PET-CT–Guided Surveillance May Reduce Need for Surgery in Some Patients with Advanced Head and Neck Cancer

Summary

Patients with advanced squamous cell carcinoma of the head and neck who underwentPET-CT imaging after chemoradiation to determine if they still needed to have surgery had overall survival rates similar to those of patients who underwent planned neck dissectionand chemoradiation. PET-CT imaging also resulted in fewer operations and was more cost-effective.

Source

New England Journal of Medicine, April 14, 2016 (see the journal abstract).

Background

Chemoradiation is the standard first-line therapy for patients newly diagnosed with squamous cell carcinoma of the head and neck. Patients with stage N2 or N3 disease, which is advanced disease involving the lymph nodes, are usually referred for further treatment. However, because of a lack of clear evidence from prospective randomizedcontrolled trials, treatment after chemoradiation varies widely.

One option is surgical dissection of the neck to remove any remaining tumor tissue. This approach has been found to improve survival but is also associated with substantial complications. Identifying patients who could avoid this surgery is therefore important.

Improvements in imaging techniques have allowed clinicians to identify patients who may be able to avoid surgical dissection. An advanced imaging techniques that combines 18F-fluorodeoxyglucose (FDG) positron-emission tomography and computed tomography (together known as PET-CT) has been shown to successfully identify both structural and metabolic abnormalities in tumors.

The Study

The prospective randomized controlled PET-NECK Trial was launched to determine the clinical usefulness and cost-effectiveness of planned neck dissection versus PET-CT–guided surveillance in patients with advanced squamous cell carcinoma of the head and neck.

From 2007 to 2012, Hisham Mehanna, Ph.D., of the University of Birmingham, and his colleagues enrolled 564 patients from 37 cancer treatment centers in the United Kingdom. The patients had squamous cell carcinoma of the head and neck with stage N2 or N3 nodal metastases confirmed by standard CT or magnetic resonance imaging. The main goal of the study was to determine if PET-CT surveillance was not inferior to planned dissection in terms of overall survival.

Patients were randomly assigned first to PET-CT surveillance or planned necked dissection. Those in the PET-CT group got chemoradiation and then PET-CT–surveillance (and neck dissection in this group was performed only if PET-CT showed an incomplete or equivocal response to chemoradiation). Those in the second group got planned neck dissection.

The trial was funded by the National Institute for Health Research Health Technology Assessment Programme and Cancer Research UK.

Results

At a median follow up of 3 years, patients in the surveillance group had fewer neck dissections than those in the planned surgery group (54 versus 221 dissections, respectively). Among those who had surgery, the rate of surgical complications was similar in the two groups (42% versus 38%, respectively), as was quality of life. The two study groups had similar 2-year overall survival rates: 84.9% for patients in the surveillance group, and 81.5% in the planned surgery group.

There was a difference in the per-patient cost of treatment between the two groups, with PET-CT surveillance resulting in savings equivalent to about $2,200 U.S. dollars per patient over the course of the trial.

Limitations

The type of neck dissection patients received varied, as the decision was made by the treating surgeon. Of the 282 patients in the planned surgery group, 61 (22%) did not undergo neck dissection for various reasons. And the time interval between the end of chemoradiation and surgery varied considerably among patients, confounding the results.

The number of patients with N3 disease was small, making it difficult to know whether the trial results are generalizable to that patient population. And the results of PET-CT imaging were assessed qualitatively, not quantitatively, which makes comparisons between patients more difficult. Different centers involved in the trial also used different PET-imaging systems, limiting the ability to reliably cross-validate the results.

Comments

“These are intriguing results that need to be verified given some of the limitations, including a heterogeneous study population,” noted Shakun Malik, M.D., of NCI’s Division of Cancer Treatment and Diagnosis. “And if we were to conduct such a trial in the future, we would want all of the investigators to use a standardized PET imaging modality.”

Dr. Malik also noted that the results are based on only 2 years of follow up. “We really need to see long-term results to know if these findings hold up.”

The fact that quality of life was similar in both study groups “is discouraging,” said Dr. Malik. However, the approximately $2,200-per-patient cost savings for the surveillance group versus the surgery group was encouraging and may be relevant to health care costs in the United States, she added.

“In fact, a number of trials similar to this one are being considered in the United States, and those trials may help answer the questions posed in this study more fully,” she concluded.