a clear margin resection or R0 resection, and that's an important endpoint of these studies—not only getting a curative surgery, a clear surgical margin, but also reducing local recurrence of the cancers.

If you look at older studies of perioperative chemotherapy without radiation, there was a large negative trial to the approach, which showed no benefit for adding 5 months of chemotherapy compared to surgery alone. That study shows that about 40% of patients could not be operated on, and among the people who were operated on, the risk of the cancer coming back locally was about 30%. So it represented quite a huge failure rate of this approach.

In Europe, there were early studies of pre-operative chemotherapy in esophageal cancer that showed marginal survival benefits of about 5%. It also showed this 40% rate of inoperability with chemotherapy alone and local failure rates of 30%. Local control with chemotherapy alone is quite poor. Based on the success of early trials combining radiation and chemotherapy for esophageal GE-junction cancers where you've got potentially better rates of negative margin resection, lower rates of local recurrence, and improved survival, this approach is increasingly been adopted in the United States.

The pivotal trial came from the Netherlands, which compared surgery alone versus a very short course of chemotherapy, weekly carboplatin paclitaxel, and radiation; that study showed improved survival. It took the curative resection rate of about 60% and bumped it up to about 90%, and survival was improved; the treatment also resulted in a reduction of this local recurrence rate from about 25% to 30% down to 14%.

The point of my lecture was to look at some recent studies from the United Kingdom that continued to pursue this chemotherapy-alone approach. One was OEO5, which was a 900-patient study of esophageal and GE-junction adenocarcinomas, and guess what? After chemotherapy alone, the R0 resection rate was about 60% to 65%, so no improvement over 20 years. This is despite the fact that patients on this trial were screened with endoscopic ultrasound and PET scanned, so you could argue that patient selection was not the problem here. They were staged with modern staging techniques, and still with chemotherapy alone, you had very poor rates of curative resection.

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