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Expert Calls for a Change in the Staging of HNSCC

Angelica Welch
Published: Monday, Nov 20, 2017

Loren K. Mell, MD
Loren K. Mell, MD
The way that cancer, especially squamous cell carcinoma of the head and neck, is staged and risk stratified is inherently flawed, according to Loren K. Mell, MD.

During his lecture at the 2017 OncLive® State of the Science SummitTM on Advanced Head and Neck Squamous Cell Carcinoma and Thyroid Cancer, Mell discussed the need to properly assess patients’ competing risks when considering their treatment options.

“We need to be patient with the research and really pin down good evidence,” said Mell. “We are making every effort to really individualize care within the context of evidence-based medicine. These are inherently in conflict with one another because for us to gather enough evidence, we need to pool a lot of people and treat them somewhat similarly so we can make some statement about the data.”

In an interview that took place during the meeting, Mell, who is an associate professor at the University of California San Diego School of Medicine, explained his research for risk-stratifying patients with head and neck cancer.

OncLive: What are the biggest issues right now with staging for head and neck cancer?

Mell: What we are interested in knowing is, essentially, which patients are most likely to benefit from more versus less intensive therapy. There are 2 components to that. First—is this therapy more effective? Usually, the gold standard for testing that is a randomized trial. The other component is the specific individual in front of us and their characteristics.

What we are trying to do is come up with a different method and approach that makes more mathematical sense than historical standards. The idea that most people will be familiar with is staging—[patients] often want to know the stage of their cancer. Staging has an interesting history to it. Essentially, it is used for a couple different purposes. One is to try to get a sense of how extensive or advanced the cancer in front of us is, and whether we should do more limited treatment. Or, is it more advanced, where surgery may be off the table? Those people typically range from 1 to 4, with 4 being quite advanced. We know that there are many other factors that we need to know about. Just knowing someone's stage isn't sufficient enough to formulate a treatment plan for them.

A lot of our attention has rightfully been focused on characteristics of the cancer itself. What tumor size is it? Has it spread to the nodes? Has it spread to distant parts of the body? But there are genetic factors that might determine [a cancer’s] behavior. Particularly, if we have drugs that act in one way for a certain mutation, that would be ideal to know.

A sort of less appreciated, but equally important, component to it are other factors that are maybe less biologically dramatic but no less important. Age is a big factor, as well as other health problems. These are things that we need to incorporate into our treatment plan. 

What led to the need for an assessment like this? Are patients being overtreated or undertreated?

The answer is both. The reason for that is the dominant paradigm that we use to risk-stratify patients is okay but fundamentally flawed. The fundamental flaw has to do with the fact that most of these model patients’ risks. If you try to sort out 100 patients, you say, “These top 25 patients are highest risk and these bottom 25 are lowest risk.” 

Those models tend to focus on 1 endpoint, or class of endpoints, called event-free survival. The typical one would be overall survival. That is very simple to quantify and it is unambiguous. It is a desirable endpoint to know, and by and large it works, but where it breaks down is where people have an appreciable risk of dying of something else. 

Those models fail because what they do is treat a death from cancer equally to a death not from cancer; those are obviously not the same thing. Someone who has a very poor survival tends to be labeled as high risk. However, imagine a patient where 75% of that risk is attributable to one of their other health problems. That makes no sense because, per the model, you would put them in the same risk pool as someone who has a horribly advanced cancer and needs more treatment.

If you do not separate those events, you have no hope of solving anything. This is part of the problem with risk-stratification schemes that focus solely on the tumor because, at best, they can only explain part of the problem. 

How would improving this risk-assessment program impact the treatment of patients with head and neck cancer?

Our treatments for other diseases have gotten better. People are aging better overall and our population is aging. We are seeing a lot more older patients presenting with cancer, have many years left to live, and look like they are 50. Yet, our current treatment paradigm tells us that those patients don't benefit from chemotherapy.


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