Active surveillance is a feasible and safe strategy in selected patients with papillary thyroid cancer and suspicious cervical lymph nodes detected after thyroidectomy.

Objective: After initial treatment, up to 30% of patients with papillary thyroid cancer (PTC) have incomplete response, mainly cervical lymph node (LN) disease. Previous studies have suggested that active surveillance (AS) is a possible option for these patients. Our aim was to report the results of AS in patients with PTC and cervical LN disease. Materials and methods: In this retrospective observational study, we included adult patients treated and followed for PTC, who presented with cervical LN disease and were managed with AS. Growth was defined as an increase ≥ 3mm in either diameter. Results: We included 32 patients: 27 (84.4%) women, age of 39 ± 14 years, all initially treated with total thyroidectomy, and 22 (69%) with therapeutic neck dissection. Cervical LN disease was diagnosed 1 year (0.3-12.6) after initial management, with a diameter of 9.0 mm (6.0-19.0). After a median AS of 4.3 years (0.6-14.1), 4 (12.5%) patients had LNgrowth: 2 (50%) of whom were surgically removed, 1 (25%) was effectively treated with radiotherapy, and 1 (25%) had a scheduled surgery. Tg increase was the only predictive factor of LN growth evaluated as both the delta Tg (p < 0.0366) and percentage of Tg change (p < 0.0140). None of the included patients died, had local complications due to LN growth or salvage therapy, or developed distant metastases during follow-up. Conclusion: In selected patients with PTC and suspicious cervical LNs diagnosed after initial treatment, AS is a feasible and safe strategy as it allows effective identification and treatment of the minority of patients who progress.

Latin American Consensus on the Treatment of Head and Neck Cancer.

Head and neck squamous cell carcinoma (HNSCC) is well known as a serious health problem worldwide, especially in low-income countries or those with limited resources, such as most countries in Latin America. International guidelines cannot always be applied to a population from a large region with specific conditions. This study established a Latin American guideline for care of patients with head and neck cancer and presented evidence of HNSCC management considering availability and oncologic benefit. A panel composed of 41 head and neck cancer experts systematically worked according to a modified Delphi process on (1) document compilation of evidence-based answers to different questions contextualized by resource availability and oncologic benefit regarding Latin America (region of limited resources and/or without access to all necessary health care system infrastructure), (2) revision of the answers and the classification of levels of evidence and degrees of recommendations of all recommendations, (3) validation of the consensus through two rounds of online surveys, and (4) manuscript composition. The consensus consists of 12 sections: Head and neck cancer staging, Histopathologic evaluation of head and neck cancer, Head and neck surgery-oral cavity, Clinical oncology-oral cavity, Head and neck surgery-oropharynx, Clinical oncology-oropharynx, Head and neck surgery-larynx, Head and neck surgery-larynx/hypopharynx, Clinical oncology-larynx/hypopharynx, Clinical oncology-recurrent and metastatic head and neck cancer, Head and neck surgery-reconstruction and rehabilitation, and Radiation therapy. The present consensus established 48 recommendations on HNSCC patient care considering the availability of resources and focusing on oncologic benefit. These recommendations could also be used to formulate strategies in other regions like Latin America countries.

A Prospective Double-Blinded Comparison of Reflectance Confocal Microscopy with Conventional Histopathology for In Vivo Assessment in Oral Cancer.

PURPOSE: We investigated reflectance confocal microscopy (RCM) as a possible non-invasive approach for the diagnosis of cancer and real-time assessment of surgical margins. PATIENTS AND METHODS: In a phase I study on 20 patients, we established the RCM imaging morphological features that distinguish OSCC from normal tissue with a newly developed intra-oral RCM probe. Our subsequent phase II prospective double-blinded study in 60 patients tested the diagnostic accuracy of RCM against histopathology. Five RCM videos from the tumor and five from normal surrounding mucosa were collected on each patient, followed by a 3-mm punch biopsy of the imaged area. An experienced RCM reader, who was blinded to biopsy location and histological diagnosis, examined the videos from both regions and classified each as "tumor" or "not-tumor" based on RCM features established in phase I. Hematoxylin and eosin slides from the biopsies were read by a pathologist who was blinded to RCM results. Using histology as the gold standard, we calculated the sensitivity and specificity of RCM. RESULTS: We report a high agreement between the blinded readers (95% for normal tissue and 81.7% for tumors), high specificity (98.3%) and negative predictive values (96.6%) for normal tissue identification, and high sensitivity (90%) and positive predictive values (88.2%) for tumor detection. CONCLUSIONS: RCM imaging is a promising technology for non-invasive in vivo diagnosis of OSCC and for real-time intraoperative evaluation of mucosal surgical margins. Its inherent constraint, however, stems from the diminished capability to evaluate structures located at more substantial depths within the tissue.

Distant metastasis in oral squamous cell carcinoma: Does the neutrophil-to-lymphocyte ratio act as a surrogate of the host immune status?

OBJECTIVES: Distant metastasis (DM) is an important prognostic factor for oral squamous cell carcinoma (OSCC). The aim of this study is to evaluate the influence of host and tumor factors in development of DM. MATERIALS AND METHODS: After IRB approval, 1369 patients with OSCC undergoing primary surgery were eligible for the study. The primary endpoint was the development of distant metastasis (DM). Patients were pathologically staged according to the American Joint Committee on Cancer, 8th Edition. Pre-operative peripheral blood counts were used to calculate neutrophil-to-lymphocyte ratio (NLR). RESULTS: Median follow-up was 39 months (range 1-221). DM were identified in 126 patients during follow-up. When analyzed as a time-dependent covariate, neck recurrence (NR) was a significant predictor of DM (HR 16.35, 95% CI: 11.39-23.47, p < 0.001). NLR, margin status, vascular invasion, perineural invasion (PNI), grade, pT, number of metastatic lymph nodes, level IV involvement, and extra nodal-extension (ENE) were also significant. In multivariable analysis, NLR, margins, PNI, number of metastatic lymph nodes, and ENE maintained independent predictive capacity. Patients with NLR ≥ 5.7 were 3 times more likely to develop DM compared to NLR ≤ 2.9 (95% CI: 1.74-5.59, p < 0.001), patients with ≥ 5 metastatic lymph nodes were 2 times more likely to develop DM (95% CI: 1.18-3.60, p = 0.011), and those with ENE were 4 times more likely (95% CI: 2.67-8.20, p < 0.001) when compared to pNx/pN0 patients. CONCLUSIONS: NLR, number of metastatic lymph nodes, and ENE were the strongest independent predictors of DM in OSCC treated with primary surgery and appropriate adjuvant therapy.

Warthin-like and classic papillary thyroid cancer have similar clinical presentation and prognosis.

OBJECTIVE: Warthin-like papillary thyroid cancer (WL-PTC) is an uncommon variant of PTC, usually associated with lymphocytic thyroiditis. Scarce evidence suggests that WL-PTC has similar clinical presentation to classic PTC (C-PTC), with no studies comparing risks of recurrence and response to treatment between both variants. Our objective was to describe the clinical presentation and prognosis of WL-PTC and compare it to C-PTC. METHODS: Retrospective analysis of a prospective cohort, including 370 (96%) patients with C-PTC and 17 (4%) with WL-PTC, consecutively treated with total thyroidectomy with or without RAI, followed for at least 6 months. We compared clinical presentation, risk of mortality and recurrence, as well as response to treatment between both variants. RESULTS: Of the total cohort: 317 (82%) female, 38 ± 13.5 years, median follow-up 4 years (0.5-28.5); most of them stage I and low/intermediate risk of recurrence. We found no differences regarding clinical-pathological data and risk of recurrence. WL-PTC was associated with a higher rate of anti-thyroglobulin antibodies (TgAb) (65% vs. 36%, p = 0.016) and lymphocytic thyroiditis (59% vs. 34%, p = 0.03). The rates of biochemical and structural incomplete responses were similar in both variants. WL-PTC had a lower rate of excellent response (23% vs. 54%, p = 0.01), which became non-significant when performing analysis by TgAb presence (50% vs. 67%, p = NS). CONCLUSION: WL-CPT and C-CPT have similar clinical presentation and rate of recurrence. The lower rate of excellent response to treatment in WL-PTC is due to a higher frequency of TgAb. WL-PCT should not be considered an aggressive variant of PTC.

Use of Ultrasmall Core-Shell Fluorescent Silica Nanoparticles for Image-Guided Sentinel Lymph Node Biopsy in Head and Neck Melanoma: A Nonrandomized Clinical Trial.

Importance: Sentinel lymph node (SLN) mapping agents approved for current surgical practice lack sufficient brightness and target specificity for high-contrast, sensitive nodal visualization. Objective: To evaluate whether an ultrasmall, molecularly targeted core-shell silica nanoparticle (Cornell prime dots) can safely and reliably identify optically avid SLNs in head and neck melanoma during fluorescence-guided biopsy. Design, Setting, and Participants: This nonrandomized clinical trial enrolled patients aged 18 years or older with histologically confirmed melanoma in whom SLN mapping was indicated. Exclusion criteria included known pregnancy, breast-feeding, or medical illness unrelated to the tumor. The trial was conducted between February 2015 and March 2018 at Memorial Sloan Kettering Cancer Center, with postoperative follow-up of 2 years. Data analysis was conducted from February 2015 to March 2018. Interventions: Patients received standard-of-care technetium Tc 99m sulfur colloid followed by a microdose administration of integrin-targeting, dye-encapsulated nanoparticles, surface modified with polyethylene glycol chains and cyclic arginine-glycine-aspartic acid-tyrosine peptides (cRGDY-PEG-Cy5.5-nanoparticles) intradermally. Main Outcomes and Measures: The primary end points were safety, procedural feasibility, lowest particle dose and volume for maximizing nodal fluorescence signal, and proportion of nodes identified by technetium Tc 99m sulfur colloid that were optically visualized by cRGDY-PEG-Cy5.5-nanoparticles. Secondary end points included proportion of patients in whom the surgical approach or extent of dissection was altered because of nodal visualization. Results: Of 24 consecutive patients enrolled (median [interquartile range] age, 64 [51-71] years), 18 (75%) were men. In 24 surgical procedures, 40 SLNs were excised. Preoperative localization of SLNs with technetium Tc 99m sulfur colloid was followed by particle dose-escalation studies, yielding optimized doses and volumes of 2 nmol and 0.4 mL, respectively, and maximum SLN signal-to-background ratios of 40. No adverse events were observed. The concordance rate of evaluable SLNs by technetium Tc 99m sulfur colloid and cRGDY-PEG-Cy5.5-nanoparticles was 90% (95% CI, 74%-98%), 5 of which were metastatic. Ultrabright nanoparticle fluorescence enabled high-sensitivity SLN visualization (including difficult-to-access anatomic sites), deep tissue imaging, and, in some instances, detection through intact skin, thereby facilitating intraoperative identification without extensive dissection of adjacent normal tissue or nerves. Conclusions and Relevance: This study found that nanoparticle-based fluorescence-guided SLN biopsy in head and neck melanoma was feasible and safe. This technology holds promise for improving lymphatic mapping and SLN biopsy procedures, while potentially mitigating procedural risks. This study serves as a first step toward developing new multimodal approaches for perioperative care. Trial Registration: ClinicalTrials.gov Identifier: NCT02106598.

Warthin-like and classic papillary thyroid cancer have similar clinical presentation and prognosis

ABSTRACT Objective Warthin-like papillary thyroid cancer (WL-PTC) is an uncommon variant of PTC, usually associated with lymphocytic thyroiditis. Scarce evidence suggests that WL-PTC has similar clinical presentation to classic PTC (C-PTC), with no studies comparing risks of recurrence and response to treatment between both variants. Our objective was to describe the clinical presentation and prognosis of WL-PTC and compare it to C-PTC. Subjects and methods Retrospective analysis of a prospective cohort, including 370 (96%) patients with C-PTC and 17 (4%) with WL-PTC, consecutively treated with total thyroidectomy with or without RAI, followed for at least 6 months. We compared clinical presentation, risk of mortality and recurrence, as well as response to treatment between both variants. Results Of the total cohort: 317 (82%) female, 38 ± 13.5 years, median follow-up 4 years (0.5-28.5); most of them stage I and low/intermediate risk of recurrence. We found no differences regarding clinical-pathological data and risk of recurrence. WL-PTC was associated with a higher rate of anti-thyroglobulin antibodies (TgAb) (65% vs. 36%, p = 0.016) and lymphocytic thyroiditis (59% vs. 34%, p = 0.03). The rates of biochemical and structural incomplete responses were similar in both variants. WL-PTC had a lower rate of excellent response (23% vs. 54%, p = 0.01), which became non-significant when performing analysis by TgAb presence (50% vs. 67%, p = NS). Conclusions WL-CPT and C-CPT have similar clinical presentation and rate of recurrence. The lower rate of excellent response to treatment in WL-PTC is due to a higher frequency of TgAb. WL-PCT should not be considered an aggressive variant of PTC.

Manejo de nódulos tiroideos y cáncer de tiroides con lobectomía: experiencia de un equipo multidisciplinario / Management of thyroid nodules and thyroid cancer with lobectomy: experience of a multidisciplinary team

INTRODUCCIÓN: La extensión de la cirugía es motivo de controversia en el manejo de nódulos y cáncer diferenciado de tiroides (CDT). En nódulos benignos e indeterminados que requieran cirugía, la lobectomía es de elección, mientras que en CDT debe considerarse en tumores intratiroideos ≤ 4 cm. NUESTRO OBJETIVO objetivo fue reportar la primera cohorte chilena de nódulos tiroideos y CDT tratados con lobectomía por un equipo multidisciplinario. SUJETOS Y MÉTODOS: Se incluyeron pacientes sometidos a lobectomía por nódulos tiroideos y CDT que cumplieran: 1) tumor intratiroideo ≤4cm si punción aspirativa (PAF) Bethesda I, III, IV, V o VI; sin límite de tamaño si PAF Bethesda II, y 2) sin hallazgos sospechosos en la ecografía preoperatoria. En pacientes con CDT se describió presentación clínica, complicaciones y tipo de respuesta a tratamiento según ATA 2015 y MINSAL 2020. RESULTADOS: Se incluyeron 105 pacientes, edad 38±11 años, 84 (80%) mujeres, diámetro 2,2±1,5cm: 41 (39%) benignos y 64 (61%) CDT. De los CDT, 44 (69%) tenían cáncer papilar, 7 (11%) cáncer folicular y 13 (20%) NIFTP. Todos eran etapa I. Según MINSAL, 55 (85,9%) de riesgo muy bajo/bajo y 9 (14,1%) intermedio. Según ATA, 51 (80%) y 13 (20%) de riesgo bajo e intermedio, respectivamente. Se indicó totalización precoz y ablación con radioyodo en 6 (9,4%) pacientes: 4 por invasión venosa y 2 por CPT variedad sólida. De los 39 no totalizados seguidos ≥6 meses, no hubo casos de respuesta incompleta. Respecto a las complicaciones, ningún paciente tuvo hipocalcemia y 10 (9,5%) tuvieron disfonía transitoria. CONCLUSIONES: En pacientes con nódulos tiroideos o CDT seleccionados, la lobectomía es una alternativa adecuada. En CDT logra buen control de enfermedad sin necesidad de tratamiento adicional en cerca de 90% de los pacientes, con muy baja morbilidad asociada.

INTRODUCTION: The extension of surgery is a matter of debate in the management of thyroid nodules and differentiated thyroid cancer (DTC). While lobectomy is the procedure of choice in benign and indeterminate nodules that require surgery, it is an option in intrathyroidal DTC up to 4 cm. OUR OBJECTIVE was to report the first Chilean cohort of patients with thyroid nodules and DTC treated with lobectomy by a multidisciplinary team. SUBJECTS AND METHODS: We included patients with thyroid nodules treated with lobectomy, who met the following inclusion criteria: 1) intrathyroidal tumor ≤ 4cm if fine-needle aspiration biopsy (FNA) was Bethesda I, III, IV, V o VI; without size limit if FNA was Bethesda II, and 2) non-suspicious findings in preoperative ultrasound. In patients with DTC we described clinical presentation, complications and response to treatment according to ATA 2015 and MINSAL 2020. RESULTS: We included 105 patients, 38±11 years old, 84 (80%) female, diameter 2.2±1.5cm: 41 (39%) benign and 64 (61%) DTC. Among DTC, 44 (69%) had papillary thyroid cancer, 7 (11%) follicular thyroid cancer and 13 (20%) NIFTP. All had stage I DTC. According to MINSAL, 55 (85.9%) were very low/low, and 9 (14.1%) intermediate risk. According to ATA, 51 (80%) and 13 (20%) were low and intermediate risk, respectively. Six (9.4%) patients required early completion thyroidectomy and radioiodine ablation: 4 due to angioinvasion and 2 due to solid variant PTC. None of the 39 non-completed patients followed for at least 6 months had incomplete response. Regarding complications, there were no cases of hypocalcemia and 10 (9.5%) patients had transient dysphonia. CONCLUSIONS: In properly selected patients with thyroid nodules or DTC, lobectomy is an appropriate treatment option. In DTC, lobectomy accomplishes adequate disease control without need of further treatment in nearly 90% of patients, with very low associated morbidity.

Survival outcomes after treatment of cancer of the oral cavity (1985-2015).

OBJECTIVES: To present treatment results of oral squamous cell carcinoma (OSCC) at a tertiary cancer care center from 1985 to 2015. MATERIALS AND METHODS: A total of 2082 patients were eligible for this study. Main outcomes measured were overall survival (OS) and disease specific survival (DSS). Prognostic variables were identified with bivariate analyses using Kaplan-Meier curves and log-rank testing for comparison. A p-value < 0.05 was considered statistically significant and significant factors were entered into multivariate analysis. Median age was 62 years (16-100), 56% were men, 66% reported a history of tobacco use and 71% of alcohol consumption. The most common subsite was tongue (51%). Seventy-three percent of patients had cT1-2 and 71% had clinically negative necks (cN0). Surgery alone was performed in 1348 patients (65%), adjuvant postoperative radiotherapy in 608 patients (29%) and postoperative chemoradiation in 126 patients (6%). Neck dissection was performed in 920 patients with cN0, and in 585 patients with a clinically involved neck. The median follow-up was 37.6 months (range 1-382). RESULTS: The 5-year OS and DSS were 64.4% and 79.3%, respectively. Age, comorbidities, margin status, vascular invasion, perineural invasion, AJCC 8th edition pT, and pN were independent prognostic factors of OS (p < 0.05). History of alcohol consumption, margin status, vascular invasion, perineural invasion, pT, and pN were independent prognostic factors of DSS (p < 0.05). CONCLUSION: pN stage is the most powerful and consistent predictor of outcome in patients with OSCC treated with primary surgery and appropriate adjuvant therapy.

Do we need a different staging system for tongue and gingivobuccal complex squamous cell cancers?

OBJECTIVES: To determine the need for a separate staging system for gingivobuccal complex squamous cell cancers (GBCSCC) based on 5-year overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) data from one institution. PATIENTS AND METHODS: An Institutional Review Board (IRB)-approved retrospective analysis was performed on an oral cavity cancer patient database. Patients from 1985 to 2012 with primary surgical treatment for biopsy-proven squamous cell cancer (SCC) from either the oral tongue (TSCC Group) or gingivobuccal complex (GBCSCC Group), were selected as two separate subgroups. The clinicopathologic data were used to stage the patients based on the American Joint Committee on Cancer 7th edition. Survival outcomes including 5-year OS, RFS, and DSS were calculated and analyzed. A multivariate analysis was performed to identify if subsite was an independent predictor for the survival outcomes, adjusting for other variables. A p-value of less than .05 was considered statistically significant. RESULTS: 936 patients with TSCC and 486 patients with GBCSCC were considered eligible for the analysis. Patients with GBCSCC were more likely to be older (p < .001) and presented with more advanced disease (p < .001) compared to patients with TSCC. Unadjusted hazard ratio (HR) suggested GBCSCC had poor OS compared to TSCC. However, after adjusting for other variables, the adjusted HR was not significant (p = .593). There was no difference in 5-year DSS or RFS in either of the study groups. CONCLUSION: With similar survival outcomes by stage, there is no justification for using a different staging system for GBCSCC.

Neck recurrence in clinically node-negative oral cancer: 27-year experience at a single institution.

OBJECTIVES: Neck failure in patients with oral squamous cell carcinoma (OSCC) carries a poor outcome, yet the management of patients who initially present with clinically node-negative (cN0) neck is not clearly defined. PATIENTS AND METHODS: Retrospective review of patients with cN0 OSCC treated at Memorial Sloan Kettering Cancer Center from 1985 to 2012, focusing on rate, pattern and predictors of neck failure, salvage treatment, and survival outcomes. RESULTS: Of 1,302 patients, 806 (62%) underwent elective neck dissection (END) and 496 (38%) had observation. 190 patients (15%) developed neck recurrence. Median follow-up was 58.5 months (range 1-343); 5-year neck recurrence-free survival (NRFS) was 85% and 80% for the END and observation group respectively (p = .06). Patients with neck failure had poorer outcomes than patients without neck failure (5-year overall survival, 37% vs. 74% [p < .001]; disease-specific survival [DSS], 41% vs. 91% [p < .001]). Independent predictors of neck failure were smoking, primary tumor subsite (hard palate and upper gum), and extranodal extension. 87% of patients underwent salvage treatment (END: 81.1%; observation: 94%). Salvage surgery with adjuvant (chemo) radiation had better DSS than surgery alone or nonsurgical salvage. CONCLUSIONS: In our cohort of patients with initially cN0 OSCC triaged to END vs. observation using clinical parameters, 15% developed neck failure. Salvage treatment was feasible in most cases but survival was poorer compared to patients without neck failure. Surgery followed by adjuvant (chemo) radiation resulted in the best outcome.

A Proposal to Redefine Close Surgical Margins in Squamous Cell Carcinoma of the Oral Tongue.

Importance: Resection of the primary tumor with negative margins is the gold standard treatment for squamous cell carcinoma of the oral tongue (SCCOT). A microscopically positive surgical margin is clearly associated with a higher risk for local recurrence, whereas a negative margin has traditionally been defined as greater than 5.0 mm clearance from the tumor, with lesser margins arbitrarily designated as close. The precise cutoff at which the risk for local recurrence with a close margin approximates that of a microscopically positive margin remains unclear. Objective: To determine whether the arbitrarily defined close margin (<5.0 mm) would portend as high a risk for local recurrence as a positive margin after resection of SCCOT. Design, Setting, and Participants: In this retrospective study, head and neck pathologists reviewed archived tumor specimens from 381 patients with SCCOT who underwent primary surgical resection at a tertiary care center from January 1, 2000, through December 31, 2012. Data were analyzed from November 15, 2015, to January 5, 2016. Time-dependent receiver operating characteristic curve analysis was used in patients who did not have a microscopically positive margin to determine an optimal margin cutoff for local recurrence-free survival (LRFS). Pathologic factors were assessed for LRFS in a multivariate Cox proportional hazards regression model. Main Outcomes and Measures: The primary end point was evaluation of the margin distance associated with LRFS. Results: Among the 381 patients included in the analysis (222 men [58.3%] and 159 women [41.7%]; mean [SD] age, 58 [14.7] years), the optimal cutoff associated with LRFS was determined to be 2.2 mm. This cutoff was compared with the traditionally accepted cutoff of 5.0 mm. Patients with a margin of 2.3 to 5.0 mm had similar LRFS as patients with a margin of greater than 5.0 mm (hazard ratio [HR], 1.31; 95% CI, 0.58-2.96), and all other comparisons were significantly different (HR for positive margin, 9.03; 95% CI, 3.45-23.67; HR for 0.01- to 2.2-mm margin, 2.83; 95% CI, 1.32-6.07). Based on this result, negative margins were redefined as those with a clearance of greater than 2.2 mm. In a multivariate model adjusting for pathologic factors, positive margins (adjusted HR, 5.73; 95% CI, 2.45-13.41) and margins of 0.01 to 2.2 mm (adjusted HR, 2.00; 95% CI, 1.13-3.55) were the variables most significantly associated with LRFS. Conclusions and Relevance: In this study, local recurrence-free survival was significantly affected only with surgical margins of less than or equal to 2.2 mm in patients with SCCOT. This new definition of close margins stratifies the risk for local recurrence better than the arbitrary 5.0-mm cutoff that has been used.

Influence of bone invasion on outcomes after marginal mandibulectomy in squamous cell carcinoma of the oral cavity.

INTRODUCTION: Marginal mandibulectomy (MM) is indicated for oral cavity squamous cell carcinomas (OCSCC) that abut or minimally erode the mandible without gross invasion. Successful implementation of MM is predicated on accurate patient selection and appropriate adjuvant treatment based on well-known host and tumor characteristics. The incidence of microscopically diagnosed bone involvement in MM specimens and its implications on outcomes have however not been reported in large contemporary series. PURPOSE: To report the incidence of bone involvement and analyze its influence on oncologic outcomes in selected patients who underwent MM in treatment of OCSCC. METHOD: A retrospective cohort study was performed on a consecutive series of previously untreated patients requiring MM, at a tertiary care cancer center, between 1985 and 2012 (n = 326). The median age was 64 years and 59% were male. The majority of patients (67%) had a primary tumor of the floor of the mouth or lower alveolus, 80% were clinically staged T1-2, and 31% were clinically N+. Postoperative radiation (PORT) was used in 27% and chemoradiation (POCTRT) in 8% of patients who had microscopic bone invasion. The median follow up period was 55 months and endpoints of interest were local and regional recurrence free (LRFS and RRFS) and disease specific (DSS) survival. RESULTS: Microscopic bone invasion was present in 15% of patients (n = 49). Among these, cortical invasion was present in 32, medullary in 13, and it was not specified in 4. Eight patients had microscopic positive bone margins. Positive bone margins were associated with medullary bone involvement (p < 0.001), floor of mouth and buccal mucosa primary site (p = 0.03), and positive soft tissue margins (p = 0.06). LRFS and DSS were similar in patients without versus with bone invasion (62.8% vs 79.7% and 76.2% vs 66% respectively, p = NS). LRFS were similar in patients with microscopic positive versus negative bone margins, as long as postoperative adjuvant treatment was administered. CONCLUSION: Microscopic bone involvement does not adversely influence outcomes but medullary bone involvement does confer a higher risk of positive bone margins. MM and appropriate adjuvant treatment is an effective strategy for treatment of OCSCC in selected patients with primary tumors adherent to or in proximity to the mandible.

Impact of elective neck dissection on the outcome of oral squamous cell carcinomas arising in the maxillary alveolus and hard palate.

BACKGROUND: Whether elective lymph neck dissection (ELND) is associated with improved survival in oral squamous cell carcinomas (SCC) of the maxillary alveolus/hard palate is not known. METHODS: One hundred ninety-nine patients presenting de novo and receiving treatment for clinically node negative SCC of the maxillary alveolus/hard palate at 2 cancer centers between 1985 and 2011 were analyzed. RESULTS: Forty-two patients (21%) received ELND. Occult nodal metastases were present in 29% of the dissected necks. The ELND group had more T3 to T4 status tumors (62% vs 34%; p < .001) and positive-margin resections (59% vs 38%; p = .019). Patients undergoing ELND experienced lower rates of neck recurrence (6% vs 21%; p = .031), superior 5-year recurrence-free survival (68% vs 45%; p = .026), and overall survival (86% vs 62%; p = .043). ELND was associated with a 2-fold decrease in risk of recurrence in multivariable analysis. CONCLUSION: ELND was associated with lower rates of recurrence and improved survival in SCC of the maxillary alveolus/hard palate. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1688-E1694, 2016.

Influence of extracapsular nodal spread extent on prognosis of oral squamous cell carcinoma.

BACKGROUND: An objective definition of clinically relevant extracapsular nodal spread (ECS) in head and neck squamous cell carcinoma (SCC) is unavailable. METHODS: Pathologic review of 245 pathologically positive oral cavity SCC neck dissection specimens was performed. The presence/absence of ECS, its extent (in millimeters), and multiple nodal and primary tumor risk factors were related to disease-specific survival (DSS) at a follow-up of 73 months. RESULTS: ECS was detected in 109 patients (44%). DSS was significantly better for patients without ECS than patients with ECS. Time-dependent receiver operator curve (ROC) analysis identified a prognostic cutoff for ECS extent at 1.7 mm. In multivariate analyses, DSS was significantly lower for patients with major ECS compared with patients with minor ECS, but not significantly different between patients with minor ECS and patients without ECS. CONCLUSION: ECS is clinically relevant in oral cavity SCC when it has extended more than 1.7 mm beyond the nodal capsule. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1192-E1199, 2016.

Individualized Risk Estimation for Postoperative Complications After Surgery for Oral Cavity Cancer.

IMPORTANCE: Postoperative complications after head and neck surgery carry the potential for significant morbidity. Estimating the risk of complications in an individual patient is challenging. OBJECTIVE: To develop a statistical tool capable of predicting an individual patient's risk of developing a major complication after surgery for oral cavity squamous cell carcinoma. DESIGN, SETTING, AND PARTICIPANTS: Retrospective case series derived from an institutional clinical oncologic database, augmented by medical record abstraction, at an academic tertiary care cancer center. Participants were 506 previously untreated adult patients with biopsy-proven oral cavity squamous cell carcinoma who underwent surgery between January 1, 2007, and December 31, 2012. MAIN OUTCOMES AND MEASURES: The primary end point was a major postoperative complication requiring invasive intervention (Clavien-Dindo classification grades III-V). Patients treated between January 1, 2007, and December 31, 2008 (354 of 506 [70.0%]) comprised the modeling cohort and were used to develop a nomogram to predict the risk of developing the primary end point. Univariable analysis and correlation analysis were used to prescreen 36 potential predictors for incorporation in the subsequent multivariable logistic regression analysis. The variables with the highest predictive value were identified with the step-down model reduction method and included in the nomogram. Patients treated between January 1, 2007, and December 31, 2008 (152 of 506 [30.0%]) were used to validate the nomogram. RESULTS: Clinical characteristics were similar between the 2 cohorts for most comparisons. Thirty-six patients in the modeling cohort (10.2%) and 16 patients in the validation cohort (10.5%) developed a major postoperative complication. The 6 preoperative variables with the highest individual predictive value were incorporated within the nomogram, including body mass index, comorbidity status, preoperative white blood cell count, preoperative hematocrit, planned neck dissection, and planned tracheotomy. The nomogram predicted a major complication with a validated concordance index of 0.79. Inclusion of surgical operative variables in the nomogram maintained predictive accuracy (concordance index, 0.77). CONCLUSIONS AND RELEVANCE: A statistical tool was developed that accurately estimates an individual patient's risk of developing a major complication after surgery for oral cavity squamous cell carcinoma.

Cancer of the oral cavity.

Cancer of the oral cavity is one of the most common malignancies worldwide. Although early diagnosis is relatively easy, presentation with advanced disease is not uncommon. The standard of care is primary surgical resection with or without postoperative adjuvant therapy. Improvements in surgical techniques combined with the routine use of postoperative radiation or chemoradiation therapy have resulted in improved survival. Successful treatment is predicated on multidisciplinary treatment strategies to maximize oncologic control and minimize impact of therapy on form and function. Prevention of oral cancer requires better education about lifestyle-related risk factors, and improved awareness and tools for early diagnosis.

Accuracy of administrative and clinical registry data in reporting postoperative complications after surgery for oral cavity squamous cell carcinoma.

BACKGROUND: The purpose of this study was to describe and compare how postoperative complications after oral cavity squamous cell carcinoma (SCC) surgery are reported in medical records, institutional billing claims, and national clinical registries. METHODS: The medical records of 355 previously untreated patients who underwent surgery for oral cavity SCC at our institution were retrospectively reviewed for postoperative complications. Information was compared with claims and National Surgical Quality Improvement Program (NSQIP) data. RESULTS: We identified 219 patients (62%) experiencing 544 complications (10% major). Billing claims identified 29% of these patients, 36% of overall complications, and 98% of major complications. Of overlapping patients, NSQIP identified 27% of patients, 33% of overall complications, and 100% of major complications noted on chart abstraction. CONCLUSION: The incidence of minor postoperative complications after oral cavity SCC surgery is relatively high. Both claims data and NSQIP accurately recorded major complications, but were suboptimal compared to chart abstraction in capturing minor complications.

Nomograms for preoperative prediction of prognosis in patients with oral cavity squamous cell carcinoma.

BACKGROUND: This study sought to develop prognostic tools that will accurately predict overall and cancer-related mortality and risk of recurrence in individual patients with oral cancer based on host and tumor characteristics. These tools would take into account numerous prognosticators beyond those covered by the traditional TNM (tumor-node-metastasis) staging system. METHODS: Demographic, host, and tumor characteristics of 1617 patients with cancer of the oral cavity, who were treated primarily with surgery at a single-institution tertiary care cancer center between 1985 and 2009, were reviewed from a preexisting database. Recurrent disease was recorded in 509 patients (456 locoregional and 116 distant); 328 patients died of cancer-related causes, and 542 died of other causes. The median follow-up was 42 months (range, 1-300 months). The following variables were analyzed as predictors of prognosis: age, sex, race, alcohol and tobacco use, oral cavity subsite, invasion of other structures, comorbidity, tumor size, and clinical nodal status. The stepdown method was used to select the statistically most influential predictors for inclusion in the final nomogram for each outcome of interest. RESULTS: The most influential predictors of both recurrence and cancer-specific mortality probability (CSMP) were tumor size, nodal status, subsite, and bone invasion. Nomograms were generated for prediction of overall survival (OS), CSMP, and locoregional recurrence-free probability (LRRFP). The nomograms were internally validated with an overfit-corrected predictive discrimination metric (concordance index) for OS of 67%, CSMP of 66%, and LRRFP of 60%. CONCLUSIONS: Nomograms have been developed that can reasonably estimate OS, CSMP, and LRRFP based on specific tumor and host characteristics in patients with oral cancer.

A novel tumor: specimen index for assessing adequacy of resection in early stage oral tongue cancer.

PURPOSE: Surgical margin status frequently affects decisions regarding adjuvant treatment; however, reporting and interpretation of surgical margins is subject to considerable subjectivity because of many factors including the adequacy of resection. We developed a novel measure of the adequacy of surgical resection, the tumor: specimen index (TSI), and tested its utility at predicting clinical outcomes in a retrospective cohort study. PATIENTS AND METHODS: An institutional database was queried to identify previously untreated patients with T1 and T2 oral tongue cancer who underwent surgery during 1985-2009 (n=433). The TSI, a geometric mean representing the percentage of the surgical specimen that is occupied by the tumor in average single dimension, was calculated from the largest measured lengths, widths, and heights of the tumor in relation to the entire surgical specimen. Multivariate analyses of locoregional recurrence-free probability (LRRFP) and disease-specific survival (DSS) were performed with commonly accepted prognosticators in addition to TSI and surgical margins status. RESULTS: The mean TSI was 41 (range 11-90; SD 14). Surgical margin status was associated with TSI; margins were negative in 84% of patients with TSI<45 and in 63% of patients with TSI⩾45 (p<0.001). TSI⩾45 was associated with worse LRRFP (57% vs. 76%, p<0.001) and worse DSS (68% vs. 85%, p<0.001). In a multivariate analysis that did not include TSI, surgical margin status independently predicted LRRFP (p=0.014) but not DSS. When TSI was included, only TSI, and not surgical margin status, was an independent predictor of both LRRFP (p=0.002) and DSS (p=0.011). CONCLUSION: The tumor: specimen index is an easily-calculated metric for estimating the adequacy of 3-dimensional resection in T1 and T2 oral tongue cancer that independently predicts oncologic outcomes.