Martina A. Broglie

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.

Quality of Life of Oropharyngeal Cancer Patients With Respect to Treatment Strategy and p16-Positivity

To assess the quality of life in long‐term survivors with oropharyngeal cancer (OPSCC), compare the results with our historic cohort in relation to the radiation technique, and explore the influence of treatment strategy and p16 expression on quality of life (QoL).

Impact of p16, p53, smoking, and alcohol on survival in patients with oropharyngeal squamous cell carcinoma treated with primary intensity-modulated chemoradiation

Analysis of the impact of risk factors on survival in patients with oropharyngeal squamous cell carcinoma (OPSCC) treated by primary intensity‐modulated radiotherapy (IMRT).

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.

Sentinel node biopsy for early oral carcinoma.

Purpose of reviewSentinel node biopsy (SNB) in oral squamous cell carcinomas (OSCCs) has been under investigation since more than a decade. Numerous published studies and recent important scientific data support its role as an alternative standard of care apart from elective neck dissection. Recent findingsDuring the past 2 years, a large-scale multicentric validation trial and long-term follow-ups of major observational trials have demonstrated the accuracy and oncological safety and efficacy of SNB to stage a cN0 early stage OSCC. Histologic and molecular parameters of the primary tumors possibly predicting occult disease in the neck have been evaluated, but SNB with the use of step-serial sectioning and immunohistochemistry remains the most accurate staging method. SNB has been shown to be clearly superior to elective neck dissection with regard to complications and morbidity. The modern technique of quantitative real-time reverse transcriptase–polymerase chain reaction has been successfully used for the rapid intraoperative assessment of the sentinel nodes, allowing a one-stage procedure in all patients. The procedure of SNB is currently expanding to other areas like the supraglottic larynx and the previously treated neck. SummarySNB in OSCC is a minimally invasive and highly reliable staging method of the cN0 neck and has become the standard of care in many centers throughout the world. Recent developments have led to a wider clinical application and improved acceptance.

Impact of clinical risk scores and BRAF V600E mutation status on outcome in papillary thyroid cancer

BACKGROUND To evaluate the relationship between the BRAF V600E mutation and clinicopathologic parameters and to assess the impact of the BRAF V600E mutation and established risk scores on survival in patients with papillary thyroid carcinoma (PTC). METHODS Retrospective analysis of a consecutive, single-institutional cohort of patients with PTC larger than 1 cm. Clinical risk scores according to the Metastases, Age, Completeness of Resection, Invasion, Size (MACIS), European Organisation for Research and Treatment of Cancer (EORTC), and tumor, node, metastases (TNM) scoring systems were determined. BRAF exon 15 mutation analysis was performed by polymerase chain reaction and Sanger sequencing. RESULTS BRAF V600E mutations were found in 75/116 (65%) PTC. The rates for 5- and 10-year overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) were 92% and 87%, 98% and 96%, and 96% and 94%, respectively. Low MACIS scores were associated with longer OS (10 y 95% vs 75%, P = .008), DSS (10 y 100% vs 89%, P = .02) and RFS (100% vs 85%, P = .006). Comparable survival advantages were observed for patients with early EORTC scores and low TNM stage. BRAF V600E mutation status was not associated with clinicopathologic characteristics of aggressive behavior such as extrathyroidal extension, lymph node metastases, higher T-categories, male sex, and greater age. Furthermore, BRAF V600E mutation status was not correlated with clinical risk scores and decreased survival. CONCLUSION In concordance with other studies, we did not find a negative prognostic impact of a positive BRAF V600E mutation status on survival. In contrast, the risk algorithms MACIS, EORTC score, and TNM stage were associated with impaired prognosis. Therefore, clinical staging systems represent better tools for risk stratification than BRAF V600E mutation status.

Validity of frozen section in sentinel lymph node biopsy for the staging in oral and oropharyngeal squamous cell carcinoma

The potential of avoiding a secondary surgery for therapeutic neck dissection (TND) by sentinel node (SN) positivity makes the intraoperative evaluation of SNs an attractive option. The aim of this study was to analyze accuracy of intraoperative frozen section (FS) for detection of occult metastases in a large single institutional patient cohort undergoing SN‐biopsy.

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 99mTc-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.

Brush cytology for the detection of high-risk HPV infection in oropharyngeal squamous cell carcinoma.

High‐risk human papillomavirus (HR‐HPV) infection is associated with improved prognosis and a better response to treatment in patients with oropharyngeal squamous cell carcinoma (OPSCC). Brush cytology is a noninvasive method with which to collect cells from the surface of mucosal lesions. The objective of the current study was to assess the performance of OPSCC brush cytology for the detection of HR‐HPV.