Initial Performance of NI-RADS to Predict Residual or Recurrent Head and Neck Squamous Cell Carcinoma

Inclusion Criteria

1. Treated primary H&N squamous cell carcinoma.

2. CECT and/or CECT/PET for surveillance.

3. NI-RADS template used for interpretation.

A total of 402 scans met the inclusion criteria.

Criteria for tumor recurrence or persistence included the following: 1) Biopsy positive for squamous cell carcinoma, 2) evidence of disease progression on subsequent imaging (per Response Evaluation Criteria In Solid Tumors criteria; http://www.radiologytutor.com/index.php/cases/oncol/139-recist), or 3) obvious tumor on physical examination. To confirm the lack of tumor recurrence, we assessed the following: 1) follow-up imaging at least 90 days after the index scan, 2) clinical follow-up for at least 6 months without evidence of recurrence, or 3) biopsy of an abnormality detected on the index scan with pathology results negative for tumor.

Exclusion Criteria

1. Insufficient outcomes data to determine positive or negative disease.

2. Score of “4, known recurrence” because recurrence had already been proved before the scan. However, it is possible to have a score of 4 for the primary site and 1, 2, or 3 for lymph nodes (or vice versa). Thus, an outcome could still be determined for nodes so that each scan had 2 possible sites for target abnormalities (primary and neck).

3. Multiple scans in the same patient if there were back-to-back scores of 1 for both primary and neck. In this case, subsequent index scans were excluded because the final outcome of “recurrence or not” for the primary or neck would be the same for these 2 data points.

These criteria yielded 287 patients, 318 scans, and 618 total targets (314 primary targets and 304 nodal targets) for which outcomes could be determined.

Surveillance Algorithm and Image Interpretation

At our institution, all patients with advanced H&N cancer (almost all patients except those with T1 N0 disease) are scanned with CECT/PET at 12-week baseline, and if the findings are negative, they undergo a CECT alone 6 months later. If these findings are negative, they undergo a CECT 12 months later. All NI-RADS surveillance scans were interpreted prospectively using the template by 1 of 4 dedicated H&N neuroradiologists (30, 15, 10, and 9 years of experience). Both the primary site and neck were assigned a NI-RADS category of 1–4. For this study, all category 2 subcategories were recorded as general category 2. For scores of 2–4, the target abnormality was described briefly in the impression after the numeric score. The NI-RADS template, created by a multidisciplinary team and implemented in 2014, has been subject to ongoing peer review through weekly tumor boards and the American College of Radiology RADPEER. Interpreting radiologists reviewed prior clinical history and endoscopic notes. Comparison with baseline imaging, including pretreatment FDG avidity when available, was made. The subjective interpretation of the PET/CECT included evaluation of disease on both fused PET and CECT. As noted in the NI-RADS template, factors incorporated into lesion assessment included the following: size, FDG avidity, morphology, and enhancement pattern. Because previous studies have established that the standard uptake value data do not improve diagnostic accuracy for disease after treatment for H&N cancer, a strict threshold for standard uptake value was not used.^6,12,13 Instead, a subjective dichotomous analysis of intense FDG uptake was determined.

Image Acquisition

All PET/CT imaging followed standard protocol, and was performed on GE Discover 600 and 690 PET/CT scanners (GE Healthcare, Milwaukee, Wisconsin). Patients fasted for 6 hours before the scan, and serum glucose concentration was obtained immediately before FDG administration. The examination was deferred if glucose was >200 mg/dL. Combined PET/CT from the skull vertex through the midthigh was obtained 1 hour after intravenous administration of 10–14 mCi of FDG. Helical noncontrast CT from the vertex through midthigh was performed before PET for attenuation correction and anatomic localization. A CECT of the neck with the arms down was performed following PET. Our split-bolus technique used 110 mL of intravenous iopamidol (Isovue-370; Bracco, Princeton, New Jersey), with 55 mL injected first at 2.5 mL/s, a 40-second delay, then another 55 mL at the same rate, with a total scan delay of 90 seconds. We acquired axial images from the frontal sinuses through the mediastinum at 1.25-mm section thickness; pitch, 0.984:1; gantry rotation, 0.7 seconds; FOV, 25 cm; 120 kV(peak); and Smart milliampere with a noise index of 13.78. Reformatted images at 2.5-mm thickness in the axial planes and 3-mm sagittal and coronal reformations were sent to the PACS.

Statistical Methods

Univariate association between recurrence and scan score (1–3) was estimated by the χ² test and the nonparametric Fisher exact test. The same analysis was repeated for primary site, lymph node, and their combination separately. The overall performance of discrimination of the scan score on recurrence status (yes versus no) is measured as the area under curve (AUC) by receiver operating characteristic (ROC) analysis with 95% confidence intervals. The sensitivity and specificity at each cut-point of the scan score were presented accordingly for score 1 versus 2–3 and for scores 1–2 versus 3. Additionally, the same ROC analyses for subgroup performed for CECT alone versus CECT + PET and for the first posttreatment examination versus the subsequent surveillance examination were explored. The interobserver agreement was measured by κ statistics among 40 scans for primary and neck sites by 2 graders. The statistical significance level was set at P < .05, and analyses were conducted in SAS 9.4 (SAS Institute, Cary, North Carolina).