Surgical planning for head and neck cancer benefits from FDG-PET/CT

A new Journal of Clinical Oncology report immediately informs practicing clinicians of the effectiveness and benefits of FDG-PET/CT in head and neck cancer patients, especially those who are clinically node-negative


Credit: Mayo Clinic

The Journal of Clinical Oncology has published the results of the largest prospective multicenter trial conducted of FDG-PET/CT in head and neck cancer, providing rigorous data about its performance. The nonrandomized phase two trial, ACRIN 6685, followed 287 patients with newly diagnosed stage T2 to T4 disease, all being considered for surgery when at least one side of the neck had no evidence of lymph node involvement based on a physical exam, preoperative MRI and/or a CT evaluation (clinically node-negative or cN0). It found that FDG-PET/CT imaging achieved a true negative in 94 percent of patients (by standardized uptake value (SUV) analysis), or 87 percent of patients (by visual assessment). The trial was designed and conducted by researchers in the ECOG-ACRIN Cancer Researcher Group with support from the National Cancer Institute, part of the National Institutes of Health.

“The information provided by FDG-PET/CT of the cN0 neck changed the surgical plan 22 percent of the time,” said the study’s principal investigator and lead author Val J. Lowe, MD, a nuclear medicine specialist at Mayo Clinic in Rochester, MN. “These findings suggest that FDG-PET/CT may assist the clinician in deciding on the best therapy for the clinically N0 neck in head and neck squamous cell carcinoma, possibly preventing patient morbidity and/or saving significant costs.”

The reliability of FDG-PET/CT in detecting lymph node metastases in head and neck cancer is well proven and is reported to be cost-effective in staging patients with cN0 necks. Most of the data is single-institutional and retrospective. Surgeons often perform elective neck dissections in patients with cN0 necks at high risk for recurrence because clinical exam and structural imaging do not reliably identify all metastatic disease. This approach has been found to improve survival but may be associated with substantial complications for patients.

“A negative scan in the cN0 neck has been demonstrated by our study to have a very high negative predictive value,” said co-principal investigator and co-author Brendan C. Stack, Jr., MD, a surgeon at the University of Arkansas for Medical Sciences. “Additionally, the positive PET leads the surgeon to consider resection of nodal levels that might harbor occult metastatic disease.”

Participants older than 18 years of age with newly diagnosed, first-time head and neck squamous cell carcinoma were recruited from 22 qualified sites in the United States and one in Beijing, China. FDG-PET/CT was compared with pathology findings at neck dissection. Participants all received a pre-surgical FDG-PET/CT scan to which the surgeon was initially blinded and a contrast-enhanced MRI or CT scan of the neck (all within four weeks of surgery).

The surgical plans were devised by the local surgeons on the basis of physical examination and CT and/or MRI results, but not PET/CT and thereafter formulated with the available PET/CT result. Both plans were collected prospectively with questionnaires. All data were anonymized to protect the identities of the participants.

FDG-PET/CT scans and pathology findings were available for 270 cN0 neck sides from 212 participants. Pathology was randomly over-read by a central pathologist and all scans were reviewed by a team of central readers. For visual assessment, the negative predictive value (NPV) specific to the cN0 sides was 0.868 (95 percent CI, 0.803 to 0.925). For dichotomized maximum SUV, the NPVs specific to the nodal basins were 0.940 (95 percent CI, 0.928 to 0.952) and 0.937 (95 percent CI, 0.925 to 0.949) at prespecified cutoffs of 2.5 and 3.5, respectively. The optimal cutoff maximum SUV was determined to be 1.8, with an NPV of 0.942 (95 percent CI, 0.930 to 0.953).

The FDG-PET/CT-informed surgical treatment plan was changed in 51 of 237 participants (22 percent) compared with the PET/CT-blinded surgical plan. In 34 participants (12 percent), this led to planned dissection of additional nodal levels. In 12 participants (5 percent), this led to fewer planned dissected nodal levels. Negative PET/CT scans in N0 necks were true negative in 87 percent and false negative in 13 percent.

“This trial is an excellent example of a means to implement personalized medicine in the setting of head and neck cancer management,” said Dr. Stack.


The results appear in print in The Journal of Clinical Oncology vol 37, no. 20 (July 10 2019), pgs 1704-1712.

The federal trial record on is NCT00983697.

About the ECOG-ACRIN Cancer Research Group

The ECOG-ACRIN Cancer Research Group is a membership-based scientific organization that designs and conducts cancer research involving adults who have or are at risk of developing cancer. ECOG-ACRIN comprises nearly 1100 member institutions in the United States and around the world. Approximately 12,000 physicians, translational scientists, and associated research professionals from the member institutions are involved in Group research, which is organized into three scientific programs: Cancer Control and Outcomes, Therapeutic Studies, and Biomarker Sciences. ECOG-ACRIN is supported primarily through National Cancer Institute research grant funding, but also receives funding from private sector organizations through philanthropy and collaborations. Its headquarters are in Philadelphia, Pa. For more information, visit, follow us on Twitter @eaonc, Facebook and LinkedIn, or call 215.789.3631.

ACRIN 6685 Participating Institutions and Their Lead Nuclear Medicine and Radiology Investigators

Biomedical Research Foundation: Amol M. Takalkar and Cherie-Ann Nathan

City of Hope Medical Center: Bihong Beth Chen and Ellie Maghami

Fox Chase Cancer Center: Jian Q. (Michael) Yuand Miriam Lango

Johns Hopkins University: Rathan Subramaniam, Lilja Solnes, and Jeremy Richmon

Mayo Clinic: Val Lowe and Eric Moore

Clinical Radiologists Springfield Illinois: Charles E. Neal and James Malone

Mercy Hospital Springfield: Robert Sonnemaker and A. Daniel Pinheiro

Morton Plant Mease Health Care: Yair Safriel and Jonathan Morgan

Peking Union Medical College: Fang Li and Lian Zhou

Thomas Jefferson University: Charles Intenzo and David Cognetti

Southern Illinois University School of Medicine: Anton Johnson and Arun Sharma

University of Alabama at Birmingham Medical Center: Janis P. O’Malley and William Carroll

University of Arkansas for Medical Sciences: Twyla Bartel and Brendan Stack

University of Florida Health Science Center: Barry M. McCook and Rui Fernandes

University of Mississippi Medical Center: Andrew D. Smith and Karen Pitman

University of Oklahoma Health Sciences Center: Charles Arnold and Greg Krempl

University of Pennsylvania: Laurie Loevner and Kelly Malloy

University of Southern California: John L. Go and Uttam Sinha

University of Texas Southwestern: Rathan Subramaniam and William Moore

University of Washington: Yoshimi Anzai and Neal Futran

Wake Forest: Carol Geer, Anita J. Thomas and Christopher Sullivan

Washington University: Farrokh Dehdashti and Brian Nussenbaum

Weill Medical College of Cornell University: Lilja Solnes, Yuliya Jhanwar and William Kuhel

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