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Background: Between the publication of the Union of International Cancer Control staging system (UICC) 7th and 8th editions, other staging algorithms for oropharyngeal squamous cell carcinoma (OPSCC) were proposed from Radiation Therapy Oncology Group (RTOG), MD Anderson Cancer Center (MDACC), and Yale University., Methods: With C-statistics, the above-mentioned five staging algorithms were compared for overall and relapse-free survival endpoints in a multi-institutional cohort of OPSCC cases (n = 338) treated with primary surgery., Results: Pathological UICC 8th ed yielded the highest C-indexes in the entire cohort and in the HPV- subset, whereas MDACC was superior for HPV+ OPSCC. RTOG was the simplest and holistic algorithm with a noninferior discriminatory power., Conclusion: UICC 8th ed, MDACC, and RTOG offer moderate and comparable efficacy for staging in this OPSCC patient cohort undergoing surgical treatment. Notable discrepancy between clinical and pathological UICC 8th ed algorithms poses potential concerns in diagnosis, treatment, research, and data management., (© 2018 Wiley Periodicals, Inc.)

Background: Epithelial-mesenchymal transition and cancer stem-like cells (CSC) have been linked to increased metastatic potential. We evaluated the prognostic impact of CD44, a CSC biomarker, on depth of invasion (DOI) and outcome in oral squamous cell carcinoma (OSCC)., Methods: Using a multivariable logistic regression model, we evaluated in early OSCCs the relationship between CD44 expression at the invasive tumor front, DOI, sentinel lymph node biopsy, extension of nodal involvement, and survival. We also assessed whether CT and/or MRI could predict DOI preoperatively., Results: CD44 expression was associated with increased DOI (P = .018), worse disease-specific survival (P = .041) but not with positive sentinel lymph node biopsy (P > .05). Each millimeter increase in DOI was associated with a 31.1% higher risk for positive sentinel lymph node biopsy (95% CI: 5.8%-62.4%, P = .013) and with higher metastatic ratio (P = .015). Preoperative estimation of DOI by CT and/or MRI and histopathological DOI showed a strong correlation (P < .0001)., Conclusions: CD44 expression correlates with DOI, which predicts occult lymph node metastasis. Preoperative CT and/or MRI provides an accurate estimation of histopathological DOI. Both pieces of information gained preoperatively can help surgeons tailor their operation in regard to the surgical management of the neck., (© 2018 Wiley Periodicals, Inc.)

Background: Knowledge about prognostic factors in surgically treated patients with oropharyngeal squamous cell carcinoma (SCC) is limited. The purpose of this study was to identify influential factors on survival in a large cohort of patients with surgically treated oropharyngeal SCC., Methods: Retrospective analysis of survival estimates in patients with surgically treated oropharyngeal SCC using tumoral positivity for human papillomavirus (HPV) and risk-of-death categories according to a study from 2010 as stratification factors., Results: The 5-year overall survival (OS) and disease-specific survival (DSS) rates after surgery alone were higher in HPV-associated oropharyngeal SCC (OS 80% vs 62%; P = .01; DSS 92% vs 76%; P = .03). Patients in the low-risk category had higher survival rates (OS 91%; DSS 99%) than patients in the intermediate-risk group (OS 63%; DSS 83%), and high-risk group (OS 61%; DSS 75%)., Conclusion: Nonsmokers with HPV-positive oropharyngeal SCC have a better prognosis than smokers with HPV-positive oropharyngeal SCC and also than patients with HPV-negative tumors when treated by surgery alone., (© 2017 Wiley Periodicals, Inc.)

Background: Applicability of sentinel node biopsy (SNB) for tumors of the floor of mouth (FOM) is controversial., Methods: Prospective evaluation of the accuracy of gamma-probe-guided superselective neck dissection of the preglandular triangle of level I for SNB in FOM squamous cell carcinoma (SCC) after preoperative lymphoscintigraphy and single photon emission CT (SPECT)/CT., Results: In total, 22 sentinel lymph nodes were harvested in level I. Eight of 22 (36%) were seen on lymphoscintigraphy and 11 (50%) on SPECT/CT. Eleven sentinel lymph nodes (50%) were only detected intraoperatively. In unilateral tumors, 20% were contralateral, and, in midline tumors, 93% showed bilateral level I sentinel lymph nodes. The false-negative rate was 8.3%, the negative predictive value was 96.4%, and the false-omission rate was 3.6%. The ultimate neck control rate, including salvage treatment, was 100%., Conclusion: SNB in FOM can be reliably performed using the presented surgical technique. Level I exploration, bilaterally in midline tumors, is mandatory irrespective of the visualization of sentinel lymph nodes in other levels. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1367-1372, 2016., (© 2016 Wiley Periodicals, Inc.)

Regional metastasis is a prominent feature of head and neck squamous cell carcinoma (HNSCC) and is an important prognostic factor. The currently available imaging techniques for assessment of the neck have limitations in accuracy; thus, elective neck dissection has remained the usual choice of management of the clinically N0 neck (cN0) for tumors with significant (≥20%) incidence of occult regional metastasis. As a consequence, the majority of patients without regional metastasis will undergo unnecessary treatment. The purpose of this review was to discuss new developments in techniques that potentially improve the accuracy of the assessment of the neck in patients with HNSCC. Although imaging has improved in the last decades, a limitation common to all imaging techniques is a lack of sensitivity for small tumor deposits. Therefore, complementary to improvements in imaging techniques, developments in more invasive diagnostic procedures, such as sentinel node biopsy (SNB) will add to the accuracy of diagnostic algorithms for the staging of the neck., (© 2014 Wiley Periodicals, Inc.)

Background: Sentinel lymph node biopsy is a reliable technique for accurate determination of the cervical lymph node status in patients with early oral and oropharyngeal cancer but analyses on the distribution pattern of metastatic spread within sentinel lymph nodes are lacking., Methods: The localizations of carcinoma deposits were analyzed with a virtual microscope by creating digital images from the microscopic glass slides., Results: Metastatic deposits were not randomly distributed within sentinel lymph nodes but were predominant in the central planes closer to the lymphatic inlet. Initial evaluation of the 4 most central slices achieved a high rate of 90% for the detection of micrometastases and of 80% for the detection of isolated tumor cells (ITCs)., Conclusion: Based on the distribution we recommend an initial cut through the hilus and to proceed with the 4 most central 150-µm slices. Complete step sectioning is only required in case of a so far negative result., (© 2014 Wiley Periodicals, Inc.)

Neck dissection is an important treatment for metastases from upper aerodigestive carcinoma; an event that markedly reduces survival. Since its inception, the philosophy of the procedure has undergone significant change from one of radicalism to the current conservative approach. Furthermore, nonsurgical modalities have been introduced, and, in many situations, have supplanted neck surgery. The refinements of imaging the neck based on the concept of neck level involvement has encouraged new philosophies to evolve that seem to benefit patient outcomes particularly as this relates to diminished morbidity. The purpose of this review was to highlight the new paradigms for surgical removal of neck metastases using an evidence-based approach., (© 2014 Wiley Periodicals, Inc.)

Background: Analysis of the impact of risk factors on survival in patients with oropharyngeal squamous cell carcinoma (OPSCC) treated by primary intensity-modulated radiotherapy (IMRT)., Methods: One hundred forty patients were included with tissue microarray (TMA) construction and immunohistochemical analysis in 124 patients (87%)., Results: Survival analysis of patients classified into 3 risk categories according to an algorithm based on p16, smoking, T classification, and N classification revealed significant differences with a low, intermediate, and high-risk group. There was a significant impact of p53 expression as surrogate marker for smoking on outcome. In multivariate analysis, p16-positivity was a positive predictor and alcohol as well as N classification was a negative predictor for survival. The algorithm was modified based on alcohol instead of smoking with even more significant differences between the groups., Conclusions: A risk model based on multiple factors instead of p16 as single marker can define different risk groups to select patients for treatment deintensification in future prospective clinical trials., (Copyright © 2013 Wiley Periodicals, Inc., A Wiley Company.)

Background: 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)., Methods: A prospective consecutive cohort analysis was conducted which included 111 patients diagnosed between 2003 and 2010. Endpoints of the study were neck control rate, overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS), depending on the size of occult metastases., Results: Forty-nine of 111 patients (38%) had positive SLNs, 10 had isolated tumor cells (ITCs), 19 had micrometastases, and 13 had macrometastases. OS, DSS, and DFS at 3 years for SLN-negative and SLN-positive patients was 98% and 71%, 95% and 76%, and 98% and 73%, respectively. Furthermore, there was a statistically significant difference between the SLN-negative group and ITCs in DSS as well as between the SLN-negative group and patients with micrometastases in OS and DSS and between the SLN-negative group and patients with macrometastases in all 3 survival estimates., Conclusion: Our study is the first to demonstrate that even small tumor deposits only detectable by the extensive histopathologic workup of the SLNB protocol have a significant impact on tumor control and survival in early Oropharyngeal SCC. Whether these findings will translate into different treatment strategies based on the upstaged neck has to be further investigated., (Copyright © 2012 Wiley Periodicals, Inc.)

Surgery is the preferred modality for curative treatment of recurrent laryngeal cancer after failure of nonsurgical treatments. Patients with initial early-stage cancer experiencing recurrence following radiotherapy often have more advanced-stage tumors by the time the recurrence is recognized. About one third of such recurrent cancers are suitable for conservation surgery. Endoscopic resection with the CO(2) laser or open partial laryngectomy (partial vertical, supracricoid, or supraglottic laryngectomies) have been used. The outcomes of conservation surgery appear better than those after total laryngectomy, because of selection bias. Transoral laser surgery is currently used more frequently than open partial laryngectomy for treatment of early-stage recurrence, with outcomes equivalent to open surgery but with less associated morbidity. Laser surgery has also been employed for selective cases of advanced recurrent disease, but patient selection and expertise are required for application of this modality to rT3 tumors. In general, conservation laryngeal surgery is a safe and effective treatment for localized recurrences after radiotherapy for early-stage glottic cancer. Recurrent advanced-stage cancers should generally be treated by total laryngectomy., (Copyright © 2011 Wiley Periodicals, Inc.)

Background: 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 [(18)F]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET)/CT with the histologic evaluation of the neck dissection as the standard of reference., Methods: In all, 76 consecutive patients were prospectively enrolled., Results: Ultrasound-guided FNAC showed the highest level of agreement with histology for exact N classification. Ultrasound-guided FNAC showed the smallest percentage of overstaged patients, 7%, versus 16% with PET/CT, 13% with CT, and 13% with ultrasound. The rate of understaged patients was comparable between the imaging modalities. With regard to the endpoint N0 versus N+ there were no statistically significant differences to be found., Conclusions: Ultrasound-guided FNAC seems to correlate best with histologic staging compared with PET/CT and CT. None of the modality is reliable enough to replace elective neck treatment in cN0 necks., (Copyright © 2011 Wiley Periodicals, Inc.)

Background: Sentinel node biopsy (SNB) has been proposed for staging of the cN0 neck in early oral/oropharyngeal squamous cell carcinomas (SCC). Because SNB is a minimally invasive procedure, it is thought to be associated with less morbidity than elective neck dissection., Methods: Sixty-two consecutive patients were included from 2000 to 2009. Two groups were analyzed consisting of 33 patients after SNB and 29 after elective neck dissection. Subjective impairment and functional shoulder status were assessed with the Neck Dissection Impairment Index (NDII) questionnaire and the modified individual relative Constant Score. Postoperative complications were retrieved from the clinical charts., Results: The investigated scores were significantly better in the SNB group. All postoperative complications occurred in the elective neck dissection group., Conclusion: SNB is associated with significantly less postoperative morbidity and better shoulder function than elective neck dissection. This supports our opinion that patients with nodal negative early SCC of the oral cavity should be offered SNB., (Copyright © 2010 Wiley Periodicals, Inc.)

Background: 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., Methods: Thirty-four patients with a tonsillar SCC undergoing a pretreatment contrast-enhanced ¹⁸F-FDG-PET/CT followed by a neck dissection as a standard of reference were included. The contrast-enhanced CT part, the ¹⁸F-FDG-PET part, the non-enhanced ¹⁸F-FDG-PET/CT part, and the contrast-enhanced ¹⁸F-FDG-PET/CT were assessed separately for correct N classification and the differentiation of N0 versus N+. RESULTS.: Contrast-enhanced ¹⁸F-FDG-PET/CT, non-enhanced ¹⁸F-FDG-PET/CT, and contrast-enhanced CT are equally accurate for correct neck staging. Regarding pN0 versus pN+, contrast-enhanced CT and contrast-enhanced ¹⁸F-FDG-PET/CT are superior to non-enhanced ¹⁸F-FDG-PET/CT (p = .017)., Conclusion: Contrast-enhanced CT and contrast-enhanced ¹⁸F-FDG-PET/CT perform equally and better than non-enhanced ¹⁸F-FDG-PET/CT in detecting CLNM in tonsillar SCC. Therefore, in patients scheduled for ¹⁸F-FDG-PET/CT, we strongly suggest performing a contrast-enhanced ¹⁸F-FDG-PET/CT, which is not routine in most centers., (Copyright © 2010 Wiley Periodicals, Inc.)

Background: This study evaluates the oncological outcome of patients with recurrent oropharyngeal squamous cell carcinoma (OPSCC) after primary radiation therapy +/- chemotherapy, primary surgical therapy, and surgical therapy followed by radiation therapy +/- chemotherapy., Methods: A total of 156 patients (36%) of a cohort of 427 treated for OPSCC between 1990 and 2006 developed recurrent disease. Fifty-one patients (12%) qualified for salvage treatment. Study endpoints were 5-year overall survival (OS) and disease-specific survival (DSS)., Results: The 5-year OS and DSS rates after salvage treatment were 29% and 40%; after initial primary radiation therapy, 25% and 40%; after initial surgery followed by radiation therapy, 40% and 40%; and after initial surgery alone, 20% and 40%., Conclusions: Patients with an advanced OPSCC have a considerable risk for recurrence. Despite poor ultimate outcome, salvage treatment should be attempted in patients with resectable disease, good performance status, and absence of distant metastases., (2009 Wiley Periodicals, Inc. Head Neck, 2010.)

Background: This study assesses the additional value of (18)F-fluoro-2-deoxy-D-glucose positron emission tomography/CT ((18)F-FDG-PET/CT) with respect to synchronous primaries in patients undergoing panendoscopy for staging of head and neck squamous cell carcinoma., Methods: In all, 311 patients underwent both modalities. Cytology, histology, and/or clinical/imaging follow-up served as reference standard., Results: The prevalence of second primary tumors detected by panendoscopy was 4.5%, compared with 6.1% detected by (18)F-FDG-PET/CT. The sensitivity for panendoscopy was 74%, the specificity was 99.7%, the positive predictive value (PPV) was 93%, and the negative predictive value (NPV) was 98%. The sensitivity for (18)F-FDG-PET/CT was 100%, the specificity was 95.7%, the PPV was 59%, and the NPV was 100%., Conclusions: (18)F-FDG-PET/CT is superior to panendoscopy. With a negative (18)F-FDG-PET/CT, the extent of endoscopy can be reduced to the area of the primary tumor. Due to the costs, (18)F-FDG-PET/CT is recommended only in advanced disease to assess potential distant disease. In early-stage cancer, panendoscopy is accurate enough to rule out secondary tumors.

Background: Malignant triton tumors are rare neoplasias consisting of a malignant peripheral nerve sheath tumor with additional rhabdomyoblastic differentiation. These tumors are highly aggressive and prognosis is poor. Our aim is to describe the outcome and to identify potential prognostic factors., Methods: From 1993 to 2005, 7 patients with a malignant triton tumor of the head and neck were treated at our institution. A literature search revealed another 46 published cases. All these cases were analyzed for outcome and prognostic factors., Results: Patients with primary tumors involving the nose and paranasal sinuses have better, patients involving the neck a poor prognosis. All other locations show an intermediate course. Complete surgical removal is of crucial importance. Additional radiation or chemotherapy show little effect., Conclusion: Location of the primary tumor is a key factor for prognosis. Complete surgical removal is the only treatment associated with survival.

Background: Treatment of head and neck squamous cell carcinoma (HNSCC) addresses the primary tumor and the lymphatic drainage. Modalities for the neck are neck dissection and/or radiation therapy. In most cases, the neck is treated by the modality that seems more appropriate for the primary. The aim of this study was to analyze the results of the neck treatments either by neck dissection alone, by radiation therapy alone or by neck dissection followed by radiation therapy., Methods: This was a retrospective chart analysis of 699 patients treated for a previously untreated HNSCC. The primary endpoint was recurrence at the treated neck., Results: Two hundred eighty-one (40%) patients underwent primary neck irradiation, 219 (31%) neck dissection alone, and 199 (29%) neck dissection followed by adjuvant irradiation. The 5-year regional control rates after neck dissection alone were 83% for pN0, 75% for pN1, 60% for pN2a, 59% for pN2b, and 50% for pN2c; after radiation alone, 89% for cN0, 87% for cN1, 40% for cN2a, 60% for cN2b, and 48% for cN2c; and after neck dissection with adjuvant radiation, 86% for pN0, 96% for pN1, 100% for pN2a, 88% for pN2b, and 88% for pN2c., Conclusions: Radiation or neck dissection alone are efficient to control early neck disease. For advanced N2/3 neck disease, neck dissection followed by adjuvant radiation is highly efficient, whereas primary radiation results in a high number of regional failures. The literature suggests planned neck dissection to improve regional control for these patients., (Copyright (c) 2007 Wiley Periodicals, Inc.)

Background: To analyze the results in early (stage I and II) glottic carcinoma of a single institution with a patient-oriented concept., Methods: After diagnostic workup and multidisciplinary counseling, either radiotherapy or CO(2) laser surgery was chosen with respect to the patient's preference., Results: Sixty-five patients underwent laser surgery and 75 had radiotherapy. For T1 tumors, the 5-year overall survival, disease-specific survival, and initial local control rate after laser surgery and radiotherapy were comparable (OS, 85% vs 88%; DSS, 96% vs 93%; LCR, 86% vs 85%). In contrast, initial local control for T2 tumors was significantly more favorable after surgery (OS, 83% vs 78%; DSS, 83% vs 88%; LCR, 89% vs 67%). Larynx preservation was significantly higher after surgery in T1 tumors (96% vs 82%) and in T2 tumors (89% vs 77%)., Conclusions: Selection of the treatment modality according to patient's preference results in a comparable control of disease for T1 tumors. The initial local control for T2 tumors is significantly better after surgery. In both stages laser surgery warrants a better larynx preservation rate., (Copyright 2003 Wiley Periodicals, Inc. Head Neck 25: 000-000, 2003)

Background: The aim of our study was to assess the value of positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) for the staging of clinically nodal negative necks in oral and oropharyngeal squamous cell carcinoma (SCC) using sentinel lymph node (SLN) biopsy and elective neck dissection (END) as "gold standard" for comparison., Methods: Twelve patients (10 men, 2 women) with oral or oropharyngeal squamous cell carcinoma and no evidence of lymph node metastasis in the physical and radiologic examinations were eligible. At least 24 hours before surgery PET with FDG were performed. The SLN was localized by preoperative lymphoscintigraphy with 99m-Tc-Nanocoll and intraoperative use of a hand-held gamma-probe and selectively excised. All patients then underwent END., Results: SLN and END revealed occult metastasis in 5 of 12 cases. SLN biopsy was accurately feasible in all 12 patients and diagnosed all 5 cases of occult metastasis (sensitivity and specificity of 100%). PET suggested two patients having occult metastasis, of which one turned out to be false positive (sensitivity 25%, specificity 88%). The mean size of the micrometastasis was 1.4 mm (range, 1.2-1.5 mm)., Conclusions: PET with FDG turned out to have a poor sensitivity and specificity in revealing occult metastasis and has no role for the evaluation of otherwise clinically N0 necks. The failure to detect micrometastasis by PET is due to the technical limitations of resolution (4-5 mm). SLN biopsy, with END in cases of positive SLN, provides a highly accurate staging of N0 necks in oral and oropharyngeal carcinoma. Patients with negative SLN could be spared the risks and the morbidity of END., (Copyright 2002 Wiley Periodicals, Inc.)