Search

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. [ABSTRACT FROM AUTHOR]

Objective: Literature analysis on the prognostic factor of the nodal yield (NY) in neck dissections (NDs), which in general surgical oncology is a strong prognosticator and quality‐of‐care marker. Methods: We performed a systematic review of all PubMed and Embase publications until June 30, 2018 screening for data on NY as prognosticator and overall survival (OS) as outcome in patients with head and neck squamous cell carcinoma (HNSCC). Risk for bias was asserted by application of the Quality In Prognosis Studies tool. Results: Of the 823 screened publications, 15 were included in this analysis. Five out of seven that compared NY ≥18 vs <18 as prognosticator, showed significantly improved survival if NY ≥18. Six studies used other cutoffs and three reported improved survival with each additionally harvested lymph node. Conclusion: Increased NY in ND specimen for HNSCC, most commonly described as ≥18 lymph nodes, is associated with improved OS and could be used as a prognosticator and quality‐of‐care marker. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction In oral squamous cell carcinoma (OSCC) the differentiation grade of the tumor is determined on the biopsy and the resection specimen. The relation between tumor grade, nodal metastasis and survival is debatable. The aims of this study were to determine the correlation between differentiation grade of the biopsy and the resection specimen. Furthermore, we wanted to correlate tumor differentiation grade with nodal stage and survival. Patients and methods One-hundred and forty-five patients with OSCC staged as T1-2, N0 of the tongue, floor of mouth or cheek with primary resection of the tumor were examined. Biopsy and resection specimen were histologically re-assessed with regard to differentiation grade, as well as infiltrative, peri-neural and vascular invasive growth. Results This study showed a poor correlation between differentiation grade in the incisional biopsy and the resection specimen of the same tumor. No significant relation between differentiation grade of the resection specimen and nodal involvement, as well as overall and disease-specific survival was found. Conclusion In early OSCC the differentiation grade determined by biopsy is of little predictive value for the grading of the resection specimen. Poor differentiation grade could not be related to the presence of nodal metastasis or survival and seems not to have any prognostic value concerning outcome. Treatment planning must be related to these findings. [ABSTRACT FROM AUTHOR]

Summary The Nucleosome Remodeling and Deacetylase (NURD) complex is a key regulator of cell differentiation that has also been implicated in tumorigenesis. Loss of the NURD subunit Deleted in Oral Cancer 1 (DOC1) is associated with human oral squamous cell carcinomas (OSCCs). Here, we show that restoration of DOC1 expression in OSCC cells leads to a reversal of epithelial-mesenchymal transition (EMT). This is caused by the DOC1-dependent targeting of NURD to repress key transcriptional regulators of EMT. NURD recruitment drives extensive epigenetic reprogramming, including eviction of the SWI/SNF remodeler, formation of inaccessible chromatin, H3K27 deacetylation, and binding of PRC2 and KDM1A, followed by H3K27 methylation and H3K4 demethylation. Strikingly, depletion of SWI/SNF mimics the effects of DOC1 re-expression. Our results suggest that SWI/SNF and NURD function antagonistically to control chromatin state and transcription. We propose that disturbance of this dynamic equilibrium may lead to defects in gene expression that promote oncogenesis. [ABSTRACT FROM AUTHOR]

Background Accurate nodal staging is pivotal for treatment planning in early (stage I-II) oral cancer. Unfortunately, current imaging modalities lack sensitivity to detect occult nodal metastases. Chromosomal region 11q13, including genes CCND1, Fas-associated death domain ( FADD), and CTTN, is often amplified in oral cancer with nodal metastases. However, evidence in predicting occult nodal metastases is limited. Methods In 158 patients with early tongue and floor of mouth (FOM) squamous cell carcinomas, both CCND1 amplification and cyclin D1, FADD, and cortactin protein expression were correlated with occult nodal metastases. Results CCND1 amplification and cyclin D1 expression correlated with occult nodal metastases. Cyclin D1 expression was validated in an independent multicenter cohort, confirming the correlation with occult nodal metastases in early FOM cancers. Conclusion Cyclin D1 is a predictive biomarker for occult nodal metastases in early FOM cancers. Prospective research on biopsy material should confirm these results before implementing its use in routine clinical practice. © 2016 Wiley Periodicals, Inc. Head Neck 39: 326-333, 2017 [ABSTRACT FROM AUTHOR]

ABSTRACT Background Gene expression profiling revealed a strong signature predicting lymph node metastases in oral squamous cell carcinoma (OSCC). Four of the most predictive genes are secretory leukocyte protease inhibitor (SLPI), lipocalin-2 (LCN2), thrombospondin-2 (THBS2), and tumor-associated calcium signal transducer 2 (TACSTD2). This study correlates their protein expression with lymph node metastases, overall survival (OS), and disease-specific survival (DSS). Methods Two hundred twelve patients with OSCC were included for protein expression analysis by immunohistochemistry. Results SLPI expression correlates with lymph node metastases in the whole cohort, not in a subgroup of cT1 to 2N0. SLPI expression correlates with OS (hazard ratio [HR] = 0.61) and DSS (HR = 0.47) in multivariate analysis. LCN2, THBS2, and TACSTD2 show no correlation with lymph node metastases, OS, or DSS. Conclusion Although SLPI expression correlates with lymph node metastases, it has no additional value in determining lymph node metastases in early oral cancer. However, it is an independent predictor for both OS and DSS and therefore a relevant prognostic biomarker in OSCC. © 2014 Wiley Periodicals, Inc. Head Neck 37: 1130-1136, 2015 [ABSTRACT FROM AUTHOR]

Summary: Objectives: The treatment strategy of early stage oral squamous cell carcinoma’s (OSCC) resected with close or involved margins is a returning point of discussion. In this study we reviewed the consequences of re-resection (RR), postoperative radiotherapy (PORT) or watchful waiting (WW). Patients and methods: Two-hundred patients with a primary resected Stage 1–2 OSCC of the tongue, floor of the mouth and cheek were included and retrospectively analysed. Local recurrence ratio was related to margin status, unfavourable histological parameters (spidery infiltrative, peri-neural and vascular-invasive growth) and postoperative treatment modality. 3-year overall survival (OS) and disease-specific survival (DSS) was calculated in relation to margin status. Results: Twenty-two of 200 (11%) patients had pathological positive margins (PM), 126 (63%) close margins (CM), and 52 (26%) free margins (FM). OS and DSS were not significantly different between these groups. Nine of 200 (4.5%) patients developed local recurrent disease. Two (9.1%) had a PM, five (4.0%) a CM and two (3.8%) a FM. Of the nine recurrences, five patients had undergone PORT, one a RR, and three follow-up. Watchful waiting for CM ⩾3mm with ⩽2 unfavourable histological parameters showed, besides margin status no significant differences with the FM group. Conclusion: With this treatment strategy, the local recurrence rate was 4.5%. No evidence was found for local adjuvant treatment in case of close margins ⩾3mm with ⩽2 unfavourable histological parameters. Current data do not support the use of one treatment modality above any other. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Early oral cancer is preferably treated by surgery. Its complete removal is essential for locoregional control and disease-free survival. Inadequate resection margins require adjuvant therapy such as re-resection or (chemo)radiation, that causes extra morbidity and oral discomfort. Intraoral ultrasonography (US) is reported to be of value in determining tumor thickness. Intraoperative visualization of the tumor may facilitate the resection and ensure adequate surgical margins. Furthermore, accurate prediction of tumor thickness could help determine the treatment strategy of the clinically node-negative neck, as thickness and depth of invasion are predictors of cervical metastasis as well as prognosticators of survival. The 8th edition of the American Joint Committee on Cancer staging system for oral squamous cell carcinoma has included depth of invasion as parameter for cT-stage. The aim of this review is to analyze the accuracy of intraoral US in determining tumor thickness in oral cancer. A systematic search was conducted, and the quality of the included papers was assessed using the QUADAS-2 tool for diagnostic accuracy studies. Subsequently, a meta-analysis was performed on the available individual participant data of 240 patients. Most of the twelve included studies focused on T1-2 tongue cancer (n = 129). Meta-analysis showed a high correlation in tumor thickness within this subgroup as measured by intraoral US and histopathology (r = 0.82, p < .001), with minor overestimation of 0.5 mm on US. It is concluded that intraoral US is very accurate in determining tumor thickness in early oral tongue cancer. [ABSTRACT FROM AUTHOR]

Objectives: Squamous cell carcinoma of the tongue (SCCT) is preferably treated by surgery. Free resection margins (≥5 mm) provide local control and disease-free survival. However, close (1-5 mm) and positive margins (<1 mm) are frequently encountered. We present our first experience of in-vivo ultrasound (US) guided SCCT resections followed by ex-vivo US control on the resection specimen to obtain free margins. We compare the results with those from a hisorical cohort of 91 conventionally treated SCCT patients.Materials and Methods: Ten patients with SCCT were included in a consecutive US-cohort. We aimed for a 5-10 mm margin during surgery, while we visualized the resection plane on US. Ex-vivo US measurements on the resection specimen determined whether there was any need for an immediate re-resection. US measurements were then compared with histopathology. Histopathological margins were compared with a consecutive cohort of 91 patients who had undergone conventional surgery for a SCCT.Results: In the US cohort, 70% of the margins were free. In the conventional cohort, this figure was 17% (P = 0.005). US predicted minimal histopathological margin distance with a mean ± SD error of 1.9 ± 1.8 mm. The mean ± SD of the histopathological overall submucosal/deep margin distance was 7.9 ± 2.1 mm in the US cohort and 7.0 ± 2.2 mm in the conventional cohort (P = 0.188). Ex-vivo examination through use of US indicated an immediate re-resection, which prevented local adjuvant treatment.Conclusion: Use of US-guided SCCT resection is feasible and improves margin control. [ABSTRACT FROM AUTHOR]

Objectives: Complete resection of tongue cancer is necessary to achieve local control. Unfortunately, deep resection margins are frequently inadequate. To improve deep margin control, accurate knowledge of tumour thickness is pivotal. Magnetic resonance imaging (MRI) and intraoral ultrasound (ioUS) are frequently applied for tumour staging. This study explores the accuracy of these techniques to estimate depth of invasion.Materials and Methods: The data of patients with a T1-2 tongue cancer that had been treated surgically between 2014 and 2018 were retrospectively analysed. Measurements that had been taken by either MRI or ioUS were compared with those taken during histopathology.Results: A total of 83 patients with tongue cancer had undergone a pre-operative MRI and 107 had been studied through an ioUS. Tumour thickness measured by MRI (r = 0.72) and ioUS (r = 0.78) correlated significantly (p < 0.001) with histopathological depth of invasion (DOI). In tumours with a DOI of 0-10 mm, MRI has a mean absolute difference with histopathology of 3.1 mm (SD 3.2 mm) and ioUS of 1.6 mm (SD 1.3 mm). In tumours with a DOI greater than 10 mm, MRI has a mean absolute difference of 3.5 mm (SD 3.0 mm) and ioUS of 4.7 mm (SD 3.5 mm).Conclusion: Estimation of histopathological DOI in tongue cancers with DOI till 10 mm is very accurate through use of ioUS. ioUS tends to underestimate DOI in tumors exceeding 10 mm DOI. MRI tends to overestimate DOI in both thin and thick tumours. Since ultrasound measurements can be performed during surgery, ioUS could potentially guide the surgeon in the achievement of adequate resection margins. [ABSTRACT FROM AUTHOR]