Lymph node metastases from head and neck squamous cell carcinoma: MR imaging with ultrasmall superparamagnetic iron oxide particles (Sinerem MR) – results of a phase-III multicenter clinical trial

Abstract

The aim of this study was to compare the clinical usefulness of ultrasmall superparamagnetic iron oxide (USPIO) MR contrast media (Sinerem, Guerbet Laboratories, Aulnay-sous-Bois, France) with precontrast MRI in the diagnosis of metastatic lymph nodes in patients with head and neck squamous cell carcinoma, using histology as gold standard. Eighty-one previously untreated patients were enrolled in a multicenter phase-III clinical trial. All patients had a noncontrast MR, a Sinerem MR, and surgery within a period of 15 days. The MR exams were analyzed both on site and by two independent radiologists (centralized readers). Correlation between histology and imaging was done per lymph node groups, and per individual lymph nodes when the short axis was > or = 10 mm. For individual lymph nodes, Sinerem MR showed a high sensitivity (> or = 88%) and specificity (> or = 77%). For lymph node groups, the sensitivity was > or = 59% and specificity > or = 81%. False-positive results were partially due to inflammatory nodes; false-negative results from the presence of undetected micrometastases. Errors of interpretation were also related to motion and/or susceptibility artifacts and problems of zone assignment. Sinerem MR had a negative predictive value (NPV) > or = 90% and a positive predictive value (PPV) > or = 51%. The specificity and PPV of Sinerem MR were better than those of precontrast MR. Precontrast MR showed an unexpectedly high sensitivity and NPV which were not increased with Sinerem MR. The potential contribution of Sinerem MR still remains limited by technical problems regarding motion and susceptibility artifacts and spatial resolution. It is also noteworthy that logistical problems, which could reduce the practical value of Sinerem MR, will be minimized in the future since Sinerem MR alone performed as good as the combination of precontrast and Sinerem MR.

USPIO‐enhanced magnetic resonance imaging for nodal staging in patients with head and neck cancer

“…Due to this inaccuracy, most surgeons prefer to overtreat patients, performing bilateral radical neck dissections that may result in increased morbidity (9). Accurate presurgical imaging studies are thus needed, in an attempt to select the most appropriate surgical procedure (23).…”

“…USPIO particles have been developed with the knowledge that they are selectively taken by cells of the reticuloendothelial system present in nonmetastatic LN, with differences in enhancement reflecting the functional status of the nodes, allowing discrimination of benign from malignant ones (17,28). Although their use for human studies has been limited (9,10,(15)(16)(17)(18)(19)(20), they have showed encouraging results, with reported high sensitivity and specificity values (9,10,16,17,19,20). Recently, combined positron emission tomography (PET)/CT has been used successfully for staging of nodal disease in Figure 3.…”

“…The clinical use of this contrast agent is still under evaluation on phase III clinical trials (15)(16)(17)(18)(19)(20). Reports show promising results, with sensitivity and specificity values ranging from 59% to 100% and 77% to 100%, respectively (9,10,16,17,19,20).The purpose of this study was to perform a direct comparison between MRI and pathological examination of selected LN in patients with head and neck cancer, determining the enhancement patterns of metastatic …”

“…Other parameters, such as morphological criteria or the pattern of enhancement, are regarded as less important in this setting. Nodal metastases in the head and neck are frequently smaller than 10 mm, sometimes even under 5 mm in diameter, a fact that accounts for the unsatisfactory performance of the current imaging techniques (8,9).…”

Diagnostic accuracy and additional value of diffusion-weighted imaging for discrimination of malignant cervical lymph nodes in head and neck squamous cell carcinoma

“…Also the introduction of lymph node specific contrast agents like ultrasmall particles iron oxide on magnetic resonance imaging (MRI) provides differentiation between benign and malignant lymph nodes in the head and neck and results are improving [11][12][13][14][15][16].…”