Stephan K. Haerle

18F-FDG-PET/CT versus panendoscopy for the detection of synchronous second primary tumors in patients with head and neck squamous cell carcinoma

This study assesses the additional value of 18F‐fluoro‐2‐deoxy‐D‐glucose positron emission tomography/CT (18F‐FDG‐PET/CT) with respect to synchronous primaries in patients undergoing panendoscopy for staging of head and neck squamous cell carcinoma.

Occult metastases detected by sentinel node biopsy in patients with early oral and oropharyngeal squamous cell carcinomas: Impact on survival†

Analysis of the lymphatic drainage pattern, the reliability of a negative sentinel lymph node biopsy (SLNB), as well as the impact of sentinel lymph node (SLN) metastases on regional control and survival in patients with early stage oral and oropharyngeal squamous cell carcinoma (SCC).

Sentinel European Node Trial (SENT): 3-year results of sentinel node biopsy in oral cancer

PURPOSE Optimum management of the N0 neck is unresolved in oral cancer. Sentinel node biopsy (SNB) can reliably detect microscopic lymph node metastasis. The object of this study was to establish whether the technique was both reliable in staging the N0 neck and a safe oncological procedure in patients with early-stage oral squamous cell carcinoma. METHODS An European Organisation for Research and Treatment of Cancer-approved prospective, observational study commenced in 2005. Fourteen European centres recruited 415 patients with radiologically staged T1-T2N0 squamous cell carcinoma. SNB was undertaken with an average of 3.2 nodes removed per patient. Patients were excluded if the sentinel node (SN) could not be identified. A positive SN led to a neck dissection within 3 weeks. Analysis was performed at 3-year follow-up. RESULTS An SN was found in 99.5% of cases. Positive SNs were found in 23% (94 in 415). A false-negative result occurred in 14% (15 in 109) of patients, of whom eight were subsequently rescued by salvage therapy. Recurrence after a positive SNB and subsequent neck dissection occurred in 22 patients, of which 16 (73%) were in the neck and just six patients were rescued. Only minor complications (3%) were reported following SNB. Disease-specific survival was 94%. The sensitivity of SNB was 86% and the negative predictive value 95%. CONCLUSION These data show that SNB is a reliable and safe oncological technique for staging the clinically N0 neck in patients with T1 and T2 oral cancer. EORTC Protocol 24021: Sentinel Node Biopsy in the Management of Oral and Oropharyngeal Squamous Cell Carcinoma.

The value of 18F-FDG PET/CT for the detection of distant metastases in high-risk patients with head and neck squamous cell carcinoma

The aims of this study were to assess a cohort of patients with head and neck squamous cell carcinoma (HNSCC) for: (1) the prevalence of synchronous distant metastases (DM) as detected by the initial staging by using (18)F-FDG PET/CT, (2) the prevalence of metachronous DM, and (3) the validity of published risk factors with special emphasis on the maximum standardized uptake value (SUV max) for the prediction of DM. Two hundred and ninety nine patients with advanced HNSCC were included. Following risk factors at the time of diagnosis and during follow-up were analyzed: advanced T/N stage, poor histological differentiation, level IV/Vb lymph nodes, primary site in the larynx/hypopharynx, and SUV max. The prevalence of DM at initial staging and during follow-up was 10% and 11%, respectively. At initial staging, primary site in the larynx/hypopharynx and neck nodes in level IV/Vb, and during follow-up only level IV/Vb nodes achieved statistical significance. The sensitivity for (18)F-FDG PET/CT with regard to the detection of DM was 96.8%, the specificity 95.4%, the positive predictive value (PV) 69.8%, and the negative PV 99.6%. Patients without DM showed a significantly better overall survival (OS) than patients developing DM (p<0.001). There was no significant difference in OS with regard to the time of diagnosis of DM. The prevalence for synchronous and metachronous DM in advanced HNSCC is considerable. (18)F-FDG PET/CT is highly accurate for initial staging and follow-up. DM carries a bad prognosis regardless of the time of diagnosis.

Is There an Additional Value of SPECT/CT Over Planar Lymphoscintigraphy for Sentinel Node Mapping in Oral/Oropharyngeal Squamous Cell Carcinoma?

BackgroundLymphatic mapping for sentinel node biopsy (SNB) has been shown to be crucial for detection of sentinel lymph nodes (SLN). Previous reports suggested a benefit of single photon emission computed tomography with CT (SPECT/CT) over dynamic planar lymphoscintigraphy (LS) alone. The aim was to assess whether there is an additional value of SPECT/CT over LS alone for lymphatic mapping of SLNs in oral/oropharyngeal SCC.MethodsA consecutive cohort of 58 patients was evaluated using SNB with additional SPECT/CT to preoperative LS.ResultsIn the entire cohort of 58 patients undergoing LS and SPECT/CT, hot spots could be revealed in all but 4 cases. The guidance of the handheld gamma probe was able to reveal 9 additional SLNs within 3 patients not detected by either modality. Lymphoscintigraphy showed full concordance with SPECT/CT in 81% of the cases. SPECT/CT was able to detect additional HS in 11 patients, in 1 case even with additional metastatic disease. The false negative rate for SNB was 6%, and the negative predictive value 98%.ConclusionsSPECT/CT has the potential to detect more SLNs, which might harbor occult disease, than LS alone. With regard to the excellent results achieved with LS and the intraoperative use of the gamma probe, SPECT/CT is not indispensable for successful SNB. Both imaging modalities have difficulties in detecting level I sentinel nodes close to the injection site.

Contrast-enhanced 18F-FDG-PET/CT for the assessment of necrotic lymph node metastases

Cystic lymph node metastasis (CLNM) is commonly found in human papillomavirus (HPV)‐associated tonsillar squamous cell carcinoma (SCC). The aim of this study was to compare the accuracy in detecting cystic lymph node metastasis from tonsillar SCC between contrast‐enhanced CT, 18F‐ fluorodeoxyglucose‐positron emission tomography (FDG‐PET), non‐enhanced 18F‐FDG‐PET/CT, and contrast‐enhanced 18F‐FDG‐PET/CT.

Podoplanin expression correlates with sentinel lymph node metastasis in early squamous cell carcinomas of the oral cavity and oropharynx

In patients with early head and neck squamous cell carcinoma (HNSCC), occult lymph node metastasis is difficult to predict by clinical or pathological parameters. However, such parameters are necessary to select patients either for elective neck dissection or the sentinel lymph node (SLN) procedure. The membrane glycoprotein podoplanin is normally expressed in lymphatic endothelial cells. Recently, expression of podoplanin by cancer cells was demonstrated to promote tumor cell motility and tumor lymphangiogenesis in vitro. The value of cancer cell‐expressed podoplanin was to be determined as a predictive marker for SLN metastasis in early HNSCC of the oral cavity and oropharynx. One hundred twenty patients with HNSCC of the oral cavity and oropharynx undergoing a SLN biopsy were enrolled in this prospective clinical trial of SLN biopsy. Cancer cell‐expressed podoplanin was determined by immunohistochemistry using tissue microarrays. Podoplanin expression was quantified by the intensity reactivity score and categorized into expression and nonexpression. SLN examination revealed occult metastasis in 45 patients (37.5%). Twenty‐nine of 120 (24.2%) primary HNSCC showed podoplanin expression. Podoplanin expression correlated significantly with SLN metastasis (p = 0.029) and remained a significant predictor for lymph node status even after controlling for tumor stage (p = 0.028). As a predictive marker for SLN metastasis, however, podoplanin expression reached a sensitivity of a mere 36% and a specificity of 83%. Podoplanin expression is associated with metastasis to lymph nodes in vivo. Podoplanin immunohistochemistry in early HNSCC of the oral cavity and oropharynx may help to select patients for the SLN procedure and to identify patients with increased risk for presence of occult lymph node metastasis in the neck.

Expression patterns of Bmi‐1 and p16 significantly correlate with overall, disease‐specific, and recurrence‐free survival in oropharyngeal squamous cell carcinoma

The objective of this study was to link expression patterns of B‐cell–specific Moloney murine leukemia virus integration site 1 (Bmi‐1) and p16 to patient outcome (recurrence and survival) in a cohort of 252 patients with oral and oropharyngeal squamous cell cancer (OSCC).

Down regulation of E-Cadherin (ECAD) - a predictor for occult metastatic disease in sentinel node biopsy of early squamous cell carcinomas of the oral cavity and oropharynx

AbstractBackgroundPrognostic factors in predicting occult lymph node metastasis in patients with head and neck squamous-cell carcinoma (HNSCC) are necessary to improve the results of the sentinel lymph node procedure in this tumour type. The E-Cadherin glycoprotein is an intercellular adhesion molecule in epithelial cells, which plays an important role in establishing and maintaining intercellular connections.ObjectivesTo determine the value of the molecular marker E-Cadherin in predicting regional metastatic disease.MethodsE-Cadherin expression in tumour tissue of 120 patients with HNSCC of the oral cavity and oropharynx were evaluated using the tissue microarray technique. 110 tumours were located in the oral cavity (91.7%; mostly tongue), 10 tumours in the oropharynx (8.3%). Intensity of E-Cadherin expression was quantified by the Intensity Reactivity Score (IRS). These results were correlated with the lymph node status of biopsied sentinel lymph nodes. Univariate and multivariate analysis was used to determine statistical significance.ResultspT-stage, gender, tumour side and location did not correlate with lymph node metastasis. Differentiation grade (p = 0.018) and down regulation of E-Cadherin expression significantly correlate with positive lymph node status (p = 0.005) in univariate and multivariate analysis.ConclusionThese data suggest that loss of E-cadherin expression is associated with increased lymhogeneous metastasis of HNSCC. E-cadherin immunohistochemistry may be used as a predictor for lymph node metastasis in squamous cell carcinoma of the oral cavity and oropharynx. Level of evidence: 2b

Initial staging of the neck in head and neck squamous cell carcinoma: A comparison of CT, PET/CT, and ultrasound‐guided fine‐needle aspiration cytology

The aim of this study was to compare imaging modalities for staging the neck in a prospective cohort of patients evaluated by CT, ultrasound with fine‐needle aspiration cytology (FNAC), and [18F]fluoro‐2‐deoxy‐D‐glucose (FDG) positron emission tomography (PET)/CT with the histologic evaluation of the neck dissection as the standard of reference.