Diagnostic accuracy of intraoperative margin assessment techniques in surgery for head and neck squamous cell carcinoma: A meta-analysis.

BACKGROUND: Positive margins following head and neck squamous cell carcinoma (HNSCC) surgery lead to significant morbidity and mortality. Existing Intraoperative Margin Assessment (IMA) techniques are not widely used due to limitations in sampling technique, time constraints and resource requirements. We performed a meta-analysis of the diagnostic performance of existing IMA techniques in HNSCC, providing a benchmark against which emerging techniques may be judged. METHODS: The study was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. Studies were included if they reported diagnostic metrics of techniques used during HNSCC surgery, compared with permanent histopathology. Screening, manuscript review and data extraction was performed by multiple independent observers. Pooled sensitivity and specificity were estimated using the bivariate random effects model. RESULTS: From an initial 2344 references, 35 studies were included for meta-analysis. Sensitivity (Sens), specificity (Spec), diagnostic odds ratio (DOR) and area under the receiver operating characteristic curve (AUROC) were calculated for each group (n, Sens, Spec, DOR, AUROC): frozen section = 13, 0.798, 0.991, 309.8, 0.976; tumour-targeted fluorescence (TTF) = 5, 0.957, 0.827, 66.4, 0.944; optical techniques = 10, 0.919, 0.855, 58.9, 0.925; touch imprint cytology = 3, 0.925, 0.988, 51.1, 0.919; topical staining = 4, 0.918, 0.759, 16.4, 0.833. CONCLUSIONS: Frozen section and TTF had the best diagnostic performance. Frozen section is limited by sampling error. TTF shows promise but involves administration of a systemic agent. Neither is currently in widespread clinical use. Emerging techniques must demonstrate competitive diagnostic accuracy whilst allowing rapid, reliable, cost-effective results.

Association of Intraoperative Frozen Section Controls With Improved Margin Assessment During Transoral Robotic Surgery for Human Papillomavirus-Positive Oropharyngeal Squamous Cell Carcinoma.

Importance: Intraoperative margin assessment is an important technique for ensuring complete tumor resection in malignant cancers. However, in patients undergoing transoral robotic surgery (TORS) for oropharyngeal carcinomas, tissue artifact may provide pathologic uncertainty. Objective: To assess the benefit of providing frozen section control samples ("positive tumor biopsies") for use during intraoperative margin assessment for patients undergoing TORS for human papillomavirus (HPV)-16-positive oropharyngeal squamous cell carcinoma (OPSCC). Design, Setting, and Participants: In this cohort study, patients receiving curative-intent TORS for biopsy-proven HPV-16-positive OPSCC performed by a single attending surgeon (A.H.M.) at Ronald Reagan UCLA Medical Center from 2017 to 2021 were included in a retrospective data analysis. Exclusion criteria included HPV-negative status, participation in clinical trials, and tumors of unknown primary origin. Main Outcomes and Measures: Survival outcomes investigated included overall and disease-free survival. Adverse pathologic outcomes measured included occurrence of nondiagnostic margins and margin reversal from frozen to fixed pathology. Results: Of the 170 patients included (mean [SD] age, 61.8 [9.9] years; 140 [82%] male), 50% of patients (n = 85) received a frozen section control. Use of a frozen section control was associated with statistically significantly improved sensitivity of intraoperative margin assessment, from 82.8% to 88.9% (difference, 6.1%; 95% CI, 3.9%-8.3%). Eleven percent (n = 18) of all tumors evaluated exhibited at least 1 nondiagnostic intraoperative margin, and 11% (n = 18) experienced margin reversal from frozen to fixed pathology. In patients with nondiagnostic margins, use of frozen section controls was associated with statistically significantly reduced time spent in the operating room (Cohen d, 1.14; 95% CI, 0.12-2.14). Conclusions and Relevance: In this cohort study, frozen intraoperative margins assessed during TORS resections of HPV-16-positive OPSCC were diagnostically challenging. Adverse pathologic outcomes, such as margin status reversal from positive on frozen pathology to negative on formal analysis, were common. Providing intraoperative frozen section control biopsies may offer clarity in cases with nondiagnostic margins, reducing the need for additional sampling and time spent in the operating room.

The impact of socioeconomic and geographic factors on access to transoral robotic/endoscopic surgery for early stage oropharyngeal malignancy.

OBJECTIVE: To evaluate the role of social and geographic factors on the likelihood of receiving transoral robotic surgery (TORS) or non-robotic transoral endoscopic surgery treatment in early stage oropharyngeal squamous cell carcinoma (OPSCC). MATERIALS AND METHODS: The National Cancer Database was queried to form a cohort of patients with T1-T2 N0-N1 M0 OPSCC (AJCC v.7) who underwent treatment from 2010 to 2016. Demographics, tumor characteristics, treatment type, social, and geographic factors were all collected. Univariate analysis and multivariate logistic regression were then performed. RESULTS: Among 9267 identified patients, 1774 (19.1%) received transoral robotic surgery (TORS), 1191 (12.9%) received transoral endoscopic surgery, and 6302 (68%) received radiation therapy. We found that lower cancer stage, lower comorbidity burden and HPV- positive status predicted a statistically significant increased likelihood of receiving surgery. Patients who reside in suburban or small urban areas (>1 million population), were low-to- middle income, or rely on Medicaid were less likely to receive surgery. Patients that reside in Medicaid-expansion states were more likely to receive TORS (p > .0001). Patients that reside in states that expanded Medicaid January 2014 and after were more likely to receive non-robotic transoral endoscopic surgery (p > .0001). CONCLUSIONS: Poorer baseline health, lower socioeconomic status and residence in small urban areas may act as barriers to accessing minimally invasive transoral surgery while residence in a Medicaid-expansion state may improve access. Barriers to accessing robotic surgery may be greater than accessing non-robotic surgery.

A closer look at 30 day hospital readmissions after head and neck cancer surgery.

PURPOSE: 30-day hospital readmissions after head and neck cancer surgery continue to be a significant source of patient harm and healthcare expenditure. While there is substantial data in the literature assessing predictive factors for readmissions after head and neck cancer surgery, there are a paucity of studies which attempt to understand if such readmissions are preventable. The goal of this paper is to determine factors associated with 30-day hospital readmissions after head and neck cancer surgery and to understand if these readmissions were preventable. MATERIALS AND METHODS: Retrospective review from a single academic tertiary care center. Patients readmitted within 30 days after undergoing surgery for cancers of the head and neck between 2015 and 2018 were identified. RESULTS: Over a 3-year period, 26 patients undergoing resection with or without reconstruction of head and neck cancers were readmitted to the hospital within 30 days of discharge. There were 15 (58%) men and 11 (42%) women with a mean age of 68 years (SD 14 years). Twenty-one (81%) patients had squamous cell carcinoma and 13 (50%) had a primary site in the oral cavity. Thirteen (50%) had undergone free or regional flap reconstruction. The indication for readmission was related to the surgical wound in 19 (73%) and to medical complications in 7 (27%). Each case was categorized as "possibly preventable" versus "uncertain if preventable" based on whether a reasonable and feasible change in management may have prevented readmission. Six (23%) readmissions were deemed possibly preventable. Four were related to the surgical wound where initial free or regional flaps may have prevented complication. Two were medical complications that may have benefited from longer inpatient observation. CONCLUSIONS: For a subset of patients readmitted within 30 days of head and neck cancer surgery, a reasonable and feasible change in management may have prevented their hospital readmission. The significance of better understanding this patient population is underscored by the high mortality rate.

Cortactin expression assessment improves patient selection for a watchful waiting strategy in pT1cN0-staged oral squamous cell carcinomas with a tumor infiltration depth below 4 mm.

BACKGROUND: In this feasibility study we aimed to evaluate the value of previously reported molecular tumor biomarkers associated with lymph node metastasis in oral squamous cell carcinoma (OSCC) to optimize neck strategy selection criteria. METHODS: The association between expression of cortactin, cyclin D1, FADD, RAB25, and S100A9 and sentinel lymph node status was evaluated in a series of 87 (cT1-2N0) patients with OSCC treated with primary resection and SLNB procedure. RESULTS: Tumor infiltration depth and tumor pattern of invasion were independent prognostic markers for SLN status, while none of the tumor makers showed a better prognostic value to replace SLNB as neck staging technique in the total cohort. However, in the subgroup of patients with pT1N0 OSCC, cortactin expression (OR 16.0, 95%CI 2.0-127.9) was associated with SLN classification. CONCLUSIONS: Expression of cortactin is a promising immunohistochemical tumor marker to identify patients at low risk that may not benefit from SLNB or END.

A Standardized Framework for Fluorescence-Guided Margin Assessment for Head and Neck Cancer Using a Tumor Acidosis Sensitive Optical Imaging Agent.

PURPOSE: Intra-operative management of the surgical margin in patients diagnosed with head and neck squamous cell carcinoma (HNSCC) remains challenging as surgeons still have to rely on visual and tactile information. Fluorescence-guided surgery using tumor-specific imaging agents can assist in clinical decision-making. However, a standardized imaging methodology is lacking. In this study, we determined whether a standardized, specimen-driven, fluorescence imaging framework using ONM-100 could assist in clinical decision-making during surgery. PROCEDURES: Thirteen patients with histologically proven HNSCC were included in this clinical study and received ONM-100 24 ± 8 h before surgery. Fluorescence images of the excised surgical specimen and of the surgical cavity were analyzed. A fluorescent lesion with a tumor-to-background ratio (TBR) > 1.5 was considered fluorescence-positive and correlated to standard of care (SOC) histopathology. RESULTS: All six tumor-positive surgical margins were detected immediately after excision using fluorescence-guided intra-operative imaging. Postoperative analysis showed a median TBR (±IQR) of the fluorescent lesions on the resection margin of 3.36 ± 1.62. Three fluorescence-positive lesions in the surgical cavity were biopsied and showed occult carcinoma and severe dysplasia, and a false-positive fluorescence lesion. CONCLUSION: Our specimen-driven fluorescence framework using a novel, pH-activatable, fluorescent imaging agent could assist in reliable and real-time adequate clinical decision-making showing that a fluorescent lesion on the surgical specimen with a TBR of 1.5 is correlated to a tumor-positive resection margin. The binary mechanism of ONM-100 allows for a sharp tumor delineation in all patients, giving the surgeon a clinical tool for real-time margin assessment, with a high sensitivity.

High rates of postoperative radiotherapy delay in head and neck cancer before and after Medicaid expansion.

BACKGROUND: The objective is to study the effect of Medicaid expansion on postoperative radiation therapy (PORT) delay in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: Patients from the National Cancer Database with HNSCC undergoing curative-intent surgery in the 2 years before and after Medicaid expansion were analyzed (n = 11 717) using the difference-in-differences technique to study the effect on PORT delay. RESULTS: The rate of PORT delay before and after expansion was 66.0% and 66.9%, respectively. Medicaid patients had more frequent PORT delay than privately insured patients (pre-expansion 77.2% vs. 59.4%, p < 0.001; post-expansion 76.5% vs. 60.9%, p < 0.001). Medicaid expansion had no effect on PORT delay [hazard ratio 0.95, 95% confidence interval 0.81-1.12]. Supplemental analyses revealed that pathologic stage, number of treating facilities, and comorbidities were among several factors associated with PORT delay in the cohort. CONCLUSION: PORT delay is unacceptably frequent. Improvement in timely adjuvant therapy requires more than Medicaid expansion.

Intraoperative free margins assessment of oropharyngeal squamous cell carcinoma with confocal laser endomicroscopy: a pilot study.

PURPOSE: This pilot study aimed to assess the feasibility of intraoperative assessment of safe margins with confocal laser endomicroscopy (CLE) during oropharyngeal squamous cell carcinoma (OPSCC) surgery. METHODS: We included five consecutive patients confirmed OPSCC and planned tumor resection in September and October 2020. Healthy appearing mucosa in the marginal zone, and the tumor margin, were examined with CLE and biopsy during tumor resection. A total of 12,809 CLE frames were correlated with the gold standard of hematoxylin and eosin staining. Three head and neck surgeons and one pathologist were asked to identify carcinoma in a sample of 169 representative images, blinded to the histological results. RESULTS: Healthy mucosa showed epithelium with uniform size and shape with distinct cytoplasmic membranes and regular vessel architecture. CLE optical biopsy of OPSCC demonstrated a disorganized arrangement of variable cellular morphology. We calculated an accuracy, sensitivity, specificity, PPV, and NPV of 86%, 90%, 79%, 88%, and 82%, respectively, with inter-rater reliability and κ-value of 0.60. CONCLUSION: CLE can be easily integrated into the intraoperative setting, generate real-time, in-vivo microscopic images of the oropharynx for evaluation and demarcation of cancer. It can eventually contribute to a less radical approach by enabling a more precise evaluation of the cancer margin.

Feasibility of intraoperative assessment of safe surgical margins during laryngectomy with confocal laser endomicroscopy: A pilot study.

OBJECTIVE: This pilot study aimed to assess the feasibility of intraoperative assessment of safe margins with Confocal Laser Endomicroscopy (CLE) during planned partial or total laryngectomy. METHODS: Eight patients with confirmed larynx squamous cell carcinoma (SCC) and planned partial or total laryngectomy were included in this study in March 2020. Two head and neck surgeons and one pathologist were asked to classify carcinoma or healthy epithelium in a sample of 94 representative sequences (5.640 images), blinded to the histological results (H&E staining). RESULTS: Healthy mucosa areas showed epithelium with cells of uniform size and shape with distinct cytoplasmic membranes and regular vessel architecture. CLE optical biopsy of SCC demonstrated a disorganized arrangement of variable cellular morphology. We calculated an accuracy, sensitivity, specificity, PPV, and NPV of 80.1%, 72.3%, 87.9%, 85.7%, and 76.1%, respectively. A distinct transition between healthy appearing tissue and suspicious lesions could also be detected. CONCLUSION: CLE can be easily integrated into the intraoperative setting, generate real-time, in-vivo microscopic images of the larynx for evaluation and demarcation of cancer. If validated in further studies, CLE could eventually contribute to a less radical approach by enabling a more precise evaluation of the cancer margin.

Intraoral ultrasonography in the assessment of DOI in oral cavity squamous cell carcinoma: a comparison with magnetic resonance and histopathology.

OBJECTIVE: The first-line therapeutic approach for oral cavity squamous cell carcinoma (OCSCC) is complete surgical resection. Preoperative assessment of depth of invasion (cDOI) is crucial to plan the surgery. Magnetic resonance (MR) and intraoral ultrasonography (IOUS) have been shown to be useful tools for assessment of DOI. The present analysis investigates the accuracy of MR and IOUS in evaluating DOI in OCSCC compared to histological evaluation (pDOI). MATERIALS AND METHODS: Forty-nine previously untreated patients with cT1-T3 OCSCC were reviewed. Nine patients were staged with MR alone, 10 with IOUS alone, and 30 with both MR and IOUS. RESULTS: Mean difference between cDOIMR and pDOI values of 0.2 mm (95% CI - 1.0-1.3 mm) and between cDOIIOUS and pDOI of 0.3 mm (95% CI - 1.0-1.6 mm). Spearman R between cDOIMR and pDOI was R = 0.83 and between cDOIIOUS and pDOI was R = 0.76. Both radiological techniques showed high performance for the correct identification, with the optimum cut-off of 5 mm, of patients with a pDOI ≥ 4 mm and amenable to a neck dissection, with an AUC of 0.92 and 0.82 for MR and IOUS, respectively. CONCLUSION: Both examinations were valid approaches for preoperative determination of DOI in OCSCC, although with different cost-effectiveness profiles and indications.

Intraoperative Radiographic Assessment of Bone Resection Margins During Mandibulectomy: A Case Series.

BACKGROUND AND PURPOSE: Mandibulectomy remains the treatment of choice for oral cavity squamous cell carcinoma with infiltration of bone and for benign tumors with full mandibular thickness involvement. Although bone resection margins are critical for patient outcomes, intraoperative immediate bone margins assessment is inadequate, and few alternative options have been described. The purpose of this study was to describe the use of an existing intraoperative radiographic system for objective determination of bone resection margins during mandibulectomy. METHODS: We conducted a retrospective case series of all patients at the Greater Baltimore Medical Center who underwent mandibulectomy and received intraoperative Faxitron radiography from January 1, 2016, to March 1, 2019. Patient characteristics including age, sex, diagnosis, tumor location, clinical and pathologic stage, procedure performed, and bone resection margins were reviewed. RESULTS: A total of 10 patients underwent mandibulectomy with intraoperative radiography. Nine (90%) received surgery for squamous cell carcinoma, with 1 (10%) for ameloblastoma. Out of those with squamous cell carcinoma, tumor location varied, and all were clinically stage T4. Final pathologic margins were negative in all cases (10/10), though in 2 cases, close margins were assessed intraoperatively, leading to further resection or change in operative plan. CONCLUSION: Intraoperative radiographic assessment of bone resection margins is a promising technique, though further validation is required.

Comparative cost analysis between definitive radiotherapy and transoral surgery for oropharyngeal squamous cell carcinoma: A SEER-Medicare analysis.

INTRODUCTION: Primary radiotherapy (RT) and transoral surgery (TOS) are effective local therapy treatments for oropharyngeal squamous cell carcinoma (OPSCC), but their cost profiles differ. We compared the one-year costs of these competing treatments using a large claims-based database. METHODS: Eligible individuals were patients in the SEER-Medicare registry diagnosed with OPSCC between 2000 and 2011. Patients were categorized as receiving either primary RT +/- chemotherapy, or TOS +/- adjuvant RT or chemoradiotherapy (CRT), and all treatment costs from 1 month prior to diagnosis to 1 year after diagnosis were calculated. Univariable and multivariable linear regression models were used to determine predictors of payer expenditure. Patient-borne pharmacy costs were also analyzed. RESULTS: The cohort included 3497 patients (73% RT, 27% TOS), of whom 73% were locally advanced. The mean total 13 month costs for RT alone, CRT, TOS alone, TOS + RT and TOS + CRT were $39,083, $63,537, $25,468, $36,592, and $99,919, respectively, for early-stage patients. For locally advanced individuals, the mean costs were $45,049, $68,099, $40,626, $53,729, and $71,397, respectively. On multivariable analysis, the adjusted increase in total costs versus RT alone were $21,844, -$5431, $7984, and $28,581 for CRT, TOS alone, TOS + RT, and TOS + CRT, respectively. The difference between CRT and TOS + RT became non-significant for TOS patients undergoing transoral surgery plus neck dissection. Cisplatin was associated with significant less cost than cetuximab and taxane-based chemotherapy. CONCLUSION: In this population of elderly patients, transoral surgery was generally associated with less expensive treatment, with the addition of chemotherapy serving as the main driver of increased cost.

Assessment of metastatic lymph nodes in head and neck squamous cell carcinomas using simultaneous 18F-FDG-PET and MRI.

In this study, we investigate the feasibility of using dynamic contrast enhanced magnetic resonance imaging (DCE-MRI), diffusion weighted imaging (DWI), and dynamic positron emission tomography (PET) for detection of metastatic lymph nodes in head and neck squamous cell carcinoma (HNSCC) cases. Twenty HNSCC patients scheduled for lymph node dissection underwent DCE-MRI, dynamic PET, and DWI using a PET-MR scanner within one week prior to their planned surgery. During surgery, resected nodes were labeled to identify their nodal levels and sent for routine clinical pathology evaluation. Quantitative parameters of metastatic and normal nodes were calculated from DCE-MRI (ve, vp, PS, Fp, Ktrans), DWI (ADC) and PET (Ki, K1, k2, k3) to assess if an individual or a combination of parameters can classify normal and metastatic lymph nodes accurately. There were 38 normal and 11 metastatic nodes covered by all three imaging methods and confirmed by pathology. 34% of all normal nodes had volumes greater than or equal to the smallest metastatic node while 4 normal nodes had SUV > 4.5. Among the MRI parameters, the median vp, Fp, PS, and Ktrans values of the metastatic lymph nodes were significantly lower (p = <0.05) than those of normal nodes. ve and ADC did not show any statistical significance. For the dynamic PET parameters, the metastatic nodes had significantly higher k3 (p value = 8.8 × 10-8) and Ki (p value = 5.3 × 10-8) than normal nodes. K1 and k2 did not show any statistically significant difference. Ki had the best separation with accuracy = 0.96 (sensitivity = 1, specificity = 0.95) using a cutoff of Ki = 5.3 × 10-3 mL/cm3/min, while k3 and volume had accuracy of 0.94 (sensitivity = 0.82, specificity = 0.97) and 0.90 (sensitivity = 0.64, specificity = 0.97) respectively. 100% accuracy can be achieved using a multivariate logistic regression model of MRI parameters after thresholding the data with Ki < 5.3 × 10-3 mL/cm3/min. The results of this preliminary study suggest that quantitative MRI may provide additional value in distinguishing metastatic nodes, particularly among small nodes, when used together with FDG-PET.

An Update on Surgical Margins in the Head Neck Squamous Cell Carcinoma: Assessment, Clinical Outcome, and Future Directions.

PURPOSE OF REVIEW: Failure to achieve tumor-free margins is the single largest cause of death for head neck cancer patients. At the same time, it is the only factor that is in complete control of the surgeon. This review summarizes evidence for the definition, clinical implications, and methods to achieve optimal margins. RECENT FINDINGS: The previous universally followed definition of adequate margin (5 mm in final histopathology) has been disputed. Various biological, optical, and imaging adjuncts can aid in achieving optimal margins. Extent of resection and margins in human papilloma virus (HPV)-positive oropharyngeal cancers and following induction chemotherapy remain controversial. Though practiced widely, frozen section-guided margin revision has not conclusively shown improved local control rates. The role of molecular assessment of margins is promising but not established. The definition of adequate margin differs according to the site in the head neck region. Currently, the 5-mm margin at final histopathology is the most commonly accepted definition of an "adequate" margin.

Revisiting a rare disease: Oral cavity basaloid squamous cell carcinoma at a high-volume tertiary center.

OBJECTIVES: Rare diseases are often poorly understood, and this study sought to investigate the incidence of a rare disease entity, basaloid squamous cell carcinoma (BSCC) of the oral cavity (OC) at a tertiary care medical center and to assess its clinical outcomes. METHODS: The aim of this study was to collect data in order to better understand how this rare disease progresses. This was a case series of patients with OC BSCC diagnosed between 2001 and 2018. RESULTS: 10 patients with primary OC BSCC were identified. Average age at diagnosis was 58 years (33-71). The median follow-up period was 11 months. Primary sites included oral tongue (n = 4), floor of mouth (n = 4), hard palate (n = 1), and retromolar trigone (n = 1). A majority (60%) of patients had pathologic T3/T4 tumors. All patients underwent primary surgical treatment. There was an overall 60% mortality rate: 2 died from metastasis at 1- and 3-months postop, 2 from unknown causes, 1 from sepsis at 1 month postop, and 1 from metastatic colon cancer. Average survival for those patients who died was 20.7 months. 4 patients were disease-free at the time of publication. CONCLUSION: There are few studies in the literature that seek to investigate cases of OC BSCC from a single institution. This is the first detailed case series of BSCC from a single American institution. Survival outcomes in our cohort were poor but demonstrate a variable course of disease burden. This study presents unique information regarding specific pathologic characteristics and patient outcomes for this rare disease.

Weighted lymph node ratio: New tool in the assessment of postoperative staging of the neck dissection in HPV-negative head and neck squamous cell carcinoma patients.

BACKGOUND: The objective of this study is to assess a new parameter, the weighted lymph node ratio (WLNR), which incorporates prognostic information regarding the number of metastatic nodes with extracapsular spread and the lymph node yield for pN0 patients to the lymph node ratio. METHODS: We studied retrospectively 1118 patients with head and neck squamous cell carcinoma (HNSCC) treated with a neck dissection. RESULTS: We obtained a classification with four categories based on the WLNR values. WLNR classification had a higher prognostic discrimination capacity and a more homogeneous distribution in the number of patients included in each of the categories than the pTNM classification. CONCLUSION: The WLNR improved the predictive capacity of the eighth edition of the pTNM classification and it can be a useful tool in the assessment of the postoperative staging of the neck dissections in HNSCC patients.

Intraoperative Margin Assessment in Head and Neck Cancer: A Case of Misuse and Abuse?

Surgical removal with negative margins is the preferred management of oral squamous cell carcinomas. This review summarizes statements by professional organizations and data supporting the specimen-driven approach to margin assessment. Practical aspects of the intraoperative margin assessment, as guided by gross examination, are presented. The most cost- and time-efficient method of intraoperative margin assessment depends on desired margin clearance and likelihood of other adverse histologic factors, such as extranodal extension, perineural invasion, which are likelier in advanced carcinomas. Intraoperative surgeon-pathologist communication can be improved by reporting to surgical team gross distances to all or selected closest margins, before choosing margins for microscopic frozen examination. Case specific mitigation strategies to minimize the negative impact of tumor-bed driven margin assessment or of suboptimal margin revision are proposed. Based on size, shape, histology, size of carcinoma at the margin, and orientation of the additional tissue, margin revision may be judged as adequate (conversion of a positive margin into a negative one), inadequate (positive margin remains positive), or indeterminate. The significance of anatomic subsite based labeling, radial margin sampling from the main resection specimen, and the relationship between the distance to closest margin and local control are highlighted. The modern definition of safe margin would account for other parameters, such as perineural invasion. An updated approach to resolution of frozen versus permanent sampling issues is outlined. Future studies are needed to design and validate risk models that would help to determine for individual patient what represents a safe margin and how to judge the quality of margin revision.

Defining secure surgical bone margins in head and neck squamous cell carcinomas: The diagnostic impact of intraoperative cytological assessment of bone resection margins compared with preoperative imaging.

BACKGROUND: Imaging provides crucial staging information for treatment planning of head and neck squamous cell carcinomas (HNSCCs). Despite technical progress in imaging techniques, defining the extent of bone involvement preoperatively remains challenging and requires intraoperative information to control for adequate resection. The intraoperative cytological assessment of the bone resection margins (ICAB) provides information whether bone is infiltrated by carcinoma. The aim of this study was to assess the diagnostic value of preoperative imaging compared with ICAB in order to achieve carcinoma-free bone margins. MATERIALS AND METHODS: 108 HNSCC patients underwent preoperative computed tomography (CT), magnetic resonance imaging (MRI) and orthopantomogram (OPG) for staging and surgical planning. Curative resection was planned based on imaging. Intraoperatively, the resection margins were controlled by ICAB. The diagnostic value of preoperative imaging and ICAB was assessed with reference to the histological findings. RESULTS: CT showed a sensitivity of 89.7%, specificity of 63.0%, positive predictive value (PPV) of 85.9%, and negative predictive value (NPV) of 70.8%. MRI revealed a sensitivity of 45.5%, specificity of 66.7%, PPV of 71.4% and NPV of 40.0%. OPG-imaging had a sensitivity of 64.7%, specificity of 76.2%, PPV of 81.5%, NPV 57.1%. In comparison, ICAB provided a sensitivity of 78.6%, specificity of 95.7%, PPV 73.3%, and NPV 96.7%. The accuracy was 82.1%, 52.9%, 69.0%, and 93.5% for CT, MRI, OPG, and ICAB, respectively. CONCLUSION: Preoperative imaging lacks accuracy in defining adequate bone resection margins, compared with ICAB. ICAB supports preoperative imaging and intraoperative frozen sections to improve bone margin control.

Probe-based fluorescence dosimetry of an antibody-dye conjugate to identify head and neck cancer as a first step to fluorescence-guided tissue preselection for pathological assessment.

BACKGROUND: Despite the rapid growth of fluorescence imaging, accurate sampling of tissue sections remains challenging. Development of novel technologies to improve intraoperative assessment of tissue is needed. METHODS: A novel contact probe-based fluorescence dosimeter device, optimized for IRDye800CW quantification, was developed. After evaluation of the device in a phantom setup, its clinical value was defined ex vivo in patients with head and neck squamous cell carcinoma who received panitumumab-IRDye800CW. RESULTS: Ten patients were enrolled with a total of 216 data points obtained. Final histopathology showed tumor in 119 spots and normal tissue in 97 spots. Fluorescence-to-excitation ratios in tumor tissue were more than three times higher than those in normal tissue. The area under the curve was 0.86 (95% CI: 0.81-0.91) for tumor detection. CONCLUSIONS: Fluorescence-guided tissue preselection using a fluorescence dosimeter could have substantial impact on tissue sampling for frozen section analysis and potentially reduce sampling errors.