Treatment of Advanced Head & Neck Squamous Cell Carcinoma - Episode 8
Transcript:Robert L. Ferris, MD, PhD, FACS: In terms of treatment selection for head and neck cancer, historically, the first and most widely used approach was surgical removal. We didn’t have radiation therapy and chemotherapies; these came in later. So, we have more decades of experience with surgery; that is a curative therapy. But, of course, removing tissue, tissues don’t regenerate, so we would use surgery if it can be done, usually through the mouth and from a functional standpoint. Surgery has evolved to where it can be done now with lighted instruments, and endoscopically and robotically. Surgery plays an important role in modern day times as well.
Because surgery was used not only for cure, but also to provide the most accurate staging—and to help us decide when we should add radiation therapy or when we could avoid it—the treatment team became disappointed by some of the functional outcomes of open surgical procedures. In addition, we saw that nonsurgical therapy could be curative, and so surgeons, in a healthy competitive environment, found new technological ways to improve the services that we offered to patients. This led to collaborations with companies to help us develop better exposure instruments, better endoscopes, better visualization, and ways to cut out a tumor using a laser or cautery attached to a surgical robot. Over the past five or 10 years, surgeons had to improve the service and the surgical technique by using technology for visualization of the tumor, for exposure of the tumor, and for removal—so we could get the same R0 resection, assessing the margins, assessing the lymph nodes. Our neck dissection is almost never a radical neck dissection anymore. It’s a so-called selective neck dissection where we don’t remove any structure, no nerves and blood vessels and muscles, only the lymph nodes because that’s the information we want. Are the lymph nodes positive or negative? So, surgical technology has advanced, as has our ability to retain all the important structures in the head and neck, to the extent the tumor will permit.
Quality of life and functional status of the patient is really critical. When a patient presents, usually the symptom is driven by the tumor—its location and its size—and that has led the patient to the physician in the first place. Now, the treatment we select, surgery, can also impact and worsen that quality of life and function. I’ve talked earlier about the importance of dissecting lymph nodes in the neck in the need for pathologic staging. This was born out in a recent study where patients were randomized to a watchful waiting approach, relying on CT scans or ultrasound when we thought the neck was negative and there was no metastasis, recognizing that 20% or 30% of those patients had micrometastasis. In many centers, we would do an upfront neck dissection in order to distinguish the 20% or 30% with disease from the 70% who had no metastasis. So, the thought was, doing a neck dissection on everybody is overtreatment for 70% of the patients and subjects them to a decrease in quality of life or functional side effects from doing a neck dissection.
What we found, however, is that there is a survival improvement of about 12.5% from an up-front neck dissection in all patients, even if the neck is clinically negative. So, there is a quality-of-life impact by dissecting the neck and identifying whether the tumor has spread to the lymph nodes, the shoulder strength, range of motion. Some dysfunction from operating on the neck ensues. But when you have a 12.5% survival benefit in a level 1 prospective randomized trial, we think that we can recommend this to patients because the selective neck dissection has a relatively modest impact on quality of life. It’s not zero, but it’s manageable, given the dramatic improvement in survival from an up-front neck dissection.
Jared Weiss, MD: Close to a decade ago, two studies were published back-to-back in the New England Journal of Medicine: the TAX-323 and TAX-324 studies of neoadjuvant TPF chemotherapy. Both of these studies randomized patients to neoadjuvant or induction—if you prefer, cisplatin/5-FU versus cisplatin/5-FU plus docetaxel—and both showed improvements with the addition of docetaxel. However, neither of them compared against standard of care at that time. Neither compared TPF followed by standard-of-care chemoradiotherapy versus standard-of-care chemoradiotherapy alone. The closest we got to that was with the subsequent DeCIDE and PARADIGM trials, which did compare TPF to no TPF, although I would call the chemoradiotherapy a little less than standard. Both trials closed early due to poor accrual. That said, they’re the best data we have on this particular regimen, and both were negative trials. So, in my practice, I do not consider TPF neoadjuvant therapy to be a clinical option.
We are desperate to do something for our very most advanced patients for whom we know the cure rate is not nearly as good as it should be. There was a phase II study done by Merrill Kies of neoadjuvant carboplatin/paclitaxel and cetuximab that had very favorable results. And there have been a series of related phase II trials with similar regimens. I do consider such regimens in my clinical practice for the very most advanced patients, and I think that one of these kinds of weekly regimens of carboplatin—a taxane—and cetuximab does deserve to go to a phase III study against definitive chemoradiotherapy alone.
Transcript Edited for Clarity