cN0 Neck Research Articles

Predictors of Occult Nodal Involvement in Clinically Node Negative Primary Parotid Carcinoma: An NCDB Analysis

<h3>Purpose/Objective(s)</h3> Primary Parotid Carcinomas (PPC) comprise a wide array of histologies, each with varying propensity for local invasion and cervical nodal involvement. Upfront surgical excision of the primary tumor constitutes the standard of care for PPC, but there exists little consensus regarding management of the clinically negative neck (cN0). We conducted a clinicopathologic correlative analysis of the National Cancer Database (NCDB) to identify predictors of occult nodal involvement in PPC to guide elective neck management. <h3>Materials/Methods</h3> The NCDB was queried for adults with a first malignant diagnosis of cN0M0 cancer of the parotid who underwent adequate surgical resection (defined as subtotal to radical parotidectomy with ³18 nodes examined) without pre-surgical treatment. Pathologic T-classification, tumor size, histology, grade, lymphovascular space invasion (LVSI), gender, and age at diagnosis were specified <i>a priori</i> as variables of interest. The primary outcome, occult nodal positivity (<i>i.e.</i> cN0 but pN+), was assessed by univariable (UVA) and multivariable (MVA) logistic regression analysis, depicted as odds ratios (OR) and corresponding 95% confidence intervals (95% CI) with a prespecified threshold for statistical significance of <i>p</i>£0.05. Recursive partitioning analysis (RPA) was subsequently performed to categorize patients according to their calculated risk of occult nodal disease. <h3>Results</h3> From an initial cohort of 41,445 patients with PPC 978 met inclusion criteria and were included for analysis, of whom 331 (33.8%) had occult nodal involvement. By UVA, the incidence of occult nodal positivity was significantly higher in male patients, those aged 72 and older, patients with high grade disease, pT4 classification, adenocarcinoma histology, a >4cm tumor, and those with positive LVSI. On MVA, tumor size, age, and gender were no longer significantly associated with occult nodal involvement; however, LVSI (OR 6.1, 95% CI 4.3-8.8), carcinoma ex-pleomorphic adenoma (OR 5.6, 95% CI 2.1-14.8), adenocarcinoma (OR 5.1, 95% CI 2.6-9.9), salivary duct (OR 4.0, 95% CI 1.8-8.6), or mucoepidermoid (OR 2.3, 95% CI 1.2-4.3) histology, pT3 (OR 2.0, 95% CI 1.1-3.7) or pT4 (OR 3.9, 95% CI 2.1-7.3) status, and high grade (OR 2.0, 95% CI 1.4-3.0) remained significant. LVSI, histology, pT status, and grade were further evaluated with RPA, which identified LVSI as the strongest predictor of occult nodal involvement (57.1% vs 42.9%, <i>p</i><0.01). <h3>Conclusion</h3> LVSI appears to supersede tumor histology, grade, size, and pT status as the strongest risk factor for occult nodal involvement in PPC. To our knowledge, this is the largest series to evaluate this pathologic feature. Further research into this heretofore underappreciated risk factor and its implications for management of the cN0 neck is warranted.

Evaluating contralateral neck failure in patients with lateralized OPSCC treated with transoral robotic surgery and neck management based on pre-operative SPECT-CT lymphatic mapping

BackgroundRisk of contralateral nodal metastases in oropharyngeal squamous cell carcinoma (OPSCC) is relatively low, however, many OPSCC patients receive bilateral neck treatment. This study evaluates the oncological outcomes with management of the contralateral cN0 neck based on lymphatic mapping with single photon emission computed tomography (SPECT-CT).MethodsRetrospective evaluation of patients with lateralized cT1-2 and contralateral cN0 OPSCC treated with primary surgery between December 2017 and October 2019. All patients underwent pre-operative lymphatic mapping using SPECT-CT. Clinical parameters including demographics, tumor characteristics and oncological outcomes were recorded.ResultsThirteen patients underwent primary site resection with transoral robotic surgery (TORS) and ipsilateral neck dissection with or without adjuvant therapy. Twelve patients (92.3%) had ipsilateral drainage on SPECT-CT, whereas 1 (7.7%) patient had bilateral neck lymphatic drainage. Four patients (30.8%) underwent post-operative radiation therapy (PORT). Three patients with unilateral drainage on SPECT-CT underwent PORT with unilateral neck irradiation, and 1 patient with bilateral drainage underwent PORT with bilateral neck irradiation. Seven (53.8%) patients were staged as pT1, 6 (46.2%) patients as pT2, 6 (46.2%) patients were pN0, 3 (23.1%) patients were pN1, 1 (7.7%) patient was pN2a for and 3 (23.1%) patients were N2b. The median distance of the tumor from midline was 1.05 cm (0.0–1.58). Primary sites included tonsil (n = 10, 76.9%) and tongue base (n = 3, 23.1%). The median follow-up time was 15.4 months. All patients were disease free at the latest follow-up with no contralateral neck failures.ConclusionsPre-operative mapping of lymphatic drainage in early stage OPSCC with SPECT-CT is a promising tool which can reduce treatment to the contralateral neck potentially without compromising oncological outcomes.Graphical

Sentinel Lymph Node Biopsy using Methylene Blue Alone in an Era of Significance of the Depth of Invasion in Oral Cancers

Aim: To evaluate the accuracy of methylene blue dye alone in identifying sentinel nodes in oral cancers with clinically N0 neck and the significance of the depth of invasion (DOI) in combination with sentinel lymph node (SLN) biopsy in predicting nodal metastasis. Methods: This is a prospective study done over 24 months accruing 67 patients with cN0 neck admitted to our center for oncology. SLN harvesting was done adhering to the standard procedure using methylene blue dye for all early-stage oral cavity cancers with N0 neck clinically. Data were collected, grouped, and analyzed for deducing DOI, sensitivity, specificity, positive predictive value, and negative predictive value of the procedure and compared with other studies in the literature. Results: Out of 67 patients, males (76.1%) outnumbered female (23.9%) patients. The mean age of the patients was 51.5 years. Tongue (61.2%) was the most common site. Sentinel nodes were identified in 89.5% of patients. The mean number of Sentinel nodes identified was 1.9. The mean DOI was 7.3 mm. SLNs were most commonly identified in Level I (78.3%). Sensitivity, specificity, positive predictive value, and negative predictive value and accuracy deduced in this study were 75%, 97.9%, 90%, 94%, and 93.3%, respectively. Conclusion: Methylene blue dye alone can be successfully used for SLN identification in clinically node-negative oral cavity cancers, particularly with less DOI. DOI alone for predicting nodal involvement can be used with caution. Combination of DOI and sentinel node biopsy may help in better identification of nodal involvement.

Review of oncological findings and complications after elective neck dissection during total laryngectomy: a case series

BackgroundThis study aims to report the rate of occult lymph node metastasis during elective neck dissection in clinically and radiologically negative neck (cN0) for patients offered total laryngectomy as either primary or salvage treatment. We also compare the rate of complications and recurrence after elective neck dissection during total laryngectomy.A retrospective review of patients treated in a single teaching hospital in the UK between 2004 and 2020 was performed. We collected the following patient information: age, sex, TNM staging, tumour location and laterality, primary treatment received if recurrent, preoperative imaging, operative details of the elective neck dissection, pathology results, postoperative complications, and recurrence. Inclusion criteria are as follows: squamous cell carcinoma and cN0 neck. Exclusion criteria are as follows: second primary tumour in the head and neck, a total laryngectomy because of a dysfunctional larynx, or a previously performed neck dissection.ResultsOf the 105 included patients, 66 (63%) had primary surgery and 39 (37%) were offered salvage surgery. All cases in the primary group were offered elective neck dissection. Thirty-six patients of the salvage group were offered elective neck dissection. The rate of occult lymph node metastasis was 35% (23/66) and 5.6% (2/36) in the primary and salvage groups, respectively. There was no difference in the overall complication rate in both groups, although the specific incidence of pharyngocutaneous fistula in the salvage group was higher compared with the primary group, 14% vs 7.5%.ConclusionsWe conclude that elective neck dissection is indicated during primary total laryngectomy due to the high rate of occult lymph node metastasis, 35% (23/66) in our series. Conversely, from our data in the salvage setting, the rate of occult lymph node was very low at 5.6% (2/36). The impact on survival is not known. The decision over elective neck dissection may be made more judiciously on an individual basis in the salvage setting.

Predicting Pathologic Lymph Node Positivity in cN0 Pharynx and Larynx Cancers in the Modern Imaging Era

<h3>Purpose/Objective(s)</h3> Neck dissection is a standard of care for pharynx and most larynx cancer patients undergoing surgery even with clinically node-negative (cN0) necks. This is based largely on historical series showing high rates of occult pathologic node-positivity (pN+) in cN0 patients. However, in the modern era with more sensitive imaging modalities, it is possible that certain patients with sufficiently low risk of pN+ could have elective neck dissection omitted, thereby reducing toxicity. <h3>Materials/Methods</h3> Patients with cN0 oropharynx, larynx (excluding T1-2 glottic), and hypopharynx cancers diagnosed from 2010-2015 and undergoing primary surgery were identified in the National Cancer Data Base. Multivariable logistic regression was performed to assess predictors of pN+. Predictive nomograms based on these predictors were generated. <h3>Results</h3> 4117 cN0 patients met inclusion criteria, including 2033 larynx (L), 293 hypopharynx (HP), 503 HPV(-) oropharynx (OP), and 1288 HPV(+) OP patients. The overall rate of pN+ among cN0 patients was 29.4%. Probability of pN+ was > 25% for all anatomic subsites (L: 26.9%; HP: 27.6%: HPV(-) OP: 32.4%; HPV(+) OP: 32.7%). In multivariable logistic regression, the presence of lymphovascular invasion (LVI) was the strongest predictor of pN+ (odds ratio [OR] = 4.19, 95% confidence interval [CI] 3.56-4.93, <i>P</i> < 0.001). Histologic grade also strongly predicted pN+ (high- vs. low-grade: OR 2.58, 95% CI 1.88-3.59, <i>P</i> < 0.001; intermediate- vs. low-grade: OR 1.90, 95% CI 1.40-2.62, <i>P</i> < 0.001). However, increasing pT-classification was not associated with increased rate of LN positivity. A nomogram predicting the probability of pN+ for cN0 patients was created. Using this nomogram, < 2% of patients had an estimated pN+ risk below 10%, < 10% of patients had pN+ risk below 15%. <h3>Conclusion</h3> LVI and histologic grade are the strongest predictors of pN+ among patients with cN0 pharynx and larynx cancers. Even with modern imaging, pN+ rates are high for cN0 patients, and the benefits of neck dissection likely outweigh the risks in virtually all patients undergoing surgery.

Value of Assessing Peripheral Vascularization with Micro-Flow Imaging, Resistive Index and Absent Hilum Sign as Predictor for Malignancy in Lymph Nodes in Head and Neck Squamous Cell Carcinoma.

Simple SummaryUltrasound-guided fine needle aspiration cytology (USgFNAC) is commonly used for N-staging in head and neck squamous cell carcinoma (HNSCC). The specificity of USgFNAC is always in the order of 100% as false positive cytology is rare. The difference in sensitivity is mainly attributable to selection of the lymph nodes to aspirate and aspiration technique. The aim of this study was to improve the selection criteria of lymph nodes to aspirate. Ultrasound features of nodes such as a short axis diameter, S/L ratio, loss of a fatty hilum sign, resistive index, and peripheral or mixed hilar and peripheral vascularization, obtained by Micro-flow imaging (MFI), which is a new technique to obtain micro-vascularization, were evaluated. To calculate the sensitivity and PPV of each feature, data of sonographic findings and cytological results of all aspirated nodes were statistically analyzed. We found that next to size, peripheral vascularisation obtained by MFI and absent hilum sign have a high predictive value for malignancy and should be added as selection criteria for fine needle aspiration in lymph nodes.Ultrasound-guided fine needle aspiration cytology (USgFNAC) is commonly used for nodal staging in head and neck squamous cell cancer (HNSCC). Peripheral vascularity is a described feature for node metastasis. Micro-flow imaging (MFI) is a new sensitive technique to evaluate micro-vascularization. Our goal is to assess the additional value of MFI to detect malignancy in lymph nodes. A total of 102 patients with HNSCC were included prospectively. USgFNAC was performed with the Philips eL18–4 transducer. Cytological results served as a reference standard to evaluate the prediction of cytological malignancy depending on ultrasound features such as resistive index (RI), absence of fatty hilum sign, and peripheral vascularization. Results were obtained for all US examinations and for the subgroup of clinically node-negative neck (cN0). USgFNAC was performed in 211 nodes. Peripheral vascularization had a positive predictive value (PPV) of 83% (cN0: 50%) and the absence of a fatty hilum had a PPV of 82% (cN0 50%) The combination of peripheral vascularization and absent fatty hilum had a PPV of 94% (cN0: 72%). RI (threshold: 0.705) had a PPV of 61% (cN0: RI-threshold 0.615, PPV 20%), whereas the PPV of short axis diameter (threshold of 6.5mm) was 59% for all patients and 19% in cN0 necks (threshold of 4 mm). Peripheral vascularization assessed by MFI and absent hilum has a high predictive value for cytological malignancy in neck metastases. Next to size, both features should be used as additional selection criteria for USgFNAC.

Effect of elective neck dissection versus sentinel lymph node biopsy on shoulder morbidity and health-related quality of life in patients with oral cavity cancer: A longitudinal comparative cohort study

ObjectiveTo research the difference in shoulder morbidity and health-related quality of life between patients with cT1-2N0 oral cavity squamous cell carcinoma that undergo either elective neck dissection (END) or a sentinel lymph node biopsy (SLNB) based approach of the neck. Materials and methodsA longitudinal study with measurements before surgery, 6 weeks, 6 months, and 12 months after surgery. Shoulder morbidity were determined with measurements of active range of motion of the shoulder and patient-reported outcomes for shoulder morbidity (SDQ, SPADI) and health-related quality of life (HR-QoL) (EQ5D, EORTC-QLQ-HN35). Linear mixed model analyses were used to analyze differences over time between patients that had END, SLNB or SLNB followed by complementing neck dissection. ResultsWe included 69 patients. Thirty-three patients were treated with END. Twenty-seven patients had SLNB without complementing neck dissection (SLNB), and nine were diagnosed lymph node positive followed by completion neck dissection (SLNB + ND). Ipsilateral shoulder abduction (P = .031) and forward flexion (P = .039) were significantly better for the SLNB group at 6 weeks post-intervention compared to the END and SLNB + ND group. No significant differences for shoulder morbidity, or health-related quality of life were found at 6 weeks, 6 months, and 12 months between the three groups. ConclusionWith oncologic equivalence for the END and SLNB as strategies for the cN0 neck already demonstrated, and the SLNB being more cost-effective, our demonstrated benefit in short-term shoulder function strengthens the choice for the SLNB as a preferred treatment strategy.

The Role of Regional Disease and Patterns of Treatment Failure in Primary Sinonasal Malignancies.

BackgroundThe question how to treat the clinically negative neck in sinonasal malignancies is controversial.ObjectivesTo investigate patterns of treatment failure and to assess outcome measures in patients with primary sinonasal malignancies.MethodsRetrospective cohort study of patients treated for primary malignant sinonasal malignancies.ResultsLymph node (LN) metastases at initial presentation were present in 8 of 152 patients (5.3%). Ipsi- and contralateral LN levels 1 and 2 were identified as nodal basins at risk. We found a 5-year overall survival (OS) of 75.2% and disease free survival of 61.1%. Among patients with cN0 neck, nodal recurrence free survival was not different between patients with and without elective neck treatment (P = .23). On logistic regression analysis, we found initial T classification as an independent factor for achievement of complete remission (CR) and OS.ConclusionsLN metastases at initial presentation are rare and initial T classification was identified as the most important prognostic factor for OS and CR, emphasizing the need for a thorough initial staging of the primary tumor.

Sentinel lymph node biopsy versus elective neck dissection in squamous cell carcinoma of the oral cavity with a clinically N0 neck: Systematic review and meta-analysis of prospective studies.

Sentinel lymph node biopsy (SLNB) is an emerging strategy for managing early-stage oral squamous cell carcinoma (SCC) with a clinically N0 (cN0) neck. However, the role of SLNB in this scenario is debatable. Herein, relevant literature was systematically reviewed, and a meta-analysis was performed to evaluate the potential dividends of SLNB compared to elective neck dissection (END) for these patients. The meta-analysis, including six prospective studies, showed comparable results of the two management strategies in terms of regional recurrence (risk ratio [RR]=0.99; 95% confidence interval [CI], 0.58-1.70), 5-year disease-free survival (RR=0.99; 95% CI, 0.87-1.11), and 5-year overall survival (RR=1.01; 95% CI, 0.90-1.13). Fewer adverse events occurred in the SLNB arm than in the END arm (RR=0.12; 95% CI, 0.02-0.70). Overall, SLNB results in as favorable an oncologic prognosis for patients with cN0 oral SCC as END, while significantly lessening side effects and unnecessary surgeries.

High-Risk Cutaneous Squamous Cell Carcinoma of the Head and Neck: A Clinical Review.

Given the rapidly evolving nature of the field, the current state of "high-risk" head and neck cutaneous squamous cell carcinoma (HNcSCC) is poorly characterized. Narrative review of the epidemiology, diagnosis, workup, risk stratification, staging and treatment of high-risk HNcSCC. Clinical and pathologic risk factors for adverse HNcSCC outcomes are nuanced (e.g., immunosuppression and perineural invasion). Frequent changes in adverse prognosticators have outpaced population-based registries and the variables they track, restricting our understanding of the epidemiology of HNcSCC and inhibiting control of the disease. Current heterogeneous staging and risk stratification systems are largely derived from institutional data, compromising their external validity. In the absence of staging system consensus, tumor designations such as "high risk" and "advanced" are variably used and insufficiently precise to guide management. Evidence guiding treatment of high-risk HNcSCC with curative intent is also suboptimal. For patients with incurable disease, an array of trials are evaluating the impact of immunotherapy, targeted biologic therapy, and other novel agents. Population-based registries that broadly track updated, nuanced, adverse clinicopathologic risk factors, and outcomes are needed to guide development of improved staging systems. Design and development of randomized controlled trials (RCTs) in advanced-stage HNcSCC populations are needed to evaluate (1) observation, sentinel lymph node biopsy, or elective neck dissection for management of the cN0 neck, (2) indications for surgery plus adjuvant radiation versus adjuvant chemoradiation, and (3) the role of immunotherapy in treatment with curative intent. Considering these knowledge gaps, the authors explore a potential high-risk HNcSCC treatment framework.

To map or not to map the cN0 neck: Impact of sentinel lymph node biopsy in canine head and neck tumours.

Tumour stage is a prognostic indicator for canine malignant head and neck tumours (MHNT). However, consensus is lacking on nodal staging in the absence of clinically apparent nodal disease (cN0 neck). This prospective observational study aims to determine the diagnostic accuracy of radiopharmaceutical and blue dye for sentinel lymph node biopsy (SLNB), to assess the correspondence between sentinel lymph node (SLN) and clinically expected regional lymph node (RLN) and the impact on staging of the procedure in dogs with MHNT and cN0 neck. Twenty-three dogs with MHNT and cN0 neck underwent tumour excision and SLNB guided by preoperative lymphoscintigraphy and intraoperative gamma-probe and blue dye. Diagnostic performances and detection rate were calculated. Correspondence between SLN and RLN, number of nodes excised, histopathological status of the SLN and complications related to the procedure were recorded. The mapping technique identified at least one SLN in 19/23 dogs, with a detection rate of 83%. The SLN did not correspond to the RLN in 52% of dogs. Multiple nodes were removed in 61% of dogs. At histopathology, eight (42%) dogs had SLN+, of which four differed from the RLN. Only minor self-limiting complications occurred in five (22%) dogs. Radiopharmaceutical and blue dye guidance is accurate (sensitivity 88.9%; specificity 100%) for SLNB in dogs with MHNT and cN0 and allowed the extirpation of unpredictable and/or multiple SLN with minimal morbidity. Incorporation of SLNB in the management of MHNT is desirable to correctly stage the cN0 neck, owing the unpredictability of the lymphatic drainage.

Elective neck dissection versus positron emission tomography-computed tomography-guided management of the neck in clinically node-negative early oral cavity cancer: A cost-utility analysis.

In early oral cavity cancer, elective neck dissection (END) for the clinically node-negative (cN0) neck improves survival compared with observation. This paradigm has been challenged recently by the use of positron emission tomography-computed tomography (PET-CT) imaging in the cN0 neck. To inform this debate, we performed an economic evaluation comparing PET-CT-guided therapy with routine END in the cN0 neck. Patients with T1-2N0 lateralized oral tongue cancer were analyzed. A Markov model over a 40-year time horizon simulated treatment, disease recurrence, and survival from a US health care payer perspective. Model parameters were derived from a review of the literature. The END strategy was dominant, with a cost savings of $1576.30 USD, an increase of 0.055 quality-adjusted life years (QALYs), a net monetary benefit of $4303 USD, and a 0.22 life-year advantage. END was sensitive to variation in cost and utilities in deterministic and probabilistic sensitivity analyses. PET-CT became the preferred strategy when decreasing occult nodal disease to 18% and increasing the negative predictive value (NPV) of PET-CT to 89% in 1-way sensitivity analyses. In probabilistic sensitivity analysis, assuming a cost effectiveness threshold of $50,000 USD/QALY, END was dominant in 64% of simulations and cost effective in 69.8%. END is a cost-effective strategy compared with PET-CT in patients who have node-negative oral cancer. Although lower PET standardized uptake value thresholds would result in fewer false negatives and improved NPV, it is still uncertain that PET-CT would be cost effective, as this would likely result in more false positive tests.

Prognostic value of elective neck dissection in adenoid cystic carcinoma of head and neck: a meta-analysis: A call for randomized trials and international consensus

Adenoid cystic carcinoma of head and neck (AdCCHN) is an uncommon salivary gland cancer characterized for infrequent neck metastases, and high rate of local and distant recurrence. The aim of this meta-analysis was to analyse the significance of elective neck dissection (END) in terms of overall survival (OS) in patients with AdCCHN. A systematic literature search and meta-analysis was performed. Endpoint assessed by this meta-analysis included 5-year OS (death from any cause). Statistical heterogeneity was assessed using the Cochrane Q test and I2 statistic. A pooled odds ratio (OR) was reported with 95% confidence interval (CI). There were 1934 patients in the END arm and 3083 in the observation group. The pooled OR, calculated for END vs. observation, was 0.94. Patients receiving END had similar risk for death compared to observation cohort (P=0.76). No significant difference in final outcome after patient stratification based on T stage was identified (OR for T1/T2 1.27, P=0.39; OR for T3/T4 0.95, P=0.90). Observation for cN0 neck is a reasonable option in AdCCHN. These findings suggest the need for prospective trials on indications and extent of END in AdCCHN.

FDG-PET/CT and Pathology in Newly Diagnosed Head and Neck Cancer: ACRIN 6685 Trial, FDG-PET/CT cN0.

FDG-PET/CT (fluorodeoxyglucose-positron emission tomography/computed tomography) is effective to assess for occult neck nodal disease. We report risks and patterns of nodal disease based on primary site and nodal level from data on the dissected cN0 per the results from ACRIN 6685. Prospective nonrandomized enrollment included participants with first-time head and neck squamous cell carcinoma and at least 1 cN0 neck side to be dissected. Twenty-four ACRIN-certified centers internationally (American College of Radiology Imaging Network). A total of 287 participants were enrolled. Preoperative FDG-PET/CT findings were centrally reviewed and compared with pathology. Incidence, relative risk, pattern of lymph node involvement, and impact upon neck dissection were reported. An overall 983 nodal levels were dissected (n = 261 necks, n = 203 participants). The highest percentages of ipsilateral positive nodes by primary location and nodal level were oral cavity (level I, 17/110, 15.5%), pharynx (level II, 6/30, 20.0%), and larynx (level VI, 1/3, 33.3%). Levels at greatest risk for nodal disease in cN0 in terms of ipsilateral neck dissection are level I (oral cavity), II (pharynx), and VI (larynx). These data should be considered when treating patients presenting with cN0. This is the first study to comprehensively report the incidence, location, and risk of metastases in cN0 in the FDG-PET/CT era.

Elective neck dissection for T3/T4 cN0 sinonasal squamous cell carcinoma.

In locally advanced sinonasal squamous cell carcinoma (SNSCC), management of the clinically node-negative (cN0) neck is variable and elective neck dissection (END) remains controversial. Patients with surgically treated T3/T4 cN0 M0 SNSCC were identified using the NCDB. Overall survival (OS) was assessed by Cox proportional hazard analysis in propensity score-matched cohorts. Factors associated with END were evaluated with logistic regression. Two hundred twenty patients underwent END (19.6%). END did not correlated with OS in propensity score-matched cohorts (HR 0.971, 95% CI 0.677-1.392), a maxillary sinus tumor subgroup (HR 1.089, 95% CI 0.742-1.599), or by radiation status [radiation: (HR 0.802, 95% CI 0.584-1.102); no radiation: (HR 0.852, 95% CI 0.502-1.445)]. The occult metastasis rate in the END cohort was 12.7%. END did not significantly improve OS in this study. Further information on disease-free survival is necessary to determine its role in advanced-stage SNSCC.

Level IV neck dissection as an elective treatment for oral tongue carcinoma—a systematic review and meta-analysis

The purpose of our systematic review was to investigate the prevalence of level IV involvement and skip metastases in patients with clinically negative neck (cN0) oral tongue squamous cell carcinoma (OTSCC). The occurrence of occult metastases to lower levels in the neck (levels IV and V) or the development of an erratic distribution of cervical metastases ("skip metastases") that bypass the upper neck levels (levels I to III) and go directly to level IV or V challenges the role of supraomohyoid neck dissection in the treatment of OTSCC; therefore, controversy exists over including level IV cervical nodes during an elective neck dissection of OTSCC. Our search included all studies published from 1989 until January 2018 in the Cochrane Library, PubMed, EMBASE, and Web of Science. Abstracts and full-text articles that were deemed potentially relevant were screened. Data from the studies were extracted by using standardized tables, and a meta-analysis was conducted. In total, 3000 abstracts and 269 full text articles were screened, and 11 studies were included in this analysis. Among the 498 patients included, 16 had level IV involvement, representing involvement of 2.8%. The incidence for skip metastasis to level IV was low as well. We recommend elective neck dissection that includes levels I to III in selected patients with OTSCC and cN0 neck.

Sentinel node biopsy versus elective neck dissection in early-stage oral cancer: a systematic review.

To provide a summary of the evidence on the comparative effectiveness of two surgical treatment strategies, sentinel node biopsy (SNB) and elective neck dissection (END), in patients with T1-T2 oral cancer and clinically negative (cN0) neck, in terms of overall survival (OS), disease-free survival (DFS) and neck recurrence rates (NRRs). A systematic review was performed by including studies published up to April 2019. Meta-analysis was performed to compare NRRs between SNB and END. A narrative summary of the results was generated for OS, DFS and morbidity outcomes. The certainty of evidence was assessed according to the GRADE methodology. No randomized studies were retrieved. Five observational studies were included in the comparative effectiveness analysis and four observational studies were included in the comparative morbidity analysis. The pooled risk ratio showed no differences in NRRs between SNB and END (10.5% vs 11.6%; pooled RR 1.09; 95% CI 0.67-1.76). No differences in OS or DFS between the two treatments were found. SNB appears to be associated with a lower rate of postoperative complications and lower shoulder dysfunction than END. Conversely, the results of the quality of life (QoL) questionnaires are not sufficient to advocate a particular strategy. Our review highlights the lack of well conducted and randomized studies comparing SNB to END, leading to poor clinical evidence. Although our findings suggest no significant differences in OS, DFS and NRR between the two strategies, the certainty of our evidence is too low to make it useful for clinical decision making.

Bilateral versus ipsilateral neck dissection in oral and oropharyngeal cancer with contralateral cN0 neck

ObjectiveContralateral elective neck dissection (cEND) in oral and oropharyngeal squamous cell cancer (OC/OPC) is still a matter of debate. The current study analyzed the outcome in OC/OPC patients with/without cEND.MethodsOC/OPC patients (n = 471) were diagnosed with contralateral N0 after CT/MRI-scan combined with neck ultrasound. Clinico-pathological features were analyzed using Chi-square/Fisher exact/Student’s t test. Survival rates were calculated using Kaplan–Meier and log-rank test. Prognostic variables were evaluated by Cox regression. Primary/secondary endpoints were overall/recurrence-free survival (OS/RFS).ResultsPre-therapeutic imaging revealed a significantly over-staged N-status (p = 0.01), while occult contra-lateral N + was diagnosed in one patient only (0.4%). OC patients did not show differences in OS/RFS between the groups (ipsi- vs. bi-lateral). There was a strong tendency towards a better OS in OPC patients who underwent ipsi-lateral ND (p = 0.07). Cox-regression demonstrated that only tumor recurrence was associated with a fivefold increased risk of recurrence-associated death (p < 0.0001) that referred to a significant higher recurrence rate at primary tumor site (rT +) and increased distant metastatic outgrowth in OPC who underwent bi-lateral neck dissection (p = 0.03). While RFS of any cause (rT + /rN + /rM +) was significantly better in OPC with ipsi-lateral ND (p < 0.05), RFS of contralateral lymph node recurrence (rN2c) was comparable in both groups.ConclusionEND of the contralateral cN0 neck is not correlated by an increased RFS or OS. Standard imaging techniques including CT/MRI scan and neck ultrasound warrant watchful waiting for neck dissection of the contralateral cN0 neck.

Individualized Prophylactic Neck Irradiation in Patients with cN0 Head and Neck Cancer Based on Sentinel Lymph Node(s) Identification: Definitive Results of a Prospective Phase 1-2 Study

This prospective, nonrandomized, interventional phase 1-2 study investigated the individualization of elective node irradiation in clinically N0 head and neck squamous cell carcinoma by sentinel lymph node (SLN) mapping with single-photon emission computed tomography/computed tomography (SPECT/CT) and its impact on tumor control and radiation-related toxicity. Forty-four patients with clinically N0 head and neck squamous cell carcinoma treated with definitive (chemo-)radiation therapy were imaged with SPECT/CT after 99mTc nanocolloid injection around the tumor. The neck levels containing up to the 4 hottest SLNs were selected for prophylactic irradiation. A comparative virtual planning was performed with the selection of neck levels based on the current international guidelines. Regional control was monitored as a function of the selected volume. Dosimetric data for the organs at risk were compared between the plans. Normal tissue complication probability (NTCP) rates were derived for xerostomia, dysphagia, and hypothyroidism to predict the clinical benefit and correlated to quality-of-life (QoL) assessments at 6 months. Sixteen percent of patients presented unpredicted lymphatic drainage, and 48% drained unilaterally. The nodal clinical target volume based on lymphoscintigraphy was smaller than the nodal clinical target volume based on international guidelines by a factor of 2 (P < .0001). After a median follow-up of 46 months, only 1 patient experienced a regional relapse in a nonirradiated area. Significant median dose reductions to organs at risk were observed, particularly to contralateral salivary glands in patients with unilateral drainage (14.6-28.1 Gy) and to the thyroid gland in all patients (22.4-48.9 Gy). Median NTCP reductions were observed for xerostomia (0.3% to 13.7%), dysphagia (1.7% to 10.8%), and hypothyroidism (14.0% to 36.1%). QoL at 6 months was improved, particularly in patients irradiated unilaterally. Neck SLN mapping with SPECT/CT individualizes and reduces the elective nodal target volumes without compromising the regional control. The NTCP rates were reduced and favorable QoL were observed in all patients, particularly in the case of unilateral irradiation.

Lymphatic mapping with SPECT-CT for evaluation of contralateral drainage in lateralized oropharyngeal cancers using an awake injection technique.

Risk of contralateral nodal metastases in oropharyngeal squamous cell carcinoma (OPSCC) is currently based on clinical risk factors. We propose lymphatic mapping with single photon emission computed tomography (SPECT-CT) for tumor-specific delineation of lymphatic drainage to guide treatment. Retrospective review of lymphatic drainage patterns in cT1-2 OPSCC and contralateral cN0 neck with a nonoperative, awake injection of 99 m-Tc sulfur colloid and SPECT-CT. Ten patients were reviewed. Primary sites included tonsil (n = 8, 80%) and tongue base (n = 2, 20%). All patients tolerated awake injections with no complications. Nine patients (90%) demonstrated satisfactory migration of radiotracer to neck node(s) with seven (78%) to the ipsilateral lateral neck, one (11%) to the ipsilateral lateral neck and retropharynx, and one (11%) to bilateral lateral neck nodes. Characterization of lymphatic drainage in OPSCC is feasible using a nonoperative injection technique and SPECT-CT. Drainage to the contralateral neck is rare, warranting further study to tailor treatment appropriately.