Histopathologic Features of Mucosal Head and Neck Cancer Cachexia.

Objective: Determine the histopathologic features that correlate with head and neck cancer (HNC) cachexia. Methods: A single-institution, retrospective study was performed on adults with HPV-negative, mucosal squamous cell carcinoma of the aerodigestive tract undergoing resection and free flap reconstruction from 2014 to 2019. Patients with distant metastases were excluded. Demographics, comorbidities, preoperative nutrition, and surgical pathology reports were collected. Comparisons of histopathologic features and cachexia severity were made. Results: The study included 222 predominantly male (64.9%) patients aged 61.3 ± 11.8 years. Cachexia was identified in 57.2% patients, and 18.5% were severe (≥15% weight loss). No differences in demographics were identified between the groups. Compared to control, patients with severe cachexia had lower serum hemoglobin (p=0.048) and albumin (p < 0.001), larger tumor diameter (p < 0.001), greater depth of invasion (p < 0.001), and elevated proportions of pT4 disease (p < 0.001), pN2-N3 disease (p=0.001), lymphovascular invasion (p=0.009), and extranodal extension (p=0.014). Multivariate logistic regression identified tumor size (OR [95% CI] = 1.36 [1.08-1.73]), oral cavity tumor (OR [95% CI] = 0.30 [0.11-0.84]), and nodal burden (OR [95% CI] = 1.16 [0.98-1.38]) as significant histopathologic contributors of cancer cachexia. Conclusions: Larger, more invasive tumors with nodal metastases and aggressive histologic features are associated with greater cachexia severity in mucosal HNC.

Transoral robotic surgery in the diagnosis and treatment of primary unknown head and neck squamous cell carcinoma: A preliminary single centre experience.

BACKGROUND: Squamous cell carcinoma of unknown primary (CUP) in the head and neck is difficult to diagnose and treat. This report outlines 11 cases of CUP treated with transoral robotic surgery (TORS), aimed at investigating the diagnostic efficiency of primary tumour and radical resection effectiveness of TORS. METHODS: 11 cases of CUP among 68 oropharyngeal cancer patients treated by TORS were analysed retrospectively. RESULTS: All the 11 cases received TORS with cervical lymph node dissection. Primary tumours were found in 8 cases (72.7%), 4 cases in the palatine tonsil and 4 cases in the base of the tongue. The average diameter of the primary tumour was 1.65 cm. All patients resumed eating by mouth within 24 h, no tracheotomy, no pharyngeal fistula and no postoperative death. The 3-year disease-free survival rate was 91%. CONCLUSIONS: TORS can improve the diagnostic efficiency of primary tumour of CUP and achieve good oncology and functional results.

Assessment of Concentration KRT6 Proteins in Tumor and Matching Surgical Margin from Patients with Head and Neck Squamous Cell Carcinoma.

Head and neck squamous cell carcinomas (HNSCCs) are one of the most frequently detected cancers in the world; not all mechanisms related to the expression of keratin in this type of cancer are known. The aim of this study was to evaluate type II cytokeratins (KRT): KRT6A, KRT6B, and KRT6C protein concentrations in 54 tumor and margin samples of head and neck squamous cell carcinoma (HNSCC). Moreover, we examined a possible association between protein concentration and the clinical and demographic variables. Protein concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Significantly higher KRT6A protein concentration was found in HNSCC samples compared to surgical margins. An inverse relationship was observed for KRT6B and KRT6C proteins. We showed an association between the KRT6C protein level and clinical parameters T and N in tumor and margin samples. When analyzing the effect of smoking and drinking on KRT6A, KRT6B, and KRT6C levels, we demonstrated a statistically significant difference between regular or occasional tobacco and alcohol habits and patients who do not have any tobacco and alcohol habits in tumor and margin samples. Moreover, we found an association between KRT6B and KRT6C concentration and proliferative index Ki-67 and HPV status in tumor samples. Our results showed that concentrations of KRT6s were different in the tumor and the margin samples and varied in relation to clinical and demographic parameters. We add information to the current knowledge about the role of KRT6s isoforms in HNSCC. We speculate that variations in the studied isoforms of the KRT6 protein could be due to the presence and development of the tumor and its microenvironment. It is important to note that the analyses were performed in tumor and surgical margins and can provide more accurate information on the function in normal and cancer cells and regulation in response to various factors.

The Importance of the Time Interval Between Preoperative 18F-FDG PET/CT Imaging and Neck Dissection for the Detection of Nodal Metastases in Patients with Head and Neck Squamous Cell Carcinoma.

BACKGROUND: Detection of nodal metastasis is critical for the treatment and prognosis of head and neck cancer (HNC). Positron emission tomography/computed tomography (PET/CT) is increasingly being used to detect cervical lymph node involvement. AIM: The purposes of this study were to (1) investigate the diagnostic accuracy of PET/CT for the detection of neck metastasis in patients with HNC and (2) determine the effect of the time interval between surgery and PET/CT. METHODS: Fifty patients with head and neck squamous cell carcinoma who underwent PET/CT before surgery were included in this study. Preoperative PET/CT images that determined lymph node metastasis were compared with the histopathological analysis of neck dissection samples. Neck dissections were divided into three groups according to the time interval between surgery and PET/CT (0-2 weeks, >2-4 weeks, and >4 weeks). The concordance between PET/CT and histopathology was measured using the neck sides at different time intervals. The specificity, sensitivity, accuracy, negative predictive value (NPV), and positive predictive value (PPV) of PET/CT in detecting metastatic lymph nodes in the neck were calculated. RESULTS: A total of 79 neck dissections were included in the study as 29 (58%) of the patients underwent bilateral neck dissection. The overall accuracy of PET/CT in detecting nodal metastasis was highest for the 0-2 weeks interval (95.6%). During this time interval, the sensitivity, specificity, NPV, and PPV of PET/CT were 100%, 90.9%, 100%, and 92.3%, respectively. CONCLUSIONS: Although PET/CT is an important and reliable diagnostic method for detecting nodal metastases in patients with HNC, its reliability decreases as the time between surgeries increases. The optimal interval was 2 weeks; however, up to 4 weeks was acceptable.

Novel prognostic nomograms for postoperative patients with oral cavity squamous cell carcinoma in the central region of China.

BACKGROUND: Oral cavity squamous cell carcinoma (OCSCC) is the most common pathological type in oral tumors. This study intends to construct a novel prognostic nomogram model based on China populations for these resectable OCSCC patients, and then validate these nomograms. METHODS: A total of 607 postoperative patients with OCSCC diagnosed between June 2012 and June 2018 were obtained from two tertiary medical institutions in Xinxiang and Zhengzhou. Then, 70% of all the cases were randomly assigned to the training group and the rest to the validation group. The endpoint time was defined as overall survival (OS) and disease-free survival (DFS). The nomograms for predicting the 3-, and 5-year OS and DFS in postoperative OCSCC patients were established based on the independent prognostic factors, which were identified by the univariate analysis and multivariate analysis. A series of indexes were utilized to assess the performance and net benefit of these two newly constructed nomograms. Finally, the discrimination capability of OS and DFS was compared between the new risk stratification and the American Joint Committee on Cancer (AJCC) stage by Kaplan-Meier curves. RESULTS: 607 postoperative patients with OCSCC were selected and randomly assigned to the training cohort (n = 425) and validation cohort (n = 182). The nomograms for predicting OS and DFS in postoperative OCSCC patients had been established based on the independent prognostic factors. Moreover, dynamic nomograms were also established for more convenient clinical application. The C-index for predicting OS and DFS were 0.691, 0.674 in the training group, and 0.722, 0.680 in the validation group, respectively. Besides, the calibration curve displayed good consistency between the predicted survival probability and actual observations. Finally, the excellent performance of these two nomograms was verified by the NRI, IDI, and DCA curves in comparison to the AJCC stage system. CONCLUSION: The newly established and validated nomograms for predicting OS and DFS in postoperative patients with OCSCC perform well, which can be helpful for clinicians and contribute to clinical decision-making.

Surgical margins in head and neck squamous cell carcinoma: A narrative review.

Head and neck squamous cell carcinoma (HNSCC), a prevalent and frequently recurring malignancy, often necessitates surgical intervention. The surgical margin (SM) plays a pivotal role in determining the postoperative treatment strategy and prognostic evaluation of HNSCC. Nonetheless, the process of clinical appraisal and assessment of the SMs remains a complex and indeterminate endeavor, thereby leading to potential difficulties for surgeons in defining the extent of resection. In this regard, we undertake a comprehensive review of the suggested surgical distance in varying circumstances, diverse methods of margin evaluation, and the delicate balance that must be maintained between tissue resection and preservation in head and neck surgical procedures. This review is intended to provide surgeons with pragmatic guidance in selecting the most suitable resection techniques, and in improving patients' quality of life by achieving optimal functional and aesthetic restoration.

Lymph node metastasis in cutaneous squamous cell carcinoma of the head and neck.

BACKGROUND: The study aimed to assess the impact of parotid lymph nodes (LNs) on the prognosis of patients with cutaneous squamous cell carcinomas of the head and neck (HNcSCC), and to develop an alternative LN assessment method to enhance locoregional control (LRC) and overall survival (OS) stratification. METHODS: We retrospectively enrolled patients with surgically treated HNcSCC. Primary outcome variables were LRC and OS. The influence of parotid LNs and different LN assessment methods on prognosis was analyzed using Cox models, and comparisons were made using the C-index, Akaike Information Criterion, and Bayesian Information Criterion. RESULTS: A total of 126 patients were included. Both intraparotid and periparotid LN statuses significantly linked with prognosis. The presence of extranodal extension (ENE) in cervical LNs, rather than parotid LNs, was predictive of decreased LRC and OS. In the Cox analysis, only N3 of the AJCC N classification, when compared to N0, showed reduced LRC and OS. In comparison to N0P1, only N0P3/N1P1 and N2P2/N2P3 of the O'Brien staging system tended to predict poorer LRC, with no subgroup emerging as an independent predictor for OS. The proposed LN assessment method, based on the number of metastatic LNs and ENE status in cervical LNs, demonstrated superior performance in terms of C-index, Akaike Information Criterion, and Bayesian Information Criterion compared to other systems. CONCLUSION: Parotid LNs were significant determinants of prognosis in metastatic HNcSCC. The novel LN assessment method proposed (1-2 vs. 3-4 vs. 5 + or ENE) displayed similar survival stratification to the AJCC N and O'Brien staging systems.

Oncological outcomes post transoral robotic surgery (TORS) for HPV-associated oropharyngeal squamous cell carcinoma, a single-centre retrospective Australian study.

We present a cohort review of TORS resection for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) and its associated oncological outcomes spanning a 10-year period. A retrospective case series review was performed of patients undergoing primary surgical treatment for HPV-associated OPSCC through the St. Vincent's Head and Neck Cancer service from 2011 to 2022. The primary outcomes were to investigate complete resection of the primary tumour, rates of recurrence, and survival analysis. Secondary outcomes included complications, rates of adjuvant therapy, sites of recurrence and rates of percutaneous endoscopic gastrostomy (PEG). 184 patients underwent TORS-based therapy with neck dissection, and guideline-directed adjuvant therapy for HPV-associated OPSCC. Our median follow-up was 46 months. The positive margin rate on final histopathology analysis was 10.9%. Adjuvant therapy was indicated in 85 patients (46%). The local recurrence rate was 10.9% with the majority (80%) of patients recurring in the first 3 years since treatment. The disease-specific survival at 3 years was 98.6% and at 5 years was 94.4%. The 3-year and 5-year OS for the cohort was 96.7% and 92.5%, respectively. The presence of extranodal extension and positive margins were associated with increased risk of recurrence, whereas adjuvant therapy was found to be a protective factor for both overall recurrence and survival. Major complications occurred in 12 patients (6.5%), resulting in one death. This study has demonstrated that primary surgical therapy for HPV-associated OPSCC is a safe and effective treatment modality with low local recurrence and complication rates, and overall survival benefits.

Prognostic effect of surgical treatment in elderly oral squamous cell carcinoma patients: A retrospective study.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is one of the most prevalent malignant tumors in head and neck. However, few studies have focused on the postoperative prognosis of elderly OSCC patients undergoing surgical resection and reconstruction. METHODS: We conducted a retrospective study of 349 patients diagnosed OSCC in the Department of Oral and Maxillofacial Surgery, The Affiliated Hospital of Qingdao University from January 2016 to December 2022. Demographic and clinicopathological characteristics were recorded. Kaplan-Meier analysis was performed to identify the impact of age and reconstruction types on the prognosis of OSCC patients. Univariable regression analysis and multivariable Cox analysis were conducted to find independent prognostic factors of the younger and elderly OSCC patients. RESULTS: Among 349 OSCC patients included in this retrospective study, 241 (69.1 %) were elderly patients and 108 (30.9 %) were younger patients. The two groups were comparable according to the demographic records. The elderly group presented a better recurrence-specific prognosis than that of the younger group (RFS: p = 0.0324). There are no remarkable differences on the prognosis of different reconstructive types. Gender, current address, life habit, invasion patterns, and TNM stage were identified as independent prognostic factors of the younger and elderly OSCC patients. CONCLUSION: Elderly OSCC patients achieve a better recurrence-free survival than that of the younger patients. Meanwhile, the recurrence of OSCC patients is independent of their demographic and clinicopathological features. Elderly OSCC patients will benefit from aggressive surgical treatment as the younger patients.

Comparing the clinical outcomes of initial surgery and primary definitive radiotherapy with a dosage of 6600 cGy or higher in cT1-2N0M0 oral cavity squamous cell carcinoma: A nationwide cohort study.

BACKGROUND: To compare the clinical outcomes of two treatment modalities, initial surgery and primary definitive radiotherapy (RT), in Taiwanese patients diagnosed with cT1-2N0M0 oral cavity squamous cell carcinoma (OCSCC). METHODS: Between 2011 and 2019, we analyzed data for 13,542 cT1-2N0M0 patients who underwent initial surgery (n = 13,542) or definitive RT with a dosage of at least 6600 cGy (n = 145) for the treatment of OCSCC. To account for baseline differences, we employed propensity score (PS) matching, resulting in two well-balanced study groups (initial surgery, n = 580; definitive RT, n = 145). RESULTS: Before PS matching, the 5-year disease-specific survival (DSS) rates were 88% for the surgery group and 58% for the RT group. After PS matching, the 5-year DSS rates of the two groups were 86% and 58%, respectively. Similarly, the 5-year overall survival (OS) rates before PS matching were 80% for the surgery group and 36% for the RT group, whereas after PS matching, they were 73% and 36%, respectively. All these differences were statistically significant (p < 0.0001). A multivariable analysis identified treatment with RT, older age, stage II tumors, and a higher burden of comorbidities as independent risk factors for both DSS and OS. We also examined the 5-year outcomes for various subgroups (margin ≥5 mm, margin <5 mm, positive margins, RT combined with chemotherapy, and RT alone) as follows: DSS, 89%/88%/79%/63%/51%, respectively, p < 0.0001; OS, 82%/79%/68%/39%/32%, respectively, p < 0.0001. CONCLUSIONS: In Taiwanese patients with cT1-2N0M0 OCSCC, a remarkably low proportion (1.1%) completed definitive RT. A significant survival disparity of 30% was observed between patients who underwent initial surgery and those who received definitive RT. Interestingly, even patients from the surgical group with positive surgical margins exhibited a significantly superior survival compared to those in the definitive RT group.

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.

Indications for oropharyngeal biopsy in head and neck squamous cell carcinoma of unknown primary: A systematic review (HNSCCUP).

INTRODUCTION: Patients presenting with head and neck squamous cell carcinoma of unknown primary (HNSCCUP) remain challenging clinical scenarios as large variation exists in practices used to locate the primary. OBJECTIVE: The objective of this systematic review is to review of the literature and offer recommendations for oropharyngeal biopsies in HNSCCUP. METHOD: Pubmed, Medline and Embase were searched to identify studies from inception to October 2021. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. RESULTS: A total of 483 articles were included and screened, 41 studies met the inclusion criteria, including over 3400 patients from the original articles (122 of these patients were reported on in two sequential articles by a single author - table 1) and 4 large metaanalyses including 1852 patients. The primary site identification rate following random biopsies or deep tissue biopsies is less than 5% in most studies. The mean detection rate following ipsilateral tonsillectomy is 34%; two pooled analyses indicate that the mean detection rate following tongue base mucosectomy is 64%, with this figure rising when the tonsils are negative. CONCLUSIONS: High level evidence is lacking, with heterogeneity in the reported studies. Published meta-analyses are based on retrospective data. There is little evidence supporting the practice of random/non-directed oropharyngeal biopsies. Available evidence supports palatine tonsillectomy and tongue base mucosectomy compared to deep tissue biopsies.

Factors associated with adjuvant treatment delays in patients treated surgically for head and neck cancer.

OBJECTIVE: To determine the patient and treatment characteristics associated with delay in post-operative radiation therapy (PORT) for patients treated surgically for head and neck squamous cell cancer (HNSCC) at our institution. DESIGN: Single institution retrospective review. SETTING: Tertiary care academic medical centre. PARTICIPANTS: Patients treated surgically for HNSCC who underwent PORT between 2013 and 2016. MAIN OUTCOME MEASURES AND RESULTS: One hundred forty patients met inclusion criteria. A majority did not start radiotherapy within 6 weeks. Factors associated with a delayed initiation of PORT included length of stay >8 days, 30-day readmission, no adjuvant chemotherapy, post-operative complications and fragmented care. CONCLUSIONS: A majority of patients did not initiate PORT within the guideline-recommended 6 weeks. Modifiable risks factors that delay initiation of PORT were identified.

Transoral Robotic Surgery and Radiation Volume Deintensification in Unknown Primary Squamous Cell Carcinoma of the Neck: The Phase 2 FIND Nonrandomized Controlled Trial.

Importance: Patients with unknown primary squamous cell carcinoma (CUP) with cervical metastases typically receive comprehensive radiotherapy (RT) of the pharynx and bilateral neck. Typically, these patients receive comprehensive RT of the pharynx and bilateral neck that may produce treatment-related toxic effects. Objective: To determine whether localization of occult oropharyngeal cancers with transoral robotic surgery (TORS) combined with reduced pharyngeal and neck RT volumes provides acceptable disease control. Design, Setting, and Participants: This phase 2, single-group nonrandomized controlled trial at a single institution accrued 32 prospective participants with p16-positive CUP without a primary squamous cell carcinoma on examination and imaging from 2017 to 2019, and 24-month follow-up. The data analysis was conducted from January 2021 to June 2022. Intervention: Diagnostic- (n = 13) or therapeutic-intent (n = 9) TORS, with pharyngeal-sparing radiotherapy (PSRT) prescribed for negative margins or pT0, and unilateral neck RT (UNRT) prescribed for unilateral lymphadenopathy with lateralized primary tumor or pT0. Main Outcomes and Measures: Out-of-radiation treatment volume failure (<15% was hypothesized to be acceptable) and reports of local and regional recurrence, overall survival, toxic effects, swallowing outcomes (per the MD Anderson Dysphagia Inventory), and videofluoroscopic swallow (per Dynamic Imaging Grade of Swallowing Toxic Effects [DIGEST]) ratings. Results: The study sample comprised 22 patients (mean [SD] age, 59.1 [5.7] years; 3 [14%] females and 19 [86%] male) with CUP. Of these, 19 patients (86%) had tumor stage cN1; 2 (9%), cN2; and 1 (5%), cN3. Five patients (23%), 14 patients (64%), and 3 patients (13%) had 0, 1, or 2 primary tumors, respectively. Twenty patients received RT; of these, 9 patients (45%) underwent PSRT and 10 patients (50%), UNRT. In the diagnostic-intent group, 8 patients (62%) and 5 patients (38%) underwent RT and RT-concurrent chemotherapy, respectively. In the therapeutic-intent group, 6 patients (67%) and 1 patient (11%) received adjuvant RT-concurrent chemotherapy, respectively; 2 patients declined RT. Two-year out-of-radiation treatment volume failure, locoregional control, distant metastasis control, and overall survival were 0%, 100%, 95%, and 100%, respectively. Grade 3 or 4 surgical, acute, and late toxic effects occurred in 2 (9%), 5 (23%), and 1 (5%) patients, respectively. PSRT was associated with lower RT dose to superior constrictors (37 vs 53 Gy; mean difference, 16 Gy; 95% CI, 6.4, 24.9), smaller decline in swallowing scores during treatment (19.3 vs 39.7; mean difference, -20.4; 95% CI, -34.1 to -6.1), and fewer patients with worsening DIGEST grade on findings of videofluoroscopic swallow studies at 2 years (0% vs 60%; difference, 60%; 95% CI, 30% to 90%). Conclusions and Relevance: These findings indicate that TORS for p16-positive CUP allows RT volume deintensification with excellent outcomes and support future investigation in randomized clinical trials. Trial Registration: ClinicalTrials.gov Identifier: NCT03281499.

Impact of outside referral and dental extractions on package time with post-operative radiation therapy for head and neck cancer.

INTRODUCTION: Patients with squamous cell carcinoma of the head and neck (HNSCC) often receive post-operative radiotherapy (RT). A package time between surgery and completion of RT of ≤100 days is associated with lower recurrence and longer survival. In this study, we investigate the impact of outside referral and dental extractions on package time, with secondary detriment to relapse-free survival (RFS) and overall survival (OS). METHODS: We conducted a retrospective chart review on patients with HNSCC who received primary surgical resection at an academic medical centre. RESULTS: Ninety-four patients met eligibility criteria, 35% experienced recurrence, and 21% died. Median package time was 89.5 days, with 76% of patients achieving a package time ≤100 days. Receiving RT in-house was associated with a shorter package time (P = 0.0004) and higher completion rate within 100 days (P = 0.01). Dental extractions did not affect package time. A Kaplan-Meier analysis was performed to study survival, and a package time ≤100 days was not associated with a change in RFS or OS. A Cox proportional hazard model was used to investigate other factors hypothesized to impact patient survival; none had an effect on RFS, but cancer stage had an effect on OS (P = 0.01). CONCLUSIONS: We identified that outside referrals, but not dental extractions, prolong treatment package times. We also saw no effect of package time on RFS or OS. These results suggest that patients requesting outside facility referrals for RT may benefit from a streamlined program that expedites the referral process.

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.

Neighborhood-Level Disadvantage and Delayed Adjuvant Therapy in Head and Neck Cancer.

Importance: For patients with head and neck squamous cell carcinoma (HNSCC), initiation of postoperative radiation therapy (PORT) within 6 weeks of surgery is recommended by the National Comprehensive Cancer Network Guidelines and the Commission on Cancer. Although individual-level measures of socioeconomic status are associated with receipt of timely, guideline-adherent PORT, the role of neighborhood-level disadvantage has not been examined. Objective: To characterize the association of neighborhood-level disadvantage with delays in receiving PORT. Design, Setting, and Participants: This retrospective cohort study included 681 adult patients with HNSCC undergoing curative-intent surgery and PORT from 2018 to 2020 at 4 US academic medical centers. The data were analyzed between June 21, 2023, and March 5, 2024. Main Outcome Measures and Measures: The primary outcome was delay in initiating guideline-adherent PORT (ie, >6 weeks after surgery). Time-to-PORT (TTP) was a secondary outcome. Census block-level Area Deprivation Index (ADI) scores were calculated and reported as national percentiles (0-100); higher scores indicate greater deprivation. The association of ADI scores with PORT delay was assessed using multivariable logistic regression adjusted for demographic, clinical, and institutional characteristics. PORT initiation across ADI score population quartiles was evaluated with cumulative incidence plots and Cox models. Results: Among 681 patients with HNSCC undergoing surgery and PORT (mean [SD] age, 61.5 [11.2] years; 487 [71.5%] men, 194 [29.5%] women) the PORT delay rate was 60.8% (414/681) and median (IQR) TTP was 46 (40-56) days. The median (IQR) ADI score was 62.0 (44.0-83.0). Each 25-point increase in ADI score was associated with a corresponding 32% increase in the adjusted odds ratio (aOR) of PORT delay (aOR, 1.32; 95% CI, 1.07-1.63) on multivariable regression adjusted for institution, age, race and ethnicity, insurance, comorbidity, cancer subsite, stage, postoperative complications, care fragmentation, travel distance, and rurality. Increasing ADI score population quartiles were associated with increasing TTP (hazard ratio of PORT initiation, 0.71; 95% CI, 0.53-0.96; 0.59; 95% CI, 0.44-0.77; and 0.54; 95% CI, 0.41-0.72; for ADI quartiles 2, 3, and 4 vs ADI quartile 1, respectively). Conclusions and Relevance: Increasing neighborhood-level disadvantage was independently associated with a greater likelihood of PORT delay and longer TTP in a dose-dependent manner. These findings indicate a critical need for the development of multilevel strategies to improve the equitable delivery of timely, guideline-adherent PORT.

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.

Impact of Postoperative Radiotherapy on the Prognosis of Early-Stage (pT1-2N0M0) Oral Tongue Squamous Cell Carcinoma.

PURPOSE: To identify subgroups of patients with early-stage (pT1-2N0M0) oral tongue squamous cell carcinoma (OTSCC) who may benefit from postoperative radiotherapy (PORT). PATIENTS AND METHODS: This retrospective cohort study included 528 patients diagnosed between October 2009 and December 2021. Clinicopathological characteristics and treatments with or without PORT were analyzed for their impact on outcomes. RESULTS: Among 528 patients who underwent radical surgery (median age, 62 years [IQR, 52-69]), 145 (27.5%) also underwent PORT. Multivariate analyses revealed that PORT was associated with improved survival outcomes, whereas moderate-to-poor differentiation, perineural infiltration (PNI), lymphovascular invasion (LVI), and increasing depth of invasion (DOI) were associated with poorer survival outcomes. For patients with moderate-to-poor differentiation, the surgery + PORT group showed improved outcomes compared with the surgery-alone group. After propensity score matching, the results were as follows: overall survival (OS), 97% versus 69%, P = .003; disease-free survival (DFS), 88% versus 50%, P = .001. After excluding cases with PNI/LVI, the differences persisted: OS, 97% versus 82%, P = .040; DFS, 87% versus 64%, P = .012. Similar survival benefits were observed in 104 patients with PNI and/or LVI (OS, 81% v 58%; P = .022; DFS, 76% v 47%; P = .002). In subgroups with DOI >5 mm or close margins, PORT contributed to improved DFS (80% v 64%; P = .006; 92% v 66%; P = .049) but did not significantly affect OS. CONCLUSION: Patients with moderately-to-poorly differentiated pT1-2N0M0 OTSCC benefited from PORT. Our study provided evidence that patients with PNI and/or LVI who underwent PORT had improved survival. PORT also offered DFS benefit among patients with DOI >5 mm.