Global Perspectives on Sequencing in Gastroesophageal Cancers - Episode 2

Gastroesophageal Cancer: Initial Approaches


Johanna C. Bendell, MD: Moving on to more advanced disease. We have somebody with a locally advanced gastric cancer, or gastric esophageal cancer. What do we think? What’s our typical workup? And let’s talk a little bit about guidelines between the United States, Europe and ESMO, and Japan. What kind of guidelines do we have, in general, for treatment of these patients? Dr. Van Cutsem, could you lead us off?

Eric Van Cutsem, MD, PhD: Well, first of all, a good workup is important and a patient has to be in good condition and good organ function, so we have to evaluate that. Then we need to know what is the extent of the disease. We typically do that in gastric cancer, in metastatic disease, with a CT scan of the chest and the abdomen. There is emerging evidence that for the detection of peritoneal metastases, patients with limited disease, then an MRI with diffusion profusion, may contribute. Although that’s not routine, although that’s not in the guidelines in this situation.

In metastatic disease in Europe, we usually don’t do a PET/CT. We do that in the evaluation of gastroesophageal junction tumors, locally advanced, but not in metastatic disease, because if the metastases are there on the CT, it’s clear it doesn’t have practical implications. The second piece of information is for an fluorodeoxyglucose (FDG)-PET. In the real gastric cancers, not the gastroesophageal junctions, but in the real gastric cancer, and especially those with signet cells, one-third of those patients are not FDG-PET positive because of some changes in the glucose metabolism in the signet cell cancers.

Then looking at the biopsy, it’s important also in the guidelines, that in patients with metastatic disease, we should have adequate biopsies to look at HER2 for HER2 testing. One or 2 biopsies in the scope of biopsies is not enough. We really need to have enough biopsies because of the heterogeneity of HER2 testing in the stomach; it is different in contrast to breast cancer. The general recommendation is still at least 6 endoscope biopsies available, even in a patient with gastric adenocarcinoma.

Johanna C. Bendell, MD: Yes, and if you have a patient with potentially resectable disease, what are the recommendations in Europe around this diagnostic laparoscopy?

Eric Van Cutsem, MD, PhD: There is not one recommendation; there are, let’s say, 2 different schools. Some people push and would recommend to do the diagnostic laparoscopy at that moment. In our center, we don’t do it in a routine way because we have shifted toward the daily operative chemotherapy. Anyway, we give the patients, with the more advanced tumors, we will give them in this situation the neoadjuvant chemotherapy.

We usually do the laparoscopy after the neoadjuvant treatment at the moment we go for, eventually, for possible surgery. There are people who, and centers, who do it initially, and both are probably correct. As I said, in this situation, especially if there’s some doubt, we and some other centers also have now implemented the strategy of a diffusion/profusion MRI for the detection of peritoneal metastases. That’s, however, not yet in the guidelines. We need it a bit more spread out. There is a need for experience also with the radiologist before we can implement that in this situation.

Lastly, and that’s in locally advanced disease, it’s not generally done, but quite a lot of centers perform ultrasonography, especially in the smaller tumors, to see one end whether it’s a tumor in the very early gastric cancers. That is, the patient is a candidate for endoscopic resection, and in patients then where there’s some T2, or T3, or an N3b-plus tumor, EUS (endoscopic ultrasound) may sometimes perform better than the CT scan in this situation. It may help us to distinguish on the neoadjuvant approach and on the perioperative chemotherapy strategy.

Johanna C. Bendell, MD: Very good, very good. Peter, these are strikingly familiar to NCCN guidelines. Do you think any there are differences across the pond?

Peter C. Enzinger, MD: Not really. I think because there’s some variability among the institutions in the United States, and variability among institutions in Europe, they overlap very clearly. I think that what Eric has just said would certainly apply to many institutions here in the United States. I would just add that we do laparoscopic evaluations if we’re concerned about the patient or we’re worried that the patient may not tolerate such aggressive therapy. Well, you’re looking for a reason not to do the aggressive treatment or if the cancer seems to be very bulky advanced and you think that there’s a high risk for doing this additional testing.

The other thing is, I would just say that endoscopic ultrasound again offers us another opportunity to get tissue, which becomes increasingly important in later lines of therapy. I agree with Eric that it’s probably the most important for early stage disease, but it becomes important in other ways for more advanced disease.

Then finally, I would just add that our radiation oncologists are very interested in PET/CTs, if they’re going to be involved in the treatment, because it really helps them to do their treatment planning and particularly for proximal gastric cancer. Of course, for all the esophageal cancers, we get PET/CTs up front. Primarily, too, to look for that 10% of patients who may have additional metastases, but also really to help radiation oncologists do their job.

Eric Van Cutsem, MD, PhD: Yes, that’s right. Also, I didn’t mention it, but the FDG-PET, if there is no clear indication in patients with clear metastases on the CT, but in patients, especially, with gastroesophageal junction tumors and signet cell cancer, we do PET/CT in all patients. There is, as Peter said, an additional value of PET/CT.

Johanna C. Bendell, MD: Yes, and it’s interesting because I think that sometimes people misinterpret guidelines thinking that means PET/CT for all, which is not true. It’s mostly in the disease where you think its localized and thinking about something surgical and then trying to catch metastases or make sure you understand.

Peter C. Enzinger, MD: Well, you have to have some logic, right? You should only order a test if you think it’s going to change how you treat patients. You should actually give it some thought and actually make a decision based on the benefits of doing the procedure or not.

Johanna C. Bendell, MD: You know at this conference there’s also some interesting data that’s going to be presented on PET scans in the neoadjuvant setting from the Alliance Group?

Peter C. Enzinger, MD: Yes, out of Dr. Janjigian’s institution, yes.

Yelena Y. Janjigian, MD: Karen Goodwin is the lead for that study, and the hypothesis there was that we will use the PET scan to understand the tumor biology and to use it to our advantage and to really maximize on systemic therapy and the local response by potentially rescuing patients who would not be responsive to induction chemotherapy. That being said, none of the studies to date, have demonstrated survival benefit for induction chemotherapy, so more chemotherapy is not necessarily better. The hypothesis here is that perhaps change in the chemotherapy and induction will give us a sense of whether or not patients do better. The path response rates are actually surprisingly good for the chemoradiation therapy in the US, including adenocarcinomas, as opposed to squamous cell cancer, but the survival data will be presented and it’s not as sort of impressive as you would have expected it.

Transcript Edited for Clarity