PET may artificially boost HNC survival rates

2014 08 08 16 04 10 879 Pet Scan Patient 200

The use of positron emission tomography (PET) is associated with a stage migration phenomenon in locally advanced head and neck cancer (HNC) patients, according to a recent report in JAMA Otolaryngology -- Head & Neck Surgery.

Multiple studies have shown the increased sensitivity of fluorodeoxyglucose (FDG)-PET over computed tomography (CT) for detecting primary tumors, regional nodal disease, and distant metastases. Because of potential treatment changes and prognostic information, as well as patient and physician preference, FDG-PET has been rapidly adopted for managing head and neck cancers.

Because FDG-PET is more sensitive than CT, it often leads to patients being assigned a higher stage than if they were staged with CT alone, the study authors noted.

In this retrospective study, the researchers sought to confirm whether the increased use of FDG-PET over time is associated with the appearance of improved stage-specific survival due to stage migration (JAMA Otolaryngol Head Neck Surg, July 1, 2014, Vol. 140:7, pp. 654-661).


In the study's model of clinically important variables, PET scan use was associated with a higher stage of disease. In addition, oropharyngeal cancers were more likely to be assigned a higher stage than oral cavity cancers.

Within the PET era, no statistically significant survival difference was found between those who underwent FDG-PET and those who did not. However, a significant increase in stage-specific survival was detected for patients with locally advanced disease. No stage-specific survival differences were found in patients with local disease or metastatic disease.

Noam VanderWalde, MD. Image courtesy of the University of Tennessee.Noam VanderWalde, MD. Image courtesy of the University of Tennessee.

Two-year survival for all patients, no PET versus PET, was 55.5% versus 53.2%. Two-year survival for locally advanced disease, no PET versus PET, was 32.1% versus 52.2%.

Recently, a large Medicare claims-based study demonstrated a similar up-staging phenomenon with the increased use of FDG PET scans in non-small cell lung cancers, the study authors noted (Journal of Clinical Oncology, August 1, 2012, Vol. 30:22, pp. 2725-2730)

Lead author Noam VanderWalde, MD, now an assistant professor of radiation oncology at the University of Tennessee West Cancer Center, said this study's findings reflected the same phenomenon.

"In general, that's what you tend to see when you have newer diagnostic tools: You get a stage migration," Dr. VanderWalde told "You get patients put into different stages that artificially looks like there's a survival benefit, but it's not a real survival benefit for that individual patient. It's just places patients better into different stages."

The researchers found an increase in the number of PET patients who received chemotherapy (43.1% versus 17.5%). However, they also noted that patients who underwent FDG-PET were less likely to receive no treatment compared with patients who did not undergo FDG-PET.


The study was conducted within four large, nonprofit, integrated health systems: Group Health Cooperative (Seattle), Health Alliance Plan -- Henry Ford Health System (Detroit), Kaiser Permanente Colorado (Denver), and Kaiser Permanente Northwest (Portland, OR).

“If you're going to be spending a lot of money on a specific type of test, you want it to actually change what you might do.”
— Noam VanderWalde, MD

The study group included patients older than 18 years who were diagnosed as having head and neck cancer between 2000 and 2008.

Disease stages were classified into three clinically relevant groups: localized (stages I and II), locally advanced (stages III, IVA, and IVB), and metastatic (stage IVC).

The PET era was defined as the period from 2005 through 2008; the pre-PET era as 2000 through 2004. The survival comparison for the PET era versus pre-PET era was limited to patients in the PET era diagnosed in 2005 and 2006 and having at least two years of follow-up.

The study included 958 patients, with 46% treated in the PET era. The oral cavity was the most common primary tumor site, and most patients were diagnosed as having localized disease.

Median patient age was 66 years; median follow-up for all patients was 31 months. The median follow-up for patients in the pre-PET era was 56 months. For surviving patients in the PET era, the median follow-up for those who underwent PET was 22 months, and the median follow-up for those who did not undergo PET was 27 months.

Pre-PET era versus PET era

The researchers found no statistically significant differences in the primary tumor sites, stage, age, sex, or comorbidities between patients in the pre-PET and PET eras. However, a significant difference in the type of treatments patients received was detected: less use of surgery (pre-PET era, 66.9% versus PET era, 53.7%) (p < 0.001) and a trend toward increasing use of chemotherapy during the PET era (pre-PET era, 20.5% versus PET era, 25.9%) (p = 0.05). No difference in two-year overall survival rates was found (pre-PET era, 75.5% versus PET era, 74.0%) (p = 0.34).

In the PET era, tumor site was significantly associated with use of PET for staging (p < 0.001). Younger patients and those with later years of diagnosis were more likely to have undergone FDG-PET scans (p < 0.001). The use of FDG-PET for staging purposes has been increasing since 2005 among this group, the study authors noted.

In 2005, about 12.5% of patients received pretreatment FDG-PET scans. By 2008, the percentage more than doubled to 34%. Compared with patients who did not undergo PET, those who underwent PET were more likely to receive radiation treatment (no PET, 48.3% versus PET, 83.3%), more likely to receive chemotherapy (no PET, 17.5% versus PET, 43.1%) and less likely to receive no treatment (no PET, 18.8% versus PET, 0%).

Within the PET-era group, the researchers noted a statistically significant increase in the number of patients staged as having locally advanced disease. In oral cavity and larynx and/or hypopharynx disease, most patients who underwent PET scans were staged as having locally advanced disease, while those without PET were mostly staged as having local disease.


The upstaging of patients with nodal disease identified only by FDG PET improved the survival of all patients with nodal disease, compared with those with obviously identified (no FDG-PET) locally advanced disease, the researchers found.

A difference in staging and survival was not found between the pre-PET and PET eras.

"This is interesting given the increasing incidence of human papillomavirus (HPV)-related oropharyngeal cancers over this period and their associated higher stages and improved prognoses," the study authors wrote.

One of the potential benefits of a staging FDG-PET scan is the identification of previously unknown metastatic disease, they noted.

"FDG-PET use appeared to be associated with upstaging at diagnosis and improved

survival in patients with locally advanced disease but no difference in overall survival for the entire cohort," the researchers concluded. "The improved stage-specific survival is likely a reflection of stage migration. The ability of FDG-PET to affect patient management for individual patients remains an important area of future research."

"The real question for clinicians is, 'Should we routinely be using PET scans to diagnose head and neck cancer patients?' " Dr. VanderWalde said. "Unfortunately, the study doesn't really answer that question. It does say there's probably not a survival benefit, and that would be the only reason to use PET scans."

A diagnostic tool's value lies in helping clinicians determine the best course of treatment, he noted.

"Other studies show PET is more sensitive, but, in general, I think it's best for clinicians, especially those treating cancer, even if the test is a lot more accurate, is it going to change how they treat a patient?" Dr. VanderWalde said. "If you're going to be spending a lot of money on a specific type of test, you want it to actually change what you might do."

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