Patients' perspective on the impact of sentinel node biopsy in oral cancer treatment.

OBJECTIVE: Assessment of the impact of a sentinel node biopsy (SNB)-based strategy in cT1/T2 N0 oral cancer on the course of health related quality of life, psychological distress, and shoulder disability, and evaluation of the patients' perspective on neck management strategies. STUDY DESIGN: Fifty-two patients (39 SNB negative; 13 SNB positive) completed the European Organization for Research and Treatment of Cancer (EORTC) questionnaires-QLQ-C30 and QLQ-H&N35, and the HADS, IES, and SDQ questionnaires at baseline, after SNB diagnosis and at 6 months of follow-up. Objective shoulder measurements were performed after 2 years and interviews were conducted after 4.5 months of follow-up. RESULTS: All the scores of the questionnaires were not significantly different between SNB negative and SNB positive patients. Objective shoulder functioning was similar. Most patients preferred a SNB-based strategy to an elective neck dissection strategy. CONCLUSIONS: The impact of a SNB-based strategy in patients with cT1/T2 N0 oral cancer is comparable for SNB-negative and SNB-positive patients in terms of health-related quality of life, psychological distress and shoulder functioning. Most patients preferred the SNB-based strategy over the elective neck dissection strategy.

Sentinel Node in Oral Cancer: The Nuclear Medicine Aspects. A Survey from the Sentinel European Node Trial.

PURPOSE: Nuclear imaging plays a crucial role in lymphatic mapping of oral cancer. This evaluation represents a subanalysis of the original multicenter SENT trial data set, involving 434 patients with T1-T2, N0, and M0 oral squamous cell carcinoma. The impact of acquisition techniques, tracer injection timing relative to surgery, and causes of false-negative rate were assessed. METHODS: Three to 24 hours before surgery, all patients received a dose of Tc-nanocolloid (10-175 MBq), followed by lymphoscintigraphy. According to institutional protocols, all patients underwent preoperative dynamic/static scan and/or SPECT/CT. RESULTS: Lymphoscintigraphy identified 723 lymphatic basins. 1398 sentinel lymph nodes (SNs) were biopsied (3.2 SN per patient; range, 1-10). Dynamic scan allowed the differentiation of sentinel nodes from second tier lymph nodes. SPECT/CT allowed more accurate anatomical localization and estimated SN depth more efficiently. After pathological examination, 9.9% of the SN excised (138 of 1398 SNs) showed metastases. The first neck level (NL) containing SN+ was NL I in 28.6%, NL IIa in 44.8%, NL IIb in 2.8%, NL III in 17.1%, and NL IV in 6.7% of positive patients. Approximately 96% of positive SNs were localized in the first and second lymphatic basin visualized using lymphoscintigraphy. After neck dissection, the SN+ was the only lymph node containing metastasis in approximately 80% of patients. CONCLUSIONS: Best results were observed using a dynamic scan in combination with SPECT/CT. A shorter interval between tracer injection, imaging, and surgery resulted in a lower false-negative rate. At least 2 NLs have to be harvested, as this may increase the detection of lymphatic metastases.

Sensitivity to chromosomal breakage as risk factor in young adults with oral squamous cell carcinoma.

OBJECTIVE: Oral squamous cell carcinoma (OSCC) may develop in young adults. In contrast to older patients, the well-known etiological factors, exposure to tobacco and alcohol, play a minor role in the carcinogenesis in this patient group. It has been suggested that an intrinsic susceptibility to environmental genotoxic exposures plays a role in the development of OSCC in these patients. The hypothesis was tested whether young OSCC patients have an increased sensitivity to induced chromosomal damage. SUBJECTS AND METHODS: Fourteen OSCC patients with an average age of 32 years (range 20-42) were selected. Peripheral blood lymphocytes and skin fibroblasts of patients and 14 healthy controls were subjected to the chromosome breakage test with Mitomycin C. This test is routinely used to identify Fanconi anemia patients, who are well-known for their inherited high sensitivity to this type of DNA damage, but also for the high risk to develop OSCC. Human papilloma virus status of the carcinomas was also determined. RESULTS: None of the 14 young patients with OSCC had an increased response in the MMC-chromosomal breakage test. All tumors tested negative for human papilloma virus. CONCLUSION: No evidence was obtained for the existence of a constitutional hypersensitivity to DNA chromosomal damage as a potential risk factor for OSCC in young adults.

Cost-utility of sentinel lymph node biopsy in cT1-T2N0 oral cancer.

OBJECTIVES: To calculate the cost-utility of different strategies for the detection of occult lymph node metastases in cT1-T2N0 oral cancer. METHODS: A decision tree followed by a Markov model was designed to compare the cost-utility of the following strategies: (a) USgFNAC (ultrasound guided fine needle aspiration cytology), (b) SLNB (sentinel lymph node biopsy), (c) USgFNAC and, if negative, SLNB (d) END (elective neck dissection). Data was collected from 62 patients in four Dutch head and neck centres. Utilities were measured with the EQ5D questionnaire and resource use was recorded from patient charts. Costs were calculated from a hospital perspective. Uncertainty was explored with scenario analyses and probabilistic sensitivity analyses. RESULTS: With a 5- or 10-year time horizon, SLNB results in the highest number of additional quality-adjusted life years (QALYs, 0.12 and 0.26, respectively) for the smallest additional costs (€56 and €74, respectively) compared to USgFNAC. With a lifetime horizon END results in the highest number of additional QALYs (0.55) for an additional €1.626 per QALY gained compared to USgFNAC. When we make different assumptions regarding the duration of disutilities (⩾5 years) or the improvement (⩾3%) of sensitivity of SLNB, SLNB is the most favourable strategy from all time horizons. CONCLUSION: SLNB is a good diagnostic strategy to evaluate cT1-T2N0 oral cancer. SLNB is the preferred strategy in a 5- or 10-year time horizon. From a lifetime horizon, END may be preferred. SLNB may become the optimal strategy from all time horizons if its sensitivity can be slightly improved.

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.

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.

Sentinel lymph node biopsy in clinically N0 T1-T2 staged oral cancer: the Dutch multicenter trial.

OBJECTIVES: Results of the Dutch multi-institutional trial on sentinel lymph node (SLN) biopsy in oral cancer. PATIENTS AND METHODS: Patients were consecutively enrolled from 4 institutions, with T1/T2 oral cancer and cN0 neck based on palpation and ultrasound guided fine needle aspiration cytology. Lymphatic mapping consisted of preoperative lymphoscintigraphy. For intraoperative SLN detection a gamma-probe was used and in some patients additional blue dye. SLN negative patients were carefully observed, SLN positive patients were treated by neck dissection, radiotherapy or a combination of both. Endpoints of the study were risk of occult lymp node metastases, neck control, accuracy, 5-year disease-free survival (DFS), overall survival (OS) and disease-specific survival (DSS). RESULTS: Twenty of 62 patients (32%) had positive SLNs. Macrometastases were found in 9 patients, micrometastases in 8, and isolated tumour cells in 3 patients. Median follow-up was 52.5 months. Of the 42 SLN negative patients, 5 developed a regional recurrence of whom 4 patients could be successfully salvaged. DFS, OS and DSS of SLN negative patients were 72.0%, 92.7% and 97.4%, and for SLN positive patients these numbers were 73.7%, 79.7%, 85.0%, respectively (DFS: p=0.916, OS: p=0.134, DSS: p=0.059, respectively). Neck control rate was 97% in SLN negative and 95% in SLN positive patients. Sensitivity was 80% and negative predictive value 88%. CONCLUSION: SLN biopsy is able to reduce the risk of occult lymph node metastases in T1/T2 oral cancer patients from 40% to 8%, and enables excellent control of the neck.

Practice variation in defining sentinel lymph nodes on lymphoscintigrams in oral cancer patients.

PURPOSE: Lymphoscintigraphic imaging and adequate interpretation of the lymphatic drainage pattern is an essential step in the sentinel lymph node biopsy (SLNB) procedure. In oral cancer, identification of the sentinel lymph node (SLN) can be challenging. In this study, interobserver variability in defining SLNs on lymphoscintigrams was evaluated in patients with T1-T2 stage N0 oral cancer. METHODS: Sixteen observers (head and neck surgeons, nuclear medicine physicians or teams of both) from various institutes were asked which criteria they use to consider a hot focus on the lymphoscintigram as SLN. Lymphoscintigrams of 9 patients with 47 hot foci (3-9 per patient) were assessed, using a scale of 'yes/equivocal/no'. Bilateral drainage was seen in four of nine cases. In three cases additional late single photon emission computed tomography (SPECT)/CT scanning was performed. Interobserver variability was evaluated by kappa (к) analysis, using linear weighted pairwise comparison of the observers. Conservative (equivocal analysed as no) and sensitive (equivocal analysed as yes) assessment strategies were investigated using pairwise kappa analysis. RESULTS: Various definitions of SLN on lymphoscintigrams were given. Interobserver variability of all cases using a 3-point scale showed fair agreement (71%, к(w) = 0.29). The conservative and sensitive analyses both showed moderate agreement: conservative approach к = 0.44 (in 80% of the hot foci the observers agreed) and sensitive approach к = 0.42 (81%) respectively. Multidisciplinary involvement in image interpretation and higher levels of observer experience appeared to increase agreement. CONCLUSION: Among 16 observers, there is practice variation in defining SLNs on lymphoscintigrams in oral cancer patients. Interobserver variability of lymphoscintigraphic interpretation shows moderate agreement. In order to achieve better agreement in defining SLNs on lymphoscintigrams specific guidelines are warranted.

Outcome of patients with early stage oral cancer managed by an observation strategy towards the N0 neck using ultrasound guided fine needle aspiration cytology: No survival difference as compared to elective neck dissection.

OBJECTIVES: Management of the clinically N0 neck in oral cancer patients remains controversial. We describe the outcome of patients with T1-T2 oral cancer and N0 neck based on ultrasound guided fine needle aspiration cytology (USgFNAC) who were treated by transoral excision and followed by a 'wait and scan' policy (W&S). PATIENTS AND METHODS: This retrospective analysis included 285 consecutive patients of whom 234 were followed by W&S and 51 underwent elective neck dissection (END). Survival rates were compared between groups and correction for confounding factors was performed. RESULTS: Of W&S patients, the 5-year disease-specific (DSS) and overall survival (OS) were 94.2% and 81.6% respectively. During follow-up 72.2% remained free of lymph node metastases and 27.8% developed delayed metastases. W&S patients with delayed metastases had a 5-year DSS and OS of 80.0% and 62.8%, respectively. In patients with positive END these rates were 81.3% and 64.2%, respectively. Between the groups, survival rates were not significantly different. Of the W&S patients with delayed metastases, 90.6% needed adjuvant radiotherapy versus 55.0% of patients with positive END. CONCLUSION: With regard to survival, in patients with early stage oral cancer and cN0 neck a 'wait and scan' policy using strict USgFNAC surveillance is justified as survival is not negatively influenced. Using a 'wait and scan' follow-up strategy instead of elective neck treatment, unnecessary neck dissection and its accompanying morbidity can be avoided in 72.2% of patients. However, for the small proportion of patients with delayed metastases, more extensive treatment with adjuvant radiotherapy is needed.

Sentinel node identification in laryngeal cancer: Feasible in primary cancer with previously untreated neck.

OBJECTIVES: With the current diagnostic techniques a considerable percentage of occult lymph node metastases are missed in the clinically negative (cN0) neck. Therefore, in patients with laryngeal cancer and cN0 neck a total laryngectomy is usually combined with elective neck dissection. Based on the risk of occult lymph node metastases the decision whether to perform a neck dissection or not is difficult. In recurrent laryngeal cancer or second primary tumors previous treatment possibly influences lymphatics and metastatic behavior. In this pilot study we investigated the feasibility of sentinel node (SN) identification and potential accuracy of sentinel node biopsy (SNB) in laryngeal cancer patients undergoing total laryngectomy with elective neck dissection. PATIENTS AND METHODS: Patients with cN0 laryngeal cancer were included. During surgery 40MBq (99m)Technetium labeled Nanocolloid was endoscopically injected around the tumor. Lymphoscintigraphy was not performed. We identified the sentinel node (SN) ex vivo in the neck dissection specimen with a gammaprobe. Histopathological examination of the neck dissection specimen served as reference test. RESULTS: We included 19 patients, 13 patients with untreated necks and six with prior neck treatment. SN identification was successful in 68.4% (13/19) of patients, and significantly higher in patients with untreated necks (92.3% versus 16.7%, p<0.01). Four of 13 (30.7%) patients would potentially be upstaged by SNB. Sensitivity and negative predictive value would have been 80.0% and 87.5%, respectively. CONCLUSION: With the current methodology, SN identification in laryngeal cancer patients undergoing total laryngectomy is feasible in patients with untreated necks. Further studies are needed to determine the exact accuracy of SNB in total laryngectomy patients.

Visualization of the sentinel node in early-stage oral cancer: limited value of late static lymphoscintigraphy.

OBJECTIVE: Various lymphoscintigraphic imaging protocols exist for sentinel node (SN) identification in early-stage oral cancer. This study aimed to evaluate the clinical value of performing additional late lymphoscintigraphic imaging. METHODS: We retrospectively analysed early (directly following injection of 99mTc-Nanocoll) and late (2-4 h after injection) imaging results of 60 early-stage (T1-T2, cN0) oral cancer patients scheduled for SN procedure. Lymphoscintigraphic results of late imaging were categorized into: (a) no visualization of additional hotspots considered to be SNs; (b) additional hotspots visualized that are considered to be SNs and (c) hotspots visualized only during late imaging. Histopathological results of the harvested SNs were related to the corresponding hotspot. RESULTS: In all patients (n=60) lymphoscintigraphy was able to visualize a hotspot that was identified as an SN. In 51/60 (85%) patients, early imaging was able to visualize at least one hotspot, whereas in 9/60 (15%) patients, mostly with oral cavity tumours other than mobile tongue and floor-of-mouth tumours, only late imaging was able to visualize hotspots. In 14/51 (27%) patients, late imaging resulted in additionally visualized hotspots marked as SNs, resulting in a more extensive surgical procedure. These additionally removed SNs appeared to be of no clinical relevance, as all SNs identified during early imaging correctly predicted whether the neck was positive or negative for cancer. CONCLUSION: Results of this study indicate that additional late lymphoscintigraphic imaging should be performed only in selected cases.

Implications of a positive sentinel node in oral squamous cell carcinoma.

BACKGROUND: The role of sentinel node biopsy in head and neck cancer is currently being explored. Patients with positive sentinel nodes were investigated to establish if additional metastases were present in the neck, their distribution, and their impact on outcome. METHODS: In all, 109 patients (n = 109) from 15 European centers, with cT1/2,N0 tumors, and a positive sentinel lymph node were identified. Kaplan-Meier and univariate and multivariate logistic regression analysis were used to identify variables that predicted for additional positive nodes and their position within the neck. RESULTS: A total of 122 neck dissections were performed in 109 patients. Additional positive nodes were found in 34.4% of cases (42/122: 18 same, 21 adjacent, and 3 nonadjacent neck level). Additional nodes, especially if outside the sentinel node basin, had an impact on outcome. CONCLUSIONS: The results are preliminary but suggest that both the number and the position of positive sentinel nodes may identify different prognostic groups that may allow further tailoring of management plans.

Sentinel node biopsy for oral and oropharyngeal squamous cell carcinoma in the previously treated neck.

In patients with early stage oral or oropharyngeal squamous cell carcinoma (OSCC) sentinel node biopsy (SNB) is a reliable method to detect occult disease in the neck. However, patients with a history of surgery or radiotherapy in the neck may have aberrant lymphatic drainage caused by disruption of lymphatic channels. Therefore, treatment of the same levels at risk as in the primary setting may not be appropriate. The aim of our prospective observational study was to evaluate the clinical application of SNB in previously treated OSCC. Between 2003 and 2010 twenty-two patients were included. Lymph node mapping consisted of preoperative lymphoscintigraphy, SPECT/CT, intraoperative use of gamma-probe and patent blue. Endpoints were the sentinel node (SN) detection rate, unexpected lymphatic drainage patterns, negative predictive value and regional tumor control. 4/22 (18%) Patients were previously treated only on the contralateral site. The SN detection rate was 100% and unexpected drainage was found in 1/4 patients. The other 18 patients had ipsi- or bilateral previous neck treatment and a SN detection rate of 83%. The upstaging rate was 7% and 67% had unexpected lymphatic drainage patterns. The median follow-up was 22 months. Regional tumor control and negative predictive value were 100%. SNB in previously treated OSCC patients is feasible. SN detection is reliable and regional tumor control after staging by SNB is excellent. Moreover, SNB renders an assessment of the individual lymphatic drainage pattern, compensating for a potential variability after previous treatment of the neck.