Surgery and Radiotherapy for HNSCC

Transcript:Ezra Cohen, MD: Tanguy, we haven’t talked about surgery too much. Kevin just brought it up. Tell us how surgery plays a role in the management of these patients.

Tanguy Y. Seiwert, MD: Well, I think surgery is an essential part of treatment, in general, and oftentimes, patients come in through surgeons first. And I think for early stage, surgery remains clearly the preferred option. Patients are done with treatment quickly, and it’s highly, highly curable. But even for more advanced tumors, especially for the HPV-positive tumors, oftentimes surgery is a consideration. There’s now a new approach—it was briefly mentioned already, transoral robotic surgery (TORS), or laser resections—that may actually provide a good alternative outcome for early intermediate stage HPV-positive tumors. We do some of that. I think the data are still emerging on when and how to best integrate it, but there a number of trials actually doing that. And some centers actually do fair amounts of volume with good results.

It’s also potentially a way to maybe de-escalate treatment. There’s an ECOG study, that I think is being led by Bob Ferris, that explores the role of TORS in certain patients and gives them less treatment otherwise. And I think it might play an important role. So, I think surgical techniques are evolving, the radiation techniques are evolving, but also, clearly, chemotherapy and systemic agents are evolving. Immunotherapy is just one of those areas that I think, right now, is really interesting as we’re starting to see really positive data.

Ezra Cohen, MD: Viktor, how does the surgeon and surgical approaches come into play at your center?

Viktor Grünwald, MD: Certainly, novel techniques are also very important for the type of surgery, for the approach of surgery, and I think we have very dedicated surgeons, as well, in Germany. They succeed on that path actually. And I think TORS is really an important tool for that part to spare toxicity, to reduce the mobility that they cause on patients with that type of approach. Laser resection will be another one for selected cases. So, certainly this is not something you would apply to any patient at any stage. These are really selective cases and for those over TORS on the horizon that play into the rebirth. We will be more and more frequently using that in the future, I think.

Ezra Cohen, MD: Yes, and in fact, I dare say that many of the German surgeons were pioneers in this field. So, we talked about the approach to the patient in general. We talked about surgery, we talked a little bit about systemic therapy. Kevin, as the token radiation oncologist on the panel, talk to us about radiation. What are the considerations in a patient with locally-advanced disease?

Kevin Harrington, MD, PhD: It’s important to emphasize, I think, that the practice of radiotherapy has been completely revolutionized in the last 15 to 20 years. Indeed, when I embarked upon a career as a radiation oncologist, one of the questions I was frequently asked was, “Why are you bothering with this? It will be obsolete by the time you’re getting ready for retirement.” And I think we’ve seen exactly the opposite. Radiotherapy is assuming an even greater role in the management of patients, and that’s because we’ve gotten away from the old-fashioned techniques of large fields applied in a fairly indiscriminate carpet-forming fashion to both tumor and normal tissues alike.

And actually the development of technology, such as intensity-modulated radiotherapy (IMRT), the use of image-guided radiotherapy, where you use very detailed and accurate scanning techniques in order to define where the tumors are and where the normal tissues are, and you can deliver radiation to the tissue you need to treat and avoid the tissues you would wish not to treat, I think that has completely changed things. I think standing out from my own practice is the work of my friend and colleague, Chris Nutting, who performed the PARSPORT study, which demonstrated intensity-modulated radiotherapy makes a huge difference to the outcomes in terms of long-term dry mouth, which was one of dominant effects of radiotherapy and one of the major impacts on quality of life. So, I think we’ve gone beyond the old star radiotherapy and, indeed, the next generation of radiotherapy tools. I’d mentioned the phrase jokingly, “arms race.” Well, the surgeons have robotic tools in order to deliver surgical approaches. We’ve increasingly now got complex methodologies to deliver radiotherapy, including the development of things like CyberKnife and stereotactic radiation, and also now the development of the MRI-guided LINAC (MRI-guided linear accelerator). And that really allows us to take images in real-time of patients receiving radiotherapy. The ultimate goal of that, of course, would be to be able to take functional images.

So, for instance, imagine a scenario where you could look at hypoxia on an MRI scan in real time during a fraction of radiotherapy and adjust the radiation dose to the hypoxic subfraction second-to-second during the radiation or to areas of high proliferation as measured, for instance, by diffusion-weighted MRI during the fraction of radiotherapy. I think it’s going to completely change the game.

And then, of course, the other big player in the field is the emergence of Proton Beam. Proton Beam really has such beautiful and exquisite dosimetry in terms of how it delivers a dose to tumor tissue and can spare normal tissue. Of course, it has financial constraints, and I come from a jurisdiction where we don’t yet have any machines, but we have plans to have 2 in the near future. And I think the understanding of where Proton Beam plays the correct role in patients with head and neck cancer is an important consideration. I think in the first instance, for those younger patients with highly curable disease who will live decades with the potential toxicities of what we do, I can foresee clinical trial scenarios where we can validate the use of Proton Beam for those patients.

Ezra Cohen, MD: Without a doubt. I can tell you from my own personal experience, the rates of xerostomia and the severity of xerostomia since the introduction of IMRT are dramatically, dramatically different. Of course, your colleague Dr. Nutting, that you mentioned, actually demonstrated that on prospective trials. The severe xerostomia that we used to see a decade ago, I think I hardly see any more in my clinic. I don’t know if your experience is very similar.

Tanguy Y. Seiwert, MD: Yes, very similar experiences. Also, when it comes to like fibrosis in the neck, actually there are much better outcomes. The other thing that I really would like to caution is, as these radiation techniques get increasingly complicated, experience again plays a big role. And I think it is very easy to say, “Oh, it’s IMRT.” But IMRT is not the same as IMRT at a center that has a lot of experience. In fact, having that experience is really essential. So, I think larger centers do better with these more advanced technologies.

Ezra Cohen, MD: It’s a real skill set to be a radiation oncologist.

Tanguy Y. Seiwert, MD: In fact, I always say the radiation oncologists are almost like the surgeons—it is a skill. Everybody can give chemotherapy, obviously, but radiation is a real skill. I hope you agree.

Kevin Harrington, MD, PhD: Thank you for that small acknowledgement.

Transcript Edited for Clarity