Head and neck cancer care has been undergoing a paradigm shift over the past decade, moving from a surgery-based approach to one that increasingly relies on chemoradiation (CRT). Few trials have directly compared the approaches, but experts agree that for some patients the two approaches can be equally efficacious. The key, they caution, is selecting the appropriate patients.
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April 2008
Historically, most patients were treated with surgery or surgery followed by radiation. However, a landmark study published in 1991 by Veterans Administration researchers showed that for some patients with stage III or IV tumors of the larynx, chemoradiation preserved the organ and resulted in the same survival as surgery followed by radiation. Based on those data, and a few trials that have followed, many physicians now offer their patients organ preservation therapy in the form of chemoradiation.
All of a sudden there appeared to be the opportunity to treat people as effectively, or more effectively, than in the past, without them being required to have the pain suffering, cosmetic deformity, and functional deformity of the surgery, said Jonas T. Johnson, MD, Professor and Chairman of the Department of Otolaryngology and Professor of Radiation Oncology at the University of Pittsburgh School of Medicine. That sounds like wonderful news, but, in fact, it is imperfect.
At least two retrospective studies have found that the five-year survival rate in laryngeal cancer has dropped over the past decade and that the use of CRT has increased over the same time period. Although such database reviews cannot show a causal link between increased use of CRT and declining survival, the observation is reason for concern, according to Christine Gourin, MD, Associate Professor and Director of the Clinical Research Program in Head and Neck Cancer at Johns Hopkins University School of Medicine in Baltimore.
My hypothesis-and others suspect the same thing-is that the decrease in survival might be because there are some patients who are receiving CRT who are not going to do well with organ preservation therapy, she said. Those are patients with gross cartilage involvement, soft tissue or skin involvement, or very extensive tumors that have a large volume. In addition, there just are no data to support the use of CRT for oral cavity tumors. Those patients benefit more from surgery with postoperative radiation to clean up microscopic residual disease.
Moreover, Dr. Gourin does not recommend CRT for patients with T4 larynx tumors and who are dependent on a feeding tube before treatment, or those whose tumor is infiltrating nerves, because that can be a sign of more aggressive disease.
Both Dr. Gourin and Dr. Johnson emphasize that patient selection must be based on clinical trial data. That means that only patients with stage III or IV tumors of the larynx and those with tumors at the base of the tongue or tonsils should be treated with CRT. After that, we continue to struggle with indications, with who needs to get this therapy, Dr. Johnson said. There is a tendency on the part of the public, and even on the part of the doctors, to think if it is good for one, it is good for everybody. And that is not true.
Early-stage patients-those with stage I and II disease-can be treated with surgery alone or radiation alone. And with improved surgical techniques and tools, such as the laser, surgeons can remove small tumors with little morbidity, according to Dr. Johnson. Thus, CRT is not appropriate for patients with early stage disease. On the other hand, stage IV tumors require multimodality therapy; however, the exact combination of treatments that should be used for these patients is still a matter of ongoing study. Unfortunately, trials that randomize patients to surgery versus organ preservation therapy are hard to do, because few patients are willing to leave that choice up to the flip of a coin. That said, more studies are needed to better determine the effectiveness of CRT in different subsets of patients.
Monitoring for Treatment Failure and Function
Monitoring patients after CRT is critical. Some patients will suffer a recurrence, and diagnosing that relapse can be difficult. Computed tomography (CT) cannot distinguish between tumor regrowth and inflammation. Instead, Dr. Johnson suggests that patients need to be followed with combined positron emission tomography/computed tomography (PET/CT) to look for anatomic abnormality with elevated metabolism.
If patients do relapse after CRT, treating them is more difficult. We know that if they have had radiation in the past, their chances of having problems after surgery are much higher, said Mark Wax, MD, Professor of Otolaryngology and Head and Neck Surgery and Program Director of Otolaryngology at Oregon Health and Science University in Portland. However, if they have CRT, and require surgery after that, complications of wound healing and rehabilitation are higher than after radiation alone.
But even for those whose cancer is eliminated by CRT, avoiding surgery may not improve or preserve function. We do know that there are some people who do terribly with CRT, Dr. Gourin said. If they have a nonfunctional organ up-front, and you try to preserve it, such patients may not do well from a functional standpoint because the organ you were preserving was not functional.
To better identify the patients who are unlikely to have good functional outcomes following CRT, Dr. Gourin and her colleagues at the Medical College of Georgia in Augusta, where she was previously on the faculty, performed fiberoptic endoscopy evaluation of swallowing (FEES) exams on patients prior to treatment. They found that 40% of their patients showed signs of aspiration, and in 25% the aspiration was silent. I suspect those cases will do poorly with CRT, she said. We are in the process of collecting the post-treatment data to correlate [the outcomes with FEES results], but this may be one way of predicting who will do poorly or not.
Similarly, Dr. Johnson pointed out that in patients in whom the tumor has destroyed the organ, surgery may be the best choice. I believe that there does exist a cohort of patients with advanced primary tumors who are probably better served with resection and reconstruction and then adjuvant therapy, because the advanced primary tumor has so disrupted function that it can not possibly be expected to fix itself, Dr. Johnson said. So even though the CRT might conceivably cure the tumor, it doesn’t fix the problem.
Coping with Toxicity
Although organ preservation therapy may prevent the need for a disfiguring surgery, it causes significant side effects of its own. One of the most significant side effects of CRT is mucositis and stenosis. The majority of patients have swallowing problems following CRT. Some patients are unable to eat solid foods and thus have trouble maintaining their weight. And aspiration is a big problem. The exact rate of such complications is not clear because different groups report different numbers, but Dr. Gourin noted that recent studies have reported as many as 75% of patients become reliant on a feeding tube long-term.
Unfortunately, there aren’t a lot of data that compare the two options head to head, said Dr. Wax. And explaining the potential problems to patients isn’t always straightforward. People can very easily conceptualize the problems they are going to have when they have surgery. But I don’t think people can conceptualize what radiation or chemotherapy does.
There are a large number of ongoing clinical trials designed to test new drug regimens, including some molecularly targeted agents. Thus, less-toxic regimens might be identified that would make the use of CRT more advantageous.
I think we are becoming more concerned with their quality of life, Dr. Wax concluded. How well can we get these patients to be able to eat in public, so they think that they have a life instead of thinking ‘Okay, you cured my cancer, but what in life is there worth me living for?’ I think we need to start to examine those types of issues.
Both Dr. Wax and Dr. Gourin led minisymposia on surgery versus CRT last year at the AAO-HNS meeting. Dr. Gourin expects that such discussions will continue over the next several years as researchers and clinicians try to sort out just how best to use organ preservation therapy.
©2008 The Triological Society