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Upper GI malignancies from a radiation oncology perspective

Interview with Prof. Maarten Hulshof

Prof Maarten Hulshof – Department of Radiation Oncology, University of Amsterdam, Amsterdam, The Netherlands

Video Summary:

In the last 15 years there has been a big change in radiation oncology. The combination of chemotherapy plus radiation has increased the effect of radiation significantly which is clinically relevant. This means that for inoperable cases the combination of radiation plus chemotherapy has changed the intention from palliative to curative. Additionally, preoperative chemoradiation has improved the outcome of surgery significantly and is clinically relevant by about 15%, so compared to about 15 years ago where only few patients were referred to a radiation oncologist, now every patient is referred to a radiation oncologist either preoperative or curative.The optimal treatment now for localised oesophageal cancer is a combination of preoperative chemoradiation followed by surgery. Adenocarcinoma is less radio-sensitive and the squamous cell carcinoma reacts very well to chemoradiation. Hence in the patients who don’t want to have surgery especially for the squamous cell carcinoma, the definite chemoradiation is a very good alternative with a high chance of cure. The effect on overall survival between chemoradiation alone for squamous cell carcinoma is comparable to the combination treatment, but the local recurrence rate is still a little bit higher if surgery is not opted for. The decision on the treatment is made by a multidisciplinary board where either the surgeon and the medical oncologist and the gastroenterologist and the radiation oncologist decide together instead of a single doctor. The standard treatment for stomach cancer is preoperative chemotherapy alone. Considering the results of oesophageal cancer, the improvement by adding preoperative chemoradiation for adenocarcinoma, also for the distal tumours and also for the junction tumours, is as great as in the upper part of the oesophagus. So it’s a small step to the stomach and we have to do studies with preoperative chemoradiation also in stomach cancer. But for pancreatic carcinoma, the standard treatment is still to be considered as it is a different entity.

Video transcript:

How has the landscape of treatment of esophageal cancer changed over the last decades?

The role of radiation oncology has tremendously changed over the last decades.  About 15 years ago radiation for oesophageal cancer was only intended for palliative care and surgery was the mainstay of treatment with bad results.  Let’s say 20 years ago the five-year survival of oesophageal cancer was about 20%, not more than that and only palliative cases and inoperable patients were sent for radiation with only about 10% cured.

In the last 15 years a big change has occurred in radiation oncology and there are several important points in that.  The combination of chemotherapy plus radiation has increased the effect of radiation significantly and not only significantly but is also clinically relevant.  That means for inoperable cases the combination of radiation plus chemotherapy has changed the intention from palliative to curative.  We can cure oesophageal cancer patients now by radiation combined with chemotherapy, concurrent chemotherapy so not adjuvant, not neoadjuvant but concurrent chemoradiation.  That’s very important.  So we don’t need to operate all patients, we can also cure them by chemoradiation.  That’s the first big change in the last decade.

The second is that preoperative chemoradiation, the combination again, has improved the outcome of surgery significantly and not only significantly but also is clinically relevant by about 15%, so compared to about 15 years ago where only a minor amount of patients were referred to a radiation oncologist, at the moment every patient is referred to a radiation oncologist either preoperative or curative when a patient is inoperable or palliative, so nearly all patients unless they are metastatic with distant metastases are seen and treated by a radiation oncologist so a tremendous change.

What is the current standard of care for localized esophageal cancer? Any differences in the treatment of patients with squamous cell cancer and with adenocarcinoma of the esophagus?

I think the optimal treatment now for localised oesophageal cancer is a combination of preoperative chemoradiation followed by surgery.  That’s still the optimal treatment with about 50% five-year survival which has dramatically changed from about 15 years ago, but we have to distinguish the squamous cell carcinoma from the adenocarcinoma.

Adenocarcinoma is less radio-sensitive and the squamous cell carcinoma reacts very well.  We know from several studies if you give only a small dose of radiation, a moderate dose of radiation plus a moderate dose of chemotherapy, we have about 50% of complete remissions, so squamous cell carcinoma is a distinct other entity to the adenocarcinoma.

Still based on the higher rate of local recurrences by chemoradiation, instead of chemoradiation plus surgery we still advocate the optimal treatment is preoperative chemoradiation followed by surgery, although the surgery is treatment with a lot of morbidity.  So in the elderly patients, in the patients who don’t want to have surgery especially for the squamous cell carcinoma, the definite chemoradiation is a very good alternative with a high chance of cure and we know that the effect on overall survival between chemoradiation alone for squamous cell carcinoma is comparable to the combination treatment, but the local recurrence rate is still a little bit higher if you skip the surgery. 

So still I think the best optimal treatment for localised cancer, both adenocarcinoma and squamous cell carcinoma is preop chemorad plus surgery.

Who decides about the optimal treatment strategy for patients with esophageal cancer?

Since the optimal treatment consists of either surgery, either chemotherapy or radiation or a combination of chemoradiation, I think it’s very important that the decision on the treatment is made by a multidisciplinary board where either the surgeon and the medical oncologist and the gastroenterologist and the radiation oncologist decide together so it’s the meeting, the board who decides and not a single doctor.  And that’s also different compared to 15 years ago where it was only one doctor, either the surgeon or the gastroenterologist decided on the treatment. 

Now at least in The Netherlands but I think in the major part of the Western world, most of those complicated patients are discussed in a multidisciplinary board and they are deciding.  I think that has improved results much and has improved also the individual result of the patient because we look from different sides to the problem and we decide together and the patient has already also, at least in Holland, he can discuss treatment with both the radiation oncologist and the surgeon and the medical oncologist and then he himself of course, the patient is the centre, he decides but we give as a multidisciplinary board, we will give the advice.

How does the experience with neoadjuvant radiochemotherapy for esophageal cancer translate to other diseases like e.g. gastric cancer or pancreatic cancer?

It is known now is that chemoradiation, preoperative chemoradiation for oesophageal cancer has improved survival, not only for the squamous but also for the adenocarcinoma.  When you go down and you go to the stomach cancer, still the standard treatment is preop chemotherapy alone and if you look at the results of oesophageal cancer, the improvement by adding preoperative chemoradiation for adenocarcinoma, also for the distal tumours and also for the junction tumours, is as great as in the upper part of the oesophagus.  So it’s a small step to the stomach, so I really believe that for the future the aspect of preoperative treatment will become more important and I think we have to do studies with preoperative chemoradiation also in stomach cancer. 

We are conducting such a trial, there are trials in Australia and also in Germany running or conducting and I really think that’s the way to go to more preoperative treatment, neoadjuvant treatment and I really think, although it has to be proven, that it’s the combination of chemoradiation, I think it will take over from preop chemoradiation also in gastric cancer.

And a step further is pancreas carcinoma.  That’s a really different entity and there are several studies of preop chemoradiation, we have a study running now in The Netherlands but I am very reluctant about positive results in pancreatic cancer, so oesophageal cancer yes, stomach cancer yes.  I think chemoradiation is very important, can improve cure but I am quite pessimistic about its role in pancreatic cancer although several studies are running but not in the near future, I’m afraid not, no.

- Ends -

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