Interdisciplinary plastic and reconstructive surgery of head and neck squamous cell carcinomas. / Interdisziplinäre Plastische und Rekonstruktive Chirurgie von Plattenepithelkarzinomen des Kopf-Hals-Bereichs.

Squamous cell carcinomas are the most common malignancies in the oral cavity, pharynx, and larynx. Even in the age of the most modern drug treatment methods, radical resection of these tumors is and currently remains the therapeutic gold standard. The loss of anatomical structures associated with surgery inevitably increases the functional deficits caused by the tumor itself. In this context, the extent of functional deficits is largely determined by the extent of resection. Complete organ resections, such as glossectomy, complete palate resection, laryngectomy, or transverse pharyngo-laryngectomy, lead to severe functional deficits, such as swallowing disturbances with life-threatening aspiration and articulation disorders up to the inability to speak. With the help of plastic reconstructive surgery, the lost tissue can be replaced and the specific functions of the upper aerodigestive tract can be preserved or restored.In recent decades, reconstructive surgical procedures have developed enormously in the treatment of malignant tumors of the head and neck. In order to make optimal use of them, a comprehensive, interdisciplinary therapy concept is a prerequisite for positive oncological and functional outcome. In addition to general medical and social parameters, surgical parameters play a crucial role in the choice of the reconstruction method. The extent to which the surgical measures must be interdisciplinary depends on the localization of the defects in the head and neck region and on the type of replacement tissue required. Here, the expertise of plastic surgery, oral and maxillofacial surgery, and abdominal surgery comes into play in particular. The use of different tissues, the combination of different grafts and flaps, or the preforming of donor regions allow reconstructions far beyond the level of simply restoring surface integrity. The functional results and thus the quality of life of patients after surgical therapy of extensive tumors of the mentioned localizations depend decisively on the type of reconstruction. Therefore, in the following review, special emphasis 1 be placed on the choice of reconstruction method and reconstruction technique for tissue loss after resections of HNSCC.

Preoperative Circulating Tumor HPV DNA and Oropharyngeal Squamous Cell Disease.

Importance: The utility of preoperative circulating tumor tissue-modified viral human papillomavirus DNA (TTMV-HPV DNA) levels in predicting human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (HPV+ OPSCC) disease burden is unknown. Objective: To determine if preoperative circulating tumor HPV DNA (ctHPVDNA) is associated with disease burden in patients with HPV+ OPSCC who have undergone transoral robotic surgery (TORS). Design, Setting, and Participants: This cross-sectional study comprised patients with HPV+ OPSCC who underwent primary TORS between September 2021 and April 2023 at one tertiary academic institution. Patients with treatment-naive HPV+ OPSCC (p16-positive) and preoperative ctHPVDNA levels were included, and those who underwent neck mass excision before ctHPVDNA collection were excluded. Main Outcomes and Measures: The main outcome was the association of increasing preoperative ctHPVDNA levels with tumor size and lymph node involvement in surgical pathology. The secondary outcome was the association between preoperative ctHPVDNA levels and adverse pathology, which included lymphovascular invasion, perineural invasion, or extranodal extension. Results: A total of 70 patients were included in the study (65 men [93%]; mean [SD] age, 61 [8] years). Baseline ctHPVDNA levels ranged from 0 fragments/milliliter of plasma (frag/mL) to 49 452 frag/mL (median [IQR], 272 [30-811] frag/mL). Overall, 58 patients (83%) had positive results for ctHPVDNA, 1 (1.4%) had indeterminate results, and 11 (15.6%) had negative results. The sensitivity of detectable ctHPVDNA for identifying patients with pathology-confirmed HPV+ OPSCC was 84%. Twenty-seven patients (39%) had pathologic tumor (pT) staging of pT0 or pT1, 34 (49%) had pT2 staging, and 9 patients (13%) had pT3 or pT4 staging. No clinically meaningful difference between detectable and undetectable preoperative ctHPVDNA cohorts was found for tumor size or adverse pathology. Although the median preoperative ctHPVDNA appeared to be higher in pT2 through pT4 stages and pN1 or pN2 stages, effect sizes were small (pT stage: η2, 0.002 [95% CI, -1.188 to 0.827]; pN stage: η2, 0.043 [95% CI, -0.188 to 2.600]). Median preoperative log(TTMV-HPV DNA) was higher in active smokers (8.79 [95% CI, 3.55-5.76]), compared with never smokers (5.92 [95% CI, -0.97 to 1.81]) and former smokers (4.99 [95% CI, 0.92-6.23]). Regression analysis did not show an association between tumor dimension or metastatic lymph node deposit size and preoperative log(TTMV-HPV DNA). After univariate analysis, no association was found between higher log(TTMV-HPV DNA) levels and adverse pathology. Conclusions and Relevance: In this cross-sectional study, preoperative ctHPVDNA levels were not associated with disease burden in patients with HPV+ OPSCC who underwent TORS.

Outcomes of transoral robotic surgery for early-stage oropharyngeal squamous cell carcinoma with low rates of adjuvant therapy: A consecutive single-institution study from 2013 to 2020.

INTRODUCTION: The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has increased in recent decades, driven by infection with human papillomavirus (HPV). Transoral robotic surgery (TORS) and neck dissection (ND) has been employed as an alternative to radiotherapy/chemoradiotherapy. The current literature is lacking studies providing an exhaustive overview of recurrence characteristics and long-term outcomes in TORS-treated OPSCC-patients. METHODS: All patients treated for OPSCC with primary TORS + ND in Eastern Denmark between 2013 and 2020 were included in the study. The aim was to explore overall survival (OS), recurrence-free survival (RFS), recurrence patterns, and ultimate failure rate (UFR). OS and RFS were examined using the Kaplan-Meier method. Cox proportional regression analyses were employed to examine effect of different variables on risk of death and recurrence. RESULTS: The study included 153 patients of which 88.9 % (n = 136) were treated with TORS alone while 11.1 % (n = 17) received adjuvant therapy. The 1-, 3-, and 5-year OS were 97.4 %, 94.1 %, and 87.6 % while 1-, 3-, and 5-year RFS were 96.6 %, 87.8 %, and 84.9 %. The UFR was 6.5 % in the cohort. Patients with HPV+/p16 + OPSCC had a significantly better 5-year OS of 92.3 % than patients with discordant or double-negative HPV/p16 status (OS = 73.3 %). No differences in outcomes between patients treated with or without adjuvant therapy were found in regression analysis. CONCLUSION: Excellent survival and disease control was obtained with TORS + ND in this cohort, despite lesser application of adjuvant therapy than other TORS-centers, implying that TORS without adjuvant therapy can be successfully applied in treatment of early-stage OPSCC.

Complications including dysphagia following transoral non-robotic surgery for pharyngeal and laryngeal squamous cell carcinoma: A retrospective multicenter study.

OBJECTIVE: Transoral surgery is a minimally invasive treatment but may cause severe dysphagia at a lower rate than chemoradiotherapy. METHODS: We compared clinical information, surgical complications, and swallowing function in patients who underwent transoral nonrobotic surgery for laryngo-pharyngeal squamous cell carcinoma between 2015 and 2021 in a multicenter retrospective study. RESULTS: Six hundred and forty patients were included. Postoperative bleeding was observed in 20 cases (3.1%), and the risk factor was advanced T category. Postoperative laryngeal edema was observed in 13 cases (2.0%), and the risk factors were prior radiotherapy, advanced T stage, and concurrent neck dissection in patients with resected HPC. Dysphagia requiring nutritional support was observed in 29 cases (4.5%) at 1 month postoperatively and in 19 cases (3.0%) at 1 year postoperatively, respectively. The risk factors for long-term dysphagia were prior radiotherapy and advanced T category. Short-term risk factors for dysphagia were prior radiotherapy, advanced T category, and concurrent neck dissection, while long-term risk factors for dysphagia were only prior radiotherapy and advanced T category. CONCLUSION: Prior radiotherapy, advanced T stage, and concurrent neck dissection increased the incidence of postoperative laryngeal edema and short-term dysphagia, but concurrent neck dissection did not affect long-term dysphagia. Such features should be considered when considering the indication for transoral surgery and postoperative management.

A diagnostic algorithm for sinonasal papillary non-keratinizing squamous cell carcinoma with DEK:: AFF2 fusion and mimickers / Algoritmo diagnóstico para carcinoma sinonasal papilar de células escamosas no queratinizante con fusión e imitadores de DEK:: AFF2

Sinonasal carcinomas represent a rare and diverse group of tumors, presenting diagnostic complexities due to their varied histological and molecular features. To ensure accurate differentiation among these malignancies, a systematic and stepwise approach is paramount. Even with the morphological similarities between poorly differentiated (non) keratinizing sinonasal squamous cell carcinoma (SNSCC) and DEK::AFF2 SNSCC, the two lesions are distinguishable using the surrogate immunohistochemical marker AFF2 or molecular testing for DEK::AFF2 mutation. We report a rare case of SMARCB1-retained DEK::AFF2 papillary non-keratinizing SNSCC in a 53-year-old female, who presented with a polypoid mass corresponding to the left middle turbinate. Following the surgical resection of the tumor and locoregional lymph nodes, adjuvant radiotherapy was administered to eradicate any residual cancer cells that may have remained after surgery. (AU)

Los carcinomas sinonasales representan un grupo diverso e infrecuente de tumores que presentan complejidades diagnósticas debidas a la variedad de sus características histológicas y moleculares. Para asegurar una diferenciación precisa entre estas neoplasias es esencial un enfoque sistemático paso a paso. Incluso con similitudes morfológicas entre carcinoma sinonasal escamoso pobremente diferenciado, no queratinizante (CSNE) y DEK::AFF2 se puede distinguir entre las lesiones con el uso del marcador inmunohistoquímico sustitutivo AFF2 o la mutación molecular DEK::AFF2. Comunicamos un raro caso de CSNE no queratinizante SMARCB1-retained DEK::AFF2 en una mujer de 53 años con una masa polipoide en pliegue turbinado medio izquierdo. Tras la resección quirúrgica del tumor y de los ganglios linfáticos, se administró radioterapia adyuvante para eliminar el tumor residual. (AU)

A diagnostic algorithm for sinonasal papillary non-keratinizing squamous cell carcinoma with DEK:: AFF2 fusion and mimickers / Algoritmo diagnóstico para carcinoma sinonasal papilar de células escamosas no queratinizante con fusión e imitadores de DEK:: AFF2

Sinonasal carcinomas represent a rare and diverse group of tumors, presenting diagnostic complexities due to their varied histological and molecular features. To ensure accurate differentiation among these malignancies, a systematic and stepwise approach is paramount. Even with the morphological similarities between poorly differentiated (non) keratinizing sinonasal squamous cell carcinoma (SNSCC) and DEK::AFF2 SNSCC, the two lesions are distinguishable using the surrogate immunohistochemical marker AFF2 or molecular testing for DEK::AFF2 mutation. We report a rare case of SMARCB1-retained DEK::AFF2 papillary non-keratinizing SNSCC in a 53-year-old female, who presented with a polypoid mass corresponding to the left middle turbinate. Following the surgical resection of the tumor and locoregional lymph nodes, adjuvant radiotherapy was administered to eradicate any residual cancer cells that may have remained after surgery. (AU)

Los carcinomas sinonasales representan un grupo diverso e infrecuente de tumores que presentan complejidades diagnósticas debidas a la variedad de sus características histológicas y moleculares. Para asegurar una diferenciación precisa entre estas neoplasias es esencial un enfoque sistemático paso a paso. Incluso con similitudes morfológicas entre carcinoma sinonasal escamoso pobremente diferenciado, no queratinizante (CSNE) y DEK::AFF2 se puede distinguir entre las lesiones con el uso del marcador inmunohistoquímico sustitutivo AFF2 o la mutación molecular DEK::AFF2. Comunicamos un raro caso de CSNE no queratinizante SMARCB1-retained DEK::AFF2 en una mujer de 53 años con una masa polipoide en pliegue turbinado medio izquierdo. Tras la resección quirúrgica del tumor y de los ganglios linfáticos, se administró radioterapia adyuvante para eliminar el tumor residual. (AU)

Development and validation of nomogram models for predicting postoperative prognosis of early-stage laryngeal squamous cell carcinoma.

BACKGROUND: We aimed to investigate the postoperative prognosis in patients with early-stage laryngeal squamous cell carcinoma (LSCC) in association with the preoperative blood markers and clinicopathological characteristics and to develop nomograms for individual risk prediction. METHODS: The clinical data of 353 patients with confirmed early-stage LSCC between 2009 and 2018 were retrospectively retrieved from the First Affiliated Hospital with Nanjing Medical University. All patients were randomly divided into the training and testing groups in a 7:3 ratio. Univariate and multivariate analyses were performed, followed by the construction of nomograms to predict recurrence-free survival (RFS) and overall survival (OS). Finally, the nomograms were verified internally, and the predictive capability of the nomograms was evaluated and compared with that of tumour T staging. RESULTS: Univariate and multivariate analyses identified platelet counts (PLT), fibrinogen (FIB), and platelet to lymphocyte ratio (PLR) were independent factors for RFS, and FIB, systemic immune-inflammation index (SII), and haemoglobin (HGB) were independent prognostic factors for OS. The nomograms showed higher predictive C-indexes than T staging. Furthermore, decision curve analysis (DCA) revealed that the net benefit of the nomograms' calculation model was superior to that of T staging. CONCLUSIONS: We established and validated nomograms to predict postoperative 1-, 3- and 5-year RFS and OS in patients with early-stage LSCC based on significant blood markers and clinicopathological characteristics. These models might help clinicians make personalized treatment decisions.

Prediction of lymph node status in patients with surgically treated head and neck squamous cell carcinoma via neck lavage cytology: A pilot study.

BACKGROUND: Neck dissection is a standardized surgical procedure for patients with head and neck squamous cell carcinoma (HNSCC) and plays a critical role in the choice of adjuvant treatment based on histopathological findings. Saline irrigation is routinely performed at the end of surgery. However, this irrigant is not used for diagnostic purposes. METHODS: Intraoperative irrigation of the neck dissection wound was performed in 56 patients with HNSCC (N = 93 neck dissections), and the cytological suspension obtained was processed via the liquid-based cytology (LBC) technique, Papanicolaou staining, and immunocytochemical staining. Microscopic preparations were screened for the presence of tumor cells and classified as positive, borderline, or negative. These results were correlated with the histopathological and clinical data. RESULTS: Neck lavage LBC demonstrated high diagnostic value in detecting lymph node metastases (N+) with extracapsular spread (ECS), with a specificity, sensitivity, negative predictive value, and positive predictive value of 93.1%, 100%, 100%, and 80%, respectively. Tumor cells were detected in 4.8% of N- cases, 20% of N+ cases without ECS, and 100% of N+ cases with ECS. Receiver operating characteristic curve analysis showed an area under the curve of 0.8429 for the prediction of N+ (p < .0001) and 0.9658 for the prediction of N+ with ECS (p < .0001). CONCLUSIONS: Differential lavage cytology can provide valid and rapid information on the lymph node status in patients with HNSCC and showed an excellent correlation with histopathology. Thus, neck lavage LBC may facilitate faster and more reasonable planning of adjuvant treatment and help improve the therapeutic management of patients with HNSCC.

Tumor-stroma ratio in preoperative biopsies and matched surgical specimens in oral squamous cell carcinoma: Concordance and impact on recurrence-free and overall survival.

Stroma-richness is commonly associated with decreased survival times as well as advanced tumor stages in various malignant tumors. A previous study on laryngeal squamous cell carcinomas showed very good agreement for tumor-stroma ratio assessment between pre-treatment biopsies and resection specimens. We therefore aimed to determine whether similar results could be shown for oral squamous cell carcinomas. 107 preoperative biopsies and matched surgical specimens were obtained from the histological archive, dating from 2011-2022. Tumor-stroma ratio was determined on all samples and cases were divided into stroma-rich (≥50% stroma) and stroma-poor (<50% stroma). Results were then correlated with recurrence-free and overall survival. Tumor-stroma ratio showed substantial agreement between preoperative biopsies and surgical specimens with a kappa correlation coefficient of 0.643. Concerning preoperative biopsies, 28 cases were stroma-rich (26.2%), in the group of tumor resections, 32 cases were stroma-rich (29.9%). No association with either recurrence-free or overall survival could be shown for both groups (p-values 0.158-0.495). Concordance between pre-treatment biopsies and resections was substantial in our study, however, as no association with survival times could be demonstrated, the prognostic significance in our cohort remains unclear. This might be attributable to the fact that almost 75% of our patients presented with early-stage tumors, which sometimes seem to show a less pronounced prognostic effect of the tumor-stroma ratio.

Improved intraoperative identification of close margins in oral squamous cell carcinoma resections using a dual aperture fluorescence ratio approach: first in-human results.

Significance: Surgical excision is the main treatment for solid tumors in oral squamous cell carcinomas, where wide local excision (achieving a healthy tissue margin of >5 mm around the excised tumor) is the goal as it results in reduced local recurrence rates and improved overall survival. Aim: No clinical methods are available to assess the complete surgical margin intraoperatively while the patient is still on the operating table; and while recent intraoperative back-bench fluorescence-guided surgery approaches have shown promise for detecting "positive" inadequate margins (<1 mm), they have had limited success in the detection of "close" inadequate margins (1 to 5 mm). Here, a dual aperture fluorescence ratio (dAFR) approach was evaluated as a means of improving detection of close margins. Approach: The approach was evaluated on surgical specimens from patients who were administered a tumor-specific fluorescent imaging agent (cetuximab-800CW) prior to surgery. The dAFR approach was compared directly against standard wide-field fluorescence imaging and pathology measurements of margin thickness in specimens from three patients and a total of 12 margin locations (1 positive, 5 close, and 6 clear margins). Results: The area under the receiver operating characteristic curve, representing the ability to detect close compared to clear margins (>5 mm) was found to be 1.0 and 0.57 for dAFR and sAF, respectively. Improvements in dAFR were found to be statistically significant (p<0.02). Conclusions: These results provide evidence that the dAFR approach potentially improves detection of close surgical margins.

Prognostic value of preoperative inflammatory ratios in early glottic cancer treated with transoral laser surgery.

BACKGROUND: There is growing evidence regarding the prognostic utility of ratios such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammatory index (SIII) in head and neck squamous cell carcinoma (HNSCC). However, most studies to date include heterogeneous series with different treatments or tumor subsites. METHODS: We collected data from 201 patients with stage I-II glottic squamous cell carcinoma treated with transoral laser surgery. NLR, PLR, and SIII were calculated from preoperative cell blood count, cut-off points were obtained by ROC curve analysis, and survival rates were calculated. RESULTS: High NLR (p = 0.012) and SIII (p = 0.037), but not PLR (p = 0.48), were associated with worse disease-specific survival (DSS). A similar trend was observed with overall survival (OS), although it did not reach statistical significance. On multivariable analyses, both high NLR (HR = 3.8, 95% CI = 1.5-9.9, p = 0.006) and high SIII (HR = 2.77, 95% CI = 1.1-6.9, p = 0.03) were significantly associated with shortened DSS. CONCLUSIONS: Preoperative NLR and SIII emerge as independent prognostic biomarkers for early-stage surgically treated glottic tumors and could guide individualized follow-up.

Compartmental surgery for T4b oral squamous cell carcinoma involving the masticatory space.

PURPOSE OF REVIEW: This review aims to describe the oncological outcomes of T4b oral squamous cell carcinomas (OSCC) with masticatory space involvement as well as the surgical approaches that are able to achieve compartmental 'en bloc' resection of these lesions. RECENT FINDINGS: The masticatory space is subdivided into infra-notch and supra-notch spaces according to the axial plane passing through the mandibular notch between the coronoid process and the condyle neck. Compartmental resection for T4b OSCC with masticatory space invasion can be successfully achieved via purely external approaches or combining external and transnasal endoscopic routes. Infra-notch T4b OSCC showed survival outcomes comparable to T4a OSCC, thus prompting treatment with curative intent. SUMMARY: Compartmental resection of the masticatory space is technically feasible with comprehensive control of tumour margins. Use of a transnasal endoscopic anterior route within a multiportal approach may provide better control of margins at the level of the pterygo-maxillary fissure. Equivalent survival outcomes between T4a and infra-notch T4b OSCC are reported. Thus, a downstaging of the latter to T4a is advisable and compartmental surgery of such advanced lesions could be considered as a first-line treatment option in selected patients.

Sentinel lymph node biopsy versus elective neck dissection in management of the clinically negative (cN0) neck in patients with oral squamous cell carcinoma: A systematic review and meta-analysis.

Oral squamous cell carcinoma (OSCC) is the most prevalent type of head and neck cancer, and lymph node metastasis is a crucial prognostic factor that has a direct correlation with the survival rate. The standard procedure for managing clinically negative (cN0) neck in OSCC patients is elective neck dissection (END), but it can lead to various complications that affect the patient's quality of life. Therefore, medical professionals are exploring the use of the sentinel lymph node biopsy (SLNB) to manage cN0 neck in OSCC patients. The aim of this systematic review and meta-analysis was to compare the overall survival (OS) and disease-free survival (DFS) of patients undergoing SLNB and END in the surgical management of early cN0 neck in OSCC patients. To conduct this study, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was used to report the systematic reviews. The study included all comparative clinical studies, including randomized clinical trials (RCTs), clinical perspective studies, and retrospective studies that compared END to SLNB for early cN0 neck in OSCC patients. The hazard ratio (HR) and risk ratio (RR) with 95% confidence interval (CI) were calculated using comprehensive meta-analysis. The primary outcome variables were OS, DFS, and disease-specific survival (DSS). The secondary outcome variable was the nodal recurrence rate without local or distant metastasis. The GRADE system was used to assess the evidence's certainty. The meta-analysis included 12 clinical studies, comprising three RCTs and seven non-RCTs. The results showed no statistically significant difference between END and SLNB concerning OS (HR = 0.993, CI: 0.814 to 1.211, P = 0.947, low-quality evidence), DFS (HR = 0.705, CI: 0.408 to 1.29, P = 0.21, low-quality evidence), and nodal recurrence (RR = 1.028, CI: 0.969 to 1.090, P = 0.907, low-quality evidence). Additionally, SLNB was non-inferior to END regarding DSS (RR = 1.028, CI: 0.969 to 1.090, P = 0.907, low-quality evidence). In conclusion, this research affirms the safety and precision of SLNB as a means to stage cN0 OSCC patients, with outcomes that are comparable to END in terms of survival and nodal recurrence. Nevertheless, it's crucial to acknowledge that the quality of evidence in this study was relatively low. Therefore, additional RCTs comparing END to SLNB are warranted to validate these results and offer more robust guidance for managing cN0 OSCC patients.

Towards effectiveness of cell free DNA based liquid biopsy in head and neck squamous cell carcinoma.

Liquid biopsy is a minimally invasive procedure, that uses body fluids sampling to detect and characterize cancer fingerprints. It is of great potential in oncology, however there are challenges associated with the proper handling of liquid biopsy samples that need to be addressed to implement such analysis in patients' care. Therefore, in this study we performed optimization of pre-analytical conditions and detailed characterization of cfDNA fraction (concentration, length, integrity score) in surgically treated HNSCC patients (n = 152) and healthy volunteers (n = 56). We observed significantly higher cfDNA concentration in patients compared to healthy controls (p < 0.0001) and a time dependent decrease of cfDNA concentration after tumor resection. Our results also revealed a significant increase of cfDNA concentration with age in both, healthy volunteers (p = 0.04) and HNSCC patients (p = 0.000002). Moreover, considering the multitude of HNSCC locations, we showed the lack of difference in cfDNA concentration depending on the anatomical location. Furthermore, we demonstrated a trend toward higher cfDNA length (range 35-10380 and 500-10380 bp) in the group of patients with recurrence during follow-up. In conclusion, our study provide a broad characterization of cfDNA fractions in HNSCC patients and healthy controls. These findings point to several aspects necessary to consider when implementing liquid biopsy in clinical practice including: (I) time required for epithelial regeneration to avoid falsely elevated levels of cfDNA not resulting from active cancer, (II) age-related accumulation of nucleic acids accompanied by less efficient elimination of cfDNA and (III) higher cfDNA length in patients with recurrence during follow-up, reflecting predominance of tumor necrosis.

Primary Site Surgery in Distantly Metastatic Oropharyngeal Squamous Cell Carcinoma.

OBJECTIVES: Determine if intensive local therapy (i.e., local surgery or radiation) has a survival benefit for patients presenting with distantly metastatic oropharyngeal squamous cell carcinoma (OPSCC). METHODS: Retrospective population-based cohort study of patients in the National Cancer Database presenting with distantly metastatic OPSCC. Overall survival (OS) was compared for patients receiving systemic therapy alone or in combination with local surgery or curative dose radiation, controlling for various clinicodemographic factors. RESULTS: Between 2010 and 2015, 627 patients presented with newly diagnosed, metastatic OPSCC and an initial treatment course including systemic chemotherapy. Multivariable analysis demonstrated that local radiation therapy was independently associated with improved OS (OR 0.64, CI [0.51-0.81]); local surgery was not independently associated with improved OS (OR 0.99, CI [0.65-1.53]). Higher T stages were associated with worse OS (OR 1.69, CI [1.14-2.50] for T3 and OR 1.77, CI [1.22-2.58] for T4 compared to T1). HPV-positive (HPV+) tumors were associated with improved OS compared to HPV- (OR 0.79, CI [0.64-0.97]). Multiagent chemotherapy was associated with improved OS compared to single-agent (OR 0.78, CI [0.62-1.00]). The best survival for the entire cohort and for HPV+ patients was for radiation with systemic therapy and the worst survival for systemic therapy alone. CONCLUSIONS: Curative dose local radiotherapy in addition to systemic therapy is associated with improved OS compared to systemic therapy alone in patients presenting with distantly metastatic OPSCC. There is not a significant survival benefit for local surgery in addition to systemic therapy in this patient population, regardless of HPV status. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:2243-2251, 2024.

Effect of preoperative programmed death-1 or programmed death ligand-1 immune check point inhibition on complications after surgery for primary head and neck cancer.

BACKGROUND: There is sparse literature on the effect of preoperative immunotherapy on complications after surgery for primary head and neck squamous cell carcinoma (HNSCC). The objectives are to compare complication rates in patients receiving surgery with and without neoadjuvant immune checkpoint inhibitors (nICI) for primary HNSCC and to evaluate factors associated with increased odds of surgical complications. METHODS: A retrospective review of patients who underwent ablation and free flap reconstruction or transoral robotic surgery (TORS) for primary HNSCC between 2017-2021 was conducted. Complications were compared between patients who underwent surgery with or without nICI before and after propensity score matching. Regression analysis to estimate odds ratios was performed. RESULTS: A total of 463 patients met inclusion criteria. Free flap reconstruction constituted 28.9% of patients and TORS constituted 71.1% of patients. nICI was administered in 83 of 463 (17.9%) patients. There was no statistically significant difference in surgical, medical, or overall complications between patients receiving surgery with or without nICI. In the unmatched cohort, multivariable model identified non-White race, former/current smoking history, free flap surgery, and perineural invasion as factors significantly associated with increased complications. In the matched cohort, multivariable model identified advanced age and free flap surgery as factors significantly associated with increased complications. PLAIN LANGUAGE SUMMARY: It is safe to give immunotherapy before major surgery in patients who have head and neck cancer. Advanced age, non-White race, current/former smoking, free flap surgery, and perineural invasion may be associated with increased the odds of surgical complications.

Subcategorization of Perineural Invasion Stratifies Oral Cavity Squamous Cell Carcinoma Prognosis.

OBJECTIVE: To evaluate whether subcategorization of perineural invasion (PNI) improves the prognostic resolution of the American Joint Committee on Cancer, Eighth Edition (AJCC8) staging system in oral cavity squamous cell carcinoma (OCSCC). METHODS: OCSCC tumor specimens from patients seen at a tertiary care institution who underwent primary surgical resection between January 2019 and June 2021 were sorted into four PNI categories: negative, intratumoral, peripheral, and extratumoral. The prognostic effect of these PNI categories were assessed through Kaplan-Meier, Cox regression, and log-rank testing using recurrence-free survival (RFS) and overall survival (OS) as primary and secondary outcomes respectively. RESULTS: A total of 158 patients were examined. The median follow-up time was 21 months. PNI subcategorization further stratified RFS (p = 0.007) and OS (p = 0.002). Extratumoral PNI was associated with a 4.5-fold increase in recurrence risk (adjusted hazards ratio [aHR]: 4.53; 95% confidence interval [CI]: 1.1-18.66) and worse OS when compared with PNI negative disease (aHR: 5.71; 95% CI: 1.0-32.67). Peripheral PNI was associated with worse OS (aHR: 5.7; 95% CI: 1.35-24.08) but not worse RFS (p = 0.18) when compared with PNI negative disease. Interestingly, intratumoral PNI was not associated with significant differences in RFS (p = 0.087) or OS (p = 0.22) when compared with PNI negative disease. CONCLUSIONS: Subcategorization of OCSCC tumors into extratumoral, peripheral, and intratumoral PNI stratifies RFS and OS when compared with patients with PNI negative disease in an incremental fashion. This pilot study suggests that there may be added benefit in subcategorization of PNI in the prognostic evaluation of OCSCC. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:1656-1662, 2024.

5-Aminolevulinic Acid Fluorescence-Guided Surgery in Head and Neck Squamous Cell Carcinoma.

OBJECTIVES: To determine the utility of 5-aminolevulinic acid (5-ALA) fluorescence for resection of head and neck carcinoma. METHODS: In this prospective pilot trial, 5-ALA was administered as an oral suspension 3-5 h prior to induction of anesthesia for resection of head and neck squamous cell carcinoma (HNSCC). Following resection, 405 nm blue light was applied, and fluorescence of the tumor as well as the surgical bed was recorded. Specimen fluorescence intensity was graded categorically as none (score = 0), mild (1), moderate (2), or robust (3) by the operating surgeon intraoperatively and corroborated with final pathologic diagnosis. RESULTS: Seven patients underwent resection with 5-ALA. Five (83%) were male with an age range of 33-82 years (mean = 60). Sites included nasal cavity (n = 3), oral cavity (n = 3), and the larynx (n = 1). All specimens demonstrated robust fluorescence when 5-ALA was administered 3-5 h preoperatively. 5-ALA fluorescence predicted the presence of perineural invasion, a positive margin, and metastatic lymphadenopathy. Two patients had acute photosensitivity reactions, and one patient had a temporary elevation of hepatic enzymes. CONCLUSIONS: 5-ALA induces robust intraoperative fluorescence of HNSCC, capable of demonstrating a positive margin, perineural invasion, and metastatic nodal disease. Although no conclusions are there about the safety of this drug in the head and neck cancer population, our study parallels the extensive safety data in the neurosurgical literature. Future applications may include intraoperative assessment of margin status, diagnostic accuracy, and impacts on survival. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:741-748, 2024.