Sentinel lymph nodes are often the first nodes to be involved in early oral cancer. The aim of this review was to assess the relation of clinicopathological factors in patients with positive sentinel lymph nodes. We propose formulating a risk prediction model that could elucidate the individual risk of nodal metastases and prognosis in early oral squamous cell carcinoma (SCC). A systematic review was undertaken in accordance with the PRISMA protocol. Study quality was assessed using STROBE, and bias was assessed using the ROBINS-I tool. Meta-analysis was carried out using the Mantel-Haenszel method for calculating the weighted pooled odds ratio under the fixed effects model. Thirty studies published between 2004 and 2023 were included. Pooled sentinel lymph node positivity from 27 studies averaged 26.7%. On meta-analysis 26% of T1N0 and 35% of T2N0 patients were sentinel-node positive. On pooled meta-analysis, there was an increased odds ratio for sentinel node positivity that was statistically significant for pT2 status, a non-cohesive tumour front, moderate differentiation, and the tongue subsite. We believe that these findings not only add to the current evidence but will also contribute to a future risk model for management of the neck in patients with early oral SCC.

OBJECTIVE:Sentinel lymph node biopsy (SLNB) is crucial in cutaneous melanoma and oral cavity squamous cell carcinoma (OCSCC) as it directs the need for systemic therapy. There has been growing interest in Technetium-99m-labeled Tilmanocept (TL) due to its specific binding capability. This study compares the efficacy of TL to 99mTc-antimony sulphide colloid (ASC), in these two biologically distinct cancers. DESIGN:In this prospective cross-sectional study, 40 patients were included in each radiotracer group. The primary outcomes measured SN identification rate on lymphoscintigraphy and surgical node retrieval rate. Secondary outcomes include pathological status of lymph nodes, false negative rates (FNR), and nodal recurrence. RESULT:TL had comparable outcome to ASC with a 100 % SN detection and retrieval rate. Both radiotracers had 100 % lymph nodal tissue specificity with an FNR rate of 0 % for both radiotracers in CM and 25 % for TL in OCSCC. There were significant differences between the SN detection and retrieval rates in ASC in CM and OCSCC but not TL, reflecting its superior binding capability. CONCLUSION:Our study is the first to demonstrate the superior molecular binding capability of TL with minimal migration to the second echelon nodes.

(1) Background: Knowledge regarding the optimal radiotherapy dose for Merkel-cell carcinoma (MCC) remains limited. (2) Methods: Following a PubMed search, equivalent doses in 2 Gy fractions (Gy2) were compared. (3) Results: Of the 949 patients, 939 were evaluable, with 728 (77.5%) cases localized to the primary site and 171 irradiated without chemotherapy. The overall local recurrence rate (LRR) was 23% (40/171). After definitive radiotherapy with EQD2 < 50 Gy2 versus ≥50 Gy2, the LRRs were 23.1% (3/13) and 12.5% a(1/8), respectively (p = 0.0004). (4) Conclusions: For definitive radiotherapy, EQD2 < 50 Gy2 demonstrates a significantly higher LRR than ≥50 Gy2 (p = 0.0004). This study is clinically useful and unique with stratification by definitive/adjuvant settings and positive/negative resection margins. A future prospective multicenter study is needed to determine the optimal radiotherapy doses.

(1) Background: It is controversial if Merkel cell carcinomas (MCCs) spread to lymph nodes or distant metastases (LNM/DM) first. (2) Methods: A total of 303 patients from six institutions (March 1982–February 2015) were combined with individual patient data from a PubMed search, totaling 949 patients. The primary outcome was recurrence patterns. (3) Results: (a) More patients presented with lymph node metastases (LNMs) than DMs at diagnosis: 17.9% (166 among the 929 patients with known staging) vs. 1.9% (18/929); (b) 310/929 (33.4%) developed lifetime DM, of whom 220/310 also developed LNM. The majority (133 patients) of patients were documented to have developed LNM before DM. (c) A shorter median time of 1.5 months (range: 0–47.0) from initial diagnosis to LNM, versus 8 months (range: 0–107.8) to DM, was also found. Another observation was that 2.4% (23/949) of patients with primary tumors ≤1 cm developed lifetime DM, with the smallest being 0.2 cm. (4) Conclusions: Three observations support the idea that prior LNM gives rise to subsequent DM as the main pathway of dissemination in MCC. This implies that patients with nodal metastases should be considered for adjuvant systemic therapy studies as an enriched population. Participation in clinical trials is strongly encouraged.

BACKGROUND:We aimed to identify predictors of distant metastatic recurrence (DMR) in patients with head and neck cutaneous squamous cell carcinoma (HNcSCC) with nodal metastases treated with curative intent. METHODS:Predictors of DMR were identified using Cox regression in a multicenter study of 1151 patients. RESULTS:The 5-year risk of DMR was 9.6%. On multivariate analysis, immunosuppression (HR 2.93; 95% CI: 1.70-5.05; p < 0.001), nodal size >6 cm [versus ≤3 cm (HR 2.77; 95% CI: 1.09-7.03; p = 0.032)], ≥5 nodal metastases [versus 1-2 (HR 2.79; 95% CI: 1.63-4.78; p < 0.001)], and bilateral disease (HR 3.11; 95% CI: 1.40-6.90; p = 0.005) predicted DMR. A DMR risk score was developed that stratified risk from 6.6% (no risk factors) to 100% (≥3 risk factors) (p < 0.001). CONCLUSIONS:The risk of DMR in nodal metastatic HNcSCC increases with immunosuppression, nodal size >6 cm, ≥5 nodal metastases, and bilateral disease. A simple DMR risk score estimated prior to treatment may be clinically useful.

Importance The eighth edition tumor, node, metastasis (TNM) staging for head and neck cutaneous squamous cell carcinoma (HNcSCC) is a poor predictor of survival in patients with lymph node metastases, possibly due to the inclusion of extranodal extension (ENE). Objective To identify the key determinants of prognosis in patients with nodal metastatic HNcSCC and analyze the association of ENE with TNM stage and investigate for prognostic heterogeneity in ENE-positive disease. Design, Setting, and Participants This retrospective, multicenter cohort study was conducted at 4 Australian tertiary referral centers using prospectively collected data in patients treated between 1980 and 2017 with a median (IQR) follow-up of 3.2 (3.9) years. The study population included 1309 consecutive patients with HNcSCC that was metastatic to parotid and/or cervical nodes. After excluding cases with perioperative mortality, missing data, or follow-up, the final study population included 1151 patients. Exposure Curative intent surgery +/- adjuvant radiotherapy. Main Outcomes and Measures Differences in locoregional control (LRC), disease-specific survival (DSS), and overall survival were determined using Cox regression analysis. Results Among 1151 patients, 976 (84.8%) were male and 175 (15.2%) female, with a median age of 73.3 years (range, 18-100 years). On multivariable analysis, immunosuppression (hazard ratio [HR], 2.48; 95% CI, 1.64-3.74), perineural invasion (HR, 1.69; 95% CI, 1.25-2.30), ENE (HR, 1.53; 95% CI, 0.95-2.44), size (>3-6 cm vs <= 3 cm [HR, 1.41; 95% CI, 1.03-1.93]; >6 cm vs <= 3 cm [HR, 5.01; 95% CI, 2.98-8.42]), and number of nodal metastases (3-4 vs 1-2 [HR, 1.54; 95% CI, 1.01-2.34]; >= 5 vs 1-2 [HR, 2.86; 95% CI, 1.99-4.11]) were associated with DSS. Similar results were found for LRC and overall survival. More than 90% of the population was categorized as TNM stage IV, with 32% attributable to ENE. In the ENE-positive subset (n = 860), DSS ranged from 8% to 88% based on stratification using other clinicopathological factors. Conclusions and Relevance The study results suggest that immunosuppression, perineural invasion, ENE, and size and number of nodal metastases are associated with reduced survival and LRC in HNcSCC with nodal metastases. The inclusion of ENE in HNcSCC staging needs to be reassessed, as it ascribes excessive importance to ENE and upstages most patients to TNM stage IV, despite many having a high chance of cure.

Background: Despite introduction of extranodal extension (ENE) into the AJCC 8th edition of oral cancer staging, previous criticisms persist, such as limited discrimination between sub-stages and doubtful prognostic value of contralateral nodal disease. The purpose of this study was to compare our novel nodal staging system, based on the number of positive nodes and ENE, to the AJCC staging system in surgically treated patients. Methods: Retrospective analysis of 4710 patients with oral squamous cell carcinoma (OSCC) treated with surgery +/- adjuvant therapy in 8 institutions in Australia, North America and Asia. With overall survival (OS) and disease specific survival (DSS) as endpoint, the prognostic performance of AJCC 8th and 7th editions were compared using hazard consistency, hazard discrimination, likelihood difference and balance. Results: Our new nodal staging system (PN) a progressive and linear increase in hazard ratio (HR) from pN0 to pN3, with good separation of Kaplan Meier curves. Using the predetermined criteria for evaluation of a staging system, our proposed staging model outperformed AJCC 8th and 7th editions in prediction of OS and DSS. Conclusion: PN was the lymph node staging system that provided the most accurate prediction of OS and DSS for patients in our cohort of OSCC. Additionally, it can be easily adopted, addresses the shortcomings of the existing systems and should be considered for future editions of the TNM staging system.

Patients with cancer and diabetes face unique challenges. Limited data are available on diabetes management in patients undergoing concurrent chemoradiotherapy (CCRT), a curative intent anticancer therapy commonly associated with glucocorticoid administration, weight fluctuations and enteral feeds. This retrospective case–control study examined the real-world incidence of acute diabetes-related complications in patients with head and neck cancer receiving CCRT, along with the impact of diabetes on CCRT tolerance and outcomes. Methods: Consecutive patients with head and neck squamous cell or nasopharyngeal cancer who underwent definitive or adjuvant CCRT between 2010 and 2019 at two large cancer centers in Australia were included. Clinicopathological characteristics, treatment complications and outcomes were collected from medical records. Results: Of 282 patients who received CCRT, 29 (10.3%) had pre-existing type 2 diabetes. None had type 1 diabetes. The majority (74.5%) required enteral feeding. A higher proportion of patients with diabetes required admission to a high-dependency or intensive care unit (17.2 versus 4.0%, p = 0.003). This difference was driven by the group who required insulin at baseline (n = 5), of which four (80.0%) were admitted to a high-dependency unit with diabetes-related complications, and three (60.0%) required omission of at least one cycle of chemotherapy. Conclusions: Patients with diabetes requiring insulin have a high risk of acute life-threatening diabetes-related complications while receiving CCRT. We recommend multidisciplinary management involving a diabetes specialist, educator, dietitian, and pharmacist, in collaboration with the cancer care team, to better avoid these complications.