Sentinel lymph node detection in oral cancer: a within-patient comparison between [99mTc]Tc-tilmanocept and [99mTc]Tc-nanocolloid.

PURPOSE: Sentinel lymph node (SLN) biopsy has proven to reliably stage the clinically negative neck in early-stage oral squamous cell carcinoma (OSCC). [99mTc]Tc-tilmanocept may be of benefit in OSCC with complex lymphatic drainage patterns and close spatial relation to SLNs. METHODS: A prospective within-patient evaluation study was designed to compare [99mTc]Tc-tilmanocept with [99mTc]Tc-nanocolloid for SLN detection. A total of 20 patients with early-stage OSCC were included, who underwent lymphoscintigraphy with both tracers. Both lymphoscintigraphic images of each patient were evaluated for SLN detection and radiotracer distribution at 2-4 h post-injection. RESULTS: The injection site's remaining radioactivity was significantly lower for [99mTc]Tc-tilmanocept (29.9%), compared with [99mTc]Tc-nanocolloid (60.9%; p < 0.001). Radioactive uptake in SLNs was significantly lower for [99mTc]Tc-tilmanocept (1.95%) compared with [99mTc]Tc-nanocolloid (3.16%; p = 0.010). No significant difference was seen in SLN to injection site ratio in radioactivity between [99mTc]Tc-tilmanocept (0.066) and [99mTc]Tc-nanocolloid (0.054; p = 0.232). A median of 3.0 and 2.5 SLNs were identified with [99mTc]Tc-tilmanocept and [99mTc]Tc-nanocolloid, respectively (p = 0.297). Radioactive uptake in higher echelon nodes was not significantly different between [99mTc]Tc-tilmanocept (0.57%) and [99mTc]Tc-nanocolloid (0.86%) (p = 0.052). A median of 2.0 and 2.5 higher echelon nodes was identified with [99mTc]Tc-tilmanocept and [99mTc]Tc-nanocolloid, respectively (p = 0.083). CONCLUSION: [99mTc]Tc-tilmanocept had a higher injection site clearance, but at the same time a lower uptake in the SLN, resulting in an SLN to injection site ratio, which was not significantly different from [99mTc]Tc-nanocolloid. The relatively low-radioactive uptake in SLNs of [99mTc]Tc-tilmanocept may limit intraoperative detection of SLNs, but can be overcome by a higher injection dose.

The added value of SPECT-CT for the identification of sentinel lymph nodes in early stage oral cancer.

PURPOSE: To assess the role of single-photon emission computed tomography with computed tomography (SPECT-CT) for the identification of sentinel lymph nodes (SLNs) in patients with early stage (T1-T2) oral cancer and a clinically negative neck (cN0). METHODS: In addition to planar lymphoscintigraphy, SPECT-CT was performed in 66 consecutive patients with early stage oral cancer and a clinically negative neck. The addition of SPECT-CT to planar images was retrospectively analyzed for the number of additional SLNs, more precise localization of SLNs, and importance of anatomical information by a team consisting of a nuclear physician, surgeon, and investigator. RESULTS: Identification rate for both imaging modalities combined was 98% (65/66). SPECT-CT identified 15 additional SLNs in 14 patients (22%). In 2/15 (13%) of these additional SLNs, the only metastasis was found, resulting in an upstaging rate of 3% (2/65). In 20% of the patients with at least one positive SLN, the only positive SLN was detected due to the addition of SPECT-CT. SPECT-CT was considered to add important anatomical information in two patients (3%). In 5/65 (8%) of the patients initially scored SLNs on planar lymphoscintigrams were scored as non-SLNs when SPECT-CT was added. There were four false-negative SLN biopsy procedures in this cohort. CONCLUSIONS: The addition of SPECT-CT to planar lymphoscintigraphy is recommended for the identification of more (positive) SLNs and better topographical orientation for surgery in sentinel lymph node biopsy for early stage oral cancer.

Additional non-sentinel lymph node metastases in early oral cancer patients with positive sentinel lymph nodes.

To determine risk factors for additional non-sentinel lymph node metastases in neck dissection specimens of patients with early stage oral cancer and a positive sentinel lymph node biopsy (SLNB). A retrospective analysis of 36 previously untreated SLNB positive patients in our institution and investigation of currently available literature of positive SLNB patients in early stage oral cancer was done. Degree of metastatic involvement [classified as isolated tumor cells (ITC), micro- and macrometastasis] of the sentinel lymph node (SLN), the status of other SLNs, and additional non-SLN metastases in neck dissection specimens were analyzed. Of 27 studies, comprising 511 patients with positive SLNs, the pooled prevalence of non-SLN metastasis in patients with positive SLNs was 31 %. Non-SLN metastases were detected (available from 9 studies) in 13, 20, and 40 % of patients with ITC, micro-, and macrometastasis in the SLN, respectively. The probability of non-SLN metastasis seems to be higher in the case of more than one positive SLN (29 vs. 24 %), the absence of negative SLNs (40 vs. 19 %), and a positive SLN ratio of more than 50 % (38 vs. 19 %). Additional non-SLN metastases were found in 31 % of neck dissections following positive SLNB. The presence of multiple positive SLNs, the absence of negative SLNs, and a positive SLN ratio of more than 50 % may be predictive factors for non-SLN metastases. Classification of SLNs into ITC, micro-, and macrometastasis in the future SLNB studies is important to answer the question if treatment of the neck is always needed after positive SLNB.

Contralateral Regional Recurrence in Lateralized or Paramedian Early-Stage Oral Cancer Undergoing Sentinel Lymph Node Biopsy-Comparison to a Historic Elective Neck Dissection Cohort.

Introduction: Nowadays, two strategies are available for the management of the clinically negative neck in early-stage (cT1-2N0) oral squamous cell carcinoma (OSCC): elective neck dissection (END) and sentinel lymph node biopsy (SLNB). SLNB stages both the ipsilateral and the contralateral neck in early-stage OSCC patients, whereas the contralateral neck is generally not addressed by END in early-stage OSCC not involving the midline. This study compares both incidence and hazard of contralateral regional recurrences (CRR) in those patients who underwent END or SLNB. Materials and Methods: A retrospective multicenter cohort study, including 816 lateralized or paramedian early-stage OSCC patients, staged by either unilateral or bilateral END (n = 365) or SLNB (n = 451). Results: The overall rate of occult contralateral nodal metastasis was 3.7% (30/816); the incidence of CRR was 2.5% (20/816). Patients who underwent END developed CRR during follow-up more often than those who underwent SLNB (3.8 vs. 1.3%; p = 0.018). Moreover, END patients had a higher hazard for developing CRR than SLNB patients (HR = 2.585; p = 0.030). In addition, tumor depth of invasion was predictive for developing CRR (HR = 1.922; p = 0.009). Five-year disease-specific survival in patients with CRR was poor (42%) compared to patients in whom occult contralateral nodal metastases were detected by SLNB or bilateral END (88%), although not statistically different (p = 0.066). Conclusion: Our data suggest that SLNB allows for better control of the contralateral clinically negative neck in patients with lateralized or paramedian early-stage OSCC, compared to END as performed in a clinical setting. The prognosis of those in whom occult contralateral nodal metastases are detected at an earlier stage may be favorable compared to those who eventually develop CRR, which highlights the importance of adequate staging of the contralateral clinically negative neck.

Elective Neck Dissection or Sentinel Lymph Node Biopsy in Early Stage Oral Cavity Cancer Patients: The Dutch Experience.

BACKGROUND: Sentinel lymph node biopsy (SLNB) has been introduced as a diagnostic staging modality for detection of occult metastases in patients with early stage oral cancer. Comparisons regarding accuracy to the routinely used elective neck dissection (END) are lacking in literature. METHODS: A retrospective, multicenter cohort study included 390 patients staged by END and 488 by SLNB. RESULTS: The overall sensitivity (84% vs. 81%, p = 0.612) and negative predictive value (NPV) (93%, p = 1.000) were comparable between END and SLNB patients. The END cohort contained more pT2 tumours (51%) compared to the SLNB cohort (23%) (p < 0.001). No differences were found for sensitivity and NPV between SLNB and END divided by pT stage. In floor-of-mouth (FOM) tumours, SLNB had a lower sensitivity (63% vs. 92%, p = 0.006) and NPV (90% vs. 97%, p = 0.057) compared to END. Higher disease-specific survival (DSS) rates were found for pT1 SLNB patients compared to pT1 END patients (96% vs. 90%, p = 0.048). CONCLUSION: In the absence of randomized clinical trials, this study provides the highest available evidence that, in oral cancer, SLNB is as accurate as END in detecting occult lymph node metastases, except for floor-of-mouth tumours.

Depth of invasion in patients with early stage oral cancer staged by sentinel node biopsy.

BACKGROUND: To investigate if depth of invasion (DOI) can predict occult nodal disease in patients with cT1-2N0 (7th TNM) oral squamous cell carcinoma (OSCC) staged by sentinel lymph node biopsy (SLNB). METHODS: In 199 OSCC patients, DOI measurements and SLNB were performed. RESULTS: Metastases were found in 64 of 199 patients (32%). Of these 64 patients, the mean DOI was 6.6 mm compared to 4.7 mm in patients without metastases (P = .003). The ROC-curve showed an area under the curve of 0.65 with a most optimal cutoff point of 3.4 mm DOI (sensitivity 83% and specificity 47%). Regional metastases were found in 15% of patients with DOI ≤ 3.4 mm. CONCLUSION: DOI seems to be a poor predictor for regional metastasis in patients with cT1-2N0 OSCC. Therefore, staging of the neck using SLNB in patients with early stage oral cancer should also be performed in tumors with limited DOI and probably in T3 (8th TNM) OSCC ≤4 cm diameter.

High rate of unexpected lymphatic drainage patterns and a high accuracy of the sentinel lymph node biopsy in oral cancer after previous neck treatment.

RATIONALE: This study evaluates the lymphatic drainage patterns and determines the accuracy of the sentinel lymph node biopsy (SLNB) in patients diagnosed with a cT1-2N0 OSCC and a history of neck surgery or radiotherapy in three Dutch head and neck centers. MATERIALS AND METHODS: Retrospective analysis of 53 cT1-2N0 OSCC patients, who underwent SLNB between 2007 and 2016, after a history of neck surgery or radiotherapy. Ten patients had previous treatment of the neck only contralateral from the current tumour. These ten patients were not used for the analysis of lymphatic drainage patterns. The 43 patients with previous ipsilateral or bilateral treatment of the neck had a history of ipsilateral SLN extirpation (n = 9; 21%), neck dissection (n = 16; 37%), radiotherapy (n = 10; 23%), or combined neck dissection and radiotherapy (n = 8; 19%). RESULTS: SLNs were detected in 45 patients, resulting in an identification rate of 85% (45/53). Three patients (7%) had at least one positive SLN. One patient (1/45; 2%) was diagnosed with regional recurrence during the follow-up after a negative SLNB (sensitivity 75%, negative predictive value 98%). The first SLN was detected in level I-III in 58% of the patients, unexpected drainage patterns were observed in 30% (first SLN level IV 9% and level V 5% and contralateral neck in well-lateralized tumours 16%). In 12% no lymphatic drainage pattern was visible. CONCLUSIONS: SLNB seems to be a reliable procedure for neck staging of cT1-2N0 OSCC patients with a previously treated neck. SLNB determines the individual lymphatic drainage patterns, enabling visualization of unexpected drainage pattern variability in 30% of these patients.

Sentinel node biopsy for early-stage oral cavity cancer: the VU University Medical Center experience.

BACKGROUND: Sentinel node biopsy (SNB) in head and neck cancer is recently introduced as the staging technique of oral squamous cell carcinoma. We report the results of SNB in patients diagnosed with a T1-T2 oral squamous cell carcinoma and clinically negative (N0) neck in a single center. METHODS: A retrospective analysis of 90 previously untreated patients who underwent SNB between 2007 and 2012 was performed. The SNB procedure consisted of preoperatively performed lymphoscintigraphy, intraoperative detection using blue dye, and gamma probe guidance and histopathologic examination including step-serial sectioning (SSS) and immunohistochemical (IHC) staining. A positive SNB was followed by neck dissection, whereas regular follow-up with ultrasound-guided fine-needle aspiration cytology (FNAC) was done in case of a negative SNB. RESULTS: The lymphoscintigraphic identification rate was 98% (88 of 90 patients) and the surgical detection rate was 99% (87 of 88 patients). The upstaging rate was 30%. Sensitivity of SNB was 93% and the negative predictive value was 97%. The median follow-up was 18 months (range, 2-62 months). Overall survival (OS) and disease-free survival (DFS) for SNB negative were 100% and 84% and for SNB positive patients 73% and 88%, respectively. CONCLUSION: SNB is a reliable diagnostic staging technique for the clinically negative neck in patients with early-stage (T1-T2, cN0) oral squamous cell carcinoma.